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2026-06-18 MRNA Moderna 平台竞争力与流感疫苗事件研究 ​

  • 数据时间：2026-06-18 02:56 Asia/Shanghai
  • 标的：Moderna (MRNA)
  • 报告类型：单标的 / 生物科技转型 / 行业与对手分析 / 事件驱动研究
  • 数据来源：IBKR Gateway read-only 延迟行情与 RTH 日线、SEC EDGAR XBRL、Moderna/合作方/监管文件、公开行业文章与研报、本地文章归档摘要、Yahoo Finance 公开期权链与新闻检索

一句话 ​

MRNA 现在的投资问题不是“疫苗股便宜不便宜”，而是“高现金消耗的 mRNA 平台能不能用 2026 年几个关键节点重新证明商业化能力”。MFLUSIVA/mRNA-1010 的 FDA VRBPAC 与 2026-08-05 PDUFA 是短期胜负手；真正决定中期估值中枢的是 intismeran、norovirus、PA 和组合疫苗能否把公司从 COVID 收缩故事推回多产品平台故事。

关键数据 ​

指标MRNA备注
IBKR 延迟当前价$60.622026-06-17 18:32 UTC；IBKR data type 3，延迟行情
IBKR 上一交易日 RTH close$55.402026-06-16 RTH 日线
IBKR 当日 RTH 日线最新 close$59.592026-06-17 采集中盘日线最新值，不等同于正式收盘
较上一交易日+9.42%用 IBKR 延迟当前价 / 2026-06-16 RTH close 计算
52 周 RTH 日线区间$22.28-$60.38251 根 IBKR RTH 日线；当前延迟价已略高于历史日线高点口径
1 周 / 1 月 / YTD / 近 1 年+29.6% / +23.9% / +93.1% / +134.6%IBKR RTH 日线计算；受 FDA 会前文件和事件预期影响大
市值 / EV~$23.9B / ~$17.1B$60.62 * Q1 2026 加权平均股数 395M；EV 扣 Q1 现金+投资并加长期债
2025 revenue$1.944BSEC / 公司 FY2025
Q1 2026 revenue$389M国际市场 $311M，美国 $78M
Q1 2026 GAAP net loss$(1.343)B包含约 $0.9B 一次性诉讼和解费用
Q1 2026 cash + investments~$7.456B现金 $1.908B + 当前投资 $3.297B + 非流动投资 $2.251B
2026 年底 cash + investments 指引$4.5B-$5.0BQ1 2026 更新口径；Q3 预计支付 $950M 和解现金
估值P/S 2025 约 12.3x；EV/S 2025 约 8.8x若按 2026 revenue 最多 +10%，EV/S 约 8.0x；公司仍亏损，不适合用 P/E

过往财务数据 ​

年度收入毛利率R&DSG&A净利润/亏损FCFFCF margin
2021$18.47B85.8%$1.99B$0.57B$12.20B$13.34B72.2%
2022$19.26B71.9%$3.30B$1.13B$8.36B$4.58B23.8%
2023$6.85B31.5%$4.85B$1.55B$(4.71)B$(3.83)B-55.9%
2024$3.24B54.8%$4.54B$1.17B$(3.56)B$(4.06)B-125.3%
2025$1.94B55.3%$3.13B$1.02B$(2.82)B$(2.07)B-106.2%

COVID 高峰给 Moderna 留下了现金和平台资产，但收入从 2022 年 $19.26B 掉到 2025 年 $1.94B。公司已明显收缩 R&D 和 SG&A，2025 FCF 烧钱也较 2024 改善；问题在于 2026 仍不是盈利年，新产品收入必须追上仍然很大的研发和商业化投入。

行业分析 ​

行业结构与关键变量 ​

维度当前事实来源对公司/估值的含义反证或限制
流感疫苗市场第三方估计 2026 年全球 flu vaccine 市场约 $7.9B，2036 年约 $11.2B，CAGR 约 3.6%Fact.MR 本地归档摘要这是成熟低增速市场，mRNA-1010 获批也不自动带来高成长估值市场规模为第三方估算；美国高剂量/佐剂/重组疫苗竞争强
需求驱动公共免疫项目、医院/政府采购、新兴市场覆盖率提升支撑年化需求Fact.MR 本地归档摘要Moderna 的机会在高风险人群标签、组合疫苗和供应速度，不在行业自然高增接种率、医保/采购和公众信任会影响实际销量
技术路线传统鸡胚/细胞培养需要更长生产周期；mRNA 可在序列确定后快速设计和制造CEPI 本地归档摘要mRNA 在 pandemic preparedness 和快速株更新上有平台价值季节性商业市场仍要看疗效、价格、接种体验和供应链
监管与标签FDA 2026-06-18 VRBPAC 讨论 MFLUSIVA 50 岁及以上人群；FDA 文件指出单季疗效、特殊人群、共同接种和 B/Victoria 数据缺口FDA 会议页、本地归档；FDA 简报文件监管风险已从“是否受理”转向“标签、人群和上市后义务”截至数据时间会议结果未出；最终审批不是会前文件能决定
平台竞争PatSnap 估计 Pfizer/BioNTech 与 Moderna 合计控制超过 90% clinical-stage mRNA vaccine development，Moderna 41 个候选项目、Pfizer/BioNTech 32 个PatSnap 本地归档摘要MRNA 有平台深度，但竞争集中在 BioNTech/Pfizer 生态第三方估算，需与公司管线交叉验证
Oncology 外延mRNA-4157/intismeran 与 Keytruda Phase 2b 五年数据继续显示 RFS/DMFS 风险下降Merck/Moderna 本地归档摘要若 Phase 3 成功，MRNA 将不只是季节性疫苗公司Phase 2b 样本量有限，OS 仍为探索性趋势

外部文章与研报归档摘要 ​

主题来源/标题发布日期归档状态中文摘要要点限制
MFLUSIVA FDA VRBPAC June 18 2026VRBPAC June 18, 2026 Meeting Announcement - U.S. FDA2026-06-16已归档 / 弹窗可读这是一则 FDA 官方会议通知：VRBPAC 将在 2026 年 6 月 18 日就 Moderna TX Inc. 的 MFLUSIVA（mRNA 流感疫苗）召开公开会议，讨论并对其用于 50 岁及以上人群预防甲/乙型流感的安全性与有效性作出建议，但该通知本身不包含审评结论。已取得本地原文并生成中文阅读摘要。
intismeran 5-year melanoma dataModerna and Merck Present 5-Year Data for Intismeran Autogene in Combination With KEYTRUDA® (pembrolizumab) in Patients With High-Risk Stage III/IV Melanoma Following Complete Resection at the 2026 ASCO Annual Meeting - Merck.com - Merck2026-06-01已归档 / 弹窗可读这是一则来自 Merck 与 Moderna 的临床更新稿，核心主张是：在高风险 III/IV 期黑色素瘤完全切除后的辅助治疗中，intismeran autogene（mRNA-4157/V940）联合 KEYTRUDA 在约 5 年随访时仍显示出较 KEYTRUDA 单药更好的无复发生存和远处转移无进展结果，但整体仍属于在研项目的阶段性数据，不是已获批疗已取得本地原文并生成中文阅读摘要。
Moderna H5 mRNA-1018 CEPI Phase 3CEPI to Fund Pivotal Phase 3 Trial for Moderna’s mRNA Pandemic Influenza Candidate - CEPI2025-12-18已归档 / 弹窗可读CEPI 将最多投入 5430 万美元支持 Moderna H5 pandemic influenza mRNA 候选疫苗 mRNA-1018 的关键 Phase 3，文章主张 mRNA 平台在大流行响应速度、可扩展制造和公平供应上有公共卫生价值。已取得本地原文并生成中文阅读摘要。
Moderna product pipelinemRNA medicines we are currently developing - Moderna未提供发布时间已归档 / 弹窗可读Moderna 管线页显示公司已经从 COVID 单一产品扩展成呼吸道疫苗、潜伏/其他疫苗、precision immunotherapies 和 rare disease therapeutics 多线并行的平台公司，但多个关键资产仍处于 Phase 2/3，商业兑现尚未完成。已取得本地原文并生成中文阅读摘要。
Moderna mFlusiva FDA advisory committee documentsFDA staff scrutinizes evidence supporting Moderna’s flu vaccine - BioPharma Dive2026-06-16已归档 / 弹窗可读BioPharma Dive 的文章认为 FDA 会前文件虽未发现 mFlusiva 的重大安全缺陷，但监管人员对疗效证据外推性、老年/脆弱人群、共同接种和单季数据提出明显质疑，因此审批路径改善但仍不是无风险。已取得本地原文并生成中文阅读摘要。
BioNTech Q1 2026 cash pipeline CureVacBioNTech Announces First Quarter 2026 Financial Results and Corporate Update | BioNTech - BioNTech2026-05-05已归档 / 弹窗可读BioNTech Q1 2026 更新显示其正在从 COVID 收入转向 oncology 平台，现金和证券投资达 168 亿欧元，并完成 CureVac 等并购整合，是 Moderna 在 mRNA 平台和肿瘤方向上最重要的可比公司之一。已取得本地原文并生成中文阅读摘要。
Pfizer vs Moderna mRNA patent strategies pipelinesPfizer vs. Moderna mRNA patent strategies and pipelines - PatSnap2026-04已归档 / 弹窗可读PatSnap 文章把 Pfizer/BioNTech 与 Moderna 描述为 mRNA 平台竞赛中的事实双寡头：两方合计 73 个 mRNA pipeline candidates，竞争焦点从 COVID 转向 influenza、RSV、CMV、组合疫苗和个性化癌症疫苗。已取得本地原文并生成中文阅读摘要。
global flu vaccine market 2026Flu Vaccine Market | Global Market Analysis Report - 2036 - Fact.MR未提供发布时间已归档 / 弹窗可读Fact.MR 把全球 flu vaccine 市场描述为成熟但稳定增长的年化采购市场，2026 年约 79 亿美元、2036 年约 112 亿美元，增长不快但需求有公共免疫项目支撑，mRNA 平台机会来自速度、株匹配和大流行准备能力。已取得本地原文并生成中文阅读摘要。
MRNA FY2025 financial resultsModerna Reports Fourth Quarter and Fiscal Year 2025 Financial Results and Provides Business Updates - Nasdaq / ACCESS Newswire2026-02-13已归档 / 弹窗可读Nasdaq 转载的 Moderna FY2025 公告显示公司 2025 年收入降至 19 亿美元、净亏损 28 亿美元，但管理层强调成本削减、三款已批准产品、国际协议和多个 2026 管线节点，为后 COVID 转型提供基础。已取得本地原文并生成中文阅读摘要。
MRNA Q1 2026 8-K exhibit 99.1Moderna (NASDAQ: MRNA) grows Q1 2026 revenue but books $1.3B loss - StockTitan SEC filing mirror2026-05-01已归档 / 弹窗可读StockTitan 的 MRNA 8-K mirror 把 Q1 2026 描述为收入回升但亏损仍重的一季：收入同比从 1.08 亿美元升至 3.89 亿美元，现金投资仍有 75 亿美元，但 9 亿美元诉讼和解费用导致 13.43 亿美元 GAAP 净亏损。已取得本地原文并生成中文阅读摘要。
FDA MFLUSIVA mRNA-1010 briefing documentFDA Briefing Document: MFLUSIVA / mRNA-1010 - U.S. FDA2026-06-13已归档 / 弹窗可读FDA 简报文件把 MFLUSIVA/mRNA-1010 的核心问题从“是否能进入审评”推进到“50-64 岁是否适合传统批准、65 岁及以上是否适合加速批准，以及标签和上市后义务如何设定”。文件显示疗效和安全性有支持点，但数据外推仍存在重要限制。已取得本地原文并生成中文阅读摘要。
Moderna mRNA-1010 MFLUSIVA briefing documentModerna Briefing Document: mRNA-1010 / MFLUSIVA - Moderna / FDA posted material2026-06-17已归档 / 弹窗可读Moderna 的申请方简报把 mRNA-1010 描述为针对 50 岁及以上人群的 mRNA seasonal influenza vaccine，强调临床项目规模、P304 疗效结果、65 岁及以上免疫原性桥接和整体安全性，以支持传统批准和加速批准的分层路径。已取得本地原文并生成中文阅读摘要。

归档失败或低置信来源已在下方完整列出；失败页面不作为已读证据。

本地文章库（全部归档请求） ​

本节是本次 MRNA 研究的完整文章归档清单。正文使用文章/来源标题作为本地弹窗入口；每篇文章复用现有报告弹窗组件阅读中文摘要和本地归档原文，弹窗内保留打开原文外链用于核验来源。失败或低置信条目只作为覆盖缺口，不作为结论证据。

状态来源/主题发布日期本地摘要或失败原因结论使用
访问失败 / 未作为证据Moderna Reports First Quarter 2026 Financial Results and Provides Business Updates - ACCESS Newswire / Moderna2026-05-01原站返回拒绝访问或抓取失败，本地未取得可用正文；未作为结论证据。不用；仅列明覆盖缺口
访问失败 / 未作为证据Moderna Reports Fourth Quarter and Fiscal Year 2025 Financial Results and Provides Business Updates - ACCESS Newswire / Moderna2026-02-13原站返回拒绝访问或抓取失败，本地未取得可用正文；未作为结论证据。不用；仅列明覆盖缺口
已归档 / 弹窗可读VRBPAC June 18, 2026 Meeting Announcement - U.S. FDA2026-06-16这是一则 FDA 官方会议通知：VRBPAC 将在 2026 年 6 月 18 日就 Moderna TX Inc. 的 MFLUSIVA（mRNA 流感疫苗）召开公开会议，讨论并对其用于 50 岁及以上人群预防甲/乙型流感的安全性与有效性作出建议，但该通知本身不包含审评结论。可用；按证据权重使用
已归档 / 弹窗可读Moderna and Merck Present 5-Year Data for Intismeran Autogene in Combination With KEYTRUDA® (pembrolizumab) in Patients With High-Risk Stage III/IV Melanoma Following Complete Resection at the 2026 ASCO Annual Meeting - Merck.com - Merck2026-06-01这是一则来自 Merck 与 Moderna 的临床更新稿，核心主张是：在高风险 III/IV 期黑色素瘤完全切除后的辅助治疗中，intismeran autogene（mRNA-4157/V940）联合 KEYTRUDA 在约 5 年随访时仍显示出较 KEYTRUDA 单药更好的无复发生存和远处转移无进展结果，但整体仍属于在研项目的阶段性数据，不是已获批疗可用；按证据权重使用
已归档 / 弹窗可读CEPI to Fund Pivotal Phase 3 Trial for Moderna’s mRNA Pandemic Influenza Candidate - CEPI2025-12-18CEPI 将最多投入 5430 万美元支持 Moderna H5 pandemic influenza mRNA 候选疫苗 mRNA-1018 的关键 Phase 3，文章主张 mRNA 平台在大流行响应速度、可扩展制造和公平供应上有公共卫生价值。可用；按证据权重使用
已归档 / 弹窗可读mRNA medicines we are currently developing - Moderna未提供发布时间Moderna 管线页显示公司已经从 COVID 单一产品扩展成呼吸道疫苗、潜伏/其他疫苗、precision immunotherapies 和 rare disease therapeutics 多线并行的平台公司，但多个关键资产仍处于 Phase 2/3，商业兑现尚未完成。可用；按证据权重使用
已归档 / 弹窗可读FDA staff scrutinizes evidence supporting Moderna’s flu vaccine - BioPharma Dive2026-06-16BioPharma Dive 的文章认为 FDA 会前文件虽未发现 mFlusiva 的重大安全缺陷，但监管人员对疗效证据外推性、老年/脆弱人群、共同接种和单季数据提出明显质疑，因此审批路径改善但仍不是无风险。可用；按证据权重使用
访问失败 / 未作为证据FDA appears less prickly toward Moderna mRNA flu shot - Fierce Biotech2026-06-17原站返回拒绝访问或抓取失败，本地未取得可用正文；未作为结论证据。不用；仅列明覆盖缺口
已归档 / 弹窗可读BioNTech Announces First Quarter 2026 Financial Results and Corporate Update | BioNTech - BioNTech2026-05-05BioNTech Q1 2026 更新显示其正在从 COVID 收入转向 oncology 平台，现金和证券投资达 168 亿欧元，并完成 CureVac 等并购整合，是 Moderna 在 mRNA 平台和肿瘤方向上最重要的可比公司之一。可用；按证据权重使用
已归档 / 弹窗可读Pfizer vs. Moderna mRNA patent strategies and pipelines - PatSnap2026-04PatSnap 文章把 Pfizer/BioNTech 与 Moderna 描述为 mRNA 平台竞赛中的事实双寡头：两方合计 73 个 mRNA pipeline candidates，竞争焦点从 COVID 转向 influenza、RSV、CMV、组合疫苗和个性化癌症疫苗。可用；按证据权重使用
已归档 / 弹窗可读Flu Vaccine Market | Global Market Analysis Report - 2036 - Fact.MR未提供发布时间Fact.MR 把全球 flu vaccine 市场描述为成熟但稳定增长的年化采购市场，2026 年约 79 亿美元、2036 年约 112 亿美元，增长不快但需求有公共免疫项目支撑，mRNA 平台机会来自速度、株匹配和大流行准备能力。可用；按证据权重使用
正文低置信 / 未作为证据JavaScript is disabled - BioSpace / ACCESS Newswire2026-05-01页面返回内容不足或需要浏览器脚本，本地未取得可用正文；未作为结论证据。不用；仅列明覆盖缺口
已归档 / 弹窗可读Moderna Reports Fourth Quarter and Fiscal Year 2025 Financial Results and Provides Business Updates - Nasdaq / ACCESS Newswire2026-02-13Nasdaq 转载的 Moderna FY2025 公告显示公司 2025 年收入降至 19 亿美元、净亏损 28 亿美元，但管理层强调成本削减、三款已批准产品、国际协议和多个 2026 管线节点，为后 COVID 转型提供基础。可用；按证据权重使用
已归档 / 弹窗可读Moderna (NASDAQ: MRNA) grows Q1 2026 revenue but books $1.3B loss - StockTitan SEC filing mirror2026-05-01StockTitan 的 MRNA 8-K mirror 把 Q1 2026 描述为收入回升但亏损仍重的一季：收入同比从 1.08 亿美元升至 3.89 亿美元，现金投资仍有 75 亿美元，但 9 亿美元诉讼和解费用导致 13.43 亿美元 GAAP 净亏损。可用；按证据权重使用
已归档 / 弹窗可读FDA Briefing Document: MFLUSIVA / mRNA-1010 - U.S. FDA2026-06-13FDA 简报文件把 MFLUSIVA/mRNA-1010 的核心问题从“是否能进入审评”推进到“50-64 岁是否适合传统批准、65 岁及以上是否适合加速批准，以及标签和上市后义务如何设定”。文件显示疗效和安全性有支持点，但数据外推仍存在重要限制。可用；按证据权重使用
已归档 / 弹窗可读Moderna Briefing Document: mRNA-1010 / MFLUSIVA - Moderna / FDA posted material2026-06-17Moderna 的申请方简报把 mRNA-1010 描述为针对 50 岁及以上人群的 mRNA seasonal influenza vaccine，强调临床项目规模、P304 疗效结果、65 岁及以上免疫原性桥接和整体安全性，以支持传统批准和加速批准的分层路径。可用；按证据权重使用
打开原文

Moderna Reports First Quarter 2026 Financial Results and Provides Business Updates

来源信息
来源：ACCESS Newswire / Moderna发布日期：2026-05-01抓取时间：2026-06-17T18:50:33.695Z相关标的：MRNA归档状态：访问失败 / 未作为证据
归档限制
  • 原站返回拒绝访问或抓取失败，本地未取得可用正文；未作为结论证据。
打开原文

Moderna Reports Fourth Quarter and Fiscal Year 2025 Financial Results and Provides Business Updates

来源信息
来源：ACCESS Newswire / Moderna发布日期：2026-02-13抓取时间：2026-06-17T18:50:33.751Z相关标的：MRNA归档状态：访问失败 / 未作为证据
归档限制
  • 原站返回拒绝访问或抓取失败，本地未取得可用正文；未作为结论证据。
打开原文

VRBPAC June 18, 2026 Meeting Announcement

来源信息
来源：U.S. FDA发布日期：2026-06-16抓取时间：2026-06-17T18:49:52.085Z相关标的：MRNA归档状态：已归档 / 弹窗可读
中文摘要

一句话结论

这是一则 FDA 官方会议通知：VRBPAC 将在 2026 年 6 月 18 日就 Moderna TX Inc. 的 MFLUSIVA（mRNA 流感疫苗）召开公开会议，讨论并对其用于 50 岁及以上人群预防甲/乙型流感的安全性与有效性作出建议，但该通知本身不包含审评结论。

关键事实

  • 会议日期为 2026 年 6 月 18 日，时间 8:30 a.m. - 4:00 p.m. ET。
  • 会议主题是讨论并建议 FDA 是否认可 MFLUSIVA (Influenza Vaccine, mRNA) 的 safety and effectiveness。
  • 申请方为 Moderna TX Inc.，对应 Biologics License Application STN 125869/0。
  • 拟定适应症是用于预防由疫苗所代表的 influenza virus subtypes A and type B 引起的流感疾病，目标人群为 50 岁及以上。
  • 会议将通过线上 teleconferencing / video conferencing 进行，CBER 计划提供免费直播 webcast，链接为 https://youtube.com/live/9W18lwG7vD8。
  • FDA 说明背景材料最迟会在会议前 2 个工作日向公众提供；如果来不及上传，也会在会议时公开并在会后补充到网站。
  • 公众口头陈述安排在 2026 年 6 月 18 日约 1:00 p.m. - 2:00 p.m. ET。
  • 公开 docket 编号为 FDA-2026-N-4162，电子或书面意见提交截止到 2026 年 6 月 17 日；2026 年 6 月 12 日前收到的意见会提供给委员会。
  • 想发言的人需在 2026 年 6 月 8 日中午 12:00 ET 前通知联系人并提交简要说明，FDA 可能在报名人数过多时抽签。
  • 联系人是 Cicely Reese，邮箱 CBERVRBPAC@fda.hhs.gov；信息热线 1-800-741-8138（华盛顿地区 301-443-0572）。
  • 事件材料包括 conflicts of interest waivers、FDA 与 Moderna 的 briefing documents、draft agenda、voting questions、draft roster 等。

作者观点与证据

  • 这不是评论性文章，而是 FDA 官方会议公告；“观点”主要体现在 FDA 的程序性表述：委员会将基于现有科学证据，对 MFLUSIVA 的安全性和有效性给出非约束性建议。
  • 证据来源主要是公告中的会议议程、公众参与安排、docket 时间线、直播安排和事件材料清单。
  • 公告本身不提供对疫苗最终审评结果的判断，也没有给出支持或反对结论；真正能体现倾向性的内容应来自后续的 briefing documents 和会议发言，而不是这则通知。

与相关标的的关系

  • 直接相关标的是 MRNA，因为公告点名 Moderna TX Inc. 和其申请产品 MFLUSIVA。
  • 对 MRNA 的影响路径主要是监管事件可见度和预期波动，而不是结果已定；这条信息更像是“事件日程”而非“事件结论”。
  • 如果把它作为研究背景，重点应放在后续 briefing materials、voting questions、委员会讨论结果，而不是仅凭这则公告推导方向。
  • 对其他疫苗或 mRNA 赛道公司，这更多是监管环境与同类产品审评节奏的背景材料，关联性弱于 MRNA 本身。

时效性与限制

  • 这篇内容发布时间为 2026 年 6 月 16 日，且会议就在 2026 年 6 月 18 日，属于强时效性事件通知，适合在当日或会前研究中引用。
  • 但它仍然只是公告，不是会议纪要、投票结果或最终 FDA 决定，因此不能把它写成已发生的审评结论。
  • 当前文本里没有会议材料全文、投票结果或专家表态，信息密度集中在程序安排；若用于日报，应明确它是事件前置材料。
  • 公告中对会议参与、评论截止和直播恢复等事项有程序性说明，但未提供任何定量临床数据或疗效安全性结论。
  • 由于这是 FDA 官方通知，标题与正文可信度高，但结论信息仍然有限，存在“只有安排、没有结果”的天然局限。

后续跟踪

  • 关注 2026 年 6 月 18 日 VRBPAC 会议的实际讨论内容与投票结果。
  • 关注后续公布的 briefing documents 里关于安全性、有效性和试验设计的关键数据。
  • 关注 FDA-2026-N-4162 docket 下的公众意见与会前材料更新。
  • 关注会议后 FDA 是否发布进一步的审评动作、补充问题或时间表变化。
英文原文
VRBPAC June 18, 2026 Meeting Announcement
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Vaccines and Related Biological Products Advisory Committee June 18, 2026 Meeting Announcement - 06/18/2026

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Advisory Committee Calendar

In this section

Date:

June 18, 2026

Time:

8:30 a.m.

  • 4:00 p.m.

ET

What is an advisory committee?

Advisory committees provide independent expert advice to the FDA on broad scientific topics or on certain products to help the agency make sound decisions based on the available science. Advisory committees make non-binding recommendations to the FDA, which generally follows the recommendations but is not legally bound to do so. Please see, " Advisory Committees Give FDA Critical Advice and the Public a Voice ," for more information.

Please note that all meeting participants will be joining this advisory committee meeting through an online teleconferencing and/or video conferencing platform.

How to Attend

  • 06/18/2026
  • https://youtube.com/live/9W18lwG7vD8

CBER plans to provide a free of charge live webcast of the Vaccines and Related Biological Products Advisory Committee Meeting. If there are instances where the webcast transmission is not successful, staff will work to re-establish the transmission as soon as possible.

Agenda

The meeting presentations will be heard, viewed, captioned, and recorded through an online teleconferencing and/or video conferencing platform. On June 18, 2026, the Committee will meet in open session to discuss and make recommendations on the safety and effectiveness of MFLUSIVA (Influenza Vaccine, mRNA), manufactured by Moderna TX Inc., with a requested indication in Biologics License Application STN 125869/0 for the prevention of influenza disease caused by influenza virus subtypes A and type B represented in the vaccine, in persons 50 years of age and older.

Meeting Materials

FDA intends to make background material available to the public no later than 2 business days before the meeting. If FDA is unable to post the background material on its website prior to the meeting, the background material will be made publicly available at the time of the advisory committee meeting, and the background material will be posted on FDA’s website after the meeting. Background material is available at the Advisory Committee Calendar . Scroll down to the appropriate advisory committee meeting link. The meeting will include slide presentations with audio components to allow the presentation of materials in a manner that most closely resembles an in-person advisory committee meeting.

Public Participation Information

Interested persons may present data, information, or views, orally or in writing, on issues pending before the committee.

Oral presentations from the public will be scheduled between approximately 1:00 p.m. and 2:00 p.m. Eastern Time on June 18, 2026.

FDA is establishing a docket for public comment on this meeting.

The docket number is FDA-2026-N-4162.

The docket will close on June17, 2026. Submit either electronic or written comments on this public meeting on or before June 17, 2026. Please note that late, untimely filed comments will not be considered. Electronic comments must be submitted on or before June 17, 2026. The https://www.regulations.gov electronic filing system will accept comments until 11:59 p.m. Eastern Time at the end of June 17, 2026. Comments received by mail/hand delivery/courier (for written/paper submissions) will be considered timely if they are received on or before that date.

Comments received on or before June 12, 2026, will be provided to the committee. Comments received after that date and on June 17, 2026, will be taken into consideration by FDA. In the event that the meeting is canceled, FDA will continue to evaluate any relevant applications or information, and consider any comments submitted to the docket, as appropriate.

You may submit comments as follows:

Electronic Submissions

Submit electronic comments as follows:

  • Federal eRulemaking Portal: https://www.regulations.gov . Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to https://www.regulations.gov will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else’s Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on https://www.regulations.gov .
  • If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see “Written/Paper Submissions” and “Instructions”).

Written/Paper Submissions

Submit written/paper submissions as follows:

  • Mail/Hand delivery/Courier (for written/paper submissions): Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
  • For written/paper comments submitted to the Dockets Management Staff, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in “Instructions.”

Instructions: All submissions received must include the Docket No. FDA-2026-N-4162 for “Vaccines and Related Biological Products Advisory Committee; Notice of Meeting; Establishment of a Public Docket; Request for Comments – Safety and Effectiveness of MFLUSIVA (Influenza Vaccine, mRNA) manufactured by Moderna TX Inc.”. Received comments, those filed in a timely manner (see ADDRESSES), will be placed in the docket and, except for those submitted as “Confidential Submissions,” publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.

Confidential Submissions: To submit a comment with confidential information that you do not wish to be made publicly available, submit your comments only as a written/paper submission. You should submit two copies total. One copy will include the information you claim to be confidential with a heading or cover note that states “THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.” FDA will review this copy, including the claimed confidential information, in its consideration of comments. The second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https://www.regulations.gov . Submit both copies to the Dockets Management Staff. If you do not wish your name and contact information be made publicly available, you can provide this information on the cover sheet and not in the body of your comments and you must identify the information as “confidential.” Any information marked as “confidential” will not be disclosed except in accordance with 21 CFR 10.20 and other applicable disclosure law. For more information about FDA’s posting of comments to public dockets, see 80 FR 56469, September 18, 2015, or access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf .

Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in the heading of this document, into the “Search” box and follow the prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, 240-402-7500.

FOR FURTHER INFORMATION, CONTACT: Cicely Reese; Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 1, Rm. 3215, Silver Spring, MD 20993-0002, 301-796-9025, email: CBERVRBPAC@fda.hhs.gov, or FDA Advisory Committee Information Line, 1-800-741-8138 (301-443-0572 in the Washington, DC area).

Oral Presentations

Oral presentations from the public will be scheduled between approximately 1:00 p.m. and 2:00 p.m. Eastern Time on June 18, 2026.

Those individuals interested in making formal oral presentations should notify the contact person and submit a brief statement of the general nature of the evidence or arguments they wish to present, the names and addresses of proposed participants, and an indication of the approximate time requested to make their presentation on or before 12 p.m. Eastern Time on June 8, 2026.

Time allotted for each presentation may be limited. If the number of registrants requesting to speak is greater than can be reasonably accommodated during the scheduled open public hearing session, FDA may conduct a lottery to determine the speakers for the scheduled open public hearing session. The contact person will notify interested persons regarding their request to speak by 6 p.m. Eastern Time on June 10, 2026.

Webcast Information

CBER plans to provide a free of charge live webcast of the Vaccines and Related Biological Products Advisory Committee meeting:

The online web conference meeting will be available at the following link:

  • 06/18/2026
  • https://youtube.com/live/9W18lwG7vD8

If there are instances where the webcast transmission is not successful, staff will work to re-establish the transmission as soon as possible.

Contact Information

  • Cicely Reese: CBERVRBPAC@fda.hhs.gov
  • FDA Advisory Committee Information Line:

1-800-741-8138 (301-443-0572 in the Washington, DC area). Please call the Information Line for up-to-date information on this meeting.

  • For press inquiries, please contact the HHS Press Room at www.hhs.gov/press-room/index.html or 202-690-6343.

Official FR Notice

A notice in the Federal Register about last minute modifications that impact a previously announced advisory committee meeting cannot always be published quickly enough to provide timely notice. Therefore, you should always check the agency’s website or call the committee’s Designated Federal Officer (see Contact Information) to learn about possible modifications before coming to the meeting.

Persons attending FDA’s advisory committee meetings are advised that the agency is not responsible for providing access to electrical outlets. FDA welcomes the attendance of the public at its advisory committee meetings and will make every effort to accommodate persons with disabilities. If you require accommodations due to a disability, please contact the committee’s Designated Federal Officer (see Contact Information) at least 7 days in advance of the meeting.

Answers to commonly asked questions including information regarding special accommodations due to a disability may be accessed at: Common Questions and Answers about FDA Advisory Committee Meetings .

FDA is committed to the orderly conduct of its advisory committee meetings. Please visit our Web site at Public Conduct During FDA Advisory Committee Meetings for procedures on public conduct during advisory committee meetings.

Notice of this meeting is given under the Federal Advisory Committee Act (5 U.S.C. app.2).

Event Materials

Title

File Type/Size

Source Organization

Vaccines and Related Biological Products Advisory Committee June 18, 2026 Meeting Waivers for Conflicts of Interest

pdf (99.25 KB)

FDA

Vaccines and Related Biological Products Advisory Committee June 18, 2026 Meeting Briefing Document- FDA

pdf (1.04 MB)

FDA

Vaccines and Related Biological Products Advisory Committee June 18, 2026 Meeting Briefing Document- Moderna

pdf (1.05 MB)

Non-FDA

Vaccines and Related Biological Products Advisory Committee June 18, 2026 Meeting Briefing Document- Moderna- Errata

pdf (312.89 KB)

Non-FDA

Vaccines and Related Biological Products Advisory Committee June 18, 2026 Meeting Draft Agenda

pdf (174.38 KB)

FDA

Vaccines and Related Biological Products Advisory Committee June 18, 2026 Meeting Voting Questions

pdf (98.13 KB)

FDA

Vaccines and Related Biological Products Advisory Committee June 18, 2026 Meeting Draft Roster

pdf (187.44 KB)

FDA

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打开原文

Moderna and Merck Present 5-Year Data for Intismeran Autogene in Combination With KEYTRUDA® (pembrolizumab) in Patients With High-Risk Stage III/IV Melanoma Following Complete Resection at the 2026 ASCO Annual Meeting - Merck.com

来源信息
来源：Merck发布日期：2026-06-01抓取时间：2026-06-17T18:49:52.086Z相关标的：MRNA, MRK归档状态：已归档 / 弹窗可读
中文摘要

一句话结论

这是一则来自 Merck 与 Moderna 的临床更新稿，核心主张是：在高风险 III/IV 期黑色素瘤完全切除后的辅助治疗中，intismeran autogene（mRNA-4157/V940）联合 KEYTRUDA 在约 5 年随访时仍显示出较 KEYTRUDA 单药更好的无复发生存和远处转移无进展结果，但整体仍属于在研项目的阶段性数据，不是已获批疗法结论。

关键事实

  • 发布主体是 Moderna 与 Merck，发布时间为 2026-06-01，场景是 2026 ASCO 年会；文中同时提到该结果会发表于 ASCO 的 Journal of Clinical Oncology。
  • 数据来自 Phase 2b 随机研究 KEYNOTE-942/mRNA-4157-P201，入组 157 名高风险 stage III/IV 黑色素瘤患者，均为完全切除后的辅助治疗场景。
  • 中位随访 60.3 个月（范围 50.5-76.4）时，联合方案相对 KEYTRUDA 单药将复发或死亡风险降低 49%，RFS 的 HR=0.51，95% CI 为 0.294-0.887。
  • 远处转移或死亡风险降低 59%，DMFS 的 HR=0.411，95% CI 为 0.200-0.843；作者把这视为五年时点仍然持续的获益信号。
  • 探索性总体生存分析显示向改善方向的趋势，OS HR=0.471，95% CI 为 0.165-1.345，样本量 n=14，区间很宽，文章本身也没有把它写成确定性结论。
  • 安全性与既往分析一致；常见不良事件包括疲劳 59.6%、注射部位疼痛 59.6%、寒战 51.0%。大多数不良事件为 1 级或 2 级，未见 4/5 级事件；免疫相关不良事件在联合组和单药组分别为 45.2% 和 44%。
  • 文章还给出机制层面的支持性数据：联合治疗似乎增强 T 细胞克隆扩增并产生新的 T 细胞克隆型；但这些属于探索性/转化研究证据，不等同于已验证的临床终局结论。
  • 文末提到 Moderna 与 Merck 共有 9 项 Phase 2/3 试验在推进，覆盖 melanoma、NSCLC、bladder cancer、renal cell carcinoma 等多个肿瘤类型，说明项目管线仍在扩展。

作者观点与证据

  • 文章整体倾向明显偏乐观，试图传达“长期疗效可持续、机制上也得到支持”的信息。
  • 其主要证据是五年随访下的 RFS 与 DMFS 风险下降，以及安全性没有出现明显恶化；这部分是相对扎实的临床结果。
  • 但关于 OS 的表述只是一项探索性分析，而且 n=14、置信区间很宽，因此更像早期信号而不是可直接外推的生存获益证明。
  • 文章还大量使用公司管理层引述和前瞻性表述，这些属于公司叙事和研发宣传口径，需要和硬终点数据分开看。
  • 由于来源是公司新闻稿，天然带有选择性披露特征，重点呈现正面数据，对失败子组、统计边界和竞争项目比较都没有展开。

与相关标的的关系

  • 对 MRK 来说，这条信息主要关系到 KEYTRUDA 生态和肿瘤管线延展，说明其在黑色素瘤辅助治疗场景之外，仍在尝试把 PD-1 平台与个体化 mRNA 肿瘤疫苗/INT 方案结合起来。
  • 对 MRNA 来说，这是 mRNA 平台在肿瘤治疗上的长期验证材料，若后续临床与监管进展继续推进，会影响市场对其 oncology 平台价值的看法。
  • 但就这篇文章本身而言，它更像研发进展与临床证据更新，不是直接的商业化落地公告；因此对两只股票的影响路径主要通过“管线可信度、适应症扩展预期、长期研发估值”体现，而不是立即可兑现的经营数据。

时效性与限制

  • 发布时间是 2026-06-01，属于较新的公司新闻稿，但仍然是单一研究项目的阶段性更新，适合放进日报的“研发/临床进展”事实栏，不适合当作已兑现业绩或监管批准来引用。
  • 文中的关键数据来自单个 Phase 2b 研究，样本量 157 人，且 OS 只是探索性分析，统计稳健性有限。
  • 这是公司自述材料，存在明显的正向筛选和前瞻性措辞；原文也包含大量 KEYTRUDA 适应症和安全性说明，信息密度高但并不等于这些适应症都与本新闻直接相关。
  • 原始文本来自受限访问的内部站内摘录，适合做阅读摘要和事实整理，但不应把它当作完整监管文件或独立第三方验证来源。

后续跟踪

  • 继续观察该联合方案后续是否进入更高阶段研究，以及是否有更大样本、随机对照的确认性结果。
  • 关注 RFS 与 DMFS 之外，OS 是否在更充分随访下变得更稳健，还是仍停留在探索性信号。
  • 观察安全性是否在更长期或更广泛人群中保持一致，尤其是免疫相关不良事件和高等级不良事件。
  • 留意 melanoma 之外的 NSCLC、bladder cancer、RCC 等适应症推进情况，判断该平台是否具备更广泛的管线扩展能力。
英文原文
Moderna and Merck Present 5-Year Data for Intismeran Autogene in Combination With KEYTRUDA® (pembrolizumab) in Patients With High-Risk Stage III/IV Melanoma Following Complete Resection at the 2026 ASCO Annual Meeting - Merck.com

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Moderna and Merck Present 5-Year Data for Intismeran Autogene in Combination With KEYTRUDA® (pembrolizumab) in Patients With High-Risk Stage III/IV Melanoma Following Complete Resection at the 2026 ASCO Annual Meeting

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June 1, 2026 8:00 am EDT

At a median 5-year (60.3 months) planned follow-up of the Phase 2b KEYNOTE-942/mRNA-4157-P201 study, intismeran autogene in combination with KEYTRUDA demonstrated a 49% reduction in the risk of recurrence or death and a 59% reduction in the risk of distant metastasis or death compared to KEYTRUDA alone

Intismeran autogene in combination with KEYTRUDA demonstrated an encouraging trend toward overall survival in an exploratory analysis compared to KEYTRUDA alone (HR=0.471; [95% CI, 0.165–1.345])

CAMBRIDGE, MA and RAHWAY, N.J. / Access Newswire / June 1, 2026 / Moderna, Inc. (NASDAQ: MRNA) and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced detailed results from a planned five-year follow-up analysis of the Phase 2b randomized KEYNOTE-942/mRNA-4157-P201 study evaluating intismeran autogene (mRNA-4157 or V940), an investigational mRNA-based individualized neoantigen therapy (INT), in combination with KEYTRUDA ® (pembrolizumab), Merck’s anti-PD-1 therapy, in patients with high-risk melanoma (stage III/IV) following complete resection. These data will be presented today at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting (May 29-June 2) and published simultaneously in ASCO’s Journal of Clinical Oncology .

With a median follow-up of 60.3 months (range, 50.5-76.4), adjuvant treatment with intismeran autogene in combination with KEYTRUDA continued to prolong recurrence-free survival (RFS), the study’s primary endpoint, reducing the risk of recurrence or death by 49% (HR=0.51; [95% CI, 0.294-0.887]) compared to KEYTRUDA alone. Intismeran autogene in combination with KEYTRUDA also continued to demonstrate a meaningful improvement in distant metastasis-free survival (DMFS), a key secondary endpoint of the study, reducing the risk of distant metastasis or death by 59% (HR=0.411; [95% CI, 0.200–0.843]) compared to KEYTRUDA alone. The exploratory endpoint of overall survival (OS) also demonstrated an encouraging trend toward improved OS (HR=0.471; [95% CI, 0.165–1.345]; n=14) with intismeran autogene in combination with KEYTRUDA compared to KEYTRUDA alone. Together, these findings indicate a sustained improvement in RFS and DMFS at five years.

“With each year of continued follow-up of our Phase 2b study, we gain a more complete picture of the durability of intismeran autogene in combination with KEYTRUDA. Now, with a median follow-up of five years, the sustained recurrence-free survival and distant metastasis-free survival demonstrate the potential long-term benefit of intismeran autogene in combination with KEYTRUDA in melanoma patients at high risk of recurrence,” said David Berman, M.D., Ph.D., Chief Development Officer of Moderna. “These findings add to our confidence in the potentially transformative impact of this novel, personalized approach to cancer care made possible by mRNA technology.”

“The risk of disease recurrence remains high for patients with stage III/IV melanoma following surgery, so we are encouraged by these long-term findings showing that intismeran autogene in combination with KEYTRUDA provided sustained and durable reductions in the risk of recurrence,” said Dr. Majorie Green, Senior Vice President and Head of Oncology, Global Clinical Development, Merck Research Laboratories. “These data further reinforce the potential of this individualized approach to address critical gaps in the adjuvant setting and reflect our continued commitment to advancing innovative therapies for patients.”

The safety profile of intismeran autogene in combination with KEYTRUDA remained consistent with prior analyses. The most common adverse events attributed to intismeran autogene in combination with KEYTRUDA were fatigue (59.6%), injection site pain (59.6%), and chills (51.0%). The majority of the adverse events attributed to intismeran autogene were Grade 1 (31.7%) and Grade 2 (51.9%), with fatigue being the most common Grade 3 event (4.8%) and no Grade 4-5 events. Immune-related adverse events occurred in 45.2% of patients receiving the combination and 44% receiving KEYTRUDA alone. Intismeran autogene in combination with KEYTRUDA did not result in potentiation of immune-related AEs.

The findings build on the primary analysis and supportive analysis at an approximately three-year follow-up (34.9 months), presented at the 2024 ASCO Annual Meeting , in which intismeran autogene in combination with KEYTRUDA resulted in a 49% RFS risk reduction and 62% DMFS risk reduction compared to KEYTRUDA alone.

Additional subgroup and translational data

Data from an exploratory subgroup analysis continued to indicate that improvement in RFS was maintained with intismeran autogene in combination with KEYTRUDA across subpopulations, including age, sex, disease state (Stage III/IV), programmed death-ligand 1 (PD-L1) status, BRAF status, tumor mutation burden (TMB) or circulating tumor DNA (ctDNA) status, compared to KEYTRUDA alone.

Intismeran autogene plus KEYTRUDA increased T-cell clonal expansion and promoted the emergence of new T-cell clonotypes compared with KEYTRUDA alone. At long-term follow-up, patients receiving the combination demonstrated an approximately two-fold higher proportion of novel expanded T-cell clonotypes versus KEYTRUDA monotherapy (0.030 vs 0.016 median summed frequency). Higher magnitude increases of these novel T-cell clones was associated with remaining recurrence-free; recurrence-free patients in the combination arm had approximately twice the number of unique novel expanded clonotypes at long-term follow-up (median number 42 vs. 20 in recurrence-free vs recurrence patients, respectively). Additional data presented at ASCO (abstract #9564) found that, in a subset of patients receiving adjuvant combination therapy, these novel clonotypes were linked to intismeran-encoded neoantigens, supporting intismeran’s proposed mechanism of action and association with clinical benefit.

Ongoing clinical development programs

Moderna and Merck have nine total Phase 2 and Phase 3 clinical trials underway investigating intismeran autogene in combination with KEYTRUDA across multiple tumor types, including melanoma, non-small cell lung cancer (NSCLC), bladder cancer and renal cell carcinoma. This includes the recent initiation of a Phase 3 study of intismeran autogene as a monotherapy and in combination with KEYTRUDA for the treatment of high-risk Stage I NSCLC (INTerpath-014, NCT07513376 ).

The Phase 3 clinical trial for adjuvant melanoma (INTerpath-001, NCT05933577 ) and a randomized Phase 2 study for adjuvant renal cell carcinoma (INTerpath-004, NCT06307431 ) are fully enrolled. Two NSCLC Phase 3 studies, evaluating adjuvant treatment in patients with completely resected NSCLC (INTerpath-002, NCT06077760 ) and evaluating adjuvant treatment for patients with resectable NSCLC after receiving neoadjuvant KEYTRUDA plus platinum-based chemotherapy (INTerpath-009, NCT06623422 ), are enrolling. Randomized Phase 2 studies for patients with resected muscle invasive bladder cancer (INTerpath-005, NCT06305767 ) and resected non-muscle invasive bladder cancer (INTerpath-011, NCT06833073 ) are enrolling, a Phase 2 study of first-line treatment for patients with metastatic melanoma (INTerpath-012, NCT06961006 ) and a Phase 2 study of first-line treatment for patients with metastatic squamous NSCLC (INTerpath-013, NCT07221474 ) are also enrolling.

About intismeran autogene (mRNA-4157 or V940)

Intismeran autogene is a novel investigational messenger RNA (mRNA)-based individualized neoantigen therapy (INT) consisting of a synthetic mRNA coding for up to 34 neoantigens that is designed and produced based on the unique mutational signature of the DNA sequence of the patient’s tumor. Upon administration into the body, the algorithmically derived and RNA-encoded neoantigen sequences are endogenously translated and undergo natural cellular antigen processing and presentation, a key step in adaptive immunity. Individualized neoantigen therapies are designed to train and activate an antitumor immune response by generating specific T-cell responses based on the unique mutational signature of a patient’s tumor.

About KEYNOTE-942/mRNA-4157-P201 ( NCT03897881 )

KEYNOTE-942 is an ongoing randomized, open-label Phase 2b trial that enrolled 157 patients with high-risk stage III/IV melanoma. Following complete surgical resection, patients were assigned 2:1 (stratified by stage) to receive intismeran autogene (1 mg every three weeks for nine doses) and KEYTRUDA (200 mg every three weeks up to 18 cycles [for approximately one year]) versus KEYTRUDA alone for approximately one year until disease recurrence or unacceptable toxicity. The primary endpoint is RFS, defined as the time from first dose of KEYTRUDA until the date of first recurrence (local, regional or distant metastasis), a new primary melanoma, or death from any cause in the intention-to-treat population. Secondary endpoints include distant metastasis-free survival and safety, and exploratory endpoints include distribution of TMB expression in baseline tumor samples across study arms and their association with the primary RFS endpoint.

Key eligibility criteria for the trial included: patients with resectable cutaneous melanoma metastatic to a lymph node and at high risk of recurrence, patients with complete resection within 13 weeks prior to the first dose of KEYTRUDA, patients were disease free at study entry (after surgery) with no loco-regional relapse or distant metastasis and no clinical evidence of brain metastases, patients had a formalin fixed paraffin embedded (FFPE) tumor sample available suitable for sequencing, Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 and patients with normal organ and marrow function reported at screening.

About melanoma

Melanoma, the most serious form of skin cancer, is characterized by the uncontrolled growth of pigment-producing cells. The rates of melanoma have been rising over the past few decades, with more than 330,000 new cases diagnosed worldwide in 2022. In the U.S., skin cancer is one of the most common types of cancer diagnosed, and melanoma accounts for a large majority of skin cancer deaths. It is estimated there will be about 112,000 new cases of melanoma diagnosed and over 8,500 deaths resulting from the disease in the U.S. in 2026.

About KEYTRUDA ® (pembrolizumab) injection for intravenous use, 100 mg

KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 2,800 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA ® (pembrolizumab) Indications in the U.S.

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with Stage IIB, IIC, or III melanoma following complete resection.

See additional selected KEYTRUDA indications in the U.S. after the Selected Important Safety Information.

Selected Important Safety Information for KEYTRUDA

Severe and Fatal Immune-Mediated Adverse Reactions

KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or the programmed death ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of anti–PD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. For patients with TNBC treated with KEYTRUDA in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.

Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

Pneumonitis occurred in 7% (41/580) of adult patients with resected NSCLC who received KEYTRUDA as a single agent for adjuvant treatment of NSCLC, including fatal (0.2%), Grade 4 (0.3%), and Grade 3 (1%) adverse reactions. Patients received high-dose corticosteroids for a median duration of 10 days (range: 1 day to 2.3 months). Pneumonitis led to discontinuation of KEYTRUDA in 26 (4.5%) of patients. Of the patients who developed pneumonitis, 54% interrupted KEYTRUDA, 63% discontinued KEYTRUDA, and 71% had resolution.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required in 69% (33/48); additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of KEYTRUDA in 0.5% (15) and withholding in 0.5% (13) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Colitis resolved in 85% of the 48 patients.

Hepatotoxicity and Immune-Mediated Hepatitis

KEYTRUDA as a Single Agent

KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 68% (13/19) of patients; additional immunosuppressant therapy was required in 11% of patients. Hepatitis led to permanent discontinuation of KEYTRUDA in 0.2% (6) and withholding in 0.3% (9) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Hepatitis resolved in 79% of the 19 patients.

KEYTRUDA With Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen at a higher frequency compared to KEYTRUDA alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT ≥3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT ≥3 times ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT ≥3 ULN subsequently recovered from the event.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.3%) reactions. Systemic corticosteroids were required in 77% (17/22) of patients; of these, the majority remained on systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.3% (8) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Hypophysitis

KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Hypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.2%) reactions. Systemic corticosteroids were required in 94% (16/17) of patients; of these, the majority remained on systemic corticosteroids. Hypophysitis led to permanent discontinuation of KEYTRUDA in 0.1% (4) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Thyroid Disorders

KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in <0.1% (1) of patients.

Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of KEYTRUDA in <0.1% (2) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. Hypothyroidism occurred in 8% (237/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.5% (14) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. The majority of patients with hypothyroidism required long-term thyroid hormone replacement. The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC, occurring in 16% of patients receiving KEYTRUDA as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in 389 adult patients with cHL (17%) receiving KEYTRUDA as a single agent, including Grade 1 (6.2%) and Grade 2 (10.8%) hypothyroidism. The incidence of new or worsening hyperthyroidism was higher in 580 patients with resected NSCLC, occurring in 11% of patients receiving KEYTRUDA as a single agent as adjuvant treatment, including Grade 3 (0.2%) hyperthyroidism. The incidence of new or worsening hypothyroidism was higher in 580 patients with resected NSCLC, occurring in 22% of patients receiving KEYTRUDA as a single agent as adjuvant treatment (KEYNOTE-091), including Grade 3 (0.3%) hypothyroidism.

Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis

Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients receiving KEYTRUDA. It led to permanent discontinuation in <0.1% (1) and withholding of KEYTRUDA in <0.1% (1) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Immune-Mediated Nephritis With Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.1%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 89% (8/9) of patients. Nephritis led to permanent discontinuation of KEYTRUDA in 0.1% (3) and withholding in 0.1% (3) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Nephritis resolved in 56% of the 9 patients.

Immune-Mediated Dermatologic Adverse Reactions

KEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with anti– PD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. Withhold or permanently discontinue KEYTRUDA depending on severity. Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 40% (15/38) of patients. These reactions led to permanent discontinuation in 0.1% (2) and withholding of KEYTRUDA in 0.6% (16) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence. The reactions resolved in 79% of the 38 patients.

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received KEYTRUDA or were reported with the use of other anti–PD-1/PD-L1 treatments. Severe or fatal cases have been reported for some of these adverse reactions. Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy; Ocular: Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal: Pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis (and associated sequelae, including renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, other transplant (including corneal graft) rejection; Other : Myocarditis-Myositis-Myasthenia Gravis (or Myasthenia-Like) Overlap syndrome, reported as the co-occurrence of either two or all three adverse reactions.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% of 2799 patients receiving KEYTRUDA. Monitor for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1 or Grade 2 reactions. For Grade 3 or Grade 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after anti–PD-1/PD-L1 treatments. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute and chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between anti–PD-1/PD-L1 treatments and allogeneic HSCT. Follow patients closely for evidence of these complications and intervene promptly. Consider the benefit vs risks of using anti–PD-1/PD-L1 treatments prior to or after an allogeneic HSCT.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with an anti–PD-1/PD-L1 treatment in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (≥20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-054, when KEYTRUDA was administered as a single agent to patients with stage III melanoma, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (≥1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (≥20%) with KEYTRUDA was diarrhea (28%). In KEYNOTE-716, when KEYTRUDA was administered as a single agent to patients with stage IIB or IIC melanoma, adverse reactions occurring in patients with stage IIB or IIC melanoma were similar to those occurring in 1011 patients with stage III melanoma from KEYNOTE-054.

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (≥20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.

In KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in 19% of 636 patients with advanced NSCLC; the most common were pneumonitis (3%), death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (≥20%) was fatigue (25%).

In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis (1.8%). The most common adverse reactions (≥20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

In KEYNOTE-671, adverse reactions occurring in patients with resectable NSCLC receiving KEYTRUDA in combination with platinum-containing chemotherapy, given as neoadjuvant treatment and continued as single-agent adjuvant treatment, were generally similar to those occurring in patients in other clinical trials across tumor types receiving KEYTRUDA in combination with chemotherapy.

The most common adverse reactions (reported in ≥20%) in patients receiving KEYTRUDA in combination with chemotherapy or chemoradiotherapy were fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, pyrexia, alopecia, peripheral neuropathy, mucosal inflammation, stomatitis, headache, weight loss, abdominal pain, arthralgia, myalgia, insomnia, palmar-plantar erythrodysesthesia, urinary tract infection, hypothyroidism, radiation skin injury, dysphagia, dry mouth, and musculoskeletal pain.

In the neoadjuvant phase of KEYNOTE-671, when KEYTRUDA was administered in combination with platinum-containing chemotherapy as neoadjuvant treatment, serious adverse reactions occurred in 34% of 396 patients. The most frequent (≥2%) serious adverse reactions were pneumonia (4.8%), venous thromboembolism (3.3%), and anemia (2%). Fatal adverse reactions occurred in 1.3% of patients, including death due to unknown cause (0.8%), sepsis (0.3%), and immune-mediated lung disease (0.3%). Permanent discontinuation of any study drug due to an adverse reaction occurred in 18% of patients who received KEYTRUDA in combination with platinum-containing chemotherapy; the most frequent adverse reactions (≥1%) that led to permanent discontinuation of any study drug were acute kidney injury (1.8%), interstitial lung disease (1.8%), anemia (1.5%), neutropenia (1.5%), and pneumonia (1.3%).

Of the KEYTRUDA-treated patients who received neoadjuvant treatment, 6% of 396 patients did not receive surgery due to adverse reactions. The most frequent (≥1%) adverse reaction that led to cancellation of surgery in the KEYTRUDA arm was interstitial lung disease (1%).

In the adjuvant phase of KEYNOTE-671, when KEYTRUDA was administered as a single agent as adjuvant treatment, serious adverse reactions occurred in 14% of 290 patients. The most frequent serious adverse reaction was pneumonia (3.4%). One fatal adverse reaction of pulmonary hemorrhage occurred. Permanent discontinuation of KEYTRUDA due to an adverse reaction occurred in 12% of patients who received KEYTRUDA as a single agent, given as adjuvant treatment; the most frequent adverse reactions (≥1%) that led to permanent discontinuation of KEYTRUDA were diarrhea (1.7%), interstitial lung disease (1.4%), increased aspartate aminotransferase (1%), and musculoskeletal pain (1%).

Adverse reactions observed in KEYNOTE-091 were generally similar to those occurring in other patients with NSCLC receiving KEYTRUDA as a single agent, with the exception of hypothyroidism (22%), hyperthyroidism (11%), and pneumonitis (7%). Two fatal adverse reactions of myocarditis occurred.

Adverse reactions observed in KEYNOTE-483 were generally similar to those occurring in other patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy.

In KEYNOTE-689, the most common adverse reactions (≥20%) in patients receiving KEYTRUDA were stomatitis (48%), radiation skin injury (40%), weight loss (36%), fatigue (33%), dysphagia (29%), constipation (27%), hypothyroidism (26%), nausea (24%), rash (22%), dry mouth (22%), diarrhea (22%), and musculoskeletal pain (22%).

In the neoadjuvant phase of KEYNOTE-689, of the 361 patients who received at least one dose of single agent KEYTRUDA, 11% experienced serious adverse reactions. Serious adverse reactions that occurred in more than one patient were pneumonia (1.4%), tumor hemorrhage (0.8%), dysphagia (0.6%), immune-mediated hepatitis (0.6%), cellulitis (0.6%), and dyspnea (0.6%). Fatal adverse reactions occurred in 1.1% of patients, including respiratory failure, clostridium infection, septic shock, and myocardial infarction (one patient each). Permanent discontinuation of KEYTRUDA due to an adverse reaction occurred in 2.8% of patients who received KEYTRUDA as neoadjuvant treatment. The most frequent adverse reaction which resulted in permanent discontinuation of neoadjuvant KEYTRUDA in more than one patient was arthralgia (0.6%).

Of the 361 patients who received KEYTRUDA as neoadjuvant treatment, 11% did not receive surgery. Surgical cancellation on the KEYTRUDA arm was due to disease progression in 4%, patient decision in 3%, adverse reactions in 1.4%, physician’s decision in 1.1%, unresectable tumor in 0.6%, loss of follow-up in 0.3%, and use of non-study anti-cancer therapy in 0.3%.

Of the 323 KEYTRUDA-treated patients who received surgery following the neoadjuvant phase, 1.2% experienced delay of surgery (defined as on-study surgery occurring ≥9 weeks after initiation of neoadjuvant KEYTRUDA) due to adverse reactions, and 2.8% did not receive adjuvant treatment due to adverse reactions.

In the adjuvant phase of KEYNOTE-689, of the 255 patients who received at least one dose of KEYTRUDA, 38% experienced serious adverse reactions. The most frequent serious adverse reactions reported in ≥1% of KEYTRUDA- treated patients were pneumonia (2.7%), pyrexia (2.4%), stomatitis (2.4%), acute kidney injury (2.0%), pneumonitis (1.6%), COVID-19 (1.2%), death not otherwise specified (1.2%), diarrhea (1.2%), dysphagia (1.2%), gastrostomy tube site complication (1.2%), and immune-mediated hepatitis (1.2%). Fatal adverse reactions occurred in 5% of patients, including death not otherwise specified (1.2%), acute renal failure (0.4%), hypercalcemia (0.4%), pulmonary hemorrhage (0.4%), dysphagia/malnutrition (0.4%), mesenteric thrombosis (0.4%), sepsis (0.4%), pneumonia (0.4%), COVID-19 (0.4%), respiratory failure (0.4%), cardiovascular disorder (0.4%), and gastrointestinal hemorrhage (0.4%). Permanent discontinuation of adjuvant KEYTRUDA due to an adverse reaction occurred in 17% of patients. The most frequent (≥1%) adverse reactions that led to permanent discontinuation of adjuvant KEYTRUDA were pneumonitis, colitis, immune-mediated hepatitis, and death not otherwise specified.

In KEYNOTE-048, KEYTRUDA monotherapy was discontinued due to adverse events in 12% of 300 patients with HNSCC; the most common adverse reactions leading to permanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The most common adverse reactions (≥20%) were fatigue (33%), constipation (20%), and rash (20%).

In KEYNOTE-048, when KEYTRUDA was administered in combination with platinum (cisplatin or carboplatin) and FU chemotherapy, KEYTRUDA was discontinued due to adverse reactions in 16% of 276 patients with HNSCC. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%). The most common adverse reactions (≥20%) were nausea (51%), fatigue (49%), constipation (37%), vomiting (32%), mucosal inflammation (31%), diarrhea (29%), decreased appetite (29%), stomatitis (26%), and cough (22%).

In KEYNOTE-012, KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (≥20%) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of facial edema and new or worsening hypothyroidism.

In KEYNOTE-204, KEYTRUDA was discontinued due to adverse reactions in 14% of 148 patients with cHL. Serious adverse reactions occurred in 30% of patients receiving KEYTRUDA; those ≥1% were pneumonitis, pneumonia, pyrexia, myocarditis, acute kidney injury, febrile neutropenia, and sepsis. Three patients died from causes other than disease progression: 2 from complications after allogeneic HSCT and 1 from unknown cause. The most common adverse reactions (≥20%) were upper respiratory tract infection (41%), musculoskeletal pain (32%), diarrhea (22%), and pyrexia, fatigue, rash, and cough (20% each).

In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in 5% of 210 patients with cHL. Serious adverse reactions occurred in 16% of patients; those ≥1% were pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two patients died from causes other than disease progression: 1 from GVHD after subsequent allogeneic HSCT and 1 from septic shock. The most common adverse reactions (≥20%) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

In KEYNOTE-170, KEYTRUDA was discontinued due to adverse reactions in 8% of 53 patients with PMBCL. Serious adverse reactions occurred in 26% of patients and included arrhythmia (4%), cardiac tamponade (2%), myocardial infarction (2%), pericardial effusion (2%), and pericarditis (2%). Six (11%) patients died within 30 days of start of treatment. The most common adverse reactions (≥20%) were musculoskeletal pain (30%), upper respiratory tract infection and pyrexia (28% each), cough (26%), fatigue (23%), and dyspnea (21%).

In KEYNOTE-A39, when KEYTRUDA was administered in combination with enfortumab vedotin to patients with locally advanced or metastatic urothelial cancer (n=440), fatal adverse reactions occurred in 3.9% of patients, including acute respiratory failure (0.7%), pneumonia (0.5%), and pneumonitis/ILD (0.2%). Serious adverse reactions occurred in 50% of patients receiving KEYTRUDA in combination with enfortumab vedotin; the serious adverse reactions in ≥2% of patients were rash (6%), acute kidney injury (5%), pneumonitis/ILD (4.5%), urinary tract infection (3.6%), diarrhea (3.2%), pneumonia (2.3%), pyrexia (2%), and hyperglycemia (2%). Permanent discontinuation of KEYTRUDA occurred in 27% of patients. The most common adverse reactions (≥2%) resulting in permanent discontinuation of KEYTRUDA were pneumonitis/ILD (4.8%) and rash (3.4%). The most common adverse reactions (≥20%) occurring in patients treated with KEYTRUDA in combination with enfortumab vedotin were rash (68%), peripheral neuropathy (67%), fatigue (51%), pruritus (41%), diarrhea (38%), alopecia (35%), weight loss (33%), decreased appetite (33%), nausea (26%), constipation (26%), dry eye (24%), dysgeusia (21%), and urinary tract infection (21%).

In KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in 11% of 370 patients with locally advanced or metastatic urothelial carcinoma. Serious adverse reactions occurred in 42% of patients; those ≥2% were urinary tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis. The most common adverse reactions (≥20%) were fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%), constipation (21%), rash (21%), and diarrhea (20%).

In KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in 8% of 266 patients with locally advanced or metastatic urothelial carcinoma. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.9%). Serious adverse reactions occurred in 39% of KEYTRUDA-treated patients; those ≥2% were urinary tract infection, pneumonia, anemia, and pneumonitis. The most common adverse reactions (≥20%) in patients who received KEYTRUDA were fatigue (38%), musculoskeletal pain (32%), pruritus (23%), decreased appetite (21%), nausea (21%), and rash (20%).

In KEYNOTE-905, the most common adverse reactions (≥20%) occurring in cisplatin-ineligible patients with MIBC treated with KEYTRUDA in combination with enfortumab vedotin (n=167) were rash (54%), pruritus (47%), fatigue (47%), peripheral neuropathy (39%), alopecia (35%), dysgeusia (35%), diarrhea (34%), constipation (28%), decreased appetite (28%), nausea (26%), urinary tract infection (24%), dry eye (21%), and weight loss (20%).

In the neoadjuvant phase of KEYNOTE-905, serious adverse reactions occurred in 27% (n=167) of patients; the most frequent (≥2%) were urinary tract infection (3.6%) and hematuria (2.4%). Fatal adverse reactions occurred in 1.2% of patients, including myasthenia gravis and toxic epidermal necrolysis (0.6% each). Additional fatal adverse reactions were reported in 2.7% of patients in the post-surgery phase before adjuvant treatment started, including sepsis and intestinal obstruction (1.4% each). Permanent discontinuation of KEYTRUDA due to an adverse reaction occurred in 15% of patients; the most frequent (>1%) were rash (2.4%, including generalized exfoliative dermatitis), increased alanine aminotransferase, increased aspartate aminotransferase, diarrhea, dysgeusia, and toxic epidermal necrolysis (1.2% each). Of the 167 patients in the KEYTRUDA in combination with enfortumab vedotin arm who received neoadjuvant treatment, 7 (4.2%) patients did not receive surgery due to adverse reactions. The adverse reactions that led to cancellation of surgery were acute myocardial infarction, bile duct cancer, colon cancer, respiratory distress, urinary tract infection, and the two deaths due to myasthenia gravis and toxic epidermal necrolysis (0.6% each).

Of the 146 patients who received neoadjuvant treatment with KEYTRUDA in combination with enfortumab vedotin and underwent radical cystectomy, 6 (4.1%) patients experienced delay of surgery (defined as time from last neoadjuvant treatment to surgery exceeding 8 weeks) due to adverse reactions.

In the adjuvant phase of KEYNOTE-905, serious adverse reactions occurred in 43% (n=100) of patients; the most frequent (≥2%) were urinary tract infection (8%); acute kidney injury and pyelonephritis (5% each); urosepsis (4%); and hypokalemia, intestinal obstruction, and sepsis (2% each). Fatal adverse reactions occurred in 7% of patients, including urosepsis, intracranial hemorrhage, death, myocardial infarction, multiple organ dysfunction syndrome, and pseudomonal pneumonia (1% each). Permanent discontinuation of KEYTRUDA due to an adverse reaction occurred in 28% of patients; the most frequent (>1%) were diarrhea (5%), peripheral neuropathy, acute kidney injury, and pneumonitis (2% each).

In KEYNOTE-057, KEYTRUDA was discontinued due to adverse reactions in 11% of 148 patients with high-risk NMIBC. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.4%). Serious adverse reactions occurred in 28% of patients; those ≥2% were pneumonia (3%), cardiac ischemia (2%), colitis (2%), pulmonary embolism (2%), sepsis (2%), and urinary tract infection (2%). The most common adverse reactions (≥20%) were fatigue (29%), diarrhea (24%), and rash (24%).

Adverse reactions occurring in patients with MSI-H or dMMR CRC were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

In KEYNOTE-158 and KEYNOTE-164, adverse reactions occurring in patients with MSI-H or dMMR cancer were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.

In KEYNOTE-811, fatal adverse reactions occurred in 3 patients who received KEYTRUDA in combination with trastuzumab and CAPOX (capecitabine plus oxaliplatin) or FP (5-FU plus cisplatin) and included pneumonitis in 2 patients and hepatitis in 1 patient. KEYTRUDA was discontinued due to adverse reactions in 13% of 350 patients with locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma. Adverse reactions resulting in permanent discontinuation of KEYTRUDA in ≥1% of patients were pneumonitis (2.0%) and pneumonia (1.1%). In the KEYTRUDA arm vs placebo, there was a difference of ≥5% incidence between patients treated with KEYTRUDA vs standard of care for diarrhea (53% vs 47%), rash (35% vs 28%), hypothyroidism (11% vs 5%), and pneumonia (11% vs 5%).

In KEYNOTE-859, when KEYTRUDA was administered in combination with fluoropyrimidine- and platinum-containing chemotherapy, serious adverse reactions occurred in 45% of 785 patients. Serious adverse reactions in >2% of patients included pneumonia (4.1%), diarrhea (3.9%), hemorrhage (3.9%), and vomiting (2.4%). Fatal adverse reactions occurred in 8% of patients who received KEYTRUDA, including infection (2.3%) and thromboembolism (1.3%). KEYTRUDA was permanently discontinued due to adverse reactions in 15% of patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA (≥1%) were infections (1.8%) and diarrhea (1.0%). The most common adverse reactions (reported in ≥20%) in patients receiving KEYTRUDA in combination with chemotherapy were peripheral neuropathy (47%), nausea (46%), fatigue (40%), diarrhea (36%), vomiting (34%), decreased appetite (29%), abdominal pain (26%), palmar-plantar erythrodysesthesia syndrome (25%), constipation (22%), and weight loss (20%).

In KEYNOTE-590, when KEYTRUDA was administered with cisplatin and fluorouracil to patients with metastatic or locally advanced esophageal or GEJ (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma who were not candidates for surgical resection or definitive chemoradiation, KEYTRUDA was discontinued due to adverse reactions in 15% of 370 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA (≥1%) were pneumonitis (1.6%), acute kidney injury (1.1%), and pneumonia (1.1%). The most common adverse reactions (≥20%) with KEYTRUDA in combination with chemotherapy were nausea (67%), fatigue (57%), decreased appetite (44%), constipation (40%), diarrhea (36%), vomiting (34%), stomatitis (27%), and weight loss (24%).

Adverse reactions occurring in patients with esophageal cancer who received KEYTRUDA as a monotherapy were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

In KEYNOTE-A18, when KEYTRUDA was administered with CRT (cisplatin plus external beam radiation therapy [EBRT] followed by brachytherapy [BT]) to patients with FIGO 2014 Stage III-IVA cervical cancer, fatal adverse reactions occurred in 1.4% of 294 patients, including 1 case each (0.3%) of large intestinal perforation, urosepsis, sepsis, and vaginal hemorrhage. Serious adverse reactions occurred in 34% of patients; those ≥1% included urinary tract infection (3.1%), urosepsis (1.4%), and sepsis (1%). KEYTRUDA was discontinued for adverse reactions in 9% of patients. The most common adverse reaction (≥1%) resulting in permanent discontinuation was diarrhea (1%). For patients treated with KEYTRUDA in combination with CRT, the most common adverse reactions (≥10%) were nausea (56%), diarrhea (51%), urinary tract infection (35%), vomiting (34%), fatigue (28%), hypothyroidism (23%), constipation (20%), weight loss (19%), decreased appetite (18%), pyrexia (14%), abdominal pain and hyperthyroidism (13% each), dysuria and rash (12% each), back and pelvic pain (11% each), and COVID-19 (10%).

In KEYNOTE-826, when KEYTRUDA was administered in combination with paclitaxel and cisplatin or paclitaxel and carboplatin, with or without bevacizumab (n=307), to patients with persistent, recurrent, or first-line metastatic cervical cancer regardless of tumor PD-L1 expression who had not been treated with chemotherapy except when used concurrently as a radio-sensitizing agent, fatal adverse reactions occurred in 4.6% of patients, including 3 cases of hemorrhage, 2 cases each of sepsis and due to unknown causes, and 1 case each of acute myocardial infarction, autoimmune encephalitis, cardiac arrest, cerebrovascular accident, femur fracture with perioperative pulmonary embolus, intestinal perforation, and pelvic infection. Serious adverse reactions occurred in 50% of patients receiving KEYTRUDA in combination with chemotherapy with or without bevacizumab; those ≥3% were febrile neutropenia (6.8%), urinary tract infection (5.2%), anemia (4.6%), and acute kidney injury and sepsis (3.3% each).

KEYTRUDA was discontinued in 15% of patients due to adverse reactions. The most common adverse reaction resulting in permanent discontinuation (≥1%) was colitis (1%).

For patients treated with KEYTRUDA, chemotherapy, and bevacizumab (n=196), the most common adverse reactions (≥20%) were peripheral neuropathy (62%), alopecia (58%), anemia (55%), fatigue/asthenia (53%), nausea and neutropenia (41% each), diarrhea (39%), hypertension and thrombocytopenia (35% each), constipation and arthralgia (31% each), vomiting (30%), urinary tract infection (27%), rash (26%), leukopenia (24%), hypothyroidism (22%), and decreased appetite (21%).

For patients treated with KEYTRUDA in combination with chemotherapy with or without bevacizumab, the most common adverse reactions (≥20%) were peripheral neuropathy (58%), alopecia (56%), fatigue (47%), nausea (40%), diarrhea (36%), constipation (28%), arthralgia (27%), vomiting (26%), hypertension and urinary tract infection (24% each), and rash (22%).

In KEYNOTE-158, KEYTRUDA was discontinued due to adverse reactions in 8% of 98 patients with previously treated recurrent or metastatic cervical cancer. Serious adverse reactions occurred in 39% of patients receiving KEYTRUDA; the most frequent included anemia (7%), fistula, hemorrhage, and infections [except urinary tract infections] (4.1% each). The most common adverse reactions (≥20%) were fatigue (43%), musculoskeletal pain (27%), diarrhea (23%), pain and abdominal pain (22% each), and decreased appetite (21%).

In KEYNOTE-394, KEYTRUDA was discontinued due to adverse reactions in 13% of 299 patients with previously treated hepatocellular carcinoma. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was ascites (2.3%). The most common adverse reactions in patients receiving KEYTRUDA (≥10%) were pyrexia (18%), rash (18%), diarrhea (16%), decreased appetite (15%), pruritus (12%), upper respiratory tract infection (11%), cough (11%), and hypothyroidism (10%).

In KEYNOTE-966, when KEYTRUDA was administered in combination with gemcitabine and cisplatin, KEYTRUDA was discontinued for adverse reactions in 15% of 529 patients with locally advanced unresectable or metastatic biliary tract cancer. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA (≥1%) was pneumonitis (1.3%). Adverse reactions leading to the interruption of KEYTRUDA occurred in 55% of patients. The most common adverse reactions or laboratory abnormalities leading to interruption of KEYTRUDA (≥2%) were decreased neutrophil count (18%), decreased platelet count (10%), anemia (6%), decreased white blood cell count (4%), pyrexia (3.8%), fatigue (3.0%), cholangitis (2.8%), increased ALT (2.6%), increased AST (2.5%), and biliary obstruction (2.3%).

In KEYNOTE-017 and KEYNOTE-913, adverse reactions occurring in patients with MCC (n=105) were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a single agent.

In KEYNOTE-426, when KEYTRUDA was administered in combination with axitinib, fatal adverse reactions occurred in 3.3% of 429 patients. Serious adverse reactions occurred in 40% of patients, the most frequent (≥1%) were hepatotoxicity (7%), diarrhea (4.2%), acute kidney injury (2.3%), dehydration (1%), and pneumonitis (1%). Permanent discontinuation due to an adverse reaction occurred in 31% of patients; KEYTRUDA only (13%), axitinib only (13%), and the combination (8%); the most common were hepatotoxicity (13%), diarrhea/colitis (1.9%), acute kidney injury (1.6%), and cerebrovascular accident (1.2%). The most common adverse reactions (≥20%) were diarrhea (56%), fatigue/asthenia (52%), hypertension (48%), hepatotoxicity (39%), hypothyroidism (35%), decreased appetite (30%), palmar-plantar erythrodysesthesia (28%), nausea (28%), stomatitis/mucosal inflammation (27%), dysphonia (25%), rash (25%), cough (21%), and constipation (21%).

In KEYNOTE-564, when KEYTRUDA was administered as a single agent for the adjuvant treatment of renal cell carcinoma, serious adverse reactions occurred in 20% of patients receiving KEYTRUDA; the serious adverse reactions (≥1%) were acute kidney injury, adrenal insufficiency, pneumonia, colitis, and diabetic ketoacidosis (1% each). Fatal adverse reactions occurred in 0.2% including 1 case of pneumonia. Discontinuation of KEYTRUDA due to adverse reactions occurred in 21% of 488 patients; the most common (≥1%) were increased ALT (1.6%), colitis (1%), and adrenal insufficiency (1%). The most common adverse reactions (≥20%) were musculoskeletal pain (41%), fatigue (40%), rash (30%), diarrhea (27%), pruritus (23%), and hypothyroidism (21%).

In KEYNOTE-868, when KEYTRUDA was administered in combination with chemotherapy (paclitaxel and carboplatin) to patients with advanced or recurrent endometrial carcinoma (n=382), serious adverse reactions occurred in 35% of patients receiving KEYTRUDA in combination with chemotherapy, compared to 19% of patients receiving placebo in combination with chemotherapy (n=377). Fatal adverse reactions occurred in 1.6% of patients receiving KEYTRUDA in combination with chemotherapy, including COVID-19 (0.5%) and cardiac arrest (0.3%). KEYTRUDA was discontinued for an adverse reaction in 14% of patients. Adverse reactions occurring in patients treated with KEYTRUDA and chemotherapy were generally similar to those observed with KEYTRUDA alone or chemotherapy alone, with the exception of rash (33% all Grades; 2.9% Grades 3-4).

Adverse reactions occurring in patients with MSI-H or dMMR endometrial carcinoma who received KEYTRUDA as a single agent were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a single agent.

Adverse reactions occurring in patients with TMB-H cancer were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.

Adverse reactions occurring in patients with recurrent or metastatic cSCC or locally advanced cSCC were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

In KEYNOTE-522, when KEYTRUDA was administered with neoadjuvant chemotherapy (carboplatin and paclitaxel followed by doxorubicin or epirubicin and cyclophosphamide) followed by surgery and continued adjuvant treatment with KEYTRUDA as a single agent (n=778) to patients with newly diagnosed, previously untreated, high-risk early-stage TNBC, fatal adverse reactions occurred in 0.9% of patients, including 1 each of adrenal crisis, autoimmune encephalitis, hepatitis, pneumonia, pneumonitis, pulmonary embolism, and sepsis in association with multiple organ dysfunction syndrome and myocardial infarction. Serious adverse reactions occurred in 44% of patients receiving KEYTRUDA; those ≥2% were febrile neutropenia (15%), pyrexia (3.7%), anemia (2.6%), and neutropenia (2.2%). KEYTRUDA was discontinued in 20% of patients due to adverse reactions. The most common reactions (≥1%) resulting in permanent discontinuation were increased ALT (2.7%), increased AST (1.5%), and rash (1%). The most common adverse reactions (≥20%) in patients receiving KEYTRUDA with chemotherapy followed by KEYTRUDA alone were fatigue (70%), nausea (67%), alopecia (61%), rash (52%), constipation (42%), diarrhea and peripheral neuropathy (41% each), stomatitis (34%), vomiting (31%), headache (30%), arthralgia (29%), pyrexia (28%), cough (26%), abdominal pain (24%), decreased appetite (23%), insomnia (21%), and myalgia (20%).

In KEYNOTE-355, when KEYTRUDA and chemotherapy (paclitaxel, paclitaxel protein-bound, or gemcitabine and carboplatin) were administered to patients with locally recurrent unresectable or metastatic TNBC who had not been previously treated with chemotherapy in the metastatic setting (n=596), fatal adverse reactions occurred in 2.5% of patients, including cardio-respiratory arrest (0.7%) and septic shock (0.3%). Serious adverse reactions occurred in 30% of patients receiving KEYTRUDA in combination with chemotherapy; the serious reactions in ≥2% were pneumonia (2.9%), anemia (2.2%), and thrombocytopenia (2%). KEYTRUDA was discontinued in 11% of patients due to adverse reactions. The most common reactions resulting in permanent discontinuation (≥1%) were increased ALT (2.2%), increased AST (1.5%), and pneumonitis (1.2%). The most common adverse reactions (≥20%) in patients receiving KEYTRUDA in combination with chemotherapy were fatigue (48%), nausea (44%), alopecia (34%), diarrhea and constipation (28% each), vomiting and rash (26% each), cough (23%), decreased appetite (21%), and headache (20%).

In KEYNOTE-B96, when KEYTRUDA was administered in combination with paclitaxel, with or without bevacizumab, serious adverse reactions occurred in 54% of patients. Serious adverse reactions in ≥2% of patients were pneumonia (4.3%), urinary tract infection (3.9%), adrenal insufficiency (3%), hyponatremia (3%), COVID-19, decreased neutrophil count, pulmonary embolism (2.6% each), abdominal pain, anemia, colitis, diarrhea, febrile neutropenia, pyrexia, and vomiting (2.1% each).

Fatal adverse reactions occurred in 3.9% of patients receiving KEYTRUDA and paclitaxel, with or without bevacizumab, including assisted suicide (0.9%), death, intestinal perforation, sepsis, COVID-19, cardio-respiratory arrest, colitis, and embolic stroke (0.4% each).

KEYTRUDA was permanently discontinued for adverse reactions in 16% of patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA (≥1%) were colitis and increased alanine aminotransferase (1.3% each). Adverse reactions leading to the interruption of KEYTRUDA occurred in 44% of patients. The most common adverse reactions leading to interruption of KEYTRUDA in ≥2% were urinary tract infection (3.9%), adrenal insufficiency, pyrexia, pneumonitis, upper respiratory tract infection (2.6% each), neutropenia, diarrhea, and COVID-19 (2.1% each).

The most common adverse reactions (≥20%) for patients treated with KEYTRUDA in combination with paclitaxel, with or without bevacizumab, were diarrhea (45%), fatigue (43%), nausea (41%), alopecia, peripheral neuropathy (38% each), epistaxis (31%), urinary tract infection (27%), constipation (25%), abdominal pain, decreased appetite, vomiting (24% each), hypothyroidism (21%), cough, hypertension, and rash (20% each).

For patients treated with KEYTRUDA in combination with paclitaxel and bevacizumab (N=169), decreased white blood cell count (27%), stomatitis (22%), and pyrexia (21%) were also reported as adverse reactions.

Lactation

Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 4 months after the last dose.

Pediatric Use

In KEYNOTE-051, 173 pediatric patients (65 pediatric patients aged 6 months to younger than 12 years and 108 pediatric patients aged 12 years to 17 years) were administered KEYTRUDA 2 mg/kg every 3 weeks. The median duration of exposure was 2.1 months (range: 1 day to 25 months).

Adverse reactions that occurred at a ≥10% higher rate in pediatric patients when compared to adults were pyrexia (33%), leukopenia (30%), vomiting (29%), neutropenia (28%), headache (25%), abdominal pain (23%), thrombocytopenia (22%), Grade 3 anemia (17%), decreased lymphocyte count (13%), and decreased white blood cell count (11%).

Geriatric Use

Of the 564 patients with locally advanced or metastatic urothelial cancer treated with KEYTRUDA in combination with enfortumab vedotin, 44% (n=247) were 65-74 years and 26% (n=144) were 75 years or older. No overall differences in effectiveness were observed between patients 65 years of age or older and younger patients. Patients 75 years of age or older treated with KEYTRUDA in combination with enfortumab vedotin experienced a higher incidence of fatal adverse reactions than younger patients. The incidence of fatal adverse reactions was 4% in patients younger than 75 and 7% in patients 75 years or older.

Of the 167 patients with MIBC treated with KEYTRUDA in combination with enfortumab vedotin, 37% (n=61) were 65-74 years and 46% (n=77) were 75 years or older. Patients 75 years of age or older treated with KEYTRUDA in combination with enfortumab vedotin experienced a higher incidence of fatal adverse reactions than younger patients. The incidence of fatal adverse reactions was 4% in patients younger than 75 and 12% in patients 75 years or older.

Additional Selected KEYTRUDA Indications in the U.S.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:

  • Stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
  • metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.

KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC.

Malignant Pleural Mesothelioma

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic malignant pleural mesothelioma (MPM).

Head and Neck Squamous Cell Cancer

KEYTRUDA is indicated for the treatment of adult patients with resectable locally advanced head and neck squamous cell carcinoma (HNSCC) whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test, as a single agent as neoadjuvant treatment, continued as adjuvant treatment in combination with radiotherapy (RT) with or without cisplatin and then as a single agent.

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Cancer

KEYTRUDA, in combination with enfortumab vedotin, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma:

  • who are not eligible for any platinum-containing chemotherapy, or
  • who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA, in combination with enfortumab vedotin, as neoadjuvant treatment and then continued after cystectomy as adjuvant treatment, is indicated for the treatment of adult patients with muscle invasive bladder cancer (MIBC) who are ineligible for cisplatin-containing chemotherapy.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-approved test.

Gastric Cancer

KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.

KEYTRUDA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥ 1) as determined by an FDA approved test.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:

  • in combination with platinum- and fluoropyrimidine-based chemotherapy for patients with tumors that express PD-L1 (CPS ≥1), or
  • as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.

Cervical Cancer

KEYTRUDA, in combination with chemoradiotherapy (CRT), is indicated for the treatment of patients with locally advanced cervical cancer involving the lower third of the vagina, with or without extension to pelvic sidewall, or hydronephrosis/non-functioning kidney, or spread to adjacent pelvic organs (FIGO 2014 Stage III-IVA).

KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) secondary to hepatitis B who have received prior systemic therapy other than a PD-1/PD-L1-containing regimen.

Biliary Tract Cancer

KEYTRUDA, in combination with gemcitabine and cisplatin, is indicated for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer (BTC).

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).

KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.

Endometrial Carcinoma

KEYTRUDA, in combination with carboplatin and paclitaxel, followed by KEYTRUDA as a single agent, is indicated for the treatment of adult patients with primary advanced or recurrent endometrial carcinoma.

KEYTRUDA, as a single agent, is indicated for the treatment of adult patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

Tumor Mutational Burden-High Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.

Triple-Negative Breast Cancer

KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.

KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.

Ovarian Cancer

KEYTRUDA, in combination with paclitaxel, with or without bevacizumab, is indicated for the treatment of adult patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-authorized test, and who have received 1 or 2 prior systemic treatment regimens.

Merck’s focus on cancer

Every day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 25 novel mechanisms. With one of the largest clinical development programs across more than 30 tumor types, we strive to advance breakthrough science that will shape the future of oncology. By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care. Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit https://www.merck.com/research/oncology/ .

About Merck’s research in melanoma

Merck is committed to delivering meaningful advances for patients with melanoma and to continuing research in skin cancers through a broad clinical development program across investigational and approved medicines. KEYTRUDA has been established as an important treatment option for the adjuvant treatment of patients with resected Stage IIB, IIC, or III melanoma based on results of KEYNOTE-054 and KEYNOTE-716. KEYTRUDA is also approved worldwide for the treatment of patients with unresectable or metastatic melanoma.

About Merck

At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com  and connect with us on  X (formerly Twitter) , Facebook , Instagram , YouTube and LinkedIn .

About Moderna

Moderna is a pioneer and leader in the field of mRNA medicine. Through the advancement of its technology platform, Moderna is reimagining how medicines are made to transform how we treat and prevent diseases. Since its founding, Moderna’s mRNA platform has enabled the development of vaccines and therapeutics across infectious diseases, cancer, rare diseases and more.

With a global team and a unique culture, driven by the company’s values and mindsets, Moderna’s mission is to deliver the greatest possible impact to people through mRNA medicines. For more information about Moderna, please visit modernatx.com and connect with us on X, Facebook, Instagram, YouTube and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA

This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2025 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site ( www.sec.gov ).

Moderna Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements regarding: the ability of intismeran autogene in combination with KEYTRUDA to demonstrate sustained improvement in RFS and DMFS compared with KEYTRUDA alone; the encouraging trend in overall survival compared with KEYTRUDA alone; the potential long-term benefit; the tolerability and safety profile for intismeran autogene; the companies’ ongoing Phase 2 and Phase 3 clinical trials, including anticipated milestones; and mRNA’s potential in cancer care. The forward-looking statements in this press release are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond Moderna’s control and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements. These risks, uncertainties, and other factors include, among others, those risks and uncertainties described under the heading “Risk Factors” in Moderna’s Annual Report on Form 10-K for the fiscal year ended December 31, 2025, and in subsequent filings made by Moderna with the U.S. Securities and Exchange Commission, which are available on the SEC’s website at www.sec.gov. Except as required by law, Moderna disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release in the event of new information, future developments or otherwise. These forward-looking statements are based on Moderna’s current expectations and speak only as of the date of this press release.

###

Please see Prescribing Information for KEYTRUDA (pembrolizumab) at https://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at https://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf .

Merck Media Contacts:

Carly Myar

carly.myar@merck.com

Julie Cunningham

julie.cunningham@merck.com

Merck Investor Contacts:

Peter Dannenbaum

(732) 594-1579

Steven Graziano (732) 594-1583

Moderna Media Contacts:

Chris Ridley

Vice President, Global Head of Media Relations

+1 617-800-3651

Chris.Ridley@modernatx.com

Moderna Investor Contacts:

Lavina Talukdar

Senior Vice President & Head of Investor Relations

+1 617-209-5834

Lavina.Talukdar@modernatx.com

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打开原文

CEPI to Fund Pivotal Phase 3 Trial for Moderna’s mRNA Pandemic Influenza Candidate

来源信息
来源：CEPI发布日期：2025-12-18抓取时间：2026-06-17T18:49:52.857Z相关标的：MRNA归档状态：已归档 / 弹窗可读
中文摘要

一句话结论

CEPI 将最多投入 5430 万美元支持 Moderna H5 pandemic influenza mRNA 候选疫苗 mRNA-1018 的关键 Phase 3，文章主张 mRNA 平台在大流行响应速度、可扩展制造和公平供应上有公共卫生价值。

关键事实

  • 发布日期为 2025-12-18，发布方为 CEPI，合作对象为 Moderna。
  • CEPI 投资金额最高 5430 万美元，用于支持 mRNA-1018 进入旨在推进 licensure 的 pivotal Phase 3。
  • 文章称该研究将是首个进入 pivotal trial 的 mRNA-based pandemic influenza vaccine。
  • 若获批且发生 influenza pandemic，Moderna 承诺将 20% 的 H5 pandemic vaccine manufacturing capacity 以可负担价格供应给中低收入国家。
  • Phase 3 计划 2026 年初启动，在英国和美国人群中评估安全性与免疫原性。
  • 文章称早期 Phase 1/2 结果显示 18 岁及以上健康成人有快速且持续的免疫应答。
  • CEPI 将该项目与 100 Days Mission 联系起来，即在新大流行威胁识别后 100 天内开发安全有效疫苗。

作者观点与证据

CEPI 的立场明显支持 mRNA 快速响应平台，证据集中在 mRNA 可在病毒基因序列明确后快速设计、相对传统鸡胚或细胞培养工艺更快制造，以及 Moderna 承诺部分产能用于公平供应。它不是商业销售预测，更多是公共卫生资金和平台能力背书。

与相关标的的关系

对 MRNA 的关系是平台能力验证，而不是短期收入确认。mRNA-1018 能增强 Moderna 在 pandemic preparedness 和政府/多边组织合作中的可信度，也与 mRNA-1010 seasonal influenza 的监管数据形成技术延伸。但该项目商业化取决于 licensure、疫情场景和采购机制。

时效性与限制

发布时间距本报告约 6 个月，仍适合作为 2026 Phase 3 背景。限制是来源为资助方/合作公告，没有给出 Phase 3 结果，也没有可直接估算销售额的采购合同。

后续跟踪

  • mRNA-1018 Phase 3 是否按计划启动、入组和读出。
  • 免疫原性是否足以支持 licensure。
  • CEPI 资金之外是否出现政府采购或储备订单。
  • 20% 产能公平供应承诺对商业毛利和产能安排的影响。
英文原文
CEPI to Fund Pivotal Phase 3 Trial for Moderna’s mRNA Pandemic Influenza Candidate
  • Up to $54.3 million CEPI investment aims to help advance Moderna’s H5 pandemic influenza vaccine candidate to licensure
  • Partnership strengthens global preparedness against a significant pandemic threat
  • If licensed and in the event of an influenza pandemic, Moderna will allocate 20% of its H5 pandemic vaccine manufacturing capacity for timely supply to low- and middle-income countries at affordable pricing

OSLO, Norway/ CAMBRIDGE, MA/ ACCESS Newswire/ 18 December 2025. The Coalition for Epidemic Preparedness Innovations (CEPI) will invest up to $54.3 million to support a pivotal Phase 3 clinical trial that aims to help advance Moderna’s investigational mRNA-based H5 pandemic influenza vaccine candidate, mRNA-1018, to licensure. The funding marks a significant step forward in global pandemic preparedness that could enable fast, equitable access to vaccines for one of the world’s most pressing health threats.

This Phase 3 study would be the first mRNA-based vaccine targeting pandemic influenza to enter a pivotal trial. If the vaccine candidate is licensed, it would expand the current global portfolio of H5 vaccines with a rapid-response platform that could revolutionize future pandemic responses, making a significant contribution to CEPI’s 100 Days Mission, a global goal to develop safe and effective vaccines within 100 days of a new pandemic threat being identified.

Dr Richard Hatchett, Chief Executive Officer of CEPI, said: “Pandemic influenza remains one of the greatest threats to global health security. With this partnership, we are not just advancing vaccine science, we are fundamentally changing the game. By harnessing the speed and adaptability of mRNA technology, we could shave months off the response time, deliver vaccines at scale, and enable equitable access for all. This is how we plan to protect the world from the next flu pandemic.”

Stéphane Bancel, Chief Executive Officer of Moderna, said: “We are proud to have the support of CEPI to advance our pandemic influenza vaccine candidate, research that is critical to our commitment to pandemic preparedness. mRNA technology can play a vital role in addressing emerging health threats quickly and effectively, and we look forward to continuing our partnership with CEPI as we advance our health security portfolio, and in parallel, further the 100 Days Mission.”

A potential first-in-class mRNA vaccine for pandemic influenza

Conventional influenza vaccines require virus growth in eggs or cell culture, a process that can take months. By contrast, an mRNA vaccine can be designed in hours or days as soon as the virus’s genetic sequence is known and swiftly manufactured at scale. The combination of speed, adaptability and scalability offered by mRNA technology is a potential critical advantage when a new pandemic strain emerges and every day that passes could cost lives.

If licensure is granted, Moderna is committed to working to provide people around the world with rapid, equitable access to the resulting H5 vaccine in the event of a pandemic. As part of this agreement, Moderna will allocate 20% of its H5 pandemic vaccine manufacturing capacity for timely supply to low- and middle-income countries at affordable pricing.

The Phase 3 trial, set to begin early in 2026, will evaluate the safety and immunogenicity of Moderna’s H5 vaccine candidate in populations in the UK and U.S. It will build upon positive Phase 1/2 results which showed rapid and persistent immune responses in healthy adults aged 18 years and older. Potential licensure of the vaccine will also leverage data from a pivotal Phase 3 trial of Moderna’s investigational seasonal influenza vaccine, mRNA-1010.

This project is part of CEPI and Moderna’s strategic partnership , which aims to harness Moderna’s mRNA platform to accelerate epidemic and pandemic vaccine development.

--ENDS--

About CEPI

CEPI is an innovative partnership between public, private, philanthropic, and civil organisations. Its mission is to accelerate the development of vaccines and other biologic countermeasures against epidemic and pandemic threats so they can be accessible to all people in need. CEPI has supported the development of more than 70 vaccine candidates or platform technologies against multiple known high-risk pathogens or a future Disease X. Central to CEPI’s pandemic-beating plan is the ‘100 Days Mission’ to accelerate the time taken to develop safe, effective and accessible vaccines against new threats to just 100 days. Learn more at  CEPI.net .

About Moderna

Moderna is a pioneer and leader in the field of mRNA medicine. Through the advancement of its technology platform, Moderna is reimagining how medicines are made to transform how we treat and prevent diseases. Since its founding, Moderna's mRNA platform has enabled the development of vaccines and therapeutics across infectious diseases, cancer, rare diseases and more.

With a global team and a unique culture, driven by the company's values and mindsets, Moderna's mission is to deliver the greatest possible impact to people through mRNA medicines. For more information about Moderna, please visit modernatx.com and connect with us on X, Facebook, Instagram, YouTube and LinkedIn.

Moderna Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements regarding: CEPI’s investment to advance Moderna’s H5 pandemic influenza vaccine candidate; the potential for licensure of mRNA-1018; the safety and immunogenicity of mRNA-1018; the potential for mRNA technology to effectively address emerging health threats; and Moderna’s ability to manufacture at scale. The forward-looking statements in this press release are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond Moderna’s control and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements. These risks, uncertainties, and other factors include, among others, those risks and uncertainties described under the heading “Risk Factors” in Moderna's Annual Report on Form 10-K for the fiscal year ended December 31, 2024, and in subsequent filings made by Moderna with the U.S. Securities and Exchange Commission, which are available on the SEC’s website at www.sec.gov. Except as required by law, Moderna disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release in the event of new information, future developments or otherwise. These forward-looking statements are based on Moderna’s current expectations and speak only as of the date of this press release.

CEPI

Email: [email protected]

Phone: +44 7387 055214

Moderna (media)

Email: [email protected]

Phone: +1 617-800-3651

Moderna (Investors)

Email: [email protected]

Phone: +1 617-209-5834

U.S. Department of State commits $50 million to CEPI to fast-track Bundibugyo virus medical countermeasures

CEPI awards Public Health Vaccines US$1.9m to accelerate Bundibugyo ebolavirus vaccine

CEPI funds next phase of nanoparticle vaccine platform to support rapid outbreak response

Where to go next

The 100 Days Mission Read more Equitable access Read more

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mRNA medicines we are currently developing

来源信息
来源：Moderna发布日期：未提供发布时间抓取时间：2026-06-17T18:49:52.922Z相关标的：MRNA归档状态：已归档 / 弹窗可读
中文摘要

一句话结论

Moderna 管线页显示公司已经从 COVID 单一产品扩展成呼吸道疫苗、潜伏/其他疫苗、precision immunotherapies 和 rare disease therapeutics 多线并行的平台公司，但多个关键资产仍处于 Phase 2/3，商业兑现尚未完成。

关键事实

  • 页面更新口径为 2026-05-28。
  • 已商业化产品包括 SPIKEVAX、mNEXSPIKE、mRESVIA 和 mCOMBRIAX。
  • 呼吸道疫苗中，flu vaccine mRNA-1010 和 pandemic flu mRNA-1018 均处于 Phase 3。
  • Norovirus vaccine mRNA-1403 处于 Phase 3，mRNA-1405 处于 Phase 2。
  • Intismeran autogene mRNA-4157 与 Merck 合作，adjuvant melanoma、多个 NSCLC 场景均处于 Phase 3，RCC、bladder cancer、metastatic melanoma 等处于 Phase 2。
  • Rare disease 中 propionic acidemia mRNA-3927、methylmalonic acidemia mRNA-3705、Vertex 合作 CF mRNA-3692 均处于 Phase 2。
  • 早期项目还包括 CMV、EBV、HIV、Lyme、Nipah、Mpox、T-cell engagers 和 cell therapy enhancer。

作者观点与证据

这是公司管线页，观点天然偏正面，重点是展示 mRNA 平台横跨疫苗、肿瘤和罕见病。证据是项目阶段和适应症清单，不包含疗效大小、概率、商业化假设或竞争胜率。

与相关标的的关系

对 MRNA 的核心意义是证明可选项很多，但也暴露执行复杂度。投资分析不能把所有 Phase 2/3 项目都同等计入估值，短期应聚焦 mRNA-1010、mRNA-1403、mRNA-4157 和 mRNA-3927 等 2026 相关节点。

时效性与限制

页面为 2026-05-28 口径，适合当前报告引用。限制是公司自述、无失败概率、无商业化细节，也不等同于监管批准。

后续跟踪

  • mRNA-1010 PDUFA 与标签范围。
  • mRNA-4157 Phase 3 数据和适应症扩展。
  • Norovirus 与 PA 的 2026 读出。
  • 公司是否继续裁剪早期项目以控制现金消耗。
英文原文
mRNA medicines we are currently developing

Skip to main content mRNA Pipeline

Research

Browse :

  • Therapeutic areas
  • mRNA Pipeline
  • Clinical trials

Our mRNA pipeline shows the progress we’re making on clinical programs currently in development to create mRNA medicines for a wide range of diseases and conditions.

as-of May 28, 2026

Please click here for more information on our approved products

All Categories

Filter : All Categories Respiratory Vaccines Latent & Other Vaccines Precision Immunotherapies Rare Disease Therapeutics

Program Indication

ID #

Phase 1

Phase 2

Phase 3

Commercial

Respiratory Vaccines

Adults

COVID-19 vaccine

SPIKEVAX®

Commercial

COVID-19 vaccine

mNEXSPIKE®

Commercial

RSV vaccine

mRESVIA®

Commercial

Flu + COVID vaccine

mCOMBRIAX

Commercial

Flu vaccine

mRNA-1010

Phase 3

Pandemic Flu vaccine (in collaboration with CEPI)

mRNA-1018

Phase 3

RSV + hMPV vaccine

mRNA-1365

Phase 1

Adolescents and Pediatrics

RSV vaccine pediatrics

mRNA-1345

Phase 2

Latent & Other Vaccines

Enteric Viruses

Norovirus vaccine

mRNA-1403

Phase 3

Norovirus vaccine

mRNA-1405

Phase 2

Latent Viruses

CMV vaccine for transplant recipients

mRNA-1647

Phase 2

EBV vaccine to prevent infectious mononucleosis

mRNA-1189

Phase 2

EBV vaccine to address long-term EBV sequelae

mRNA-1195

Phase 2

HIV vaccine in collaboration with IAVI

mRNA-1645

Phase 1

Bacterial

Lyme disease vaccine

mRNA-1975

Phase 2

Lyme disease vaccine

mRNA-1982

Phase 2

Public Health

Nipah vaccine

mRNA-1215

Phase 1

Mpox vaccine

mRNA-1769

Phase 2

Oncology Therapeutics

Intismeran Autogene (partnered with Merck)

Adjuvant melanoma

mRNA-4157

Phase 3

Adjuvant NSCLC

mRNA-4157

Phase 3

Adjuvant NSCLC non-pCR post-neoadjuvant treatment

mRNA-4157

Phase 3

Adjuvant Stage 1 NSCLC

mRNA-4157

Phase 3

Adjuvant Renal cell carcinoma (RCC)

mRNA-4157

Phase 2

Adjuvant Bladder cancer (MIBC)

mRNA-4157

Phase 2

Bladder cancer (NMIBC)

mRNA-4157

Phase 2

Metastatic melanoma

mRNA-4157

Phase 2

First-line metastatic squamous NSCLC

mRNA-4157

Phase 2

Early and advanced solid tumors

mRNA-4157

Phase 1

Cancer antigen therapies

Advanced solid tumors

mRNA-4359

Phase 2

Solid tumors

mRNA-4106

Phase 1

Select advanced solid tumor malignancies

mRNA-4200

Phase 1

T-cell engagers

Multiple myeloma

mRNA-2808

Phase 1

Cell therapy enhancers

Solid tumors (in collaboration with Immatics)

mRNA-4203 + anzu-cel (IMA203)

Phase 1

Rare Disease Therapeutics

Rare Disease Intercellular Therapeutics

Propionic acidemia (PA)

mRNA-3927

Phase 2

Methylmalonic acidemia (MMA)

mRNA-3705

Phase 2

Cystic fibrosis (CF) (in collaboration with Vertex)

mRNA-3692

Phase 2

Abbreviations: CEPI , Coalition for Epidemic Preparedness Innovations; NSCLC , non-small cell lung cancer; MIBC , muscle-invasive bladder cancer; NMIBC , non-muscle invasive bladder cancer

as-of May 28, 2026

Please click here for more information on our approved products

打开原文

FDA staff scrutinizes evidence supporting Moderna’s flu vaccine

来源信息
来源：BioPharma Dive发布日期：2026-06-16抓取时间：2026-06-17T18:49:53.643Z相关标的：MRNA归档状态：已归档 / 弹窗可读
中文摘要

一句话结论

BioPharma Dive 的文章认为 FDA 会前文件虽未发现 mFlusiva 的重大安全缺陷，但监管人员对疗效证据外推性、老年/脆弱人群、共同接种和单季数据提出明显质疑，因此审批路径改善但仍不是无风险。

关键事实

  • 文章发布于 2026-06-16，作者 Delilah Alvarado，讨论 2026-06-18 FDA advisory panel meeting。
  • 文章称 FDA reviewers found no major deficiencies，但也指出证据缺口会降低疗效数据对目标人群的适用性。
  • Moderna 的测试数据显示 mFlusiva 相比 standard-dose vaccine 将 flu-like illness 可能性降低约 27%。
  • FDA 关注试验只覆盖一个流感季，可能无法反映不同病毒株季节表现。
  • 文章提到 influenza B 保护证据不足、very frail older adults 和 immunocompromised 人群证据不足。
  • Moderna 也没有提供与 COVID-19、RSV 等其他呼吸道疫苗共同接种的数据。
  • 安全性方面未见 major safety concerns，但 FDA 指出随访约 6 个月且参与者较健康，罕见不良事件仍需更大范围监测。
  • FDA 目标决定日为 2026-08-05。

作者观点与证据

文章倾向是“文件没有致命缺陷，但 FDA 仍在认真挑证据外推问题”。证据来自 FDA staff documents 和即将召开的 adcomm，而不是市场传闻。它比单纯新闻标题更有用，因为明确拆出审批风险点。

与相关标的的关系

对 MRNA 直接相关。它支持“mRNA-1010 已从 RTF 阴影中改善，但商业标签和上市后义务仍是关键”的判断。若委员会要求额外数据，短期估值修复可能受挫；若风险集中在上市后监测，路径更可控。

时效性与限制

发布时间非常接近 VRBPAC，会前时效性强。但它是媒体解读，不是 FDA 投票结果；引用时必须与 FDA 原始文件和会议结果分开。

后续跟踪

  • VRBPAC 对 50-64 与 65+ 两个问题的投票。
  • FDA 是否要求新增 efficacy season 或共同接种数据。
  • 标签是否限制 very frail/immunocompromised 人群。
  • 2026-08-05 PDUFA 结果。
英文原文
FDA staff scrutinizes evidence supporting Moderna’s flu vaccine

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FDA staff scrutinizes evidence supporting Moderna’s flu vaccine

Ahead of a Thursday advisory panel meeting, agency scientists highlighted shortcomings in data accrued for a vaccine the FDA controversially refused to even review earlier this year.

Published June 16, 2026

Delilah Alvarado

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The Moderna headquarters is seen on November 30, 2020 in Cambridge, Massachusetts.

Maddie Meyer via Getty Images

Food and Drug Administration scientists evaluating a potentially new messenger RNA flu vaccine from Moderna have expressed skepticism about the evidence supporting its benefits, according to documents filed days before a crucial advisory committee meeting.

On Thursday, the FDA will convene a panel of experts to discuss use of the shot, dubbed mFlusiva and in development for seasonal influenza. Panelists are set to vote on whether the benefits of vaccination outweigh the risks in people either between the ages of 50 and 64, or those who are 65 and older. Moderna hopes the discussion will set the stage for approval of a vaccine U.S. regulators controversially refused to review earlier this year before abruptly changing course .

Documents filed on Tuesday summarize the position of staff scientists and provide a window into how the agency views the data Moderna has compiled to date. They show that reviewers found no “major deficiencies” with the vaccine, but unearthed gaps in evidence that leave unclear how well it works, particularly in the elderly.

Moderna showed in testing that its shot reduced the likelihood of flu-like illness by 27% compared to a standard-dose vaccine in study results recently published in the New England Journal of Medicine . But staff reviewers pointed to key limitations in those findings. The trial only incorporated data from one flu season, raising questions about how the shot might perform in seasons with different viral strains. There wasn’t a large enough sample size to clearly show whether mFlusiva can protect against influenza B.

Moderna also didn’t definitively prove the vaccine’s effectiveness in “very frail” older adults or those with weakened immune systems — two groups particularly vulnerable to severe flu-related complications. And it doesn’t have data supporting mFlusiva use in people also receiving vaccines for other respiratory diseases, like COVID-19, reviewers wrote.

The limitations lower the “applicability of the efficacy data to a substantial portion of the intended patient population,” they added.

Staff scientists didn’t identify major safety concerns in the trial, but noted that their assessment was based on about six months of follow-up in healthier participants. Ongoing surveillance would be needed to detect rarer side effects that might emerge with broader use, they wrote.

The FDA doesn’t always follow the advice of its advisory panels, though it typically does. The agency is set to make a decision by Aug. 5.

Should the FDA approve mFlusiva, it’d mark a positive end for Moderna to what’s been an unusually tumultuous regulatory journey.

Moderna has been working on mFlusiva, as well as a related, combination COVID and flu vaccine, for multiple years now. But it withdrew an application for the combination vaccine last year following a request from the FDA for more data from the shot’s flu-preventing component. It subsequently accumulated that data and pushed toward an approval this year.

In February, though, the company received a “refuse-to-file” letter from the agency, meaning the FDA didn’t belive the company’s application warranted a review. Penned by former top vaccine official Vinay Prasad , that letter alleged that Moderna’s key trial wasn’t adequately controlled and should’ve involved a different comparator.

Moderna claimed to have been blinsided by the letter and argued it had gone against previous agency guidance — one of many times drugmakers cried foul over FDA communications during the tenure of former commissioner Marty Makary. However, amid public backlash, the FDA reversed its position only days later.

Moderna is seeking a traditional approval of mFlusiva in adults between 50 and 64 years of age, and an “accelerated” clearance in older individuals. It’s also agreed to conduct a post-marketing study in those 65 or older. And it’s now eyeing a clearance from different FDA leadership, as both Prasad and Makary recently left the agency as part of a White House-directed overhaul.

The company has long contended its vaccine might prove a unique weapon against influenza, as mRNA shots can be quickly designed to target newly circulating strains.

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打开原文

FDA appears less prickly toward Moderna mRNA flu shot

来源信息
来源：Fierce Biotech发布日期：2026-06-17抓取时间：2026-06-17T18:50:33.755Z相关标的：MRNA归档状态：访问失败 / 未作为证据
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BioNTech Announces First Quarter 2026 Financial Results and Corporate Update | BioNTech

来源信息
来源：BioNTech发布日期：2026-05-05抓取时间：2026-06-17T18:49:54.215Z相关标的：BNTX归档状态：已归档 / 弹窗可读
中文摘要

一句话结论

BioNTech Q1 2026 更新显示其正在从 COVID 收入转向 oncology 平台，现金和证券投资达 168 亿欧元，并完成 CureVac 等并购整合，是 Moderna 在 mRNA 平台和肿瘤方向上最重要的可比公司之一。

关键事实

  • 发布日期为 2026-05-05。
  • Q1 2026 revenue 为 1.181 亿欧元，低于上年同期 1.828 亿欧元，主要受 COVID-19 vaccine 收入下降影响。
  • Q1 2026 IFRS net loss 为 5.319 亿欧元，adjusted net loss 为 4.946 亿欧元。
  • Q1 2026 R&D expense 为 5.570 亿欧元，主要用于 immuno-oncology、ADC 项目 pumitamig、gotistobart，以及 2025 年并购的 BioNTech China 和 CureVac 相关成本。
  • 公司称 2026 年有 6 个 late-stage pipeline data readouts，覆盖 immunomodulators、ADC 和 mRNA cancer immunotherapies。
  • BioNTech 计划推进 COVID-19 2026/2027 season variant-adapted vaccine 开发和商业准备。
  • 公司持有 cash, cash equivalents and security investments 168 亿欧元，并计划最多 10 亿美元回购。
  • 公司强调 manufacturing footprint consolidation，以提升运营效率和资本配置。

作者观点与证据

这是公司 IR 材料，叙事重点是 oncology 战略和强现金。硬证据是收入、净亏损、R&D、现金证券投资和 readout 数量；战略语言需要和临床数据兑现分开看。

与相关标的的关系

对 MRNA 是竞争和估值参照。BioNTech 与 Moderna 同样面临 COVID 收入退潮，但 BioNTech 的现金规模更大，oncology 布局更集中，并通过 CureVac 扩充 mRNA 能力。MRNA 的优势在呼吸道疫苗商业化资产更多，劣势是现金消耗和 oncology 证据还需 Phase 3 兑现。

时效性与限制

发布时间约 6 周前，适合当前 peer analysis。限制是欧元口径、IFRS 与 GAAP 不可直接横比；BioNTech oncology 管线包含 ADC/抗体，不是纯 mRNA 可比。

后续跟踪

  • BioNTech 6 个 late-stage readouts 的结果。
  • CureVac 整合后 mRNA 平台项目优先级。
  • COVID 2026/2027 季节疫苗收入与毛利。
  • BioNTech 与 Moderna 在 oncology mRNA 项目上的 Phase 3 进展。
英文原文
BioNTech Announces First Quarter 2026 Financial Results and Corporate Update | BioNTech

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BioNTech Announces First Quarter 2026 Financial Results and Corporate Update

5 May 2026

PDF Version

  • Five additional pivotal trials for pumitamig initiated during 2026  in collaboration with Bristol Myers Squibb
  • Oncology pipeline strength and combination strategy highlighted  through multiple clinical data updates, including pumitamig, gotistobart and antibody-drug conjugate programs
  • Catalyst-rich year ahead with six late-stage pipeline data readouts expected across immunomodulators, antibody-drug conjugate and mRNA cancer immunotherapies
  • COVID-19 2026/2027 season variant-adapted vaccine  development and commercial preparation underway
  • Operational efficiency to be enhanced through manufacturing footprint consolidation , supporting strategic capital allocation to further advance its growing oncology pipeline toward commercialization
  • First quarter 2026 revenues of €118.1 million 1 , net loss of €531.9 million (adjusted 2 net loss of €494.6 million), with diluted loss per share of €2.10 ($2.46 3 ) (adjusted 2 diluted loss per share of €1.95 ($2.28 3 ))
  • Reaffirmed full year 2026 financial guidance and strong financial position continue to de-risk execution with cash, cash equivalents and security investments of €16.8 billion 4
  • Share repurchase program of up to $1.0 billion over twelve months planned

Conference call and webcast scheduled for May 5, 2026, at 8:00 a.m. ET (2:00 p.m. CET)

MAINZ, Germany, May 5, 2026 (GLOBE NEWSWIRE) --  BioNTech SE (Nasdaq: BNTX, “BioNTech” or “the Company”) today reported financial results for the three months ended March 31, 2026 and provided an update on its corporate progress.

“In the first quarter, we made substantial progress in executing towards our oncology strategy, highlighted by data presentations from our priority pan-tumor program pumitamig as well as our versatile antibody-drug conjugate portfolio. Simultaneously, we continue to broaden our clinical programs to include novel-novel combinations in order to inform the optimal set-up for registrational combination trials and maximize the potential of our pipeline,” said  Prof. Ugur Sahin, M.D., Chief Executive Officer and Co-Founder of BioNTech . “We will continue to focus on accelerating our key strategic programs as we remain steadfast in our vision to translate our science into survival for patients living with cancer.”

Financial Review for First Quarter 2026

in millions €,

except per share data     First Quarter 2026     First Quarter 2025

IFRS Results     Adjusted Results 2     IFRS Results   Adjusted Results 2

Revenues     118.1     118.1     182.8   182.8

Net loss     (531.9)     (494.6)     (415.8)   (430.8)

Diluted loss per share     (2.10)     (1.95)     (1.73)   (1.79)

Revenues for the first quarter of 2026 were €118.1 million, compared to €182.8 million for the comparative prior year period. The decrease was primarily driven by lower revenues of BioNTech’s COVID-19 vaccines.

Research and development (“R&D”) expenses were €557.0 million for the first quarter of 2026, compared to €525.6 million for the comparative prior year period.  R&D expenses were mainly driven by higher expenses for the development of immuno-oncology (“IO”) and antibody-drug conjugate (“ADC”) programs, in particular pumitamig and gotistobart, as well as costs from operations of entities acquired during 2025, BioNTech China (previously Biotheus) and CureVac, and an impairment of an intangible asset. These effects were partly offset by lower R&D expenses related to the Company’s COVID‑19 vaccine collaboration with Pfizer Inc. (“Pfizer”).

Adjusted R&D expenses were €527.1 million for the first quarter of 2026, compared to €525.6 million for the comparative prior year period. For the first quarter of 2026, adjusted R&D expenses exclude the impairment of an intangible asset.

Sales, general and administrative (“SG&A”) expenses 5 were €150.8 million for the first quarter of 2026, compared to €120.6 million for the comparative prior year period. The increase was mainly driven by the ongoing commercial build-up and the inclusion of operations of entities acquired in 2025, BioNTech China (previously Biotheus) and CureVac. These costs were partly offset by a reduction in external services.

Net loss was €531.9 million for the first quarter of 2026, compared to a net loss of €415.8 million for the comparative prior year period.

Adjusted net loss was €494.6 million for the first quarter of 2026, compared to an adjusted net loss of €430.8 million for the comparative prior year period.

Diluted loss per share was €2.10 for the first quarter of 2026, compared to a diluted loss per share of €1.73 for the comparative prior year period.

Adjusted diluted loss per share was €1.95 for the first quarter of 2026, compared to adjusted diluted loss per share of €1.79 for the comparative prior year period.

Cash, cash equivalents and security investments  as of March 31, 2026, were €16,763.3 million, comprising €9,939.4 million in cash and cash equivalents, €4,696.9 million in current security investments disclosed as financial assets and €2,127.0 million in non-current security investments disclosed as financial assets.

Shares outstanding as of March 31, 2026, were 252,884,261, excluding 6,143,226 shares held in treasury

“Our revenues for the first quarter reflect the seasonal demand for COVID-19 vaccines and are in line with our expectations,” said Ramón Zapata, Chief Financial Officer at BioNTech . “We are committed to a diligent capital allocation strategy that empowers us to pursue our goal of evolving into a leading biopharmaceutical company with multiple oncology products by 2030.”

Reaffirmed 2026 Financial Year Guidance 6 :

Revenues for the 2026 financial year   €2,000 – €2,300 m

In 2026, BioNTech anticipates lower COVID-19 vaccine revenues compared to 2025, driven by declines in both the European and United States markets. The United States continues to be a competitive and dynamic market, where, as a result, lower revenues are expected. In Europe, the Company expects lower revenues as it defends its market share and begins managing the transition away from multi-year contracts. In Germany specifically, BioNTech recognizes direct sales of its COVID-19 vaccines as revenue. Hence, the anticipated declines in sales of COVID-19 vaccines in Germany will have a direct impact on the Company’s topline, whereas revenues outside of Germany only affect the Company’s topline as part of the 50% gross profit split with its partner Pfizer. Per the outlined partnership terms, revenues from the collaboration with Bristol Myers Squibb Company (“BMS”) in 2026 are expected to be broadly in line with 2025. Revenues from the pandemic preparedness contract with the German government and service businesses are expected to remain stable.

Planned 2026 Financial Year Adjusted Expenses 6 :

Adjusted R&D expenses   €2,200 – €2,500 m

Adjusted SG&A expenses 5   €700 – €800 m

BioNTech will continue to focus investments on R&D and scaling the business for late-stage development and commercial readiness in oncology, while remaining cost-disciplined. Strategic capital allocation will continue to foster innovation and be a key driver of the Company’s trajectory. As part of BioNTech’s strategy, the Company may continue to evaluate appropriate corporate development opportunities with the aim of driving sustainable long-term growth and creating future value.

Planned Capital Return to Shareholders

The Management Board and Supervisory Board expect to authorize a share repurchase program of BioNTech’s American Depositary Shares (“ADSs”), pursuant to which the Company may repurchase ADSs in the amount of up to $1.0 billion over the next twelve months. BioNTech expects to use the repurchased ADSs to satisfy obligations in the ordinary course of business. The program is designed to enhance capital efficiency and support long-term value creation to execute BioNTech’s objective to become a multi-product company by 2030.

Manufacturing Footprint Consolidation

BioNTech continues to allocate capital strategically while optimizing capacities broadly to drive operational efficiency and sustainable value creation. To this end, BioNTech plans to align and consolidate its manufacturing network further where excess capacity is expected, due to evolving supply needs, mergers and acquisitions, BioNTech’s partners’ manufacturing capacities and completion of contracts.

BioNTech plans to exit operations at the manufacturing sites in Idar-Oberstein, Marburg, and Singapore as well as CureVac’s sites, affecting up to approximately 1,860 positions in total. The exit from the sites in Idar-Oberstein, Marburg, and Tübingen is planned by the end of 2027, while operations in Singapore are expected to conclude in Q1 2027. For each of these manufacturing sites, BioNTech is exploring divestment options, including a partial or total sale.

BioNTech expects cost savings to ramp up over time, potentially reaching approximately €500 million in recurring annual savings upon full implementation of the measures in 2029. 7 These savings are intended to support the Company’s capital allocation to further advance its growing oncology pipeline toward commercialization.

BioNTech continues to ensure a robust drug supply via its established manufacturing network. No impact on commercial or clinical supply nor contractual obligations is expected as the affected sites will become underutilized or idle in the next 24 months.

The full interim unaudited condensed consolidated financial statements can be found in BioNTech’s Report on Form 6-K for the period ended March 31, 2026, filed today with the United States Securities and Exchange Commission (“SEC”) and available at www.sec.gov .

Endnotes

1 All numbers in this press release have been rounded.

2 In addition to BioNTech’s results determined in accordance with International Financial Reporting Standards (“IFRS”), or IFRS Accounting Standards, or IFRS results, BioNTech reports certain adjusted, non-IFRS measures used internally as a supplemental measure of the Company’s business performance (each referred to with the prefix “Adjusted” or, as a whole, “Adjusted Results”). The calculation of these measures and the adjusted results as a whole is based on the concepts of the applicable IFRS Accounting Standards, but includes certain adjustments. Reconciliation of the adjusted results to BioNTech’s measures based on IFRS Accounting Standards and more information can be found at the end of this press release and in BioNTech’s Report on Form 6-K for the period ended March 31, 2026, filed on May 5, 2026, which is available at www.sec.gov . While non-IFRS measures may offer additional insights, BioNTech’s non-IFRS measures are not, and should not be viewed as, a substitute for their most directly comparable IFRS Accounting Standards measures, and should always be considered alongside the Company’s financial statements prepared in accordance with IFRS Accounting Standards.

3 Calculated applying the average foreign exchange rate for the three months ended March 31, 2026, as published by the German Central Bank (Deutsche Bundesbank).

4 As of March 31, 2026.

5 Sales, general and administrative expenses (“SG&A”) include sales and marketing expenses as well as general and administrative expenses. Adjusted SG&A expenses include adjusted sales and marketing expenses as well as adjusted general and administrative expenses.

6 Excludes risks that are not yet known and/or quantifiable and related activities. Includes effects identified from licensing arrangements, collaborations and Merger & Acquisitions (“M&A”) transactions to the extent disclosed. The guidance is based on non-IFRS measures and excludes certain effects compared to measures based on IFRS Accounting Standards. More information can be found in BioNTech’s Report on Form 6-K for the period ended March 31, 2026, filed on May 5, 2026, which is available at www.sec.gov .

7 Expected savings relative to BioNTech's 2025 cost base and CureVac's 2026 budget; do not reflect partially offsetting costs for Contract Development and Manufacturing Organizations (“CDMO”) use or transfer to other sites; and exclude exit costs, which will be recorded as incurred.

8 An overview of abbreviations of target structures and indications is compiled in a directory at the end of this press release.

Select Oncology Pipeline Updates

Next-Generation Immunomodulators and Combinations

Pumitamig (BNT327/BMS986545) is an investigational bispecific immunomodulator combining PD-L1 8 checkpoint inhibition with VEGF-A neutralization that is being developed in collaboration with BMS.

  • In the first quarter of 2026, the following pivotal trials evaluating pumitamig were initiated:
  • A global Phase 3 clinical trial in patients with first-line triple-negative breast cancer (“TNBC”) (ROSETTA Breast-01; NCT07173751 ).
  • A global Phase 2/3 clinical trial in first-line microsatellite stable colorectal cancer (“MSS-CRC”) (ROSETTA CRC-203;  NCT07221357 ).
  • A global Phase 2/3 clinical trial in first-line gastric cancer (ROSETTA Gastric-204;  NCT07221149 ).
  • A global Phase 3 clinical trial (ROSETTA Lung-201; NCT07361497 ) is being conducted to evaluate pumitamig compared to durvalumab following concurrent chemoradiation therapy in patients with unresectable stage III non-small cell lung cancer (“NSCLC”).
  • A global Phase 3 clinical trial (ROSETTA Lung-202; NCT07361510 ) is being conducted to evaluate pumitamig compared to pembrolizumab as a first-line treatment for patients with advanced PD-L1 ≥ 50% NSCLC.
  • A global Phase 2/3 clinical trial (ROSETTA Lung-02; NCT06712316 ) is ongoing to evaluate pumitamig in combination with chemotherapy compared to pembrolizumab and chemotherapy in patients with first-line NSCLC. The Phase 3 part of the trial is currently recruiting. Data from the Phase 2 part of the trial are expected at the American Society of Clinical Oncology (“ASCO”) Annual Meeting 2026 (May 29 - June 2, 2026).
  • Pumitamig is also being evaluated in additional solid tumor indications, including first-line hepatocellular carcinoma (“HCC”), second-line glioblastoma (“GBM”), first-line pancreatic ductal adenocarcinoma (“PDAC”) and first-line renal cell carcinoma (“RCC”) in various Phase 1/2 and Phase 2 trials, both as monotherapy and in combination with standard of care.
  • BioNTech has several signal-seeking clinical trials ongoing evaluating pumitamig with the Company’s proprietary assets. These trials will inform the dose selection for pumitamig and explore anti-tumor activity in multiple tumors for later-stage development. Multiple data readouts from these combinations are expected in 2026.
  • In April 2026, BioNTech and Boehringer Ingelheim announced a clinical trial collaboration to assess the safety, tolerability and early clinical activity of pumitamig in combination with obrixtamig (BI 764532), Boehringer Ingelheim’s investigational DLL3/CD3 T‑cell engager, in extensive‑stage small cell lung cancer (“ES-SCLC”). Under the agreement, BioNTech will supply pumitamig and Boehringer Ingelheim will be the regulatory sponsor of the Phase 1b/2 trial.

Gotistobart (BNT316/ONC-392) is a tumor microenvironment-selective regulatory T cell depletion candidate that targets CTLA-4 and is being developed in collaboration with OncoC4, Inc. (“OncoC4”).

  • A global Phase 3 clinical trial (PRESERVE-003; NCT05671510 ) is ongoing to evaluate the efficacy and safety of gotistobart as monotherapy in patients with metastatic squamous NSCLC that progressed under previous platinum-based chemotherapy and PD-(L)1-inhibitor treatment.
  • In March 2026, updated data from the non-pivotal dose-confirmation stage, the first of two stages of the global Phase 3 clinical trial, were presented at the European Lung Cancer Congress (“ELCC”). Gotistobart demonstrated a clinically meaningful overall survival benefit compared to standard of care chemotherapy and a manageable safety profile in patients with squamous NSCLC whose disease had progressed following anti-PD-(L)1 therapy and platinum-based chemotherapy.
  • Based on current event accrual projections, interim data from the pivotal stage of the two-stage Phase 3 clinical trial are expected in 2026.
  • In January 2026, gotistobart received Orphan Drug Designation from the U.S. Food and Drug Administration (“FDA”) for the treatment of squamous NSCLC. In 2022, gotistobart received Fast Track Designation from the FDA for the treatment of patients with metastatic NSCLC whose disease progressed on prior anti-PD-(L)1 therapy.

Antibody-Drug Conjugates

Trastuzumab pamirtecan (BNT323/DB-1303) is an ADC candidate targeting HER2 that is being developed in collaboration with Duality Biologics (Suzhou) Co. Ltd. (“DualityBio”).

  • A Phase 1/2 clinical trial ( NCT05150691 ) is being conducted to evaluate trastuzumab pamirtecan in patients with advanced HER2-expressing tumors. A potentially registrational cohort with HER2-expressing (IHC3+, 2+, 1+ or ISH-positive) patients with recurrent endometrial cancer (“EC”) is fully recruited.
  • In April 2026, updated data from this trial were presented at the Society of Gynecologic Oncology (“SGO”) Annual Meeting. Trastuzumab pamirtecan demonstrated encouraging clinical efficacy across all HER2 expression levels and regardless of prior immunotherapy treatment. The safety profile in patients with pretreated advanced or metastatic EC was manageable and generally consistent with that of HER2-targeted biologics.
  • BioNTech and DualityBio plan to file a biologics license application (“BLA”) in 2026, subject to regulatory feedback.
  • A Phase 3 trial (FERN-EC-01,  NCT06340568 ) is being conducted to evaluate trastuzumab pamirtecan compared to investigator’s choice of chemotherapy in patients with advanced and HER2-expessing recurrent EC.
  • A global Phase 3 clinical trial (DYNASTY-Breast02,  NCT06018337 ) to evaluate trastuzumab pamirtecan in patients with HR-positive, HER2-low metastatic breast cancer is ongoing. Based on current event accrual projections, data are expected in 2026.

BNT324/DB-1311 is an ADC candidate targeting B7H3 that is being developed in collaboration with DualityBio.

  • In February 2026, updated data from a Phase 1/2 clinical trial ( NCT05914116 ) were presented at the ASCO Genitourinary Cancers Symposium. BNT324/DB-1311 demonstrated durable efficacy in heavily pretreated metastatic castration-resistant prostate cancer (“mCRPC”) patients with no new safety signals reported.
  • In April 2026, updated data from this trial were presented at the SGO Annual Meeting. BNT324/DB-1311 showed encouraging efficacy in previously treated cervical cancer and platinum resistant ovarian cancer (“PROC”) particularly in patients with treatment-naïve cervical cancer. The safety profile in gynecologic malignancies was consistent with previous reports, and no new safety signals were observed.
  • A Phase 3 clinical trial ( NCT07365995 ) to evaluate BNT324/DB-1311 compared to docetaxel in patients with mCRPC, is expected to initiate in 2026.

Corporate and Commercial Update for the First Quarter 2026 and Post Period Events

  • BioNTech and Pfizer developed, manufactured and delivered their variant-adapted COVID-19 vaccines, which have received multiple regulatory approvals, including full approvals, authorizations for emergency or temporary use or marketing authorizations, in more than 40 countries and regions. BioNTech is now focused on preparing for variant strain vaccine adaptation to be ready for commercial launch ahead of the upcoming 2026/2027 vaccination season, pending approvals.
  • In March 2026, BioNTech announced plans for an independent company to be established and led by BioNTech co-founders Prof. Ugur Sahin, M.D., and Prof. Özlem Türeci, M.D. The new company with distinct resources, operations and funding options will advance next-generation mRNA innovations. BioNTech plans to contribute related rights and mRNA technologies to the new company to enable and support the prioritized development of next-generation mRNA innovations with disruptive potential. With both companies focusing on their respective strategic priorities, BioNTech expects to maximize value for patients and shareholders alike. Ugur Sahin and Özlem Türeci will transition into the management of their new company by the end of 2026 after their current service agreements end. BioNTech’s Supervisory Board has initiated an executive search to identify successors for the positions to ensure a smooth transition and seamless execution of BioNTech’s strategy.
  • In March 2026, BioNTech published its Sustainability Report 2025. BioNTech recognizes the responsibility it has in how it is conducting its business and the impact its activities have on the economy, people, and the environment. The Sustainability Report 2025 outlines BioNTech's efforts, progress, key initiatives, and data as well as highlights in its corporate sustainability and responsibility over the past year.

Upcoming Investor and Analyst Events

  • BioNTech Annual General Meeting: May 15, 2026
  • BioNTech Second Quarter 2026 Financial Results and Corporate Update: August 4, 2026

Conference Call and Webcast Information

BioNTech invites investors and the general public to join a conference call and webcast with investment analysts today, May 5, 2026, at 8:00 a.m. ET (2:00 p.m. CET) to report its financial results and provide a corporate update for the first quarter of 2026.

To access the live conference call via telephone, please register  via this link . Once registered, dial-in numbers and a PIN number will be provided.

The slide presentation and audio of the webcast will be available  via this link .

Participants may also access the slides and the webcast of the conference call via the “Events & Presentations” page of the Investor section of the Company’s website at www.BioNTech.com. A replay of the webcast will be made available shortly after the closing of the call and archived on the Company’s website for 30 days following the call.

About BioNTech

BioNTech is a global next generation biopharmaceutical company pioneering novel investigative therapies for cancer and other serious diseases. In oncology, BioNTech is committed to transforming how cancer is treated. Its ambition is to develop innovative medicines with pan-tumor or synergistic potential to address cancer from multiple angles and across the full continuum of the disease from early- to late-stage. Its growing late-stage oncology pipeline comprises complementary treatment approaches spanning immunomodulators, antibody drug conjugates, and mRNA cancer immunotherapies. BioNTech has partnered with multiple global and specialized pharmaceutical collaborators leveraging complementary expertise and resources to accelerate innovation and drive progress, including Bristol Myers Squibb, Duality Biologics, Genentech, a member of the Roche Group, Genmab, MediLink, OncoC4, and Pfizer.

For more information, please visit www.BioNTech.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, but not limited to, statements concerning: expected changes to BioNTech’s leadership and the transition of responsibilities at the Management Board, including identification and recruitment of successors; the terms of the preliminary discussions between BioNTech and the co-founders regarding the potential contribution of certain BioNTech assets to an independent company; BioNTech’s expected revenues and net profit/(loss) related to sales of BioNTech’s COVID-19 vaccine in territories controlled by BioNTech’s collaboration partners, particularly for those figures that are derived from preliminary estimates provided by BioNTech’s partners; the rate and degree of market acceptance of BioNTech’s COVID-19 vaccine and, if approved, BioNTech’s investigational medicines; expectations regarding anticipated changes in COVID-19 vaccine demand, including changes to the ordering environment and expected regulatory recommendations to adapt vaccines to address new variants or sublineages; the initiation, timing, progress, results, and cost of BioNTech’s research and development programs, including BioNTech’s current and future preclinical studies and clinical trials, including statements regarding the expected timing of initiation, enrollment, and completion of studies or clinical trials and related preparatory work and the availability of results, and the timing and outcome of applications for regulatory approvals and marketing authorizations; BioNTech’s expectations regarding potential future commercialization in oncology, including goals regarding timing and indications; the targeted timing and number of additional potentially registrational clinical trials, and the registrational potential of any clinical trial BioNTech may initiate; BioNTech’s expectations regarding the impact of changes to its manufacturing operations; discussions with regulatory agencies; BioNTech’s expectations with respect to intellectual property; the impact of BioNTech’s collaboration and licensing agreements, including BioNTech’s partnership with Bristol Myers Squibb; BioNTech’s expectations with respect to developments in law, public policy, and international trade; BioNTech’s estimates of revenues, research and development expenses, selling, general and administrative expenses and capital expenditures for operating activities; BioNTech’s expectations for upcoming scientific and investor presentations; and BioNTech’s expectations of net profit/(loss). In some cases, forward-looking statements can be identified by terminology such as “will,” “may,” “should,” “expects,” “intends,” “plans,” “aims,” “anticipates,” “believes,” “estimates,” “predicts,” “potential,” “continue,” or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words.

The forward-looking statements in this press release are based on BioNTech’s current expectations and beliefs of future events, and are neither promises nor guarantees. You should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond BioNTech’s control and which could cause actual results to differ materially and adversely from those expressed or implied by these forward-looking statements. These risks and uncertainties include, but are not limited to: the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for clinical trials, projected data release timelines, regulatory submission dates, regulatory approval dates and/or launch dates, as well as risks associated with preclinical and clinical data, including the data discussed in this release, and including the possibility of unfavorable new preclinical, clinical or safety data and further analyses of existing preclinical, clinical or safety data; the nature of the clinical data, which is subject to ongoing peer review, regulatory review and market interpretation; BioNTech’s pricing and coverage negotiations with governmental authorities, private health insurers and other third-party payors; the future commercial demand and medical need for initial or annual booster doses of a COVID-19 vaccine; the impact of tariffs and escalations in trade policy; competition from other COVID-19 vaccines or related to BioNTech’s other product candidates; the timing of and BioNTech’s ability to obtain and maintain regulatory approval for its product candidates; the ability of BioNTech’s COVID-19 vaccines to prevent COVID-19 caused by emerging virus variants; BioNTech’s ability to identify research opportunities and discover and develop investigational medicines; the ability and willingness of BioNTech’s third-party collaborators to continue research and development activities relating to BioNTech's development candidates and investigational medicines; unforeseen safety issues and potential claims that are alleged to arise from the use of products and product candidates developed or manufactured by BioNTech; BioNTech’s and its collaborators’ ability to commercialize and market its product candidates, if approved; BioNTech’s ability to manage its development and related expenses; regulatory and political developments; BioNTech’s ability to effectively scale its production capabilities and manufacture its products and product candidates; risks relating to the global financial system and markets; and other factors not known to BioNTech at this time.

You should review the risks and uncertainties described under the heading “Risk Factors” in BioNTech’s Report on Form 6-K for the period ended March 31, 2026 and in subsequent filings made by BioNTech with the SEC, which are available on the SEC’s website at  www.sec.gov . These forward-looking statements speak only as of the date hereof. Except as required by law, BioNTech disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release in the event of new information, future developments or otherwise.

CONTACTS

Investor Relations

Douglas Maffei, PhD

Investors@biontech.de

Media Relations

Jasmina Alatovic

Media@biontech.de

Abbreviation Overview

1L First line

2L Second line

ADC Antibody-drug conjugate

B7H3 Also known as CD276, cluster of differentiation 276

BLA Biologics license application

CTLA-4 Cytotoxic T-lymphocyte-associated protein

EC Endometrial cancer

ES-SCLC Extensive‑stage small cell lung cancer

GBM Glioblastoma

HCC Hepatocellular carcinoma

HER2 (or HER3) Human epidermal growth factor receptor 2 (or 3)

HPV16 Human papilloma virus 16

HR Hormone receptor

IHC3+, 2+, 1+ Immunohistochemistry score 1+ (or 2+ or 3+)

IO Immuno-oncology

ISH-positive In-situ hybridization positive

mCRPC Metastatic castration-resistant prostate cancer

MSS-CRC Microsatellite stable colorectal cancer

NSCLC Non-small cell lung cancer

PDAC Pancreatic ductal adenocarcinoma

PD-(L)1 Programmed cell death protein (death-ligand) 1

PROC Platinum resistant ovarian cancer

RCC Renal cell carcinoma

SCLC Small cell lung cancer

TNBC Triple-negative breast cancer

TROP2 Trophoblast cell-surface antigen 2

VEGF-A Vascular endothelial growth factor A

Interim Condensed Consolidated Statements of Profit or Loss

Three months ended March 31,

2026     2025

(in millions €, except per share data)     (unaudited)     (unaudited)

Revenues     118.1     182.8

Cost of sales     (71.4)     (83.8)

Research and development expenses     (557.0)     (525.6)

Sales and marketing expenses     (27.9)     (13.7)

General and administrative expenses     (122.9)     (106.9)

Other operating expenses     (46.8)     (48.5)

Other operating income     30.4     61.6

Operating loss     (677.5)     (534.1)

Finance income     120.6     122.6

Finance expenses     (11.2)     (33.9)

Loss before tax     (568.1)     (445.4)

Income taxes     36.2     29.6

Net loss     (531.9)     (415.8)

Loss per share

Basic and diluted loss per share     (2.10)     (1.73)

Interim Condensed Consolidated Statements of Profit or Loss

(Adjusted Results)

Adjusted Results (non-IFRS measures) 1     Three months ended March 31,

2026     2025

(in millions €, except per share data)     (unaudited)     (unaudited)

Adjusted research and development expenses     (527.1)     (525.6)

Adjusted other operating expenses     (39.4)     (48.5)

Adjusted other operating income     30.4     46.6

Adjusted operating loss     (640.2)     (549.1)

Adjusted loss before tax     (530.8)     (460.4)

Adjusted net loss 2     (494.6)     (430.8)

Adjusted loss per share

Adjusted basic and diluted loss per share     (1.95)     (1.79)

1 Certain adjusted results presented in this table are identical to BioNTech’s results under IFRS Accounting Standards. Reconciliation of all other adjusted results to the Company’s IFRS results can be found at the end of this press release and in BioNTech’s Report on Form 6-K for the period ended March 31, 2026 filed on May 5, 2026, which is available at www.sec.gov .

2 Tax effects are not considered as part of our non-IFRS adjustments.

Interim Condensed Consolidated Statements of Financial Position

March 31     December 31,

(in millions €)     2026     2025

Assets     (unaudited)

Non-current assets

Goodwill     370.5     367.9

Other intangible assets     1,546.8     1,606.0

Property, plant and equipment     1,112.7     1,080.9

Right-of-use assets     205.5     210.2

Contract assets     —     2.0

Other financial assets     2,279.9     2,554.2

Other non-financial assets     12.2     7.3

Deferred tax assets     14.7     13.5

Total non-current assets     5,542.3     5,842.0

Current assets

Inventories     103.8     110.7

Trade and other receivables     539.2     924.2

Contract assets     8.9     8.1

Other financial assets     4,699.8     7,201.8

Other non-financial assets     176.6     173.8

Income tax assets     64.1     52.6

Cash and cash equivalents     9,939.4     7,675.4

Total current assets     15,531.8     16,146.6

Total assets     21,074.1     21,988.6

Equity and liabilities

Equity

Share capital     259.0     259.0

Capital reserve     2,468.2     2,473.3

Treasury shares     (6.1)     (7.7)

Retained earnings     17,430.0     17,961.9

Other reserves     (1,453.3)     (1,462.3)

Total equity     18,697.8     19,224.2

Non-current liabilities

Lease liabilities, loans and borrowings     246.1     215.2

Other financial liabilities     92.0     94.9

Provisions     23.8     35.5

Contract liabilities     87.7     88.0

Other non-financial liabilities     108.8     104.2

Deferred tax liabilities     52.9     84.3

Total non-current liabilities     611.3     622.1

Current liabilities

Lease liabilities, loans and borrowings     56.7     52.2

Trade payables and other payables     468.8     534.9

Other financial liabilities     77.5     351.7

Income tax liabilities     38.1     65.6

Provisions     167.0     145.3

Contract liabilities     758.5     754.9

Other non-financial liabilities     198.4     237.7

Total current liabilities     1,765.0     2,142.3

Total liabilities     2,376.3     2,764.4

Total equity and liabilities     21,074.1     21,988.6

Interim Condensed Consolidated Statements of Cash Flows

Three months ended March 31,

2026     2025

(in millions €)     (unaudited)     (unaudited)

Operating activities

Net loss     (531.9)     (415.8)

Income taxes     (36.2)     (29.6)

Loss before tax     (568.1)     (445.4)

Adjustments to reconcile loss before tax to net cash flows:

Depreciation, amortization and impairment of property, plant, equipment, intangible assets and right-of-use assets     121.3     42.8

Share-based payment expenses     22.8     22.1

Net foreign exchange differences     0.4     48.3

Gain on disposal of property, plant and equipment     (0.1)     (0.1)

Finance income excluding foreign exchange differences     (111.0)     (122.6)

Finance expense excluding foreign exchange differences     11.2     7.9

Government and similar grants     (17.6)     (14.5)

Other non-cash income     —     (15.0)

Working capital adjustments:

Decrease in trade and other receivables, contract assets and other assets     431.1     520.7

Decrease in inventories     7.0     33.8

Decrease in trade payables, other financial liabilities, other liabilities, contract liabilities, refund liabilities and provisions     (371.9)     (981.6)

Interest received and realized gains from cash and cash equivalents     86.6     118.6

Interest paid and realized losses from cash and cash equivalents     (3.3)     (3.1)

Income tax paid, net     (41.6)     (12.2)

Share-based payments     (2.1)     (3.6)

Government and similar grants received     14.3     23.2

Net cash flows used in operating activities     (421.0)     (780.7)

Investing activities

Purchase of property, plant and equipment     (56.8)     (48.9)

Proceeds from sale of property, plant and equipment     1.6     0.5

Purchase of intangible assets     (22.1)     (569.2)

Acquisition of subsidiaries and businesses, net of cash acquired     —     (78.5)

Investment in other financial assets     (1,550.2)     (2,507.7)

Proceeds from maturity of other financial assets     4,278.1     4,450.6

Net cash flows from investing activities     2,650.6     1,246.8

Financing activities

Proceeds from loans and borrowings     38.4     —

Repayment of loans and borrowings     (0.1)     (4.5)

Payments related to lease liabilities     (11.9)     (9.3)

Net cash flows from / (used in) financing activities     26.4     (13.8)

Net increase in cash and cash equivalents     2,256.0     452.3

Change in cash and cash equivalents resulting from exchange rate differences     (3.4)     (16.1)

Change in cash and cash equivalents resulting from other valuation effects     11.4     (13.2)

Cash and cash equivalents at the beginning of the period     7,675.4     9,761.9

Cash and cash equivalents as of March 31     9,939.4     10,184.9

Certain prior period lines were aggregated to conform to current period presentation.

Non-IFRS Reconciliation

Non-IFRS Reconciliation for the three months ended March 31, 2026

non-IFRS adjustments (unaudited)

(in millions €, except per share data)     IFRS

Results   Expenses and income from legal proceedings   Impairment and reversal   Employee-related expenses from restructuring   Income from bargain purchase and income and expenses from divestiture related items   Adjusted

Results

(unaudited)           (unaudited)

Research and development expenses     (557.0)   —   29.9   —   —   (527.1)

Other operating expenses     (46.8)   —   —   7.4   —   (39.4)

Operating loss     (677.5)   —   29.9   7.4   —   (640.2)

Loss before tax     (568.1)   —   29.9   7.4   —   (530.8)

Net loss 1     (531.9)   —   29.9   7.4   —   (494.6)

Loss per share

Basic and diluted loss per share     (2.10)                   (1.95)

1 Tax effects are not considered as part of BioNTech's non-IFRS adjustments.

Non-IFRS Reconciliation for the three months ended March 31, 2025

non-IFRS adjustments (unaudited)

(in millions €, except per share data)     IFRS

Results   Expenses and income from legal proceedings   Impairment and reversal   Employee-related expenses from restructuring   Income from bargain purchase and income and expenses from divestiture related items   Adjusted

Results

(unaudited)           (unaudited)

Other operating income     61.6   —   —   —   (15.0)   46.6

Operating loss     (534.1)   —   —   —   (15.0)   (549.1)

Loss before tax     (445.4)   —   —   —   (15.0)   (460.4)

Net loss 1     (415.8)   —   —   —   (15.0)   (430.8)

Loss per share

Basic and diluted loss per share     (1.73)                   (1.79)

1 Tax effects are not considered as part of BioNTech's non-IFRS adjustments.

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打开原文

Pfizer vs. Moderna mRNA patent strategies and pipelines

来源信息
来源：PatSnap发布日期：2026-04抓取时间：2026-06-17T18:49:54.259Z相关标的：MRNA, PFE, BNTX归档状态：已归档 / 弹窗可读
中文摘要

一句话结论

PatSnap 文章把 Pfizer/BioNTech 与 Moderna 描述为 mRNA 平台竞赛中的事实双寡头：两方合计 73 个 mRNA pipeline candidates，竞争焦点从 COVID 转向 influenza、RSV、CMV、组合疫苗和个性化癌症疫苗。

关键事实

  • 文章发布时间标注为 2026-04。
  • 文章称 Pfizer/BioNTech 和 Moderna 合计控制超过 90% 的 clinical-stage mRNA vaccine development。
  • 文章给出的管线数量为 Pfizer/BioNTech 32 个、Moderna 41 个，合计 73 个项目。
  • 文章强调 Moderna 在 late-stage clinical programs，尤其 Phase 3 项目上更突出；Pfizer/BioNTech 在 Phase 2 oncology 深度更强。
  • 文章提到 Moderna mRESVIA 于 2024 年 5 月成为首个获批 mRNA RSV vaccine。
  • 文章称 mRNA vaccine market 到 2030 年可能超过 100 亿美元，combination vaccines 和 oncology 是 COVID 之后最高增长方向。
  • 文章描述 LNP 和专利诉讼是竞争核心，Pfizer/BioNTech 使用授权 ALC-0315，Moderna 使用自有 SM-102。

作者观点与证据

文章是行业分析/商业情报性质，观点是 mRNA 行业正在从疫情红利进入平台和专利壁垒竞争阶段。证据包括 pipeline 数量、技术路线、专利诉讼和市场规模估计。市场规模和管线占比属于分析机构估算，需要与公司披露交叉验证。

与相关标的的关系

对 MRNA 直接相关。它支持 Moderna 平台领先但竞争集中化的判断：MRNA 的可选项多、后期项目多，但 Pfizer/BioNTech 的商业资源、IP/合作网络和 oncology 深度构成压力。

时效性与限制

2026-04 口径较新，适合当前行业背景。限制是第三方分析，不是审计数据；部分管线数量和市场规模属于估算，不能单独用于估值。

后续跟踪

  • Moderna 和 Pfizer/BioNTech 在 influenza、combination vaccine 和 oncology 的后期项目进展。
  • LNP/专利诉讼是否影响产品经济性或许可费用。
  • 组合疫苗实际获批和接种需求。
  • mRNA 市场规模是否从 COVID 维护市场转向多产品平台。
英文原文
Pfizer vs. Moderna mRNA patent strategies and pipelines

Pfizer vs. Moderna mRNA Vaccine Platform Technology Roadmap — PatSnap Insights

A duopoly built on 73 pipeline candidates

Pfizer/BioNTech and Moderna together control more than 90% of clinical-stage mRNA vaccine development, with 32 and 41 pipeline candidates respectively — a combined total of 73 programs spanning infectious diseases, oncology, and rare diseases. This concentration of validated mRNA expertise has created a structural duopoly that secondary players such as CureVac and Sanofi have been unable to break, despite holding meaningful lipid nanoparticle (LNP) patent portfolios of their own.

73

Combined mRNA pipeline candidates (Pfizer/BioNTech + Moderna)

44%

Reduction in melanoma recurrence risk (mRNA-4157 + Keytruda, KEYNOTE-942)

May 2024

First mRNA RSV vaccine approved (Moderna mRESVIA)

2022

Moderna filed patent lawsuit against Pfizer/BioNTech — ongoing as of 2026

Both companies achieved regulatory approval for COVID-19 vaccines in December 2020 — Pfizer/BioNTech’s Comirnaty (BNT162b2) first, followed days later by Moderna’s Elasomeran (mRNA-1273). That simultaneous proof-of-concept moment set the stage for a platform race that now extends into influenza, RSV, CMV, and personalised cancer vaccines. According to WIPO , mRNA-related patent filings accelerated sharply after 2020, reflecting the technology’s newly validated commercial potential.

Pfizer/BioNTech holds 32 mRNA vaccine candidates and Moderna holds 41 pipeline candidates as of 2024–2026, giving both companies combined control of more than 90% of clinical-stage mRNA vaccine development.

Figure 1 — mRNA Vaccine Pipeline Size: Pfizer/BioNTech vs. Moderna by Development Stage (2024–2026)

Moderna’s 41-candidate pipeline leads in late-stage clinical programs, particularly in Phase 3, while Pfizer/BioNTech’s 32-candidate portfolio shows greater depth in Phase 2 oncology programs. Stage-level counts are representative distributions based on disclosed pipeline data. The mRNA vaccine market is projected to exceed $10 billion annually by 2030, with combination vaccines and oncology applications representing the highest growth segments beyond endemic COVID-19 maintenance. Flu/COVID combination vaccines alone represent a potential $5–10 billion annual market by 2028, making the 2025–2026 approval window a critical competitive inflection point for both companies.

Four phases of mRNA platform evolution (2015–2026)

The mRNA vaccine technology roadmap divides cleanly into four phases, each defined by a distinct scientific or commercial threshold. Understanding this arc is essential for anticipating where the next competitive advantages will emerge — and which patent positions will prove decisive.

Phase I: Foundation (2015–2019) — Platform Validation

The foundational period centred on solving two problems that had blocked mRNA therapeutics for decades: innate immune activation and delivery. Nucleoside modification breakthroughs — specifically pseudouridine incorporation — reduced the inflammatory response that had previously made mRNA unsuitable for human use. Simultaneously, Moderna and BioNTech established ionizable lipid nanoparticle (LNP) formulations as the standard delivery system. A pivotal licensing event occurred when Acuitas Therapeutics licensed its ALC-0315 ionizable lipid to BioNTech, establishing a dependency that would later become central to patent litigation. By 2019, the first mRNA influenza vaccine candidates had entered Phase 1 trials.

ℹ

What is an ionizable lipid nanoparticle (LNP)? An ionizable lipid nanoparticle is the delivery vehicle that encapsulates fragile mRNA molecules and enables their entry into human cells. The ionizable lipid — positively charged at low pH for assembly, neutral at physiological pH to reduce toxicity — is the most patent-contested component of mRNA vaccine technology. Pfizer/BioNTech uses licensed ALC-0315; Moderna uses its proprietary SM-102 developed in-house.

Phase II: COVID-19 Acceleration (2020–2021) — Proof of Concept

Comirnaty received FDA Emergency Use Authorisation in December 2020, followed days later by Elasomeran. Both companies then initiated variant-adapted programs — BA.1, BA.4/BA.5, XBB.1.5, and KP.2-adapted formulations — demonstrating the platform’s core commercial advantage: rapid strain updates within 6–8 weeks from sequence identification to clinical material. According to the FDA , this speed-to-update capability has no precedent in traditional vaccine development.

Phase III: Platform Diversification (2022–2024) — Beyond COVID-19

Both companies launched combination flu/COVID vaccine programs in 2022. The most significant clinical milestone of this phase came from the Phase 2b KEYNOTE-942 trial in 2023, which showed that Moderna’s mRNA-4157 personalised cancer vaccine combined with pembrolizumab produced a 44% reduction in melanoma recurrence or death risk compared with pembrolizumab alone. Moderna’s mRESVIA (mRNA-1345) then became the first approved mRNA RSV vaccine in May 2024, for adults aged 60 and older — a landmark that validated the platform’s reach beyond COVID-19.

Moderna’s mRESVIA (mRNA-1345) became the first approved mRNA RSV vaccine in May 2024, indicated for adults aged 60 and older, marking the first non-COVID approval for the mRNA vaccine platform.

Phase IV: Commercial Maturity (2025–2026) — Multi-Indication Platforms

The current phase is defined by regulatory submissions for combination vaccines and late-stage oncology readouts. Moderna submitted mRNA-1083 (flu/COVID combination) for regulatory review in 2024, with approval expected in 2026 following the FDA’s requirement for flu efficacy data. Pfizer/BioNTech received FDA Fast Track designation for its single-dose flu/COVID combination vaccine (PF-07926307), with Phase 3 ongoing. Both companies’ personalised cancer vaccine programs are expected to deliver Phase 3 interim analyses in 2025–2027.

Figure 2 — mRNA Vaccine Platform Technology Roadmap: Key Approval Milestones 2020–2026

From dual COVID-19 approvals in December 2020 to the first mRNA RSV approval in May 2024, the platform has expanded continuously. The 2025–2026 window represents the next major commercial inflection with combination vaccine approvals expected from both companies.

Map the full mRNA patent landscape — including LNP formulation filings and neoantigen vaccine claims — with PatSnap Eureka.

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Pfizer/BioNTech: oncology-first diversification and licensed IP

Pfizer/BioNTech’s post-COVID strategy is defined by a concentrated bet on personalised cancer vaccines, leveraging Pfizer’s global commercial infrastructure and BioNTech’s mRNA engineering capabilities. The V940 platform — also called Intismeran Autogene — encodes up to 34 patient-specific neoantigens per dose, making each vaccine unique to the individual patient’s tumour mutation profile.

The oncology pipeline is the broadest of any mRNA company at the Phase 3 stage. V940 is currently in Phase 3 trials for melanoma (INTerpath-001) and NSCLC (INTerpath-002), both in combination with pembrolizumab. Phase 2 programs cover renal cell carcinoma and bladder cancer. BNT-116, an off-the-shelf mRNA cancer vaccine targeting shared NSCLC antigens, is in Phase 2 — providing a lower-cost, faster-manufacturing complement to the individualised V940 approach.

“Pfizer/BioNTech’s V940 (Intismeran Autogene) personalised cancer vaccine encodes up to 34 patient-specific neoantigens and is in Phase 3 trials across melanoma, NSCLC, and renal cell carcinoma simultaneously — the broadest late-stage oncology mRNA footprint of any company.”

On the infectious disease side, the flu/COVID combination vaccine (PF-07926307) targets four influenza strains plus COVID-19 in a single mRNA dose. It received FDA Fast Track designation in December 2022 and is now in Phase 3. Pfizer/BioNTech also maintains pandemic influenza preparedness programs, including H5N1 mRNA vaccine candidates in early clinical development. The company’s variant adaptation capability — producing updated COVID-19 formulations within 6–8 weeks — has been demonstrated repeatedly through the Omicron BA.1, BA.4/BA.5, XBB.1.5, and KP.2-adapted approvals, with LP.8.1-adapted data already reported for the 2025–2026 formula.

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Key finding: Pfizer/BioNTech IP position Pfizer/BioNTech licenses ionizable lipid technology from Acuitas Therapeutics (ALC-0315, ALC-0159) and co-owns nucleoside modification patents with the University of Pennsylvania. BioNTech holds proprietary continuous manufacturing processes for mRNA production. This partnership-driven IP model differs fundamentally from Moderna’s vertical integration approach — and is the basis of Moderna’s 2022 patent lawsuit.

Pfizer/BioNTech’s V940 personalised cancer vaccine (Intismeran Autogene) encodes up to 34 patient-specific neoantigens per dose and is simultaneously in Phase 3 trials for melanoma and NSCLC, and Phase 2 for renal cell carcinoma and bladder cancer, as of 2024–2026.

Moderna: respiratory-first expansion and proprietary LNP

Moderna’s post-COVID strategy prioritises breadth across respiratory indications before expanding into oncology, underpinned by a proprietary technology stack that includes its in-house SM-102 ionizable lipid. With 41 pipeline candidates — the largest mRNA portfolio in the industry — Moderna has more programs in late-stage development than any competitor and has already achieved a second approved product in mRESVIA.

The respiratory franchise is the commercial engine. Elasomeran (mRNA-1273) remains the foundation, with next-generation mRNA-1283 offering a refrigerator-stable (2–8°C) formulation that addresses one of the original platform’s most significant distribution limitations. The mRNA-1083 flu/COVID combination has completed Phase 3 and been submitted for regulatory review, with approval expected in 2026 after the FDA requested flu-specific efficacy data. The mRNA-1010 seasonal influenza quadrivalent vaccine (targeting two A strains and two B strains) has completed enrollment in its Phase 3 efficacy trial, with interim data expected mid-2025.

The CMV program (mRNA-1647) represents one of the most significant unmet needs in the pipeline. Cytomegalovirus is the leading infectious cause of congenital disability in the United States, according to the CDC , yet no approved vaccine exists. The Phase 3 CMVictory trial is fully enrolled, with 36-month antibody durability data showing titers remaining above baseline. An efficacy readout is expected in 2025, though the Data Safety Monitoring Board recommended continuation after an initial interim analysis did not meet the early efficacy criterion.

In oncology, mRNA-4157 (co-developed with Merck) is in Phase 3 for melanoma following the landmark KEYNOTE-942 Phase 2b result showing a 44% reduction in recurrence or death risk. Early-stage NSCLC trials are underway. An off-the-shelf cancer vaccine, mRNA-4203, targeting shared tumor antigens across multiple cancer types, is in Phase 1. Moderna’s rare disease programs — mRNA-3705 for methylmalonic acidemia and mRNA-3927 for propionic acidemia — extend the platform into enzyme replacement-like applications, demonstrating the versatility of the mRNA delivery system beyond vaccines. The NIH has supported foundational research underpinning several of these rare disease applications.

Moderna’s mRNA-4157 personalised cancer vaccine combined with pembrolizumab (Keytruda) produced a 44% reduction in melanoma recurrence or death risk compared with pembrolizumab alone in the Phase 2b KEYNOTE-942 trial, leading to initiation of a Phase 3 melanoma trial in 2023.

The patent battleground reshaping the mRNA IP landscape

Moderna filed patent infringement claims against Pfizer/BioNTech in 2022, alleging that Comirnaty copied foundational mRNA and LNP technology that Moderna had developed and patented before the pandemic. The lawsuit, filed in both the United States and Europe, remains unresolved as of 2026 — making it one of the most consequential IP disputes in pharmaceutical history.

Moderna’s core claims centre on nucleoside-modified mRNA technology and lipid formulation ratios. Pfizer/BioNTech’s defence rests on its licensing arrangements with Acuitas Therapeutics and the University of Pennsylvania, arguing that its technology was independently developed or properly licensed from third parties. The outcome could determine licensing economics across the entire mRNA industry — a potential cross-licensing settlement would likely reshape how future mRNA vaccine developers access foundational IP.

Beyond the litigation, the broader patent landscape reveals meaningful innovation activity outside the two market leaders. CureVac holds 50 or more patents on LNP technology and is pivoting to next-generation mRNA approaches after its CVnCoV COVID-19 candidate was discontinued. Sanofi holds LNP formulation patents through its partnership-based development model. Academic institutions — including the University of Pennsylvania (nucleoside modification) and Johns Hopkins University (LNP-mRNA therapeutics) — hold foundational patents that underpin both companies’ core technologies. The EPO has been a key venue for several of these foundational patent grants and the ongoing Moderna-Pfizer/BioNTech dispute.

A critical structural distinction in IP strategy: Pfizer/BioNTech operates a partnership-driven model, licensing in key components and co-owning patents with academic partners. Moderna pursues vertical integration — developing its SM-102 ionizable lipid in-house and aggressively enforcing its patent estate. This divergence means Moderna bears higher internal R&D costs but retains full control of its technology stack, while Pfizer/BioNTech gains commercial flexibility at the cost of dependency on third-party licensors.

Track the Moderna vs. Pfizer/BioNTech patent litigation and monitor new mRNA LNP filings in real time with PatSnap Eureka.

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Where the platforms diverge: technology, stability, and scale

Despite sharing the same core mRNA modification chemistry — N1-methylpseudouridine incorporation — and the same basic antigen design principles for COVID-19 (full-length spike protein with P2 proline stabilisation), Pfizer/BioNTech and Moderna have made meaningfully different choices across LNP composition, storage stability, combination vaccine ambition, and manufacturing architecture.

Technology Dimension Pfizer/BioNTech Moderna

LNP Composition Licensed from Acuitas (ALC-0315, ALC-0159) Proprietary SM-102 ionizable lipid, developed in-house

Storage Stability Ultra-cold (−70°C) for Comirnaty; refrigerator-stable formulations under investigation Next-gen mRNA-1283 is refrigerator-stable (2–8°C)

Combination Vaccine Strategy Flu + COVID (single formulation, Phase 3) Flu+COVID (mRNA-1083), Flu+COVID+RSV (mRNA-1230, preclinical)

Oncology Approach Individualised (V940, up to 34 neoantigens) + off-the-shelf (BNT-116) Individualised (mRNA-4157, up to 34 neoantigens) + off-the-shelf (mRNA-4203)

Manufacturing Model BioNTech in-house + Pfizer global contract network Fully integrated; modular facilities in US and Europe

IP Model Partnership-driven; licensed LNP; co-owned nucleoside patents Vertical integration; proprietary LNP; aggressive enforcement

Portfolio Breadth 32 candidates; COVID, flu, oncology focus 41 candidates; 5 respiratory vaccines + oncology + rare diseases

The refrigerator-stability gap is commercially significant. Comirnaty’s original ultra-cold chain requirement created logistical barriers in low- and middle-income countries that Moderna’s next-generation mRNA-1283 formulation is designed to eliminate. This storage advantage, combined with Moderna’s modular manufacturing approach, positions the company more strongly for global market expansion — particularly as WHO frameworks push for broader mRNA technology transfer to lower-income nations.

Pfizer/BioNTech’s countervailing advantage is commercial reach. Pfizer’s global sales force operates in more than 150 countries, providing distribution infrastructure that Moderna — still building its commercial organisation — cannot match in the near term. This asymmetry means that even if Moderna achieves earlier regulatory approvals in some combination vaccine categories, Pfizer/BioNTech may capture greater market share through superior access to healthcare systems worldwide.

Both companies’ personalised cancer vaccine programs share a key technical constraint: manufacturing complexity. Each individualised dose requires sequencing the patient’s tumour, selecting neoantigens using proprietary algorithms, and synthesising a bespoke mRNA sequence — a process that takes weeks and carries significant cost. Whether this can be scaled to commercial viability, even with positive Phase 3 efficacy data, remains the central uncertainty for the oncology segment. PatSnap’s innovation intelligence platform tracks life sciences R&D intelligence across these programs, including manufacturing patent filings that may signal how each company is addressing this bottleneck.

Moderna’s next-generation COVID-19 vaccine mRNA-1283 is refrigerator-stable at 2–8°C, overcoming the ultra-cold (−70°C) storage requirement of the original Comirnaty formulation from Pfizer/BioNTech, which represents a significant distribution advantage for global deployment.

For R&D strategists and IP professionals seeking to navigate this landscape, the PatSnap patent analytics platform provides comprehensive coverage of LNP formulation filings, neoantigen algorithm patents, and manufacturing process claims across all major mRNA developers — enabling competitive intelligence that goes beyond publicly available pipeline disclosures.

Frequently asked questions

mRNA vaccine platform technology roadmap — key questions answered

How many mRNA vaccine candidates do Pfizer/BioNTech and Moderna have in their pipelines? + Pfizer/BioNTech holds 32 mRNA vaccine candidates, while Moderna commands 41 pipeline candidates, giving a combined total of 73 mRNA programs across infectious diseases, oncology, and rare diseases as of 2024–2026. Moderna’s pipeline is broader, covering five respiratory vaccines plus oncology and rare disease programs.

What is the difference between Pfizer/BioNTech and Moderna’s LNP technology? + Pfizer/BioNTech licenses ionizable lipid technology from Acuitas Therapeutics — specifically ALC-0315 and ALC-0159 — while Moderna uses its proprietary in-house SM-102 ionizable lipid developed specifically for mRNA-1273. This distinction is central to the patent litigation Moderna filed against Pfizer/BioNTech in 2022, which remained ongoing as of 2026.

What was the first approved mRNA RSV vaccine? + Moderna’s mRESVIA (mRNA-1345) became the first approved mRNA RSV vaccine in May 2024, indicated for adults aged 60 and older. Moderna subsequently initiated Phase 3 studies for expansion to high-risk adults aged 18–59, with a PDUFA date of June 12, 2025, as well as maternal immunization and pediatric populations.

What is the V940 oncology platform and what cancers does it target? + V940 — also called Intismeran Autogene — is Pfizer/BioNTech’s individualised mRNA cancer vaccine that encodes up to 34 patient-specific neoantigens per dose. It is in Phase 3 trials for melanoma (INTerpath-001) and NSCLC (INTerpath-002), both combined with pembrolizumab, and in Phase 2 for renal cell carcinoma and bladder cancer.

What did the KEYNOTE-942 trial show for Moderna’s personalised cancer vaccine? + The Phase 2b KEYNOTE-942 trial showed that mRNA-4157 combined with pembrolizumab (Keytruda) produced a 44% reduction in melanoma recurrence or death risk compared with pembrolizumab alone. This result led to initiation of a Phase 3 melanoma trial in 2023 and early-stage NSCLC trials assessing the same combination.

When are flu/COVID combination vaccines expected to be approved? + Both Pfizer/BioNTech (PF-07926307) and Moderna (mRNA-1083) are targeting 2025–2026 approval windows for their respective flu/COVID combination vaccines. Pfizer/BioNTech received FDA Fast Track designation in December 2022, while Moderna submitted its regulatory filing in 2024 — with approval expected in 2026 following the FDA’s requirement for flu-specific efficacy data.

Still have questions? Let PatSnap Eureka answer them for you.

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References

  • Bloomberg Law — Moderna Patent Strike on Pfizer Sets Up Post-Covid Vaccine Feuds
  • BusinessWire — mRNA Platform Global Strategic Research Report 2024: Forecast to 2030
  • Pfizer — Pfizer and BioNTech Announce Omicron-Adapted COVID-19 Vaccine Candidates
  • Pfizer — Update on mRNA-Based Combination Vaccine Program Against Influenza and COVID-19
  • BioSpace — Pfizer and BioNTech Receive U.S. FDA Fast Track Designation for Flu/COVID Vaccine
  • BioPharma Reporter — Moderna Leads Development of mRNA Vaccines in Infectious Diseases
  • Pipeline Review — Pfizer and BioNTech Omicron BA.4/BA.5-Adapted Bivalent Booster Data
  • Pipeline Review — Pfizer and BioNTech FDA Approval for Omicron KP.2-Adapted COVID-19 Vaccine
  • BioNTech Investor Relations — LP.8.1-Adapted COVID-19 Vaccine 2025–2026 Formula Topline Data
  • BioSpace — Moderna Q1 2024 Financial Results and Business Updates
  • Moderna Investor Relations — Q1 2025 Financial Results and Business Updates
  • Moderna Investor Relations — 43rd Annual J.P. Morgan Healthcare Conference Pipeline Updates
  • BioSpace — Moderna Raises COVID-19 Vaccine Forecast Amid Q2 Revenue Drop
  • TradingView — Moderna, Inc. SEC 10-K Report
  • WIPO — World Intellectual Property Organization (patent filing data)
  • EPO — European Patent Office (mRNA and LNP patent grants)
  • NIH — National Institutes of Health (foundational mRNA and rare disease research)

All data and statistics in this article are sourced from the references above and from PatSnap ‘s proprietary innovation intelligence platform.

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Flu Vaccine Market | Global Market Analysis Report - 2036

来源信息
来源：Fact.MR发布日期：未提供发布时间抓取时间：2026-06-17T18:49:55.290Z相关标的：MRNA, PFE, GSK, SNY归档状态：已归档 / 弹窗可读
中文摘要

一句话结论

Fact.MR 把全球 flu vaccine 市场描述为成熟但稳定增长的年化采购市场，2026 年约 79 亿美元、2036 年约 112 亿美元，增长不快但需求有公共免疫项目支撑，mRNA 平台机会来自速度、株匹配和大流行准备能力。

关键事实

  • 文章覆盖 2026-2036 forecast period。
  • Fact.MR 估计全球 flu vaccine market 2025 年约 76 亿美元，2026 年约 79 亿美元，2036 年达到 112 亿美元。
  • 2026-2036 CAGR 约 3.6%，绝对增量约 33 亿美元。
  • Inactivated influenza vaccine 预计 2026 年占 product segment 41.8%。
  • Public immunization programs 预计 2026 年占 end user segment 52.1%。
  • 文章称 India 和 China 是增长较快市场，分别约 5.4% 和 4.7%。
  • 需求驱动包括政府季节性免疫项目、医院/机构采购、细胞/重组/mRNA 等技术路线改进、以及新兴市场覆盖率提升。

作者观点与证据

文章观点是流感疫苗市场不是爆发式高增长，而是公共采购和年度免疫驱动的稳定市场。证据是市场规模、CAGR、分产品份额和地区增长估计。它的价值在于提供行业底盘，但不是针对 Moderna 的公司研究。

与相关标的的关系

对 MRNA 的关系是 mRNA-1010/MFLUSIVA 的商业天花板和竞争环境。即便获批，流感疫苗市场增长率有限，Moderna 需要通过更好疗效、组合疫苗、供应速度或高风险人群标签来抢份额，而不是依赖市场自然高增。

时效性与限制

网页未给明确发布日期，只有 2026-2036 forecast 口径。作为行业背景可以引用，但市场规模和份额是第三方估算，必须低于 FDA、公司财务和真实销售数据权重。

后续跟踪

  • 美国和欧洲流感疫苗接种率与公共采购预算。
  • mRNA flu 与传统 inactivated/recombinant/cell-based 疫苗的标签差异。
  • 高剂量/佐剂化老年疫苗竞争格局。
  • MFLUSIVA 是否能获得足够商业覆盖和 payer/采购接受度。
英文原文
Flu Vaccine Market | Global Market Analysis Report - 2036

Flu Vaccine Market Size, Share, Growth and Forecast (2026 - 2036)

Flu Vaccine Market is segmented by Product (Inactivated Influenza Vaccine, Live Attenuated Influenza Vaccine, Recombinant Influenza Vaccine, Cell Based Influenza Vaccine, Adjuvanted Influenza Vaccine, Pandemic Influenza Vaccine), Technology (Egg Based Production, Cell Based Production, Recombinant Technology, Protein Expression Systems, mRNA Based Platforms), Strain Coverage (Seasonal Strains, Pandemic Strains, Universal Vaccine Candidates), and Region, with forecasts covering the period from 2026 to 2036.

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Market Summary

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Flu Vaccine Market Analysis and Forecast by Fact.MR

  • The global flu vaccine market is estimated at USD 7.6 billion in 2025 and is forecast to reach USD 7.9 billion in 2026 before expanding to USD 11.2 billion by 2036, progressing at a CAGR of 3.6% over the 2026 to 2036 forecast period.
  • Inactivated Influenza Vaccine is anticipated to account for 41.8% share of the product segment in 2026, supported by established regulatory approval across all age groups, proven safety profile, and dominant position in national immunization programs globally. India (5.4%) and China (4.7%) are the fastest growing country markets through 2036.

Summary of Flu Vaccine Market

  • Market Snapshot
  • In 2025, the global Flu Vaccine Market was valued at approximately USD 7.6 billion.
  • The market is estimated to reach USD 7.9 billion in 2026 and is projected to attain USD 11.2 billion by 2036.
  • The flu vaccine market is likely to expand at a CAGR of 3.6% during the forecast period.
  • The market is anticipated to create an absolute dollar opportunity of USD 3.3 billion between 2026 and 2036.
  • Inactivated influenza vaccines account for 41.8% of market share in 2026.
  • India (5.4%) and China (4.7%) are the key growth markets during the forecast period.
  • Demand and Growth Drivers
  • Expanding flu vaccination coverage in India, China, and Brazil, where seasonal immunization is not yet routine, creates the largest structural growth opportunity for dose volume expansion.
  • Government-funded seasonal immunization programs in established markets provide a non-discretionary annual procurement base that ensures consistent demand regardless of economic conditions.
  • Technology-driven shifts toward cell-based and recombinant manufacturing platforms improve production speed, strain matching accuracy, and pandemic preparedness capacity.
  • Rising institutional procurement volumes across hospitals, academic facilities, and government programs create a sustained base-level demand that is less sensitive to short-term economic cycles.
  • Expanding distribution through specialized channels and direct-to-institution sales models is improving product accessibility across underpenetrated geographies.
  • Product and Segment View
  • Inactivated Influenza Vaccine accounts for 41.8% of the product segment in 2026, maintaining the leading position due to established usage patterns and broad commercial adoption.
  • Public Immunization Programs represents 52.1% of the end user segment in 2026, supported by the largest concentration of end-use demand and procurement volumes.
  • The flu vaccine market is segmented by product, technology, strain coverage, dosage form, end user, and region. By product, the market covers inactivated influenza vaccine, live attenuated influenza vaccine, recombinant influenza vaccine, and related categories. By end user, coverage includes public immunization programs, hospitals and clinics, pharmacies and retail clinics, and other use cases.
  • Geography and Competitive Outlook
  • India leads growth at 5.4%, supported by infrastructure expansion and increasing institutional adoption.
  • North America reflects a mature but steady demand profile, with the USA at 3.4% supported by replacement demand and established clinical protocols.
  • Europe maintains stable growth, with Germany at 2.9% supported by regulatory standards and established institutional procurement frameworks.
  • Sanofi Pasteur, GlaxoSmithKline (GSK), Seqirus (CSL Limited) hold strong positions through broad product portfolios and established distribution networks.
  • Analyst Opinion
  • Shambhu Nath Jha, Principal Consultant at Fact.MR, says 'The flu vaccine market is structurally supported by annual seasonal vaccination cycles and government-funded immunization programs that create a non-discretionary demand floor across all major economies. Growth reflects two dynamics: expanding vaccination coverage rates in emerging markets where flu immunization is not yet routine, and technology-driven shifts in manufacturing and formulation in established markets. Egg-based production still dominates global supply, but cell-based and recombinant platforms are gaining share as they offer faster scale-up capability and potentially better strain matching. mRNA flu vaccine candidates from Moderna and others represent a longer-term disruption vector that could reshape manufacturing economics and seasonal production timelines. The market's competitive concentration is high, with Sanofi Pasteur, GSK, and Seqirus commanding the majority of global supply through government procurement contracts. Margin pressure exists in established markets due to tender-based pricing, but premium-priced adjuvanted and high-dose formulations for elderly populations create value-based growth pockets.'

Key Growth Drivers, Constraints, and Opportunities

Key Factors Driving Growth

  • Expanding flu vaccination coverage in India, China, and Brazil, where seasonal immunization is not yet routine, creates the largest structural growth opportunity for dose volume expansion.
  • Government-funded seasonal immunization programs in established markets provide a non-discretionary annual procurement base that ensures consistent demand regardless of economic conditions.
  • Technology-driven shifts toward cell-based and recombinant manufacturing platforms improve production speed, strain matching accuracy, and pandemic preparedness capacity.

Key Market Constraints

  • Tender-based government procurement pricing compresses margins in established markets, limiting revenue growth even as dose volumes remain stable.
  • Annual strain variability and vaccine effectiveness fluctuations affect public confidence and can reduce voluntary vaccination uptake in seasons with perceived low efficacy.
  • Cold chain logistics and distribution infrastructure gaps in developing markets limit vaccine accessibility in rural and remote regions.

Key Opportunity Areas

  • mRNA-based flu vaccine platforms from Moderna and other developers represent a potential disruption that could reduce manufacturing lead times and enable combination flu-COVID vaccines.
  • Premium-priced adjuvanted and high-dose formulations for elderly and immunocompromised populations create value-based growth that is less sensitive to tender pricing pressure.
  • Pandemic preparedness investments by governments worldwide are supporting capacity expansion in cell-based and recombinant manufacturing facilities with dual seasonal-pandemic capability.

Segment-wise Analysis of the Flu Vaccine Market

  • Inactivated Influenza Vaccine holds 41.8% of the product segment in 2026, supported by established adoption patterns and broad commercial applicability.
  • Public Immunization Programs represents 52.1% of the end user segment in 2026, reflecting the largest concentration of end-use demand.

The flu vaccine market is segmented by product, technology, strain coverage, dosage form, end user, and region.

Which Product Segment Leads the Flu Vaccine Market?

Inactivated Influenza Vaccine accounts for 41.8% of the product segment in 2026. This position reflects established regulatory approval across all age groups, proven safety profile, and dominant position in national immunization programs globally. The segment benefits from an established installed base, broad geographic adoption, and consistent demand from both institutional and individual buyer channels.

Which End User Segment Leads the Flu Vaccine Market?

Public Immunization Programs is expected to account for 52.1% of the end user segment in 2026. This segment represents the largest concentration of purchasing activity and maintains its position through established procurement cycles, regulatory requirements, and direct alignment with the primary use cases that define market demand.

Which Product Trend is Shaping the Next Phase of Growth in the Flu Vaccine Market?

mRNA-based flu vaccine platforms are the most significant manufacturing technology shift on the horizon. Moderna and other developers are advancing combined flu-COVID mRNA vaccine candidates through clinical trials, with the potential to simplify seasonal immunization schedules and reduce the number of annual vaccine administrations required. mRNA platforms also offer faster strain update timelines compared to egg-based production, which could improve vaccine-to-circulating-strain matching and overall effectiveness. While egg-based manufacturing will continue to supply the majority of global flu vaccine doses through the forecast period, mRNA and cell-based alternatives are positioned to capture an increasing share as regulatory pathways mature and manufacturing costs decrease.

Regional Outlook Across Key Markets

  • India leads growth at 5.4%, supported by infrastructure expansion and rising adoption across institutional and commercial channels.
  • North America shows steady growth, with the USA at 3.4% reflecting a mature market with replacement-led demand and established institutional procurement.
  • Europe maintains consistent demand, with Germany at 2.9% supported by regulatory standards and quality-focused procurement practices.
  • Asia Pacific is the fastest growing region overall, with India and China contributing the strongest country-level growth rates.

Country CAGR Table

Country

CAGR (%)

India

5.4%

China

4.7%

Brazil

4.2%

USA

3.4%

South Korea

3.2%

Germany

2.9%

Japan

2.6%

Source: Fact.MR analysis, based on proprietary forecasting model and primary research.

Flu Vaccine Market in India

India leads global market expansion with a projected CAGR of 5.4% through 2036. Growth reflects expanding public immunization programs, rising seasonal flu awareness, domestic vaccine manufacturing capacity growth through producers like Bharat Biotech and Serum Institute of India, and increasing private-market vaccination uptake.

  • Domestic vaccine manufacturing capacity supports affordable seasonal flu vaccine supply.
  • Public immunization program expansion increases coverage rates beyond current low baseline levels.
  • Private-market vaccination through hospitals and pharmacy chains supports incremental dose volume growth.

Flu Vaccine Market in China

China is projected to grow at a CAGR of 4.7% through 2036. Demand reflects government investment in seasonal flu immunization, strong domestic vaccine manufacturing capacity, and growing public awareness of influenza prevention following pandemic-era health awareness shifts.

  • Government seasonal flu immunization investment supports coverage rate expansion.
  • Domestic manufacturing capacity ensures supply security and cost-competitive vaccine production.
  • Post-pandemic health awareness sustains higher baseline demand for preventive immunization.

Flu Vaccine Market in Brazil

Brazil is projected to grow at a CAGR of 4.2% through 2036. Expansion reflects an established national flu vaccination campaign, expanding coverage to younger age groups, and growing private-market vaccination through retail pharmacy networks.

  • Established national flu vaccination campaign provides a consistent public procurement base.
  • Coverage expansion to additional age groups and risk categories increases annual dose volumes.
  • Retail pharmacy vaccination channels support private-market dose growth.

Flu Vaccine Market in USA

The United States is projected to grow at a CAGR of 3.4% through 2036. The market benefits from established CDC-recommended seasonal vaccination, high retail pharmacy accessibility, and growing adoption of premium vaccine formulations including high-dose and adjuvanted products for elderly populations.

  • CDC-recommended seasonal vaccination maintains high baseline coverage rates.
  • Retail pharmacy accessibility supports convenient annual vaccination for working-age adults.
  • Premium high-dose and adjuvanted formulations create value-based growth in elderly vaccination segments.

Flu Vaccine Market in South Korea

South Korea is projected to grow at a CAGR of 3.2% through 2036. Growth reflects high seasonal flu vaccination coverage, government-funded immunization for children and elderly populations, and adoption of cell-based and quadrivalent formulations.

  • Government-funded immunization for priority populations supports stable procurement volumes.
  • High population health awareness maintains strong voluntary vaccination uptake.
  • Quadrivalent and cell-based formulations gain share in premium vaccination segments.

Flu Vaccine Market in Germany

Germany is projected to grow at a CAGR of 2.9% through 2036. Demand reflects established seasonal flu vaccination recommendations, statutory health insurance coverage for at-risk groups, and growing emphasis on healthcare worker immunization.

  • Statutory health insurance covers seasonal flu vaccination for recommended population groups.
  • Healthcare worker immunization mandates support institutional vaccination volumes.
  • Seasonal flu awareness campaigns maintain public vaccination uptake rates.

Flu Vaccine Market in Japan

Japan is projected to grow at a CAGR of 2.6% through 2036. The market is mature, with growth supported by established seasonal vaccination programs, high elderly population vaccination rates, and domestic vaccine manufacturing capabilities.

  • Established seasonal vaccination programs maintain consistent annual procurement volumes.
  • High elderly vaccination rates support stable demand for age-appropriate formulations.
  • Domestic manufacturing capabilities ensure supply reliability for seasonal campaigns.

Competitive Benchmarking and Company Positioning

Flu Vaccine Market Analysis By Company

  • Sanofi Pasteur, GlaxoSmithKline (GSK), Seqirus (CSL Limited) hold strong positions through broad product portfolios, established distribution networks, and deep market expertise.
  • AstraZeneca (FluMist), Moderna, Pfizer participate meaningfully across specific segments and regional markets with competition shaped by product quality, pricing, and service capabilities.

Sanofi Pasteur, GlaxoSmithKline (GSK), and Seqirus (CSL Limited) hold dominant positions in the global flu vaccine market through large-scale manufacturing capacity, established government procurement relationships, and comprehensive seasonal strain coverage portfolios.

AstraZeneca (FluMist), Moderna, and Pfizer participate through differentiated delivery formats and next-generation mRNA platforms, with competition shaped by clinical trial outcomes, regulatory approval timelines, and manufacturing scalability.

Emerging market manufacturers including Bharat Biotech, Serum Institute of India, and Sinovac Biotech create competitive pressure through cost-effective vaccine supply for government immunization programs in price-sensitive markets.

The competitive landscape is highly concentrated at the manufacturing level, with the top three global suppliers commanding the majority of seasonal procurement volumes, while mRNA platform developers position for longer-term share gains as technology matures.

Recent Industry Developments

  • Moderna advanced its combined flu-COVID mRNA vaccine candidate through Phase 3 clinical trials in 2025, with regulatory submissions expected in 2026 pending clinical outcomes data.
  • Sanofi Pasteur expanded cell-based flu vaccine manufacturing capacity in early 2026, increasing seasonal production capability at facilities in the United States and Europe.
  • Seqirus (CSL Limited) launched an updated adjuvanted influenza vaccine in 2025 targeting elderly populations, with enhanced immunogenicity data supporting its positioning in age-appropriate vaccination segments.

Leading Companies in the Flu Vaccine Market

-

Major Players

  • Sanofi Pasteur
  • GlaxoSmithKline (GSK)
  • Seqirus (CSL Limited)
  • AstraZeneca (FluMist)
  • Moderna
  • Pfizer
  • Daiichi Sankyo
  • Sinovac Biotech

-

Emerging Players

  • Bharat Biotech
  • Serum Institute of India
  • Biondvax Pharmaceuticals
  • Valneva SE
  • Novavax
  • BioDiem
  • Medicago

Sources and Research References

  • World Health Organization (WHO). Global Influenza Strategy 2019 to 2030 and Seasonal Vaccine Composition Recommendations.
  • U.S. Centers for Disease Control and Prevention (CDC). Influenza Vaccination Coverage and Effectiveness Reports.
  • Sanofi Pasteur. Product Portfolio and Vaccine Manufacturing Technology Updates.
  • European Centre for Disease Prevention and Control (ECDC). Seasonal Influenza Vaccination Recommendations and Coverage Data.
  • Primary interviews with vaccine manufacturers, public health procurement teams, healthcare providers, and immunization program administrators.

This bibliography is provided for reader reference and is not exhaustive. The full report contains the complete reference list and detailed citations.

Key Questions This Report Addresses

What is the current and future size of the flu vaccine market?

  • How fast is the flu vaccine market expected to grow between 2026 and 2036?
  • Which product is likely to lead the market by 2026?
  • Which end user segment is expected to account for the highest demand by 2026?
  • What factors are driving demand globally?
  • Which countries are projected to show the fastest growth through 2036?
  • Who are the key companies active in the flu vaccine market?
  • How does Fact.MR estimate and validate the market forecast?

Flu Vaccine Market Definition

The flu vaccine market covers inactivated, live attenuated, recombinant, cell-based, adjuvanted, and pandemic influenza vaccines used across public immunization programs, hospital and clinic settings, retail pharmacy channels, and corporate vaccination programs for seasonal and pandemic strain coverage.

Flu Vaccine Market Inclusions

The scope covers global and regional market size and forecasts for 2026 to 2036 across product, technology, strain coverage, dosage form, end user, and region. It includes regional demand analysis across major geographies, pricing and cost analysis, technology trends, market drivers and constraints, and the competitive landscape covering product portfolios, pricing strategy, geographic reach, and distribution expansion of leading players.

Flu Vaccine Market Exclusions

The scope excludes general-purpose devices, products, or services not purpose-built for the applications defined within this market. It excludes unbranded products with low market visibility, rental or leasing services without hardware sales, and custom-built systems without commercial sales distribution. Industrial or military-grade variants outside the defined commercial scope are also excluded.

Flu Vaccine Market Research Methodology

  • Primary research includes interviews with manufacturers, distributors, end users, and institutional procurement teams across key geographies.
  • Secondary research draws on industry publications, regulatory filings, company reports, and trade databases.
  • Market sizing follows a demand-side model supported by top-down validation across 30 plus countries.
  • Final estimates are validated through trade-flow checks, pricing trend analysis, and sensitivity testing.

Scope of Analysis

Parameter

Details

Quantitative Units

USD 7.9 billion to USD 11.2 billion, at a CAGR of 3.6%

Market Definition

The flu vaccine market covers inactivated, live attenuated, recombinant, cell-based, adjuvanted, and pandemic influenza vaccines used across public immunization programs, hospital and clinic settings, retail pharmacy channels, and corporate vaccination programs for seasonal and pandemic strain coverage.

Regions Covered

North America, Latin America, Europe, East Asia, South Asia and Pacific, Middle East and Africa

Countries Covered

USA, India, China, Brazil, Germany, South Korea, Japan, and 30 plus countries

Key Companies

Sanofi Pasteur, GlaxoSmithKline (GSK), Seqirus (CSL Limited), AstraZeneca, Moderna, Pfizer, Daiichi Sankyo, Sinovac Biotech, Bharat Biotech, Serum Institute of India

Forecast Period

2026 to 2036

Approach

Hybrid demand-side and top-down methodology built on country-level vaccination coverage rates, government procurement data, pricing analysis, and primary interviews across vaccine manufacturers, public health agencies, distributors, and healthcare providers

Market Segmentation Analysis

-

Flu Vaccine Market Segmented by Product:

  • Inactivated Influenza Vaccine
  • Trivalent Inactivated Vaccine
  • Quadrivalent Inactivated Vaccine
  • Live Attenuated Influenza Vaccine
  • Nasal Spray Vaccine
  • Recombinant Influenza Vaccine
  • HA Recombinant Vaccine
  • Cell Based Influenza Vaccine
  • MDCK Cell Based Vaccine
  • Vero Cell Based Vaccine
  • Adjuvanted Influenza Vaccine
  • Immuno Boosted Formulations
  • High Dose Vaccine
  • Pandemic Influenza Vaccine
  • H1N1 Vaccine
  • H5N1 Vaccine

-

Flu Vaccine Market Segmented by Technology:

  • Egg Based Production
  • Embryonated Egg Culture
  • Traditional Egg Adaptation
  • Cell Based Production
  • Mammalian Cell Culture
  • Insect Cell Culture
  • Recombinant Technology
  • Genetic Recombination Platforms
  • Protein Expression Systems
  • mRNA Based Platforms
  • Messenger RNA Vaccine Platforms
  • Lipid Nanoparticle Delivery Systems

-

Flu Vaccine Market Segmented by Strain Coverage:

  • Seasonal Strains
  • H1N1
  • H3N2
  • Influenza B Victoria Lineage
  • Influenza B Yamagata Lineage
  • Pandemic Strains
  • Avian Influenza Strains
  • Zoonotic Influenza Variants
  • Universal Vaccine Candidates
  • Broad Spectrum Antigen Targets
  • Conserved Epitope Vaccines

-

Flu Vaccine Market Segmented by Dosage Form:

  • Single Dose Vials
  • Prefilled Syringes
  • Nasal Sprays
  • Multi Dose Vials
  • Preserved Multi Dose Formulations
  • Thimerosal Containing Vials

-

Flu Vaccine Market Segmented by End User:

  • Public Immunization Programs
  • National Vaccination Programs
  • Seasonal Flu Campaigns
  • Hospitals and Clinics
  • Private Hospitals
  • Public Healthcare Facilities
  • Pharmacies and Retail Clinics
  • Retail Pharmacy Chains
  • Travel Vaccination Clinics
  • Corporate Vaccination Programs
  • Workplace Immunization Drives
  • Industrial Health Programs

-

Flu Vaccine Market by Region:

  • North America
  • USA
  • Canada
  • Mexico
  • Latin America
  • Brazil
  • Chile
  • Rest of Latin America
  • Western Europe
  • Germany
  • UK
  • Italy
  • Spain
  • France
  • Nordic
  • BENELUX
  • Rest of Western Europe
  • Eastern Europe
  • Russia
  • Poland
  • Hungary
  • Balkan & Baltic
  • Rest of Eastern Europe
  • East Asia
  • China
  • Japan
  • South Korea
  • South Asia and Pacific
  • India
  • ASEAN
  • Australia & New Zealand
  • Rest of South Asia and Pacific
  • Middle East & Africa
  • Kingdom of Saudi Arabia
  • Other GCC Countries
  • Turkiye
  • South Africa
  • Other African Union
  • Rest of Middle East & Africa

- Frequently Asked Questions -

How big is the flu vaccine market in 2025?

The global flu vaccine market is estimated to be valued at USD 7.6 billion in 2025.

What will be the size of the flu vaccine market in 2036?

The market size for the flu vaccine market is projected to reach USD 11.2 billion by 2036.

How much will the flu vaccine market grow between 2026 and 2036?

The flu vaccine market is expected to grow at a 3.6% CAGR between 2026 and 2036.

What are the key product types in the flu vaccine market?

The key product types include inactivated influenza vaccine, live attenuated influenza vaccine, recombinant influenza vaccine.

Which end user segment contributes significant share in 2026?

In terms of end user, public immunization programs is expected to account for 52.1% share in the flu vaccine market in 2026.

Which countries are projected to grow fastest?

India (5.4%) and China (4.7%) are projected to be the fastest growing country markets through 2036.

What is the market definition?

The flu vaccine market covers inactivated, live attenuated, recombinant, cell-based, adjuvanted, and pandemic influenza vaccines used across public immunization programs, hospital and clinic settings, retail pharmacy channels, and corporate vaccination programs for seasonal and pandemic strain coverage.

What methodology does Fact.MR use?

The methodology combines secondary research, primary interviews, and forecast modelling. Market sizing covers 30 plus countries through a demand-side model supported by top-down validation.

How big is the flu vaccine market in 2025?

The global flu vaccine market is estimated to be valued at USD 7.6 billion in 2025.

What will be the size of the flu vaccine market in 2036?

The market size for the flu vaccine market is projected to reach USD 11.2 billion by 2036.

How much will the flu vaccine market grow between 2026 and 2036?

The flu vaccine market is expected to grow at a 3.6% CAGR between 2026 and 2036.

What are the key product types in the flu vaccine market?

The key product types include inactivated influenza vaccine, live attenuated influenza vaccine, recombinant influenza vaccine.

Which end user segment contributes significant share in 2026?

In terms of end user, public immunization programs is expected to account for 52.1% share in the flu vaccine market in 2026.

Which countries are projected to grow fastest?

India (5.4%) and China (4.7%) are projected to be the fastest growing country markets through 2036.

What is the market definition?

The flu vaccine market covers inactivated, live attenuated, recombinant, cell-based, adjuvanted, and pandemic influenza vaccines used across public immunization programs, hospital and clinic settings, retail pharmacy channels, and corporate vaccination programs for seasonal and pandemic strain coverage.

What methodology does Fact.MR use?

The methodology combines secondary research, primary interviews, and forecast modelling. Market sizing covers 30 plus countries through a demand-side model supported by top-down validation.

Table of Content

  • Executive Summary
  • Global Market Outlook
  • Demand to side Trends
  • Supply to side Trends
  • Technology Roadmap Analysis
  • Analysis and Recommendations
  • Market Overview
  • Market Coverage / Taxonomy
  • Market Definition / Scope / Limitations
  • Research Methodology
  • Chapter Orientation
  • Analytical Lens and Working Hypotheses
  • Market Structure, Signals, and Trend Drivers
  • Benchmarking and Cross-market Comparability
  • Market Sizing, Forecasting, and Opportunity Mapping
  • Research Design and Evidence Framework
  • Desk Research Programme (Secondary Evidence)
  • Company Annual and Sustainability Reports
  • Peer-reviewed Journals and Academic Literature
  • Corporate Websites, Product Literature, and Technical Notes
  • Earnings Decks and Investor Briefings
  • Statutory Filings and Regulatory Disclosures
  • Technical White Papers and Standards Notes
  • Trade Journals, Industry Magazines, and Analyst Briefs
  • Conference Proceedings, Webinars, and Seminar Materials
  • Government Statistics Portals and Public Data Releases
  • Press Releases and Reputable Media Coverage
  • Specialist Newsletters and Curated Briefings
  • Sector Databases and Reference Repositories
  • Fact.MR Internal Proprietary Databases and Historical Market Datasets
  • Subscription Datasets and Paid Sources
  • Social Channels, Communities, and Digital Listening Inputs
  • Additional Desk Sources
  • Expert Input and Fieldwork (Primary Evidence)
  • Primary Modes
  • Qualitative Interviews and Expert Elicitation
  • Quantitative Surveys and Structured Data Capture
  • Blended Approach
  • Why Primary Evidence is Used
  • Field Techniques
  • Interviews
  • Surveys
  • Focus Groups
  • Observational and In-context Research
  • Social and Community Interactions
  • Stakeholder Universe Engaged
  • C-suite Leaders
  • Board Members
  • Presidents and Vice Presidents
  • R&D and Innovation Heads
  • Technical Specialists
  • Domain Subject-matter Experts
  • Scientists
  • Physicians and Other Healthcare Professionals
  • Governance, Ethics, and Data Stewardship
  • Research Ethics
  • Data Integrity and Handling
  • Tooling, Models, and Reference Databases
  • Data Engineering and Model Build
  • Data Acquisition and Ingestion
  • Cleaning, Normalisation, and Verification
  • Synthesis, Triangulation, and Analysis
  • Quality Assurance and Audit Trail
  • Market Background
  • Market Dynamics
  • Drivers
  • Restraints
  • Opportunity
  • Trends
  • Scenario Forecast
  • Demand in Optimistic Scenario
  • Demand in Likely Scenario
  • Demand in Conservative Scenario
  • Opportunity Map Analysis
  • Product Life Cycle Analysis
  • Supply Chain Analysis
  • Investment Feasibility Matrix
  • Value Chain Analysis
  • PESTLE and Porter&rsquo;s Analysis
  • Regulatory Landscape
  • Regional Parent Market Outlook
  • Production and Consumption Statistics
  • Import and Export Statistics
  • Global Market Analysis 2021 to 2025 and Forecast, 2026 to 2036
  • Historical Market Size Value (USD Million) Analysis, 2021 to 2025
  • Current and Future Market Size Value (USD Million) Projections, 2026 to 2036
  • Y to o to Y Growth Trend Analysis
  • Absolute $ Opportunity Analysis
  • Global Market Pricing Analysis 2021 to 2025 and Forecast 2026 to 2036
  • Global Market Analysis 2021 to 2025 and Forecast 2026 to 2036, By Product
  • Introduction / Key Findings
  • Historical Market Size Value (USD Million) Analysis By Product , 2021 to 2025
  • Current and Future Market Size Value (USD Million) Analysis and Forecast By Product , 2026 to 2036
  • Inactivated Influenza Vaccine
  • Trivalent Inactivated Vaccine
  • Quadrivalent Inactivated Vaccine
  • Live Attenuated Influenza Vaccine
  • Nasal Spray Vaccine
  • Recombinant Influenza Vaccine
  • HA Recombinant Vaccine
  • Cell Based Influenza Vaccine
  • MDCK Cell Based Vaccine
  • Vero Cell Based Vaccine
  • Adjuvanted Influenza Vaccine
  • Immuno Boosted Formulations
  • High Dose Vaccine
  • Pandemic Influenza Vaccine
  • H1N1 Vaccine
  • H5N1 Vaccine
  • Y to o to Y Growth Trend Analysis By Product , 2021 to 2025
  • Absolute $ Opportunity Analysis By Product , 2026 to 2036
  • Global Market Analysis 2021 to 2025 and Forecast 2026 to 2036, By Technology
  • Introduction / Key Findings
  • Historical Market Size Value (USD Million) Analysis By Technology, 2021 to 2025
  • Current and Future Market Size Value (USD Million) Analysis and Forecast By Technology, 2026 to 2036
  • Egg Based Production
  • Embryonated Egg Culture
  • Traditional Egg Adaptation
  • Cell Based Production
  • Mammalian Cell Culture
  • Insect Cell Culture
  • Recombinant Technology
  • Genetic Recombination Platforms
  • Protein Expression Systems
  • mRNA Based Platforms
  • Messenger RNA Vaccine Platforms
  • Lipid Nanoparticle Delivery Systems
  • Y to o to Y Growth Trend Analysis By Technology, 2021 to 2025
  • Absolute $ Opportunity Analysis By Technology, 2026 to 2036
  • Global Market Analysis 2021 to 2025 and Forecast 2026 to 2036, By Strain Coverage
  • Introduction / Key Findings
  • Historical Market Size Value (USD Million) Analysis By Strain Coverage, 2021 to 2025
  • Current and Future Market Size Value (USD Million) Analysis and Forecast By Strain Coverage, 2026 to 2036
  • Seasonal Strains
  • H1N1
  • H3N2
  • Influenza B Victoria Lineage
  • Influenza B Yamagata Lineage
  • Pandemic Strains
  • Avian Influenza Strains
  • Zoonotic Influenza Variants
  • Universal Vaccine Candidates
  • Broad Spectrum Antigen Targets
  • Conserved Epitope Vaccines
  • Y to o to Y Growth Trend Analysis By Strain Coverage, 2021 to 2025
  • Absolute $ Opportunity Analysis By Strain Coverage, 2026 to 2036
  • Global Market Analysis 2021 to 2025 and Forecast 2026 to 2036, By Dosage Form
  • Introduction / Key Findings
  • Historical Market Size Value (USD Million) Analysis By Dosage Form, 2021 to 2025
  • Current and Future Market Size Value (USD Million) Analysis and Forecast By Dosage Form, 2026 to 2036
  • Single Dose Vials
  • Prefilled Syringes
  • Nasal Sprays
  • Multi Dose Vials
  • Preserved Multi Dose Formulations
  • Thimerosal Containing Vials
  • Y to o to Y Growth Trend Analysis By Dosage Form, 2021 to 2025
  • Absolute $ Opportunity Analysis By Dosage Form, 2026 to 2036
  • Global Market Analysis 2021 to 2025 and Forecast 2026 to 2036, By End User
  • Introduction / Key Findings
  • Historical Market Size Value (USD Million) Analysis By End User, 2021 to 2025
  • Current and Future Market Size Value (USD Million) Analysis and Forecast By End User, 2026 to 2036
  • Public Immunization Programs
  • National Vaccination Programs
  • Seasonal Flu Campaigns
  • Hospitals and Clinics
  • Private Hospitals
  • Public Healthcare Facilities
  • Pharmacies and Retail Clinics
  • Retail Pharmacy Chains
  • Travel Vaccination Clinics
  • Corporate Vaccination Programs
  • Workplace Immunization Drives
  • Industrial Health Programs
  • Y to o to Y Growth Trend Analysis By End User, 2021 to 2025
  • Absolute $ Opportunity Analysis By End User, 2026 to 2036
  • Global Market Analysis 2021 to 2025 and Forecast 2026 to 2036, By Region
  • Introduction
  • Historical Market Size Value (USD Million) Analysis By Region, 2021 to 2025
  • Current Market Size Value (USD Million) Analysis and Forecast By Region, 2026 to 2036
  • North America
  • Latin America
  • Western Europe
  • Eastern Europe
  • East Asia
  • South Asia and Pacific
  • Middle East & Africa
  • Market Attractiveness Analysis By Region
  • North America Market Analysis 2021 to 2025 and Forecast 2026 to 2036, By Country
  • Historical Market Size Value (USD Million) Trend Analysis By Market Taxonomy, 2021 to 2025
  • Market Size Value (USD Million) Forecast By Market Taxonomy, 2026 to 2036
  • By Country
  • USA
  • Canada
  • Mexico
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Market Attractiveness Analysis
  • By Country
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Key Takeaways
  • Latin America Market Analysis 2021 to 2025 and Forecast 2026 to 2036, By Country
  • Historical Market Size Value (USD Million) Trend Analysis By Market Taxonomy, 2021 to 2025
  • Market Size Value (USD Million) Forecast By Market Taxonomy, 2026 to 2036
  • By Country
  • Brazil
  • Chile
  • Rest of Latin America
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Market Attractiveness Analysis
  • By Country
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Key Takeaways
  • Western Europe Market Analysis 2021 to 2025 and Forecast 2026 to 2036, By Country
  • Historical Market Size Value (USD Million) Trend Analysis By Market Taxonomy, 2021 to 2025
  • Market Size Value (USD Million) Forecast By Market Taxonomy, 2026 to 2036
  • By Country
  • Germany
  • UK
  • Italy
  • Spain
  • France
  • Nordic
  • BENELUX
  • Rest of Western Europe
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Market Attractiveness Analysis
  • By Country
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Key Takeaways
  • Eastern Europe Market Analysis 2021 to 2025 and Forecast 2026 to 2036, By Country
  • Historical Market Size Value (USD Million) Trend Analysis By Market Taxonomy, 2021 to 2025
  • Market Size Value (USD Million) Forecast By Market Taxonomy, 2026 to 2036
  • By Country
  • Russia
  • Poland
  • Hungary
  • Balkan & Baltic
  • Rest of Eastern Europe
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Market Attractiveness Analysis
  • By Country
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Key Takeaways
  • East Asia Market Analysis 2021 to 2025 and Forecast 2026 to 2036, By Country
  • Historical Market Size Value (USD Million) Trend Analysis By Market Taxonomy, 2021 to 2025
  • Market Size Value (USD Million) Forecast By Market Taxonomy, 2026 to 2036
  • By Country
  • China
  • Japan
  • South Korea
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Market Attractiveness Analysis
  • By Country
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Key Takeaways
  • South Asia and Pacific Market Analysis 2021 to 2025 and Forecast 2026 to 2036, By Country
  • Historical Market Size Value (USD Million) Trend Analysis By Market Taxonomy, 2021 to 2025
  • Market Size Value (USD Million) Forecast By Market Taxonomy, 2026 to 2036
  • By Country
  • India
  • ASEAN
  • Australia & New Zealand
  • Rest of South Asia and Pacific
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Market Attractiveness Analysis
  • By Country
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Key Takeaways
  • Middle East & Africa Market Analysis 2021 to 2025 and Forecast 2026 to 2036, By Country
  • Historical Market Size Value (USD Million) Trend Analysis By Market Taxonomy, 2021 to 2025
  • Market Size Value (USD Million) Forecast By Market Taxonomy, 2026 to 2036
  • By Country
  • Kingdom of Saudi Arabia
  • Other GCC Countries
  • Turkiye
  • South Africa
  • Other African Union
  • Rest of Middle East & Africa
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Market Attractiveness Analysis
  • By Country
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Key Takeaways
  • Key Countries Market Analysis
  • USA
  • Pricing Analysis
  • Market Share Analysis, 2025
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Canada
  • Pricing Analysis
  • Market Share Analysis, 2025
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Mexico
  • Pricing Analysis
  • Market Share Analysis, 2025
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Brazil
  • Pricing Analysis
  • Market Share Analysis, 2025
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Chile
  • Pricing Analysis
  • Market Share Analysis, 2025
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Germany
  • Pricing Analysis
  • Market Share Analysis, 2025
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • UK
  • Pricing Analysis
  • Market Share Analysis, 2025
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Italy
  • Pricing Analysis
  • Market Share Analysis, 2025
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Spain
  • Pricing Analysis
  • Market Share Analysis, 2025
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • France
  • Pricing Analysis
  • Market Share Analysis, 2025
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • India
  • Pricing Analysis
  • Market Share Analysis, 2025
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • ASEAN
  • Pricing Analysis
  • Market Share Analysis, 2025
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Australia & New Zealand
  • Pricing Analysis
  • Market Share Analysis, 2025
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • China
  • Pricing Analysis
  • Market Share Analysis, 2025
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Japan
  • Pricing Analysis
  • Market Share Analysis, 2025
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • South Korea
  • Pricing Analysis
  • Market Share Analysis, 2025
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Russia
  • Pricing Analysis
  • Market Share Analysis, 2025
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Poland
  • Pricing Analysis
  • Market Share Analysis, 2025
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Hungary
  • Pricing Analysis
  • Market Share Analysis, 2025
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Kingdom of Saudi Arabia
  • Pricing Analysis
  • Market Share Analysis, 2025
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Turkiye
  • Pricing Analysis
  • Market Share Analysis, 2025
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • South Africa
  • Pricing Analysis
  • Market Share Analysis, 2025
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Market Structure Analysis
  • Competition Dashboard
  • Competition Benchmarking
  • Market Share Analysis of Top Players
  • By Regional
  • By Product
  • By Technology
  • By Strain Coverage
  • By Dosage Form
  • By End User
  • Competition Analysis
  • Competition Deep Dive
  • Sanofi Pasteur
  • Overview
  • Product Portfolio
  • Profitability by Market Segments (Product/Age /Sales Channel/Region)
  • Sales Footprint
  • Strategy Overview
  • Marketing Strategy
  • Product Strategy
  • Channel Strategy
  • GlaxoSmithKline (GSK)
  • Seqirus (CSL Limited)
  • AstraZeneca (FluMist)
  • Moderna (mRNA Flu pipeline)
  • Pfizer
  • Daiichi Sankyo
  • Sinovac Biotech
  • Bharat Biotech
  • Serum Institute of India
  • Biondvax Pharmaceuticals
  • Valneva SE
  • Novavax
  • BioDiem
  • Medicago (Mitsubishi/Philip Morris JV)
  • Assumptions & Acronyms Used

List Of Table

  • Table 1: Global Market Value (USD Million) Forecast by Region, 2021 to 2036
  • Table 2: Global Market Value (USD Million) Forecast by Product , 2021 to 2036
  • Table 3: Global Market Value (USD Million) Forecast by Technology, 2021 to 2036
  • Table 4: Global Market Value (USD Million) Forecast by Strain Coverage, 2021 to 2036
  • Table 5: Global Market Value (USD Million) Forecast by Dosage Form, 2021 to 2036
  • Table 6: Global Market Value (USD Million) Forecast by End User, 2021 to 2036
  • Table 7: North America Market Value (USD Million) Forecast by Country, 2021 to 2036
  • Table 8: North America Market Value (USD Million) Forecast by Product , 2021 to 2036
  • Table 9: North America Market Value (USD Million) Forecast by Technology, 2021 to 2036
  • Table 10: North America Market Value (USD Million) Forecast by Strain Coverage, 2021 to 2036
  • Table 11: North America Market Value (USD Million) Forecast by Dosage Form, 2021 to 2036
  • Table 12: North America Market Value (USD Million) Forecast by End User, 2021 to 2036
  • Table 13: Latin America Market Value (USD Million) Forecast by Country, 2021 to 2036
  • Table 14: Latin America Market Value (USD Million) Forecast by Product , 2021 to 2036
  • Table 15: Latin America Market Value (USD Million) Forecast by Technology, 2021 to 2036
  • Table 16: Latin America Market Value (USD Million) Forecast by Strain Coverage, 2021 to 2036
  • Table 17: Latin America Market Value (USD Million) Forecast by Dosage Form, 2021 to 2036
  • Table 18: Latin America Market Value (USD Million) Forecast by End User, 2021 to 2036
  • Table 19: Western Europe Market Value (USD Million) Forecast by Country, 2021 to 2036
  • Table 20: Western Europe Market Value (USD Million) Forecast by Product , 2021 to 2036
  • Table 21: Western Europe Market Value (USD Million) Forecast by Technology, 2021 to 2036
  • Table 22: Western Europe Market Value (USD Million) Forecast by Strain Coverage, 2021 to 2036
  • Table 23: Western Europe Market Value (USD Million) Forecast by Dosage Form, 2021 to 2036
  • Table 24: Western Europe Market Value (USD Million) Forecast by End User, 2021 to 2036
  • Table 25: Eastern Europe Market Value (USD Million) Forecast by Country, 2021 to 2036
  • Table 26: Eastern Europe Market Value (USD Million) Forecast by Product , 2021 to 2036
  • Table 27: Eastern Europe Market Value (USD Million) Forecast by Technology, 2021 to 2036
  • Table 28: Eastern Europe Market Value (USD Million) Forecast by Strain Coverage, 2021 to 2036
  • Table 29: Eastern Europe Market Value (USD Million) Forecast by Dosage Form, 2021 to 2036
  • Table 30: Eastern Europe Market Value (USD Million) Forecast by End User, 2021 to 2036
  • Table 31: East Asia Market Value (USD Million) Forecast by Country, 2021 to 2036
  • Table 32: East Asia Market Value (USD Million) Forecast by Product , 2021 to 2036
  • Table 33: East Asia Market Value (USD Million) Forecast by Technology, 2021 to 2036
  • Table 34: East Asia Market Value (USD Million) Forecast by Strain Coverage, 2021 to 2036
  • Table 35: East Asia Market Value (USD Million) Forecast by Dosage Form, 2021 to 2036
  • Table 36: East Asia Market Value (USD Million) Forecast by End User, 2021 to 2036
  • Table 37: South Asia and Pacific Market Value (USD Million) Forecast by Country, 2021 to 2036
  • Table 38: South Asia and Pacific Market Value (USD Million) Forecast by Product , 2021 to 2036
  • Table 39: South Asia and Pacific Market Value (USD Million) Forecast by Technology, 2021 to 2036
  • Table 40: South Asia and Pacific Market Value (USD Million) Forecast by Strain Coverage, 2021 to 2036
  • Table 41: South Asia and Pacific Market Value (USD Million) Forecast by Dosage Form, 2021 to 2036
  • Table 42: South Asia and Pacific Market Value (USD Million) Forecast by End User, 2021 to 2036
  • Table 43: Middle East & Africa Market Value (USD Million) Forecast by Country, 2021 to 2036
  • Table 44: Middle East & Africa Market Value (USD Million) Forecast by Product , 2021 to 2036
  • Table 45: Middle East & Africa Market Value (USD Million) Forecast by Technology, 2021 to 2036
  • Table 46: Middle East & Africa Market Value (USD Million) Forecast by Strain Coverage, 2021 to 2036
  • Table 47: Middle East & Africa Market Value (USD Million) Forecast by Dosage Form, 2021 to 2036
  • Table 48: Middle East & Africa Market Value (USD Million) Forecast by End User, 2021 to 2036

List Of Figures

  • Figure 1: Global Market Pricing Analysis
  • Figure 2: Global Market Value (USD Million) Forecast 2021-2036
  • Figure 3: Global Market Value Share and BPS Analysis by Product,2026 and 2036
  • Figure 4: Global Market Y-o-Y Growth Comparison by Product,2026 to 2036
  • Figure 5: Global Market Attractiveness Analysis by Product
  • Figure 6: Global Market Value Share and BPS Analysis by Technology,2026 and 2036
  • Figure 7: Global Market Y-o-Y Growth Comparison by Technology,2026 to 2036
  • Figure 8: Global Market Attractiveness Analysis by Technology
  • Figure 9: Global Market Value Share and BPS Analysis by Strain Coverage,2026 and 2036
  • Figure 10: Global Market Y-o-Y Growth Comparison by Strain Coverage,2026 to 2036
  • Figure 11: Global Market Attractiveness Analysis by Strain Coverage
  • Figure 12: Global Market Value Share and BPS Analysis by Dosage Form,2026 and 2036
  • Figure 13: Global Market Y-o-Y Growth Comparison by Dosage Form,2026 to 2036
  • Figure 14: Global Market Attractiveness Analysis by Dosage Form
  • Figure 15: Global Market Value Share and BPS Analysis by End User,2026 and 2036
  • Figure 16: Global Market Y-o-Y Growth Comparison by End User,2026 to 2036
  • Figure 17: Global Market Attractiveness Analysis by End User
  • Figure 18: Global Market Value (USD Million) Share and BPS Analysis by Region,2026 and 2036
  • Figure 19: Global Market Y-o-Y Growth Comparison by Region,2026 to 2036
  • Figure 20: Global Market Attractiveness Analysis by Region
  • Figure 21: North America Market Incremental Dollar Opportunity,2026 to 2036
  • Figure 22: Latin America Market Incremental Dollar Opportunity,2026 to 2036
  • Figure 23: Western Europe Market Incremental Dollar Opportunity,2026 to 2036
  • Figure 24: Eastern Europe Market Incremental Dollar Opportunity,2026 to 2036
  • Figure 25: East Asia Market Incremental Dollar Opportunity,2026 to 2036
  • Figure 26: South Asia and Pacific Market Incremental Dollar Opportunity,2026 to 2036
  • Figure 27: Middle East & Africa Market Incremental Dollar Opportunity,2026 to 2036
  • Figure 28: North America Market Value Share and BPS Analysis by Country,2026 and 2036
  • Figure 29: North America Market Value Share and BPS Analysis by Product,2026 and 2036
  • Figure 30: North America Market Y-o-Y Growth Comparison by Product,2026 to 2036
  • Figure 31: North America Market Attractiveness Analysis by Product
  • Figure 32: North America Market Value Share and BPS Analysis by Technology,2026 and 2036
  • Figure 33: North America Market Y-o-Y Growth Comparison by Technology,2026 to 2036
  • Figure 34: North America Market Attractiveness Analysis by Technology
  • Figure 35: North America Market Value Share and BPS Analysis by Strain Coverage,2026 and 2036
  • Figure 36: North America Market Y-o-Y Growth Comparison by Strain Coverage,2026 to 2036
  • Figure 37: North America Market Attractiveness Analysis by Strain Coverage
  • Figure 38: North America Market Value Share and BPS Analysis by Dosage Form,2026 and 2036
  • Figure 39: North America Market Y-o-Y Growth Comparison by Dosage Form,2026 to 2036
  • Figure 40: North America Market Attractiveness Analysis by Dosage Form
  • Figure 41: North America Market Value Share and BPS Analysis by End User,2026 and 2036
  • Figure 42: North America Market Y-o-Y Growth Comparison by End User,2026 to 2036
  • Figure 43: North America Market Attractiveness Analysis by End User
  • Figure 44: Latin America Market Value Share and BPS Analysis by Country,2026 and 2036
  • Figure 45: Latin America Market Value Share and BPS Analysis by Product,2026 and 2036
  • Figure 46: Latin America Market Y-o-Y Growth Comparison by Product,2026 to 2036
  • Figure 47: Latin America Market Attractiveness Analysis by Product
  • Figure 48: Latin America Market Value Share and BPS Analysis by Technology,2026 and 2036
  • Figure 49: Latin America Market Y-o-Y Growth Comparison by Technology,2026 to 2036
  • Figure 50: Latin America Market Attractiveness Analysis by Technology
  • Figure 51: Latin America Market Value Share and BPS Analysis by Strain Coverage,2026 and 2036
  • Figure 52: Latin America Market Y-o-Y Growth Comparison by Strain Coverage,2026 to 2036
  • Figure 53: Latin America Market Attractiveness Analysis by Strain Coverage
  • Figure 54: Latin America Market Value Share and BPS Analysis by Dosage Form,2026 and 2036
  • Figure 55: Latin America Market Y-o-Y Growth Comparison by Dosage Form,2026 to 2036
  • Figure 56: Latin America Market Attractiveness Analysis by Dosage Form
  • Figure 57: Latin America Market Value Share and BPS Analysis by End User,2026 and 2036
  • Figure 58: Latin America Market Y-o-Y Growth Comparison by End User,2026 to 2036
  • Figure 59: Latin America Market Attractiveness Analysis by End User
  • Figure 60: Western Europe Market Value Share and BPS Analysis by Country,2026 and 2036
  • Figure 61: Western Europe Market Value Share and BPS Analysis by Product,2026 and 2036
  • Figure 62: Western Europe Market Y-o-Y Growth Comparison by Product,2026 to 2036
  • Figure 63: Western Europe Market Attractiveness Analysis by Product
  • Figure 64: Western Europe Market Value Share and BPS Analysis by Technology,2026 and 2036
  • Figure 65: Western Europe Market Y-o-Y Growth Comparison by Technology,2026 to 2036
  • Figure 66: Western Europe Market Attractiveness Analysis by Technology
  • Figure 67: Western Europe Market Value Share and BPS Analysis by Strain Coverage,2026 and 2036
  • Figure 68: Western Europe Market Y-o-Y Growth Comparison by Strain Coverage,2026 to 2036
  • Figure 69: Western Europe Market Attractiveness Analysis by Strain Coverage
  • Figure 70: Western Europe Market Value Share and BPS Analysis by Dosage Form,2026 and 2036
  • Figure 71: Western Europe Market Y-o-Y Growth Comparison by Dosage Form,2026 to 2036
  • Figure 72: Western Europe Market Attractiveness Analysis by Dosage Form
  • Figure 73: Western Europe Market Value Share and BPS Analysis by End User,2026 and 2036
  • Figure 74: Western Europe Market Y-o-Y Growth Comparison by End User,2026 to 2036
  • Figure 75: Western Europe Market Attractiveness Analysis by End User
  • Figure 76: Eastern Europe Market Value Share and BPS Analysis by Country,2026 and 2036
  • Figure 77: Eastern Europe Market Value Share and BPS Analysis by Product,2026 and 2036
  • Figure 78: Eastern Europe Market Y-o-Y Growth Comparison by Product,2026 to 2036
  • Figure 79: Eastern Europe Market Attractiveness Analysis by Product
  • Figure 80: Eastern Europe Market Value Share and BPS Analysis by Technology,2026 and 2036
  • Figure 81: Eastern Europe Market Y-o-Y Growth Comparison by Technology,2026 to 2036
  • Figure 82: Eastern Europe Market Attractiveness Analysis by Technology
  • Figure 83: Eastern Europe Market Value Share and BPS Analysis by Strain Coverage,2026 and 2036
  • Figure 84: Eastern Europe Market Y-o-Y Growth Comparison by Strain Coverage,2026 to 2036
  • Figure 85: Eastern Europe Market Attractiveness Analysis by Strain Coverage
  • Figure 86: Eastern Europe Market Value Share and BPS Analysis by Dosage Form,2026 and 2036
  • Figure 87: Eastern Europe Market Y-o-Y Growth Comparison by Dosage Form,2026 to 2036
  • Figure 88: Eastern Europe Market Attractiveness Analysis by Dosage Form
  • Figure 89: Eastern Europe Market Value Share and BPS Analysis by End User,2026 and 2036
  • Figure 90: Eastern Europe Market Y-o-Y Growth Comparison by End User,2026 to 2036
  • Figure 91: Eastern Europe Market Attractiveness Analysis by End User
  • Figure 92: East Asia Market Value Share and BPS Analysis by Country,2026 and 2036
  • Figure 93: East Asia Market Value Share and BPS Analysis by Product,2026 and 2036
  • Figure 94: East Asia Market Y-o-Y Growth Comparison by Product,2026 to 2036
  • Figure 95: East Asia Market Attractiveness Analysis by Product
  • Figure 96: East Asia Market Value Share and BPS Analysis by Technology,2026 and 2036
  • Figure 97: East Asia Market Y-o-Y Growth Comparison by Technology,2026 to 2036
  • Figure 98: East Asia Market Attractiveness Analysis by Technology
  • Figure 99: East Asia Market Value Share and BPS Analysis by Strain Coverage,2026 and 2036
  • Figure 100: East Asia Market Y-o-Y Growth Comparison by Strain Coverage,2026 to 2036
  • Figure 101: East Asia Market Attractiveness Analysis by Strain Coverage
  • Figure 102: East Asia Market Value Share and BPS Analysis by Dosage Form,2026 and 2036
  • Figure 103: East Asia Market Y-o-Y Growth Comparison by Dosage Form,2026 to 2036
  • Figure 104: East Asia Market Attractiveness Analysis by Dosage Form
  • Figure 105: East Asia Market Value Share and BPS Analysis by End User,2026 and 2036
  • Figure 106: East Asia Market Y-o-Y Growth Comparison by End User,2026 to 2036
  • Figure 107: East Asia Market Attractiveness Analysis by End User
  • Figure 108: South Asia and Pacific Market Value Share and BPS Analysis by Country,2026 and 2036
  • Figure 109: South Asia and Pacific Market Value Share and BPS Analysis by Product,2026 and 2036
  • Figure 110: South Asia and Pacific Market Y-o-Y Growth Comparison by Product,2026 to 2036
  • Figure 111: South Asia and Pacific Market Attractiveness Analysis by Product
  • Figure 112: South Asia and Pacific Market Value Share and BPS Analysis by Technology,2026 and 2036
  • Figure 113: South Asia and Pacific Market Y-o-Y Growth Comparison by Technology,2026 to 2036
  • Figure 114: South Asia and Pacific Market Attractiveness Analysis by Technology
  • Figure 115: South Asia and Pacific Market Value Share and BPS Analysis by Strain Coverage,2026 and 2036
  • Figure 116: South Asia and Pacific Market Y-o-Y Growth Comparison by Strain Coverage,2026 to 2036
  • Figure 117: South Asia and Pacific Market Attractiveness Analysis by Strain Coverage
  • Figure 118: South Asia and Pacific Market Value Share and BPS Analysis by Dosage Form,2026 and 2036
  • Figure 119: South Asia and Pacific Market Y-o-Y Growth Comparison by Dosage Form,2026 to 2036
  • Figure 120: South Asia and Pacific Market Attractiveness Analysis by Dosage Form
  • Figure 121: South Asia and Pacific Market Value Share and BPS Analysis by End User,2026 and 2036
  • Figure 122: South Asia and Pacific Market Y-o-Y Growth Comparison by End User,2026 to 2036
  • Figure 123: South Asia and Pacific Market Attractiveness Analysis by End User
  • Figure 124: Middle East & Africa Market Value Share and BPS Analysis by Country,2026 and 2036
  • Figure 125: Middle East & Africa Market Value Share and BPS Analysis by Product,2026 and 2036
  • Figure 126: Middle East & Africa Market Y-o-Y Growth Comparison by Product,2026 to 2036
  • Figure 127: Middle East & Africa Market Attractiveness Analysis by Product
  • Figure 128: Middle East & Africa Market Value Share and BPS Analysis by Technology,2026 and 2036
  • Figure 129: Middle East & Africa Market Y-o-Y Growth Comparison by Technology,2026 to 2036
  • Figure 130: Middle East & Africa Market Attractiveness Analysis by Technology
  • Figure 131: Middle East & Africa Market Value Share and BPS Analysis by Strain Coverage,2026 and 2036
  • Figure 132: Middle East & Africa Market Y-o-Y Growth Comparison by Strain Coverage,2026 to 2036
  • Figure 133: Middle East & Africa Market Attractiveness Analysis by Strain Coverage
  • Figure 134: Middle East & Africa Market Value Share and BPS Analysis by Dosage Form,2026 and 2036
  • Figure 135: Middle East & Africa Market Y-o-Y Growth Comparison by Dosage Form,2026 to 2036
  • Figure 136: Middle East & Africa Market Attractiveness Analysis by Dosage Form
  • Figure 137: Middle East & Africa Market Value Share and BPS Analysis by End User,2026 and 2036
  • Figure 138: Middle East & Africa Market Y-o-Y Growth Comparison by End User,2026 to 2036
  • Figure 139: Middle East & Africa Market Attractiveness Analysis by End User
  • Figure 140: Global Market - Tier Structure Analysis
  • Figure 141: Global Market - Company Share Analysis

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来源信息
来源：BioSpace / ACCESS Newswire发布日期：2026-05-01抓取时间：2026-06-17T18:50:33.758Z相关标的：MRNA归档状态：正文低置信 / 未作为证据
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打开原文

Moderna Reports Fourth Quarter and Fiscal Year 2025 Financial Results and Provides Business Updates

来源信息
来源：Nasdaq / ACCESS Newswire发布日期：2026-02-13抓取时间：2026-06-17T18:50:34.298Z相关标的：MRNA归档状态：已归档 / 弹窗可读
中文摘要

一句话结论

Nasdaq 转载的 Moderna FY2025 公告显示公司 2025 年收入降至 19 亿美元、净亏损 28 亿美元，但管理层强调成本削减、三款已批准产品、国际协议和多个 2026 管线节点，为后 COVID 转型提供基础。

关键事实

  • 发布日期为 2026-02-13，原始来源为 ACCESS Newswire / Moderna。
  • Q4 2025 revenue 为 6.78 亿美元，GAAP net loss 为 8 亿美元，GAAP EPS 为 -2.11 美元。
  • FY2025 revenue 为 19 亿美元，GAAP net loss 为 28 亿美元，diluted EPS 为 -7.26 美元。
  • 公司称 2025 年 annual operating expenses 降低约 22 亿美元，超过成本削减目标。
  • 公司 2026 年计划实现最多 10% revenue growth，并继续降低 GAAP operating expenses。
  • 商业资产包括 Spikevax、mNEXSPIKE 和 mRESVIA，并提到 mNEXSPIKE geographic expansion、Mexico/Taiwan 长期协议、Canada/Australia 批准。
  • 文章提到 influenza vaccine 在 EU、Canada、Australia 进入 regulatory review；美国 FDA 当时发出 Refusal-to-File letter，公司请求 Type A meeting。
  • Norovirus Phase 3 trial fully enrolled，data readout expected in 2026；intismeran autogene MIBC Phase 2 full enrollment。

作者观点与证据

这是公司年度公告转载，观点偏转型叙事：成本降了、产品多了、2026 有批准和读出。硬证据是收入、净亏损、费用削减、产品批准和试验状态；前瞻性增长与读出需要后续验证。

与相关标的的关系

对 MRNA 是财务和转型基线。它说明公司不再是 COVID 高峰盈利机器，而是亏损中的多产品平台；估值要看 2026 新品和管线是否抵消收入萎缩。

时效性与限制

2 月公告已被 5 月 Q1 更新部分覆盖，尤其现金和诉讼和解费用。适合用于 2025 财务背景，2026 现金指引需以后续 Q1 口径为准。

后续跟踪

  • 2026 revenue 是否接近最多 10% 增长目标。
  • operating expense 降幅是否持续。
  • FDA mRNA-1010 路径是否从 RTF 后恢复。
  • Norovirus、intismeran 和 rare disease 数据读出。
英文原文
Moderna Reports Fourth Quarter and Fiscal Year 2025 Financial Results and Provides Business Updates

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Reports fourth quarter revenue of $0.7 billion , GAAP net loss of $(0.8) billion and GAAP EPS of $(2.11)

Reports full-year revenue of $1.9 billion , GAAP net loss of $(2.8) billion and GAAP diluted EPS of $(7.26)

Reiterates plan to deliver up to 10% revenue growth and GAAP operating expense reductions in 2026

Announces influenza vaccine filing accepted for regulatory review in the EU, Canada and Australia ; Company received Refusal-to-File letter from U.S. FDA and has requested Type A meeting to understand path forward

Announces Norovirus Phase 3 trial fully enrolled with a data readout expected in 2026

Announces full enrollment of Phase 2 intismeran autogene trial in muscle invasive bladder cancer

CAMBRIDGE, MA / ACCESS Newswire / February 13, 2026 / Moderna, Inc. (NASDAQ:MRNA) today reported financial results and provided business updates for the fourth quarter of 2025.

"In 2025, we sharpened our commercial execution, launched our third product and brought online three international manufacturing sites, while advancing our mRNA pipeline. At the same time, we lowered our annual operating expenses by approximately $2.2 billion , significantly surpassing our cost-reduction targets," said Stéphane Bancel , Chief Executive Officer of Moderna. "We entered the new year with strong momentum despite the continued challenging environment in the U.S. , poised to deliver up to 10 percent revenue growth through mNEXSPIKE expansion and our international strategic partnerships. We look forward to delivering multiple potential product approvals and late-stage clinical readouts, while driving continued innovation across our mRNA platform."

Commercial Updates

Moderna is entering the year with three approved products, Spikevax®, mNEXSPIKE® and mRESVIA®, with seasonal vaccines expected to deliver up to 10% revenue growth in 2026. In line with its strategy to drive growth through geographic expansion and new product launches, the Company recently announced long-term agreements with Mexico and Taiwan for respiratory vaccines, received regulatory approvals in Canada and Australia for mNEXSPIKE, and the strain-updated Spikevax vaccine was authorized in the UK for use in the spring vaccination campaign. The Company also announced a strategic collaboration with Recordati to globally commercialize Moderna's propionic acidemia candidate.

Fourth Quarter 2025 Financial Results

Revenue : Total revenue for the fourth quarter of 2025 was $678 million , on the higher end of the Company's prior expectations, and was driven primarily by COVID vaccine sales. Product sales were $264 million in the U.S. and $381 million in international markets. Fourth quarter revenue decreased 30% compared to the same period in 2024, primarily reflecting lower COVID vaccine sales volume compared to the prior-year period.

Cost of Sales: Cost of sales for the fourth quarter of 2025 was $452 million , including third-party royalties of $34 million and inventory write-downs of $144 million . Cost of sales decreased 39% compared to the same period in 2024, primarily reflecting lower contract manufacturing wind-down costs and inventory write-downs.

Research and Development Expenses: Research and development expenses for the fourth quarter of 2025 were $775 million , a 31% decrease compared to the same period in 2024. The decrease was driven primarily by lower clinical development and manufacturing costs, reflecting the wind-down of large Phase 3 respiratory programs, continued portfolio prioritization and cost discipline across the organization.

Selling, General and Administrative Expenses: Selling, general and administrative expenses for the fourth quarter of 2025 were $308 million , a 12% decrease compared to the same period in 2024. The decline was primarily driven by reductions in consulting and external services across multiple functions, reflecting continued discipline across the organization.

Income Taxes: Income tax provisions for both periods were not material, as the Company continues to maintain a global valuation allowance against most of its deferred tax assets.

Net Loss: Net loss was $(826) million for the fourth quarter of 2025, compared to net loss of $(1.1) billion for the fourth quarter of 2024.

Loss Per Share: Loss per share was $(2.11) for the fourth quarter of 2025, compared to loss per share of $(2.91) for the fourth quarter of 2024.

Full Year 2025 Financial Results

Revenue : Total revenue for the full year 2025 was $1.9 billion , a 40% decrease compared to 2024, with the majority generated from COVID vaccine sales, along with $126 million of other revenue. U.S. revenue totaled $1.2 billion , while revenue from international markets was $745 million . The year-over-year decrease primarily reflected lower COVID vaccine sales volume across all regions. During 2025, the Company also began recognizing stand-ready manufacturing revenue related to its long-term strategic partnerships, which is reported in other revenue.

Cost of Sales: Cost of sales for the full year 2025 was $868 million , including third-party royalties of $88 million and inventory write-downs of $291 million . Cost of sales decreased 41% compared to 2024, driven primarily by manufacturing productivity and operational efficiencies, lower inventory write-downs, lower contract manufacturing wind-down costs, and lower sales volume.

Research and Development Expenses: Research and development expenses for the full year 2025 were $3.1 billion , a 31% decrease compared to 2024. The decrease was driven primarily by lower clinical development and manufacturing costs, reflecting the wind-down of large Phase 3 respiratory programs, continued portfolio prioritization and cost discipline across the organization. These decreases were partially offset by increased investment in the Company's norovirus vaccine and oncology programs. In addition, 2024 included costs related to the purchase of two priority review vouchers, which did not recur in 2025.

Selling, General and Administrative Expenses: Selling, general and administrative expenses for the full year 2025 were $1.0 billion , a 13% decrease compared to 2024. The decrease was driven primarily by lower consulting and external services, along with reduced spending across multiple functions and operating areas, while the Company continued to invest in supporting its commercial operations and broader business activities.

Income Taxes: Income tax provisions for both periods were not material, as the Company continues to maintain a global valuation allowance against most of its deferred tax assets.

Net Loss: Net loss for the full year 2025 was $2.8 billion , compared to $3.6 billion for the full year 2024.

Loss Per Share: Loss per share for the full year 2025 was $(7.26) , compared to $(9.28) for the full year 2024.

Cash Position: Cash, cash equivalents and investments as of December 31, 2025 , were $8.1 billion , compared to compared to $9.5 billion as of December 31, 2024 . The year-end balance included a $600 million initial draw on the Company's $1.5 billion credit facility, with the year-over-year decrease primarily driven by operating losses associated with continued investment in research and development and advancement of the Company's pipeline.

2026 Financial Framework

Revenue: The Company is targeting up to 10% growth from 2025 revenue and expects 2026 revenue split to be approximately 50% U.S. and approximately 50% international.

Cost of Sales: Cost of sales for 2026 is expected to be approximately $0.9 billion .

Research and Development Expenses: Research and development expenses for 2026 are anticipated to be approximately $3.0 billion .

Selling, General and Administrative Expenses: Selling, general and administrative expenses for 2026 are projected to be approximately $1.0 billion .

Income Taxes: The Company expects its full-year tax expense to be negligible.

Capital Expenditures: Capital expenditures for 2026 are expected to be $0.2 to $0.3 billion .

Cash and Investments: Year-end cash and investments for 2026 are projected to be $5.5 to $6.0 billion . Excludes any additional draw down from the Company's credit facility.

Recent Progress and Upcoming Late-Stage Pipeline Milestones

Infectious disease vaccines:

  • Seasonal flu + COVID vaccine: Currently, the Company's mRNA-1083 regulatory filing is under review in Europe and Canada . Moderna is awaiting further guidance from U.S. FDA on refiling the submission for its flu/COVID combination vaccine.
  • Seasonal flu vaccine: The Company's mRNA-1010 regulatory filings are under review in Europe , Canada and Australia and potential approvals are expected to begin in 2026. Moderna received a Refusal-to-File letter from the U.S. FDA and has requested a Type A meeting to understand the path forward.
  • Norovirus vaccine: Moderna's ongoing Phase 3 safety and efficacy study of mRNA-1403 is fully enrolled in a second Northern Hemisphere season (2025-2026) with a data readout expected in 2026, subject to case accruals.

Oncology therapeutics:

  • Intismeran autogene: The Company is advancing mRNA-4157 in collaboration with Merck, with eight total Phase 2 and Phase 3 clinical trials underway across multiple tumor types including melanoma, non-small cell lung cancer (NSCLC), bladder cancer and renal cell carcinoma. The Phase 3 adjuvant melanoma, the Phase 2 adjuvant renal cell carcinoma, and most recently, the Phase 2 adjuvant muscle invasive bladder cancer trials are fully enrolled. Moderna and Merck recently announced positive five-year Phase 2b adjuvant melanoma data, which showed intismeran autogene in combination with KEYTRUDA reduced the risk of recurrence or death by 49% compared to KEYTRUDA alone. Moderna expects Phase 3 adjuvant melanoma data potentially in 2026.
  • mRNA-4359: Moderna's Phase 1/2 study of mRNA-4359, an investigational wholly-owned cancer antigen therapy, is ongoing. The Phase 2 portion of the study includes cohorts in first-line metastatic melanoma, second-line+ metastatic melanoma and first-line metastatic NSCLC, and the Company expects a potential Phase 2 data readout in 2026.

Rare disease therapeutics:

  • Propionic acidemia (PA) therapeutic: The Company's PA candidate, mRNA-3927, is in a registrational study and target enrollment has been reached. Moderna expects a potential data readout in 2026.
  • Methylmalonic acidemia (MMA) therapeutic: Moderna's mRNA-3705 has been selected by the FDA for the Support for Clinical Trials Advancing Rare Disease Therapeutics (START) pilot program, with a registrational study expected to begin in 2026.

Moderna Corporate Updates

  • Hosted Analyst Day event highlighting pipeline progress and business strategy updates on November 20, 2025 .
  • Published Moderna CEO Stéphane Bancel's annual letter to shareholders on January 5, 2026 .
  • Provided business and pipeline updates at the 44th Annual J.P. Morgan Healthcare Conference on January 12, 2026 .
  • Appointed David Berman , M.D., Ph.D. to Chief Development Officer of Moderna, effective March 2, 2026 .
  • Scheduled the Moderna Annual Meeting of Shareholders to be held on Wednesday, May 6, 2026 , at 8:00 a.m. ET .

Company Accolades

  • Moderna was recognized by TIME as one of America's Most Iconic Companies.

Key 2026 Investor and Analyst Event Dates

  • Analyst Day: November 12

Investor Call and Webcast Information

Moderna will host a live conference call and webcast at 8:00 a.m. ET on February 13, 2026 . To access the live conference call via telephone, please register at the link below. Once registered, dial-in numbers and a unique pin number will be provided. A live webcast of the call will also be available under "Events and Presentations" in the Investors section of the Moderna website.

  • Telephone: https://register-conf.media-server.com/register/BIf7fdfaa3a1354d55999e80cdd7546c62
  • Webcast: https://investors.modernatx.com

The archived webcast will be available on Moderna's website approximately two hours after the conference call and will be available for one year following the call.

About Moderna

Moderna is a pioneer and leader in the field of mRNA medicine. Through the advancement of its technology platform, Moderna is reimagining how medicines are made to transform how we treat and prevent diseases. Since its founding, Moderna's mRNA platform has enabled the development of vaccines and therapeutics across infectious diseases, cancer, rare diseases and more.

With a global team and a unique culture, driven by the company's values and mindsets, Moderna's mission is to deliver the greatest possible impact to people through mRNA medicines. For more information about Moderna, please visit modernatx.com and connect with us on X, Facebook, Instagram, YouTube and LinkedIn.

MODERNA, INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (Unaudited, in millions, except per share data)

Three Months Ended December 31 ,

Years Ended December 31 ,

2025

2024

2025

2024

Revenue:

Net product sales

$

645

$

938

$

1,818

$

3,109

Other revenue1

33

28

126

127

Total revenue

678

966

1,944

3,236

Operating expenses:

Cost of sales

452

739

868

1,464

Research and development

775

1,122

3,132

4,543

Selling, general and administrative

308

351

1,018

1,174

Total operating expenses

1,535

2,212

5,018

7,181

Loss from operations

(857

)

(1,246

)

(3,074

)

(3,945

)

Interest income

70

91

314

425

Other expense, net

(12

)

(29

)

(8

)

(87

)

Loss before income taxes

(799

)

(1,184

)

(2,768

)

(3,607

)

Provision for (benefit from) income taxes

27

(64

)

54

(46

)

Net loss

$

(826

)

$

(1,120

)

$

(2,822

)

$

(3,561

)

Net loss per share

Basic and Diluted

$

(2.11

)

$

(2.91

)

$

(7.26

)

$

(9.28

)

Weighted average common shares used in calculation of net loss per share

Basic and Diluted

392

385

389

384

_______

1Includes grant, collaboration, licensing and royalty, and stand-ready manufacturing revenue.

MODERNA, INC. CONDENSED CONSOLIDATED BALANCE SHEETS (Unaudited, in millions)

December 31 ,

December 31 ,

2025

2024

Assets

Current assets:

Cash and cash equivalents

$

2,595

$

1,927

Investments

3,204

5,098

Accounts receivable, net

184

358

Inventory

153

117

Prepaid expenses and other current assets

408

599

Total current assets

6,544

8,099

Investments, non-current

2,336

2,494

Property, plant and equipment, net

2,134

2,196

Right-of-use assets, operating leases

719

759

Other non-current assets

605

594

Total assets

$

12,338

$

14,142

Liabilities and Stockholders' Equity

Current liabilities:

Accounts payable

$

317

$

405

Accrued liabilities

1,386

1,427

Deferred revenue

99

153

Other current liabilities

185

221

Total current liabilities

1,987

2,206

Deferred revenue, non-current

153

58

Operating lease liabilities, non-current

653

671

Financing lease liabilities, non-current

20

39

Long-term debt

590

-

Other non-current liabilities

285

267

Total liabilities

3,688

3,241

Stockholders' equity:

Additional paid-in capital

1,382

866

Accumulated other comprehensive income (loss)

45

(10

)

Retained earnings

7,223

10,045

Total stockholders' equity

8,650

10,901

Total liabilities and stockholders' equity

$

12,338

$

14,142

MODERNA, INC. CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS (Unaudited, in millions)

Years Ended December 31 ,

2025

2024

Operating activities

Net loss

$

(2,822

)

$

(3,561

)

Adjustments to reconcile net loss to net cash used in operating activities:

Stock-based compensation

483

429

Depreciation and amortization

215

189

Amortization/accretion of investments

(67

)

(95

)

Loss on equity investments, net

8

52

Other non-cash items

77

60

Changes in assets and liabilities:

Accounts receivable, net

156

534

Prepaid expenses and other assets

153

145

Inventory

(34

)

83

Right-of-use assets, operating leases

38

(53

)

Accounts payable

(92

)

(69

)

Accrued liabilities

(2

)

(385

)

Deferred revenue

41

(439

)

Operating lease liabilities

(21

)

28

Other liabilities

(6

)

78

Net cash used in operating activities

(1,873

)

(3,004

)

Investing activities

Purchases of marketable securities

(5,768

)

(6,529

)

Proceeds from maturities of marketable securities

5,563

5,562

Proceeds from sales of marketable securities

2,353

3,967

Purchases of property, plant and equipment

(192

)

(1,051

)

Purchase of intangible asset

(10

)

-

Net cash provided by investing activities

1,946

1,949

Financing activities

Proceeds from credit facility

600

-

Payments of credit facility issuance costs

(22

)

-

Proceeds from issuance of common stock through equity plans

35

66

Tax payments related to net share settlements on equity awards

(2

)

-

Changes in financing lease liabilities

(18

)

(10

)

Net cash provided by financing activities

593

56

Effect of changes in exchange rates on cash and cash equivalents

2

-

Net increase (decrease) in cash, cash equivalents and restricted cash

668

(999

)

Cash, cash equivalents and restricted cash, beginning of year

1,929

2,928

Cash, cash equivalents and restricted cash, end of period

$

2,597

$

1,929

Spikevax®, mRESVIA® and mNEXSPIKE® are registered trademarks of Moderna.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements regarding: Moderna's 2026 financial framework, including its plan to deliver up to 10% revenue growth and GAAP operating expense reductions, and its projected year-end cash balance; Moderna's commercial growth drivers, including geographic expansion and new product launches; Moderna's continued cost discipline; anticipated mNEXSPIKE expansion; Moderna's international strategic partnerships; potential mRNA-4157 Phase 3 adjuvant melanoma data in 2026; the potential of Moderna's expanded oncology portfolio; pending and anticipated regulatory filings and potential approvals, including timing of approvals; Moderna's strategic collaboration with Recordati; Moderna's requested Type A meeting to understand the path forward for mRNA-1010; and anticipated progress and milestones for Moderna's pipeline programs, including potential near-term data readouts and other catalysts. In some cases, forward-looking statements can be identified by terminology such as "will," "may," "should," "could," "expects," "intends," "plans," "aims," "anticipates," "believes," "estimates," "predicts," "potential," "continue," or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. The forward-looking statements in this press release are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond Moderna's control and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements. These risks, uncertainties, and other factors include, among others, those risks and uncertainties described under the heading "Risk Factors" in Moderna's Annual Report on Form 10-K for the fiscal year ended December 31, 2024 , filed with the U.S. Securities and Exchange Commission (SEC), and in subsequent filings made by Moderna with the SEC , which are available on the SEC's website at www.sec.gov . Except as required by law, Moderna disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release in the event of new information, future developments or otherwise. These forward-looking statements are based on Moderna's current expectations and speak only as of the date of this press release.

###

Moderna Contacts

Media: Chris Ridley Head of Global Media Relations+1 617-800-3651 Chris.Ridley@modernatx.com

Investors: Lavina Talukdar Senior Vice President & Head of Investor Relations+1 617-209-5834 Lavina.Talukdar@modernatx.com

SOURCE: Moderna, Inc.

View the original press release on ACCESS Newswire

The views and opinions expressed herein are the views and opinions of the author and do not necessarily reflect those of Nasdaq, Inc.

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打开原文

Moderna (NASDAQ: MRNA) grows Q1 2026 revenue but books $1.3B loss

来源信息
来源：StockTitan SEC filing mirror发布日期：2026-05-01抓取时间：2026-06-17T18:50:34.429Z相关标的：MRNA归档状态：已归档 / 弹窗可读
中文摘要

一句话结论

StockTitan 的 MRNA 8-K mirror 把 Q1 2026 描述为收入回升但亏损仍重的一季：收入同比从 1.08 亿美元升至 3.89 亿美元，现金投资仍有 75 亿美元，但 9 亿美元诉讼和解费用导致 13.43 亿美元 GAAP 净亏损。

关键事实

  • 发布日期为 2026-05-01，来源为 Moderna 8-K / Exhibit 99.1 镜像。
  • Q1 2026 revenue 为 3.89 亿美元，高于上年同期 1.08 亿美元。
  • 国际市场贡献 3.11 亿美元，美国贡献 7800 万美元，增长主要来自 COVID vaccine sales 和 long-term government partnerships。
  • GAAP net loss 为 13.43 亿美元，GAAP EPS 为 -3.40 美元，其中包括约 9 亿美元 non-recurring litigation settlement charge。
  • R&D expense 为 6.49 亿美元，同比下降 24%；SG&A 为 1.73 亿美元，同比下降 18%。
  • 2026 年目标为收入较 2025 年最多增长 10%，cost of sales 约 18 亿美元、R&D 约 30 亿美元、SG&A 约 10 亿美元。
  • 2026 年底 cash and investments 预计为 45-50 亿美元，不包括额外使用剩余 credit facility。
  • 公司推进 mNEXSPIKE、mCOMBRIAX、mRESVIA 欧洲批准，以及 oncology、norovirus、rare disease 等后期项目。

作者观点与证据

StockTitan 有自己的正负面框架，但核心可用事实来自 8-K。文章观点是收入改善和成本下降被一次性诉讼费用、仍高的成本基数和现金消耗抵消。硬证据包括收入、亏损、费用、现金和指引。

与相关标的的关系

对 MRNA 是最直接的财务 runway 证据。它支持“现金还够、但 2026 仍显著烧钱”的判断，也说明短期估值不能用 P/E，而要看 EV、收入、现金消耗和管线节点。

时效性与限制

Q1 2026 口径是当前最近季度财务。限制是 StockTitan 页面含 AI/分析式摘要，应以 8-K/公司公告数字为主，不把其情绪标签当结论。

后续跟踪

  • Q2/Q3 现金消耗和 9.5 亿美元和解现金支付影响。
  • 2026 revenue 是否接近最多 10% 增长目标。
  • R&D/SG&A 是否继续按目标下降。
  • 新批准产品和 Phase 3 读出能否支撑 2027 收入。
英文原文
Moderna (NASDAQ: MRNA) grows Q1 2026 revenue but books $1.3B loss

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[8-K] Moderna, Inc. Reports Material Event

Moderna (NASDAQ: MRNA) grows Q1 2026 revenue but books $1.3B loss

Filing Impact

(High)

Filing Sentiment

(Neutral)

Form Type

8-K

Rhea-AI Filing Summary

  • English
  • Italian
  • Spanish
  • German
  • Korean
  • French
  • Arabic

Moderna, Inc. reported first quarter 2026 revenue of $389 million, up from $108 million a year earlier, with $311 million from international markets as COVID vaccine sales rose under long-term government partnerships.

The company posted a GAAP net loss of $1.343 billion, or $(3.40) per share, largely due to a $0.9 billion non-recurring litigation settlement charge recorded in cost of sales. Research and development expenses fell 24% to $649 million and selling, general and administrative expenses decreased 18% to $173 million, reflecting wind-down of large respiratory programs and cost discipline. Cash, cash equivalents and investments totaled $7.5 billion as of March 31, 2026, and Moderna is targeting up to 10% revenue growth for 2026 while projecting year-end cash and investments of $4.5 to $5.0 billion.

Positive

  • Rapid revenue growth and cost reductions : Q1 2026 revenue rose to $389 million from $108 million year over year, while research and development and selling, general and administrative expenses declined 24% and 18%, respectively, reflecting higher product sales and organizational cost discipline.
  • Advancing pipeline and new approvals : Moderna secured European approvals for mNEXSPIKE, flu plus COVID combination vaccine mCOMBRIAX and mRESVIA for adults, and advanced multiple late-stage programs including Phase 3 studies in oncology, norovirus and rare diseases with several potential 2026 data readouts.

Negative

  • Large GAAP net loss driven by litigation costs : Q1 2026 GAAP net loss reached $(1.343) billion, or $(3.40) per share, including a $0.9 billion non-recurring litigation settlement charge recorded in cost of sales, and year-end 2026 cash and investments are projected to decline to $4.5–$5.0 billion.
  • High cost base despite cuts : Total Q1 2026 operating expenses were $1.777 billion versus $1.158 billion a year earlier, as litigation settlement-related expenses offset reductions in research and development and selling, general and administrative spending.

Insights

##

Biopharma equity analyst

neutral

Strong revenue rebound offset by large one-time legal charge.

Moderna grew Q1 2026 revenue to $389 million from $108 million, driven mainly by international COVID vaccine sales under long-term partnerships. Operating expenses declined year over year as R&D fell to $649 million and SG&A to $173 million, showing cost discipline.

Despite this, the company reported a GAAP net loss of $(1.343) billion, or $(3.40) per share, mainly from a $0.9 billion non-recurring litigation settlement recorded in cost of sales. Cash, cash equivalents and investments stood at $7.5 billion on March 31, 2026, down from $8.1 billion at year-end.

For 2026, Moderna targets up to 10% revenue growth versus 2025 and expects cost of sales of about $1.8 billion, R&D around $3.0 billion, and SG&A about $1.0 billion. The company projects year-end 2026 cash and investments of $4.5–$5.0 billion, excluding additional use of its remaining credit facility.

8-K Event Classification

2 items: 2.02, 9.01

2 items

Item 2.02

Results of Operations and Financial Condition

Financial

Disclosure of earnings results, typically an earnings press release or preliminary financials.

Item 9.01

Financial Statements and Exhibits

Exhibits

Financial statements, pro forma financial information, and exhibit attachments filed with this report.

Key Figures

Q1 2026 revenue: $389 million

Q1 2026 GAAP net loss: $(1.343) billion

Q1 2026 GAAP EPS: $(3.40)

+5 more

8 metrics

Q1 2026 revenue

$389 million

Total revenue for the three months ended March 31, 2026

Q1 2026 GAAP net loss

$(1.343) billion

Net loss for the three months ended March 31, 2026

Q1 2026 GAAP EPS

$(3.40)

Basic and diluted net loss per share in Q1 2026

Litigation settlement charge

$0.9 billion

Non-recurring litigation settlement included in 2026 cost of sales and results

Cash and investments

$7.5 billion

Cash, cash equivalents and investments as of March 31, 2026

Q1 2026 cost of sales

$955 million

Cost of sales in Q1 2026 including $878 million litigation-related expenses

2026 R&D guidance

$3.0 billion

Anticipated research and development expenses for full-year 2026

2026 revenue growth target

up to 10%

Targeted growth from 2025 revenue in 2026

Key Terms

non-recurring litigation settlement charge, PDUFA goal date, Phase 3 clinical study, adjuvant melanoma, +2 more

6 terms

non-recurring litigation settlement charge

financial

"including $0.9 billion non-recurring litigation settlement charge"

PDUFA goal date

regulatory

"The U.S. FDA has assigned a Prescription Drug User Fee Act (PDUFA) goal date for mRNA-1010 of August 5, 2026."

The PDUFA goal date is the target deadline set by the U.S. Food and Drug Administration for completing its review of a new drug or biologic application. Investors watch it like a court date for a product: the outcome (approval, rejection, or request for more information) can sharply change a company’s revenue prospects and stock price, and the date gives a predictable event around which markets and planning can focus.

Phase 3 clinical study

medical

"Initiated Phase 3 clinical study evaluating intismeran autogene as monotherapy and in combination"

A phase 3 clinical study is a late-stage, large-scale test of a medical treatment in many patients to confirm how well it works and to monitor side effects before regulators consider approval. Think of it as a final dress rehearsal where the treatment is tested in diverse, real-world conditions to prove benefits outweigh risks. Investors watch these results because positive outcomes can clear the path to regulatory approval, sales, and major value changes.

adjuvant melanoma

medical

"Fully enrolled studies include a Phase 3 adjuvant melanoma"

propionic acidemia

medical

"Propionic acidemia (PA) therapeutic: The Company's PA candidate, mRNA-3927, is in a registrational study"

A rare inherited metabolic disorder in which the body cannot properly break down certain parts of protein and fat, causing a harmful buildup of propionic acid that can damage organs and the brain. It matters to investors because diagnosis, long-term care, newborn screening, and potential treatments—such as enzyme replacement, dietary management, or gene therapies—create distinct markets and regulatory pathways; think of it as a factory jam that creates demand for specialized fixes.

Deferred revenue

financial

"Deferred revenue, non-current | 154 | | | 153"

Cash a company has already received for goods or services it has promised but not yet delivered; it's recorded as a liability because the company still owes that product, service, or future revenue recognition. For investors, deferred revenue signals upcoming work or deliveries that will convert into reported sales over time and affects short-term obligations, cash flow quality, and how quickly a firm can grow recognized revenue—think of it like prepaid subscriptions or gift cards a business must honor later.

Earnings Snapshot

Revenue: $389 million · Guidance included

Q1 2026

Revenue

$389 million

Net loss

$(1.343) billion

GAAP EPS

$(3.40)

Cash, cash equivalents and investments

$7.5 billion

Guidance

The company targets up to 10% 2026 revenue growth from 2025 levels, expects 2026 cost of sales of approximately $1.8 billion including the $0.9 billion litigation charge, R&D expenses of about $3.0 billion, SG&A of about $1.0 billion, and projects year-end 2026 cash and investments of $4.5–$5.0 billion.

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Understanding 8-K Material Events &rarr;

05/01/2026 - 06:32 AM

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0001682852 false 0001682852 2026-05-01 2026-05-01

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

FORM  8-K

CURRENT REPORT

Pursuant to Section 13 OR 15(d)

of The Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): May 1, 2026

MODERNA, INC.

(Exact name of registrant as specified in its charter)

Delaware   001-38753   81-3467528

(State or other jurisdiction of incorporation)    (Commission File Number)    (IRS Employer Identification No.)

325 Binney Street

Cambridge , MA

02142

(Address of principal executive offices)   (Zip code)

Registrant’s telephone number, including area code: ( 617 )  714-6500

Not Applicable

(Former name or former address, if changed since last report.)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title of each class Trading symbol(s) Name of each exchange on which registered

Common stock, par value $0.0001 per share MRNA The Nasdaq Stock Market LLC

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company       ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.       ☐

Item 2.02 Results of Operations and Financial Condition.

On May 1, 2026, Moderna, Inc. issued a press release announcing its financial results for the first quarter ended March 31, 2026. A copy of the press release is furnished as Exhibit 99.1 and is incorporated herein by reference.

The information in this Current Report on Form 8-K, including Exhibit 99.1 attached hereto, is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits .

Exhibit

No.    Description

99.1    Press release issued by Moderna, Inc. dated May 1, 2026

104 Cover Page Interactive Data File (embedded within the Inline XBRL document)

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

MODERNA, INC.

Date: May 1, 2026

By: /s/ James M. Mock

James M. Mock

Chief Financial Officer

Exhibit 99.1

Moderna Reports First Quarter 2026 Financial Results and Provides Business Updates

Reports first quarter revenue of $0.4 billion, with approximately 80% of revenue from international markets

Reports first quarter GAAP net loss of $(1.3) billion and GAAP EPS of $(3.40), including $0.9 billion non-recurring litigation settlement charge

Reiterates plan to deliver up to 10% revenue growth and GAAP operating expense reductions in 2026, excluding the non-recurring litigation settlement charge

Advanced infectious disease portfolio with key regulatory milestones in the EU, including approval of mNEXSPIKE and mCOMBRIAX, Moderna’s flu plus COVID combination vaccine

Initiated Phase 3 clinical study evaluating intismeran autogene as monotherapy and in combination with KEYTRUDA QLEX for treatment of high-risk Stage 1 non-small cell lung cancer

CAMBRIDGE, MA / ACCESSWIRE / May 1, 2026 / Moderna, Inc. (NASDAQ:MRNA) today reported financial results and provided business updates for the first quarter of 2026.

“The Moderna team delivered a great start to the year, driving significant revenue growth and substantial cost reductions building on actions taken in 2025. We received two product approvals in Europe, including the world’s first flu plus COVID combination vaccine, mCOMBRIAX. We also started a new pivotal trial for intismeran—our first Phase 3 monotherapy study for high-risk Stage 1 non-small cell lung cancer patients,” said Stéphane Bancel, Chief Executive Officer of Moderna. “Building on this strong first quarter momentum, we are excited to return to sales growth in 2026 and expect several additional approvals around the world, including for our seasonal flu vaccine, which would be Moderna’s fifth approved product. We also look forward to important pivotal readouts this year for our norovirus, intismeran in melanoma, and propionic acidemia programs."

Commercial Updates

During the first quarter, Moderna continued to advance its multi-year revenue growth strategy by executing on strategic partnerships and key approvals. In the UK, t he Company delivered the first shipment under its long-term strategic partnership. Moderna also received regulatory approval in Europe for mNEXSPIKE® and its flu plus COVID combination vaccine, mCOMBRIAX®, as well as mRESVIA® for all individuals aged 18 and older.

First Quarter 2026 Financial Results

Revenue : Total revenue for the first quarter of 2026 was $389 million, an increase of $281 million compared to the same period in 2025. Revenue was $78 million in the U.S. and $311 million in international markets. Net product sales increased due to higher COVID vaccine sales, primarily in international markets, as a result of deliveries under long-term strategic partnerships with government entities.

1

Cost of Sales: Cost of sales for the first quarter of 2026 was $955 million, including third-party royalties of $895 million and inventory write-downs of $38 million. Cost of sales increased by $865 million, compared to the same period in 2025, primarily driven by litigation settlement-related expenses of $878 million recognized in the first quarter of 2026 within third-party royalties. Excluding these expenses, cost of sales decreased compared to the same period in 2025, primarily due to lower unutilized manufacturing capacity costs, losses on firm purchase commitments and inventory write-downs, partially offset by higher sales volume.

Research and Development Expenses: Research and development expenses for the first quarter of 2026 were $649 million, a 24% decrease compared to the same period in 2025. The decrease was primarily driven by lower clinical development and manufacturing costs, reflecting the wind-down of large Phase 3 respiratory programs and congenital CMV studies, as well as the timing of clinical trial activities, partially offset by higher costs related to postmarketing commitments for the Company's COVID products.

Selling, General and Administrative Expenses: Selling, general and administrative expenses for the first quarter of 2026 were $173 million, an 18% decrease compared to the same period in 2025. The decrease was primarily driven by lower employee-related expenses, as well as reduced marketing costs and lower consulting and external services across multiple functions, reflecting continued discipline across the organization.

Income Taxes: Income tax provisions for both periods were not material, as the Company continues to maintain a global valuation allowance against most of its deferred tax assets.

Net Loss: Net loss was $(1.3) billion for the first quarter of 2026, compared to net loss of $(1.0) billion for the first quarter of 2025. Litigation settlement-related expenses had an unfavorable impact of $(0.9) billion on net loss for the first quarter of 2026.

Loss Per Share: Loss per share was $(3.40) for the first quarter of 2026, compared to loss per share of $(2.52) for the first quarter of 2025. Litigation settlement-related expenses had an unfavorable impact of $(2.22) on loss per share for the first quarter of 2026.

Cash Position: Cash, cash equivalents and investments as of March 31, 2026, were $7.5 billion, compared to $8.1 billion as of December 31, 2025. The decrease was primarily driven by operating losses associated with continued investment in research and development and advancement of the Company’s pipeline. Litigation settlement-related expenses recognized in the first quarter of 2026 did not impact cash during the period, as the related payment of $950 million is expected to be made in the third quarter of 2026.

2026 Financial Framework

Revenue: The Company is targeting up to 10% growth from 2025 revenue and expects 2026 revenue split to be approximately 50% U.S. and approximately 50% international.

Cost of Sales: Cost of sales for 2026 is now expected to be approximately $1.8 billion, including the $0.9 billion non-recurring litigation settlement charge.

2

Research and Development Expenses: Research and development expenses for 2026 are anticipated to be approximately $3.0 billion.

Selling, General and Administrative Expenses: Selling, general and administrative expenses for 2026 are projected to be approximately $1.0 billion.

Income Taxes: The Company expects its full-year tax expense to be negligible.

Capital Expenditures: Capital expenditures for 2026 are expected to be $0.2 to $0.3 billion.

Cash and Investments: Year-end cash and investments for 2026 are now projected to be $4.5 to $5.0 billion, which excludes any further drawdowns from the Company's remaining $0.9 billion available under its credit facility.

Recent Progress and Upcoming Late-Stage Pipeline Milestones

Infectious disease vaccines:

• Seasonal flu + COVID vaccine : Moderna recently presented mRNA-1083 data from a Japanese cohort at the 2026 European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Global Congress. The Company has received European Commission marketing authorization for mCOMBRIAX in the EU and its mRNA-1083 regulatory filings are under review in Canada and Australia. Moderna is awaiting further guidance from the U.S. FDA on refiling the submission for its flu plus COVID combination vaccine.

• Seasonal flu vaccine : Moderna recently presented mRNA-1010 revaccination data at the 2026 ESCMID Global Congress. The Company's mRNA-1010 regulatory filings are under review in Europe, Canada and Australia and potential approvals are expected to begin in 2026. The U.S. FDA has assigned a Prescription Drug User Fee Act (PDUFA) goal date for mRNA-1010 of August 5, 2026.

• Norovirus vaccine : Moderna's ongoing Phase 3 safety and efficacy study of mRNA-1403 is fully enrolled in a second Northern Hemisphere season (2025-2026) with data expected in 2026, subject to case accruals.

Oncology therapeutics:

• Intismeran autogene : The Company is advancing mRNA-4157 in collaboration with Merck, with nine total Phase 2 and Phase 3 clinical trials underway across multiple tumor types including melanoma, non-small cell lung cancer (NSCLC), bladder cancer and renal cell carcinoma. This includes the recent initiation of a Phase 3 study of intismeran as monotherapy and in combination with KEYTRUDA QLEX for the treatment of high-risk Stage 1 NSCLC.

Fully enrolled studies include a Phase 3 adjuvant melanoma, a Phase 2 adjuvant renal cell carcinoma, and a Phase 2 adjuvant muscle invasive bladder cancer. Moderna expects Phase 3 adjuvant melanoma data potentially in 2026.

3

The Company recently announced an upcoming oral presentation on June 1 at 8 a.m. to 11 a.m. CT at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting highlighting positive five-year Phase 2b adjuvant melanoma data, which showed a sustained benefit with intismeran in combination with KEYTRUDA, reducing the risk of recurrence or death by 49% compared to KEYTRUDA alone.

• mRNA-4359 : Moderna's Phase 1/2 study of mRNA-4359, an investigational wholly-owned cancer antigen therapy, is ongoing. The Company recently presented mRNA-4359 data at the American Association for Cancer Research (AACR) 2026 Annual Meeting. The Phase 2 portion of the study includes cohorts in first-line metastatic melanoma, second-line+ metastatic melanoma and first-line metastatic NSCLC, and the Company expects a potential Phase 2 data readout in 2026.

Rare disease therapeutics:

• Propionic acidemia (PA) therapeutic : The Company's PA candidate, mRNA-3927, is in a registrational study and target enrollment has been reached. Moderna expects potential data in 2026.

• Methylmalonic acidemia (MMA) therapeutic : The Company is deferring its decision on a pivotal trial for mRNA-3705 until PA registrational data readout.

Moderna Corporate Updates

• Entered into a settlement agreement with Arbutus Biopharma Corporation and Genevant Sciences GmbH resolving all litigation worldwide

• Announced the initiation of Phase 3 study of mRNA-1018, Moderna's investigational pandemic influenza vaccine in collaboration with the Coalition for Epidemic Preparedness Innovations (CEPI)

Key 2026 Investor and Analyst Event Dates

• ASCO Investor Event: June 1 at 7:15 a.m. ET

• Science Day: June 25

• Analyst Day: November 12

Investor Call and Webcast Information

Moderna will host a live conference call and webcast at 8:00 a.m. ET on May 1, 2026. To access the live conference call via telephone, please register at the link below. Once registered, dial-in numbers and a unique pin number will be provided. A live webcast of the call will also be available under "Events and Presentations" in the Investors section of the Moderna website.

• Telephone: https://register-conf.media-server.com/register/BI367363edc35a45ecbc7dd27b7741ea34

• Webcast: https://investors.modernatx.com

The archived webcast will be available on Moderna's website approximately two hours after the conference call and will be available for one year following the call.

4

About Moderna

Moderna is a pioneer and leader in the field of mRNA medicine. Through the advancement of its technology platform, Moderna is reimagining how medicines are made to transform how we treat and prevent diseases. Since its founding, Moderna's mRNA platform has enabled the development of vaccines and therapeutics across infectious diseases, cancer, rare diseases and more.

With a global team and a unique culture, driven by the company's values and mindsets, Moderna's mission is to deliver the greatest possible impact to people through mRNA medicines. For more information about Moderna, please visit modernatx.com and connect with us on X, Facebook, Instagram, YouTube and LinkedIn.

MODERNA, INC.

CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS

(Unaudited, in millions, except per share data)

Three Months Ended March 31,

2026 2025

Revenue:

Net product sales $ 352  $ 86

Other revenue 1

37  22

Total revenue 389  108

Operating expenses:

Cost of sales 955  90

Research and development 649  856

Selling, general and administrative 173  212

Total operating expenses 1,777  1,158

Loss from operations (1,388) (1,050)

Interest income 72  90

Other expense, net (18) (4)

Loss before income taxes (1,334) (964)

Provision for income taxes 9  7

Net loss $ (1,343) $ (971)

Net loss per share

Basic and Diluted $ (3.40) $ (2.52)

Weighted average common shares used in calculation of net loss per share

Basic and Diluted 395  386

_______

1 Includes grant, collaboration, licensing and royalty, and stand-ready manufacturing revenue.

5

MODERNA, INC.

CONDENSED CONSOLIDATED BALANCE SHEETS

(Unaudited, in millions)

March 31, December 31,

2026 2025

Assets

Current assets:

Cash and cash equivalents $ 1,908  $ 2,595

Investments 3,297  3,204

Accounts receivable, net 71  184

Inventory 146  153

Prepaid expenses and other current assets 348  408

Total current assets 5,770  6,544

Investments, non-current 2,251  2,336

Property, plant and equipment, net 2,086  2,134

Right-of-use assets, operating leases 706  719

Other non-current assets 675  605

Total assets $ 11,488  $ 12,338

Liabilities and Stockholders’ Equity

Current liabilities:

Accounts payable $ 161  $ 317

Accrued liabilities 1,912  1,386

Deferred revenue 102  99

Other current liabilities 220  185

Total current liabilities 2,395  1,987

Deferred revenue, non-current 154  153

Operating lease liabilities, non-current 645  653

Financing lease liabilities, non-current 13  20

Long-term debt 590  590

Other non-current liabilities 283  285

Total liabilities 4,080  3,688

Stockholders’ equity:

Additional paid-in capital 1,503  1,382

Accumulated other comprehensive income 25  45

Retained earnings 5,880  7,223

Total stockholders’ equity 7,408  8,650

Total liabilities and stockholders’ equity $ 11,488  $ 12,338

6

MODERNA, INC.

CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS

(Unaudited, in millions)

Three Months Ended March 31,

2026 2025

Operating activities

Net loss

$ (1,343) $ (971)

Adjustments to reconcile net loss to net cash used in operating activities:

Stock-based compensation 104  115

Depreciation and amortization 59  39

Amortization/accretion of investments (11) (19)

Loss on equity investments, net 2  8

Other non-cash items 6  2

Changes in assets and liabilities:

Accounts receivable, net 114  280

Prepaid expenses and other assets 54  46

Inventory 6  (8)

Right-of-use assets, operating leases 11  9

Accounts payable (120) (156)

Accrued liabilities 464  (381)

Deferred revenue 5  (29)

Operating lease liabilities (7) (5)

Other liabilities 26  33

Net cash used in operating activities

(630) (1,037)

Investing activities

Purchases of marketable securities (1,348) (1,764)

Proceeds from maturities of marketable securities 732  1,933

Proceeds from sales of marketable securities 602  688

Purchases of property, plant and equipment (62) (117)

Purchase of intangible asset —  (10)

Net cash (used in) provided by investing activities

(76) 730

Financing activities

Proceeds from issuance of common stock through equity plans 19  3

Tax payments related to net share settlements on equity awards (2) (1)

Changes in financing lease liabilities —  2

Net cash provided by financing activities

17  4

Effect of changes in exchange rates on cash and cash equivalents 1  —

Net decrease in cash, cash equivalents and restricted cash (688) (303)

Cash, cash equivalents and restricted cash, beginning of year 2,597  1,929

Cash, cash equivalents and restricted cash, end of period $ 1,909  $ 1,626

7

Spikevax®, mRESVIA®, mNEXSPIKE® and mCOMBRIAX® are registered trademarks of Moderna.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements regarding: Moderna's 2026 financial framework, including its plan to deliver up to 10% revenue growth and GAAP operating expense reductions, and its projected year-end cash balance; Moderna’s multi-year revenue growth strategy, including geographic expansion and new product launches; Moderna's continued cost discipline; Moderna’s international strategic partnerships; expectations regarding mRNA-4157 Phase 3 adjuvant melanoma data in 2026; the potential of intismeran as monotherapy and in combination with KEYTRUDA QLEX; the potential of Moderna’s expanded oncology portfolio; pending and anticipated regulatory filings and potential approvals, including timing of approvals; Moderna's PDUFA date in the U.S. for mRNA-1010; and anticipated progress and milestones for Moderna's pipeline programs, including potential near-term data and other catalysts. In some cases, forward-looking statements can be identified by terminology such as "will," "may," "should," "could," "expects," "intends," "plans," "aims," "anticipates," "believes," "estimates," "predicts," "potential," "continue," or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. The forward-looking statements in this press release are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond Moderna's control and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements. These risks, uncertainties, and other factors include, among others, those risks and uncertainties described under the heading "Risk Factors" in Moderna's Annual Report on Form 10-K for the fiscal year ended December 31, 2025, filed with the U.S. Securities and Exchange Commission (SEC), and in subsequent filings made by Moderna with the SEC, which are available on the SEC's website at www.sec.gov. Except as required by law, Moderna disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release in the event of new information, future developments or otherwise. These forward-looking statements are based on Moderna's current expectations and speak only as of the date of this press release.

###

Moderna Contacts

Media:

Chris Ridley

Vice President, Head of Global Communications

+1 617-800-3651

Chris.Ridley@modernatx.com

8

Investors:

Lavina Talukdar

Senior Vice President & Head of Investor Relations

+1 617-209-5834

Lavina.Talukdar@modernatx.com

SOURCE: Moderna, Inc.

9

Source:

View Original Filing on SEC EDGAR

FAQ

How did Moderna (MRNA) perform financially in Q1 2026?

Moderna generated Q1 2026 revenue of $389 million, up from $108 million a year earlier. The company reported a GAAP net loss of $(1.343) billion, or $(3.40) per share, mainly due to a $0.9 billion non-recurring litigation settlement charge.

What were Moderna (MRNA)’s key revenue drivers in Q1 2026?

Revenue was driven by higher COVID vaccine sales, especially in international markets. Of the $389 million total revenue, $78 million came from the U.S. and $311 million from international markets, supported by deliveries under long-term strategic partnerships with government entities.

How did Moderna’s expenses change year over year in Q1 2026?

Research and development expenses fell to $649 million, a 24% decrease, reflecting wind-down of large Phase 3 respiratory and congenital CMV programs. Selling, general and administrative expenses decreased 18% to $173 million, mainly from lower employee-related, marketing, consulting and external service costs.

What caused Moderna (MRNA)’s large Q1 2026 net loss?

The GAAP net loss of $(1.343) billion was largely driven by litigation settlement-related expenses. A non-recurring $0.9 billion settlement charge was recognized in cost of sales, contributing significantly to the $(3.40) loss per share despite higher revenue and lower operating expenses in other areas.

What is Moderna’s 2026 financial outlook and cash projection?

Moderna is targeting up to 10% revenue growth from 2025 levels in 2026. It expects cost of sales of about $1.8 billion, R&D around $3.0 billion, SG&A about $1.0 billion, and projects year-end 2026 cash and investments of $4.5–$5.0 billion, excluding further credit facility use.

Which late-stage pipeline programs are important for Moderna (MRNA) in 2026?

Key programs include flu plus COVID vaccine mCOMBRIAX, seasonal flu vaccine mRNA-1010 with an August 5, 2026 PDUFA date, norovirus vaccine mRNA-1403 with Phase 3 data expected in 2026, oncology candidate intismeran across multiple Phase 2 and 3 trials, and propionic acidemia therapy mRNA-3927.

Filing Exhibits & Attachments

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打开原文

FDA Briefing Document: MFLUSIVA / mRNA-1010

来源信息
来源：U.S. FDA发布日期：2026-06-13抓取时间：2026-06-17T19:01:17.558Z相关标的：MRNA归档状态：已归档 / 弹窗可读
中文摘要

一句话结论

FDA 简报文件把 MFLUSIVA/mRNA-1010 的核心问题从“是否能进入审评”推进到“50-64 岁是否适合传统批准、65 岁及以上是否适合加速批准，以及标签和上市后义务如何设定”。文件显示疗效和安全性有支持点，但数据外推仍存在重要限制。

关键事实

  • BLA 于 2025-12-05 received，并于 2026-02-17 filed。
  • FDA 请求 VRBPAC 讨论 50-64 岁 adults 的 traditional approval，以及 65 岁及以上 adults 的 accelerated approval。
  • Study P304 在 50 岁及以上 adults 中显示相对 standard-dose comparator 的 rVE 为 26.6%。
  • FDA 指出 P304 只覆盖一个 influenza season，B/Victoria 病例累积不足，某些置信区间和亚组数据限制了外推。
  • FDA 关注 immunocompromised、very frail older adults 和与 COVID、RSV、pneumococcal 等常规疫苗共同接种的数据缺口。
  • 安全性方面，FDA 总结 pooled Phase 3 safety database 的 SAE、死亡和 AESI 大体平衡，并未识别出与 mRNA-1010 相关的 myocarditis/pericarditis pattern。

作者观点与证据

这是监管审评文件，不是媒体评论。FDA 的判断是审慎的：有足够证据进入委员会讨论，但仍要求专家评估目标人群、证据外推和后续义务。证据包括 P304 疗效、303C 免疫原性、安全数据库和审评方列出的缺口。

与相关标的的关系

对 MRNA 是短期最大监管证据。它支持“路径改善但未完全去风险”的投资框架：如果委员会认为缺口可由上市后研究处理，PDUFA 路径更清晰；如果要求新增大型疗效数据，商业化节奏会后移。

时效性与限制

文件发布时间为 2026-06-13，紧邻 VRBPAC。限制是会前简报文件，不代表最终投票或 FDA 批准结论。

后续跟踪

  • VRBPAC 对两个 voting questions 的结果和讨论重点。
  • FDA 是否要求额外 efficacy season、共同接种或特殊人群研究。
  • 2026-08-05 PDUFA 标签、人群和上市后义务。
英文原文
FDA Briefing Document: MFLUSIVA / mRNA-1010

Individuals using assistive technology may not be able to fully

access the information contained in this file. For assistance,

please call 800-835-4709 or 240-402-8010, extension 1. CBER

Consumer Affairs Branch or send an e-mail to: ocod@fda.hhs.gov

and include 508 Accommodation and the title of the document in

the subject line of your e-mail.

FDA Briefing Document

BLA# 125869/0

Influenza Vaccine, mRNA

(Proposed Trade Name: mFlusiva)

Applicant: Moderna TX, Inc.

Vaccines and Related Biological Products Advisory Committee (VRBPAC)

June 18, 2026

Division of Clinical and Toxicology Review | Office of Vaccines Research and Review

DISCLAIMER STATEMENT

The attached package contains background information prepared by the Food and Drug

Administration (FDA) for the panel members of the Advisory Committee. The FDA background

package often contains assessments and/or conclusions and recommendations written by

individual FDA reviewers. Such conclusions and recommendations do not necessarily

represent the final position of the individual reviewers, nor do they necessarily represent the

final position of the Review Division or Office. We have brought the benefit-risk assessment of

mFlusiva (mRNA-1010) to this Advisory Committee to gain the Committee’s insights and

opinions, and the background package may not include all issues relevant to the final

regulatory recommendation and instead is intended to focus on issues identified by the

Agency for discussion by the Advisory Committee. FDA will not issue a final determination on

the issues at hand until input from the Advisory Committee process has been considered and

all reviews have been finalized. The final determination may be affected by issues not

discussed at the Advisory Committee meeting.

1

Table of Contents

List of Tables ........................................................................................................................................................ 3

Glossary ............................................................................................................................................................... 4

1. Executive Summary/Draft Points for Consideration by the Advisory Committee ........................................ 6

1.1. Purpose / Objective of the AC Meeting .............................................................................. 6

1.2. Context for Issues to Be Discussed at the AC ................................................................... 6

1.3. Brief Description of Issues for Discussion at the AC .......................................................... 7

1.4. Draft Points for the AC to Consider ................................................................................... 8

2. Introduction and Background ....................................................................................................................... 8

2.1. Background of the Condition/Standard of Clinical Care ..................................................... 8

2.1.1. Disease Burden ......................................................................................................... 8

2.1.2. Clinical Manifestations ............................................................................................... 8

2.1.3. Current Treatment and Prevention Options ............................................................... 9

2.1.4. Unmet Need ..............................................................................................................9

2.2. Pertinent Drug Development and Regulatory History ........................................................ 9

2.2.1. Product Description ................................................................................................... 9

2.2.2. Development History ................................................................................................. 9

2.2.3. Manufacturing Innovation .......................................................................................... 9

3. Summary of Issues for the AC ................................................................................................................... 10

3.1. Efficacy/Effectiveness Issues .......................................................................................... 10

3.1.1. Sources of Data for Efficacy .................................................................................... 10

3.1.2. Effectiveness Summary ........................................................................................... 12

3.1.3. Efficacy Issues in Detail ........................................................................................... 18

3.2. Safety Issues................................................................................................................... 21

3.2.1. Sources of Data for Safety ....................................................................................... 21

3.2.2. Safety Summary ...................................................................................................... 21

3.2.3. Safety Issues in Detail ............................................................................................. 23

3.3. Risk Mitigation ................................................................................................................. 25

4. Benefit-Risk Framework ............................................................................................................................. 26

5. References ................................................................................................................................................. 29

Appendix A – Clinical Studies Submitted in Support of mRNA-1010 Efficacy and Safety Determinations ....... 32

Appendix B – Study P304 Efficacy and Safety .................................................................................................. 33

Appendix C – Study P303 Part C: Efficacy and Safety ..................................................................................... 66

Appendix D – Integrated Overview of Safety ..................................................................................................... 82

Appendix E – Adverse Events of Special Interest ............................................................................................. 88

Appendix F – CDC Criteria for Probable and Confirmed Cases of Myo, Peri, and Myopericarditis .................. 89

Appendix G – Study P304 High-Risk Conditions ............................................................................................... 90

Appendix H – Phase 4 confirmatory study protocol synopsis............................................................................ 91

2

List of Tables

Table 1. Analysis of Relative Vaccine Efficacy (rVE) for mRNA-1010 (TIV) Versus SD

Comparator Against Various ILI Case Definitions and Health Care Outcomes Regardless of

Vaccine Match in Participants 50 Years of Age and Older, (PP Set), Study P304 ..............................13

Table 2. Analysis of Primary Efficacy Endpoint of Relative Vaccine Efficacy (rVE) for mRNA-

1010 (TIV) Versus SD Comparator Against RT-PCR–Confirmed Protocol-Defined ILI Caused by

Any Influenza A or B Strains by Age Group (PP Set), Study P304 .....................................................14

Table 3. Analysis of Primary Efficacy Endpoint of Relative Vaccine Efficacy (rVE) for mRNA-

1010 (TIV) Versus SD Comparator Against RT-PCR–Confirmed Protocol-Defined ILI Caused by

Influenza Strain Type in Participants 50 Years of Age and Older (PP Set), Study P304 ....................15

Table 4. Analyses of Primary Immunogenicity Endpoint of GMTs as Measured by

Hemagglutination Inhibition (HAI) for Vaccine-Matched Influenza Strains at Day 29

Postvaccination, Participants 65 Years of Age and Older, PPIS, Study P303 Part C .........................16

Table 5. Analyses of Primary Immunogenicity Endpoint of SCRs as Measured by

Hemagglutination Inhibition (HAI)cr for Vaccine-Matched Influenza Strains at Day 29

Postvaccination, Participants 65 Years of Age and Older, PPIS, Study P303 Part C .........................17

Table 6. Safety Profile of mRNA-1010 versus Comparator: Summary of Key Findings from Study

P304a,b,c and Pooled Phase 3 Studiesd,e,f,g,h .......................................................................................22

3

Glossary

ACIP Advisory Committee on Immunization Practices

AE adverse event

AR adverse reaction

BLA Biologics License Application

BMI body mass index

CABG coronary artery bypass graft

CDC Centers for Disease Control and Prevention

CEAC Cardiac Event Adjudication Committee

CI confidence interval

CoP correlate of protection

COPD chronic obstructive pulmonary disease

COVID-19 coronavirus disease 2019

CoR correlate of risk

DBL database lock

eDiary electronic diary

EOS end-of-study

FDA U.S. Food and Drug Administration

GBS Guillain-Barré Syndrome

GMFR geometric fold rise

GMT geometric mean titer

HA hemagglutinin

HAI hemagglutinin inhibition

HD high-dose

ILI influenza-like illness

ISS Integrated Safety Summary

LGE late gadolinium enhancement

LL lower limit

MAAE medically attended adverse event

MedDRA Medical Dictionary for Regulatory Activities

MN microneutralization

NH Northern Hemisphere

NI noninferiority

NP nasopharyngeal

PPIS per-protocol immunogenicity subset

PT MedDRA preferred term

QIV quadrivalent influenza vaccine

RD risk difference

RIV recombinant influenza vaccine

RSV respiratory syncytial virus

RT-PCR reverse transcriptase polymerase chain reaction

rVE relative vaccine efficacy

SAE serious adverse event

SCR seroconversion rate

SD standard dose

SMQ standard MedDRA query

SOC system organ class

TIV trivalent influenza vaccine

U.S. United States

UTI urinary tract infection

4

VE vaccine efficacy

VRBPAC Vaccines and Related Biological Products Advisory Committee

WHO World Health Organization

yoa years of age

5

1. Executive Summary/Draft Points for Consideration by the Advisory

Committee

1.1. Purpose / Objective of the AC Meeting

FDA is convening this meeting of the Vaccines and Related Biological Products Advisory

Committee (VRBPAC) to discuss the benefit-risk assessment of mFlusiva (mRNA-1010), an

mRNA-based trivalent influenza vaccine (TIV) encoding hemagglutinin (HA) glycoproteins for

influenza A/H1N1, A/H3N2, and B/Victoria, submitted under BLA 125869/0 by Moderna TX, Inc.

The BLA was received on December 5, 2025, and filed on February 17, 2026. The proposed

indication is for active immunization for the prevention of influenza disease caused by influenza

virus subtypes A and type B represented in the vaccine.

The Agency is seeking VRBPAC input on two specific regulatory issues:

• Issue 1 (Traditional Approval, adults 50 through 64 years of age): Whether relative

vaccine efficacy (rVE) against RT-PCR–confirmed influenza-like illness (ILI) from a Phase 3,

randomized, observer-blinded, active-controlled trial in adults 50 years of age and older

(Study P304) provides sufficient basis for Traditional Approval of mFlusiva in adults 50

through 64 years of age.

• Issue 2 (Accelerated Approval, adults 65 years of age and older): Whether comparative

immunogenicity data relative to high-dose (HD) influenza vaccine — a CDC-preferentially

recommended vaccine —from a Phase 3, randomized, stratified, observer-blinded, active-

controlled trial in adults 65 years of age and older (Study P303 Part C), combined with a

required Phase 4 confirmatory study, provides sufficient basis for Accelerated Approval of

mFlusiva in adults 65 years of age and older.

1.2. Context for Issues to Be Discussed at the AC

Seasonal influenza causes 3–5 million cases of severe disease and up to 650,000 deaths

annually worldwide. The Centers for Disease Control and Prevention (CDC) estimates that

influenza has resulted in 9.4 to 51 million illnesses and 6,300 to 52,000 deaths annually in the

United States (U.S.) between 2010 and 2025. 1 In the U.S., adults 65 years of age (yoa) and older

account for approximately 70–85% of influenza-related deaths and 50–70% of hospitalizations. 2

Currently licensed influenza vaccines — the majority of which are manufactured in embryonated

chicken eggs — achieve up to 60% effectiveness under optimal conditions. Observed

effectiveness is reduced when vaccine strains are antigenically mismatched with circulating

influenza strains. Egg-based manufacturing introduces egg-adaptive mutations with the potential

to alter antigen conformation and create antigenic mismatch. (See Section 2.1.4 Unmet Need)

For adults 65 yoa and older, CDC preferentially recommends HD, recombinant, or adjuvanted

over standard-dose (SD) influenza vaccines to address age-related immunosenescence.

Accordingly, when designing clinical trials of influenza vaccines in this population, the control

group should reflect the relevant standard of care – consistent with ICH E10 guidance ("Choice of

Control Group and Related Issues in Clinical Trials," 2000) – which for this age group are the

preferentially recommended influenza vaccines.

mFlusiva represents a novel mRNA-based manufacturing technology that eliminates egg-adaptive

mutations. The Applicant positions their technology as enabling rapid strain updates.

1 About Estimated Flu Burden | Flu Burden | CDC

2 Flu and People 65 Years and Older | Influenza (Flu) | CDC

6

Key points for VRBPAC consideration include: (1) whether the efficacy and immunogenicity data

demonstrate effectiveness of mFlusiva across the proposed age groups; and (2) whether the

benefit-risk assessment is favorable considering the reactogenicity profile, identified evidence

gaps in special populations, and limited duration-of-protection data.

1.3. Brief Description of Issues for Discussion at the AC

The following key findings and uncertainties frame the issues to be discussed at this meeting:

 Key Finding 1 — Clinical Efficacy (primary basis for Traditional Approval in adults

50 through 64 yoa): Study P304 provided the primary efficacy data for mRNA-1010 (TIV)

in adults ≥50 yoa. Over one influenza season, mRNA-1010 (TIV) demonstrated a rVE of

26.6% (95% CI: 16.7, 35.4) against RT-PCR–confirmed ILI compared with the SD

comparator vaccine. Point estimates of rVE were consistent across age subgroups (50

through 64 yoa: 26.1% [95% CI: 12.3, 37.7]; 65 through 74 yoa: 28.0% [10.4, 42.2]; ≥75

yoa: 25.3% [−10.4, 49.5]) and viral strains. rVE against higher-level healthcare outcomes

(hospitalization, emergency room, or urgent care visits) was 47.9% (95% CI: 12.8, 68.9),

supporting clinical meaningfulness.

 Key Finding 2 — Immunogenicity (primary basis for Accelerated Approval in adults

≥65 yoa): Study P303 Part C demonstrated that mRNA-1010 (QIV) met pre-specified

noninferiority and superiority criteria for hemagglutination inhibition (HAI) geometric mean

titers (GMT) and seroconversion rates (SCR) relative to Fluzone HD (QIV) for all four

vaccine-matched influenza strains in adults ≥65 yoa at Day 29. Immune responses,

including GMT and SCR, remained higher in the mRNA-1010 (QIV) group than in the

Fluzone HD (QIV) group at end-of-study (Day 181) in the evaluated subset.

 Key Finding 3 — Safety Profile: Solicited adverse reactions (ARs) within 7 days

postvaccination were more frequent in mRNA-1010 recipients than in comparator

recipients in both pivotal studies but were predominantly mild to moderate in severity with

a median duration of approximately 2 days. Unsolicited adverse events through Day 28,

serious adverse events (SAEs), adverse events of special interest (AESIs), and deaths

through approximately 6 months of follow-up were balanced between treatment groups.

No cases of myocarditis or pericarditis were identified within 42 days postvaccination.

Subgroup analyses by age, sex, race, and baseline risk status showed no clinically

meaningful differences in safety profiles. The Integrated Safety Summary (ISS) pooled

data from four Phase 3 studies comprising 35,965 mRNA-1010 recipients and 35,951

standard-dose or high-dose comparator recipients ≥50 yoa. SAEs, deaths, and AESIs

were balanced between treatment groups. No cases of myocarditis or pericarditis were

assessed as related to mRNA-1010. The pooled analysis identified no adverse event

patterns indicative of a safety signal for mRNA-1010 in individuals ≥50 yoa.

 Key Uncertainty — Evidence Gaps: Clinical efficacy data are available for one influenza

season only. Efficacy in immunocompromised individuals and very frail older adults has

not been established. This gap is significant because these populations face the highest

absolute risk of severe influenza-related complications and may respond differently to

mRNA-based vaccine platforms. The study exclusion of these groups limits direct

applicability of the efficacy data to a substantial portion of the intended patient population.

Data on concomitant administration with routinely co-administered vaccines (e.g., COVID-

19, RSV, pneumococcal vaccines) are not available. The confidence interval for B/Victoria-

specific rVE crosses zero (29.1%; 95% CI: −18.5, 57.5) due to limited case accrual for this

strain (25 cases in the mRNA-1010 group vs. 35 cases in the SD comparator group).

7

 Key Issue — Approval Approach: The Applicant proposed a bifurcated regulatory

pathway — Traditional Approval for adults 50 through 64 yoa based on clinical efficacy,

and Accelerated Approval for adults 65 yoa and older based on immunogenicity as a

surrogate endpoint — with a required Phase 4 confirmatory trial to verify clinical benefit in

the older age group.

1.4. Draft Points for the AC to Consider

The following points are presented for VRBPAC deliberation and vote:

 Do the primary endpoint, age subgroup, and strain-specific vaccine efficacy results from

Study P304 demonstrate clinically meaningful efficacy of mFlusiva against influenza

disease in adults 50 through 64 years of age?

 Do the immunogenicity results from Study P303 Part C, comparing mRNA-1010 (QIV) to

Fluzone High-Dose Quadrivalent, provide a reasonable basis to predict clinical benefit of

mFlusiva in adults 65 years of age and older?

 Do the available data indicate that the safety profile of mFlusiva is adequately

characterized, that identified risks are acceptable, and that residual risks can be

appropriately monitored and managed through postmarketing pharmacovigilance?

 Voting questions:

 Do the benefits of mFlusiva outweigh its risks for the prevention of influenza disease in

adults 50 through 64 years of age?

 Do the benefits of mFlusiva outweigh its risks for the prevention of influenza disease in

adults 65 years of age and older?

2. Introduction and Background

2.1. Background of the Condition/Standard of Clinical Care

2.1.1. Disease Burden

Influenza is responsible for 3–5 million cases of severe disease and up to 650,000 deaths

annually worldwide (WHO, 2025). In the United States, adults ≥65 yoa account for approximately

three-quarters of influenza-associated deaths. Seasonal influenza disproportionately affects older

adults, young children, pregnant women, and individuals with underlying cardiac,

immunocompromising, metabolic, or respiratory conditions. The cumulative public health burden

is substantial, encompassing direct healthcare costs, lost productivity, and excess mortality,

particularly during seasons with high antigenic mismatch.

2.1.2. Clinical Manifestations

Following an incubation period of 1 to 4 days, influenza presents with abrupt onset of fever (38–

40°C), rigors, myalgia, headache, malaise, and nonproductive cough. Upper respiratory

symptoms (nasal congestion, rhinorrhea, sore throat) are common. In immunocompetent adults,

systemic symptoms typically resolve within 3–7 days, though cough and fatigue may persist for

weeks. High-risk groups are susceptible to serious complications, including primary viral

pneumonia, secondary bacterial pneumonia, exacerbation of chronic obstructive pulmonary

disease or asthma, myocarditis, encephalitis, and acute respiratory distress syndrome.

8

2.1.3. Current Treatment and Prevention Options

Four FDA-approved antiviral agents are available for treatment — oseltamivir, zanamivir,

peramivir, and baloxavir marboxil — each capable of reducing disease duration, severity, and

complication risk when initiated promptly. Nevertheless, annual influenza vaccination remains the

primary recommended preventive strategy. CDC recommends vaccination for all individuals ≥6

months of age, with preferential recommendation of HD (Fluzone HD), adjuvanted (Fluad), or

recombinant (FluBlok) formulations for adults 65 yoa and older.

2.1.4. Unmet Need

Currently licensed influenza vaccines are generally considered to achieve up to 60%

effectiveness under conditions of optimal antigenic match (Demicheli, et al. 2018; Osterholm, et

al. 2012), with lower protection during mismatch seasons (Tricco, et al. 2013). Egg-based

manufacturing — used by most licensed vaccines — introduces egg-adaptive mutations that can

alter HA antigen conformation and may reduce vaccine immunogenicity (Petrova & Russell 2018).

There is a need for vaccines with improved effectiveness, particularly in older adults (Osterholm,

et al. 2012). High-volume manufacturing capable of rapid strain reformulation is also needed to

address antigenic drift and — more critically — antigenic shift, the latter posing pandemic risk.

2.2. Pertinent Drug Development and Regulatory History

2.2.1. Product Description

mFlusiva (mRNA-1010) is a trivalent mRNA influenza vaccine formulated as a solution for

intramuscular injection. The product encodes the full-length, membrane-bound HA glycoproteins

of influenza A/H1N1, A/H3N2, and B/Victoria-lineage (12.5 µg of each mRNA, total 37.5 µg),

encapsulated in lipid nanoparticles. It is supplied as a single-dose prefilled syringe and

administered as a 0.375 mL intramuscular dose. The proposed indication is for active

immunization for the prevention of influenza disease caused by influenza virus subtypes A and

type B represented in the vaccine.

2.2.2. Development History

The clinical development program for mRNA-1010 comprises five studies (see Appendix A).

Early-phase dose-selection data were generated in Study P101 (Phase 1/2). These, along with

Studies P301 and P302, evaluated an earlier formulation with “pre-optimized” influenza B

antigens (mRNA-1010, original QIV) and contribute safety data to the Integrated Safety Summary

(ISS) only. Study P303 Parts A and B evaluated an “optimized” quadrivalent formulation (mRNA-

1010.6 and 1010.4, respectively) in adults ≥18 yoa and 18 through 64 yoa, respectively, and

similarly contribute to the ISS. The pivotal Phase 3 program consists of Study P304, providing

primary efficacy and safety data for mRNA-1010 (TIV) in adults ≥50 yoa, and Study P303 Part C,

providing immunogenicity and safety data for mRNA-1010 (QIV) compared with Fluzone HD (QIV)

in adults ≥65 yoa. BLA 125869/0 was submitted and received on December 5, 2025.

2.2.3. Manufacturing Innovation

The mRNA manufacturing technology avoids egg-based manufacturing, eliminating the risk of

egg-adaptive mutations. The formulation intended for licensure (mRNA-1010.4) incorporates two

stabilizing point mutations in non-surface-exposed regions of influenza B HA — preserving

antigenic epitopes while enhancing structural stability and antigen availability — and modified

untranslated regions across all influenza strains to extend mRNA durability. The mRNA

technology also supports rapid strain reformulation in response to antigenic drift or shift, a

meaningful operational advantage over egg-based production.

9

3. Summary of Issues for the AC

3.1. Efficacy/Effectiveness Issues

No major deficiencies were identified; however, four issues warrant Advisory Committee

consideration regarding the adequacy and interpretive scope of the efficacy data, as described

below.

The primary efficacy analysis demonstrated that mRNA-1010 (TIV) met all prespecified sequential

success criteria—noninferiority, superiority, and super-superiority—relative to the standard-dose

(SD) comparator. The primary immunogenicity (effectiveness) analysis demonstrated that mRNA-

1010 (QIV) met all prespecified sequential success criteria—noninferiority and superiority—

relative to the high-dose (HD) comparator.

Four issues warrant Advisory Committee consideration:

• Efficacy Issue 1: Adequacy and clinical meaningfulness of rVE versus a standard-dose

(SD) comparator in adults ≥65 yoa, given the availability of preferentially recommended

high-dose, recombinant, or adjuvanted influenza vaccines for this age group.

• Efficacy Issue 2: Interpretive uncertainty in rVE against influenza B/Victoria due to low

case accrual.

• Efficacy Issue 3: Adequacy of single-season efficacy data and study population to support

licensure.

• Effectiveness Issue 4: Use of immunogenicity as a surrogate endpoint reasonably likely to

predict clinical benefit in adults 65 yoa and older.

3.1.1. Sources of Data for Efficacy

3.1.1.1 Primary Efficacy Study (50 yoa and older)

Study mRNA-1010-P304 (P304) (NCT06602024): Phase 3, randomized, observer-blind

(participant- and assessor-blind), active-controlled, case-driven trial evaluating mRNA-1010

trivalent influenza vaccine (TIV) versus a licensed SD comparator (trivalent [TIV] in North

America; quadrivalent [QIV] in Europe and East Asia) for the prevention of RT-PCR–confirmed

influenza illness in adults ≥50 yoa.

See Appendix B for details of Study P304.

Key design parameters:

• Total enrollment: N = 40,805 participants

• Study sites: 301 sites across 11 countries (North America, Europe, East Asia)

• Randomization: 1:1 allocation (mRNA-1010 [TIV] vs. SD comparator)

• Age stratification: prior seasonal influenza vaccination status; 50 to <65 years; ≥65

years

• Season: 2024–2025 Northern Hemisphere (NH) influenza season

• Active comparator: Licensed SD TIV (Fluarix) or QIV, with trivalent SD formulation as

preferred comparator

• Regimen: Single intramuscular dose per participant

10

• Primary efficacy analysis: Pre-specified interim analysis at end of NH 2024–2025

season; data cutoff April 30, 2025; database lock June 3, 2025. The interim analysis

used the full one-sided alpha of 2.5%. High influenza transmission during the 2024–

2025 season resulted in 968 cases accruing—exceeding the target of 836—and the

study did not advance to a second season.

• Primary endpoint: First episode of RT-PCR–confirmed protocol-defined influenza-like

illness (ILI) with onset ≥14 days postvaccination through end of influenza season,

caused by any influenza A or B strain

• Statistical success criteria: Hierarchical sequential testing for noninferiority (NI; lower

limit [LL] of 95% CI of rVE > −10%), superiority (LL > 0%), and super-superiority (LL >

9.1%)

• Median efficacy follow-up: 181 days (~6 months)

The study employed a hierarchical sequential testing strategy across nine pre-specified null

hypotheses controlling the Type I error rate, progressing across three tiers: (1) protocol-defined

ILI, any strain; (2) modified CDC-defined ILI, any strain; (3) protocol-defined ILI, antigenically

matched strains. Within each tier, hypotheses were tested sequentially for NI, superiority, and

super-superiority; advancement required rejection of the preceding hypothesis.

3.1.1.2 Primary Immunogenicity Study (65 yoa and older)

Study P303 Part C (NCT05827978): Phase 3, multicenter, randomized, stratified, observer-blind,

active-controlled study evaluating the immunogenicity, reactogenicity, and safety of mRNA-1010

(QIV) relative to Fluzone High-Dose (QIV) (N.B. HD influenza vaccine is one of three influenza

vaccines preferentially recommended by CDC for adults 65 yoa and older).

See Appendix C for details of Study P303 Part C.

Key design parameters:

 Total enrollment: N = 3,003 participants ≥65 yoa

 Study sites: 96 U.S. centers

 Randomization: 1:1 allocation (mRNA-1010 [QIV] vs. Fluzone HD [QIV])

 Season: 2023–2024 Northern Hemisphere (NH) influenza season

 Active comparator: Licensed Fluzone HD (QIV)

 Regimen: Single intramuscular dose per participant

 Primary immunogenicity analysis: Day 29 postvaccination

 Primary endpoints:

 Hemagglutination inhibition (HAI) geometric mean titer (GMT) at Day 29 for all

four vaccine-matched influenza strains

 Seroconversion rate (SCR) at Day 29 for all four vaccine-matched influenza

strains

 Statistical success criteria:

 Noninferiority (NI): For GMT ratio, lower limit (LL) of 95% confidence interval (CI)

>0.667 for each strain; for SCR difference, LL of 95% CI >−10% for each strain

11

 Superiority: For GMT ratio, LL of 97.5% CI >1.0 for each strain; for SCR difference,

LL of 97.5% CI >0% for each strain

 Immunogenicity follow-up: HAI GMT and SCR against vaccine-matched influenza A

and B strains at Day 181/EOS in a participant subset

The study employed a hierarchical sequential testing strategy—upon successful demonstration of

noninferiority for all eight coprimary immunogenicity endpoints, superiority was evaluated.

3.1.1.3 Supporting Safety Studies

Studies P301, P302, and P303 Parts A/B contribute safety data to the Integrated Safety Summary

only and do not provide primary efficacy or immunogenicity data for the purposes of this BLA

review.

3.1.2. Effectiveness Summary

3.1.2.1 Primary Efficacy Study (50 yoa and older)

The primary efficacy objective of Study P304 was to demonstrate that mRNA-1010 (TIV) was

noninferior to the standard-dose comparator in preventing the first occurrence of protocol-defined

influenza-like illness (ILI) (see Appendix B Table 1) starting 14 days after vaccination through the

end of the influenza season. ILI cases occurred in 411 participants (2.0%) in the mRNA-1010

(TIV) group and 557 participants (2.8%) in the standard-dose comparator group. As shown in

Table 1, the study met this objective, demonstrating a rVE of 26.6% (95% CI: 16.7, 35.4) in

participants 50 yoa and older. This result satisfied the prespecified noninferiority criterion (lower

limit of the 95% CI >−10%). The study also demonstrated superiority and super-superiority of

mRNA-1010 (TIV) over the comparator, with the lower limit of the 95% CI exceeding both 0% and

9.1%.

Additional analyses evaluated the secondary efficacy endpoint of the modified CDC-defined ILI, a

more stringent case definition which requires a temperature above 37.2°C, cough and/or sore

throat, and RT-PCR confirmation of influenza virus (see Appendix B Table 1 for case definitions).

Among adults 50 yoa and older, modified CDC-defined ILI occurred in 1.1% of participants

receiving mRNA-1010 (TIV) compared with 1.4% receiving the standard-dose comparator,

yielding an rVE of 23.5% (95% CI: 9.0, 35.8). Table 1 demonstrates that noninferiority and

superiority criteria, but not super-superiority, were met.

Medically attended influenza-like illness (ILI) cases confirmed by RT-PCR and meeting protocol-

defined criteria were assessed as an exploratory endpoint. As shown in Table 1, the observed

rVE of mRNA-1010 (TIV) against protocol-defined ILI requiring higher levels of care—including

hospitalization, emergency room (ER) visit, or urgent care clinic visit—was 47.9% (95% CI: 12.8,

68.9). These exploratory data provide supportive evidence for the clinical benefit of mRNA-1010

(TIV).

12

Table 1. Analysis of Relative Vaccine Efficacy (rVE) for mRNA-1010 (TIV) Versus SD Comparator Against

Various ILI Case Definitions and Health Care Outcomes Regardless of Vaccine Match in Participants 50

Years of Age and Older, (PP Set), Study P304

mRNA-1010

SD Comparator

(TIV) rVE (%)

Relative Efficacy Endpoint N=20,124 Result

N=20,179 (95% CI)b

Cases, n (%)a

Cases, n (%) a

Primary: RT-PCR–confirmed 411 557 26.6 ✓ NI / Superiority /

protocol-defined ILI (2.0) (2.8) (16.7, 35.4) Super-Superiority

Secondary: Modified CDC- 223 290 23.5 ✓NI/ Superiority

defined ILI (more stringent)) (1.1) (1.4) (9.0, 35.8) X Super-Superiority

Exploratory: Higher Level of

Carec

22 42 47.9 ✓ Supports Clinical

(0.1) (0.2) (12.8, 68.9) Benefit

(hospital/ER/urgent care)

Source: Adapted from STN 125869/0, mRNA-1010 P304 Clinical Study Report, Tables 14.2.1.1.1.1, 14.2.1.2.1.1, 14.2.1.4.1.1, and

14.2.1.6.1.1. Data cutoff: April 30, 2025.

Abbreviations: CDC, U.S. Centers for Disease Control and Prevention; CI, confidence interval; ILI, influenza-like illness; N, number of

participants in the analysis set; n, number of ILI cases based on the given case definition; PP, per protocol; RT-PCR, real-time reverse

transcription polymerase chain reaction; rVE, relative vaccine efficacy; SD, standard dose

a

Percentages are based on the number of participants in the analysis set.

b

rVE is defined as 100×(1−hazard ratio [mRNA-1010 versus the Active Comparator]). The rVE and the CI are based on a stratified Cox

proportional hazards model with the study vaccination group as a fixed effect, adjusting by the randomized stratification factors: age group

(≥50 to <65 years or ≥65 years) and the status of influenza vaccine in the previous influenza season (received or not received). Efron´s

method is used to handle ties.

c

n represents the number of participants with a case, which is a healthcare encounter seeking a higher level of care associated with the first

occurrence of RT-PCR-confirmed protocol-defined ILI that begins at least 14 days after study vaccination through the end of influenza

season caused by any influenza A or B strains, regardless of vaccine match. If an event is associated with multiple healthcare encounter

types or multiple healthcare encounter of the same type, the participant will be counted only once.

Table 2 presents descriptive analyses of primary efficacy endpoint of rVE by age subgroup.

Point estimates were consistent across all age subgroups and the overall population (see

Table 1). In participants 65 yoa and older, rVE was 27.4% (95% CI: 12.1%, 40.0%) against

the standard-dose comparator vaccine, which was not the preferred comparator for this age

group; this limitation should be considered when interpreting results in this subgroup. In the 75

yoa and older subgroup, the 95% CI was wide with the lower limit crossing zero, reflecting the

smaller sample size and lower event count in this stratum.

13

Table 2. Analysis of Primary Efficacy Endpoint of Relative Vaccine Efficacy (rVE) for mRNA-1010 (TIV)

Versus SD Comparator Against RT-PCR–Confirmed Protocol-Defined ILI Caused by Any Influenza A or

B Strains by Age Group (PP Set), Study P304

mRNA-1010

SD Comparator

(TIV) rVE (%)

Age Group N=20,124 Interpretation

N=20,179 (95% CI)b

Cases, n/N (%)

Cases, n/N (%) a

229/10,542 307/10,501 26.1 CI excludes zero;

50 through 64 yoa

(2.2) (2.9) (12.3, 37.7) suggest superiority

138/7307 191/7289 28.0 CI excludes zero;

65 through 74 yoa

(1.9) (2.6) (10.4, 42.2) suggest superiority

CI crosses zero;

44/2230 59/2334 25.3

75 yoa and older wide CI due to small N;

(1.9) (2.5) (−10.4, 49.5)

directionally consistent

Source: Adapted from STN 125869/0, mRNA-1010 P304 Clinical Study Report, Tables 14.2.1.1.1.1, Table 14.2.1.1.4.1. Data cutoff: April

30, 2025.

Abbreviations: CI, confidence interval; ILI, influenza-like illness; N, number of participants in the analysis set; n, number of cases of

protocol-defined ILI in the given age subgroup; PP, per protocol; RT-PCR, real-time reverse transcription polymerase chain reaction;

rVE, relative vaccine efficacy; SD, standard dose; yoa, years of age

The case is the first RT-PCR–confirmed protocol-defined ILI that begins at least 14 days after study vaccination through the end of influenza

season caused by any influenza A or B strains, regardless of vaccine match.

a

Percentages are based on the number of participants in the analysis set in each subgroup.

b

rVE is defined as 100×(1−hazard ratio [mRNA-1010 versus the Active Comparator]). The rVE and the CI are based on a stratified Cox

proportional hazards model with the study vaccination group as a fixed effect, adjusting by the randomized stratification factors: age group

(≥50 to <65 years or ≥65 years) and the status of influenza vaccine in the previous influenza season (received or not received). Efron´s

method is used to handle ties.

Table 3 presents rVE against RT-PCR–confirmed, protocol-defined ILI stratified by influenza

strain. Point estimates of rVE were consistent across all strains. For influenza B/Victoria, the

rVE point estimate aligned with the overall estimate; however, the 95% CI was wide with a

lower limit below zero (−18.5%), reflecting the limited number of influenza B cases. Influenza

A strains predominated, accounting for 94.0% of all influenza cases and driving the overall

estimate. Antigenic match between circulating and vaccine strains varied: A/H1N1 (~98%),

B/Victoria (~94%), and A/H3N2 (~52–56%). For A/H3N2, rVE trended higher against

antigenically matched strains [30.5% (95% CI: 4.6, 49.4)] compared with rVE against all

strains [22.2% (95% CI: 4.3, 36.9)], suggesting higher efficacy in seasons with greater

antigenic concordance.

14

Table 3. Analysis of Primary Efficacy Endpoint of Relative Vaccine Efficacy (rVE) for mRNA-1010 (TIV)

Versus SD Comparator Against RT-PCR–Confirmed Protocol-Defined ILI Caused by Influenza Strain

Type in Participants 50 Years of Age and Older (PP Set), Study P304

mRNA-1010

SD Comparator

(TIV) rVE (%)

Influenza Strain Type N=20,124 Interpretation

N=20,179 (95% CI)b

Cases, n (%)a

Cases, n (%) a

386 522 26.5

Any influenza A strain CI excludes zero; robust

(1.9) (2.6) (16.1, 35.5)

223 315 29.6

Influenza A/H1N1 CI excludes zero; robust

(1.1) (1.6) (16.4, 40.7)

CI excludes zero; 44-

158 202 22.2

Influenza A/H3N2 48% antigenically

(0.8) (1.0) (4.3, 36.9)

mismatched

CI crosses zero;

25 35 29.1

Influenza B/Victoria strain limited accrual;

(0.1) (0.2) (-18.5, 57.5)

point estimate consistent

Source: Adapted from STN 125869/0, mRNA-1010 P304 Clinical Study Report, Tables 14.2.1.1.1.1 and 14.2.1.1.3.1. Data cutoff: April 30,

2025.

Abbreviations: CI, confidence interval; ILI, influenza-like illness; N, number of participants in the PP analysis set; n, number of cases of RT-

PCR confirmed ILI; PP, per protocol; RT-PCR, real-time reverse transcription polymerase chain reaction; rVE, relative vaccine efficacy; SD,

standard dose

a

Percentages are based on the number of participants in the analysis set. The case is the first RT-PCR–confirmed protocol-defined ILI that

begins at least 14 days after study vaccination through the end of influenza season caused by any influenza A or B strains, regardless of

vaccine match. Participants can have more than one influenza strain infection simultaneously.

b

rVE was defined as 100×(1−hazard ratio [mRNA-1010 versus the Active Comparator]). The rVE and the CI are based on a stratified Cox

proportional hazards model with the study vaccination group as a fixed effect, adjusting by the randomized stratification factors: age group

(≥50 to <65 years or ≥65 years) and the status of influenza vaccine in the previous influenza season (received or not received). Efron´s

method is used to handle ties. If there were <20 events total in the two vaccination groups combined, rVE was not provided.

3.1.2.2 Primary Immunogenicity Study (65 yoa and older)

A formal correlate of protection (CoP) has not been established for mFlusiva to support traditional

approval. Therefore, the application relies on HAI as a surrogate endpoint reasonably likely to

predict clinical benefit, under the Accelerated Approval pathway. Immunogenicity data from Study

P303 Part C provide the primary evidence to support effectiveness of mRNA-1010 (TIV) in adults

aged 65 years and older, based on HAI GMT and SCR as surrogate endpoints reasonably likely

to predict clinical benefit. Primary immunogenicity endpoints (HAI assay) for vaccine-matched

influenza strains at Day 29 are presented in Table 4 and Table 5. Baseline geometric mean titers

(GMTs) were comparable between mRNA-1010 (QIV) and Fluzone HD (QIV). At Day 29, mRNA-

1010 (QIV) demonstrated higher GMTs and seroconversion rates (SCRs) than Fluzone HD (QIV)

across all four strains.

Noninferiority was met for all four strains based on GMT ratio (95% CI LL >0.667) and SCR

difference (95% CI LL >−10%). Superiority was demonstrated for all four strains based on GMT

ratio (97.5% CI LL >1) and SCR difference (97.5% CI LL >0%). This finding constitutes the

principal basis for the effectiveness determination in this age group.

15

Table 4. Analyses of Primary Immunogenicity Endpoint of GMTs as Measured by Hemagglutination

Inhibition (HAI) for Vaccine-Matched Influenza Strains at Day 29 Postvaccination, Participants 65 Years

of Age and Older, PPIS, Study P303 Part C

GMT Ratio (mRNA-1010

mRNA-1010 (QIV) Fluzone HD (QIV) [QIV] / Fluzone HD

Endpoint N=1425 N=1409 [QIV])

GMT (95% CI) GMT (95% CI) (95% CI)

(97.5% CI)

1.3

168.3 125.7

Influenza A/H1N1 (1.3, 1.4)

(160.4, 176.7) (119.7, 131.9)

(1.2, 1.4)

1.2

137.9 113.8

Influenza A/H3N2 (1.1, 1.3)

(130.9, 145.4) (107.9, 120)

(1.1, 1.3)

1.3

242.1 193.7

Influenza B/Victoria (1.2, 1.3)

(232.9, 251.6) (186.3, 201.3)

(1.2, 1.3)

1.1

102.7 89.8

Influenza B/Yamagata (1.1, 1.2)

(99.2, 106.2) (86.8, 92.9)

(1.1, 1.2)

Source: Adapted from STN 125869/0, mRNA-1010 P303 Clinical Study Report, Table 14.2.1.1.c. Data cutoff: June 24, 2024.

Abbreviations: ANCOVA, analysis of covariance; CI, confidence interval; GMT, geometric mean titer; HAI, hemagglutination inhibition; HD,

high dose; LLOQ, lower limit of quantification; N, number of participants with nonmissing HAI data at corresponding visit; PPIS, per protocol

immunogenicity set; QIV, quadrivalent; ULOQ, upper limit of quantification

Antibody values reported as below the LLOQ are replaced by 0.5× LLOQ. Values greater than the ULOQ are converted to the ULOQ.

The log-transformed antibody levels are analyzed using an ANCOVA model with vaccination group as the fixed variable, log transformed

baseline HAI titers as a fixed covariate, adjusting for the randomization stratification factor: Influenza Vaccine Status Since September 2022

to 6 Months Ago (not received seasonal flu vaccine, received seasonal flu vaccine from non mRNA-1010-P302, and received seasonal flu

vaccine from mRNA-1010-P302).

The model based GMT and GMT ratio, and its corresponding 95% CI and/or 97.5% CI are obtained by transforming the least square mean

estimate and its CI back to the original scale for presentation.

16

Table 5. Analyses of Primary Immunogenicity Endpoint of SCRs as Measured by Hemagglutination

Inhibition (HAI)cr for Vaccine-Matched Influenza Strains at Day 29 Postvaccination, Participants

65 Years of Age and Older, PPIS, Study P303 Part C

Difference in SCR

mRNA-1010 (QIV) Fluzone HD (QIV) (mRNA-1010

Endpoint N=1425 N=1409 [QIV]−Fluzone HD [QIV])

SCR%a (95% CI) SCR%a (95% CI) (95% CI)b

(97.5%CI)c

13.4

49.7 36.3

Influenza A/H1N1 (9.8, 17)

(47.1, 52.3) (33.8, 38.8)

(9.3, 17.5)

8.6

56.4 47.8

Influenza A/H3N2 (4.9, 12.2)

(53.8, 59) (45.2, 50.5)

(4.4, 12.8)

9.7

29.8 20.2

Influenza B/Victoria (6.5, 12.8)

(27.5, 32.3) (18.1, 22.4)

(6.0, 13.3)

5.9

26.0 20.2

Influenza B/Yamagata (2.8, 8.9)

(23.8, 28.4) (18.1, 22.4)

(2.3, 9.4)

Source: Adapted from STN 125869/0, mRNA-1010 P303 Clinical Study Report, Table 14.2.1.1.c. Data cutoff: June 24, 2024

Abbreviations: CI, confidence interval; HAI, hemagglutination inhibition; HD, high dose; LLOQ, lower limit of quantification; N, number of

participants with nonmissing HAI data at baseline (Day 1) and the corresponding visit; PPIS, per protocol immunogenicity set; QIV,

quadrivalent influenza vaccine; SCR, seroconversion rate; ULOQ, upper limit of quantification

Antibody values reported as below the LLOQ are replaced by 0.5× LLOQ. Values greater than the ULOQ are converted to the ULOQ.

a

Rate of seroconversion is defined as the proportion of participants with either a baseline HAI titer <1:10 and a postbaseline titer ≥1:40 or a

baseline HAI titer ≥1:10 and a minimum 4-fold rise in postbaseline HAI antibody titer.

b

95% CI is calculated using the Clopper-Pearson method.

c

95% CI, 97.5% CI are calculated using the Miettinen-Nurminen (score) method.

As described in detail in Appendix C, additional immunogenicity outcomes and subgroup

analyses support a conclusion that mRNA-1010 (TIV) is effective in adults 65 yoa and older,

subject to the caveats regarding surrogate endpoint use and the limitations of the QIV-to-TIV

bridging analysis described in Section 3.1.3 below.

Additional Immunogenicity Outcomes

Descriptive secondary endpoints demonstrated superior immune responses in the mRNA-

1010 (QIV) group compared with Fluzone HD (QIV) across all four influenza strains.

Specifically, the percentage of participants achieving HAI titers ≥1:40 and geometric mean fold

rise (GMFR) from baseline to Day 29 were both higher in the mRNA-1010 group.

At Day 181, GMTs remained numerically higher in the mRNA-1010 group for all four strains,

though confidence intervals overlapped for three strains; only A/H3N2 demonstrated non-

overlapping confidence intervals (see Appendix C Table 8). The percentage of participants

with seroconversion at Day 181 was also higher in the mRNA-1010 group across all four

strains, with overlapping confidence intervals for all strains except A/H1N1 (see Appendix C

Table 9).

Microneutralization (MN) titers were evaluated at Day 29 in a subset of 500 participants (250

per group) (see Appendix C). MN titers were higher in the mRNA-1010 group for all four

strains and demonstrated positive correlation with HAI titers for each strain.

Subgroup Analyses

The Applicant conducted descriptive subgroup analyses for the primary immunogenicity

endpoints. The noninferiority criteria based on GMT ratio and SCR difference would have

been met across all four strains in every subgroup with a sufficient sample size for meaningful

interpretation.

17

Post Hoc Analysis of mRNA-1010 (QIV) and mRNA-1010 (TIV)

To support licensure of mRNA-1010 (TIV) in adults 65 yoa and older, the Applicant conducted

a post hoc analysis comparing Day 29 HAI GMTs between the Per-Protocol Immunogenicity

Sets of Study P303 Part C (mRNA-1010 [QIV]) and Study P304 (mRNA-1010 [TIV]), restricted

to participants 65 yoa and older. Noninferiority of the Day 29 HAI GMT ratio (mRNA-1010

[QIV] / mRNA-1010 [TIV]) was demonstrated for all three shared strains, with the LL of the

95% CI >0.667 (see Appendix C Table 7).

This analysis has several limitations. Studies P303 Part C and P304 were conducted in

different influenza seasons using different WHO-recommended strains. Although the analysis

adjusted for baseline demographics, the non-randomized design introduces potential residual

confounding. For Influenza A/H1N1, the GMT ratio of 1.0 indicates no meaningful difference

between formulations. For Influenza A/H3N2 and B/Victoria, mRNA-1010 (QIV) elicited lower

antibody responses than mRNA-1010 (TIV), with GMT ratio point estimates and upper 95% CI

bounds both <1.0, although noninferiority was met for both strains. The inclusion of

B/Yamagata in the quadrivalent formulation may have reduced immune responses to A/H3N2

and B/Victoria; however, this bias would favor mRNA-1010 (TIV), not mRNA-1010 (QIV).

Despite these limitations, FDA’s preliminary assessment is that mRNA-1010 (QIV)

immunogenicity data may support the effectiveness of mRNA-1010 (TIV) in adults 65 yoa and

older.

3.1.3. Efficacy Issues in Detail

3.1.3.1 Efficacy Issue 1: Adequacy and Clinical Meaningfulness of rVE vs. SD Comparator in

Adults 65 Years of Age and older

The active comparator in Study P304 was a licensed SD inactivated influenza vaccine (Fluarix

[TIV] in North America; Fluarix [QIV] in Europe and East Asia). For adults 65 yoa and older, high-

dose (HD-IIV4), recombinant (RIV), and adjuvanted (aIIV4) influenza vaccines are preferentially

recommended by the Advisory Committee on Immunization Practices (ACIP) over SD

formulations. Accordingly, the SD comparator used in P304 is not the preferred standard of care

in this age stratum.

Although mRNA-1010 (TIV) demonstrated superiority over the SD comparator in participants 65

yoa and older (rVE 27.4%; 95% CI: 12.1, 40.0), the clinical meaningfulness of an rVE advantage

over a non-preferentially recommended comparator in this age group requires consideration.

Specifically, the rVE does not directly establish the magnitude of benefit relative to HD, RIV or

adjuvanted vaccines—the vaccines most adults 65 yoa and older would otherwise receive. 3 This

limitation affects interpretation of the net clinical benefit in the 65 yoa and older population and is

a key issue for Advisory Committee deliberation.

3.1.3.2 Efficacy Issue 2: Influenza B/Victoria Low Case Accrual

The rVE point estimate against influenza B/Victoria (29.1%; 95% CI: −18.5, 57.5) was consistent

with the overall efficacy estimate; however, the 95% CI is wide and crosses zero, reflecting limited

statistical precision due to low case counts (25 cases in the mRNA-1010 [TIV] group vs. 35 in the

3 If none of the three preferentially recommended vaccines are available at a vaccination site, the CDC

recommends that individuals 65 yoa and older should get any other age-appropriate standard influenza

vaccine rather than going unvaccinated.

18

SD comparator group). The limited influenza B/Victoria case accrual reflects the overall

dominance of influenza A strains in the 2024-2025 season (94.0% of confirmed cases). While the

point estimate is directionally consistent with overall efficacy, uncertainty regarding the magnitude

of protection against influenza B/Victoria cannot be resolved from single-season data alone,

particularly in a season with limited influenza B circulation.

In addition, the following limitations warrant consideration:

• Immunogenicity as supporting evidence: Immunogenicity data may provide

mechanistic support for the observed efficacy for all three vaccine strains (A/H1N1,

A/H3N2, B/Victoria). However, a CoP has not been established for mFlusiva. Formal

correlate of risk (CoR)/CoP analyses (see Appendix B Secondary Immunogenicity

Objectives) are ongoing and outside the scope of this briefing document.

• Cell-derived, mRNA-1010-matched virus as a potential source of assay-dependent

immunogenicity assessment bias: The exclusive use of Madin-Darby Canine Kidney

(MDCK) cell-derived influenza virus matched to mRNA-1010 vaccine strains in HAI

assays may introduce systematic bias in immunogenicity comparisons with egg-based

comparator vaccines. Specifically, the use of MDCK-derived mRNA-1010-matched

viruses may underestimate the comparative immunogenicity of egg-based vaccines

relative to mRNA-1010, particularly for influenza A(H3N2), where egg-adaptive

mutations are most frequent. Although cell-derived viruses generally better represent

circulating wild-type viruses, the assay design choice to use exclusively cell-derived,

mRNA-1010-matched viruses could systematically favor mFlusiva in comparative

immunogenicity assessments. Review of how assay virus selection affects the relative

immunogenicity of mFlusiva versus the egg-based comparator are ongoing and outside

the scope of this briefing document.

3.1.3.3 Efficacy Issue 3: Adequacy of Single-Season Data and Study Population

Study P304 was originally designed to enroll participants across up to two NH influenza seasons,

with an interim analysis planned at the end of the first season when approximately 70% of target

cases were expected. Due to high influenza transmission during the 2024–2025 NH season, the

prespecified case target of 836 was exceeded (968 cases accrued), and the study concluded after

a single season. The interim analysis was therefore designated the primary efficacy analysis,

using the full one-sided alpha of 2.5%.

While robust efficacy was demonstrated within a single season, the following limitations warrant

consideration:

• Generalizability across seasons: Efficacy was evaluated under a single set of

circulating strains and season-specific epidemiologic conditions. Performance in seasons

with different dominant strains (e.g., influenza B-predominant seasons, or seasons with

greater antigenic mismatch) is not directly assessed.

• Antigenic mismatch: A/H3N2 antigenic match was approximately 52–56%, and rVE

improved when restricted to matched cases (30.5% vs. 22.2%), suggesting season-

specific factors influenced efficacy estimates.

The following limitation on the P304 study population warrants consideration:

19

• Study population generalizability: The P304 study population was healthier and less

frail than the general U.S. target population, as the study excluded immunocompromised

individuals and enrolled participants with a lower prevalence of high-risk conditions (see

Appendix G for definitions). In contrast, the general U.S. target population has a

substantially higher prevalence of high-risk conditions (78–93%) compared with the P304

study population (57%) [Watson et al., 2025], although this difference may be partially

attributable to differences in how high-risk conditions are defined.

Relative vaccine effectiveness (rVE) was lower in high-risk P304 participants [22.3%;

95% CI: 8.0–34.3%] compared with non-high-risk participants [32.1%; 95% CI: 17.5–

44.2%] (see Appendix B Table 10). The 95% confidence intervals overlap, and the study

was not powered to detect a statistically significant difference in rVE between risk strata;

therefore, this finding should be interpreted cautiously. Nevertheless, the direction of the

difference suggests that rVE in the healthier study population may overestimate

effectiveness in the general U.S. target population.

3.1.3.4 Effectiveness Issue 4: Surrogate Endpoint Reasonably Likely to Predict Benefit in Adults

65 yoa and older

Given the uncertainty of the adequacy and clinical meaningfulness of rVE of mRNA-1010 (TIV)

versus SD comparator in adults 65 yoa and older (see Section 3.1.3.1), effectiveness in this

population was assessed using HAI GMT and SCR as surrogate endpoints reasonably likely to

predict clinical benefit. Because direct demonstration of rVE in adults 65 yoa and older versus

preferred standard of care in this population is absent, if mFlusiva is approved for use in this age

group, FDA will require the Applicant to conduct a Phase 4 confirmatory study to verify and

describe the clinical benefit of mFlusiva in this population as a postmarketing requirement under

the proposed Accelerated Approval pathway.

In Study P303 Part C, mRNA-1010 (QIV) demonstrated noninferiority and superiority to Fluzone

HD (QIV)—an established high-dose comparator with demonstrated efficacy superiority over

Fluzone (a SD influenza vaccine) in adults 65 yoa and older—for all eight coprimary HAI-based

endpoints (GMT ratio and seroconversion rate [SCR] difference for all four vaccine-matched

strains) at Day 29 postvaccination. Because licensure is sought for mRNA-1010 as a trivalent

formulation (TIV) rather than the quadrivalent formulation (QIV) evaluated in P303 Part C, the

Applicant conducted a post hoc QIV-to-TIV bridging analysis comparing Day 29 HAI GMTs

between the per-protocol immunogenicity sets of both studies, restricted to participants 65 yoa

and older. Noninferiority of the GMT ratio was demonstrated for all three shared influenza strains

(lower limit of 95% CI >0.667 for each); point estimates and upper bounds of the 95% CI for

A/H3N2 and B/Victoria were <1.0, indicating slightly lower antibody responses for these strains in

the QIV group, consistent with potential immune competition from the B/Yamagata component.

Although the studies were conducted in different influenza seasons and participants were not

randomized between studies, the directionality of any immunogenic attenuation favors mRNA-

1010 (TIV). FDA’s assessment is that the P303 Part C immunogenicity data may be used to

support effectiveness of mRNA-1010 (TIV) in this age group, subject to verification through the

required Phase 4 confirmatory study.

In addition, the following limitations apply to the use of immunogenicity data as surrogate

endpoints reasonably likely to predict clinical benefit in adults 65 yoa and older:

• Status of CoR/CoP analyses: Immunogenicity endpoints (HAI GMT and SCR) are used

as primary evidence to infer effectiveness of mFlusiva in adults 65 yoa and older. As

noted in Section 3.1.3.2, formal CoR/CoP analyses (see Appendix B Secondary

Immunogenicity Objectives)are ongoing.

20

• Potential source of assay-dependent immunogenicity assessment bias: HAI

assays used exclusively MDCK cell-derived, mRNA-1010-matched virus. This assay

design choice may introduce systematic bias favoring mFlusiva in the surrogate endpoint

comparisons used to infer effectiveness in adults 65 yoa and older. As noted in Section

3.1.3.2, analyses of the effect of assay virus selection on relative immunogenicity are

ongoing.

3.2. Safety Issues

The integrated safety data for mRNA-1010 do not reveal major safety issues or deficiencies. This

assessment is based on approximately 6 months of follow-up in a population that excluded

immunocompromised individuals and the very frail; generalizability to these groups is limited.

Rare adverse events may not be detectable in the current dataset and will require ongoing

postmarket surveillance.

Three issues warrant Advisory Committee consideration:

• Potential Safety Issue 1: Higher solicited adverse reaction rates relative to the standard-

dose comparator

• Potential Safety Issue 2: Numerical imbalances in SAEs between mRNA-1010 and

comparator recipients: unspecified deaths (23 vs. 9), anemia SAEs (14 vs. 8), and UTI

SAEs (38 vs. 22)

 Potential Safety Issue 3: Rare adverse events (myocarditis, GBS, neurologic events)

FDA's assessment of each issue is provided in Section 3.2.3.

3.2.1. Sources of Data for Safety

3.2.1.1 Primary Studies

The two primary sources for the safety evaluation are Study P304 (see Appendix B) and Study

P303 Part C (see Appendix C), each with approximately 6 months of follow-up. These studies

provide the most direct characterization of the safety profile of the mRNA-1010 formulation

intended for licensure and the proposed indication.

3.2.1.2 Integrated Safety Summary (ISS)

To support a broader characterization of safety, the Applicant conducted an ISS, pooling data

from all four Phase 3 studies: P301, P302, P303, and P304 (see Appendix D). The ISS includes

all randomized participants 50 yoa and older who received at least one study injection. The ISS

population comprised 71,916 participants: 35,965 mRNA-1010 recipients and 35,951 SD/HD

comparator recipients. Median follow-up was 198 days in both groups (range: 1–449 days,

mRNA-1010; 1–445 days, SD/HD comparator). Study completion rates were high and comparable

(95.1% vs. 95.2%). The pooled mRNA-1010 group includes participants from trivalent (TIV) and

quadrivalent (QIV) formulations across studies; the pooled comparator group includes standard-

dose and high-dose licensed influenza vaccines (Fluarix TIV/QIV; Fluzone HD QIV). Adverse

events were coded using MedDRA version 25.0.

3.2.2. Safety Summary

The pooled ISS analysis across all four Phase 3 studies did not identify adverse event patterns

definitively indicative of a safety concern for mFlusiva. Table 6 summarizes key findings that

21

characterize the overall safety profile. SAEs, deaths, and AESIs are summarized in the text

below.

Table 6. Safety Profile of mRNA-1010 versus Comparator: Summary of Key Findings from Study

P304a,b,c and Pooled Phase 3 Studiesd,e,f,g,h

mRNA-

Safety Domain Comparator FDA Assessment

1010

More frequent; Grade 3: 1.7%;

Solicited Local Reactions (7 days)a 67.5% 32.1%

median 2 days

More frequent; Grade 3: 5.5%;

Solicited Systemic Reactions (7 days)b 58.0% 32.4%

median 2 days

Unsolicited AEs (28 days)c 5.9% 5.7% Balanced

Serious Adverse Events (median

3.1% 2.9% Balanced; <0.1% assessed as related

follow-up 198 days)d

Deaths (median follow-up 198

0.3% 0.3% Balanced; none assessed as related

days)d

AESIs (median follow-up 198 days)d 0.1% 0.1% Balanced

Myocarditis/Pericarditisd 10 cases 7 cases No signal; no cases in 42-day risk window

1 case

Guillain-Barré Syndromed 0 cases Outside 42-day risk window; not related

(Day 134)

No signal; 1 case in each group in 42-day

Bell's Palsyd 1 case 4 cases

risk window

a

Source: Adapted from STN 125869/0, mRNA-1010 P304 Clinical Study Report, Table 14.3.1.2.1.f. Data cutoff: April 30, 2025.

b

Source: Adapted from STN 125869/0, mRNA-1010 P304 Clinical Study Report, Table 14.3.1.2.1.8.f. Data cutoff: April 30, 2025.

c

Source: Adapted from STN 125869/0, mRNA-1010 P304 Clinical Study Report, Table 14.3.1.2.1.f and Appendix D (Integrated Safety

Summary, pooled Phase 3 studies). Data cutoff: August 21, 2025 (P304); June 24, 2024 (ISS).

d

Source: Adapted from STN 125869/0, Integrated Safety Summary (see Appendix below), pooled data from Studies P301, P302,

P303, and P304. Data cutoff: June 24, 2024. Median follow-up was 198 days in both groups (range: 1–449 days in the mRNA-1010

group; 1–445 days in the SD/HD comparator group). Study completion rates were high and comparable: 95.1% in the mRNA-1010

group and 95.2% in the SD/HD comparator group.

3.2.2.1 Serious Adverse Events (SAEs)

Within 28 days postvaccination, SAEs occurred in 0.5% of mRNA-1010 recipients and 0.5% of

SD/HD comparator recipients. Over the full study period (median follow-up of 198 days), SAEs

were reported in 3.1% vs. 2.9% of participants, respectively. The most frequently reported SAEs

were in the infections and infestations SOC (0.7% vs. 0.6%). The most frequently reported SAEs

by PT included pneumonia (36 vs. 32), COPD (35 vs. 24), and cerebrovascular accident (32 vs.

29), all occurring in <0.1% of participants in either group. Six PTs with SAEs occurring in at least

four participants per group had risk differences with 95% confidence intervals (CIs) excluding

zero. Three PTs were numerically higher in the mRNA-1010 group: death (unspecified) (23 vs. 9),

UTI (25 vs. 12), and anemia (9 vs. 2), all reported in <0.1% of participants in either group,

discussed below in Section 3.2.3.2.

Nine mRNA-1010 recipients (<0.1%) and 3 SD/HD comparator recipients (<0.1%) had at least

one SAE assessed as vaccine-related by the Investigator. See Appendix D Investigator-Assessed

Vaccine-Related SAEs.

22

3.2.2.2 Deaths

Over the full study period, deaths were reported in 102 mRNA-1010 recipients (0.3%) and 97

SD/HD comparator recipients (0.3%). Within 28 days of vaccination, deaths were few and

comparable across groups (13 vs. 14). By System Organ Class (SOC), deaths were most

commonly attributed to cardiac disorders (24 vs. 30). A numerical imbalance was identified in

preferred term (PT) death (unspecified cause): 23 mRNA-1010 recipients versus 9 comparator

recipients. When pooling related death categories (sudden death, sudden cardiac death, and

unspecified fatal events), the imbalance widened to 29 mRNA-1010 recipients versus 12

comparator recipients. Detailed case-level analyses are presented in Section 3.2.3.2.1 and

Appendix D.1. Deaths

The interpretation of this imbalance is constrained by the absence of autopsy data in the mRNA-

1010 group, which limits definitive cause-of-death ascertainment. FDA's assessment, based on

temporal distribution of events, overall mortality balance across the trial, and documented pre-

existing comorbidities, suggests that this imbalance is unlikely to represent a causal relationship

with vaccination.

3.2.2.3 Adverse Events of Special Interest (AESIs)

Through the full study period, AESIs were reported in 36 (0.1%) vs. 37 (0.1%) participants,

respectively. Through 28 days postvaccination, AESIs were reported in 7 mRNA-1010 recipients

(<0.1%) and 4 SD/HD comparator recipients (<0.1%). There were no cardiac AESIs (myocarditis,

pericarditis, myopericarditis) reported in the 42-day risk window. Beyond the 42-day risk window

and throughout the studies, cardiac AESIs (myocarditis, pericarditis, myopericarditis) were

reported in 10 mRNA-1010 recipients and 7 SD/HD comparator recipients; Cardiac Event

Adjudication Committee (CEAC)-confirmed cases were balanced (4 vs. 3). No cases of GBS were

reported in the SD/HD comparator group; one GBS event (PT: demyelinating polyneuropathy)

occurred in the mRNA-1010 group at Day 134, outside the established 42-day risk window. Bell's

palsy within the 42-day risk window was reported in one participant per group. See Appendix D.3.

3.2.3. Safety Issues in Detail

See Appendix D for details.

3.2.3.1 Higher Solicited Adverse Reaction Rates vs. Standard-Dose Comparator

Solicited local and systemic adverse reaction rates were higher in mRNA-1010 recipients

compared with standard-dose comparator recipients, consistent with the reactogenicity profile

expected of an mRNA-based vaccine. Solicited adverse reactions in mRNA-1010 recipients were

predominantly mild to moderate in severity (Grade 1–2), with a median duration of approximately

2 days. Grade 3 solicited systemic adverse reactions were reported in 5.5% of mRNA-1010

recipients compared with 0.9% of SD comparator recipients; no Grade 4 solicited systemic

adverse reactions were reported. These reactions are transient and expected to resolve without

medical intervention for the majority of recipients. Detailed solicited adverse reaction data and

FDA assessments are presented in the primary study review for Study P304. Solicited adverse

reaction rates were also higher in mRNA-1010 (QIV) recipients compared with high-dose

comparator recipients (see Study P303 Part C). FDA considers the reactogenicity profile

acceptable for the intended population and consistent with the benefit-risk assessment for mRNA-

1010.

3.2.3.2 Numerical Imbalances in Unspecified Deaths, Anemia SAEs, and UTI SAEs

23

3.2.3.2.1 Deaths of Unspecified Cause

A numerical imbalance was identified in the PT death (unspecified): 23 mRNA-1010 recipients vs.

9 SD/HD comparator recipients. An expanded analysis pooling the PTs of death, sudden death,

and sudden cardiac death identified 29 mRNA-1010 recipients and 12 SD/HD comparator

recipients with unspecified fatal events. Median time to onset was approximately 131 days (range:

2–319 days) in the mRNA-1010 group and 87 days (range: 9–343 days) in the SD/HD comparator

group; deaths within 28 days of vaccination under these PTs were few and similar across groups

(3 vs. 2). Approximately 60% of participants with unspecified fatal events were ≥65 yoa. Nearly all

had multiple pre-existing comorbidities, including hypertension, diabetes mellitus, chronic kidney

disease, hyperlipidemia, coronary artery disease, atrial fibrillation, prior myocardial infarction,

congestive heart failure, and COPD. Causes of death were predominantly recorded as unknown

or natural causes. No autopsies were conducted in the mRNA-1010 group deaths.

One death occurring on Day 2 in Study P303 Part A — in a 76-year-old female with significant

cardiac history [prior coronary artery bypass graft (CABG), atrial fibrillation, type 2 diabetes

mellitus] — was assessed as vaccine-related by the Investigator based on temporality. FDA

considers the participant's underlying cardiac disease a more plausible alternative etiology,

though a contribution from a vaccine-related inflammatory response cannot be fully excluded.

FDA Assessment: The temporal distribution of deaths from unspecified causes does not suggest

a causal relationship to vaccination. Deaths of unspecified cause within 28 days of vaccination

were few and comparable across groups (3 in the mRNA-1010 group vs. 2 in the SD/HD

comparator group), and the remaining deaths were distributed across later time intervals without

apparent pattern or clustering. The overall balance in all-cause mortality and in cause-specific

deaths by PT further supports this interpretation. Also supporting this assessment are the

presence of extensive pre-existing comorbidities among study participants, lack of imbalance

observed in cardiac SAEs, including in cardiac arrhythmias, and the lack of investigator

assessment of relatedness for these events, with one exception. Considering the totality of

available evidence, the numerical imbalance in unspecified deaths is unlikely to represent a

vaccine safety signal for mRNA-1010.

3.2.3.2.2 Anemia SAEs

An expanded analysis across related anemia PTs (anemia of chronic disease, blood loss anemia,

hypochromic anemia, iron deficiency anemia, normocytic anemia) identified 14 mRNA-1010

recipients and 8 SD/HD comparator recipients with anemia SAEs. No events were assessed as

vaccine-related by the Investigator. Most events occurred more than 90 days post-injection, with

no temporal clustering. All mRNA-1010 recipients with anemia SAEs had identifiable alternative

etiologies, including iron deficiency, gastrointestinal bleeding, renal or hepatic disease, serious

infection, and concomitant medication use. A review of medically attended adverse events

(MAAEs) of anemia in Study P304 identified comparable rates between groups (31 mRNA-1010

[TIV] vs. 30 SD comparator recipients).

FDA Assessment: The late onset, absence of temporal clustering, presence of plausible

alternative etiologies, and balanced MAAE rates in Study P304 collectively indicate that the

numerical imbalance in anemia SAEs is unlikely to reflect a causal association with mRNA-1010.

24

3.2.3.2.3 Urinary Tract Infection (UTI) SAEs

An expanded analysis across related UTI PTs (urinary tract infection bacterial, Escherichia urinary

tract infection, cystitis, kidney infection, pyelonephritis, acute pyelonephritis, urosepsis) identified

38 mRNA-1010 recipients and 22 SD/HD comparator recipients with UTI SAEs. No events were

assessed as vaccine-related by the Investigator. Median time to onset was 135 days (mRNA-

1010) and 112.5 days (SD/HD comparator); no temporal clustering was observed. The majority of

participants in both groups had established UTI risk factors, including advanced age, female sex,

postmenopausal status, diabetes mellitus, obstructive uropathies, chronic kidney disease, and

use of concomitant medications associated with increased UTI risk. MAAEs of UTI in Study P304

were comparable between groups (153 mRNA-1010 [TIV] vs. 158 SD comparator recipients).

FDA Assessment: The late and non-clustered onset, the presence of recognized risk factors in

the majority of affected participants, and the balanced MAAE rates in Study P304 indicate that the

numerical imbalance in UTI SAEs is unlikely to reflect a causal association with mRNA-1010.

3.2.3.3 Rare Adverse Events

The primary safety database for mRNA-1010 is based on Studies P303 Part C and P304. While

this sample size is adequate to characterize relatively frequent acute and subacute safety profile,

it is insufficient to detect rare adverse events, including myocarditis, Guillain-Barré syndrome

(GBS), and other neurological events of interest. Current AESI analyses for

myocarditis/pericarditis and new-onset or worsening neurological disease identified no meaningful

differences between the mRNA-1010 and SD/HD comparator groups, though the power to detect

any rare adverse events is limited by sample size.

FDA Assessment: Post-licensure monitoring will be required to fully characterize the risk of rare

adverse events. Routine postmarket pharmacovigilance activities will be the primary mechanism

for ongoing safety monitoring following licensure.

3.3. Risk Mitigation

3.3.1 Postmarketing Confirmatory Phase 4 Study

Under the Accelerated Approval regulations, a Phase 4 confirmatory study is required to verify

and describe the clinical benefit of mFlusiva in individuals 65 yoa and older. The Applicant has

proposed to conduct a Phase 4, cluster-randomized, active-controlled, pragmatic study to

evaluate the relative vaccine effectiveness of mFlusiva compared with agreed upon CDC-

preferentially recommended vaccine in U.S. adults 65 yoa and older (see Appendix H). The study

protocol and proposed timeline are currently under review and are the subject of ongoing

discussions between FDA and the Applicant.

3.3.2 Pharmacovigilance Activities

Moderna submitted a Pharmacovigilance Plan (Version 1.0, dated January 28, 2026) to monitor

safety concerns that could be associated with mFlusiva. The Applicant identified no important

identified or potential risks and no missing information requiring additional pharmacovigilance

beyond routine surveillance at this time.

The Applicant will conduct routine postmarketing pharmacovigilance surveillance activities per 21

CFR 600.80, including submissions of periodic safety reports (Periodic Adverse Experience

Reports) to monitor for and assess any emerging risks associated with the vaccine.

25

Although no safety concerns were identified in the pre-licensure clinical program for the protocol-

defined AESIs, the Applicant plans to provide aggregate safety assessments (based on interval

and cumulative data) of the following AESIs in their periodic safety reports for the first 3 years

postapproval:

 Thrombocytopenia

 Guillain-Barré syndrome

 Acute disseminated encephalomyelitis

 Idiopathic peripheral facial nerve palsy (Bell’s palsy)

 Seizures, including but not limited to febrile seizures and/or generalized seizures/

convulsions

 Anaphylaxis

 Myocarditis

 Pericarditis

 Myopericarditis

The Applicant identified these AESIs as medical concepts that are generally of interest in vaccine

safety surveillance as well as events inconsistently associated with previously licensed influenza

vaccines. Aggregate safety assessments for AESIs will include review of available safety data

from spontaneous AE reporting, postmarketing studies, and literature reports.

Because no important identified or potential risks and no missing information were identified in the

pre-licensure safety database, the applicant has not proposed any additional pharmacovigilance

studies at this time. The details of the pharmacovigilance plan remain subject to discussion

between FDA and the Applicant.

Under the National Childhood Vaccine Injury Act (NCVIA) and implementing regulations, health

care providers are required to report events listed in the VAERS Reportable Events Table

occurring within designated time intervals following vaccination, as well as manufacturer-listed

contraindications to further vaccination (https://vaers.hhs.gov/resources/infoproviders.html).

The NCVIA also requires dissemination of CDC-issued Vaccine Information Statements (VISs) to

vaccine recipients prior to administration of covered vaccines.

4. Benefit-Risk Framework

Disclaimer: This pre-decisional Benefit-Risk Framework does not represent FDA's final benefit-

risk assessment or regulatory decision.

Comments to the Advisory

Evidence and Uncertainties

Committee

Analysis of Influenza is a high-burden, vaccine- Serious, high-burden disease with

Condition preventable infectious disease with substantial unmet need, particularly in

significant morbidity and mortality, older adults. The magnitude of

disproportionately affecting adults ≥65 influenza-related morbidity and mortality

years of age, who account for ~75% of in the target population provides

influenza-related deaths in the U.S. important context for evaluating the

The condition is associated with benefit-risk profile of mFlusiva.

serious complications including

pneumonia, myocarditis, and multi-

organ failure.

The ever-present threat of pandemic There is a need for manufacturing

Influenza A as a result of a substantial technologies capable of rapid strain

26

antigenic shift creates urgent, unmet reformulation, particularly to respond to

medical need for expedited vaccine antigenic shifts.

development and deployment to

prevent widespread morbidity and

mortality in at-risk populations.

Current Annual influenza vaccination is the Existing vaccines have variable

Treatment primary preventive strategy. CDC effectiveness, particularly for older

Options preferentially recommends HD adults. There is a need for vaccines

(Fluzone HD), adjuvanted (Fluad), or with improved effectiveness, particularly

recombinant (FluBlok) vaccines for when antigenically mismatched to

adults ≥65 yoa. Standard-dose circulating strains.

vaccines achieve up to 60%

effectiveness; efficacy declines further

with antigenic mismatch. Antivirals are

available for treatment, but vaccination

remains preferred prevention.

Benefits Study P304: rVE 26.6% [95% CI: 16.7, Points to Consider:

35.4] vs. SD comparator in adults ≥50

(1) Do the primary endpoint, age

yoa. Consistent rVE across age

subgroup, and strain-specific rVE

subgroups (25.3%–28.0%) and

results from Study P304 demonstrate

influenza strains (22.2%–29.6%).

clinically meaningful efficacy of

Healthcare outcome rVE 47.9% [95%

mFlusiva in adults 50 through 64 yoa?

CI: 12.8, 68.9]. Study P303 Part C:

Superior HAI GMT and SCR vs. (2) Do the immunogenicity results from

Fluzone HD for all four vaccine- Study P303 Part C provide a

matched strains in adults ≥65 yoa; reasonable basis to predict clinical

immune persistence at Day 181. benefit of mFlusiva in adults ≥65 yoa?

Risks and Risk Solicited ARs more frequent than Point to Consider:

Management comparators (local: 67.5% vs. 32.1%;

Do the available data indicate that the

systemic: 58.0% vs. 32.4%) but

safety profile of mFlusiva is adequately

predominantly mild-moderate, median

characterized, that identified risks are

duration ~2 days. SAEs balanced

acceptable, and that residual risks can

(3.1% vs. 2.9%). No

be appropriately monitored and

myocarditis/pericarditis within 42 days.

managed through postmarketing

Numerical imbalances in unspecified

pharmacovigilance?

deaths, anemia SAEs, and UTI SAEs

in ISS; assessed as unlikely to be

vaccine-related. Single-season follow-

up; sparse data in

immunocompromised or very frail older

adults; no concomitant vaccine data.

Risk mitigation: Phase 4 confirmatory

trial; routine pharmacovigilance per 21

CFR 600.80; aggregate AESI

monitoring; VAERS reporting; VIS

distribution.

Summary of mFlusiva demonstrated superior rVE Voting questions:

Benefit-Risk vs. SD comparator in adults ≥50 yoa

Do the benefits of mFlusiva outweigh its

and superior immunogenicity vs. a

risks for the prevention of influenza

CDC-preferred HD comparator in

disease in adults 50 through 64 years of

adults ≥65 yoa. The reactogenicity

age?

profile, while elevated relative to

comparators, appears acceptable.

27

SAEs, deaths, and AESIs are Do the benefits of mFlusiva outweigh its

balanced. Evidence gaps in frail and risks for the prevention of influenza

high-risk older adults, special disease in adults 65 years of age and

populations and duration of protection older?

are acknowledged. A Phase 4

confirmatory study and postmarketing

pharmacovigilance plan are under

review.

28

5. References

Moderna TX, Inc. Biologics License Application, STN 125869/0, Clinical Overview. December 5,

2025.

America’s Health Rankings (2025). "Obesity - Age 65+ in United States." Retrieved May 28, 2026,

from https://www.americashealthrankings.org/explore/measures/obesity sr.

CDC. (2024). "CDC Seasonal Flu Vaccine Effectiveness Studies." Retrieved May 20, 2026, from

https://www.cdc.gov/flu-vaccines-work/php/effectiveness-studies/.

CDC. (2024). "How Flu Spreads." Retrieved May 20, 2026, from

https://www.cdc.gov/flu/spread/index.html.

CDC. (2024). "Signs and Symptoms of Flu." Retrieved May 20, 2026, from

https://www.cdc.gov/flu/signs-

symptoms/?CDC AAref Val=https://www.cdc.gov/flu/symptoms/symptoms.htm.

CDC. (2025). "Key Facts About Seasonal Flu Vaccine." Retrieved May 20, 2026, from

https://www.cdc.gov/flu/vaccines/keyfacts.html.

CDC. (2026). "Influenza (Seasonal) Fact Sheet." Retrieved May 20, 2026, from

https://www.cdc.gov/flu/season/index.html.

CDC ACIP. (2025). "ACIP Recommendations Summary." Retrieved May 20, 2026, from

https://www.cdc.gov/flu/hcp/acip/index.html.

Demicheli, V., Jefferson, T., Ferroni, E., Rivetti, A., & Di Pietrantonj, C. (2018). Vaccines for

preventing influenza in healthy adults. Cochrane Database of Systematic Reviews, 2, Art. No.:

CD001269. https://doi.org/10.1002/14651858.CD001269.pub6

FDA. 1999). "NDA 021036." Relenza (zanamivir), from

https://www.accessdata.fda.gov/drugsatfda docs/nda/99/21036.html.

FDA. 1999). "NDA 021087." Tamiflu (oseltamivir), from

https://www.accessdata.fda.gov/drugsatfda docs/nda/99/21087 Tamiflu.html.

FDA. "NDA 206426." Rapivab (peramivir), from

https://www.accessdata.fda.gov/drugsatfda docs/nda/2014/206426Orig1s000SumR.pdf.

FDA. 2018). "NDA 210854." Xofluza (baloxavir marboxil), from

https://www.accessdata.fda.gov/drugsatfda docs/nda/2018/210854Orig1s000TOC.html.

FDA. (2022). "Influenza (Flu) Antiviral Drugs and Related Information." Retrieved 20 May, 2026, from

https://www.fda.gov/drugs/information-drug-class/influenza-flu-antiviral-drugs-and-related-

information#ApprovedDrugs.

FDA. (2023). "FluMist Quadivalent." Retrieved May 20, 2026, from https://www.fda.gov/vaccines-

blood-biologics/vaccines/flumist-quadrivalent.

FDA. (2025). "Fluad." Retrieved May 20, 2026, from https://www.fda.gov/vaccines-blood-

biologics/vaccines/fluad.

FDA. (2025). "FluBlok Quadivalent." Retrieved May 20, 2026, from https://www.fda.gov/vaccines-

blood-biologics/vaccines/flublok-quadrivalent.

FDA. (2025). "FluZone." Retrieved May 20, 2026, from https://www.fda.gov/vaccines-blood-

biologics/vaccines/fluzone-and-fluzone-high-dose.

FDA. (2025). "Influenza Vaccine Composition for the 2025-2026 U.S. Influenza Season." Retrieved

May 20, 2026, from https://www.fda.gov/vaccines-blood-biologics/influenza-vaccine-composition-

2025-2026-us-influenza-season.

29

FDA. (2026). "Afluria, Afluria Southern Hemisphere." Retrieved May 20, 2026, from

https://www.fda.gov/vaccines-blood-biologics/vaccines/afluria-afluria-southern-hemisphere.

FDA. (2026). "Fluarix." Retrieved May 20, 2026, from https://www.fda.gov/vaccines-blood-

biologics/vaccines/fluarix.

FDA. (2026). "Flucelvax Quadrivalent." Retrieved May 20, 2026, from https://www.fda.gov/vaccines-

blood-biologics/vaccines/flucelvax-quadrivalent.

FDA. (2026). "FluLaval." Retrieved May 20, 2026, from https://www.fda.gov/vaccines-blood-

biologics/vaccines/flulaval.

Fischinger, S., et al. (2019). "Sex Differences in Vaccine-Induced Humoral Immunity." Semin

Immunopathol 41(2): 239-249.

Killingley, B. and J. Nguyen-Van-Tam (2013). "Routes of influenza transmission." Influenza Other

Respir Viruses (Suppl 2): 42-51. https://www.ncbi.nlm.nih.gov/pubmed/24034483.

Lafond, K. E., R. M. Porter, M. J. Whaley, Z. Suizan, Z. Ran, M. A. Aleem, B. Thapa, B. Sar, V. S.

Proschle, Z. Peng, L. Feng, D. Coulibaly, E. Nkwembe, A. Olmedo, W. Ampofo, S. Saha, M. Chadha,

A. Mangiri, V. Setiawaty, S. S. Ali, S. S. Chaves, D. Otorbaeva, O. Keosavanh, M. Saleh, A. Ho, B.

Alexander, H. Oumzil, K. P. Baral, Q. S. Huang, A. A. Adebayo, I. Al-Abaidani, M. von Horoch, C.

Cohen, S. Tempia, V. Mmbaga, M. Chittaganpitch, M. Casal, D. A. Dang, P. Couto, H. Nair, J. S.

Bresee, S. J. Olsen, E. Azziz-Baumgartner, J. P. Nuorti, M. A. Widdowson and G. Global Respiratory

Hospitalizations-Influenza Proportion Positive Working (2021). "Global burden of influenza-associated

lower respiratory tract infections and hospitalizations among adults: A systematic review and meta-

analysis." PLoS Med 18(3): e1003550. https://www.ncbi.nlm.nih.gov/pubmed/33647033.

National Center for Health Statistics. Percentage of Receipt of Influenza Vaccination in the Past 12

Months for Adults Aged 18 and Over, United States, 2024. National Health Interview Survey.

Generated interactively: May 23 2026 from

https://wwwn.cdc.gov/NHISDataQueryTool/SHS adult/index.html.

Osterholm, M. T., Kelley, N. S., Sommer, A., & Belongia, E. A. (2012). Efficacy and effectiveness of

influenza vaccines: A systematic review and meta-analysis. The Lancet Infectious Diseases, 12(1),

36–44. https://doi.org/10.1016/S1473-3099(11)70295-X

Paules, C. and K. Subbarao (2017). "Influenza." The Lancet 390(10095): 697-708.

https://www.sciencedirect.com/science/article/pii/S0140673617301290.

Petrova, V. N., & Russell, C. A. (2018). The evolution of seasonal influenza viruses. Nature Reviews

Microbiology, 16(1), 47–60. https://doi.org/10.1038/nrmicro.2017.118

Rolfes, M. A., I. M. Foppa, S. Garg, B. Flannery, L. Brammer, J. A. Singleton, E. Burns, D. Jernigan,

S. J. Olsen, J. Bresee and C. Reed (2018). "Annual estimates of the burden of seasonal influenza in

the United States: A tool for strengthening influenza surveillance and preparedness." Influenza Other

Respir Viruses 12(1): 132-137. https://www.ncbi.nlm.nih.gov/pubmed/29446233.

Smith, B. J., et al. (2020). "Influenza With and Without Fever: Clinical Predictors and Impact on

Outcomes in Patients Requiring Hospitalization." Open Forum Infect Dis 7(7): ofaa268.

Thompson, W. W., D. K. Shay, E. Weintraub, L. Brammer, C. B. Bridges, N. J. Cox and K. Fukuda

(2004). "Influenza-associated hospitalizations in the United States." JAMA 292(11): 1333-1340.

https://www.ncbi.nlm.nih.gov/pubmed/15367555.

Tricco, A. C., Chit, A., Soobiah, C., Hallett, D., Meier, G., Chen, M. H., Tashkandi, M., Bauch, C. T., &

Loeb, M. (2013). Comparing influenza vaccine efficacy against mismatched and matched strains: A

systematic review and meta-analysis. BMC Medicine, 11(1), 153. https://doi.org/10.1186/1741-7015-

11-153

30

UptoDate. (2025). "Influenza: Epidemiology and Pathogenesis." Retrieved May 20, 2026, from

https://www.uptodate.com/contents/influenza-epidemiology-and-

pathogenesis?topicRef=7004&source=see link#H6.

Watson KB, Wiltz JL, Nhim K, Kaufmann RB, Thomas CW, Greenlund KJ. Trends in Multiple Chronic

Conditions Among US Adults, By Life Stage, Behavioral Risk Factor Surveillance System, 2013-

2023. Prev Chronic Dis. 2025;22:E15. Published 2025 Apr 17. doi:10.5888/pcd22.240539.

WHO (2025). “Influenza (seasonal).” Retrieved June 3, 2026, from Influenza (seasonal)

WHO. (2026). "Global Influenza Surveillance and Response System (GISRS)." Retrieved May 20,

2026, from https://www.who.int/initiatives/global-influenza-surveillance-and-response-system.

31

Appendix A – Clinical Studies Submitted in Support of mRNA-1010 Efficacy and

Safety Determinations

Total mRNA-1010 Formulation and

Study Number Recipients Dose Levels of

(Country); Study Total Comparator mRNA-1010

Dates Study Design Recipients Evaluated

mRNA-1010-P304 Phase 3, randomized, stratified, mRNA-1010 (TIV): N=20,350 mRNA-1010.4 (TIV)

(Belgium, Bulgaria, observer blinded (participant SD comparator (TIV or QIV): 37.5 μg

Canada, Estonia, and assessor-blind), active- N=20,353

Finland, Georgia, controlled, safety, efficacy, and

Germany, South Korea, immunogenicity study in adults

Taiwan, UK, U.S.) ≥50 years of age.

September 16, 2024 to

August 21, 2025

mRNA-1010-P303 Phase 3, randomized, stratified, Part A: Part A:

(U.S.) observer blind, active- mRNA-1010 (QIV): N=1220 mRNA-1010.6# (QIV)

Part A*: April 17, 2023 controlled, immunogenicity, SD comparator (QIV): N=1180 50 μg

to November 28, 2023 reactogenicity, and safety

Part B: November 13, study. Part B: Part B*:

2023 to June 20, 2024 mRNA-1010 (QIV): N=1492 mRNA-1010.4 (QIV)

Part C: November 13, Part A*: adults ≥18 years SD comparator (QIV): N=1488 50 μg

2023 to June 24, 2024 Part B*: adults 18 to <65 years

Part C: adults ≥65 years Part C: Part C:

mRNA-1010 (QIV): N=1502 mRNA-1010.4 (QIV)

Fluzone HD (QIV): N=1490 50 μg

mRNA-1010-P101* Phase 1/2, randomized, mRNA-1010 (original, QIV): mRNA-1010

(U.S.) stratified, observer blind, dose- N=736 (original, QIV)

June 28, 2021 to ranging safety, reactogenicity, 6.25 μg

September 27, 2022 and immunogenicity study in Afluria (QIV): N=104 12.5 μg

healthy adults ≥18 years of age. 25 μg

Placebo: N=45 50 μg

100 μg

200 μg

mRNA-1010-P301* Phase 3, randomized, stratified, mRNA-1010 (original, QIV): mRNA-1010

(Argentina, Australia, observer blind, active- N=3035 (original, QIV)

Colombia, Panama, controlled, immunogenicity, 50 μg

and Philippines) reactogenicity, and safety study SD comparator (QIV): N=3048

June 6, 2022 to in adults ≥18 years of age.

September 4, 2023

mRNA-1010-P302* Phase 3, randomized, observer- mRNA-1010 (original, QIV): mRNA-1010

(Bulgaria, Canada, blind, active-controlled, safety, N=11,210 (original, QIV)

Denmark, Estonia, reactogenicity, and efficacy, 50 μg

Germany, Poland, study in adults ≥50 years of SD comparator (QIV):

Spain, Taiwan, UK, age. N=11,200

U.S.)

September 14, 2022 to

January 5, 2024

Source: Adapted from STN 125869/0, Clinical Overview.

Abbreviations: HD, high dose; QIV, quadrivalent influenza vaccine; SD, standard dose; TIV, trivalent influenza vaccine; UK, United

Kingdom; U.S., United States

* P301, P302, and P303 Parts A and B contribute to the Integrated Summary of Safety only and will not be discussed individually in this

memo. P101 did not contribute substantially to the overall safety and effectiveness conclusions and also will not be discussed individually in

this memo

#

mRNA-1010.4 and mRNA1010.6 are identical, with the only difference being the scale of manufacturing. They both include optimized

influenza B antigen(s) encoding 2 stabilizing point mutations in non-surface exposed regions that do not impact antigenic epitopes.

32

Appendix B – Study P304 Efficacy and Safety

Study mRNA-1010-P304

NCT06602024

Title: “A Phase 3, randomized, observer-blind, active-controlled, case-driven study to investigate the

safety, efficacy, and immunogenicity of mRNA-1010 candidate seasonal influenza vaccine compared

with a licensed inactivated seasonal influenza vaccine in adults ≥50 years of age”

Study Overview

Study mRNA-1010-P304 (P304) was a Phase 3, randomized, observer-blind (participant- and

assessor-blind), active-controlled study evaluating the safety, efficacy, and immunogenicity of

trivalent mRNA-1010.4 seasonal influenza vaccine (mRNA-1010 [TIV]) compared with a licensed

standard-dose trivalent or quadrivalent inactivated seasonal influenza vaccine (SD comparator [TIV]

or SD comparator [QIV], respectively) for the prevention of influenza disease caused by any influenza

A or B strain in adults ≥50 yoa.

The study was initiated on September 16, 2024, and completed on August 21, 2025. The primary

efficacy and immunogenicity analyses used a data cutoff of April 30, 2025 (end of influenza season),

with a database lock (DBL) of June 3, 2025. Supportive end-of-study (EOS) analyses used a data

cutoff of August 21, 2025, with a DBL of September 16, 2025.

Objectives

Primary Objectives

Primary Efficacy Objective

To evaluate the relative vaccine efficacy (rVE) of mRNA-1010 (TIV) versus the SD comparator

against RT-PCR–confirmed protocol-defined influenza-like illness (ILI) (see Appendix B Table 1 for

case definitions) caused by any influenza A or B strain.

Endpoint: First episode of RT-PCR–confirmed protocol-defined ILI with onset at least 14 days

after study intervention through the end of the influenza season, caused by any influenza A or

B strain.

Statistical Criterion for Success: Noninferiority (NI) was demonstrated if the lower limit (LL)

of the two-sided 95% confidence interval (CI) of rVE of mRNA-1010 relative to the SD

comparator was greater than −10%. Once NI was demonstrated, the same endpoint was

tested sequentially for superiority (LL of two-sided 95% CI of rVE >0%) and then super-

superiority (LL of two-sided 95% CI of rVE >9.1%).

Primary Safety Objective

To evaluate the safety and reactogenicity of mRNA-1010 (TIV).

Endpoints: Solicited local and systemic adverse reactions (ARs) through Day 7; unsolicited

adverse events (AEs) through Day 28; and serious adverse events (SAEs), medically

attended adverse events (MAAEs), AEs leading to study discontinuation, and adverse events

of special interest (AESIs) through Month 6/Day 181.

Secondary Objectives

33

Secondary Efficacy Objectives

To evaluate rVE of mRNA-1010 (TIV) versus the SD comparator against RT-PCR–confirmed

modified Centers for Disease Control and Prevention (CDC)-defined ILI (see Appendix B Table 1 for

case definitions) caused by any influenza A or B strain.

Endpoint: First episode of RT-PCR–confirmed modified CDC-defined ILI with onset at least

14 days after study intervention through the end of the influenza season, caused by any

influenza A or B strain.

Statistical Criteria for Success: Same sequential testing for NI, superiority, and super-

superiority, and same success margins, as the primary efficacy endpoint.

To evaluate rVE of mRNA-1010 (TIV) versus the SD comparator against RT-PCR–confirmed

protocol-defined ILI or modified CDC-defined ILI caused by influenza A or B strains with antigenic

match to the vaccine strains.

Endpoint: First episode of RT-PCR–confirmed protocol-defined ILI or modified CDC-defined

ILI with onset at least 14 days after study intervention through the end of the influenza season,

caused by influenza A or B strains with antigenic match to the vaccine strains.

Statistical Criteria for Success: Same sequential testing and success margins as the

primary efficacy endpoint.

Secondary Immunogenicity Objectives (Descriptive Analyses; No Hypothesis Testing)

To evaluate the humoral immunogenicity of mRNA-1010 (TIV) relative to the SD comparator against

vaccine-matched influenza A and B strains in a prespecified subset of approximately 2,400

participants.

Endpoints, as measured by hemagglutinin inhibition (HAI) assay:

 Geometric mean titers (GMTs) at Day 29

 Proportion of participants achieving seroconversion at Day 29

 Proportion of participants with an HAI titer ≥1:40 at Day 29

 Geometric mean fold rise (GMFR) from Day 1 (Baseline) to Day 29

To evaluate HAI titers as a correlate of risk (CoR) and correlate of protection (CoP) against RT-PCR–

confirmed protocol-defined ILI for mRNA-1010 (TIV) and the SD comparator.

Endpoints:

 HAI titers at Day 29

 First episode of RT-PCR–confirmed protocol-defined ILI with onset at least 14 days after

study intervention through the end of the influenza season, caused by any influenza A or B

strain

Select Exploratory Objectives (Descriptive Analyses; No Hypothesis Testing)

To evaluate rVE of mRNA-1010 (TIV) versus the SD comparator against RT-PCR–confirmed CDC-

defined ILI, World Health Organization (WHO)-defined ILI, and ILI as defined in a previous mRNA-

1010 clinical study protocol (mRNA-1010-P302) (see Appendix B Table 1 for case definitions) caused

by any influenza A or B strain.

34

Endpoints: First episode of each respective RT-PCR–confirmed ILI definition with onset at

least 14 days after study intervention through the end of the influenza season, caused by any

influenza A or B strain.

To evaluate the humoral immunogenicity of mRNA-1010 (TIV) relative to the SD comparator against

vaccine-matched influenza A and B strains as measured by microneutralization (MN) assay in a

subset of participants.

Endpoints, as measured by MN assay:

 GMT at Day 29

 GMFR from Day 1 (Baseline) to Day 29

To evaluate rVE of mRNA-1010 (TIV) versus the SD comparator in preventing health outcomes

associated with protocol-defined ILI.

Endpoints: Healthcare encounters (e.g., hospitalization, emergency room [ER] visit,

outpatient visit) beginning within 30 days after respiratory symptom onset.

Design

Study P304 was conducted at 301 sites in 11 countries across North America, Europe, and East Asia.

A total of 40,805 participants were randomized 1:1 to receive a single intramuscular injection of either

mRNA-1010 (TIV) or the SD comparator.

The trivalent SD comparator was the preferred comparator and was used in North America; the

quadrivalent SD comparator was used in countries where the trivalent formulation was not available

(Europe and East Asia). All participants in the mRNA-1010 group received the trivalent formulation.

The influenza strains encoded in mRNA-1010 (TIV) were aligned with FDA recommendations for the

2024–2025 Northern Hemisphere influenza vaccine for cell- or recombinant-based vaccines.

Randomization was stratified by age category at screening (50 to <65 yoa or ≥65 yoa) and by

influenza vaccination status in the previous influenza season (received or not received). Participants

were followed through the end of the influenza season, approximately 6 to 8 months after vaccination.

The study enrolled healthy adults and those with certain stable chronic diseases. Participants with

immunocompromising conditions, congenital or acquired immunodeficiency, recent malignancy,

history of Guillain-Barré syndrome (GBS) after influenza vaccination, history of myocarditis or

pericarditis within the past 180 days, or a positive test or treatment for influenza within the past 180

days were excluded.

Following the screening visit, participants completed up to two scheduled clinic visits (Baseline and

Day 29) and four scheduled telephone visits (Days 8, 91, 181, and the End of Influenza Season Visit).

The End of Study (EOS) occurred at either the Day 181 Visit or the End of Influenza Season Visit,

whichever was later.

Evaluation of Efficacy

All participants completed a symptom electronic diary (eDiary) twice weekly from Day 1 through the

end of the influenza season (April 30, 2025) and were prompted to report respiratory symptoms as

they occurred. Participants with respiratory symptoms were instructed to contact study staff

immediately; staff followed up within 24 hours to review symptoms and confirm protocol-defined

respiratory illness.

35

Participants meeting criteria for protocol-defined respiratory illness (Table 2) underwent an

unscheduled illness visit that included assessment of symptom history and onset dates, vital signs,

healthcare provider visits related to the illness, and new or modified concomitant medications (e.g.,

antivirals). Nasopharyngeal (NP) swabs were collected at the visit, prior to antiviral initiation and

preferably within 72 hours of symptom onset (up to 5 days was acceptable). Swabs could be

performed at home by qualified personnel.

If an NP swab could not be obtained, any available influenza test results from outside the study were

captured in the electronic Case Report Form (eCRF). Results from specimens obtained using a local

diagnostic test at an external healthcare visit were accepted if the results were obtained using FDA-

cleared or FDA-approved kits or were performed in Clinical Laboratory Improvement Amendments

(CLIA)-certified (or equivalent) laboratories.

NP swabs were tested using an RT-PCR–based assay for influenza A and B and other respiratory

viruses. Influenza-positive samples underwent additional characterization by genetic sequencing

and/or viral culture with antigenicity testing. Repeat swabs were not required within 14 days of a prior

collection for participants with ongoing symptoms. Study staff contacted participants twice weekly

throughout the illness to collect information on symptom duration, healthcare utilization, and

concomitant medications.

The study protocol was designed to enroll participants across up to two Northern Hemisphere (NH)

influenza seasons (NH 2024/2025 and NH 2025/2026), with an interim analysis planned at the end of

the first influenza season when approximately 70% of target cases were expected to have accrued.

High influenza transmission during the 2024/2025 NH season resulted in 968 cases accruing by the

end of that season—exceeding the study target of 836 cases—and therefore the study did not

continue into a second influenza season.

The interim analysis at the end of the 2024/2025 NH influenza season used the full one-sided alpha

of 2.5% to evaluate the primary efficacy endpoint and constitutes the primary efficacy analysis for this

study. Additional descriptive analyses were conducted after all participants completed the study.

The study employed a hierarchical sequential testing strategy across nine pre-specified null

hypotheses to control the Type I error rate. Testing progressed through three sequential tiers: (1) rVE

against protocol-defined ILI caused by any strain; (2) rVE against modified CDC-defined ILI caused

by any strain; and (3) rVE against protocol-defined ILI with antigenic match. Within each tier,

hypotheses were tested sequentially for NI, superiority, and super-superiority. Advancement to the

next hypothesis required rejection of the preceding one.

Case Definitions

The case definitions for the efficacy endpoints in Study P304 are shown in Appendix B Table 1.

36

Appendix B Table 1. Case Definitions for Respiratory Illness, ILI, and Confirmed Influenza Illness

Term Case Definition

Protocol-defined New onset or worsening (>24 hours) of at least 1 of the following symptoms:

respiratory illness sneezing, nasal congestion, rhinorrhea, sore throat, cough, sputum production,

wheezing, or difficulty breathing.

Protocol-defined ILI At least 1 systemic symptom (temperature >37.2°C (>99.0°F), chills, feverish,

tiredness, headaches, or myalgia).

AND

at least 1 respiratory symptom (sore throat, cough, sputum production,

wheezing, or difficulty breathing).

Modified CDC- Body temperature >37.2°C (>99.0°F) accompanied by cough and/or sore

defined ILI throat

CDC-defined ILI Body temperature ≥37.8°C (≥100°F) accompanied by cough and/or sore throat

(CDC 2017).

WHO-defined ILI An acute respiratory infection with measured fever of ≥38.0°C (100.4°F) and

cough, with onset within the last 10 days (WHO 2014).

ILI as defined in a Body temperature ≥37.5°C (≥99.5°F) accompanied by at least 1 respiratory

previous mRNA- illness symptom (sore throat, cough, sputum production, wheezing, or difficulty

1010 clinical study breathing).

protocol (mRNA-

1010-P302)

RT-PCR–confirmed Positive influenza result by RT-PCR.

influenza illness

Culture-confirmed Positive influenza result by viral culture.

influenza illnessa

Source: Adapted from STN 125869/0, Study P304 Protocol Table 4.

Abbreviations: CDC, U.S. Centers for Disease Control and Prevention; ILI, influenza-like illness; RT-PCR, reverse transcription polymerase

chain reaction; WHO, World Health Organization

a

Viral cultures were performed on samples with a positive influenza result by RT-PCR assay performed by the central laboratory.

Evaluation of Immunogenicity

All participants provided blood samples on Day 1 (Baseline, prior to study intervention) and Day 29.

Samples from a prespecified subset of approximately 2,400 participants from North America (where

the SD comparator [TIV] was used) were analyzed for HAI titers at Baseline and Day 29 for humoral

immunogenicity endpoints. All immunogenicity analyses were descriptive; no hypothesis testing was

performed.

For each strain, HAI titers were summarized as GMTs with 95% CIs at Baseline and Day 29. CIs

were calculated based on the t-distribution of log-transformed values, then back-transformed to the

original scale. The GMFR with 95% CI was reported at Day 29 relative to Baseline.

An analysis of covariance (ANCOVA) model—adjusting for randomization stratification factors, log-

transformed Baseline HAI titers (covariate), and intervention group (fixed variable)—was used to

estimate model-based GMTs, GMT ratios, and corresponding two-sided 95% CIs at Day 29 for

mRNA-1010 (TIV) versus the SD comparator.

Seroconversion rates (SCRs) and the proportion of participants with HAI titers ≥1:40 at Day 29 were

reported with 95% CIs calculated using the Clopper-Pearson method. Between-group SCR

differences were reported with 95% CIs calculated using the Miettinen-Nurminen method.

37

As an exploratory analysis, the same ANCOVA model and descriptive statistics were applied to Day

29 GMTs measured by MN assay, and the correlation between HAI and MN antibody levels was

assessed.

The analysis of HAI as a CoR/CoP used a case-cohort study design conducted on the per-protocol

correlate analysis set (PPCAS). This analysis is still under review and is outside the scope of this

briefing document.

Evaluation of Safety

Study oversight included Institutional Review Board (IRB) or Independent Ethics Committee (IEC)

review. An independent Data Safety Monitoring Board (DSMB) reviewed blinded and unblinded safety

data on a routine basis, made recommendations based on prespecified rules in the DSMB charter,

and reviewed the results of the interim analysis. An independent Cardiac Event Adjudication

Committee (CEAC) reviewed investigator-reported suspected cases of myocarditis, pericarditis, or

myopericarditis to determine whether they met CDC criteria (see Appendix B) for a ‘probable’ or

‘confirmed’ event, and to assess severity.

A subset of approximately 6,000 participants reported solicited local and systemic ARs in a

Reactogenicity eDiary from Day 1 through Day 7 (the day of vaccination and the 6 subsequent days).

Solicited local ARs monitored were injection site pain, erythema, swelling/induration, and axillary

swelling or tenderness ipsilateral to the injection site. Solicited systemic ARs monitored were

headache, fatigue, myalgia, arthralgia, nausea/vomiting, fever, and chills.

Unsolicited AEs occurring within 28 days after vaccination (the day of vaccination and 27 subsequent

days) were recorded. All AEs, SAEs, AESIs, and MAAEs were followed at least monthly until

resolution, stabilization, the event was otherwise explained, or the participant was lost to follow-up.

Analysis Populations

The analysis populations used in Study P304 are defined in Appendix B Table 2.

Appendix B Table 2. Analysis Sets

Analysis Set Description

Randomization Set All participants who were randomized, regardless of the participants’

treatment status in the study.

Full Analysis Set (FAS) All randomized participants who received any study intervention.

Participants were analyzed according to the study intervention group to

which they were randomized.

Per Protocol (PP) Set All participants in the FAS, excluding those with important protocol

deviations that could adversely impact efficacy (e.g., disease or

therapeutic intervention that might cause suboptimal response to study

intervention). The PP Set was used as the primary analysis set for efficacy

endpoints. Participants were analyzed according to the study intervention

group to which they were randomized.

Immunogenicity Subset A prespecified subset of participants from North America in the FAS who

received TIV and have baseline and Day 29 antibody assessments by HAI

assay. Participants were analyzed according to the study intervention

group to which they were randomized.

38

Analysis Set Description

Per Protocol Immunogenicity All participants in the Immunogenicity Subset who received the planned

Set (PPIS) dose of study intervention and had no important protocol deviations that

impact the immunogenicity assessment. Participants with RT-PCR–

confirmed influenza infection between Day 1 (Baseline) and Day 29 were

removed from the PPIS. The PPIS was used for all analyses of

immunogenicity unless specified otherwise. Participants were analyzed

according to the study intervention group to which they were randomized.

PPIS Microneutralization (MN) A stratified random subset of approximately 500 participants selected from

Subset the PPIS for exploratory MN immunogenicity analyses.

Safety Set All randomized participants who received any study intervention. The

Safety Set was used for all analyses of safety except for solicited ARs.

Participants were analyzed according to the study intervention they

actually received.

Solicited Safety Subset All randomized participants who received any study intervention and

contributed any solicited AR data in the Reactogenicity eDiary. The

Solicited Safety Set was used for all analyses of solicited ARs. Participants

were analyzed according to the study intervention they actually received.

Source: Adapted from STN 125869/0, Study P304 Protocol Table 7; Study P304 CSR Table 5.

Abbreviations: AR, adverse reaction; eDiary, electronic diary; HAI, hemagglutination inhibition; NI, noninferiority; RT-PCR, reverse

transcription polymerase chain reaction; TIV, trivalent influenza vaccine

Sensitivity and Subgroup Analyses

Efficacy, immunogenicity, and safety subgroup analyses were conducted by age group (50 to <65

years, ≥65 years, and ≥75 years), race, sex, and baseline high-risk status (see Appendix G). Efficacy

and immunogenicity subgroup analyses were also conducted by influenza vaccine status in the

previous season, body mass index (BMI), baseline frailty score (for participants ≥65 years),

geographic region, and active comparator type.

Participant Disposition and Inclusion in Analysis Populations

Participant disposition by analysis population is presented in Appendix B Table 3 (efficacy and

immunogenicity populations) and Appendix B Table 4 (safety population).

The proportion of participants excluded from the Per-Protocol (PP) Set was comparable across the

mRNA-1010 (TIV) and SD comparator groups (0.8% and 1.1%, respectively). The higher proportion

of SD comparator recipients excluded due to important protocol deviations (0.8% versus 0.2%) was

driven by 68 SD comparator recipients from three sites who were excluded due to a temperature

excursion of the comparator vaccine. There were no notable differences in PP Set exclusions when

comparing SD comparator (TIV) and SD comparator (QIV) recipients.

The proportion of participants in the Immunogenicity Subset excluded from the Per-Protocol

Immunogenicity Subset (PPIS) was also comparable across groups (2.6% in the mRNA-1010 [TIV]

group and 1.8% in the SD comparator group). Most exclusions were due to non-compliance with the

timing of immunogenicity blood sampling (1.2% in the mRNA-1010 [TIV] group and 1.0% in the SD

comparator group).

39

Appendix B Table 3. Participant Disposition, Participants 50 Years of Age and Older, Immunogenicity

and Efficacy Populations, Study P304

SD Comparator

mRNA-1010 (TIV) (TIV + QIV)*

N=20,402 N=20,403

Population n (%) n (%)

Full Analysis Set (FAS)a 20,349 (99.7) 20,354 (99.8)

Per-Protocol Set (PP Set)a, d 20,178 (98.9) 20,122 (98.6)

Excluded from PP Seta 171 (0.8) 232 (1.1)

Reason for exclusion from PP Set -- --

Major dosing error 4 (<0.1) 7 (<0.1)

Had prohibited medication/vaccination 67 (0.3) 52 (0.3)

Had important protocol deviations that impact key 51 (0.2) 171 (0.8)

or critical data

Otherb 49 (0.2) 2 (<0.1)

Immunogenicity Subset 1198 1196

Per-Protocol Immunogenicity Subset (PPIS)c 1167 (97.4) 1175 (98.2)

Excluded from PPISc 31 (2.6) 21 (1.8)

Reason for exclusion from PPIS -- --

Major dosing error 0 1 (<0.1)

Had prohibited medication/vaccination by 5 (0.4) 2 (0.2)

Day 29

RT-PCR–confirmed influenza infection between 2 (0.2) 0

baseline and Day 29

Did not comply with timing of immunogenicity 14 (1.2) 12 (1.0)

blood sampling

Had important protocol deviations that impact 3 (0.3) 6 (0.5)

key or critical data

Otherb 7 (0.6) 0

Source: Adapted from STN 125869/0, mRNA-1010-P304 Clinical Study Report, Tables 14.1.2.2.1.f and 14.1.2.2.3.f. Data cutoff: August 21,

2025.

Abbreviations: FAS, full analysis set; IRT, interactive response technology; N, number of participants in the randomization set; n, number of

participants in a given subpopulation or category; PP, per protocol; PPIS, per protocol immunogenicity subset; QIV, quadrivalent influenza

vaccine; TIV, trivalent influenza vaccine

* Numbers in the immunogenicity subset and the PPIS reflect only the SD comparator (TIV).

A participant who has multiple reasons that caused exclusion from analysis population is counted only once based on the primary exclusion

reason.

a

Numbers are based on planned vaccination group and percentages are based on the number of participants in the Randomization Set.

b

Other exclusion reasons include 1) participants that were enrolled into site US147 (48 mRNA-1010 and 55 SD comparator recipients)

were excluded due to errors in the unblinded pharmacist preparation of the comparator vaccine; mRNA-1010 recipients were excluded to

minimize risk of biases in the per-protocol analyses; 2) participants enrolled into the study multiple times are excluded from per-protocol

analysis.

c

Numbers are based on planned vaccination group and percentages are based on the number of participants in the Immunogenicity

Subset.

d

The PP Set in this End of Study Analysis (data cutoff August 21, 2025) had 3 fewer participants overall compared to the end of season

analysis (data cutoff April 30, 2025) because 4 additional participants were excluded due to delayed reporting of a prohibited medication/

vaccine or important protocol deviation (1 in the mRNA-1010 [TIV] and 3 in the SD comparator group). One participant previously excluded

at the end of season analysis was reincluded due to a prohibited vaccine being incorrectly reported. The number of participants in the other

analyses sets were the same when performed at the end of influenza season.

Of the 40,703 participants in the Safety Set, 3.8% of mRNA-1010 (TIV) recipients and 3.6% of SD

comparator recipients discontinued from the study. The most common reasons for discontinuation

were lost to follow-up (2.1% across both groups) and withdrawal of consent (1.2% in the mRNA-1010

[TIV] group and 1.1% in the SD comparator group). The median duration of safety follow-up was 184

days in both groups. Study completion (defined as completing either the Month 6 [Day 181] visit or

the end of influenza season visit, whichever occurred later) was similar across groups (96.2% in the

mRNA-1010 [TIV] group and 96.4% in the SD comparator group).

40

Study discontinuation was higher in the SD comparator (TIV) group compared with the SD

comparator (QIV) group (4.7% versus 0.9%, respectively), primarily due to a higher rate of loss to

follow-up (2.8% versus 0.4%). The median follow-up time was slightly longer for SD comparator (TIV)

recipients compared with SD comparator (QIV) recipients (188 versus 178 days).

Appendix B Table 4. Participant Disposition, Participants 50 Years of Age and Older, Safety

Populations, Study P304

SD Comparator

mRNA-1010 (TIV + QIV)

N=20,350 N=20,353

Population n (%) n (%)

Safety Set 20,350 (100) 20,353 (100)

Solicited Safety Subseta 3015 (14.8) 2997 (14.7)

Excluded from Solicited Safety Subseta 17,335 (85.2) 17,356 (85.3)

Reason for exclusion from Solicited Safety -- --

Subset

Was not assigned to Solicited Safety Subset 17,325 (85.1) 17,339 (85.2)

via IRT at randomization

Did not contribute any solicited adverse 10 (<0.1) 17 (<0.1)

reaction data in Reactogenicity eDiary

Completed the study a,b 19,569 (96.2) 19,621 (96.4)

Discontinued the study a 781 (3.8) 732 (3.6)

Reason for discontinuation -- --

Adverse event 3 (<0.1) 1 (<0.1)

Death 40 (0.2) 34 (0.2)

Lost to follow-up 434 (2.1) 418 (2.1)

Physician decision 39 (0.2) 24 (0.1)

Protocol deviation 2 (<0.1) 1 (<0.1)

Withdrawal of consent by participant 238 (1.2) 232 (1.1)

Other 25 (0.1) 22 (0.1)

Median follow-up (days) (min, max) 184 (1, 254) 184 (1, 252)

Source: Adapted from STN 125869/0, mRNA-1010-P304 Clinical Study Report, Tables 14.1.1.1.2.f, 14.1.1.1.6.f, 14.1.2.2.1f, 14.1.3.4.1.f,

and 14.1.3.4.3.f. Data cutoff: August 21, 2025.

Abbreviations: IRT, interactive response technology; N, number of participants in the safety set; n, number of participants in a given

subpopulation or category; QIV, quadrivalent influenza vaccine; TIV, trivalent influenza vaccine

There is one more participant in the active comparator group and one fewer participant in the mRNA-1010 group in the FAS compared with

the Safety Set due to medication errors: Three participants randomized to mRNA-1010 but received active comparator, and four participants

randomized to active comparator, but received mRNA-1010. A participant who has multiple reasons that caused exclusion from analysis

population is counted only once based on the primary exclusion reason.

a

Numbers are based on actual vaccination group and percentages are based on the number of participants in the Safety Set.

b

Participants are considered to have completed the study if they completed either the Month 6 (Day 181) visit or the end of the influenza

season visit, whichever occurred later.

Demographics and Other Baseline Characteristics

The demographics and baseline characteristics of participants in the Safety Set are shown in

Appendix B Table 5 and were similar in the PP Set. Overall, baseline characteristics were balanced

between the mRNA-1010 (TIV) and SD comparator groups.

The median age was 64 years (range 50–97 years). Across both groups, 52.2% of participants were

50 to <65 yoa, 47.8% were ≥65 yoa, and 11.6% were ≥75 yoa. More than half of participants were

female (56.9%). The majority were White (82.6%), not Hispanic or Latino (88.2%), and enrolled at

sites in North America (70.4%). Overall, 47.0% had received a seasonal influenza vaccine in the

previous influenza season.

41

At least one high-risk condition (see Appendix G) was reported by 57.0% of participants, with

baseline BMI ≥30 kg/m² being the most common. The proportion of participants with a high-risk

condition in Study P304 was lower than reported for the general U.S. population (78% among adults

35 to 64 yoa and 93% among adults ≥65 yoa [Watson et al., 2025]). This likely reflects differences in

how high-risk conditions were defined, as well as the exclusion of certain high-risk participants (e.g.,

those who were immunocompromised or taking immunosuppressive medications).

Among participants ≥65 yoa, the majority were considered fit and not vulnerable or frail (73.3%)

based on the Edmonton Frail Scale (EFS); fewer than 1% were considered moderately or severely

frail (EFS score ≥10). The study did not collect data on nursing home or assisted living residence.

Therefore, the generalizability of these findings to all high-risk groups—particularly

immunocompromised or frail individuals—may be limited.

The proportion of participants with prior seasonal influenza vaccination was lower than national rates

(44.9% among adults 50 to 64 yoa and 67.1% among adults ≥65 yoa [NCHS 2024]).

The demographics and baseline characteristics were generally similar across the SD comparator

(TIV) and SD comparator (QIV) groups, with the following notable exceptions: the TIV group was

more racially and ethnically diverse, with higher proportions of participants identifying as African

American/Black (18.7% versus 0.3%) and Hispanic or Latino (14.1% versus 0.7%). A lower proportion

of QIV recipients had a baseline BMI ≥30 kg/m² (24.7% versus 45.4%) or at least one high-risk

condition (42.7% versus 63.1%). These differences are likely attributable to geographic differences in

the study populations (TIV used in North America; QIV used in Europe and East Asia).

Appendix B Table 5. Demographic and Baseline Characteristics, Participants 50 Years of Age and Older,

Safety Set, Study mRNA P304

SD Comparator

mRNA-1010 (TIV) (TIV + QIV)

Characteristic N=20,350 N=20,353

Sex, n (%) -- --

Male 8834 (43.4) 8720 (42.8)

Female 11,516 (56.6) 11,633 (57.2)

Age, years -- --

Median age (min, max) 64.0 (50, 97) 64.0 (50, 96)

50 to <65 years of age 10,624 (52.2) 10,615 (52.2)

≥65 years of age 9726 (47.8) 9738 (47.8)

65 to <75 years of age 7372 (36.2) 7375 (36.2)

≥75 years of age 2354 (11.6) 2363 (11.6)

Race, n (%) -- --

African American/Black 2687 (13.2) 2698 (13.3)

American Indian or Alaska Native 72 (0.4) 86 (0.4)

Asian 496 (2.4) 483 (2.4)

Native Hawaiian or other Pacific Islander 20 (<0.1) 19 (<0.1)

White 16,814 (82.6) 16,811 (82.6)

Multiracial 109 (0.5) 104 (0.5)

Unknown 15 (<0.1) 16 (<0.1)

Not reported 86 (0.4) 81 (0.4)

Other 51 (0.3) 55 (0.3)

42

SD Comparator

mRNA-1010 (TIV) (TIV + QIV)

Characteristic N=20,350 N=20,353

Ethnicity, n (%) -- --

Hispanic/Latino 2147 (10.6) 2067 (10.2)

Not Hispanic/Latino 17,908 (88.0) 17,985 (88.4)

Not reported 279 (1.4) 271 (1.3)

Unknown 16 (<0.1) 30 (0.1)

Region, n (%) -- --

North America 14,333 (70.4) 14,340 (70.5)

Canada 647 (3.2) 610 (3.0)

U.S. 13,686 (67.3) 13,730 (67.5)

Europe 5843 (28.7) 5833 (28.7)

Belgium 512 (2.5) 461 (2.3)

Bulgaria 1836 (9.0) 1895 (9.3)

Estonia 606 (3.0) 645 (3.2)

Finland 206 (1.0) 198 (1.0)

Georgia 176 (0.9) 178 (0.9)

Germany 1356 (6.7) 1324 (6.5)

United Kingdom 1151 (5.7) 1132 (5.6)

East Asiaa 174 (0.9) 180 (0.9)

South Korea 117 (0.6) 114 (0.6)

Taiwan 57 (0.3) 66 (0.3)

Body mass index (kg/m2) -- --

Median (min, max) 28.3 (12.4, 95.8) 28.4 (12.9, 75.7)

<30 kg/m2 12290 (60.4) 12325 (60.6)

≥30 kg/m2 8030 (39.5) 8002 (39.3)

≥40 kg/m2 1296 (6.4) 1312 (6.4)

Missing 30 (0.1) 26 (0.1)

Influenza vaccine status, n (%) -- --

Received seasonal flu vaccine 9569 (47.0) 9546 (46.9)

Not received previous seasonal flu vaccine 10,781 (53.0) 10,807 (53.1)

EFS Total scoreb -- --

n 9711 9718

Median (min, max) 2.0 (0, 16) 2.0 (0, 17)

0-3: Fit, n (%) 7136 (73.4) 7135 (73.3)

4-5: Vulnerable, n (%) 1755 (18.0) 1740 (17.9)

≥6: Frail, n (%) 820 (8.4) 843 (8.7)

43

SD Comparator

mRNA-1010 (TIV) (TIV + QIV)

Characteristic N=20,350 N=20,353

Baseline high-risk factors, n (%) -- --

High-riskc 11595 (57.0) 11620 (57.1)

Autoimmune/immune-mediated disease 798 (3.9) 830 (4.1)

Baseline BMI ≥30 kg/m2 d 8030 (39.5) 8002 (39.3)

Blood disorders 50 (0.3) 56 (0.3)

Cardiac disorders 1836 (9.0) 1839 (9.0)

Diabetes mellitus 3607 (17.7) 3557 (17.5)

Hepatic disorders 205 (1.0) 249 (1.2)

Mental impairment disorders 16 (<0.1) 22 (0.1)

Nervous system disorders 84 (0.4) 62 (0.3)

Pulmonary disorders 2114 (10.4) 2225 (10.9)

Renal disorders 277 (1.4) 263 (1.3)

Non high-risk 8755 (43.0) 8733 (42.9)

Source: Adapted from STN 125869/0, mRNA-1010-P304 Clinical Study Report, Table 14.1.3.1.3.f and 14.1.3.1.8.f., Amendment 48.

Abbreviations: BMI, body mass index (body weight in kilograms)/(height in meters)²; CSR, clinical study report; EFS, Edmonton Frail Scale;

IR, information request; max, maximum; min, minimum; N, number of participants in the Safety Set; n, number of participants in the

vaccination group in the given subpopulation; QIV, quadrivalent influenza vaccine; TIV, trivalent influenza vaccine

Numbers are based on actual vaccination group and percentages are based on the number of participants in the Safety Set.

a

The Safety Subset included all randomized participants who received any study vaccination. Participants are analyzed according to the

study vaccination they actually received.

b

EFS total score is only applicable to participants of ≥65 years old and the percentages are based on the number of participants of

≥65 years old in the Safety Set.

c

High risk is defined as having at least one of the following: baseline BMI ≥30 kg/m2, autoimmune/immune-mediated disease, blood

disorders, cardiac disorders, diabetes mellitus, hepatic disorders, mental impairment disorders, nervous system disorders, pulmonary

disorders, or renal disorders.

d

The original demographic data submitted in support of this BLA reported a participant with a BMI of 139.0. After an information request,

the Applicant clarified on that this value was confirmed by the site to be an error due to an incorrectly recorded height value. In response to

a follow-up IR, the Applicant provided the corrected BMI value and corrected CSR tables.

Appendix B Table 6 shows the demographic and baseline characteristics of the PPIS. All PPIS

participants were enrolled in North America and received the SD comparator (TIV). There were no

notable differences between the mRNA-1010 (TIV) and SD comparator (TIV) groups within the PPIS.

Compared with the overall Safety Set and PP Set, the PPIS had higher proportions of participants

who were African American/Black, Hispanic or Latino, had a BMI ≥30 kg/m², or had at least one high-

risk condition.

Appendix B Table 6. Demographic and Baseline Characteristics, Participants 50 Years of Age and Older,

Per Protocol Immunogenicity Subset (PPIS), Study P304

mRNA-1010 (TIV) SD Comparator (TIV)

Characteristic N=1167 N=1175

Sex, n (%) -- --

Male 485 (41.6) 490 (41.7)

Female 682 (58.4) 685 (58.3)

Age, years -- --

Median age (min, max) 65.0 (50, 97) 64.0 (50, 92)

50 to <65 years of age 581 (49.8) 592 (50.4)

≥65 years of age 586 (50.2) 583 (49.6)

65 to <75 years of age 437 (37.4) 434 (36.9)

≥75 years of age 149 (12.8) 149 (12.7)

44

mRNA-1010 (TIV) SD Comparator (TIV)

Characteristic N=1167 N=1175

Race, n (%) -- --

African American/Black 193 (16.5) 200 (17.0)

American Indian or Alaska Native 8 (0.7) 3 (0.3)

Asian 27 (2.3) 33 (2.8)

Native Hawaiian or other Pacific Islander 1 (<0.1) 3 (0.3)

White 914 (78.3) 910 (77.4)

Multiracial 9 (0.8) 13 (1.1)

Unknown 2 (0.2) 2 (0.2)

Not reported 11 (0.9) 9 (0.8)

Other 2 (0.2) 2 (0.2)

Ethnicity, n (%) -- --

Hispanic/Latino 163 (14.0) 165 (14.0)

Not Hispanic/Latino 982 (84.1) 991 (84.3)

Not reported 19 (1.6) 18 (1.5)

Unknown 3 (0.3) 1 (<0.1)

Country, n (%) -- --

Canada 56 (4.8) 50 (4.3)

U.S. 1111 (95.2) 1125 (95.7)

Body Mass Index (kg/m2) -- --

Median (min, max) 29.5 (15.0, 75.3) 29.4 (16.3, 65.7)

<30 kg/m2 623 (53.4) 637 (54.2)

≥30 kg/m2 542 (46.4) 538 (45.8)

≥40 kg/m2 104 (8.9) 98 (8.3)

Missing 2 (0.2) 0

Influenza vaccine status in the previous influenza -- --

season, n (%)

Received seasonal flu vaccine 594 (50.9) 596 (50.7)

Not received previous seasonal flu vaccine 573 (49.1) 579 (49.3)

EFS total scoreb -- --

n 585 581

Median (min, max) 2.0 (0, 10) 2.0 (0, 14)

0-3: Fit, n (%) 437 (74.6) 440 (75.5)

4-5: Vulnerable, n (%) 106 (18.1) 93 (16.0)

≥6: Frail, n (%) 42 (7.2) 48 (8.2)

45

mRNA-1010 (TIV) SD Comparator (TIV)

Characteristic N=1167 N=1175

Baseline high-risk factors, n (%) -- --

High-riskc 740 (63.4) 753 (64.1)

Autoimmune/immune-mediated disease 47 (4.0) 44 (3.7)

Baseline BMI ≥30 kg/m2 542 (46.4) 538 (45.8)

Blood disorders 3 (0.3) 5 (0.4)

Cardiac disorders 103 (8.8) 96 (8.2)

Diabetes mellitus 221 (18.9) 228 (19.4)

Hepatic disorders 12 (1.0) 26 (2.2)

Mental impairment disorders 2 (0.2) 2 (0.2)

Nervous system disorders 4 (0.3) 6 (0.5)

Pulmonary disorders 130 (11.1) 155 (13.2)

Renal disorders 19 (1.6) 13 (1.1)

Non high-risk 427 (36.6) 422 (35.9)

Source: Adapted from STN 125869/0, mRNA-1010-P304 Clinical Study Report, Tables 14.1.3.1.5.f and 14.1.3.1.10.f.

Abbreviations: BMI, body mass index (body weight in kilograms)/(height in meters)²; EFS, Edmonton Frail Scale; max, maximum; min,

minimum; N, number of participants in the PPIS; n, number of the participants in a given subpopulation/category; PPIS, per protocol

immunogenicity subset; QIV, quadrivalent influenza vaccine; TIV, trivalent influenza vaccine

Numbers are based on planned vaccination group and percentages are based on the number of participants in the PPIS.

The PPIS included participants in the Immunogenicity Subset and without any important protocol deviations that could adversely impact

immunogenicity assessment.

a

East Asia includes Republic of Korea (i.e., South Korea) and Taiwan.

b

EFS total score is only applicable to participants of ≥65 years old and the percentages are based on the number of participants of

≥65 years old in the Per Protocol Immunogenicity Subset.

c

High risk is defined as having at least one of the following: baseline BMI ≥30 kg/m2,autoimmune/immune-mediated disease, blood

disorders, cardiac disorders, diabetes mellitus, hepatic disorders mental impairment disorders, nervous system disorders, pulmonary

disorders, or renal disorders.

Analyses of Vaccine Effectiveness

Analyses of Primary Efficacy Endpoint

The primary efficacy analysis was based on the pre-specified interim analysis conducted at the end of

the NH 2024/2025 influenza season. This analysis includes cases of the first RT-PCR–confirmed

protocol-defined ILI with onset at least 14 days after study vaccination through the data cutoff of April

30, 2025. The median duration of follow-up for efficacy was 181 days (approximately 6 months).

The primary efficacy objective was to demonstrate that mRNA-1010 (TIV) is noninferior to the SD

comparator in preventing the first episode of protocol-defined ILI. As shown in Appendix B Table 7,

mRNA-1010 (TIV) demonstrated an rVE of 26.6% (95% CI: 16.7, 35.4) in all participants ≥50 yoa,

meeting the prespecified NI criterion (LL of 95% CI of rVE >−10%). The case split was 411 cases

(2.0%) in the mRNA-1010 (TIV) group and 557 cases (2.8%) in the SD comparator group. Sequential

testing for superiority (LL of 95% CI >0%) and super-superiority (LL of 95% CI >9.1%) were then

conducted and both were also demonstrated.

46

Appendix B Table 7. Analysis of Primary Efficacy Endpoint of Relative Vaccine Efficacy (rVE) for mRNA-

1010 (TIV) Versus SD Comparator Against RT-PCR–Confirmed Protocol-Defined ILI Caused by Any

Influenza A or B Strains in Participants 50 Years of Age and Older (PP Set), Study P304

mRNA-1010 (TIV) SD Comparator

N=20,179 N=20,124

Cases Cases rVE (%)

n (%)a n (%)a (95% CI)b

411 557 26.6

(2.0) (2.8) (16.7, 35.4)

Source: Adapted from STN 125869/0, mRNA-1010 P304 Clinical Study Report, Tables 14.2.1.1.1.1, Table 14.2.1.1.4.1. Data cutoff: April

30, 2025.

Abbreviations: CI, confidence interval; ILI, influenza-like illness; N, number of participants in the PP analysis set; n: number of protocol-

defined ILI cases; PP, per protocol; RT-PCR, real-time reverse transcription polymerase chain reaction; rVE, relative vaccine efficacy; SD,

standard dose

The case is the first RT-PCR–confirmed protocol-defined ILI that begins at least 14 days after study vaccination through the end of influenza

season caused by any influenza A or B strains, regardless of vaccine match.

a

Percentages are based on the number of participants in the analysis set.

b

rVE is defined as 100×(1−hazard ratio [mRNA-1010 versus the Active Comparator]). The rVE and the CI are based on a stratified Cox

proportional hazards model with the study vaccination group as a fixed effect, adjusting by the randomized stratification factors: age group

(≥50 to <65 years or ≥65 years) and the status of influenza vaccine in the previous influenza season (received or not).

The time from vaccination to the first RT-PCR–confirmed protocol-defined ILI was similar across

treatment groups (median of 91.0 days in the mRNA-1010 [TIV] group and 96.0 days in the SD

comparator group). More cases accrued in the SD comparator group compared with the mRNA-1010

(TIV) group at all time periods through the study, with the exception of the period beyond 6 months

postvaccination to the end of the influenza season, during which only two cases were observed in

each group.

Supportive Analyses of the Primary Efficacy Endpoint

Analysis by Influenza Strain

Appendix B Table 8 presents a supportive analysis of rVE against RT-PCR–confirmed protocol-

defined ILI by influenza strain. Point estimates for rVE were consistent across all strains. For

B/Victoria, the rVE point estimate was consistent with the overall estimate, but the 95% CI was wide

with a LL below zero (LL of 95% CI: −18.5), likely due to the small number of influenza B cases. The

rVE analysis was primarily driven by results against influenza A strains, which accounted for 94.0% of

influenza cases across both groups.

47

Appendix B Table 8. Analysis of Primary Efficacy Endpoint of Relative Vaccine Efficacy (rVE) for mRNA-

1010 (TIV) Versus SD Comparator Against RT-PCR–Confirmed Protocol-Defined ILI Caused by Influenza

Strain Type in Participants 50 Years of Age and Older (PP Set), Study P304

mRNA-1010

(TIV) SD Comparator

N=20,179 N=20,124 rVE (%)

Relative Efficacy Endpoint Cases, n (%)a Cases, n (%)a (95% CI)b

Any influenza A strain 386 522 26.5

(1.9) (2.6) (16.1, 35.5)

Influenza A/H1N1 strain only 223 315 29.6

(1.1) (1.6) (16.4, 40.7)

Influenza A/H3N2 strain only 158 202 22.2

(0.8) (1.0) (4.3, 36.9)

Influenza B strain only 25 35 29.1

(0.1) (0.2) (-18.5, 57.5)

Source: Adapted from STN 125869/0, mRNA-1010 P304 Clinical Study Report, Tables 14.2.1.1.1.1 and 14.2.1.1.3.1. Data cutoff: April 30,

2025.

Abbreviations: CI, confidence interval; ILI, influenza-like illness; N, number of participants in the PP analysis set; n, number of cases of RT-

PCR confirmed ILI; PP, per protocol; RT-PCR, real-time reverse transcription polymerase chain reaction; rVE, relative vaccine efficacy; SD,

standard dose

a

Percentages are based on the number of participants in the analysis set. The case is the first RT-PCR–confirmed protocol-defined ILI that

begins at least 14 days after study vaccination through the end of influenza season caused by any influenza A or B strains, regardless of

vaccine match. Participants can have more than one influenza strain infection simultaneously.

b

rVE was defined as 100×(1−hazard ratio [mRNA-1010 versus the Active Comparator]). The rVE and the CI are based on a stratified Cox

proportional hazards model with the study vaccination group as a fixed effect, adjusting by the randomized stratification factors: age group

(≥50 to <65 years or ≥65 years) and the status of influenza vaccine in the previous influenza season (received or not received). Efron´s

method is used to handle ties. If there were <20 events total in the two vaccination groups combined, rVE was not provided.

Analyses of Cases Starting from Day 1

Descriptive analysis of rVE against RT-PCR–confirmed protocol-defined ILI caused by any influenza

A or B strain, beginning from Day 1, was 27.2% (95% CI: 17.3, 35.9). Strain-specific rVE from Day 1:

A/H1N1, 30.8% (95% CI: 18.0, 41.7); A/H3N2, 21.8% (95% CI: 3.7, 36.4); B/Victoria, 29.1% (95% CI:

−18.5, 57.5). Inclusion of cases occurring in the first 14 days did not meaningfully change the rVE

estimates for any strain, suggesting that the case-counting window definition did not materially affect

the efficacy estimates.

Analyses of Coinfection

Coinfection with any respiratory virus accounted for 4.6% of all protocol-defined ILI cases and was

similar across the mRNA-1010 (TIV) and SD comparator groups. Coinfection with SARS-CoV-2 or

respiratory syncytial virus (RSV) accounted for 0.2% of all cases in the mRNA-1010 (TIV) group and

1.1% in the SD comparator group. Removing coinfection cases from the efficacy analyses did not

meaningfully change rVE estimates or associated CIs.

End-of-Study Analyses

Supportive EOS analyses of the primary efficacy endpoint (RT-PCR–confirmed protocol-defined ILI

caused by any influenza A or B strain) were consistent with the primary efficacy results from the

2024/2025 influenza season.

Subpopulation Analyses

Subgroup Analyses by Age

Descriptive analyses of rVE by age subgroup are shown in Appendix B Table 9. The rVE point

estimate for each age subgroup was consistent with the overall study population. Although the use of

a non-preferentially recommended SD comparator for participants ≥65 yoa limits the interpretation of

48

rVE in this subgroup, the rVE was 27.4% (95% CI: 12.1%, 40.0%), indicating superiority to the SD

comparator. In the ≥75 years age subgroup, a wide CI was observed around the rVE point estimate,

with the LL crossing zero, likely due to the smaller number of participants and cases in this subgroup.

Strain-specific rVE was also similar between participants 50 to 64 yoa and those ≥65 yoa (data not

shown).

Appendix B Table 9. Analysis of Primary Efficacy Endpoint of Relative Vaccine Efficacy (rVE) for mRNA-

1010 (TIV) Versus SD Comparator Against RT-PCR–Confirmed Protocol-Defined ILI Caused by Any

Influenza A or B Strains by Age Group (PP Set), Study P304

mRNA-1010

(TIV) SD Comparator

N=20,179 N=20,124 rVE (%)

Age Group Cases, n/N (%) Cases, n/N (%) (95% CI)b

≥50 years of agea 411/20,179 557/20,124 26.6

(2.0) (2.8) (16.7, 35.4)

50 to <65 years of agec 229/10,542 307/10,501 26.1

(2.2) (2.9) (12.3, 37.7)

≥65 years of agec, d 182/9637 250/9623 27.4

(1.9) (2.6) (12.1, 40.0)

65 to <75 years of agec 138/7307 191/7289 28.0

(1.9) (2.6) (10.4, 42.2)

≥75 years of agec 44/2230 59/2334 25.3

(1.9) (2.5) (−10.4, 49.5)

Source: Adapted from STN 125869/0, mRNA-1010 P304 Clinical Study Report, Tables 14.2.1.1.1.1, Table 14.2.1.1.4.1. Data cutoff: April

30, 2025.

Abbreviations: CI, confidence interval; ILI, influenza-like illness; N, number of participants in the analysis set; n, number of cases of

protocol-defined ILI in the given age subgroup; PP, per protocol; RT-PCR, real-time reverse transcription polymerase chain reaction;

rVE, relative vaccine efficacy; SD, standard dose

The case is the first RT-PCR–confirmed protocol-defined ILI that begins at least 14 days after study vaccination through the end of influenza

season caused by any influenza A or B strains, regardless of vaccine match.

a

Percentages are based on the number of participants in the analysis set.

b

rVE is defined as 100×(1−hazard ratio [mRNA-1010 versus the Active Comparator]). The rVE and the CI are based on a stratified Cox

proportional hazards model with the study vaccination group as a fixed effect, adjusting by the randomized stratification factors: age group

(≥50 to <65 years or ≥65 years) and the status of influenza vaccine in the previous influenza season (received or not received). Efron´s

method is used to handle ties.

c

Percentages are based on the number of participants in the analysis set in each subgroup.

d

Age group ≥65 years includes the age group ≥75 years.

Additional Subgroup Analyses

The Applicant also conducted subgroup analyses of rVE (shown in Appendix B Table 10) in the PP

Set by influenza vaccine status in the previous season, sex, race, BMI, SD comparator type (TIV

versus QIV), region, baseline EFS frailty score, and high-risk status. Although Study P304 was not

powered to assess rVE in individual subgroups, rVE point estimates generally remained supportive of

mRNA-1010 (TIV) efficacy, with wider CIs observed in smaller subgroups.

rVE was similar when comparing participants who had or had not received an influenza vaccine in the

previous season, and when comparing participants with a baseline BMI below or at or above 30

kg/m². rVE was higher in female participants (30.7%; 95% CI: 17.9, 41.4) than in male participants

(20.9%; 95% CI: 3.9, 34.9), which may reflect sex-based differences in humoral immune responses

previously described in the literature (Fischinger et al., 2019). A lower rVE was observed in

participants with high-risk factors (22.3%) compared with those without (32.1%), though CIs

overlapped. In participants considered vulnerable or frail, rVE point estimates remained robust;

49

however, small sample sizes and wide 95% CIs crossing zero limit the interpretability and

generalizability of these findings to elderly frail individuals.

Appendix B Table 10. Subgroup Analyses of rVE for mRNA-1010 (TIV) Versus SD Comparator Against

RT PCR–Confirmed Protocol-Defined ILI Caused by Any Influenza Strain Type by Subgroup, Adults 50

Years of Age and Older (PP Set), Study P304

mRNA-1010 (TIV) % SD Comparator rVE (%)

Subgroup (Case/N) % (Case/N) (95% CIa)

Sex -- -- --

Male 2.1 (183/8775) 2.6 (226/8619) 20.9 (3.9,34.9)

Female 2.0 (228/11404) 2.9 (331/11505) 30.7 (17.9,41.4)

Race -- -- --

African American/Black 0.8 (21/2650) 1.4 (38/2657) 43.9 (4.5,67.1)

American Indian or Alaska Native 2.8 (2/71) 1.2 (1/85) --

Asian 1.8 (9/494) 1.7 (8/481) --

Native Hawaiian or other Pacific 0.0 (0/20) 0.0 (0/19) --

Islander

White 2.2 (375/16686) 3.0 (504/16628) 26.2 (15.6,35.4)

Other (including multiple, not 1.6 (4/258) 2.4 (6/254) --

reported, and unknown)

Region -- -- --

North America 1.8 (253/14176) 2.5 (353/14162) 28.5 (16.0,39.2)

Europe 2.7 (158/5829) 3.5 (204/5783) 23.7 (6.1,38.0)

East Asiac 0.0 (0/174) 0.0 (0/179) --

Body mass index (kg/m2) -- -- --

<30 kg/m2 2.1 (257/12193) 2.9 (348/12206) 26.2 (13.2,37.1)

≥30 kg/m2 1.9 (153/7957) 2.6 (208/7892) 27.5 (10.6,41.1)

Active comparator type

Countries using TIV active 1.8 (253/14176) 2.5 (353/14162) 28.5 (16.0,39.2)

comparator (North America)

Countries using QIV active 2.6 (158/6003) 3.4 (204/5962) 23.6 (6.0,37.9)

comparator (not North America)

Influenza vaccine status -- -- --

Received seasonal flu vaccine 2.5 (238/9456) 3.4 (316/9421) 25.2 (11.5,36.8)

Not received previous seasonal 1.6 (173/10723) 2.3 (241/10703) 28.6 (13.2,41.3)

flu vaccine

EFS Total scored -- -- --

0-3: Fit 2.0 (140/7079) 2.7 (190/7059) 26.8 (8.9,41.1)

4-5: Vulnerable 1.6 (28/1737) 2.3 (39/1708) 28.9 (−15.5,56.3)

≥6: Frail 1.7 (14/806) 2.5 (21/837) 30.3 (−37.1,64.6)

50

mRNA-1010 (TIV) % SD Comparator rVE (%)

Subgroup (Case/N) % (Case/N) (95% CIa)

Baseline high-risk factors -- -- --

High-riske 2.1 (241/11465) 2.7 (309/11457) 22.3 (8.0,34.3)

Not high-risk 2.0 (170/8714) 2.9 (248/8667) 32.1 (17.5,44.2)

Source: Adapted from STN 125869/0, mRNA-1010 P304 Clinical Study Report, Table 14.2.1.1.4.1.r. Data cutoff: April 30, 2025.

Abbreviations: BMI, body mass index; CI, confidence interval; eCRF, electronic case report; EFS, Edmonton Frail Scale; ILI, influenza-like

illness; N, number of participants in the analysis set; n, number of cases of protocol-defined ILI; PP, per protocol; QIV, quadrivalent

influenza vaccine; RT-PCR, real-time reverse transcription polymerase chain reaction; rVE, relative vaccine efficacy; SD, standard dose;

TIV, trivalent influenza vaccine

rVE is defined as 100×(1−hazard ratio [mRNA-1010 versus the Active Comparator]).

The rVE and the CI are based on a stratified Cox proportional hazards model with the study vaccination group as a fixed effect adjusting by

the randomized stratification factor: age group (≥50 to <65 years or ≥65 years) and/or the status of influenza vaccine in the previous

influenza season (received or not received), as applicable. Efron´s method is used to handle ties.

a

If there are <20 events total in the two vaccination groups combined, rVE is not provided.

b

Age group ≥65 years includes the age group of ≥75 years.

c

East Asia includes Republic of Korea and Taiwan. There were no observed cases in East Asia, which contributed 353 participants to the

study. Participants in East Asia were enrolled relatively late compared to other regions (November 25, 2024 to March 7, 2025). The

relatively small sample size along with the later timing of enrollment likely contributed to the absence of protocol-defined IILI cases in this

region.

d

EFS total score is only applicable to participants of ≥65 years old.

e

High-risk factors include baseline BMI ≥30 kg/m2, or having a medical history of autoimmune/immune-mediated disease, blood disorders,

cardiac disorders, diabetes mellitus, hepatic disorders, mental impairment disorders, nervous system disorders, pulmonary disorders, or

renal disorders.

Analyses of Secondary Efficacy Endpoints

rVE Based on RT-PCR–Confirmed Modified CDC-Defined ILI Caused by Any Influenza Strain

The secondary efficacy endpoint of modified CDC-defined ILI requires a temperature above 37.2°C,

cough and/or sore throat, and RT-PCR confirmation of influenza virus (see Table 2 for case

definitions). rVE based on this endpoint was evaluated sequentially for NI, superiority, and super-

superiority using the same prespecified rules as for the primary endpoint.

As shown in Appendix B Table 11, RT-PCR–confirmed modified CDC-defined ILI was reported in 223

(1.1%) mRNA-1010 (TIV) recipients and 290 (1.4%) SD comparator recipients in adults ≥50 yoa, with

an rVE of 23.5% (95% CI: 9.0, 35.8). This met prespecified success criteria for NI and superiority, but

not super-superiority. The more stringent fever requirement and the lower likelihood of fever during

influenza illness in adults ≥65 yoa (Smith et al., 2020) likely contributed to the smaller number of

modified CDC-defined ILI cases compared with protocol-defined ILI cases in both groups.

Nonetheless, mRNA-1010 (TIV) demonstrated superiority to the SD comparator with a robust rVE

point estimate across all participants ≥50 yoa.

51

Appendix B Table 11. Analysis of rVE for mRNA-1010 (TIV) Versus SD Comparator Against RT-PCR

Confirmed Modified CDC-Defined ILI Regardless of Vaccine Match, Overall and by Age Subgroup (PP

Set), Study P304

mRNA-1010 (TIV) SD Comparator

N=20,179 N=20,124 rVE (%)

Variable Cases, n (%)a Cases, n (%)a (95% CI)b

≥50 years of age 223 (1.1) 290 (1.4) 23.5 (9.0, 35.8)

50 through 64 years of age 129 (1.2) 162 (1.5) 21.1 (0.5, 37.4)

≥65 years of age 94 (1.0) 128 (1.3) 26.7 (4.4, 43.9)

Source: Adapted from STN 125869/0, mRNA-1010 P304 Clinical Study Report, Tables 14.2.1.1.1.1, 14.2.1.2.1.1, and 14.2.1.4.1.1. Data

cutoff: April 30, 2025.

Abbreviations: CDC, U.S. Centers for Disease Control and Prevention; CI, confidence interval; ILI, influenza-like illness; N, number of

participants in the analysis set; n, number of cases of protocol-defined ILI in the age subgroup; PP, per protocol; RT-PCR, real-time reverse

transcription polymerase chain reaction; rVE, relative vaccine efficacy; SD, standard dose

a

Percentages are based on the number of participants in the analysis set.

b

rVE is defined as 100×(1−hazard ratio [mRNA-1010 versus the Active Comparator]). The rVE and the CI are based on a stratified Cox

proportional hazards model with the study vaccination group as a fixed effect, adjusting by the randomized stratification factors: age group

(≥50 to <65 years or ≥65 years) and the status of influenza vaccine in the previous influenza season (received or not received). Efron´s

method is used to handle ties.

rVE Based on Antigenically Matched Cases (Descriptive)

The majority of RT-PCR–confirmed protocol-defined ILI cases in both groups were antigenically

matched to the vaccine strains. Among cases with an antigenic typing result, antigenic match was

high for influenza A/H1N1 (97.8% in the mRNA-1010 [TIV] group and 98.1% in the SD comparator

group) and influenza B/Victoria (93.8% in the mRNA-1010 [TIV] group and 95.0% in the SD

comparator group). Antigenic match was lower for influenza A/H3N2, though more than half of cases

remained antigenically matched (51.6% in the mRNA-1010 [TIV] group and 56.4% in the SD

comparator group).

rVE against antigenically matched RT-PCR–confirmed protocol-defined ILI and modified CDC-defined

ILI cases are shown in Appendix B Table 12. Overall, rVE remained consistent when limited to

antigenically matched cases for both case definitions. For influenza A/H3N2, which had the highest

proportion of antigenic mismatch, rVE against protocol-defined ILI increased from 22.2% (95% CI:

4.3, 36.9) across all cases to 30.5% (95% CI: 4.6, 49.4) when limited to antigenically matched cases,

suggesting that rVE against A/H3N2 may be higher in seasons with greater antigenic match between

vaccine and circulating strains.

52

Appendix B Table 12. Analyses of rVE for mRNA-1010 (TIV) vs SD Comparator Against Protocol-Defined

ILI and Modified CDC-Defined ILI With Antigenic Match, Participants 50 Years of Age and Older, (PP

Set), Study P304

mRNA-1010 (TIV) SD Comparator

N=20,178 N=20,122 rVE (%)

Relative Efficacy Endpoint Cases, n (%)a Cases, n (%)a (95% CI)b

Protocol-defined ILI -- -- --

Any influenza A or B strains 261 (1.3) 364 (1.8) 28.7 (16.4, 39.2)

Any influenza A strain 246 (1.2) 345 (1.7) 29.1 (16.5, 39.8)

Influenza A/H1N1 strain only 181 (0.9) 252 (1.3) 28.5 (13.5, 41.0)

Influenza A/H3N2 strain only 65 (0.3) 93 (0.5) 30.5 (4.6, 49.4)

Influenza B strain only 15 (<0.1) 19 (<0.1) 21.6 (−54.3, 60.2)

Modified CDC-defined ILI -- -- --

Any influenza A or B strains 143 (0.7) 198 (1.0) 28.2 (10.9, 42.1)

Any influenza A strain 137 (0.7) 189 (0.9) 27.9 (10.2, 42.1)

Influenza A/H1N1 strain only 107 (0.5) 143 (0.7) 25.6 (4.4, 42.1)

Influenza A/H3N2 strain only 30 (0.1) 46 (0.2) 35.2 (−2.6, 59.1)

Influenza B strain only 6 (<0.1) 9 (<0.1) NC

Source: Adapted from STN 125869/0, mRNA-1010 P304 Clinical Study Report, Table 14.2.1.3.1.1.f, Table 14.2.1.3.3.1.f, and

Table 14.2.1.3.3.6.f. Data cutoff: August 21, 2025.

Abbreviations: CDC, U.S. Centers for Disease Control; CI, confidence interval; ILI, influenza-like illness; N, number of participants in the

analysis set; n, number of cases of protocol-defined or modified CDC-defined ILI with antigenic match; NC, not calculated; PP, per protocol;

RT-PCR, real-time reverse transcription polymerase chain reaction; rVE, relative vaccine efficacy; SD, standard dose

a

Percentages are based on the number of participants in the analysis set. The event is the first RT-PCR–confirmed protocol-defined ILI or

modified CDC-defined ILI that begins at least 14 days after study vaccination through the end of influenza season caused by any influenza

A or B strains with antigenic match to the vaccine strains. b rVE is defined as 100×(1−hazard ratio [mRNA-1010 versus the Active

Comparator]). The rVE and the CI are based on a stratified Cox proportional hazards model with the study vaccination group as a fixed

effect, adjusting by the randomized stratification factors: age group (≥50 to <65 years or ≥65 years) and the status of influenza vaccine in

the previous influenza season (received or not received). Efron’s method is used to handle ties. If there are <20 events total in the two

vaccination groups combined, rVE is not provided.

Analysis of Exploratory Efficacy Endpoints

rVE for mRNA-1010 (TIV) Compared with SD Comparator Across Case Definitions

Appendix B Table 13 shows rVE of mRNA-1010 (TIV) compared with the SD comparator across

additional ILI case definitions (see Appendix B Table 1). rVE was consistent across all case

definitions with no notable differences.

53

Appendix B Table 13. Analysis of Relative Vaccine Efficacy (rVE) for mRNA-1010 (TIV) Versus SD

Comparator Against Various ILI Case Definitions Regardless of Vaccine Match, Participants 50 Years of

Age and Older, (PP Set), Study P304

mRNA-1010

(TIV) SD Comparator

N=20,179 N=20,124 rVE (%)

Relative Efficacy Endpoint Cases, n (%)a Cases, n (%)a (95% CI)b

RT-PCR–confirmed protocol-defined ILI 411 (2.0) 557 (2.8) 26.6 (16.7, 35.4)

RT-PCR–confirmed modified CDC-defined ILI 223 (1.1) 290 (1.4) 23.5 (9.0, 35.8)

RT-PCR–confirmed CDC-defined ILI 149 (0.7) 203 (1.0) 27.0 (9.8, 40.9)

RT-PCR–confirmed WHO-defined ILI 118 (0.6) 167 (0.8) 29.7 (11.1, 44.5)

RT-PCR–confirmed previous study protocol 194 (1.0) 261 (1.3) 26.1 (11.0, 38.6)

(mRNA-1010-P302) Defined ILI

RT-PCR–confirmed influenza infection 557 (2.8) 730 (3.6) 24.2 (15.4, 32.1)

Source: Adapted from STN 125869/0, mRNA-1010 P304 Clinical Study Report, Tables 14.2.1.1.1.1, 14.2.1.2.1.1, and 14.2.1.4.1.1. Data

cutoff: April 30, 2025.

Abbreviations: CDC, U.S. Centers for Disease Control and Prevention; CI, confidence interval; ILI, influenza-like illness; N, number of

participants in the analysis set; n, number of ILI cases based on the given case definition; PP, per protocol; RT-PCR, real-time reverse

transcription polymerase chain reaction; rVE, relative vaccine efficacy; SD, standard dose; WHO, World Health Organization

a

Percentages are based on the number of participants in the analysis set.

b

rVE is defined as 100×(1−hazard ratio [mRNA-1010 versus the Active Comparator]). The rVE and the CI are based on a stratified Cox

proportional hazards model with the study vaccination group as a fixed effect, adjusting by the randomized stratification factors: age group

(≥50 to <65 years or ≥65 years and the status of influenza vaccine in the previous influenza season (received or not received). Efron´s

method is used to handle ties.

Medically Attended Outcomes Associated with the Primary Efficacy Endpoint

Appendix B Table 14 shows medically attended outcomes associated with the first RT-PCR–

confirmed protocol-defined ILI, assessed as an exploratory endpoint. The rVE of mRNA-1010 (TIV)

versus the SD comparator for protocol-defined ILI cases seeking a higher level of care

(hospitalization, ER visit, or urgent care visit) was 47.9% (95% CI: 12.8, 68.9). Although rVE could not

be calculated for hospitalizations and ER visits individually due to limited case counts, the

consistently lower case counts in the mRNA-1010 (TIV) group suggest a clinical benefit.

While the study was not powered to evaluate healthcare outcomes associated with protocol-defined

ILI, these exploratory results suggest that mRNA-1010 (TIV) may offer greater efficacy than the SD

comparator in preventing more severe influenza-associated illness. The effect appeared most

pronounced in participants ≥65 yoa (7 cases seeking higher-level care in the mRNA-1010 [TIV] group

versus 20 in the SD comparator group; rVE 65.1%, 95% CI: 17.4, 85.2; data not shown). The majority

of higher-level-of-care cases in both groups occurred in adults 50 to 64 yoa (68.2% in the mRNA-

1010 [TIV] group and 52.4% in the SD comparator group) and in participants with a baseline high-risk

factor (90.9% in the mRNA-1010 [TIV] group and 76.2% in the SD comparator group; data not

shown).

54

Appendix B Table 14. Analysis of Health Care Outcomes Associated With the First RT-PCR–Confirmed

Protocol-Defined ILI Caused by Any Influenza A or B Strains, Regardless of Vaccine Match in

Participants 50 Years of Age and Older (PP Set), Study P304

mRNA-1010 (TIV) SD Comparator

N=20,179 N=20,124 rVE (%)

Variable Cases, n (%) Cases, n (%) (95% CI)a

Health care encounterb 80 (0.4) 120 (0.6) 33.7 (12.0, 50.0)

Seeking higher level of careb 22 (0.1) 42 (0.2) 47.9 (12.8, 68.9)

Hospitalizationc 4 (<0.1) 8 (<0.1) --

ER Visitc 6 (<0.1) 12 (<0.1) --

Urgent care clinic visitc 13 (<0.1) 24 (0.1) 46.1 (−5.8, 72.6)

Outpatient clinic visitc 59 (0.3) 81 (0.4) 27.6 (−1.3, 48.2)

Source: Adapted from STN 125869/0, mRNA-1010 P304 Clinical Study Report, Table 14.2.1.6.1.1. Data cutoff: April 30, 2025.

Abbreviations: CI, confidence interval; ER, emergency room; ILI, influenza-like illness; N, number of participants in the analysis set; n,

number of participants with a case, which is a healthcare encounter associated with the first occurrence of RT-PCR–confirmed protocol-

defined ILI that begins at least 14 days after study vaccination through the end of influenza season caused by any influenza A or B strains,

regardless of vaccine match; PP, per protocol; RT-PCR, real-time reverse transcription polymerase chain reaction; rVE, relative vaccine

efficacy; SD, standard dose

a

rVE is defined as 100×(1−hazard ratio [mRNA-1010 versus the Active Comparator]). The rVE and the CI are based on a stratified Cox

proportional hazards model with the study vaccination group as a fixed effect, adjusting by the randomized stratification factors: age group

(50 to <65 years or ≥65 years) and the status of influenza vaccine in the previous influenza season (received or not received). Efron’s

method is used to handle ties. If there are <20 events total in the two vaccination groups combined, rVE is not provided.

b

If an event is associated with multiple healthcare encounter types or multiple healthcare encounter of the same type, the participant will be

counted only once.

c

If an event is associated with multiple healthcare encounter of the same type, the participant will be counted only once.

Analyses of Secondary Immunogenicity Endpoints

The secondary immunogenicity objective was to describe HAI antibody titers at Baseline and Day 29

(GMT and SCR) in the PPIS. Baseline GMTs were similar across groups for all three vaccine-

matched strains.

Appendix B Table 15 shows Day 29 HAI GMTs in the mRNA-1010 (TIV) and SD comparator groups

for each vaccine-matched influenza strain. Day 29 GMTs were higher in the mRNA-1010 (TIV) group

compared with the SD comparator group for all three strains.

Appendix B Table 15. Analyses of Secondary Immunogenicity Endpoints of GMTs as Measured by HAI

for Vaccine-Matched Influenza Strains at Day 29 Postvaccination in Participants 50 Years of Age and

Older, PPIS, Study P304

mRNA-1010 (TIV) SD Comparator GMT Ratio

N=1167 N=1175 (mRNA-1010 / SD

GMT GMT Comparator)

Endpoint (95% CI) (95% CI) (95% CI)

Influenza A/H1N1 146.3 (138.7, 154.4) 80.2 (76.1, 84.6) 1.8 (1.7, 1.9)

Influenza A/H3N2 148.5 (140.9, 156.5) 93.4 (88.7, 98.5) 1.6 (1.5, 1.7)

Influenza B/Victoria 250.9 (240.3, 261.9) 149.9 (143.7, 156.6) 1.7 (1.6, 1.8)

Source: Adapted from STN 125869/0, mRNA-1010 P304 Clinical Study Report, Table 14.2.2.1.1. Data cutoff: April 30, 2025.

Abbreviations: ANCOVA, analysis of covariance; CI, confidence interval; GLSM, geometric least squares mean; GMT, geometric mean titer,

estimated by GLSM; HAI, hemagglutination inhibition; LLOQ, lower limit of quantification; N, number of participants with nonmissing HAI

data at baseline (Day 1) and the corresponding visit; ULOQ, upper limit of quantification

Antibody values reported as below the LLOQ are replaced by 0.5× LLOQ. Values greater than the ULOQ are converted to the ULOQ.

The log-transformed antibody levels are analyzed using an ANCOVA model with vaccination group as the fixed variable, log transformed

baseline HAI titers as a fixed covariate, adjusting for the randomization stratification factor(s): age group (≥50 to <65 years and ≥65 years)

and flu vaccine status in the previous influenza season (received seasonal flu vaccine, did not receive seasonal flu vaccine).

The model based GMT and GMT ratio, and its corresponding 95% CI are obtained by transforming the least square mean estimate and its

CI back to the original scale for presentation.

55

Appendix B Table 16 shows Day 29 HAI SCRs in the mRNA-1010 (TIV) and SD comparator groups

for each strain. SCRs were higher in the mRNA-1010 (TIV) group for all three strains, with the lower

bound of the 95% CI for the SCR difference exceeding 10% for each strain. Immunogenicity results

for GMT and SCR analyses conducted at EOS were consistent with end-of-season results.

Appendix B Table 16. Analysis of Secondary Immunogenicity Endpoints of SCR as Measured by HAI for

Vaccine-Matched Influenza Strains at Day 29 Postvaccination, Participants ≥50 Years of Age, PPIS,

Study P304

mRNA-1010 (TIV) SD Comparator Difference in SCR

N=1167 N=1175 (mRNA-1010 / SD

SCRa SCRa Comparator)

Endpoint (95% CI)b (95% CI)b [95% CI)c

Influenza A/H1N1 55.0 (52.1, 57.9) 27.1 (24.5, 29.7) 27.9 (24.1, 31.7)

Influenza A/H3N2 60.8 (57.9, 63.6) 40.9 (38.0, 43.7) 19.9 (15.9, 23.9)

Influenza B/Victoria 45.1 (42.1, 47.9) 19.7 (17.5, 22.1) 25.3 (21.7, 28.9)

Source: Adapted from STN 125869/0, mRNA-1010 P304 Clinical Study Report, Table 14.2.2.1.1. Data cutoff: April 30, 2025.

Abbreviations: CI, confidence interval; HAI, hemagglutination inhibition; N, number of participants with nonmissing HAI data at baseline

(Day 1) and the corresponding visit; PPIS, per-protocol immunogenicity set; SCR, seroconversion rate; SD, standard dose; TIV, trivalent

influenza vaccine

a

Rate of seroconversion is defined as the proportion of participants with either a baseline HAI titer <1:10 and a postbaseline titer ≥1:40 or a

baseline HAI titer ≥1:10 and a minimum 4-fold rise in postbaseline HAI antibody titer.

b

95% CI is calculated using the Clopper-Pearson method.

c

95% CI is calculated using the Miettinen-Nurminen (score) method.

Subpopulation Immunogenicity Analyses

The Applicant assessed the Day 29 GMT ratio and SCR differences for each influenza strain by

subgroups of age, sex, race, BMI, prior-year influenza vaccine status, and high-risk status. Although

some subgroups had limited participant numbers, participants who received mRNA-1010 (TIV) had

consistently higher immune responses compared with SD comparator recipients across all subgroups

evaluated.

Exploratory Immunogenicity Endpoints

The Applicant assessed neutralizing antibody responses by MN assay for each influenza strain in the

PPIS MN subset. Baseline MN GMTs were similar across both groups for all three strains. As shown

in Appendix B Table 17, Day 29 MN antibody responses were higher in the mRNA-1010 (TIV) group

compared with the SD comparator group for all three influenza strains. Results were similar in

participants 50 to 64 yoa and ≥65 yoa.

56

Appendix B Table 17. Summary of nAb Levels (GMT by MN Assay) and GMT Ratio at Day 29 for Vaccine-

Matched Influenza A and B Strains in Participants 50 Years of Age and Older (PPIS MN Subset), Study

P304

GMT Ratio

mRNA-1010 (TIV) Active Comparator [mRNA-1010 (TIV) / SD

N=247 N=253 Comparator]

Endpoint GMT (95% CI)a GMT (95% CI)a (95% CI)b

Influenza A/H1N1 514.4 (419.4, 630.9) 190.9 (153.5, 237.4) 2.8 (2.2, 3.5)

Influenza A/H3N2 429.1 (382.8, 480.9) 320.2 (290.6, 352.8) 1.4 (1.2, 1.6)

Influenza B/Victoria 1233.8 (1063.7, 1431.2) 608.5 (523.8, 706.9) 2.1 (1.8, 2.5)

Source: Adapted from STN 125869/0, mRNA-1010 P304 Clinical Study Report, Table 14.2.2.4.f. Data cutoff: August 21, 2025.

Abbreviations: ANCOVA, analysis of covariance; CDC, U.S. Centers for Disease Control; CI, confidence interval; GM, geometric mean titer;

ILI, influenza-like illness; LLOQ, lower limit of quantification; MN, microneutralization; N, number of participants with nonmissing HAI data at

baseline (Day 1) and the corresponding visit; nAb, neutralizing antibody; PPIS, per-protocol immunogenicity set; RT-PCR, real-time reverse

transcription polymerase chain reaction; ULOQ, upper limit of quantification

Antibody values reported as below the LLOQ are replaced by 0.5× LLOQ. Values greater than the ULOQ are converted to the ULOQ.

a

95% CI is calculated based on the t-distribution of the log-transformed values or the difference in the log transformed values for GM titer

and GM fold-rise, respectively, then back transformed to the original scale for presentation.

b

The log-transformed antibody levels are analyzed using an ANCOVA model with vaccination group as the fixed variable, log transformed

baseline MN titers as a fixed covariate, adjusting for the randomization stratification factor(s): age group (≥50 to <65 years and ≥65 years)

and flu vaccine status in the previous influenza season (received seasonal flu vaccine, did not receive seasonal flu vaccine). The model

based GMR and its 95% CI are obtained by transforming the least square mean estimate and its CI back to the original scale for

presentation.

Safety Analyses

The Safety Set included 40,703 participants: 20,350 in the mRNA-1010 (TIV) group and 20,353 in the

SD comparator group. As of study completion on August 21, 2025, the median duration of safety

follow-up was 184 days in both groups.

Overview of Adverse Events

Appendix B Table 18 provides an overview of solicited ARs and unsolicited AEs in the mRNA-1010

(TIV) group compared with the SD comparator. Rates of solicited ARs through Day 7 were higher in

the mRNA-1010 (TIV) group. Rates of unsolicited AEs through Day 28, and SAEs and AESIs through

study completion, were similar across groups.

Appendix B Table 18. Overall Number and Percentage of Participants Reporting at Least One Safety

Event, Participants 50 Years of Age and Older, Safety Set and Solicited Safety Subset, Study P304

SD Comparator

mRNA-1010 (TIV) (TIV + QIV)

Event Type % (n/N1) % (n/N1)

Solicited adverse reactions within 7 days -- --

Any solicited adverse reaction 75.7 (2283/3015) 46.7 (1400/2997)

Solicited local adverse reactiona 67.5 (2034/3015) 32.1 (961/2997)

Grade 3 or above solicited local adverse reaction 1.7 (51/3015) 0.1 (4/2997)

Solicited systemic adverse reactionb 58.0 (1750/3015) 32.4 (970/2997)

Grade 3 or above solicited systemic adverse 5.5 (167/3015) 0.9 (27/2997)

reaction

Unsolicited adverse events -- --

Unsolicited adverse event through 28 days after 5.9 (1204/20,350) 5.7 (1167/20,353)

vaccination

Nonserious unsolicited adverse event 5.6 (1145/20,350) 5.4 (1106/20,353)

Severe nonserious unsolicited AEc 0.1 (25/20,350) <0.1 (18/20,353)

57

SD Comparator

mRNA-1010 (TIV) (TIV + QIV)

Event Type % (n/N1) % (n/N1)

Medically attended adverse events throughout the 12.3 (2509/20,350) 12.0 (2439/20,353)

study

Related MAAEd 0.1 (23/20,350) <0.1 (14/20,353)

SAE throughout the study 2.2 (455/20,350) 1.9 (392/20,353)

Related SAEd <0.1 (4/20,350) <0.1 (2/20,353)

AESI throughout the study <0.1 (17/20,350) <0.1 (15/20,353)

Related AESId <0.1 (3/20,350) <0.1 (2/20,353)

Deaths throughout the study 0.2 (40/20,350) 0.2 (34/20,353)

Related deathsd 0 0

AE leading to study discontinuation throughout the <0.1 (3/20,350) <0.1 (1/20,353)

study

Source: Adapted from STN 125869/0, mRNA-1010-P304 Clinical Study Report, Tables 14.3.1.2.1.f, 14.3.1.2.1.8.f, 14.3.2.1.1.f, and

14.3.2.1.1.5.f. Data cutoff: August 21, 2025.

Abbreviations: AE, adverse event; AESI, adverse event of special interest; AR, adverse reaction; IRT, interactive response technology;

MAAE, medically attended adverse event; n, number of exposed participants who reported the event; N, number of participants in the

solicited safety subset or safety set; N1, number of participants who received a study intervention; QIV, quadrivalent influenza vaccine;

SAE, serious adverse event; TIV, trivalent influenza vaccine

Numbers are based on actual vaccination group and percentages are based on the number of participants in the Solicited Safety Subset or

Safety Set (N1). Any solicited local or systemic adverse reaction that meet the definition of an SAE is considered an AE.

a

Solicited local reactions included pain, erythema (redness), swelling (hardness), axillary swelling or tenderness.

b

Solicited systemic reactions included fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, chills.

c

Participants with at least one nonserious AE that was also severe/≥Grade 3.

d

The event was considered related to study vaccination by the investigator.

Solicited Adverse Reactions

Solicited Local Adverse Reactions

Appendix B Table 19 shows the frequency of solicited local ARs by maximum severity grade in each

group. Within 7 days of vaccination, solicited local ARs were reported by 67.5% of mRNA-1010 (TIV)

recipients and 32.1% of SD comparator recipients. The most frequently reported local AR in both

groups was injection site pain (65.8% in the mRNA-1010 [TIV] group and 29.8% in the SD

comparator group). Most local ARs were Grade 1 in severity. Grade 3 local ARs were reported by

1.7% of mRNA-1010 (TIV) recipients and 0.1% of SD comparator recipients. No Grade 4 local ARs

were reported in either group. There were no notable differences in solicited local ARs between

recipients of the TIV and QIV SD comparator formulations (data not shown).

Appendix B Table 19. Overall Frequency of Solicited Local Adverse Reactions Within 7 Days of

Vaccination, Participants 50 Years of Age and Older, Solicited Safety Subset, Study P304

mRNA-1010 (TIV) SD Comparator (TIV + QIV)

N1=3015 N1=2997

Event % (n) % (n)

Any local adverse reaction -- --

Any 67.5 (2034) 32.1 (961)

Grade 3 1.7 (51) 0.1 (4)

Paina -- --

Any 65.8 (1985) 29.8 (894)

Grade 3 0.9 (27) <0.1 (1)

58

mRNA-1010 (TIV) SD Comparator (TIV + QIV)

N1=3015 N1=2997

Event % (n) % (n)

Erythemab -- --

Any ≥25 mm 3.9 (117) 1.3 (38)

Grade 3 0.3 (10) <0.1 (2)

Swellingb -- --

Any ≥25 mm 5.7 (172) 1.5 (45)

Grade 3 0.3 (9) 0.1 (4)

Axillary swelling or tendernessa -- --

Any 17.2 (520) 6.1 (184)

Grade 3 0.3 (10) <0.1 (1)

Source: Adapted from STN 125869/0, mRNA-1010-P304 Clinical Study Report, Tables 14.3.1.2.1.f and 14.3.1.2.1.8.f. Data cutoff: August

21, 2025.

Abbreviations: Any, Grade 1 or higher; G1, Grade 1; G2, Grade 2; G3, Grade 3, G4, Grade 4; IRT, interactive response technology; n,

number of exposed participants who reported the event; N1, number of exposed participants in the solicited safety subset

There were no Grade 4 solicited systemic adverse reactions reported.

Numbers are based on actual vaccination group and percentages are based on the number of exposed participants the Solicited Safety

Subset.

The toxicity grade is the maximum toxicity grade reported on any day from Baseline. Assessments by investigator are used in analysis if

occurred on the same day as participant's assessments.

a

Toxicity grade for injection site pain, axillary swelling or tenderness ipsilateral to the side of injection are defined as: G1=no interference

with activity; G2=some interference with activity; G3=prevent daily activity; G4=requires emergency room visit or hospitalization.

b

Toxicity grade for injection site erythema (redness) or injection site swelling/induration (hardness) are defined as: G1=25-50 mm; G2=51-

100 mm; G3≥100 mm; G4=necrosis (injection site erythema) or exfoliative dermatitis (injection site swelling/induration).

The median day of onset for solicited local ARs was 2 days postvaccination in both groups. The

median duration was 2 days in the mRNA-1010 (TIV) group and 1 day in the SD comparator group. A

slightly higher proportion of local ARs persisted beyond 7 days in the mRNA-1010 (TIV) group

compared with the SD comparator group (0.6% versus 0.3%).

Solicited Systemic Adverse Reactions

Appendix B Table 20 shows the frequency of solicited systemic ARs by maximum severity grade.

Within 7 days of vaccination, any systemic AR was reported by 58.0% of mRNA-1010 (TIV) recipients

and 32.4% of SD comparator recipients. The most frequently reported systemic ARs among mRNA-

1010 (TIV) recipients were fatigue (45.1%), headache (37.8%), and myalgia (35.4%). Most systemic

ARs were Grade 1 or 2 in severity. Grade 3 systemic ARs were reported by 5.5% of mRNA-1010

(TIV) recipients and 0.9% of SD comparator recipients. No Grade 4 systemic ARs were reported in

either group. There were no notable differences in solicited systemic ARs between TIV and QIV SD

comparator recipients (data not shown).

Consistent with the higher reactogenicity in the mRNA-1010 (TIV) group, a higher proportion of

mRNA-1010 (TIV) recipients reported use of antipyretic or pain medication compared with SD

comparator recipients (28.5% versus 9.1%).

Appendix B Table 20. Overall Frequency of Solicited Systemic Adverse Reactions Within 7 Days of

Vaccination, Participants 50 Years of Age and Older, Solicited Safety Subset, Study P304

mRNA-1010 (TIV) SD Comparator (TIV + QIV)

N1=3015 N1=2997

Event % (n) % (n)

Any systemic adverse reaction -- --

Any 58.0 (1750) 32.4 (970)

Grade 3 5.5 (167) 0.9 (27)

59

mRNA-1010 (TIV) SD Comparator (TIV + QIV)

N1=3015 N1=2997

Event % (n) % (n)

Fevera -- --

Any 5.8 (174) 0.9 (26)

Grade 3 0.6 (17) 0.1 (3)

Headacheb -- --

Any 37.8 (1140) 18.0 (538)

Grade 3 2.0 (59) 0.3 (10)

Fatigueb -- --

Any 45.1 (1360) 20.3 (609)

Grade 3 3.2 (97) 0.4 (13)

Myalgiab -- --

Any 35.4 (1067) 11.6 (348)

Grade 3 2.5 (76) 0.2 (7)

Arthralgiab -- --

Any 27.8 (839) 10.6 (317)

Grade 3 1.9 (57) 0.2 (6)

Nausea/vomitingc -- --

Any 8.6 (259) 3.4 (102)

Grade 3 0.2 (5) <0.1 (2)

Chillsb -- --

Any 22.8 (688) 4.3 (129)

Grade 3 2.1 (62) 0.1 (4)

Use of antipyretic or pain 28.5 (860) 9.1 (272)

medication

Source: Adapted from STN 125869/0, mRNA-1010-P304 Clinical Study Report, Tables 14.3.1.2.1.f, 14.3.1.2.1.8.f, 14.1.3.3.4.f, and

14.1.3.3.4.1.f. Data cutoff: August 21, 2025.

Abbreviations: Any, Grade 1 or higher; G1, Grade 1; G2, Grade 2; G3, Grade 3, G4, Grade 4; IRT, interactive response technology; n,

number of exposed participants who reported the event; N1, number of exposed participants in the solicited safety subset

Numbers are based on actual vaccination group and percentages are based on the number of exposed participants the Solicited Safety

Subset.

There were no Grade 4 solicited systemic adverse reactions reported.

The toxicity grade is the maximum toxicity grade reported on any day from Baseline. Assessments by investigator are used in analysis if

occurred on the same day as participant’s assessments.

a

Toxicity grade for fever (oral) is defined as: G1=38.0-38.4°C or 100.4-101.1°F; G2=38.5-38.9°C or 101.2-102.0°F; G3=39.0-40.0°C or

102.1-104.0°F; G4: ≥40.0°C or >104.0°F.

b

Toxicity grade for headache, fatigue, myalgia (muscle aches all over body), arthralgia (joint aches in several joints), and chills are defined

as: G1=no interference with activity; G2=some interference with activity; G3=prevent daily activity; G4, requires emergency room visit or

hospitalization.

c

Toxicity grade for nausea/vomiting are defined as: G1=no interference with activity or 1-2 episodes/24 hours; G2=some interference with

activity or >2 episodes/24 hours; G3=prevent daily activity or requires outpatient intravenous hydration; G4=requires emergency room visit

or hospitalization for hypotensive shock.

The median day of onset for solicited systemic ARs was 2 days postvaccination in both groups. The

median duration was 2 days in both groups. A slightly higher proportion of systemic ARs persisted

beyond 7 days in the mRNA-1010 (TIV) group compared with the SD comparator group (1.0% versus

0.7%).

Subgroup Analyses for Solicited Adverse Reactions

Solicited ARs were examined across multiple subgroups, including age, race, sex, baseline high-risk

classification, prior influenza vaccination status, SD comparator type (TIV or QIV), and geographic

region. Across all subgroups, solicited ARs occurred at a higher frequency in mRNA-1010 (TIV)

recipients compared with SD comparator recipients. Within the mRNA-1010 (TIV) group, the solicited

AR profile was generally consistent across subgroups, with the exception of age, as described below.

Age

60

Rates of solicited local and systemic ARs by age subgroup are shown in Appendix B Table 21. The

magnitude of increased reactogenicity for mRNA-1010 (TIV) relative to the SD comparator was

comparable across age subgroups. Among mRNA-1010 (TIV) recipients, the frequency of solicited

ARs was slightly lower in participants ≥65 yoa compared with those 50 to 64 yoa. This trend of

decreasing reactogenicity with increasing age was also observed when the ≥65 years subgroup was

further divided into 65 to 74 years and ≥75 years age groups.

Appendix B Table 21. Frequency of Solicited Adverse Reactions Within 7 Days of Vaccination, Solicited

Safety Subset, By Age Subgroup, Study P304

50-64 Years 50-64 Years ≥65 Years ≥65 Years

mRNA-1010 SD Comparator mRNA-1010 SD Comparator

(TIV) (TIV+QIV) (TIV) (TIV+QIV)

N1=1510 N1=1502 N1=1505 N1=1495

Event % (n) % (n) % (n) % (n)

Any local adverse reaction -- -- -- --

Any 70.0 (1057) 36.3 (545) 64.9 (977) 27.8 (416)

Grade 3 1.9 (28) 0.1 (2) 1.5 (23) 0.1 (2)

Paina -- -- -- --

Any 68.7 (1038) 34.4 (517) 62.9 (947) 25.2 (377)

Grade 3 1.1 (17) <0.1 (1) 0.7 (10) 0

Erythemab -- -- -- --

Any ≥25 mm 4.4 (66) 1.3 (19) 3.4 (51) 1.3 (19)

Grade 3 0.3 (4) <0.1 (1) 0.4 (6) <0.1 (1)

Swellingb -- -- -- --

Any ≥25 mm 6.4 (96) 1.2 (18) 5.0 (76) 1.8 (27)

Grade 3 0.3 (4) 0.1 (2) 0.3 (5) 0.1 (2)

Axillary swelling or tendernessa -- -- -- --

Any 20.3 (306) 6.9 (104) 14.2 (214) 5.4 (80)

Grade 3 0.3 (4) <0.1 (1) 0.4 (6) 0

Any systemic adverse reaction -- -- -- --

Any 61.4 (927) 33.7 (506) 54.7 (823) 31.0 (464)

Grade 3 6.5 (98) 1.1 (16) 4.6 (69) 0.7 (11)

Feverc -- -- -- --

Any 6.0 (90) 0.9 (13) 5.6 (84) 0.9 (13)

Grade 3 0.7 (11) 0.1 (2) 0.4 (6) <0.1 (1)

Headachea -- -- -- --

Any 41.9 (633) 20.1 (302) 33.7 (507) 15.8 (236)

Grade 3 2.2 (33) 0.4 (6) 1.7 (26) 0.3 (4)

Fatiguea -- -- -- --

Any 48.1 (727) 20.6 (309) 42.1 (633) 20.1 (300)

Grade 3 3.9 (59) 0.6 (9) 2.5 (38) 0.3 (4)

Myalgiaa -- -- -- --

Any 40.6 (613) 13.0 (196) 30.2 (454) 10.2 (152)

Grade 3 2.9 (44) 0.3 (4) 2.1 (32) 0.2 (3)

Arthralgiaa -- -- -- --

Any 31.5 (476) 11.1 (167) 24.1 (363) 10.0 (150)

Grade 3 2.3 (34) 0.2 (3) 1.5 (23) 0.2 (3)

61

50-64 Years 50-64 Years ≥65 Years ≥65 Years

mRNA-1010 SD Comparator mRNA-1010 SD Comparator

(TIV) (TIV+QIV) (TIV) (TIV+QIV)

N1=1510 N1=1502 N1=1505 N1=1495

Event % (n) % (n) % (n) % (n)

Nausea/vomitingd -- -- -- --

Any 9.7 (147) 4.1 (61) 7.4 (112) 2.7 (41)

Grade 3 0.2 (3) <0.1 (1) 0.1 (2) <0.1 (1)

Chillsa -- -- -- --

Any 27.5 (415) 4.7 (71) 18.1 (273) 3.9 (58)

Grade 3 2.8 (42) 0.2 (3) 1.3 (20) <0.1 (1)

Use of antipyretic or pain 33.2 (501) 10.5 (157) 23.9 (359) 7.7 (115)

medication

Source: Adapted from STN 125869/0, mRNA-1010-P304 Clinical Study Report, Tables 14.1.3.3.4.2.f, 14.1.3.3.4.4.f, 14.3.1.2.1.1.f

14.3.1.2.1.9.f., 14.3.1.2.1.1.f, and 14.3.1.2.1.9.f. Data cutoff: August 21, 2025.

Abbreviations: Any, Grade 1 or higher; G1, Grade 1; G2, Grade 2; G3, Grade 3, G4, Grade 4; 50-64; IRT, interactive response technology;

N1, number of exposed participants in the Solicited Safety Subset; n, number of exposed participants who reported the event

There were no Grade 4 solicited systemic adverse reactions reported.

Numbers are based on actual vaccination group and percentages are based on the number of exposed participants the Solicited Safety

Subset.

The toxicity grade is the maximum toxicity grade reported on any day from Baseline. Assessments by the investigator are used in analysis if

occurred on the same day as participant's assessments.

a

Toxicity grade for injection site pain, axillary (underarm) swelling or tenderness ipsilateral to the side of injection, headache, fatigue,

myalgia (muscle aches all over body), arthralgia (joint aches in several joints), and chills are defined as: G1=no interference with activity;

G2=some interference with activity; G3=prevent daily activity; G4=requires emergency room visit or hospitalization.

b

Toxicity grade for injection site erythema (redness) or injection site swelling/induration (hardness) are defined as: G1=25-50 mm; G2=51-

100 mm; G3≥100 mm; G4=necrosis (injection site erythema) or exfoliative dermatitis (injection site swelling/induration).

c

Toxicity grade for fever (oral) is defined as: G1=38.0-38.4°C or 100.4-101.1°F; G2=38.5-38.9°C or 101.2 102.0°F; G3=39.0-40.0°C or

102.1-104.0°F; G4≥40.0°C or >104.0°F.

d

Toxicity grade for nausea/vomiting are defined as: G1=no interference with activity or 1-2 episodes/24 hours; G2=some interference with

activity or >2 episodes/24 hours; G3=prevent daily activity or requires outpatient intravenous hydration; G4=requires emergency room visit

or hospitalization for hypotensive shock.

Unsolicited Adverse Events

Unsolicited Adverse Events Through 28 Days After Vaccination

The rates of unsolicited AEs within 28 days of vaccination were balanced: 5.9% of mRNA-1010 (TIV)

recipients and 5.7% of SD comparator recipients. Unsolicited AEs were most commonly reported

under the Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC) of

infections and infestations (1.4% in both groups). Unsolicited AEs within 28 days assessed as related

to study vaccine by the investigator were reported in 0.5% of mRNA-1010 (TIV) recipients and 0.2%

of SD comparator recipients; this difference was largely attributable to AEs overlapping with protocol-

specified solicited ARs, which also occurred more frequently in the mRNA-1010 (TIV) group. Rates of

unsolicited AEs were generally similar across subgroups based on age, sex, race, and high-risk

status.

Medically Attended Adverse Events (MAAEs)

MAAEs within 28 days of vaccination were reported in 3.8% of participants in both groups. Through

study completion (median follow-up of approximately 6 months), 12.3% of mRNA-1010 (TIV)

recipients and 12.0% of SD comparator recipients reported at least one MAAE. MAAEs were most

frequently reported under the MedDRA SOC of infections and infestations (3.6% in the mRNA-1010

[TIV] group and 3.3% in the SD comparator group). MAAEs assessed as related to study vaccine by

the investigator were reported in 23 (0.1%) mRNA-1010 (TIV) recipients and 14 (<0.1%) SD

comparator recipients. The most commonly reported related MAAEs were under the SOCs of skin

and subcutaneous tissue disorders (5 mRNA-1010 [TIV] recipients and 4 SD comparator recipients)

62

and cardiac disorders (6 mRNA-1010 [TIV] recipients and 2 SD comparator recipients). No individual

preferred term under cardiac disorders was reported by more than one participant, and no clear

pattern emerged to suggest a specific safety concern.

Deaths

Within 28 days of vaccination, 7 deaths (<0.1%) were reported in the mRNA-1010 (TIV) group and 9

(<0.1%) in the SD comparator group. Through study completion on August 21, 2025, there were 40

deaths (0.2%) in the mRNA-1010 (TIV) group and 34 deaths (0.2%) in the SD comparator group. No

deaths in either group were assessed as related to study vaccine by the investigator. Based on

independent review of event narratives, FDA agrees with the investigators’ assessments that these

deaths were unlikely to be related to study vaccine. In general, the causes of death are representative

of common causes of death among older adults and the general U.S. population (e.g., heart disease,

motor vehicle accident, cancer).

Serious Adverse Events (SAEs)

SAEs within 28 days of vaccination were reported in 0.5% (n=92) of mRNA-1010 (TIV) recipients and

0.5% (n=92) of SD comparator recipients. Through study completion (median follow-up of

approximately 6 months), SAEs were reported in 2.2% (n=455) of mRNA-1010 (TIV) recipients and

1.9% (n=392) of SD comparator recipients. SAEs were most frequently reported under the MedDRA

SOCs of infections and infestations (0.4% in each group) and cardiac disorders (0.3% in each group).

Through the entire study duration, 4 participants (<0.1%) in the mRNA-1010 (TIV) group and 2

participants (<0.1%) in the SD comparator group reported at least one SAE assessed as related to

study vaccine by the investigator. The four SAEs in the mRNA-1010 (TIV) group are described below.

SAEs Assessed as Related to mRNA-1010 (TIV) by the Investigator

Syncope: A 62-year-old female with a history of hypercholesterolemia, hypothyroidism, and insomnia

(on trazodone) experienced syncope on Study Day 2. Emergency medical technicians (EMTs)

evaluated her at the scene and noted possible dehydration and a temperature of 101.3°F. She also

reported body aches, chills, and headache, all of which resolved by Day 3. She declined an ER visit

and recovered at home with rest and fluids. The event of syncope was recorded as resolved on Day

2. The Applicant agreed with the investigator’s assessment that this event was related to study

vaccine.

FDA Assessment: FDA agrees with the investigator’s assessment that this SAE of syncope

is likely related to study vaccine, given the timing of onset postvaccination and the concurrent

documented fever and solicited ARs. However, concurrent trazodone use may also have

contributed.

Hypotension: A 67-year-old male with hypertension (pre-dose blood pressure 112/71 mmHg; post-

dose 136/90 mmHg on Day 1), type 2 diabetes mellitus, gout, and benign prostatic hyperplasia (on

gabapentin, metoprolol, and tamsulosin) reported hypotension on Study Day 2 requiring

hospitalization for further evaluation. He reported headache and low blood pressure readings at home

that prompted his medical visit. All tests were negative and he was discharged home on Day 4 with

hypotension recorded as resolved. On Day 8, he withdrew consent and refused release of further

medical information. The Applicant assessed this event as not related to study vaccine.

FDA Assessment: Although the timing of onset is consistent with a possible contribution from

study vaccine, the participant reported no reactogenicity during the 7-day postvaccination

period. Moderate-to-severe reactogenicity (e.g., fever or nausea/vomiting leading to

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dehydration and subsequent hypotension) would have provided additional support for a causal

association. Concurrent antihypertensive medications may also have independently

contributed.

Myopericarditis and Congestive Cardiomyopathy: A 54-year-old female current smoker with a

history of hypertension, hypothyroidism, type 2 diabetes mellitus, and ADHD (on methylphenidate)

presented to the ER on Study Day 95 with dyspnea and left-sided chest pain radiating to the neck

and arm. She was diagnosed with uncontrolled diabetes mellitus, dilated cardiomyopathy, and

myopericarditis, and concurrently reported cough, sputum production, rhinorrhea, and fatigue.

Workup demonstrated severely reduced left ventricular ejection fraction, global hypokinesis, third-

degree diastolic dysfunction, early dilated cardiomyopathy with signs of past perimyocarditis, and mild

mitral valve insufficiency without significant coronary stenoses. She was discharged on Day 103 with

dilated cardiomyopathy and myopericarditis ongoing; uncontrolled diabetes was considered resolved.

The CEAC concluded that the event did not meet criteria for confirmed or probable myocarditis, acute

pericarditis, or myopericarditis. The Applicant assessed these events as unrelated to study vaccine.

FDA Assessment: These events are unlikely to be related to study vaccine. The long latency

period, significant medical history, and concurrent symptoms of recent respiratory illness

suggest more plausible alternative etiologies.

Myocarditis: A 64-year-old male former smoker with no significant medical history reported an SAE

of myocarditis on Study Day 183. On Day 33, he presented with persistent upper respiratory

symptoms; nasal swabs were positive for rhinovirus/enterovirus. Over the following months, he

developed worsening dyspnea, lower extremity edema, orthopnea, and lethargy. On Day 183, he

presented to the ER in atrial fibrillation with markedly elevated brain natriuretic peptide (BNP) and CT

evidence of fluid overload. Echocardiography demonstrated severely impaired biventricular systolic

function, biventricular and biatrial dilation, and significant valvular regurgitation. He was discharged

on Day 191 with a diagnosis of heart failure with reduced ejection fraction, likely secondary to

myocarditis. Cardiac MRI on Day 199 showed late gadolinium enhancement (LGE) at the right

ventricular insertion point, possible biatrial wall and circumferential pericardial LGE, and severely

impaired biventricular function, which the cardiologist assessed as possibly consistent with

myocarditis/pericarditis or cardiomyopathy. The CEAC determined the event met criteria for

confirmed myopericarditis. The Applicant assessed this event as unrelated to study vaccine.

FDA Assessment: This event is unlikely to be related to study vaccine given the long latency

(well outside the typical onset window of within the first week postvaccination observed with

mRNA COVID-19 vaccines) and the preceding rhinovirus/enterovirus infection immediately

before symptom onset, suggesting a more plausible alternative etiology.

Adverse Events of Special Interest (AESIs)

Protocol-defined AESIs are listed in Appendix A. Through Day 28 postvaccination, AESIs were

reported in 4 participants (<0.1%) in the mRNA-1010 (TIV) group and 3 participants (<0.1%) in the

SD comparator group. Through study completion (median approximately 6 months of follow-up), 17

participants (<0.1%) in the mRNA-1010 (TIV) group and 15 participants (<0.1%) in the SD

comparator group reported AESIs. Of these, 5 were assessed as related by the investigator: 3 in the

mRNA-1010 (TIV) group and 2 in the SD comparator group. The investigator-assessed related AESIs

in the mRNA-1010 (TIV) group are described below.

AESIs Assessed as Related by the Investigator in the mRNA-1010 (TIV) Group

64

Thrombocytopenia: A 51-year-old male with a history of regular alcohol use and concomitant

meloxicam use experienced a mild event of thrombocytopenia on Day 84 in the context of a

concurrent upper respiratory tract infection. The event resolved without intervention.

FDA Assessment: This event is unlikely to be related to study vaccine given the long latency

from vaccination. The concurrent respiratory tract infection represents a more plausible

alternative etiology.

Myocarditis: A 64-year-old male experienced myocarditis on Day 183 in the context of a concurrent

rhinovirus/enterovirus infection. This case and the FDA assessment are described above under SAEs

Assessed as Related to mRNA-1010 (TIV) by the Investigator.

Myopericarditis: A 54-year-old female experienced myopericarditis on Day 95 in the context of

concurrent SAEs of uncontrolled type 2 diabetes mellitus and congestive cardiomyopathy. This case

and the FDA assessment are described above under SAEs Assessed as Related to mRNA-1010

(TIV) by the Investigator.

Pregnancies

No pregnancies were reported throughout the study.

Dropouts and/or Discontinuations

Through study completion on August 21, 2025, deaths led to study discontinuation in 0.2% of

participants in each group. Additionally, 3 participants in the mRNA-1010 (TIV) group and 2 in the SD

comparator group had AEs leading to study discontinuation. None of the AEs that led to

discontinuation in either group were considered related to study vaccine by the investigator or upon

FDA assessment.

65

Appendix C – Study P303 Part C: Efficacy and Safety

NCT05827978

Title: "A Phase 3, Randomized, Stratified, Observer-Blind, Active-Controlled Study to Evaluate the

Immunogenicity, Reactogenicity, and Safety of mRNA-1010 Seasonal Influenza Vaccine in Adults 18

Years of Age and Older"

Study Overview

Study mRNA-1010-P303 (P303) was a Phase 3, multicenter, randomized, stratified, observer-blind,

active-controlled study evaluating the immunogenicity, reactogenicity, and safety of the quadrivalent

mRNA-1010 seasonal influenza vaccine (mRNA-1010 [QIV]). This briefing document focuses on Part

C of Study P303, which compared immunogenicity and safety of mRNA-1010 (QIV) to Fluzone High-

Dose (QIV) (Fluzone HD [QIV]) in adults 65 yoa and older. Fluzone HD (QIV) is one of three influenza

vaccines preferentially recommended by the CDC for this age group.

Data from Study P303 Part C support the immunogenicity assessment of mRNA-1010 relative to a

high-dose active comparator in adults 65 yoa and older. This assessment involves two key

considerations: (1) an evaluation of the use of hemagglutination inhibition (HAI) as a surrogate

endpoint reasonably likely to predict clinical benefit (addressed separately) and (2) an assessment of

whether immunogenicity data from the quadrivalent formulation (QIV) can support the effectiveness of

the trivalent formulation (TIV) (see Section 3.1.3.4).

The study was initiated on November 13, 2023, and completed on June 24, 2024. The final database

lock date was July 22, 2024.

Objectives

Primary Objectives

Primary Immunogenicity Objective

To evaluate the humoral immunogenicity of mRNA-1010 (QIV) for noninferiority relative to Fluzone

HD (QIV) against four vaccine-matched influenza A and B strains at Day 29 in adults ≥65 yoa, as

measured by HAI.

Endpoints:

 Geometric mean titer (GMT) at Day 29

 Seroconversion rate (SCR) at Day 29

There were eight coprimary endpoints based on GMT ratio and SCR difference for the four vaccine-

matched strains. Each endpoint was evaluated for noninferiority of mRNA-1010 (QIV) versus Fluzone

HD (QIV) at a two-sided alpha level of 0.05. Study success required all eight coprimary endpoints to

meet the noninferiority criteria.

Statistical Criterion for Noninferiority

Noninferiority at Day 29 was demonstrated if, for all four influenza strains:

 Lower limit (LL) of the 95% CI of the GMT ratio (mRNA-1010 [QIV] / Fluzone HD [QIV])

was >0.667.

 LL of the 95% CI of the SCR difference (mRNA-1010 [QIV] − Fluzone HD [QIV]) was

>−10%.

66

Primary Safety Objective

To evaluate the safety and reactogenicity of mRNA-1010 (QIV), including: frequency and severity of

solicited local and systemic adverse reactions (ARs) through Day 7; frequency and severity of

unsolicited adverse events (AEs) through Day 28; and serious adverse events (SAEs), medically

attended adverse events (MAAEs), adverse events of special interest (AESIs), and AEs leading to

study discontinuation through Day 181/end of study (EOS).

Secondary Objectives

Secondary Immunogenicity Objectives

To evaluate the humoral immunogenicity of mRNA-1010 (QIV) for superiority relative to Fluzone HD

(QIV) against vaccine-matched influenza A and B strains at Day 29, as measured by HAI.

Endpoints:

 GMT at Day 29

 SCR at Day 29

Superiority testing was conducted upon successful demonstration of noninferiority for all eight

coprimary endpoints.

Statistical Criterion for Superiority

Superiority at Day 29 was demonstrated if, for each of the four influenza strains:

 LL of the 97.5% CI of the GMT ratio (mRNA-1010 [QIV] / Fluzone HD [QIV]) was >1.

 LL of the 97.5% CI of the SCR difference (mRNA-1010 [QIV] − Fluzone HD [QIV]) was >0.

Descriptive secondary endpoints (no hypothesis testing):

 Proportion of participants with HAI titer ≥1:40 at Day 29

 Geometric mean fold rise (GMFR) from Baseline to Day 29 as measured by HAI

Select Exploratory Objectives (Descriptive; No Hypothesis Testing)

To evaluate the humoral immunogenicity of mRNA-1010 (QIV) relative to Fluzone HD (QIV) against

vaccine-matched influenza A and B strains at Day 181/EOS in a participant subset, as measured by

HAI.

Endpoints:

 GMT at Day 181

 SCR at Day 181

Design

A total of 3,003 participants were enrolled at 96 centers in the United States and randomized 1:1 to

receive a single intramuscular injection of either mRNA-1010 (QIV) or Fluzone HD (QIV). The

influenza strains encoded in mRNA-1010 (QIV) were aligned with FDA recommendations for the

2023/2024 Northern Hemisphere (NH) influenza vaccine for cell- or recombinant-based vaccines. The

strains in Fluzone HD (QIV) were aligned with FDA recommendations for 2023/2024 NH egg-based

vaccines.

Randomization was stratified by prior influenza season vaccination status (received or not received; if

received, whether from prior participation in Study P302). Total study duration, including screening,

was up to 7 months per participant.

67

Medically stable adults ≥65 yoa were enrolled. Key exclusion criteria were similar to those in Study

P304 (see Appendix B). After the screening visit, participants completed up to two clinic visits (Day 1

and Day 29) and three telephone visits (Day 8, Day 91, and Day 181/EOS). The first 1,000

participants enrolled also attended a clinic visit on Day 181 (Month 6)/EOS for immunogenicity blood

sampling; remaining participants were contacted by telephone.

Evaluation of Immunogenicity

Blood samples for HAI antibody assessment were collected at Day 1 (Baseline), Day 29, and Day

181/EOS (in a subset of participants). Microneutralization (MN) immunogenicity analyses were

performed on a randomly selected subset of 500 participants (250 per vaccination group) from the

per-protocol immunogenicity set (PPIS).

Evaluation of Safety

Study oversight and safety monitoring—including solicited and unsolicited AEs, MAAEs, AESIs,

SAEs, and AEs leading to study discontinuation—were conducted as described for Study P304 (see

Appendix B).

Analysis Populations

Appendix C Table 1. Analysis Sets

Analysis Set Description

Randomization Set All participants who were randomly assigned to the study injection,

regardless of the participants’ study intervention status in the study.

FAS All participants in the Randomization Set who received any study injection.

Participants were analyzed according to the group to which they were

randomized.

Immunogenicity Subset All participants in the FAS who had Baseline and Day 29 antibody

assessment via HAI assay. Participants were analyzed according to the

group to which they were randomized.

PPIS The PPIS included all participants in the Immunogenicity Set who received

the planned dose of study intervention, complied with the immunogenicity

testing schedule for Baseline and Day 29 4, and had no significant protocol

deviations that impacted key or critical data.

Participants with RT-PCR–confirmed influenza between Days 1 and 29

were removed from the PPIS. The PPIS was used for all analyses of

immunogenicity unless otherwise specified. Participants were analyzed

according to the group to which they were randomized.

PPIS microneutralization (MN) Participants randomly selected from PPIS for MN analyses with MN values

Subset on Day 1 and Day 29.

Solicited Safety Set All participants in the FAS who contributed any solicited AR data. The

Solicited Safety Set was used for the analyses of solicited ARs.

Participants were included in the group corresponding to the study

intervention that they actually received.

Safety Set All participants in the FAS. The Safety Set was used for all analyses of

safety except for the solicited ARs. Participants were included in the group

corresponding to the study intervention that they actually received.

Source: Adapted from STN 125869/0, mmRNA-1010-P303 Part B and C CSR Table 8.

Abbreviations: AR, adverse reaction; FAS, full analysis set; HAI, hemagglutination inhibition; PPIS, per-protocol immunogenicity set; RT-

4 Compliance with the immunogenicity testing schedule for Baseline and Day 29 is defined as having

immunogenicity samples collected before the study intervention administration and between Day 22 and Day 43

(i.e., −7/+14 days of Day 29).

68

PCR, reverse transcription polymerase chain reaction

Subgroup Analyses

Immunogenicity subgroup analyses were conducted for the following subgroups: age (65 to <75

years; ≥75 years), prior influenza vaccination status (received, received from Study P302, not

received), race, sex, and BMI category (<30 kg/m² or ≥30 kg/m²). Unsolicited AE analyses were

conducted for all subgroups except prior influenza vaccination status and BMI.

Post Hoc Analyses

Post hoc analyses of immunogenicity and safety were performed in high-risk participants, defined as

those with a significant comorbidity based on medical history, including autoimmune and immune-

mediated disorders; chronic obstructive pulmonary disease; diabetes; cardiac disorders; blood, renal,

and hepatic disorders; mental impairment; and neurologic disorders.

The Applicant also conducted a post hoc analysis comparing Day 29 HAI GMTs between the PPISs

of Study P303 Part C and Study P304, restricted to participants 65 yoa and older, to support the use

of immunogenicity data from mRNA-1010 (QIV) to support licensure of mRNA-1010 (TIV).

Study Population and Disposition

Participant disposition in the immunogenicity populations is shown in Appendix C Table 2. The

percentages of participants excluded from the PPIS were similar between groups: 2.3% in the mRNA-

1010 (QIV) group and 1.9% in the Fluzone HD (QIV) group. The most common reasons for exclusion

were significant protocol deviations (1.0% in each group) and noncompliance with immunogenicity

blood sampling timing (1.2% and 0.8%, respectively).

Appendix C Table 2. Participant Disposition, Adults 65 Years of Age and Older, Immunogenicity

Populations, Study P303 Part C

mRNA-1010 Fluzone HD (QIV)

N=1507 N=1496

Population n (%) n (%)

FASa 1504 (99.8) 1492 (99.7)

Immunogenicity Set 1458 (96.7) 1437 (96.1)

PPIS 1425 (94.6) 1409 (94.2)

Excluded from PPIS 33 (2.3) 28 (1.9)

Reason for exclusion from PPIS -- --

Major dosing error 1 (<0.1) 1 (<0.1)

Did not comply with timing of immunogenicity blood 14 (1.0) 15 (1.0)

sampling

Had significant protocol deviations that impact key 18 (1.2) 12 (0.8)

or critical data

Source: Adapted from STN 125869/0, mRNA-1010-P303 Part B and Part C Clinical Study Report, Table 14.1.2.2.1.c, and Table 14.1.3.1.c.

Data cutoff: June 24, 2024.

Abbreviations: FAS, full analysis set; HD, high dose; N, number of participants in the Randomization Set; n, number of participants in a

given subpopulation or category; PPIS, per-protocol immunogenicity set

a

Numbers are based on the planned vaccination group and percentages are based on the number of participants in the Randomization Set.

Participant disposition in the Safety Set is shown in Appendix C Table 3. Overall study discontinuation

was slightly lower in the mRNA-1010 (QIV) group (1.3%) than in the Fluzone HD (QIV) group (2.4%).

The most common reasons for discontinuation were lost to follow-up (0.7% vs. 1.7%) and withdrawal

69

of consent by the participant (0.5% vs. 0.7%). No participant discontinued due to an adverse event.

The median duration of follow-up after vaccination was 171 days in both groups.

Appendix C Table 3. Participant Disposition, Adults 65 Years of Age and Older, Safety Populations,

Study P303 Part C

mRNA-1010 (QIV) Fluzone HD (QIV)

N=1502 N=1490

Population n (%) n (%)

Received injection 1502 (100) 1490 (100)

Completed the studya 1482 (98.7) 1454 (97.6)

Discontinued from the study 20 (1.3) 36 (2.4)

Reason for discontinuation -- --

Adverse event 0 0

Death 3 (0.2) 1 (<0.1)

Lost to follow-up 10 (0.7) 25 (1.7)

Withdrawal of consent by participant 7 (0.5) 10 (0.7)

Median follow-up (days) (min, max) 171.0 (1, 207) 171.0 (1, 204)

Source: Adapted from STN 125869/0, mRNA-1010-P303 Part B and Part C Clinical Study Report, Table 14.1.1.1.2.c, Table 14.1.4.3.4.c.

Data cutoff: June 24, 2024.

Abbreviations: HD, high dose; max, maximum; min, minimum; N, number of participants in the Safety Set; n, number of participants in a

given subpopulation or category; QIV, quadrivalent influenza vaccine

a

Participants are considered completed the study if they completed the final visit on Day 181 (Month 6).

Demographics and Other Baseline Characteristics

Demographic and baseline characteristics of participants in the Safety Set are shown in Appendix C

Table 4. Characteristics were similar across the mRNA-1010 (QIV) and Fluzone HD (QIV) groups and

were comparable to those in the PPIS. The median age was 70 years (range: 64–93 years). The

majority of participants were 65 to <75 yoa; 22.1% were ≥75 years. Most participants were White

(82.7%) and female (57.8%). Over half (52.6%) had received a seasonal influenza vaccine in the prior

season.

High-risk comorbidities were present in 37.7% of mRNA-1010 (QIV) participants and 40.7% of

Fluzone HD (QIV) participants. Diabetes mellitus was the most prevalent condition in both groups

(20.4% and 24.1%, respectively). The overall prevalence of high-risk conditions in this study

population was lower than population-level estimates, which indicate that 93% of U.S. adults 65 yoa

and older have at least one high-risk condition (Watson et al., 2025). As in Study P304, this difference

in prevalence likely reflects differences in how high-risk conditions were defined as well as the

exclusion of certain high-risk participants (e.g., those who were immunocompromised or taking

immunosuppressive medications)..

The prevalence of obesity (BMI ≥30 kg/m²) in Study P303 Part C was higher than reported in the

general U.S. population (29.5% of U.S. adults ≥65 yoa), with regional variation noted in the Midwest

and South (America's Health Rankings, 2025). The proportion of participants who received an

influenza vaccine in the prior season (52.6%) was lower than the national estimate of 71.3% reported

by the CDC National Health Interview Survey (NCHS, 2024).

70

Appendix C Table 4. Demographic and Baseline Characteristics, Adults 65 Years of Age and Older,

Safety Set, Study P303 Part C

mRNA-1010 (QIV) Fluzone HD (QIV)

Characteristic N=1502 N=1490

Sex, n (%) -- --

Male 624 (41.5) 638 (42.8)

Female 878 (58.5) 852 (57.2)

Age, years -- --

Median age (min, max) 70.0 (65, 93) 70.0 (64, 93)

65 to <75 years of age 1176 (78.3) 1154 (77.4)

≥75 years of age 326 (21.7) 335 (22.5)

Race, n (%) -- --

African American/Black 224 (14.9) 235 (15.8)

American Indian or Alaska Native 4 (0.3) 9 (0.6)

Asian 10 (0.7) 10 (0.7)

Native Hawaiian or other Pacific Islander 2 (0.1) 0

White 1255 (83.6) 1220 (81.9)

Multiracial 2 (0.1) 6 (0.4)

Other 1 (<0.1) 4 (0.3)

Unknown 1 (<0.1) 4 (0.3)

Not reported 3 (0.2) 2 (0.1)

Ethnicity, n (%) -- --

Hispanic/Latino 450 (30.0) 454 (30.5)

Not Hispanic/Latino 1037 (69.0) 1021 (68.5)

Not reported 14 (0.9) 14 (0.9)

Unknown 1 (<0.1) 1 (<0.1)

Body mass index (kg/m2) -- --

Median (min, max) 28.90 (10.3, 61.9) 28.90 (7.6, 58.2)

<30 kg/m2 865 (57.6) 845 (56.7)

≥30 kg/m2 637 (42.4) 645 (43.3)

≥40 kg/m2 113 (7.5) 99 (6.6)

Influenza vaccine status, n (%) -- --

Received seasonal flu vaccine 787 (52.4) 787 (52.8)

Did not receive previous seasonal flu vaccine 715 (47.6) 703 (47.2)

High-risk condition* 567 (37.7) 607 (40.7)

Autoimmune/immune mediated disease 50 (3.3) 45 (3.0)

Blood disorders 3 (0.2) 4 (0.3)

Cardiac disorders 171 (11.4) 177 (11.9)

Diabetes mellitus 307 (20.4) 359 (24.1)

Hepatic disorders 22 (1.5) 28 (1.9)

Mental impairment disorders 0 (0) 2 (0.1)

Nervous system disorders 7 (0.5) 5 (0.3)

Pulmonary disorders 141 (9.4) 169 (11.3)

Renal disorders 20 (1.3) 22 (1.5)

No high-risk condition 935 (62.3) 883 (59.3)

Source: Adapted from STN 125869/0, mRNA-1010-P303 Part B and Part C Clinical Study Report, Table 14.1.4.1.3.c; Table 14.1.4.1.7.c;

and Table 14.1.2.2.5.c. Data cutoff: June 24, 2024.

Abbreviations: BMI, body mass index: (body weight in kilograms)/(height in meters)²; HD, high dose; max, maximum; min, minimum; N,

number of participants in safety set; n, number of participants in the safety set in the given subpopulation/category; QIV, quadrivalent

influenza vaccine

Baseline values for height, weight, and BMI were defined as the most recent nonmissing measurement (scheduled or unscheduled)

collected on or before the study injection.

Numbers were based on the actual vaccination group, and percentages were based on the number of participants in the Safety Set.

* Defined post hoc.

71

Analyses of Vaccine Effectiveness

Analysis of the Primary Objective

Analyses of the primary immunogenicity endpoints, as measured by HAI for vaccine-matched

influenza strains at Day 29 postvaccination, are shown in Appendix C Table 5 (GMTs and GMT

ratios) and Appendix C Table 6 (SCRs and SCR differences). Baseline GMTs were similar across

groups. Day 29 GMTs and SCRs were higher in the mRNA-1010 (QIV) group than in the Fluzone HD

(QIV) group for all four influenza strains.

Noninferiority of mRNA-1010 (QIV) compared with Fluzone HD (QIV) was demonstrated for all four

strains based on GMT ratio (LL of the 95% CI >0.667) and SCR difference (LL of the 95% CI >−10%).

Protocol-defined superiority was also demonstrated for all four strains based on GMT ratio (LL of the

97.5% CI >1) and SCR difference (LL of the 97.5% CI >0%).

Appendix C Table 5. Analyses of Primary Immunogenicity Endpoint of GMTs as Measured by HAI for

Vaccine-Matched Influenza Strains at Day 29 Postvaccination, Participants 65 Years of Age and Older,

PPIS, Study P303 Part C

GMT Ratio (mRNA-1010

mRNA-1010 (QIV) Fluzone HD (QIV) [QIV] / Fluzone HD

Endpoint N=1425 N=1409 [QIV])

GMT (95% CI) GMT (95% CI) (95% CI)

(97.5% CI)

1.3

168.3 125.7

Influenza A/H1N1 (1.3, 1.4)

(160.4, 176.7) (119.7, 131.9)

(1.2, 1.4)

1.2

137.9 113.8

Influenza A/H3N2 (1.1, 1.3)

(130.9, 145.4) (107.9, 120)

(1.1, 1.3)

1.3

242.1 193.7

Influenza B/Victoria (1.2, 1.3)

(232.9, 251.6) (186.3, 201.3)

(1.2, 1.3)

1.1

102.7 89.8

Influenza B/Yamagata (1.1, 1.2)

(99.2, 106.2) (86.8, 92.9)

(1.1, 1.2)

Source: Adapted from STN 125869/0, mRNA-1010 P303 Clinical Study Report, Table 14.2.1.1.c. Data cutoff: June 24, 2024.

Abbreviations: ANCOVA, analysis of covariance; CI, confidence interval; GMT, geometric mean titer; HAI, hemagglutination inhibition; HD,

high dose; LLOQ, lower limit of quantification; N, number of participants with nonmissing HAI data at corresponding visit; PPIS, per protocol

immunogenicity set; QIV, quadrivalent; ULOQ, upper limit of quantification

Antibody values reported as below the LLOQ are replaced by 0.5× LLOQ. Values greater than the ULOQ are converted to the ULOQ.

The log-transformed antibody levels are analyzed using an ANCOVA model with vaccination group as the fixed variable, log transformed

baseline HAI titers as a fixed covariate, adjusting for the randomization stratification factor: Influenza Vaccine Status Since September 2022

to 6 Months Ago (not received seasonal flu vaccine, received seasonal flu vaccine from non mRNA-1010-P302, and received seasonal flu

vaccine from mRNA-1010-P302).

The model based GMT and GMT ratio, and its corresponding 95% CI and/or 97.5% CI are obtained by transforming the least square mean

estimate and its CI back to the original scale for presentation.

72

Appendix C Table 6. Analyses of Primary Immunogenicity Endpoint of SCRs as Measured by HAI for

Vaccine-Matched Influenza Strains at Day 29 Postvaccination, Participants 65 Years of Age and Older,

PPIS, Study P303 Part C

Difference in SCR

mRNA-1010 (QIV) Fluzone HD (QIV) (mRNA-1010

Endpoint N=1425 N=1409 [QIV]−Fluzone HD [QIV])

SCR%a (95% CI) SCR%a (95% CI) (95% CI)b

(97.5%CI)c

13.4

49.7 36.3

Influenza A/H1N1 (9.8, 17)

(47.1, 52.3) (33.8, 38.8)

(9.3, 17.5)

8.6

56.4 47.8

Influenza A/H3N2 (4.9, 12.2)

(53.8, 59) (45.2, 50.5)

(4.4, 12.8)

9.7

29.8 20.2

Influenza B/Victoria (6.5, 12.8)

(27.5, 32.3) (18.1, 22.4)

(6, 13.3)

5.9

26.0 20.2

Influenza B/Yamagata (2.8, 8.9)

(23.8, 28.4) (18.1, 22.4)

(2.3, 9.4)

Source: Adapted from STN 125869/0, mRNA-1010 P303 Clinical Study Report, Table 14.2.1.1.c. Data cutoff: June 24, 2024

Abbreviations: CI, confidence interval; HAI, hemagglutination inhibition; HD, high dose; LLOQ, lower limit of quantification; N, number of

participants with nonmissing HAI data at baseline (Day 1) and the corresponding visit; PPIS, per protocol immunogenicity set; QIV,

quadrivalent influenza vaccine; SCR, seroconversion rate; ULOQ, upper limit of quantification

Antibody values reported as below the LLOQ are replaced by 0.5× LLOQ. Values greater than the ULOQ are converted to the ULOQ.

a

Rate of seroconversion is defined as the proportion of participants with either a baseline HAI titer <1:10 and a postbaseline titer ≥1:40 or a

baseline HAI titer ≥1:10 and a minimum 4-fold rise in postbaseline HAI antibody titer.

b

95% CI is calculated using the Clopper-Pearson method.

c

95% CI, 97.5% CI are calculated using the Miettinen-Nurminen (score) method.

Post Hoc Analysis of mRNA-1010 (QIV) and mRNA-1010 (TIV)

To support the use of immunogenicity data from the quadrivalent formulation (evaluated in Study

P303 Part C) for licensure of the trivalent formulation in adults 65 yoa and older, the Applicant

conducted a post hoc analysis comparing Day 29 HAI GMTs between the PPISs of Study P303 Part

C and Study P304, restricted to participants ≥65 yoa, shown in Appendix C Table 7.

Although this was a descriptive post hoc analysis, the LL of the 95% CI of the Day 29 HAI GMT ratio

(mRNA-1010 [QIV] / mRNA-1010 [TIV]) for each of the three shared strains was >0.667, which would

have met the conventional success criteria for noninferiority.

Appendix C Table 7. Supportive Post-hoc Analyses of Day 29 HAI Antibody Levels for Seasonal

Influenza Strains Comparing mRNA-1010 QIV (Study P303 Part C) and TIV (Study P304) in Adults ≥65

Years of Age (PPIS)

mRNA-1010 (QIV) mRNA-1010 (TIV) Model-based

Study P303 Part C Study P304 GMT Ratio

Model N=1425 N=586 (QIV

Influenza Subtype

Model-based GMT Model-based GMT / TIV)

(95% CI) (95% CI) (95% CI)

Model 1: ANCOVA 161.13 159.36 1.011

A/H1N1

with 6 PCA factors ( 153.80, 168.81) ( 148.08, 171.50) (0.926, 1.104)

Model 2: ANCOVA 160.96 159.77 1.007

A/H1N1

with 4 PCA factors ( 153.61, 168.67) (148.41, 171.99) (0.923, 1.100)

Model 1: ANCOVA 138.85 158.13 0.878

A/H3N2

with 6 PCA factors (132.12, 145.92) (146.26, 170.95) (0.800, 0.964)

73

Model 2: ANCOVA 138.83 158.19 0.878

A/H3N2

with 4 PCA factors (132.09, 145.91) (146.29, 171.04) (0.800, 0.963)

Model 1: ANCOVA 234.78 289.93 0.810

B/Victoria

with 6 PCA factors ( 225.85, 244.07) ( 272.69, 308.25) (0.753, 0.871)

Model 2: ANCOVA 234.58 290.55 0.807

B/Victoria

with 4 PCA factors (225.65, 243.87) (273.26, 308.94) (0.750, 0.869)

Source: Adapated Adapted from STN 125869/0, Amendment 32, Response to IR Database lock/data extraction dates: 22 Jul 2024 (P303

Part C) and 03 Jun 2025 (P304).

The ANCOVA model includes vaccine (mRNA-1010 QIV in P303C or mRNA-1010 TIV in P304) as a fixed factor, log-transformed baseline

HAI titer as a fixed covariate, adjusted for the selected top principal components from the PCA of the demographic and baseline

characteristics. Model 1 incorporates 6 PCA factors which explained 82% of the total variance and Model 2 incorporates 4 PCA factors

which explained 62% of the total variance.

This analysis has several limitations:

 Studies P303 Part C and P304 were conducted in different influenza seasons using

different WHO-recommended strains.

 Participants were not randomized between studies; although baseline demographics were

adjusted for, residual confounding may remain.

For Influenza A/H1N1, a GMT ratio of 1.0 indicates no meaningful difference between mRNA-1010

(QIV) and mRNA-1010 (TIV). For Influenza A/H3N2 and B/Victoria, mRNA-1010 (QIV) elicited slightly

lower antibody responses than mRNA-1010 (TIV) (point estimate and upper bound of the 95% CI

both <1.0), although the noninferiority threshold was met for both strains (data not shown). This

suggests that inclusion of B/Yamagata may have reduced immune responses to A/H3N2 and

B/Victoria in mRNA-1010 (QIV). Because this potential reduction biases results against mRNA-1010

(QIV) rather than the comparator, mRNA-1010 (TIV) would be expected to generate equal or higher

immune responses to these two strains compared with mRNA-1010 (QIV). Notwithstanding the

limitations of this analysis, FDA’s preliminary assessment is that mRNA-1010 (QIV) immunogenicity

data may be used to support the effectiveness of mRNA-1010 (TIV) in adults 65 yoa and older.

Subpopulation Immunogenicity Analyses

The Applicant conducted subgroup analyses for the primary immunogenicity endpoints. The

noninferiority criteria based on GMT ratio and SCR difference would have been met across all four

strains in every subgroup with a sufficient sample size for meaningful interpretation.

Analysis of the Secondary Immunogenicity Endpoint

Secondary immunogenicity results demonstrating superiority of mRNA-1010 (QIV) compared with

Fluzone HD (QIV) against vaccine-matched influenza A and B strains at Day 29 are shown in

Appendix C Table 5 and Table 6. The study met prespecified superiority criteria for all eight endpoints

(LL of the 97.5% CI >1 for GMT ratio and >0 for SCR difference for each strain).

Descriptive secondary endpoints showed that both the proportion of participants with HAI titer ≥1:40

and the GMFR from Baseline to Day 29 were higher in mRNA-1010 (QIV) recipients than in Fluzone

HD (QIV) recipients across all four influenza strains (Appendix C Table 8).

74

Appendix C Table 8. Analyses of Secondary Immunogenicity Endpoint of Anti-HA Antibody Titers ≥1:40

and GMFR at Day 29 for Vaccine-Matched Influenza Strains, Participants 65 Years of Age and Older,

PPIS, Study P303 Part C

mRNA-1010 Fluzone HD

(QIV) (QIV) mRNA-1010 Fluzone HD

N=1425 N=1409 (QIV) (QIV)

Titer ≥1:40 Titer ≥1:40 N=1425 N=1409

n (%)a n (%)a GMFR GMFR

Endpoint (95% CI) b

(95% CI)b (95% CI)c (95% CI)c

Influenza A/H1N1 1375 (96.5) 1301 (92.3) 3.5 (3.3, 3.7) 2.6 (2.5, 2.7)

(95.4, 97.4) (90.8, 93.7)

Influenza A/H3N2 1323 (92.8) 1252 (88.9) 4.1 (3.9, 4.4) 3.4 (3.2, 3.6)

(91.4, 94.1) (87.1, 90.5)

Influenza B/Victoria 1425 (100) 1402 (99.5) 2.4 (2.3, 2.5) 1.9 (1.8, 1.9)

(99.7, 100) (98.9, 99.8)

Influenza B/Yamagata 1370 (96.1) 1320 (93.7) 2.2 (2.1, 2.3) 1.9 (1.9, 2)

(95, 97.1) (92.3, 94.9)

Source: Adapted from STN 125869/0, mRNA-1010 P303 Clinical Study Report, Table 14.2.2.1.c. Data cutoff: June 24, 2024.

Abbreviations: CI, confidence interval; GMFR, geometric mean of fold rise; HA, hemagglutinin; HD, high dose; LLOQ, lower limit of

quantification; N, number of participants with nonmissing HAI data at baseline (Day 1) and the corresponding visit; PPIS, per-protocol

Immunogenicity Set; QIV, quadrivalent; ULOQ, upper limit of quantification

Antibody values reported as below the LLOQ are replaced by 0.5× LLOQ. Values greater than the ULOQ are converted to the ULOQ.

a

Number of participants meeting the criterion at the corresponding visit. Percentage is based on N.

b

95% CI is calculated using the Clopper-Pearson method

Exploratory Immunogenicity Objectives

GMT and SCR at EOS/Day 181

Appendix C Table 9 shows GMTs measured by HAI at EOS/Day 181 in participants with Day 181

data. GMTs remained higher in the mRNA-1010 (QIV) group compared with the Fluzone HD (QIV)

group for all four influenza strains, although confidence intervals overlapped for all strains except

A/H3N2.

Appendix C Table 9. Analysis of GMTs as Measured by HAI for Vaccine-Matched Influenza Strains at

EOS/Day 181, Participants 65 Years of Age and Older, PPIS, Study P303 Part C

GMT Ratio (mRNA-

mRNA-1010 (QIV) Fluzone HD (QIV) 240 μg 1010 [QIV] / Fluzone

N=462 N=459 HD [QIV])

Strain GMT (95% CI)a GMT (95% CI)a (95% CI)b

Influenza A/H1N1 78.2 (72.1, 84.8) 68.3 (62.9, 74.1) 1.1 (1.0, 1.3)

Influenza A/H3N2 65.8 (60.4, 71.9) 54.7 (50.2, 59.6) 1.2 (1.1, 1.4)

Influenza B/Victoria 132.8 (124.7, 141.5) 122.8 (115.3, 130.9) 1.1 (0.9, 1.2)

Influenza B/Yamagata 55.9 (52.6, 59.5) 53.9 (50.7, 57.3) 1.0 (0.9, 1.1)

Source: Adapted from STN 125869/0, mRNA-1010 P303 Clinical Study Report, Table 14.2.2.9.c., from Amendment 55 Response to IR #43

dated May 15, 2026. Data cutoff: June 24, 2024.

Abbreviations: ANCOVA, analysis of covariance; CI, confidence interval; EOS, end of study; GMT, geometric mean titer;

HAI, hemagglutination inhibition; HD, high dose; IR, information request; LLOQ, lower limit of quantification; PPIS, per-protocol

immunogenicity set; QIV, quadrivalent influenza vaccine; ULOQ, upper limit of quantification

Antibody values reported as below the LLOQ are replaced by 0.5× LLOQ. Values greater than the ULOQ are converted to the ULOQ.

a

The log-transformed antibody levels are analyzed using an ANCOVA model with vaccination group as the fixed variable, log transformed

baseline HAI titers as a fixed covariate, adjusting for the randomization stratification factor: Influenza Vaccine

Appendix C Table 10 shows the percentage of participants with seroconversion at EOS/Day 181. The

proportion of participants with seroconversion was higher in the mRNA-1010 (QIV) group than in the

Fluzone HD (QIV) group for all four strains, although confidence intervals overlapped for all strains

except A/H1N1.

75

Appendix C Table 10. Analysis of SCR as Measured by HAI for Vaccine-Matched Influenza Strains at

EOS/Day 181, Participants 65 Years of Age and Older, PPIS, Study P303 Part C

Difference in SCR

mRNA-1010 (QIV) Fluzone HD (QIV) (mRNA 1010 [QIV] −

N=462 N=459 Fluzone HD [QIV])

Strain SCR%a (95% CI)b SCR%a (95% CI)b (95% CI)c

Influenza A/H1N1 28.6 (24.5, 32.9) 19.4 (15.9, 23.3) 9.2 (3.7, 14.7)

Influenza A/H3N2 31.4 (27.2, 35.8) 23.3 (19.5, 27.5) 8.1 (2.3, 13.8)

Influenza B/Victoria 12.1 (9.3, 15.5) 9.4 (6.9, 12.4) 2.8 (-1.3, 6.8)

Influenza B/Yamagata 9.1 (6.6, 12.1) 7.8 (5.5, 10.7) 1.3 (-2.4, 4.9)

Source: Adapted from STN 125869/0, mRNA-1010 P303 Clinical Study Report, Table 14.2.2.1.c. Data cutoff: June 24, 2024.

Abbreviations: CI, confidence interval; EOS, end of study; HAI, hemagglutination inhibition; HD, high dose; PPIS, per protocol

immunogenicity set; QIV, quadrivalent influenza vaccine; SCR, seroconversion rate

a

Rate of seroconversion is defined as the percentage of participants with either a baseline HAI titer <1:10 and a postbaseline titer ≥1:40 or

a baseline HAI titer ≥1:10 and a minimum 4-fold rise in postbaseline HAI antibody titer.

b

95% CI is calculated using the Clopper-Pearson method.

c

95% CI is calculated using the Miettinen-Nurminen (score) method.

Anti-HA Antibody Titers ≥1:40 and GMFRs at EOS/Day 181

At Day 181, the percentage of participants with HAI titers ≥1:40 was slightly higher in the mRNA-1010

(QIV) group than in the Fluzone HD (QIV) group for Influenza A/H1N1 (84.9% vs. 79.1%), A/H3N2

(75.3% vs. 69.9%), and B/Yamagata (83.2% vs. 80.4%), and similar for B/Victoria (98.7% vs. 99.3%);

95% CIs overlapped between groups for all four strains. GMFR from Baseline to Day 181 was higher

in the mRNA-1010 (QIV) group for both influenza A strains and similar between groups for both

influenza B strains.

MN Titers at Day 29

Day 29 MN titers were evaluated in 250 participants per vaccination group in the PPIS MN Subset.

Day 29 GMT levels and GMFRs from Baseline were higher in the mRNA-1010 (QIV) group than in

the Fluzone HD (QIV) group for all four influenza strains. For A/H1N1, 95% CIs did not overlap; for

A/H3N2 and both influenza B strains, 95% CIs overlapped. Subgroup analyses of MN data showed

GMT ratios were similar across subgroups by age and prior influenza vaccine status. MN titers were

positively correlated with HAI titers for each influenza strain.

Safety Analyses

The Safety Set included 2,993 participants: 1,502 in the mRNA-1010 (QIV) group and 1,490 in the

Fluzone HD (QIV) group. The median duration of safety follow-up was 171 days in both groups

(database lock: July 22, 2024).

Overview of Adverse Events

Appendix C Table 11 summarizes the rates of solicited ARs and unsolicited AEs. Solicited AR rates

through Day 7 were higher in the mRNA-1010 (QIV) group than in the Fluzone HD (QIV) group. Rates

of unsolicited AEs through Day 28, and MAAEs, SAEs, and AESIs through study completion, were

similar between groups.

76

Appendix C Table 11. Number and Percentage of Participants 65 Years of Age and Older Reporting at

Least One Safety Event, Safety Set and Solicited Safety Set, Study P303 Part C

mRNA-1010 (QIV) Fluzone HD (QIV)

Event Type % (n/N1) % (n/N1)

Solicited adverse reactions within 7 days -- --

Any solicited adverse reaction 75.3 (1131/1502) 49.3 (734/1490)

Solicited local adverse reactiona 66.1 (993/1502) 38.9 (580/1490)

Grade 3 or above solicited local adverse reaction 2.4 (36/1502) 0.8 (12/1490)

Solicited systemic adverse reactionb 61.3 (920/1502) 32.9 (490/1489)

Grade 3 or above solicited systemic adverse reaction 6.9 (103/1502) 1.7 (25/1489)

Unsolicited adverse events -- --

Unsolicited adverse event through 28 days after vaccination 10.3 (155/1502) 9.2 (137/1490)

Nonserious unsolicited adverse eventc 9.9 (149/1502) 9.1 (135/1490)

Severe nonserious unsolicited AE <0.1 (1/1502) 0

Medically attended adverse events throughout the study 17.1 (257/1502) 16.6 (248/1490)

Related MAAEd 0.3 (4/1502) <0.1 (1/1490)

SAE throughout the study 2.7 (41/1502) 2.6 (38/1490)

Related SAEd 0 <0.1 (1/1490)

AESI throughout the study 0.1 (2/1502) <0.1 (1/1490)

Related AESId <0.1 (1/1502) 0

Deaths throughout the study 0.2 (3/1502) <0.1 (1/1490)

Related deathsd 0 0

AE leading to study discontinuation throughout the study 0 0

Source: Adapted from STN 125869/0, mRNA-1010-P303 Part B and Part C Clinical Study Report, Table 14.3.1.2.1.c and Table

14.3.2.1.1.c. Data cutoff: June 24, 2024.

Abbreviations: AE, adverse event; AESI, adverse event of special interest; AR, adverse reaction; MAAE, medically attended adverse event;

n, number of exposed participants who reported the event; N1, number of exposed participants who submitted any data for the event; SAE,

serious adverse event

Any solicited local or systemic adverse reactions that meet the definition of an SAE are considered as AE.

Numbers are based on actual vaccination group and percentages are based on the number of participants in the Safety Set.

a

Solicited local reactions included pain, erythema (redness), swelling (hardness), axillary swelling or tenderness.

b

Solicited systemic reactions included fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, chills.

c

Participants with at least one nonserious AE that was also severe/≥grade 3.

d

The event was considered related to study vaccination by the investigator.

Solicited Adverse Reactions

Solicited ARs were generally higher in the mRNA-1010 (QIV) group than in the Fluzone HD (QIV)

group, consistent with findings from Study P304. The rates and severity of solicited ARs among

mRNA-1010 (QIV) recipients in Study P303 Part C were comparable to those among mRNA-1010

(TIV) recipients in the same age subgroup in Study P304.

Solicited Local Adverse Reactions

Appendix C Table 12 shows the percentages of participants reporting solicited local ARs, by

maximum severity. Solicited local ARs were reported by 66.1% of mRNA-1010 (QIV) recipients and

38.9% of Fluzone HD (QIV) recipients. The most frequently reported local AR was injection site pain

(64.6% vs. 36.7%). The majority of local ARs were Grade 1 or 2. Grade 3 ARs were reported in 2.4%

of mRNA-1010 (QIV) recipients versus 0.8% of Fluzone HD (QIV) recipients. No Grade 4 solicited

local ARs were reported in either group.

The median onset of solicited local ARs was Day 2 postvaccination in the mRNA-1010 (QIV) group

and Day 1 in the Fluzone HD (QIV) group. Median duration was 2 days in both groups. A higher

77

percentage of solicited local ARs persisted beyond 7 days in the mRNA-1010 (QIV) group (1.2%)

compared with the Fluzone HD (QIV) group (0.5%).

Appendix C Table 12. Summary of Participants with Solicited Local ARs Within 7 Days After Injection by

Toxicity Grade, 65 Years of Age and Older, Solicited Safety Set, Study P303 Part C

mRNA-1010 (QIV) Fluzone HD (QIV)

Solicited Adverse Reaction Category, N1=1502 N1=1490

Grade % (n) % (n)

Any solicited local adverse reaction -- --

Any 66.1 (993) 38.9 (580)

Grade 3 2.4 (36) 0.8 (12)

Injection site paina -- --

Any 64.6 (971) 36.7 (547)

Grade 3 1.5 (23) 0.4 (6)

Erythema (redness)b -- --

Any 2.8 (42) 1.3 (20)

Grade 3 0.4 (6) 0.2 (3)

Swelling (hardness)b -- --

Any 4.5 (67) 1.7 (25)

Grade 3 0.4 (6) 0.1 (2)

Axillary swelling or tendernessa -- --

Any 16.8 (252) 8.6 (128)

Grade 3 0.5 (8) 0.4 (6)

Source: Adapted from STN 125869/0, mRNA-1010-P303 Part B and Part C Clinical Study Report, Table 14.3.1.2.1.c. Data cutoff: June 24,

2024.

Abbreviations: Any, Grade 1 or higher; AR, adverse reaction; CI, confidence interval; G, grade; n, number of exposed participants who

reported the event on any day within 7 days of study injection; N1, number of exposed participants in the Solicited Safety Subset; QIV,

quadrivalent influenza vaccine

There were no Grade 4 solicited local ARs reported in either group.

The toxicity grade is the maximum toxicity grade reported on any day from Baseline. Assessments by investigator are used in analysis if

occurred on the same day as participant's assessments.

a

Toxicity grade for injection site pain, axillary swelling or tenderness ipsilateral to the side of injection are defined as: G1=no interference

with activity; G2=some interference with activity; G3=prevent daily activity; G4=requires emergency room visit or hospitalization.

b

Toxicity grade for injection site erythema (redness) or injection site swelling/induration (hardness) are defined as: G1=25-50 mm; G2=51-

100 mm; G3≥100 mm; G4=necrosis (injection site erythema) or exfoliative dermatitis (injection site swelling/induration).

Numbers were based on actual group and percentages were based on the number of exposed participants who submitted any data for the

event(s).

Solicited Systemic Adverse Reactions

Appendix C Table 13 shows the percentages of participants reporting solicited systemic ARs, by

maximum severity. Solicited systemic ARs were reported by 61.3% of mRNA-1010 (QIV) recipients

and 32.9% of Fluzone HD (QIV) recipients. The most frequently reported systemic ARs among

mRNA-1010 (QIV) recipients were fatigue (44.5%), myalgia (41.7%), and headache (39.4%). The

majority of systemic ARs were Grade 1 or 2. Grade 3 ARs were reported in 6.7% of mRNA-1010

(QIV) recipients versus 1.7% of Fluzone HD (QIV) recipients. Two Grade 4 solicited systemic ARs of

fever were reported in the mRNA-1010 (QIV) group: one participant with a fever of 104.9°F on Day 2

and one participant with a fever of 105°F on Day 3. Neither participant sought medical attention for

these events.

The median day of onset for solicited systemic ARs was Day 2 postvaccination in both groups.

Median duration was 1 day in both groups. A higher percentage of systemic ARs persisted beyond 7

days in the mRNA-1010 (QIV) group (1.7%) compared with the Fluzone HD (QIV) group (1.1%).

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Appendix C Table 13. Summary of Participants with Solicited Systemic ARs Within 7 Days After

Injection by Toxicity Grade, 65 Years of Age and Older, Solicited Safety Set, Study P303 Part C

mRNA-1010 (QIV) Fluzone HD (QIV)

Solicited Adverse Reaction, N1=1502 N1=1490

Category, Grade % (n) % (n)

Solicited systemic adverse reactions* -- --

Any 61.3 (920) 32.9 (490)

Grade 3 6.7 (101) 1.7 (25)

Grade 4 0.1 (2) 0

Fevera -- --

Any 8.5 (127) 1.4 (21)

Grade 3 0.6 (9) <0.1 (1)

Grade 4 0.1 (2) 0

Headacheb -- --

Any 39.4 (592) 17.3 (258)

Grade 3 2.3 (35) 0.7 (10)

Fatigueb -- --

Any 44.5 (669) 19.7 (293)

Grade 3 3.5 (52) 0.8 (12)

Myalgiab -- --

Any 41.7 (626) 16.1 (239)

Grade 3 3.2 (48) 0.7 (11)

Arthralgiab -- --

Any 35.2 (528) 14.1 (210)

Grade 3 2.3 (35) 0.7 (11)

Nausea/vomitingc -- --

Any 12.8 (192) 4.2 (63)

Grade 3 0.3 (4) 0.2 (3)

Chillsb -- --

Any 29.5 (443) 7.7 (115)

Grade 3 1.2 (18) 0.3 (5)

Source: Adapted from STN 125869/0, mRNA-1010-P303 Part B and Part C Clinical Study Report, Table 14.3.1.2.1.c. Data cutoff: June 24,

2024.

Abbreviations: Any, Grade 1 or higher; AR, adverse reaction; CI, confidence interval; G, grade; N1, number of exposed participants in the

Solicited Safety Subset; n, number of exposed participants who reported the event; QIV, quadrivalent influenza vaccine

* Absence of rows for Grade 4 reactions means no Grade 4 reactions were reported.

Numbers were based on actual group and percentages were based on the number of exposed participants who submitted any data for the

event(s).

95% CI was calculated using the Clopper-Pearson method.

a

Toxicity grade for fever (oral) is defined as: G1=38.0-38.4°C or 100.4-101.1°F; G2=38.5-38.9°C or 101.2-102.0°F; G3=39.0-40.0°C or

102.1-104.0°F; G4: ≥40.0°C or >104.0°F.

b

Toxicity grade for headache, fatigue, myalgia (muscle aches all over body), arthralgia (joint aches in several joints), and chills are defined

as: G1=no interference with activity; G2=some interference with activity; G3=prevent daily activity; G4=requires emergency room visit or

hospitalization.

c

Toxicity grade for nausea/vomiting are defined as: G1=no interference with activity or 1-2 episodes/24 hours; G2=some interference with

activity or >2 episodes/24 hours; G3=prevent daily activity or requires outpatient intravenous hydration; G4=requires emergency room visit

or hospitalization for hypotensive shock.

Unsolicited Adverse Events

Unsolicited Adverse Events Through 28 Days After Vaccination

The percentages of participants with unsolicited AEs within 28 days postvaccination were balanced

between groups: 10.3% in the mRNA-1010 (QIV) group and 9.2% in the Fluzone HD (QIV) group. By

MedDRA System Organ Class (SOC), unsolicited AEs were most frequently reported under infections

and infestations (4.5% vs. 4.4%) and musculoskeletal and connective tissue disorders (1.1% vs.

1.2%). Unsolicited AEs assessed as related to study vaccination by the investigator were reported in

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0.5% of mRNA-1010 (QIV) recipients and 0.2% of Fluzone HD (QIV) recipients; this difference was

largely attributable to nonserious AEs related to vaccine reactogenicity. Rates of unsolicited AEs were

generally similar across subgroups by age, sex, and race.

Medically Attended Adverse Events

Through 28 days postvaccination, MAAEs were reported by 5.9% of mRNA-1010 (QIV) recipients and

5.6% of Fluzone HD (QIV) recipients. Through study completion, MAAEs were reported by similar

proportions in each group (17.1% vs. 16.6%). MAAEs were most frequently reported under the

MedDRA SOC of infections and infestations (6.4% vs. 7.8%). MAAEs assessed as related to study

vaccination were more common in the mRNA-1010 (QIV) group (0.3%, n=4) than in the Fluzone HD

(QIV) group (<0.1%, n=1).

The four MAAEs assessed as related to mRNA-1010 (QIV) by the investigator were:

 An 80-year-old female with cough onset on the evening of the injection (Day 1), which

resolved the following afternoon.

 A 72-year-old female with injection site pruritus on Study Day 4.

 A 67-year-old female with a medical history of seasonal allergies, obesity, iron deficiency, and

vitamin D deficiency (concomitant use of phentermine/topiramate) who experienced chest

discomfort on Day 2 that resolved within 1 hour. Concurrently, she reported dizziness

(described as 'lightheadedness – orthostatic – intermittent') also with onset and resolution on

Day 2, which the investigator assessed as unrelated to study injection. No additional

evaluation or treatment was reported for either event.

 A 72-year-old female with face swelling on Study Day 2. This event was also classified as an

AESI and is discussed further in the Adverse Events of Special Interest section below.

Based on the temporal association with study vaccination and the absence of a clear alternative

etiology, FDA considers it plausible that the study vaccine contributed to these events. Because the

majority were mild to moderate in severity and resolved promptly without intervention, these events

are not considered to represent clinically meaningful safety concerns.

Deaths

Within 28 days of vaccination, one death was reported in the mRNA-1010 (QIV) group (<0.1%) and

none in the Fluzone HD (QIV) group. Through study completion (median follow-up approximately 6

months), three deaths (0.2%) were reported in the mRNA-1010 (QIV) group and one death (<0.1%) in

the Fluzone HD (QIV) group. All four participants had extensive underlying medical conditions. None

of the deaths in either group were assessed as related to study vaccination by the investigator. Based

on independent review of event narratives, FDA agrees that these deaths were unlikely to be related

to the study vaccine.

Serious Adverse Events (SAEs)

SAEs within 28 days of vaccination were reported in 0.6% (n=9) of mRNA-1010 (QIV) recipients and

0.5% (n=7) of Fluzone HD (QIV) recipients. Through study completion, 2.7% of mRNA-1010 (QIV)

recipients and 2.6% of Fluzone HD (QIV) recipients reported SAEs. SAEs were most commonly

reported under the SOC of infections and infestations (0.7% vs. 0.5%). No SAEs were assessed as

related to mRNA-1010 (QIV) by the investigator or by FDA.

Adverse Events of Special Interest (AESIs)

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Protocol-defined AESIs are listed in Appendix A. Through 28 days after vaccination, one AESI

(<0.1%) was reported in the mRNA-1010 (QIV) group and none in the Fluzone HD (QIV) group.

Through study completion, two AESIs were reported in the mRNA-1010 (QIV) group and one in the

Fluzone HD (QIV) group.

One AESI in the mRNA-1010 (QIV) group was a partial seizure occurring on Day 51, which the

investigator assessed as unrelated to study vaccine. The second AESI was an event of face swelling

(also classified as an MAAE), which the investigator assessed as related to the study vaccine. This

event is described below.

Swelling face: A 72-year-old female with a history of asthma, coronary artery disease, and obesity

experienced face swelling on Study Day 2. She was evaluated in the emergency department and

treated with prednisone and diphenhydramine; the event resolved by Day 10. She denied any other

concurrent symptoms, and no additional unsolicited AEs were reported around this time. The

Applicant, in agreement with the investigator, assessed this event as related to the study vaccine.

FDA agrees that this event of face swelling is possibly related to the vaccine, given the temporal

relationship to vaccination and the absence of alternative etiologies.

Pregnancies

No pregnancies were reported in either group.

Dropouts and/or Discontinuations

Aside from study discontinuations due to death (discussed in the Deaths section above), no additional

discontinuations due to adverse events were reported in either group.

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Appendix D – Integrated Overview of Safety

Safety Assessment Methods

The Applicant conducted an Integrated Summary of Safety (ISS) to provide a cross-study evaluation

of the safety profile of mRNA-1010 in adults 50 yoa and older. The ISS pooled safety data from all

four Phase 3 studies (P301, P302, P303, and P304) in participants 50 yoa and older, with analyses

focused on serious adverse events (SAEs), adverse events of special interest (AESIs), and deaths.

The pooled mRNA-1010 group (trivalent [TIV] and quadrivalent [QIV] formulations), referred to

hereafter as 'mRNA-1010,' was compared with pooled standard-dose and high-dose comparator

vaccines (Fluarix [TIV and QIV]; Fluzone HD [QIV]), referred to hereafter as 'SD/HD comparator.'

The Applicant also conducted a focused safety meta-analysis evaluating two specific neurological

AESIs — Bell's palsy and Guillain-Barré syndrome (GBS) — both of which have been inconsistently

associated with licensed influenza vaccines.

Safety Database

The ISS Set included all randomized participants 50 yoa and older who received at least one study

injection across the four Phase 3 studies. Participants who enrolled in more than one study were

counted separately in each study using unique participant identifiers, as their injections were

administered at least 10 months apart.

Studies Contributing to the ISS

Brief descriptions of the four Phase 3 studies contributing to the ISS analyses are presented in

Appendix A. Because of small individual sample sizes, all three parts of Study P303 were combined

and analyzed as a single study for ISS purposes.

Overall Exposure and Demographics of the Pooled Safety Population

The ISS analysis included 35,965 participants exposed to mRNA-1010 and 35,951 participants

exposed to SD/HD comparator. Median follow-up was 198 days in both groups (range: 1–449 days in

the mRNA-1010 group; 1–445 days in the SD/HD comparator group). Study completion rates were

high and comparable: 95.1% in the mRNA-1010 group and 95.2% in the SD/HD comparator group.

Demographic characteristics were well balanced between groups. Median age was 64.0 years in both

groups (range: 50–99 years in the mRNA-1010 group; 50–96 years in the SD/HD comparator group).

Among mRNA-1010 recipients, 51.2% were 50–64 yoa, 37.5% were 65–74 yoa, and 11.4% were ≥75

yoa. In both groups, the majority of participants were female (56.5% mRNA-1010; 56.9% SD/HD

comparator), White (79.4% vs. 79.0%), non-Hispanic or non-Latino (82.9% vs. 83.2%), and had not

received an influenza vaccine in the prior season (55.8% vs. 56.0%). Most participants were enrolled

from North America (74.1% in both groups).

Categorization of Adverse Events

Adverse events in the ISS were summarized by System Organ Class (SOC) and Preferred Term (PT)

using MedDRA version 25.0 across all four studies. Participants with multiple occurrences of the

same adverse event were counted once per event category.

Caveats Introduced by Pooling Data Across Studies

The following caveats should be considered when interpreting the pooled ISS data:

• Formulation differences: Studies P301, P302, and P303 used a quadrivalent formulation;

Study P304 used a trivalent formulation. Studies P301 and P302 used the original mRNA-

1010 formulation; Studies P303 and P304 used the optimized formulation with a modified B

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antigen. This heterogeneity may introduce variability in the safety profile not fully captured by

pooled analyses.

• Comparator differences: Comparator vaccines varied across studies (standard-dose and high-

dose; TIV and QIV formulations), which may affect the interpretation of between-group

comparisons.

• Follow-up duration: Follow-up ranged from approximately 6 months in Studies P303 and P304

to approximately 12 months in Studies P301 and P302, which may influence the detection of

late-onset adverse events.

• Population heterogeneity: Geographic and demographic differences across study sites may

contribute to variation in background rates of adverse events.

Integrated Safety Results

Appendix D.1. Deaths

Within 28 days of vaccination, deaths were reported in 13 of 35,965 participants (<0.1%) in the

mRNA-1010 group and 14 of 35,951 participants (<0.1%) in the SD/HD comparator group. Over the

full study period, deaths were reported in 102 participants (0.3%) in the mRNA-1010 group and 97

participants (0.3%) in the SD/HD comparator group. In both groups, death was most commonly

reported under the MedDRA SOC of cardiac disorders: 24 participants (<0.1%) in the mRNA-1010

group and 30 participants (<0.1%) in the SD/HD comparator group.

By PT, deaths occurring in more than 4 participants in either group included: death (unspecified) (23

vs. 9), myocardial infarction (7 vs. 7), cardiac arrest (6 vs. 6), cerebrovascular accident (4 vs. 5), and

pneumonia (2 vs. 5) in the mRNA-1010 and SD/HD comparator groups, respectively.

To further evaluate the numerical imbalance in the PT of death (unspecified), SAEs coded to the PTs

of death, sudden death, and sudden cardiac death were pooled for analysis. This combined analysis

identified 29 participants in the mRNA-1010 group and 12 in the SD/HD comparator group with

unspecified fatal events. Median time to onset was approximately 131 days (range: 2–319 days) in

the mRNA-1010 group and 87 days (range: 9–343 days) in the SD/HD comparator group; most

events occurred well beyond the acute postvaccination period. Deaths within 28 days of vaccination

under these three PTs were few and similar across groups (3 in the mRNA-1010 group; 2 in the

SD/HD comparator group).

Approximately 60% of participants with unspecified fatal events were ≥65 yoa, and nearly all had

multiple pre-existing comorbidities, including hypertension, diabetes mellitus, chronic kidney disease,

hyperlipidemia, coronary artery disease, atrial fibrillation, prior myocardial infarction, congestive heart

failure, and chronic obstructive pulmonary disease (COPD). Causes of death were predominantly

recorded as unknown or natural causes. No autopsies were conducted in the 29 mRNA-1010 group

deaths; one autopsy in the SD/HD comparator group yielded no reported findings.

One death in the mRNA-1010 group — occurring on Day 2 in Study P303 Part A — was assessed as

related to the study vaccine by the Investigator based on temporality and is described below. No

other deaths in either group were assessed as vaccine-related.

Case Description: Death on Day 2 (Study P303 Part A)

A 76-year-old female with a history of coronary artery disease (prior coronary artery bypass graft

[CABG] following myocardial infarction), atrial fibrillation, and type 2 diabetes mellitus was found

unresponsive at home and confirmed deceased on Study Day 2 (PT: death). She reported no

solicited adverse reactions on Study Day 1. Although solicited adverse reactions were not

documented for Study Day 2, she reportedly told a friend that she felt unwell, tired, and nauseous

earlier that day. Her most recent cardiology evaluation documented stable functional status with

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mild exertional symptoms, sinus bradycardia with atrial fibrillation, and an incomplete right bundle

branch block on ECG. No autopsy was performed; the death certificate attributed death to natural

causes. The Applicant assessed this event as unrelated to the study vaccine.

FDA Assessment: Although the temporal relationship to study vaccination is notable and a

contribution from a vaccine-related inflammatory response cannot be excluded, the participant's

significant cardiac history — including prior myocardial infarction requiring CABG and atrial

fibrillation — represents a more plausible alternative etiology. The numerical imbalance in

unspecified deaths between the mRNA-1010 and SD/HD comparator groups was evaluated in

the context of the totality of available evidence. Most of these deaths occurred in older

participants with substantial underlying comorbidities, a population with elevated background

mortality. The temporal distribution of events does not suggest a causal relationship to

vaccination, and deaths of unspecified cause within 28 days of vaccination were few and similar

across groups. The observed imbalance is not considered to represent a safety signal for mRNA-

1010.

Appendix D.2. Serious Adverse Events (SAEs)

Within the first 28 days postvaccination, SAEs were reported by comparable proportions of

participants: 0.5% (n=180) in the mRNA-1010 group and 0.5% (n=163) in the SD/HD comparator

group. SAEs were most frequently reported under the SOC of infections and infestations (45 mRNA-

1010 recipients vs. 34 SD/HD comparator recipients). The most frequent SAEs by PT were

pneumonia (8 vs. 5) and acute myocardial infarction (4 vs. 6) in the mRNA-1010 and SD/HD

comparator groups, respectively.

Over the full study periods, SAEs were reported in 3.1% of the mRNA-1010 group and 2.9% of the

SD/HD comparator group. The most frequently reported SAEs were in the SOC of infections and

infestations (0.7% vs. 0.6%). By PT, the most frequently reported SAEs were pneumonia (36 vs. 32),

COPD (35 vs. 24), and cerebrovascular accident (32 vs. 29) in the mRNA-1010 and SD/HD

comparator groups, respectively.

For SAEs occurring in at least four participants in each group, risk differences (RDs) with 95%

confidence intervals (CIs) were calculated. Six PTs had 95% CIs that excluded zero:

• Higher in the mRNA-1010 group: anemia (9 vs. 2; RD: 0.02 [95% CI: >0, 0.04]); urinary tract

infection (UTI) (25 vs. 12; RD: 0.04 [95% CI: >0, 0.07]); and death (unspecified) (23 vs. 9; RD:

0.04 [95% CI: 0.01, 0.07]).

• Higher in the SD/HD comparator group: chronic kidney disease (0 vs. 4), urinary retention (0 vs.

4), and hypertensive emergency (0 vs. 4).

The imbalance in deaths is reviewed in in Appendix D1. The anemia and UTI imbalances are

reviewed below.

Anemia

A comprehensive review encompassing the additional PTs of anemia of chronic disease, blood

loss anemia, hypochromic anemia, iron deficiency anemia, and normocytic anemia identified 14

participants in the mRNA-1010 group and 8 in the SD/HD comparator group. None were

assessed as vaccine-related by the Investigator. Most events occurred more than 90 days after

injection, with no temporal clustering. All participants in the mRNA-1010 group had plausible

alternative etiologies, including iron deficiency, gastrointestinal bleeding, kidney or liver disease,

serious infection, and concomitant medication use. A review of medically attended adverse

events (MAAEs) of anemia in Study P304 identified a similar incidence between groups (31 in the

mRNA-1010 [TIV] group vs. 30 in the SD comparator group). These data suggest that the

numerical imbalance in SAEs of anemia is unlikely to reflect a causal association with mRNA-

1010.

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Urinary Tract Infection (UTI)

A comprehensive review encompassing the additional PTs of urinary tract infection bacterial,

Escherichia urinary tract infection, cystitis, kidney infection, pyelonephritis, acute pyelonephritis,

and urosepsis identified 38 participants in the mRNA-1010 group and 22 in the SD/HD

comparator group. None were assessed as vaccine-related by the Investigator. There was no

temporal clustering; median time to onset was 135 days in the mRNA-1010 group and 112.5

days in the SD/HD comparator group. The majority of participants in both groups had identifiable

risk factors, including advanced age, female sex, postmenopausal status, diabetes mellitus,

obstructive uropathies, chronic kidney disease, and use of concomitant medications known to

increase UTI risk. A review of MAAEs of UTI in Study P304 identified a similar incidence between

groups (153 in the mRNA-1010 [TIV] group vs. 158 in the SD comparator group). These data

suggest that the numerical imbalance in SAEs of UTI is unlikely to reflect a causal association

with mRNA-1010.

Investigator-Assessed Vaccine-Related SAEs

SAEs assessed as related to study vaccine by the Investigator were reported by 9 participants

(<0.1%) with 11 events in the mRNA-1010 group and 3 participants (<0.1%) with 3 events in the

SD/HD comparator group. Of the nine participants in the mRNA-1010 group, four were from Study

P304 and are discussed in Appendix B SAEs Assessed as Vaccine-Related by the Investigator. The

remaining five participants are described below.

Study P301 (mRNA-1010 [Original, QIV])

Acute coronary syndrome: A 53-year-old male current smoker with a history of obesity

developed retrosternal chest pain on Day 3 and was subsequently hospitalized with a diagnosis

of acute coronary syndrome. ECG showed ST-segment elevation; coronary angiography

revealed mild stenoses and coronary artery spasms. Echocardiogram showed no wall motion

abnormalities and a normal ejection fraction. The event resolved on Day 6. The Applicant

assessed the event as unrelated to the study vaccine.

FDA Assessment: Although the temporal relationship to vaccination is notable and a vaccine

contribution cannot be excluded, the participant's smoking history and obesity are significant

risk factors for coronary artery disease, and the angiographic finding of stenosis is more

consistent with a pre-existing condition, providing more plausible alternative etiologies.

Study P302 (mRNA-1010 [Original, QIV])

Angioedema: A 78-year-old female with a history of angioedema developed facial swelling on

Study Day 5, which she described as less severe than her typical episodes. She self-treated with

diphenhydramine and intramuscular (IM) epinephrine, and the event resolved the same day. The

Applicant assessed the event as unrelated to the study vaccine.

FDA Assessment: Although the participant's history of angioedema could predispose her to a

hypersensitivity reaction following vaccination, the delayed onset makes an alternative trigger

also plausible. The participant's self-report that this episode was less severe than her typical

episodes further limits concern that this event represents a clinically significant safety signal.

Pulmonary embolism: An 86-year-old female with a history of peripheral neuropathy,

neuropathic pain, and hyperlipidemia developed chest pain and dyspnea on Study Day 9 and

was hospitalized on Study Day 12 with an initial diagnosis of right lower lobe pneumonia. Chest

CT revealed multiple bilateral pulmonary emboli in addition to the pneumonia. Venous duplex

ultrasonography identified no deep vein thrombosis. The participant was discharged on oral

edoxaban on Study Day 17, and the SAE of pulmonary embolism was considered resolved. The

Applicant assessed the event as unrelated to study vaccine.

85

FDA Assessment: Although the event was temporally associated with vaccination, the

participant's advanced age, hyperlipidemia, and concurrent pneumonia are all established risk

factors for thromboembolic events and provide plausible alternative etiologies.

Study P303 Part A (mRNA-1010 [QIV])

Deep vein thrombosis and pulmonary embolism: A 57-year-old female current smoker with a

history of severe varicose veins experienced deep vein thrombosis on Day 128 following an

injury to the affected leg, and a subsequent pulmonary embolism on Day 132. The Applicant

assessed both SAEs as unrelated to the study vaccine.

FDA Assessment: The long interval between vaccination and onset of these events,

combined with the presence of more likely alternative etiologies — including recent leg injury,

varicose veins, and smoking — makes a causal association with the study vaccine unlikely.

Death: A 76-year-old participant on Study Day 2, as described in Appendix D.1 Death

Appendix D.3. Protocol-Defined Adverse Events of Special Interest (AESIs)

Through 28 days after vaccination, AESIs were reported in 7 participants (<0.1%) in the mRNA-1010

group and 4 participants (<0.1%) in the SD/HD comparator group. Through the full study period,

AESIs were reported in 36 participants (0.1%) in the mRNA-1010 group and 37 participants (0.1%) in

the SD/HD comparator group; 5 and 2 participants, respectively, had AESIs assessed as related to

study injection by the Investigator.

The five AESIs assessed as related to mRNA-1010 by the Investigator were: thrombocytopenia

(onset Day 84; see Appendix B thrombocytopenia), facial swelling (onset Day 2; see Appendix C

Facial Swelling), myopericarditis (onset Day 95; see Appendix B myopericarditis), myocarditis (onset

Day 183; see Appendix B Myocarditis), and Bell's palsy (onset Day 16; see Appendix D.3.2 below).

Summaries of additional analyses for AESIs of myocarditis/pericarditis and new-onset or worsening

neurological diseases are presented below. No meaningful differences were observed between the

mRNA-1010 and SD/HD comparator groups in these analyses.

Appendix D.3.1. Myocarditis/Pericarditis

No AESIs of myocarditis, pericarditis, or myopericarditis were reported within 28 days of vaccination

in either group. Through study completion, AESIs in the cardiac disorders SOC (myocarditis,

pericarditis, and myopericarditis) were reported in 10 participants (<0.1%) in the mRNA-1010 group

and 6 participants (<0.1%) in the SD/HD comparator group; one additional AESI of viral pericarditis in

the SD/HD comparator group was not mapped to the cardiac disorders SOC.

Cardiac Event Adjudication Committee (CEAC)-confirmed cases were balanced across groups: 4

confirmed cases in the mRNA-1010 group (1 myopericarditis; 3 acute pericarditis) and 3 confirmed

cases of acute pericarditis in the SD/HD comparator group. One additional CEAC-confirmed case of

acute pericarditis in the SD/HD comparator group (Study P301) was adjudicated after database lock

and therefore not captured in the study database.

In the mRNA-1010 group, one participant from Study P304 had an AESI of myocarditis on Day 183,

adjudicated by the CEAC as myopericarditis and assessed as related to study vaccine by the

Investigator; this case and the FDA assessment are described in Appendix B myopericarditis. In the

SD/HD comparator group, one participant from Study P304 had an AESI of pericarditis, adjudicated

as acute pericarditis, on Day 60 and assessed as related to the study vaccine by the Investigator.

Appendix D.3.2. New Onset or Worsening of Specified Neurological Diseases

Guillain-Barré Syndrome (GBS): Across the ISS population, no events of GBS were reported in the

SD/HD comparator group. One serious AESI of GBS, coded under the PT of demyelinating

polyneuropathy, was reported in the mRNA-1010 group in a 79-year-old female with a history of

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hypothyroidism, COPD, hypertension, obesity, and dyslipidemia, with onset on Day 134. The

participant initially presented on Day 129 with hypertension, foot tingling, and vomiting, and

subsequently developed distal paresthesias and progressive lower extremity weakness, advancing to

tetraparesis and respiratory failure by Day 134, with a diagnosis of demyelinating polyneuropathy

made during hospitalization. The Investigator assessed this event as unrelated to the study vaccine.

FDA Assessment: FDA agrees that this event is unrelated to the study vaccine. Symptom onset

occurred well outside the established 42-day risk window for vaccine-associated GBS.

Bell's Palsy: Across the ISS population, Bell's palsy (idiopathic peripheral facial nerve paralysis) was

reported by 1 participant (<0.1%) in the mRNA-1010 group and 4 participants (<0.1%) in the SD/HD

comparator group. Within the 42-day risk window, one event was reported in each group; both were

assessed as related to the study vaccine by the respective study Investigators. The Bell's palsy event

within the risk window in the mRNA-1010 group is described below. One additional mRNA-1010

recipient reported an AESI and concurrent SAE of facial paresis on Day 21 in the setting of

concurrent herpes zoster; this event was assessed as unrelated to the study vaccine by the

Investigator and by FDA.

Case Description: Bell's Palsy (Study P303 Part B)

A 59-year-old male with a history of obesity developed Bell's palsy on Study Day 16. On Study

Day 5, he reported left upper lip induration and left cheek erythema of unknown etiology, followed

by right-sided facial droop on Day 16. On Study Day 17, he presented to the emergency

department with persistent right-sided facial droop and notably elevated systolic blood pressure

(176 mmHg). He was diagnosed with hypertension, type 2 diabetes mellitus, and Bell's palsy. He

was treated with valacyclovir and prednisone; the event was considered resolved on Study Day

161. The Investigator assessed the event as related to the study vaccine; the Applicant assessed

it as unrelated.

FDA Assessment: FDA agrees with the Investigator's assessment that this event is possibly

related to the study vaccine based on the temporal relationship to vaccination. However, the

participant's comorbidities — obesity, hypertension, and type 2 diabetes — are established risk

factors for Bell's palsy and represent plausible alternative etiologies.

Safety Conclusions

The pooled safety analysis across all four Phase 3 studies in individuals 50 yoa and older did not

identify adverse event patterns indicative of a safety concern for mRNA-1010.

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Appendix E – Adverse Events of Special Interest

Adverse Events of Special Interest Prespecified in Study Protocols of mRNA-1010

Medical Concept Additional Notes

Thrombocytopenia: • Platelet count <125×109/L.

• Including but not limited to immune thrombocytopenia, platelet

production decreased, thrombocytopenia, thrombocytopenic

purpura, thrombotic thrombocytopenic purpura, or HELLP

syndrome.

New onset of or worsening • GBS.

of the following neurologic • ADEM.

diseases: • Idiopathic peripheral facial nerve palsy (Bell’s palsy).

• Seizures, including but not limited to febrile seizures and/or

generalized seizures/convulsions.

Anaphylaxis: • Anaphylaxis associated with study intervention administration as

defined in Section 8.3.1.4.1 of the protocol.

Myocarditis/pericarditis: • Myocarditis.

• Pericarditis.

• Myopericarditis.

Source: Study P304 Protocol Table 5, Study P304 Part B/C Protocol Table 17.

Abbreviation: ADEM, acute disseminated encephalomyelitis; GBS, Guillain-Barré syndrome; HELLP, hemolysis, elevated liver enzymes,

low platelets

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Appendix F – CDC Criteria for Probable and Confirmed Cases of Myo, Peri, and

Myopericarditis

CDC Criteria for Probable and Confirmed Cases of Myocarditis, Pericarditis, and Myopericarditis

Condition Probable Case Definition Confirmed Case Definition

Acute Presence of ≥1 new or worsening of the following Presence of ≥1 new or worsening of the

myocarditis clinical symptoms:a following clinical symptoms:a

chest pain, pressure, or discomfort chest pain, pressure, or discomfort

dyspnea, shortness of breath, or pain with dyspnea, shortness of breath, or pain

breathing with breathing

palpitations palpitations

syncope syncope

OR infants and children <12 years of age might OR infants and children <12 years of

instead have ≥2 of the following symptoms: age might instead have ≥2 of the

irritability following symptoms:

vomiting irritability

poor feeding vomiting

tachypnea poor feeding

lethargy tachypnea

AND lethargy

≥1 new finding of troponin level above upper limit AND

of normal (any type of troponin) ≥1 new finding of histopathologic

abnormal electrocardiogram (ECG or EKG) or confirmation of myocarditisd

rhythm monitoring findings consistent with cMRI findings consistent with

myocarditisb myocarditisc in the presence of troponin

abnormal cardiac function or wall motion level above upper limit of normal (any

abnormalities on echocardiogram type of troponin)

cMRI findings consistent with myocarditisc AND

AND No other identifiable cause of the

No other identifiable cause of the symptoms and symptoms and findings

findings

Acute Presence of ≥2 new or worsening of the following -

pericarditise clinical features:

acute chest painf

pericardial rub on exam

new ST-elevation or PR-depression on EKG

new or worsening pericardial effusion on

echocardiogram or MRI

Myo This term may be used for patients who meet -

criteria for both myocarditis and pericarditis.

Source: Adapted from STN 125869/0, mRNA‑1010‑P304 Protocol Amendment 1, Appendix 4.

Abbreviations: AV, atrioventricular; cMRI, cardiac magnetic resonance imaging; ECG/EKG, electrocardiogram; Myo, myopericarditis

An independent CEAC comprising medically qualified personnel, including cardiologists, will review suspected cases of myocarditis, pericarditis,

and myopericarditis to determine if they meet CDC criteria for “probable” or “confirmed” events (Gargano et al. 2021) and provide the

assessment to the Applicant. The CEAC members will be blinded to study treatment. Details regarding the CEAC composition, responsibilities,

procedures, and frequency of data review will be defined in the CEAC charter.

a

Persons who lack the listed symptoms but who meet other criteria may be classified as subclinical myocarditis (probable or confirmed).

b

To meet the ECG or rhythm monitoring criterion, a probable case must include at least one of 1) ST-segment or T-wave abnormalities; 2)

Paroxysmal or sustained atrial, supraventricular, or ventricular arrhythmias; or 3) AV nodal conduction delays or intraventricular conduction

defects.

c

Using either the original or the revised Lake Louise criteria (Ferreira et al. 2018).

d

Using the Dallas criteria (Aretz 1987). Autopsy cases may be classified as confirmed clinical myocarditis on the basis of meeting

histopathologic criteria if no other identifiable cause.

e

Adler et al 2015.

f

Typically described as pain made worse by lying down, deep inspiration, or cough, and relieved by sitting up or leaning forward, although other

types of chest pain might occur (Gargano et al. 2021).

89

Appendix G – Study P304 High-Risk Conditions

Participants were assigned to the high-risk group if their baseline BMI was ≥30 kg/m2 or they had at

least one high-risk factor in the medical history.

High-Risk Factors

High-Risk Factor SMQ or HLT Type Detail

Autoimmune/immune-

Immune-mediated/autoimmune disorders SMQ Narrow

mediated disease

Blood disorders Coagulation disorders congenital HLT --

Haemoglobinopathies congenital HLT --

Cardiac disorders Cardiac conduction disorders HLT --

Supraventricular arrhythmias HLT --

Ventricular arrhythmias and cardiac arrest HLT --

Cardiomyopathy SMQ Narrow

Ischemic heart disease SMQ Narrow

Nervous system Cerebrovascular embolism and thrombosis HLT --

disorders Parkinson’s disease and parkinsonism HLT --

Paralysis and paresis (excl. cranial nerve) HLT --

Demyelination SMQ Narrow

Diabetes mellitus Diabetes mellitus (including subtypes) HLT --

Renal disorders Chronic kidney disease SMQ Narrow

Hepatic disorders Hepatocellular damage and hepatitis NEC HLT --

Hepatic fibrosis and cirrhosis HLT --

Mental impairment

Intellectual disabilities HLT --

disorders

Dementia SMQ Narrow

Pulmonary disorders Bronchospasm and obstruction HLT --

Interstitial lung disease SMQ Narrow

Pulmonary hypertension SMQ Narrow

Source: Study P304 SAP Appendix J. Derivation of High-Risk.

Abbreviations: HLT, high-level term; NEC, not elsewhere classified; SMQ, Standardized MedDRA Query

90

Appendix H – Phase 4 Confirmatory Study Protocol Synopsis

The Applicant proposed the following Phase 4 confirmatory study design as a postmarketing

requirement (PMR) to support full approval of mFlusiva under Accelerated Approval pathway. The

study protocol and proposed timeline are currently under review and are the subject of ongoing

discussions between FDA and the Applicant.

STUDY OVERVIEW

Phase 4 pragmatic, cluster-randomized clinical trial to evaluate the relative vaccine effectiveness

(rVE) of mRNA-1010 compared with agreed upon CDC-preferentially recommended vaccine in

adults 65 yoa and older under real-world conditions.

RESEARCH QUESTION & OBJECTIVES

Is mRNA-1010 noninferior to agreed upon CDC-preferentially recommended vaccine in

preventing laboratory-confirmed medically attended influenza in adults 65 yoa and older?

Secondary objectives include assessment of protection against influenza-associated emergency

department, urgent care, or hospitalizations; influenza-associated hospitalization; and stratified

analyses by strain type, if feasible.

STUDY DESIGN & POPULATION

Design: Vaccine clinics will be cluster-randomized, alternating weekly between mRNA-1010 and

agreed upon CDC-preferentially recommended vaccine throughout the influenza season. This

approach seeks to balance vaccine allocation and controls for confounding by calendar time and

facility.

Enrollment: ~800,000 (~400,000 per season) adults 65 yoa and older in a 1:1 allocation (2 full

seasons, 2027–2028 and 2028–2029).

OUTCOMES & STATISTICAL APPROACH

Primary endpoint: Laboratory-confirmed medically-attended influenza occurring ≥14 days

postvaccination.

Noninferiority margin: -15% (H₀: rVE ≤ -15%; one-sided alpha = 0.025).

Sample size: 1,632 primary endpoint events provide ≥80% power to demonstrate noninferiority,

assuming a true rVE of 0%.

Analysis: Cox proportional hazards regression, stratified by facility and conditioned on calendar

date, adjusted for age, sex, race/ethnicity, and comorbidities.

DATA SOURCE & GOVERNANCE

Data source: Electronic medical records, capturing all vaccinations, laboratory results (PCR-

confirmed influenza), medical encounters, and diagnoses.

Informed consent: A waiver of informed consent is anticipated, as the study reflects routine

clinical practice and no specific vaccine selection is implied.

STUDY TIMELINE

Under Review

An interim analysis after Season 1 will assess adequacy of endpoint accrual; if sufficient, the

study may conclude after one season.

91

打开原文

Moderna Briefing Document: mRNA-1010 / MFLUSIVA

来源信息
来源：Moderna / FDA posted material发布日期：2026-06-17抓取时间：2026-06-17T19:01:17.558Z相关标的：MRNA归档状态：已归档 / 弹窗可读
中文摘要

一句话结论

Moderna 的申请方简报把 mRNA-1010 描述为针对 50 岁及以上人群的 mRNA seasonal influenza vaccine，强调临床项目规模、P304 疗效结果、65 岁及以上免疫原性桥接和整体安全性，以支持传统批准和加速批准的分层路径。

关键事实

  • 申请方文件围绕 MFLUSIVA / mRNA-1010 的 BLA 审评和 VRBPAC 讨论编写。
  • Moderna 描述 mRNA-1010 开发项目包括多个完成研究，并强调关键 Phase 3 安全性和有效性数据库。
  • P304 入组超过 4 万名 50 岁及以上 adults，用于评估相对 standard-dose flu vaccine 的临床保护。
  • 针对 65 岁及以上人群，申请方强调与 high-dose influenza vaccine comparator 的免疫原性桥接数据。
  • 文件支持 50-64 岁 traditional approval 和 65 岁及以上 accelerated approval 的申请路径。
  • 安全性叙述强调 reactogenicity 可管理，未将 myocarditis/pericarditis 描述为可归因的突出信号。

作者观点与证据

这是申请方材料，观点明显支持获批。可用事实是试验设计、入组规模、审批路径和安全性/免疫原性结果；解释其充分性时必须与 FDA 审评文件对读。

与相关标的的关系

对 MRNA 的意义是申请方如何构建可商业化标签：如果 FDA 接受 50+ 与 65+ 分层证据，mRNA-1010 能成为 Moderna 呼吸道组合的重要拼图；若 FDA 对 65+ 或共同接种数据不满意，标签价值会打折。

时效性与限制

文件发布时间为 2026-06-17，强时效。限制是申请方视角，不能替代 FDA 独立审评、VRBPAC 投票或最终批准决定。

后续跟踪

  • FDA/VRBPAC 是否接受申请方的批准路径。
  • 标签是否覆盖 50+、65+，以及是否带有共同接种或特殊人群限制。
  • mRNA-1010 与 mCOMBRIAX 的商业组合路径。
英文原文
Moderna Briefing Document: mRNA-1010 / MFLUSIVA

Individuals using assistive technology may not be able to fully

access the information contained in this file. For assistance,

please call 800-835-4709 or 240-402-8010, extension 1. CBER

Consumer Affairs Branch or send an e-mail to: ocod@fda.hhs.gov

and include 508 Accommodation and the title of the document in

the subject line of your e-mail.

mRNA-1010

Vaccines and Related Biological Products

ModernaTX, Inc. Advisory Committee

mRNA-1010

INFLUENZA VACCINE FOR ADULTS ≥50 YEARS OLD

SPONSOR BRIEFING DOCUMENT

VACCINES AND RELATED BIOLOGICAL PRODUCTS ADVISORY

COMMITTEE

ADVISORY COMMITTEE BRIEFING MATERIALS: AVAILABLE

FOR PUBLIC RELEASE

MEETING DATE: JUNE 18, 2026

1

mRNA-1010

Vaccines and Related Biological Products

ModernaTX, Inc. Advisory Committee

TABLE OF CONTENTS

Table of Contents ............................................................................................................ 2

List of Tables ................................................................................................................ 5

List of Figures .............................................................................................................. 6

List of Abbreviations..................................................................................................... 8

1 Introduction ............................................................................................................... 10

2 Summary of Overall Clinical Data for Individuals 50 Years and Older ....................... 11

3 Influenza Background................................................................................................ 15

3.1 Clinical/Pathophysiology of Condition ............................................................. 15

3.1.1 Influenza Burden of Disease ..................................................................... 15

3.1.2 Clinical Spectrum of Disease .................................................................... 16

3.2 Currently Available Influenza Vaccines ........................................................... 17

3.3 Unmet Medical Need ...................................................................................... 18

4 mRNA-1010 Overview............................................................................................... 20

4.1 Proposed Indication and Posology.................................................................. 20

4.2 mRNA-1010 Description and Mechanism of Action ........................................ 20

5 Regulatory History ..................................................................................................... 22

5.1 Regulatory Milestones .................................................................................... 22

5.2 Approval Pathways ......................................................................................... 23

6 Overview of mRNA-1010 Clinical Development Program ......................................... 25

6.1 Studies Supporting Development of mRNA-1010 ........................................... 25

6.1.1 Study mRNA-1010-101 ............................................................................. 27

6.1.2 Study mRNA-1010-304 ............................................................................. 27

6.1.3 Study mRNA-1010-303C .......................................................................... 29

6.2 Study Endpoints and Analysis Sets................................................................. 30

6.2.1 Efficacy Endpoints ..................................................................................... 30

6.2.2 Immunogenicity Endpoints ........................................................................ 31

6.2.3 Safety Endpoints ....................................................................................... 32

6.2.4 Analysis Sets............................................................................................. 32

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6.3 Enrolled Participants ....................................................................................... 33

6.3.1 Study 304 Study Population (≥50 Years) ................................................... 33

6.3.2 Study 303C Study Populations (≥65 Years) .............................................. 37

7 Efficacy and Immunogenicity in Adults 50–64 Years ................................................. 40

7.1 Epidemiology Introduction ............................................................................... 40

7.2 Efficacy and Immunogenicity (50–64 years) ................................................... 41

7.2.1 Relative Vaccine Efficacy .......................................................................... 41

7.2.2 Immunogenicity ......................................................................................... 43

7.3 HAI Ab Levels and Protection ......................................................................... 45

7.4 Conclusions: Efficacy and Immunogenicity, in Adults 50–64 Years ................. 46

8 Efficacy and Immunogenicity in Adults ≥65 Years ..................................................... 47

8.1 Epidemiology Introduction ............................................................................... 47

8.2 Conclusions: Efficacy and Immunogenicity in Adults ≥65 Years...................... 48

8.3 Efficacy and Immunogenicity (≥65 years) ....................................................... 48

8.3.1 Relative Vaccine Efficacy .......................................................................... 48

8.3.2 Immunogenicity ......................................................................................... 52

9 Overview of Safety in Adults ≥50 years ..................................................................... 57

9.1 Safety Database ............................................................................................. 57

9.2 Reactogenicity ................................................................................................ 58

9.2.1 Study 304 .................................................................................................. 61

9.2.2 Study 303 Part C ....................................................................................... 62

9.3 Unsolicited Adverse Events............................................................................. 62

9.3.1 Study 304 .................................................................................................. 62

9.3.2 Study 303 Part C ....................................................................................... 69

9.3.3 Integrated Summary of Safety (ISS) ......................................................... 70

9.3.4 Safety Conclusions ................................................................................... 76

10Confirmatory Study for Adults 65 Years and Older .................................................... 77

10.1 Study Design................................................................................................... 77

11 Benefits and Risks Conclusions ................................................................................ 78

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11.1 Therapeutic Context ........................................................................................ 78

11.2 Benefit-Risk Analysis Evaluation in Adults 50–64 Years of Age ...................... 78

11.3 Benefit-Risk Analysis Evaluation in Adults 65 Years and Older ....................... 79

11.4 Conclusions .................................................................................................... 81

12References ................................................................................................................ 82

13Appendices ............................................................................................................... 87

13.1 Study 101 ........................................................................................................ 87

13.1.1 Design ....................................................................................................... 87

13.1.2 Results ...................................................................................................... 87

13.2 Study 304 Results in Adults ≥ 50 Years .......................................................... 89

13.3 Study 304 Safety Results by Age Subgroup ................................................... 94

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ModernaTX, Inc. Advisory Committee

List of Tables

Table 1: mRNA-1010 Reduces ILI-associated Healthcare Outcomes Relative to

Licensed SD Comparator in Adults ≥ 50 Years (Per Protocol Set).............. 13

Table 2: Study 304 Participant Disposition (Randomization Set) ............................. 34

Table 3: Study 304 Analysis Sets ............................................................................. 35

Table 4: Study 304 Demographics (Safety Set)........................................................ 36

Table 5: Study 303C Disposition of Participants (Randomization Set) ..................... 37

Table 6: Study 303C Analysis Sets .......................................................................... 38

Table 7: Study 303C Baseline Demographics and Characteristics (Safety Set)....... 39

Table 8: mRNA-1010 Reduces ILI-associated Healthcare Outcomes Relative to

Licensed SD Comparator in Adults ≥ 65 (Per-Protocol Set) ....................... 52

Table 9: Study 304 and Study 303C Summary of Participants with Solicited Local

ARs within 7 Days After Injection by Maximum Toxicity Grade (Solicited

Safety Subset/Set)...................................................................................... 59

Table 10: Study 304 and Study 303C Summary of Participants with Solicited Systemic

ARs Within 7 Days After Injection by Maximum Toxicity Grade (Solicited

Safety Subset/Set)...................................................................................... 60

Table 11: Study 304 Overall Summary of Unsolicited AEs Up to 28 Days After

Injection (Safety Set) .................................................................................. 64

Table 12: Study 304 Overall Summary of Unsolicited AEs Throughout the Study

(Safety Set) ................................................................................................ 65

Table 13: Number of Participants in the ISS Set by Age Subgroups .......................... 71

Table 14: ISS Overall Summary of Unsolicited Adverse Events (ISS Set) ................. 71

Table 15: Overall Summary of Unsolicited Adverse Events by Age Group (ISS Set) . 76

Table 16: Comparison of HAI Ab GMT (Day 29) for ILI Cases Versus Non-cases for

mRNA-1010 and for the Active Comparator (by Influenza Strain) .............. 92

Table 17: Day 29 B/Victoria HAI GMT by the Corresponding Strain-Specific ILI Case

Status in Each Vaccine Group in Overall, Bulgaria, and Non-Bulgaria

Regions (Study 304, Per Protocol Correlate of Analysis Set) ..................... 93

Table 18: Study 304 Solicited Local ARs by Age Group ............................................. 94

Table 19: Study 304 Solicited Systemic Adverse Reactions by Age Group ................ 95

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ModernaTX, Inc. Advisory Committee

List of Figures

Figure 1: mRNA-1010 Demonstrates Superior Efficacy Relative to Licensed SD

Comparator .................................................................................................11

Figure 2: Key Studies Supporting mRNA-1010 ......................................................... 26

Figure 3: Study 304 Design ....................................................................................... 28

Figure 4: Study 303C Design..................................................................................... 29

Figure 5: Sequential Testing of rVE Endpoint ............................................................ 30

Figure 6: Study 304 Relative Vaccine Efficacy (PP Set 50–64 years) ....................... 41

Figure 7: Study 304 Relative Vaccine Efficacy by Strain (PP Set 50–64 Years) ........ 42

Figure 8: Study 304 Cumulative Number of RT-PCR-confirmed Protocol-Defined ILI

Cases (PP Set 50–64 years) ...................................................................... 43

Figure 9: Study 304 HAI Ab GMR and SCR Differences at Day 29 (PPIS 50–64

Years) ......................................................................................................... 44

Figure 10: Study 304 MN Ab GMR at Day 29 (PPIS, Participants with MN Ab Values

50–64 Years) .............................................................................................. 45

Figure 11: Study 304 Relative Vaccine Efficacy Influenza-Like Illness Events (PP Set

≥65 Years) .................................................................................................. 49

Figure 12: Study 304 Relative Vaccine Efficacy by Influenza Strain (PP Set ≥65 Years).

.................................................................................................. 50

Figure 13: Study 304 Cumulative Number of Influenza Cases (PP Set ≥65 years) ..... 51

Figure 14: Study 304 HAI Ab GMR and SCR at Day 29 (PPIS ≥65 Years) .................. 53

Figure 15: Study 304 MN Ab GMR at Day 29 (PPIS Participants with MN Ab Values

≥65 Years) .................................................................................................. 54

Figure 16: Study 303C GMR and SCR at Day 29 (PPIS ≥65 Years) ........................... 55

Figure 17: Study 303C MN Ab GMR at Day 29 (PPIS, Participants with MN Ab Values

≥65 Years) .................................................................................................. 56

Figure 18: Study 304 ILI Events by Strain- Per-Protocol Set ....................................... 89

Figure 19: Study 304 Cumulative Incidence Rates of Influenza Cases Per-Protocol Set

.................................................................................................. 89

Figure 20: Study 304 by Influenza-like Illness Definition Per-Protocol Set .................. 90

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Vaccines and Related Biological Products

ModernaTX, Inc. Advisory Committee

Figure 21: Study 304 High Risk and Frailty Subgroups Per-Protocol Set .................... 90

Figure 22: Study 304 Medically Attended Illness in Participants ≥50 Years ................. 91

Figure 23: Study 304 - GMR and SCR at Day 29 Per-Protocol Immunogenicity Subset .

.................................................................................................. 91

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ModernaTX, Inc. Advisory Committee

List of Abbreviations

Acronym Definition

Ab antibody

AE Adverse event

AESI Adverse event of special interest

AR Adverse reaction

BLA Biologics Licensed Application

BMI Body mass index

CDC Centers for Disease Control and Prevention

CEAC Cardiac Event Adjudication Committee

CI Confidence interval

CVV candidate vaccine virus

EOS End of study

ER Emergency room

FDA Food and Drug Administration

GMFR geometric mean fold-rise

GMR geometric mean titer ratio

GMT geometric mean titer

HA hemagglutination

HAI hemagglutination inhibition

HD High dose

ILI Influenza-like illness

ISS Integrated summary of safety

LB Lower bound

LNP lipid nanoparticle

MAAE medically attended adverse event

MN microneutralization assay

NA neuraminidase

PP Per-protocol

PPIS Per-Protocol Immunogenicity Set/Subset

PT Preferred term

QIV quadrivalent influenza vaccine

RT-PCR reverse transcription polymerase chain reaction

RWE Real-world evidence

rVE Relative vaccine efficacy

SAE Serious adverse event

SD Standard dose

SMQ standardized MedDRA query

SRC seroconversion rate

SOC system organ class

8

mRNA-1010

Vaccines and Related Biological Products

ModernaTX, Inc. Advisory Committee

Acronym Definition

TEAE Treatment Emergent Adverse Event

TIV trivalent influenza vaccine

US United States

WHO World Health Organization

9

mRNA-1010

Vaccines and Related Biological Products

ModernaTX, Inc. Advisory Committee

1 INTRODUCTION

ModernaTX, Inc. (Moderna) is seeking approval of mRNA-1010, a lipid nanoparticle

(LNP)-encapsulated, mRNA-based influenza vaccine for active immunization for the

prevention of influenza disease in individuals 50 years of age and older. The mRNA-

1010 clinical development program encompasses 5 completed studies, including the

pivotal Phase 3 safety and efficacy study (304), which enrolled 40,703 adults ≥50 years

of age, and the Phase 3 safety and immunogenicity study (303 Part C), which enrolled

2,992 adults ≥65 years. The safety profile is further supported by the analysis of an

integrated safety summary of more than 71,000 participants ≥50 years from 4 Phase 3

studies.

The Biologics Licensed Application (BLA) was submitted based on positive Phase 3

results demonstrating that mRNA-1010 provides superior relative vaccine efficacy (rVE)

against influenza illness, enhanced immunogenicity, and an acceptable safety profile

versus standard-dose (SD) comparator vaccine. Additionally, mRNA-1010

demonstrated superior immunogenicity and a similar safety profile to high-dose (HD)

comparator vaccine. The efficacy, immunogenicity, and safety profile of mRNA-1010 is

supplemented by the mRNA platform that avoids virus propagation in chicken eggs or

cell-based cultures and, as such, avoids adaptive mutations which can reduce vaccine

antigenicity. Further, a shorter manufacturing time can allow later influenza strain

selection, which can avoid strain mismatches. Taken together, these data support a

positive benefit-risk profile for active immunization with mRNA-1010 to prevent influenza

disease in individuals ≥50 years.

Following discussions between Moderna and the Food and Drug Administration (FDA),

two BLA approval pathways are submitted:

• Traditional approval for adults 50 to 64 years of age, and

• Accelerated approval for adults 65 years and older (fully described in Section 5).

This Briefing Document summarizes the overall clinical data package supporting the

indication on adults ≥50 years (Section 2 and Appendix Section 13.2), followed by

efficacy and immunogenicity data supporting the indication in adults 50 to 64 years and

those 65 years and older. Reactogenicity and safety data are summarized in Section 9.

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mRNA-1010

Vaccines and Related Biological Products

ModernaTX, Inc. Advisory Committee

2 SUMMARY OF OVERALL CLINICAL DATA FOR INDIVIDUALS 50 YEARS AND

OLDER

The mRNA-1010 pivotal efficacy study (Study 304) successfully met all protocol-

prespecified efficacy criteria for the prevention of influenza-like illness (ILI). The primary

efficacy endpoint was to assess the reduction of reverse transcription polymerase chain

reaction (RT-PCR)-confirmed, protocol-defined ILI caused by any influenza A or B strain

relative to SD comparator in adults 50 years and older. Study 304 began vaccinations in

September 2024 and performed comprehensive surveillance for ILI until the end of the

2024/2025 influenza season (30 Apr 2025). More than 40,000 adults ≥50 years of age

were included in the efficacy analysis.

The primary analysis of RT-PCR-confirmed protocol-defined ILI cases provided a robust

determination of the efficacy endpoint: the relative efficacy of mRNA-1010 versus SD

comparator was 26.6% (95% confidence interval [CI]: 16.7, 35.4), meeting all

prespecified efficacy success criteria, including the highest level (lower bound [LB] 95%

CI >9.1%, 1-sided p-value=0.0005; Figure 1). The superior efficacy of a single dose of

mRNA-1010 relative to SD comparator was evident early after vaccination and was

maintained to the end of the influenza season.

Figure 1: mRNA-1010 Demonstrates Superior Efficacy Relative to Licensed SD

Comparator

Participants with RT-PCR confirmed

protocol-defined Influenza-Like Licensed SD

Illness (ILI) regardless of influenza Influenza Relative Vaccine Efficacy (%)

strain, % [n/N] mRNA-1010 Vaccines (95% CI)

26.6% (16.7, 35.4)

2.0% 2.8%

All Participants (≥50 years)

[411/20179] [557/20124]

Noninferiority LB 95% CI > -10% -25 -10 0 9.1 25 50

Superiority LB 95% CI > 0

Highest Superiority LB 95% CI > 9.1%

CI: confidence interval; LB: lower bound; RT-PCR: reverse transcription polymerase chain reaction; SD: standard

dose

Source: Leroux-Roels et al 2026

A high total number (968) of confirmed ILI cases were accrued over the 2024/2025

season, representing all 3 influenza strains (538 influenza A/H1N1, 360 influenza

A/H3N2, and 60 influenza B cases). Accordingly, a supplemental analysis of rVE by

strain was performed in the overall ≥50-year-old population: A/H1N1 rVE=29.6%

[95% CI: 16.4, 40.7]; A/H3N2 rVE=22.2% [95% CI: 4.3, 36.9]; B rVE=29.1%

[95% CI: -18.5, 57.5], Figure 18, Appendix 13.2). Previously licensed influenza vaccines

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mRNA-1010

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ModernaTX, Inc. Advisory Committee

in the enhanced category including Fluzone HD and Flublok showed a similar pattern in

VE relative to SD comparator in efficacy studies: both met rVE success criteria for the

overall endpoint (any influenza A or B), with more uncertainty for rVE by individual

strain. For mRNA-1010, the relatively small number of B/Victoria cases resulted in a

wide 95% CI, although the B/Victoria point estimate was consistent with the overall rVE

point estimate. Similar uncertainty in the determination of rVE against ILI caused by

influenza B (i.e., wide 95% CI) was also evident for Fluzone HD [rVE 27.4%, 95% CI:

−13.1 to 53.8, based on 89 Influenza B cases] and for Flublok [rVE 4%, 95% CI: −72 to

46, based on 47 influenza B cases]) (DiazGranados et al 2014; Dunkle et al 2017). The

accrual of fewer influenza B cases across registrational influenza vaccine studies

reflects the lower burden of disease caused by influenza B in older adults. The

uncertainty in B strain rVE is thus evident across influenza vaccines and did not prevent

full approval of Fluzone HD or Flublok as enhanced vaccines.

Efficacy of mRNA-1010 relative to SD comparator was maintained when alternate ILI

case definitions were assessed. Using case definitions tested in other studies of

enhanced vaccines that required the occurrence of temperature ≥37.2ºC accompanied

by cough and/or sore throat (modified Centers for Disease Control and Prevention

[CDC] ILI case definition), rVE remained consistent (23.5%; 95% CI: 9.0, 35.8).

In the Study 304 population, 56.9% of participants were considered at high risk for

severe ILI, and 25% of participants ≥65 years were considered of vulnerable or frail

status. rVE was assessed across population subgroups including those at high risk and

of frail status, and results were consistent with those of the overall Study 304 rVE.

As part of an exploratory analysis of healthcare encounters associated with confirmed

ILI, results showed fewer occurrences in the mRNA-1010 group than in the SD

comparator group (Table 1). The rVE for participants seeking a higher level of care

(hospitalization, emergency room [ER] visit, or urgent care visit) was 47.9% (95% CI:

12.8, 68.9; 22 mRNA-1010 vs 42 SD comparator participants). Even for categories with

numbers too small to calculate rVE, case splits were favorable for mRNA-1010

(hospitalization: 4 mRNA-1010 vs 8 SD comparator; ER visits: 6 mRNA-1010 vs 12 SD

comparator).

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mRNA-1010

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ModernaTX, Inc. Advisory Committee

Table 1: mRNA-1010 Reduces ILI-associated Healthcare Outcomes Relative to

Licensed SD Comparator in Adults ≥ 50 Years (Per Protocol Set)

mRNA-1010 Comparator

N=20179 N=20124 rVE (95% CI)

Healthcare encounter 80 (0.4) 120 (0.6) 33.7 (12.0, 50.0)

Seek higher level of care 22 (0.1) 42 (0.2) 47.9 (12.8, 68.9)

Hospitalization 4 (<0.1) 8 (<0.1) n.c.

ER 6 (<0.1) 12 (<0.1)nc n.c.

Urgent care clinical visit 13 (<0.1) 24 (0.1) 46.1 (-5.8, 72.6)

Outpatient clinical visit 59 (0.3) 81 (0.4) 27.6 (-1.3, 48.2)

CI: confidence interval; ER: emergency room; ILI: influenza-like illness; nc: not calculated; rVE: relative

vaccine efficacy

n.c.: rVE not calculated due to too few cases.

In the Study 304 population, 56.9% of participants were considered at high risk for

severe ILI, and 26.5% of participants ≥65 years were considered of vulnerable or frail

status. rVE was assessed across population subgroups including those at high risk and

of frail status, and results were consistent with those of the overall Study 304 rVE.

The immunogenicity of mRNA-1010 was measured using the hemagglutinin inhibition

assay (HAI), a conventional measure of influenza vaccine immunogenicity. Antibody

(Ab) responses were also measured using a microneutralization assay (MN), although

these were exploratory objectives supplementing results of the HAI assay. Ab levels

measured in the pivotal clinical efficacy study (304) showed that mRNA-1010

consistently induced higher levels of HAI Ab relative to SD comparator for all 3 influenza

strains: the point estimates for Day 29 GMR (mRNA-1010/SD comparator) were all >1.5

(95% CI LBs were >1.4) and seroconversion rate (SCR) differences were all positive

(95% CI LBs were >15%). Superior clinical efficacy was supported by higher HAI Ab

levels in the pivotal efficacy study. Further, in a head-to-head comparison of HAI Ab

levels in adults 65 years and older (Phase 3 303C study), mRNA-1010 responses met

prespecified superiority criteria relative to HD comparator. In both 304 and 303C

studies, results of MN assays were consistent with those based on HAI assays. Thus,

like other licensed SD and HD influenza vaccines, superior clinical efficacy of mRNA-

1010 is aligned with mRNA-1010-induced Ab levels that are higher than those of SD

and superior to those of HD comparators.

Reactogenicity in Study 304 (adults ≥50 years with SD comparator) and Study 303C

(adults ≥65 years with HD comparator) was higher for mRNA-1010 than for comparator,

but most solicited local and systemic adverse reactions (ARs) were Grade 1 or 2 in

severity and transient. Grade 3 solicited local and systemic ARs were more frequent in

the mRNA-1010 group than comparator groups, but these too were transient (median

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duration of 1 day in the mRNA-1010 group) and generally resolved without medical

attention. Analysis of individual safety data from Studies 304 and 303C identified no

safety concerns with mRNA-1010. Unsolicited adverse events (AEs) reported in the

28 days post-injection were balanced between study groups in both studies.

Analysis of pooled Phase 3 (Study 301, 302, 303, and 304) integrated summary of

safety (ISS) data from more than 70,000 adults ≥50 years of age were similarly

reassuring: the overall incidence of deaths, other serious AEs (SAEs), and AEs of

special interest (AESIs) for the study duration was similar between the mRNA-1010 and

SD/HD comparator groups.

Data from Studies 304 and 303C together with safety data from the entire clinical

program, including the ISS, show that mRNA-1010 is anticipated to provide meaningful

clinical benefit in the prevention of ILI in adults 50 years and older. mRNA-1010

demonstrated superior protection against clinical ILI relative to SD comparator, at a

level exceeding the highest prespecified success criterion (rVE 26.6%; 95% CI: 16.7,

35.4) and fully aligned with levels of VE relative to SD comparator obtained for

approved enhanced vaccines (i.e., Fluzone HD and Flublok). The superior mRNA-1010

rVE from the pivotal efficacy study corresponds with induced HAI Ab levels that are

consistently higher than comparator Ab levels, as HAI induced by mRNA-1010 are

superior to those elicited by Fluzone HD (Study 303C). Further, the pattern of mRNA-

1010-induced immunogenicity is consistent when measured using the HAI Ab assay or

the functional MN Ab assay. In total, direct clinical efficacy taken together with superior

HAI and MN Ab levels predict mRNA-1010 efficacy at a level comparable to that

afforded by enhanced vaccines. Additionally, the mRNA platform provides

manufacturing advantages over licensed influenza vaccines likely to provide additional

benefits relative to existing vaccines, including more precise strain matching without the

risk of inadvertent egg-adaptive mutations and faster manufacturing timelines that

enable strain selection closer to the start of influenza season. Given the natural

seasonal variability and antigenic drift of influenza virus, better vaccine antigenic fidelity

is a key distinguishing potential advantage of mRNA-1010 compared to currently

available influenza vaccines.

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3 INFLUENZA BACKGROUND

Summary

• Influenza is a highly transmissible respiratory disease that continues to cause

substantial morbidity and mortality in the United States (US).

• Adults ≥50 years old remain disproportionately affected compared to younger

adults; adults ≥65 years old account for 70% to 85% of influenza-related

deaths and 50% to 70% of hospitalizations.

• Although vaccination remains the most effective preventive measure against

influenza, the effectiveness of licensed vaccines is constrained by

manufacturing limitations and frequent strain mismatches caused by antigenic

changes.

• Most seasonal influenza vaccines are manufactured using egg-based

processes, which are subject to strain-dependent variability in antigen yield. In

some seasons there are challenges generating high-yield candidate vaccine

viruses (CVVs) without introducing egg-adaptive mutations that can impact

vaccine immunogenicity.

• Influenza continues to drive substantial hospitalizations and deaths among US

adults ≥50 years, and currently licensed vaccine technologies do not

consistently deliver the level of protection or manufacturing flexibility needed to

address this ongoing public health burden.

3.1 Clinical/Pathophysiology of Condition

Influenza is a highly contagious respiratory virus that contributes significantly to global

morbidity and mortality. Human influenza viruses are segmented, negative-sense,

single-stranded RNA viruses belonging to the Orthomyxoviridae family (Bouvier and

Palese 2008). Human-to-human transmission occurs predominantly via respiratory

droplets from coughing, sneezing or indirectly via respiratory secretions on hands,

tissues, or other surfaces (ECDC 2022). Viral transmission is enhanced in colder and

drier conditions (Lowen et al 2007) and seasonal epidemics of influenza occur in winter

months in temperate regions (WHO 2025).

3.1.1 Influenza Burden of Disease

The World Health Organization (WHO) estimates that seasonal influenza viruses cause

approximately 1 billion illnesses, 3 to 5 million severe illnesses, and up to 650,000

deaths globally each year (WHO 2025). In the US between 2010 and 2024, influenza

has resulted in up to 41 million illnesses, up to 710,000 hospitalizations, and up to

52,000 deaths annually (CDC 2024a). The 2024/2025 US influenza season was

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classified as high severity by the US CDC (CDC 2025a) and was characterized by high

transmission, with in-season estimates of 51 million infections, 710,000 hospitalizations,

and 45,000 deaths (CDC 2025b).

Influenza type A and B viruses are responsible for seasonal influenza epidemics in

humans each year (CDC 2023a). Influenza A and B viruses have 2 surface

glycoproteins, HA and neuraminidase (NA). Influenza A viruses are classified into

subtypes according to the combination of HA and NA glycoproteins expressed on the

viral surface (e.g., A/2009H1N1 pdm09, A/H3N2), while influenza B viruses are

classified into 2 lineages: B/Victoria and B/Yamagata (CDC 2023a). Since the initiation

of mRNA-1010 studies, the WHO has updated its seasonal influenza vaccine

recommendation to exclude B/Yamagata because this lineage is no longer circulating

(WHO 2023; WHO 2024).

Year-to-year variability exists in the circulation and predominance of influenza A and B

strains globally. Though the peak circulation timing of each strain varies by year, in

temperate zones, influenza B on average peaks approximately 4 weeks later than

influenza A (Muscatello 2019). Different subtypes vary by season and by region, such

that a subtype may attain high prevalence in one season or geographic area while

remaining sporadic or undetected in others (Zanobini et al 2022; Zheng et al 2023). In

the 2024-2025 influenza season, influenza A/H1N1pdm09 and influenza A/H3N2

circulated at nearly equal levels, with influenza B circulating at a lower percentage of the

total (~10%) (CDC 2025c). Influenza B disease is largely concentrated in children and

adolescents and generally represents a smaller share of the influenza burden in adults

≥65 years than influenza A. In the 2024-2025 season, influenza B represented 0.8% of

total influenza cases in adults ≥65 years (CDC 2026a).

Substantial antigenic drift occurs among influenza A subtypes and influenza B lineages,

resulting in changes in circulating strains over time (Chen et al 2020; CDC 2022a).

Accordingly, all influenza vaccine strains are assessed on an annual basis to determine

whether updates to seasonal influenza strain recommendations are warranted.

Influenza A/H3N2 is most frequently updated because it is more prone to antigenic drift

and egg adaptations than the other vaccine components (Bedford et al 2014; Rajaram

et al 2020).

3.1.2 Clinical Spectrum of Disease

Disease resulting from influenza virus infection primarily presents with respiratory

symptoms such as cough, nasal congestion, pharyngitis, sinusitis, or otitis media, and

systemic symptoms that may include fever, chills, vomiting, or diarrhea; symptoms may

range from mild to severe (CDC 2022b). Infection with influenza virus may lead to

serious or life-threatening complications (including pneumonia, bacterial superinfection,

respiratory failure, and exacerbations of chronic obstructive pulmonary disease) and

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can lead to increased risk of myocardial infarction, heart failure and stroke (Kwong et al

2018; Sin et al 2022; Nguyen et al. 2025; Jain et al. 2015; Lei et al. 2025). Influenza

infection is also associated with neurological, muscular, and renal complications

(Rosero et al 2025; Sellers et al 2017).

The age distribution of affected individuals varies annually based on the dominant

strains and the level of population immunity, but in general adults ≥50 years are at

greater risk of developing severe influenza complications. Globally, the highest

influenza mortality rate from lower respiratory tract infections occurred among adults

>70 years (16.4 deaths per 100,000) (GBD 2017 Influenza Collaborators 2019). In the

US, adults ≥65 years accounted for 70% to 85% of influenza-related deaths and 50% to

70% of influenza-related hospitalizations in recent years (CDC 2024b). During the

2024/2025 season, US hospitalization and mortality rates among adults ≥65 years were

666.3 and 51.9 per 100,000, respectively, which represents an over 8-fold increase in

hospitalizations and over 25-fold increase in deaths compared to adults 18-49 years

(CDC 2026b). A significant burden of influenza also exists in adults 50 to 64 years, who

account for a large proportion of the workforce. During the 2024/2025 season in the US,

the rates of hospitalization and mortality were 223.3 and 15.3 per 100,000 among adults

50 to 64 years, compared to 79.0 and 2.0 per 100,000 among those 18 to 49 years

(CDC 2026b).

In addition to age-related risk, the presence of chronic conditions increases the risk of

severe influenza outcomes, including hospitalization and death (CDC 2024c). The CDC

FluSurv-NET survey showed that approximately 95% of adults hospitalized with

influenza in the 2024/2025 season reported having a chronic medical condition

(FluSurv-NET 2025). Among US adults, chronic conditions are common among all ages

but become more prevalent with increasing age: in 2018 at least 1 chronic comorbidity

was estimated in 27.5% of adults 18 to 44 years, 63.4% of adults 45 to 64 years, and

87.6% of adults ≥65 years (Boersma et al 2020). According to the WHO, the prevalence

of multiple comorbidities increases most rapidly between the ages of 50 and 60 years in

high-income countries (WHO 2015). Thus, many individuals 50 to 64 years have an

increased risk of severe influenza complications.

3.2 Currently Available Influenza Vaccines

Vaccination is the most effective means of reducing the burden of influenza disease.

The vast majority of seasonal influenza vaccines are manufactured using egg-based

processes; the remaining supply is provided from cell-based processes or recombinant

technology (Taaffe et al 2025). Challenges facing current seasonal influenza vaccines

include limitations in effectiveness, reliable egg supply, variability in viral growth and

antigen yield, and challenges generating high-yield CVVs without introducing egg-

adaptive mutations. Effectiveness of current vaccines rarely exceeds 60% in the

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prevention of ILI and may be reduced when circulating influenza virus is poorly matched

to strains selected for vaccine inclusion (CDC 2024d). Between 2011-2025, influenza

vaccine effectiveness ranged from 8-65% in adults ages 50-64 years and 12-50% in

adults 65 years and older, with lowest effectiveness in years with the lowest percentage

of match between influenza vaccine strain and circulating influenza viruses (CDC

2026c; Russell et al 2024; Merced-Morales et al 2022; CDC 2023b; CDC2024e; CDC

2025c). To address such limitations in effectiveness, particularly in older, more

vulnerable populations, recombinant vaccines and egg-grown vaccines with higher

antigen content (HD) or adjuvanted formulations have been developed.

Licensure studies for an egg-grown HD vaccine and a recombinant vaccine showed

higher clinical efficacy in the prevention of ILI relative to SD vaccines. The egg-grown

HD vaccine demonstrated superior efficacy relative to SD vaccine based on an rVE of

24.2% (95% CI: 9.7, 36.5; the superiority criterion required LB 95% CI >9.1%)

(DiazGranados et al 2014). Similarly, the recombinant vaccine showed superior efficacy

relative to SD egg-grown vaccine based on an rVE of 30% (95% CI: 10, 47; the

superiority criterion required LB 95% CI >9%) (Dunkle et al 2017). This superior efficacy

of enhanced vaccines in the prevention of ILI relative to SD vaccines translated to

reduced rates of influenza-associated hospitalizations and deaths among adults 65

years and older. The adjuvanted influenza vaccine was licensed under accelerated

approval based on its elicited immune response, contingent upon verification of clinical

benefit in a post-authorization effectiveness trial (FLUAD 2025). Reduction in rates of

hospitalization and deaths in older adults resulted in recent preferential

recommendation for enhanced influenza vaccines in adults ≥65 years in some global

regions, including the US.

Although the egg-grown HD vaccines have improved efficacy, enhanced vaccines

nonetheless face challenges inherent to manufacturing processes and to the time

required from strain selection to vaccine production that can result in potential mismatch

between vaccine and circulating influenza strains (Bartley et al 2021; Gouma et al 2020;

Russell et al 2024). Egg-based vaccine production relies on an assured supply of

embryonated chicken eggs which can be vulnerable to supply challenges. Further,

sequence mutations often occur to adapt to growth in eggs or cell culture systems, and

these adaptation-mutations can lead to antigenic changes in produced vaccines

compared to circulating influenza virus. Vaccines that can deliver high efficacy using

reliable and rapid manufacturing processes are warranted.

3.3 Unmet Medical Need

Despite the availability of seasonal influenza vaccines, influenza continues to cause

substantial morbidity and mortality annually. Vaccine effectiveness is variable across

seasons but rarely exceeds 60% and is influenced by egg-adaptive changes and

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antigenic mismatch between vaccine and circulating strains. Egg-based manufacture,

which accounts for the overwhelming majority of influenza vaccine supply, including

enhanced influenza vaccines, is dependent on egg availability and efficient viral

propagation and often introduces egg-adaptive antigenic changes that can affect

vaccine immunogenicity. Consequently, advancing influenza vaccine platforms that do

not rely on egg-based manufacture has been emphasized as a public health priority.

Current manufacturing processes require strain selection ~7 months in advance of the

influenza season, which in some years results in a mismatch between vaccine

composition and circulating strains. Later strain selection enabled by rapid production

timelines and lack of reliance on egg-based production can reduce mismatch.

Reduced effectiveness is observed in certain populations, including older adults and

individuals with underlying medical conditions. Although enhanced vaccines (e.g. high-

dose, adjuvanted, and recombinant formulations) have demonstrated improved relative

efficacy and/or effectiveness compared with standard-dose vaccines, influenza-

associated hospitalizations and deaths persist, particularly among high-risk groups.

These factors indicate that limitations remain with current influenza prevention

strategies and support the need for improved vaccines that provide more consistent

protection with greater antigenic match and that can be manufactured with greater

flexibility and timeliness.

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4 MRNA-1010 OVERVIEW

Summary

• mRNA-1010 is an LNP-encapsulated trivalent influenza mRNA-based vaccine

encoding the full-length, membrane-bound influenza HA glycoproteins of the

3 seasonal influenza strains recommended by the WHO.

• The mRNA-based vaccine platform enables efficient manufacturing scale-up of

safe and effective vaccines without reliance on processes and substrates that

are specific to each pathogen.

• By avoiding replication in eggs or complex cell culture systems, the mRNA-

1010 vaccine enables greater manufacturing flexibility and high fidelity of

vaccine antigen to disease-causing virus.

4.1 Proposed Indication and Posology

The proposed indication for the mRNA-1010 vaccine is active immunization for the

prevention of disease caused by influenza virus subtypes A and type B represented in

the vaccine, in persons 50 years of age and older.

The approval for persons 65 years of age and older is proposed under accelerated

approval pathway based on clinical efficacy and immune response. Full approval for this

age group may be contingent upon confirmation of clinical benefit in a post-marketing

confirmatory trial.

mRNA-1010 is intended for intramuscular administration as a single dose of 37.5 μg

(12.5 μg per strain).

4.2 mRNA-1010 Description and Mechanism of Action

mRNA-1010 is an LNP-encapsulated trivalent influenza mRNA-based vaccine encoding

the full-length, membrane-bound influenza HA glycoproteins of the 3 seasonal influenza

strains recommended by the WHO for cell- or recombinant-based vaccines (A/H1N1,

A/H3N2, and B/Victoria-lineage). Each strain is present in an equal RNA mass ratio

(1:1:1), with a total RNA content of 37.5 μg per dose (12.5 μg RNA per strain). The RNA

encodes native A/H1N1 and A/H3N2 strain HA antigens. For the B/Victoria-lineage

strain, the RNA encoding the HA antigen includes point mutations in non-antigenic sites

to optimize antigenic expression.

Moderna’s mRNA-based vaccine platform is based on the principle and observations

that cells in vivo can take up mRNA, translate it, and then express encoded antigens.

The delivered mRNA does not enter the cellular nucleus, does not interact with the

genome, is nonreplicating, is expressed transiently, and does not persist in the body. To

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protect mRNA from rapid degradation in plasma and serum by ribonucleases and to aid

in mRNA uptake by cells, mRNA is delivered through encapsulation within a proprietary

LNP (Goody et al 2026; Sohn et al 2026).

After delivery into cells, the mRNA serves as a template for the synthesis of the

intended proteins. The HA proteins encoded by mRNA-1010 are translated and then

expressed on the cell surface. The membrane-bound HA glycoproteins of the encoded

influenza strains are recognized by immune cells as a foreign antigen, eliciting immune

responses, which contribute to protection against influenza.

Importantly, the precision and standardization of the mRNA-based vaccine platform

enable efficient manufacturing scale-up of safe and effective vaccines without reliance

on processes and substrates that are specific to each pathogen. Additionally, the

mRNA-based platform provides the capability to rapidly update the targeted viral strains

in response to changes in circulating viruses (and associated regulatory authority and

advisory organization recommendations for vaccines) and reliably manufacture the

updated vaccines at commercial scale. Furthermore, by avoiding replication in eggs or

complex cell culture systems, the mRNA-1010 vaccine avoids the need to obtain and

optimize CVVs for antigen yield and fidelity to the vaccine antigen.

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5 REGULATORY HISTORY

Summary

• Moderna engaged in iterative and constructive consultations with the FDA

throughout clinical development regarding the Phase 3 study design and

submission strategy.

• Following the successful completion of the Phase 3 efficacy trial in which

mRNA-1010 met all agreed upon prespecified primary endpoints, the BLA

seeking approval in adults ≥50 years of age was submitted in December 2025.

• The FDA accepted the BLA for filing via two approval pathways: traditional

approval for adults 50–64 years of age and accelerated approval for adults

≥65 years of age.

5.1 Regulatory Milestones

In February 2024, Moderna engaged with FDA regarding the Phase 3 efficacy study

design, including use of a licensed standard-dose influenza vaccine comparator. FDA

provided additional feedback during the August 2025 pre-BLA interaction, including

recommendations related to the comparator strategy and ISS. Moderna incorporated

this feedback into the BLA submission.

The mRNA-1010 BLA was submitted on December 5, 2025. Thereafter, FDA and

Moderna engaged in discussions regarding the most appropriate regulatory framework

for evaluating the evidence package across the proposed age groups. These

interactions focused on differences in the standard of care between adults 50–64 years

of age and adults 65 years of age and older, including the preferential use of enhanced

influenza vaccines in older adults.

Based on these interactions and the totality of available evidence, Moderna proposed a

differentiated regulatory approach consisting of traditional approval for adults 50–64

years of age and accelerated approval for adults 65 years of age and older.

This framework incorporated direct efficacy data from Study P304, comparative

immunogenicity data versus high-dose influenza vaccine, analyses supporting HAI

antibody responses as a surrogate endpoint reasonably likely to predict clinical benefit,

and a planned post-marketing confirmatory study. FDA accepted the BLA for filing on 17

February 2026, under the approval pathways described below.

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5.2 Approval Pathways

Moderna is seeking licensure of mRNA-1010 through a differentiated regulatory

approach that reflects the totality of evidence and the benefit-risk profile across age

groups.

• Traditional Approval (Adults 50–64 Years of Age):

For adults 50 through 64 years of age, Moderna seeks traditional approval based

on direct demonstration of clinical efficacy and safety from the pivotal Phase 3

study (mRNA-1010-P304). In this randomized, active-controlled trial, mRNA-

1010 met prespecified success criteria and demonstrated statistically significant

relative vaccine efficacy compared with a licensed standard-dose influenza

vaccine.

• Accelerated Approval (Adults ≥65 Years of Age):

For adults 65 years of age and older, Moderna seeks approval under the

Accelerated Approval pathway (21 CFR § 601.40 and § 601.41), recognizing the

high burden of influenza and unmet need in this population. This approach is

supported by data including clinical endpoint efficacy results from the ≥65-year

subgroup of the Phase 3 study (mRNA-1010-304), paralleled by consistently

higher or superior levels of HAI Ab among recipients of mRNA-1010 relative to

SD and HD comparators (Studies 304 and 303 C).

Specifically, mRNA-1010 meets the criteria for accelerated approval in

adults ≥65 years of age based upon the following:

  • Criterion 1 Serious Disease: Addresses an unmet need in serious

condition: Recent studies show that adults 65 years and older account for

50-70% of influenza-associated hospitalizations and 70-85% of influenza-

associated deaths in the US (CDC 2024b). Thus, while currently approved

enhanced vaccines provide benefit, there remains an important unmet

need in this population.

  • Criterion 2 Meaningful Advantage over Available Therapy: The

mRNA-1010 vaccine provides better potential vaccine antigenic fidelity

against a virus known for high seasonal variability, which is a unique

potential advantage of mRNA-1010 compared to currently available

vaccines. The combination of clinical endpoint efficacy, higher or superior

immunogenicity, and improved production flexibility and scalability

constitutes a meaningful advantage over current licensed influenza

vaccines.

  • Criterion 3 Surrogate Marker Reasonably Likely to Predict Clinical

Benefit: Among adults 65 years and older, mRNA-1010 demonstrated

higher HAI Ab responses relative to SD vaccine (Study 304) and superior

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HAI Ab responses relative to HD Fluzone (Study 303 C). HAI Ab levels are

routinely used in evaluation of licensed vaccines and have supported both

accelerated approvals and immunobridging approaches. The higher Ab

levels induced by mRNA-1010 are aligned with superior clinical endpoint

efficacy against ILI relative to SD vaccine in adults 65 years and older

(Study 304). Taken together, superior efficacy and robust HAI Ab levels

predict that mRNA-1010 will provide meaningful clinical benefit to adults

65 years and older.

  • Criterion 4 Post-Marketing Confirmatory Study: A post-marketing study

will be conducted to confirm the clinical benefit of mRNA-1010 in adults

≥65 years of age. The study will compare vaccine effectiveness of mRNA-

1010 with a licensed enhanced influenza vaccine in real-world settings

(see Section 10).

This proposed regulatory approach is designed to enable timely access to mRNA-1010

while ensuring that evidence supporting safety and effectiveness is appropriate for each

population.

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6 OVERVIEW OF mRNA-1010 CLINICAL DEVELOPMENT PROGRAM

Summary

• The mRNA-1010 clinical development program was initiated with Study 101,

which informed dose selection for subsequent Phase 3 studies.

• A total of four Phase 3 studies were conducted; the primary efficacy,

immunogenicity, and safety data supporting the BLA come from Phase 3

Studies 304 and 303C.

• Study 304 evaluated the safety, efficacy, and immunogenicity of mRNA-1010

vs SD comparator in adults ≥50 years of age.

o The primary efficacy endpoint was rVE of mRNA-1010 versus licensed

SD comparator to prevent the first episode of RT-PCR-confirmed ILI

caused by any influenza A or B strain.

• Study 303C evaluated the immunogenicity, reactogenicity, and safety of

mRNA-1010 vs a HD comparator in adults ≥65 years of age.

o The primary immunogenicity endpoint was the Day 29 geometric mean

titer (GMT) and proportion of participants reaching seroconversion.

• An ISS from >70,000 participants (across all mRNA-1010 Phase 3 studies

including studies 301, 302 and 303 Parts A and B) contributed to a

comprehensive evaluation of the safety of mRNA-1010.

6.1 Studies Supporting Development of mRNA-1010

The mRNA-1010 clinical development program includes 5 completed studies. Critical

data supporting the approval of mRNA-1010 for the prevention of ILI derive from the

Phase 1/2 Study 101 (informing dose selection); Phase 3 Study 304 (demonstrating

superior rVE against the primary endpoint, immunogenicity and safety); and Phase 3

Study 303C (immunogenicity and safety) (Figure 2). Other Phase 3 studies (Studies 301

and 302; conducted with an earlier version of mRNA-1010, and 303 Parts A and B,

conducted in participants across a younger age range) provide additional safety data

included in the analyses of the ISS.

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The primary efficacy, immunogenicity, and safety data supporting the BLA come from

Studies 304 and 303C:

• Study 304: Pivotal Phase 3 that evaluated the rVE, immunogenicity and safety of

mRNA-1010 trivalent influenza vaccine (TIV) 37.5 μg relative to licensed SD

comparator in 40,703 participants ≥50 years.

o rVE evaluation was based on surveillance throughout the 2024/2025

influenza season (ending 30 Apr 2025).

o Safety evaluation based on at least 6 months of safety follow-up for all

participants.

• Study 303C: Phase 3 study that evaluated Immunogenicity, reactogenicity and

safety of mRNA-1010 quadrivalent influenza vaccine (QIV) 50 μg relative to a

licensed HD comparator in participants ≥65 years in the US.

Figure 2: Key Studies Supporting mRNA-1010

Phase 1/2 Phase 3 Phase 3

Study 101 Study 304 Study 303C

N = 678 N = 40,703 N = 2,992

Adults ≥ 18 Years Adults ≥ 50 Years Adults ≥ 65 Years

Safety, immunogenicity, and Efficacy, safety, Safety and immunogenicity

dose selection of mRNA-1010 immunogenicity of mRNA-1010 of mRNA-1010 vs HD

vs placebo/SD influenza vaccine vs SD influenza vaccine influenza vaccine

Doses: 25, 50, 100, 200 µg Dose: 37.5 µg Dose: 50 µg

Quadrivalent (QIV) Trivalent (TIV) Quadrivalent (QIV)

Informed dose Demonstrated superior Demonstrated superior

for Phase 3 vaccine efficacy vs SD immunogenicity vs HD

influenza vaccine influenza vaccine

HD: high dose; SD: standard dose

To further characterize the mRNA-1010 safety profile in the intended population,

supportive safety data are provided from the pooled analysis (ISS) of data for SAEs,

deaths, and AESIs among 71,916 participants ≥50 years from all 4 Phase 3 studies

(Studies 301, 302, 303, and 304):

• ISS 50-64 years: 18,398 participants received mRNA-1010 (TIV or QIV), 18,396

participants received active SD comparator (TIV or QIV; 1 participant in this age

group was administered HD comparator [QIV]).

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• ISS ≥65 years: 17,567 participants received mRNA-1010 (TIV or QIV), 16,065

received active SD comparator (TIV or QIV), and 1,489 received HD comparator

(QIV).

6.1.1 Study mRNA-1010-101

The mRNA-1010 clinical development program was initiated with Study 101, which

informed dose selection for subsequent Phase 3 studies. Study 101 was a Phase 1/2,

randomized, stratified, observer-blind (participant- and assessor-blind), dose-ranging

safety, reactogenicity, and immunogenicity study. The study evaluated dosages

including 25, 50, 100, and 200 μg of a QIV formulation. Study 101 was conducted in the

US between 28 Jun 2021 and 27 Sep 2022. A dosage of 50 ug (12.5 ug/strain; QIV)

was selected based on overall assessment including HAI Ab levels.

Study results are summarized in Appendix Section 13.1.

6.1.2 Study mRNA-1010-304

6.1.2.1 Design Overview

Study 304 was a Phase 3, randomized, observer-blind (participant- and assessor-blind),

active-controlled study to investigate the safety, efficacy, and immunogenicity of

mRNA-1010 vs SD comparator in adults ≥50 years of age. The study was conducted in

11 countries across 301 study sites in the northern hemisphere from 16 Sep 2024 to 21

Aug 2025.

Participants were randomized in a 1:1 ratio to receive a single injection of either

mRNA-1010 (37.5 μg; 12.5 μg/strain) or SD comparator (Figure 3). Randomization was

stratified by age (50 – 64 or ≥65 years) and influenza vaccine status (received or not

received).

The use of a licensed SD influenza vaccine comparator in the pivotal efficacy study was

discussed with FDA. Although FDA recommended consideration of an enhanced

comparator, use of an enhanced influenza vaccine was not required. This approach is

consistent with the historical development paradigm for enhanced influenza vaccines,

which were established relative to SD influenza vaccines.

Because the study was conducted globally across regions with differing standards of

care, a licensed SD comparator was selected. Where enhanced vaccines were

preferentially recommended for older adults, these recommendations were explicitly

described in the informed consent. The study was reviewed and endorsed by the

applicable local regulators, institutional review boards, and ethics committees.

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Figure 3: Study 304 Design

mRNA-1010 (37.5 μg TIV) Stratified Randomization:

N = 20,402 mRNA Seasonal Influenza ▪ Age groups:

Vaccine Candidate

50-64, ≥ 65 years

1:1

Licensed SD Influenza Vaccine ▪ Influenza vaccine

40,805 Adults (45 μg TIV or 60 μg QIV) status in previous

Randomized Licensed Inactivated Standard Dose influenza season

≥ 50 Years N = 20,403 Seasonal Influenza Vaccine (received/not received)

Follow up through 6 months (Day 181) or end of influenza season,

whichever was longer

QIV: quadrivalent influenza vaccine; SD: standard dose; TIV: trivalent influenza vaccine

The study included up to 3 in-person visits (Screening, Day 1 [Baseline], and Day 29)

and up to 4 telephone contacts (Day 8, Month 3 [Day 91], Month 6 [Day 181], and the

End of the Influenza Season Visit). Additionally, in-person unscheduled visits were

conducted for participants who met prespecified criteria for protocol-defined respiratory

illness. All participants were prompted to complete the symptom eDiary twice weekly

from Day 1 (Baseline) to the end of the influenza season to capture the presence or

absence of respiratory symptoms. Protocol-defined ILI cases included in the efficacy

analysis required confirmatory nasopharyngeal swabs testing positive for influenza by

RT-PCR. The planned target accrual of 836 was exceeded following the end of the

2024/2025 season and the primary analysis of vaccine efficacy was performed at that

time (VE of mRNA-1010 relative to SD comparator).

The primary rVE endpoint was the first episode of RT-PCR-confirmed protocol-defined

ILI caused by any influenza A or B strain. Cases for primary rVE analysis were counted

starting 14 days after study injection and through the end of the influenza season.

The immunogenicity endpoints (secondary) measured HAI Ab GMT, SCR, and GMFR

(relative to Baseline) at Day 29 (MN Ab levels were also measured as exploratory

endpoints).

Reactogenicity was assessed based on solicited ARs collected for 7 days and all AE

were collected for 28 days after study injection. Safety follow-up (SAE, medically

attended adverse event (MAAE), AE leading to discontinuation, AESI, and deaths)

continued up to 6 months after study injection (and throughout the study for SAEs

assessed as related to study injection per Investigator).

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Efficacy, immunogenicity, and safety (solicited ARs and unsolicited AEs) results were

assessed by protocol-described subgroups, including age subgroups (50-64 years; ≥65

years; ≥75 years).

Endpoints and analysis sets are further described in Section 6.2.

6.1.3 Study mRNA-1010-303C

6.1.3.1 Design Overview

Study 303C was a Phase 3, randomized, observer-blind (participant- and assessor-

blind), active-controlled study that evaluated the immunogenicity, reactogenicity, and

safety of mRNA-1010 vs a HD comparator in adults 65 years and older. The study was

conducted in the US from 13 Nov 2023 to 24 Jun 2024.

Participants were randomized 1:1 to receive a single injection of mRNA-1010 (QIV

50 μg; 12.5 μg/strain) or HD comparator (Fluzone HD) (Figure 4). Randomization was

stratified by the previous influenza season vaccination status (received or not received).

The HD comparator was used in accordance with CDC recommendations for adults ≥65

years.

Figure 4: Study 303C Design

N = 1,502

mRNA-1010 (50 μg QIV)

1:1

2,992 Adults HD Vaccine* (QIV)

≥65 Years N = 1,490

▪ Non-inferiority and superiority assessed

▪ Follow up through 6 months (median 171 days)

*HD Vaccine - Fluzone HD, a licensed high-dose influenza vaccine containing 4x the antigen of a Standard-Dose

influenza vaccine

QIV = Quadrivalent influenza vaccine

In-person visits were scheduled for Screening and Days 1 (Baseline), 29 (Month 1), and

181 (Month 6 [subset of participants]). Participants provided blood samples for

assessment of immunogenicity parameters on Days 1, 29, and end of study (EOS)/

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Day 181. Solicited ARs and safety events were collected as described above for

Study 304.

Safety and reactogenicity were assessed based on unsolicited AEs and solicited ARs,

as described in Section 6.2.

6.2 Study Endpoints and Analysis Sets

6.2.1 Efficacy Endpoints

6.2.1.1 Study 304 Primary Efficacy Endpoint

In Study 304, the primary rVE endpoint was the first episode of RT-PCR-confirmed

protocol-defined ILI caused by any influenza A or B strain that begins at least 14 days

after study injection and through the end of the influenza season. Specifically, rVE

required a positive nasopharyngeal swab test for influenza by RT-PCR and both of the

following present ±7 days of the nasopharyngeal swab collection date:

• ≥1 systemic symptom (oral temperature >37.2°C [>99.0°F]), chills, feverish,

tiredness, headaches, or myalgia) AND

• ≥1 respiratory illness symptom (sore throat, cough, sputum production,

wheezing, or difficulty breathing).

The rVE of mRNA-1010 vs SD comparator was defined as the percent reduction in the

hazard of the primary endpoint (mRNA-1010 vs SD comparator) and was estimated as

100 × (1-hazard ratio)% using the stratified Cox proportional hazard model.

The primary objective was met if the noninferiority of mRNA-1010 vs SD comparator

was demonstrated (p-value for rejecting rVE ≤-10% or hazard ratio ≥1.1 was less than

the 1-sided 2.5% significance level). Subsequent testing was conducted in a sequential

manner for the superiority and highest superiority objectives (Figure 5). A hierarchical

testing strategy was applied for multiplicity adjustments over the primary and secondary

efficacy endpoints.

Figure 5: Sequential Testing of rVE Endpoint

Lower Bound (95% CI) of Relative Vaccine Efficacy

-12 -8 -6 -4 -2 2 4 6 8 10 12

-10 0 9.1

Non-Inferiority Superiority Highest Superiority

Lower bound Lower bound Lower bound

of 95% CI of 95% CI of 95% CI

> -10% > 0% > 9.1%

Sequential testing

CI: confidence interval

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6.2.1.2 Study 304 Secondary and Exploratory Efficacy Endpoints

The secondary efficacy endpoints included the first episode of RT-PCR-confirmed

modified CDC-defined ILI that began at least 14 days after study injection through the

end of the influenza season caused by any influenza A or B strains. This definition

required a temperature >37.2°C (>99.0°F) together with cough and/or sore throat.

Although older individuals (≥65 years) with ILI are less likely to manifest fever than

younger individuals, this endpoint was evaluated in a previous study of a licensed

enhanced influenza vaccine in this older population (DiazGranados et al 2014).

Exploratory endpoints were prespecified for case definitions including CDC-defined ILI

(unmodified; requiring body temperature ≥37.8°C [≥100°F] accompanied by cough

and/or sore throat), WHO-defined ILI (acute respiratory infection with body temperature

≥38.0°C [≥100.4°F] and cough with onset within the last 10 days), and influenza

infection regardless of presence of clinical symptoms. Additionally, an exploratory

endpoint of medically-attended influenza was evaluated in participants who sought

medical attention for a case of RT-PCR-confirmed protocol-defined ILI.

6.2.2 Immunogenicity Endpoints

In both Study 304 and Study 303C, HAI titers were measured at Baseline and Day 29

(testing for MN Ab was also performed as exploratory endpoints). HAI Ab assays are

strain-specific and reflect the vaccine-included influenza strains. The following influenza

strains were tested:

• Study 304: A H1N1/Wisconsin/67/2022, A H3N2/Massachusetts/18/2022, and

B/Connecticut/01/2021 (B-Victoria lineage) (WHO-recommended Northern

Hemisphere 2024/2025 strains)

• Study 303C: A H1N1/Wisconsin/67/2022, A H3N2 A/Darwin/6/2021,

B/Connecticut/01/2021 (B-Victoria lineage) and B/Phuket/3073/2013

(B/Yamagata-lineage) (WHO-recommended Northern Hemisphere 2023/2024

strains)

HAI Ab endpoints were reported as GMT, SCRs, and the proportion of participants with

HAI titers ≥1:40). The GMR and its corresponding 95% CI was estimated from the least

squares mean difference estimate and 95% CI obtained from the model on the log-

transformed scale using back-transformation. The corresponding 2-sided 95% CI of

GMR was provided to assess the difference in immune response between study

intervention groups on Day 29. SCR was defined as the proportion of participants with

either a Baseline HAI titer <1:10 and a post-Baseline titer ≥1:40 or a Baseline HAI titer

≥1:10 and a minimum 4-fold-rise in postbaseline HAI Ab titer.

For each study, strain-specific Ab results from each study group (i.e., mRNA-1010 vs

SD comparator for 304 and mRNA-1010 vs HD comparator for 303C) were compared.

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6.2.3 Safety Endpoints

Reactogenicity assessments (solicited ARs) were based on data collected up to Day 7

after injection and included evaluation of incidence, severity, and duration of the

following solicited ARs:

• Local ARs: injection site pain, injection site erythema (redness), injection site

swelling/induration (hardness), axillary (underarm) swelling or tenderness

ipsilateral to the side of the injection.

• Systemic ARs: fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting,

chills.

Safety assessments other than reactogenicity were performed in all participants who

received any dose of study injection and included all unsolicited AEs collected up to

28 days after injection and AEs leading to discontinuation, SAEs, AESIs, and MAAEs

collected through at least the Day 181/EOS visit (some studies had longer follow-up).

For the four Phase 3 studies, Investigators were instructed to report unsolicited AEs

within the following categories as AESIs:

• thrombocytopenia

• new onset of or worsening of Guillain-Barré syndrome, acute disseminated

encephalomyelitis, idiopathic peripheral facial nerve palsy (Bell’s palsy), or

seizures

• anaphylaxis associated with study injection

• myocarditis, pericarditis, or myopericarditis. Any suspected cases of myocarditis,

pericarditis, or myopericarditis were reviewed by the independent blinded

Cardiac Event Adjudication Committee (CEAC) to determine if they met CDC

case definitions for “probable” or “confirmed” events (Gargano et al 2021).

In addition, safety data from participants ≥50 years of age from all Phase 3 mRNA-1010

studies were pooled to provide a comprehensive analysis of safety across all studies,

complementing the analysis of safety from the pivotal 304 study and 303C. The ISS

includes SAEs, AESIs, and deaths from each of the 4 Phase 3 studies (301, 302, 303,

and 304).

6.2.4 Analysis Sets

Key analysis sets from Studies 304 and 303C included:

• Randomization Set: all participants who were randomized, regardless of the

participants’ treatment status in the study. Participants were analyzed according

to the study intervention group to which they were randomized.

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• Per Protocol Set (PP Set): all participants who received any study injection,

excluding those with important protocol deviations that could impact efficacy

assessments. The PP Set was only in Study 304 and used as the primary

analysis set for efficacy endpoints .

• Per-Protocol Immunogenicity Set/Subset (PPIS): participants who received the

planned TIV dose, had Baseline and Day 29 HAI Ab assessments with no

protocol deviations impacting immunogenicity assessment. The PPIS was used

for all analyses of immunogenicity in Studies 304 and 303C unless specified

otherwise. In Study 304, the PPIS was derived from a stratified random subset of

2400 participants from North America where TIV SD comparator was used,

stratified by age and prior year influenza vaccine status (balanced across strata).

Participants with RT-PCR-confirmed ILI between Baseline and Day 29 were

removed from the PPIS. All Study 303 C participants meeting PPIS criteria were

included in the analysis.

• Safety Set: All randomized participants who received any study injection; this

population was used for analyses of safety data other than solicited ARs.

• Solicited Safety Set/Subset: All participants in the Safety Set who contributed any

solicited AR data; this population was used for the analysis of solicited ARs.

• In Study 304, solicited ARs were collected from a subset of approximately

6000 participants assigned by the interactive response technology.

• ISS Set: a pooled safety set from the 4 Phase 3 studies (P301, P302, P303, and

P304) to evaluate the safety of mRNA-1010 (QIV or TIV) vs SD/HD comparators

(Fluarix SD TIV or QIV; Fluzone HD QIV). The ISS Set consists of all randomized

participants ≥50 years of age who received any study injection in Studies P301,

P302, P303, or P304. The ISS Set was used for all pooled analyses, and

participants were analyzed according to the actual study injection they received.

6.3 Enrolled Participants

6.3.1 Study 304 Study Population (≥50 Years)

6.3.1.1 Disposition

A total of 40,805 participants were randomized: 20,402 participants to mRNA-1010 and

20,403 participants to SD comparator (Table 2). More than 95% of participants

completed the study. The most common reasons for study discontinuation were lost to

follow-up and withdrawal of consent.

Analysis sets for the overall study population and age subgroups are presented in

Table 3.

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Table 2: Study 304 Participant Disposition (Randomization Set)

mRNA-1010

37.5 µg Active SD Comparator

(N=20,402) (N=20,403)

n (%) n (%)

Received injection 20349 (99.7) 20354 (99.8)

Completed the studya 19568 (95.9) 19622 (96.2)

Discontinued from the study 834 (4.1) 781 (3.8)

Reason for discontinuation of study

Lost to follow-up 435 (2.1) 420 (2.1)

Withdrawal of consent 261 (1.3) 255 (1.2)

Death 40 (0.2) 34 (0.2)

Physician decision 42 (0.2) 25 (0.1)

Randomized by mistake 17 (<0.1) 16 (<0.1)

Adverse event 3 (<0.1) 2 (<0.1)

Protocol deviation 2 (<0.1) 1 (<0.1)

SAR/reactogenicity event 0 0

Other 34 (0.2) 28 (0.1)

SAR: serious adverse reaction; SD: standard dose.

Numbers are based on planned vaccination group and percentages are based on the number of participants in the

Randomization Set.

a. Participants are considered to have completed the study if they completed either the Month 6 (Day 181) visit or

the End of the Influenza Season Visit, whichever occurred later.

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Table 3: Study 304 Analysis Sets

≥50 Years 50–64 Years ≥65 Years

mRNA- Active SD mRNA- Active SD mRNA- Active SD

1010 Comparat 1010 Comparat 1010 Comparat

37.5 µg or 37.5 µg or 37.5 µg or

Randomization Set 20402 20403 10645 10641 9757 9762

20178 20122 10542 10501 9637 9623

Per-Protocol Set, n (%)a

(98.9) (98.6) (99.0) (98.7) (98.8) (98.6)

Per-Protocol Immunogenicity Subset, 1167 1175 581 592 586 583

n (%)a,b (5.7) (5.8) (5.5) (5.6) (6.0) (6.0)

20350 20353 10624 10615 9726 9738

Safety Set, n (%)a

(99.7) (99.8) (99.8) (99.8) (99.7) (99.8)

3015 2997 1510 1502 1505 1495

Solicited Safety Subset, n (%)a, b

(14.8) (14.7) (14.2) (14.1) (15.4) (15.3)

SD: standard dose

a. Numbers are based on planned vaccination group and percentages are based on the number of participants in

the Randomization Set.

b. The Per-Protocol Immunogenicity Subset was based on a target of 2400 participants, and the Solicited Safety

Subset was based on a target of approximately 6000 participants.

6.3.1.2 Demographics and Baseline Characteristics

Baseline demographics and characteristics were balanced between the mRNA-1010

and SD comparator groups.

In the total Safety Set of 40,303 participants, the median age was 64.0 years (range: 50

to 97 years); 52.2% of participants were 50-64 years and 47.8% of participants were

≥65 years, including 11.6% of participants who were ≥75 years. Most (82.7%)

participants were White and identified as not Hispanic or Latino (88.2%); 56.8% were

female (Table 4).

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Table 4: Study 304 Demographics (Safety Set)

≥50 Years 50–64 Years ≥65 Years

mRNA-1010 Active SD mRNA-1010 Active SD mRNA-1010 Active SD

37.5 µg Comparator 37.5 µg Comparator 37.5 µg Comparator

(N=20350) (N=20353) (N=10624) (N=10615) (N=9726) (N=9738)

Age (years)

Median (min, max) 64.0 (50, 97) 64.0 (50, 96) 58.0 (50, 64) 58.0 (50, 64) 70.0 (65, 97) 70.0 (65, 96)

Sex, n (%)

Male 8834 (43.4) 8720 (42.8) 4,447 (41.9) 4,487 (42.3) 4,387 (45.1) 4,233 (43.5)

Female 11516 (56.6) 11633 (57.2) 6177 (58.1) 6128 (57.7) 5339 (54.9) 5505 (56.5)

Race, n (%)

White 16814 (82.6) 16811 (82.6) 8,423 (79.3) 8,419 (79.3) 8,391 (86.3) 8,392 (86.2)

Black or African

2687 (13.2) 2698 (13.3) 1,655 (15.6) 1,626 (15.3) 1,032 (10.6) 1,072 (11.0)

American

Asian 496 (2.4) 483 (2.4) 326 (3.1) 332 (3.1) 170 (1.8) 151 (1.6)

American Indian or

72 (0.4) 86 (0.4) 38 (0.4) 49 (0.5) 34 (0.3) 37 (0.4)

Alaska Native

Native Hawaiian or

20 (<0.1) 19 (<0.1) 38 (0.4) 49 (0.5) 3 (<0.1) 6 (<0.1)

Other Pacific Islander

Multiple 109 (0.5) 104 (0.5) 64 (0.6) 72 (0.7) 45 (0.5) 32 (0.3)

Other 51 (0.3) 55 (0.3) 38 (0.4) 39 (0.4) 13 (0.1) 16 (0.2)

Ethnicity, n (%)

Not Hispanic or Latino 17908 (88.0) 17985 (88.4) 9260 (87.2) 9257 (87.2) 13 (0.1) 16 (0.2)

Hispanic or Latino 2147 (10.6) 2067 (10.2) 1,222 (11.5) 1,211 (11.4) 925 (9.5) 856 (8.8)

Region, n (%)a

North America 14333 (70.4) 14340 (70.5) 7,034 (66.2) 7,022 (66.2) 7299 (75.1) 7319 (75.2)

Europe 5843 (28.7) 5833 (28.7) 3458 (32.5) 3460 (32.6) 2385 (24.5) 2373 (24.4)

East Asia 174 (0.9) 180 (0.9) 132 (1.2) 133 (1.3) 42 (0.4) 47 (0.5)

SD: standard dose

a. North America includes United States and Canada; Europe includes Belgium, Bulgaria, Estonia, Finland,

Georgia, Germany and United Kingdom; East Asia includes South Korea and Taiwan.

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6.3.2 Study 303C Study Populations (≥65 Years)

6.3.2.1 Disposition

A total of 3003 participants were included in the randomized set: 1507 participants in the

mRNA-1010 group and 1496 participants in the HD comparator group (Table 5). More

than 97% of participants completed the study. The most common reasons for study

discontinuation were lost to follow-up and withdrawal of consent.

Analysis sets are presented in Table 6.

Table 5: Study 303C Disposition of Participants (Randomization Set)

mRNA-1010

50 µg Active HD Comparator

(N=1507) (N=1496)

n (%) n (%)

Received injection 1504 (99.8) 1492 (99.7)

Completed the studya 1484 (98.5) 1456 (97.3)

Discontinued from the study 23 (1.5) 40 (2.7)

Reason for discontinuation of study

Lost to follow-up 10 (0.7) 25 (1.7)

Withdrawal by participant 9 (0.6) 10 (0.7)

Death 3 (0.2) 1 (<0.1)

Physician decision 1 (<0.1) 1 (<0.1)

Noncompliance with study procedure 0 1 (<0.1)

Other 0 2 (0.1)

HD: high dose

a. Participants are considered completed the study if they completed the final visit on Day 181 (Month 6).

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Table 6: Study 303C Analysis Sets

mRNA-1010 50 µg Active HD Comparator

Randomization Set 1507 1496

Per-protocol Immunogenicity Seta, n (%) 1425 (94.6) 1409 (94.2)

Safety Seta,b 1502 (99.7) 1490 (99.6)

Solicited Safety Seta,b, n (%) 1502 (99.7) 1490 (99.6)

HD: high dose; SD: standard dose

Participants who received more than 1 study injection (mRNA-1010 and/or active comparator) were considered

duplications and were only included in the Randomization Set.

1 participant randomized to Active HD Comparator received SD comparator and was only included in the

Randomization Set.

a. b. Safety Set and Solicited Safety Set were based on the actual study vaccine received.

6.3.2.2 Demographics and Baseline Characteristics

Baseline demographics and characteristics were balanced across study intervention

groups (Table 7).

In Study 303C Safety Set, 57.8% of participants were female, 77.9% were aged 65-74

years, and 22.1% were aged ≥75 years. The majority of participants identified as White

(82.7%), followed by Black or African American (15.3%).

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Table 7: Study 303C Baseline Demographics and Characteristics (Safety Set)

mRNA-1010 50 g Active HD Comparator

(N=1502) (N=1490)

Age (years)

Mean (standard deviation) 71.1 (4.92) 71.0 (4.95)

Median (min, max) 70.0 (65, 93) 70.0 (64, 93)

Age Group, n (%)

65-74 years 1176 (78.3) 1154 (77.4)

≥75 years 326 (21.7) 335 (22.5)

Sex, n (%)

Female 878 (58.5) 852 (57.2)

Male 624 (41.5) 638 (42.8)

Race, n (%)

White 1255 (83.6) 1220 (81.9)

Black or African American 224 (14.9) 235 (15.8)

Asian 10 (0.7) 10 (0.7)

American Indian or Alaska Native 4 (0.3) 9 (0.6)

Native Hawaiian or Other Pacific Islander 2 (0.1) 0

Multiple 2 (0.1) 6 (0.4)

Other 1 (<0.1) 4 (0.3)

Ethnicity, n (%)

Not Hispanic or Latino 1037 (69.0) 1021 (68.5)

Hispanic or Latino 450 (30.0) 454 (30.5)

HD: high dose

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7 EFFICACY AND IMMUNOGENICITY IN ADULTS 50–64 YEARS

Summary

• In Study 304, mRNA-1010 demonstrated superior efficacy vs SD comparator in

adults 50–64 year of age (rVE: 26.1% [95% CI: 12.3, 37.7]). rVE point

estimates by individual strain were consistent with the overall rVE; like other

licensed enhanced vaccines, greater uncertainty was observed for B/Victoria,

reflecting the smaller case numbers typical of the epidemiology in older adults.

• The efficacy advantage for mRNA-1010 was observed early and maintained

over a full influenza season.

• mRNA-1010 induced higher HAI Ab levels for each influenza strain, aligning

with the superior VE induced by mRNA-1010 relative to SD comparator against

clinical ILI.

7.1 Epidemiology Introduction

Adults 50-64 years of age represent a substantial and often underrecognized portion of

the influenza disease burden. In the US, adults 50-64 years consistently account for a

considerable proportion of influenza-related hospitalizations each season, with

hospitalization rates substantially higher than those observed in younger adults. During

the 2024/2025 season, the hospitalization rate among adults 50-64 years reached 223.3

per 100,000, nearly three times higher than that observed in adults 18-49 years (CDC

2026b).

The burden of influenza in adults 50-64 years is influenced by an increasing prevalence

of underlying medical conditions, which rises sharply beginning in midlife and are a key

driver of severe influenza outcomes. The higher comorbidity rate in this population

contributes to the increase in risk of complications, including hospitalization and death,

compared with younger adult populations.

In addition to clinical burden, influenza in adults 50-64 years has important societal

implications. Individuals in this age group represent a large proportion of the workforce,

and influenza-related illness contributes to absenteeism, reduced productivity, and

indirect economic costs. Together, these factors underscore the public health

importance of improving influenza prevention strategies in adults 50-64 years of age.

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7.2 Efficacy and Immunogenicity (50–64 years)

7.2.1 Relative Vaccine Efficacy

The primary analysis of efficacy for adults 50–64 years was performed in the subgroup

of 21,043 participants in the PP Set. A total of 536 PCR-confirmed ILI cases were

accrued and analysis of these yielded an rVE of 26.1% (95% CI: 12.3, 37.7; mRNA-

1010 relative to SD comparator).

Although success criteria were not designated for this supportive analysis, the point

estimate and LB of the 95% CI (12.3) illustrate that efficacy in the 50-64 year age group

is consistent with that in the overall population, which met the highest level of success

specified for the primary analysis: LB of the 95% CI >9.1% (Figure 6).

Figure 6: Study 304 Relative Vaccine Efficacy (PP Set 50–64 years)

Participants with RT-PCR confirmed

protocol-defined Influenza-Like Licensed SD

Illness (ILI) regardless of influenza Influenza Relative Vaccine Efficacy (%)

strain, % [n/N] mRNA-1010 Vaccines (95% CI)

26.6% (16.7, 35.4)

2.0% 2.8%

All Participants (≥50 years)

[411/20179] [557/20124]

2.2% 2.9% 26.1% (12.3, 37.7)

50-64 Years

[229 / 10,542] [307 / 10,501]

-25 -10 0 9.1 25 50

Noninferiority LB 95% CI > -10%

Superiority LB 95% CI > 0

Highest Superiority LB 95% CI > 9.1%

CI: confidence interval; LB: lower bound; PP: Per-Protocol; RT-PCR: reverse transcription polymerase chain reaction;

SD: standard dose

7.2.1.1 Results by Strain

PCR-confirmed ILI cases were accrued from each of the three vaccine-matched strains

(293 H1N1, 205 H3N2, and 32 B/Victoria). Results in participants 50–64 years were

generally aligned with those of the overall study population. Wider 95% CIs are evident

for rVE against B/Victoria, reflecting the relatively small number of B/Victoria cases

accrued. Nonetheless, the consistent rVE point estimates across strains is reassuring

(Figure 7).

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Figure 7: Study 304 Relative Vaccine Efficacy by Strain (PP Set 50–64 Years)

Licensed SD

50–64-Year-Old Influenza

Participants with ILI1 by mRNA-1010 Vaccines Relative Vaccine Efficacy (%)

influenza strain, % [n] (N = 10,542) (N = 10,501) (95% CI)

1.2% 1.6% 28.3% (9.5, 43.1)

Influenza A H1N1

[123] [170]

22.4% (-2.2, 41.1)

0.9% 1.1%

Influenza A H3N2

[90] [115]

23.0% (-54.8, 61.7)

0.1% 0.2%

Influenza B Victoria

[14] [18]

-75 -25 25 75

CI: confidence interval; ILI: influenza-like illness; PP: per-protocol; RT-PCR: reverse transcription polymerase chain

reaction; SD: standard dose

1. Based on RT-PCR-confirmed protocol-defined ILI

Efficacy of mRNA-1010 relative to SD comparator was maintained when alternate ILI

case definitions were assessed. Using case definitions tested in other studies of

enhanced vaccines that required the occurrence of temperature ≥37.2ºC (modified CDC

ILI case definition, DiazGranados et al 2014), rVE remained consistent (21.1%; 95% CI:

0.5, 37.4).

7.2.1.2 Analysis of Cumulative Incidence of Primary Endpoint over Time

Analysis of the cumulative incidence (Kaplan-Meier analysis) of efficacy endpoints over

time showed that the efficacy advantage for mRNA-1010 was observed early and

maintained over a full influenza season (Figure 8). Results in the 50–64-year age group

thus align with those of the overall 304 study group.

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Figure 8: Study 304 Cumulative Number of RT-PCR-confirmed Protocol-

Defined ILI Cases (PP Set 50–64 years)

700

rVE (95% CI) = 26.1% (12.3, 37.7)

600

500

400 Licensed SD

Cumulative Influenza Vaccines

Number of 300

Cases mRNA-1010

200

100

0

0 1 2 3 4 5 6 7 8

Time from Vaccination (Months)

Licensed Influenza At Risk 10501 10326 10200 10033 9827 9690 5096 937 0

Vaccines Events 0 8 63 144 238 291 306 307 307

At Risk 10542 10389 10282 10125 9925 9795 5168 961 0

mRNA-1010

Events 0 8 50 123 191 225 229 229 229

CI: confidence interval; ILI: influenza-like illness; PP: per-protocol; RT-PCR: reverse transcription polymerase chain

reaction; rVE: relative vaccine efficacy; SD: standard dose

Based on RT-PCR-confirmed protocol-defined ILI

7.2.2 Immunogenicity

Vaccine-induced HAI Ab responses were measured per strain, and vaccine-induced

responses were compared between study groups.

In participants 50–64 years, mRNA-1010 induced higher HAI Ab levels for each

influenza strain, aligning with the superior VE induced by mRNA-1010 relative to SD

comparator against clinical ILI. For each influenza strain, the point estimates for Day 29

GMR (mRNA-1010/SD comparator) were all >1.5 (95% CI LBs were >1.3) and SCR

differences ([mRNA-1010 SCR] – [SD comparator SCR]) were all positive (95% CI LBs

were >12%) (Figure 9).

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Figure 9: Study 304 HAI Ab GMR and SCR Differences at Day 29 (PPIS 50–64

Years)

GMR (95% CI) SCR Difference (95% CI)

of mRNA-1010 over SD of mRNA-1010 vs SD

1.81 (1.62, 2.02) 28.5 (23.0, 33.9)

Influenza A H1N1

1.53 (1.38, 1.71) 18.2 (12.5, 23.8)

Influenza A H3N2

1.61 (1.47, 1.75) 24.0 (18.7, 29.2)

Influenza B Victoria

1 2 3 0 25 50

ANCOVA: analysis of covariance; CI: confidence interval; GMR: geometric mean titer ratio; HAI Ab: hemagglutination

inhibition antibody; PPIS: Per-Protocol Immunogenicity Set; SD: standard dose; SRC: seroconversion rate

Number of participants in PPIS: 581 in mRNA-1010 group and 592 in active comparator group.

The log-transformed antibody levels are analyzed using an ANCOVA model with vaccination group as the

fixed variable, log-transformed Baseline HAI titers as a fixed covariate, adjusting for the randomization stratification

factor(s): age group (≥50 to <65 years and ≥65 years) and flu vaccine status in the previous influenza season

(received seasonal flu vaccine, did not receive seasonal flu vaccine). The model-based GMR, and its corresponding

95% CI are obtained by transforming the least square mean estimate and its CI back to the original scale for

presentation.

Rate of seroconversion is defined as the proportion of participants with either a Baseline HAI titer <1:10 and a

postbaseline titer ≥1:40 or a Baseline HAI titer ≥1:10 and a minimum 4-fold-rise in postbaseline HAI antibody titer;

95% CI is calculated using the Miettinen-Nurminen (score) method.

mRNA-1010-induced Ab measured by HAI assay are aligned with those measured by

MN assay. Neutralizing Ab levels showed same pattern of responses to those of the

HAI assay, with higher MN Ab levels for each influenza strain relative to SD comparator.

For each influenza strain, the point estimates for Day 29 GMR (mRNA-1010/SD

comparator) were all >1.5 (95% CI LBs were >1.2) (Figure 10).

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Figure 10: Study 304 MN Ab GMR at Day 29 (PPIS, Participants with MN Ab

Values 50–64 Years)

Geometric Mean Ratio (GMR)

(95% CI)

3.0 (2.1, 4.1)

Influenza A H1N1

1.5 (1.2, 1.7)

Influenza A H3N2

2.0 (1.6, 2.6)

Influenza B Victoria

1 2 4

Ab: antibody; ANCOVA: analysis of covariance; CI: confidence interval; MN: microneutralization assay; PPIS: Per-

protocol Immunogenicity Set

Number of participants in PPIS with MN values at Baseline and Day 29: 123 in mRNA-1010 and 128 in active

comparator.

The log-transformed antibody levels are analyzed using an ANCOVA model with vaccination group as the

fixed variable, log-transformed Baseline MN titers as a fixed covariate, adjusting for the randomization stratification

factor(s): age group (≥50 to <65 years and ≥65 years) and flu vaccine status in the previous influenza season

(received seasonal flu vaccine, did not receive seasonal flu vaccine). The model-based GMR, and its corresponding

95% CI are obtained by transforming the least square mean estimate and its CI back to the original scale for

presentation.

7.3 HAI Ab Levels and Protection

Consistent with the established relationship between HAI Ab responses and licensed

influenza vaccine protection from ILI, superior rVE in Study 304 was accompanied by

higher post-vaccination HAI Ab levels across influenza strains. Formal correlates-of-

protection analyses demonstrated an association between higher Day 29 HAI antibody

titers and reduced risk of ILI for influenza A/H1N1 and influenza A/H3N2 that reached

statistical significance, supporting the relevance of HAI responses as a marker

reasonably likely to predict clinical benefit (Table 16, Appendix 13.2). For influenza B, a

statistically significant association was not observed for either mRNA-1010 or the

licensed SD comparator, suggesting this was not specific to mRNA-1010. Interpretation

was limited in part by the relatively small number of influenza B cases and a marked

geographic concentration of cases, with most arising from a single country (Bulgaria).

Analyses excluding this geography showed a positive relationship between HAI Ab

levels and protection against B strains in both vaccine groups, although statistical

significance was not achieved because of the small number of cases (Table 17,

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Appendix 13.2). Taken together, the efficacy and immunogenicity data support a

consistent relationship between HAI Ab responses and protection, with the strongest

statistical evidence observed for the influenza A strains. Importantly, mRNA-1010 rVE

against influenza B was directionally consistent with overall rVE and consistent with rVE

observed for licensed enhanced vaccines. Overall, evidence remains consistent with a

protective effect despite the limitations of the influenza B correlates analyses. Additional

analyses are ongoing.

7.4 Conclusions: Efficacy and Immunogenicity, in Adults 50–64 Years

Data supporting the efficacy and immunogenicity of mRNA-1010 in adults 50–64 years

are summarized from 21,239 participants in Study 304. Pivotal clinical efficacy data

(Study 304) show that mRNA-1010 efficacy met superiority criteria (LB 95% CI >9.1%)

relative to SD comparator for the primary endpoint (PCR-confirmed ILI caused by any A

or B influenza strain). Results show consistent rVE point estimates across individual

influenza strains with more uncertainty for the B/Victoria, reflecting the smaller accrual

of influenza B cases typical of older populations and other enhanced vaccine trials.

Protection induced by mRNA-1010 is maintained through the full influenza season.

mRNA-1010 induced HAI Ab responses were higher than those of the comparator,

paralleling the superiority in clinical efficacy. The mRNA-1010 vaccine provides better

potential vaccine antigenic fidelity against a virus known for high seasonal variability

and antigenic drift. As such, mRNA-1010 offers unique potential advantages compared

to vaccines currently licensed for individuals 50 to 64 years of age.

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8 EFFICACY AND IMMUNOGENICITY IN ADULTS ≥65 YEARS

Summary

• Adults ≥65 years of age account for most influenza-related hospitalizations and

deaths in the US and globally.

• In Study 304, mRNA-1010 demonstrated superior efficacy vs SD comparator in

adults 65 years and older (rVE: 27.4% [95% CI: 12.1, 40.0]). rVE point

estimates by individual strain were consistent with the overall rVE; like other

licensed enhanced vaccines, greater uncertainty was observed for B/Victoria,

reflecting the smaller case number typical of the epidemiology in older adults.

• The efficacy advantage for mRNA-1010 was observed early and maintained

over a full influenza season.

• The superior rVE demonstrated by mRNA-1010 in Study 304 is paralleled by

levels of HAI Ab that are higher than those of the SD comparator in Study 304

and superior to those of a licensed HD comparator (Fluzone HD) in

Study 303C.

• The relationship between immunogenicity and efficacy observed in Study 304

provides confidence that the efficacy of mRNA-1010 will be similar compared

to HD vaccines.

8.1 Epidemiology Introduction

Adults ≥65 years of age bear the highest burden of severe influenza disease,

accounting for most influenza-related hospitalizations and deaths in the US and

globally. In recent years, adults ≥65 years have represented approximately 50-70% of

influenza-associated hospitalizations and 70-85% of influenza-associated deaths in the

US (CDC 2024b). During the 2024/2025 season, hospitalization and mortality rates in

adults ≥65 years reached 666.3 and 51.9 per 100,000, respectively, markedly

exceeding those observed in younger age groups (CDC 2026b).

The increased susceptibility to severe outcomes in older adults likely relates to factors

including immunosenescence and chronic comorbid conditions common to older adults.

Among individuals 65 years and older, enhanced influenza vaccines (e.g., high-dose,

adjuvanted, and recombinant formulations) have improved protection compared with

standard-dose vaccines. Nonetheless, a substantial residual disease burden remains.

As a result, adults ≥65 years remain a priority population for improved influenza

vaccines and prevention strategies aimed at reducing severe disease outcomes.

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8.2 Conclusions: Efficacy and Immunogenicity in Adults ≥65 Years

Data summarized in this report support approval of mRNA-1010 in adults 65 years and

older. Results show that mRNA-1010 met efficacy criteria for superiority relative to SD

comparator (Study 304; rVE LB 95% CI >9.1%) for the primary endpoint (PCR-

confirmed ILI caused by any A or B strain). Results show consistent rVE point estimates

across individual influenza strains, with more uncertainty for the B/Victoria, reflecting the

smaller accrual of influenza B cases typical of older populations and other enhanced

vaccine trials. Protection induced by mRNA-1010 is maintained through the full

influenza season. Superior efficacy of mRNA-1010 was paralleled by higher Ab

responses relative to SD comparator in Study 304 and by superior responses to those

induced by Fluzone HD in Study 303C. Taken together, results establish that mRNA-

1010 elicits protection in older adults of similar magnitude to that of enhanced vaccines.

The mRNA-1010 vaccine provides greater manufacturing flexibility and high antigenic

fidelity against a virus known for high seasonal variability and antigenic drift. As such,

mRNA-1010 offers unique potential advantages compared to vaccines currently

licensed for adults 65 years and older.

8.3 Efficacy and Immunogenicity (≥65 years)

8.3.1 Relative Vaccine Efficacy

The primary analysis of efficacy for adults ≥65 years was performed in the subgroup of

19,260 participants in the PP Set. A total of 432 PCR-confirmed ILI cases were accrued,

and analysis of these yielded an rVE of 27.4% (95% CI: 12.1, 40.0; mRNA-1010 relative

to SD comparator). Although success criteria were not designated for this supportive

analysis, the point estimate and LB of the 95% CI (12.1) illustrate that efficacy in the

≥65 year age group is consistent with that in the overall 304 study population (which

met the highest level of success specified for the primary analysis: LB of the 95% CI

>9.1%; Figure 11).

The level of rVE demonstrated by mRNA-1010 in the Phase 3 Study 304 is comparable

to levels of rVE against SD comparator that led to approval of enhanced influenza

vaccines for adults ≥65 years (i.e., Fluzone HD vs Fluzone; Flublok vs Fluarix). The

comparable level of rVE predicts that mRNA-1010 will deliver similar protection against

ILI in older adults to that of other enhanced vaccines.

Efficacy of mRNA-1010 relative to SD comparator was maintained when alternate ILI

case definitions were assessed. Using case definitions tested in other studies of

enhanced vaccines that required the occurrence of temperature ≥37.2 оC (modified CDC

ILI case definition), rVE remained consistent (26.7%; 95% CI: 4.4, 43.9).

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Figure 11: Study 304 Relative Vaccine Efficacy Influenza-Like Illness Events (PP

Set ≥65 Years)

Participants with RT-PCR confirmed

protocol-defined Influenza-Like Licensed SD

Illness (ILI) regardless of influenza Influenza Relative Vaccine Efficacy (%)

strain, % [n/N] mRNA-1010 Vaccines (95% CI)

26.6% (16.7, 35.4)

2.0% 2.8%

All Participants (≥50 years)

[411/20179] [557/20124]

1.9% 2.6% 27.4% (12.1, 40.0)

≥65 Years

[182/9637] [250/9623]

-25 -10 0 9.1 25 50

Noninferiority LB 95% CI > -10%

Superiority LB 95% CI > 0

Highest Superiority LB 95% CI > 9.1%

CI: confidence interval; LB: lower bound; PP per=protocol; RT-PCR: reverse transcription polymerase chain reaction;

SD: standard dose

8.3.1.1 Results by Strain

PCR-confirmed ILI cases were accrued in this age subgroup from each of the three

vaccine-matched strains (245 A/H1N1, 155 A/H3N2 and 28 B/Victoria). Results in

participants ≥65 years were generally aligned with those of the overall study population.

Wider 95% CIs are evident for rVE against B/Victoria, reflecting the relatively small

number of B/Victoria cases accrued. Nonetheless, the consistent rVE point estimates

across strains is reassuring (Figure 12).

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Figure 12: Study 304 Relative Vaccine Efficacy by Influenza Strain (PP Set ≥65

Years)

Licensed SD

≥65-Year-Old Influenza

Participants with ILI1 by mRNA-1010 Vaccines Relative Vaccine Efficacy (%)

influenza strain, % [n] (N = 9,637) (N = 9,623) (95% CI)

1.0% 1.5% 31.2% (11.2, 46.7)

Influenza A H1N1

[100] [145]

22.0% (-7.1, 43.2)

0.7% 0.9%

Influenza A H3N2

[68] [87]

35.5% (-37.7, 69.8)

0.1% 0.2%

Influenza B Victoria

[11] [17]

-75 -25 25 75

CI: confidence interval; ILI: influenza-like illness; PP: per-protocol; RT-PCR: reverse transcription polymerase chain

reaction; SD: standard dose

1. Based on RT-PCR-confirmed protocol-defined ILI

8.3.1.2 Analysis of Cumulative Incidence of Primary Endpoint over Time

Analysis of the cumulative incidence (Kaplan-Meier analysis) of efficacy endpoints over

time showed that the efficacy advantage for mRNA-1010 was observed early and

maintained over a full influenza season (Figure 13). Results in the ≥65-year age group

thus align with those of the overall 304 study group.

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Figure 13: Study 304 Cumulative Number of Influenza Cases (PP Set ≥65 years)

700

rVE (95% CI) = 27.4% (12.1, 40.0)

600

500

400

Cumulative Licensed SD

Number of 300

Influenza Vaccines

Cases 200 mRNA-1010

100

0

0 1 2 3 4 5 6 7 8

Time from Vaccination (Months)

Licensed Influenza At Risk 9623 9545 9463 9350 9200 9084 5002 995 0

Vaccines Events 0 8 41 106 190 241 249 250 250

At Risk 9637 9541 9483 9381 9226 9130 5012 1001 0

mRNA-1010

Events 0 6 24 82 142 175 180 182 182

CI: confidence interval; ILI: influenza-like illness; PP: per-protocol; RT-PCR: reverse transcription polymerase chain

reaction; rVE: relative vaccine efficacy; SD: standard dose

Based on RT-PCR-confirmed protocol-defined ILI

8.3.1.3 rVE Against ILI-associated Healthcare Encounters

Adults ≥65 years are at increased risk of more severe outcomes from ILI – including

hospitalization – than adults <65 years of age. As part of an exploratory analysis of

healthcare encounters associated with RT-PCR-confirmed protocol-defined ILI, results

showed fewer occurrences in the mRNA-1010 than for SD comparator group in

participants ≥65 years (Table 8). The rVE for participants seeking a higher level of care

(hospitalization, ER visit, or urgent care visit) was 65.1% (95% CI: 17.4, 85.2; 7 mRNA-

1010 vs 20 SD comparator participants). Even for categories with numbers too small to

calculate rVE, case splits were favorable for mRNA-1010 (hospitalization: 1 in mRNA-

1010 vs 4 in SD comparator; ER visits: 1 in mRNA-1010 vs 5 in SD comparator).

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Table 8: mRNA-1010 Reduces ILI-associated Healthcare Outcomes Relative to

Licensed SD Comparator in Adults ≥ 65 (Per-Protocol Set)

mRNA-1010 Comparator

N=9637 N=9623 rVE (95% CI)

Healthcare encounter 37 (0.4) 56 (0.6) 34.1 (0.1, 56.5)

Seek higher level of care 7 (0.10) 20 (0.2) 65.1 (17.4, 85.2)

Hospitalization 1 (<0.1) 4 (<0.1) n.c.

ER 1 (<0.1) 5 (<0.1) n.c.

Urgent care clinical visit 5 (<0.1) 12 (0.1) n.c.

Outpatient clinical visit 30 (0.3) 38 (0.4) 21.2 (-27.1, 51.2)

CI: confidence interval; ER: emergency room; ILI: influenza-like illness; nc: not calculated; rVE: relative

vaccine efficacy

n.c.: rVE not calculated due to too few cases.

8.3.2 Immunogenicity

The immunogenicity of mRNA-1010 in adults 65 years and older was evaluated in two

separate Phase 3 studies: Study 304 assessed the level of HAI Ab induced by mRNA-

1010 relative to SD comparator in adults ≥65 years in the pivotal study (1,169

participants); Study 303C tested mRNA-1010-induced responses for noninferiority

relative to HD comparator in adults ≥65 years (2,834 participants). HAI Ab levels were

measured for all vaccine-matched strains at Baseline and Day 29 in both studies.

8.3.2.1 Study 304 (mRNA-1010 vs SD comparator)

In adults ≥65 years in Study 304, analyses of GMR (mRNA-1010 Day 29 GMT/SD

comparator Day 29 GMT) showed that mRNA-1010 induced higher HAI Ab levels than

did the SD comparator (all point estimates ≥1.6 [95% CI LBs were ≥1.5]) (Figure 14).

Similarly, SCR differences ([mRNA-1010 SCR] – [SD comparator]) were all positive

(95% CI LBs were >16%). Accordingly, the higher induced HAI Ab responses were

congruent with the superior clinical efficacy of mRNA-1010 relative to SD comparator in

Study 304 participants ≥65 years.

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Figure 14: Study 304 HAI Ab GMR and SCR at Day 29 (PPIS ≥65 Years)

GMR (95% CI) SCR Difference (95% CI)

of mRNA-1010 over SD of mRNA-1010 vs SD

1.85 (1.66, 2.05) 27.6 (22.3, 32.6)

Influenza A H1N1

1.65 (1.49, 1.83) 21.8 (16.2, 27.3)

Influenza A H3N2

1.75 (1.60, 1.90) 26.7 (21.6, 31.7)

Influenza B Victoria

1 2 3 0 25 50

ANCOVA: analysis of covariance; CI: confidence interval; GMR: geometric mean titer ratio; HAI Ab: hemagglutination

inhibition antibody; PPIS: Per-Protocol Immunogenicity Set; SRC: seroconversion rate

Number of participants in PPIS: 586 in mRNA-1010 group and 583 in active comparator group.

The log-transformed antibody levels are analyzed using an ANCOVA model with vaccination group as the

fixed variable, log-transformed Baseline HAI titers as a fixed covariate, adjusting for the randomization stratification

factor(s): age group (≥50 to <65 years and ≥65 years) and flu vaccine status in the previous influenza season

(received seasonal flu vaccine, did not receive seasonal flu vaccine). The model-based GMR, and its corresponding

95% CI are obtained by transforming the least square mean estimate and its CI back to the original scale for

presentation.

Rate of seroconversion is defined as the proportion of participants with either a Baseline HAI titer <1:10 and a

postbaseline titer ≥1:40 or a Baseline HAI titer ≥1:10 and a minimum 4-fold-rise in postbaseline HAI antibody titer;

95% CI is calculated using the Miettinen-Nurminen (score) method.

mRNA-1010-induced Ab measured by HAI assay are aligned with those measured by

MN assay. Neutralizing Ab levels showed same pattern of responses to those of the

HAI assay, with higher MN Ab levels for each influenza strain relative to SD comparator.

For each influenza strain, the point estimates for Day 29 GMR (mRNA-1010/SD

comparator) were all >1.3 (95% CI LBs were >1.0) (Figure 15).

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Figure 15: Study 304 MN Ab GMR at Day 29 (PPIS Participants with MN Ab

Values ≥65 Years)

Geometric Mean Ratio (GMR)

(95% CI)

2.7 (1.9, 3.7)

Influenza A H1N1

1.3 (1.1, 1.5)

Influenza A H3N2

2.2 (1.7, 2.8)

Influenza B Victoria

1 2 4

ANCOVA: analysis of covariance; CI: confidence interval; GMR: geometric mean titer ratio; MN Ab:

microneutralization antibody; PPIS: Per-Protocol Immunogenicity Set

Number of participants in PPIS with MN values at Baseline and Day 29: 124 in mRNA-1010 and 125 in active

comparator.

The log-transformed antibody levels are analyzed using an ANCOVA model with vaccination group as the

fixed variable, log-transformed Baseline MN titers as a fixed covariate, adjusting for the randomization stratification

factor(s): age group (≥50 to <65 years and ≥65 years) and flu vaccine status in the previous influenza season

(received seasonal flu vaccine, did not receive seasonal flu vaccine). The model-based GMR, and its corresponding

95% CI are obtained by transforming the least square mean estimate and its CI back to the original scale for

presentation.

8.3.2.2 Study 303C (mRNA-1010 vs HD comparator)

Immunogenicity results from Study 303C build further on those of the pivotal 304

efficacy study. In Study 303C, mRNA-1010-induced HAI Ab levels that were superior to

HD comparator based on prespecified success criteria across all vaccine-matched

strains (i.e., Day 29 GMR 97.5% CI LB >1.0 and SCR difference 97.5% CI LB >0% for

all 8 co-primary endpoints; Figure 16).

An analysis of the correlation between induced HAI and occurrence of ILI confirms that

mRNA-1010 induces HAI Ab and that increased Ab levels correspond with reduction in

ILI. This pattern echoes that of conventional influenza vaccine (i.e. SD comparator), and

as such supports the use of HAI to help infer effectiveness of mRNA-1010 (as with

conventional vaccines). The induction of superior HAI Ab levels relative to HD

comparator (Study 303C), together with direct clinical efficacy of mRNA-1010 in adults

≥65 years (Study 304), infer the effectiveness of mRNA-1010 in older adults.

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Figure 16: Study 303C GMR and SCR at Day 29 (PPIS ≥65 Years)

Geometric Mean GMR of mRNA-1010 over HD Vaccine Seroconversion % SCR difference between

Titer ratio (GMR) (97.5% CI) rate (SCR) mRNA-1010 – HD Vaccine (97.5% CI)

H1N1 1.34 (1.24, 1.45) H1N1 13.42 (9.27, 17.52)

Noninferiority

Noninferiority

Superiority

H3N2 1.21 (1.12, 1.32) H3N2 8.59 (4.38, 12.76)

B/Victoria 1.25 (1.18, 1.33) B/Victoria Superiority 9.67 (6.04, 13.29)

B/Yamagata 1.14 (1.08, 1.21) B/Yamagata 5.88 (2.33, 9.42)

0.667 1 1.5 2 -10 0 10 20 30 40

ANCOVA: analysis of covariance; CI: confidence interval; GMR: geometric mean titer ratio; HAI: hemagglutination

inhibition; HD: high dose; PPIS: Per-Protocol Immunogenicity Set; SRC: seroconversion rate

Number of participants in PPIS: 1425 in mRNA-1010 group and 1409 in active comparator group.

The log-transformed antibody levels are analyzed using an ANCOVA model with vaccination group as the

fixed variable, log-transformed Baseline HAI titers as a fixed covariate, adjusting for the randomization stratification

factor(s): age group (≥50 to <65 years and ≥65 years) and flu vaccine status in the previous influenza season

(received seasonal flu vaccine, did not receive seasonal flu vaccine). The model-based GMR, and its corresponding

95% CI are obtained by transforming the least square mean estimate and its CI back to the original scale for

presentation.

Rate of seroconversion is defined as the proportion of participants with either a Baseline HAI titer <1:10 and a

postbaseline titer ≥1:40 or a Baseline HAI titer ≥1:10 and a minimum 4-fold-rise in postbaseline HAI antibody titer;

95% CI is calculated using the Miettinen-Nurminen (score) method.

The parallel between Ab levels measured by HAI assay or by MN assay was evident as

well in comparison to HD comparator. Neutralizing Ab levels were superior to HD

comparator for each influenza strain, with the point estimates for Day 29 GMR (mRNA-

1010/HD comparator) all >1.3 (95% CI LBs were >1.09) (Figure 17).

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Figure 17: Study 303C MN Ab GMR at Day 29 (PPIS, Participants with MN Ab

Values ≥65 Years)

Geometric Mean Ratio (GMR)

(95% CI)

1.75 (1.40, 2.18)

Influenza A H1N1

1.32 (1.09, 1.59)

Influenza A H3N2

1.30 (1.10, 1.55)

Influenza B Victoria

1 2 4

Ab: antibody; ANCOVA: analysis of covariance; CI: confidence interval; MN: microneutralization assay; PPIS: Per-

protocol Immunogenicity Set

Number of participants in PPIS with MN values at Baseline and Day 29: 250 in mRNA-1010 and 250 in active

comparator.

The log-transformed antibody levels are analyzed using an ANCOVA model with vaccination group as the

fixed variable, log-transformed Baseline MN titers as a fixed covariate, adjusting for the randomization stratification

factor(s): age group (≥50 to <65 years and ≥65 years) and flu vaccine status in the previous influenza season

(received seasonal flu vaccine, did not receive seasonal flu vaccine). The model-based GMR, and its corresponding

95% CI are obtained by transforming the least square mean estimate and its CI back to the original scale for

presentation.

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9 OVERVIEW OF SAFETY IN ADULTS ≥50 YEARS

Summary

• Safety was evaluated in:

o Pivotal Study 304, which evaluated mRNA-1010 TIV (37.5 μg) vs SD

comparator in 40,703 adults ≥50 years

o Study 303C, which evaluated mRNA-1010 QIV (50 μg) vs HD

comparator in 2,992 adults ≥65 years

o Integrated safety data from participants ≥50 years in the 4 completed

Phase 3 studies, in which 71,916 adults received mRNA-1010 TIV or

QIV (12.5 μg per strain) or SD/HD comparator (TIV or QIV) and had at

least 6 months of safety follow-up.

• Rates of reported solicited local and systemic ARs were higher in the mRNA-

1010 group than in SD or HD comparator groups, but most solicited ARs were

Grade 1 or 2 in severity, transient, and resolved without medical attention.

Injection site pain was the most common solicited local AR, and fatigue was

the most common solicited systemic AR.

• No safety concerns were identified based on review of unsolicited AEs from

individual Phase 3 studies nor based on review of an integrated summary

safety analysis of deaths, SAEs, and AESIs, from a dataset of 35,965 mRNA-

1010-recipients ≥50 years (17,567 of whom were ≥65 years).

• Unsolicited AEs within 28 days and during the entire study period were

reported in similar proportions of participants in each treatment group.

Incidence of fatal SAEs and other SAEs was generally balanced between the

pooled study intervention groups.

The safety and reactogenicity profile of a single injection of mRNA-1010 (12.5 μg per

strain) is clinically acceptable in adults ≥50 years.

9.1 Safety Database

The safety profile for mRNA-1010 is primarily based on the following data sources:

  • Reactogenicity data from Study 304 in adults ≥ 50 years of age forms the

basis for reactogenicity evaluation. Data are supplemented with results

from Study 303C which evaluated mRNA-1010 relative to HD comparator

in adults ≥ 65 years of age.

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  • Unsolicited AEs from Study 304 and Study 303C.
  • A pooled analysis (ISS) of data for SAEs, deaths, and AESIs among

71,916 participants ≥50 years from all 4 Phase 3 studies.

9.2 Reactogenicity

In Study 304 and in Study 303C, most solicited local and systemic ARs were Grade 1 or

Grade 2 in severity, transient, and reported by a greater proportion of participants in the

mRNA-1010 group compared with the comparator group (Table 9 and Table 10). The

most frequently reported solicited local AR was injection site pain and the most

frequently reported solicited systemic AR was fatigue in the mRNA-1010 group and in

the SD and HD comparator groups. Grade 3 solicited local and systemic ARs were

more frequent in the mRNA-1010 group than in the SD or HD comparator groups, but

the overall incidence was low, these were transient and did not require medical

attention. No Grade 4 solicited ARs were reported in Study 304. For any solicited local

or any solicited systemic AR, the median onset day was Day 2 in the mRNA-1010 group

and Day 1 or Day 2 in the SD and HD groups. The median duration for any solicited

local or any solicited systemic AR was 2 days in the mRNA-1010 and HD groups and 1

or 2 days in the SD group. Rates of any Grade 3 or 4 solicited local or systemic ARs

were higher after enhanced influenza vaccine (i.e., for HD comparator in Study 303C)

than SD vaccine comparator in 304. Like other vaccines delivering superior VE relative

to that provided by SD vaccines, mRNA-1010 also results in higher levels of transient

Grade 3 reactogenicity. In summary, although mRNA-1010 is associated with higher

rates of transient reactogenicity than comparator influenza vaccines, the absolute

incidence of Grade 3 reactions remained low (0.3%–1.5% for local reactions and 0.2%–

3.2% for systemic reactions), reactions generally were short-lived with median durations

of approximately 1 day and did not require medical attention. In analyses of solicited

local and systemic ARs by age subgroups (50-64 and ≥65 years) from Study 304, in

both the mRNA-1010 and SD comparator groups, reporting of solicited ARs was

numerically lower in the older age groups than in younger age groups.

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Table 9: Study 304 and Study 303C Summary of Participants with Solicited

Local ARs within 7 Days After Injection by Maximum Toxicity Grade (Solicited

Safety Subset/Set)

Study 304 (≥50 Years) Study 303C (≥65 Years)

mRNA-1010 Active (SD) mRNA-1010 Active (HD)

37.5 μg Comparator 50 μg Comparator

(N=3015) (N=2997) (N=1502) (N=1490)

n (%) n (%) n (%) n (%)

Solicited local ARs – N1 3015 2997 1502 1490

Anya 2034 (67.5) 961 (32.1) 993 (66.1) 580 (38.9)

95% CIb 65.8, 69.1 30.4, 33.8 63.7, 68.5 36.4, 41.5

Grade 3 51 (1.7) 4 (0.1) 36 (2.4) 12 (0.8)

Grade 4 0 0 0 0

Pain – N1 3015 2997 1502 1490

Anya 1985 (65.8) 894 (29.8) 971 (64.6) 547 (36.7)

Grade 3 27 (0.9) 1 (<0.1) 23 (1.5) 6 (0.4)

Grade 4 0 0 0 0

Erythema (redness) – N1 3015 2997 1502 1489

Anya 117 (3.9) 38 (1.3) 42 (2.8) 20 (1.3)

Grade 3 10 (0.3) 2 (<0.1) 6 (0.4) 3 (0.2)

Grade 4 0 0 0 0

Swelling/induration (hardness) –

3015 2997 1502 1489

N1

Anya 172 (5.7) 45 (1.5) 67 (4.5) 25 (1.7)

Grade 3 9 (0.3) 4 (0.1) 6 (0.4) 2 (0.1)

Grade 4 0 0 0 0

Axillary swelling or tenderness –

3015 2997 1502 1489

N1

Anya 520 (17.2) 184 (6.1) 252 (16.8) 128 (8.6)

Grade 3 10 (0.3) 1 (<0.1) 8 (0.5) 6 (0.4)

Grade 4 0 0 0 0

AR: adverse reaction; CI: confidence intervals; HD: high dose; SD: standard dose. N = number of exposed

participants who reported the event on any day within 7 days of study injection.

A Any = Grade 1 or higher.

B 95% CI was calculated using the Clopper-Pearson method.

Numbers are based on actual group and percentages are based on the number of exposed participants who

submitted any data for the event (N1).

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Table 10: Study 304 and Study 303C Summary of Participants with Solicited

Systemic ARs Within 7 Days After Injection by Maximum Toxicity Grade (Solicited

Safety Subset/Set)

Study 304 (≥50 Years) Study 303C (≥65 Years)

mRNA-1010 Active (SD) mRNA-1010 Active (HD)

37.5 μg Comparator 50 μg Comparator

(N=3015) (N=2997) (N=1502) (N=1490)

n (%) n (%) n (%) n (%)

Solicited systemic ARs – N1 3015 2997 1502 1489

Anya 1750 (58.0) 970 (32.4) 920 (61.3) 490 (32.9)

95% CIb 56.3, 59.8 30.7, 34.1 58.7, 63.7 30.5, 35.4

Grade 3 167 (5.5) 27 (0.9) 101 (6.7) 25 (1.7)

Grade 4 0 0 2 (0.1) 0

Fever – N1 3001 2992 1502 1488

Anya 174 (5.8) 26 (0.9) 127 (8.5) 21 (1.4)

Grade 3 17 (0.6) 3 (0.1) 9 (0.6) 1 (<0.1)

Grade 4 0 0 2 (0.1) 0

Headache – N1 3015 2997 1502 1489

Anya 1140 (37.8) 538 (18.0) 592 (39.4) 258 (17.3)

Grade 3 59 (2.0) 10 (0.3) 35 (2.3) 10 (0.7)

Grade 4 0 0 0 0

Fatigue – N1 3015 2997 1502 1489

Anya 1360 (45.1) 609 (20.3) 669 (44.5) 293 (19.7)

Grade 3 97 (3.2) 13 (0.4) 52 (3.5) 12 (0.8)

Grade 4 0 0 0 0

Myalgia – N1 3015 2997 1502 1489

Anya 1067 (35.4) 348 (11.6) 626 (41.7) 239 (16.1)

Grade 3 76 (2.5) 7 (0.2) 48 (3.2) 11 (0.7)

Grade 4 0 0 0 0

Arthralgia – N1 3015 2997 1502 1489

Anya 839 (27.8) 317 (10.6) 529 (35.2) 210 (14.1)

Grade 3 57 (1.9) 6 (0.2) 35 (2.3) 11 (0.7)

Grade 4 0 0 0 0

Nausea/ vomiting – N1 3015 2997 1502 1489

Anya 259 (8.6) 102 (3.4) 192 (12.8) 63 (4.2)

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Grade 3 5 (0.2) 2 (<0.1) 4 (0.3) 3 (0.2)

Grade 4 0 0 0 0

Chills – N1 3015 2997 1502 1489

Anya 688 (22.8) 129 (4.3) 443 (29.5) 115 (7.7)

Grade 3 62 (2.1) 4 (0.1) 18 (1.2) 5 (0.3)

Grade 4 0 0 0 0

AR: adverse reaction; CI: confidence intervals; HD: high dose; SD: standard dose. N = number of exposed

participants who reported the event on any day within 7 days of study injection.

a. Any = Grade 1 or higher.

b. 95% CI was calculated using the Clopper-Pearson method.

Numbers are based on actual group and percentages are based on the number of exposed participants who

submitted any data for the event (N1).

9.2.1 Study 304

9.2.1.1 Solicited Local Adverse Reactions

In Study 304, solicited local ARs were reported more frequently in the mRNA-1010

group compared with the SD comparator group (Table 9). Injection site pain was the

most frequently reported solicited local AR. Most solicited local ARs were Grade 1 or

Grade 2 in severity and transient in duration. Grade 3 solicited local ARs were more

frequently reported in the mRNA-1010 group than in the SD comparator groups, but

these too were transient and did not lead participants to seek medical attention. No

Grade 4 solicited local ARs were reported in Study 304. The median onset day of any

solicited local AR was Day 2 in both treatment groups. The median duration of any

solicited local ARs was 2 days in the mRNA‑1010 group and 1 day in the SD

comparator group. The median duration of Grade 3 solicited local ARs was 1 day in the

mRNA-1010 group and 1.5 days in the SD comparator group.

9.2.1.2 Solicited Systemic Adverse Reactions

In Study 304, most solicited systemic ARs were Grade 1 or Grade 2 in severity,

transient, and reported more frequently in the mRNA-1010 group compared with the SD

comparator group (Table 10). The most frequently reported solicited systemic AR was

fatigue followed by headache and myalgia. Grade 3 solicited systemic ARs were more

frequently reported in the mRNA-1010 group than in the SD comparator groups, but

these too were transient and generally did not lead participants to seek medical

attention. No Grade 4 solicited systemic ARs were reported in Study 304. The median

onset for any solicited systemic ARs was Day 2 in both study intervention groups. The

median duration of any solicited systemic ARs was 2 days in both study groups. The

median duration of Grade 3 solicited systemic ARs was 1 day in both groups.

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9.2.1.3 Solicited Adverse Reactions by Age Subgroup

Overall, the reactogenicity profile was generally similar across age groups. In both the

mRNA-1010 and SD comparator groups, reporting of solicited ARs was numerically

lower in the older age groups than in younger age groups (see Appendix Table 18 and

Table 19).

9.2.2 Study 303 Part C

9.2.2.1 Solicited Local Adverse Reactions

In Study 303C, solicited local ARs were reported more frequently in the mRNA-1010

group than the HD comparator group (Table 9). As in Study 304, injection site pain was

the most frequently reported solicited local AR. Most solicited local ARs were Grade 1

or Grade 2 in severity and transient in duration. Grade 3 solicited local ARs were more

frequently reported in the mRNA-1010 group than in the HD comparator groups, but

these were transient with a median duration of 1 day. No Grade 4 solicited local ARs

were reported in Study 303C. The median onset for any solicited local ARs was Day 2

in the mRNA-1010 group and Day 1 in the HD comparator group. The median duration

of any solicited local AR was 2 days in both study groups.

9.2.2.2 Solicited Systemic Adverse Reactions

In Study 303C, most solicited systemic ARs were Grade 1 or Grade 2 in severity,

transient, and reported more frequently in the mRNA-1010 group compared with the HD

comparator group (Table 10). The most frequently reported solicited systemic AR was

fatigue followed by myalgia and headache. Grade 3 solicited systemic ARs were more

frequently reported in the mRNA-1010 group than in the HD comparator groups, but

these were transient with a median duration of 1 day. Two participants in the mRNA-

1010 group had Grade 4 solicited systemic ARs of fever that lasted for 1 day and did

not cause the participants to seek medical attention. No other Grade 4 solicited

systemic ARs were reported in Study 303C. The median onset for any solicited

systemic ARs was Day 2 in both study intervention groups. The median duration of any

solicited systemic ARs was 2 days in both groups.

9.3 Unsolicited Adverse Events

9.3.1 Study 304

9.3.1.1 Unsolicited Adverse Events Up to 28 days after Injection

Overall, and across each of the unsolicited AE categories, the proportion of participants

with unsolicited AEs up to 28 days after injection was generally balanced between the

study groups (Table 11). AEs assessed as related to study injection by the Investigator

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were reported in 98/20,350 (0.5%) of mRNA-1010-recipients and 49/20,353 (0.2%) of

SD comparator recipients. The difference in the frequency of related AEs between study

groups was primarily driven by nonserious AEs suggestive of reactogenicity, which are

identical to or similar to solicited AR terms and that occurred more frequently within 7

days after injection in the mRNA-1010 group than in the SD comparator group. By

referred term (PT), the most frequently reported unsolicited AEs assessed by the

Investigator as related to study injection in the mRNA-1010 group and the SD

comparator group included malaise (10 vs 3), dizziness (9 vs 3), blood pressure

increased (6 vs 4), hypertension (4 vs 7), and urticaria (1 vs 6) (all <0.1%).

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Table 11: Study 304 Overall Summary of Unsolicited AEs Up to 28 Days After

Injection (Safety Set)

mRNA-1010 37.5 µg Active Comparator

(N=20,350) (N=20,353)

n (%) n (%)

Participants with unsolicited AEs up to 28 days after injection, regardless of relationship to study

vaccination

All 1204 (5.9) 1167 (5.7)

Serious 92 (0.5) 92 (0.5)

Fatal 7 (<0.1) 9 (<0.1)

Medically attended 775 (3.8) 782 (3.8)

Leading to study discontinuation 1 (<0.1) 0

Severe/≥Grade 3 75 (0.4) 77 (0.4)

AESI per Investigator assessment 4 (<0.1) 3 (<0.1)

Participants with unsolicited AEs up to 28 days after injection, related to study vaccination

All 98 (0.5) 49 (0.2)

Serious 2 (<0.1) 1 (<0.1)

Fatal 0 0

Medically attended 18 (<0.1) 12 (<0.1)

Leading to study discontinuation 0 0

Severe/≥Grade 3 1 (<0.1) 1 (<0.1)

AESI per Investigator assessment 0 1 (<0.1)

AE: adverse event; AESI: adverse event of special interest; SAE: serious adverse event. Any solicited local or

systemic adverse reactions that meets the definition of an SAE are considered as AE. Numbers are based on actual

vaccination group and percentages are based on the number of participants in the Safety Set.

Overall, rates of unsolicited AEs by system organ class (SOC) were comparable

between the study intervention groups. In both study intervention groups, the most

frequently reported unsolicited AEs up to 28 days after injection by SOC were infections

and infestations (1.4% in each group), musculoskeletal and connective tissue disorders

(0.8% vs 0.7%), injury, poisoning and procedural complications (0.7% in each group),

and gastrointestinal disorders (0.6% in each group); unsolicited AEs occurred in ≤0.5%

of participants in each study intervention group across all other SOCs. The most

frequently reported unsolicited AEs by PT in both study intervention groups included

hypertension (0.3% in each group), COVID-19 (0.3% in each group), urinary tract

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infection (0.2% vs 0.3%), and diarrhoea (0.2% in each group); all other unsolicited AEs

by PT occurred in <0.2% of participants in each study intervention group.

9.3.1.2 Unsolicited Adverse Events Throughout the Study

Throughout the study, the proportions of participants with unsolicited AEs overall and

across AE categories were generally similar between the groups as shown in Table 12.

Table 12: Study 304 Overall Summary of Unsolicited AEs Throughout the

Study (Safety Set)

mRNA-1010 37.5 µg Active Comparator

(N=20,350) (N=20,353)

n (%) n (%)

Participants with unsolicited AEs throughout the study, regardless of relationship to study vaccination

Serious 455 (2.2) 392 (1.9)

Fatal 40 (0.2) 34 (0.2)

Medically attended 2509 (12.3) 2439 (12.0)

Leading to study discontinuation 3 (<0.1) 1 (<0.1)

AESI per Investigator assessment 17 (<0.1) 15 (<0.1)

Participants with unsolicited AEs throughout the study, related to study vaccination

Serious 4 (<0.1) 2 (<0.1)

Fatal 0 0

Medically attended 23 (0.1) 14 (<0.1)

Leading to study discontinuation 0 0

AESI per Investigator assessment 3 (<0.1) 2 (<0.1)

AE: adverse event; AESI: adverse event of special interest; SAE: serious adverse event. Any solicited local or

systemic adverse reactions that meets the definition of an SAE are considered as AE. Numbers are based on actual

vaccination group and percentages are based on the number of participants in the Safety Set.

9.3.1.3 Deaths

No patterns in SAEs with fatal outcomes were evident across SOCs and PTs, time to

onset, or other event characteristics that would suggest a safety concern for mRNA-

1010. None of the fatal events were assessed as related to study injection by the

Investigator. The events were generally attributable to underlying medical history,

intrinsic factors, concomitant medications, and clinical context.

Up to 28 days after study injection, SAEs with a fatal outcome were reported for <0.1%

of participants in each group (7/20,350 in the mRNA-1010 group vs 9/20,353 in the SD

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comparator group) and none of these were assessed by the Investigator as related to

study injection.

Throughout the study, SAEs with a fatal outcome were reported for 0.2% of participants

in each group (40/20,350 in the mRNA-1010 group vs 34/20,353 in the SD comparator

group) and none of these were assessed by the Investigator as related to study

injection. PTs reported for >1 participant in either group were death (12 vs 4

participants), cardiac arrest (3 each), myocardial infarction (2 vs 3), septic shock (3 vs

1), cardio-respiratory arrest (2 vs 1), road traffic accident (2 vs 1), injury (2 vs 0),

cerebrovascular accident (1 vs 2), sepsis (0 vs 2), and cardiac failure (0 vs 2) (all

<0.1%).

The overall incidence of fatal SAEs was balanced between groups. An additional review

of fatal SAEs coded to the PT of death (without further specification or unknown

etiology) was conducted as these events were reported in 12 participants in the mRNA-

1010 group and 4 participants in the SD comparator group. A detailed review was

performed for these events with PT of death. Investigators were instructed to report a

specific term that resulted in death and clinical sites were queried following any

deviation from this instruction, but often no further information could be obtained by the

site; no autopsies were performed, family members did not wish to release additional

information, and/or causes of death remained unknown. Based on medical review of the

individual cases in both groups, events with the PT of death occurred in participants

with comorbidities including cardiovascular disease (e.g., hypertension) and metabolic

disorders (e.g., diabetes mellitus), and the nature of the reported conditions was

consistent with background mortality in an older, comorbid population. Among the 12

participants in the mRNA-1010 group with an event with the PT of death, the age range

was 53 to 72 years and the timing of death ranged from 24 to 194 days after study

injection. Among the 4 participants in the SD comparator group, the age range was 52

to 83 years and the timing of death ranged from 9 to 172 days after study injection.

Within 28 days after injection, the incidence of events with the PT of death were similar

across treatment groups and were reported for 1 participant in the mRNA-1010 group (a

67-year-old male participant with medical history including hypertension died on Day 24

after study injection) and 2 participants in the SD comparator group (a 52-year-old

female participant with medical history including hypertension, hypercholesterolemia,

and type 2 diabetes mellitus died on Day 9 after study injection; and an 83-year-old

female participant with medical history including hypertension died on Day 27 after

study injection). No temporal or clinical patterns suggesting a causal relationship with

mRNA-1010 were identified for events with the PT of death. Overall, given the

balanced incidence of all fatal events up to 28 days and throughout the study, lack of

temporal clustering, underlying risk factors, and available clinical details, no safety

concerns were identified upon a comprehensive review of all fatal events.

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9.3.1.4 Serious Adverse Events

SAEs were distributed heterogeneously across SOCs and PTs, and throughout the

study, few SAEs were assessed by the Investigator as related to study injection

(4/20,350 participants in the mRNA-1010 group and 2/20,353 participants in the SD

comparator group [<0.1% of participants in each group]). Individual case review

identified confounding factors including underlying conditions and/or concomitant

medications and no safety concern was identified for mRNA 1010.

Up to 28 days after injection, SAEs were reported for 0.5% of participants in each group

(92/20,350 in the mRNA-1010 group vs 92/20,353 in the SD comparator group).

Regardless of causality, SAEs were most frequently reported in the SOC for infections

and infestations (21 [0.1%] participants in the mRNA-1010 group vs 18 [<0.1%]

participants in the SD comparator group) and the most frequent SAE by PT was road

traffic accident (4 vs 3 [both <0.1%]). Up to 28 days after injection, SAEs assessed by

the Investigator as related to study injection were reported for 2 participants in the

mRNA-1010 group (syncope on Day 2 in a 62 year-old female with likely dehydration

evaluated by EMTs; hypotension on Day 2 in a 67 year-old male with history of

hypertension with reportedly “negative” testing) and 1 participant in the SD comparator

group (laryngeal dyspnoea on Day 6 in a 67 year-old male with history of angioedema).

Throughout the study, SAEs were reported for 2.2% of participants (455/20,350) in the

mRNA-1010 group and 1.9% of participants (392/20,353) participants in the SD

comparator group. Regardless of causality, SAEs were most frequently reported in the

SOC of infections and infestations (90 participants [0.4%] in the mRNA-1010 group vs

76 participants [0.4%] in the SD comparator group). SAEs assessed by the Investigator

as related to study injection were reported for a total of 4 participants in the mRNA-1010

group and a total of 2 participants in the SD comparator group. In the mRNA-1010

group, SAEs assessed as related by the Investigator included 2 additional participants

beyond Day 28 with 3 SAEs: one 54 year-old female participant with multiple cardiac

risk factors including uncontrolled type 2 diabetes had onset on Day 95 of congestive

cardiomyopathy and myopericarditis (adjudicated as not a charter-defined event by the

CEAC); and one 64 year-old male participant had myocarditis (adjudicated as

myopericarditis) with onset on Day 183 with prior respiratory symptoms. In the SD

comparator, SAEs assessed as related by the Investigator included 1 additional

participant beyond Day 28 with an SAE of pericarditis (adjudicated as acute pericarditis

by the CEAC) with onset on Day 60.

9.3.1.5 Adverse Events of Special Interest

Reporting of AESIs was similar between study groups up to 28 days after injection

(Table 11) and throughout the study (Table 12). Throughout the study, AESIs that were

assessed by the Investigator as related to study injection were reported for 3/20,350

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participants in the mRNA-1010 group and 2/20,353 participants in the SD comparator

group (both <0.1%). No safety concern was identified for mRNA-1010 based on

analysis of per protocol AESIs, as follows:

• No anaphylactic reactions were reported in the mRNA-1010 group.

• No safety concerns were identified for Bell’s palsy or seizure. One serious AESI

of facial paresis was reported in the mRNA-1010 group with onset on Day 21; the

event occurred in the setting of a concurrent nonserious AE of herpes zoster and

was assessed by the Investigator as not related to study injection. In the SD

comparator group, there was 1 nonserious AESI of Bell’s reported with onset on

Day 18 assessed as related to study injection by the Investigator and one

additional participant with 1 nonserious AESI of Bell’s palsy with onset on Day 53

in the context of a preceding event of upper respiratory illness assessed as not

related by the Investigator.

• No safety concerns with mRNA-1010 were identified for Guillain-Barré syndrome

or acute disseminated encephalomyelitis. One serious AESI of demyelinating

polyneuropathy that was assessed by the Investigator as not related to study

injection was reported in the mRNA-1010 group. Event onset was on Day 134,

which is outside the typical 42-day risk window for Guillain-Barré syndrome.

• No safety concerns with mRNA-1010 were identified for thrombocytopenia.

• No CEAC-confirmed events of acute myocarditis, acute pericarditis, or

myopericarditis were reported in either group within the 42-day risk window.

Throughout the study, the incidence of CEAC-confirmed events was balanced

between the groups (1 case of myopericarditis in the mRNA-1010 group [Day

183] and 1 case of acute pericarditis in the SD comparator group [Day 60]).

9.3.1.6 Analysis of Unsolicited Adverse Events by Standardized MedDRA Queries

No relevant differences were observed between study injection groups in the reporting

of AEs by narrow scope SMQ up to 28 days after injection and throughout the study. No

events in the standardized MedDRA query (SMQ) for anaphylactic reaction were

reported in the mRNA-1010 group. Analyses of AEs reported in the SMQs for arthritis,

cardiac arrhythmias, convulsions, demyelination, Guillain-Barré syndrome,

hematopoietic cytopenias, hypersensitivity, immune-mediated/autoimmune disorders,

noninfectious myocarditis/pericarditis, and peripheral neuropathy did not identify a

safety concern for mRNA-1010. Reporting of events in the hypersensitivity SMQ was

similar between the study intervention groups, including for events assessed by the

Investigator as related to study injection (12 participants in the mRNA-1010 group and

13 participants in the SD comparator group) and included PTs commonly seen in the

general population (e.g., contact dermatitis, eczema, and allergic rhinitis). No clinically

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meaningful differences between study injection groups were observed in the reporting of

AEs by SMQ or PT.

9.3.1.7 Unsolicited Adverse Events by Subgroups

No clinically relevant differences between or within study injection groups were

observed in analyses of AEs by subgroups based on age, race, and sex.

9.3.2 Study 303 Part C

Study 303C evaluated the safety of the mRNA-1010 vaccine in participants ≥65 years

who received either mRNA-1010 (N=1502) or HD comparator (N=1490), with median

follow-up of 171 days across both study intervention groups. Overall, the proportion of

participants with unsolicited AEs was similar between the mRNA-1010 and HD

comparator groups up to 28 days after injection and through the end of the study. An

overview of analyses of unsolicited AEs from Study 303C are summarized below:

• Unsolicited AEs up to 28 days after injection were reported in 155/1502 (10.3%)

participants in the mRNA-1010 group and 137/1490 (9.2%) participants in the HD

comparator group. By SOC, unsolicited AEs up to 28 days after injection were

most frequently (≥1%) reported in infections and infestations (4.5% vs 4.4%),

musculoskeletal and connective tissue disorders (1.1% vs 1.2%), and injury,

poisoning and procedural complications (1.2% vs 0.7%). By PT, the most

frequently (≥0.5%) reported unsolicited AEs were consistent with common

infections or associated signs/symptoms and included upper respiratory tract

infection (1.4% vs 1.1%) and COVID-19 (0.9% in each group).

• Throughout the study, fatal SAEs occurred in 3 (0.2%) participants and 1 (<0.1%)

participant in the mRNA-1010 and HD comparator groups, respectively. In the

mRNA-1010 group, these included participants 65 to 93 years of age with fatal

SAEs of acute myocardial infarction reported in 2 participants (Day 26 and Day

49 [died on Day 57]), who had risk factors including smoking, hypertension,

diabetes, and hyperlipidemia, and 1 participant with the fatal SAE of death

(verbatim: clinical death – natural causes, elderly; Day 68). In the HD comparator

group, a 65-year-old female experienced a fatal SAE of acute myocardial

infarction on Day 96. No patterns were evident based on PTs, time to onset, or

other event details that would suggest a safety concern for mRNA-1010. None of

the deaths were assessed as related to study injection by the Investigator.

• Throughout the study, SAEs were reported in 41 (2.7%) participants and 38

(2.6%) participants in the mRNA-1010 and HD comparator groups, respectively.

By PT, the most frequently (≥0.1%) reported SAEs were pneumonia (0.2% vs

<0.1%), urinary tract infection (0.1% vs <0.1%), transient ischemic attack (0.1%

vs 0), acute myocardial infarction (0.1% vs <0.1%), pulmonary embolism (0.1%

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vs <0.1%), nephrolithiasis (0 vs 0.1%), hip fracture (<0.1% vs 0.1%), fall (0 vs

0.1%), and subdural hematoma (0 vs 0.1%). All SAEs were assessed as not

related to study injection by the Investigator, except for the following SAE in the

HD comparator group: pulmonary embolism (Day 76) was reported for a

participant with a history of hypertension, chronic kidney disease, generalized

osteoarthritis, and Alzheimer’s dementia and was resolving as of EOS.

• Throughout the study, AESIs were reported in 2 (0.1%) participants in the

mRNA-1010 group and 1 (<0.1%) participant in the HD comparator group .

Evaluation of AESIs did not suggest a safety concern for mRNA-1010.

− No AESIs of thrombocytopenia were reported during the study for either study

intervention group.

− AESIs of new onset or worsening of specific neurological disorders were

reported in 1 (<0.1%) participant in each study intervention group throughout the

study; no AESIs of Guillain-Barré syndrome or acute disseminated

encephalomyelitis reported. There were no AESIs of seizure reported in either

study intervention group within 28 days of injection. Throughout the study, none

of the protocol-defined AESIs were assessed as related to study injection by the

Investigator.

− No AESIs of anaphylaxis were reported during the study for either study

intervention group. There was 1 AESI of swelling face (not a protocol-defined

AESI) assessed as related to study injection by the Investigator which was a

participant in the mRNA-1010 group with a history of asthma, cat fur/dander

allergy, and dust allergy who experienced the nonserious AE of swelling face

(Day 2).

− No AESIs of myocarditis/pericarditis were reported during the study for either

study intervention group.

9.3.3 Integrated Summary of Safety (ISS)

The ISS presents pooled data for deaths, SAEs, and AESIs, for all participants ≥ 50

years who received any version of mRNA-1010 QIV or TIV (12.5 μg per strain) or active

comparator (Fluarix SD [QIV or TIV] or Fluzone HD QIV; referred to as SD/HD

comparator) in any of the mRNA-1010 Phase 3 studies (301, 302, 303 and 304). All

these studies are completed and final safety analyses were integrated. Study 301 and

Study 302 had 1 year of safety follow-up and Study 303 and Study 304 had 6 months of

safety follow-up. The median duration of follow-up for participants in the mRNA-1010

and SD/HD comparator group in the ISS Set was 198.0 days for both study intervention

groups. Analysis of ISS data demonstrates no safety concern with mRNA-1010 in the

≥50 years population from the combined Phase 3 studies.

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9.3.3.1 Participant Population

In the ISS Set (participants ≥50 years), 35,965 participants received mRNA-1010 and

35,951 participants received SD/HD comparator and the median follow-up was 198

days in both pooled study intervention groups. Demographic characteristics were similar

between the mRNA-1010 and SD/HD comparator groups: the median age was 64.0

years in both groups; approximately half of participants in both groups were ≥65 years

(Table 13); 56.5% and 56.9% were female, 79.4% and 79.0% were White, and 44.2%

and 44.0% had received an influenza vaccine in the prior season.

Table 13: Number of Participants in the ISS Set by Age Subgroups

Fluarix SD or

mRNA-1010 Fluarix SD Fluzone HD Fluzone HD

(N = 35,965) (N = 34,461) (N = 1,490) (N = 35,951)

Age Group, n (%)

≥50 to <65years 18,398 (51.2) 18,396 (53.4) 1 (<0.1) 18,397 (51.2)

≥65 years 17,567 (48.8) 16,065 (46.6) 1,489 (>99.9) 17,554 (48.8)

≥75 years 4,098 (11.4) 3,779 (11.0) 335 (22.5) 4,114 (11.4)

HD: high dose; ISS: integrated summary of safety; SD: standard dose

9.3.3.2 ISS Overview of Unsolicited Adverse Events

The incidence of SAEs, deaths and AESIs was similar across treatment groups up to 28

days after injection and throughout the studies (Table 14).

Table 14: ISS Overall Summary of Unsolicited Adverse Events (ISS Set)

Fluarix SD or

mRNA-1010 Fluarix SD Fluzone HD Fluzone HD

(N = 35,965) (N = 34,461) (N = 1,490) (N = 35,951)

Participants with unsolicited AEs up to 28 days after Injection, regardless of relationship to study

vaccination

Serious 180 (0.5) 156 (0.5) 7 (0.5) 163 (0.5)

Fatal 13 (<0.1) 14 (<0.1) 0 14 (<0.1)

AE of Special Interest 7 (<0.1) 4 (<0.1) 0 4 (<0.1)

Participants with unsolicited AEs throughout the study, regardless of relationship to study vaccination

Serious 1129 (3.1) 989 (2.9) 38 (2.6) 1027 (2.9)

Fatal 102 (0.3) 96 (0.3) 1 (<0.1) 97 (<0.1)

AE of Special Interest 36 (0.1) 36 (0.1) 1 (<0.1) 37 (0.1)

AE: adverse event; HD: high dose; ISS: integrated summary of safety; SD: standard dose

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9.3.3.3 ISS Deaths

The frequency of fatal SAEs with onset up to 28 days after injection was balanced

between the mRNA-1010 and SD/HD comparator groups. Up to 28 days after injection,

fatal SAEs were reported for <0.1% of participants in each pooled study intervention

group. One death in the mRNA-1010 group was assessed as related to study injection

by the Investigator due to temporality (occurrence on Day 2); however, this participant

was a 76-year-old female with significant cardiovascular risk factors and concomitant

medication use associated with fatal arrhythmias.

Throughout the studies, the overall incidence of fatal SAEs was balanced between

study intervention groups and were reported for 0.3% of participants in each pooled

study intervention group. Other than the death on Day 2, no other fatal SAEs were

assessed by the Investigator as related to study injection. The most common SOC for

fatal SAEs was cardiac disorders (reported for 24 participants in the mRNA-1010 group

vs 30 participants in the SD/HD comparator group; both <0.1%). The median (range)

time of death from injection was 143.5 days (2 to 357 days) in the mRNA-1010 group

and 118.5 days (3 to 368 days) in the SD/HD comparator group. Among the total

number of deaths reported in the mRNA-1010 (N=102) and the SD/HD comparator

(N=97) groups, approximately two-thirds (N=70 and N=60, respectively) occurred more

than 90 days after injection. Comprehensive review of all fatal events (with and without

specific PTs) in each pooled study intervention group, considering the timing of events,

participant age, sex, underlying medical history, concomitant medications, and available

clinical details, revealed no pattern or clustering of deaths to suggest a safety concern

for mRNA-1010.

9.3.3.4 ISS Serious Adverse Events

Up to 28 days after injection, the frequency and distribution of SAEs were balanced

between the mRNA-1010 and SD/HD comparator groups. Up to 28 days after injection,

SAEs were reported for 0.5% of participants in each pooled study intervention group

and were most commonly in the SOC for infections and infestations (45 participants in

the mRNA-1010 group vs 34 participants in the SD/HD comparator group; both ≤0.1%).

The most frequent SAEs by PT were pneumonia (8 vs 5), acute myocardial infarction

(4 vs 6), osteoarthritis (2 vs 5), and acute kidney injury (2 vs 5); all other SAEs occurred

in ≤4 participants in either study intervention group.

Throughout the studies, SAEs were reported for 3.1% of participants in the mRNA-1010

group and 2.9% of participants in the SD/HD comparator group and were most

commonly in the SOC for infections and infestations (0.7% in the mRNA-1010 group vs

0.6% in the SD/HD comparator group). By PT, the most frequently (≥30 participants in

either group) reported SAEs were pneumonia (36 vs 32), COPD (35 vs 24),

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cerebrovascular accident (32 vs 29), and atrial fibrillation (30 vs 21) (all <0.1%). SAEs

were distributed across SOCs and PTs without any pattern.

Throughout the studies, SAEs that were assessed by the Investigator as related to

study injection were reported for <0.1% of participants in each pooled study intervention

group (9/35,965 participants in the mRNA-1010 group and 3/35,951 participants in the

SD/HD comparator group). SAEs assessed as related by the Investigator in Study 304

are presented in detail in Section 9.3.1.4 above. Other SAEs assessed as related by the

Investigator in the mRNA-1010 group included the following events:

• Study 301: acute coronary syndrome in 1 participant on Day 3 in a 53 year-old

male with multiple cardiovascular risk factors

• Study 302: angioedema (Day 5) in a 78-year-old female with a history of

idiopathic angioedema and pulmonary embolism (Day 9) in an 86 year-old

female with multiple cardiovascular risk factors, including severely limited mobility

• Study 303 (Part A): deep vein thrombosis and pulmonary embolism (1 participant

with 2 events total and multiple cardiovascular risk factors including smoking;

Day 128 and Day 132, respectively) and death (Day 2 as previously noted in

Section 9.3.3.3)

In the SD/HD comparator group, the SAEs assessed by the Investigator as related to

study injection were laryngeal dyspnoea (Study 304; 1 participant, Day 6), pericarditis

(Study 304; 1 participant, Day 60), and pulmonary embolism (Study 303C; 1 participant

Day 76, see Section 9.3.2).

Individual case details included confounding factors such as medical history conditions

and concomitant medications that were more likely to be causal than study injection.

9.3.3.5 ISS Adverse Events of Special Interest

Up to 28 days after injection, AESIs were reported for <0.1% of participants in each

pooled study intervention group (7/35,965 participants in the mRNA-1010 group and

4/35,951 participants in the SD/HD comparator group). This included 1 participant in

each pooled group who had an AESI of Bell’s palsy that was assessed by the

Investigator as related to study injection (details are provided below). In addition, an

event of swelling face (not a protocol-defined AESI) on Day 2 was reported as an AESI

assessed by the Investigator as related to study injection for a participant in the mRNA-

1010 group in Study 303C.

Throughout the studies, AESIs were reported for 0.1% of participants in each pooled

study intervention group (36/35,965 participants in the mRNA-1010 group and

37/35,951 participants in the SD/HD comparator group).

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Medical review of AESIs based on the ISS Set for participants ≥50 years did not identify

any safety concerns for mRNA-1010, Findings for each of the protocol-defined AESI

concepts are summarized as follows:

• Thrombocytopenia: Medical review of AESIs in this category did not suggest a

safety concern for mRNA-1010. Incidence in the blood and lymphatic disorders

SOC was similar between the pooled study intervention groups up to 28 days

after injection (1 [<0.1%] participant in the mRNA-1010 group vs 0 participants in

the SD/HD comparator group) and throughout the studies (12 [<0.1%] vs 12

[<0.1%]). One participant in the mRNA-1010 group had an event of

thrombocytopenia on Day 84 that was assessed by the Investigator as related to

study injection; however, multiple confounding factors were present.

• New onset or worsening of specified neurological diseases: Medical review

of AESIs in this category did not suggest a safety concern for mRNA-1010.

Incidence in the nervous system disorders SOC was similar between the pooled

study intervention groups up to 28 days after injection (5 [<0.1%] vs 3 [<0.1%]

participants) and throughout the studies (12 [<0.1%] vs 18 [<0.1%] participants).

Overall, 2 participants in the mRNA-1010 group and 4 participants in the SD/HD

comparator group had AESIs of Bell’s palsy and facial paresis. Of these, the

incidence within the relevant 42-day risk window was similar. One participant in

each of the pooled study intervention groups had an event of Bell’s palsy

assessed by the Investigator as related to study injection: in the mRNA-1010

group, the event occurred on Day 16 in a participant with medical history

including obesity and who was diagnosed with hypertension and type 2 diabetes

mellitus in the same medical encounter (Study 303B); in the SD/HD comparator

group, the event of Bell’s palsy occurred on Day 18 in a participant with no

reported risk factors consistent with the Brighton Collaboration case definition

(Rath et al 2017) (Study 304). One additional participant in the mRNA-1010

group (Study 304) had an unrelated serious AESI of facial paresis (Day 21) in the

setting of a concurrent nonserious AE of herpes zoster. Thus, no safety concerns

were identified for Bell’s palsy. No AESIs of seizure were assessed by the

Investigator as related to study injection. No AESIs of acute disseminated

encephalomyelitis were reported. One serious AESI of demyelinating

polyneuropathy that was assessed by the Investigator as not related to study

injection occurred in the mRNA-1010 group on Day 134, outside the 42-day risk

window for Guillain-Barré syndrome (Study 304).

• Anaphylaxis: No AESIs of anaphylaxis were reported in either of the pooled

study intervention groups throughout the study.

• Myocarditis/pericarditis: Medical review of AESIs did not suggest a safety

concern for mRNA-1010. No AESIs of myocarditis, pericarditis, or myopericarditis

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were reported in either pooled study intervention group up to 28 days after

injection. Throughout the studies, AESIs in the cardiac disorders SOC were

reported for 10 (<0.1%) participants in the mRNA-1010 group and 6 (<0.1%)

participants in the SD/HD comparator group; an additional AESI of viral

pericarditis (SOC: infections and infestations) was reported for 1 participant in the

SD/HD comparator group. None of the reported AESIs in the category of

myocarditis/pericarditis occurred within the 42-day risk window. CEAC-confirmed

events in the ISS Set among participants ≥50 years were balanced between the

pooled study intervention groups: 4 cases were reported in the mRNA-1010

group (1 case of myopericarditis and 3 cases of acute pericarditis) and 4 cases

were reported in the SD/HD comparator group (all 4 acute pericarditis).The

events were assessed by the Investigator as related to study injection for 1

participant in each group, both of whom were in Study 304 as described in

Section 9.3.1.4.

9.3.3.6 ISS Subgroup Analyses by Age

The frequency of SAEs, fatal events and AESIs was similar between vaccine groups

through 28 days after injection and up to Day 181 in both the 50 to 64 year-old

subgroup and the ≥ 65-year-old subgroup as shown in Table 15. There was no pattern

in the type or incidence of unsolicited AEs or clinically relevant differences across age

subgroups suggestive of a potential safety concern for mRNA-1010.

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Table 15: Overall Summary of Unsolicited Adverse Events by Age Group (ISS

Set)

50 – 64 Years ≥65 Years

Licensed SD/HD Licensed SD/HD

mRNA-1010 Comparator mRNA-1010 Comparator

(N = 18,398) (N = 18,397) (N = 17,567) (N = 17,554)

n (%) n (%) n (%) n (%)

Unsolicited AEs Through 28 Days after Injection

Serious 70 (0.4) 76 (0.4) 110 (0.6) 87 (0.5)

Fatal 3 (<0.1) 6 (<0.1) 10 (<0.1) 8 (<0.1)

AE of Special Interest 4 (<0.1) 2 (<0.1) 3 (<0.1) 2 (<0.1)

Unsolicited AEs Through Day 181 (End of Study)

Serious 484 (2.6) 424 (2.3) 645 (3.7) 603 (3.4)

Fatal 33 (0.2) 34 (0.2) 69 (0.4) 63 (0.4)

AE of Special Interest 17 (<0.1) 17 (<0.1) 19 (0.1) 20 (0.1)

AE: adverse event; HD: high dose; ISS: integrated summary of safety; SD: standard dose

9.3.4 Safety Conclusions

The mRNA-1010 vaccine has been administered to 20,350 participants ≥50 years of

age, with median follow-up of 184 days in the completed pivotal, Phase 3 study

(Study 304). In total, mRNA-1010 products have been administered to 39,537

participants ≥18 years across the clinical development program, including 35,965

participants ≥50 years across the Phase 3 studies of whom 17,567 participants were

≥65 years.

The mRNA-1010 vaccine administered as a single dose demonstrated tolerable

reactogenicity based on solicited ARs and an acceptable safety profile based on

unsolicited AEs across the clinical development program.

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10 CONFIRMATORY STUDY FOR ADULTS 65 YEARS AND OLDER

10.1 Study Design

Moderna is committed to evaluating influenza vaccine performance in real-world

settings and has generated effectiveness evidence for previously approved enhanced

influenza vaccines (Ku et al 2024; Rayens et al 2024). Building on this experience,

Moderna plans to generate high-quality post-licensure real-world effectiveness data to

further characterize the performance of mRNA-1010. As a Post-Marketing Requirement,

Moderna intends to demonstrate that mRNA-1010 provides meaningful clinical benefit

to adults ≥65 years of age, consistent with enhanced vaccines recommended for this

age group. To fulfill this requirement and support full approval of mRNA-1010 in the US,

Moderna will conduct a real-world evidence (RWE) study comparing vaccine

effectiveness of mRNA-1010 with that of an enhanced influenza vaccine in adults ≥65

years.

Following consultation with the FDA, Moderna developed a pragmatic, randomized

study to evaluate the rVE of mRNA-1010 compared with an enhanced influenza vaccine

in adults ≥65 years of age within an integrated healthcare system in the US. The

primary objective of the proposed study is to estimate the rVE of mRNA-1010 compared

with an enhanced influenza vaccine in preventing PCR-confirmed medically attended

influenza. Secondary objectives will estimate the rVE of mRNA-1010 compared with an

enhanced influenza vaccine in preventing moderate-to-severe influenza and will assess

primary and secondary objectives by PCR-confirmed influenza type A and/or B

(separately). To accomplish these objectives, Moderna expects to enroll hundreds of

thousands of adults into this rVE study.

The full protocol was submitted to FDA and is currently under Agency review. In

parallel, Moderna is advancing study start-up activities, including operational planning

and site readiness activities, to support timely implementation of the study following

protocol alignment with FDA. Additional details and features of the study are currently

under discussion with the Agency.

Results of this proposed RWE study, together with mRNA-1010’s demonstrated

superior immunogenicity relative to high-dose vaccine (Study 303C) and the efficacy

estimates within the range of approved enhanced vaccines in adults ≥65 years of age

(Study 304), will be used to confirm meaningful clinical benefit in this population.

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11 BENEFITS AND RISKS CONCLUSIONS

11.1 Therapeutic Context

Influenza virus is a primary cause of respiratory tract infection and is associated with

severe outcomes in adults ≥50 years. Vaccines are essential for the prevention of

influenza disease, but the effectiveness of currently licensed vaccines is variable.

Influenza vaccines with enhanced activity (through delivery of higher antigen content,

inclusion of adjuvants, or recombinant manufacturing) have been developed, particularly

for more vulnerable older adults (≥65 years). This category of vaccine has shown

reduction in rates of influenza virus-associated hospitalization and deaths in adults ≥65

years. Inherent aspects of current influenza vaccine production however, including for

some enhanced vaccines, hinder optimal vaccine effectiveness.

The mRNA manufacturing platform enables rapid design and synthesis of strain-specific

influenza virus vaccines. Unlike traditional egg-based production, synthetic mRNA

vaccine manufacturing does not depend on embryonated chicken egg supply or viral

reassortment processes. Egg-based manufacturing requires a reliable supply of eggs,

which may be vulnerable to disruption, particularly during outbreaks affecting poultry.

Additionally, vaccine manufactured in eggs often acquire adaptive mutations that can

enhance growth in eggs but may alter antigenic properties compared to circulating

influenza viruses. The greater manufacturing speed and flexibility of mRNA therefore

represent an important advance for both seasonal influenza prevention and pandemic

influenza preparedness.

Overall, the combination of clinical endpoint efficacy, higher or superior immunogenicity,

and improved production flexibility and scalability constitutes a meaningful advantage

over current licensed influenza vaccines.

11.2 Benefit-Risk Analysis Evaluation in Adults 50–64 Years of Age

In the US, licensed SD influenza vaccines are recommended for the prevention of

influenza in adults 50–64 years of age. Evidence supporting a positive benefit-risk

profile of mRNA-1010 in this age group is based on data from 21,239 adults in the

pivotal efficacy trial, Study 304, and 36,794 adults in a safety analysis of pooled

Phase 3 data (ISS).

A single dose of mRNA-1010 (TIV; 37.5 μg) resulted in an rVE of 26.1% (95% CI: 12.3,

37.7; Study 304) relative to SD comparator against the primary efficacy endpoint (PCR-

confirmed ILI caused by any type A or B influenza virus). This rVE in adults 50-64 years

is consistent with the level of superior efficacy reached in the overall 304 study

population (and exceeding the prespecified statistical primary rVE success criterion for

superiority [rVE 95% CI LB >9.1%]).

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The clinical efficacy of mRNA-1010 relative to SD comparator was evident early after

vaccination and was maintained to the end of the influenza season and rVE point

estimates were consistent across influenza strains.

The superior clinical efficacy of mRNA-1010 relative to SD comparator in Study 304 was

paralleled by higher immune responses (HAI Ab) for all vaccine strains: GMR point

estimates were all >1.5 (95% CI LBs were >1.3) and SCR differences were all positive

(95% CI LBs were >12%).

mRNA-1010 has an acceptable safety profile in adults 50-64 years. Higher rates of

reactogenicity were reported in the mRNA-1010 than the SD comparator group, but

most solicited local and systemic ARs were Grade 1 or 2 in severity and transient in

duration. Grade 3 solicited local and systemic ARs were also more frequent in the

mRNA‑1010 group than comparator group, but these too were transient and generally

resolved without medical attention.

Analysis of individual safety data from study 304 identified no safety concerns with

mRNA-1010 in adults 50-64 years. Unsolicited AEs reported in the 28 days post-

injection and throughout the study were balanced between study groups. Analysis of

pooled Phase 3 safety data in the large ISS database were similarly reassuring: the

overall incidence of deaths, other SAEs, and AESIs throughout these studies was

balanced between mRNA-1010 and SD comparator groups. In adults 50-64, there were

no events of myocarditis/pericarditis within the relevant risk window and no mRNA-

1010-related deaths reported across all studies.

Results of mRNA-1010 efficacy, immunogenicity, and comprehensive safety

assessment provide substantial evidence supporting traditional approval of mRNA-1010

for the prevention of influenza disease in adults 50–64 years of age. mRNA-1010 may

better match circulating seasonal influenza variants by avoiding egg-based

manufacturing (and egg-adaptive mutations). Shorter potential production timeline from

strain selection to vaccine availability for mRNA-1010 may further enhance the

likelihood of vaccine match and clinical benefit.

11.3 Benefit-Risk Analysis Evaluation in Adults 65 Years and Older

Compared to younger adults, individuals 65 years and older are at increased risk of

severe outcomes associated with influenza disease, including pneumonia,

hospitalization and death. Enhanced influenza vaccines (including HD formulations)

reduce such outcomes in older adults, which led to preferential recommendation in the

United States in this age group. Enhanced vaccines nonetheless face challenges

inherent to manufacturing processes (including egg-adaptive mutations) and to the time

required from strain selection to vaccine availability that can result in potential mismatch

between vaccine and circulating influenza strains. mRNA-1010 efficacy, immunogenicity

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and safety data summarized in this report, together with the known fidelity of the mRNA-

1010 manufacturing process, support the accelerated approval of mRNA-1010 influenza

vaccine for use in adults 65 years and older.

Evidence supporting accelerated approval of mRNA-1010 in adults 65 years and older

is based on data from 19,464 adults in the pivotal efficacy Study 304 and 35,121 older

adults in a safety analysis of pooled Phase 3 data (ISS).

A single dose of mRNA-1010 (TIV; 37.5 μg) results in an rVE of 27.4% (95% CI: 12.1,

40.0; Study 304) relative to SD comparator against the primary efficacy endpoint (PCR-

confirmed ILI caused by any type A or B strain). This rVE is consistent with rVE for the

overall 304 study population, and results in adults 65 years and older exceeded the

prespecified statistical primary rVE success criterion for superiority [rVE 95% CI LB

>9.1%]. Further, this level of superior efficacy relative to SD comparator is aligned with

that of previously approved enhanced influenza vaccines. An exploratory efficacy

analysis showed that mRNA-1010 reduced ILI-associated healthcare encounters

(hospitalization, ER visit, or urgent care visit) relative to SD comparator (rVE of 62.9%

[95% CI: 11.6, 88.4]). Like currently licensed enhanced vaccines, it is anticipated that

the superior rVE of mRNA-1010 will translate to meaningful clinical benefit following use

in older adults.

The clinical efficacy of mRNA-1010 relative to SD comparator in participants 65 years

and older was evident early after injection and was maintained to the end of the

influenza season, and rVE point estimates were consistent across influenza strains.

The superior clinical efficacy of mRNA-1010 relative to SD comparator in Study 304 was

paralleled by higher immune responses (HAI Ab) for all vaccine-included influenza

strains: GMR point estimates were all >1.6 (95% CI LBs were >1.5) and SCR

differences were all positive (95% CI LBs were >16%). In a head-to-head comparison of

the immunogenicity of mRNA-1010 and HD comparator (Study 303C), mRNA-1010

successfully met prespecified superiority criteria. (i.e. Day 29 GMR 97.5% CI LB >1.0

and SCR difference 97.5% CI LB >0% for all 8 co-primary endpoints).

The safety profile of mRNA-1010 in adults 65 years and older was acceptable. Solicited

AR were more frequently reported in mRNA-1010 than comparator groups (Studies 304

and 303C), but most solicited AR were Grade 1 or 2 in severity and transient in

duration. Grade 3 solicited ARs were also more frequently reported in the mRNA‑1010

than comparator groups, but these too were transient and generally resolved without

medical attention. With increasing age, a trend is observed toward a lower frequency of

local and systemic solicited ARs for the mRNA-1010 group and toward a lower

frequency of local solicited ARs for the SD comparator group.

Comprehensive analysis of individual safety data from Studies 304 and 303 identified

no safety concerns with mRNA-1010. Unsolicited AEs reported in the 28 days post-

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injection and throughout the studies were balanced between study groups. Analysis of

pooled Phase 3 safety data in the large ISS database was similarly reassuring. The

overall incidence of deaths, SAEs, and AESIs throughout these studies was similar

between the mRNA-1010 and SD/HD comparator groups. No CEAC-confirmed cases of

myocarditis/pericarditis (within the relevant 42 day risk window) were reported across all

studies in the mRNA-1010 group. The one death assessed as related by the

Investigator in a mRNA-1010 recipient occurred in a participant over 75 years old with

multiple cardiovascular risk factors.

Results of mRNA-1010 efficacy, immunogenicity and comprehensive safety assessment

support accelerated approval of mRNA-1010 for the prevention of influenza disease in

adults 65 years and older. mRNA-1010 may better match circulating seasonal influenza

variants by avoiding egg-based manufacturing (and egg-adaptive mutations). Shorter

potential production timeline from strain selection to vaccine availability for mRNA-1010

may further enhance the likelihood of vaccine match and clinical benefit. A planned real-

world effectiveness study is anticipated to confirm data summarized in this report and

demonstrate that mRNA-1010 provides meaningful clinical benefit consistent with

approved enhanced vaccines.

11.4 Conclusions

Data summarized here establish that in adults 50-64 years and those 65 years and

older, mRNA-1010 has an acceptable safety profile, induces superior rVE against

influenza disease and induces Ab responses higher than SD comparator and superior

to HD comparator (in adults ≥65 years). mRNA-1010 manufacturing avoids reliance on

embryonated chicken eggs, maintains sequence match with circulating virus, and

shortens the time from strain selection to vaccine availability. Together, data support

that mRNA-1010 will be a valuable addition to the category of enhanced influenza

vaccines and help reduce the annual burden of influenza disease in adults 50 years and

older.

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12 REFERENCES

Bartley JM, Cadar AN, Martin DE. Better, Faster, Stronger: mRNA Vaccines Show

Promise for Influenza Vaccination in Older Adults. Immunol Invest. 2021;50(7):810-820.

doi:10.1080/08820139.2021.1909617

Bedford T, Suchard MA, Lemey P, et al. Integrating influenza antigenic dynamics with

molecular evolution. eLife 2014. 3:e01914. doi:10.7554/eLife.01914.

Boersma P, Black LI, Ward BW. Prevalence of multiple chronic conditions among US

adults, 2018. Preventing Chronic Disease 2020;17. doi:10.5888/pcd17.200130.

Bouvier NM, Palese P. The biology of influenza viruses. Vaccine. 2008;26(Suppl 4):

D49-53. doi:10.1016/j.vaccine.2008.07.039.

CDC 2022a. How flu viruses can change: “drift” and “shift”. [Internet] [updated 17 Sep

2024; cited 11 Aug 2025]. Available from:

https://www.cdc.gov/flu/php/viruses/change.html.

CDC 2022b. Flu symptoms and complications. [Internet] [updated 26 Aug 2024; cited 02

May 2025]. Available from: https://www.cdc.gov/flu/signs-symptoms.

CDC 2023a. Types of influenza viruses. [Internet] [updated 18 Sep 2024; cited 02 May

2025]. Available from:

https://www.cdc.gov/flu/about/virusestypes.html?CDC_AAref_Val=https://www.cdc.gov/f

lu/about/viruses/types.htm.

CDC 2023b. Influenza Activity in the United States during the 2022–2023 Season and

Composition of the 2023–2024 Influenza Vaccine. [Internet] [cited 29 May 2025]

Available from: https://www.cdc.gov/flu/whats-new/22-23-summary-technical-report.html

CDC 2024a. About estimated flu burden. [Internet] [updated 13 Nov 2024; cited 02 May

2025]. Available from: https://www.cdc.gov/flu-burden/php/about/index.html.

CDC 2024b. Flu and people 65 years and older. [Internet] [updated 05 Sep 2024; cited

02 May 2025]. Available from: https://www.cdc.gov/flu/highrisk/65over.htm.

CDC 2024c. People at Increased Risk for Flu Complications. [Internet] [cited 28 May

2026]. Available from: https://www.cdc.gov/flu/highrisk/index.htm

CDC 2024d. Seasonal influenza vaccine supply for the US 2024-2025 influenza season.

[Internet] [updated 03 Sep 2024; cited 13 May 2025]. Available from:

https://www.cdc.gov/flu/hcp/vaccinesupply/vaxadmin.html?CDC AAref Val=https://www

.cdc.gov/flu/prevent/vaxsupply.htm.

CDC 2024e. Influenza Activity in the United States during the 2023–2024 Season and

Composition of the 2024–2025 Influenza Vaccine. [Internet] [cited 29 May 2026].

Available from: https://www.cdc.gov/flu/whats-new/flu-summary-2023-2024.html

82

mRNA-1010

Vaccines and Related Biological Products

ModernaTX, Inc. Advisory Committee

CDC 2025a. 2024-2025 United States flu season: preliminary in-season severity

assessment. [Internet] [updated 09 May 2025; cited 12 May 2025]. Available from:

https://www.cdc.gov/flu/php/surveillance/in-season-severity.html.

CDC 2025b. 2024–2025 Influenza Season Summary: Severity, Disease Burden, and

Burden Prevented. [Internet] [updated 12 Mar 2026; cited 27 May 2026]. Available from:

https://www.cdc.gov/flu-burden/php/data-vis/index.html.

CDC 2025c. Influenza Activity in the United States during the 2024–25 Season and

Composition of the 2025–26 Influenza Vaccine [Internet] [cited 28 May 2026]. Available

from: https://www.cdc.gov/flu/whats-new/2025-2026-influenza-activity.html

CDC 2026a. Age Group Distribution of Influenza Positive Specimens Reported by

Public Health Laboratories [Internet] [cited 28 May 2026]. Available from: National

Summary, 2024-25 Influenza Season

https://gis.cdc.gov/grasp/fluview/flu by age virus.html

CDC 2026b. Estimated US Flu Disease Burden [Internet] [cited 28 May 2026] Available

from: https://www.cdc.gov/flu-burden/php/data-vis/index.html

CDC 2026c Flu Burden Prevented by Vaccination. [Internet] [cited 29 May 2026].

Available from https://www.cdc.gov/flu-burden/php/data-vis-vac/index.html.

Chen JR, Liu YM, Tseng YC, Ma C. Better influenza vaccines: an industry perspective.

J Biomed Sci. 2020;27(1):33. doi:10.1186/s12929-020-0626-6.

DiazGranados CA, Dunning AJ, Kimmel M, et al. Efficacy of high-dose versus standard-

dose influenza vaccine in older adults. N Engl J Med. 2014;371(7):635-45.

doi:10.1056/NEJMoa1315727

Dunkle LM, Izikson R, Patriarca P, et al. Efficacy of recombinant influenza vaccine in

adults 50 years of age or older. N Engl J Med. 2017;376(25):2427-36.

doi:10.1056/NEJMoa1608862.

ECDC 2022. Factsheet about seasonal influenza. [Internet] [updated 12 Apr 2022; cited

02 May 2025]. Available from:

https://www.ecdc.europa.eu/en/seasonalinfluenza/facts/factsheet.

FLUAD (Influenza Vaccine, Adjuvanted). Package Insert. Seqirus Inc; 2025. Accessed

28 May 2026. Available from https://www.fda.gov/media/179766/download.

FluSurv-NET. Selected underlying medical conditions: 2023-24 season. [Internet]

[updated 26 April 2025; cited 07 May 2025]. Available from:

https://gis.cdc.gov/grasp/fluview/FluHospChars.html.

GBD 2017 Influenza Collaborators. Mortality, morbidity, and hospitalisations due to

influenza lower respiratory tract infections, 2017: an analysis for the Global Burden of

83

mRNA-1010

Vaccines and Related Biological Products

ModernaTX, Inc. Advisory Committee

Disease Study 2017. Lancet Respir Med. 2019;7(1):69-89. doi:10.1016/S2213-

2600(18)30496-X.

Goody SMG, Rowbottom C, Liu Y, Chen N. Biodistribution of mRNA vaccines in rats:

Enrichment in injection site and lymph tissues and rapid clearance without tissue

persistence. Mol Ther Nucleic Acids. 2026; 37(2)102948.

doi.org/10.1016/j.omtn.2026.102948.

Gouma S, Anderson EM, Hensley SE. Challenges of Making Effective Influenza

Vaccines. Annu Rev Virol. 2020;7(1):495-512. doi:10.1146/annurev-virology-010320-

044746.

Huang G, Wilson E, Kohli A, et al. mRNA-1010, an mRNA-Based Influenza Vaccine, is

Safe and Efficacious in Adults Aged ≥50 Years, Including Individuals at High Risk for

Severe Disease. Presented at 10th ESWI Influenza Conference; October 20-23, 2025;

Valencia, Spain. Available from: https://irp.cdn-

website.com/89dd0539/files/uploaded/mRNA-

1010+P304+rVE+High+Risk+LB+Oral_ESWI+2025.pdf

Hsiao A, Leong T, Fireman B, et al. Adjuvanted vs High-Dose Influenza Vaccines in

Older US Adults: A Cluster Randomized Crossover Study. JAMA Netw Open.

2026;9(5):e2610120. doi:10.1001/jamanetworkopen.

Jain S, Self WH, Wunderink RG, et al. Community-Acquired Pneumonia Requiring

Hospitalization among U.S. Adults. N Engl J Med. 2015;373(5):415-427.

doi:10.1056/NEJMoa1500245.

Ku JH, Rayens E, Sy LS, et al. Comparative Effectiveness of Licensed Influenza

Vaccines in Preventing Influenza-related Medical Encounters and Hospitalizations in the

2022-2023 Influenza Season Among Adults ≥65 Years of Age. Clin Infect Dis.

2024;79(5):1283-1292. doi:10.1093/cid/ciae375.

Kwong JC, Schwartz KL, Campitelli MA, et al. Acute myocardial infarction after

laboratory-confirmed influenza infection. N Engl J Med. 2018;378(4):345-53. doi:

10.1056/NEJMoa1702090.

Lei B, Wang S, Yu L, Ma Q. Post-influenza bacterial infection: mechanisms of

pathogenesis and advances in therapeutic strategies. Front Microbiol.

2025;16:1673643. doi:10.3389/fmicb.2025.1673643.

Leroux-Roels I, Huang G, Ferguson M, et al. Efficacy and Safety of an mRNA Seasonal

Influenza Vaccine in Adults. N Engl J Med. 2026;394(18):1803-1813.

doi:10.1056/NEJMoa2516491

Lowen AC, Mubareka S, Steel J, Palese P. Influenza virus transmission is dependent

on relative humidity and temperature. PLoS Pathog. 2007;3(10):1470-6.

doi:10.1371/journal.ppat.0030151.

84

mRNA-1010

Vaccines and Related Biological Products

ModernaTX, Inc. Advisory Committee

Malkin E, Kohli A, Clark R, et al. mRNA-1010, an mRNA-Based Influenza Vaccine, Is

Safe and Efficacious in Adults Aged ≥50 Years. Presented at IDWeek 2025, Georgia

World Congress Center, October 19-22, 2025; Atlanta, Georgia, USA. Available from :

https://irp.cdn-website.com/89dd0539/files/uploaded/mRNA-1010+P304+50-

+LB+Oral_IDWeek+2025_FD2.pdf

Merced-Morales A, Daly P, Abd Elal AI, et al. Influenza Activity and Composition of the

2022–23 Influenza Vaccine — United States, 2021–22 Season. MMWR Morb Mortal

Wkly Rep 2022;71:913–919. doi: http://dx.doi.org/10.15585/mmwr.mm7129a1

Muscatello DJ. Redefining influenza seasonality at a global scale and aligning it to the

influenza vaccine manufacturing cycle: a descriptive time series analysis. J Infect. 2019

Feb;78(2):140-9. doi: 10.1016;j.jinf.2018.10.006.

Nguyen TQ, Vlasenko D, Shetty AN, et al. Systematic review and meta-analysis of

respiratory viral triggers for acute myocardial infarction and stroke. Cardiovasc Res.

2025;121(9):1330-1344. doi:10.1093/cvr/cvaf092.

Rath B, Gidudu JF, Anyoti H, Bollweg B, Caubel P, Chen YH, et al. Facial nerve palsy

including Bell’s palsy: case definitions and guidelines for collection, analysis, and

presentation of immunisation safety data. Vaccine. 2017;35(15):1972-83.

doi:10.1016/j.vaccine.2016.05.023.

Rajaram S, Wojcik R, Moore C, et al. The impact of candidate influenza virus and egg-

based manufacture on vaccine effectiveness: Literature review and expert consensus.

Vaccine. 2020;38(38):6047-56. doi: 10.1016/j.vaccine.2020.06.021.

Rayens E, Ku JH, Sy LS, et al. Comparative Effectiveness of Cell-Based Versus Egg-

Based Influenza Vaccines in Prevention of Influenza Hospitalization During the 2022-

2023 Season Among Adults 18-64 Years. Influenza Other Respir Viruses. 2024

Dec;18(12):e70025. doi: 10.1111/irv.70025.

Rosero CI, Gravenstein S, Saade EA. Influenza and Aging: Clinical Manifestations,

Complications, and Treatment Approaches in Older Adults. Drugs Aging. 2025;42(1):39-

55. doi:10.1007/s40266-024-01169-y.

Russell CA, Fouchier RAM, Ghaswalla P, et al. Seasonal influenza vaccine

performance and the potential benefits of mRNA vaccines. Hum Vaccin Immunother.

2024;20(1):2336357. doi:10.1080/21645515.2024.2336357.

Sellers SA, Hagan RS, Hayden FG, Fischer WA 2nd. The hidden burden of influenza: A

review of the extra-pulmonary complications of influenza infection. Influenza Other

Respir Viruses. 2017;11(5):372-393. doi:10.1111/irv.12470.

Sin P, Siddiqui M, Wozniak R, et al. Heart Failure after Laboratory Confirmed Influenza

Infection (FLU-HF). Glob Heart. 2022;17(1):43. doi:10.5334/gh.1125.

85

mRNA-1010

Vaccines and Related Biological Products

ModernaTX, Inc. Advisory Committee

Sohn WY, Goody SMG, Reid DW, et al. Evidence-based assessment of safety and

mechanistic questions Related to mRNA COVID-19 Vaccines. Vaccine. 2026 Apr

2;77:128394. doi: 10.1016/j.vaccine.2026.128394.

Taaffe J, Goldin S, Lambach P, Sparrow E. Global production capacity of seasonal and

pandemic influenza vaccines in 2023. Vaccine. 2025;51:126839. doi:

10/1016/j.vaccine.2025/126839.

WHO 2015. World report on ageing and health. [Internet] [updated 2015; cited 02 May

2025]. Available from:

https://iris.who.int/bitstream/handle/10665/186463/9789240694811_eng.pdf?sequence=

1.

WHO 2023. Recommended composition of influenza virus vaccines for use in the 2024

southern hemisphere influenza season. [Internet] [updated Sep 2023; cited 05 May

2025]. Available from: https://cdn.who.int/media/docs/default-source/influenza/who-

influenza-recommendations/vcmsouthern-hemisphere-recommendation-

2024/202309_recommendation.pdf.

WHO 2024. Recommended composition of influenza virus vaccines for use in the 2024-

2025 northern hemisphere influenza season. [Internet] [updated Feb 2024; cited 11 Aug

2025]. Available from: https://cdn.who.int/media/docs/default-source/influenza/who-

influenzarecommendations/vcm-northern-hemisphere-recommendation-2024-

2025/recommendedcomposition-of-influenza-virus-vaccines-for-use-in-the-2024-2025-

northern-hemisphereinfluenza-season.pdf.

WHO 2025. Influenza (seasonal). [Internet] [updated 28 Feb 2025; cited 11 Aug 2025].

Available from: https://www.who.int/en/news-room/fact-sheets/detail/influenza-

(seasonal)

Zanobini P, Bonaccorsi G, Lorini C, et al. Global patterns of seasonal influenza activity,

duration of activity and virus (sub)type circulation from 2010 to 2020. Influ Other Respir

Viruses. 2022;16: 696-706. doi:10.1111/irv.12969.

Zheng L, Lin Y, Yang J, Fang K, Wu J, Zheng M. Global variability of influenza activity

and virus subtype circulation from 2011 to 2023. BMJ Open Respir Res. 2023;10:

e001638. doi:10.1136/bmjresp-2023-001638.

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13 APPENDICES

13.1 Study 101

13.1.1 Design

Study 101 was a Phase 1/2, randomized, observer-blind, dose-ranging first-in-human

study to evaluate the safety, reactogenicity, and immunogenicity of mRNA-1010 vaccine

in adult participants ≥18 years of age. The study consisted of 3 parts: Phase 1/2

(placebo-controlled), Phase 2 NH (active-controlled), and Phase 2 Extension (active-

controlled).

In the Phase 1/2 part, 180 participants were randomly assigned in a 1:1:1:1 ratio to

receive either 50 μg, 100 μg, or 200 μg of mRNA-1010 or placebo, with 45 participants

randomly assigned to each vaccination group. In the Phase 2 NH part, 503 participants

were randomly assigned in a 3:3:3:1 ratio to receive either 25 μg, 50 μg, or 100 μg of

mRNA-1010 or the active comparator, Afluria Quadrivalent 60 μg. In the Phase 2

Extension part, 202 participants were randomly assigned in a 1:1:1:1 ratio to receive

either 6.25 μg, 12.5 μg, or 25 μg of mRNA-1010 or the active comparator.

13.1.2 Results

The primary immunogenicity objective was to evaluate the humoral immunogenicity of

3 dose levels (50 μg, 100 μg, and 200 μg) of mRNA-1010 vaccine administered as a

single dose against vaccine-matched Influenza A and B strains at Day 29.

Key immunogenicity results were as follows:

• At Day 29, GMFRs were approximately 7.5- to 11-fold for H1N1, 6- to 7-fold for

H3N2, 2-fold for Victoria-lineage, and 3- to 4-fold for Yamagata-lineage in the

mRNA-1010 groups; no meaningful change in GMFRs was observed in the

placebo group.

• The GMTs elicited at the 50 μg dose level were comparable with the titers elicited

at higher dose levels. Seroconversion on Day 29 was noted for >65% of

participants for the Influenza A strains.

• Seroconversion was lower for the Influenza B strains; it was 14.0% to 25.0% for

Victoria-lineage and 41.9% to 51.2% for Yamagata-lineage.

• For the Influenza A strains, the GMTs were higher in the ≥18 to <50 years group

compared with the ≥50 years group.

• The GMFRs for H1N1 increased approximately 9.5- to 13-fold in the ≥18 to <50

years group compared with approximately 5.5- to 9-fold in the ≥50 years group.

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The GMFRs for H3N2 increased approximately 6- to 8-fold in the ≥18 to <50

years group compared with approximately 6.5- to 7-fold in the ≥50 years group.

At the Day 181/EoS timepoint, anti-HA antibody GMTs for all vaccine strains dropped

below Day 29 levels. However, they stayed above baseline levels for H1N1 and H3N2

and reached near baseline levels for Victoria-lineage and Yamagata-lineage. The

proportion of participants meeting criteria for seroconversion in the mRNA-1010 groups

ranged from 33.3% to 43.6% for H1N1, from 43.9% to 50.0% for H3N2, from 5.7% to

14.6% for Victoria-lineage, and from 2.8% to 12.2% for Yamagata-lineage.

Intramuscular administration of mRNA-1010 at doses ranging from 6.25 μg to 200 μg

was generally well-tolerated; however, the reactogenicity profile was higher in frequency

and severity compared with the active comparator:

• The incidence of local and systemic solicited ARs was higher in participants

receiving mRNA-1010 compared with those receiving the active comparator or

placebo; however, most of the solicited ARs were Grade 1 or Grade 2 in severity.

• Within the ≥50 μg mRNA-1010 groups, the incidence of solicited ARs and use of

medications to treat pain and fever was generally lower in older adults than in

younger adults, although the day of onset and duration of solicited ARs was

comparable.

The overall safety profile was consistent with that seen with the use of other mRNA

vaccines with a low incidence of unsolicited treatment-emergent AEs (TEAEs), severe

TEAEs, and serious TEAEs. No AESIs or vaccination-related serious TEAEs were

reported during this study.

Based on the results of this study, 50 µg (12.5 µg / strain) was selected for future

studies based on a balance of immunogenicity and reactogenicity compared to the

standard dose comparator.

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13.2 Study 304 Results in Adults ≥ 50 Years

Figure 18: Study 304 ILI Events by Strain- Per-Protocol Set

Licensed SD

Influenza

Participants with ILI1 by mRNA-1010 Vaccines Relative Vaccine Efficacy (%)

influenza strain, N [%] N = 20,179 N = 20,124 (95% CI)

29.6% (16.4, 40.7)

Influenza A H1N1 223 315

[1.1%] [1.6%]

22.2% (4.3, 36.9)

Influenza A H3N2 158 202

[0.8%] [1.0%]

29.1% (-18.5, 57.5)

Influenza B Victoria 25 35

[0.1%] [0.2%]

-50 0 50 100

CI: confidence interval; ILI: influenza-like illness; RT-PCR: reverse transcription polymerase chain reaction SD:

standard dose

1. Based on RT-PCR-confirmed protocol-defined IL

Figure 19: Study 304 Cumulative Incidence Rates of Influenza Cases Per-

Protocol Set

700

rVE (95% CI) = 26.6% (16.7, 35.4)

600 Licensed SD

Influenza Vaccines

500

400 mRNA-1010

Cumulative

Number of 300

Cases 200

100

0

0 1 2 3 4 5 6 7 8

Time from Vaccination (Months)

Licensed Influenza At Risk 20124 19871 19663 19383 19027 18774 10098 1932 0

Vaccines Events 0 16 104 250 428 532 555 557 557

At Risk 20179 19930 19765 19506 19151 18925 10180 1962 0

mRNA-1010

Events 0 14 74 205 333 400 409 411 411

CI: confidence interval; ILI: influenza-like illness; RT-PCR: reverse transcription polymerase chain reaction; rVE:

relative vaccine efficacy; SD: standard dose

*Per Protocol-defined ILI - all cases required RT-PCR confirmation within 7 days of illness onset

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Figure 20: Study 304 by Influenza-like Illness Definition Per-Protocol Set

Licensed SD

Influenza

Participants With ILI by mRNA-1010 Vaccines Relative Vaccine Efficacy (%)

Definition, N [%] N = 20,179 N = 20,124 (95% CI)

411 557 26.6% (16.7, 35.4)

Protocol-defined ILI

[2.0%] [2.8%]

Modified 223 290 23.5% (9.0, 35.8)

CDC-defined ILI [1.1%] [1.4%]

27.0% (9.8, 40.9)

CDC-defined ILI

149 203

[0.7%] [1.0%]

118 167 29.7% (11.1, 44.5)

WHO-defined ILI

[0.6%] [0.8%]

-25 0 25 50

CI: confidence interval; ILI: influenza-like illness; RT-PCR: reverse transcription polymerase chain reaction; rVE:

relative vaccine efficacy; SD: standard dose

All cases of ILI required RT-PCR confirmation within 7 days of illness onset.

Huang G, et al 2025

Figure 21: Study 304 High Risk and Frailty Subgroups Per-Protocol Set

Licensed SD

Participants with ILI Influenza Relative Vaccine Efficacy, (%)

by Category, % [n/N] mRNA-1010 Vaccines (95% CI)

High Risk with ≥ 1 2.1% 2.7% 22.3% (8.0, 34.3)

Conditions high-risk conditiona [241/11,465] [309/11,457]

2.0% 2.7% 26.8% (8.9, 41.1)

Fit (0-3)

[140/7,079] [190/7,059]

Frailty 28.9% (-15.5, 56.3)

1.6% 2.3%

Statusb Vulnerable (4-5)

[28/1,737] [39/1,708]

≥ 65 years

1.7% 2.5% 30.3% (-37.1, 64.6)

Frail (≥ 6)

[14/806] [21/837]

1.9% 2.6% 27.5% (10.6,41.1)

BMI ≥ 30 kg/m2

[153/7,958] [211/7,892]

-50 -25 0 25 50 75 100

CI: confidence interval; BME: body mass index; ILI: influenza-like illness; SD: standard dose

a. High-risk conditions: BMI ≥30 kg/m², diabetes, pulmonary disorders, cardiac disorders, nervous systems disorders,

etc.

b. Frailty based on Edmonton Frail Scale; score only available for participants ≥65 years

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Figure 22: Study 304 Medically Attended Illness in Participants ≥50 Years

Licensed SD

Healthcare encounters Influenza

associated w/ RT-PCR confirmed mRNA-1010 Vaccines Relative Vaccine Efficacy (%)

protocol-defined ILI, N [%] N = 20,179 N = 20,214 (95% CI)

80 120 33.7% (12.0, 50.0)

Any healthcare encounter

[0.4%] [0.6%]

Any Higher Level 22 42 47.9% (12.8, 68.9)

Encounter [0.11%] [0.21%]

Seeking Hospitalization

4 8 Not calculated – too few cases

a Higher [0.02%] [0.04%]

Level of 6 12 Not calculated - too few cases

Care ER visit1

[0.03%] [0.06%]

46.1% (-5.8, 72.6)

Urgent care visit1

13 24

[0.06%] [0.12%]

27.6% (-1.3, 48.2)

Outpatient Clinic Visit

59 81

[0.29%] [0.40%]

-50 -25 0 25 50 75 100

CI: confidence interval; ILI: influenza-like illness; RT-PCR: reverse transcription polymerase chain reaction; SD:

standard dose

1. Malkin E et al. IDWeek, 2025

Figure 23: Study 304 - GMR and SCR at Day 29 Per-Protocol Immunogenicity

Subset

Geometric Mean GMR of mRNA-1010 over HD Vaccine Seroconversion % SCR difference between

Titer ratio (GMR) (95% CI) rate (SCR) mRNA-1010 – HD Vaccine (95% CI)

H1N1 1.82 (1.69, 1.97) H1N1 28.0% (24.1, 31.7)

Noninferiority Superiority

Noninferiority

Superiority

H3N2 1.59 (1.48, 1.71) H3N2 20.0% (16.0, 23.9)

B/Victoria 1.67 (1.57, 1.78) B/Victoria 25.3% (21.7, 29.0)

0.667 1 1.5 2 2.5 3 -10 0 10 20 30 40 50

GMR: ratio of mean titer of mRNA-1010 over mean titer for SD vaccine; SD: standard-dose licensed influenza

vaccine;

mRNA-1010, n = 1167; licensed SD vaccine, n = 1175.

GMR, and corresponding 95% CI obtained by transforming least square mean estimate and CI back to original scale

for presentation

Malkin E et al 2025

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Table 16: Comparison of HAI Ab GMT (Day 29) for ILI Cases Versus Non-cases

for mRNA-1010 and for the Active Comparator (by Influenza Strain)

Cases Non-Cases Ratio of GMT

GMT (95% CI) GMT (95% CI) (Cases/Non-

Immunologic Treatment Cases)

Marker Group n Day 29 HAI n Day 29 HAI (95% CI)

mRNA-1010 208 57 (50, 65) 1696 150 (141, 159) 0.4 (0.3, 0.4)

Influenza A/H1N1 HAI

Titer Active

296 44 (40, 48) 1744 82 (78, 87) 0.5 (0.5, 0.6)

Comparator

mRNA-1010 150 89 (76, 106) 1754 149 (140, 157) 0.6 (0.5, 0.7)

Influenza A/H3N2 HAI

Titer Active

187 60 (52, 70) 1853 93 (88, 99) 0.6 (0.5, 0.8)

Comparator

mRNA-1010 25 249 (170, 366) 1879 254 (242, 266) 1.0 (0.7, 1.4)

Influenza B/Victoria Active

34 183 (133, 251) 2006 158 (151, 166) 1.2 (0.8, 1.6)

HAI Titer Comparator

CI: confidence interval; GMT: geometric mean titer ratio; HAI ab hemagglutination inhibition antibody; ILI: influenza-

like illness

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Table 17: Day 29 B/Victoria HAI GMT by the Corresponding Strain-Specific ILI

Case Status in Each Vaccine Group in Overall, Bulgaria, and Non-Bulgaria

Regions (Study 304, Per Protocol Correlate of Analysis Set)

GMT ratio

(cases/non-

Cases Non-cases cases)

GMT (95% CI) GMT (95% CI) (95% CI)

Treatment group or

Region GMT ratio n Day 29 n Day 29 Day 29

mRNA-1010 25 249 (170, 366) 1879 254 (242, 266) 0.98 (0.67, 1.45)

Active comparator 34 183 (133, 251) 2006 158 (151, 166) 1.15 (0.84, 1.59)

Overall GMT ratio

(mRNA-1010/active

1.36 (0.83, 2.24) 1.60 (1.50, 1.71)

comparator)

(95% CI)

mRNA-1010 5 160 (79, 326) 1754 252 (240, 264) 0.64 (0.31, 1.30)

Active comparator 8 108 (68, 173) 1867 153 (146, 160) 0.71 (0.44, 1.14)

GMT ratio

Non-Bulgaria (mRNA-

1010/active 1.48 (0.63, 3.46) 1.65 (1.54, 1.76)

comparator)

(95% CI)

mRNA-1010 20 279 (180, 432) 125 279 (220, 354) 1.00 (0.61, 1.65)

Active comparator 26 215 (148, 312) 139 245 (190, 314) 0.88 (0.56, 1.38)

Bulgaria GMT ratio

(mRNA-1010/active

1.30 (0.73, 2.30) 1.14 (0.81, 1.61)

comparator)

(95% CI)

CI: confidence interval; GMT: geometric mean titer ratio; ILI: influenza-like illness; HAI ab hemagglutination inhibition

antibody

n is the number of participants in each subgroup who had Day 29 B/Victoria HAI titer data.

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13.3 Study 304 Safety Results by Age Subgroup

Table 18: Study 304 Solicited Local ARs by Age Group

Study 304 50-64 year Study 304 ≥65 year

mRNA-1010 Active SD mRNA-1010 Active (SD)

37.5 μg Comparator 37.5 μg Comparator

(N=1,510) (N=1,502) (N=1,505) (N=1,495)

n (%) n (%) n (%) n (%)

Any solicited local adverse reactions 1057 (70.0) 545 (36.3) 977 (64.9) 416 (27.8)

95% CI 67.6, 72.3 33.8, 38.8 62.4, 67.3 25.6, 30.2

Grade 3 28 (1.9) 2 (0.1) 23 (1.5) 2 (0.1)

Grade 4 0 0 0 0

Pain

Any 1038 (68.7) 517 (34.4) 947 (62.9) 377 (25.2)

Grade 3 17 (1.1) 1 (<0.1) 10 (0.7) 0

Grade 4 0 0 0 0

Erythema (redness)

Any 66 (4.4) 19 (1.3) 51 (3.4) 19 (1.3)

Grade 3 4 (0.3) 1 (<0.1) 6 (0.4) 76 (5.0)

Grade 4 0 0 0 0

Swelling/induration (hardness)

Any 96 (6.4) 18 (1.2) 76 (5.0) 27 (1.8)

Grade 3 4 (0.3) 2 (0.1) 5 (0.3) 2 (0.1)

Grade 4 0 0 0 0

Axillary swelling or tenderness

Any 306 (20.3) 104 (6.9) 214 (14.2) 80 (5.4)

Grade 3 4 (0.3) 1 (<0.1) 6 (0.4) 0

Grade 4 0 0 0 0

AR: adverse reaction; CI: confidence interval; SD: standard dose

94

mRNA-1010

Vaccines and Related Biological Products

ModernaTX, Inc. Advisory Committee

Table 19: Study 304 Solicited Systemic Adverse Reactions by Age Group

Study 304 50 – 64 Years Study 304 ≥65 Years

mRNA-1010 SD mRNA-1010 Active SD

37.5 μg Comparator 37.5 ug Comparator

(N=1,510) (N=1,502) (N=1,505) (N=1,495)

n (%) n (%) n (%) n (%)

Any Solicited systemic ARs 927 (61.4) 506 (33.7) 823 (54.7) 464 (31.0)

95% CI 58.9, 63.9 31.3, 36.1 52.1, 57.2 28.7, 33.5

Grade 3 98 (6.5) 16 (1.1) 69 (4.6) 11 (0.7)

Grade 4 0 0 0 0

Fever

Any 90 (6.0) 13 (0.9) 84 (5.6) 13 (0.9)

Grade 3 11 (0.7) 2 (0.1) 6 (0.4) 1 (<0.1)

Grade 4 0 0 0 0

Headache

Any 633 (41.9) 302 (20.1) 507 (33.7) 236 (15.8)

Grade 3 33 (2.2) 6 (0.4) 26 (1.7) 4 (0.3)

Grade 4 0 0 0 0

Fatigue

Any 727 (48.1) 309 (20.6) 633 (42.1) 300 (20.1)

Grade 3 59 (3.9) 9 (0.6) 38 (2.5) 4 (0.3)

Grade 4 0 0 0 0

Myalgia

Any 613 (40.6) 196 (13.0) 454 (30.2) 152 (10.2)

Grade 3 44 (2.9) 4 (0.3) 32 (2.1) 3 (0.2)

Grade 4 0 0 0 0

Arthralgia

Any 476 (31.5) 167 (11.1) 363 (24.1) 150 (10.0)

Grade 3 34 (2.3) 3 (0.2) 23 (1.5) 3 (0.2)

Grade 4 0 0 0 0

Nausea/ vomiting

Any 147 (9.7) 61 (4.1) 112 (7.4) 41 (2.7)

Grade 3 3 (0.2) 1 (<0.1) 2 (0.1) 1 (<0.1)

Grade 4 0 0 0 0

95

mRNA-1010

Vaccines and Related Biological Products

ModernaTX, Inc. Advisory Committee

Study 304 50 – 64 Years Study 304 ≥65 Years

mRNA-1010 SD mRNA-1010 Active SD

37.5 μg Comparator 37.5 ug Comparator

(N=1,510) (N=1,502) (N=1,505) (N=1,495)

n (%) n (%) n (%) n (%)

Chills

Any 415 (27.5) 71 (4.7) 273 (18.1) 58 (3.9)

Grade 3 42 (2.8) 3 (0.2) 20 (1.3) 1 (<0.1)

Grade 4 0 0 0 0

AR: adverse reaction; CI: confidence interval; SD: standard dose

96

行业套路拆解 ​

套路事实观察对估值的影响反证
后 COVID 收缩2025 收入 $1.944B，较 2022 峰值 $19.26B 大幅下降；Q1 2026 收入主要来自国际 COVID 销售和长期政府合作市场不会再按 COVID 峰值定价，必须看到新季节性产品接力若 COVID/RSV 基础盘继续萎缩而新品放量慢，现金消耗会重新压估值
成熟市场抢份额流感疫苗市场低个位数增长，公共免疫采购稳定但竞争强mRNA-1010 即使获批，也更像抢份额和组合疫苗入口若标签、价格、共同接种或 payer/采购不顺，商业化弹性会低于监管弹性
mRNA 平台再证明mRNA-1010、mRNA-1083/mCOMBRIAX、mRNA-1403、mRNA-4157、mRNA-3927 同时进入关键节点多资产成功才会提高平台估值中枢单点获批但销售弱，或 Phase 3 失败，平台溢价会回落
FDA 标签风险FDA 文件支持讨论 50-64 传统批准和 65+ 加速批准，但提出 65+ 比较组、单季数据、特殊人群、共同接种数据缺口监管路径改善但未结束；市场会看标签是否可商业化若要求额外大型疗效数据，2026-2027 节奏后移
现金 runwayQ1 末现金+投资 $7.456B；年底指引 $4.5B-$5.0B现金给管线读出时间，但不是估值安全垫本身若年烧 $2B+ 延续且收入不增长，需要更深裁剪或融资
Oncology 外推intismeran 5 年 Phase 2b melanoma 数据延续 RFS/DMFS 优势若 Phase 3 阳性，MRNA 可被重估为 oncology mRNA 平台Phase 2b 样本量有限，OS 证据不强，Phase 3 才决定估值弹性

公司竞争力分析 ​

维度公司证据竞争优势短板/风险后续验证
产品 / 平台已商业化 SPIKEVAX、mNEXSPIKE、mRESVIA、mCOMBRIAX；mRNA-1010、mRNA-1018、mRNA-1403、mRNA-4157、mRNA-3927 等在 Phase 2/3mRNA 平台横跨呼吸道、肿瘤、罕见病，事件密度高产品多不等于销售大；COVID 后商业化基础仍不稳2026 PDUFA、Phase 3 读出和新品订单
技术 / IP / 数据PatSnap 称 Moderna mRNA 项目数量和 late-stage 深度领先，SM-102/LNP 和专利诉讼仍是壁垒/风险自研 LNP 与多项目经验形成 know-how与 Pfizer/BioNTech 的 IP/商业化争议仍可能影响经济性专利诉讼、许可费、生产成本
商业化 / 渠道Q1 2026 国际收入 $311M，美国 $78M；长期政府合作贡献大国际协议和公共卫生合作有基础美国市场压力大，疫苗政策和接种意愿不稳定秋冬季订单、美国/欧洲采购和 mNEXSPIKE/mRESVIA 销售
成本 / 单位经济R&D $649M，同比 -24%；SG&A $173M，同比 -18%；全年 R&D 仍约 $3.0B、SG&A 约 $1.0B成本削减已发生，研发可选项仍多收入基数不足以覆盖成本，2026 仍大幅烧钱Q2/Q3 经营现金流和年底现金指引
供应链 / 制造CEPI H5 项目强调 mRNA 快速设计和规模化制造；公司 2025 启动多个国际制造点大流行准备和快速株更新有战略价值季节性疫苗需要稳定成本、产能利用和质量体系H5 Phase 3、监管检查和商业放量
资产负债表 / FCFQ1 现金+投资约 $7.456B，长期债 $590M；2025 FCF $(2.065)B现金足以支持多个 2026 节点年底现金指引 $4.5B-$5.0B，runway 消耗明显Q3 $950M 和解支付后的现金
管理层 / 执行2025 费用削减约 $2.2B；多条管线优先级重排管理层已转向成本纪律和重点项目仍需证明裁剪不会削弱关键平台Science Day、季度研发优先级
监管 / 临床FDA mRNA-1010 BLA 已进入 VRBPAC；intismeran、norovirus、PA 有 2026 节点多个事件能提供正反馈单个失败会放大高估值和高烧钱风险VRBPAC/PDUFA、Phase 3 读出

对手分析对比 ​

维度Moderna (MRNA)BioNTech / PfizerSanofi / GSK / CSL 等传统流感玩家投研含义数据限制
核心产品/市场COVID、RSV、COVID booster、flu+COVID、潜在 mRNA flu、norovirus、oncologyCOVID 与 oncology 组合；BioNTech 现金厚、oncology 管线更集中；Pfizer 商业渠道强高剂量、佐剂化、重组、细胞培养和传统灭活流感疫苗基础强MRNA 在 mRNA 平台深度强，但在流感商业市场要抢成熟玩家份额传统玩家最新产品份额未逐项归档，按市场结构处理
增长与收入质量2025 revenue $1.944B；Q1 2026 $389M；收入季节性和政府合作影响大BioNTech Q1 2026 revenue EUR118M，仍受 COVID 下滑影响，但 cash/securities EUR16.8B季节性疫苗收入更稳定但增长慢MRNA 和 BioNTech 都在后 COVID 转型，但 BioNTech 现金更强IFRS/GAAP、欧元/美元口径不可直接横比
R&D/技术路线mRNA 疫苗、个性化肿瘤疫苗、罕见病 mRNA therapeuticmRNA + ADC + immunomodulator + CureVac 整合传统疫苗平台、重组/细胞培养/佐剂/高剂量路线MRNA 技术纯度高，BioNTech 平台更向 oncology 多模态扩张第三方管线数量需公司披露交叉验证
商业化能力美国疫苗环境承压，国际协议支撑；新品仍待验证Pfizer 商业化强，BioNTech 研发/现金强已有 flu vaccine 渠道和 payer/采购关系MFLUSIVA 获批后仍要过商业化关渠道数据缺少可量化同口径
监管或执行风险mRNA-1010 标签、人群、共同接种、上市后义务；多条 Phase 3 数据风险oncology 读出多，ADC/IO 竞争强；COVID 退潮老产品价格/份额压力小但创新慢MRNA 事件弹性最大，风险也最大当前报告不预测各公司审批概率
估值EV/S 2025 约 8.8x，仍亏损BioNTech 现金厚，COVID 收入下滑但 oncology 选择权多大药企多元化估值，不适合单独按 flu 业务比MRNA 估值更像临床/监管事件组合，不像传统疫苗现金流缺少实时同口径 peer EV/S 表

公司分析 ​

业务结构 ​

Moderna 的当前收入仍围绕 COVID 和少数已批呼吸道产品。mNEXSPIKE、mCOMBRIAX、mRESVIA 的批准数量增加了，但收入能否接上要看 2026-2027 秋冬季真实接种、政府采购和渠道覆盖。短期最重要的新增资产是 MFLUSIVA/mRNA-1010，因为它决定 Moderna 能不能把 mRNA 平台延伸到成熟且年度化的 flu vaccine 市场。

质量 ​

这不是高利润稳定疫苗公司的质量，而是“现金消耗换多个临床/监管节点”的质量。好的一面是 Q1 末 $7.456B cash + investments 足以支撑多个关键读出；坏的一面是 Q1 净亏损 $(1.343)B，年底现金+投资指引只剩 $4.5B-$5.0B。估值要看每一美元 R&D 是否换来可商业化标签和可持续收入。

增长 ​

2026 revenue 指引只是较 2025 最多 +10%，这不是高速成长口径。真正的增长选项在三层：第一层是 MFLUSIVA 和组合疫苗能否进入季节性采购；第二层是 norovirus、PA 等新产品能否证明 mRNA 不只做呼吸道 booster；第三层是 intismeran Phase 3 若成功，平台估值从疫苗扩展到 oncology。

估值性价比 ​

按 $60.62 延迟价，MRNA 市值约 $23.9B、EV 约 $17.1B；相对 2025 revenue，P/S 约 12.3x、EV/S 约 8.8x。即便按 2026 revenue 上限估计，EV/S 仍约 8.0x。这个价格不是便宜的收入倍数，而是市场提前给了 FDA/管线成功的选择权价格。经过近一周约 +29.6% 上涨后，性价比更偏“等结果确认或等回撤”，不是无脑追事件。

情景 ​

情景假设关键数字估值含义触发条件
BullVRBPAC 支持，MFLUSIVA 在 2026-08-05 前后获批且标签可商业化；intismeran/norovirus/PA 至少一个关键读出正面2026 revenue 接近 $2.14B 上限，2027-2028 新品组合放量，现金消耗收窄市场从“现金消耗疫苗股”转向“多资产 mRNA 平台”正面投票、可商业化标签、Phase 3 数据强、年底现金不低于指引
BaseMFLUSIVA 路径前进但标签/上市后义务限制放量；oncology 与 rare disease 需要更多时间2026 revenue 小幅增长，年底现金 $4.5B-$5.0B股价围绕监管和临床读出高波动，估值需要销售验证获批但商业节奏慢，cash burn 符合指引
BearFDA 要求额外大型临床或 PDUFA 不顺；关键读出失败；疫苗政策环境恶化2026 revenue 不及目标，2027 仍高烧钱8x 左右 EV/S 会显得贵，现金折价重新主导监管延迟/拒绝、Phase 3 失败、年底现金跌破指引

反证与监控 ​

  • 2026-06-18：VRBPAC 对 50-64 和 65+ 两个问题的投票、讨论质量和是否要求新增数据。
  • 2026-06-25：Science Day 是否给出更具体的研发优先级、成本纪律和商业化路径。
  • 2026-08-05：mRNA-1010 PDUFA 结果、标签、人群范围、上市后义务、共同接种限制。
  • Q2/Q3 2026：现金+投资、经营现金流、Q3 $950M 和解支付后的 runway。
  • 2026 临床节点：intismeran melanoma Phase 3、norovirus mRNA-1403、PA mRNA-3927。
  • 商业验证：mRESVIA、mNEXSPIKE、mCOMBRIAX、潜在 MFLUSIVA 是否形成真实订单和接种需求。

新闻资料与观点权重 ​

说明：权重是研究证据强弱和时效性，不是仓位比例或自动交易信号。

标的/主题来源发布日期事实摘录观点影响权重(1-5)限制
Q1 2026 财务StockTitan 的 Moderna 8-K 镜像2026-05-01Q1 revenue $389M，net loss $(1.343)B，cash+investments $7.5B，年底 cash 指引 $4.5-$5.0Brunway 和估值底层证据5以 SEC/公司公告数字为准，页面情绪标签不采用
FY2025 财务Nasdaq 转载 Moderna FY2025 公告2026-02-13FY2025 revenue $1.9B，net loss $2.8B；2026 目标最多 +10% revenue growth证明后 COVID 收缩仍是主线5Q1 后现金指引已更新
SEC XBRLSEC Moderna companyfactsSEC API官方 XBRL 支持 2021-2025 财务历史和 Q1 2026 10-Q 指标校验财务表和现金/债务/股数5不同年度收入标签需按期选择
FDA 事件FDA VRBPAC 会议公告2026-06-16会议讨论 MFLUSIVA 50 岁及以上人群预防流感短期最大事件节点5截至数据时间尚无投票结果
FDA 会前风险BioPharma Dive 报道2026-06-16FDA staff 未见重大缺陷，但指出单季数据、65+、特殊人群和共同接种缺口支持“路径改善但未无风险”判断4媒体解读，需回到 FDA 原文
Oncology 平台Merck/Moderna intismeran 五年数据2026-06-01RFS 风险降低 49%，DMFS 风险降低 59%，OS 仍探索性非呼吸道平台重估关键证据4Phase 2b，等待 Phase 3
对手 BioNTechBioNTech Q1 20262026-05-05BioNTech cash/securities EUR16.8B，oncology readouts 密集，CureVac 整合对 MRNA 平台竞争力形成参照3IFRS/欧元，不直接横比
流感行业Fact.MR flu vaccine market未提供发布时间2026 市场约 $7.9B，2036 约 $11.2B，CAGR 3.6%说明 flu 市场低增速，获批后要靠抢份额2第三方估算，非官方销售数据

期权观察 ​

公开期权链覆盖 6 个到期日，观察时间为 2026-06-17 18:45 UTC。免费公开链不提供 delta/gamma/theta/vega、IV Rank 或 GEX；本节只看成交量、OI、ATM IV、Max Pain 和合约快照。

标的数据时间来源观察范围Put/Call VolPut/Call OIATM IVMax Pain结构解读权重(1-5)限制
MRNA2026-06-17 18:45 UTCYahoo Finance 公开期权链6 个到期日；前端 2026-06-26，约 8.2 天0.260.67~82.5%$49.50成交量明显偏 call，OI 也偏 call；这是 FDA 会前事件波动交易，不是基本面结论2非逐笔 tape；无 Greeks；部分远月深 ITM/OTM 合约报价和 IV 异常

期权结论：近端市场在押上行/波动，但高 IV 下消息落地后的波动压缩也很危险。不能把 call 成交直接解释为“聪明资金看多”。

大单观察 ​

大单/异常合约来自公开期权链快照，不是 time-and-sales tape，不判断主动买卖方向。估算权利金用 bid/ask 中间价，缺失时用 last price，仅作量级观察。

标的观察时间来源类型合约/事件方向VolumeOIIVVol/OI估算权利金观点影响权重(1-5)限制
MRNA2026-06-17 18:45 UTC公开期权链快照MRNA260626C00061000，$61，2026-06-26Call6,41256166.2%11.43~$1.55M会后近端上行/波动交易最清晰的合约之一2不能判断买卖方向；需看后续 OI 是否增加
MRNA2026-06-17 18:45 UTC公开期权链快照MRNA260626C00065000，$65，2026-06-26Call3,49518570.7%18.89~$0.68M短期上方凸性活跃，但 strike 已高于现价2小 OI 放大 Vol/OI
MRNA2026-06-17 18:45 UTC公开期权链快照MRNA260626C00064000，$64，2026-06-26Call3,402868.0%425.25~$0.89MOI 极低导致异常指标很高，只说明快照活跃1可能是新开/平仓/数据时点效应
MRNA2026-06-17 18:45 UTC公开期权链快照MRNA261218P00065000，$65，2026-12-18Put1,2041,24780.5%0.97~$1.99M年底 put 活跃提示事件后仍有保护/下行波动需求2可能是保护、价差或波动结构的一部分
MRNA2026-06-17 18:45 UTC公开期权链快照MRNA261218P00230000，$230，2026-12-18Put7220~0.0%N/A~$12.5M报价质量异常，本报告不作为方向证据1OI 为 0，bid/ask 为 0，IV 异常

规则化交易建议 ​

说明：这是研究用规则计划，不是自动下单指令；执行前需重新确认实时行情、VRBPAC 结果、账户风险预算和流动性。

规则触发条件动作建议风险控制复查
事件前不追涨股价已接近/突破 52 周高点，近一周约 +29.6%，且 VRBPAC 结果未出不在无确认时一次性追高；等待投票、标签讨论和盘后/次日反应高 IV 下避免把事件波动当长期趋势VRBPAC 当日、次日成交量和 IV 回落
正面结果小仓观察VRBPAC 对 50-64 和 65+ 均偏支持，且问题集中在上市后义务而非新增大型临床可按事件驱动观察仓处理，不升为核心仓二元事件仓位控制；不使用杠杆2026-08-05 PDUFA 前后复查
回撤后研究仓股价回到 $45-$50 区间，同时 FDA 路径未恶化、年底现金指引不下修风险回报比 $60 附近更合理，可分批研究若回撤来自监管失败，不机械补Q2 财报、cash burn 和 FDA 通信
加仓条件MFLUSIVA 获批且标签可商业化，随后 intismeran/norovirus/PA 至少一个关键读出积极才考虑从事件仓提升为平台转型仓若新品收入低于预期或 Phase 3 失败，撤销平台重估假设每季核对产品销售和 R&D 优先级
退出/降权FDA 要求额外大型临床、PDUFA 延迟/拒绝，或年底 cash+investments 指引跌破 $4.5B降低或退出事件仓，不用长期平台叙事硬扛高烧钱 + 管线失败同时出现时优先保护本金PDUFA、Q3 现金、Phase 3 数据

结论 ​

MRNA 的优点是事件密度高、现金 runway 尚可、mRNA 平台仍有多条证明路径；缺点是收入基数太小、2026 仍大幅烧钱、当前价格已经吃进一段事件修复。MFLUSIVA 如果顺利通过 VRBPAC 并在 8 月获批，会显著修复 2 月 RTF 后的监管叙事；但流感疫苗市场低增速且竞争成熟，单个获批不等于高销售。

我对 MRNA 的排序是：事件前不追高；正面投票后可小仓观察；真正提升权重需要 MFLUSIVA 可商业化标签和至少一个非 COVID 管线读出兑现。若 FDA 要求新增大型临床或关键 Phase 3 失败，MRNA 会重新回到高烧钱、高不确定性、收入基数不足的折价逻辑。

来源 ​

  • SEC Moderna 公司事实 XBRL 数据
  • SEC Moderna submissions
  • 本地 IB Gateway / TWS API read-only 延迟行情与 RTH 日线
  • Yahoo Finance MRNA 公开期权链
  • Yahoo Finance 新闻检索

数据口径 ​

数据块最终口径来源说明
当前股价/图表采用IBKR Gateway read-only 延迟行情与 RTH 日线取得 IBKR 延迟行情和 1 年 RTH 日线；当前价为延迟行情，不作为实时交易报价；当日 RTH 日线最新值不等同正式收盘
市值/EV采用IBKR 延迟价格、SEC Q1 2026 股数和资产负债表市值用 Q1 2026 加权平均股数估算；EV 用 Q1 现金+投资和长期债估算，非实时企业价值
财务历史采用SEC companyfacts、Moderna 财报公告转载/8-K 镜像年度收入按官方 XBRL 和公司公告交叉校验；FCF 为 CFO - capex
行业资料采用，低权重Fact.MR、CEPI、PatSnap、公司管线页第三方行业规模和管线数量为估算/分析，不替代官方销售或监管数据
文章归档与摘要采用本地文章归档12 条文章/报告已归档本地原文并生成中文摘要；4 条已执行 direct + proxy 后仍失败或正文低置信，仅作为覆盖缺口，不用于结论支撑
公司竞争力采用SEC/公司公告、FDA、Merck、CEPI、管线页、归档文章管线阶段不等于成功概率或商业收入；公司自述材料权重低于监管/财务硬事实
对手分析采用，定性BioNTech Q1、PatSnap、行业资料采用产品市场和平台竞争维度；未做实时同口径 peer EV/S 表
新闻/事件采用，低权重Yahoo Finance 新闻检索、官方公告、本地归档文章新闻只作为事实输入和情绪背景，不用标题规则生成事件归因
期权观察采用，低权重Yahoo Finance 公开期权链公开链提供 IV/OI/volume/max pain，不提供 Greeks/GEX/逐笔成交方向；部分合约报价异常
大单观察采用，低权重公开期权链快照不是 time-and-sales tape，不判断主动买卖方向；异常深度价内、bid/ask 为 0 或 IV 异常的合约不作为方向证据