mRNA-3927

Reports fourth quarter revenues of $1.0 billion, GAAP net loss of $(1.1) billion and GAAP EPS of $(2.91); loss includes approximately $0.2 billion of non-cash charges related to manufacturing resizing Reports full-year revenues of $3.2 billion, GAAP net loss of $(3.6) billion and GAAP diluted EPS of $(9.28) Expects 2025 revenue range of $1.5 to 2.5 billion andending cash balance of approximately $6 billion Submitted three investigational mRNA products for regulatory approval, including Moderna's next-generation COVID vaccine, RSV vaccine for high-risk adults aged 18 to 59, and flu/COVID combination vaccine CAMBRIDGE, MA / ACCESS Newswire / February 14, 2025 / Moderna, Inc. (NASDAQ:MRNA) today reported financial results and provided business updates for the fourth quarter and fiscal year 2024. "We have made progress in 2024 across our late-stage pipeline and cost reduction efforts. Our team successfully filed three Biologics License Applications in the final months of the year and reduced our costs by 27 percent compared to 2023," said Stéphane Bancel, Chief Executive Officer of Moderna. "In 2025, we remain focused on driving sales, delivering up to 10 product approvals through 2027, and expanding cost efficiencies across our business. By the end of 2025, we aim to remove nearly $1 billion in costs. With strong momentum in our late-stage pipeline, we anticipate multiple approvals starting this year, along with key Phase 3 readouts that will support our long-term growth." Recent progress includes: Commercial Updates Moderna is entering 2025 with two approved products, Spikevax® and mRESVIA®. COVID-19: The Company reported $923 million in Spikevax® sales in the fourth quarter of 2024, which includes $244 million of U.S. sales and $679 million of international sales. Spikevax sales for the full year 2024 were $3.1 billion. RSV: The Company reported $15 million in mRESVIA® sales in the fourth quarter of 2024. mRESVIA sales for the full year 2024 were $25 million. Moderna's RSV vaccine for adults aged 60 years and older has been approved in the United States, Canada, EU, Norway, Iceland, Liechtenstein, the United Arab Emirates, Qatar and Taiwan. Fourth Quarter 2024Financial Results Revenue: Total revenue for the fourth quarter of 2024 was $1.0 billion, compared to $2.8 billion in the same period in 2023. Net product sales for the fourth quarter of 2024 were $938 million, reflecting a 66% year-over-year decrease. The decrease was primarily due to the earlier launch of the updated COVID-19 vaccine in the United States, which shifted sales into the third quarter. The U.S. Food and Drug Administration (FDA) approval granted three weeks earlier than in the previous year enabled the Company to meet demand more effectively ahead of the fourth quarter. Additionally, international sales were lower compared to the same period in 2023, reflecting the continued phase-out of advance purchase agreements. Cost of Sales: Cost of sales for the fourth quarter of 2024 was $739 million, which included third-party royalties of $45 million, inventory write-downs of $193 million, and wind-down costs of $259 million, including a non-cash charge of$238 million related to the termination of a contract manufacturing agreement during the quarter. Compared to the same period in 2023, cost of sales decreased by $190 million, or 20%, primarily due to lower third-party royalties from reduced product sales and a decline in inventory write-downs. Despite the overall reduction in cost of sales, cost of sales as a percentage of net product sales increased to 79%, compared to 33% in the fourth quarter of 2023, reflecting the impact of lower net product sales. Excluding the $238 million wind-down costs related to the termination of the contract manufacturing agreement, cost of sales as a percentage of net product sales would have been 53%. Research and Development Expenses: Research and development expenses for the fourth quarter of 2024decreased by 20% to $1.1 billion, compared to the fourth quarter in 2023. The decrease was primarily driven by lower clinical development and manufacturing expenses related to the COVID-19, RSV, seasonal flu, and combination vaccine programs, partially offset by increased spending on the norovirus and individualized neoantigen therapy (INT) programs. The reduction in flu program expenses reflects funding provided by Blackstone Life Sciences during the quarter. The absence of a $120 million upfront payment for the strategic research and development collaboration with Immatics recorded in the fourth quarter of 2023, also contributed to the year-over-year decline. Selling, General and Administrative Expenses: Selling, general and administrative expenses for the fourth quarter of 2024decreased by 25% to $351 million, compared to the fourth quarter in 2023. The reduction was primarily driven by lower consulting and outside services, reflecting the Company's continued focus on cost management and operational efficiencies achieved through prior investments in foundational capabilities. Income Taxes: The Company recognized an income tax benefit of $64 million for the fourth quarter of 2024, compared to $147 million in the same period last year. In both periods, the income tax benefit was not material as the Company continues to maintain a global valuation allowance against most of its deferred tax assets. Net (Loss) Income: Net loss was $(1.1) billion for the fourth quarter of 2024, compared to net income of $217 million for the fourth quarter of 2023. (Loss) Earnings Per Share: Loss per share was $(2.91) for the fourth quarter of 2024, compared to earnings per share of $0.55 for the fourth quarter of 2023. Cash Position: Cash, cash equivalents and investments as of December 31, 2024, were $9.5 billion, compared to $9.2 billion as of September 30, 2024. The increase during the quarter was primarily attributable to the timing of accounts receivable collections. Full Year 2024 Financial Results Revenue: Total revenue was $3.2 billion for the full year 2024, compared to $6.8 billion in 2023. The decrease in total revenue was mainly due to lower sales of the Company's COVID-19 vaccine. Net product sales for 2024 were $3.1 billion, a decrease of 53% from 2023. This decline reflects the transition to a seasonal commercial market for COVID-19 vaccines, with significantly lower sales volumes in Europe and other international markets as advance purchase agreements phased out. In the U.S., product sales remained consistent year-over-year, with an approximately $216 million benefit from the reversal of prior-year sales provisions. Excluding this adjustment, U.S. sales volumes decreased slightly compared to 2023, primarily due to lower vaccination rates and increased market competition. Additionally, the Company commenced sales of its RSV vaccine during the third quarter of 2024, generating $25 million in revenue for the year. Cost of Sales: Cost of sales for the full year 2024 was $1.5 billion, or 47% of net product sales, inclusive of third-party royalties of $155 million, inventory write-downs of $495 million, wind-down costs of $263 million, and unutilized manufacturing capacity of $105 million. This represents a $3.2 billiondecrease, compared to $4.7 billion in 2023, when cost of sales was 70% of net product sales. The decline reflects the impact of a strategic cost initiative launched in the third quarter of 2023 to resize manufacturing operations, which incurred $1.6 billion in charges in 2023. In addition to the initiative, cost of sales also benefited from lower inventory write-downs and reduced unutilized manufacturing capacity, contributing to improved efficiency. Of the wind-down costs incurred in 2024, a non-cash charge of $238 million related to the termination of a contract manufacturing agreement during the fourth quarter. Excluding the $238 million related to this termination, cost of sales as a percentage of net product sales for 2024 would have been approximately 39%. Research and Development Expenses: Research and development expenses decreased by 6% to $4.5 billion for 2024, compared to 2023. The decrease was primarily driven by lower clinical trial and clinical manufacturing expenses, as well as reduced upfront payments for collaboration agreements. These reductions were partially offset by the purchase of two priority review vouchers during the year. Selling, General and Administrative Expenses: Selling, general and administrative expenses decreased by 24% to $1.2 billion for 2024, compared to 2023. The decrease was primarily driven by reductions in consulting and outside services across all functions, as well as lower commercial and marketing expenses. These reductions reflect the Company's focus on cost discipline and operational efficiencies gained by reducing reliance on external consultants and bringing more functions in-house. Income Taxes: Income tax benefit for the full year 2024 was $46 million, compared to an income tax expense of $772 million in 2023. The shift was primarily due to the establishment of a global valuation allowance on most deferred tax assets in the third quarter of 2023. Net Loss: Net loss for the full year 2024 was $(3.6) billion, compared to $(4.7) billion in 2023. Loss Per Share: Loss per share for the full year 2024 was $(9.28), compared to $(12.33) in 2023. Cash Position: Cash, cash equivalents and investments as of December 31, 2024, and December 31, 2023, were $9.5 billion and $13.3 billion, respectively. The decrease in cash during 2024 was largely attributable to the full year's operating loss. 2025 Financial Framework Revenue: The Company reiterates 2025 expected revenue of $1.5 to $2.5 billion. Moderna expects revenue of approximately $0.2 billion in the first half of the year, reflecting the seasonality of its respiratory business. Cost of Sales: Cost of sales for 2025 is expected to be approximately $1.2 billion. Research and Development Expenses: Full-year 2025 research and development expenses are anticipated to be approximately $4.1 billion. Selling, General and Administrative Expenses: Selling, general and administrative expenses for 2025 are projected to be approximately $1.1 billion. Income Taxes: The Company continues to expect its full-year tax expense to be negligible. Capital Expenditures: Capital expenditures for 2025 are expected to be approximately $0.4 billion. Cash and Investments: Year-end cash and investments for 2025 are projected to be approximately $6 billion. Recent Progress and Upcoming Late-Stage Pipeline Milestones The Company remains focused on a prioritized research and development portfolio, delivering up to 10 product approvals through 2027. Respiratory vaccines: Next-generation COVID-19 vaccine: Moderna shared positive Phase 3 vaccine efficacy and immunogenicity data for its next-generation COVID-19 vaccine (mRNA-1283) at its R&D Day event in September 2024. The Company has filed for regulatory approval of mRNA-1283 with the FDA using a priority review voucher. The FDA has accepted Moderna's Biologics License Application (BLA) for mRNA-1283 and has assigned a Prescription Drug User Fee Act (PDUFA) goal date of May 31, 2025. Respiratory syncytial virus (RSV) vaccine: Moderna received regulatory approval of its RSV vaccine mRESVIA (mRNA-1345) for adults aged 60 years and older in 2024. The Company shared positive Phase 3 data for mRNA-1345 in high-risk adults aged 18-59 at its 2024 R&D Day event and has since submitted an application to the FDA for regulatory approval using a priority review voucher. The FDA has accepted Moderna's BLA and has assigned a PDUFA goal date of June 12, 2025. Seasonal flu + COVID vaccine: Moderna shared positive Phase 3 immunogenicity data for its flu/COVID combination vaccine (mRNA-1083) for adults aged 50 years and older at its 2024 R&D Day event. The Company has filed with the FDA for regulatory approval of mRNA-1083, which may require vaccine efficacy data from Moderna's ongoing Phase 3 seasonal flu vaccine study. Seasonal flu vaccine: Moderna has shared positive Phase 3 immunogenicity and safety data for its seasonal flu vaccine (mRNA-1010). The Company is conducting a two-season Phase 3 efficacy study (P304), where the timing of the efficacy readout depends on case accrual and could happen in the current season. Next-generation COVID-19 vaccine: Moderna shared positive Phase 3 vaccine efficacy and immunogenicity data for its next-generation COVID-19 vaccine (mRNA-1283) at its R&D Day event in September 2024. The Company has filed for regulatory approval of mRNA-1283 with the FDA using a priority review voucher. The FDA has accepted Moderna's Biologics License Application (BLA) for mRNA-1283 and has assigned a Prescription Drug User Fee Act (PDUFA) goal date of May 31, 2025. Respiratory syncytial virus (RSV) vaccine: Moderna received regulatory approval of its RSV vaccine mRESVIA (mRNA-1345) for adults aged 60 years and older in 2024. The Company shared positive Phase 3 data for mRNA-1345 in high-risk adults aged 18-59 at its 2024 R&D Day event and has since submitted an application to the FDA for regulatory approval using a priority review voucher. The FDA has accepted Moderna's BLA and has assigned a PDUFA goal date of June 12, 2025. Seasonal flu + COVID vaccine: Moderna shared positive Phase 3 immunogenicity data for its flu/COVID combination vaccine (mRNA-1083) for adults aged 50 years and older at its 2024 R&D Day event. The Company has filed with the FDA for regulatory approval of mRNA-1083, which may require vaccine efficacy data from Moderna's ongoing Phase 3 seasonal flu vaccine study. Seasonal flu vaccine: Moderna has shared positive Phase 3 immunogenicity and safety data for its seasonal flu vaccine (mRNA-1010). The Company is conducting a two-season Phase 3 efficacy study (P304), where the timing of the efficacy readout depends on case accrual and could happen in the current season. Latent and other vaccines: Cytomegalovirus (CMV) vaccine: The pivotal Phase 3 study of Moderna's CMV vaccine candidate (mRNA-1647) is fully enrolled and accruing cases, evaluating its efficacy, safety and immunogenicity in the prevention of primary infection in women of childbearing age. The Data Safety Monitoring Board (DSMB) met to review the initial study data and has informed the Company that the criterion for early efficacy was not met. The DSMB recommended that the study continue as planned. The Company remains blinded and anticipates efficacy data from the study in 2025. Norovirus vaccine: The two-season Phase 3 study evaluating the efficacy, safety and immunogenicity of Moderna's trivalent vaccine against norovirus (mRNA-1403) is fully enrolled in the Northern Hemisphere and the Company is preparing second season enrollment in the Southern Hemisphere. The trial is currently on FDA clinical hold following a single adverse event report of a case of Guillain-Barré syndrome, which is currently under investigation. The Company does not expect an impact on the study's efficacy readout timeline as enrollment in the Northern Hemisphere has already been completed. The timing of the Phase 3 readout will be dependent on case accruals. Cytomegalovirus (CMV) vaccine: The pivotal Phase 3 study of Moderna's CMV vaccine candidate (mRNA-1647) is fully enrolled and accruing cases, evaluating its efficacy, safety and immunogenicity in the prevention of primary infection in women of childbearing age. The Data Safety Monitoring Board (DSMB) met to review the initial study data and has informed the Company that the criterion for early efficacy was not met. The DSMB recommended that the study continue as planned. The Company remains blinded and anticipates efficacy data from the study in 2025. Norovirus vaccine: The two-season Phase 3 study evaluating the efficacy, safety and immunogenicity of Moderna's trivalent vaccine against norovirus (mRNA-1403) is fully enrolled in the Northern Hemisphere and the Company is preparing second season enrollment in the Southern Hemisphere. The trial is currently on FDA clinical hold following a single adverse event report of a case of Guillain-Barré syndrome, which is currently under investigation. The Company does not expect an impact on the study's efficacy readout timeline as enrollment in the Northern Hemisphere has already been completed. The timing of the Phase 3 readout will be dependent on case accruals. Oncology therapeutics: Individualized Neoantigen Therapy (INT): Moderna continues to demonstrate the potential clinical benefit of its individualized neoantigen therapy (INT) (mRNA-4157). In collaboration with Merck, the Phase 3 clinical trial for adjuvant melanoma is fully enrolled. Two Phase 3 studies for non-small cell lung cancer are enrolling. A randomized Phase 2 study for high-risk muscle invasive bladder cancer is enrolling, and a randomized Phase 2 study for adjuvant renal cell carcinoma is enrolling. Individualized Neoantigen Therapy (INT): Moderna continues to demonstrate the potential clinical benefit of its individualized neoantigen therapy (INT) (mRNA-4157). In collaboration with Merck, the Phase 3 clinical trial for adjuvant melanoma is fully enrolled. Two Phase 3 studies for non-small cell lung cancer are enrolling. A randomized Phase 2 study for high-risk muscle invasive bladder cancer is enrolling, and a randomized Phase 2 study for adjuvant renal cell carcinoma is enrolling. Rare disease therapeutics: Propionic acidemia (PA) therapeutic: In an ongoing Phase 1/2 study designed to evaluate safety and pharmacology in trial participants with PA, Moderna's investigational therapeutic (mRNA-3927) has been generally well-tolerated to date with no events meeting protocol-defined dose-limiting toxicity criteria. Early results suggest potential decreases in annualized metabolic decompensation event (MDE) frequency compared to pre-treatment, and the majority of patients have elected to continue on the open label extension study. The Company began generating registrational trial data in 2024. Methylmalonic acidemia (MMA) therapeutic: Moderna's investigational therapeutic for MMA (mRNA-3705) has been selected by the FDA for the Support for Clinical Trials Advancing Rare Disease Therapeutics (START) pilot program. The FDA and Moderna have agreed on the pivotal study design. The Company expects to start a registrational study in 2025. Propionic acidemia (PA) therapeutic: In an ongoing Phase 1/2 study designed to evaluate safety and pharmacology in trial participants with PA, Moderna's investigational therapeutic (mRNA-3927) has been generally well-tolerated to date with no events meeting protocol-defined dose-limiting toxicity criteria. Early results suggest potential decreases in annualized metabolic decompensation event (MDE) frequency compared to pre-treatment, and the majority of patients have elected to continue on the open label extension study. The Company began generating registrational trial data in 2024. Methylmalonic acidemia (MMA) therapeutic: Moderna's investigational therapeutic for MMA (mRNA-3705) has been selected by the FDA for the Support for Clinical Trials Advancing Rare Disease Therapeutics (START) pilot program. The FDA and Moderna have agreed on the pivotal study design. The Company expects to start a registrational study in 2025. Moderna Corporate Updates Published Moderna CEO Stéphane Bancel's annual letter to shareholders on January 6, 2025. Provided business and pipeline updates at the 43rd Annual J.P. Morgan Healthcare Conference on January 13, 2025. Announced updates on the Company's pandemic influenza program. Entered into a framework agreement with the European Union, Norway and North Macedonia that provides 17 participating countries a framework for tendering for Moderna's mRNA COVID-19 vaccine for up to four years should there be demand in addition to the current competitor contract. Scheduled the Moderna Annual Meeting of Shareholders to be held on Wednesday, April 30, 2025, at 8:00 a.m. ET. Published Moderna CEO Stéphane Bancel's annual letter to shareholders on January 6, 2025. Provided business and pipeline updates at the 43rd Annual J.P. Morgan Healthcare Conference on January 13, 2025. Announced updates on the Company's pandemic influenza program. Entered into a framework agreement with the European Union, Norway and North Macedonia that provides 17 participating countries a framework for tendering for Moderna's mRNA COVID-19 vaccine for up to four years should there be demand in addition to the current competitor contract. Scheduled the Moderna Annual Meeting of Shareholders to be held on Wednesday, April 30, 2025, at 8:00 a.m. ET. Company Accolades Moderna topped BioSpace's Best Places to Work in Biopharma ranking for fourth consecutive year. Moderna topped BioSpace's Best Places to Work in Biopharma ranking for fourth consecutive year. Key 2025 Investor and Analyst Event Dates Analyst Day: November 20 Analyst Day: November 20 Investor Call and Webcast Information Moderna will host a live conference call and webcast at 8:00 a.m. ET on February 14, 2025. 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/BI694d51cf38c44a3183177f19559ddb80 Webcast: https://investors.modernatx.com Telephone: https://register-conf.media-server.com/register/BI694d51cf38c44a3183177f19559ddb80 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 leader in the creation of the field of mRNA medicine. Through the advancement of mRNA technology, Moderna is reimagining how medicines are made and transforming how we treat and prevent disease for everyone. By working at the intersection of science, technology and health for more than a decade, the company has developed medicines at unprecedented speed and efficiency, including one of the earliest and most effective COVID-19 vaccines. Moderna's mRNA platform has enabled the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases and autoimmune diseases. With a unique culture and a global team driven by the Moderna values and mindsets to responsibly change the future of human health, Moderna strives 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 (formerly Twitter), 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, 2024 2023 2024 2023 $ 938 $ 2,793 $ 3,109 $ 6,671 28 18 127 177 966 2,811 3,236 6,848 739 929 1,464 4,693 1,122 1,406 4,543 4,845 351 470 1,174 1,549 2,212 2,805 7,181 11,087 (1,246 ) 6 (3,945 ) (4,239 ) 91 103 425 421 (29 ) (39 ) (87 ) (124 ) (1,184 ) 70 (3,607 ) (3,942 ) (64 ) (147 ) (46 ) 772 $ (1,120 ) $ 217 $ (3,561 ) $ (4,714 ) $ (2.91 ) $ 0.57 $ (9.28 ) $ (12.33 ) $ (2.91 ) $ 0.55 $ (9.28 ) $ (12.33 ) 385 381 384 382 385 395 384 382 _______ 1Includes grant, collaboration, and licensing and royalty revenue MODERNA, INC.CONDENSED CONSOLIDATED BALANCE SHEETS(Unaudited, in millions) December 31, December 31, 2024 2023 $ 1,927 $ 2,907 5,098 5,697 358 892 117 202 599 627 8,099 10,325 2,494 4,677 2,196 1,945 759 713 594 766 $ 14,142 $ 18,426 $ 405 $ 520 1,427 1,798 153 568 221 129 2,206 3,015 58 83 671 643 39 575 267 256 3,241 4,572 866 371 (10 ) (123 ) 10,045 13,606 10,901 13,854 $ 14,142 $ 18,426 MODERNA, INC.CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS(Unaudited, in millions) Years Ended December 31, 2024 2023 $ (3,561 ) $ (4,714 ) 429 305 189 621 (95 ) (61 ) 52 35 60 7 534 493 145 1,802 83 747 (53 ) (605 ) (69 ) 13 (385 ) (340 ) (439 ) (2,060 ) 28 551 78 88 (3,004 ) (3,118 ) (6,529 ) (3,760 ) 5,562 5,575 3,967 3,206 (1,051 ) (707 ) - (85 ) - (23 ) 1,949 4,206 66 46 - (1,153 ) (10 ) (270 ) 56 (1,377 ) (999 ) (289 ) 2,928 3,217 $ 1,929 $ 2,928 Spikevax® and mRESVIA® 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 ability to deliver up to 10 product approvals through 2027; Moderna's ability to deliver cost efficiencies across its business and reduce cash costs over the next two years; Moderna's 2025 financial framework, including its expected revenue range and ending cash balance; and anticipated milestones for Moderna's pipeline programs. 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, 2023, 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 ContactsMedia:Chris RidleyHead of Global Media Relations+1 617-800-3651Chris.Ridley@modernatx.com Investors:Lavina TalukdarSenior Vice President & Head of Investor Relations+1 617-209-5834Lavina.Talukdar@modernatx.com SOURCE: Moderna, Inc.

忽如一夜春风来 2024 年 5 月 31 日，mRESVIA（mRNA-1345）获美国 FDA 批准上市，用于预防 60 岁及以上老年人因呼吸道合胞病毒（RSV）感染引发的下呼吸道疾病。作为继新冠疫苗后 Moderna 第二款商业化产品，其获批标志着 mRNA 技术向常规疫苗领域的突破性拓展。我难掩雀跃之情，深夜爬起来写稿子，同大家分享这个好消息背后的信号：mRNA 技术的成功绝非局限于新冠疫情，其快速研发和规模化生产优势将成为未来疫苗开发的主流选择。 然而，市场的反应却令人唏嘘。在医药行业整体低迷的背景下，mRESVIA 的成功上市未能激起预期波澜。上市后首个季度（2024 年第三季度），mRESVIA 仅实现 1000 万美元销售额，与 GSK 的 Arexvy（同期销售额 2.29 亿美元）和辉瑞的 Abrysvo（同期 1.46 亿美元）形成鲜明对比。更深层的挑战来自临床数据的争议：尽管 mRESVIA 在短期随访中展现出 83.7%的保护效力，但中位随访 8.6 个月后效力降至 62.5%，显著低于 GSK 疫苗 Arexvy 在 6.7 个月随访期的 82.6%和辉瑞疫苗 Abrysvo 的 66.7%。更糟糕的是，在针对婴儿的临床试验中，Moderna 开发的 RSV 疫苗不仅未能保护他们，反而使一些人在感染 RSV 或其他呼吸道病毒时病情加重。目前，FDA 已经叫停所有针对儿童和婴幼儿的 RSV 疫苗临床研究。因此，最终行业普遍将其定位为三款 RSV 疫苗中预防效果最弱的产品。 困于新冠 新冠疫情将 mRNA 技术从生物制药的细分赛道，推向了引领新一轮医药革命的风口浪尖上。Moderna 新冠疫苗在 2022 年和 2023 年的销售额分别为 180 亿美元和 67 亿美元。截至 2025 年 1 月 13 日，Moderna 2024 年产品实际销售额统计数值为 30~31 亿美元，其中，美国为 17 亿美元，世界其他地区为 13~14 亿美元。与 2023 年相比，Moderna 2024 年销售额腰斩。 最近，Moderna 下调了 2025 年全年收入指引，并且是大幅下调。之前预计 2025 年的销售额为 25 亿至 35 亿美元，但更新后的指引销售额预计为 15 亿至 25 亿美元，下调幅度为 10 亿美元。如今，新冠疫苗接种率不可逆地骤降，mRESVIA 疫苗无法接棒 Spikevax，Moderna 收入结构过于单一，面临巨大营收压力，处境艰难。 奋力破茧 为扭转困境，Moderna 在 2024 年做出了一系列努力。从公司整个研发管线来看，除了成功推动 RSV 疫苗 mRESVIA 上市，Moderna 集全力打造由新冠病毒、呼吸道合胞病毒及流感病毒组成的呼吸道疫苗产品矩阵，以此巩固自身的基本盘。经过去一年，4 个呼吸道 mRNA 疫苗产品的 3 期临床试验结果达到预期，并且，仅仅在 3 个月内，创纪录地完成了其中 3 个 mRNA 疫苗产品的上市申请（BLA）。作为新一代新冠 mRNA 疫苗，mRNA-1283 仅编码 NTD-RBD（NTD 与 RBD 通过 G3SG3 接头连接，且拥有膜锚定区），并且， 在抗原表达、诱导抗体反应和冷藏温度 (2-8°C) 下的稳定性方面表现出明显提升。在 18-59 岁高危成年人群中展开的 mRESVIA（mRNA-1345）3 期临床试验，免疫原性满足临床试验终点，50 μg 剂量耐受性良好，未发现安全问题。在 3 期临床试验中，季节性流感疫苗 mRNA-1010 始终展现出可接受的安全性和耐受性，达到所有免疫原性主要终点，与获得许可的标准剂量流感疫苗 （Fluarix®） 相比，表现出更高的抗体滴度。深受瞩目的流感/新冠联合疫苗 mRNA-1083 同样达到 3 期临床试验主要终点，并在 50 岁及以上的成年人中触发了比获批的流感疫苗或者新冠疫苗更强烈的免疫反应。Moderna 打算不再向监管寻求 mRNA-1010 的加速获批，而是集中精力推动 mRNA-1083 的尽早获批上市。 对疱疹病毒科的潜伏病毒疫苗产品，也是 Moderna 的重点推进管线，主要包括单纯疱疹病毒（HSV）、水痘-带状疱疹病毒（VZV）、爱泼斯坦-巴尔病毒疫苗（EBV）及巨细胞病毒（CMV）。在美国，每 200 名婴儿中就有 1 名出生时患有先天性 CMV 感染，是美国出生缺陷最常见的传染性原因。CMV 候选疫苗 （mRNA-1647） 的关键 3 期研究已全面入组并累积病例，旨评估其在预防育龄妇女（16 至 40 岁）原发性感染方面的疗效、安全性和免疫原性。 作为一种肠道病毒，诺如病毒（Norovirus）具有高度传染性，是引发腹泻的主要原因，尤其是在幼儿和老年人中，会造成严重的发病率和死亡率。全球尚无上市获批的诺如病毒疫苗，Moderna 认为，这是一个非常大的未被满足的医疗需求。Moderna 用于预防诺如病毒的三价候选疫苗 （mRNA-1403）已正式展开 3 期临床试验，拥有极大可能在一段时间内成为全球唯一一款上市的诺如病毒疫苗。 与默克合作开发的个性化肿瘤新抗原疫苗 mRNA-4157(V940)是 Moderna 重点布局的肿瘤管线之一，其编码多达 34 种新抗原，与 PD-1 抑制剂 Keytruda 组合联合使用时，可使经手术切除高风险黑色素瘤（III/IV 期）患者的复发或死亡风险降低 49%，远处转移或死亡风险降低 62%。Moderna 和默克迅速将临床研究扩展到其他肿瘤类型，包括肾细胞癌或肾癌患者的 2 期辅助治疗;高危肌层浸润性膀胱癌患者的 2 期辅助治疗;以及皮肤鳞状细胞癌（第二种最常见的皮肤癌）患者的 2/3 期新辅助和辅助治疗。同时，黑色素瘤的辅助治疗 3 期临床试验于 2024 年完成入组。此外，mRNA-4359 是 Moderna 给寄予厚望的另外一款肿瘤疫苗，其编码的免疫原性肽旨在产生抗 PD-L1/IDO1 特异性 T 细胞，以杀死免疫抑制调节细胞以及表达这些抗原的癌细胞，从而使平衡偏向炎症和/或免疫允许的肿瘤微环境。 在罕见病领域，Moderna 选择优先推进的管线是针对代谢酶缺乏引起的两种有机酸血症的 mRNA 药物，分别为治疗甲基丙二酸血症（MMA）的 mRNA-3705 和治疗丙酸血症（PA）的 mRNA-3927。这两种疾病的典型特殊是代谢失代偿事件（MDE），可导致严重和危及生命的症状，如呕吐、嗜睡、癫痫发作和昏迷。在目前正在进行的临床 1/2 期试验中，mRNA-3705 和 mRNA-3927 总体耐受性良好，与治疗前相比，年化 MDE 频率可能会降低。 国内市场的迷茫内卷 当石药与蓝鹊研发的新冠 mRNA 疫苗各自获得紧急使用授权时，这场始于疫情暴发的国产mRNA新冠疫苗竞赛已悄然草草收尾。三年资本狂热催生的十余家 mRNA 初创企业版图中，航文总出走海外、斯微生物启动破产重整等标志性事件，宣告着国内 mRNA 行业正式步入去泡沫化周期。 融资市场温度计显示着剧烈变化：2021 年艾博单笔融资超 7 亿元美元的公告曾火爆刷屏，而今全年过亿级融资已近乎绝迹。创始人从被资本簇拥的"闭门谢客"，转向带着数据四处奔波，“笑迎八方客”。多数初创 Biotech 在年终核算时面临的却是融资颗粒无收与现金流持续失血的残酷现实。 在旧文愿2024国内mRNA行业：开出一朵小红花，我们曾统计，在 2023 年，国内总共有 14 家企业获得 NMPA 批准的临床试验共 16 项，其中仅新冠疫苗项目就占据到 5 个，其他疫苗项目为 9 个。值得庆幸的是，与 2023 年相比，过去一年中，国内 mRNA 企业发起或者获得批准的新药临床试验项目总数显著增加：在 2024 年，总共有 24 家企业，提交了 50 项新药临床试验申请，其中 NMPA 批准 24 项，FDA 批准 12 项，NMPA 受理 13 项，FDA 受理 1 项。 与 2023 年相比，2024 年国内仅仅只剩下深信生物一家还在推进新冠 mRNA 疫苗的临床试验：2024 年 4 月 17 日，深信生物宣布其在研广谱新型冠状病毒 mRNA 疫苗 IN002.5.1 获得 FDAⅡ期临床试验批准。 放弃新冠疫苗后，国内绝大多 mRNA 疫苗初创公司开始在呼吸道合胞病毒（RSV）、单纯-疱疹病毒（VZV）及人乳头瘤病毒（HPV）疫苗三大赛道形成严重内卷。在 RSV 疫苗赛道中，国内共有 12 家企业发起临床试验申请，其中有 4 家获得 FDA 批准，4 家获得 NMPA 批准，4 家获得 NMPA 受理；在 VZV 疫苗赛道中，国内共有 8 家企业发起临床试验申请，其中有 1 家获得 FDA 批准，2 家获得 NMPA 批准，6 家获得 NMPA 受理；在 HPV 疫苗赛道中，国内共有 6 家企业发起临床试验申请，其中有 1 家获得 FDA 批准，5 家获得 NMPA 批准，1 家获得 NMPA 受理。 尤其值得关注的是，国内环状 RNA 领域取得重大突破，转录本和环码提交的临床试验申请分别获得 FDA 和 NMPA 的批准，这在全球属于首发。基于 mRNA 技术的基因编辑、蛋白替代疗法及 CAR-T 疗法也纷纷拿到 NMPA 批准的临床试验申请。 未来勒紧裤腰带，好钢用在刀刃上 为扭转营收下滑，Moderna 在未来会采取 3 个策略： 第一，持续推动已经获批上市的两款产品—新冠疫苗 Spikevax 和 RSV 疫苗 mRESVIA 的市场销售。 根据美国疾病控制和预防中心的数据，COVID-19 导致 65 岁及以上人群住院的人数是流感的三倍。此外，在 2023-2024 年因 COVID-19 住院的成年人中，超过 95% 没有接种最新疫苗的记录。从零售销售额来看，2024 年美国新冠疫苗零售市场是相对稳定的。相比 2023 年新冠疫苗零售总额（2840 万美元），2024 年度美国新冠疫苗零售额（2640 万美元）仅下降 7%，这比过去要少得多。在 65 岁以上人群中，2024 年度新冠疫苗零售额（1450 万美元）比 2023 年度（1420 万美元）降低 2%，而在 64 岁及以下的人群中，2024 年度新冠疫苗零售额（1220 万美元）比 2023 年度（1390 万美元）降低 12%。在 2025 年，随着美国市场之外越来越多的国家地区批准 RSV 疫苗上市，将有极大可能提升公司产品销售额。 第二条，在未来三年，将会大力推动 10 个产品的获批上市，以此带动公司营收的增加。在过一年中的三个月内，Moderna 提交了连续 3 个产品的 BLA 上市申请。 第三，持续降低企业成本。对于公司来说，管理现金一直是非常重要的。Bancel 称，在新冠疫情期间，为保证疫苗质量，尽可能多地挽救生命，他们不得不专注于速度。成本控制自然成为一个不需要优先考虑的事项，因为他们必须拥有快速的执行力。随着新冠疫情的消散，在研发生产、销售及日常运营等多个方面，Moderna 已经开启长达超过 18 个月的降本增效。与 2023 年相比，Moderna 将现金运营成本降低了 25% 以上，并计划在 2025 年将现金成本降低 10 亿美元，之后在 2026 年再节省 5 亿美元的成本。 未来两到三年，Moderna 的日子不会太好过，国内 mRNA 行业更将迎来一场生死考验。除了资本的收缩，国内很多 mRNA 疫苗初创公司的死穴是从一开始就没弄清楚自己究竟要用 mRNA 技术解决什么样的医学问题。大家一股脑地去卷那些常规的疫苗赛道，不是真正地想研发一款 mRNA 产品，仅仅是为继续融资而申请临床试验。迷茫的内卷只会让这些初创 Biotech 一步步走向崩塌，清晰规划管线，排除万难，坚定走自己的路才会等到冰雪消融，春暖花开。 识别微信二维码，添加生物制品圈小编，符合条件者即可加入 生物制品微信群！ 请注明：姓名+研究方向！ 版 权 声 明 本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。