모더나(MRNA) 리스크 요인 변화

이번 보고서

2025 연차보고서

10-K · 기간 말 2025. 12. 31. · 제출 2026. 2. 20.

비교 기준

2024 연차보고서

10-K · 기간 말 2024. 12. 31.

SEC 원문 ↗

새 리스크 항목

신규 문단

110

수정 문단

삭제

+2%

분량 변화

AI 한국어 요약

한 줄 요약

2025년 미국 규제기관(FDA·CDC·ACIP)의 정책 변화가 백신 수요와 비용에 이미 영향을 줬다는 내용을 별도 리스크로 새로 넣었어요.

주목할 변화

신규미국 규제·접종 권고 변화2025년 FDA 정책과 CDC·ACIP 접종 권고 변화가 백신 수요에 영향을 줬을 수 있다고 적었어요. 새 시판 후 의무(post-marketing commitments)로 비용도 늘었다고 했어요("have impacted and may in the future impact our costs"). 코로나 백신은 FDA가 요구하는 근거 수준이 바뀌어 추가 임상이 필요하거나, 허가 대상 인구가 좁아질 수 있다고 덧붙였어요.
신규최혜국(MFN) 약가 정책2025년 5월 대통령 행정명령으로 미국 약가를 선진국 최저가에 맞추라는 압박이 생겼어요. 이걸 독립된 리스크로 신설했어요. 미국 가격이 해외 기준가에 묶이면 해외 가격 결정과 보험 급여에도 영향이 갈 수 있다고 썼어요("If our U.S. pricing becomes tied to international reference prices"). Medicaid 리베이트 부담이 커질 수 있다는 문장도 추가됐어요.
신규대출 약정 위반 위험Ares Capital이 주도하는 대주단과 맺은 신용 계약이 새로 등장했어요. 약정(covenants)을 어기면 대출금을 한꺼번에 갚으라는 요구를 받을 수 있다고 했어요. 담보 자산이 처분될 수도 있다고 적었어요. 이 계약 때문에 배당에도 제한이 있다고 명시했어요.
강화코로나 백신 제조물 책임지금은 PREP Act로 책임 보호를 받고 있다고 처음 밝혔어요. 하지만 보건부 장관이 이 보호를 철회하거나 백신이 VICP(백신 피해 보상 프로그램)로 옮겨지지 않으면 책임 노출이 커질 수 있다고 썼어요("significantly greater product liability exposure"). VICP 자체가 크게 바뀔 위험도 추가했어요.
강화경쟁, 특히 항암 분야유럽 다수 시장에서 코로나 백신 판매가 막힌 상태가 2026년 말까지 이어진다고 시점을 적었어요. 항암 시장은 "intensely competitive, innovative and fast-moving"이라고 새로 썼어요. 치료 표준이 빨리 바뀌면 초기 결과가 좋아도 임상 설계나 상업화가 어려워질 수 있다고 했어요.
강화구조조정에 따른 조직 리스크기존 제목은 '성장 관리'였는데 '규모·구조 변화 관리'로 바뀌었어요. 인력 감축과 구조조정으로 인재 유지, 사내 지식 보존, 직원 사기 유지가 어려워질 수 있다고 추가했어요("workforce reductions, restructuring").
강화심근염 위험 언급 확대기존에는 Spikevax만 언급했어요. 이번에는 신제품 mNEXSPIKE 접종 뒤에도 심근염·심낭염이 보고됐다고 새로 적었어요("including mNEXSPIKE").
신규관세·무역정책관세나 보복 조치로 공급 비용이 오르거나 공급처를 바꿔야 할 수 있다는 리스크가 새로 생겼어요. 다만 "we have not experienced adverse impacts of tariffs to date"라고 밝혔어요.

참고

2024년 말 약 95억 달러였던 현금·투자자산은 2025년 말 약 81억 달러로 기재됐어요. 이 금액에는 정기대출(term loan)에서 인출한 6억 달러가 포함돼 있어요. 기존에 있던 연도별 제품 매출 수치(2024년 31억 달러 등)와 코로나·RSV 시장 불확실성 리스크 항목은 삭제되고, 위의 규제·시장 불확실성 항목으로 대체됐어요.

원문 비교

새 리스크 항목
Regulatory and market uncertainty have and may continue to impact our business and the markets for our products.
신규Regulatory and market uncertainty have and may continue to impact our business and the markets for our products.
Our ability to successfully commercialize our approved vaccines and any future products depends in part on evolving regulatory requirements, public health recommendations and market acceptance. In 2025, changes at U.S. regulatory agencies impacted policies and priorities related to our industry. For example, changes in FDA regulatory policies, post-marketing safety monitoring, and evidentiary expectations, as well as CDC and Advisory Committee on Immunization Practices (ACIP) recommendations regarding eligibility, target populations, and vaccination practices, may have affected and may continue to affect demand for our vaccines. Some of these changes, including new post-marketing commitments, have impacted and may in the future impact our costs. Ongoing regulatory uncertainty and evolving regulatory and public health guidance could impact future approvals, advisory committee recommendations, acceptance and demand for our existing or future products.
새 리스크 항목
We may experience difficulties executing our near-term strategy and prioritized pipeline.
신규We may experience difficulties executing our near-term strategy and prioritized pipeline.
While we expect to launch multiple new products over the next several years, our ability to commercialize our pipeline is subject to many risks, including those described elsewhere in these Risk Factors under “Risks related to our pipeline, product development and regulatory review” and “Risks related to the manufacturing of our commercial products and product candidates.” If we do not successfully execute our near-term plan for growing our infectious disease vaccine franchise, our ability to invest in our pipeline, including our oncology and rare disease programs, may suffer.
신규The commercial success of our products depends on the degree of market acceptance by physicians, patients, third-party payors and others in the medical community.
•whether our product presentation meets customer demand;
새 리스크 항목
Federal legislative and regulatory efforts to implement reference pricing or most-favored-nation pricing models and other, similar regulatory actions could impact our product revenues and materially harm our business.
신규Federal legislative and regulatory efforts to implement reference pricing or most-favored-nation pricing models and other, similar regulatory actions could impact our product revenues and materially harm our business.
On May 12, 2025, President Trump issued an executive order calling on pharmaceutical manufacturers to voluntarily reduce the prices of medicines in the U.S. and directing the Secretary of Health and Human Services (HHS) to communicate price targets to pharmaceutical manufacturers to align prices with those in comparably developed nations, an approach commonly referred to as "most-favored-nation" (MFN) pricing and, in the event significant progress towards MFN pricing is not delivered, to propose rulemaking to impose MFN pricing.
신규Federal legislative and regulatory efforts to implement reference pricing or most-favored-nation pricing models and other, similar regulatory actions could impact our product revenues and materially harm our business.
MFN pricing models in the U.S. could also affect our international pricing strategy and future decisions on reimbursement and commercialization in certain jurisdictions. If our U.S. pricing becomes tied to international reference prices, we may face decisions regarding pricing in foreign markets that could result in reduced patient access internationally, affect our relationships with foreign regulatory authorities and payers, or impact our ability to obtain or maintain reimbursement approvals in ex-U.S. markets.
신규Federal legislative and regulatory efforts to implement reference pricing or most-favored-nation pricing models and other, similar regulatory actions could impact our product revenues and materially harm our business.
These reforms remain subject to change, potential legal challenges, or expansion through additional rulemaking or sub‑regulatory guidance, creating uncertainty for our overall pricing strategy. It remains to be seen whether and how these drug pricing initiatives will apply to our products, how they will affect the broader pharmaceutical industry, and whether similar reform measures may be adopted in the future.
신규If we cannot obtain, or are delayed in obtaining, regulatory approvals and advisory committee recommendations, we will be unable to effectively commercialize, or will be delayed in commercializing, our product candidates.
For example, recent FDA policy updates regarding COVID vaccine approvals and the evidence expected for certain populations could require additional clinical data or trials to support broader indications, delay approvals or supplemental applications, or result in more limited labeled populations, which could adversely affect the timing and scope of commercialization for our COVID vaccines, including updated or variant-adapted formulations.
신규We may experience delays in enrolling participants in our clinical trials.
•availability of competing therapies and clinical trials, and clinicians’ and participants’ perceptions of the relative advantages, risks and side effects of our product candidates compared to other available therapies, including any new drugs or treatments;
새 리스크 항목
mRNA drug development involves substantial clinical and regulatory risks, and negative perceptions of our platform, products and product candidates could adversely affect our business and ability to obtain regulatory approvals.
새 리스크 항목
Although we have obtained rare pediatric disease designation for mRNA-3927, we may not be eligible to receive a priority review voucher in the event the FDA determines we no longer meet the criteria for designation, revokes the designation or FDA approval does not occur by September 30, 2029.
신규Although we have obtained rare pediatric disease designation for mRNA-3927, we may not be eligible to receive a priority review voucher in the event the FDA determines we no longer meet the criteria for designation, revokes the designation or FDA approval does not occur by September 30, 2029.
The sponsor of an application for a rare pediatric disease drug product may be eligible for a voucher that can be used or sold to obtain a priority review for a subsequent application submitted under section 505(b)(1) of the Federal Food, Drug, and Cosmetic Act or section 351 of the Public Health Service Act. We received rare pediatric disease designation from the FDA for mRNA-3927. We may, in the future, apply for rare pediatric disease designation from the FDA for future product candidates that may qualify for designation. Vouchers for rare pediatric disease drugs are awarded for qualifying applications when the drug receives approval. Under current law, after September 30, 2029, the FDA may not award any rare pediatric disease priority review vouchers, although the FDA's authority to do so could be extended by Congress in the future.
신규Our manufacturing facilities or those of third-party manufacturers or suppliers may fail to meet regulatory requirements, which could delay approval of or increase production costs for our products.
•ineffective corrective or preventative actions taken to address such deviations as processes scale;
신규Our manufacturing facilities or those of third-party manufacturers or suppliers may fail to meet regulatory requirements, which could delay approval of or increase production costs for our products.
•product or facility contamination, including due to ineffective quality control strategies or failures identified through environmental monitoring programs;
새 리스크 항목
Failure to comply with the covenants in our credit agreement could adversely affect our business
신규Failure to comply with the covenants in our credit agreement could adversely affect our business
A failure to comply with the covenants in our credit agreement with lenders led by Ares Capital Corporation, as administrative agent, could result in an event of default, which, if not cured or waived, could have a material, adverse effect on our business, financial condition, and results of operations. In the event of any such default, the holders of our indebtedness (i) would not be required to lend any additional amounts to us; and (ii) could elect to declare all then outstanding indebtedness, including accrued interest and unpaid fees, to be due and payable and terminate all commitments to extend further credit, if applicable.
신규Failure to comply with the covenants in our credit agreement could adversely affect our business
If we are unable to repay those amounts, the holders of our secured indebtedness could proceed against their secured collateral to seek repayment from the proceeds of the sale or liquidation of our assets. If our indebtedness were to be accelerated, there can be no assurance that our assets would be sufficient to repay such indebtedness in full.
신규We may encounter difficulties in managing changes to the size, structure and scope of our company.
We have experienced significant growth in our operations and workforce in recent years and, more recently, have undertaken initiatives to reduce costs, prioritize our portfolio and adjust the size and structure of our organization. As a result, we must continue to adapt and improve our managerial, operational, and financial systems to effectively support our evolving business, including potential future growth and expansion initiatives. These efforts may require our management to devote substantial time and attention away from day-to-day operations and strategic execution.
신규Healthcare legislative reform discourse and potential or enacted measures may have a material adverse impact on our business and results of operations and legislative or political discussions surrounding the desire for and implementation of pricing reforms may adversely impact our business.
In addition, the U.S. government is pursuing measures intended to reduce the cost of drugs in the United States. For example, in May 2025, the President issued an executive order directing the U.S. Department of Health and Human Services and other federal agencies to take certain steps intended to, among other things, reduce the prices of drugs sold in the United States to match the lowest price available for the same drugs in comparably developed nations. It is currently unclear how and to what extent these measures may be implemented and what impact any such implementation would have on us.
신규We are subject to various and evolving laws and regulations governing the privacy and security of personal data, and our failure to comply could result in fines or criminal penalties and damage our reputation.
Regulators and legislators are also increasingly scrutinizing and restricting certain personal data transfers and transactions involving foreign countries. For example, the Department of Justice’s January 8, 2025, rule on “Preventing Access to U.S. Sensitive Personal Data and Government-Related Data by Countries of Concern or Covered Persons,” prohibits data brokerage transactions involving certain sensitive personal data categories, including health data, genetic data, and biospecimens, to countries of concern, including China. The regulations also restrict certain investment agreements, employment agreements and vendor agreements involving such data and countries of concern, absent specified cybersecurity controls. Actual or alleged violations of these rules may be punishable by criminal and/or civil sanctions, result in exclusion from participation in federal and state programs or restrict our ability to use certain vendors, sites, investigators, or service providers in global clinical trials.
신규Our use of generative AI ("GenAI") and other AI technologies presents certain risks and challenges given the emerging nature of AI technologies.
In the United States, over the past year, states have advanced, and in some cases passed, dozens of laws focusing on AI and GenAI governance and regulation, including on deployment of AI Technologies in healthcare settings. At the same time, the Trump Administration has endorsed a federal moratorium on the enforcement of state AI laws, including through an executive order on “Ensuring a National Policy Framework for Artificial Intelligence.” So far, these efforts have not been successful at curtailing state action on AI regulation, contributing to a complicated legislative patchwork, which may be litigated in state and federal courts. Moreover, the FDA has advanced guidance and proposed frameworks for regulating AI Technologies in drug discovery, marketing submissions, and medical device development.
신규Evolving environmental, social and governance (ESG) standards and expectations may expose us to numerous risks.
Many investors use ESG screening criteria to determine whether we qualify for inclusion in their investment portfolios, and such investors and other stakeholders expect us to set ESG goals and provide robust disclosure regarding such goals, progress toward goals and other ESG matters of interest. Potential changes in voting practices and the fragmented influence of proxy advisors may impact investor expectations. In addition, we also face ESG-related expectations from certain customers outside the U.S. that can impact our competitiveness in commercial tenders. In response, we have established ESG goals and adapted our tracking and reporting to various ESG frameworks; however, these goals reflect our current plans and aspirations and may not be achieved.
새 리스크 항목
We do not expect to pay cash dividends for the foreseeable future.
새 리스크 항목
Changes in tariffs and other governmental trade policies could negatively affect our business and results of operations.
신규Changes in tariffs and other governmental trade policies could negatively affect our business and results of operations.
Recent governmental actions and proposals relating to tariffs and other trade policies have created uncertainty about future trading arrangements and the possibility of imposing or increasing tariffs on certain goods. For example, certain governments (including the U.S. and other countries where we do business) have imposed or may impose tariffs on a wide range of products, raw materials, and intermediate goods. Additional tariffs, or retaliatory measures by other countries in response, may be implemented at any time. Should these or similar tariffs remain in place (or be re-imposed or increased), or if additional tariffs or trade restrictions are enacted in the future, they could cause us or our customers to face higher supply costs, delays or a need to switch suppliers. These actions could adversely affect our margins, profitability, financial condition, and results of operations. While we have not experienced adverse impacts of tariffs to date, we cannot predict future changes in trade policy or the terms of any renegotiated trade agreements, nor can we determine the impact they may have on our business. Any such changes could have a material adverse effect on our business, financial condition, and results of operations.
수정Regulatory and market uncertainty have and may continue to impact our business and the markets for our products.
Vaccination rates in the future may also be lower than our ~~expectations, and are likely~~ expectations due to ~~be impacted by a number of~~ other factors, including ~~public health authority recommendations,~~ viral evolution, medical ~~need, viral evolution~~ need and consumer motivation to vaccinate. These and other factors may make it difficult to accurately forecast vaccination rates for our products. If demand for COVID vaccines continues to decline, we lose significant market share, or our products are subject to significant competitive pricing pressure, our product sales may not materialize consistent with our projections. Beyond COVID, we have experienced challenges in the RSV market, in part due to advisory committee recommendations that were more limited than anticipated.
수정Regulatory and market uncertainty have and may continue to impact our business and the markets for our products.
~~Additionally,~~ Furthermore, our decisions regarding seasonal vaccine ~~development~~ development, including for COVID-19, will be informed by annual guidance from the FDA and foreign regulators, which may impact the timing of development for our COVID vaccines. Different regulators have in the past and may in the future issue varying guidance regarding vaccine composition or populations who should receive a vaccine. If Additionally, if our efforts to develop variant-specific vaccines are delayed or not as successful as our competitors’, we could suffer reputational harm, loss of market share and adverse financial results. ~~Additionally, we~~ We may expend significant resources adapting our vaccines or conducting clinical trials to protect against variants, but a market for our adapted vaccines may fail to develop or demand may not align with our projections or cost expenditures.
수정We may experience difficulties executing our near-term strategy and prioritized pipeline.
~~Our~~ Furthermore, our broad clinical success and ~~recent~~ post-pandemic commercial challenges have necessitated a more selective and paced approach to our research and development investment. If we do not successfully implement our cost efficiency and prioritization programs, we may fail to meet our cash breakeven ~~goals.~~ goal. ~~Furthermore,~~ Additionally, as we pursue ~~and fund the~~ development of our prioritized programs, we may forego or delay pursuit of other opportunities that could ~~later~~ prove to have greater commercial potential. If our prioritized programs are unsuccessful, or not as successful as ~~other programs~~ others could have been, we may be unable to realize a sustainable return on our investments and or achieve long-term growth.
수정The vaccine market, and pharmaceutical market more generally, is intensely competitive, and we may be unable to compete effectively in the market for existing or new products, treatment methods or technologies.
The vaccine market, and pharmaceutical market more generally, is intensely competitive, and we may ~~not~~ be unable to compete effectively in the market for existing or new products, treatment methods or technologies.
수정The vaccine market, and pharmaceutical market more generally, is intensely competitive, and we may be unable to compete effectively in the market for existing or new products, treatment methods or technologies.
We compete with ~~well-established, larger~~ larger, well-established and experienced pharmaceutical companies for sales of our products, including against Pfizer and Sanofi for sales of our COVID ~~vaccine~~ vaccines and Pfizer and GSK for our RSV vaccine. Additionally, we have been excluded from selling our COVID vaccines in many European markets due to a competitor’s contract with the European Commission, which does not lapse until year-end 2026. For RSV vaccines, we entered a market already occupied by two larger competitors and may continue to face difficulties achieving market share. These competitors have exploited and may in the future exploit their greater size, infrastructure, resources and experience to gain advantages in contracting with customers by, among other things, bundling their products, leveraging larger supply chains and greater purchasing power and utilizing their global networks.
수정The vaccine market, and pharmaceutical market more generally, is intensely competitive, and we may be unable to compete effectively in the market for existing or new products, treatment methods or technologies.
In addition, certain U.S. private vaccine market practices, including regarding discounts, rebates and returns, may cause us to realize significantly lower revenues than list prices. We may also be adversely affected by similar market practices outside of the United States. In some instances, our competitors have been able to offer more attractive terms than we can, and they may continue to do so in the future.
수정The vaccine market, and pharmaceutical market more generally, is intensely competitive, and we may be unable to compete effectively in the market for existing or new products, treatment methods or technologies.
More generally, the pharmaceutical market is highly competitive and certain of the disease areas we are targeting present particularly high competitive risk. For example, the oncology market is intensely competitive, innovative and fast-moving. Other companies, academic institutions, governmental agencies and public and private research organizations are developing products that may compete with programs in our development pipeline. These competitors may have products that have already been approved and accepted by the medical community or are in later stages of development. We For example, we are developing a seasonal flu vaccine, for which there is a well-developed market, and we may need to offer more favorable terms to gain market share (which we may be unable to do), which may negatively impact our profitability. Additionally, competitive products may make any products we develop obsolete or noncompetitive before we can recover the expenses of developing and commercializing our products. In oncology, standards of care often evolve rapidly, and changes during the development or commercialization of our product candidates could reduce their clinical relevance, complicate clinical trial design, increase development costs or timelines, or limit commercial adoption, even for programs that show promising early results.
수정The vaccine market, and pharmaceutical market more generally, is intensely competitive, and we may be unable to compete effectively in the market for existing or new products, treatment methods or technologies.
Additionally, ~~any~~ our products ~~that we develop~~ may struggle to compete against ~~those of our competitors~~ competitors’ products for a variety of reasons, including relative safety and effectiveness, degree of any side effects, shelf-life, ease of administration and the extent to which patients accept relatively new routes of administration, the timing and scope of regulatory approvals, the availability and cost of manufacturing, distribution, marketing and sales capabilities, price, reimbursement coverage and patent protection. Even if our products demonstrate superiority to ~~those of competitors, consumers,~~ competitors’ products, consumers and retailers ~~and the public~~ may fail to appreciate that benefit, or existing purchase commitments ~~for a competitor’s product~~ with competitors may discourage them from purchasing from us. These factors, or the perception of these factors, could lead to a competitor’s product being more successfully commercialized. Further, the mRNA medicines field is growing rapidly, with increased competitive pressure from large and more established pharmaceutical companies. The actual or perceived success or failure of others may adversely impact our ability to commercialize our products. See “Business—Government Regulation—Coverage and reimbursement.”
수정We have experienced commercial challenges and may experience additional challenges in the future.
We have experienced commercial challenges and ~~are likely to~~ may experience additional challenges in the future.
수정We have experienced commercial challenges and may experience additional challenges in the future.
We face risks and uncertainties related to successfully commercializing our products. ~~For example, in 2024, we faced~~ In the past, commercial challenges ~~that~~ have led to lower-than-expected sales and required us to adapt our business strategy. Moving forward, we may need to dedicate greater resources to our commercial efforts than we anticipate, and we may not realize a return on this investment. Additionally, we may be unsuccessful in accurately anticipating future rates of return for our products, which may adversely impact our accounting estimates.
수정The commercial success of our products depends on the degree of market acceptance by physicians, patients, third-party payors and others in the medical community.
Even if a ~~potential~~ product ~~displays~~ candidate shows a favorable efficacy and safety profile in clinical trials, market acceptance will be unknown until after it is launched. Our efforts to educate the medical community and third-party payors on the benefits of our products may require significant resources and may never be successful.
수정Sales of pharmaceutical products depend on the availability and extent of reimbursement from third-party payors, and we may be adversely impacted by changes to such reimbursement policies or rules.
Sales of pharmaceutical products ~~in general depends to a significant extent~~ depend on adequate coverage, pricing and reimbursement from third-party payors. When a new product is approved, the availability and extent of government and private reimbursement, and the pricing, for that product may be uncertain. Additionally, pricing and reimbursement for any product we develop may be adversely affected by various factors, including:
수정Sales of pharmaceutical products depend on the availability and extent of reimbursement from third-party payors, and we may be adversely impacted by changes to such reimbursement policies or rules.
Additionally, target patient populations for some of our product candidates may be small (e.g., for rare ~~genetic~~ diseases) or require individual customization (e.g., for ~~our INTs).~~ intismeran autogene). The pricing and reimbursement of our medicines, if approved, must be adequate to support commercial infrastructure. If we cannot obtain adequate levels of reimbursement, we may be unable to successfully market and sell our products. ~~Inadequate~~ Further, inadequate reimbursement for ~~such~~ services related to our products (e.g., for administration to patients) may discourage physicians from prescribing or recommending our products, adversely affecting our ability to market or sell those products.
수정The market opportunities for our products and product candidates may be smaller than we believe, or we may be unable to successfully identify clinical trial participants.
We focus certain of our research and ~~product~~ development activities on treatments for severe rare genetic diseases, where ~~the~~ patient populations are small and difficult to ~~ascertain or small.~~ ascertain. Additionally, our products may only be approved for certain populations or lines of treatment.
수정The market opportunities for our products and product candidates may be smaller than we believe, or we may be unable to successfully identify clinical trial participants.
Our estimates of addressable patient populations are based on our ~~beliefs,~~ beliefs and ~~have been~~ are derived from a variety of sources, including scientific literature, surveys of clinics, patient foundations or market research, and may prove to be incorrect. Further, new studies may change the estimated incidence or prevalence of these diseases. The number of trial participants may be lower than expected and potential clinical trial participants or patients may not be otherwise amenable to treatment with our product candidates or products, or new clinical trial participants or patients may become increasingly difficult to identify or gain access to. Even if we obtain significant market share for our products, if approved, because the potential target populations are small, these medicines may never be profitable. Furthermore, the size of markets that we target may be impacted by health authority recommendations regarding who should receive our products, which may be impacted by the new U.S. federal government administration.
수정Clinical development is lengthy and uncertain, and our clinical programs may be delayed or terminated, or may be more costly to conduct than we anticipate.
Clinical testing is expensive, complex and lengthy, and its outcome is inherently uncertain. Most product candidates that commence clinical trials are never approved as products. Although we have demonstrated historical success with our platform technology, we may not continue to realize the same levels of success with clinical trials in the future. We and our strategic collaborators also may experience unforeseen events during, or as a result of, ~~any~~ clinical trials ~~that we or they conduct~~ that could delay or prevent us or them from successfully developing our product candidates and gaining approval from regulators. Such events could include:
수정Clinical development is lengthy and uncertain, and our clinical programs may be delayed or terminated, or may be more costly to conduct than we anticipate.
•adverse side effects could be observed in future clinical trials where our product candidates are administered in combination with other therapies (such as the co-administration of ~~our INT product candidate, mRNA-4157);~~ intismeran autogene);
수정There are risks unique to each of our programs and modalities and risks applicable across programs and modalities, which may delay or prevent our ability to advance one or more of our programs in clinical development, obtain regulatory approval or commercialize our products.
There are many clinical and manufacturing challenges specific to ~~our INT product candidates~~ intismeran autogene and any other neoantigen ~~cancer vaccines~~ therapies we may develop. These ~~risks~~ include a rapid production turn-around time measured in weeks in order to supply patients ~~in our clinical trials~~ before further progression and mutation of their tumors, the significant costs incurred in making individualized medicines and potential lack of immune responses due to the biology of the tumor or patient’s immune ~~status of the patient.~~ status. These risks apply to ~~our INT product candidates~~ intismeran and other neoepitope investigational medicine programs.
수정There are risks unique to each of our programs and modalities and risks applicable across programs and modalities, which may delay or prevent our ability to advance one or more of our programs in clinical development, obtain regulatory approval or commercialize our products.
In addition, the ~~uncertain~~ translatability of target selection from preclinical animal ~~models, including mouse and non-human primate models,~~ models to successful clinical trial results is uncertain and may ~~be impossible,~~ fail, particularly for systemic therapies and cancer ~~vaccines.~~ antigen therapies. In general, several biological steps are required for delivery of mRNA to translate into therapeutically active medicines. These processing steps may differ between individuals or tissues, potentially leading to variable levels of therapeutic protein, ~~variable~~ activity, immunogenicity or ~~variable~~ distribution to tissues for a therapeutic effect. mRNA medicines may elicit innate or adaptive immune responses to the mRNA, delivery vehicle (such as an LNP) or the encoded protein, which could result in adverse events or reduced tolerability. In certain settings, immune responses to the encoded protein limit the effectiveness or durability of treatment, including upon repeat administration, or require changes to dosing, formulation or clinical development plans.
수정We may experience delays in enrolling participants in our clinical trials.
Enrolling participants in our clinical trials is critical to our success. Difficulties or delays in enrolling a sufficient number of ~~clinical trial~~ participants ~~may result in increased~~ could increase costs or ~~affect~~ impact the timing or outcome of our planned clinical trials, which could prevent trial completion and adversely affect our ability to advance the development of and obtain regulatory approval for our product candidates. Participant enrollment is affected by many factors, including:
수정We may experience delays in enrolling participants in our clinical trials.
~~•eligibility~~ •size of the patient population and eligibility criteria for the clinical trial in question, including age-based eligibility criteria limiting subject enrollment to adolescent or pediatric populations;
수정We may experience delays in enrolling participants in our clinical trials.
•adverse results or other ~~adverse~~ safety signals in our trials or related to other product candidates, and ~~the~~ any resulting negative publicity, which could discourage potential ~~clinical trial~~ participants and their ~~doctors~~ physicians from participating in our trials; and
수정We may experience delays in enrolling participants in our clinical trials.
Additionally, we may have limited or no ability to influence enrollment in clinical trials where our collaborators control clinical development. Even if we or our collaborators successfully enroll participants, some may not be dosed or complete the trial.
수정mRNA drug development involves substantial clinical and regulatory risks, and negative perceptions of our platform, products and product candidates could adversely affect our business and ability to obtain regulatory approvals.
~~Very few~~ Few mRNA medicines have been ~~authorized or~~ approved to date by the FDA or other regulators, and efficacy, ~~safety~~ safety, tolerability and immunogenicity data and real-world evidence with respect to mRNA medicines continue to accumulate. We may observe new, more frequent or more severe adverse events in ~~subjects participating in ongoing~~ clinical ~~trials~~ trial participants or among ~~individuals~~ vaccinated ~~with mRNA vaccines.~~ individuals. For example, some studies have suggested that ~~our COVID vaccine~~ Spikevax may be associated with higher rates of myocarditis and pericarditis in young males compared to other COVID vaccines. Myocarditis and pericarditis have also been reported following vaccination with other COVID vaccines, including mNEXSPIKE. If similar observations are made in recipients of our other products or product candidates, or if other unexpected safety issues arise, we could suffer significant damage to our reputation and that of our mRNA platform. Such events could lead to other issues, including delays in our other programs, the need to re-design our clinical trials and the need for significant additional financial resources. In addition, the FDA and other regulators may interpret data from our clinical trials differently than we do and such agencies may require us to conduct additional studies or analyses, which could delay or prevent us from obtaining full regulatory approvals in certain jurisdictions or for certain demographics. ~~In addition,~~ Further, local legislatures may attempt to regulate or restrict the use of mRNA medicines in their jurisdictions.
수정mRNA drug development involves substantial clinical and regulatory risks, and negative perceptions of our platform, products and product candidates could adversely affect our business and ability to obtain regulatory approvals.
Successful discovery and development of mRNA medicines by us or our strategic collaborators is highly uncertain and depends on many factors beyond our or their ~~control.~~ control, and our business decisions and development efforts relating to mRNA technology, delivery systems and manufacturing processes may ultimately be unsuccessful. ~~Our~~ Promising early-phase product candidates ~~that appear promising in the early phases of development~~ may fail to advance, ~~experience delays~~ be delayed in the clinic, ~~experience~~ be subject to clinical holds or fail to reach the market for many reasons, including:
수정mRNA drug development involves substantial clinical and regulatory risks, and negative perceptions of our platform, products and product candidates could adversely affect our business and ability to obtain regulatory approvals.
~~•nonclinical or~~ •nonclinical, preclinical ~~study,~~ or clinical ~~trial,~~ trial results may show potential mRNA medicines to be less effective than desired or to have harmful or problematic side effects or toxicities;
수정Because we are developing some of our product candidates for the treatment of diseases in which there is little clinical experience and, in some cases, using new endpoints or methodologies, the FDA or other regulators may not consider the endpoints of our clinical trials to provide clinically meaningful results.
There are no pharmacologic therapies approved to treat the underlying causes of many diseases that we are currently attempting to address or may address in the future. For many rare diseases, few clinical trials have been attempted. As a result, the design and conduct of clinical trials of product candidates for the treatment of these disorders may take longer, be more costly or be less ~~effective due to the novelty of development in these diseases.~~ effective.
수정Because we are developing some of our product candidates for the treatment of diseases in which there is little clinical experience and, in some cases, using new endpoints or methodologies, the FDA or other regulators may not consider the endpoints of our clinical trials to provide clinically meaningful results.
Even if the FDA ~~does find~~ finds our success criteria to be sufficiently validated and clinically meaningful, we may not achieve the pre-specified endpoint to a degree of statistical significance in our pivotal or other clinical ~~trials.~~ trials, or our results may be inconsistent or unpredictable compared to traditional efficacy endpoints. ~~The~~ Further, the FDA ~~could~~ may give overriding weight to other efficacy endpoints over a primary endpoint, even if we achieve statistically significant results on that endpoint, if we do not do so on our secondary efficacy endpoints. The FDA also weighs the benefits of a product against its risks and may view the efficacy results in the context of safety as not being supportive of licensure. Regulators in other countries may make similar findings with respect to these endpoints.
수정Certain mRNA therapies are classified as gene therapies by the FDA and the EMA. The association of our products with gene therapies could result in increased regulatory burdens, impair the reputation of our products or negatively impact our platform or our business.
There are only a few approved gene therapy products in the United States ~~or foreign~~ and other jurisdictions, and ~~there have been well-reported~~ significant adverse events associated with their testing and ~~use.~~ use have been reported. Regulatory requirements governing ~~gene therapy~~ these products have evolved and may continue to change in the future, and the implications for mRNA therapies are unknown. For example, the FDA has established ~~an office, now called~~ the Office of Therapeutics Products ~~(OTP),~~ within its Center for Biologics Evaluation and Research (CBER) to consolidate ~~the~~ review of gene therapy and related products, and convenes the Cellular, Tissue and Gene Therapies Advisory Committee to advise ~~CBER on its review.~~ CBER. In the EU, certain mRNA therapies have been characterized as gene therapy medicinal products, which ~~falls within a broader category known as Advanced Therapy Medicinal Products (ATMPs), which~~ are subject to additional regulatory requirements. In certain other countries, such as Japan, mRNA therapies have not yet been classified. Notwithstanding the differences between mRNA medicines and gene therapies, the classification of some of our mRNA product candidates as gene therapies ~~in the U.S., the EU and potentially other countries~~ could adversely impact our ability to develop our product candidates, including if a clinical hold applicable to gene therapy products were applied to our mRNA product candidates.
수정Certain mRNA therapies are classified as gene therapies by the FDA and the EMA. The association of our products with gene therapies could result in increased regulatory burdens, impair the reputation of our products or negatively impact our platform or our business.
Additionally, if any such therapeutic is approved, ~~physicians~~ physicians, health care providers, third-party payors and patients may be slow or fail to accept these novel and personalized treatments. Physicians may ~~not~~ be ~~willing~~ unwilling to undergo ~~training to adopt these novel and potentially personalized therapies, may decide the~~ necessary training, view a particular therapy is as too complex or potentially risky to adopt without appropriate training and ~~may~~ choose not to administer the therapy. Further, certain patients may not be candidates for the therapies, for many reasons, including due to health conditions or genetic profile. In addition, responses by federal and state agencies, congressional committees and foreign governments to negative public perception, ethical concerns or financial considerations may result in new legislation, regulations or medical standards that could limit our ability to develop or commercialize any product candidates, obtain or maintain regulatory approval or otherwise achieve profitability. Based on these and other factors, health care providers and payors may decide that the benefits of these new therapies do not or will not outweigh their costs.
수정Our products are, and any future products will be, subject to regulatory scrutiny.
Even if we obtain regulatory approval in a jurisdiction, we may remain subject to significant restrictions on the indicated uses or marketing of our product and ongoing requirements for potentially costly post-approval ~~studies-such~~ studies, such as those required under an accelerated approval by the FDA or other similar type of ~~approval-or~~ approval, or post-market surveillance. For example, ~~the~~ a BLA holder ~~of an approved BLA~~ must monitor and report adverse events and ~~monitor and report~~ any failure of a product to meet ~~the specifications in the BLA,~~ applicable specifications, as well as submit ~~new or supplemental applications~~ and obtain FDA approval for certain ~~changes~~ new or supplemental applications relating to the approved product, ~~product labeling,~~ labeling or manufacturing process. Additionally, pharmacovigilance obligations under the regulatory regimes of the jurisdictions where our products are distributed require us to collect, process, analyze and monitor safety data and to identify and evaluate adverse reactions to our products as they are administered in those jurisdictions. If we or any of our partners assisting us in meeting these obligations cannot comply with relevant regulations, we may be subject to sanctions, increased costs and reputational harm, or our regulatory authorizations to distribute our vaccines in the relevant jurisdiction may be revoked or curtailed. In addition, regulators may increasingly rely on post-approval studies or real-world evidence to determine whether to maintain, modify or expand approved indications or population eligibility, which could increase costs, delay commercialization or limit the scope of approved use of our products.
수정Our products are, and any future products will be, subject to regulatory scrutiny.
We are required by the FDA to conduct post-marketing studies for ~~our COVID vaccine (mRNA-1273),~~ mRNA-1273, including to assess the risk of myocarditis and pericarditis and to evaluate outcomes in pregnant women and infants post-vaccination. We or others could identify previously unknown side effects, or known side effects could be observed as being more frequent or severe than in clinical trials or earlier post-marketing periods. If we, our contract manufacturers or other ~~strategic~~ collaborators fail to comply with ~~applicable~~ any post-approval regulatory requirements, a regulator may issue a warning letter asserting that we are in violation of the law, seek an injunction or impose civil or criminal penalties or monetary fines, suspend or withdraw regulatory approval or revoke a license, suspend any ongoing clinical trials, refuse to approve a pending BLA or supplements to a BLA submitted by us, seize or recall products or product candidates, or require field alerts to physicians, pharmacists and hospitals or refuse to allow us to enter into supply contracts. We could also be required to conduct additional nonclinical studies or clinical trials or implement changes in labeling or to our manufacturing processes, specifications or facilities. Initiation of any government investigation or lawsuit, including class-action lawsuits, would require us to expend significant time and resources in response and would likely generate negative publicity. The occurrence of any event or penalty described above may inhibit our ability to commercialize our COVID vaccine, or any future approved products, and generate revenues.
수정Preclinical development is lengthy and uncertain, especially for mRNA medicines.
Much of our pipeline is in preclinical development, and these programs could be delayed or not advanced into the clinic. Before ~~we can initiate~~ initiating clinical trials for a product candidate, we must complete extensive preclinical studies, including IND-enabling good laboratory practice (GLP) toxicology ~~testing.~~ testing, as well as significant Chemistry, Manufacturing, and Controls (CMC) activities for inclusion in an IND submission. CMC activities for mRNA medicines ~~require extensive~~ involve complex manufacturing processes and analytical development, which is are uncertain and lengthy. We have had and may in the future have difficulty identifying appropriate buffers and storage conditions to enable sufficient shelf life of batches of our product candidates. If we must produce new batches, our preclinical studies could be delayed. We cannot be certain of the timely completion of our preclinical testing and studies, whether the FDA or other regulators will accept the results or if the outcome of our preclinical testing, studies and CMC activities will ultimately support further development of our programs. As a result, we may be unable to submit INDs or similar applications for our preclinical programs on the timelines we expect, if at all, and such applications may not result in the FDA or other regulators allowing clinical trials to begin.
수정We or our third-party manufacturers may encounter difficulties in manufacturing, product release, shelf life, testing, storage, supply chain management or shipping for any of our products.
~~Our~~ Additionally, our high rate of innovation ~~causes~~ may result in a high degree of technology change that ~~can~~ could negatively impact product comparability during and after clinical development. ~~Furthermore,~~ These technology changes may ~~drive the need for~~ necessitate changes ~~in, modification~~ to, or the sourcing of of, new manufacturing infrastructure or may adversely affect third-party relationships.
수정We or our third-party manufacturers may encounter difficulties in manufacturing, product release, shelf life, testing, storage, supply chain management or shipping for any of our products.
In many cases, we may need to utilize multiple batches of drug substance and drug product to meet the supply requirement of a single preclinical study or clinical trial. Failure in our ability to scale up batch size or failure in any batch, which we have experienced in the past, may lead to a substantial delay in our clinical trials or in the commercialization of any approved product. For example, the changes we make as we continue developing new manufacturing processes for our drug substance and drug product may impact specification and stability of the drug product, and may lead to failure of batches, resulting in a substantial delay in delivery of commercial product or conduct of our clinical trials. Our mRNA product candidates may prove to have a stability profile that leads to a lower than desired shelf life of the final approved medicine. This poses risk in supply requirements, wasted stock and higher cost of goods. We may also experience wasted stock from other factors such as volatile demand forecasts or our inability to scale down for products that have low demand.
수정As we grow as a commercial company and our drug development pipeline matures, the increased demand for clinical and commercial supplies from our facilities and third parties may impact our ability to operate.
Completion of our trials and commercialization of our ~~product candidates require access to, or development of,~~ products depend on the availability of facilities ~~to manufacture~~ capable of manufacturing our ~~vaccine candidates~~ vaccines at sufficient yields and at commercial scale. We expect to continue to make significant investments in our manufacturing ~~capacity and commercial~~ network as we ~~continue to~~ expand our commercial launch efforts. Our new manufacturing plants in Australia, Canada and the United Kingdom are subject to risks associated with operating these facilities, and we may encounter difficulties in optimizing our global manufacturing network.
수정As we grow as a commercial company and our drug development pipeline matures, the increased demand for clinical and commercial supplies from our facilities and third parties may impact our ability to operate.
To supplement our internal manufacturing infrastructure, we may rely on third parties for product manufacturing, packaging, testing, warehousing, distribution and other logistical services, and the manufacture and testing of raw materials, components, parts and consumables, and we may need to engage additional third parties in the future to meet capacity needs. If we cannot enter into or maintain such arrangements on favorable terms, or at all, our ability to develop, manufacture and distribute our products ~~would~~ could be adversely affected. Further, efforts to establish and scale these capabilities may not meet ~~initial~~ expectations ~~as to~~ regarding scheduling, scale-up, reproducibility, yield, purity, cost, potency or quality. If we are unable to institute necessary controls related to product development, manufacturing and quality, we may encounter difficulties producing our products on the timelines and in the quantities ~~set forth in our supply agreements or~~ required to meet ~~potential future demand.~~ demand or supply obligations.
수정As we grow as a commercial company and our drug development pipeline matures, the increased demand for clinical and commercial supplies from our facilities and third parties may impact our ability to operate.
Demand for third-party manufacturing, raw materials or testing facilities may grow faster than available capacity, which could disrupt our ability to secure sufficient quantities of materials and services. The use of service providers and suppliers could expose us to risks, including:
수정As we grow as a commercial company and our drug development pipeline matures, the increased demand for clinical and commercial supplies from our facilities and third parties may impact our ability to operate.
Our reliance on third-party manufacturers may ~~adversely affect our operations or~~ also result in unforeseen delays or ~~other~~ operational problems beyond our control. Because of contractual ~~restraints~~ restrictions and the limited number of ~~third-party~~ manufacturers with the expertise, required regulatory approvals and facilities to manufacture our bulk vaccines on a commercial scale, ~~replacement of~~ replacing a third-party manufacturer may be ~~expensive and~~ expensive, time-consuming ~~and may cause interruptions in the production of our vaccine.~~ or disruptive. Regulators may ~~also~~ require us to register our facilities or those of another supplier if we terminate an existing third-party manufacturer relationship, which could ~~lead to delays~~ delay or limit our ~~inability~~ ability to supply a particular market. In addition, third-party manufacturers may experience production interruptions due to factors such as production cost pressures, scale-up challenges, shortages of qualified personnel, availability of raw materials and supplies, quality control failures, compliance with regulatory requirements or lack of capital funding.
수정We are subject to operational risks associated with the physical and digital infrastructure at our manufacturing facilities and those of our external service providers.
Our facilities and infrastructure or those of our contract manufacturers or other ~~third-party providers~~ third-parties may also be subject to attacks or acts of sabotage by outside actors, contractors or employees. Any disruption in ~~our or our contract manufacturers’~~ these manufacturing capabilities could delay scaling up production capacity for our drug substances or products or shut down facilities, ~~impose additional~~ add costs, cause us to fail to meet certain product volume or delivery timing obligations, or may require us to identify, qualify and establish an alternative manufacturing site, which could adversely affect our business.
수정We are subject to operational risks associated with the physical and digital infrastructure at our manufacturing facilities and those of our external service providers.
As we expand our development and commercial capacities, we have and expect that we will continue to establish additional manufacturing capabilities in ~~the United States, as well as in other countries, such as Australia, Canada and the United Kingdom.~~ our global network. This expansion may lead to regulatory delays or prove more costly than anticipated. If we fail to select suitable locations, complete construction in an efficient manner, engage effectively with local regulators, recruit the required personnel or manage our growth effectively, the development and production of products or our product candidates could be delayed or curtailed.
수정Our products and product candidates are sensitive to shipping and storage conditions, which, in some cases, requires cold-chain logistics and subjects them to risk of loss or damage.
Our products and product candidates are sensitive to temperature, storage and handling conditions, and we could lose medicines if the product or product intermediates are not stored or handled properly. Shelf life for our products and product candidates is variable, and they may expire prior to use. If Further, if we or third-party distributors do not maintain effective cold-chain supply ~~logistics, then we may experience returned or out~~ logistics required for certain of ~~date~~ our products and product candidates, products may be returned, become out-of-date or be rendered unusable. This has led and could lead to ~~additional~~ added manufacturing costs and delays in our ability to supply required quantities for clinical trials or commercial sale. In addition, the cost associated with such transportation services and the limited pool of vendors could cause supply disruptions.
수정Our manufacturing facilities or those of third-party manufacturers or suppliers may fail to meet regulatory requirements, which could delay approval of or increase production costs for our products.
Our manufacturing facilities or those of ~~our~~ third-party manufacturers or suppliers may fail to meet regulatory ~~requirements.~~ requirements, which could delay approval of or increase production costs for our products.
수정Our manufacturing facilities or those of third-party manufacturers or suppliers may fail to meet regulatory requirements, which could delay approval of or increase production costs for our products.
The manufacturing of medicines for clinical trials or commercial sale is subject to extensive regulation, and components of such products must be manufactured in accordance with cGMP ~~requirements, which are enforced, in the case of the FDA, in part through its facilities inspection program.~~ requirements. ~~The~~ These regulations govern manufacturing processes and procedures, including record ~~keeping,~~ keeping and the implementation and operation of quality systems to control and assure the quality of products and materials used in clinical ~~trials.~~ trials and for commercial supply. Poor control of cGMP ~~production~~ manufacturing processes can lead to product quality failures that ~~can~~ may impact our ability to supply product, resulting in cost overruns and cause significant delays to clinical ~~timelines, which could be extensive.~~ development timelines. Such ~~production~~ manufacturing process issues may include:
수정Our manufacturing facilities or those of third-party manufacturers or suppliers may fail to meet regulatory requirements, which could delay approval of or increase production costs for our products.
~~•raw material failures~~ •failures of raw materials, components or consumables, including due to ineffective supplier qualification or regulatory compliance issues at critical suppliers; and
수정Our manufacturing facilities or those of third-party manufacturers or suppliers may fail to meet regulatory requirements, which could delay approval of or increase production costs for our products.
Regulators typically require representative manufacturing site inspections to assess ~~adequate~~ compliance with cGMP and manufacturing controls. Such inspections may occur at any time during product development or commercialization, may be unannounced, and may be product- or facility-specific or conducted in response to issues identified by regulators. If one of our, or a third-party manufacturer’s, sites fails to maintain sufficient quality assurance or control, or receives a deficient inspection outcome, a product may not receive or maintain regulatory approval, and our manufacturers or suppliers may be unable to meet their supply obligations, impacting or delaying supply or programs.
수정Our manufacturing facilities or those of third-party manufacturers or suppliers may fail to meet regulatory requirements, which could delay approval of or increase production costs for our products.
If In addition, the manufacturing processes for our products are subject to regulatory approval, and if we or our third-party manufacturers are unable to reliably produce products or product candidates to specifications acceptable to regulators, we or our strategic collaborators may not obtain or maintain the approvals needed to commercialize such products. Even if after regulatory approval is ~~obtained for any of our mRNA medicines,~~ obtained, there is no assurance that ~~either~~ we or our CMOs will be able to manufacture the approved medicine to specifications acceptable to the FDA or other regulators. Any of these challenges could delay or prevent completion of clinical trials, require bridging ~~clinical trials~~ or ~~the repetition of one or more~~ repeat clinical trials, increase ~~clinical~~ trial costs, delay ~~approval of our product candidates,~~ regulatory approval, impair commercialization efforts or increase our cost of goods, ~~which, in turn,~~ any of which could have an adverse effect on our business.
수정Our manufacturing facilities or those of third-party manufacturers or suppliers may fail to meet regulatory requirements, which could delay approval of or increase production costs for our products.
The FDA, the EMA and other ~~foreign~~ regulators may require us to submit product samples of any lot of any approved product, together with the protocols showing the results of applicable tests, at any time. In some cases, regulators may prohibit us from distributing a lot ~~or lots~~ until it authorizes release. Deviations in the manufacturing process, including those affecting quality attributes and stability, may cause unacceptable changes in the product, resulting in lot failures or product recalls. ~~Our~~ In the past, our third-party contract manufacturers ~~have~~ experienced lot failures resulting in product recalls of our COVID vaccine. Lot failures have caused, and lot failures or product recalls in the future with respect to product produced by either our own or our third-party manufacturers’ facilities could cause, us and ~~our~~ strategic collaborators to delay clinical trials or product launches.
수정Our manufacturing facilities or those of third-party manufacturers or suppliers may fail to meet regulatory requirements, which could delay approval of or increase production costs for our products.
We and our manufacturing partners also may encounter problems hiring and retaining the experienced scientific, quality control and manufacturing ~~personnel needed to operate our manufacturing processes and operations or those of our manufacturing partners,~~ personnel, which could result in delays in production or difficulties in maintaining compliance with applicable regulatory requirements. Additionally, we may not be able to control for or detect intentional sabotage or negligence by any employee or contractor.
수정Our intismeran autogene product candidates are uniquely manufactured for each patient using a novel, complex manufacturing process and we may encounter difficulties in production.
Our ~~INT~~ intismeran autogene product candidates are uniquely manufactured for each patient using a novel, complex manufacturing process and we may encounter difficulties in production.
수정Our intismeran autogene product candidates are uniquely manufactured for each patient using a novel, complex manufacturing process and we may encounter difficulties in production.
We custom design and manufacture ~~INTs~~ intismeran tailored for each patient. ~~Manufacturing unique lots of INTs~~ As a result, manufacturing is susceptible to product loss or failure due to issues with:
수정Our intismeran autogene product candidates are uniquely manufactured for each patient using a novel, complex manufacturing process and we may encounter difficulties in production.
We have purpose-built our facility in Marlborough, Massachusetts for intismeran, and it may encounter difficulties or it take longer than anticipated to scale up the facility to meet future commercial demand, if intismeran is approved. Manufacturing demand for intismeran may also increase as we continue our current late-stage trials and expand to additional tumor types. Further, we may encounter difficulties executing our plans to improve turnaround time and reduce costs. ~~This expansion and~~ The addition of new facilities could also lead to product comparability issues, which could further delay introduction of new capacity. ~~This~~ In addition, if our equipment ~~may~~ does not function as designed, ~~resulting in~~ we could experience deviations in the drug product produced, which could lead to increased batch failure and the inability to supply patients enrolled in a clinical trial.
수정Our intismeran autogene product candidates are uniquely manufactured for each patient using a novel, complex manufacturing process and we may encounter difficulties in production.
Because ~~our INTs are~~ intismeran is manufactured for each individual patient, we are required to maintain a chain of identity with respect to each patient’s tissue sample, sequence data derived from such tissue sample, results of analysis of such patient’s genomic analysis and the custom manufactured product for each patient. Maintaining such a chain of identity is difficult and complex, and failure to do so has resulted and may in the future result in product mix up, adverse patient outcomes, loss of product or regulatory action, including withdrawal of any approved products from the market. Further, as ~~our INTs are~~ intismeran is developed through clinical trials towards approval and commercialization, ~~we expect that~~ multiple aspects of the complicated collection, analysis, manufacture and delivery process ~~will~~ may be modified ~~in an effort~~ to optimize processes and results. These changes may not achieve the intended objectives, and any of these changes could cause ~~our INTs~~ intismeran to perform differently than we expect, potentially affecting the results of clinical trials.
수정We are dependent on single-source suppliers for some of the components and materials used in, and the manufacturing processes required to develop and commercialize, our products and product candidates.
There are, in general, few alternative sources of supply for substitute components. If we must switch suppliers, the manufacture and delivery of our products or product candidates could be interrupted for an extended period. Establishing additional or replacement suppliers for any of the components or processes used in our products or product ~~candidates, if required,~~ candidates may not be accomplished quickly, if at all. Any replacement supplier (or us, if we produced directly) would need to be qualified and may require additional regulatory approval, resulting in further delay. Any such interruption or ~~delay in the supply of components or materials,~~ delay, or our inability to obtain components or materials from alternate sources at on acceptable ~~prices in a timely manner,~~ terms, could impair our ability to meet ~~the~~ demand for our products or product candidates. Additionally, as part of the FDA’s approval of our product candidates, the FDA will review the manufacturing processes and facilities of our single-source suppliers.
수정We have entered into strategic alliances with third parties for product development and commercialization. If these alliances are unsuccessful, our business could be adversely affected.
We have ~~entered, and may enter into,~~ entered into strategic alliances with third parties for product development and commercialization. If these alliances are unsuccessful, our business could be adversely affected.
수정We have entered into strategic alliances with third parties for product development and commercialization. If these alliances are unsuccessful, our business could be adversely affected.
We have entered into strategic alliances with collaborators that have ~~provided, and may in the future provide,~~ provided funding, intellectual property licenses and other resources for developing, manufacturing and commercializing our product candidates. Additionally, we have entered ~~into, and may in the future enter into,~~ into strategic alliances where we agree to provide funding, intellectual property licenses and other resources to third parties. Our ~~existing and any future~~ strategic alliances may pose a number of risks, including:
수정We have entered into strategic alliances with third parties for product development and commercialization. If these alliances are unsuccessful, our business could be adversely affected.
Our strategic collaborators generally may materially amend or terminate their agreements with ~~us,~~ us in accordance with the terms of those agreements, which has happened in the past. If any collaboration agreement is terminated, we may not receive anticipated future research or development funding or milestone, earn-out royalty, profit share or other contingent payments and the research or development of our product candidates may be delayed or discontinued. It may also be difficult to attract new strategic collaborators to continue development or commercialization of the applicable product candidate, and our reputation could be adversely affected. All the risks relating to product development, regulatory approval and commercialization described elsewhere in these Risk Factors apply to our strategic collaboration activities.
수정We may seek to establish additional strategic alliances and, if we are unable to do so on commercially reasonable terms, we may have to alter our development and commercialization plans. Certain of our strategic alliance agreements may restrict our ability to develop certain products.
We may seek to establish additional strategic alliances and, if we are unable to ~~establish them~~ do so on commercially reasonable terms, we may have to alter our development and commercialization plans. Certain of our strategic alliance agreements may restrict our ability to develop certain products.
수정We may seek to establish additional strategic alliances and, if we are unable to do so on commercially reasonable terms, we may have to alter our development and commercialization plans. Certain of our strategic alliance agreements may restrict our ability to develop certain products.
Our development programs and the potential commercialization of our product candidates will require substantial cash to fund expenses. We may collaborate with ~~pharmaceutical~~ other companies to develop and ~~biotechnology companies for the development and potential commercialization of~~ potentially commercialize some of our product candidates, and we face significant competition in seeking ~~appropriate strategic~~ collaborators. Our ability to establish additional strategic alliances will depend, among other things, on our assessment of the collaborator’s resources and expertise, ~~the~~ proposed terms and conditions ~~of the proposed strategic alliance~~ and the ~~proposed~~ collaborator’s evaluation of a number of factors. Those factors may include the design or results of clinical trials, the likelihood of ~~approval by the FDA or foreign regulators, the~~ regulatory approval, potential market ~~for the subject product candidate,~~ sizes and competition, the costs and complexities of manufacturing and delivering ~~such~~ a product candidate to trial participants, ~~the potential of competing drugs, the existence of~~ uncertainty with respect to our or the proposed collaborator’s ownership of ~~technology, which can exist if there is a challenge to such ownership without regard to~~ technology (regardless of the merits of the ~~challenge,~~ challenge), and industry and market conditions generally.
수정We expect to continue to rely on third parties to conduct aspects of our research, preclinical studies, protocol development and clinical trials. If these third parties do not perform satisfactorily or comply with regulatory requirements, we may be unable to obtain regulatory approval for or commercialize our product candidates.
We rely on third parties such as CROs to help manage certain preclinical ~~work and our clinical trials,~~ work, and on medical institutions, clinical investigators and CROs to assist in the ~~design~~ design, review and ~~review of, and to conduct,~~ conduct of our clinical trials, including enrolling qualified patients. In addition, we engage third-party contractors and collaborators to support ~~numerous~~ other research, commercial and administrative activities, which reduces our control over these activities but does not relieve us of our responsibilities, such as ensuring that each ~~of our~~ clinical ~~trials~~ trial is conducted in accordance with its general investigational plan and protocols. Moreover, the FDA requires us to comply with GLPs and good clinical practices for conducting, recording and reporting the results of preclinical studies and clinical trials to assure that data and reported results are credible and accurate and that in the case of clinical trials the rights, integrity and confidentiality of trial participants are protected. Such standards will evolve and subject us and third parties to new or changing requirements.
수정We expect to continue to rely on third parties to conduct aspects of our research, preclinical studies, protocol development and clinical trials. If these third parties do not perform satisfactorily or comply with regulatory requirements, we may be unable to obtain regulatory approval for or commercialize our product candidates.
If third parties do not successfully carry out their contractual duties or meet expected deadlines, we may need to replace them, which could delay ~~the affected~~ clinical ~~trial,~~ trials, drug development ~~program~~ or ~~applicable~~ other activity. If clinical trials are not conducted in accordance with our contractual expectations or regulatory requirements, action by regulators may significantly and adversely affect the conduct or progress of such trials or ~~even~~ require a clinical trial to be redone. Accordingly, our efforts to obtain regulatory approvals ~~for~~ and commercialize our drug candidates could be delayed. ~~Failure~~ In addition, failure of any third-party contractor to timely provide access to our data in a format acceptable to us may result in delays or impediments to our regulatory submissions or other development activities.
수정We may be unable to obtain and enforce patent protection for our discoveries and the intellectual property rights therein, or protect the confidentiality of our trade secrets.
Despite our and our strategic collaborators’ efforts to protect our proprietary rights, unauthorized parties may obtain and use information that we regard as proprietary. While issued patents are presumed valid, they may not survive a validity challenge and could be held unenforceable. Any patents we have obtained, or obtain in the future, may be challenged, invalidated, adjudged unenforceable or circumvented by parties seeking to design around our IP. Also, third parties or through the USPTO or European Patent Office (EPO) may commence patent office proceedings involving our patents or patent applications. Any challenge to, finding of unenforceability or invalidation, or circumvention of, our patents or patent applications, would be costly, would require significant time and attention of our management, could reduce or eliminate royalty payments to us from third-party licensors and could have a material adverse impact on our business.
수정Uncertainty over IP in the pharmaceutical and biotechnology industry has been the source of litigation and other disputes, which is inherently costly and unpredictable and can have adverse financial and freedom-to-operate consequences.
We have issued patents and pending patent applications in the United States and in key markets ~~around the world~~ globally that claim many different methods, compositions and processes relating to the discovery, development, manufacture and commercialization of mRNA medicines and our delivery technology, including LNPs. Oppositions and inter partes review petitions have been filed against some of our patents, and we expect that further proceedings will be filed in the ~~European Patent Office (EPO),~~ EPO, USPTO and elsewhere relating to patents and patent applications in our portfolio. In many cases, the possibility of appeal exists for any party, and it may be years before final, unappealable rulings are made with respect to these patents in certain jurisdictions. The timing and outcome of these and other proceedings is uncertain and may adversely affect our business if we are not successful in defending the patentability and scope of our pending and issued patent claims. We cannot be certain that any patent will survive or that the claims will remain in the current form. Even if our rights are not directly challenged, disputes could lead to the weakening of our IP rights.
수정If we fail to comply with our obligations in the agreements under which we license IP rights from third parties or otherwise experience disruptions to our business relationships with our licensors, we could lose license rights that are important to our business.
If disputes over IP that we have licensed prevent or impair our ability to maintain our current licensing arrangements on favorable terms, we may be unable to successfully develop and commercialize the affected product candidates. We are generally also subject to ~~all of~~ the same risks with respect to protection of IP that we license as we are for IP that we own. If we or our licensors fail to adequately protect this IP, our ability to commercialize products could suffer.
수정Our reliance on government funding and collaboration from governmental and quasi-governmental entities for certain of our programs adds uncertainty to our research and development efforts with respect to those programs and may impose requirements related to IP rights and requirements that increase the costs of development, commercialization and production of any programs developed under those government-funded programs.
Contracts and grants funded by the U.S. government and its agencies, including our agreements funded by BARDA and DARPA and our collaboration with NIAID, and with foreign governments and agencies, including in the United Kingdom, Canada and Australia, may include provisions that reflect the government’s substantial rights and remedies, many of which are not typically found in commercial contracts, including powers of the government to:
수정Our reliance on government funding and collaboration from governmental and quasi-governmental entities for certain of our programs adds uncertainty to our research and development efforts with respect to those programs and may impose requirements related to IP rights and requirements that increase the costs of development, commercialization and production of any programs developed under those government-funded programs.
Any exercise of the march-in rights by the U.S. government could harm our competitive position, business, financial condition, results of operations and prospects. In December 2023, the Biden administration released a proposed framework specifying for the first time that price can be a factor in considering whether an invention is sufficiently available to the public. The proposed framework could potentially enable march-in rights to be used as a tool to regulate drug pricing. The potential inclusion of price as a factor in a march-in determination is expected to draw extensive criticism and challenge, and the ultimate impact is currently unknown. If the U.S. government exercises such march-in rights, we may receive compensation deemed reasonable by the U.S. ~~government in its sole discretion,~~ government, which may be less than what we might be able to obtain in the open market. IP generated under a government-funded program is also subject to certain reporting requirements, compliance with which may require us to expend substantial resources.
수정We incurred net losses in 2025 and 2024, and expect to incur additional losses in the future; we may not achieve long-term sustainable profitability.
We incurred net losses of $2.8 billion and $3.6 billion in 2025 and ~~$4.7 billion in 2024 and 2023,~~ 2024, respectively, and other than in 2022 and 2021, we have incurred net losses in each year since our inception. Currently, our COVID and RSV vaccines are our only commercial products and our RSV sales have been minimal. Although we anticipate near-term product launches, their occurrence and timing is uncertain. Our ability to ~~generate revenue and~~ achieve profitability depends on our ability to successfully develop and obtain the regulatory approvals necessary to commercialize our products.
수정We incurred net losses in 2025 and 2024, and expect to incur additional losses in the future; we may not achieve long-term sustainable profitability.
We have incurred, and expect to continue to incur, significant costs associated with commercializing our products and our clinical development activities. Although we continue to implement cost ~~efficiency~~ reduction and prioritization measures, we these efforts may ~~be unsuccessful in reducing~~ fail to reduce our costs in line with ~~our~~ expectations, which could require us to seek additional funding to continue operations. Our expenses could increase for many reasons, including if and as we:
수정Our quarterly and annual operating results may fluctuate. As a result, we may fail to meet or exceed the expectations of research analysts or investors, which could cause our stock price to decline and negatively impact our financing or funding ability, as well as our ability to exist as a standalone company.
Our financial condition and operating results may fluctuate from quarter-to-quarter and year-to-year due to many factors, many of which are beyond our control. As such, a period-to-period comparison of our operating results may not be predictive of our future performance. In any ~~particular~~ quarter, our operating results could be below ~~the expectations of securities analysts or investors,~~ market expectations, which could cause our stock price to decline. Our stock price could be affected by events not necessarily tied to our actual operating results, including recommendations by securities analysts, the timing of certain public disclosures by us, our collaborators or our competitors and our ability to accurately report our financial results in a timely manner. Other factors relating to our business that may contribute to these fluctuations include those described in these Risk Factors and elsewhere in this Annual Report on Form 10-K.
수정The investment of our cash, cash equivalents and investments is subject to risks which may cause losses and affect the liquidity of these investments.
As of December 31, ~~2024,~~ 2025, we had approximately ~~$9.5~~ $8.1 billion in cash, cash equivalents and investments, which ~~are~~ includes a $600 million draw down from our term loan facility, which is subject to general credit, liquidity, market, inflation and interest rate risks. We may realize losses in the fair value of these investments. In addition, if our investments cease paying or reduce the amount of interest paid to us, our interest income would suffer. These and other market risks associated with our investment portfolio may adversely affect our results of operations, liquidity and financial condition.
수정We may encounter difficulties in managing changes to the size, structure and scope of our company.
We may encounter difficulties in managing changes to the ~~development~~ size, structure and ~~expansion~~ scope of our company.
수정We may encounter difficulties in managing changes to the size, structure and scope of our company.
Successfully ~~developing~~ developing, manufacturing and commercializing products ~~for and fully understanding the regulatory and manufacturing pathways for~~ across the many therapeutic areas and diseases we seek to address requires significant depth of talent, resources and robust corporate processes to ~~allow~~ support simultaneous ~~execution across multiple areas.~~ execution. Organizational changes, including workforce reductions, restructuring, and shifts in strategic priorities, may make it more difficult to retain personnel, recruit and train qualified employees, maintain institutional knowledge, and preserve employee morale and productivity. If we are unable to effectively manage these challenges, we may experience weaknesses in our infrastructure, operational mistakes or inefficiencies, loss of business opportunities and reduced productivity.
수정We may encounter difficulties in managing changes to the size, structure and scope of our company.
In addition, we continue to operate and expand a global manufacturing and operational footprint, including our Norwood and Marlborough campuses in Massachusetts and manufacturing facilities outside the United States. Managing the costs, operational complexity, regulatory requirements, and execution risks associated with these facilities may require significant financial and managerial resources and could divert capital from other priorities, including the development of our product candidates. If ~~our management is~~ we are unable to effectively manage ~~our development~~ organizational change, operational scale, and ~~expansion,~~ resource allocation, our financial performance and ability to commercialize our products may be affected negatively.
수정We are subject to the risks of doing business outside of the United States.
Our business is subject to risks associated with doing business ~~outside of the United States.~~ globally. We are not permitted to market or promote any of our product candidates before ~~we receive~~ receiving regulatory approval or other authorization from an applicable ~~authority, and~~ authorities, which we may never ~~receive such approval.~~ obtain. To obtain regulatory approval in various jurisdictions, we must comply with numerous regulatory requirements regarding safety and efficacy and governing, among other things, clinical trials, manufacturing, commercial sales, pricing and distribution of our product candidates, and we may fail to obtain approval. We have rapidly expanded our global operations, establishing commercial subsidiaries and entering into arrangements to support the worldwide manufacture and distribution of our products, which is a complex task. For example, we are building regional manufacturing facilities and investing in research and development in several countries. Our business may be adversely affected by many factors associated with our expanding global business, including:
수정Our failure to maintain our enterprise resource planning (ERP) system could adversely impact our business and results of operations.
Any disruptions or difficulties using our ~~newly upgraded~~ global ERP system could adversely affect our controls, resulting in harm to our business, including our ability to forecast or make sales and collect our receivables. Significant delays in documenting, reviewing and testing our internal controls could cause our non-compliance with our SEC reporting obligations related to our management’s assessment of our internal control over financial reporting, resulting in unanticipated costs and the diversion of management’s attention.
수정Our success depends on our ability to retain key employees, consultants and advisors and to attract, retain and motivate qualified personnel.
Our ability to compete in the highly competitive biotechnology and pharmaceutical industries depends on our ability to attract and retain highly qualified managerial, scientific, technical, quality-control, manufacturing, medical, regulatory and commercial personnel. The turnover rate in our industry is high and we compete with other companies, as well as academic institutions, for individuals with certain skill sets. Failure to attract and retain personnel, or to maintain relationships with key consultants, contractors and advisors, could result in delays in production or difficulties in maintaining compliance with regulatory requirements. In addition, negative business developments and changes in immigration laws, policies or enforcement patterns, or announcements thereof, that make it more difficult or less desirable for immigrants to work in the U.S. or introduce greater uncertainty into the immigration system may make it difficult to recruit and retain qualified personnel.
수정If we cannot maintain our corporate culture, we could lose the innovation, teamwork and passion that we believe contribute to our success.
It may be increasingly difficult to maintain our culture, which we have invested substantial resources in building. The ~~dramatic growth~~ evolution of our ~~workforce, coupled with recent~~ workforce and shifts in workplace and ~~workstyle,~~ workstyle increase this risk. Failure to preserve our culture could negatively affect our future success.
수정Our internal computer systems and physical premises, or those of third parties with which we share sensitive data or information, may fail or suffer security breaches, including from cybersecurity incidents, which could materially disrupt our product development programs and manufacturing operations.
Our internal computer systems and infrastructure and those of our strategic collaborators, vendors, contractors, consultants or regulators with whom we share confidential, protected or sensitive data or information, or upon which our business relies, are vulnerable to damage from computer viruses, unauthorized access, misuse, natural disasters, terrorism, cybersecurity threats, war and telecommunication and electrical failures, as well as security compromises or data breaches, which may compromise our systems, infrastructure, data or that of those with whom we share such data or information or upon which our business relies, or lead to data compromise, misuse, misappropriation or leakage. We have experienced, and may experience additional, cyber-attacks on our information technology systems and infrastructure by threat actors of all types (including nation states, criminal enterprises, individual actors or advanced persistent threat groups). ~~Further, bad~~ Bad actors around the world use increasingly sophisticated methods, including the use of ~~AI technologies,~~ artificial intelligence, to engage in illegal activities involving the theft and misuse of personal information, confidential information and intellectual property. In addition, the use of generative AI models in our internal or third-party systems may create new attack surfaces or methods for adversaries, which could impact us and our vendors. Any of these effects could damage our reputation, result in the loss of valuable property and information, cause us to breach applicable laws and regulations, and adversely impact our business. In addition, we may experience intrusions on our physical premises by these threat actors. In addition to extracting sensitive information, such attacks could include the deployment of harmful malware, ransomware, digital extortion, business email compromises and denial-of-service attacks, social engineering (including phishing attacks) and other means to affect server reliability and threaten the confidentiality, integrity and availability of information, systems or infrastructure. If any such cyber-attack or physical intrusion against us or those with whom we share confidential, protected or sensitive data or information, or upon which our business relies, were to result in a loss of or damage to our data, systems or infrastructure, or interrupt our operations, such as a material disruption of our development programs or our manufacturing operations, or due to a loss of any of our proprietary or confidential information, it would have a material adverse effect on us. For example, the loss of clinical trial data could delay our regulatory approval efforts and increase our costs to recover or reproduce the data. In addition, because we run multiple clinical trials in parallel, any breach or compromise of our computer systems or infrastructure or physical premises may result in a loss of data or compromised data integrity across multiple programs in many stages of development. While we seek to take steps to address cybersecurity risks, our efforts may not wholly mitigate such risks. Further, our contracts may not contain limitations of liability, and even where they do, there can be no assurance that limitations of liability in our contracts are sufficient to protect us from liabilities, damages or claims related to our privacy and data security obligations. Further, although we maintain cyber liability insurance, this insurance may not provide adequate coverage against potential liabilities related to any experienced cybersecurity incident or breach.
수정We may use our financial and human capital to pursue a particular research program or product candidate and fail to capitalize on programs that may be more profitable or for which there is a greater likelihood of success.
We pursue and fund the development of selected research programs or product candidates and may choose to forego or delay pursuit of other opportunities that could later prove to have greater commercial potential. For example, we are currently focusing our efforts on certain prioritized programs that we expect to file for approval over the next several years. Our resource allocation decisions, or our contractual commitments to provide resources to our strategic collaborators, may cause us to fail to capitalize on ~~certain~~ other commercial products or ~~profitable~~ market opportunities. Additionally, spending on research and development programs ~~for product candidates~~ may not yield commercially viable products. We may also seek to enter into strategic collaborations or financing arrangements pursuant to which we may relinquish valuable rights to product candidates, including the rights to a portion of future revenues, through a strategic alliance, licensing or other royalty arrangements in cases where it would have been more advantageous for us to retain sole development and commercialization rights. Additionally, we may allocate internal resources to a product candidate in a therapeutic area in which it would have been more advantageous to enter into a strategic alliance.
수정Product liability lawsuits against us could cause us to incur substantial liabilities and limit commercialization of our products.
With respect to our COVID vaccine, although the U.S. and certain foreign governments contractually agreed to indemnify us or make statutory immunity available to us for sales during the pandemic public health emergency, which has since ended, such indemnification or statutory immunity may be unavailable to cover potential claims or liabilities resulting from the research, development, manufacture, distribution or commercialization of the vaccine. In the United States, our COVID vaccine currently benefits from liability protections under the Public Readiness and Emergency Preparedness (PREP) Act. However, if the Secretary of the U.S. Department of Health and Human Services were to revoke or materially modify the declaration underlying such PREP Act coverage, or if our COVID vaccine is not successfully transitioned to the National Vaccine Injury Compensation Program (VICP), our COVID vaccine could become subject to significantly greater product liability exposure in the United States. In addition, any significant changes to, or overhaul of, the VICP could increase our potential liability exposure. Additionally, other foreign governments that we contract with have not provided us with similar contractual indemnity or statutory immunity, and we generally no longer have the benefit of such indemnities or immunities for future sales of our commercial products. Substantial claims arising from the vaccine outside the scope of or in excess of U.S. or foreign government indemnity or statutory immunity could harm our financial condition and operating results. Moreover, any adverse event or injury for which we are liable, even if fully covered under an indemnity or immunity, could negatively affect our reputation.
수정Product liability lawsuits against us could cause us to incur substantial liabilities and limit commercialization of our products.
We may be unable to maintain our product liability insurance coverage at a reasonable cost or in sufficient amounts to protect us against losses due to liability. If the costs of maintaining adequate insurance coverage increase significantly in the future, our operating results could be materially adversely affected. Likewise, if insurance coverage ~~should become~~ became unavailable to us or ~~become~~ economically impractical, we would be required to operate our business without indemnity from commercial insurance providers. Additionally, even if we maintain insurance coverage for a type of liability, a particular claim may not be covered if it is subject to a coverage exclusion or we do not otherwise meet the conditions for coverage. If we operate our business with inadequate insurance, we could be responsible for paying claims or judgments against us, which could adversely affect our results of operations or financial condition.
수정Federal legislation and actions by federal, state and local governments may permit reimportation into the United States of drugs from foreign countries where the drugs are sold at lower prices.
We may face competition in the United States ~~for our products~~ from ~~therapies~~ medicines sourced from foreign countries with price controls on pharmaceutical products. For example, in October 2020, the FDA published a final rule that would allow for the importation of certain prescription drugs from Canada, where there are government price controls. In January 2024, the FDA approved Florida’s request to import certain lower-priced medications from Canada. While the full implications of the final rule are ~~currently~~ unknown, legislation or regulations allowing the reimportation of drugs could decrease the price we receive for ~~any~~ our products ~~we may develop~~ and adversely affect our future revenues and potential profitability.
수정Healthcare legislative reform discourse and potential or enacted measures may have a material adverse impact on our business and results of operations and legislative or political discussions surrounding the desire for and implementation of pricing reforms may adversely impact our business.
In the United States, federal and state legislatures, health agencies and third-party payors continue to focus on containing the cost of health care. Legislative and regulatory proposals, enactments to reform health care insurance programs and increasing pressure from social sources could significantly influence ~~the manner in which~~ how our products are prescribed and purchased. For example, provisions of the ACA ~~have~~ resulted in changes in the way health care is paid for by ~~both~~ governmental and private insurers, including increased rebates owed by manufacturers under the Medicaid Drug Rebate Program, annual fees and taxes on manufacturers of certain branded prescription drugs, the requirement that manufacturers participate in a discount program for certain outpatient drugs under Medicare Part D and the expansion of the number of hospitals eligible for discounts under Section 340B of the PHSA. Additionally, the Inflation Reduction Act of 2022 includes ~~several provisions~~ provisions, such as drug pricing controls and Medicare ~~redesign~~ redesign, that have begun to be implemented and are likely to impact our ~~business to varying degrees,~~ business, but its ultimate effect on our business and the healthcare industry in general is not yet known. See “Business—Government Regulation-Current and future healthcare reform legislation.”
수정Healthcare legislative reform discourse and potential or enacted measures may have a material adverse impact on our business and results of operations and legislative or political discussions surrounding the desire for and implementation of pricing reforms may adversely impact our business.
There is also significant economic pressure on state budgets that may result in states increasingly seeking to achieve budget savings through mechanisms that limit coverage or payment for drugs or that would allow for importation of pharmaceutical products from lower cost jurisdictions outside the United States. State Medicaid programs are increasingly requesting manufacturers to pay supplemental rebates and requiring prior authorization by the state program for use of any drug for which supplemental rebates are not being paid. In addition, changes to federal Medicaid rebate requirements may increase manufacturer rebate liabilities. Government efforts to reduce Medicaid expenses may lead to increased use of managed care organizations by Medicaid programs. This may result in managed care organizations influencing prescription decisions for a larger segment of the population and a corresponding limitation on prices and reimbursement for our products, if approved.
수정We are subject, directly or indirectly, to federal and state healthcare fraud and abuse laws and false claims laws. If we cannot comply, or have not fully complied, with such laws, we could face substantial penalties.
Healthcare providers, physicians and third-party payors in the United States and elsewhere play a primary role in the recommendation and prescription of pharmaceutical products. Arrangements with third-party payors and customers can expose pharmaceutical manufacturers to broadly applicable fraud and abuse and other healthcare laws and regulations, which may constrain the business or financial arrangements and relationships through which such companies sell, market and distribute pharmaceutical products. In particular, the promotion, sales and marketing of healthcare items and services, as well as a wide range of pricing, discounting, ~~marketing and promotion,~~ structuring and ~~commission(s),~~ commissions, certain customer incentive programs and other business arrangements, are subject to extensive laws designed to prevent fraud, kickbacks, self-dealing and other abusive ~~practices.~~ practices, which may restrict or prohibit such activities and arrangements. Activities subject to these laws also involve the improper use of information obtained during patient recruitment for clinical trials. See “Business—Government Regulation—Other healthcare laws.”
수정We are subject, directly or indirectly, to federal and state healthcare fraud and abuse laws and false claims laws. If we cannot comply, or have not fully complied, with such laws, we could face substantial penalties.
The scope and enforcement of each of these laws is uncertain and subject to rapid change in the current environment of healthcare ~~reform, especially in light of the lack of applicable precedent and regulations.~~ reform. Ensuring business arrangements comply with applicable healthcare laws, as well as responding to possible ~~investigations by~~ government ~~authorities,~~ investigations, is time- and resource-consuming and can divert a company’s attention from the business. If our operations are found to violate any of these laws or any other regulations, we may be subject to significant sanctions, including civil, criminal and administrative penalties, damages, fines, disgorgement, imprisonment, reputational harm, exclusion from participation in federal and state funded healthcare programs, contractual damages and the curtailment or restricting of our operations, as well as additional reporting obligations and oversight if we become subject to a corporate integrity agreement or other agreement to resolve allegations of non-compliance. Furthermore, if any physician or other healthcare provider or entity with whom we do business is found to be not in compliance with applicable laws, they may be subject to similar penalties. Any action for violation of these laws, even if successfully defended, could cause us to incur significant legal expenses and divert management’s attention from the operation of the business. In addition, the approval and commercialization of any product candidate we develop outside the United States will subject us to foreign healthcare laws.
수정We are subject, directly or indirectly, to federal and state healthcare fraud and abuse laws and false claims laws. If we cannot comply, or have not fully complied, with such laws, we could face substantial penalties.
The provision of benefits or advantages to physicians to induce or encourage the prescription, recommendation, endorsement, purchase, supply, order or use of medicinal products is prohibited in the EU and the UK. The provision of benefits or advantages to induce or reward improper performance generally is also governed by the national anti-bribery laws of EU Member States, and the Bribery Act 2010 in the UK. Infringement of these laws could result in substantial fines and imprisonment. The EU Directive (2001/83/EC, as amended) governing medicinal products for human use provides that, where medicinal products are being promoted to persons qualified to prescribe or supply them, no gifts, pecuniary advantages or benefits in kind may be supplied, offered or promised to such persons unless they are inexpensive and relevant to the practice of medicine or pharmacy. This provision has been retained in UK law despite the UK's departure from the EU.
수정We are subject, directly or indirectly, to federal and state healthcare fraud and abuse laws and false claims laws. If we cannot comply, or have not fully complied, with such laws, we could face substantial penalties.
Payments made to physicians in certain EU Member States must be publicly disclosed, and agreements with physicians often are the subject of prior notification and approval by the physician’s employer, competent professional organization or applicable regulatory authorities. Failure to comply with these requirements could result in reputational ~~risk,~~ harm, public reprimands, administrative penalties, fines or imprisonment.
수정We are subject to various and evolving laws and regulations governing the privacy and security of personal data, and our failure to comply could result in fines or criminal penalties and damage our reputation.
~~Privacy~~ We are subject to data privacy and ~~data~~ security ~~are significant issues~~ laws and regulations in the United States, Europe and ~~many~~ other jurisdictions where we operate or collect personal information. ~~We are subject to data privacy and security~~ These laws and regulations ~~in various jurisdictions that~~ apply to the collection, storage, use, sharing and security of personal data, including health information, and impose significant compliance obligations. In addition, numerous other federal and state laws, including state security breach notification laws, state health information privacy laws and federal and state consumer protection and privacy laws, ~~govern the collection, use, disclosure and security of~~ impose additional requirements with respect to personal information.
수정We are subject to various and evolving laws and regulations governing the privacy and security of personal data, and our failure to comply could result in fines or criminal penalties and damage our reputation.
The EU GDPR and UK GDPR are wide-ranging in scope and impose numerous requirements on companies that process personal data, including imposing special requirements in respect of the processing of health and other sensitive data, requiring that consent of individuals to whom the personal data relates is obtained in certain circumstances, requiring additional disclosures to individuals regarding data processing activities, requiring that safeguards are implemented to protect the security and confidentiality of personal data, limiting retention periods for personal data, creating mandatory data breach notification requirements in certain circumstances, and requiring that certain measures (including contractual requirements) are put in place when engaging third-party service providers. Different EEA Member States have interpreted the EU GDPR differently and many have imposed additional requirements, adding to the complexity of processing personal data in the EEA. The EU GDPR and UK GDPR also impose strict rules on the transfer of personal data to countries outside the EEA that are not considered to provide “adequate” protection to personal data, including the United States, and permits data protection authorities to impose large penalties for violations. Compliance with the EU GDPR and UK GDPR is a rigorous and time-intensive process that may increase our cost of doing business or require us to change our business practices. We could be subject to fines and penalties, litigation and reputational harm in connection with any activities falling within the scope of the EU GDPR or UK GDPR.
수정We are subject to various and evolving laws and regulations governing the privacy and security of personal data, and our failure to comply could result in fines or criminal penalties and damage our reputation.
In the United States, at the federal level, failing to take appropriate steps to keep consumers’ personal information secure may constitute unfair acts or practices in or affecting commerce in violation of Section 5(a) of the Federal Trade Commission Act. In addition, ~~certain state~~ numerous states have introduced comprehensive laws which govern the privacy and security of personal information. For example, California has passed the CCPA and ~~numerous~~ more than a dozen other states have passed their own similar comprehensive consumer privacy laws. Other states proposed or passed laws that target particular aspects of privacy, including health, genetic and biometric information, which could have particular impact for our business. For example, Washington passed a law that protects the privacy of consumer health-related information that is not covered by HIPAA and includes a private right of action. In addition, state laws such as the Texas Genomic Privacy Act and others focus specifically on genetic information and could materially impact our business.
수정We are subject to various and evolving laws and regulations governing the privacy and security of personal data, and our failure to comply could result in fines or criminal penalties and damage our reputation.
Additionally, many foreign jurisdictions have passed or are considering various proposals for data privacy and protection laws, and data privacy remains an evolving landscape at the domestic and international levels, subject to continued legal challenges. We must devote significant resources to understanding and complying with the changing landscape in this area. Each law is also subject to various interpretations by courts and regulatory agencies, creating additional uncertainty, and any failure or perceived failure to comply with the evolving data protection laws could expose us to risk of enforcement actions taken by authorities, private rights of action in some jurisdictions and potential significant ~~penalties~~ penalties, including criminal sanctions, if we are found to be non-compliant. For example, we could be subject to penalties, including criminal penalties, if we knowingly obtain or disclose individually identifiable health information from a HIPAA-covered health care provider or research institution that has not complied with HIPAA’s requirements for disclosing such information. Furthermore, the number of government investigations related to data security incidents and privacy violations continues to increase and government investigations typically require significant resources and generate negative publicity, which could harm our business and our reputation.
수정We are subject to various and evolving laws and regulations governing the privacy and security of personal data, and our failure to comply could result in fines or criminal penalties and damage our reputation.
The Clinical Trials Regulation (EU) No. 536/2014 (the Clinical ~~Trial~~ Trials Regulation) and the EMA policy on publication of clinical data for medicinal products for human use ~~both permit~~ provide for the ~~EMA to publish~~ publication of certain clinical information submitted in marketing authorization ~~approvals~~ applications (MAAs). The ability of third parties to review or analyze data from our clinical trials may increase the risk of commercial confidentiality breaches and result in enhanced scrutiny of our clinical trial results. Such scrutiny could result in public misconceptions regarding our drugs and drug candidates. These publications could also result in the disclosure of information to our competitors that we might otherwise deem confidential, which could harm our business.
수정Our use of generative AI ("GenAI") and other AI technologies presents certain risks and challenges given the emerging nature of AI technologies.
Our use of ~~GenAI~~ generative AI ("GenAI") and other AI technologies presents certain risks and challenges given the emerging nature of AI technologies.
수정Our use of generative AI ("GenAI") and other AI technologies presents certain risks and challenges given the emerging nature of AI technologies.
The development and use of GenAI and other AI technologies (collectively, AI Technologies), ~~along~~ together with an uncertain and rapidly evolving global regulatory landscape, pose risks that could harm our reputation, expose us to ~~liability~~ liability, increase compliance costs, or otherwise adversely affect our business. In particular, new and emerging regulations, such as the European Union Artificial Intelligence Act (the EU AI Act), impose or are expected to impose enhanced obligations related to the development, deployment, transparency, governance, risk management, and use of certain AI systems, including those classified as high-risk, and may subject us to significant fines, penalties, operational restrictions, or changes to our business practices if we fail to comply. These requirements may apply extraterritorially, including to AI systems developed or deployed outside the European Union if their outputs are used in the EU.
수정Our use of generative AI ("GenAI") and other AI technologies presents certain risks and challenges given the emerging nature of AI technologies.
The integration of AI Technologies into our and our vendors’ systems (potentially without the vendor disclosing such use to us) subjects us to the risk that the providers of AI Technologies may not meet existing or ~~rapidly~~ evolving legal, regulatory or industry standards ~~with respect~~ relating to ~~privacy and~~ privacy, data ~~protection.~~ protection, cybersecurity, intellectual property, product safety, human oversight, or algorithmic accountability. Compliance with these requirements may require substantial investments in governance, documentation, monitoring, testing, or operational controls, and may limit our ability to deploy or scale certain AI-enabled tools or features.
수정Our use of generative AI ("GenAI") and other AI technologies presents certain risks and challenges given the emerging nature of AI technologies.
In addition, bad actors globally use increasingly sophisticated methods, including AI Technologies, to engage in illegal activities involving the theft and misuse of personal information, confidential information and intellectual property. The use of GenAI models in our internal or third-party systems may create new attack surfaces or methods for adversaries, which could impact us and our vendors. These factors may lead to breaches of security or privacy, reduced ~~levels of service~~ system performance or ~~experience,~~ availability, loss of intellectual ~~property or exposure~~ property, unauthorized disclosure of confidential or proprietary information. Sophisticated cyber-attacks, including those ~~using~~ leveraging AI, could exacerbate these risks.
수정Our use of generative AI ("GenAI") and other AI technologies presents certain risks and challenges given the emerging nature of AI technologies.
~~Additionally,~~ Further, GenAI’s potential for producing ~~false~~ false, misleading or ~~misleading~~ biased outputs, ~~reflecting biases~~ or ~~generating~~ to generate content that may not be subject to IP protection or that ~~infringes~~ may infringe the proprietary rights of ~~others,~~ third parties, poses additional risks to our business. Regulatory changes or reinterpretations could introduce new compliance risks, including potential government enforcement actions or civil lawsuits. Our competitors’ faster or more effective adoption of AI could also disadvantage us.
수정Climate change or legal, regulatory or market measures to address climate change may negatively affect our business, results of operations and financial condition.
New legal or regulatory requirements may be enacted to prevent, mitigate or adapt to the implications of ~~a changing~~ climate change and its effects on the environment. These regulations, which may differ across jurisdictions, could subject us to new or expanded carbon pricing or taxes, increased compliance costs, restrictions on greenhouse gas emissions, investment in new technologies, increased carbon disclosure and transparency, investments in data gathering and reporting systems, upgrades of facilities to meet new building codes and the redesign of utility systems, which could increase our operating costs, including the cost of electricity and ~~energy we use.~~ energy. Our supply chain would likely be subject to these same transitional risks and would likely pass along any increased costs to us, which may affect our ~~ability to procure~~ procurement of raw materials or other supplies required to operate our business at the quantities and levels we require.
수정Evolving environmental, social and governance (ESG) standards and expectations may expose us to numerous risks.
~~Our aspirations, goals and disclosures related to~~ Evolving environmental, social and governance (ESG) ~~matters~~ standards and expectations may expose us to numerous risks.
수정Evolving environmental, social and governance (ESG) standards and expectations may expose us to numerous risks.
ESG reporting standards are relatively new, have not been harmonized and continue to evolve, and differing interpretations, changing frameworks and evolving regulatory expectations could make compliance more complex and result in inconsistent or revised disclosures over time. If our ESG practices, disclosures or progress do not meet evolving stakeholder or regulatory expectations, or if we fail or are perceived to fail to achieve or accurately report progress toward our goals, our reputation, ability to attract and retain employees and attractiveness as an investment or business partner could be adversely affected, and we could be subject to enforcement actions or litigation. Additionally, the increased focus on ESG matters by policymakers, regulators and investors has in some instances resulted in diverging expectations and standards, which could make it more difficult to comply with ESG-related regulations across our global business.
수정The price of our common stock has been volatile, which could result in substantial losses for shareholders.
Our stock price has been, and is expected to continue to be, subject to substantial volatility. Since our IPO in December 2018, our stock price has ranged from a high of $497.49 to a low of $11.54 per share. Over the last several years, our stock has experienced pronounced and extended periods of volatility, which could cause our shareholders to incur substantial losses. Public statements by us, government agencies, the media, competitors, financial analysts or ~~others, including those related to COVID-19,~~ others have resulted, and may result, in significant fluctuations in our stock price. ~~Information in the public arena, whether or not accurate,~~ Public information, regardless of accuracy, has had and will likely continue to have an outsized impact ~~(positive or negative)~~ on our stock price.
수정The price of our common stock has been volatile, which could result in substantial losses for shareholders.
The stock market ~~in general,~~ generally, and the ~~market for~~ biopharmaceutical ~~companies~~ sector in particular, has experienced ~~extreme~~ significant volatility that ~~has often been~~ may be unrelated to ~~the~~ company operating ~~performance of particular companies,~~ performance, and you may ~~not~~ be ~~able~~ unable to sell your shares at or above your initial purchase price. ~~The market~~ Our stock price ~~for our common stock~~ may be influenced by many factors, including:
수정The price of our common stock has been volatile, which could result in substantial losses for shareholders.
•announcement by us or our competitors of the commencement or termination of significant acquisitions, strategic ~~partnerships,~~ collaborations, joint ventures or capital commitments.
수정The price of our common stock has been volatile, which could result in substantial losses for shareholders.
Securities class-action litigation often has been instituted against companies following periods of volatility in their stock price. In 2024, class action and derivative litigations were filed against us related to statements made about our RSV vaccine. See Item 3. “Legal Proceedings.” We could incur substantial costs in defense of such ~~litigation,~~ litigation or ~~in defense of~~ any future lawsuits that may be filed against us, and management’s attention and resources could be diverted.
수정Our principal shareholders and management own a significant percentage of our stock and will be able to exert significant control over matters subject to shareholder approval.
As of February ~~14, 2025,~~ 13, 2026, our executive officers, directors and affiliated shareholders owned, directly or indirectly, approximately 8% of our outstanding common stock. In addition, non-affiliated five percent or greater shareholders owned approximately ~~27%~~ 32% of our outstanding common stock. These shareholders ~~will~~ have the ability to influence us through their ownership positions. For example, if they were to act together, they could exert significant influence over matters such as elections of directors, amendments of our organizational documents or approval of any merger, sale of assets or other major corporate transaction. This may prevent or discourage unsolicited acquisition proposals or offers for our common stock that our shareholders may believe to be in their best interests.
수정Provisions in our organizational documents and Delaware law could make it more difficult or costly for a third party to acquire us or remove our current management, even if doing so would benefit our shareholders.
Provisions in our organizational ~~documents, as well as provisions of~~ documents and Delaware ~~law,~~ law could make it more difficult or costly for a third party to acquire us or remove our current management, even if doing so would benefit our shareholders.
수정We do not expect to pay cash dividends for the foreseeable future.
We do not currently intend to declare or pay cash dividends on our capital stock and instead intend to retain ~~all of our~~ any future ~~earnings, if any,~~ earnings to finance the growth and development of our business or to return cash to shareholders through share repurchases. In addition, ~~the terms of~~ our existing credit agreement contains restrictions on our ability to pay dividends, and any future debt agreements may preclude us from paying dividends. As a result, capital appreciation, if any, of our common stock will be your sole source of gain for the foreseeable future.
수정We could face unfavorable U.S. or global economic conditions, including as a result of disease outbreak, war, conflict or other political instability, or geopolitical risks.
Our results of operations could be adversely affected by general conditions in the global economy and financial markets, including disruptions caused by pandemic, war, conflict or other political ~~instability, including related to Russia’s invasion of Ukraine and resulting sanctions against Russia or conflict in the Middle East.~~ instability. Adverse macroeconomic conditions, and perceptions or expectations about current or future conditions, such as inflation, slowing growth, rising interest rates, the imposition of tariffs (either on imports or exports, which may impact us directly or indirectly through increased costs in our supply chain), rising unemployment and recession, could negatively affect our business and financial condition. Additionally, global events, including war, conflict, political instability or other adverse economic conditions have and may in the future cause governments to divert spending away from healthcare, negatively impacting the market for our products.
수정Inadequate funding for the FDA, CDC and other government agencies, including from government shut downs, or other disruptions to these agencies’ operations, could hinder their ability to hire and retain key leadership and other personnel, prevent new products and services from being developed or commercialized in a timely manner or otherwise prevent those agencies from performing normal business functions on which the operation of our business may rely.
The FDA’s ability ~~of the FDA~~ to review and approve new products can be affected by a variety of factors, including government priorities, budget and funding levels, the ability to hire and retain key personnel and accept the payment of user fees, and statutory, regulatory and policy changes. Average FDA review times ~~at the agency~~ have fluctuated in recent years as a result. In addition, ~~government~~ funding of other government agencies on which our operations may rely, including those that fund research and development activities, is subject to the political process, which is inherently fluid and unpredictable. Disruptions at the FDA, CDC and other agencies may delay the review or approval of new product candidates, or the development of usage recommendations. If a prolonged government shutdown occurred, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions.
삭제된 항목
Uncertainty and evolving dynamics in the markets for COVID and RSV vaccines, and respiratory vaccines more generally, have in the past impacted and are likely to continue to impact our financial results.
문장 삭제Uncertainty and evolving dynamics in the markets for COVID and RSV vaccines, and respiratory vaccines more generally, have in the past impacted and are likely to continue to impact our financial results.
There is significant uncertainty around the amount of future revenue we will recognize from sales of our COVID vaccine—which is our primary source of revenue—as well as sales of RSV and other respiratory vaccines. Accurately forecasting vaccination rates for our products, which directly impacts overall market size, has been difficult, and these difficulties may persist. Additionally, the recent Presidential election in the U.S. may impact policies and priorities related to our industry.
문장 삭제Uncertainty and evolving dynamics in the markets for COVID and RSV vaccines, and respiratory vaccines more generally, have in the past impacted and are likely to continue to impact our financial results.
In 2024, we recognized $3.1 billion of product sales, compared to $6.7 billion, $18.4 billion and $17.7 billion in 2023, 2022 and 2021, respectively. Beyond COVID vaccines, in 2024, the overall RSV vaccine market was smaller than anticipated, in part due to recommendations from the CDC’s Advisory Committee on Immunization Practices (ACIP) regarding the frequency of vaccination and recommendations related to who, in terms of age or risk factors, should receive an RSV vaccine. These recommendations were more limited than anticipated and future advisory committee recommendations (including with respect to RSV re-vaccination and age group recommendations) may continue to negatively impact the size of the market. If we cannot effectively manage evolving market dynamics, our business, financial condition, results of operations and prospects may suffer.
문장 삭제We have experienced commercial challenges and are likely to experience additional challenges in the future.
We experienced difficulties maintaining our COVID vaccine market share and gaining market share in the U.S. for our RSV vaccine, where we were third to market.
문장 삭제The vaccine market, and pharmaceutical market more generally, is intensely competitive, and we may not compete effectively in the market for existing or new products, treatment methods or technologies.
These competitors (and others against whom we may compete now or in the future) have greater resources and experience than us across all stages of drug development and commercialization. For example, in 2024, our share of the COVID vaccine market declined due in part to increased commercial competition. Additionally, we faced continued exclusion from many European markets by a pandemic-era competitor contract with the European Commission.
문장 삭제The vaccine market, and pharmaceutical market more generally, is intensely competitive, and we may not compete effectively in the market for existing or new products, treatment methods or technologies.
States.
문장 삭제The vaccine market, and pharmaceutical market more generally, is intensely competitive, and we may not compete effectively in the market for existing or new products, treatment methods or technologies.
More generally, the pharmaceutical market is intensely competitive and evolving. For example, we are developing a seasonal flu vaccine, for which there is a well-developed market, and we may be unsuccessful in developing a product or achieving market share.
삭제된 항목
We may be unsuccessful in executing our cost efficiency and portfolio prioritization efforts.
삭제된 항목
We may be unsuccessful or delayed in updating our COVID vaccine to protect against future variants of the SARS-CoV-2 virus.
문장 삭제We may be unsuccessful or delayed in updating our COVID vaccine to protect against future variants of the SARS-CoV-2 virus.
New SARS-CoV-2 strains may be more transmissible or cause more severe disease than earlier strains. Our COVID vaccines could be ineffective, or less effective than desired, in protecting against these new variants.
삭제The commercial success of our products depends on the degree of market acceptance by physicians, patients, third-party payors and others in the medical community.
•whether our product presentation meets customer demand (e.g., for single-dose presentations, or combination vaccines);
문장 삭제Sales of pharmaceutical products depend on the availability and extent of reimbursement from third-party payors, and we may be adversely impacted by changes to such reimbursement policies or rules.
The manner and level at which reimbursement is provided for services related to our products (e.g., for administration to patients) is also important.
문장 삭제Clinical development is lengthy and uncertain, and our clinical programs may be delayed or terminated, or may be more costly to conduct than we anticipate.
Events that might prevent us from proceeding with clinical trials could include:
문장 삭제There are risks unique to each of our programs and modalities and risks applicable across programs and modalities, which may delay or prevent our ability to advance one or more of our programs in clinical development, obtain regulatory approval or commercialize our products.
Additionally, there may be challenges in delivering an adequate quantity of active pharmaceutical ingredient (API) required to drive efficacy due to the limitation in volume of API that can be delivered to a specific location, like a tumor or injured tissue. Our investigational therapies for local injections often require specialized skills for conducting a clinical trial that could delay clinical trials or slow or impair commercialization of a product due to the poor adoption of injected local therapeutics. Gene therapies and mRNA medicines may activate one or more immune responses against any and all components of the drug product (e.g., the mRNA or the delivery vehicle, such as an LNP) as well as against the encoded protein, giving rise to potential immune reaction related adverse events. Eliciting an immune response against the encoded protein may impede our ability to achieve a pharmacologic effect upon repeat administration or a side effect.
삭제We may experience delays in enrolling participants in our clinical trials.
•size of the patient population;
삭제We may experience delays in enrolling participants in our clinical trials.
•availability of competing therapies and clinical trials;
삭제We may experience delays in enrolling participants in our clinical trials.
•clinicians’ and trial participants’ perceptions as to the potential advantages and side effects of the product candidate being studied in relation to other available therapies, including any new drugs or treatments that may be approved for the indications we are investigating;
문장 삭제We may experience delays in enrolling participants in our clinical trials.
Even if we or our strategic collaborators can enroll clinical trial participants, there is no guarantee that such participants will ultimately be dosed as part of, or complete, a clinical trial.
삭제된 항목
mRNA drug development has substantial clinical development and regulatory risks due to the novel nature of this new class of medicines, and the negative perception of the efficacy, safety or tolerability profile of any product candidates that we or others develop could adversely affect our ability to conduct our business, advance our product candidates or obtain regulatory approvals.
문장 삭제mRNA drug development has substantial clinical development and regulatory risks due to the novel nature of this new class of medicines, and the negative perception of the efficacy, safety or tolerability profile of any product candidates that we or others develop could adversely affect our ability to conduct our business, advance our product candidates or obtain regulatory approvals.
For example, in October 2021, the FDA requested that we explore a lower dosage for our COVID vaccine in adolescents, which extended the length of clinical trials in this population prior to receiving regulatory authorization.
문장 삭제mRNA drug development has substantial clinical development and regulatory risks due to the novel nature of this new class of medicines, and the negative perception of the efficacy, safety or tolerability profile of any product candidates that we or others develop could adversely affect our ability to conduct our business, advance our product candidates or obtain regulatory approvals.
We constantly make business decisions and take calculated risks to advance our development efforts and pipeline, including those related to mRNA technology, delivery technology and manufacturing processes, which ultimately may be unsuccessful.
문장 삭제Because we are developing some of our product candidates for the treatment of diseases in which there is little clinical experience and, in some cases, using new endpoints or methodologies, the FDA or other regulators may not consider the endpoints of our clinical trials to provide clinically meaningful results.
For instance, for many of the rare diseases for which we are developing treatments, few clinical trials have been attempted, and there are no approved drugs to treat these diseases.
문장 삭제Because we are developing some of our product candidates for the treatment of diseases in which there is little clinical experience and, in some cases, using new endpoints or methodologies, the FDA or other regulators may not consider the endpoints of our clinical trials to provide clinically meaningful results.
Further, even if we achieve the pre- specified criteria, our clinical trials may produce unpredictable or inconsistent results compared against the more traditional efficacy endpoints in the trial.
문장 삭제Certain mRNA therapies are classified as gene therapies by the FDA and the EMA. The association of our products with gene therapies could result in increased regulatory burdens, impair the reputation of our products or negatively impact our platform or our business.
In certain countries, mRNA therapies have not yet been classified or any such classification is not known to us; for example, in Japan, the Pharmaceuticals and Medical Devices Agency has not taken a position on the regulatory classification of mRNA therapies. For instance, a clinical hold on gene therapy products may apply to our mRNA product candidates irrespective of the differences between gene therapies and mRNA.
문장 삭제Certain mRNA therapies are classified as gene therapies by the FDA and the EMA. The association of our products with gene therapies could result in increased regulatory burdens, impair the reputation of our products or negatively impact our platform or our business.
Physicians, health care providers and third-party payors often are slow to adopt new products, technologies and treatment practices, particularly those that may also require additional upfront costs and training. Further, due to health conditions, genetic profile or other reasons, certain patients may not be candidates for the therapies.
문장 삭제Our products are, and any future products will be, subject to regulatory scrutiny.
Our COVID vaccine is still subject to an emergency use authorization (EUA) for pediatric populations, and this EUA could be revoked for a variety of reasons, including if the FDA determines that the underlying health emergency no longer exists or warrants such authorization.
문장 삭제Preclinical development is lengthy and uncertain, especially for mRNA medicines.
We must also complete extensive work on Chemistry, Manufacturing, and Controls (CMC) activities to be included in an IND submission.
문장 삭제As we grow as a commercial company and our drug development pipeline increases and matures, the increased demand for clinical and commercial supplies from our facilities and third parties may impact our ability to operate. We rely on third-party service providers, all of whom have inherent risks in their operations.
We rely on third-party service providers, all of whom have inherent risks in their operations.
문장 삭제As we grow as a commercial company and our drug development pipeline increases and matures, the increased demand for clinical and commercial supplies from our facilities and third parties may impact our ability to operate. We rely on third-party service providers, all of whom have inherent risks in their operations.
We expect to bring manufacturing plants online in Australia, Canada and the United Kingdom in 2025 and are subject to risks associated with operationalizing these facilities, including with respect to plant licensures.
문장 삭제As we grow as a commercial company and our drug development pipeline increases and matures, the increased demand for clinical and commercial supplies from our facilities and third parties may impact our ability to operate. We rely on third-party service providers, all of whom have inherent risks in their operations.
To supplement our internal manufacturing infrastructure, we have entered into agreements for the production, as well as for commercial fill-finish manufacturing, of our products to supply markets globally. We may need to engage additional third parties in the future to meet our capacity needs.
문장 삭제As we grow as a commercial company and our drug development pipeline increases and matures, the increased demand for clinical and commercial supplies from our facilities and third parties may impact our ability to operate. We rely on third-party service providers, all of whom have inherent risks in their operations.
We currently utilize, and expect to continue to utilize, third parties to, among other things, manufacture raw materials, components, parts, and consumables and to perform quality testing. If the field of mRNA and other nucleic acid medicines continues to expand, we may encounter increasing competition for these materials and services. Demand for third-party manufacturing or testing facilities may grow at a faster rate than their existing capacity, which could disrupt our ability to find and retain third-party manufacturers capable of producing sufficient quantities of such raw materials, components, parts and consumables required to manufacture our mRNA product candidates.
문장 삭제As we grow as a commercial company and our drug development pipeline increases and matures, the increased demand for clinical and commercial supplies from our facilities and third parties may impact our ability to operate. We rely on third-party service providers, all of whom have inherent risks in their operations.
A third-party manufacturer may also encounter difficulties, delays or interruptions in production, including:
삭제As we grow as a commercial company and our drug development pipeline increases and matures, the increased demand for clinical and commercial supplies from our facilities and third parties may impact our ability to operate. We rely on third-party service providers, all of whom have inherent risks in their operations.
•difficulties with production costs, scale up and yields;
삭제As we grow as a commercial company and our drug development pipeline increases and matures, the increased demand for clinical and commercial supplies from our facilities and third parties may impact our ability to operate. We rely on third-party service providers, all of whom have inherent risks in their operations.
•availability of raw materials and supplies;
삭제As we grow as a commercial company and our drug development pipeline increases and matures, the increased demand for clinical and commercial supplies from our facilities and third parties may impact our ability to operate. We rely on third-party service providers, all of whom have inherent risks in their operations.
•quality control and assurance;
삭제As we grow as a commercial company and our drug development pipeline increases and matures, the increased demand for clinical and commercial supplies from our facilities and third parties may impact our ability to operate. We rely on third-party service providers, all of whom have inherent risks in their operations.
•shortages of qualified personnel;
삭제As we grow as a commercial company and our drug development pipeline increases and matures, the increased demand for clinical and commercial supplies from our facilities and third parties may impact our ability to operate. We rely on third-party service providers, all of whom have inherent risks in their operations.
•compliance with strictly enforced regulations that vary in each country where products might be sold; and
삭제As we grow as a commercial company and our drug development pipeline increases and matures, the increased demand for clinical and commercial supplies from our facilities and third parties may impact our ability to operate. We rely on third-party service providers, all of whom have inherent risks in their operations.
•lack of capital funding.
문장 삭제Our products and product candidates are sensitive to shipping and storage conditions, which, in some cases, requires cold-chain logistics and subjects them to risk of loss or damage.
Cold-chain logistics are required for certain of our products and product candidates.
문장 삭제Our manufacturing facilities or those of our third-party manufacturers or suppliers may fail to meet regulatory requirements. Failure to meet cGMP requirements could delay approval of or increase production costs for our products.
Failure to meet cGMP requirements could delay approval of or increase production costs for our products.
삭제Our manufacturing facilities or those of our third-party manufacturers or suppliers may fail to meet regulatory requirements. Failure to meet cGMP requirements could delay approval of or increase production costs for our products.
•contamination of the product due to an ineffective quality control strategy;
삭제Our manufacturing facilities or those of our third-party manufacturers or suppliers may fail to meet regulatory requirements. Failure to meet cGMP requirements could delay approval of or increase production costs for our products.
•facility contamination as assessed by the facility and utility environmental monitoring program;
삭제Our manufacturing facilities or those of our third-party manufacturers or suppliers may fail to meet regulatory requirements. Failure to meet cGMP requirements could delay approval of or increase production costs for our products.
•ineffective corrective actions or preventative actions taken to correct or avoid critical deviations due to our developing understanding of the manufacturing process as we scale; and
삭제Our manufacturing facilities or those of our third-party manufacturers or suppliers may fail to meet regulatory requirements. Failure to meet cGMP requirements could delay approval of or increase production costs for our products.
•failed or defective components or consumables.
문장 삭제Our manufacturing facilities or those of our third-party manufacturers or suppliers may fail to meet regulatory requirements. Failure to meet cGMP requirements could delay approval of or increase production costs for our products.
If we or one of our third-party manufacturing sites fails to provide sufficient quality assurance or control, the product approval to commercialize may not be granted. Inspections by regulators may occur at any time during the development or commercialization of products and may be unannounced. The inspections may be product specific or facility specific, or as a follow up to market or development issues that the regulatory agency may identify. Deficient inspection outcomes, such as failure to comply with cGMP requirements, may negatively impact the ability of our third-party manufacturers or suppliers to fulfill their supply obligations, impacting or delaying supply or delaying programs.
문장 삭제Our manufacturing facilities or those of our third-party manufacturers or suppliers may fail to meet regulatory requirements. Failure to meet cGMP requirements could delay approval of or increase production costs for our products.
The manufacturing process for our products is subject to regulatory approval.
문장 삭제Our INT product candidates are uniquely manufactured for each patient using a novel, complex manufacturing process and we may encounter difficulties in production.
We have built and installed custom manufacturing equipment for INTs incorporated into a dedicated unit at our Norwood, Massachusetts facility. Additionally, as we continue our current Phase 3 INT trials, expand to additional tumor types and prepare for commercialization, we anticipate an increase in manufacturing demand for our INTs that will require ongoing investments. Some of the additional equipment that will be required will be custom-made for us, which will lead to long lead times and expedited procurement to meet our timelines. In addition, it may take longer than anticipated to scale up our facilities and to complete our Marlborough, Massachusetts facility (which we expect to dedicate to INTs) to meet commercial demand, if our INT product candidate is approved.
문장 삭제We expect to continue to rely on third parties to conduct aspects of our research, preclinical studies, protocol development and clinical trials. If these third parties do not perform satisfactorily or comply with regulatory requirements, we may be unable to obtain regulatory approval for or commercialize our product candidates.
In addition, failure of any third-party contractor to conduct activities in accordance with our expectations could adversely affect the relevant research, development, commercial or administrative activity.
문장 삭제Changes in U.S. patent and regulatory law could impair our ability to protect our products.
Our success is heavily dependent on IP, particularly patents.
문장 삭제We may be unable to protect our IP rights throughout the world.
For example, during the COVID pandemic, certain countries threatened steps to facilitate compulsory licenses to permit the distribution of a COVID vaccine in those countries.
문장 삭제We incurred net losses in 2024 and 2023, and expect to incur additional losses in the future; we may not achieve long-term sustainable profitability.
While preparations are underway for additional potential product launches, the ultimate occurrence and timing of these launches is uncertain.
삭제We may encounter difficulties in managing the development and expansion of our company.
We have expanded our scope of operations and number of employees rapidly over the last several years and we must continue to implement and improve our managerial, operational and financial systems. Our management may need to divert significant attention away from our day-to-day activities to manage these development activities.
문장 삭제We may encounter difficulties in managing the development and expansion of our company.
We may be unable to effectively manage this simultaneous execution and expansion of our operations or recruit and train qualified personnel, which could cause weaknesses in our infrastructure, give rise to operational mistakes, loss of business opportunities, loss of employees and reduced productivity among remaining employees. The physical expansion of our operations, including the expansion of our Norwood and Marlborough campuses in Massachusetts and the construction of manufacturing facilities overseas, may lead to significant costs and may divert financial resources from other projects, such as the development of our product candidates.
문장 삭제Our success depends on our ability to retain key employees, consultants and advisors and to attract, retain and motivate qualified personnel.
In addition, negative business developments may make it difficult to recruit and retain qualified personnel.
문장 삭제If we cannot maintain our corporate culture, we could lose the innovation, teamwork and passion that we believe contribute to our success.
Any failure to preserve our culture could negatively affect our future success, including our ability to retain and recruit personnel and to effectively pursue our strategic plans.
문장 삭제We are subject, directly or indirectly, to federal and state healthcare fraud and abuse laws and false claims laws. If we cannot comply, or have not fully complied, with such laws, we could face substantial penalties.
These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, structuring and commissions, certain customer incentive programs and other business arrangements generally.
문장 삭제We are subject, directly or indirectly, to federal and state healthcare fraud and abuse laws and false claims laws. If we cannot comply, or have not fully complied, with such laws, we could face substantial penalties.
This provision has been transposed into the Human Medicines Regulations 2012 and so remains applicable in the UK despite its departure from the EU.
문장 삭제We are subject, directly or indirectly, to federal and state healthcare fraud and abuse laws and false claims laws. If we cannot comply, or have not fully complied, with such laws, we could face substantial penalties.
Payments made to physicians in certain EU Member States must be publicly disclosed. Moreover, agreements with physicians often are the subject of prior notification and approval by the physician’s employer, his or her competent professional organization, or the regulatory authorities of the individual EU Member States. These requirements are provided in the national laws, industry codes or professional codes of conduct, applicable in the EU Member States.
문장 삭제We are subject to various and evolving laws and regulations governing the privacy and security of personal data, and our failure to comply could result in fines or criminal penalties and damage our reputation.
The GDPR and UK GDPR impose stringent obligations on us with respect to our processing and the cross-border transfer of personal data, including higher standards of obtaining consent or ensuring another appropriate legal basis or condition applies to the processing of personal data, more robust transparency requirements, data breach notification requirements, requirements for contractual language with our processors and stronger individual data rights.
문장 삭제We are subject to various and evolving laws and regulations governing the privacy and security of personal data, and our failure to comply could result in fines or criminal penalties and damage our reputation.
There are also states that are specifically regulating health information. Further, a small number of states have passed laws that regulate biometric data specifically. In addition, numerous states and the federal government are actively considering proposed legislation governing the protection of personal data. State laws are changing rapidly and there have been discussions in the U.S. Congress of new comprehensive federal data privacy laws to which we could become subject, if enacted.
문장 삭제We are subject to various and evolving laws and regulations governing the privacy and security of personal data, and our failure to comply could result in fines or criminal penalties and damage our reputation.
Additionally, many foreign jurisdictions have passed data privacy legislation and others are considering various proposals for new privacy and data protection laws. Data privacy remains an evolving landscape at the domestic and international levels, with new laws and regulations being considered and coming into effect and continued legal challenges. Some of these laws and regulations also carry the possibility of criminal sanctions.
문장 삭제Our aspirations, goals and disclosures related to environmental, social and governance (ESG) matters expose us to numerous risks.
Many institutional and individual investors use ESG screening criteria to determine whether we qualify for inclusion in their investment portfolios. We are frequently asked by investors and other stakeholders to set ESG goals and provide new and more robust disclosure on goals, progress toward goals and other matters of interest to ESG stakeholders. In response, we have adapted the tracking and reporting of our corporate responsibility program to various evolving ESG frameworks, and we have established and announced goals and other objectives related to ESG matters. Statements about these goals reflect our current plans and aspirations and are not guarantees that we will be able to achieve them. Our efforts to accomplish and accurately report on these goals and objectives, including with respect to environmental and diversity initiatives, are subject to numerous risks, many of which are outside of our control, which could have a material negative impact, including on our reputation and stock price.
삭제Our aspirations, goals and disclosures related to environmental, social and governance (ESG) matters expose us to numerous risks.
Further, the standards for tracking and reporting on ESG matters are relatively new, have not been harmonized and continue to evolve. Our selection of disclosure frameworks that seek to align with various reporting standards may change from time to time and may result in a lack of consistent or meaningful comparative data from period to period. In addition, our processes and controls may not always comply with evolving standards for identifying, measuring and reporting ESG metrics, our interpretation of reporting standards may differ from those of others and such standards may change over time, any of which could result in significant revisions to our goals or reported progress in achieving such goals.
삭제Our aspirations, goals and disclosures related to environmental, social and governance (ESG) matters expose us to numerous risks.
If our ESG practices do not meet evolving investor or other stakeholder expectations and standards, then our reputation, our ability to attract or retain employees and our attractiveness as an investment, business partner or acquiror could be negatively impacted. Similarly, our failure or perceived failure to pursue or fulfill our goals, targets and objectives or to satisfy various reporting standards within the timelines we announce, or at all, could also have similar negative impacts and expose us to government enforcement actions and private litigation.
삭제된 항목
Because we do not anticipate paying any cash dividends on our capital stock in the foreseeable future, capital appreciation, if any, will be your sole source of gain.
문장 삭제Because we do not anticipate paying any cash dividends on our capital stock in the foreseeable future, capital appreciation, if any, will be your sole source of gain.
We do not currently intend to declare or pay cash dividends on our capital stock.
문장 삭제Our employees, principal investigators and consultants may engage in misconduct or other improper activities, including non-compliance with regulatory standards and requirements and insider trading.
Sales, marketing and business arrangements in the healthcare industry are subject to extensive laws and regulations intended to prevent fraud, misconduct, kickbacks, self-dealing and other abusive practices. These laws and regulations restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs and other business arrangements.
문장 삭제Inadequate funding for the FDA, CDC and other government agencies, including from government shut downs, or other disruptions to these agencies’ operations, could hinder their ability to hire and retain key leadership and other personnel, prevent new products and services from being developed or commercialized in a timely manner or otherwise prevent those agencies from performing normal business functions on which the operation of our business may rely.
Currently, federal agencies in the U.S. are operating under a continuing resolution that is set to expire on March 14, 2025. Without appropriation of additional funding to federal agencies, our business operations related to our product development activities for the U.S. market could be impacted. Disruptions at the FDA, CDC and other agencies may also slow the time necessary for new product candidates to be reviewed or approved, or for recommendations on use to be developed.
사소If we cannot obtain, or are delayed in obtaining, regulatory approvals and advisory committee recommendations, we will be unable to effectively commercialize, or will be delayed in commercializing, our product candidates.
The FDA and comparable foreign regulators have substantial discretion in the approval process and may refuse to accept any marketing approval application or may decide that our data are insufficient for marketing approval and require additional preclinical, clinical or other studies. In addition, varying interpretations of the data obtained from preclinical and clinical testing could delay, limit or prevent marketing approval of a product candidate. Additional delays or non-approval may result if an FDA advisory committee or other regulator recommends non-approval or restrictions on approval.
사소Our products are, and any future products will be, subject to regulatory scrutiny.
Furthermore, advertising and promotional materials must comply with FDA rules and regulations and are subject to FDA review, in addition to other ~~potentially~~ applicable federal and state laws. In addition, regulatory agencies may not approve the labeling claims that are necessary or desirable for the successful commercialization of our product candidates.
사소Our products are, and any future products will be, subject to regulatory scrutiny.
Additionally, the FDA or other ~~foreign~~ regulators could require us to adopt Risk Evaluation and Mitigation Strategies (REMS) for any product to ensure that the benefits of treatment outweigh the risks for each potential patient, which may include, among other things, a medication guide outlining the risks of the product for distribution to patients, a communication plan to health care practitioners, extensive patient monitoring or distribution systems and processes that are highly controlled, restrictive and more costly than what is typical for the industry. Furthermore, if we or others later identify undesirable side effects caused by any product that we develop, several potentially significant negative consequences could result, including the suspension or withdrawal of approvals and licenses, the addition of warning labels, changes to the way a product is administered, the requirement to conduct further clinical trials, lawsuits or increased liability for harm to patients and their children and reputational harm to us. Any of these events could prevent us from achieving or maintaining market acceptance of any products we develop.
사소We or our third-party manufacturers may encounter difficulties in manufacturing, product release, shelf life, testing, storage, supply chain management or shipping for any of our products.
We utilize a number of raw materials and excipients that may have a single source of supply, are new to the pharmaceutical industry and are being employed in a novel manner. Some of these raw materials and excipients have not been scaled to a level to support commercial supply and could experience unexpected manufacturing or testing failures or supply shortages. Such issues with raw materials and excipients could cause delays or interruptions to clinical and commercial supply of our products or product candidates.
사소
As we grow as a commercial company and our drug development pipeline ~~increases and~~ matures, the increased demand for clinical and commercial supplies from our facilities and third parties may impact our ability to operate.
사소We may seek to establish additional strategic alliances and, if we are unable to do so on commercially reasonable terms, we may have to alter our development and commercialization plans. Certain of our strategic alliance agreements may restrict our ability to develop certain products.
Strategic alliances are complex and time-consuming to negotiate and document. If we cannot enter ~~into new strategic~~ alliances on a timely basis, on favorable terms or at all, we may need to curtail the development of the product candidate for which we are seeking to collaborate, reduce or delay its development program or one or more of our other development programs, delay its potential commercialization or reduce the scope of any sales or marketing activities, or increase our expenditures and undertake development or commercialization activities at our own expense.
사소Our reliance on government funding and collaboration from governmental and quasi-governmental entities for certain of our programs adds uncertainty to our research and development efforts with respect to those programs and may impose requirements related to IP rights and requirements that increase the costs of development, commercialization and production of any programs developed under those government-funded programs.
•impose ~~U.S.~~ manufacturing requirements for products that embody inventions conceived or first reduced to practice under such agreements;
사소
We incurred net losses in ~~2024~~ 2025 and ~~2023,~~ 2024, and expect to incur additional losses in the future; we may not achieve long-term sustainable profitability.