Moderna Inc.: 10-K Risk Factor Changes

We have entered into strategic alliances with collaborators that have provided funding, intellectual property licenses and other resources for developing, manufacturing and commercializing our product candidates. Additionally, we have entered into strategic alliances where we agree to provide funding, intellectual property licenses and other resources to third parties. Our strategic alliances may pose a number of risks, including: •strategic collaborators may not perform their obligations as expected; •strategic collaborators may cease or deprioritize development or commercialization of our products due to unfavorable clinical trial results, changes in their focus or funding, or other factors that divert their resources or create competing priorities, such as potential competition with their own products or candidates; •strategic collaborators may delay, stop or provide insufficient funding or resources for clinical trials (whether as a result of a business decision or necessitated by financial difficulties of such collaborator); •a strategic collaborator with marketing and distribution rights to one or more of our products may commit insufficient resources to the marketing and distribution of any such product; 56 56 56 56 56 56 •disagreements with strategic collaborators, including over proprietary rights, contract interpretation or the course of development of any product candidates, may cause delays or termination of the research, development or commercialization of such product candidates, lead to additional responsibilities for us with respect to such product candidates or result in litigation or arbitration, any of which would be time-consuming and expensive; •strategic collaborators may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our IP or proprietary information; •disputes may arise with respect to the ownership of IP developed pursuant to our strategic alliances; •strategic collaborators may infringe the IP rights of third parties, exposing us to potential litigation and liability; •future relationships may require us to incur non-recurring and other charges, increase our near- and long-term expenditures, issue securities that dilute our existing shareholders or disrupt our management and business; •any equity investments we make in collaborators could decrease in value or become worthless; and •our international operations through any future collaborations, acquisitions or joint ventures may expose us to certain operating, legal and other risks not encountered in the United States. Our strategic collaborators generally may materially amend or terminate their agreements with 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.

We have entered into strategic alliances with collaborators that have provided, and may in the future provide, 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, 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: •strategic collaborators may not perform their obligations as expected; •strategic collaborators may cease or deprioritize development or commercialization of our products due to unfavorable clinical trial results, changes in their focus or funding, or other factors that divert their resources or create competing priorities, such as potential competition with their own products or candidates; •strategic collaborators may delay, stop or provide insufficient funding or resources for clinical trials (whether as a result of a business decision or necessitated by financial difficulties of such collaborator); •a strategic collaborator with marketing and distribution rights to one or more of our products may commit insufficient resources to the marketing and distribution of any such product; •disagreements with strategic collaborators, including over proprietary rights, contract interpretation or the course of development of any product candidates, may cause delays or termination of the research, development or commercialization of such product candidates, lead to additional responsibilities for us with respect to such product candidates or result in litigation or arbitration, any of which would be time-consuming and expensive; •strategic collaborators may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our IP or proprietary information; •disputes may arise with respect to the ownership of IP developed pursuant to our strategic alliances; •strategic collaborators may infringe the IP rights of third parties, exposing us to potential litigation and liability; •future relationships may require us to incur non-recurring and other charges, increase our near- and long-term expenditures, issue securities that dilute our existing shareholders or disrupt our management and business; •any equity investments we make in collaborators could decrease in value or become worthless; and •our international operations through any future collaborations, acquisitions or joint ventures may expose us to certain operating, legal and other risks not encountered in the United States. Our strategic collaborators generally may materially amend or terminate their agreements with us, 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. 58 58 58 58 58 58

Our development programs and the potential commercialization of our product candidates will require substantial cash to fund expenses. We may collaborate with other companies to develop and potentially commercialize some of our product candidates, and we face significant competition in seeking collaborators. Our ability to establish additional strategic alliances will depend, among other things, on our assessment of the collaborator’s resources and expertise, proposed terms and conditions and the collaborator’s evaluation of a number of factors. Those factors may include the design or results of clinical trials, the likelihood of regulatory approval, potential market sizes and competition, the costs and complexities of manufacturing and delivering a product candidate to trial participants, uncertainty with respect to our or the proposed collaborator’s ownership of technology (regardless of the merits of the challenge), and industry and market conditions generally. We are also restricted under some of our existing strategic alliance agreements from entering into agreements on certain terms with potential strategic collaborators to pursue other targets on our own. These restrictions on working with targets, polypeptides, routes of administration and fields could limit our ability to enter into strategic collaborations with other collaborators or to pursue certain potentially valuable product candidates. Strategic alliances are complex and time-consuming to negotiate and document. If we cannot enter 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.

Our development programs and the potential commercialization of our product candidates will require substantial cash to fund expenses. We may collaborate with pharmaceutical and biotechnology companies for the development and potential commercialization of 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 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 potential market for the subject product candidate, the costs and complexities of manufacturing and delivering such 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 the merits of the challenge, and industry and market conditions generally. We are also restricted under some of our existing strategic alliance agreements from entering into agreements on certain terms with potential strategic collaborators to pursue other targets on our own. These restrictions on working with targets, polypeptides, routes of administration and fields could limit our ability to enter into strategic collaborations with other collaborators or to pursue certain potentially valuable product candidates. 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.

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. We are highly dependent on members of our management and scientific teams. Each of our executive officers and key employees are employed “at will,” and the loss of any of their services may adversely impact the achievement of our business objectives. We do not have “key person” insurance on any of our employees. Several of our executives have valuable, fully vested stock options or other long-term equity awards. Additionally, significant declines in our stock price have in the past reduced, and may in the future reduce, the retentive power of equity awards for our executives or other key personnel. We may not be able to retain these employees due to the competitive environment in the biotechnology industry, particularly in Cambridge, Massachusetts.

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 may make it difficult to recruit and retain qualified personnel. We are highly dependent on members of our management and scientific teams. Each of our executive officers and key employees are employed “at will,” and the loss of any of their services may adversely impact the achievement of our business objectives. We do not have “key person” insurance on any of our employees. Several of our executives have valuable, fully vested stock options or other long-term equity awards. Additionally, significant declines in our stock price have in the past reduced, and may in the future reduce, the retentive power of equity awards for our executives or other key personnel. We may not be able to retain these employees due to the competitive environment in the biotechnology industry, particularly in Cambridge, Massachusetts. 66 66 66 66 66 66

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. Even if the FDA 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, or our results may be inconsistent or unpredictable compared to traditional efficacy endpoints. Further, the FDA 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.

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 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. 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. Even if the FDA does find 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. Further, even if we achieve the pre- 51 51 51 51 51 51 specified criteria, our clinical trials may produce unpredictable or inconsistent results compared against the more traditional efficacy endpoints in the trial. The FDA could 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.

68 68 68 68 68 68 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, structuring and 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, 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.” The scope and enforcement of each of these laws is uncertain and subject to rapid change in the current environment of healthcare reform. Ensuring business arrangements comply with applicable healthcare laws, as well as responding to possible government 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. 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. 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 harm, public reprimands, administrative penalties, fines or imprisonment.

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 69 69 69 69 69 69 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), certain customer incentive programs and other business arrangements, are subject to extensive laws designed to prevent fraud, kickbacks, self-dealing and other abusive practices. 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. 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.” 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. Ensuring business arrangements comply with applicable healthcare laws, as well as responding to possible investigations by government authorities, 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. 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 transposed into the Human Medicines Regulations 2012 and so remains applicable in the UK despite its departure from the EU. 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. Failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines or imprisonment.

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 as those required under an accelerated approval by the FDA or other similar type of approval, or post-market surveillance. For example, a BLA holder must monitor and report adverse events and any failure of a product to meet applicable specifications, as well as submit and obtain FDA approval for certain new or supplemental applications relating to the approved product, 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. Furthermore, advertising and promotional materials must comply with FDA rules and regulations and are subject to FDA review, in addition to other 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. We are required by the FDA to conduct post-marketing studies for 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 collaborators fail to comply with 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. Additionally, the FDA or other 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. 51 51 51 51 51 51 Additionally, the U.S. Supreme Court’s June 2024 decision in Loper Bright Enterprises v. Raimondo overturned the longstanding Chevron doctrine, under which courts were required to give deference to regulatory agencies’ reasonable interpretations of ambiguous federal statutes. The Loper decision could result in additional legal challenges to regulations and guidance issued by federal agencies, including the FDA, on which we rely. Additionally, the Loper decision may result in increased regulatory uncertainty, inconsistent judicial interpretations and other impacts to the agency rule-making process. We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action or as a result of legal challenges, either in the United States or abroad. If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, our business could be materially harmed.

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 as those required under an accelerated approval by the FDA or other similar type of approval-or post-market surveillance. For example, the 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, as well as submit new or supplemental applications and obtain FDA approval for certain changes to the approved product, product 52 52 52 52 52 52 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. 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. We are required by the FDA to conduct post-marketing studies for our COVID vaccine (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 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. 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. 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. Additionally, the U.S. Supreme Court’s June 2024 decision in Loper Bright Enterprises v. Raimondo overturned the longstanding Chevron doctrine, under which courts were required to give deference to regulatory agencies’ reasonable interpretations of ambiguous federal statutes. The Loper decision could result in additional legal challenges to regulations and guidance issued by federal agencies, including the FDA, on which we rely. Additionally, the Loper decision may result in increased regulatory uncertainty, inconsistent judicial interpretations and other impacts to the agency rule-making process. We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action or as a result of legal challenges, either in the United States or abroad. If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, our business could be materially harmed.

Certain features in our product candidates, including those related to mRNA, chemical modifications, surface chemistries, LNPs and their components, may result in risks that apply to some or all of our programs and modalities. As our product candidates progress, we or others may determine that certain of our risk allocation decisions were incorrect or insufficient, we made platform-level technology mistakes, individual programs or our mRNA science in general has technology or biology risks that were unknown or under-appreciated, our choices on how to develop our infrastructure to support our scale will result in an inability to manufacture our product candidates for clinical trials or otherwise impair our manufacturing or we have allocated resources in such a way that we cannot recover large investments or rapidly re-direct capital. We utilize earlier programs in a modality to understand the technology risks within the modality, including the program’s manufacturing and pharmaceutical properties. Even if our earlier programs in a modality are successful in any phase of development, other programs may fail at that stage, and any program may fail at a later phase of development. This may be a result of technical challenges or biology risk unique to that program. The biology risk across much of our pipeline represents targets and pathways not clinically validated by one or more approved drugs, and the risk that the targets or pathways that we have selected may not be effective will continue to apply across our current and future programs. As we progress our programs through clinical development, new technical challenges may arise that cause an entire modality to fail. Additionally, any portfolio-spanning risks, whether known or unknown, such as an increased risk of a particular type of side effect, if realized in any one of our programs, would have a material and adverse effect on our other programs and on our overall business. There are also specific additional risks to certain of our modalities and programs. For example, prophylactic vaccines typically require clinical testing in up to tens of thousands of healthy volunteers to define an approvable benefit-risk profile. The need to show a high degree of safety and tolerability when dosing healthy individuals could result in rare and even spurious safety findings, negatively impacting a program prior to or after commercial launch. Even if we observe positive safety, tolerability and levels of immunogenicity in early clinical trials, we may not observe acceptable safety or efficacy profiles in later-stage trials required for approval of these programs. There are many clinical and manufacturing challenges specific to intismeran autogene and any other neoantigen therapies we may develop. These include a rapid production turn-around time measured in weeks in order to supply patients 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. These risks apply to intismeran and other neoepitope investigational medicine programs. In addition, the translatability of target selection from preclinical animal models to successful clinical trial results is uncertain and may fail, particularly for systemic therapies and cancer 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, activity, immunogenicity or 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.

Certain features in our product candidates, including those related to mRNA, chemical modifications, surface chemistries, LNPs and their components, may result in risks that apply to some or all of our programs and modalities. As our product candidates progress, we or others may determine that certain of our risk allocation decisions were incorrect or insufficient, we made platform-level technology mistakes, individual programs or our mRNA science in general has technology or biology risks that were unknown or under-appreciated, our choices on how to develop our infrastructure to support our scale will result in an inability to manufacture our product candidates for clinical trials or otherwise impair our manufacturing or we have allocated resources in such a way that we cannot recover large investments or rapidly re-direct capital. We utilize earlier programs in a modality to understand the technology risks within the modality, including the program’s manufacturing and pharmaceutical properties. Even if our earlier programs in a modality are successful in any phase of development, other programs may fail at that stage, and any program may fail at a later phase of development. This may be a result of technical challenges or biology risk unique to that program. The biology risk across much of our pipeline represents targets and pathways not clinically validated by one or more approved drugs, and the risk that the targets or pathways that we have selected may not be effective will continue to apply across our current and future programs. As we progress our programs through clinical development, new technical challenges may arise that cause an entire modality to fail. Additionally, any portfolio-spanning risks, whether known or unknown, such as an increased risk of a particular type of side effect, if realized in any one of our programs, would have a material and adverse effect on our other programs and on our overall business. There are also specific additional risks to certain of our modalities and programs. For example, prophylactic vaccines typically require clinical testing in up to tens of thousands of healthy volunteers to define an approvable benefit-risk profile. The need to show a high degree of safety and tolerability when dosing healthy individuals could result in rare and even spurious safety findings, negatively impacting a program prior to or after commercial launch. Even if we observe positive safety, tolerability and levels of immunogenicity in early clinical trials, we may not observe acceptable safety or efficacy profiles in later-stage trials required for approval of these programs. 49 49 49 49 49 49 There are many clinical and manufacturing challenges specific to our INT product candidates and any other neoantigen cancer vaccines 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 immune status of the patient. These risks apply to our INT product candidates and other neoepitope investigational medicine programs. 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. In addition, the uncertain translatability of target selection from preclinical animal models, including mouse and non-human primate models, to successful clinical trial results may be impossible, particularly for systemic therapies and cancer vaccines. 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. 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.

The degree of market acceptance of our products will depend on numerous factors, including: •efficacy and potential advantages over alternative treatments; •the duration of protection provided by our products compared to those of our competitors; •acceptance of mRNA products generally and the availability of competing non-mRNA medicines that may be preferred by the medical community or the public; •safety and the prevalence and severity of any side effects, including any limitations, restrictions (including for use together with other medicines) or warnings contained in a product’s approved labeling; •the prevalence and severity of any side effects resulting from checkpoint inhibitors or other products or therapies with which our products are co-administered; •relative convenience and ease of administration; •the willingness of the target patient population to try, and physicians to prescribe, new therapies; •the strength of marketing and distribution support and timing of market introduction of competitive products; •whether our product presentation meets customer demand; •publicity and health authority communications concerning our products or competing products and treatments; and 44 44 44 44 44 44 •product cost and sufficient third-party insurance coverage or reimbursement, and patients’ willingness to pay out-of-pocket in the absence of third-party coverage or adequate reimbursement. Even if a product 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.

The degree of market acceptance of our products will depend on numerous factors, including: •efficacy and potential advantages over alternative treatments; •the duration of protection provided by our products compared to those of our competitors; •acceptance of mRNA products generally and the availability of competing non-mRNA medicines that may be preferred by the medical community or the public; •safety and the prevalence and severity of any side effects, including any limitations, restrictions (including for use together with other medicines) or warnings contained in a product’s approved labeling; 46 46 46 46 46 46 •the prevalence and severity of any side effects resulting from checkpoint inhibitors or other products or therapies with which our products are co-administered; •relative convenience and ease of administration; •the willingness of the target patient population to try, and physicians to prescribe, new therapies; •the strength of marketing and distribution support and timing of market introduction of competitive products; •whether our product presentation meets customer demand (e.g., for single-dose presentations, or combination vaccines); •publicity and health authority communications concerning our products or competing products and treatments; and •product cost and sufficient third-party insurance coverage or reimbursement, and patients’ willingness to pay out-of-pocket in the absence of third-party coverage or adequate reimbursement. Even if a potential product displays 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.

We face risks and uncertainties related to successfully commercializing our products. In the past, commercial challenges 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. Furthermore, we may seek to enter into agreements with others to utilize their marketing and distribution capabilities, but may be unable to enter into agreements on favorable terms, if at all. If we rely on others to commercialize our products, our revenues may be lower than if we commercialized these products ourselves. In addition, we may have little or no control over such third parties’ sales efforts. If our partners commit insufficient resources to commercialize our products, and we cannot independently develop necessary marketing capabilities, we may be unable to generate sufficient product revenue to sustain our business.

We face risks and uncertainties related to successfully commercializing our products. For example, in 2024, we faced commercial challenges that led to lower-than-expected sales and required us to adapt our business strategy. 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. 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. Furthermore, we may seek to enter into agreements with others to utilize their marketing and distribution capabilities, but may be unable to enter into agreements on favorable terms, if at all. If we rely on others to commercialize our products, our revenues may be lower than if we commercialized these products ourselves. In addition, we may have little or no control over such third parties’ sales efforts. If our partners commit insufficient resources to commercialize our products, and we cannot independently develop necessary marketing capabilities, we may be unable to generate sufficient product revenue to sustain our business.

Much of our pipeline is in preclinical development, and these programs could be delayed or not advanced into the clinic. Before initiating clinical trials for a product candidate, we must complete extensive preclinical studies, including IND-enabling good laboratory practice (GLP) toxicology testing, as well as significant Chemistry, Manufacturing, and Controls (CMC) activities for inclusion in an IND submission. CMC activities for mRNA medicines involve complex manufacturing processes and analytical development, which 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.

Much of our pipeline is in preclinical development, and these programs could be delayed or not advanced into the clinic. Before we can initiate clinical trials for a product candidate, we must complete extensive preclinical studies, including IND-enabling good laboratory practice (GLP) toxicology testing. We must also complete extensive work on Chemistry, Manufacturing, and Controls (CMC) activities to be included in an IND submission. CMC activities for mRNA medicines require extensive manufacturing processes and analytical development, which is 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. 53 53 53 53 53 53

We are subject to evolving and complex tax laws in the jurisdictions in which we operate. The rules dealing with U.S. federal, state, local and non-U.S. income taxation are constantly under review by legislative and tax authorities. Changes to tax laws (which could apply retroactively) could adversely affect us and our shareholders. In recent years, such changes have been made and changes are likely to occur in the future, which could have a material adverse effect on our business, cash flow, financial condition and results of operations.

We are subject to evolving and complex tax laws in the jurisdictions in which we operate. The rules dealing with U.S. federal, state, local and non-U.S. income taxation are constantly under review by legislative and tax authorities. Changes to tax laws (which could apply retroactively) could adversely affect us and our shareholders. In recent years, such changes have been made and changes are likely to occur in the future, which could have a material adverse effect on our business, cash flow, financial condition and results of operations. 76 76 76 76 76 76

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. These regulations govern manufacturing processes and procedures, including record keeping and the implementation and operation of quality systems to control and assure the quality of products and materials used in clinical trials and for commercial supply. Poor control of cGMP manufacturing processes can lead to product quality failures that may impact our ability to supply product, resulting in cost overruns and cause significant delays to clinical development timelines. Such manufacturing process issues may include: 54 54 54 54 54 54 •critical deviations in the manufacturing process; •ineffective corrective or preventative actions taken to address such deviations as processes scale; •facility and equipment failures; •product or facility contamination, including due to ineffective quality control strategies or failures identified through environmental monitoring programs; •failures of raw materials, components or consumables, including due to ineffective supplier qualification or regulatory compliance issues at critical suppliers; and •ineffective product stability; Regulators typically require representative manufacturing site inspections to assess 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. 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 after regulatory approval is obtained, there is no assurance that 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 or repeat clinical trials, increase trial costs, delay regulatory approval, impair commercialization efforts or increase our cost of goods, any of which could have an adverse effect on our business. In addition, we may not have direct control over the ability of our contract manufacturers to maintain adequate quality control, quality assurance and qualified personnel. Our contract manufacturers supply or manufacture materials or products for other companies and their failure to meet applicable regulatory requirements may affect the regulatory status of their facilities. In addition, to the extent that we rely on foreign contract manufacturers, we are subject to additional risks, including the need to comply with import and export regulations. The FDA, the EMA and other 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 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. In the past, our third-party contract manufacturers 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 strategic collaborators to delay clinical trials or product launches. We and our manufacturing partners also may encounter problems hiring and retaining the experienced scientific, quality control and manufacturing 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.

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. The regulations govern manufacturing processes and procedures, including record keeping, and the implementation and operation of quality systems to control and assure the quality of products and materials used in clinical trials. Poor control of cGMP production processes can lead to product quality failures that can impact our ability to supply product, resulting in cost overruns and delays to clinical timelines, which could be extensive. Such production process issues include: •critical deviations in the manufacturing process; •facility and equipment failures; •contamination of the product due to an ineffective quality control strategy; •facility contamination as assessed by the facility and utility environmental monitoring program; •raw material failures due to ineffective supplier qualification or regulatory compliance issues at critical suppliers; •ineffective product stability; •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 •failed or defective components or consumables. Regulators typically require representative manufacturing site inspections to assess adequate compliance with cGMP and manufacturing controls. 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. The manufacturing process for our products is subject to regulatory approval. 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 regulatory approval is obtained for any of our mRNA medicines, 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 completion of clinical trials, require bridging clinical trials or the repetition of one or more clinical trials, increase clinical trial costs, delay approval of our product candidates, impair commercialization efforts or increase our cost of goods, which, in turn, could have an adverse effect on our business. In addition, we may not have direct control over the ability of our contract manufacturers to maintain adequate quality control, quality assurance and qualified personnel. Our contract manufacturers supply or manufacture materials or products for other companies and their failure to meet applicable regulatory requirements may affect the regulatory status of their facilities. In addition, to the extent that 56 56 56 56 56 56 we rely on foreign contract manufacturers, we are subject to additional risks, including the need to comply with import and export regulations. 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 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. 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, 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.

We are subject to data privacy and security laws and regulations in the United States, Europe and other jurisdictions where we operate or collect personal information. These laws and regulations 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, impose additional requirements with respect to personal information. 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. 69 69 69 69 69 69 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, numerous states have introduced comprehensive laws which govern the privacy and security of personal information. For example, California has passed the CCPA and 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. 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. 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, 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. The Clinical Trials Regulation (EU) No. 536/2014 (the Clinical Trials Regulation) and the EMA policy on publication of clinical data for medicinal products for human use provide for the publication of certain clinical information submitted in marketing authorization 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.

Privacy and data security are significant issues in the United States, Europe and many other jurisdictions where we operate or collect personal information. We are subject to data privacy and security 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 personal information. 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. Different EEA Member States have interpreted the GDPR differently and many have imposed additional requirements, adding to the complexity of processing personal data in the EEA. The 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 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 GDPR or UK GDPR. 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 70 70 70 70 70 70 addition, certain state laws govern privacy and security of personal information. For example, California has passed the CCPA and numerous other states have passed their own similar comprehensive consumer privacy laws. 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. 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. 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 if we are found to be non-compliant. Some of these laws and regulations also carry the possibility of criminal sanctions. 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. The Clinical Trials Regulation (EU) No. 536/2014 (the Clinical Trial Regulation) and the EMA policy on publication of clinical data for medicinal products for human use both permit the EMA to publish clinical information submitted in marketing authorization approvals (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.

Enrolling participants in our clinical trials is critical to our success. Difficulties or delays in enrolling a sufficient number of participants could increase costs or 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: •severity of the disease under investigation; •complexity and design of the clinical trial protocol; •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; •proximity and availability of clinical trial sites for prospective trial participants; •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; •patient referral practices of physicians; 48 48 48 48 48 48 •ability to monitor trial participants adequately during and after treatment; •ability to recruit qualified clinical trial investigators; •adverse results or other safety signals in our trials or related to other product candidates, and any resulting negative publicity, which could discourage potential participants and their physicians from participating in our trials; and •our ability to obtain and maintain participant informed consent. 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.

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 costs or affect 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: •severity of the disease under investigation; •complexity and design of the clinical trial protocol; •size of the patient population; •eligibility criteria for the clinical trial in question, including age-based eligibility criteria limiting subject enrollment to adolescent or pediatric populations; •proximity and availability of clinical trial sites for prospective trial participants; •availability of competing therapies and clinical trials; •patient referral practices of physicians; •ability to monitor trial participants adequately during and after treatment; •ability to recruit qualified clinical trial investigators; •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; •adverse results or other adverse safety signals in our trials or related to other product candidates, and the resulting negative publicity, could discourage potential clinical trial participants and their doctors from participating in our trials; and •our ability to obtain and maintain participant informed consent. 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 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.

We compete with larger, well-established and experienced pharmaceutical companies for sales of our products, including against Pfizer and Sanofi for sales of our COVID 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. 43 43 43 43 43 43 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. 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. 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. Additionally, our products may struggle to compete against 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 competitors’ products, consumers and retailers may fail to appreciate that benefit, or existing purchase commitments 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.”

We compete with well-established, larger pharmaceutical companies for sales of our products, including against Pfizer and Sanofi for sales of our COVID vaccine and Pfizer and GSK for our RSV vaccine. 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. 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. 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 45 45 45 45 45 45 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. More generally, the pharmaceutical market is intensely competitive and evolving. 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. 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. 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. Additionally, any products that we develop may struggle to compete against those of our competitors 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, retailers and the public may fail to appreciate that benefit, or existing purchase commitments for a competitor’s product 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.

We incurred net losses of $2.8 billion and $3.6 billion in 2025 and 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 achieve profitability depends on our ability to successfully develop and obtain the regulatory approvals necessary to commercialize our products. 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 reduction and prioritization measures, these efforts may fail to reduce our costs in line with expectations, which could require us to seek additional funding to continue operations. Our expenses could increase for many reasons, including if and as we: •initiate additional clinical trials, particularly large pivotal trials; •continue to build out our manufacturing capabilities; •build out a sales, marketing and distribution infrastructure to commercialize any products; •acquire or in-license other product candidates and technologies; and •experience any delays or encounter issues with any of the above.

We incurred net losses of $3.6 billion and $4.7 billion in 2024 and 2023, 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. While preparations are underway for additional potential product launches, the ultimate occurrence and timing of these launches 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. 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 and prioritization measures, we may be unsuccessful in reducing 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: •initiate additional clinical trials, particularly large pivotal trials; •continue to build out our manufacturing capabilities; •build out a sales, marketing and distribution infrastructure to commercialize any products; •acquire or in-license other product candidates and technologies; and •experience any delays or encounter issues with any of the above. 64 64 64 64 64 64

Few mRNA medicines have been approved to date by the FDA or other regulators, and efficacy, 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 clinical trial participants or among vaccinated individuals. For example, some studies have suggested that 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. Further, local legislatures may attempt to regulate or restrict the use of mRNA medicines in their jurisdictions. 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, and our business decisions and development efforts relating to mRNA technology, delivery systems and manufacturing processes may ultimately be unsuccessful. Promising early-phase product candidates may fail to advance, be delayed in the clinic, be subject to clinical holds or fail to reach the market for many reasons, including: •nonclinical, preclinical or clinical trial results may show potential mRNA medicines to be less effective than desired or to have harmful or problematic side effects or toxicities; •adverse results in our clinical trials, or in those of others developing similar products, or adverse effects relating to mRNA, or our LNPs, may lead to negative publicity or delays in or termination of our programs; •the efficacy or safety of a combination vaccine product candidate could be less than that seen with the administration of the vaccines separately, which could prevent the combination product from obtaining regulatory approval; •adverse events related to products that are perceived to be similar to mRNA medicines, such as those related to gene therapy or gene editing, could result in a decrease in the perceived benefit of one or more of our programs, increased regulatory scrutiny, decreased confidence by patients and clinical trial collaborators in our product candidates and less demand for any product that we may develop; •the insufficient ability of our translational models to reduce risk or predict outcomes in humans, particularly given that each component of our product candidates may have a dependent or independent effect on safety, tolerability and efficacy, which may be species-dependent; •manufacturing failures or insufficient supply of current Good Manufacturing Practice (cGMP) materials for clinical trials, or higher than expected cost could delay or set back clinical trials, or make mRNA medicines commercially unattractive; •changes that we make to optimize our manufacturing, testing or formulating of cGMP materials could impact the safety, tolerability and efficacy profile of our product candidates; •pricing or reimbursement issues or other factors that delay clinical trials or make any mRNA medicine uneconomical or noncompetitive with other therapies; •our large pipeline of product candidates could result in a greater quantity of reportable adverse events, including suspected unexpected serious adverse reactions, other reportable negative clinical outcomes, manufacturing reportable events or material clinical events that could lead to clinical delay or hold by the FDA or applicable regulatory authority or other clinical delays, any of which could negatively impact the perception of one or more of our programs, as well as our business as a whole; •failure to timely advance our programs or a failure or delay in receiving necessary regulatory approvals due to, among other factors, slow or failure to complete enrollment in clinical trials, withdrawal by trial participants from trials, failure to achieve trial endpoints, additional time requirements for data analysis, data integrity issues, preparation of a BLA or the equivalent application, discussions with the FDA or EMA, a regulatory request for additional nonclinical or clinical data or safety formulation or manufacturing issues may lead to our inability to obtain sufficient funding; 49 49 49 49 49 49 •new legislation or regulations passed by U.S., state or foreign governments in response to negative public perception of mRNA medicines; and •the proprietary rights of others and their competing products and technologies that may prevent our mRNA medicines from being commercialized.

Very few mRNA medicines have been authorized or approved to date by the FDA or other regulators, and efficacy, safety 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 or among individuals vaccinated with mRNA vaccines. For example, some studies have suggested that our COVID vaccine may be associated with higher rates of myocarditis and pericarditis in young males compared to other COVID vaccines. 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 50 50 50 50 50 50 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. 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. In addition, local legislatures may attempt to regulate or restrict the use of mRNA medicines in their jurisdictions. 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. 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. Our product candidates that appear promising in the early phases of development may fail to advance, experience delays in the clinic, experience clinical holds or fail to reach the market for many reasons, including: •nonclinical or preclinical study, or clinical trial, results may show potential mRNA medicines to be less effective than desired or to have harmful or problematic side effects or toxicities; •adverse results in our clinical trials, or in those of others developing similar products, or adverse effects relating to mRNA, or our LNPs, may lead to negative publicity or delays in or termination of our programs; •the efficacy or safety of a combination vaccine product candidate could be less than that seen with the administration of the vaccines separately, which could prevent the combination product from obtaining regulatory approval; •adverse events related to products that are perceived to be similar to mRNA medicines, such as those related to gene therapy or gene editing, could result in a decrease in the perceived benefit of one or more of our programs, increased regulatory scrutiny, decreased confidence by patients and clinical trial collaborators in our product candidates and less demand for any product that we may develop; •the insufficient ability of our translational models to reduce risk or predict outcomes in humans, particularly given that each component of our product candidates may have a dependent or independent effect on safety, tolerability and efficacy, which may be species-dependent; •manufacturing failures or insufficient supply of current Good Manufacturing Practice (cGMP) materials for clinical trials, or higher than expected cost could delay or set back clinical trials, or make mRNA medicines commercially unattractive; •changes that we make to optimize our manufacturing, testing or formulating of cGMP materials could impact the safety, tolerability and efficacy profile of our product candidates; •pricing or reimbursement issues or other factors that delay clinical trials or make any mRNA medicine uneconomical or noncompetitive with other therapies; •our large pipeline of product candidates could result in a greater quantity of reportable adverse events, including suspected unexpected serious adverse reactions, other reportable negative clinical outcomes, manufacturing reportable events or material clinical events that could lead to clinical delay or hold by the FDA or applicable regulatory authority or other clinical delays, any of which could negatively impact the perception of one or more of our programs, as well as our business as a whole; •failure to timely advance our programs or a failure or delay in receiving necessary regulatory approvals due to, among other factors, slow or failure to complete enrollment in clinical trials, withdrawal by trial participants from trials, failure to achieve trial endpoints, additional time requirements for data analysis, data integrity issues, preparation of a BLA or the equivalent application, discussions with the FDA or EMA, a regulatory request for additional nonclinical or clinical data or safety formulation or manufacturing issues may lead to our inability to obtain sufficient funding; •new legislation or regulations passed by U.S., state or foreign governments in response to negative public perception of mRNA medicines; and •the proprietary rights of others and their competing products and technologies that may prevent our mRNA medicines from being commercialized.

We custom design and manufacture intismeran tailored for each patient. As a result, manufacturing is susceptible to product loss or failure due to issues with: •logistics associated with the collection and shipping of a patient’s tumor, blood or other tissue sample; •next-generation sequencing of the tumor mRNA and identification of appropriate tumor-specific mutations; •the use of a software program, including proprietary and open source components, which is hosted in the cloud and a part of our product candidate, to assist with the design of the patient-specific mRNA, which software must be maintained and secured; •effective design of the patient-specific mRNA that encodes for the required neoantigens; •batch specific manufacturing failures or issues that arise due to the uniqueness of each patient-specific batch; •quality control testing failures; •unexpected failures of batches placed on stability; 55 55 55 55 55 55 •shortages or quality control issues with single-use assemblies, consumables or critical parts sourced from third-party vendors that must be changed out for each patient-specific batch; •significant costs associated with individualized manufacturing that may adversely affect our ability to continue development; •successful and timely manufacture and release of the patient-specific batch; •shipment issues encountered during transport of the batch to the patient site of care; and •the ability to define a consistent safety profile at a given dose when each participant receives a unique therapy. 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. The addition of new facilities could also lead to product comparability issues, which could further delay introduction of new capacity. In addition, if our equipment does not function as designed, 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. Because 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 intismeran is developed through clinical trials towards approval and commercialization, multiple aspects of the complicated collection, analysis, manufacture and delivery process may be modified to optimize processes and results. These changes may not achieve the intended objectives, and any of these changes could cause intismeran to perform differently than we expect, potentially affecting the results of clinical trials.

We custom design and manufacture INTs tailored for each patient. Manufacturing unique lots of INTs is susceptible to product loss or failure due to issues with: •logistics associated with the collection and shipping of a patient’s tumor, blood or other tissue sample; •next-generation sequencing of the tumor mRNA and identification of appropriate tumor-specific mutations; •the use of a software program, including proprietary and open source components, which is hosted in the cloud and a part of our product candidate, to assist with the design of the patient-specific mRNA, which software must be maintained and secured; •effective design of the patient-specific mRNA that encodes for the required neoantigens; •batch specific manufacturing failures or issues that arise due to the uniqueness of each patient-specific batch; •quality control testing failures; •unexpected failures of batches placed on stability; •shortages or quality control issues with single-use assemblies, consumables or critical parts sourced from third-party vendors that must be changed out for each patient-specific batch; •significant costs associated with individualized manufacturing that may adversely affect our ability to continue development; •successful and timely manufacture and release of the patient-specific batch; •shipment issues encountered during transport of the batch to the patient site of care; and •the ability to define a consistent safety profile at a given dose when each participant receives a unique therapy. We have built and installed custom manufacturing equipment for INTs incorporated into a dedicated unit at our Norwood, Massachusetts facility. This equipment may not function as designed, resulting in deviations in the drug product produced, which could lead to increased batch failure and the inability to supply patients enrolled in a clinical trial. 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. This expansion and addition of new facilities could also lead to product comparability issues, which could further delay introduction of new capacity. Because our INTs are 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 developed through clinical trials towards approval and commercialization, we expect that multiple aspects of the complicated collection, analysis, manufacture and delivery process will 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 to perform differently than we expect, potentially affecting the results of clinical trials. 57 57 57 57 57 57

The development and use of GenAI and other AI technologies (collectively, AI Technologies), together with an uncertain and rapidly evolving global regulatory landscape, pose risks that could harm our reputation, expose us to 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. 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. 70 70 70 70 70 70 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 evolving legal, regulatory or industry standards relating to privacy, data 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. 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 system performance or availability, loss of intellectual property, unauthorized disclosure of confidential or proprietary information. Sophisticated cyber-attacks, including those leveraging AI, could exacerbate these risks. Further, GenAI’s potential for producing false, misleading or biased outputs, or to generate content that may not be subject to IP protection or that may infringe the proprietary rights of 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.

The development and use of GenAI and other AI technologies (collectively, AI Technologies), along with an uncertain regulatory landscape, pose risks that could harm our reputation, expose us to liability or otherwise adversely affect our business. 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 regulatory or industry standards with respect to privacy and data protection. Further, bad actors around the world use increasingly sophisticated methods, including the use of AI technologies, to engage in illegal activities involving the theft and misuse of personal information, confidential information and intellectual property. These factors may lead to breaches of security or privacy, reduced levels of service or experience, loss of intellectual property or exposure of confidential or proprietary information. Sophisticated cyber-attacks, including those using AI, could exacerbate these risks. Additionally, GenAI’s potential for producing false or misleading outputs, reflecting biases or generating content that may not be subject to IP protection or that infringes proprietary rights of others, 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.

Completion of our trials and commercialization of our products depend on the availability of facilities capable of manufacturing our vaccines at sufficient yields and at commercial scale. We expect to continue to make significant investments in our manufacturing network as we 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. 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 could be adversely affected. Further, efforts to establish and scale these capabilities may not meet expectations 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 required to meet demand or supply obligations. We have in the past, and may in the future, seek to resize our manufacturing infrastructure to reflect anticipated demand for our products. This resizing may result in our incurring costs associated with exiting commitments, such as with suppliers for raw materials and contract manufacturing organizations (CMOs). Additionally, as a result of lower demand for our products, we have experienced, and may in the future experience, increased costs with respect to raw material suppliers as we seek to exit or modify our purchase commitments. Further, we have entered, and may in the future enter, into non-cancellable or take-or-pay purchase commitments for raw materials that require a long lead time to procure, increasing our commitment exposure. 53 53 53 53 53 53 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: •termination or non-renewal of supply and service agreements in a manner or at a time that is costly or damaging to us; •disruptions to the operations of these suppliers and service providers caused by conditions unrelated to our business or operations, including the bankruptcy of the supplier or service provider; and •inspections of third-party facilities by regulators that could have a negative outcome and result in delays to or termination of their ability to supply our requirements. Our reliance on third-party manufacturers may also result in unforeseen delays or operational problems beyond our control. Because of contractual restrictions and the limited number of manufacturers with the expertise, required regulatory approvals and facilities to manufacture our bulk vaccines on a commercial scale, replacing a third-party manufacturer may be expensive, time-consuming or disruptive. Regulators may require us to register our facilities or those of another supplier if we terminate an existing third-party manufacturer relationship, which could delay or limit our 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.

Completion of our trials and commercialization of our product candidates require access to, or development of, facilities to manufacture our vaccine candidates 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. 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. 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. If we cannot enter into such arrangements on favorable terms, or at all, our ability to develop, manufacture and distribute our products would be adversely affected. Further, efforts to establish these capabilities may not meet initial expectations as to 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 to meet potential future demand. 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. The use of service providers and suppliers could expose us to risks, including: •termination or non-renewal of supply and service agreements in a manner or at a time that is costly or damaging to us; •disruptions to the operations of these suppliers and service providers caused by conditions unrelated to our business or operations, including the bankruptcy of the supplier or service provider; and •inspections of third-party facilities by regulators that could have a negative outcome and result in delays to or termination of their ability to supply our requirements. Our reliance on third-party manufacturers may adversely affect our operations or result in unforeseen delays or other problems beyond our control. Because of contractual restraints 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 a manufacturer may be expensive and time-consuming and may cause interruptions in the production of our vaccine. 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 or our inability to supply a particular market. A third-party manufacturer may also encounter difficulties, delays or interruptions in production, including: •difficulties with production costs, scale up and yields; •availability of raw materials and supplies; •quality control and assurance; •shortages of qualified personnel; •compliance with strictly enforced regulations that vary in each country where products might be sold; and •lack of capital funding.

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. 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.

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 72 72 72 72 72 72 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. 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. 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. 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.

We do not currently intend to declare or pay cash dividends on our capital stock and instead intend to retain any future earnings to finance the growth and development of our business or to return cash to shareholders through share repurchases. In addition, 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.

We do not currently intend to declare or pay cash dividends on our capital stock. We currently intend to retain all of our future earnings, if any, to finance the growth and development of our business or to return cash to shareholders through share repurchases. In addition, the terms of 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.

63 63 63 63 63 63 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. Successfully developing, manufacturing and commercializing products across the many therapeutic areas and diseases we seek to address requires significant depth of talent, resources and robust corporate processes to support simultaneous 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. 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 we are unable to effectively manage organizational change, operational scale, and resource allocation, our financial performance and ability to commercialize our products may be affected negatively.

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. Successfully developing products for and fully understanding the regulatory and manufacturing pathways for the many therapeutic areas and diseases we seek to address requires significant depth of talent, resources and corporate processes to allow simultaneous execution across multiple areas. 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. If our management is unable to effectively manage our development and expansion, our financial performance and ability to commercialize our products may be affected negatively.