--- ticker: MRNA company: Moderna Inc. filing_type: 10-K year_current: 2024 year_prior: 2023 risks_added: 5 risks_removed: 5 risks_modified: 39 risks_unchanged: 29 source: SEC EDGAR url: https://riskdiff.com/mrna/2024-vs-2023/ markdown_url: https://riskdiff.com/mrna/2024-vs-2023/index.md generated: 2026-05-10 --- # Moderna Inc.: 10-K Risk Factor Changes 2024 vs 2023 > Source: U.S. Securities and Exchange Commission (EDGAR) > Generated: 2026-05-10 > All data extracted directly from official filings. No hallucinated content. > **[AI-Generated Summary]** The paragraph below was produced by a language > model and may contain errors. All other content on this page is deterministically > extracted from the original SEC filing. > Moderna's risk disclosures shifted focus from COVID-19 specific challenges - removing five risks related to vaccine production, supply agreements, and evolving regulatory pathways - to broader operational and technological concerns, adding five new risks covering AI/GenAI use, climate change impacts, and internal controls. The 39 substantively modified risks indicate significant rewording and emphasis changes, particularly in data privacy/security, patent protection, and intellectual property enforcement. This rebalancing reflects Moderna's transition from a pandemic-dependent company to one managing diversified pipeline risks alongside emerging corporate governance and technology adoption challenges. --- ## Summary | Status | Count | |--------|-------| | New risks added | 5 | | Risks removed | 5 | | Risks modified | 39 | | Unchanged | 29 | --- ## New in Current Filing: We may encounter difficulties producing or shipping our products consistent with our projections or future contractual commitments. We may encounter difficulties producing or shipping our products, including our COVID-19 vaccine or other future products, consistent with our current expectations or on the terms set forth in our supply agreements or future sales contracts. Our ability to commercialize our products depends on our manufacturing capability, both at our own facilities and those of our partners, particularly for fill-finish capabilities. Further, adapting our COVID-19 vaccine to new variants requires significant coordination with our partners, including for the sourcing of raw materials and production. Any capacity or production issues or delays experienced by our partners may cause us to fail to meet obligations under our supply agreements. --- ## New in Current Filing: Emergency authorizations that we have received for our COVID-19 vaccine for certain demographics, including pediatrics, are temporary and could be revoked. We currently operate under an EUA provided by the FDA for our COVID-19 vaccines that are administered as a primary series in pediatric populations. The FDA may revoke this authorization for a variety of reasons, including if it determines that the underlying health emergency no longer exists or warrants such authorization. If new data emerges that shows the benefits of our vaccine do not continue to outweigh its risks, emergency authorizations that we have received for our COVID-19 vaccines from the FDA or other regulators could be revoked if the conditions for granting such authorizations no longer apply. If such authorizations were revoked, without receiving final approval to distribute our COVID-19 vaccines, our business would be adversely impacted. 54 54 54 54 54 54 --- ## New in Current Filing: Our use of GenAI and other AI technologies presents certain risks and challenges given the emerging nature of AI technologies. The development and use of GenAI and other AI technologies (collectively, AI Technologies), along with an uncertain regulatory landscape, pose risks that could harm our reputation, expose us to liability or 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. This 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 intellectual property 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. --- ## New in Current Filing: Climate change or legal, regulatory or market measures to address climate change may negatively affect our business, results of operations and financial condition. We are exposed to physical risks (such as rising temperatures, flooding and severe storms), risks in transitioning to a low-carbon economy (such as additional legal or regulatory requirements, changes in customer behavior and cost and availability of raw materials) and social and human effects (such as population dislocations and harm to health and well-being) associated with climate change. These risks can be either acute (short-term) or chronic (long-term). Climate-related physical risks to our facilities and those of our suppliers could disrupt our operations and supply chain, which may result in increased costs. New legal or regulatory requirements may be enacted to prevent, mitigate or adapt to the implications of a changing climate and its effects on the environment. These regulations, which may differ across jurisdictions, could subject us to new or expanded carbon pricing or taxes, increased compliance costs, restrictions on greenhouse gas emissions, investment in new technologies, increased carbon disclosure and transparency, investments in data gathering and reporting systems, upgrades of facilities to meet new building codes and the redesign of utility systems, which could increase our operating costs, including the cost of electricity and energy we use. Our supply chain would likely be subject to these same transitional risks and would likely pass along any increased costs to us, which may affect our ability to procure raw materials or other supplies required to operate our business at the quantities and levels we require. --- ## New in Current Filing: Ineffective internal controls could adversely impact our business and operating results. Our internal control over financial reporting may not prevent or detect misstatements because of its inherent limitations, including the possibility of human error, failure or interruption of information technology systems, the circumvention or overriding of controls, or fraud. Even effective internal controls can provide only reasonable assurance with respect to the preparation and fair presentation of financial statements. If we fail to maintain the adequacy of our internal controls, including any failure to implement required new or improved controls, or if we experience difficulties in their implementation, our business and operating results could be harmed and we could fail to meet our financial reporting obligations. --- ## No Match in Current: We may encounter difficulties producing, shipping or successfully commercializing our COVID-19 vaccines consistent with our existing or potential contractual obligations, including due to delays or difficulties experienced by our third-party commercial partners. *This section from the 2023 filing does not have a high-confidence textual match in 2024. It may have been removed, merged, or substantially reworded.* We continue to pursue the rapid manufacture, distribution and clinical testing of our COVID-19 vaccines, which are our only commercial products and source of product revenues. We may encounter difficulties producing COVID-19 vaccines on the timelines and in the quantities set forth in our supply agreements. We may also be unsuccessful in entering into contracts for future sales of COVID-19 vaccines. Our ability to commercialize our vaccines depends on our manufacturing capability, both at our own facilities and those of our partners. We are committing substantial financial resources and personnel to the development, manufacture and distribution of our COVID-19 vaccines, including updating our vaccines in response to new variants of concern, and these efforts may delay or otherwise negatively impact our other development programs. Although we have expanded our internal manufacturing capacity, we rely on third-party manufacturing partners to produce our COVID-19 vaccines. We have entered into strategic collaborations for the production, as well as for commercial fill-finish manufacturing, of our COVID-19 vaccines to supply markets both in and outside the United States. We may need to engage additional partners in the future, including additional contract manufacturing organizations (CMOs), to assist in meeting our production needs. If we cannot enter into such arrangements on favorable terms, or at all, our ability to develop, manufacture and distribute our COVID-19 vaccines would be adversely affected. Adapting our COVID-19 vaccines to new variants requires significant coordination with our partners and rapid adaptation. During the height of the pandemic, we were also subject to challenges sourcing sufficient raw materials to produce our vaccine and other supply chain pressures, and we may experience such challenges again in the future. Any capacity or production issues or delays experienced by our partners, whether in connection with updates to our COVID-19 vaccines, satisfying regulatory or quality requirements or other issues, may cause us to fail to meet certain product volume or delivery timing obligations under our supply agreements. Further, we will require significant additional investment, whether from our own capital resources or other sources of funding, as we continue to expand our commercial efforts. --- ## No Match in Current: We have only recently established capabilities to facilitate our compliance with global pharmacovigilance obligations, and failure to build out and maintain this infrastructure may result in increased costs, reputational harm or the loss of our ability to commercialize our products. *This section from the 2023 filing does not have a high-confidence textual match in 2024. It may have been removed, merged, or substantially reworded.* The commercialization and distribution of our COVID-19 vaccines subjects us to pharmacovigilance obligations under regulatory regimes in the jurisdictions where our vaccine is distributed, and we will also be subject to these requirements in connection with future products. These regulations require us to collect, process, analyze and monitor safety data and to identify and evaluate adverse reactions to our vaccines as they are administered in those jurisdictions. We partner with third-party organizations to assist us in collecting and processing this safety data as it is reported from healthcare providers, vaccine recipients and others. If we or these third parties cannot comply with relevant regulations, including with respect to the timely processing of safety data, 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. There are a limited number of service providers who are qualified and capable of providing global pharmacovigilance services, and our inability to identify or contract with them may impede our commercial activities. --- ## No Match in Current: The terms of certain of our supply agreements may require us to refund certain prepayments from customers of our COVID-19 vaccines if they reduce purchase commitments or if we fail to deliver the purchased volume. *This section from the 2023 filing does not have a high-confidence textual match in 2024. It may have been removed, merged, or substantially reworded.* 62 62 62 62 62 62 Table of Content Table of Content Table of Content Some customers for our COVID-19 vaccines prepay us for a portion of the product payment for the vaccine doses that they expect to receive from us. Such prepayments can be substantial. Under certain supply agreements, if we fail to deliver a portion or all of the committed number of doses by a certain date, or if we are unable to successfully obtain regulatory authorization or approval for the commercialization of the vaccine in the relevant jurisdiction, we may be required to pay refunds or other obligations based on the number of days we are late, or a customer may reduce the volume of vaccine doses that it commits to purchase or terminate the contract. Upon termination, we may be required to refund a portion of that customer's prepayment. Customers may not agree to prepay us for our services in the future. --- ## No Match in Current: The regulatory pathway for COVID-19 vaccines is continually evolving and may result in unexpected or unforeseen challenges. *This section from the 2023 filing does not have a high-confidence textual match in 2024. It may have been removed, merged, or substantially reworded.* Our COVID-19 vaccines have advanced rapidly through the regulatory review, authorization and approval processes in the U.S. and other jurisdictions. The speed at which COVID-19 vaccines have been created and tested is atypical as compared to other vaccine development processes. Evolving or changing plans or priorities within the FDA or other regulatory authorities, including changes based on new knowledge of how the SARS-CoV-2 virus, and new variants thereof, affect the human body, may significantly affect the regulatory timeline for further authorizations or approvals for our COVID-19 vaccines, including variant-specific versions. We cannot predict with certainty the timelines or types of clinical trials or regulatory processes that may be required for the authorization or approval of updated versions of our COVID-19 vaccines. We currently operate under a BLA approved by the FDA for our COVID-19 vaccine in certain demographics and an EUA provided by the FDA for our COVID-19 vaccines that are administered as boosters and as a primary series in certain demographics. The FDA may revoke these authorizations for a variety of reasons, including if it determines that the underlying health emergency no longer exists or warrants such authorization. Additionally, we have received certain conditional marketing authorizations in the EEA. Although a conditional marketing authorization is a formal marketing authorization and covers all of our current COVID-19 vaccines produced for the EU, we must provide certain additional information and data by specified timelines as conditions of the conditional authorization in the EU, and the EMA can take regulatory action if we fail to comply. Conditional marketing authorizations are valid for one year and must be renewed annually to remain valid; however, the EMA may decide not to renew. If new data emerges that shows the benefits of our vaccine do not continue to outweigh its risks, the EMA can suspend or revoke our conditional marketing authorization. Similar temporary, emergency authorizations that we have received for our COVID-19 vaccines in other jurisdictions could be revoked if the conditions for granting such authorizations no longer apply. If such authorizations were revoked, without receiving final approval to distribute our COVID-19 vaccines, our business would be adversely impacted. --- ## No Match in Current: Our investigational medicines may face competition from biosimilars approved through an abbreviated regulatory pathway. *This section from the 2023 filing does not have a high-confidence textual match in 2024. It may have been removed, merged, or substantially reworded.* During the 12-year period of exclusivity provided by the Biologics Price Competition and Innovation Act of 2009 (BPCI Act), another company may market a competing version of one of our products if the FDA approves a BLA for the competing product containing the company's own preclinical data and data from adequate and well-controlled clinical trials demonstrating the safety, purity and potency of the other company's product. The BPCI Act is complex and is still being interpreted and implemented by the FDA. As a result, its ultimate impact, implementation and meaning are subject to uncertainty. There is also a risk that any exclusivity we receive for an investigational medicine could be shortened due to U.S. Congressional action or otherwise, or that the FDA will not consider our investigational medicines to be reference products for competing products, potentially creating the opportunity for generic competition sooner than anticipated. Other aspects of the BPCI Act, some of which may impact the BPCI Act's exclusivity provisions, have also been the subject of recent litigation. Moreover, the extent to which a biosimilar, once approved, will be substituted for any one of our reference products in a way that is similar to traditional generic substitution for non-biological products is not yet clear, and will depend on a number of marketplace and regulatory factors that are still developing. --- ## Modified: We are subject to various and evolving laws and regulations governing the privacy and security of personal data, and our failure to comply could result in fines or criminal penalties and damage our reputation. **Key changes:** - Reworded sentence: "Privacy and data security are significant issues in the United States, Europe and many other jurisdictions where we operate or collect personal information." - Reworded sentence: "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." - Reworded sentence: "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." - Added sentence: "State laws are changing rapidly and there is discussion in the U.S." - Added sentence: "Congress of a new comprehensive federal data privacy law to which we may likely become subject, if enacted." **Prior (2023):** Privacy and data security have become 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 legislative and regulatory landscape for privacy and data protection continues to evolve and receive increased focus. The GDPR imposes stringent obligations on us with respect to our processing and the cross-border transfer of personal data, including higher standards of obtaining consent, more robust transparency requirements, data breach notification requirements, requirements for contractual language with our data 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 also imposes 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 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. 87 87 87 87 87 87 Table of Content Table of Content Table of Content In the United States, California has passed the CCPA and Connecticut, Colorado, Utah and Virginia each passed their own comprehensive consumer privacy laws. In addition, numerous states and the federal government are actively considering proposed legislation governing the protection of personal data. 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 we may fail to comply with the evolving data protection laws, which may 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 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. **Current (2024):** 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, 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 is discussion in the U.S. Congress of a new comprehensive federal data privacy law to which we may likely 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 we may fail to comply with the evolving data protection laws, which may expose us to risk of enforcement actions taken by authorities, private rights of action in some jurisdictions and potential significant 73 73 73 73 73 73 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 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. --- ## Modified: We may be subject to claims challenging the inventorship or ownership of our patents and other IP. **Key changes:** - Reworded sentence: "Ownership disputes may arise, for example, from conflicting obligations of consultants or others who are involved in developing our product candidates." - Reworded sentence: "If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable IP 64 64 64 64 64 64 rights, including exclusive ownership of, or right to use, valuable IP." **Prior (2023):** We may be and have been subject to claims that former employees, collaborators or other third parties have an ownership interest in our patents or other IP. Ownership disputes may arise, for example, from conflicting obligations of consultants or others who are involved in developing our development candidates. Litigation may be necessary to defend against these and other claims challenging inventorship or ownership. If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable IP rights, including exclusive ownership of, or right to use, valuable IP. Such an outcome could have a material adverse impact on our business. Even if we are successful in defending against such claims, litigation could result in substantial costs and distract management and other employees, and could impact or patenting strategy. **Current (2024):** We may be and have been subject to claims that former employees, collaborators or other third parties have an ownership interest in our patents or other IP. Ownership disputes may arise, for example, from conflicting obligations of consultants or others who are involved in developing our product candidates. Litigation may be necessary to defend against these and other claims challenging inventorship or ownership. If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable IP 64 64 64 64 64 64 rights, including exclusive ownership of, or right to use, valuable IP. Such an outcome could have a material adverse impact on our business. Even if we are successful in defending against such claims, litigation could result in substantial costs and distract management and other employees, and could impact or patenting strategy. --- ## Modified: We may be unable to obtain and enforce patent protection for our discoveries and the intellectual property rights therein, or protect the confidentiality of our trade secrets. **Key changes:** - Reworded sentence: "Our success depends, in part, on our ability to protect proprietary methods and technologies that we develop under the patent and other IP laws of the United States and other countries, so that we can prevent others from unlawfully using our inventions and proprietary information." - Reworded sentence: "In addition, publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are typically not published until 18 months after filing, if at all." - Reworded sentence: "In the past, we have obtained licenses under third-party patents to market our products or conduct our research and development or other activities, and we may do so in the future if necessary." - Reworded sentence: "The process of obtaining and enforcing patent protection is expensive and time-consuming and our pending patent applications may not result in issued patents." - Reworded sentence: "Also, third parties or the USPTO may commence patent office proceedings involving our patents or patent applications." **Prior (2023):** 75 75 75 75 75 75 Table of Content Table of Content Table of Content Our success depends, in part, on our ability to protect proprietary methods and technologies that we develop under the patent and other IP laws of the United States and other countries, so that we can prevent others from unlawfully using our inventions and proprietary information. Because certain U.S. patent applications are confidential until the patents issue, third parties may have filed patent applications for technology covered by our pending patent applications without our being aware of those applications, and our patent applications may not have priority over those applications. In addition, publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are typically not published until 18 months after filing, or in some cases not at all. Therefore, we cannot be certain that we were the first to make the inventions claimed in our patents or pending patent applications or that we were the first to file for patent protection of such inventions, including our COVID-19 vaccine. We therefore may be unable to secure desired patent rights, thereby losing exclusivity. Further, we may be required to obtain licenses under third-party patents to market our proposed products or conduct our research and development or other activities. If licenses are not available to us on favorable terms, we may not be able to market the affected products or conduct the desired activities. The process of obtaining patent protection is expensive and time-consuming and our pending patent applications may not result in issued patents. Obtaining and maintaining our patent protection depends on compliance with various procedural, document submission, fee payment and other requirements imposed by governmental patent agencies, and our patent applications may fail to result in valid enforceable patents, or our patent protection could be reduced or eliminated, for non-compliance with these requirements. If we or our strategic collaborators fail to file and prosecute all necessary and desirable patent applications at a reasonable cost and in a timely manner, our business may be adversely affected. Despite our and our strategic collaborators' efforts to protect our proprietary rights, unauthorized parties may obtain and use information that we regard as proprietary. While issued patents are presumed valid, they may not survive a validity challenge and could be held unenforceable. Any patents we have obtained, or obtain in the future, may be challenged, invalidated, adjudged unenforceable or circumvented by parties seeking to design around our IP. Also, third parties or the USPTO may commence interference proceedings involving our patents or patent applications. Any challenge to, finding of unenforceability or invalidation, or circumvention of, our patents or patent applications, would be costly, would require significant time and attention of our management, could reduce or eliminate royalty payments to us from third-party licensors and could have a material adverse impact on our business. The standards that the USPTO and its foreign counterparts use to grant patents are not always applied predictably or uniformly and can change. Similarly, the ultimate degree of protection that will be afforded to biotechnology inventions, including ours, in the United States and foreign countries, remains uncertain and is dependent upon the scope of the protection decided upon by patent offices, courts and lawmakers. For example, the America Invents Act included a number of changes to the patent laws of the United States. If any of the enacted changes prevent us from adequately protecting our discoveries, including our ability to pursue infringers of our patents to obtain injunctive relief or for substantial damages, our business could be adversely affected. One major provision of the America Invents Act changed U.S. patent practice from a first-to-invent to a first-to-file system. If we fail to file an invention before a competitor files on the same invention, we no longer have the ability to provide proof that we were in possession of the invention prior to the competitor's filing date, and thus would not be able to obtain patent protection for our invention. There is also no uniform, worldwide policy regarding the subject matter and scope of claims granted or allowable in pharmaceutical or biotechnology patents. In certain countries, for example, methods for the medical treatment of humans are not patentable. Accordingly, we do not know the degree of future protection for our proprietary rights or the breadth of claims that will be allowed in any patents issued to us or to others. We also rely to a certain extent on trade secrets, know-how and technology, which are not protected by patents, to maintain our competitive position. We also rely on non-disclosure agreements and invention assignment agreements entered into with our employees, consultants and third parties. If any trade secret, know-how or other technology not protected by a patent were to be disclosed to or independently developed by a competitor, our business and financial condition could be materially adversely affected. Failure to obtain and maintain all available regulatory exclusivities and broad patent scope and to maximize patent term restoration or extension on patents covering our products may lead to loss of exclusivity and early biosimilar entry resulting in a loss of market share or revenue. In addition, we may choose not to enforce our IP rights in certain circumstances or for certain periods of time. For example, in March 2022, we announced that we will not enforce our patents for COVID-19 vaccines against companies manufacturing in or for the Gavi COVAX Advance Market Commitment countries, provided that the manufactured vaccines are solely for use in the AMC 92 countries. In addition, we are willing to license our IP for COVID-19 vaccines to manufacturers, but we may never enter into such licenses of our IP, and our business may be otherwise adversely impacted if we are unable to enforce our IP. In August 2022, we filed patent infringement lawsuits against Pfizer and BioNTech in the United States, Germany and other jurisdictions, alleging that their COVID-19 vaccine Comirnaty® infringes patents we filed between 2010 and 2016 covering our foundational mRNA technology. We have invested billions of dollars in creating our patented mRNA platform, which is integral to the development of our mRNA medicines. We expect to expend substantial financial and managerial resources pursuing this litigation and defending against counterclaims filed by Pfizer and BioNTech, and the ultimate outcome of the litigation is uncertain. 76 76 76 76 76 76 Table of Content Table of Content Table of Content **Current (2024):** Our success depends, in part, on our ability to protect proprietary methods and technologies that we develop under the patent and other IP laws of the United States and other countries, so that we can prevent others from unlawfully using our inventions and proprietary information. Because certain U.S. patent applications are confidential until the patents issue, third parties may have filed patent applications for technology covered by our pending patent applications without our being aware of those applications, and our patent applications may not have priority over those applications. In addition, publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are typically not published until 18 months after filing, if at all. Therefore, we cannot be certain that we were the first to make the inventions claimed in our patents or 61 61 61 61 61 61 pending patent applications or that we were the first to file for patent protection of such inventions. We therefore may be unable to secure desired patent rights, thereby losing exclusivity. In the past, we have obtained licenses under third-party patents to market our products or conduct our research and development or other activities, and we may do so in the future if necessary. If licenses are not available to us on favorable terms, we may not be able to market the affected products or conduct the desired activities. The process of obtaining and enforcing patent protection is expensive and time-consuming and our pending patent applications may not result in issued patents. Obtaining and maintaining our patent protection depends on compliance with various procedural, document submission, fee payment and other requirements imposed by governmental patent agencies, and our patent applications may fail to result in valid enforceable patents, or our patent protection could be reduced or eliminated, for non-compliance with these requirements. If we or our strategic collaborators fail to file and prosecute all necessary and desirable patent applications at a reasonable cost and in a timely manner, our business may be adversely affected. Despite our and our strategic collaborators' efforts to protect our proprietary rights, unauthorized parties may obtain and use information that we regard as proprietary. While issued patents are presumed valid, they may not survive a validity challenge and could be held unenforceable. Any patents we have obtained, or obtain in the future, may be challenged, invalidated, adjudged unenforceable or circumvented by parties seeking to design around our IP. Also, third parties or the USPTO may commence patent office proceedings involving our patents or patent applications. Any challenge to, finding of unenforceability or invalidation, or circumvention of, our patents or patent applications, would be costly, would require significant time and attention of our management, could reduce or eliminate royalty payments to us from third-party licensors and could have a material adverse impact on our business. The standards that the USPTO and its foreign counterparts use to grant patents are not always applied predictably or uniformly and can change. Similarly, the ultimate degree of protection that will be afforded to biotechnology inventions, including ours, in the United States and foreign countries, remains uncertain and is dependent upon the scope of the protection decided upon by patent offices, courts and lawmakers. For example, the America Invents Act included a number of changes to the patent laws of the United States. If any of the enacted changes prevent us from adequately protecting our discoveries, including our ability to pursue infringers of our patents to obtain injunctive relief or for substantial damages, our business could be adversely affected. One major provision of the America Invents Act changed U.S. patent practice from a first-to-invent to a first-to-file system. If we fail to file an invention before a competitor files on the same invention, we no longer have the ability to provide proof that we were in possession of the invention prior to the competitor's filing date, and thus would not be able to obtain patent protection for our invention. There is also no uniform, worldwide policy regarding the subject matter and scope of claims granted or allowable in pharmaceutical or biotechnology patents. In certain countries, for example, methods for the medical treatment of humans are not patentable. Accordingly, we do not know the degree of future protection for our proprietary rights or the breadth of claims that will be allowed in any patents issued to us or to others. We also rely to a certain extent on trade secrets, know-how and technology, which are not protected by patents, to maintain our competitive position. We also rely on non-disclosure agreements and invention assignment agreements entered into with our employees, consultants and third parties. If any trade secret, know-how or other technology not protected by a patent were to be disclosed to or independently developed by a competitor, our business and financial condition could be materially adversely affected. Failure to obtain and maintain all available regulatory exclusivities and broad patent scope and to maximize patent term restoration or extension on patents covering our products may lead to loss of exclusivity and early biosimilar entry resulting in a loss of market share or revenue. In addition, we may choose not to enforce our IP rights in certain circumstances or for certain periods of time. For example, in March 2022, we announced that we will not enforce our patents for COVID-19 vaccines against companies manufacturing in or for the Gavi COVAX Advance Market Commitment countries, provided that the manufactured vaccines are solely for use in the AMC 92 countries. In addition, we are willing to license our IP for COVID-19 vaccines to manufacturers, but we may never enter into such licenses of our IP, and our business may be otherwise adversely impacted if we are unable to enforce our IP. --- ## Modified: Certain mRNA therapies are classified as gene therapies by the FDA and the EMA. The association of our medicines with gene therapies could result in increased regulatory burdens, impair the reputation of our investigational medicines or negatively impact our platform or our business. **Key changes:** - Reworded sentence: "In the EU, certain mRNA therapies have been characterized as gene therapy medicinal products, which falls within a broader category known as Advanced Therapy Medicinal Products (ATMPs), which are subject to additional regulatory requirements." - Reworded sentence: "Notwithstanding the differences between mRNA medicines and gene therapies, the classification of some of our mRNA product candidates as gene therapies in the United States, the EU and potentially other countries could adversely impact our ability to develop our product candidates." - Reworded sentence: "Although our mRNA product candidates are designed not to make any permanent changes to cell DNA, regulatory agencies or others could believe that adverse effects of gene therapies caused by introducing new DNA and irreversibly changing the DNA in a cell could also be a risk for our mRNA investigational therapies, and as a result may delay one or more of our clinical trials or impose additional testing for long-term side effects." - Reworded sentence: "53 53 53 53 53 53 Additionally, if any such therapeutic is approved, physicians and patients may be slow or fail to accept these novel and personalized treatments." **Prior (2023):** There are only a few approved gene therapy products in the United States or foreign jurisdictions, and there have been well-reported significant adverse events associated with their testing and use. Regulatory requirements governing gene therapy products have evolved and may continue to change in the future, and the implications for mRNA therapies are unknown. For example, the FDA has established an office, now called the Office of Therapeutics Products (OTP), within its Center for Biologics Evaluation and Research (CBER) to consolidate the review of gene therapy and related products, and convenes the Cellular, Tissue and Gene Therapies Advisory Committee to advise CBER on its review. In the EU, mRNA has been characterized as a gene therapy medicinal product, which falls within a broader category known as Advanced Therapy Medicinal Products (ATMPs), which are subject to additional regulatory requirements. In certain countries, mRNA therapies have not yet been classified or any such classification is not known to us; for example, in Japan, the Pharmaceuticals and Medical Devices Agency has not taken a position on the regulatory classification of mRNA therapies. Notwithstanding the differences between mRNA medicines and gene therapies, the classification of some of our mRNA investigational medicines as gene therapies in the United States, the EU and potentially other countries could adversely impact our ability to develop our investigational medicines, negatively impacting our platform and our business. For instance, a clinical hold on gene therapy products may apply to our mRNA investigational medicines irrespective of the differences between gene therapies and mRNA. Adverse events reported with respect to gene therapies could adversely impact one or more of our programs. Although our mRNA development candidates and investigational medicines are designed not to make any permanent changes to cell DNA, regulatory agencies or others could believe that adverse effects of gene therapies caused by introducing new DNA and irreversibly changing the DNA in a cell could also be a risk for our mRNA investigational therapies, and as a result may delay one or more of our clinical trials or impose additional testing for long-term side effects. Any new requirements and guidelines promulgated by regulatory agencies may negatively affect our business by lengthening the regulatory review process, requiring us to perform additional or larger studies or increasing our development costs, any of which could lead to changes in regulatory positions and interpretations, delay or prevent advancement or approval and commercialization of our investigational medicines, or lead to significant post-approval studies, limitations or restrictions. As we advance our investigational medicines, we will be required to consult with these regulatory agencies and advisory committees and comply with applicable requirements and guidelines. If we fail to do so, we may be required to delay or discontinue development of some or all of our investigational medicines. 67 67 67 67 67 67 Table of Content Table of Content Table of Content Additionally, we have established Moderna Genomics (MGX) with the vision of becoming a leader in large, complex genomic editing. In November 2021, we announced a multi-year research collaboration with Metagenomi to leverage its discovery platform and expertise to develop next-generation in vivo gene editing therapies. Our work in genomic editing is subject to all risks associated with gene therapies. Although there have been significant advances in recent years in fields of gene therapy and genome editing, in vivo CRISPR-based genome editing technologies are relatively new and their therapeutic utility is largely unproven. Public perception and related media coverage of potential therapy-related efficacy or safety issues, as well as ethical concerns related specifically to genome editing, may adversely influence the willingness of subjects to participate in clinical trials. In addition, any review conducted by an institutional biosafety committee may result in delay or prevent initiation of a gene therapy clinical trial. Additionally, if any such therapeutic is approved, physicians and patients may be slow or fail to accept these novel and personalized treatments. Physicians, health care providers and third-party payors often are slow to adopt new products, technologies and treatment practices, particularly those that may also require additional upfront costs and training. Physicians may not be willing to undergo training to adopt these novel and potentially personalized therapies, may decide the particular therapy is too complex or potentially risky to adopt without appropriate training and may choose not to administer the therapy. Further, due to health conditions, genetic profile or other reasons, certain patients may not be candidates for the therapies. In addition, responses by federal and state agencies, congressional committees and foreign governments to negative public perception, ethical concerns or financial considerations may result in new legislation, regulations or medical standards that could limit our ability to develop or commercialize any product candidates, obtain or maintain regulatory approval or otherwise achieve profitability. Based on these and other factors, health care providers and payors may decide that the benefits of these new therapies do not or will not outweigh their costs. **Current (2024):** There are only a few approved gene therapy products in the United States or foreign jurisdictions, and there have been well-reported significant adverse events associated with their testing and use. Regulatory requirements governing gene therapy products have evolved and may continue to change in the future, and the implications for mRNA therapies are unknown. For example, the FDA has established an office, now called the Office of Therapeutics Products (OTP), within its Center for Biologics Evaluation and Research (CBER) to consolidate the review of gene therapy and related products, and convenes the Cellular, Tissue and Gene Therapies Advisory Committee to advise CBER on its review. In the EU, certain mRNA therapies have been characterized as gene therapy medicinal products, which falls within a broader category known as Advanced Therapy Medicinal Products (ATMPs), which are subject to additional regulatory requirements. In certain countries, mRNA therapies have not yet been classified or any such classification is not known to us; for example, in Japan, the Pharmaceuticals and Medical Devices Agency has not taken a position on the regulatory classification of mRNA therapies. Notwithstanding the differences between mRNA medicines and gene therapies, the classification of some of our mRNA product candidates as gene therapies in the United States, the EU and potentially other countries could adversely impact our ability to develop our product candidates. For instance, a clinical hold on gene therapy products may apply to our mRNA product candidates irrespective of the differences between gene therapies and mRNA. Adverse events reported with respect to gene therapies could adversely impact one or more of our programs. Although our mRNA product candidates are designed not to make any permanent changes to cell DNA, regulatory agencies or others could believe that adverse effects of gene therapies caused by introducing new DNA and irreversibly changing the DNA in a cell could also be a risk for our mRNA investigational therapies, and as a result may delay one or more of our clinical trials or impose additional testing for long-term side effects. Any new requirements and guidelines promulgated by regulatory agencies may negatively affect our business by lengthening the regulatory review process, requiring us to perform additional or larger studies or increasing our development costs, any of which could lead to changes in regulatory positions and interpretations, delay or prevent advancement or approval and commercialization of our product candidates, or lead to significant post-approval studies, limitations or restrictions. As we advance our product candidates, we will be required to consult with these regulatory agencies and advisory committees and comply with applicable requirements and guidelines. If we fail to do so, we may be required to delay or discontinue development of some or all of our product candidates. Our work in genomic editing is subject to all risks associated with gene therapies. Although there have been significant advances in recent years in fields of gene therapy and genome editing, in vivo CRISPR-based genome editing technologies are relatively new and their therapeutic utility is largely unproven. Public perception and related media coverage of potential therapy-related efficacy or safety issues, as well as ethical concerns related specifically to genome editing, may adversely influence the willingness of subjects to participate in clinical trials. In addition, any review conducted by an institutional biosafety committee may result in delay or prevent initiation of a gene therapy clinical trial. 53 53 53 53 53 53 Additionally, if any such therapeutic is approved, physicians and patients may be slow or fail to accept these novel and personalized treatments. Physicians, health care providers and third-party payors often are slow to adopt new products, technologies and treatment practices, particularly those that may also require additional upfront costs and training. Physicians may not be willing to undergo training to adopt these novel and potentially personalized therapies, may decide the particular therapy is too complex or potentially risky to adopt without appropriate training and may choose not to administer the therapy. Further, due to health conditions, genetic profile or other reasons, certain patients may not be candidates for the therapies. In addition, responses by federal and state agencies, congressional committees and foreign governments to negative public perception, ethical concerns or financial considerations may result in new legislation, regulations or medical standards that could limit our ability to develop or commercialize any product candidates, obtain or maintain regulatory approval or otherwise achieve profitability. Based on these and other factors, health care providers and payors may decide that the benefits of these new therapies do not or will not outweigh their costs. --- ## Modified: Preclinical development is lengthy and uncertain, especially for mRNA medicines, and our preclinical programs or product candidates may be delayed or terminated. **Key changes:** - Reworded sentence: "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." - Reworded sentence: "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." - Reworded sentence: "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." **Prior (2023):** 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 development 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 development candidates. If we must produce new batches, our preclinical studies could be delayed. We cannot be certain of the timely completion or outcome 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. **Current (2024):** 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. --- ## Modified: Our mRNA products and product candidates are based on novel technologies and are complex and difficult to manufacture. We or our third-party manufacturers may encounter difficulties in manufacturing, product release, shelf life, testing, storage, supply chain management or shipping for any of our products. **Key changes:** - Reworded sentence: "In an effort to optimize product features, we have in the past and may in the future make changes to our product candidates in their manufacturing and stability formulation and conditions." - Reworded sentence: "Our mRNA product candidates may prove to have a stability profile that leads to a lower than desired shelf life of the final approved medicine." - Reworded sentence: "Due to the number of different programs, we may have cross contamination of product candidates inside of our factories, CROs, suppliers or in the clinic that affect the integrity of our product candidates." - Reworded sentence: "Such issues with raw materials and excipients could cause delays or interruptions to clinical and commercial supply of our products or product candidates." - Reworded sentence: "This may lead to an inability to release mRNA product candidates until the manufacturing or testing process is rectified." **Prior (2023):** The manufacturing processes for our mRNA medicines are novel and complex. We and our collaborators have experienced and may continue to encounter difficulties in manufacturing, product release, shelf life, testing, storage, supply chain management or shipping, including delays as our supply chain expands and grows more complex. We could experience issues resulting from complexities of producing batches at larger scale, equipment failure, human error, choice and quality of raw materials and excipients, analytical testing technology and product instability. Further, mRNA medicines encapsulated in LNPs must be developed and manufactured under well-controlled conditions, or pharmacological activity can be adversely impacted. 69 69 69 69 69 69 Table of Content Table of Content Table of Content In an effort to optimize product features, we have in the past and may in the future make changes to our development candidates or investigational medicines in their manufacturing and stability formulation and conditions. This has in the past and may in the future result in our having to resupply batches for preclinical or clinical activities when there is insufficient product stability during storage and insufficient supply. Insufficient stability or shelf life of our development candidates and investigational medicines could materially delay our or our strategic collaborators' ability to continue clinical trials or require us to begin a new clinical trial with a newly formulated drug product, due to the need to manufacture additional preclinical or clinical supply. Our high rate of innovation causes a high degree of technology change that can negatively impact product comparability during and after clinical development. Furthermore, technology changes may drive the need for changes in, modification to, or the sourcing of new manufacturing infrastructure or may adversely affect third-party relationships. In many cases, we may need to utilize multiple batches of drug substance and drug product to meet the supply requirement of a single preclinical study or clinical trial. Failure in our ability to scale up batch size or failure in any batch, which we have experienced in the past, may lead to a substantial delay in our clinical trials or in the commercialization of any approved product. For example, the changes we make as we continue developing new manufacturing processes for our drug substance and drug product may impact specification and stability of the drug product, and may lead to failure of batches, resulting in a substantial delay in delivery of commercial product or conduct of our clinical trials. Our mRNA investigational medicines may prove to have a stability profile that leads to a lower than desired shelf life of the final approved medicine. This poses risk in supply requirements, wasted stock and higher cost of goods. We are dependent on a number of equipment providers who are also implementing novel technology. Further, we have developed our own custom manufacturing equipment for certain of our medicines. If we encounter unexpected performance issues with such equipment, we could encounter delays or interruptions to clinical and commercial supply. Due to the number of different programs, we may have cross contamination of investigational medicines inside of our factories, CROs, suppliers or in the clinic that affect the integrity of our investigational medicines. As we scale the manufacturing output for commercial production and particular programs, we plan to continuously improve yield, purity and the pharmaceutical properties of our commercial products, development candidates and investigational medicines from IND-enabling studies through commercial launch, including shelf life stability, and solubility properties of drug product and drug substance. Because of continuous improvement in manufacturing processes, we may switch processes for a particular program during development. However, after a change in process, more time will be required for pharmaceutical property testing, such as 6 or 12 month stability testing. That may require resupplying clinical material or making additional cGMP batches to keep up with clinical trial demand before such pharmaceutical property testing is completed. We are utilizing a number of raw materials and excipients that have a single source of supply, are new to the pharmaceutical industry and are being employed in a novel manner. Some of these raw materials and excipients have not been scaled to a level to support commercial supply and could experience unexpected manufacturing or testing failures or supply shortages. Such issues with raw materials and excipients could cause delays or interruptions to clinical and commercial supply of our investigational medicines. We have established a number of analytical assays, and may have to establish several more, to assess the quality of our mRNA investigational medicines. We may identify gaps in our analytical testing strategy that might prevent release of product or could require product withdrawal or recall. For example, we may discover new impurities that have an impact on product safety, efficacy or stability. This may lead to an inability to release mRNA investigational medicines until the manufacturing or testing process is rectified. **Current (2024):** The manufacturing processes for our mRNA medicines are novel and complex. We and our collaborators have experienced and may continue to encounter difficulties in manufacturing, product release, shelf life, testing, storage, supply chain management or shipping, including delays as our supply chain expands and grows more complex. We could experience issues resulting from complexities of producing batches at larger scale, equipment failure, human error, choice and quality of raw materials and excipients, analytical testing technology and product instability. Further, mRNA medicines encapsulated in LNPs must be developed and manufactured under well-controlled conditions, or pharmacological activity can be adversely impacted. In an effort to optimize product features, we have in the past and may in the future make changes to our product candidates in their manufacturing and stability formulation and conditions. This has in the past and may in the future result in our having to resupply 55 55 55 55 55 55 batches for preclinical or clinical activities when there is insufficient product stability during storage and insufficient supply. Insufficient stability or shelf life of our product candidates could materially delay our or our strategic collaborators' ability to continue clinical trials or require us to begin a new clinical trial with a newly formulated drug product, due to the need to manufacture additional preclinical or clinical supply. Our high rate of innovation causes a high degree of technology change that can negatively impact product comparability during and after clinical development. Furthermore, technology changes may drive the need for changes in, modification to, or the sourcing of new manufacturing infrastructure or may adversely affect third-party relationships. In many cases, we may need to utilize multiple batches of drug substance and drug product to meet the supply requirement of a single preclinical study or clinical trial. Failure in our ability to scale up batch size or failure in any batch, which we have experienced in the past, may lead to a substantial delay in our clinical trials or in the commercialization of any approved product. For example, the changes we make as we continue developing new manufacturing processes for our drug substance and drug product may impact specification and stability of the drug product, and may lead to failure of batches, resulting in a substantial delay in delivery of commercial product or conduct of our clinical trials. Our mRNA product candidates may prove to have a stability profile that leads to a lower than desired shelf life of the final approved medicine. This poses risk in supply requirements, wasted stock and higher cost of goods. We are dependent on a number of equipment providers who are also implementing novel technology. Further, we have developed our own custom manufacturing equipment for certain of our medicines. If we encounter unexpected performance issues with such equipment, we could encounter delays or interruptions to clinical and commercial supply. Due to the number of different programs, we may have cross contamination of product candidates inside of our factories, CROs, suppliers or in the clinic that affect the integrity of our product candidates. As we scale the manufacturing output for commercial production and particular programs, we plan to continuously improve yield, purity and the pharmaceutical properties of our products and product candidates from IND-enabling studies through commercial launch, including shelf-life stability, and solubility properties of drug product and drug substance. Because of continuous improvement in manufacturing processes, we may switch processes for a particular program during development. However, after a change in process, more time will be required for pharmaceutical property testing, such as 6 or 12 month stability testing. That may require resupplying clinical material or making additional cGMP batches to keep up with clinical trial demand before such pharmaceutical property testing is completed. We are utilizing a number of raw materials and excipients that have a single source of supply, are new to the pharmaceutical industry and are being employed in a novel manner. Some of these raw materials and excipients have not been scaled to a level to support commercial supply and could experience unexpected manufacturing or testing failures or supply shortages. Such issues with raw materials and excipients could cause delays or interruptions to clinical and commercial supply of our products or product candidates. We have established several analytical assays and may have to establish several more to assess the quality of our mRNA product candidates. We may identify gaps in our analytical testing strategy that might prevent release of product or could require product withdrawal or recall. For example, we may discover new impurities that have an impact on product safety, efficacy or stability. This may lead to an inability to release mRNA product candidates until the manufacturing or testing process is rectified. --- ## Modified: As we grow as a commercial company and our drug development pipeline increases and matures, the increased demand for clinical and commercial supplies from our facilities and third parties may impact our ability to operate. We rely on third-party service providers, all of whom have inherent risks in their operations. **Key changes:** - Reworded sentence: "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." - Reworded sentence: "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." - Reworded sentence: "If we are unable to institute 56 56 56 56 56 56 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." - Reworded sentence: "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." - Added sentence: "Regulatory authorities 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." **Prior (2023):** We have limited experience at larger scale production necessary to support large-scale clinical trials and commercial sales. Completion of our trials and commercialization of our vaccine 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 are building regional manufacturing capability globally and are subject to risks associated with building and operating in foreign jurisdictions. 70 70 70 70 70 70 Table of Content Table of Content Table of Content 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 assist in meeting our capacity needs. If we cannot enter into such arrangements on favorable terms, or at all, our ability to develop, manufacture and distribute our COVID-19 vaccines and any future 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. In addition, other companies, many with substantial resources, compete with us for access to the materials needed to manufacture our vaccines. 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 investigational medicines. The use of service providers and suppliers could expose us to risks, including: •termination or non-renewal of supply and service agreements with third parties 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 regulatory authorities 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. A third-party manufacturer may also encounter difficulties 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. Any delay or interruption could adversely affect our business, financial condition or results of operations. **Current (2024):** We have limited experience at larger scale production necessary to support large-scale clinical trials and commercial sales. 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 are building regional manufacturing capability globally and are subject to risks associated with building and operating in foreign jurisdictions. 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 56 56 56 56 56 56 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 regulatory authorities 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. Regulatory authorities 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 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. Any delay or interruption could adversely affect our business, financial condition or results of operations. --- ## Modified: We may seek to establish additional strategic alliances and, if we are unable to establish them on commercially reasonable terms, we may have to alter our development and commercialization plans. Certain of our strategic alliance agreements may restrict our ability to develop certain products. **Key changes:** - Reworded sentence: "60 60 60 60 60 60 Our development programs and the potential commercialization of our product candidates will require substantial additional cash to fund expenses." - Reworded sentence: "Those factors may include the design or results of clinical trials, the likelihood of approval by the FDA or similar foreign regulatory authorities, 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." - Reworded sentence: "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." **Prior (2023):** Our development programs and the potential commercialization of our development candidates and investigational medicines will require substantial additional cash to fund expenses. We may collaborate with pharmaceutical and biotechnology companies for the development and potential commercialization of some of our investigational medicines, 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 similar regulatory authorities outside the United States, the potential market for the subject investigational medicine, the costs and complexities of manufacturing and delivering such investigational medicine to trial participants, the potential of competing drugs, the existence of uncertainty with respect to our 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. Any potential strategic collaborator may ultimately collaborate on alternative investigational medicines or technologies for similar indications rather than collaborate with us. We are also restricted under 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 development candidates or investigational medicines. Strategic alliances are complex and time-consuming to negotiate and document. If we cannot negotiate and enter into new strategic alliances on a timely basis, on favorable terms, or at all, we may need to curtail the development of the investigational medicine 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. **Current (2024):** 60 60 60 60 60 60 Our development programs and the potential commercialization of our product candidates will require substantial additional 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 similar foreign regulatory authorities, 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. --- ## Modified: Our reliance on government funding and collaboration from governmental and quasi-governmental entities for certain of our programs adds uncertainty to our research and development efforts with respect to those programs and may impose requirements related to intellectual property rights and requirements that increase the costs of development, commercialization and production of any programs developed under those government-funded programs. **Key changes:** - Removed sentence: "79 79 79 79 79 79 Table of Content Table of Content Table of Content The development of our Zika vaccine (mRNA-1893) is funded by BARDA and our COVID-19 vaccine was developed in collaboration with NIAID." - Removed sentence: "BARDA has agreed to fund the advancement of our COVID-19 vaccine to FDA licensure." - Reworded sentence: "manufacturing requirements for products that embody inventions conceived or first reduced to practice under such agreements; •suspend or debar the contractor or grantee from doing future business with the government; 65 65 65 65 65 65 •control and potentially prohibit the export of products; •pursue criminal or civil remedies under the False Claims Act, False Statements Act and similar remedy provisions specific to government agreements; and •limit the government's financial liability to amounts appropriated by the U.S." - Reworded sentence: "government from using certain technologies developed by us and we may be unable to prohibit other companies, including our competitors, from using those technologies in providing products and services to the U.S." - Added sentence: "In December 2023, the Biden administration released a proposed framework specifying for the first time that price can be a factor in considering whether an invention is sufficiently available to the public." **Prior (2023):** 79 79 79 79 79 79 Table of Content Table of Content Table of Content The development of our Zika vaccine (mRNA-1893) is funded by BARDA and our COVID-19 vaccine was developed in collaboration with NIAID. BARDA has agreed to fund the advancement of our COVID-19 vaccine to FDA licensure. Contracts and grants funded by the U.S. government and its agencies, including our agreements funded by BARDA and DARPA and our collaboration with NIAID, include provisions that reflect the government's substantial rights and remedies, many of which are not typically found in commercial contracts, including powers of the government to: •terminate agreements, in whole or in part, for any reason or no reason; •reduce or modify the government's obligations under such agreements without the consent of the other party; •claim rights, including IP rights, in products and data developed under such agreements; •audit contract-related costs and fees, including allocated indirect costs; •suspend the contractor or grantee from receiving new contracts pending resolution of alleged violations of procurement laws or regulations; •impose U.S. manufacturing requirements for products that embody inventions conceived or first reduced to practice under such agreements; •suspend or debar the contractor or grantee from doing future business with the government; •control and potentially prohibit the export of products; •pursue criminal or civil remedies under the False Claims Act, False Statements Act and similar remedy provisions specific to government agreements; and •limit the government's financial liability to amounts appropriated by the U.S. Congress on a fiscal-year basis, thereby leaving some uncertainty about the future availability of funding for a program even after it has been funded for an initial period. We may not have the right to prohibit the U.S. government from using certain technologies developed by us and we may not be able to prohibit third-party companies, including our competitors, from using those technologies in providing products and services to the U.S. government. The U.S. government generally takes the position that it has the right to royalty-free use of technologies that are developed under U.S. government contracts. In addition, government contracts and grants, and subcontracts and subawards awarded in the performance of those contracts and grants, normally contain additional requirements that may increase our costs of doing business, reduce our profits and expose us to liability for failure to comply with these terms and conditions. These requirements include, for example: •specialized accounting systems unique to government contracts and grants; •mandatory financial audits and potential liability for price adjustments or recoupment of government funds after such funds have been spent; •public disclosures of certain contract and grant information, which may enable competitors to gain insights into our research program; and •mandatory socioeconomic compliance requirements, including labor standards, non-discrimination, and affirmative action programs and environmental compliance requirements. Further, under these agreements we are subject to the obligations to and the rights of the U.S. government set forth in the Bayh-Dole Act of 1980 (Bayh-Dole Act). As a result, the U.S. government may have rights in certain inventions developed under these government-funded programs, including a non-exclusive, non-transferable, irrevocable worldwide license to use inventions for any governmental purpose. In addition, the U.S. government has the right to require us to grant exclusive, partially exclusive or nonexclusive licenses to any of these inventions to a third party if it determines that: (i) adequate steps have not been taken to commercialize the invention; (ii) government action is necessary to meet public health or safety needs; or (iii) government action is necessary to meet requirements for public use under federal regulations, also referred to as "march-in rights." Any exercise of the march-in rights by the U.S. government could harm our competitive position, business, financial condition, results of operations and prospects. If the U.S. government exercises such march-in rights, we may receive compensation that is deemed reasonable by the U.S. government in its sole discretion, which may be less than what we might be able to obtain in the open market. IP generated under a government-funded program is also subject to certain reporting requirements, compliance with which may require us to expend substantial resources. In addition, the U.S. government requires that any products embodying any invention generated through the use of U.S. government-funding be manufactured substantially in the United States. The manufacturing preference requirement can be waived if the owner of the IP can show that it made reasonable but unsuccessful efforts to grant licenses on similar terms to potential licensees that would be likely to manufacture substantially in the United States or that under the circumstances domestic manufacture is not commercially feasible. This preference for U.S. manufacturers may limit our ability to contract with non-U.S. manufacturers for products covered by such IP. As an organization, we are relatively new to government contracting and the related regulatory compliance obligations. If we fail to maintain compliance with those obligations, we may be subject to potential liability and to termination of our contracts. 80 80 80 80 80 80 Table of Content Table of Content Table of Content As a U.S. government contractor, we are subject to financial audits and other reviews by the U.S. government of our costs and performance on their contracts, as well as our accounting and general business practices related to these contracts. Based on the results of its audits, the government may adjust our contract-related costs and fees, including allocated indirect costs. We cannot assure you that future audits and reviews will not have a material adverse impact on our financial condition or results of operations. **Current (2024):** Contracts and grants funded by the U.S. government and its agencies, including our agreements funded by BARDA and DARPA and our collaboration with NIAID, include provisions that reflect the government's substantial rights and remedies, many of which are not typically found in commercial contracts, including powers of the government to: •terminate agreements, in whole or in part, for any reason or no reason; •reduce or modify the government's obligations under such agreements without the consent of the other party; •claim rights, including IP rights, in products and data developed under such agreements; •audit contract-related costs and fees, including allocated indirect costs; •suspend the contractor or grantee from receiving new contracts pending resolution of alleged violations of procurement laws or regulations; •impose U.S. manufacturing requirements for products that embody inventions conceived or first reduced to practice under such agreements; •suspend or debar the contractor or grantee from doing future business with the government; 65 65 65 65 65 65 •control and potentially prohibit the export of products; •pursue criminal or civil remedies under the False Claims Act, False Statements Act and similar remedy provisions specific to government agreements; and •limit the government's financial liability to amounts appropriated by the U.S. Congress on a fiscal-year basis, thereby leaving some uncertainty about the future availability of funding for a program even after it has been funded for an initial period. We may not have the right to prohibit the U.S. government from using certain technologies developed by us and we may be unable to prohibit other companies, including our competitors, from using those technologies in providing products and services to the U.S. government. The U.S. government generally takes the position that it has the right to royalty-free use of technologies that are developed under U.S. government contracts. In addition, government contracts and grants, and subcontracts and subawards awarded in the performance of those contracts and grants, normally contain additional requirements that may increase our costs of doing business, reduce our profits and expose us to liability for failure to comply with these terms and conditions. These requirements include, for example: •specialized accounting systems unique to government contracts and grants; •mandatory financial audits and potential liability for price adjustments or recoupment of government funds after such funds have been spent; •public disclosures of certain contract and grant information, which may enable competitors to gain insights into our research program; and •mandatory socioeconomic compliance requirements, including labor standards, non-discrimination, and affirmative action programs and environmental compliance requirements. Further, under these agreements we are subject to the obligations to and the rights of the U.S. government set forth in the Bayh-Dole Act of 1980 (Bayh-Dole Act). As a result, the U.S. government may have rights in certain inventions developed under these government-funded programs, including a non-exclusive, non-transferable, irrevocable worldwide license to use inventions for any governmental purpose. In addition, the U.S. government has the right to require us to grant exclusive, partially exclusive or nonexclusive licenses to any of these inventions to a third party if it determines that: (i) adequate steps have not been taken to commercialize the invention; (ii) government action is necessary to meet public health or safety needs; or (iii) government action is necessary to meet requirements for public use under federal regulations, also referred to as "march-in rights." Any exercise of the march-in rights by the U.S. government could harm our competitive position, business, financial condition, results of operations and prospects. In December 2023, the Biden administration released a proposed framework specifying for the first time that price can be a factor in considering whether an invention is sufficiently available to the public. The proposed framework could potentially enable march-in rights to be used as a tool to regulate drug pricing. The potential inclusion of price as a factor in a march-in determination is expected to draw extensive criticism and challenge, and the ultimate impact is currently unknown. If the U.S. government exercises such march-in rights, we may receive compensation that is deemed reasonable by the U.S. government in its sole discretion, which may be less than what we might be able to obtain in the open market. IP generated under a government-funded program is also subject to certain reporting requirements, compliance with which may require us to expend substantial resources. As an organization, we are relatively new to government contracting and the related regulatory compliance obligations. If we fail to maintain compliance with those obligations, we may be subject to potential liability and to termination of our contracts. --- ## Modified: Clinical development is lengthy and uncertain, and our clinical programs may be delayed or terminated, or may be more costly to conduct than we anticipate. **Key changes:** - Reworded sentence: "Most product candidates that commence clinical trials are never approved as products." - Removed sentence: "Further, the assays used to estimate the effectiveness of our COVID-19 vaccines continue to evolve." - Removed sentence: "Validation reports for these assays have been submitted for review to regulatory agencies." - Removed sentence: "Results obtained in clinical trials of our COVID-19 vaccines with later versions of these assays may be less positive than the results observed to date." - Reworded sentence: "Significant preclinical or nonclinical testing and studies or clinical trial delays for our product candidates could allow our competitors to bring products to market before we do and could harm our business, financial condition and prospects significantly." **Prior (2023):** Clinical testing is expensive, complex and lengthy, and its outcome is inherently uncertain. Most investigational medicines that commence clinical trials are never approved as products. We may be unable to initiate, may experience delays in or may have to discontinue clinical trials for our investigational medicines. We and our strategic collaborators also may experience unforeseen events during, or as a result of, any clinical trials that we or they conduct that could delay or prevent us or them from successfully developing our investigational medicines and gaining approval from regulators. Events that might prevent us from proceeding with clinical trials could include: •regulators, Institutional Review Boards (IRBs) or ethics committees may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial at a prospective trial site; •we may experience delays in reaching, or fail to reach, agreement on favorable terms with prospective trial sites and prospective contract research organizations (CROs); •changes to the scale or site of our manufacturing could cause significant delays or changes in our clinical trial designs; 63 63 63 63 63 63 Table of Content Table of Content Table of Content •the outcome of our preclinical studies and our early clinical trials may not be predictive of the success of later clinical trials, and interim results of a clinical trial do not necessarily predict final results; •we may be unable to establish or achieve clinically meaningful endpoints for our studies; •if we make changes to our investigational medicines after clinical trials have commenced (which we have done in the past), we may be required to repeat earlier stages or delay later stages of clinical testing; •clinical trials of any investigational medicines may fail to show safety or efficacy, or may produce negative or inconclusive results, and we may decide, or regulators may require us, to conduct additional nonclinical studies or clinical trials, or we may decide to abandon product development programs; •our investigational medicines, or other medicines in the same class as ours, may have undesirable side effects, such as the immunogenicity of the LNPs or their components, the immunogenicity of the protein made by the mRNA or degradation products, any of which could lead to serious adverse events, or other effects; •administration of our LNPs could lead to systemic side effects related to the components of the LNPs and could contribute to immune reactions, infusion reactions, complement reactions, opsonization reactions, antibody reactions or reactions to PEG-lipids; •significant adverse events or other side effects could be observed in our clinical trials, including those involving dosing young, human subjects; •our third-party contractors may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all, or may deviate from the applicable clinical trial protocol or withdraw from the applicable clinical trial, which may require that we add new clinical trial sites; •regulators may impose a complete or partial clinical hold on a clinical trial, or we or our investigators, IRBs or ethics committees may suspend or terminate clinical research or trials for various reasons, including noncompliance with regulatory requirements or a finding that participants are being exposed to an unacceptable benefit-risk ratio; •regulators may impose a complete or partial clinical hold on clinical trials of other companies working on mRNA medicines; •the cost of preclinical or nonclinical testing and studies and clinical trials of any investigational medicines may be greater than we anticipate; •the supply or quality of our investigational medicines or other materials necessary to conduct clinical trials may be insufficient or inadequate; •safety and efficacy concerns regarding our investigational medicines will be considered by us and by the FDA and other global regulators as we pursue clinical trials of new investigational medicines, develop effective informed consent documentation and work with IRBs and scientific review committees (SRCs); •safety or efficacy concerns could arise from nonclinical or clinical testing of other therapies targeting a similar disease state or other therapies, such as gene therapy, that are perceived as similar to ours; •adverse side effects could be observed in future clinical trials where our investigational medicines are administered in combination with other therapies (such as the co-administration of our PCV investigational medicine, mRNA-4157); and •a lack of adequate funding to continue a particular clinical trial. Before commencing later-stage clinical trials for our programs, we must develop assays to measure and predict the potency of a given dose of our investigational medicines. Any delay in developing assays that are acceptable to the FDA or other regulators could delay the start of future clinical trials. Further, the assays used to estimate the effectiveness of our COVID-19 vaccines continue to evolve. Validation reports for these assays have been submitted for review to regulatory agencies. Results obtained in clinical trials of our COVID-19 vaccines with later versions of these assays may be less positive than the results observed to date. Additionally, we have conducted and may conduct in the future "open-label" clinical trials, where both the patient and investigator know whether the patient is receiving the investigational product candidate, an approved drug or a placebo. The results from an open-label clinical trial may not be predictive of future clinical trial results from a controlled environment with a placebo or active control. Further, the FDA or other regulators may change the requirements for approval even after they have reviewed and commented on the design for our clinical trials. Significant preclinical or nonclinical testing and studies or clinical trial delays for our investigational medicines could allow our competitors to bring products to market before we do and could harm our business, financial condition and prospects significantly. **Current (2024):** Clinical testing is expensive, complex and lengthy, and its outcome is inherently uncertain. Most product candidates that commence clinical trials are never approved as products. We may be unable to initiate, may experience delays in or may have to discontinue clinical trials for our product candidates. We and our strategic collaborators also may experience unforeseen events during, or as a result of, any clinical trials that we or they conduct that could delay or prevent us or them from successfully developing our product candidates and gaining approval from regulators. Events that might prevent us from proceeding with clinical trials could include: •regulators, Institutional Review Boards (IRBs) or ethics committees may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial at a prospective trial site; •we may experience delays in reaching, or fail to reach, agreement on favorable terms with prospective trial sites and prospective contract research organizations (CROs); •changes to the scale or site of our manufacturing could cause significant delays or changes in our clinical trial designs; •the outcome of our preclinical studies and our early clinical trials may not be predictive of the success of later clinical trials, and interim results of a clinical trial do not necessarily predict final results; •we may be unable to establish or achieve clinically meaningful endpoints for our studies; •if we make changes to our product candidates after clinical trials have commenced (which we have done in the past), we may be required to repeat earlier stages or delay later stages of clinical testing; •clinical trials of any product candidates may fail to show safety or efficacy, or may produce negative or inconclusive results, and we may decide, or regulators may require us, to conduct additional nonclinical studies or clinical trials, or we may decide to abandon product development programs; 49 49 49 49 49 49 •our product candidates, or other medicines in the same class as ours, may have undesirable side effects, such as the immunogenicity of the LNPs or their components, the immunogenicity of the protein made by the mRNA or degradation products, any of which could lead to serious adverse events, or other effects; •administration of our LNPs could lead to systemic side effects related to the components of the LNPs and could contribute to immune reactions, infusion reactions, complement reactions, opsonization reactions, antibody reactions or reactions to PEG-lipids; •significant adverse events or other side effects could be observed in our clinical trials; •our third-party contractors may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all, or may deviate from the applicable clinical trial protocol or withdraw from the applicable clinical trial, which may require that we add new clinical trial sites; •regulators may impose a complete or partial clinical hold on a clinical trial, or we or our investigators, IRBs or ethics committees may suspend or terminate clinical research or trials for various reasons, including noncompliance with regulatory requirements or a finding that participants are being exposed to an unacceptable benefit-risk ratio; •regulators may impose a complete or partial clinical hold on clinical trials of other companies working on mRNA medicines; •the cost of preclinical or nonclinical testing and studies and clinical trials of product candidates may be greater than anticipated; •the supply or quality of our product candidates or other materials necessary to conduct clinical trials may be insufficient or inadequate; •safety and efficacy concerns regarding our product candidates will be considered by us and by the FDA and other regulators as we pursue clinical trials of new product candidates, develop effective informed consent documentation and work with IRBs and scientific review committees (SRCs); •safety or efficacy concerns could arise from nonclinical or clinical testing of other therapies targeting a similar disease state or other therapies, such as gene therapy, that are perceived as similar to ours; •adverse side effects could be observed in future clinical trials where our product candidates are administered in combination with other therapies (such as the co-administration of our INT product candidate, mRNA-4157); and •a lack of adequate funding to continue a particular clinical trial. Before commencing later-stage clinical trials for our programs, we must develop assays to measure and predict the potency of a given dose of our product candidates. Any delay in developing assays that are acceptable to the FDA or other regulators could delay the start of future clinical trials. Additionally, we have conducted and may conduct in the future "open-label" clinical trials, where both the patient and investigator know whether the patient is receiving the investigational product candidate, an approved drug or a placebo. The results from an open-label clinical trial may not be predictive of future clinical trial results from a controlled environment with a placebo or active control. Further, the FDA or other regulators may change the requirements for approval even after they have reviewed and commented on the design for our clinical trials. Significant preclinical or nonclinical testing and studies or clinical trial delays for our product candidates could allow our competitors to bring products to market before we do and could harm our business, financial condition and prospects significantly. --- ## Modified: mRNA drug development has substantial clinical development and regulatory risks due to the novel nature of this new class of medicines, and the negative perception of the efficacy, safety or tolerability profile of any product candidates that we or others develop could adversely affect our ability to conduct our business, advance our product candidates or obtain regulatory approvals. **Key changes:** - Reworded sentence: "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." - Reworded sentence: "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." - Reworded sentence: "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." - Reworded sentence: "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 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 52 52 52 52 52 52 •the proprietary rights of others and their competing products and technologies that may prevent our mRNA medicines from being commercialized." **Prior (2023):** COVID-19 vaccines are the only mRNA medicines that have been authorized or approved to date by the FDA or other regulators, and efficacy, safety and immunogenicity data with respect to our COVID-19 vaccines, as well as real-world evidence, continue to accumulate. Further results from clinical trials, as well as the experience of vaccinated individuals, could show diminished protection compared to the results released to date. Additionally, we may observe new, more frequent or more severe adverse events in subjects participating in ongoing clinical trials or individuals vaccinated with our COVID-19 vaccines. For example, some studies have suggested that our COVID-19 vaccine may be associated with higher rates of myocarditis and pericarditis in young males compared to other COVID-19 vaccines. Unexpected safety issues could significantly damage our reputation and that of our mRNA platform, and 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 cause delays in obtaining regulatory authorizations. For example, in October 2021, the FDA requested that we explore a lower dosage for our COVID-19 vaccine in adolescents, which extended the length of clinical trials in this population prior to receiving regulatory authorization. These factors could delay or prevent us from receiving full regulatory approval of our COVID-19 vaccines in certain jurisdictions or for certain demographics. Successful discovery and development of mRNA medicines by us or our strategic collaborators is highly uncertain and depends on numerous factors, many of which are 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 mRNA investigational medicines 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; •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 investigational medicines 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 investigational medicines and development candidates may have a dependent or independent effect on safety, tolerability and efficacy, which may be species-dependent; •manufacturing failures or insufficient supply of 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 investigational medicines and development 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 development candidates and investigational medicines 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; 66 66 66 66 66 66 Table of Content Table of Content Table of Content •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. **Current (2024):** 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 our COVID-19 vaccine. For example, some studies have suggested that our COVID-19 vaccine may be associated with higher rates of myocarditis and pericarditis in young males compared to other COVID-19 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 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-19 vaccine in adolescents, which extended the length of clinical trials in this population prior to receiving regulatory authorization. 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 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 52 52 52 52 52 52 •the proprietary rights of others and their competing products and technologies that may prevent our mRNA medicines from being commercialized. --- ## Modified: The price of our common stock has been volatile, which could result in substantial losses for stockholders. **Key changes:** - Reworded sentence: "Our stock price has been, and is expected to continue to be, subject to substantial volatility." - Reworded sentence: "Public statements by us, government agencies, the media, competitors, financial analysts or others relating to COVID-19 have resulted, and may result, in significant fluctuations in our stock price." - Reworded sentence: "The market price for our common stock may be influenced by many factors, including: •our COVID-19 vaccine sales and anticipated product revenue; •the commercial launch of any additional products; •timing and results of clinical trials or progress of our product candidates or those of our competitors; •the success of competitive products or technologies; •the emergence or decline of new or existing variants of the SARS-CoV-2 virus; •developments regarding our manufacturing, regulatory and commercialization efforts, or information regarding such efforts by competitors; •regulatory or legal developments in the United States and other countries; •developments or disputes concerning patent applications, issued patents or other proprietary rights; •the recruitment or departure of key personnel; •expenses related to any of our products or clinical development programs; •the results of our efforts to discover, develop, acquire or in-license additional product candidates; •actual or anticipated changes in estimates of financial results, development timelines or recommendations by securities analysts; •variations in our financial results or those of companies that are perceived to be similar to us; •changes in the structure of healthcare payment systems; •economic, industry and market conditions generally, and in the biopharmaceutical sector specifically; and •announcement by us or our competitors of the commencement or termination of significant acquisitions, strategic partnerships, joint ventures or capital commitments." **Prior (2023):** 89 89 89 89 89 89 Table of Content Table of Content Table of Content Our stock price has been, and is expected to continue to be, subject to substantial volatility. From December 7, 2018, our first day of public trading, through December 31, 2022, our stock price has ranged from a high of $497.49 to a low of $11.54 per share. Since we began our COVID-19 vaccine development efforts in early 2020, our stock has experienced pronounced and extended periods of volatility, which could cause our stockholders to incur substantial losses. Public statements by us, government agencies, the media, competitors, financial analysts or others relating to the COVID-19 pandemic and efforts to combat it have resulted, and may result, in significant fluctuations in our stock price. Information in the public arena on this topic, whether or not accurate, has had and will likely continue to have an outsized impact (positive or negative) on our stock price. The stock market in general, and the market for biopharmaceutical companies in particular, has experienced extreme volatility that has often been unrelated to the operating performance of particular companies, and you may not be able to sell your shares at or above your initial purchase price. The market price for our common stock may be influenced by many factors, including: •the success of our COVID-19 vaccine sales and anticipated product revenue; •the commercial launch of any additional products; •timing and results of clinical trials or progress of our investigational medicines or those of our competitors; •the success of competitive products or technologies, particularly vaccines or treatments for COVID-19; •the emergence or decline of new or existing variants of the SARS-CoV-2 virus; •developments regarding our manufacturing, regulatory and commercialization efforts, or information regarding such efforts by competitors; •regulatory or legal developments in the United States and other countries; •developments or disputes concerning patent applications, issued patents or other proprietary rights; •the recruitment or departure of key personnel; •expenses related to any of our products, investigational medicines or clinical development programs; •the results of our efforts to discover, develop, acquire or in-license additional investigational medicines; •actual or anticipated changes in estimates of financial results, development timelines or recommendations by securities analysts; •variations in our financial results or those of companies that are perceived to be similar to us; •changes in the structure of healthcare payment systems; •market conditions in the pharmaceutical and biotechnology sectors; •economic, industry and market conditions generally, and in the biopharmaceutical sector specifically; •the numerous programs in our pipeline, the development of which could each generate news or significant adverse events that could impact financial results or recommendations by securities analysts; and •announcement by us or our competitors of the commencement or termination of significant acquisitions, strategic partnerships, joint ventures or capital commitments. Securities class-action litigation often has been instituted against companies following periods of volatility in their stock price. If such litigation were instituted against us, we could incur substantial costs in defense and management's attention and resources could be diverted, which could adversely affect our business, financial condition and results of operations and prospects. **Current (2024):** Our stock price has been, and is expected to continue to be, subject to substantial volatility. Since our IPO in December 2018, our stock price has ranged from a high of $497.49 to a low of $11.54 per share. Since we began our COVID-19 vaccine development efforts in early 2020, our stock has experienced pronounced and extended periods of volatility, which could cause our stockholders to incur substantial losses. Public statements by us, government agencies, the media, competitors, financial analysts or others relating to COVID-19 have resulted, and may result, in significant fluctuations in our stock price. Information in the public arena on this topic, whether or not accurate, has had and will likely continue to have an outsized impact (positive or negative) on our stock price. The stock market in general, and the market for biopharmaceutical companies in particular, has experienced extreme volatility that has often been unrelated to the operating performance of particular companies, and you may not be able to sell your shares at or above your initial purchase price. The market price for our common stock may be influenced by many factors, including: •our COVID-19 vaccine sales and anticipated product revenue; •the commercial launch of any additional products; •timing and results of clinical trials or progress of our product candidates or those of our competitors; •the success of competitive products or technologies; •the emergence or decline of new or existing variants of the SARS-CoV-2 virus; •developments regarding our manufacturing, regulatory and commercialization efforts, or information regarding such efforts by competitors; •regulatory or legal developments in the United States and other countries; •developments or disputes concerning patent applications, issued patents or other proprietary rights; •the recruitment or departure of key personnel; •expenses related to any of our products or clinical development programs; •the results of our efforts to discover, develop, acquire or in-license additional product candidates; •actual or anticipated changes in estimates of financial results, development timelines or recommendations by securities analysts; •variations in our financial results or those of companies that are perceived to be similar to us; •changes in the structure of healthcare payment systems; •economic, industry and market conditions generally, and in the biopharmaceutical sector specifically; and •announcement by us or our competitors of the commencement or termination of significant acquisitions, strategic partnerships, joint ventures or capital commitments. Securities class-action litigation often has been instituted against companies following periods of volatility in their stock price. If such litigation were instituted against us, we could incur substantial costs in defense and management's attention and resources could be diverted, which could adversely affect our business, financial condition and results of operations and prospects. 76 76 76 76 76 76 --- ## Modified: Our business could be harmed if we suffer damage to our reputation, including as a result of a product recall. **Key changes:** - Reworded sentence: "The FDA or foreign regulators could require the recall of our products." - Reworded sentence: "Our reputation could be further impacted by public discourse regarding our business and perception of our business strategy." **Prior (2023):** The FDA and similar foreign regulators could require the recall of our commercial products. In the case of the FDA, the authority to require a recall of a biologic product must be based on an FDA finding that a batch, lot or other quantity of the biologic product presents an imminent or substantial hazard to the public health. In addition, foreign governmental bodies may require the recall of any investigational medicine in the event of material deficiencies or defects in design or manufacture. Manufacturers may, under their own initiative, recall a product if any material deficiency in a product is found. A government-mandated or voluntary recall by us or our strategic collaborators could occur as a result of manufacturing errors, design or labeling defects or other deficiencies and issues, as occurred with the recall of certain batches of our COVID-19 vaccine shipped to Japan that were found to contain foreign particulate. Recalls of any of our products would divert managerial and financial resources and adversely affect our financial condition and results of operations. A recall announcement could harm our reputation and negatively affect our sales. Our reputation could be further impacted by public discourse regarding our business and the perception of our business strategy. **Current (2024):** The FDA or foreign regulators could require the recall of our products. The FDA has authority to recall a biologic product if it finds that a batch, lot or other quantity of the biologic product presents an imminent or substantial hazard to the public health. In addition, foreign governmental bodies may require the recall of any products in the event of material deficiencies or defects in design or manufacture. Manufacturers may independently recall a product if a material deficiency in a product is found. A government-mandated or voluntary recall by us or our strategic collaborators could occur as a result of manufacturing errors, design or labeling defects or other deficiencies and issues, as occurred with the recall in 2021 of certain batches of our COVID-19 vaccine shipped to Japan that were found to contain foreign particulate. Recalls of any of our products would divert managerial and financial resources and adversely affect our financial condition and results of operations. A recall announcement could harm our reputation and negatively affect our sales. Our reputation could be further impacted by public discourse regarding our business and perception of our business strategy. 70 70 70 70 70 70 --- ## Modified: If we cannot maintain our corporate culture, we could lose the innovation, teamwork and passion that we believe contribute to our success. **Key changes:** - Removed sentence: "83 83 83 83 83 83 Table of Content Table of Content Table of Content" **Prior (2023):** We invest substantial time and resources in building and maintaining our culture and developing our personnel; however, as we continue to expand, it may be increasingly difficult to maintain our culture. The dramatic growth of our workforce, coupled with recent shifts in workplace and workstyle, increase the risk of our ability to maintain culture. Any failure to preserve our culture could negatively affect our future success, including our ability to retain and recruit personnel and to effectively pursue our strategic plans. 83 83 83 83 83 83 Table of Content Table of Content Table of Content **Current (2024):** We invest substantial time and resources in building and maintaining our culture and developing our personnel; however, as we continue to expand, it may be increasingly difficult to maintain our culture. The dramatic growth of our workforce, coupled with recent shifts in workplace and workstyle, increase the risk of our ability to maintain culture. Any failure to preserve our culture could negatively affect our future success, including our ability to retain and recruit personnel and to effectively pursue our strategic plans. --- ## Modified: The commercial success of our products will depend on the degree of market acceptance by physicians, patients, third-party payors and others in the medical community. **Key changes:** - Reworded sentence: "The degree of market acceptance of our products will depend on numerous factors, including: •the potential efficacy and advantages over alternative treatments; 47 47 47 47 47 47 •the ability to offer products at competitive prices; •the duration of protection provided by our products compared to those of 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; •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 (e.g., for single-dose presentations, or combination vaccines); •publicity concerning our products or competing products and treatments; 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." **Prior (2023):** The commercial success of our products will depend in part on the medical community, patients and third-party or governmental payors accepting mRNA medicines, and our products in particular, as medically useful, cost-effective and safe. The degree of market acceptance of our investigational medicines will depend on numerous factors, including: •the potential efficacy and advantages over alternative treatments; •the ability to offer products at competitive prices; •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; •publicity concerning our products or competing products and treatments; 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 preclinical studies and clinical trials, market acceptance of the product 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, especially due to the complexity of our programs, and may never be successful. **Current (2024):** The commercial success of our products will depend in part on the medical community, patients and third-party or governmental payors accepting mRNA medicines, and our products in particular, as medically useful, cost-effective and safe. The degree of market acceptance of our products will depend on numerous factors, including: •the potential efficacy and advantages over alternative treatments; 47 47 47 47 47 47 •the ability to offer products at competitive prices; •the duration of protection provided by our products compared to those of 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; •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 (e.g., for single-dose presentations, or combination vaccines); •publicity concerning our products or competing products and treatments; 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, especially due to the complexity of our programs, and may never be successful. --- ## Modified: Changes in U.S. patent and regulatory law could impair our ability to protect our products. **Key changes:** - Reworded sentence: "patent law continues to evolve, and certain U.S." - Reworded sentence: "Congress, the federal courts and the USPTO, the laws and regulations governing patents could change in unpredictable ways that would weaken our ability to obtain new patents or to enforce our existing patents and patents that we might obtain in the future." **Prior (2023):** Our success is heavily dependent on IP, particularly patents. Obtaining and enforcing patents in the biotechnology industry involve both technological and legal complexity, and the process is costly, time-consuming and inherently uncertain. In addition, the United States has enacted and is implementing wide-ranging patent reform legislation. Recent U.S. Supreme Court rulings have narrowed the scope of patent protection available in certain circumstances and weakened the rights of patent owners in certain situations. These rulings have increased uncertainty with regard to our ability to obtain patents in the future, as well as with respect to the value of patents, once obtained. Depending on decisions by the U.S. Congress, the federal courts, and the USPTO, the laws and regulations governing patents could change in unpredictable ways that would weaken our ability to obtain new patents or to enforce our existing patents and patents that we might obtain in the future. See " - Risks related to our pipeline, product development and regulatory review - Our investigational medicines may face competition from biosimilars approved through an abbreviated regulatory pathway." **Current (2024):** Our success is heavily dependent on IP, particularly patents. U.S. patent law continues to evolve, and certain U.S. Supreme Court rulings have narrowed the scope of patent protection available in certain circumstances and weakened the rights of patent owners in certain situations. These rulings have increased uncertainty with regard to our ability to obtain patents in the future, as well as with respect to the value of patents, once obtained. Depending on decisions by the U.S. Congress, the federal courts and the USPTO, the laws and regulations governing patents could change in unpredictable ways that would weaken our ability to obtain new patents or to enforce our existing patents and patents that we might obtain in the future. --- ## Modified: If we cannot obtain, or are delayed in obtaining, required regulatory approvals, we will be unable to commercialize, or will be delayed in commercializing, product candidates we may develop. **Key changes:** - Reworded sentence: "To obtain required regulatory approvals to commercialize any product candidate, we and our strategic collaborators must demonstrate through extensive preclinical studies and clinical trials that our products are safe, pure and potent in humans, including the target population." - Reworded sentence: "Although we expect to submit BLAs for our mRNA product candidates in the United States, other jurisdictions may consider our mRNA product candidates to be new drugs, not biologics, and require different marketing approval applications." - Reworded sentence: "In addition, varying interpretations of the data obtained from preclinical and clinical testing could delay, limit or prevent marketing approval of a product candidate." - Reworded sentence: "The FDA and other foreign regulators review the CMC section of regulatory filings." - Reworded sentence: "Any negative findings by regulatory agencies and failure to comply with requirements may lead to delay in approval and failure to commercialize the product candidate." **Prior (2023):** Any mRNA medicine we may develop and the activities associated with its development and commercialization are subject to comprehensive regulation by the FDA and comparable foreign regulators. To obtain required regulatory approvals to commercialize any of our investigational medicines, we and our strategic collaborators must demonstrate through extensive preclinical studies and clinical trials that our products are safe, pure and potent in humans, including the target population. Successful completion of clinical trials is a prerequisite to submitting a BLA to the FDA, a marketing authorization application (MAA) to the EMA, and similar marketing applications to comparable foreign regulators, for each investigational medicine and, consequently, the ultimate approval and commercial marketing of any investigational medicines. To date, we have only received regulatory authorizations for our COVID-19 vaccines, and our current or future investigational medicines may never obtain regulatory approval. We have limited experience in filing and supporting the necessary applications for marketing approvals and may need to rely on third parties to assist us in this process. Although we expect to submit BLAs for our mRNA investigational medicines in the United States, other jurisdictions may consider our mRNA investigational medicines to be new drugs, not biologics, and require different marketing approval applications. Preclinical studies and clinical trials conducted in one country may not be accepted by regulatory authorities in other countries, and approval in one country does not guarantee regulatory approval in another. Additionally, the process of obtaining marketing approvals, both in the United States and abroad, is expensive, time-consuming and uncertain, and can vary substantially based upon a variety of factors, including the type, complexity and novelty of the investigational medicines involved. Changes in marketing approval policies during the development period, changes in law or changes in regulatory review may delay the review of a submitted product application. The FDA and comparable foreign regulators have substantial discretion in the approval process and may refuse to accept any marketing approval application or may decide that our data are insufficient for marketing approval and require additional preclinical, clinical or other studies. In addition, varying interpretations of the data obtained from preclinical and clinical testing could delay, limit or prevent marketing approval of an investigational medicine. Additional delays or non-approval may result if an FDA Advisory Committee or other regulatory authority recommends non-approval or restrictions on approval. 68 68 68 68 68 68 Table of Content Table of Content Table of Content The FDA and other foreign regulators review the CMC section of regulatory filings. Any aspects found unsatisfactory by regulatory agencies may result in delays in clinical trials and commercialization. In addition, the regulatory agencies conduct pre-approval inspections at the time of a BLA. Any negative findings by regulatory agencies and failure to comply with requirements may lead to delay in approval and failure to commercialize the potential investigational medicine. If we experience delays in obtaining regulatory approval or if we fail to obtain regulatory approval of any investigational medicines we may develop, the commercial prospects for those investigational medicines will be harmed, and our ability to generate revenues will be materially impaired. **Current (2024):** Any mRNA medicine we may develop and the activities associated with its development and commercialization are subject to comprehensive regulation by the FDA and comparable foreign regulators. To obtain required regulatory approvals to commercialize any product candidate, we and our strategic collaborators must demonstrate through extensive preclinical studies and clinical trials that our products are safe, pure and potent in humans, including the target population. Successful completion of clinical trials is a prerequisite to submitting a BLA to the FDA, a marketing authorization application (MAA) to the EMA, and similar marketing applications to comparable foreign regulators, for each product candidate and, consequently, the ultimate approval and commercial marketing of any product. To date, we have only received regulatory authorizations for our COVID-19 vaccine, and our current or future product candidates may never obtain regulatory approval. We have limited experience in filing and supporting the necessary applications for marketing approvals and may need to rely on third parties to assist us in this process. Although we expect to submit BLAs for our mRNA product candidates in the United States, other jurisdictions may consider our mRNA product candidates to be new drugs, not biologics, and require different marketing approval applications. Preclinical studies and clinical trials conducted in one country may not be accepted by regulatory authorities elsewhere, and approval in one country does not guarantee regulatory approval in another. Additionally, the process of obtaining marketing approvals, both in the United States and abroad, is expensive, time-consuming and uncertain, and can vary substantially based upon a variety of factors, including the type, complexity and novelty of the product candidates involved. Changes in marketing approval policies during the development period, changes in law or changes in regulatory review may delay the review of a submitted product application. The FDA and comparable foreign regulators have substantial discretion in the approval process and may refuse to accept any marketing approval application or may decide that our data are insufficient for marketing approval and require additional preclinical, clinical or other studies. In addition, varying interpretations of the data obtained from preclinical and clinical testing could delay, limit or prevent marketing approval of a product candidate. Additional delays or non-approval may result if an FDA Advisory Committee or other regulatory authority recommends non-approval or restrictions on approval. The FDA and other foreign regulators review the CMC section of regulatory filings. Any aspects found unsatisfactory by regulatory agencies may result in delays in clinical trials and commercialization. In addition, the regulatory agencies conduct pre-approval inspections at the time of a BLA. Any negative findings by regulatory agencies and failure to comply with requirements may lead to delay in approval and failure to commercialize the product candidate. If we experience delays in obtaining, or fail to obtain, regulatory approval of any product candidate we develop, the commercial prospects for such product candidate would be harmed, and our ability to generate revenues will be materially impaired. --- ## Modified: If we are not successful in discovering, developing and commercializing additional products, our ability to expand our business and achieve our strategic objectives would be impaired. **Key changes:** - Reworded sentence: "Identifying new product candidates requires substantial technical, financial and human resources." **Prior (2023):** A key element of our strategy is to discover, develop and commercialize products beyond our current portfolio to treat various conditions and in a variety of therapeutic areas. We intend to do so by investing in our drug discovery efforts, exploring potential strategic alliances for the development of new products and in-licensing technologies. Identifying new investigational medicines requires substantial technical, financial and human resources. We may fail to identify promising investigational medicines and, even if we do identify such medicines, we may fail to successfully develop and commercialize products for many reasons, which would impair our potential for growth. 84 84 84 84 84 84 Table of Content Table of Content Table of Content **Current (2024):** A key element of our strategy is to discover, develop and commercialize products beyond our current portfolio to treat various conditions and in a variety of therapeutic areas. We intend to do so by investing in our drug discovery efforts, exploring potential strategic alliances for the development of new products and in-licensing technologies. Identifying new product candidates requires substantial technical, financial and human resources. We may fail to identify promising candidates or to successfully develop and commercialize products for many reasons, which would impair our potential for growth. --- ## Modified: Changes in tax law could adversely affect our business and financial condition. **Key changes:** - Removed sentence: "92 92 92 92 92 92 Table of Content Table of Content Table of Content" **Prior (2023):** 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 stockholders. 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. 92 92 92 92 92 92 Table of Content Table of Content Table of Content **Current (2024):** 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 stockholders. 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. --- ## Modified: Our INT product candidates are uniquely manufactured for each patient using a novel, complex manufacturing process and we may encounter difficulties in production. **Key changes:** - Reworded sentence: "We custom design and manufacture INTs that are unique and tailored specifically for each patient." **Prior (2023):** We custom design and manufacture PCVs that are unique and tailored specifically for each patient. Manufacturing unique lots of PCVs is susceptible to product loss or failure due to issues with: •logistics associated with the collection of a patient's tumor, blood or other tissue sample; •shipping such samples to a facility for genetic sequencing; •next generation sequencing of the tumor mRNA; •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 investigational medicine, 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 vaccine. We have built and installed custom manufacturing equipment for PCVs that has been incorporated into a personalized vaccine unit in the MTC. 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 the clinical trial. Additionally, as we prepare for a potential Phase 3 trial for our PCV candidate, we anticipate an increase in manufacturing demand that will require significant additional 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 would take considerable time to scale up our facilities or build new facilities to meet any commercial demand if our PCV product is approved. This expansion or addition of new facilities could also lead to product comparability issues, which could further delay introduction of new capacity. Because our PCVs 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 PCV is developed through early-stage clinical trials to later-stage 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 PCVs to perform differently than we expect, potentially affecting the results of clinical trials. **Current (2024):** We custom design and manufacture INTs that are unique and tailored specifically for each patient. Manufacturing unique lots of INTs is susceptible to product loss or failure due to issues with: •logistics associated with the collection of a patient's tumor, blood or other tissue sample; •shipping such samples to a facility for genetic sequencing; •next-generation sequencing of the tumor mRNA; •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. --- ## Modified: Unfavorable U.S. or global economic conditions, including as a result of disease outbreak, war, conflict or other political instability, or geopolitical risks, could adversely affect our business, financial condition or results of operations. **Key changes:** - Reworded sentence: "Our results of operations could be adversely affected by general conditions in the global economy and financial markets, including disruptions caused by pandemic, war, conflict or other political instability, including Russia's invasion of Ukraine and resulting sanctions against Russia or conflict in the Middle East." - Reworded sentence: "Any severe or prolonged economic downturn could create a variety of risks to our business, including weakened demand for our medicines, and negatively impacting our ability to raise additional capital or financing when needed on favorable terms, if at all." - Reworded sentence: "Any of the foregoing could harm our business and we cannot anticipate all the ways in which the current economic climate and financial market conditions could adversely impact our business." **Prior (2023):** Our results of operations could be adversely affected by general conditions in the global economy and financial markets, including disruptions caused by the COVID-19 pandemic or any other health epidemic, war, conflict or other political instability, including Russia's invasion of Ukraine and resulting sanctions against Russia. Adverse macroeconomic conditions, and perceptions or expectations about current or future conditions, such as inflation, slowing growth, rising interest rates, rising unemployment and recession, could negatively affect our business and financial condition. Additionally, global events, including war, conflict, political instability or other adverse economic conditions have and may in the future cause governments to divert spending away from healthcare, negatively impacting the marketability of our products. The most recent global financial crisis caused extreme volatility and disruptions in the capital and credit markets. A similar severe or prolonged economic downturn could create a variety of risks to our business, including weakened demand for our medicines, and negatively impacting our ability to raise additional capital when needed on favorable terms, if at all. A weak or declining economy could strain our suppliers, possibly resulting in supply disruption, or cause delays in payments for our services by third-party payors or our collaborators. Any of the foregoing could harm our business and we cannot anticipate all of the ways in which the current economic climate and financial market conditions could adversely impact our business. **Current (2024):** Our results of operations could be adversely affected by general conditions in the global economy and financial markets, including disruptions caused by pandemic, war, conflict or other political instability, including Russia's invasion of Ukraine and resulting sanctions against Russia or conflict in the Middle East. Adverse macroeconomic conditions, and perceptions or expectations about current or future conditions, such as inflation, slowing growth, rising interest rates, rising unemployment and recession, could negatively affect our business and financial condition. Additionally, global events, including war, conflict, political instability or other adverse economic conditions have and may in the future cause governments to divert spending away from healthcare, negatively impacting the marketability of our products. Any severe or prolonged economic downturn could create a variety of risks to our business, including weakened demand for our medicines, and negatively impacting our ability to raise additional capital or financing when needed on favorable terms, if at all. A weak or declining economy could strain our suppliers, possibly resulting in supply disruption, or cause delays in payments for our services by third-party payors or our collaborators. Any of the foregoing could harm our business and we cannot anticipate all the ways in which the current economic climate and financial market conditions could adversely impact our business. Additionally, geopolitical tensions could adversely impact our business and our commercial plans. For instance, restrictions by the U.S. government on the export of mRNA technology or our products to certain markets, or restrictions on the establishment of manufacturing in certain foreign jurisdictions, may prevent us from seeking commercial growth opportunities in a manner that harms our competitive position. 78 78 78 78 78 78 --- ## Modified: The pharmaceutical market is intensely competitive, and we may not compete effectively in the market for existing products, new treatment methods and new technologies. **Key changes:** - Reworded sentence: "The pharmaceutical market is intensely competitive and evolving." - Reworded sentence: "The actual or perceived success or failure of others may adversely impact our ability to commercialize our products." - Reworded sentence: "Our RSV vaccine, which we expect to launch beginning in 2024, will also face competition from existing RSV vaccines." **Prior (2023):** The pharmaceutical market is intensely competitive and rapidly changing. Many companies, academic institutions, governmental agencies and public and private research organizations are pursuing the development of products for the same diseases that we are targeting or expect to target and many of these institutions and competitors have: •greater resources and experience than we have at every stage of the discovery, development, testing, approval, manufacturing and commercialization of products; •multiple products that have been approved or are in late stages of development; and •arrangements in our target markets with purchasers, leading companies and research institutions. We face intense competition with respect to our COVID-19 vaccines, which may not continue to compete favorably with existing or future vaccines and treatments. Many COVID-19 vaccines have been authorized in various jurisdictions, including the mRNA COVID-19 vaccine produced by Pfizer/BioNTech. These vaccines and other treatments, such as Pfizer's antiviral pill, may prove to be safer, more effective, more convenient, have fewer side effects, be easier to ship or distribute or able to be developed at a lower cost than our vaccines. Even if our products demonstrate superiority to those of competitors, consumers and the public may fail to appreciate that benefit. These factors, or the perception of these factors, could lead to a competitor's vaccine or treatment being more successfully commercialized, and we may be unable to compete effectively for future sales of our COVID-19 vaccines. 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 other entities may adversely impact our ability to commercialize our COVID-19 vaccines and future products. We also will face competition from products that have already been approved and accepted by the medical community for the treatment of certain conditions we target. 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 also may compete with products that are under development for the treatment of conditions we target, and these other products may be more effective, safer, less expensive or marketed and sold more effectively. If we successfully develop and obtain approval for investigational medicines, we will face competition based on many factors, including the safety and effectiveness of our products relative to any alternative therapies; the ease with which our products can be administered 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, marketing, and sales capabilities; the price of any approved medicine; reimbursement coverage; and patent position. If our competitors are more successful in commercializing their products than we are, our competitive position and business would be adversely affected. Competitive products may make any products we develop obsolete or noncompetitive before we can recover the expenses of developing and commercializing our products, if approved. **Current (2024):** The pharmaceutical market is intensely competitive and evolving. Many companies, academic institutions, governmental agencies and public and private research organizations are developing products for the same diseases that we are targeting or expect to target and such other parties may have: •greater resources and experience than us at every stage of drug discovery, development, testing, approval, manufacturing and commercialization; •multiple products that have been approved or are in late stages of development; and •arrangements in our target markets with purchasers, governments, leading companies and research institutions. We face intense competition with respect to our COVID-19 vaccine, and it may not continue to compete favorably with existing or future vaccines and treatments. Other vaccines or treatments could prove to be safer, more effective, more convenient, have fewer side effects, be easier to ship or distribute or able to be developed at a lower cost than our vaccine. Even if our products demonstrate superiority to those of competitors, consumers 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 vaccine or treatment 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 also will face competition from products that have already been approved and accepted by the medical community to treat certain conditions we target. 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. Our RSV vaccine, which we expect to launch beginning in 2024, will also face competition from existing RSV vaccines. In markets that we enter after competitors have already introduced a competing product, we may have difficulty achieving market share. Further, we may need to offer more favorable terms to gain market share in an existing market or to compete in a new market, which may negatively impact our profitability. If we successfully develop and obtain approval for other product candidates, we may compete with products under development by competitors based on many factors, including the relative safety and effectiveness of our products, the ease with which our products can be administered 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, marketing and sales capabilities, price, reimbursement coverage and patent position. Our competitors may be more successful in commercializing their products, which would adversely affect our business. Competitive products may make any products we develop obsolete or noncompetitive before we can recover the expenses of developing and commercializing our products, if approved. --- ## Modified: Our products and product candidates are sensitive to shipping and storage conditions, which, in some cases, requires cold-chain logistics and subjects them to risk of loss or damage. **Key changes:** - Reworded sentence: "Our products and product candidates are sensitive to temperature, storage and handling conditions, and we could lose medicines if the product or product intermediates are not stored or handled properly." **Prior (2023):** Our COVID-19 vaccines and investigational medicines are sensitive to temperature, storage and handling conditions, and we could lose medicines if the product or product intermediates are not stored or handled properly. Shelf life for our products and investigational medicines is variable, and our investigational medicines may expire prior to use. Cold-chain logistics are required for certain of our investigational medicines and our COVID-19 vaccines. If we or third-party distributors do not maintain effective cold-chain supply logistics, then we may experience returned or out of date products and product may be rendered unusable. This has led and could lead to additional manufacturing costs and delays in our ability to supply required quantities for clinical trials or commercial sale. In addition, the cost associated with such transportation services and the limited pool of vendors could cause supply disruptions. **Current (2024):** Our products and product candidates are sensitive to temperature, storage and handling conditions, and we could lose medicines if the product or product intermediates are not stored or handled properly. Shelf life for our products and product candidates is variable, and they may expire prior to use. Cold-chain logistics are required for certain of our products and product candidates. If we or third-party distributors do not maintain effective cold-chain supply logistics, then we may experience returned or out of date products and product may be rendered unusable. This has led and could lead to additional manufacturing costs and delays in our ability to supply required quantities for clinical trials or commercial sale. In addition, the cost associated with such transportation services and the limited pool of vendors could cause supply disruptions. --- ## Modified: We have entered into, and in the future may enter into, strategic alliances with third parties for the development and commercialization of products and product candidates. If these strategic alliances are not successful, our business could be adversely affected. **Key changes:** - Reworded sentence: "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." **Prior (2023):** We have entered into strategic alliances with collaborators that have provided, and may in the future provide, funding and other resources for developing, manufacturing and commercializing our investigational medicines. Additionally, we have entered into, and expect to enter into future, strategic alliances where we agree to provide funding 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; •the clinical trials conducted as part of such strategic alliance may not be successful; •strategic collaborators may not pursue development and commercialization of any investigational medicines that achieve regulatory approval or may elect not to continue or renew development or commercialization of programs based on clinical trial results, changes in the strategic collaborators' focus or available funding or external factors, such as an acquisition, that divert resources or create competing priorities; •strategic collaborators may delay clinical trials, provide insufficient funding for clinical trials, stop a clinical trial, abandon an investigational medicine, repeat or conduct new clinical trials or require a new formulation of an investigational medicine for clinical testing; •strategic collaborators could develop, independently or with third parties, products that compete with our products or investigational medicines if such collaborators believe that competitive products are more likely to be successfully developed or can be commercialized on more economically attractive terms than ours; •products or investigational medicines developed in strategic alliances with us may be viewed by our collaborators as competitive with their own investigational medicines or products, which may cause them to cease to devote resources to development or commercialization; •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 investigational medicines, may cause delays or termination of the research, development or commercialization of such investigational medicines, lead to additional responsibilities for us with respect to such investigational medicines or result in litigation or arbitration, any of which would be time-consuming and expensive; •strategic collaborators may not properly maintain or defend our IP rights or 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 stockholders or disrupt our management and business; 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 for convenience, which has happened in the past. If any collaboration agreement is terminated, we may not receive future research funding or milestone, earn-out royalty or other contingent payments and the development of our investigational medicines may be delayed. It may also be difficult to attract new strategic collaborators to continue development or commercialization of the applicable investigational medicine, and the perception of us in the business and financial communities could be adversely affected. All of the risks relating to product development, regulatory approval and commercialization described in this Annual Report on Form 10-K apply to the activities of our strategic collaborators. 74 74 74 74 74 74 Table of Content Table of Content Table of Content **Current (2024):** 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 expect to enter into future, 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 not pursue development and commercialization of any products that achieve regulatory approval or may elect not to continue or renew development or commercialization of programs based on clinical trial results, changes in the strategic collaborators' focus or available funding or external factors that divert resources or create competing priorities; •strategic collaborators may delay clinical trials, provide insufficient funding or resources for clinical trials (whether as a result of a business decision or necessitated by financial difficulties of such collaborator), stop a clinical trial, abandon a product candidate or repeat or conduct new clinical trials; •products or product candidates developed in strategic alliances with us may be viewed by our collaborators as competitive with their own products or product candidates, which may cause them to cease to devote resources to development or commercialization; •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 stockholders 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. --- ## Modified: We are dependent on single-source suppliers for some of the components and materials used in, and the processes required to develop, our products and product candidates. **Key changes:** - Reworded sentence: "We depend on single-source suppliers for some of the components and materials used in, and manufacturing processes required to develop and commercialize, our products and product candidates." - Reworded sentence: "If we have to switch suppliers, the manufacture and delivery of our products or product candidates could be interrupted for an extended period." **Prior (2023):** 73 73 73 73 73 73 Table of Content Table of Content Table of Content We depend on single-source suppliers for some of the components and materials used in, and manufacturing processes required to develop and commercialize, our COVID-19 vaccines, development candidates and investigational medicines. We cannot ensure that these suppliers will remain in business, have sufficient capacity or supply to meet our needs, or that they will not be purchased by one of our competitors or another company that will cease working with us. Our use of single-source suppliers exposes us to several risks, including disruptions in supply, price increases or late deliveries. Any disruption in supply could lead to supply delays or interruptions that would damage our business, financial condition, results of operations and prospects. There are, in general, few alternative sources of supply for substitute components. If we have to switch to a replacement supplier, the manufacture and delivery of our products, development candidates or investigational medicines could be interrupted for an extended period. Establishing additional or replacement suppliers for any of the components or processes used in our products or investigational medicines, if required, may not be accomplished quickly, if at all. Any replacement supplier would need to be qualified and may require additional regulatory authority approval, resulting in further delay. Any interruption or delay in the supply of components or materials, or our inability to obtain components or materials from alternate sources at acceptable prices in a timely manner, could impair our ability to meet the demand for our investigational medicines. Additionally, as part of the FDA's approval of our investigational medicines, the FDA will review the manufacturing processes and facilities of our single-source suppliers. **Current (2024):** We depend on single-source suppliers for some of the components and materials used in, and manufacturing processes required to develop and commercialize, our products and product candidates. We cannot ensure that these suppliers will remain in business, have 59 59 59 59 59 59 sufficient capacity or supply to meet our needs or that they will not be purchased by one of our competitors or another company that will cease working with us. Our use of single-source suppliers exposes us to several risks, including disruptions in supply, price increases, late deliveries or business interruptions. There are, in general, few alternative sources of supply for substitute components. If we have to switch suppliers, the manufacture and delivery of our products or product candidates could be interrupted for an extended period. Establishing additional or replacement suppliers for any of the components or processes used in our products or product candidates, if required, may not be accomplished quickly, if at all. Any replacement supplier (or us, if we produced directly) would need to be qualified and may require additional regulatory authority approval, resulting in further delay. Any interruption or delay in the supply of components or materials, or our inability to obtain components or materials from alternate sources at acceptable prices in a timely manner, could impair our ability to meet the demand for our products or product candidates. Additionally, as part of the FDA's approval of our product candidates, the FDA will review the manufacturing processes and facilities of our single-source suppliers. --- ## Modified: We may encounter difficulties in managing the development and expansion of our company. **Key changes:** - Reworded sentence: "As of December 31, 2023, we had approximately 5,600 full-time employees in 19 countries, and we may increase our number of employees and the scope of our operations." - Reworded sentence: "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." **Prior (2023):** 81 81 81 81 81 81 Table of Content Table of Content Table of Content As of December 31, 2022, we had approximately 3,900 full-time employees in 17 countries, and we expect to continue to increase our employees and the scope of our operations. To manage this global expansion, we must continue to implement and improve our managerial, operational and financial systems, expand our facilities and recruit and train qualified personnel. 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 construction of the Moderna Science Center in Cambridge, the expansion of our Norwood campus 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 investigational medicines. 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, and we may not be able to implement our business strategy. **Current (2024):** As of December 31, 2023, we had approximately 5,600 full-time employees in 19 countries, and we may increase our number of employees and the scope of our operations. To manage this global expansion, we must continue to implement and improve our managerial, operational and financial systems, expand our facilities and recruit and train qualified personnel. 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, and we may not be able to implement our business strategy. 67 67 67 67 67 67 --- ## Modified: We may use our financial and human capital to pursue a particular research program or product candidate and fail to capitalize on programs that may be more profitable or for which there is a greater likelihood of success. **Key changes:** - Reworded sentence: "We pursue and fund the development of selected research programs or product candidates and may choose to forego or delay pursuit of other opportunities that could later prove to have greater commercial potential." - Reworded sentence: "Additionally, we are increasing our investments in our INT programs." - Reworded sentence: "Our spending on research and development programs for product candidates may not yield commercially viable products." **Prior (2023):** We pursue and fund the development of selected research programs or investigational medicines and may choose to forego or delay pursuit of other opportunities that could later prove to have greater commercial potential. For example, we have focused a significant amount of resources on our COVID-19 vaccines and other respiratory programs, for which preparations are underway for multiple vaccine launches. Additionally, we are increasing our investments in production capacity for our PCV program. Our resource allocation decisions, or our contractual commitments to provide resources to our strategic collaborators, may cause us to fail to capitalize on certain commercial products or profitable market opportunities. Our spending on research and development programs for investigational medicines may not yield commercially viable products. If we do not accurately evaluate the commercial potential or target market for a particular investigational medicine, we may relinquish valuable rights to that investigational medicine through a strategic alliance, licensing or other royalty arrangements in cases where it would have been more advantageous for us to retain sole development and commercialization rights, or we may allocate internal resources to an investigational medicine in a therapeutic area in which it would have been more advantageous to enter into a strategic alliance. **Current (2024):** We pursue and fund the development of selected research programs or product candidates and may choose to forego or delay pursuit of other opportunities that could later prove to have greater commercial potential. For example, we have focused a significant amount of resources on our COVID-19 vaccines and other respiratory programs, for which preparations are underway for multiple vaccine launches. Additionally, we are increasing our investments in our INT programs. Our resource allocation decisions, or our contractual commitments to provide resources to our strategic collaborators, may cause us to fail to capitalize on certain commercial products or profitable market opportunities. Our spending on research and development programs for product candidates may not yield commercially viable products. We may also seek to enter into strategic collaborations or financing arrangements pursuant to which we may relinquish valuable rights to product candidates, including the rights to a portion of future revenues, through a strategic alliance, licensing or other royalty arrangements in cases where it would have been more advantageous for us to retain sole development and commercialization rights. Additionally, we may allocate internal resources to a product candidate in a therapeutic area in which it would have been more advantageous to enter into a strategic alliance. --- ## Modified: Engaging in acquisitions, joint ventures or strategic collaborations may increase our capital requirements, dilute our stockholders and cause us to incur debt or assume contingent liabilities. **Key changes:** - Reworded sentence: "Such transactions and relationships may entail numerous risks, including: •increased operating expenses and cash requirements; •assimilation of operations, IP and products, including difficulties associated with integrating new personnel; •the diversion of management's attention from our existing product programs and initiatives; •the loss of key personnel and uncertainties in our ability to maintain key business relationships; •risks and uncertainties associated with the other party to such a transaction, including the prospects of that party and their existing products or product candidates and regulatory approvals; and •our inability to generate revenue from acquired technology or products sufficient to meet our objectives in undertaking the acquisition or even to offset the associated acquisition and maintenance costs." - Removed sentence: "In the first quarter of 2023, we acquired OriCiro Genomics K.K., a pioneer in cell-free DNA synthesis and amplification technologies." - Removed sentence: "We may fail to recognize the potential benefits of this acquisition or integrating OriCiro's business into our own may prove more difficult or costly than anticipated." **Prior (2023):** We may engage in acquisitions, joint ventures and collaborations, including licensing or acquiring complementary products, IP rights, technologies or businesses. Such transactions and relationships may entail numerous risks, including: •increased operating expenses and cash requirements; •assimilation of operations, IP and products, including difficulties associated with integrating new personnel; •the diversion of management's attention from our existing product programs and initiatives; •the loss of key personnel and uncertainties in our ability to maintain key business relationships; 88 88 88 88 88 88 Table of Content Table of Content Table of Content •risks and uncertainties associated with the other party to such a transaction, including the prospects of that party and their existing products or investigational medicines and regulatory approvals; and •our inability to generate revenue from acquired technology or products sufficient to meet our objectives in undertaking the acquisition or even to offset the associated acquisition and maintenance costs. If we undertake acquisitions, we may utilize cash, issue dilutive securities, assume or incur debt obligations, incur large one-time expenses and acquire intangible assets that could result in significant future amortization expense. Moreover, if we cannot locate suitable acquisition or strategic collaboration opportunities, our ability to grow or obtain access to technology or products that may be important to the development of our business may be impaired. In the first quarter of 2023, we acquired OriCiro Genomics K.K., a pioneer in cell-free DNA synthesis and amplification technologies. We may fail to recognize the potential benefits of this acquisition or integrating OriCiro's business into our own may prove more difficult or costly than anticipated. **Current (2024):** We may engage in acquisitions, joint ventures and collaborations, including licensing or acquiring complementary products, IP rights, technologies or businesses. Such transactions and relationships may entail numerous risks, including: •increased operating expenses and cash requirements; •assimilation of operations, IP and products, including difficulties associated with integrating new personnel; •the diversion of management's attention from our existing product programs and initiatives; •the loss of key personnel and uncertainties in our ability to maintain key business relationships; •risks and uncertainties associated with the other party to such a transaction, including the prospects of that party and their existing products or product candidates and regulatory approvals; and •our inability to generate revenue from acquired technology or products sufficient to meet our objectives in undertaking the acquisition or even to offset the associated acquisition and maintenance costs. 74 74 74 74 74 74 If we undertake acquisitions, we may utilize cash, issue dilutive securities, assume or incur debt obligations, incur large one-time expenses and acquire intangible assets that could result in significant future amortization expense. Moreover, if we cannot locate suitable acquisition or strategic collaboration opportunities, our ability to grow or obtain access to technology or products that may be important to the development of our business may be impaired. --- ## Modified: Sales of pharmaceutical products depend on the availability and extent of reimbursement from third-party payors, and we may be adversely impacted by changes to such reimbursement policies or rules. **Key changes:** - Reworded sentence: "Sales of pharmaceutical products in general depends to a significant extent on adequate coverage, pricing and reimbursement from third-party payors." - Reworded sentence: "For example, it is uncertain whether any combination respiratory vaccine we develop, if approved, would qualify for coverage under Medicare Part B." - Reworded sentence: "This may create the opportunity for third-party cross-border trade or influence our decision whether to sell a product, thus adversely affecting our geographic expansion plans and revenues." - Reworded sentence: "Additional discounts, rebates, coverage or plan changes, restrictions or exclusions as described above could have a material adverse effect on sales of our affected products, particularly our therapeutic products or those that are individualized for a particular patient." - Reworded sentence: "Additionally, target patient populations for some of our product candidates may be small (e.g., for rare genetic diseases) or require individual customization (e.g., for our INTs)." **Prior (2023):** Third-party payor coverage and reimbursement for our COVID-19 vaccines is not currently available and there is no guarantee payors will provide coverage and reimbursement for the vaccine in the future. Even if coverage is provided, we may be unable to establish or maintain pricing sufficient to realize a sufficient return on our investment. While coverage is expected to be provided under Medicare Part B, it is unclear to what extent other payors, including certain federal entitlement programs, such as the Vaccines for Children Program, will provide coverage. Additionally, it is uncertain whether any combination respiratory vaccine we develop, if approved, would qualify for coverage under Medicare Part B. In addition, sales of pharmaceutical products in general depends, to a significant extent, on adequate coverage, pricing and reimbursement from third-party payors. When a new product is approved, the availability and extent of government and private reimbursement, and the pricing, for that product may be uncertain. Pricing and reimbursement for any product we develop may be adversely affected by a number of factors, including: •changes in, and implementation of, federal, state or foreign government regulations or private third-party payors' reimbursement policies; 61 61 61 61 61 61 Table of Content Table of Content Table of Content •pressure by employers on private health insurance plans to reduce costs; and •consolidation and increasing assertiveness of payors seeking price discounts or rebates in connection with the placement of our products on their formularies and, in some cases, the imposition of restrictions on access or coverage of particular drugs or pricing determined based on perceived value. Our ability to set the price for any product we develop will vary significantly from country to country. Our inability to obtain and maintain adequate prices in a particular country may limit the revenues from our products within that country and adversely affect our ability to secure acceptable prices in existing and potential new markets, which may limit market growth. This may create the opportunity for third-party cross-border trade or influence our decision to sell or not to sell a product, thus adversely affecting our geographic expansion plans and revenues. Drug prices are under significant scrutiny in many countries. We expect drug pricing and other health care costs to continue to be subject to intense political and societal pressures on a global basis. Competition may negatively impact our ability to maintain pricing and our market share. New products marketed by competitors could cause our revenues to decrease due to potential price reductions and lower sales volumes. Additionally, the introduction of competing versions of our products or products approved under abbreviated regulatory pathways may reduce the price that we are able to charge for our products and lower our sales volume. Many payors continue to adopt benefit plan changes that shift a greater portion of prescription costs to patients, including more limited benefit plan designs, higher patient co-pay or co-insurance obligations and limitations on patients' use of commercial manufacturer co-pay payment assistance programs. Significant consolidation in the health insurance industry has resulted in a few large insurers and pharmacy benefit managers exerting greater pressure in pricing and usage negotiations with drug manufacturers, significantly increasing discounts and rebates required of manufacturers and limiting patient access and usage. Further consolidation among insurers, pharmacy benefit managers and other payors would increase the negotiating leverage such entities have over us and other drug manufacturers. Additional discounts, rebates, coverage or plan changes, restrictions or exclusions as described above could have a material adverse effect on sales of our affected products. Coverage and reimbursement by a third-party payor may depend upon a number of factors, including the third-party payor's determination that use of a product is a covered benefit under its health plan, safe, effective and medically necessary, appropriate for the specific patient, cost-effective and neither experimental nor investigational. Additionally, target patient populations for some of our investigational medicines, including for rare genetic diseases, may be small, and some of our investigational medicines, like our PCVs, require individual customization. The pricing and reimbursement of our medicines, if approved, must be adequate to support commercial infrastructure. If we cannot obtain adequate levels of reimbursement, we may be unable to successfully market and sell our investigational medicines. The manner and level at which reimbursement is provided for services related to our investigational medicines (e.g., for administration of our product to patients) is also important. Inadequate reimbursement for such services may lead to physician resistance and adversely affect our ability to market or sell our products. **Current (2024):** Sales of pharmaceutical products in general depends to a significant extent on adequate coverage, pricing and reimbursement from third-party payors. When a new product is approved, the availability and extent of government and private reimbursement, and the pricing, for that product may be uncertain. For example, it is uncertain whether any combination respiratory vaccine we develop, if approved, would qualify for coverage under Medicare Part B. Additionally, pricing and reimbursement for any product we develop may be adversely affected by a number of factors, including: •changes in, and implementation of, federal, state or foreign government regulations or private third-party payors' reimbursement policies; •pressure by employers on private health insurance plans to reduce costs; and •consolidation and increasing assertiveness of payors seeking price discounts or rebates in connection with the placement of our products on their formularies and, in some cases, the imposition of restrictions on access or coverage of particular drugs or pricing determined based on perceived value. Our ability to set the price for any product we develop will vary significantly by country. Our inability to obtain and maintain adequate prices in a particular country may limit the revenues from our products within that country and adversely affect our ability to secure acceptable prices in existing and potential new markets, which may limit market growth. This may create the opportunity for third-party cross-border trade or influence our decision whether to sell a product, thus adversely affecting our geographic expansion plans and revenues. Many payors continue to adopt benefit plan changes that shift a greater portion of prescription costs to patients, including more limited benefit plan designs, higher patient co-pay or co-insurance obligations and limitations on patients' use of commercial manufacturer co-pay payment assistance programs. Significant consolidation in the health insurance industry has resulted in a few large insurers and pharmacy benefit managers exerting greater pressure in pricing and usage negotiations with drug manufacturers, significantly increasing discounts and rebates required of manufacturers and limiting patient access and usage. Further consolidation among insurers, pharmacy benefit managers and other payors would increase the negotiating leverage such entities have over us and other drug manufacturers. Additional discounts, rebates, coverage or plan changes, restrictions or exclusions as described above could have a material adverse effect on sales of our affected products, particularly our therapeutic products or those that are individualized for a particular patient. Coverage and reimbursement by a third-party payor may depend upon a number of factors, including the third-party payor's determination that use of a product is a covered benefit under its health plan, safe, effective and medically necessary, appropriate for the specific patient, cost-effective and neither experimental nor investigational. Additionally, target patient populations for some of our product candidates may be small (e.g., for rare genetic diseases) or require individual customization (e.g., for our INTs). The pricing and reimbursement of our medicines, if approved, must be adequate to support commercial infrastructure. If we cannot obtain adequate levels of reimbursement, we may be unable to successfully market and sell our products. The manner and level at which reimbursement is provided for services related to our products (e.g., for administration to patients) is also important. Inadequate reimbursement for such services may discourage physicians from prescribing or recommending our products, adversely affecting our ability to market or sell those products. 48 48 48 48 48 48 --- ## Modified: Uncertainty over IP in the pharmaceutical and biotechnology industry has been the source of litigation and other disputes, which is inherently costly and unpredictable and can have adverse financial and freedom-to-operate consequences. **Key changes:** - Reworded sentence: "mRNA medicines are a relatively new scientific field and, as the field continues to mature, patent applications are being processed by national patent offices globally." - Reworded sentence: "Litigation is ongoing over the underlying technology to mRNA medicines between many mRNA market participants." - Reworded sentence: "We cannot be certain that any patent will survive or that the claims will remain in the current form." - Removed sentence: "There are many issued and pending third-party patents that claim aspects of oligonucleotide and delivery technologies that we may need for our mRNA therapeutic and vaccine candidates or marketed products, including our COVID-19 vaccine." - Removed sentence: "There are also many issued third-party patents that claim targeting genes or portions of genes that may be relevant for mRNA medicines we wish to develop." **Prior (2023):** mRNA medicines are a relatively new scientific field and, as the field continues to mature, patent applications are being processed by national patent offices around the world. There is uncertainty about which patents will issue, and, if they do, as to when, to whom and with what claims. Litigation is ongoing over the underlying technology to mRNA vaccines. In addition to our ongoing litigation against Pfizer and BioNTech, CureVac has filed suit against BioNTech, Alnylam Pharmaceuticals has sued Pfizer and us and Acuitas Therapeutics has sued Arbutus Biopharma Corporation and Genevant Sciences. It is likely that there will continue to be significant litigation and other proceedings, such as patent infringement lawsuits, interference, reexamination and opposition proceedings, as well as inter-partes and post-grant-review proceedings introduced by provisions of the America Invents Act, in various patent offices relating to patent rights in the mRNA field. We have issued patents and pending patent applications in the United States and in key markets around the world that claim many different methods, compositions and processes relating to the discovery, development, manufacture and commercialization of mRNA medicines and our delivery technology, including LNPs. An opposition has been filed against one of our European platform patents covering uridine-modified mRNAs, and we expect that further oppositions will be filed in the European Patent Office (EPO) and elsewhere relating to patents and patent applications in our portfolio. In many cases, the possibility of appeal exists for either us or our opponents, and it may be years before final, unappealable rulings are made with respect to these patents in certain jurisdictions. The timing and outcome of these and other proceedings is uncertain and may adversely affect our business if we are not successful in defending the patentability and scope of our pending and issued patent claims. We cannot be certain that such patent will survive or that the claims will remain in the current form. Even if our rights are not directly challenged, disputes could lead to the weakening of our IP rights. There are many issued and pending third-party patents that claim aspects of oligonucleotide and delivery technologies that we may need for our mRNA therapeutic and vaccine candidates or marketed products, including our COVID-19 vaccine. There are also many issued third-party patents that claim targeting genes or portions of genes that may be relevant for mRNA medicines we wish to develop. For example, there are issued and pending patent applications that may be asserted against us in a court proceeding or otherwise based upon the asserting party's belief that we may need such patents for our mRNA therapeutic candidates. Thus, it is possible that one or more organizations hold patent rights to which we may need a license or which could be asserted against us. If those organizations refuse to license such patent rights on reasonable terms or a court rules that we need such patent rights that have been asserted against us and we are not able to obtain a license on reasonable terms, we may owe damages to such party, and may be unable to market products, including our COVID-19 vaccine, covered by such patents. In certain instances, we have instituted and may in the future institute inter partes review proceedings against issued U.S. patents and opposition proceedings against European patents owned by third parties in the field of mRNA medicines. We have a number of these proceedings ongoing against third-party patents related to RNA vaccinations and mRNA delivery. If we are unsuccessful in invalidating such third-party patents, those third parties may attempt to assert those patents against investigational medicines that obtain regulatory approval, including our COVID-19 vaccine. As the biotechnology and pharmaceutical industries expand and more patents are issued, the risk increases that our development candidates may be subject to claims of infringement of the patent rights of third parties. **Current (2024):** mRNA medicines are a relatively new scientific field and, as the field continues to mature, patent applications are being processed by national patent offices globally. There is uncertainty about which patents will issue, and, if they do, as to when, to whom and with what claims. Litigation is ongoing over the underlying technology to mRNA medicines between many mRNA market participants. It is likely that there will continue to be significant litigation and patent office proceedings in various patent offices relating to patent rights in the mRNA field. 62 62 62 62 62 62 We have issued patents and pending patent applications in the United States and in key markets around the world that claim many different methods, compositions and processes relating to the discovery, development, manufacture and commercialization of mRNA medicines and our delivery technology, including LNPs. Oppositions and inter partes review petitions have been filed against some of our patents, and we expect that further proceedings will be filed in the European Patent Office (EPO), USPTO and elsewhere relating to patents and patent applications in our portfolio. In many cases, the possibility of appeal exists for any party, and it may be years before final, unappealable rulings are made with respect to these patents in certain jurisdictions. The timing and outcome of these and other proceedings is uncertain and may adversely affect our business if we are not successful in defending the patentability and scope of our pending and issued patent claims. We cannot be certain that any patent will survive or that the claims will remain in the current form. Even if our rights are not directly challenged, disputes could lead to the weakening of our IP rights. In certain instances, we have instituted and may in the future institute inter partes review proceedings against issued U.S. patents and opposition proceedings against European patents owned by third parties in the field of mRNA medicines. We have a number of these proceedings ongoing against third-party patents. If we are unsuccessful in narrowing or invalidating such third-party patents, those third parties may attempt to assert those patents against our products. As the biotechnology and pharmaceutical industries expand and more patents are issued, the risk increases that our products or product candidates may be subject to claims of infringement of the patent rights of third parties. We have invested billions of dollars in creating our patented mRNA platform, which is integral to the development of our mRNA medicines, and we are involved in various intellectual property litigation as described under Part I, Item 3, "Legal Proceedings." We expect to expend substantial financial and managerial resources in connection with these legal proceedings, and the ultimate outcome of each proceeding is uncertain. --- ## Modified: We may experience delays in enrolling participants in our clinical trials. **Key changes:** - Reworded sentence: "Difficulties or delays in enrolling a sufficient number of clinical trial participants, or those with required or desired characteristics, 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." **Prior (2023):** Enrolling participants in our clinical trials is critical to our success. Difficulties or delays in enrolling a sufficient number of clinical trial participants, or those with required or desired characteristics to achieve diversity in a clinical trial, may result in increased costs or may affect the timing or outcome of our planned clinical trials, which could prevent completion of these clinical trials and adversely affect our ability to advance the development of our investigational medicines and obtain regulatory approval of potential products. We may slow enrollment in a trial to focus on achieving greater diversity in the subject population, as we did in our Phase 3 clinical trial of our COVID-19 vaccine. Participant enrollment is affected by 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, including by third parties or our own 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 investigational medicine being studied in relation to other available therapies, including any new drugs or treatments that may be approved for the indications we are investigating; 65 65 65 65 65 65 Table of Content Table of Content Table of Content •adverse results or other adverse safety signals in our trials or related to other investigational medicines, and the resulting negative publicity, could discourage potential clinical trial participants and their doctors from participating in our trials; •in the case of PCV, the need to wait for the manufacture of the personalized drug product; 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 we have entered into strategic alliances pursuant to which our collaborators control development of certain of our investigational medicines. Even if we or our strategic collaborators are able to enroll clinical trial participants, there is no guarantee that such participants will ultimately be dosed as part of, or complete, a clinical trial. **Current (2024):** Enrolling participants in our clinical trials is critical to our success. Difficulties or delays in enrolling a sufficient number of clinical trial participants, or those with required or desired characteristics, 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. We may slow enrollment in a trial to focus on achieving greater diversity in the subject population, as we did in the Phase 3 clinical trial of our original COVID-19 vaccine. 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. 51 51 51 51 51 51 Additionally, we may have limited or no ability to influence enrollment in clinical trials where we have entered into strategic alliances pursuant to which 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. --- ## Modified: The market opportunities for our products and product candidates may be smaller than we believe, or we may be unable to successfully identify clinical trial participants. **Key changes:** - Reworded sentence: "Additionally, we expect to initially seek approval of our INT and intratumoral immuno-oncology product candidates for use by patients with relapsed or refractory advanced disease, i.e., the populations the FDA often approves new therapies for initially." - Reworded sentence: "The number of trial participants may be lower than expected and potential clinical trial participants or patients may not be otherwise amenable to treatment with our product candidates or products, or new clinical trial participants or patients may become increasingly difficult to identify or gain access to." **Prior (2023):** We focus certain of our research and product development activities on treatments for severe rare genetic diseases, where the patient populations are difficult to ascertain or small. Additionally, we expect to initially seek approval of our PCV and intratumoral immuno-oncology investigational medicines for use by patients with relapsed or refractory advanced disease, i.e., the populations the FDA often approves new therapies for initially. If any such medicines prove to be sufficiently beneficial, we would expect to seek approval in earlier lines of treatment and potentially as a first line therapy. There is no guarantee that our investigational medicines, even if approved, would be approved for earlier lines of therapy, and, prior to any such approvals, we may have to conduct additional clinical trials. Our estimates of the number of people who have these diseases, as well as the subset of those with the potential to benefit from treatment with our medicines, are based on our beliefs, and have been derived from a variety of sources, including scientific literature, surveys of clinics, patient foundations or market research, and may prove to be incorrect. Further, new studies may change the estimated incidence or prevalence of these diseases. The number of trial participants, both in and outside the United States, may be lower than expected and potential clinical trial participants or patients may not be otherwise amenable to treatment with our investigational medicines or products, or new clinical trial participants or patients may become increasingly difficult to identify or gain access to, all of which would adversely affect our results of operations and our business. Even if we obtain significant market share for our products, if approved, because the potential target populations are small, these medicines may never be profitable. **Current (2024):** We focus certain of our research and product development activities on treatments for severe rare genetic diseases, where the patient populations are difficult to ascertain or small. Additionally, we expect to initially seek approval of our INT and intratumoral immuno-oncology product candidates for use by patients with relapsed or refractory advanced disease, i.e., the populations the FDA often approves new therapies for initially. If any such medicines prove to be sufficiently beneficial, we would expect to seek approval in earlier lines of treatment and potentially as a first-line therapy. There is no guarantee that our products, if approved, would be approved for earlier lines of therapy and, prior to any such approvals, we may have to conduct additional clinical trials. Our estimates of addressable patient populations are based on our beliefs, and have been derived from a variety of sources, including scientific literature, surveys of clinics, patient foundations or market research, and may prove to be incorrect. Further, new studies may change the estimated incidence or prevalence of these diseases. The number of trial participants may be lower than expected and potential clinical trial participants or patients may not be otherwise amenable to treatment with our product candidates or products, or new clinical trial participants or patients may become increasingly difficult to identify or gain access to. Even if we obtain significant market share for our products, if approved, because the potential target populations are small, these medicines may never be profitable. --- ## Modified: We are subject to operational risks associated with the physical and digital infrastructure at our manufacturing facilities and those of our external service providers. **Key changes:** - Reworded sentence: "Our manufacturing facilities incorporate a significant level of automation of equipment with integration of several digital systems to improve efficiency of operations." - Reworded sentence: "Our facilities and infrastructure or those of our contract manufacturers or other third-party providers may also be subject to attacks or acts of sabotage by outside actors, contractors or employees." - Reworded sentence: "As we expand our development and commercial capacities, we have and expect that we will continue to establish additional manufacturing capabilities in the United States, as well as in other countries, such as Australia, Canada and the United Kingdom." - Reworded sentence: "If we fail to select suitable locations, complete construction in an efficient manner, engage effectively with local regulators, recruit the required personnel or manage our growth effectively, the development and production of products or our product candidates could be delayed or curtailed." **Prior (2023):** Our MTC facility in Norwood, Massachusetts incorporates a significant level of automation of equipment with integration of several digital systems to improve efficiency of operations. Our high level of digitalization poses risk of process equipment malfunction and even overall manufacturing system failure or shutdown due to internal or external factors including, design issues, system compatibility or potential cybersecurity compromises, incidents or breaches. Upgrades or changes to our systems, infrastructure or the software that we implement, use, or upon which our business relies, may result in the introduction of new cybersecurity vulnerabilities and risks. Our facilities and infrastructure or those of our contract manufacturers or other third-party providers may also be subject to intentional attacks or acts of sabotage by outside actors, contractors or employees. Any disruption in our or our contract manufacturers' manufacturing capabilities could cause delays in production capacity for our drug substances or products or a shutdown of facilities, could impose additional costs, cause us to fail to meet certain product volume or delivery timing obligations, or may require us to identify, qualify and establish an alternative manufacturing site, the occurrence of which could adversely affect our business, financial condition, results of operations, and prospects. As we expand our development and commercial capacities, we have and expect that we will continue to establish additional manufacturing capabilities inside the MTC footprint and that we will expand to other locations and geographies, such as Africa, Australia, Canada and the United Kingdom. This expansion may lead to regulatory delays or prove more costly than anticipated. If we fail to select a suitable location, complete construction in an efficient manner, engage effectively with local regulators, recruit the required personnel or manage our growth effectively, the development and production of commercial products or our investigational medicines could be delayed or curtailed. We will require significant additional investments in our manufacturing processes as we expand the MTC and our other manufacturing infrastructure. 71 71 71 71 71 71 Table of Content Table of Content Table of Content **Current (2024):** Our manufacturing facilities incorporate a significant level of automation of equipment with integration of several digital systems to improve efficiency of operations. The digitization of our facilities exposes us to the risk of process equipment malfunctions. These risks include potential system failures or shutdowns due to internal or external factors including, design issues, system compatibility or potential cybersecurity compromises, incidents or breaches. Upgrades or changes to our systems, infrastructure or the software that we implement, use, or upon which our business relies, may result in the introduction of new cybersecurity vulnerabilities and risks. Our facilities and infrastructure or those of our contract manufacturers or other third-party providers may also be subject to attacks or acts of sabotage by outside actors, contractors or employees. Any disruption in our or our contract manufacturers' manufacturing capabilities could cause delays in production capacity for our drug substances or products or a shutdown of facilities, could impose additional costs, cause us to fail to meet certain product volume or delivery timing obligations, or may require us to identify, qualify and establish an alternative manufacturing site, the occurrence of which could adversely affect our business, financial condition, results of operations, and prospects. As we expand our development and commercial capacities, we have and expect that we will continue to establish additional manufacturing capabilities in the United States, as well as in other countries, such as Australia, Canada and the United Kingdom. This expansion may lead to regulatory delays or prove more costly than anticipated. If we fail to select suitable locations, complete construction in an efficient manner, engage effectively with local regulators, recruit the required personnel or manage our growth effectively, the development and production of products or our product candidates could be delayed or curtailed. We will require significant additional investments in our manufacturing processes as we expand our manufacturing infrastructure. 57 57 57 57 57 57 --- ## Modified: We have limited sales, distribution and marketing experience and may be unable to effectively establish such capabilities or supplement our capabilities by entering into agreements with third parties. **Key changes:** - Reworded sentence: "We have limited experience as a commercial organization and face risks and uncertainties as we shift to an endemic COVID-19 vaccine market and prepare for the commercial launch of other medicines, including our anticipated RSV vaccine launch in 2024." **Prior (2023):** Our commercial organization was only established in 2020 in connection with the launch of our COVID-19 vaccine. Accordingly, we have limited experience with the commercialization of our products, and we face risks and uncertainties as we likely shift to an endemic market for COVID-19 vaccines and as we prepare for the commercial launch of other medicines. We continue to invest in the development of sales, marketing, distribution, managerial and other non-technical capabilities in and out of the United States. 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 will be lower than if we commercialized these products ourselves. In addition, we may have little or no control over the sales efforts of such third parties. 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. **Current (2024):** We have limited experience as a commercial organization and face risks and uncertainties as we shift to an endemic COVID-19 vaccine market and prepare for the commercial launch of other medicines, including our anticipated RSV vaccine launch in 2024. As a result of this limited commercial experience, we may be unsuccessful in accurately anticipating future rates of return for our products, which may adversely impact our accounting estimates. Additionally, 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. 46 46 46 46 46 46 --- ## Modified: Federal legislation and actions by federal, state and local governments may permit reimportation into the United States of drugs from foreign countries where the drugs are sold at lower prices. **Key changes:** - Reworded sentence: "We may face competition in the United States for our products from therapies sourced from foreign countries with price controls on pharmaceutical products." - Reworded sentence: "In January 2024, the FDA approved Florida's request to import certain lower-priced medications from Canada." **Prior (2023):** 85 85 85 85 85 85 Table of Content Table of Content Table of Content We may face competition in the United States for our products from therapies sourced from foreign countries with price controls on pharmaceutical products. For example, in October 2020, the FDA published a final rule that would allow for the importation of certain prescription drugs from Canada, where there are government price controls. Since the issuance of the final rule, several industry groups filed a joint federal lawsuit requesting injunctive relief to prevent the rule from taking effect and challenging multiple aspects of the final rule. This litigation was dismissed in February 2023 for lack of standing, and the market implications of the final rule are currently unknown, but legislation or regulations allowing the reimportation of drugs, if enacted, could decrease the price we receive for any products we may develop and adversely affect our future revenues and potential profitability. **Current (2024):** We may face competition in the United States for our products from therapies sourced from foreign countries with price controls on pharmaceutical products. For example, in October 2020, the FDA published a final rule that would allow for the importation of certain prescription drugs from Canada, where there are government price controls. In January 2024, the FDA approved Florida's request to import certain lower-priced medications from Canada. While the full implications of the final rule are currently unknown, legislation or regulations allowing the reimportation of drugs could decrease the price we receive for any products we may develop and adversely affect our future revenues and potential profitability. 71 71 71 71 71 71 --- ## Modified: We incurred net losses in 2023 and we may incur losses again in the future; we have a limited history of recognizing revenue from product sales and may be unable to achieve long-term sustainable profitability. **Key changes:** - Reworded sentence: "We incurred a net loss of $4.7 billion in 2023, and other than in 2021 and 2022, we have incurred net losses in each year since our inception." - Reworded sentence: "We anticipate that our expenses may increase substantially if and as we: 66 66 66 66 66 66 •expand our research or development of our programs in preclinical development; •initiate additional preclinical, clinical or other studies for our product candidates, particularly large pivotal trials; •continue to invest in our platform to conduct research to identify novel mRNA technology improvements; •change or add to internal manufacturing capabilities, or additional manufacturers or suppliers; •add additional infrastructure to our quality control and quality assurance groups to support our operations as we progress our product candidates toward commercialization; •attract and retain skilled personnel; •create additional infrastructure to support our product development and commercialization efforts, including new sites globally; •seek marketing approvals and reimbursement for our product candidates; •build out a sales, marketing and distribution infrastructure to commercialize any products; •acquire or in-license other product candidates and technologies; •make milestone or other payments under any in-license agreements; and •experience any delays or encounter issues with any of the above." **Prior (2023):** Before 2021, we incurred net losses in each year since our inception. Currently, our COVID-19 vaccines are our only commercial products. While preparations are underway for additional potential product launches, it will be years, if ever, before most of the candidates in our pipeline are ready for commercialization. Our ability to generate revenue and maintain profitability depends on our ability to successfully develop and obtain the regulatory approvals necessary to commercialize our products and investigational medicines. We have incurred, and expect to continue to incur, significant costs associated with commercializing our COVID-19 vaccines and our clinical and preclinical development activities. We may be unable to achieve long-term sustainable profitability and may need additional funding to continue operations. We anticipate that our expenses will increase substantially if and as we: •continue or expand our research or development of our programs in preclinical development; •initiate additional preclinical, clinical or other studies for our development candidates and investigational medicines, including with collaborators; •continue to invest in our platform to conduct research to identify novel mRNA technology improvements, including to identify methods of mRNA delivery, such as improvements to our LNPs; •change or add to internal manufacturing capacity or capability, or additional manufacturers or suppliers; •add additional infrastructure to our quality control and quality assurance groups to support our operations as we progress our investigational medicines toward commercialization; •attract and retain skilled personnel; •create additional infrastructure to support our product development and commercialization efforts, including new sites in the United States and abroad; •seek marketing approvals and reimbursement for our investigational medicines; •establish a sales, marketing and distribution infrastructure to commercialize any products; •acquire or in-license other development candidates, investigational medicines and technologies; •make milestone or other payments under any in-license agreements; and •experience any delays or encounter issues with any of the above. **Current (2024):** We incurred a net loss of $4.7 billion in 2023, and other than in 2021 and 2022, we have incurred net losses in each year since our inception. Currently, our COVID-19 vaccine is our only commercial product. While preparations are underway for additional potential product launches, including our anticipated RSV launch in 2024, the ultimate occurrence and timing of these launches is uncertain. Our ability to generate revenue and maintain 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 COVID-19 vaccine and our clinical and preclinical development activities. In addition, we incurred significant costs in 2023 as we resized our manufacturing capacity. We may be unable to achieve long-term sustainable profitability and may need additional funding to continue operations. We anticipate that our expenses may increase substantially if and as we: 66 66 66 66 66 66 •expand our research or development of our programs in preclinical development; •initiate additional preclinical, clinical or other studies for our product candidates, particularly large pivotal trials; •continue to invest in our platform to conduct research to identify novel mRNA technology improvements; •change or add to internal manufacturing capabilities, or additional manufacturers or suppliers; •add additional infrastructure to our quality control and quality assurance groups to support our operations as we progress our product candidates toward commercialization; •attract and retain skilled personnel; •create additional infrastructure to support our product development and commercialization efforts, including new sites globally; •seek marketing approvals and reimbursement for our product candidates; •build out a sales, marketing and distribution infrastructure to commercialize any products; •acquire or in-license other product candidates and technologies; •make milestone or other payments under any in-license agreements; and •experience any delays or encounter issues with any of the above. --- ## Modified: We could be adversely affected by outbreaks of epidemic, pandemic or other contagious diseases. **Key changes:** - Reworded sentence: "In the event of a future epidemic or pandemic, our clinical trials could be paused or delayed due to restrictions (such as quarantines or travel limitations) or reprioritization of resources." - Reworded sentence: "If these third parties were to experience delays or disruptions in providing their services in response to an epidemic or pandemic, our supply chain could be disrupted, limiting our ability to manufacture and sell our products and manufacture product candidates for our clinical trials, as well as negatively impacting our research and development operations." - Reworded sentence: "Any such action could cause us to experience delays in the development, production, distribution or export of our products and product candidates and increased expenses." **Prior (2023):** Certain of our clinical trials were adversely affected by the COVID-19 pandemic, resulting in paused enrollment or delayed site initiations. In the future, site initiation, participant recruitment and enrollment, participant dosing, distribution of clinical trial materials, study monitoring and data analysis could be paused or delayed due to changes in hospital or university policies, federal, state or local regulations or restrictions, prioritization of hospital resources toward pandemic efforts, travel restrictions, concerns for patient safety in a pandemic environment or other pandemic-related reasons. Future quarantines or travel limitations could impede participant movement, affect sponsor access to study sites or interrupt healthcare services, impairing our ability to conduct clinical trials. Such travel limitations could also create challenges and potential delays in our development and production activities, increasing the expense and timelines for producing our products and development candidates. The COVID-19 pandemic has disrupted and may continue to disrupt the United States' healthcare and healthcare regulatory systems. Such disruptions could divert healthcare resources away from, or materially delay the review or approval by the FDA and other regulatory agencies with respect to our clinical trials or product approvals, which could materially delay our clinical trials for development candidates or our commercial efforts. We utilize third parties to, among other things, manufacture raw materials, components, parts and consumables, perform quality testing and ship our products. Certain of our third-party manufacturers and suppliers have encountered, and may in the future encounter, delays in providing their services in response to an epidemic or pandemic. If we or any third parties in our supply chain are adversely impacted by restrictions resulting from an epidemic or pandemic, our supply chain may be disrupted, limiting our ability to manufacture and sell our products and manufacture investigational medicines for our clinical trials, as well as negatively impacting our research and development operations. In addition, delays and disruptions experienced by our strategic collaborators due to an epidemic or pandemic could adversely impact their ability to fulfill their obligations, which could affect the clinical development or regulatory approvals of development candidates and investigational medicines under joint development. In addition, during a global health crisis, one or more government entities could take actions (such as via the Defense Production Act in the U.S.) that diminish our rights or economic opportunities with respect to our products. Our third-party service providers could be impacted by government-imposed restrictions on services they might otherwise offer. Any such action could cause us to experience delays in the development, production, distribution or export of our products and development candidates and increased expenses. **Current (2024):** In the event of a future epidemic or pandemic, our clinical trials could be paused or delayed due to restrictions (such as quarantines or travel limitations) or reprioritization of resources. Travel limitations could also create challenges and potential delays in our development and production activities, increasing the expense and timelines for producing our products and product candidates. We utilize third parties to, among other things, manufacture raw materials, components, parts and consumables, perform quality testing and ship our products. If these third parties were to experience delays or disruptions in providing their services in response to an epidemic or pandemic, our supply chain could be disrupted, limiting our ability to manufacture and sell our products and manufacture product candidates for our clinical trials, as well as negatively impacting our research and development operations. Such delays or disruptions could adversely impact our strategic collaborators' ability to fulfill their obligations, which could affect the clinical development or regulatory approvals of product candidates under joint development. In addition, during a global health crisis, one or more government entities could take actions (such as via the Defense Production Act in the U.S.) that diminish our rights or economic opportunities with respect to our products. Our third-party service providers could be impacted by government-imposed restrictions on services they might otherwise offer. Any such action could cause us to experience delays in the development, production, distribution or export of our products and product candidates and increased expenses. --- ## Modified: We may be unsuccessful or delayed in updating our COVID-19 vaccine to protect against future variants of the SARS-CoV-2 virus, and updated versions of our COVID-19 vaccine may not protect against such variants. **Key changes:** - Reworded sentence: "As the SARS-CoV-2 virus continues to evolve, new strains of the virus may prove more transmissible or cause more severe forms of COVID-19 than earlier strains." - Reworded sentence: "Additionally, we may expend significant resources adapting our vaccines or conducting clinical trials to protect against variants, but a market for our adapted vaccines may fail to develop or demand may not align with our projections or cost expenditures." **Prior (2023):** Our original COVID-19 vaccine was developed based upon the genetic sequence of the SARS-CoV-2 virus that was first detected in Wuhan, China. As the virus continues to evolve, new strains of the virus, or those that are already in circulation, may prove more transmissible or cause more severe forms of COVID-19 disease than earlier strains. There is a risk that our current COVID-19 vaccines and boosters will be ineffective, or less effective than desired, in protecting against these new variants. Additionally, our decisions regarding booster development may be directed by guidance from the FDA or other foreign regulatory authorities, which may impact the timing of development for our COVID-19 vaccines. For example, we developed mRNA-1273.222 in accordance with FDA guidance from June 2022 to develop a BA.4/BA.5-targeting bivalent COVID-19 vaccine. 60 60 60 60 60 60 Table of Content Table of Content Table of Content In the future, we may not adequately anticipate demand for, or we may experience delays in producing, variant-specific boosters. Further, different regulators may issue differing guidance regarding composition of variant-specific boosters. If our efforts to develop variant-specific vaccines against future variants are unsuccessful, we are slower than competitors to develop such vaccines or our vaccines prove less effective than competitors' vaccines, we could suffer reputational harm, loss of market share and adverse financial results. Additionally, we may expend significant resources adapting our vaccines or conducting clinical trials to protect against COVID-19 variants, but a market for our adapted vaccines fails to develop or demand does not align with our projections or cost expenditures. **Current (2024):** As the SARS-CoV-2 virus continues to evolve, new strains of the virus may prove more transmissible or cause more severe forms of COVID-19 than earlier strains. Our current COVID-19 vaccines could be ineffective, or less effective than desired, in protecting against these new variants. Additionally, our decisions regarding vaccine development will be informed by guidance from the FDA and foreign regulatory authorities, which may impact the timing of development for our COVID-19 vaccines. We may experience delays in producing variant-specific vaccines. Further, different regulators may issue differing guidance regarding vaccine composition or populations who should receive a vaccine. If our efforts to develop variant-specific vaccines against future variants are unsuccessful, we are slower than competitors to develop such vaccines or our vaccines prove less effective than competitors' vaccines, we could suffer reputational harm, loss of market share and adverse financial results. Additionally, we may expend significant resources adapting our vaccines or conducting clinical trials to protect against variants, but a market for our adapted vaccines may fail to develop or demand may not align with our projections or cost expenditures. --- ## Modified: Evolving dynamics in the market for COVID-19 vaccines are likely to impact our financial results, which are likely to result in lower product revenues in 2024 than we have experienced in recent years. **Key changes:** - Reworded sentence: "Through 2023, our only approved product and sole source of product sales has been our COVID-19 vaccine." - Reworded sentence: "Additionally, we may not see demand materialize for our products consistent with our projections." **Prior (2023):** To date, our product sales have consisted of sales of our COVID-19 vaccines to the U.S. Government, other international governments and organizations. We will face many factors that are likely to impact our results as we likely transition to an endemic, commercial market in the United States and globally, including a more fragmented customer base, less predictability in orders, greater seasonality of demand, increased distribution costs, higher costs of goods sold due to single-dose or lower-dose presentations and increased research and development costs, including for clinical trials, when updating our COVID-19 vaccines for new variants of concern. In addition, we will be exposed to market practices that characterize the U.S. private market for vaccines, including practices regarding discounts, rebates and returns, which can result in the realization of significantly lower revenues than list prices. 59 59 59 59 59 59 Table of Content Table of Content Table of Content As we likely shift to an endemic market for COVID-19 vaccines, we have in the past and may in the future experience increased costs associated with exiting commitments with suppliers for raw materials and CMOs. As a result of potentially lower demand, and shifting to a lower dose for boosters than our primary series, we may experience increased costs with raw material suppliers as we seek to exit or modify our purchase commitments. Additionally, decreased overall demand for COVID-19 vaccines, as well as a shift in demand to the fall and winter seasons in each hemisphere, is also likely to result in our need to exit or modify commitments with certain CMOs, which could also result in increased costs. Further, we have entered and may in the future enter into significant non-cancellable or take-or-pay purchase commitments for raw materials that require a long lead time to procure, which increases our commitment exposure. If we cannot effectively manage evolving demand dynamics, our business, financial condition, results of operations and prospects may suffer. Additionally, although we anticipate a decline in demand for COVID-19 vaccines compared to recent years, the medical burden for the likely shift to an endemic COVID-19 and annual booster volumes may not be as large as we currently expect. The market for our vaccines will depend on many evolving factors, such as medical need, viral evolution, public health authority recommendations and consumer motivation to vaccinate. We may be unsuccessful in entering into contracts for the supply of COVID-19 vaccines, and existing contracts may be subject to cancellation or deferrals. **Current (2024):** Through 2023, our only approved product and sole source of product sales has been our COVID-19 vaccine. The global market is transitioning to an endemic, commercial market for COVID-19 vaccine sales, resulting in different market and production dynamics than during the pandemic, including a more fragmented customer base, less predictability in orders, greater seasonality of demand, increased distribution costs, and higher costs of goods sold. Furthermore, our assumptions regarding the product presentation that will be accepted or preferred by the market (e.g., single-dose presentation), which could vary by market, may prove incorrect. 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. We recognized $6.7 billion of sales for COVID-19 vaccines delivered in 2023, compared to $18.4 billion in 2022 and $17.7 billion in 2021, as demand for COVID-19 vaccines declined. We anticipate that sales of COVID-19 vaccines are likely to be lower in 2024 than 2023. We expect the market for COVID-19 vaccines to evolve based on a number of factors, including medical need, viral evolution, public health authority recommendations and consumer motivation to vaccinate. In the third quarter of 2023, we significantly resized our manufacturing infrastructure as we shifted to an endemic COVID-19 vaccine market, and we may in the future incur additional costs associated with exiting commitments with suppliers for raw materials and contract manufacturing organization (CMOs). As a result of lower demand, 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. If we cannot effectively manage evolving demand dynamics, our business, financial condition, results of operations and prospects may suffer. Additionally, we may not see demand materialize for our products consistent with our projections. This may lead to lower than expected commercial sales or requests to defer, renegotiate or cancel existing contracts. Further, we may find that we need to dedicate greater resources to our commercial efforts than anticipated, and we may not realize a return on this investment. --- *Data sourced from SEC EDGAR. Last updated 2026-05-10.*