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What changed in Generation Bio Co.'s 10-K — 2023 vs 2024

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Paragraph-level year-over-year comparison of Generation Bio Co.'s 2023 and 2024 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2024 report.

+648 added−697 removedSource: 10-K (2025-03-13) vs 10-K (2024-03-06)

Top changes in Generation Bio Co.'s 2024 10-K

648 paragraphs added · 697 removed · 413 edited across 8 sections

Item 1. Business

Business — how the company describes what it does

155 edited+120 added−146 removed278 unchanged
Biggest changeAny U.S. or foreign patents issued from the pending licensed U.S. or foreign patent applications would be scheduled to expire in March 2037, without taking into account any possible patent term adjustments or extensions and assuming payment of all appropriate maintenance, renewal, annuity and other governmental fees.
Biggest changeAny U.S. or foreign patents issued from the pending U.S. or foreign non-provisional patent applications or from non-provisional applications we may file in connection with the pending provisional patent applications would be scheduled to expire on various dates from 2038 through 2044, without taking into account any possible patent term adjustments or extensions and assuming payment of all appropriate maintenance, renewal, annuity and other governmental fees. ceDNA and iqDNA manufacturing processes As of December 31, 2024, we owned approximately five patent families (four of which cover technologies related to our proprietary cell-free rapid enzymatic synthesis, or RES, to produce ceDNA and iqDNA and one of which specifically covers iqDNA manufacturing combined with RES), including one pending PCT patent application and four PCT applications that have entered the national stage in the United States and a number of jurisdictions outside the United States.
This assessment is also informed by other factors, including: the severity of the underlying condition and how well patients’ medical needs are addressed by currently available therapies; uncertainty about how the premarket clinical trial evidence will extrapolate to real-world use of the product in the post-market setting; and whether risk management tools are necessary to manage specific risks.
This assessment is also informed by other factors, including: the severity of the underlying condition and how well patients’ medical needs are addressed by currently available therapies; uncertainty about how the premarket clinical trial evidence will extrapolate to real-world use of the product in the post-market setting; and whether risk management tools are necessary to manage specific risks.
Patent term restoration cannot be used to extend the remaining term of a patent past a total of 14 years from the product’s approval date in the United States.
Patent term restoration cannot be used to extend the remaining term of a patent past a total of 14 years from the product’s approval date in the United States.
Restrictions under applicable federal and state healthcare laws and regulations, include the federal Anti-Kickback Statute, which prohibits, among other things, persons and entities from knowingly and willfully soliciting, offering, paying, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward either the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made, in whole or in part, under a federal healthcare program such as Medicare and Medicaid; the federal civil and criminal false claims laws, including the civil False Claims Act, and civil monetary penalties laws, which prohibit individuals or entities 42 Table of Contents from, among other things, knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false, fictitious or fraudulent or knowingly making, using or causing to made or used a false record or statement to avoid, decrease or conceal an obligation to pay money to the federal government; the Foreign Corrupt Practices Act, or FCPA, which prohibits companies and their intermediaries from making, or offering or promising to make, improper payments to non-U.S. officials for the purpose of obtaining or retaining business or otherwise seeking favorable treatment; and the federal transparency requirements known as the federal Physician Payments Sunshine Act, which requires certain manufacturers of drugs, devices, biologics and medical supplies to report annually to the Centers for Medicare & Medicaid Services, or CMS, within the United States Department of Health and Human Services, information related to payments and other transfers of value made by that entity to physicians and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members.
Restrictions under applicable federal and state healthcare laws and regulations, include the federal Anti-Kickback Statute, which prohibits, among other things, persons and entities from knowingly and willfully soliciting, offering, paying, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward either the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made, in whole or in part, under a federal healthcare program such as Medicare and Medicaid; the federal civil and criminal false claims laws, including the civil False Claims Act, and civil monetary penalties laws, which prohibit individuals or entities from, among other things, knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false, fictitious or fraudulent or knowingly making, using or causing to made or used a false record or statement to avoid, decrease or conceal an obligation to pay money to the federal government; the Foreign Corrupt Practices Act, or FCPA, which prohibits companies and their intermediaries from making, or offering or promising to make, improper payments to non-U.S. officials for the purpose of obtaining or retaining business or otherwise seeking favorable treatment; and the federal transparency requirements known as the federal Physician Payments Sunshine Act, which requires certain manufacturers of drugs, devices, biologics and medical supplies to report annually to the Centers for Medicare & Medicaid Services, or CMS, within the United States Department of Health and Human Services, information related to payments and other transfers of value made by that entity to physicians and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members.
Conditional Approval In particular circumstances, European Union legislation (Article 14–a Regulation (EC) No 726/2004 (as amended by Regulation (EU) 2019/5 and Regulation (EC) No 507/2006 on Conditional Marketing Authorizations for Medicinal Products for Human Use) enables sponsors to obtain a conditional marketing authorization prior to obtaining the comprehensive clinical data required for an application for a full marketing authorization.
Conditional Marketing Authorization In particular circumstances, European Union legislation (Article 14–a Regulation (EC) No 726/2004 (as amended by Regulation (EU) 2019/5 and Regulation (EC) No 507/2006 on Conditional Marketing Authorizations for Medicinal Products for Human Use) enables sponsors to obtain a conditional marketing authorization prior to obtaining the comprehensive clinical data required for an application for a full marketing authorization.
Intellectual property We strive to protect our proprietary technology, inventions, improvements, platforms, product candidates and components thereof, their methods of use and processes for their manufacture that we believe are important to our business, including by obtaining, maintaining, defending and enforcing patent and other intellectual property rights for the foregoing in the United States and in certain foreign jurisdictions.
Intellectual property We strive to protect our proprietary technology, inventions, improvements, product candidates and components thereof, their methods of use and processes for their manufacture that we believe are important to our business, including by obtaining, maintaining, defending and enforcing patent and other intellectual property rights for the foregoing in the United States and in certain foreign jurisdictions.
There have been several recent U.S. congressional inquiries, as well as proposed and enacted state and federal legislation designed to, among other things, bring more transparency to pharmaceutical pricing, review the relationship between pricing and manufacturer patient programs, and reduce the prices of pharmaceuticals under Medicare and Medicaid.
There have been recent U.S. congressional inquiries, as well as proposed and enacted state and federal legislation designed to, among other things, bring more transparency to pharmaceutical pricing, review the relationship between pricing and manufacturer patient programs, and reduce the prices of pharmaceuticals under Medicare and Medicaid.
We have agreed not to, directly or indirectly, alone or with, for or through any third party, develop, manufacture, commercialize or exploit (a) products containing mRNA that are directed to any of the Cell Target Types, during an agreed-upon exclusivity period, which may be extended by payment of extension fees, (b) products directed to any liver target or non-liver target during the option periods for those targets, (c) products directed to any liver target or non-liver target for which Moderna has exercised its exclusive license option or (d) products containing mRNA that are directed to any Exclusive Target for which Moderna has exercised its exclusive license option. 20 Table of Contents Under the terms of the Collaboration Agreement, Moderna made an upfront payment to us of $40 million, as well as $7.5 million in prepaid research funding.
We have agreed not to, directly or indirectly, alone or with, for or through any third party, develop, manufacture, commercialize or exploit (a) products containing mRNA that are directed to any of the Cell Target Types, during an agreed-upon exclusivity period, which may be extended by payment of extension fees, (b) products directed to any liver target or non-liver target during the option periods for those targets, (c) products directed to any liver target or non-liver target for which Moderna has exercised its exclusive license option or (d) products containing mRNA that are directed to any Exclusive Target for which Moderna has exercised its exclusive license option. 18 Table of Contents Under the terms of the Collaboration Agreement, Moderna made an upfront payment to us of $40 million, as well as $7.5 million in prepaid research funding.
FDA regulations also require, among other things, the investigation and correction of any deviations from cGMP and the imposition of reporting and documentation requirements upon the NDA sponsor and any third-party manufacturers involved in producing the approved product.
FDA regulations also require, among other things, the investigation and correction of any deviations from cGMP and the imposition of reporting and documentation requirements upon the sponsor and any third-party manufacturers involved in producing the approved product.
A sponsor seeking approval to market and distribute a new biologic in the United States generally must satisfactorily complete each of the following steps: ● preclinical laboratory tests, animal studies and formulation studies all performed in accordance with the FDA’s Good Laboratory Practices, or GLP regulations; ● completion of the manufacture, under cGMP conditions, of the drug substance and drug product that the sponsor intends to use in human clinical trials along with required analytical and stability testing; ● design of a clinical protocol and its submission to the FDA as part of an Investigational New Drug, or IND, application for human clinical testing, which must become effective before human clinical trials may begin; ● approval by an independent institutional review board, or IRB, representing each clinical site before each clinical trial may be initiated; ● performance of adequate and well-controlled human clinical trials to establish the safety, potency and purity of the product candidate for each proposed indication, in accordance with current Good Clinical Practices, or GCP; ● preparation and submission to the FDA of a biologics license application, or BLA, for a biologic product requesting marketing for one or more proposed indications, including submission of detailed information on the manufacture and composition of the product in clinical development and proposed labelling; ● review of the product by an FDA advisory committee, where appropriate or if applicable; ● satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities, including those of third parties, at which the product, or components thereof, are produced to assess compliance with cGMP requirements and to assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality and purity; 22 Table of Contents ● satisfactory completion of any FDA audits of the preclinical studies and clinical trial sites to assure compliance with GLP, as applicable, and GCP, and the integrity of clinical data in support of the BLA; ● payment of user Prescription Drug User Fee Act, or PDUFA, securing FDA approval of the BLA and licensure of the new biologic product; and ● compliance with any post-approval requirements, including the potential requirement to implement a Risk Evaluation and Mitigation Strategy, or REMS, and any post-approval studies or other post-marketing commitments required by the FDA.
A sponsor seeking approval to market and distribute a new biologic in the United States generally must satisfactorily complete each of the following steps: ● preclinical laboratory tests, animal studies and formulation studies all performed in accordance with the FDA’s Good Laboratory Practices, or GLP regulations; ● completion of the manufacture, under cGMP conditions, of the substance and biologic product that the sponsor intends to use in human clinical trials along with required analytical and stability testing; ● design of a clinical protocol and its submission to the FDA as part of an Investigational New Drug, or IND, application for human clinical testing, which must become effective before human clinical trials may begin; ● approval by an independent institutional review board, or IRB, representing each clinical site before each clinical trial may be initiated; ● performance of adequate and well-controlled human clinical trials to establish the safety, potency and purity of the product candidate for each proposed indication, in accordance with current Good Clinical Practices, or GCP; ● preparation and submission to the FDA of a biologics license application, or BLA, for a biologic product requesting licensure for marketing for one or more proposed indications, including submission of detailed information on the manufacture and composition of the product in clinical development and proposed labelling; ● review of the product by an FDA advisory committee, where appropriate or if applicable; ● satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities, including those of third parties, at which the product, or components thereof, are produced to assess compliance with cGMP requirements and to assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality and purity; 20 Table of Contents ● satisfactory completion of any FDA audits of the preclinical studies and clinical trial sites to assure compliance with GLP, as applicable, and GCP, and the integrity of clinical data in support of the BLA; ● payment of application and program fees pursuant to the Prescription Drug User Fee Act, or PDUFA; ● securing FDA approval of the BLA and licensure of the new biologic product authorizing marketing of the product for particular indications in the United States; and ● compliance with any post-approval requirements, including the potential requirement to implement a Risk Evaluation and Mitigation Strategy, or REMS, and any post-approval studies or other post-marketing commitments required by the FDA.
Orphan drug designation and exclusivity Regulation (EC) No 141/2000 and Regulation (EC) No. 847/2000 provide that a product can be designated as an orphan drug by the European Commission if its sponsor can establish: that the product is intended for the diagnosis, prevention or treatment of (i) a life-threatening or chronically debilitating condition affecting not more than five in ten thousand persons in the European Union when the application is made, or (ii) a life-threatening, seriously debilitating or serious and chronic condition in the European Union and that without incentives it is unlikely that the marketing of the drug in the European Union would generate sufficient return to justify the necessary investment.
Orphan drug designation and exclusivity Regulation (EC) No 141/2000 and Regulation (EC) No. 847/2000 provide that a product can be designated as an orphan drug by the European Commission if its sponsor can establish: that the product is intended for the diagnosis, prevention or treatment of (i) a life-threatening or chronically debilitating condition affecting not more than five in ten thousand 38 Table of Contents persons in the European Union when the application is made, or (ii) a life-threatening, seriously debilitating or serious and chronic condition in the European Union and that without incentives it is unlikely that the marketing of the drug in the European Union would generate sufficient return to justify the necessary investment.
The term “substantial evidence” is defined under the FDCA as “evidence consisting of adequate and well-controlled investigations, including clinical investigations, by experts qualified by scientific training and experience to evaluate the effectiveness of the product involved, on the basis of which it could fairly and responsibly be concluded by such experts that the product will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the labeling or proposed labeling thereof.” The FDA has interpreted this evidentiary standard to require at least two adequate and well-controlled clinical investigations to establish effectiveness of a new product.
The term “substantial evidence” is defined under the FDCA as “evidence consisting of adequate and well-controlled investigations, including clinical investigations, by experts qualified by scientific training and experience to evaluate the effectiveness of the product involved, on the basis of which it could fairly and responsibly be concluded by such experts that the product will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the labeling or proposed labeling thereof.” 27 Table of Contents The FDA has interpreted this evidentiary standard to require at least two adequate and well-controlled clinical investigations to establish effectiveness of a new product.
The updates are intended to help pave the way for more efficient clinical trials to facilitate the development of medical products. The draft guidance is adopted from the International Council for Harmonisation’s, or ICH, recently updated E6(R3) draft guideline that was developed to enable the incorporation of rapidly developing technological and methodological innovations into the clinical trial enterprise.
The updates are intended to help pave the way for more efficient clinical trials to facilitate the development of medical products. The draft guidance is adopted from the International Council for Harmonisation’s recently updated E6(R3) draft guideline that was developed to enable the incorporation of rapidly developing technological and methodological innovations into the clinical trial enterprise.
The guidance documents provide additional factors that the FDA will consider at each of the above stages of development and relate to, among other things: the proper preclinical assessment of gene therapies; the chemistry, manufacturing and control information that should be included in an IND application; the proper design of tests to measure product potency in support of an IND or BLA application; and measures to observe for potential delayed adverse effects in participants who have received investigational gene therapies with the duration of follow-up based on the potential for risk of such effects.
The guidance documents provide additional factors that the FDA will consider at each of the above stages of development and relate to, among other things: 25 Table of Contents the proper preclinical assessment of gene therapies; the chemistry, manufacturing and control information that should be included in an IND application; the proper design of tests to measure product potency in support of an IND or BLA application; and measures to observe for potential delayed adverse effects in participants who have received investigational gene therapies with the duration of follow-up based on the potential for risk of such effects.
Our success depends in part on our ability to: ● obtain, maintain, enforce and defend patent and other intellectual property rights for our commercially important technology, inventions and improvements; ● preserve the confidentiality of our trade secrets and other confidential information; ● obtain and maintain licenses to use and exploit intellectual property owned or controlled by third parties; ● operate without infringing, misappropriating or otherwise violating any valid and enforceable patents and other intellectual property rights of third parties; and ● defend against challenges and assertions by third parties challenging the validity or enforceability of our intellectual property rights, or our rights in our intellectual property, or asserting that the operation of our business infringes, misappropriates or otherwise violates their intellectual property rights.
Our success depends in part on our ability to: ● obtain, maintain, enforce and defend patent and other intellectual property rights for our commercially important technology, inventions and improvements; ● preserve the confidentiality of our trade secrets and other confidential information; ● obtain and maintain licenses to use and exploit intellectual property owned or controlled by third parties; ● operate without infringing, misappropriating or otherwise violating any valid and enforceable patents and other intellectual property rights of third parties; and 14 Table of Contents ● defend against challenges and assertions by third parties challenging the validity or enforceability of our intellectual property rights, or our rights in our intellectual property, or asserting that the operation of our business infringes, misappropriates or otherwise violates their intellectual property rights.
For this and other risks related to our proprietary technology, inventions, improvements, platforms and product candidates and intellectual property rights related to the foregoing, please see the section entitled “Risk factors—Risks related to our intellectual property.” Patent term extensions The term of individual patents depends upon the laws of the jurisdictions in which they are obtained.
For this and other risks related to our proprietary technology, inventions, improvements, technologies and product candidates and intellectual property rights related to the foregoing, please see the section entitled “Risk factors—Risks related to our intellectual property.” Patent term extensions The term of individual patents depends upon the laws of the jurisdictions in which they are obtained.
Additional studies may be required after approval. ● Phase 1 clinical trials are initially conducted in a limited population to test the product candidate for safety, including adverse effects, dose tolerance, absorption, metabolism, distribution, excretion and pharmacodynamics in healthy humans or, on occasion, in patients, such as cancer patients. ● Phase 2 clinical trials are generally conducted in a limited patient population to identify possible adverse effects and safety risks, evaluate the efficacy of the product candidate for specific targeted indications and determine dose 24 Table of Contents tolerance and optimal dosage.
Additional studies may be required after approval. ● Phase 1 clinical trials are initially conducted in a limited population to test the product candidate for safety, including adverse effects, dose tolerance, absorption, metabolism, distribution, excretion and pharmacodynamics in healthy humans or, on occasion, in patients, such as cancer patients. ● Phase 2 clinical trials are generally conducted in a limited patient population to identify possible adverse effects and safety risks, evaluate the efficacy of the product candidate for specific targeted indications and determine dose tolerance and optimal dosage.
Further, depending on the specific risk(s) to be addressed, the FDA may require that contraindications, warnings, or precautions be included in the product labeling; post-approval trials, including Phase 4 clinical trials, be conducted to further assess a product’s safety after approval; and/or testing and 29 Table of Contents surveillance programs to monitor the product after commercialization, or impose other conditions, including distribution and use restrictions or other risk management mechanisms under a REMS, which can materially affect the potential market and profitability of the product.
Further, depending on the specific risk(s) to be addressed, the FDA may require that contraindications, warnings, or precautions be included in the product labeling; post-approval trials, including Phase 4 clinical trials, be conducted to further assess a product’s safety after approval; and/or testing and surveillance programs to monitor the product after commercialization, or impose other conditions, including distribution and use restrictions or other risk management mechanisms under a REMS, which can materially affect the potential market and profitability of the product.
The area of patent and other intellectual property rights in biotechnology is evolving and has many risks and uncertainties, and third parties may have blocking patents and other intellectual property that could be used to prevent us from commercializing our platforms and product candidates and practicing our proprietary technology.
The area of patent and other intellectual property rights in biotechnology is evolving and has many risks and uncertainties, and third parties may have blocking patents and other intellectual property that could be used to prevent us from commercializing our technologies and product candidates and practicing our proprietary technology.
For AAV vectors specifically, the FDA typically recommends that sponsors continue to monitor participants for potential gene therapy-related adverse events for up to a 5-year period. Other types of gene therapy or gene editing products may require longer follow up, potentially up to a maximum 15-year period.
For AAV vectors specifically, the FDA typically recommends that sponsors continue to monitor participants for potential gene therapy-related adverse events for up to a five-year period. Other types of gene therapy or gene editing products may require longer follow up, potentially up to a maximum 15-year period.
Any U.S. or foreign patents issued from the pending U.S. or foreign non-provisional patent applications or from non-provisional applications we may file in connection with the pending provisional patent applications would be scheduled to expire on various dates from 2038 through 2044, without taking into account any possible patent term adjustments or extensions and assuming payment of all appropriate maintenance, renewal, annuity and other governmental fees.
Any U.S. or foreign patents issued from the pending U.S. or foreign non-provisional patent applications or from any non-provisional applications we may file in connection with these provisional patent applications would be scheduled to expire on various dates from 2038 through 2045, without taking into account any possible patent term adjustments or extensions and assuming payment of all appropriate maintenance, renewal, annuity and other governmental fees.
Our patent rights may be challenged, narrowed, circumvented, invalidated or ruled unenforceable, which could limit our ability to stop third parties from marketing and commercializing related platforms or product candidates or limit the term of patents that cover our platforms and product candidates.
Our patent rights may be challenged, narrowed, circumvented, invalidated or ruled unenforceable, which could limit our ability to stop third parties from marketing and commercializing related technologies or product candidates or limit the term of patents that cover our technologies and product candidates.
An IND is an exemption from the FDCA that allows an unapproved product candidate to be shipped in interstate commerce for use in an investigational clinical trial and a request for FDA authorization to administer such investigational product to humans.
The IND and IRB Processes An IND is an exemption from the FDCA that allows an unapproved product candidate to be shipped in interstate commerce for use in an investigational clinical trial and a request for FDA authorization to administer such investigational product to humans.
In addition to California, at least eleven other states have passed comprehensive privacy laws similar to the CCPA and CPRA. These laws are either in effect or will go into effect sometime before the end of 2026.
In addition to California, at least eighteen other states have passed comprehensive privacy laws similar to the CCPA and CPRA. These laws are either in effect or will go into effect sometime before the end of 2026.
We believe it is crucial to, and our directors and senior management strongly support, a no-tolerance stance for workplace harassment, biases and unethical behavior. All employees, including senior management, are required to abide by, review and confirm compliance with our Code of Business Conduct and Ethics and other internal policies that outline our high expectations.
We believe it is crucial to, and our directors and senior management strongly support, a no-tolerance stance for workplace harassment, biases and unethical behavior. All employees, including senior 44 Table of Contents management, are required to abide by, review and confirm compliance with our Code of Business Conduct and Ethics and other internal policies that outline our high expectations.
For example, with enactment of the Tax Cuts and Jobs Act of 2017, or the Tax Act, which was signed by President Trump on December 22, 2017, Congress repealed the “individual mandate.” The repeal of this provision, which requires most Americans to carry a minimal level of health insurance, became effective in 2019.
For example, with enactment of the Tax Cuts and Jobs Act of 2017, or the Tax 42 Table of Contents Act, which was signed by President Trump on December 22, 2017, Congress repealed the “individual mandate.” The repeal of this provision, which requires most Americans to carry a minimal level of health insurance, became effective in 2019.
We also non-exclusively license one patent application family, which includes issued patents in each of the United States, Australia, Brazil, China, South Korea and Israel and national stage patent applications in several other jurisdictions, including Europe and Japan. In addition, we own approximately 11 U.S. provisional patent applications within the priority year.
We also non-exclusively license one patent family, which includes issued patents in each of the United States, Australia, Brazil, China, South Korea and Israel and national stage patent applications in several other jurisdictions, including Europe and Japan. In addition, we own approximately 5 U.S. provisional patent applications within the priority year.
While we believe that our technology, development experience and scientific knowledge in the field of genetic medicine, nucleic acid delivery and manufacturing provide us with competitive advantages, we face potential competition from many different sources, including major pharmaceutical, specialty pharmaceutical and biotechnology companies, academic institutions and governmental agencies and public and private research institutions.
While we believe that our technology, development experience and scientific knowledge in the field of nucleic acid delivery provide us with competitive advantages, we face potential competition from many different sources, including major pharmaceutical, specialty pharmaceutical and biotechnology companies, academic institutions and governmental agencies and public and private research institutions.
Examples of obligations imposed by the GDPR on companies processing personal data that fall within the scope of the GDPR include providing information to individuals regarding data processing activities, implementing safeguards to protect the security and confidentiality of personal data, appointing a data protection officer, providing notification of data breaches and taking certain measures when engaging third-party processors.
Examples of obligations imposed by 40 Table of Contents the GDPR on companies processing personal data that fall within the scope of the GDPR include providing information to individuals regarding data processing activities, implementing safeguards to protect the security and confidentiality of personal data, appointing a data protection officer, providing notification of data breaches and taking certain measures when engaging third-party processors.
For example, in the United States, a patent claiming a new biologic product, its method of use or its method of manufacture may be eligible for a limited patent term extension under the Drug Price 17 Table of Contents Competition and Patent Term Restoration Act of 1984, or the Hatch-Waxman Act, for up to five years beyond the normal expiration date of the patent.
For example, in the United States, a patent claiming a new biologic product, its method of use or its method of manufacture may be eligible for a limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984, or the Hatch-Waxman Act, for up to five years beyond the normal expiration date of the patent.
In the health care industry generally, under the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, the Department of Health and Human Services, or HHS, has issued regulations to protect the privacy and security of protected health information, or PHI, used or disclosed by covered entities including certain healthcare providers, health plans and healthcare clearinghouses.
In the health care industry generally, under the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, the Department of Health and Human Services, or HHS, 32 Table of Contents has issued regulations to protect the privacy and security of protected health information, or PHI, used or disclosed by covered entities including certain healthcare providers, health plans and healthcare clearinghouses.
Regulation 1394/2007/EC lays down specific rules concerning the authorization, supervision and pharmacovigilance of gene therapy medicinal products, somatic cell therapy medicinal products and tissue engineered products. Manufacturers of advanced therapy medicinal products must demonstrate the quality, safety and efficacy of their products to EMA which provides an opinion regarding the application for marketing authorization.
Regulation 1394/2007/EC lays down specific rules concerning the authorization, supervision and pharmacovigilance of gene therapy medicinal products, somatic cell therapy medicinal 35 Table of Contents products and tissue engineered products. Manufacturers of advanced therapy medicinal products must demonstrate the quality, safety and efficacy of their products to EMA which provides an opinion regarding the application for marketing authorization.
In addition, we cannot provide any assurances that all of the foregoing non-disclosure and invention assignment agreements have been duly executed, and any of the counterparties to such agreements may breach them and disclose our trade secrets and other confidential and proprietary information.
In addition, we cannot provide any assurances that all of the foregoing non-disclosure and invention assignment agreements have been duly executed, and any of the counterparties to such agreements may breach them and disclose our trade secrets and other 17 Table of Contents confidential and proprietary information.
Only one patent applicable to an approved product is eligible for the extension, and the application for the extension must be submitted prior to the expiration of the patent for which extension is sought. A patent that covers multiple products for which approval is sought can only be 33 Table of Contents extended in connection with one of the approvals.
Only one patent applicable to an approved product is eligible for the extension, and the application for the extension must be submitted prior to the expiration of the patent for which extension is sought. A patent that covers multiple products for which approval is sought can only be extended in connection with one of the approvals.
Our website address is http://www.generationbio.com. The information contained on, or accessible through, 45 Table of Contents our website does not constitute part of this Annual Report. We have included our website address in this Annual Report solely as an inactive textual reference. Available Information Our Internet address is www.generationbio.com.
Our website address is http://www.generationbio.com. The information contained on, or accessible through, our website does not constitute part of this Annual Report. We have included our website address in this Annual Report solely as an inactive textual reference. Available Information Our Internet address is www.generationbio.com.
Manufacturers and certain of their subcontractors are required to register their establishments with the FDA and certain state agencies and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with ongoing regulatory requirements, including cGMP regulations, which impose certain procedural and documentation requirements upon manufacturers.
Manufacturers and certain of their subcontractors are required to register their establishments with the FDA and certain state agencies and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with ongoing regulatory requirements, including cGMP 29 Table of Contents regulations, which impose certain procedural and documentation requirements upon manufacturers.
Data Privacy Framework to rely on it as a valid data transfer mechanism for data transfers from the European Union to the United States. However, some privacy advocacy groups have already suggested that they will be challenging the EU-U.S. Data Privacy Framework. If these challenges are successful, they may not only impact the EU- 41 Table of Contents U.S.
Data Privacy Framework to rely on it as a valid data transfer mechanism for data transfers from the European Union to the United States. However, some privacy advocacy groups have already suggested that they will be challenging the EU-U.S. Data Privacy Framework. If these challenges are successful, they may not only impact the EU-U.S.
A product candidate is eligible for priority review if it treats a serious condition and, if approved, it would be a significant improvement in the safety or effectiveness of the treatment, diagnosis or prevention compared to marketed products.
A product candidate is eligible for priority review if it treats a serious condition and, if approved, it would be a significant improvement in the safety or effectiveness of the treatment, diagnosis or prevention compared to 28 Table of Contents marketed products.
Under the new coordinated procedure for the approval of clinical trials, the sponsor of a clinical trial to be conducted in more than one Member State of the European Union, or EU Member State, will only be required to submit a single application for approval.
Under the new coordinated procedure for the approval of clinical trials, the sponsor of a clinical trial to be conducted in more than one Member State of the European 34 Table of Contents Union, or EU Member State, will only be required to submit a single application for approval.
Securing FDA approval for new indications is similar to the process for approval of the original indication and requires, among other things, submitting data from adequate and well-controlled clinical trials to demonstrate the product’s safety and efficacy in the new indication.
Securing FDA approval for new indications is similar to the process for approval of the original indication and requires, among other things, submitting data from adequate and well-controlled clinical trials to demonstrate the product’s safety, purity and potency in the new indication.
Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. 21 Table of Contents Our commercial opportunity could be substantially limited if our competitors develop and commercialize products that are more effective, safer, less toxic, more convenient or less expensive than products we may develop.
Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. Our commercial opportunity could be substantially limited if our competitors develop and commercialize products that are more effective, safer, less toxic, more convenient or less expensive than products we may develop.
Competition The biotechnology and biopharmaceutical industries generally, and the genetic medicine field specifically, are characterized by rapid evolution of technologies, sharp competition and strong defense of intellectual property. Any product candidates that we successfully develop and commercialize will have to compete with existing therapies and new therapies that may become available in the future.
Competition The biotechnology and biopharmaceutical industries generally are characterized by rapid evolution of technologies, sharp competition and strong defense of intellectual property. Any product candidates that we successfully develop and commercialize will have to compete with existing therapies and new therapies that may become available in the future.
In December 2022, with the passage of Food and Drug Omnibus Reform Act, or FDORA, Congress began requiring sponsors to develop and submit a diversity action plan for each Phase 3 clinical trial or any other “pivotal study” of a new drug or biological product.
In December 2022, with the passage of Food and Drug Omnibus Reform Act, or FDORA, Congress began requiring sponsors to develop and submit a diversity action plan, or DAP, for each Phase 3 clinical trial or any other “pivotal study” 23 Table of Contents of a new drug or biological product.
Human Capital Resources As of December 31, 2023, we had approximately 174 employees, all of whom are full-time employees. None of our employees are represented by labor unions or covered by collective bargaining agreements. Our success is dependent on our ability to attract and retain highly talented individuals.
Human Capital Resources As of December 31, 2024, we had approximately 115 employees, all of whom are full-time employees. None of our employees are represented by labor unions or covered by collective bargaining agreements. Our success is dependent on our ability to attract and retain highly talented individuals.
During the additional two-year period of market exclusivity, a generic marketing authorization application can be submitted, and the innovator’s data may be referenced, but no generic medicinal product can be 38 Table of Contents marketed until the expiration of the market exclusivity.
During the additional two-year period of market exclusivity, a generic marketing authorization application can be submitted, and the innovator’s data may be referenced, but no generic medicinal product can be marketed until the expiration of the market exclusivity.
In addition, the HHS and the FDA published a final rule allowing states and other entities to develop a Section 804 Importation Program, or SIP, to import certain prescription drugs from Canada into the United States.
In October 2020, the HHS and the FDA published a final rule allowing states and other entities to develop a Section 804 Importation Program, or SIP, to import certain prescription drugs from Canada into the United States.
There are also states that are strongly considering or have already passed comprehensive privacy laws during the 2023 legislative sessions that will go into effect in 2024 and beyond. Other states will be considering these laws in the future, and Congress has also been debating passing a federal privacy law.
There are also states that are strongly considering or have already passed comprehensive privacy laws during the 2024 legislative sessions that will go into effect in 2025 and beyond. Other states will be considering similar laws in the future, and Congress has also been debating passing a federal privacy law.
We have also non-exclusively licensed one patent application family from the National Institutes of Health, or NIH, and the Institut de Myologie, Universite Pierre et Marie Curie, Centre National de la Recherche Scientifique and Inserm Transfert SA, which we refer to as the French Institutions, which includes issued patents in each of the United States, Australia, Brazil, China, South Korea and Israel and national stage patent applications in other jurisdictions, including Europe and Japan, which cover our ceDNA construct, certain disease-targeted ceDNA compositions and methods of use.
We have also non-exclusively licensed one patent family from the National Institutes of Health, or NIH, and the Institut de Myologie, Universite Pierre et Marie Curie, Centre National de la Recherche Scientifique and Inserm Transfert SA, which we refer to as the French Institutions, which includes issued patents in each of the United States, Australia, Brazil, China, South Korea and Israel and national stage patent applications in other jurisdictions, including Europe and Japan, which cover ceDNA compositions and use.
An IRB must operate in compliance with FDA regulations. The FDA, IRB, or the clinical trial sponsor may suspend or discontinue a clinical trial at any time for various reasons, including a finding that the clinical trial is not being conducted in accordance with FDA requirements or that the participants are being exposed to an unacceptable health risk.
The FDA, IRB, or the clinical trial sponsor may suspend or discontinue a clinical trial at any time for various reasons, including a finding that the clinical trial is not being conducted in accordance with FDA requirements or that the participants are being exposed to an unacceptable health risk.
A conditional marketing authorization may 37 Table of Contents contain specific obligations to be fulfilled by the marketing authorization holder, including obligations with respect to the completion of ongoing or new studies and with respect to the collection of pharmacovigilance data.
A conditional marketing authorization may contain specific obligations to be fulfilled by the marketing authorization holder, including obligations with respect to the completion of ongoing or new studies and with respect to the collection of pharmacovigilance data.
Patent portfolio As of December 31, 2023, we own approximately 58 patent application families related to our business, including 12 pending Patent Cooperation Treaty, or PCT, patent applications and 35 PCT applications that have entered the national stage in the United States and certain foreign jurisdictions, including Europe and Japan (one of which is jointly owned with the University of Massachusetts Medical School, or UMass), and we exclusively license one patent application family, which includes issued patents in each of the United States, Europe, China, South Korea, Japan, Russia, Hong Kong, Israel, Macau, Mexico and South Africa, and pending national stage applications in several other jurisdictions, including Australia, Canada, New Zealand, and Singapore.
Patent portfolio As of December 31, 2024, we owned approximately 58 patent families related to our business, including 14 pending Patent Cooperation Treaty, or PCT, patent applications and 39 PCT applications that have entered the national stage in the United States and certain foreign jurisdictions, including Europe and Japan (one of which is jointly owned with the University of Massachusetts Medical School, or UMass), and we exclusively license one patent family, which includes issued patents in each of the United States, Europe, China, South Korea, Japan, Russia, Hong Kong, Israel, Macau, Mexico and South Africa, and pending national stage applications in several other jurisdictions, including Australia, Canada, New Zealand, and Singapore.
Preclinical studies and investigational new drug application Before testing any biologic product candidate in humans, including a genetic medicine product candidate, the product candidate must undergo preclinical testing. Preclinical tests include laboratory evaluations of product chemistry, formulation and stability, as well as studies to evaluate the potential for efficacy and toxicity in animal studies.
Preclinical studies Before testing any biologic product candidate in humans, including a genetic medicine product candidate, the product candidate must undergo preclinical testing. Preclinical tests include laboratory evaluations of product chemistry, formulation and stability, as well as studies to evaluate the potential for efficacy and toxicity in animal studies.
Other potential consequences include, among other things: ● restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls; ● safety alerts, Dear Healthcare Provider letters, press releases or other communications containing warnings or other safety information about a product; ● mandated modification of promotional materials and labeling and issuance of corrective information; ● fines, warning letters or holds on post-approval clinical trials; ● refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of product license approvals; ● product recall, seizure or detention, or refusal to permit the import or export of products; ● injunctions or the imposition of civil or criminal penalties; and ● consent decrees, corporate integrity agreements, debarment, or exclusion from federal health care programs. 31 Table of Contents The FDA strictly regulates the marketing, labeling, advertising and promotion of prescription drug products placed on the market.
Other potential consequences include, among other things: ● restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls; ● safety alerts, Dear Healthcare Provider letters, press releases or other communications containing warnings or other safety information about a product; ● mandated modification of promotional materials and labeling and issuance of corrective information; ● fines, warning letters or holds on post-approval clinical trials; ● refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of product license approvals; ● product recall, seizure or detention, or refusal to permit the import or export of products; ● injunctions or the imposition of civil or criminal penalties; and ● consent decrees, corporate integrity agreements, debarment, or exclusion from federal health care programs.
The second research program will be focused on the use of ctLNPs developed under the Non-Liver ctLNP Program to discover and develop products directed to agreed-upon targets outside of the liver, or the Non-Liver Targets.
The second research program will be focused on the use of ctLNPs to discover and develop products directed to agreed-upon targets outside of the liver, or the Non-Liver Targets.
The FDA reviews the application to determine, among other things, whether the proposed product is safe and effective for its intended use, whether it has an acceptable purity profile and whether the product is being manufactured in accordance with cGMP.
The FDA reviews the application to determine, among other things, whether the proposed product is safe and effective for its 26 Table of Contents intended use, whether it has an acceptable purity profile and whether the product is being manufactured in accordance with cGMP.
We have designed our programs to cultivate employee engagement, diversity, equity and inclusion, growth and development while consistently providing competitive compensation and benefits. Our benefit programs are designed to meet the diverse needs of our employees and focus on promoting well-being across all aspects of their lives. These programs include healthcare, retirement planning, education planning, and extensive time off.
We have designed our programs to cultivate employee engagement, equal employment opportunity, growth and development while consistently providing competitive compensation and benefits. Our benefit programs are designed to meet the diverse needs of our employees and focus on promoting well-being across all aspects of their lives. These programs include healthcare, retirement planning, education planning, and extensive time off.
Competitors, however, may receive approval of a different gene therapy for the indication for which the orphan product has exclusivity or obtain approval for the same product but for a different indication for which the orphan product has 32 Table of Contents exclusivity.
Competitors, however, may receive approval of a different gene therapy for the indication for which the orphan product has exclusivity or obtain approval for the same product but for a different indication for which the orphan product has exclusivity.
Since that time, the FDA has issued additional guidance documents that outline the requirements and expectations for companion diagnostic products. Under the FDCA, in vitro diagnostics, including companion diagnostics, are regulated as medical devices.
Since that time, 33 Table of Contents the FDA has issued additional guidance documents that outline the requirements and expectations for companion diagnostic products. Under the FDCA, in vitro diagnostics, including companion diagnostics, are regulated as medical devices.
Clinical testing also must satisfy extensive GCP rules and the requirements for informed consent. Additionally, some clinical trials are overseen by an independent group of qualified experts organized by the clinical trial sponsor, known as a data safety monitoring board, or DSMB.
Clinical testing also must satisfy extensive GCP rules and the requirements for informed consent. Additionally, some clinical trials are overseen by an independent group of qualified experts organized by the clinical trial sponsor, known as a data monitoring committee, or DMC.
The NIH, including the Novel and Exceptional Technology and Research Advisory Committee, or the NExTRAC, also advises the FDA on gene therapy issues and other issues related to emerging biotechnologies. The FDA and the NIH have published guidance documents with respect to the development and submission of gene therapy protocols. The FDA has issued various guidance documents regarding gene therapies.
The NIH, including the Novel and Exceptional Technology and Research Advisory Committee, or the NExTRAC, also advises the FDA on gene therapy issues and other issues related to emerging biotechnologies. The FDA and the NIH have published guidance documents with respect to the development and submission of gene therapy protocols.
The data do not need to show the product to be effective in the pediatric population studied; rather, if the clinical trial is deemed to fairly respond to the FDA’s request, the additional protection is granted.
The data do not need to show the product to be effective in the pediatric population studied; rather, if the clinical trial is deemed to fairly respond to the FDA’s 31 Table of Contents request, the additional protection is granted.
The FDA may, on its own initiative or at the request of the sponsor, grant deferrals for submission of some or all pediatric data until after approval of the product for use in adults, or full or partial waivers from the pediatric data requirements.
The FDA or the sponsor may request an amendment to the plan at any time. The FDA may, on its own initiative or at the request of the sponsor, grant deferrals for submission of some or all pediatric data until after approval of the product for use in adults, or full or partial waivers from the pediatric data requirements.
To reach this determination, the FDA must determine that the drug is effective and that its expected benefits outweigh its potential risks to patients. This “benefit-risk” assessment is informed by the extensive body of evidence about the product’s safety and efficacy in the NDA or BLA.
To reach this determination, the FDA must determine that the drug is effective and that its expected benefits outweigh its potential risks to patients. This “benefit-risk” assessment is informed by the extensive body of evidence about the product in the BLA.
Approval of a 351(k) application may not be made effective until twelve years after the date of first licensure of the reference product, which under the statute excludes the date of licensure of supplements and certain other applications.
A reference biologic is granted twelve years of exclusivity from the time of first licensure of the reference product. Approval of a 351(k) application may not be made effective until twelve years after the date of first licensure of the reference product, which under the statute excludes the date of licensure of supplements and certain other applications.
The MDR is meant to establish a uniform, transparent, predictable, and sustainable regulatory framework across the European Union for medical devices. ​ Separately, the regulatory authorities in the European Union also adopted a new In Vitro Diagnostic Regulation, or the IVDR, (EU) 2017/746 , which became effective in May 2022.
The MDR is meant to establish a uniform, transparent, predictable, and sustainable regulatory framework across the European Union for medical devices. ​ Separately, the European Union also adopted a new In Vitro Diagnostic Regulation, or the IVDR, (EU) 2017/746 , which became effective in May 2022. The new regulation replaces the In Vitro Diagnostics Directive, or the IVDD, 98/79/EC.
Subsequently, a number of other parties, including the U.S. Chamber of Commerce, or Chamber, Bristol Myers Squibb Company, the Pharmaceutical Research and Manufacturers of America, Astellas, Novo Nordisk, Janssen Pharmaceuticals, Novartis, AstraZeneca and Boehringer Ingelheim, also filed lawsuits in various courts with similar constitutional claims against HHS and CMS.
Chamber of Commerce, or Chamber, Bristol Myers Squibb Company, the Pharmaceutical Research and Manufacturers of America, Astellas, Novo Nordisk, Janssen Pharmaceuticals, Novartis, AstraZeneca and Boehringer Ingelheim, also filed lawsuits in various courts with similar constitutional claims against HHS and CMS.
The fee required for the submission and review of an application under the PDUFA is substantial (for example, for fiscal year 2024, this application fee is $4.05 million), and the sponsor of an approved application is also subject to an annual program fee, which for federal fiscal year 2024 is more than $410,000 per eligible prescription product.
The fee required for the submission and review of an application under the PDUFA is substantial (for example, for fiscal year 2025, this application fee is $4.3 million), and the sponsor of an approved application is also subject to an annual program fee, which for federal fiscal year 2025 is more than $403,889 per eligible prescription product.
Any U.S. or foreign patents issued from any non-provisional applications we may file in connection with the PCT patent application would be scheduled to expire in 2043, without taking into account any possible patent term adjustments or extensions and assuming payment of all appropriate maintenance, renewal, annuity and other governmental fees. ceDNA As of December 31, 2023, we own approximately 33 patent application families, including four pending PCT patent applications and 18 PCT applications that have entered the national stage in the United States and a number of jurisdictions outside the United States (one of which is jointly owned with UMass and one of which is jointly owned with Vir Biotechnology), including 3 issued patents in Russia covering various ceDNA constructs in combination with LNP formulation comprising the ceDNA constructs, and its uses in, for example, treatment of various diseases and gene editing.
Any U.S. or foreign patents issued from any non-provisional applications we may file in connection with the PCT patent application would be scheduled to expire on various dates from 2040 through 2045, without taking into account any possible patent term adjustments or extensions and assuming payment of all appropriate maintenance, renewal, annuity and other governmental fees. ceDNA As of December 31, 2024, we owned approximately 33 patent families, including two pending PCT patent applications and 20 PCT applications that have entered the national stage in the United States and a number of jurisdictions outside the United States (one of which is jointly owned with UMass and one of which is jointly owned with Vir Biotechnology), including one issued patent in New Zealand, six issued patents in Russia, and two issued patents in Singapore, covering 15 Table of Contents various ceDNA constructs in combination with LNP formulation comprising the ceDNA constructs, and its uses in, for example, treatment of various diseases and gene editing.
Any U.S. or foreign patents issued from national stage filings of our owned or exclusively in-licensed patent applications and any U.S. patents issued from non-provisional applications we may file in connection with our provisional and pending PCT patent applications would be scheduled to expire on various dates from 2037 through 2044, without taking into account any possible patent term adjustments or extensions and assuming payment of all appropriate maintenance, renewal, annuity and other governmental fees. 15 Table of Contents ctLNP platform As of December 31, 2023, we own approximately 19 patent application families, including five pending PCT patent applications and 14 PCT applications that have entered the national stage in the United States and a number of jurisdictions outside the United States within the priority year with respect to our ctLNP delivery system, including certain lipid and lipid nanoparticle compositions and optionally in combinations with one or more nucleic acid cargos such as iqDNA, ceDNA, mRNA and/or specific cell-targeting agents and methods of use.
Any U.S. or foreign patents issued from national stage filings of our wholly-owned or exclusively in-licensed patent applications and any U.S. patents issued from non-provisional applications we may file in connection with our provisional and pending PCT patent applications would be scheduled to expire on various dates from 2037 through 2045, without taking into account any possible patent term adjustments or extensions and assuming payment of all appropriate maintenance, renewal, annuity and other governmental fees. ctLNP delivery system As of December 31, 2024, we owned approximately 22 patent families, including nine pending PCT patent applications and 11 PCT applications that have entered the national stage in the United States and a number of jurisdictions outside the United States within the priority year with respect to our ctLNP delivery system, including certain lipid and lipid nanoparticle compositions and optionally in combinations with one or more nucleic acid cargos such as iqDNA, ceDNA, mRNA, siRNA and/or specific cell-targeting agents ( e.g ., T cell and hematopoietic stem cell targeting moieties) and methods of use.
As of January 1, 2021, the Medicines and Healthcare products Regulatory Agency, or the MHRA, became responsible for supervising medicines and medical devices in Great Britain, or GB, comprising England, Scotland, and Wales under domestic law whereas Northern Ireland continues to be subject to European Union rules under the Northern Ireland Protocol.
As of January 1, 2021, the Medicines and Healthcare Products Regulatory Agency, or the MHRA, became responsible for supervising medicines and medical devices in Great Britain comprising England, Scotland, and Wales under domestic law; whereas, Northern Ireland continues to be subject to European Union rules under the Northern Ireland Protocol, as amended, by the so called Windsor Framework agreed to in February 2023.
The BPCIA amended the PHSA to create an abbreviated approval pathway for biological products that are biosimilar to or interchangeable with an FDA-licensed reference biological product.
The BPCIA amended the PHSA to create an abbreviated approval pathway for biological products that are biosimilar to or interchangeable with an FDA-licensed reference biological product. To date, the FDA has approved both biosimilars and interchangeable biosimilar products.
The European Union and the United Kingdom reached an agreement on their new partnership in the Trade and Cooperation Agreement, or the Agreement, which was applied provisionally beginning on January 1, 2021, and which entered into force on May 1, 2021.
The European Union and the United Kingdom reached an agreement on their new partnership in the Trade and Cooperation Agreement, and which entered into force on May 1, 2021.
For the federal fiscal year 2024, the standard fee is $483,560 and the small business fee is $120,890. After a device is placed on the market, it remains subject to significant regulatory requirements. Medical devices may be marketed only for the uses and indications for which they are cleared or approved.
For the federal fiscal year 2025, the standard fee is $540,783 and the small business fee is $135,196. After a device is placed on the market, it remains subject to significant regulatory requirements. Medical devices may be marketed only for the uses and indications for which they are cleared or approved.
The new regulation replaces the In Vitro Diagnostics Directive, or the IVDD, 98/79/EC. Manufacturers wishing to apply to a notified body for a conformity assessment of their in vitro diagnostic medical device had until May 2022 to update their technical documentation to meet the requirements and comply with the new, more stringent IVDR.
Manufacturers wishing to apply to a notified body for a conformity assessment of their in vitro diagnostic medical device had until May 2022 to update their technical documentation to meet the requirements and comply with the new, more stringent IVDR.
The IVDR, among other things: strengthens the rules on placing devices on the market and reinforces surveillance once they are available; establishes explicit provisions on manufacturers’ responsibilities for the follow-up of the quality, performance, and safety of devices placed on the market; improves the traceability of medical devices throughout the supply chain to the end-user or patient through a unique identification number; sets up a central database to provide patients, healthcare professionals, and the public with comprehensive information on products available in the European Union; and strengthens rules for the assessment of certain high-risk devices, such as implants, which may have to undergo an additional check by experts before they are placed on the market. ​ The IVDR became effective in May 2022.
The IVDR, among other things: strengthens the rules on placing devices on the market and reinforces surveillance once they are available; establishes explicit provisions on manufacturers’ responsibilities for the follow-up of the quality, performance, and safety of devices placed on the market; improves the traceability of medical devices throughout the supply chain to the end-user or patient through a unique identification number; sets up a central database to provide patients, healthcare professionals, and the public with comprehensive information on products available in the European Union; and strengthens rules for the assessment of certain high-risk devices, such as implants, which may have to undergo an additional check by experts before they are placed on the market. ​ 39 Table of Contents Companion diagnostic devices are classified at least as a class C IVD and thus require involvement of the notified body in the regulatory approval process under the IVDR.
As a condition of approval, the FDA may require that a sponsor of a drug or biologic product candidate receiving accelerated approval perform adequate and well controlled post-marketing clinical trials.
As a condition of approval, the FDA may require that a sponsor of a drug or biologic product candidate receiving accelerated approval perform adequate and well controlled post-marketing clinical trials. In addition, the FDA currently requires as a condition for accelerated approval pre-approval of promotional materials.
Some countries may require the completion of additional studies that compare the cost-effectiveness of a particular product candidate to currently available therapies (so called health technology assessments) in order to obtain reimbursement or pricing approval.
Some countries provide that products may be marketed only after a reimbursement price has been agreed. Some countries may require the completion of additional studies that compare the cost-effectiveness of a particular product candidate to currently available therapies (so called health technology assessments) in order to obtain reimbursement or pricing approval.
While this guidance is currently only in draft form and will ultimately not be legally binding even when finalized, sponsors typically observe FDA’s guidance closely to ensure that their investigational products qualify for accelerated approval. ● Regenerative medicine advanced therapy.
While these guidances are currently only in draft form and will ultimately not be legally binding even when finalized, sponsors typically observe the FDA’s guidance closely to ensure that their investigational products qualify for accelerated approval.
In particular, non-clinical studies, both in vitro and in vivo, must be planned, performed, monitored, recorded, reported and archived in accordance with the GLP principles, which define a set of rules and criteria for a quality system for the organizational process and the conditions 35 Table of Contents for non-clinical studies.
In particular, non-clinical studies, both in vitro and in vivo, must be planned, performed, monitored, recorded, reported and archived in accordance with the GLP principles, which define a set of rules and criteria for a quality system for the organizational process and the conditions for non-clinical studies. These GLP standards reflect the Organization for Economic Co-operation and Development requirements.
The FDA’s regulations are intended to help ensure the protection of human subjects enrolled in non-IND foreign clinical studies, as well as the quality and integrity of the resulting data.
The FDA’s regulations are intended to help ensure the protection of human subjects enrolled in non-IND foreign clinical studies, as well as the quality and integrity of the resulting data. They further help ensure that non-IND foreign studies are conducted in a manner comparable to that required for IND studies.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeThese companies include viral gene therapy companies such as BioMarin Pharmaceuticals, Inc., Homology Medicines, Inc., Adverum Biotechnologies, Inc., Ultragenyx Pharmaceutical Inc., Sana Biotechnology, Inc., Umoja BioPharma, Inc., Pfizer Inc. and Hoffmann La Roche Ltd; gene editing companies such as CRISPR Therapeutics AG, Intellia Therapeutics, Inc., bluebird bio, Inc., Ensoma, Inc., Editas Medicine, Inc., Beam Therapeutics Inc., Tessera Therapeutics, Inc., and Prime Medicine, Inc.; in vivo LNP delivery companies such as Capstan Therapeutics Inc. and Orna Therapeutics, Inc.; and mRNA companies such as Moderna, Inc. 68 Table of Contents Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than our product candidates or that would render any product candidates that we may develop obsolete or non-competitive.
Biggest changeOur commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than our potential product candidates or that would render any product candidates that we may develop obsolete or non-competitive.
Restrictions under applicable federal and state healthcare laws and regulations include the following: ● the federal healthcare anti-kickback statute prohibits, among other things, persons from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward either the referral of an individual for, or the purchase, order, or recommendation of, any good or service, for which payment may be made under federal and state healthcare programs such as Medicare and Medicaid; ● the federal False Claims Act imposes criminal and civil penalties, including civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting or causing to be presented, to the federal government, claims for payment or approval from Medicare, Medicaid or other government payers that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government, with potential liability including mandatory treble damages and significant per-claim penalties; ● HIPAA, as further amended by the Health Information Technology for Economic and Clinical Health Act, which imposes certain requirements, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information without appropriate authorization by entities subject to the rule, such as health plans, healthcare clearinghouses and healthcare providers; ● the federal false statements statute, which prohibits knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement in connection with the delivery of or payment for healthcare benefits, items or services; ● the federal transparency requirements under the federal Physician Payment Sunshine Act, which requires manufacturers of drugs, devices, biologics and medical supplies to report to HHS information related to payments and other transfers of value to physicians and teaching hospitals and other covered recipients and ownership and investment interests held by physicians and their immediate family members and applicable group purchasing organizations; and ● analogous state laws and regulations, such as state anti-kickback and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party 95 Table of Contents payers, including private insurers, and certain state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government in addition to requiring drug manufacturers to report information related to payments to physicians and other healthcare providers or marketing expenditures.
Restrictions under applicable federal and state healthcare laws and regulations include the following: ● the federal healthcare anti-kickback statute prohibits, among other things, persons from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward 90 Table of Contents either the referral of an individual for, or the purchase, order, or recommendation of, any good or service, for which payment may be made under federal and state healthcare programs such as Medicare and Medicaid; ● the federal False Claims Act imposes criminal and civil penalties, including civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting or causing to be presented, to the federal government, claims for payment or approval from Medicare, Medicaid or other government payers that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government, with potential liability including mandatory treble damages and significant per-claim penalties; ● HIPAA, as further amended by the Health Information Technology for Economic and Clinical Health Act, which imposes certain requirements, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information without appropriate authorization by entities subject to the rule, such as health plans, healthcare clearinghouses and healthcare providers; ● the federal false statements statute, which prohibits knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement in connection with the delivery of or payment for healthcare benefits, items or services; ● the federal transparency requirements under the federal Physician Payment Sunshine Act, which requires manufacturers of drugs, devices, biologics and medical supplies to report to HHS information related to payments and other transfers of value to physicians and teaching hospitals and other covered recipients and ownership and investment interests held by physicians and their immediate family members and applicable group purchasing organizations; and ● analogous state laws and regulations, such as state anti-kickback and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payers, including private insurers, and certain state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government in addition to requiring drug manufacturers to report information related to payments to physicians and other healthcare providers or marketing expenditures.
Collaborations involving our research programs or any product candidates we may develop, including our existing collaboration with Moderna, pose numerous risks to us, including the following: ● collaborators have significant discretion in determining the efforts and resources that they will apply to these collaborations; ● collaborators may not pursue development and commercialization of any product candidates we may develop or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborator’s strategic focus or available funding or external factors such as an acquisition that diverts resources or creates competing priorities; ● collaborators may delay programs, preclinical studies or clinical trials, provide insufficient funding for programs, preclinical studies or clinical trials, stop a preclinical study or clinical trial or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; ● collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with any product candidates we may develop if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours; ● collaborators may be acquired by a third party having competitive products or different priorities; ● collaborators with marketing and distribution rights to one or more medicines may not commit sufficient resources to the marketing and distribution of such medicine or medicines; ● collaborators may not properly obtain, maintain, enforce or defend our intellectual property or proprietary rights or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our proprietary information or expose us to potential litigation; ● disputes may arise between the collaborators and us that result in the delay or termination of the research, development, or commercialization of our medicines or any product candidates we may develop or that result in costly litigation or arbitration that diverts management attention and resources; 66 Table of Contents ● we may lose certain valuable rights under certain circumstances, including if we undergo a change of control; ● collaborations may be terminated and, if terminated, may result in a need for additional capital to pursue further development or commercialization of the applicable product candidates we may develop; and ● collaboration agreements, including our Collaboration Agreement with Moderna, may not lead to development or commercialization of product candidates in the most efficient manner or at all.
Collaborations involving our research programs or any product candidates we may develop, including our existing collaboration with Moderna, pose numerous risks to us, including the following: ● collaborators have significant discretion in determining the efforts and resources that they will apply to these collaborations; ● collaborators may not pursue development and commercialization of any product candidates we may develop or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborator’s strategic focus or available funding or external factors such as an acquisition that diverts resources or creates competing priorities; ● collaborators may delay programs, preclinical studies or clinical trials, provide insufficient funding for programs, preclinical studies or clinical trials, stop a preclinical study or clinical trial or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; 63 Table of Contents ● collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with any product candidates we may develop if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours; ● collaborators may be acquired by a third party having competitive products or different priorities; ● collaborators with marketing and distribution rights to one or more medicines may not commit sufficient resources to the marketing and distribution of such medicine or medicines; ● collaborators may not properly obtain, maintain, enforce or defend our intellectual property or proprietary rights or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our proprietary information or expose us to potential litigation; ● disputes may arise between the collaborators and us that result in the delay or termination of the research, development, or commercialization of our medicines or any product candidates we may develop or that result in costly litigation or arbitration that diverts management attention and resources; ● we may lose certain valuable rights under certain circumstances, including if we undergo a change of control; ● collaborations may be terminated and, if terminated, may result in a need for additional capital to pursue further development or commercialization of the applicable product candidates we may develop; and ● collaboration agreements, including our Collaboration Agreement with Moderna, may not lead to development or commercialization of product candidates in the most efficient manner or at all.
Other events that may prevent successful or timely completion of clinical development include: ● delays in reaching a consensus with regulatory authorities on trial design; ● delays in reaching agreement on acceptable terms with prospective clinical research organizations, or CLROs, and clinical trial sites; ● delays in opening clinical trial sites or obtaining required institutional review board, or IRB, or independent ethics committee approval, or the equivalent review groups for sites outside the United States, at each clinical trial site; 53 Table of Contents ● imposition of a clinical hold by regulatory authorities as a result of a serious adverse event or after an inspection of our clinical trial operations or trial sites; ● failure by us, any CLROs we engage or any other third parties to adhere to clinical trial requirements; ● failure to manufacture in accordance with the FDA’s GCPs; ● failure by physicians to adhere to delivery protocols leading to variable results; ● delays in the testing, validation, manufacturing and delivery of any product candidates we may develop to the clinical sites, including delays by third parties with whom we have contracted to perform certain of those functions; ● delays or difficulties faced by the external cleanroom facilities and/or CMOs we intend to use to manufacture our drug substance and drug product; ● delays in having subjects complete participation in a trial or return for post-treatment follow-up; ● clinical trial sites or subjects dropping out of a trial; ● selection of clinical endpoints that require prolonged periods of clinical observation or analysis of the resulting data; ● occurrence of serious adverse events, including unexpected events, associated with the product candidate that are viewed to outweigh its potential benefits; ● occurrence of serious adverse events associated with a product candidate in development by another company, which are viewed to outweigh its potential benefits, and which may negatively impact the perception of our product due to a similarity in technology or approach; ● changes in regulatory requirements and guidance that require amending or submitting new clinical protocols; ● changes in the legal or regulatory regimes domestically or internationally related to patient rights and privacy; or ● lack of adequate funding to continue the clinical trial.
Other events that may prevent successful or timely completion of clinical development include: ● delays in reaching a consensus with regulatory authorities on trial design; ● delays in reaching agreement on acceptable terms with prospective clinical research organizations, or CLROs, and clinical trial sites; ● delays in opening clinical trial sites or obtaining required institutional review board, or IRB, or independent ethics committee approval, or the equivalent review groups for sites outside the United States, at each clinical trial site; ● imposition of a clinical hold by regulatory authorities as a result of a serious adverse event or after an inspection of our clinical trial operations or trial sites; ● failure by us, any CLROs we engage or any other third parties to adhere to clinical trial requirements; ● failure to manufacture in accordance with the FDA’s GCPs; ● failure by physicians to adhere to delivery protocols leading to variable results; ● delays in the testing, validation, manufacturing and delivery of any product candidates we may develop to the clinical sites, including delays by third parties with whom we have contracted to perform certain of those functions; ● delays or difficulties faced by the external cleanroom facilities and/or CMOs we intend to use to manufacture our drug substance and drug product; ● delays in having subjects complete participation in a trial or return for post-treatment follow-up; 52 Table of Contents ● clinical trial sites or subjects dropping out of a trial; ● selection of clinical endpoints that require prolonged periods of clinical observation or analysis of the resulting data; ● occurrence of serious adverse events, including unexpected events, associated with the product candidate that are viewed to outweigh its potential benefits; ● occurrence of serious adverse events associated with a product candidate in development by another company, which are viewed to outweigh its potential benefits, and which may negatively impact the perception of our product due to a similarity in technology or approach; ● changes in regulatory requirements and guidance that require amending or submitting new clinical protocols; ● changes in the legal or regulatory regimes domestically or internationally related to patient rights and privacy; or ● lack of adequate funding to continue the clinical trial.
The market price for our common stock may be influenced by many factors, including: ● results of or developments in preclinical studies and clinical trials of any product candidates we may develop or those of our competitors or potential collaborators; ● timing of the results of our preclinical studies and clinical trials or those of our competitors; ● our success in commercializing any product candidates we may develop, if and when approved; ● the success of competitive products or technologies; ● regulatory or legal developments in the United States and other countries; ● developments or disputes concerning patent applications, issued patents or other intellectual property or proprietary rights; ● the recruitment or departure of key personnel; ● the level of expenses related to any product candidates we may develop; 105 Table of Contents ● the results of our efforts to discover, develop, acquire or in-license products, product candidates, technologies or data referencing rights, the costs of commercializing any such products and the costs of development of any such product candidates or technologies; ● actual or anticipated changes in estimates as to financial results, development timelines or recommendations by securities analysts; ● variations in our financial results or the financial results of companies that are perceived to be similar to us; ● sales of common stock by us, our executive officers, directors or principal stockholders or others; ● changes in the structure of healthcare payment systems; ● market conditions in the pharmaceutical and biotechnology sectors; ● general economic, industry, political and market conditions, such as geopolitical conflicts, inflation and sustained high interest rates; and ● the other factors described in this “Risk Factors” section.
The market price for our common stock may be influenced by many factors, including: ● results of or developments in preclinical studies and clinical trials of any product candidates we may develop or those of our competitors or potential collaborators; ● timing of the results of our preclinical studies and clinical trials or those of our competitors; ● our success in commercializing any product candidates we may develop, if and when approved; ● the success of competitive products or technologies; ● regulatory or legal developments in the United States and other countries; ● developments or disputes concerning patent applications, issued patents or other intellectual property or proprietary rights; ● the recruitment or departure of key personnel; ● the level of expenses related to any product candidates we may develop; 101 Table of Contents ● the results of our efforts to discover, develop, acquire or in-license products, product candidates, technologies or data referencing rights, the costs of commercializing any such products and the costs of development of any such product candidates or technologies; ● actual or anticipated changes in estimates as to financial results, development timelines or recommendations by securities analysts; ● variations in our financial results or the financial results of companies that are perceived to be similar to us; ● sales of common stock by us, our executive officers, directors or principal stockholders or others; ● changes in the structure of healthcare payment systems; ● market conditions in the pharmaceutical and biotechnology sectors; ● general economic, industry, political and market conditions, such as geopolitical conflicts, inflation and sustained high interest rates; and ● the other factors described in this “Risk Factors” section.
For example: ● others may be able to make genetic medicine products that are similar to any product candidates we may develop but that are not covered by the intellectual property, including the claims of the patents, that we own or license currently or in the future; ● we, or our license partners or current or future collaborators, might not have been the first to make the inventions covered by the issued patent or pending patent application that we own or license currently or in the future; ● we, or our license partners or current or future collaborators, might not have been the first to file patent applications covering certain of our or their inventions; ● others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing, misappropriating or otherwise violating our owned or licensed intellectual property rights; ● it is possible that our or our licensors’ current or future pending patent applications will not lead to issued patents; ● issued patents that we hold rights to may be held invalid or unenforceable, including as a result of legal challenges by third parties; ● third parties might conduct research and development activities in jurisdictions where we do not have patent or other intellectual property rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; ● we may not develop additional proprietary technologies that are patentable; ● the patents or other intellectual property rights of others may have an adverse effect on our business; and ● we may choose not to file a patent for certain trade secrets or know-how, and a third party may subsequently file a patent covering such intellectual property.
For example: ● others may be able to make products that are similar to any product candidates we may develop but that are not covered by the intellectual property, including the claims of the patents, that we own or license currently or in the future; ● we, or our license partners or current or future collaborators, might not have been the first to make the inventions covered by the issued patent or pending patent application that we own or license currently or in the future; ● we, or our license partners or current or future collaborators, might not have been the first to file patent applications covering certain of our or their inventions; ● others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing, misappropriating or otherwise violating our owned or licensed intellectual property rights; ● it is possible that our or our licensors’ current or future pending patent applications will not lead to issued patents; ● issued patents that we hold rights to may be held invalid or unenforceable, including as a result of legal challenges by third parties; ● third parties might conduct research and development activities in jurisdictions where we do not have patent or other intellectual property rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; ● we may not develop additional proprietary technologies that are patentable; ● the patents or other intellectual property rights of others may have an adverse effect on our business; and ● we may choose not to file a patent for certain trade secrets or know-how, and a third party may subsequently file a patent covering such intellectual property.
The success of product candidates we may identify and develop will depend on many factors, including the following: ● timely and successful completion of IND-enabling preclinical studies, including toxicology studies, biodistribution studies and minimally efficacious dose studies in animals, where applicable; ● effective IND applications or comparable foreign applications that allow commencement of our planned clinical trials or future clinical trials for any product candidates we may develop; ● successful enrollment and completion of clinical trials, including under the FDA’s GCPs, cGLPs, and any additional regulatory requirements from foreign regulatory authorities; ● positive results from our future clinical programs that support a finding of safety and effectiveness and an acceptable risk-benefit profile in the intended populations of any product candidates we may develop; ● receipt of marketing approvals from applicable regulatory authorities; ● establishment of arrangements through our own facilities or with third-party manufacturers for clinical supply and, where applicable, commercial manufacturing capabilities that satisfy cGMP requirements; ● establishment, maintenance, defense and enforcement of patent, trademark, trade secret and other intellectual property protection or non-patent regulatory exclusivity for any product candidates we may develop; ● commercial launch of any product candidates we may develop, if approved, whether alone or in collaboration with others; 51 Table of Contents ● acceptance of the benefits and use of any product candidates we may develop, including method of administration, if and when approved, by patients, the medical community and third-party payers; ● effective competition with other therapies; ● maintenance of a continued acceptable safety, tolerability and efficacy profile of any product candidates we may develop following approval; and ● establishment and maintenance of healthcare insurance coverage and adequate reimbursement by payers.
The success of product candidates we may identify and develop will depend on many factors, including the following: ● timely and successful completion of IND-enabling preclinical studies, including toxicology studies, biodistribution studies and minimally efficacious dose studies in animals, where applicable; ● effective IND applications or comparable foreign applications that allow commencement of our planned clinical trials or future clinical trials for any product candidates we may develop; ● successful enrollment and completion of clinical trials, including under the FDA’s GCPs, cGLPs, and any additional regulatory requirements from foreign regulatory authorities; ● positive results from our future clinical programs that support a finding of safety and effectiveness and an acceptable risk-benefit profile in the intended populations of any product candidates we may develop; ● receipt of marketing approvals from applicable regulatory authorities; ● establishment of arrangements through our own facilities or with third-party manufacturers for clinical supply and, where applicable, commercial manufacturing capabilities that satisfy cGMP requirements; ● establishment, maintenance, defense and enforcement of patent, trademark, trade secret and other intellectual property protection or non-patent regulatory exclusivity for any product candidates we may develop; ● commercial launch of any product candidates we may develop, if approved, whether alone or in collaboration with others; ● acceptance of the benefits and use of any product candidates we may develop, including method of administration, if and when approved, by patients, the medical community and third-party payers; ● effective competition with other therapies; ● maintenance of a continued acceptable safety, tolerability and efficacy profile of any product candidates we may develop following approval; and ● establishment and maintenance of healthcare insurance coverage and adequate reimbursement by payers.
The degree of market acceptance of any product candidates we may develop, if approved for commercial sale, will depend on a number of factors, including: ● the efficacy and safety of such product candidates as demonstrated in clinical trials; ● the potential advantages and limitations compared to alternative treatments; ● the effectiveness of sales and marketing efforts; ● the cost of treatment in relation to alternative treatments; ● the clinical indications for which the product is approved; ● the convenience and ease of administration compared to alternative treatments; ● the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies; ● the strength of marketing and distribution support; ● the timing of market introduction of competitive products; 69 Table of Contents ● the availability of third-party coverage and adequate reimbursement; ● the prevalence and severity of any side effects; and ● any restrictions on the use of our products, if approved, together with other medications.
The degree of market acceptance of any product candidates we may develop, if approved for commercial sale, will depend on a number of factors, including: ● the efficacy and safety of such product candidates as demonstrated in clinical trials; ● the potential advantages and limitations compared to alternative treatments; 66 Table of Contents ● the effectiveness of sales and marketing efforts; ● the cost of treatment in relation to alternative treatments; ● the clinical indications for which the product is approved; ● the convenience and ease of administration compared to alternative treatments; ● the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies; ● the strength of marketing and distribution support; ● the timing of market introduction of competitive products; ● the availability of third-party coverage and adequate reimbursement; ● the prevalence and severity of any side effects; and ● any restrictions on the use of our products, if approved, together with other medications.
Disputes may arise regarding intellectual property subject to a licensing agreement, including: ● the scope of rights granted under the license agreement and other interpretation-related issues; ● our or our licensors’ ability to obtain, maintain and defend intellectual property and to enforce intellectual property rights against third parties; ● the extent to which our technology, product candidates and processes infringe, misappropriate or otherwise violate the intellectual property of the licensor that is not subject to the license agreement; 75 Table of Contents ● the sublicensing of patent and other intellectual property rights under our license agreements; ● our diligence, development, regulatory, commercialization, financial or other obligations under the license agreement and what activities satisfy those diligence obligations; ● the inventorship and ownership of inventions and know-how resulting from the joint creation or use of intellectual property by our current or future licensors and us and our partners; and ● the priority of invention of patented technology.
Disputes may arise regarding intellectual property subject to a licensing agreement, including: ● the scope of rights granted under the license agreement and other interpretation-related issues; ● our or our licensors’ ability to obtain, maintain and defend intellectual property and to enforce intellectual property rights against third parties; ● the extent to which our technology, product candidates and processes infringe, misappropriate or otherwise violate the intellectual property of the licensor that is not subject to the license agreement; ● the sublicensing of patent and other intellectual property rights under our license agreements; ● our diligence, development, regulatory, commercialization, financial or other obligations under the license agreement and what activities satisfy those diligence obligations; ● the inventorship and ownership of inventions and know-how resulting from the joint creation or use of intellectual property by our current or future licensors and us and our partners; and 72 Table of Contents ● the priority of invention of patented technology.
Our restated certificate of incorporation provides that, unless we consent in writing to the selection of an alternative forum, the Court of Chancery of the State of Delaware (or, if the Court of Chancery of the State of Delaware does not have 109 Table of Contents jurisdiction, the federal district court for the District of Delaware) will be the sole and exclusive forum for the following types of proceedings: ● any derivative action or proceeding brought on our behalf; ● any action asserting a claim of breach of a fiduciary duty owed by any of our directors, officers, employees or stockholders to our company or our stockholders; ● any action asserting a claim arising pursuant to any provision of the DGCL or as to which the DGCL confers jurisdiction on the Court of Chancery of the State of Delaware; or ● any action asserting a claim arising pursuant to any provision of our restated certificate of incorporation or amended and restated bylaws (in each case, as they may be amended from time to time) or governed by the internal affairs doctrine.
Our restated certificate of incorporation provides that, unless we consent in writing to the selection of an alternative forum, the Court of Chancery of the State of Delaware (or, if the Court of Chancery of the State of Delaware does not have 105 Table of Contents jurisdiction, the federal district court for the District of Delaware) will be the sole and exclusive forum for the following types of proceedings: ● any derivative action or proceeding brought on our behalf; ● any action asserting a claim of breach of a fiduciary duty owed by any of our directors, officers, employees or stockholders to our company or our stockholders; ● any action asserting a claim arising pursuant to any provision of the DGCL or as to which the DGCL confers jurisdiction on the Court of Chancery of the State of Delaware; or ● any action asserting a claim arising pursuant to any provision of our restated certificate of incorporation or amended and restated bylaws (in each case, as they may be amended from time to time) or governed by the internal affairs doctrine.
There is also a risk that future acquisitions will result in the incurrence of debt, contingent liabilities, amortization expenses or incremental operating expenses, any of which could harm our financial condition or results of operations. 103 Table of Contents Our internal information technology systems, or those of our third-party vendors, collaborators or other contractors or consultants, may fail or suffer security breaches, loss or leakage of data and other disruptions, which could result in a material disruption of our product development programs, compromise sensitive information related to our business or prevent us from accessing critical information, potentially exposing us to liability or otherwise adversely affecting our business.
There is also a risk that future acquisitions will result in the incurrence of debt, contingent liabilities, amortization expenses or incremental operating expenses, any of which could harm our financial condition or results of operations. 99 Table of Contents Our internal information technology systems, or those of our third-party vendors, collaborators or other contractors or consultants, may fail or suffer security breaches, loss or leakage of data and other disruptions, which could result in a material disruption of our product development programs, compromise sensitive information related to our business or prevent us from accessing critical information, potentially exposing us to liability or otherwise adversely affecting our business.
The process by which we identify and disclose product candidates may fail to yield product candidates for clinical development for a number of reasons, including those discussed in these risk factors and also: ● we may not be able to assemble sufficient resources to acquire or discover product candidates; ● competitors may develop alternatives that render our potential product candidates obsolete or less attractive; ● potential product candidates we develop may nevertheless be covered by third parties’ patents or other intellectual property rights; ● potential product candidates may, on further study, be shown to have harmful side effects, toxicities or other characteristics that indicate that they are unlikely to be products that will receive marketing approval and achieve market acceptance; ● potential product candidates may not be effective in treating their targeted diseases or disorders; ● the market for a potential product candidate may change so that the continued development of that product candidate is no longer reasonable; ● a potential product candidate may not be capable of being produced in commercial quantities at an acceptable cost, or at all; or ● the regulatory pathway for a potential product candidate may be too complex and difficult to navigate successfully or economically.
The process by which we identify and disclose product candidates may fail to yield product candidates for clinical development for a number of reasons, including those discussed in these risk factors and also: ● we may not be able to assemble sufficient resources to acquire or discover product candidates; ● competitors may develop alternatives that render our potential product candidates obsolete or less attractive; ● potential product candidates we develop may nevertheless be covered by third parties’ patents or other intellectual property rights; ● potential product candidates may, on further study, be shown to have harmful side effects, toxicities or other characteristics that indicate that they are unlikely to be products that will receive marketing approval and achieve market acceptance; ● potential product candidates may not be effective in treating their targeted diseases or disorders; 56 Table of Contents ● the market for a potential product candidate may change so that the continued development of that product candidate is no longer reasonable; ● a potential product candidate may not be capable of being produced in commercial quantities at an acceptable cost, or at all; or ● the regulatory pathway for a potential product candidate may be too complex and difficult to navigate successfully or economically.
Furthermore, any such event that leads to unauthorized access, use, or disclosure of personal information, including personal information regarding our customers or employees, could harm our reputation, compel us to comply with federal and/or state breach notification laws and foreign law equivalents, subject us to mandatory corrective action, and otherwise subject us to liability under laws and regulations that protect the privacy and security of personal information, which could result in significant legal and financial exposure and reputational damages. 104 Table of Contents Any of the above could have a material adverse effect on our business, financial condition, results of operations or prospects.
Furthermore, any such event that leads to unauthorized access, use, or disclosure of personal information, including personal information regarding our customers or employees, could harm our reputation, compel us to comply with federal and/or state breach notification laws and foreign law equivalents, subject us to mandatory corrective action, and otherwise subject us to liability under laws and regulations that protect the privacy and security of personal information, which could result in significant legal and financial exposure and reputational damages. 100 Table of Contents Any of the above could have a material adverse effect on our business, financial condition, results of operations or prospects.
For drugs and biologics that have been designated as breakthrough therapies, interaction and communication between the FDA and the sponsor of the trial can help to identify the most efficient path for clinical development while minimizing the number of patients placed in ineffective control regimens. 89 Table of Contents Additionally, a product is eligible for RMAT designation if it is intended to treat, modify, reverse or cure a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the product candidate has the potential to address unmet medical needs for such disease or condition.
For drugs and biologics that have been designated as breakthrough therapies, interaction and communication between the FDA and the sponsor of the trial can help to identify the most efficient path for clinical development while minimizing the number of patients placed in ineffective control regimens. 85 Table of Contents Additionally, a product is eligible for RMAT designation if it is intended to treat, modify, reverse or cure a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the product candidate has the potential to address unmet medical needs for such disease or condition.
Accordingly, in the event of contamination or injury, we could be held liable for damages or be penalized with fines in an amount exceeding our resources, and our clinical trials or regulatory approvals could be suspended, which could have a material adverse effect on our business, financial condition, results of operations and prospects. 85 Table of Contents In addition, we may incur substantial costs in order to comply with current or future environmental, health and safety laws, regulations and permitting requirements.
Accordingly, in the event of contamination or injury, we could be held liable for damages or be penalized with fines in an amount exceeding our resources, and our clinical trials or regulatory approvals could be suspended, which could have a material adverse effect on our business, financial condition, results of operations and prospects. 82 Table of Contents In addition, we may incur substantial costs in order to comply with current or future environmental, health and safety laws, regulations and permitting requirements.
We may from time to time depend on single-source suppliers for some of the components and materials used in, space necessary for and manufacturing processes required to develop our development candidates and investigational medicines.
We may from time to time depend on single-source suppliers for some of the components and materials used in, space necessary for and manufacturing processes required to develop our future development candidates and investigational medicines.
The exclusivity period in the European Union can be reduced to six years if a product no longer meets the criteria for orphan drug designation, in particular if the product is sufficiently profitable so that market exclusivity is no longer justified. 90 Table of Contents In order for the FDA to grant orphan drug exclusivity to one of our products, the agency must find that the product is indicated for the treatment of a condition or disease with a patient population of fewer than 200,000 individuals annually in the United States.
The exclusivity period in the European Union can be reduced to six years if a product no longer meets the criteria for orphan drug designation, in particular if the product is sufficiently profitable so that market exclusivity is no longer justified. 86 Table of Contents In order for the FDA to grant orphan drug exclusivity to one of our products, the agency must find that the product is indicated for the treatment of a condition or disease with a patient population of fewer than 200,000 individuals annually in the United States.
We may from time to time be dependent on single-source suppliers for some of the components and materials used in, and the space and processes required to develop, our development candidates and investigational medicines.
We may from time to time be dependent on single-source suppliers for some of the components and materials used in, and the space and processes required to develop, our future development candidates and investigational medicines.
We and our licensors have sought, and will seek, to protect our proprietary position by filing patent applications in the United States and abroad related to certain technologies and our platforms that are important to our business.
We and our licensors have sought, and will seek, to protect our proprietary position by filing patent applications in the United States and abroad related to certain technologies that are important to our business.
Consequently, we would not be able to prevent any third party from using any of our technology that is in the public domain to compete with our product candidates. 73 Table of Contents The patent position of biotechnology and pharmaceutical companies generally is highly uncertain, involves complex legal and factual questions and has, in recent years, been the subject of much litigation.
Consequently, we would not be able to prevent any third party from using any of our technology that is in the public domain to compete with our product candidates. 70 Table of Contents The patent position of biotechnology and pharmaceutical companies generally is highly uncertain, involves complex legal and factual questions and has, in recent years, been the subject of much litigation.
The IRA in particular includes a one percent excise tax imposed on certain stock repurchases by publicly 108 Table of Contents traded companies, which generally applies to any acquisition of stock by the publicly traded company (or certain of its affiliates) from a stockholder of the company in exchange for money or other property (other than stock of the company itself), subject to a de minimis exception.
The IRA in particular includes a one percent excise tax imposed on certain stock repurchases by publicly 104 Table of Contents traded companies, which generally applies to any acquisition of stock by the publicly traded company (or certain of its affiliates) from a stockholder of the company in exchange for money or other property (other than stock of the company itself), subject to a de minimis exception.
The expansion of our operations may lead to significant costs and may divert our management and business development resources. Any inability to achieve and manage our future growth could delay the execution of our business plans or disrupt our operations. We are actively pursuing new platforms and product candidates in many therapeutic areas and across a wide range of diseases.
The expansion of our operations may lead to significant costs and may divert our management and business development resources. Any inability to achieve and manage our future growth could delay the execution of our business plans or disrupt our operations. We are actively pursuing new technologies and product candidates in many therapeutic areas and across a wide range of diseases.
We currently rely, and expect to continue to rely, on third parties with respect to many of these items, including CMOs for the manufacturing of any product candidates we test in preclinical or clinical development, cleanroom facilities to provide space to manufacture our drug substance, and CROs for the conduct of our animal testing and research.
We currently rely, and expect to continue to rely, on third parties with respect to many of these items, including CMOs for the manufacturing of any product candidates we test in preclinical or clinical development, cleanroom facilities to provide space to manufacture our drug substance, and contract research organizations, or CROs, for the conduct of our animal testing and research.
Further, on November 20, 2020, the HHS finalized a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Medicare Part D, which is a program available to individuals who are entitled to Medicare Part A or enrolled in Medicare Part B to give them the option of paying a monthly premium for outpatient prescription drug coverage, either directly or through pharmacy benefit managers, unless the price reduction is required by law.
Further, on November 20, 2020, the HHS finalized a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Medicare Part D, which is a program available to individuals who are entitled to Medicare Part A or enrolled in Medicare Part B to give them the option of paying a monthly premium for 92 Table of Contents outpatient prescription drug coverage, either directly or through pharmacy benefit managers, unless the price reduction is required by law.
Our ability to stop third parties from making, using, selling, marketing, offering to sell, importing and commercializing any product candidates we may develop and our technology is dependent upon the extent to which we have rights under valid and enforceable patents and other intellectual property that cover our platforms and technology.
Our ability to stop third parties from making, using, selling, marketing, offering to sell, importing and commercializing any product candidates we may develop and our technology is dependent upon the extent to which we have rights under valid and enforceable patents and other intellectual property that cover our technologies.
Moreover, in 2012, the USPTO issued a guidance memo to patent examiners indicating that process claims directed to a law of nature, a natural phenomenon or a naturally occurring relation or correlation that do not include additional elements or steps that integrate the natural principle into the claimed invention such that the natural principle is practically applied and the claim amounts to 82 Table of Contents significantly more than the natural principle itself should be rejected as directed to patent-ineligible subject matter.
Moreover, in 2012, the USPTO issued a guidance memo to patent examiners indicating that process claims directed to a law of nature, a natural phenomenon or a naturally occurring relation or correlation that do not include additional elements or steps that integrate the natural principle into the claimed invention such that the natural principle is practically applied and the claim amounts to significantly more than the natural principle itself should be rejected as directed to patent-ineligible subject matter.
Any of the foregoing could 106 Table of Contents 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. Furthermore, our stock price may decline due in part to the volatility of the stock market and any general economic downturn.
Any of the foregoing could 102 Table of Contents 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. Furthermore, our stock price may decline due in part to the volatility of the stock market and any general economic downturn.
We may require more time and incur greater costs than our competitors and may not succeed in obtaining regulatory approvals of product candidates that we may develop. Failure to commence or complete, or delays in, our clinical trials could prevent us from or delay us in commercializing our product candidates.
We may require more time and incur greater costs than our competitors and may not succeed in obtaining regulatory approvals for product candidates that we may develop. Failure to commence or complete, or delays in, our clinical trials could prevent us from or delay us in commercializing our product candidates.
As a result, our owned and licensed patent and other intellectual property rights may not provide us with sufficient rights to 74 Table of Contents exclude others from commercializing products similar or identical to our technology and any product candidates we may develop.
As a result, our owned and licensed patent and other intellectual property rights may not provide us with sufficient rights to 71 Table of Contents exclude others from commercializing products similar or identical to our technology and any product candidates we may develop.
Further, we could face heightened risks with respect to obtaining marketing authorization in the United Kingdom as a result of the withdrawal of the United Kingdom from the European Union, commonly referred to as Brexit. The United Kingdom is no longer part of the European Single Market and EU Customs Union.
Additionally, we could face heightened risks with respect to obtaining marketing authorization in the United Kingdom as a result of the withdrawal of the United Kingdom from the European Union, commonly referred to as Brexit. The United Kingdom is no longer part of the European Single Market and EU Customs Union.
If third parties do not successfully carry out their contractual duties, meet expected deadlines or conduct our studies in accordance with regulatory requirements or our stated study plans and protocols, we will not be able to complete, or may 64 Table of Contents be delayed in completing, the preclinical studies and clinical trials required to support future IND submissions and approval of any product candidates we may develop.
If third parties do not successfully carry out their contractual duties, meet expected deadlines or conduct our studies in accordance with regulatory requirements or our stated study plans and protocols, we will not be able to complete, or may be delayed in completing, the preclinical studies and clinical trials required to support future IND submissions and approval of any product candidates we may develop.
If our CROs or CLROs do not successfully carry out their contractual duties or obligations, fail to meet expected deadlines, or if the quality or accuracy of the data they obtain is compromised due to the failure to adhere to our protocols or regulatory requirements, or for any other reasons, our studies may be extended, delayed or terminated, and we may not be able to obtain regulatory approval 65 Table of Contents for, or successfully commercialize any product candidates we may develop.
If our CROs or CLROs do not successfully carry out their contractual duties or obligations, fail to meet expected deadlines, or if the quality or accuracy of the data they obtain is compromised due to the failure to adhere to our protocols or regulatory requirements, or for any other reasons, our studies may be extended, delayed or terminated, and we may not be able to obtain regulatory approval for, or successfully commercialize any product candidates we may develop.
We are in the early stage of research in the development of our platforms and have not identified any product candidates or conducted any IND-enabling studies or any clinical trials. As a result, our belief in the capabilities of our platforms is based on early research and preclinical studies.
We are in the early stage of research in the development of our technologies and have not identified any product candidates or conducted any IND-enabling studies or any clinical trials. As a result, our belief in the capabilities of our technologies is based on early research and preclinical studies.
Risks related to our dependence on third parties We currently depend on a small number of third-party suppliers for our drug substance and drug product, and we expect to continue to depend on third-party suppliers for materials used in the manufacture of any product candidates we may develop, and the loss of these third-party suppliers or their inability to supply us with adequate materials, particularly those raw materials that are in short supply, could harm our business.
Risks related to our dependence on third parties We currently depend on a small number of third-party suppliers for our research materials, and we expect to continue to depend on third-party suppliers for materials used in the manufacture of any product candidates we may develop, and the loss of these third-party suppliers or their inability to supply us with adequate materials, particularly those raw materials that are in short supply, could harm our business.
In particular, the Tax Act, as amended by the CARES Act, reduces the corporate tax rate from a top marginal rate of 35% to a flat rate of 21% and imposes a limit on the deduction for net operating losses arising in taxable years beginning after December 31, 2017 to 80% of current year taxable income (though any such net operating losses may be carried forward indefinitely).
In particular, the Tax Act, as amended by the CARES Act, reduces the corporate tax rate from a top marginal rate of 35% to a flat rate of 21%, for taxable year beginning after December 31, 2020, and imposed a limit on the deduction for net operating losses arising in taxable years beginning after December 31, 2017 to 80% of current year taxable income (though any such net operating losses may be carried forward indefinitely).
Any of the foregoing could have a material effect on our financial position and materially harm our business. Risks related to commercialization We face substantial competition, which may result in others discovering, developing or commercializing products before us or more successfully than we do. The development and commercialization of new drug products is highly competitive.
Any of the foregoing could have a material effect on our financial position and materially harm our business. 65 Table of Contents Risks related to commercialization We face substantial competition, which may result in others discovering, developing or commercializing products before us or more successfully than we do. The development and commercialization of new drug products is highly competitive.
Our efforts to enforce or protect our proprietary rights related to trademarks, trade secrets, domain names, copyrights or other intellectual property may be ineffective and could result in substantial costs and diversion of resources. Any of the foregoing could have a material adverse effect on our business, financial condition, results of operations or prospects.
Our efforts to enforce or protect our proprietary rights related to trademarks, trade secrets, domain names, copyrights or other intellectual property may be ineffective and could result in substantial 80 Table of Contents costs and diversion of resources. Any of the foregoing could have a material adverse effect on our business, financial condition, results of operations or prospects.
Even when assays are developed, they may need to be further tested, qualified and validated, which may take substantial time and resources. Because of the lagging nature of analytical testing, we may proceed with additional manufacturing and other development activities 61 Table of Contents without having first fully characterized our manufactured materials.
Even when assays are developed, they may need to be further tested, qualified and validated, which may take substantial time and resources. Because of the lagging nature of analytical testing, we may proceed with additional manufacturing and other development activities without having first fully characterized our manufactured materials.
Components of a finished therapeutic product approved for commercial sale or used in late-stage clinical trials must be manufactured in accordance with cGMP. These regulations govern manufacturing processes and procedures (including record keeping) and the implementation and operation of quality systems to control and assure the quality of investigational products and products approved for sale.
Components of a finished therapeutic product approved for commercial sale or used in late-stage clinical trials must be manufactured in accordance with cGMP. These regulations govern manufacturing processes and procedures (including record keeping) and the implementation and operation of quality systems to control and assure the quality of investigational products and products 59 Table of Contents approved for sale.
The FCPA also obligates companies whose securities are listed in the United States to comply with certain accounting provisions requiring the company to maintain books and records that accurately and fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations.
The FCPA also obligates companies whose securities are listed in the United States to comply with certain accounting provisions requiring 94 Table of Contents the company to maintain books and records that accurately and fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations.
Competitors or third parties could purchase any product candidates we may develop or our technology and attempt to replicate some or all of the competitive advantages we derive from our development efforts, willfully infringe our intellectual property rights, design around our intellectual property rights or develop their own competitive technologies that fall outside the scope of our intellectual property rights.
Competitors or third parties could purchase any product candidates we may develop or our technology and attempt 76 Table of Contents to replicate some or all of the competitive advantages we derive from our development efforts, willfully infringe our intellectual property rights, design around our intellectual property rights or develop their own competitive technologies that fall outside the scope of our intellectual property rights.
In addition, beginning in 2022, the Tax Act eliminates the option to deduct research and development expenditures currently and requires corporations to capitalize and amortize them over five years or fifteen years (for expenditures attributable to foreign research).
In addition, beginning in 2022, the Tax Act eliminated the option to deduct research and development expenditures currently and requires corporations to capitalize and amortize them over five years or fifteen years (for expenditures attributable to foreign research).
In addition, state NOLs generated in one state cannot be used to offset income generated in another state. For these reasons, even if we attain profitability, we may be unable to use a material portion of our NOLs and other tax attributes. 50 Table of Contents Risks related to discovery and development We are very early in our development efforts.
In addition, state NOLs generated in one state cannot be used to offset income generated in another state. For these reasons, even if we attain profitability, we may be unable to use a material portion of our NOLs and other tax attributes. Risks related to discovery and development We are very early in our development efforts.
To obtain reimbursement or pricing approval in some countries, we may be required to conduct a clinical trial that compares the cost-effectiveness of our product candidate to other available therapies. In general, the prices of products under such systems are substantially lower than in the United States.
To obtain reimbursement 67 Table of Contents or pricing approval in some countries, we may be required to conduct a clinical trial that compares the cost-effectiveness of our product candidate to other available therapies. In general, the prices of products under such systems are substantially lower than in the United States.
If we are not able to expand our genetic medicine capabilities, we may not be able to develop in the way we intend or desire any promising product candidates that emerge from our program or our other collaborative genetic medicine sponsored research programs, which would limit our prospects for future growth.
If we are not able to expand our nucleic acid therapy capabilities, we may not be able to develop in the way we intend or desire any promising product candidates that emerge from our program or our other collaborative genetic medicine sponsored research programs, which would limit our prospects for future growth.
In addition, under some relatively recent guidance from the FDA and the PIE Act, companies may also promote information that is consistent with the prescribing information and proactively speak to formulary committee members of payors regarding data for an unapproved drug or unapproved uses of an approved drug.
In addition, under some relatively recent guidance from the FDA and the PIE Act, companies may also promote information that is consistent with the prescribing information 89 Table of Contents and proactively speak to formulary committee members of payors regarding data for an unapproved drug or unapproved uses of an approved drug.
If a prolonged government shutdown occurs, it could significantly impact the ability of the FDA to timely review and process 94 Table of Contents our regulatory submissions, which could have a material adverse effect on our business. In addition, disruptions may result from events similar to the COVID-19 pandemic.
If a prolonged government shutdown occurs, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions, which could have a material adverse effect on our business. In addition, disruptions may result from events similar to the COVID-19 pandemic.
The regulatory approval process for novel product candidates can be more expensive and take longer than for other, better known or extensively studied pharmaceutical or other product candidates, and even more so for product candidates intended to treat diseases for which there are approved therapies that may allow a normal life span as compared with those intended to treat serious and life-threatening diseases for which there are no other treatment options available.
The regulatory approval process for novel product candidates can be more expensive and take longer than for other, better known or extensively studied pharmaceutical or other product candidates, and even more so for product candidates intended to treat diseases for which 54 Table of Contents there are approved therapies that may allow a normal life span as compared with those intended to treat serious and life-threatening diseases for which there are no other treatment options available.
Furthermore, in March 2023 we entered into a Collaboration Agreement with Moderna pursuant to which each party granted to the other a worldwide, non-exclusive, sublicensable license under certain LNP-related intellectual property arising out of the non-liver ctLNP program to be developed under the Collaboration Agreement.
For example, in March 2023 we entered into a Collaboration Agreement with Moderna pursuant to which each party granted to the other a worldwide, non-exclusive, sublicensable license under certain LNP-related intellectual property arising out of the non-liver ctLNP program to be developed under the Collaboration Agreement.
Any of these events could have a material adverse effect on our competitive position, business, financial conditions, results of operations and prospects. 76 Table of Contents Furthermore, our owned and in-licensed patent rights may be subject to a reservation of rights by one or more third parties.
Any of these events could have a material adverse effect on our competitive position, business, financial conditions, results of operations and prospects. Furthermore, our owned and in-licensed patent rights may be subject to a reservation of rights by one or more third parties.
Moreover, even when we obtain agreements assigning intellectual property to us, the assignment of intellectual property rights may not be self-executing or the assignment agreements may be breached, and we may be forced to bring claims against third parties, or defend claims that they may bring against us, to determine the ownership of what we regard as our intellectual property.
Moreover, even when we obtain agreements assigning intellectual property to us, the assignment of 78 Table of Contents intellectual property rights may not be self-executing or the assignment agreements may be breached, and we may be forced to bring claims against third parties, or defend claims that they may bring against us, to determine the ownership of what we regard as our intellectual property.
Even if we are not determined to have violated these laws, government investigations into these issues 101 Table of Contents typically require the expenditure of significant resources and generate negative publicity, which could harm our reputation and our business, financial condition, results of operations or prospects.
Even if we are not determined to have violated these laws, government investigations into these issues typically require the expenditure of significant resources and generate negative publicity, which could harm our reputation and our business, financial condition, results of operations or prospects.
It is often the case that early-stage process development is conducted with materials that are not manufactured using cGMP starting materials, techniques or processes and which are not subject to the same level of analysis that would be required for clinical grade material.
It is often the case that early-stage process 58 Table of Contents development is conducted with materials that are not manufactured using cGMP starting materials, techniques or processes and which are not subject to the same level of analysis that would be required for clinical grade material.
Any 63 Table of Contents performance failure on the part of our suppliers could delay the development and potential commercialization of any product candidates we may develop, including limiting supplies necessary for clinical trials and regulatory approvals, which would have a material adverse effect on our business.
Any performance failure on the part of our suppliers could delay the development and potential commercialization of any product candidates we may develop, including limiting supplies necessary for clinical trials and regulatory approvals, which would have a material adverse effect on our business.
Any product candidate for which we obtain marketing approval, along with the manufacturing processes, post-approval clinical data, labeling, advertising and promotional activities for such medicine, will be subject to continual requirements of and review by the FDA and other regulatory authorities.
Any product candidate for which we obtain marketing approval, along with the manufacturing processes, post-approval clinical data, labeling, advertising and promotional activities for such medicine, will be subject to continual requirements 87 Table of Contents of and review by the FDA and other regulatory authorities.
For example, in December 2022, with the passage of FDORA, Congress required sponsors to develop and submit a diversity action plan for each Phase 3 clinical trial or any other “pivotal study” of a new drug or biological product. These plans are meant to encourage the enrollment of more diverse patient populations in late-stage clinical trials of FDA regulated products.
For example, in December 2022, with the passage of FDORA, Congress required sponsors to develop and submit a DAP for each Phase 3 clinical trial or any other “pivotal study” of a new drug or biological product. These plans are meant to encourage the enrollment of more diverse patient populations in late-stage clinical trials of FDA regulated products.
The downward pressure on healthcare costs in general, particularly 70 Table of Contents prescription drugs and surgical procedures and other treatments, has become very intense. As a result, increasingly high barriers are being erected to the entry of new products into the healthcare market.
The downward pressure on healthcare costs in general, particularly prescription drugs and surgical procedures and other treatments, has become very intense. As a result, increasingly high barriers are being erected to the entry of new products into the healthcare market.
A loss of key personnel or their work product could hamper or prevent our ability to commercialize any product candidates we may develop and our technology, which would have a material adverse effect on our business, results of operations, financial condition and 81 Table of Contents prospects.
A loss of key personnel or their work product could hamper or prevent our ability to commercialize any product candidates we may develop and our technology, which would have a material adverse effect on our business, results of operations, financial condition and prospects.
Failure to comply with laws regarding data protection would expose us to risk of enforcement actions taken by data protection authorities in the EEA and elsewhere and carries with it the potential for significant penalties if we are found to be non-compliant.
Failure to comply with laws regarding data protection would expose us to risk of enforcement actions taken by data protection authorities in the EEA and elsewhere 97 Table of Contents and carries with it the potential for significant penalties if we are found to be non-compliant.
At the state level, individual states are increasingly aggressive in passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.
At the state level, individual states are increasingly aggressive in passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, 93 Table of Contents discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.
Furthermore, if our suppliers fail to meet contractual requirements, and we are unable to secure one or more replacement suppliers capable of production at a substantially equivalent cost, our clinical trials may be delayed or we could lose potential revenue.
Furthermore, if our suppliers fail to meet contractual requirements, and we are unable to secure one or more replacement 60 Table of Contents suppliers capable of production at a substantially equivalent cost, our clinical trials may be delayed or we could lose potential revenue.
Nevertheless, we will be responsible for ensuring that each of these studies is conducted in accordance with the applicable protocol, legal, regulatory and scientific standards, and our reliance on the CROs and CLROs does not relieve us of our regulatory responsibilities.
Nevertheless, we will be responsible for ensuring that each of these studies is conducted in accordance with the applicable 62 Table of Contents protocol, legal, regulatory and scientific standards, and our reliance on the CROs and CLROs does not relieve us of our regulatory responsibilities.
We anticipate that our expenses will increase substantially as we: ● continue our current research programs and conduct additional research programs, including pursuant to our collaboration with Moderna; ● expand the capabilities of our proprietary non-viral genetic medicine platforms; ● advance any product candidates we identify into preclinical and clinical development; ● obtain, expand, maintain, defend and enforce our intellectual property portfolio; ● seek marketing approvals for any product candidates that successfully complete clinical trials; 46 Table of Contents ● hire additional clinical, regulatory and scientific personnel; ● establish manufacturing sources and secure supply chain capacity sufficient to provide necessary quantities of any product candidates we may develop for clinical or commercial use; ● ultimately establish a sales, marketing and distribution infrastructure to commercialize any products for which we may obtain marketing approval; and ● add operational, legal, compliance, financial and management information systems and personnel to support our research, product development, and future commercialization efforts.
We anticipate that our expenses will increase substantially as we: ● continue our current research programs and conduct additional research programs, including pursuant to our collaboration with Moderna; 45 Table of Contents ● expand the capabilities of our proprietary technologies; ● advance any product candidates we identify into preclinical and clinical development; ● obtain, expand, maintain, defend and enforce our intellectual property portfolio; ● seek marketing approvals for any product candidates that successfully complete clinical trials; ● hire additional clinical, regulatory and scientific personnel; ● establish manufacturing sources and secure supply chain capacity sufficient to provide necessary quantities of any product candidates we may develop for clinical or commercial use; ● ultimately establish a sales, marketing and distribution infrastructure to commercialize any products for which we may obtain marketing approval; and ● add operational, legal, compliance, financial and management information systems and personnel to support our research, product development, and future commercialization efforts.
Outside parties may: ● have staffing difficulties; ● fail to comply with contractual obligations; ● experience regulatory compliance issues; ● undergo changes in priorities or become financially distressed; or ● form relationships with other entities, some of which may be our competitors.
Outside parties may: ● have staffing difficulties; ● fail to comply with contractual obligations; 61 Table of Contents ● experience regulatory compliance issues; ● undergo changes in priorities or become financially distressed; or ● form relationships with other entities, some of which may be our competitors.
If we are unable to raise additional funds through equity or debt 49 Table of Contents financings or other arrangements when needed or on terms acceptable to us, we would be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.
If we are unable to raise additional funds through equity or debt financings or other arrangements when needed or on terms acceptable to us, we would be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.
Competing products, either developed by the collaborators or strategic partners or to which the collaborators or strategic partners have rights, may result in the withdrawal of partner support for our product candidates we may develop. Some of our collaborators or strategic partners could also become our competitors in the future.
Competing 64 Table of Contents products, either developed by the collaborators or strategic partners or to which the collaborators or strategic partners have rights, may result in the withdrawal of partner support for our product candidates we may develop. Some of our collaborators or strategic partners could also become our competitors in the future.
Any failure to obtain or maintain patent protection with respect to our ctLNP delivery system, iqDNA, manufacturing processes or our other product candidates and technology would have a material adverse effect on our business, financial condition, results of operations and prospects.
Any failure to obtain or maintain patent protection with respect to our ctLNP delivery system, or our other product candidates and technology would have a material adverse effect on our business, financial condition, results of operations and prospects.
Changes in tax laws or in their implementation or interpretation may adversely affect our business and financial condition. Recent changes in tax law may adversely affect our business or financial condition. On December 22, 2017, the U.S. government enacted the Tax Act, which contained significant changes to corporate taxation.
Changes in tax laws or in their implementation or interpretation may adversely affect our business and financial condition. Changes in tax law may adversely affect our business or financial condition. For example, on December 22, 2017, the U.S. government enacted the Tax Act, which contained significant changes to corporate taxation.
Moreover, preclinical and clinical data are often susceptible to varying interpretations and 57 Table of Contents analyses, and many companies that have believed their product candidates performed satisfactorily in preclinical studies and clinical trials have nonetheless failed to obtain marketing approval of their products.
Moreover, preclinical and clinical data are often susceptible to varying interpretations and analyses, and many companies that have believed their product candidates performed satisfactorily in preclinical studies and clinical trials have nonetheless failed to obtain marketing approval of their products.
We expect that current laws, as well as other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria and in additional downward pressure on the price that we, or any future collaborators, may receive for any approved products. In March 2010, the United States Congress enacted PPACA.
We expect that current laws, as well as other healthcare reform measures that may be adopted in the future, may result in more rigorous 91 Table of Contents coverage criteria and in additional downward pressure on the price that we, or any future collaborators, may receive for any approved products. In March 2010, the United States Congress enacted PPACA.
We and our CMOs may face disruptions in the future that affect our ability to initiate and complete preclinical studies and may experience procurement challenges in the event of a future global health issue. Clinical testing is expensive, is difficult to design and implement, can take many years to complete and is uncertain as to outcome.
We and our contract manufacturing organizations, or CMOs, may face disruptions in the future that affect our ability to initiate and complete preclinical studies and may experience procurement challenges in the event of a future global health issue. Clinical testing is expensive, is difficult to design and implement, can take many years to complete and is uncertain as to outcome.
Our existing license agreements, including our license agreements with the NIH and UMass, impose, and we expect that future license agreements will impose, specified diligence, milestone payment, royalty, commercialization, development and other obligations on us and require us to meet development timelines, or to exercise diligent or commercially reasonable efforts to develop and commercialize licensed products, in order to maintain the licenses.
Our existing license agreements impose, and we expect that future license agreements will impose, specified diligence, milestone payment, royalty, commercialization, development and other obligations on us and require us to meet development timelines, or to exercise diligent or commercially reasonable efforts to develop and commercialize licensed products, in order to maintain the licenses.
In the event that the FDA requires us to complete additional preclinical studies or we are required to satisfy other FDA requests prior to commencing clinical trials, the start of our first clinical trials may be delayed.
In the event that the FDA requires us to complete additional preclinical studies or we are required to satisfy other FDA requests prior to commencing clinical 49 Table of Contents trials, the start of our first clinical trials may be delayed.
Requirements by regulatory authorities for any product candidate we may develop may change in response to the availability of other therapies for the indication our product candidates are designed to treat or to issues observed in clinical trials of genetic medicines of other companies, even if using technology that differs from ours.
Requirements by regulatory authorities for any product candidate we may develop may change in response to the availability of other therapies for the indication our product candidates are designed to treat or to issues observed in clinical trials of nucleic acid therapies of other companies, even if using technology that differs from ours.
In addition, in many countries outside the United States, it is required that the product be approved for reimbursement before the product can be approved for sale in that country. We or these third parties may not obtain approvals from regulatory 88 Table of Contents authorities outside the United States on a timely basis, if at all.
In addition, in many countries outside the United States, it is required that the product be approved for reimbursement before the product can be approved for sale in that country. We or these third parties may not obtain approvals from regulatory authorities outside the United States on a timely basis, if at all.
As a result, the regulatory burden to initiate clinical trials or to obtain regulatory approval of any product candidate we may develop for those indications may be more extensive in those jurisdictions than for product candidates intended to treat diseases that are life threatening and for which no therapies are approved.
The regulatory burden to initiate clinical trials or to obtain regulatory approval of any product candidate we may develop for those indications with approved therapies may be more extensive in those jurisdictions than for product candidates intended to treat diseases that are life threatening and for which no therapies are approved.
We currently rely on a small number of third-party suppliers for our drug substance and drug product and expect to continue to rely on third-party suppliers for certain materials and components required for the production of any product candidates we may develop.
We currently rely on a small number of third-party suppliers for our research materials and expect to continue to rely on third-party suppliers for certain materials and components required for the production of any product candidates we may develop.
Whether we reach a definitive agreement for a collaboration will depend, among other things, upon our assessment of the collaborator’s resources and expertise, the terms 67 Table of Contents and conditions of the proposed collaboration, and the proposed collaborator’s evaluation of a number of factors.
Whether we reach a definitive agreement for a collaboration will depend, among other things, upon our assessment of the collaborator’s resources and expertise, the terms and conditions of the proposed collaboration, and the proposed collaborator’s evaluation of a number of factors.
The U.S. government’s rights may also permit it to disclose the funded inventions and technology, which may include our confidential information, to third parties and to exercise march-in rights to use or allow third parties to use the technology we have licensed that was developed using U.S. government funding.
The U.S. government’s rights may also permit it to 73 Table of Contents disclose the funded inventions and technology, which may include our confidential information, to third parties and to exercise march-in rights to use or allow third parties to use the technology we have licensed that was developed using U.S. government funding.
Our executive officers and directors and their affiliates, if they choose to act together, will continue to have the ability to influence matters submitted to stockholders for approval. As of February 29, 2024, our executive officers and directors and their affiliates, in the aggregate, beneficially owned shares representing approximately 21% of our common stock.
Our executive officers and directors and their affiliates, if they choose to act together, will continue to have the ability to influence matters submitted to stockholders for approval. As of February 28, 2025, our executive officers and directors and their affiliates, in the aggregate, beneficially owned shares representing approximately 21% of our common stock.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeWe consider the internal risk oversight programs of third-party service providers before engaging them in order to help protect us from any related vulnerabilities. ​ We do not believe that there are currently any known risks from cybersecurity threats that are reasonably likely to materially affect us or our business strategy, results of operations or financial condition. ​ Our Audit Committee provides direct oversight over cybersecurity risk and provides updates to the Board of Directors regarding such oversight.
Biggest changeWe consider the internal risk oversight programs of third-party service providers before engaging them in order to help protect us from any related vulnerabilities. ​ Based on an assessment using the previously described risk management program, we do not believe that there are currently any known risks from cybersecurity threats, including as a result of any prior cybersecurity incidents, that have materially affected or are reasonably likely to materially affect us or our business strategy, results of operations or financial condition.
ITEM 1C. CYBERSECURITY ​ We have certain processes for assessing, identifying and managing cybersecurity risks, which are built into our overall risk management program and overseen by our information technology function and are designed to help protect our information assets and operations from internal and external cyber threats, as well as secure our networks and systems.
ITEM 1C. CYBERSECURITY ​ We have certain processes for assessing, identifying and managing cybersecurity risks, which are built into our overall risk management program and overseen by our information technology function, that are designed to help protect our information assets and operations from internal and external cyber threats, as well as secure our networks and systems.
He began his IT career overseeing datacenter operations for a pharmaceutical company and has held multiple IT leadership positions at biotechnology companies, including serving as the director of cybersecurity and infrastructure at a biopharmaceutical company prior to joining us over three years ago. ​ We have also established a cross-functional cybersecurity working team led by our chief financial officer serving as the chair and consisting of executive-level leaders, that is responsible for reviewing, revising and testing our cybersecurity policies and procedures. ​ In an effort to deter and detect cyber threats, we regularly provide all employees, including part-time and temporary employees, with data protection, cybersecurity and incident response and prevention trainings, which cover timely and relevant topics, including social engineering, phishing, password protection, confidential data protection, asset use and mobile security, and educate employees on the importance of reporting all incidents immediately.
He began his IT career overseeing datacenter operations for a pharmaceutical company and has held multiple IT leadership positions at biotechnology companies, including serving as the director of cybersecurity and infrastructure at a biopharmaceutical company prior to joining us over four years ago. ​ We have also established a cross-functional cybersecurity working team led by our chief financial officer serving as the chair and consisting of executive-level leaders, that is responsible for reviewing, revising and testing our cybersecurity policies and procedures. ​ In an effort to deter and detect cyber threats, we regularly provide all employees, including part-time and temporary employees, with data protection, cybersecurity and incident response and prevention trainings, which cover a range of timely and relevant topics, including social engineering, phishing, password protection, confidential data protection, asset use and mobile security.
Our Senior Director of IT has 25 years of experience in building, running, and managing diverse functional areas of IT, including but not limited to enterprise cybersecurity, IT infrastructure, operations, 110 Table of Contents business continuity, and service delivery.
Our Senior Director of IT has over 25 years of experience in building, running, and managing diverse functional areas of IT, including but not limited to enterprise cybersecurity, IT infrastructure, operations, business continuity, and service delivery.
We also use technology-based tools to mitigate cybersecurity risks and to bolster our employee-based cybersecurity programs. ​ ​
This incident response and prevention training functions to educate employees on the importance of reporting all incidents immediately. We also use technology-based tools to mitigate cybersecurity risks and to bolster our employee-based cybersecurity programs. ​
Added
See “ Our internal information technology systems, or those of our third-party vendors, collaborators or other contractors or consultants, may fail or suffer security breaches, loss or leakage of data and other disruptions, which could result in a material disruption of our product development programs, compromise sensitive information related to our business or prevent us from accessing critical information, potentially exposing us to liability or otherwise adversely affecting our business ” in Part I, Item 1A, “Risk Factors” for additional information. ​ 106 Table of Contents Our Audit Committee provides direct oversight over cybersecurity risk and provides updates to the Board of Directors regarding such oversight.

Item 2. Properties

Properties — owned and leased real estate

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Biggest changeOn February 20, 2024, the landlord served us with a complaint, filed in Massachusetts Superior Court, with respect to the Seyon Lease. The complaint seeks declaratory judgment that we unlawfully terminated the Seyon Lease and also asserts a claim for breach of contract damages. Our responsive pleading is due April 1, 2024.
Biggest changeOn February 14, 2024, the Landlord sent us a notice of the termination of the Seyon Lease due to our non-payment of rent. On February 20, 2024, the Landlord served us with a complaint, filed in the Court, with respect to the Seyon Lease.
ITEM 2. PROPERTIES Our headquarters are located at 301 Binney Street, Cambridge, Massachusetts, where we occupy approximately 71,562 square feet of research and development, laboratory and office space. This lease expires in 2029. In July 2021, we entered into a 12-year operating lease to build out an approximately 104,000 square foot cGMP compliant manufacturing facility in Waltham, Massachusetts .
ITEM 2. PROPERTIES Our headquarters are located at 301 Binney Street, Cambridge, Massachusetts, where we occupy approximately 71,562 square feet of research and development, laboratory and office space. This lease expires in 2029. In July 2021, we entered into the Seyon Lease.
We will vigorously defend the action and our rights with respect to this matter. In the future, we may lease, operate, purchase or construct additional facilities in which to conduct expanded research, development and manufacturing activities and support future commercial operations.
For additional information, refer to Note 7, Leases. In the future, we may lease, operate, purchase or construct additional facilities in which to conduct expanded research, development and manufacturing activities and support future commercial operations.
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The complaint sought declaratory judgment that we unlawfully terminated the Seyon Lease and also asserted a claim for breach of contract damages. Following receipt of the complaint, we filed a counterclaim against the Landlord asserting breach of contract and violation of Massachusetts General Law Chapter 93A.
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On October 29, 2024, the Court determined that although we did not have the right to terminate the Seyon Lease, the Landlord’s subsequent termination was effective, and that we had alleged sufficient facts to state a claim for breach of contract and violation of Massachusetts General Law Chapter 93A by the Landlord.
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On January 21, 2025, the Court granted the Landlord’s motion for preliminary injunction and ordered us to pay, until further notice, monthly amounts equal to the rent and other charges that would have been due to the Landlord under the Seyon Lease had it not been terminated.
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On February 14, 2025, we filed a notice of appeal of the Court’s preliminary injunction ruling. We are continuing to make monthly payments under the Seyon Lease during the pendency of the appeal. We will continue to vigorously defend the action and prosecute our counterclaims against the Landlord with respect to this matter.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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ITEM 3. LEGAL PROCEEDINGS From time to time, we may be subject to legal proceedings and claims in the ordinary course of business. We were not subject to any material legal proceedings during the years ended December 31, 2023 and 2022. ​ ITEM 4. MINE SAFETY DISCLOSURES Not applicable. ​ 111 Table of Contents PART II
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ITEM 3. LEGAL PROCEEDINGS We, from time to time, may be party to litigation arising in the ordinary course of business. On February 20, 2024, the Landlord served us with a complaint, filed in the Court with respect to the Seyon Lease.
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The complaint sought declaratory judgment that we unlawfully terminated the Seyon Lease and also asserted a claim for breach of contract damages. Following receipt of the complaint, we filed a counterclaim against the Landlord asserting breach of contract and violation of Massachusetts General Law Chapter 93A.
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On October 29, 2024, the Court determined that although we did not have 107 Table of Contents the right to terminate the Seyon Lease, the Landlord’s subsequent termination was effective, and that we had alleged sufficient facts to state a claim for breach of contract and violation of Massachusetts General Law Chapter 93A by the Landlord.
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On January 21, 2025, the Court granted the Landlord’s motion for preliminary injunction and ordered us to pay, until further notice, monthly amounts equal to the rent and other charges that would have been due to the Landlord under the Seyon Lease had it not been terminated.
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On February 14, 2025, we filed a notice of appeal of the Court’s preliminary injunction ruling. We are continuing to make monthly payments under the Seyon Lease during the pendency of the appeal. We will continue to vigorously defend the action and prosecute our counterclaims against the Landlord with respect to this matter.
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As a result, we may continue to incur costs and expenses relating to this facility, and we may remain responsible for payments under the Seyon Lease, which may have a material adverse effect on our business, results of operations or financial condition. ​ ​ ITEM 4. MINE SAFETY DISCLOSURES Not applicable. ​ 108 Table of Contents PART II

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeThe stockholder return shown on the graph below is not necessarily indicative of future performance, and we do not make or endorse any predictions as to future stockholder return. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ 6/12/2020 12/31/2020 ​ 12/31/2021 ​ 12/31/2022 ​ 12/31/2023 Generation Bio Co. ​ $ 100 ​ $ 115 ​ $ 29 ​ $ 16 ​ $ 7 Nasdaq Composite Total Return (IXIC) ​ $ 100 ​ $ 134 ​ $ 163 ​ $ 109 ​ $ 157 Nasdaq Biotechnology Total Return (NBI) ​ $ 100 ​ $ 118 ​ $ 118 ​ $ 105 ​ $ 109 ​ 112 Table of Contents This graph shall not be deemed “soliciting material” or be deemed “filed” for purposes of Section 18 of the Exchange Act, or otherwise subject to the liabilities under that Section, and shall not be deemed to be incorporated by reference into any of our filings under the Securities Act of 1933, as amended, or the Securities Act, whether made before or after the date hereof and irrespective of any general incorporation language in any such filing.
Biggest changeThe stockholder return shown on the graph below is not necessarily indicative of future performance, and we do not make or endorse any predictions as to future stockholder return. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ 6/12/2020 12/31/2020 ​ 12/31/2021 ​ 12/31/2022 ​ 12/31/2023 ​ 12/31/2024 Generation Bio Co. ​ $ 100 ​ $ 115 ​ $ 29 ​ $ 16 ​ $ 7 ​ $ 4 Nasdaq Composite Total Return (IXIC) ​ $ 100 ​ $ 134 ​ $ 163 ​ $ 109 ​ $ 157 ​ $ 201 Nasdaq Biotechnology Total Return (NBI) ​ $ 100 ​ $ 118 ​ $ 118 ​ $ 105 ​ $ 109 ​ $ 107 ​ 109 Table of Contents This graph shall not be deemed “soliciting material” or be deemed “filed” for purposes of Section 18 of the Exchange Act, or otherwise subject to the liabilities under that Section, and shall not be deemed to be incorporated by reference into any of our filings under the Securities Act of 1933, as amended, or the Securities Act, whether made before or after the date hereof and irrespective of any general incorporation language in any such filing.
Stock Performance Graph The following graph shows the total stockholder’s return on an investment of $100 in cash at market close on June 12, 2020 (the first day of trading of our common stock), through December 31, 2023 for (i) our common stock, (ii) the Nasdaq Composite Index and (iii) the Nasdaq Biotechnology Index.
Stock Performance Graph The following graph shows the total stockholder’s return on an investment of $100 in cash at market close on June 12, 2020 (the first day of trading of our common stock), through December 31, 2024 for (i) our common stock, (ii) the Nasdaq Composite Index and (iii) the Nasdaq Biotechnology Index.
Prior to this time, there was no public market for our common stock. Holders of Our Common Stock As of February 29, 2024, there were approximately 61 holders of record of shares of our common stock. This number does not include stockholders for whom shares are held in “nominee” or “street” name.
Prior to this time, there was no public market for our common stock. Holders of Our Common Stock As of February 28, 2025, there were approximately 70 holders of record of shares of our common stock. This number does not include stockholders for whom shares are held in “nominee” or “street” name.
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Use of Proceeds from Initial Public Offering In June 2020, we closed our initial public offering, or IPO, of our common stock, pursuant to which we issued and sold 12,105,263 shares of our common stock, including 1,578,947 shares sold by us pursuant to the full exercise of the underwriters’ option to purchase additional shares, at a price to the public of $19.00 per share for aggregate gross proceeds of $230.0 million.
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Recent Sales of Unregistered Securities None. Purchases of Equity Securities None. ​ ITEM 6. [RESERVED] ​ 110 Table of Contents
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All of the shares issued and sold in the IPO were registered under the Securities Act pursuant to a Registration Statement on Form S-1 (File No. 333-238608), which was declared effective by the SEC on June 11, 2020. J.P.
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Morgan Securities LLC, Jefferies LLC and Cowen and Company, LLC acted as joint book-running managers and Wedbush PacGrow acted as lead manager of our IPO. We received aggregate net proceeds of approximately $210.7 million after deducting underwriting discounts and commissions and other offering expenses payable by us.
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None of the underwriting discounts and commissions or offering expenses were incurred or paid to directors or officers of ours or their associates or to persons owning 10 percent or more of our common stock or to any of our affiliates.
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There has been no material change in our planned use of the net proceeds from the IPO as described in our final prospectus filed pursuant to Rule 424(b)(4) under the Securities Act with the SEC on June 12, 2020. Recent Sales of Unregistered Securities None. Purchases of Equity Securities None. ​ ITEM 6. [RESERVED] ​ 113 Table of Contents

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

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Biggest changeResults of Operations The following table summarizes our results of operations: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ Change ​ Change (in thousands) 2023 2022 ​ 2021 2023 vs 2022 ​ 2022 vs 2021 Revenue: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Collaboration revenue ​ $ 5,904 ​ $ — ​ $ — ​ $ 5,904 ​ $ — Operating expenses: ​ ​ ​ ​ ​ ​ ​ ​ Research and development ​ ​ 93,617 ​ ​ 96,718 ​ ​ 85,247 ​ ​ (3,101) ​ ​ 11,471 General and administrative ​ 50,850 ​ 44,464 ​ 33,854 ​ 6,386 ​ 10,610 Total operating expenses ​ 144,467 ​ 141,182 ​ 119,101 ​ 3,285 ​ 22,081 Loss from operations ​ (138,563) ​ (141,182) ​ (119,101) ​ 2,619 ​ (22,081) Other income (expense): ​ ​ ​ ​ ​ Other income (expense) and interest income, net ​ 11,951 ​ 4,543 ​ (50) ​ 7,408 ​ 4,593 Net loss ​ $ (126,612) ​ $ (136,639) ​ $ (119,151) ​ $ 10,027 ​ $ (17,488) ​ 119 Table of Contents Comparison of the Years Ended December 31, 2023 and 2022 ​ Collaboration revenue During the year ended December 31, 2023, we recognized $5.9 million in collaboration revenue under the Collaboration Agreement.
Biggest changeDue to our history of cumulative net losses since inception and uncertainties surrounding our ability to generate future taxable income, we have recorded a full valuation allowance against our net deferred tax assets at each balance sheet date. ​ 116 Table of Contents ​ Results of Operations The following table summarizes our results of operations: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ Change ​ Change (in thousands) 2024 2023 ​ 2022 2024 vs 2023 ​ 2023 vs 2022 Revenue: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Collaboration revenue ​ $ 19,892 ​ $ 5,904 ​ $ — ​ $ 13,988 ​ $ 5,904 Operating expenses: ​ ​ ​ ​ ​ ​ ​ ​ Research and development ​ ​ 61,305 ​ ​ 93,617 ​ ​ 96,718 ​ ​ (32,312) ​ ​ (3,101) General and administrative ​ 37,780 ​ 50,850 ​ 44,464 ​ (13,070) ​ 6,386 Loss on lease termination ​ ​ 63,197 ​ ​ — ​ ​ — ​ ​ 63,197 ​ ​ — Total operating expenses ​ 162,282 ​ 144,467 ​ 141,182 ​ 17,815 ​ 3,285 Loss from operations ​ (142,390) ​ (138,563) ​ (141,182) ​ (3,827) ​ 2,619 Other income: ​ ​ ​ ​ ​ Other income and interest income, net ​ 10,722 ​ 11,951 ​ 4,543 ​ (1,229) ​ 7,408 Net loss ​ $ (131,668) ​ $ (126,612) ​ $ (136,639) ​ $ (5,056) ​ $ 10,027 ​ Collaboration revenue During the year ended December 31, 2024, we recognized $19.9 million in collaboration revenue, compared to $5.9 million for the year ended December 31, 2023.
Other income (expense) and interest income, net Other income (expense) and interest income, net consists of interest income earned on our invested cash balances and other income (expense) income from miscellaneous expenses and income unrelated to our core operations.
Other income and interest income, net Other income and interest income, net consists of interest income earned on our invested cash balances and other expense and income from miscellaneous expenses and income unrelated to our core operations.
We could use our available capital resources sooner than we currently expect, in which case we would be required to obtain additional financing, which may not be available to us on acceptable terms, or at all.
We could use our available capital resources sooner than we currently expect, in which case we would be required to obtain additional financing, which may not be available to us on acceptable terms, or at all.
This is due to the numerous risks and uncertainties associated with product development, including the following: ● the timing and progress of preclinical studies, including IND-enabling studies; ● the number and scope of preclinical and clinical programs we decide to pursue; ● our ability to raise additional funds necessary to complete preclinical and clinical development of any product candidates we may develop; ● the timing of the submission and acceptance of IND applications or comparable foreign applications that allow commencement of future clinical trials for any product candidates we may develop; ● the successful initiation, enrollment and completion of clinical trials, including under GCPs; ● our ability to achieve positive results from our future clinical programs that support a finding of safety and effectiveness and an acceptable risk-benefit profile in the intended patient populations of any product candidates we may develop; ● our ability to scale RES to produce clinical and initial commercial supply; ● our ability to establish arrangements with third-party manufacturers for preclinical, clinical and initial commercial supply; ● the availability of specialty raw materials for use in production of any product candidates we may develop; ● our ability to establish new licensing or collaboration arrangements; ● the receipt and related terms of regulatory approvals from the FDA, and other applicable regulatory authorities; ● our ability to establish, obtain, maintain, enforce and defend patent, trademark, trade secret protection and other intellectual property rights or regulatory exclusivity for any product candidates we may develop and our technology; ● our ability to maintain a continued acceptable safety, tolerability and efficacy profile of our product candidates following approval; and ● the terms and timing of any existing or future collaboration, license or other arrangement, including the terms and timing of any achievement of milestones and the receipt of payments thereunder.
This is due to the numerous risks and uncertainties associated with product development, including the following: ● the timing and progress of preclinical studies, including IND-enabling studies; ● the number and scope of preclinical and clinical programs we decide to pursue; ● our ability to raise additional funds necessary to complete preclinical and clinical development of any product candidates we may develop; ● the timing of the submission and acceptance of IND applications or comparable foreign applications that allow commencement of future clinical trials for any product candidates we may develop; ● the successful initiation, enrollment and completion of clinical trials, including under GCPs; ● our ability to achieve positive results from our future clinical programs that support a finding of safety and effectiveness and an acceptable risk-benefit profile in the intended patient populations of any product candidates we may develop; ● our ability to establish arrangements with third-party manufacturers for preclinical, clinical and initial commercial supply; ● the availability of specialty raw materials for use in production of any product candidates we may develop; ● our ability to establish new licensing or collaboration arrangements; ● the receipt and related terms of regulatory approvals from the FDA, and other applicable regulatory authorities; ● our ability to establish, obtain, maintain, enforce and defend patent, trademark, trade secret protection and other intellectual property rights or regulatory exclusivity for any product candidates we may develop and our technology; ● our ability to maintain a continued acceptable safety, tolerability and efficacy profile of our product candidates following approval; and ● the terms and timing of any existing or future collaboration, license or other arrangement, including the terms and timing of any achievement of milestones and the receipt of payments thereunder.
Operating expenses Research and development expenses Research and development expenses consist primarily of costs incurred for our research activities, including our discovery efforts, and the development of our programs, which include: ● personnel-related costs, including salaries, benefits, stock-based compensation, and severance expense, for employees engaged in research and development functions; ● expenses incurred in connection with our research programs, including under agreements with third parties, such as consultants, contractors and CROs, and regulatory agency fees; ● the cost of developing and scaling our manufacturing process and capabilities and manufacturing drug substance and drug product for use in our research and preclinical studies, including under agreements with third parties, such as consultants, contractors and CDOs; ● laboratory supplies and research materials; ● facilities, depreciation and amortization and other expenses, which include direct and allocated expenses for rent and maintenance of facilities and insurance; and ● payments made under third-party licensing agreements.
Operating expenses Research and development expenses Research and development expenses consist primarily of costs incurred for our research activities, including our discovery efforts, and the development of our programs, which include: ● personnel-related costs, including salaries, benefits, stock-based compensation, and severance expense, for employees engaged in research and development functions; ● expenses incurred in connection with our research programs, including under agreements with third parties, such as consultants, contractors and CROs, and regulatory agency fees; ● the cost of developing and scaling our manufacturing process and capabilities and manufacturing drug substance and drug product for use in our research and preclinical studies, including under agreements with third parties, such as consultants, contractors and contract development organizations, or CDOs; ● laboratory supplies and research materials; ● facilities, depreciation and amortization and other expenses, which include direct and allocated expenses for rent and maintenance of facilities and insurance; and ● payments made under third-party licensing agreements.
The increase in personnel-related costs of $3.7 million was primarily driven by restructuring costs recognized in connection with the RIF announced in November 2023.
The increase in personnel-related costs of $3.7 million was primarily driven by restructuring costs recognized in connection with the November 2023 RIF.
To determine the appropriate amount of revenue to be recognized for contracts determined to be within the scope of ASC 606, 124 Table of Contents we perform the following five steps: (i) identification of the promised goods or services in the contract; (ii) determination of whether the promised goods or services are performance obligations, including whether they are distinct in the context of the contract; (iii) measurement of the transaction price, including the constraint on variable consideration; (iv) allocation of the transaction price to the performance obligations; and (v) recognition of revenue when, or as, we satisfy each performance obligation.
To determine the appropriate amount of revenue to be recognized for contracts determined to be within the scope of ASC 606, we perform the following five steps: (i) identification of the promised goods or services in the contract; (ii) determination of whether the promised goods or services are performance obligations, including whether they are distinct in the context of the contract; (iii) measurement of the transaction price, including the constraint on variable consideration; (iv) allocation of the transaction price to the performance obligations; and (v) recognition of revenue when, or as, we satisfy each performance obligation.
We expect that our expenses and capital requirements will increase substantially in connection with our ongoing activities, particularly if and as we: ● continue our current research programs and conduct additional research programs, including pursuant to our collaboration with Moderna; ● expand the capabilities of our proprietary non-viral genetic medicine platforms; ● advance any product candidates we identify into preclinical and clinical development; ● obtain, expand, maintain, defend and enforce our intellectual property portfolio; ● seek marketing approvals for any product candidates that successfully complete clinical trials; ● hire additional clinical, regulatory and scientific personnel; ● establish additional manufacturing sources and secure supply chain capacity sufficient to provide necessary quantities of any product candidates we may develop for clinical or commercial use; ● ultimately establish a sales, marketing and distribution infrastructure to commercialize any products for which we may obtain marketing approval; and ● add operational, legal, compliance, financial and management information systems and personnel to support our research, product development, future commercialization efforts.
We expect that our expenses and capital requirements will increase substantially in connection with our ongoing activities, particularly if and as we: ● continue our current research programs and conduct additional research programs, including pursuant to our collaboration with Moderna; ● expand the capabilities of our proprietary technologies; ● advance any product candidates we identify into preclinical and clinical development; ● obtain, expand, maintain, defend and enforce our intellectual property portfolio; ● seek marketing approvals for any product candidates that successfully complete clinical trials; ● hire additional clinical, regulatory and scientific personnel; ● establish additional manufacturing sources and secure supply chain capacity sufficient to provide necessary quantities of any product candidates we may develop for clinical or commercial use; ● ultimately establish a sales, marketing and distribution infrastructure to commercialize any products for which we may obtain marketing approval; and ● add operational, legal, compliance, financial and management information systems and personnel to support our research, product development, and future commercialization efforts.
Until such time as we can generate significant revenue from product sales, if ever, we expect to finance our operations through a combination of equity offerings, debt financings, collaborations, strategic alliances and/or licensing arrangements, including our collaboration with Moderna.
Until such time as we can generate significant revenue from product sales, if ever, we expect to finance our 113 Table of Contents operations through a combination of equity offerings, debt financings, collaborations, strategic alliances and/or licensing arrangements, including our collaboration with Moderna.
There may be instances in which payments made to our vendors will exceed the level of services provided and result in a prepayment of the expense. We record these as prepaid expenses on our consolidated balance sheet.
There may be instances in which payments made to our vendors will exceed the level of services provided and result in a prepayment of the expense. We record these as prepaid expenses on our consolidated balance sheet. ​ ​ 122 Table of Contents
General and administrative expenses General and administrative expenses consist primarily of personnel-related costs, including salaries, benefits, stock-based compensation and severance expense, for employees engaged in executive, legal, finance and accounting and other administrative functions.
General and administrative expenses General and administrative expenses consist primarily of personnel-related costs, including salaries, benefits, stock-based compensation and severance expense, for employees engaged in executive, legal, finance and accounting and other 115 Table of Contents administrative functions.
Historically, we have funded our operations with proceeds from the sale of instruments convertible into convertible preferred stock (which converted into convertible preferred stock in 2017), sales of convertible preferred stock (which converted into common stock in 2020) and sales of common stock in underwritten public offerings, “at-the-market” offerings, and in a private placement, as well as collaboration revenue under our collaboration with Moderna.
Historically, we have funded our operations with proceeds from the sale of instruments convertible into convertible preferred stock, sales of convertible preferred stock and sales of common stock in underwritten public offerings, “at-the-market” offerings, and in a private placement, as well as collaboration revenue under our collaboration with Moderna.
In March 2023, in connection with the Share Purchase Agreement with Moderna, we issued and sold 5,859,375 shares of our common stock to Moderna at a price of $6.14 per share for an aggregate purchase price of $36.0 million. As of December 31, 2023, we had cash, cash equivalents, and marketable securities of $264.4 million.
In March 2023, in connection with the Share Purchase Agreement with Moderna, we issued and sold 5,859,375 shares of our common stock to Moderna at a price of $6.14 per share for an aggregate purchase price of $36.0 million. As of December 31, 2024, we had cash, cash equivalents, and marketable securities of $185.2 million.
In August 2021, we entered into an “at-the-market” sales agreement pursuant to which we may, from time to time, sell shares of our common stock having an aggregate offering price of up to $250.0 million.
In August 2024, we entered into an “at-the-market” sales agreement pursuant to which we may, from time to time, sell shares of our common stock having an aggregate offering price of up to $237.0 million.
In August 2021, we entered into an “at-the-market” sales agreement pursuant to which we may, from time to time, sell shares of our common stock having an aggregate offering price of up to $250.0 million.
In August 2024, we entered into an “at-the-market” sales agreement pursuant to which we may, from time to time, sell shares of our common stock having an aggregate offering price of up to $237.0 million.
Our ability to generate any product revenue or product revenue sufficient to achieve profitability will depend on the successful development and eventual commercialization of one or more product candidates we may develop. For the years ended December 31, 2023, 2022, and 2021, we reported net losses of $126.6 million, $136.6 million, and $119.2 million, respectively.
Our ability to generate any product revenue or product revenue sufficient to achieve profitability will depend on the successful development and eventual commercialization of one or more product candidates we may develop. For the years ended December 31, 2024, 2023, and 2022, we reported net losses of $131.7 million, $126.6 million, and $136.6 million, respectively.
The increase in facilities-related costs of $2.6 million was primarily driven by rent expense related to the Seyon Facility after our decision to transition from building out the Seyon Facility to utilizing an external cleanroom facility.
The increase in facilities-related costs of $3.8 million was primarily driven by rent expense related to the Seyon Facility after our decision to transition from building out the Seyon Facility to utilizing an external cleanroom facility.
We expect that our research and development expenses will increase substantially as we advance our programs into clinical development and expand our discovery, research and preclinical 117 Table of Contents activities in the near term and in the future.
We expect that our research and development expenses will increase substantially as we advance our programs into clinical development and expand our discovery, research and preclinical activities in the near term and in the future.
We expense research and development costs as incurred. Advance payments that we make for goods or services to be received in the future for use in research and development activities are recorded as prepaid expenses. The prepaid amounts are expensed as the related goods are delivered or the services are performed.
We expense research and development costs as incurred. Advance payments that we make for goods or services to be received in the future for use in research and development activities are recorded as prepaid expenses.
General and administrative expenses also include professional fees for legal, patent, consulting, investor and public relations and accounting and audit services as well as direct and allocated facility-related costs. 118 Table of Contents We anticipate that our general and administrative expenses will increase in the future as our research progresses towards clinical studies and we will increase our headcount.
General and administrative expenses also include professional fees for legal, patent, consulting, investor and public relations and accounting and audit services as well as direct and allocated facility-related costs. We anticipate that our general and administrative expenses will increase in the future as our research progresses towards clinical studies and will increase our headcount to support our operational growth.
In addition, as of December 31, 2023, we had state net operating loss carryforwards of $360.8 million, which may be available to offset future taxable income and expire at various dates beginning in 2036.
In addition, as of December 31, 2024, we had state net operating loss carryforwards of $397.2 million, which may be available to offset future taxable income and expire at various dates beginning in 2036.
As of December 31, 2023, we also had federal and state research and development tax credit carryforwards of $14.5 million and $8.0 million, respectively, which may be available to reduce future tax liabilities and expire at various dates beginning in 2036 and 2033, respectively.
As of December 31, 2024, we also had federal and state research and development tax credit carryforwards of $16.3 million and $8.8 million, respectively, which may be available to reduce future tax liabilities and expire at various dates beginning in 2036 and 2033, respectively.
Even if we are able to generate product sales, we may not become profitable. If we fail to become profitable or are unable to sustain profitability on a continuing basis, then we may be unable to continue our operations at planned levels and be forced to reduce or terminate our operations.
If we fail to become profitable or are unable to sustain profitability on a continuing basis, then we may be unable to continue our operations at planned levels and be forced to reduce or terminate our operations.
As of December 31, 2023, we had federal net operating loss carryforwards of $353.0 million, which may be available to offset future taxable income, of which $8.2 million of the total net operating loss carryforwards begin to expire in 2036, while the remaining $344.8 million do not expire but may be limited in their usage to an annual deduction equal to 80% of annual taxable income.
As of December 31, 2024, we had federal net operating loss carryforwards of $380.7 million, which may be available to offset future taxable income, of which $8.2 million of the total net operating loss carryforwards begin to expire in 2036, while the remaining $372.5 million do not expire but may be limited in their usage to an annual deduction equal to 80% of annual taxable income.
As of December 31, 20223, we had an accumulated deficit of $571.4 million. We expect to continue to incur significant expenses and increasing operating losses for at least the next several years.
As of December 31, 2024, we had an accumulated deficit of $703.0 million. We expect to continue to incur significant expenses and increasing operating losses for at least the next several years.
We expect that any revenue recognized for the next several years will be derived primarily from our current collaboration with Moderna and any additional collaborations that we may enter into in the future. Through December 31, 2023, we have recognized $5.9 million in collaboration revenue under the Collaboration Agreement with Moderna.
We expect that any revenue recognized for the next several years will be derived primarily from our current collaboration with Moderna and any additional collaborations that we may enter into in the future. During the year ended December 31, 2024, we have recognized $19.9 million in collaboration revenue under the Collaboration Agreement with Moderna.
The timing and amount of our operating expenditures will depend largely on: ● the costs and scope of the continued development of our non-viral genetic medicine platforms; ● the identification of additional research programs and product candidates; ● the costs and timing of preparing, filing and prosecuting applications for patents; obtaining, maintaining, defending and enforcing our intellectual property rights and defending against any intellectual property-related claims, including claims of infringement, misappropriation or other violation of third-party intellectual property; ● the scope, progress, costs and results of preclinical and clinical development for any product candidates we may develop; ● our research and development costs and the receipt of milestone payments under our collaboration with Moderna; ● the costs, timing and outcome of regulatory review of any product candidates we may develop; ● the cost and timing of completion of commercial-scale manufacturing activities, including the costs and resources required to manufacture our drug substance and drug product using external cleanroom facilities and/or CMOs; 122 Table of Contents ● the costs and timing of future commercialization activities, including product manufacturing, marketing, sales and distribution, for any product candidates we may develop for which we receive marketing approval; ● the costs of satisfying any post-marketing requirements; ● the revenue, if any, received from commercial sales of product candidates we may develop for which we receive marketing approval; ● the costs of operational, financial and management information systems and associated personnel; ● the extent to which our previously announced RIF achieves the anticipated cost savings; ● the associated costs in connection with any acquisition of in-licensed products, intellectual property and technologies; and ● the costs of operating as a public company.
The timing and amount of our operating expenditures will depend largely on: ● the costs and scope of the continued development of our technologies; ● the identification of additional research programs and product candidates; ● the costs and timing of preparing, filing and prosecuting applications for patents; obtaining, maintaining, defending and enforcing our intellectual property rights and defending against any intellectual property-related claims, including claims of infringement, misappropriation or other violation of third-party intellectual property; ● the scope, progress, costs and results of preclinical and clinical development for any product candidates we may develop; ● our research and development costs and the receipt of milestone payments under our collaboration with Moderna; ● the costs, timing and outcome of regulatory review of any product candidates we may develop; ● the cost and timing of completion of commercial-scale manufacturing activities; ● the costs and timing of future commercialization activities, including product manufacturing, marketing, sales and distribution, for any product candidates we may develop for which we receive marketing approval; ● the costs of satisfying any post-marketing requirements; ● the revenue, if any, received from commercial sales of product candidates we may develop for which we receive marketing approval; ● the costs of operational, financial and management information systems and associated personnel; ● the associated costs in connection with any acquisition of in-licensed products, intellectual property and technologies; and ● the costs of operating as a public company.
Under ASC 606, an entity recognizes revenue when its customer obtains control of promised goods or services, in an amount that reflects the consideration which the entity expects to receive in exchange for those goods or services.
Under ASC 606, we recognize revenue when the customer obtains control of promised goods or services, in an amount that reflects the consideration which we expect to receive in exchange for those goods or services.
Historically, we have funded our operations with proceeds from the sale of instruments convertible into convertible preferred stock (which converted into convertible preferred stock in 2017), sales of convertible preferred stock (which converted into common stock in 2020) and sales of common stock in underwritten public offerings, “at-the-market” offerings and in a private placement, as well as payments pursuant to our collaboration with Moderna.
Historically, we have funded our operations with proceeds from the sale of instruments convertible into convertible preferred stock, sales of convertible preferred stock and sales of common stock in underwritten public offerings, “at-the-market” offerings and in a private placement, as well as collaboration revenue under our collaboration with Moderna.
If we raise additional funds through collaborations or licensing arrangements with third parties, we may have to relinquish valuable rights to future revenue streams or product candidates or grant licenses on terms that may not be favorable to us.
If we raise additional funds through collaborations or licensing arrangements with third parties, we may have to relinquish valuable rights to future revenue streams or product candidates or grant licenses on terms that may not be favorable to us. See “Risk Factors” for additional risks associated with our substantial capital requirements.
The decrease in facilities-related costs of $8.7 million was primarily driven by our decision to transition from building out the Seyon Facility to utilizing an external cleanroom facility. These decreases were offset by an increase in preclinical and manufacturing costs of $5.6 million, driven primarily by activities to support advancements in our iqDNA platform.
The decrease in facilities-related costs of $9.5 million was primarily driven by our decision to transition from building out the Seyon Facility to utilizing an external cleanroom facility. This decrease was offset by an increase in preclinical and manufacturing costs of $5.1 million, driven primarily by activities to support advancements in our iqDNA technology.
Cash flows The following table summarizes our sources and uses of cash for each of the periods presented: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, (in thousands) 2023 2022 ​ 2021 Net cash used in operating activities ​ $ (52,745) ​ $ (102,448) ​ $ (91,821) Net cash (used in) provided by investing activities ​ (9,698) ​ (192,515) ​ 193,047 Net cash provided by financing activities ​ 35,817 ​ 12,989 ​ 214,671 Net (decrease) increase in cash, cash equivalents and restricted cash ​ $ (26,626) ​ $ (281,974) ​ $ 315,897 ​ ​ ​ 121 Table of Contents Operating activities During the year ended December 31, 2023, operating activities used $52.7 million of cash, primarily resulting from our net loss of $126.6 million, offset by non-cash charges of $20.4 million and changes in our operating assets and liabilities of $53.5 million.
Cash flows The following table summarizes our sources and uses of cash for each of the periods presented: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, (in thousands) 2024 2023 ​ 2022 Net cash used in operating activities ​ $ (88,563) ​ $ (52,745) ​ $ (102,448) Net cash provided by (used in) investing activities ​ 94,529 ​ (9,698) ​ (192,515) Net cash provided by financing activities ​ 250 ​ 35,817 ​ 12,989 Net increase (decrease) in cash, cash equivalents and restricted cash ​ $ 6,216 ​ $ (26,626) ​ $ (281,974) ​ ​ Operating activities During the year ended December 31, 2024, operating activities used $88.6 million of cash, primarily resulting from our net loss of $131.7 million and the net changes in our operating assets and liabilities of $31.4 million and offset by the net of non-cash charges of $74.5 million.
On February 20, 2024, the landlord served us with a complaint, filed in Massachusetts Superior Court, with respect to the Seyon Lease. The complaint seeks declaratory judgment that we unlawfully terminated the Seyon Lease and also asserts a claim for breach of contract 114 Table of Contents damages. Our responsive pleading is due April 1, 2024.
On February 20, 2024, the Landlord served us with a complaint, filed in the Court, with respect to the Seyon Lease. The complaint seeks declaratory judgment that we unlawfully terminated the Seyon Lease and also asserts a claim for breach of contract damages.
We will vigorously defend the action and our rights with respect to this matter. In March 2023, we entered into a Collaboration and License Agreement, or the Collaboration Agreement, with Moderna, to collaborate on developing treatments for certain diseases by targeting delivery of nucleic acids to liver cells and certain cells outside of the liver.
In March 2023, we entered into the Collaboration Agreement, with Moderna, to collaborate on developing treatments for certain diseases by targeting delivery of nucleic acids to liver cells and certain cells outside of the liver.
See “Risk Factors” for additional risks associated with our substantial capital requirements. 123 Table of Contents Critical accounting policies and significant judgments and estimates Our consolidated financial statements are prepared in accordance with generally accepted accounting principles in the United States of America, or GAAP.
Critical accounting policies and significant judgments and estimates Our consolidated financial statements are prepared in accordance with generally accepted accounting principles in the United States of America, or GAAP.
Since our inception in October 2016, we have focused substantially all of our resources on building our non-viral genetic medicine platforms, establishing and protecting our intellectual property portfolio, conducting research and development activities, developing our manufacturing process, organizing and staffing our company, business planning, raising capital and providing general and administrative support for these operations.
For additional information on our collaboration with Moderna and the accounting thereunder, refer to Note 4, Collaboration and License Agreement. 112 Table of Contents Since our inception in October 2016, we have focused substantially all of our resources on building our technologies, establishing and protecting our intellectual property portfolio, conducting research and development activities, developing our manufacturing process, organizing and staffing our company, business planning, raising capital and providing general and administrative support for these operations.
Further, we expect to continue to incur additional costs associated with operating as a public company. As a result, we will need substantial additional funding to support our continuing operations and pursue our growth strategy.
As a result, we will need substantial additional funding to support our continuing operations and pursue our growth strategy.
As of March 6, 2024, the issuance date of this Annual Report on Form 10-K, we have issued and sold 1,795,524 shares of our common stock pursuant to this sales agreement resulting in net proceeds of $12.3 million.
As of the issuance date of this Annual Report on Form 10-K, we have not issued and sold any shares of our common stock pursuant to the August 2024 sales agreement.
Investing activities During the year ended December 31, 2023, net cash used by investing activities was $9.7 million, due to an increase in purchases of marketable securities of $405.3 million and property and equipment of $7.4 million during the year, offset by $403.0 million in maturities of marketable securities.
Investing activities During the year ended December 31, 2024, net cash provided by investing activities was $94.5 million, primarily due to $232.0 million in maturities of marketable securities offset by purchases of marketable securities of $135.3 million and property and equipment of $2.4 million during the period.
The increase in other income (expense) and interest income, net during the year ended December 31, 2023 was primarily due to an increase in interest earned on our invested cash balances.
The increase in other income and interest income, net during the year ended December 31, 2023 was primarily due to an increase in interest earned on our invested cash balances. ​ 118 Table of Contents Liquidity and Capital Resources Since our inception, we have incurred significant operating losses.
We have not yet commercialized any product candidates and we do not expect to generate revenue from sales of any product candidates for several years, if at all.
We expect to incur significant expenses and operating losses for the foreseeable future as we support our continued research activities and development of our programs and technologies. We have not yet commercialized any product candidates and we do not expect to generate revenue from sales of any product candidates for several years, if at all.
If we fail to raise capital or enter into such agreements when needed or on terms acceptable to us, we would be required to delay, limit, reduce or terminate our product development or future commercialization of one or more of our product candidates. 116 Table of Contents Because of the numerous risks and uncertainties associated with pharmaceutical product development, we are unable to accurately predict the timing or amount of increased expenses or when, or if, we will be able to achieve or maintain profitability.
If we fail to raise capital or enter into such agreements when needed or on terms acceptable to us, we would be required to delay, limit, reduce or terminate our product development or future commercialization of one or more of our product candidates.
As of March 6, 2024, the issuance date of this Annual Report on Form 10-K, we have issued and sold 1,795,524 shares of our common stock pursuant to this sales agreement resulting in net proceeds of $12.3 million.
As the issuance date of this Annual Report on Form 10-K, we have not issued and sold any shares of our common stock pursuant to the August 2024 sales agreement. Historically, we have incurred significant operating losses.
We believe that our existing cash, cash equivalents and marketable securities will enable us to fund our operating expenses and capital expenditures into the second half of 2027. We have based our estimates as to how long we expect we will be able to fund our operations on assumptions that may prove to be wrong.
We have based our estimates as to how long we expect we will be able to fund our operations on assumptions that may prove to be wrong.
The increases in personnel-related costs and stock-based compensation costs of $2.0 million and $0.8 million, respectively, were primarily driven by restructuring costs recognized in connection with the RIF announced in November 2023. 120 Table of Contents Other income (expense) and interest income, net ​ Other income (expense) and interest income, net for the year ended December 31, 2023 was $12.0 million in income compared to $4.5 million in expense for the year ended December 31, 2022.
The increases in personnel-related costs and stock-based compensation costs of $2.0 million and $0.8 million, respectively, were primarily driven by restructuring costs recognized in connection with the November 2023 RIF. Loss on lease termination During the year ended December 31, 2024, we recognized a non-cash charge of $63.2 million in connection with the termination of the Seyon Lease.
For a discussion of our sources and uses of cash for the years ended December 31, 2022 and 2021 please refer to “Management's Discussion and Analysis of Financial Condition and Results of Operations” in our Annual Report on Form 10-K for the fiscal year ended December 31, 2022 that was filed with the SEC on February 23, 2023.
Financing activities During the year ended December 31, 2024, net cash provided by financing activities was $0.3 million, consisting of $0.4 million in proceeds from employee stock option exercises and sales of common stock in connection to the 2020 Employee Stock Purchase Plan, offset $0.2 million in payments for repurchases of common stock for employee tax withholdings. 119 Table of Contents For a discussion of our sources and uses of cash for the years ended December 31, 2023 and 2022 please refer to “Management's Discussion and Analysis of Financial Condition and Results of Operations” in our Annual Report on Form 10-K for the fiscal year ended December 31, 2023 that was filed with the SEC on March 6, 2024.
Our external research and development expenses consist of costs that include fees and other costs paid to consultants, contractors, CDOs and CROs in connection with our research, preclinical and manufacturing activities. We do not allocate our research and development costs to specific programs because costs are deployed across multiple programs and our platforms and, as such, are not separately classified.
The prepaid amounts are expensed as the related goods are delivered or the services are performed. 114 Table of Contents Our external research and development expenses consist of costs that include fees and other costs paid to consultants, contractors, CDOs and CROs in connection with our research, preclinical and manufacturing activities.
We only apply the five-step model to contracts when it is probable that we will collect consideration we are entitled to in exchange for the goods or services we transfer to the customer. For further discussion, please refer to Note 2, Revenue Recognition.
We only apply the five-step model to contracts when it is probable that we will collect consideration we are entitled to in exchange for the goods or services we transfer to the customer. 121 Table of Contents We recognize consideration allocated to the combined license and research services performance obligation pursuant to our Collaboration Agreement with Moderna under the proportional performance method.
For additional information on our collaboration with Moderna and the accounting thereunder, refer to Note 4, Collaboration and License Agreements. ​ Research and development expenses ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ Change ​ (in thousands) 2023 2022 ​ 2021 2023 vs 2022 2022 vs 2021 ​ Personnel-related ​ $ 33,403 ​ $ 29,693 ​ $ 24,908 ​ $ 3,710 ​ $ 4,785 ​ Preclinical and manufacturing ​ ​ 20,675 ​ ​ 15,084 ​ ​ 23,128 ​ ​ 5,591 ​ ​ (8,044) ​ Facilities-related ​ 13,802 ​ 22,518 ​ 10,527 ​ (8,716) ​ 11,991 ​ Stock-based compensation ​ 11,496 ​ 12,405 ​ 9,316 ​ (909) ​ 3,089 ​ Lab supplies ​ 4,729 ​ 5,063 ​ 7,445 ​ (334) ​ (2,382) ​ Consulting and professional services ​ 1,975 ​ 3,357 ​ 3,164 ​ (1,382) ​ 193 ​ Other ​ 7,537 ​ 8,598 ​ 6,759 ​ (1,061) ​ 1,839 ​ Total research and development expenses ​ $ 93,617 ​ $ 96,718 ​ $ 85,247 ​ $ (3,101) ​ $ 11,471 ​ ​ Research and development expenses were $93.6 million for the year ended December 31, 2023, compared to $96.7 million for the year ended December 31, 2022.
For additional information on our collaboration with Moderna, refer to Note 4, Collaboration and License Agreement. ​ Research and development expenses ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ Change ​ (in thousands) 2024 2023 (1) ​ 2022 (1) 2024 vs 2023 2023 vs 2022 ​ Personnel-related ​ $ 19,404 ​ $ 33,403 ​ $ 29,693 ​ $ (13,999) ​ $ 3,710 ​ Facilities-related ​ 13,533 ​ 16,678 ​ 26,154 ​ (3,145) ​ (9,476) ​ Preclinical and manufacturing ​ ​ 13,645 ​ ​ 21,574 ​ ​ 16,511 ​ ​ (7,929) ​ ​ 5,063 ​ Stock-based compensation ​ 5,728 ​ 11,496 ​ 12,405 ​ (5,768) ​ (909) ​ Lab supplies ​ 3,804 ​ 3,830 ​ 4,234 ​ (26) ​ (404) ​ Consulting and professional services ​ 1,636 ​ 1,975 ​ 2,760 ​ (339) ​ (785) ​ License fees ​ ​ 214 ​ ​ 1,012 ​ ​ 1,534 ​ ​ (798) ​ ​ (522) ​ Other ​ 3,341 ​ 3,649 ​ 3,427 ​ (308) ​ 222 ​ Total research and development expenses ​ $ 61,305 ​ $ 93,617 ​ $ 96,718 ​ $ (32,312) ​ $ (3,101) ​ (1) Certain prior period amounts have been reclassified to conform to the current period presentation. ​ Research and development expenses were $61.3 million for the year ended December 31, 2024, compared to $93.6 million for the year ended December 31, 2023.
As part of the restructuring, we intend to prioritize investment in the development of our ctLNP delivery system for wholly-owned programs in extrahepatic cell types and to develop iqDNA for our lead program in hemophilia A. In July 2021, we entered into a lease agreement to build out a cGMP-compliant manufacturing facility, or the Seyon Facility, in Waltham, Massachusetts.
We expect to submit our IND application for our lead program in the second half of 2026. 111 Table of Contents In July 2021, we entered into the Seyon Lease to build out a cGMP-compliant manufacturing facility, or the Seyon Facility, in Waltham, Massachusetts.
Net cash provided by changes in our operating assets and liabilities for the year ended December 31, 2023 consisted of a $41.6 million increase of deferred revenue, $1.4 million decrease of other noncurrent assets, a $16.2 million increase in operating lease liability, a $5.4 million increase of accrued expense and other current liabilities and accounts payable, a $3.2 million decrease in prepaid expenses and other current assets, a $10.6 million increase in operating lease right-of-use assets and a $3.6 million increase in tenant receivable.
Net changes in our operating assets and liabilities for the year ended December 31, 2024 were primarily driven by a $15.1 million decrease of deferred revenue from reimbursable activities performed under our Collaboration Agreement with Moderna, a $8.3 million decrease of accrued expense and other current liabilities and accounts payable primarily due to severance payments in connection with the November 2023 RIF and a $8.6 million decrease in operating lease liability due to rent payments for our leased facility.
As of December 31, 2023, our material cash requirements consisted of: ● $136.7 million in total lease payments under our noncancelable operating lease for our office and laboratory space that was entered into in August 2018, as amended, and expires in 2029 and our noncancelable operating lease to operate an approximately 104,000 square foot cGMP-compliant manufacturing facility that was entered into July 2021 and which we notified the landlord of the termination of the lease due to the landlord’s breach of its obligations to us under the lease and returned possession of the premises to the landlord in January 2024; and ● $4.2 million in cancellable purchase obligations to CMOs and CROs for preclinical activities during 2024 and 2025.
As of December 31, 2024, our material cash requirements consisted of: ● $30.4 million in total lease payments under our noncancelable operating lease for our office and laboratory space that was entered into in August 2018, as amended, and expires in 2029; ● $4.0 million in cancelable purchase obligations to CMOs and CROs for preclinical activities; and ● $5.6 million for monthly payments due through January 2025 and additional monthly payments related to the Seyon Lease pursuant to the Court’s preliminary injunction order . 120 Table of Contents We believe that our existing cash, cash equivalents and marketable securities will enable us to fund our operating expenses and capital expenditures into the second half of 2027.
General and administrative expenses ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Three Months Ended December 31, ​ Change (in thousands) 2023 2022 ​ 2021 2023 vs 2022 2022 vs 2021 Personnel-related ​ $ 17,507 ​ $ 15,465 ​ $ 13,609 ​ $ 2,042 ​ $ 1,856 Stock-based compensation ​ 12,845 ​ 12,047 ​ 8,541 ​ 798 ​ 3,506 Professional and consultant fees ​ 8,744 ​ 7,909 ​ 7,819 ​ 835 ​ 90 Facilities-related ​ 9,499 ​ 6,909 ​ 1,011 ​ 2,590 ​ 5,898 Other ​ 2,255 ​ 2,134 ​ 2,874 ​ 121 ​ (740) Total general and administrative expenses ​ $ 50,850 ​ $ 44,464 ​ $ 33,854 ​ $ 6,386 ​ $ 10,610 ​ General and administrative expenses were $50.9 million for the year ended December 31, 2023, compared to $44.5 million for the year ended December 31, 2022.
General and administrative expenses ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year Ended December 31, ​ Change (in thousands) 2024 2023 (1) ​ 2022 (1) 2024 vs 2023 2023 vs 2022 Personnel-related ​ $ 12,165 ​ $ 17,507 ​ $ 15,465 ​ $ (5,342) ​ $ 2,042 Stock-based compensation ​ 8,881 ​ 12,845 ​ 12,047 ​ (3,964) ​ 798 Facilities-related ​ 6,452 ​ 10,546 ​ 6,715 ​ (4,094) ​ 3,831 Consulting and professional services ​ 9,012 ​ 8,744 ​ 9,206 ​ 268 ​ (462) Other ​ 1,270 ​ 1,208 ​ 1,031 ​ 62 ​ 177 Total general and administrative expenses ​ $ 37,780 ​ $ 50,850 ​ $ 44,464 ​ $ (13,070) ​ $ 6,386 (1) Certain prior period amounts have been reclassified to conform to the current period presentation.
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Overview We are innovating non-viral genetic medicines to provide durable, redosable treatments for potentially hundreds of millions of patients living with rare and prevalent diseases. We are developing two distinct and complementary platforms that we believe will enable highly differentiated therapeutic applications.
Added
Overview We are a biotechnology company working to change what’s possible for people living with T cell-driven autoimmune diseases. Our strategy is to discover, develop, and commercialize redosable therapeutics that reprogram T cells in vivo to reduce or eliminate the production and persistence of autoreactive T cells, which erroneously recognize and attack the body’s own tissues, causing autoimmune disease.
Removed
Our first platform is a potent, highly selective ctLNP delivery system for nucleic acids, which is designed to avoid off-target clearance by the liver and spleen, enabling ctLNPs to persist in systemic circulation and allowing for highly selective and potent ligand-driven targeting to specific tissues and cell types.
Added
We are leveraging our ctLNP to selectively deliver siRNA to T cells, and we believe that the combination of selective delivery and an intracellular, genetically precise mechanism of target engagement unlocks a series of high-value historically undruggable disease-driving genes in autoimmunity.
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The identification and optimization of new ligands to target new tissues and cell types is an efficient, flexible, and modular process, which we believe may allow us to rapidly expand our portfolio.
Added
T cells are central to the normal function of the immune system, but when inactivated or naïve T cells are inappropriately activated against proteins or molecules naturally present in the body, known as autoantigens, they expand, differentiate, and drive tissue inflammation that results in the development of autoimmune disease.
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Our second platform is our novel iqDNA, which is an optimized variant of our ceDNA designed to enable long-lasting high levels of gene expression from non-integrating episomes, while avoiding innate immune sensors that have long prevented DNA from use in non-viral systems.
Added
Modulating T cell activity has historically been limited by a lack of selectivity along two dimensions – selective delivery to T cells while sparing other immune cell types, and precisely inhibiting or silencing the intended genetic sequence to block disease causing pathways.
Removed
Underpinning the iqDNA platform is our highly scalable capsid-free manufacturing process that uses our proprietary cell-free RES to produce highly pure iqDNA at scale. We are advancing a portfolio of programs guided by the potent and highly selective delivery of messenger RNA, or mRNA, and/or iqDNA to T cells, hematopoietic stem cells, or HSCs, and hepatocytes.
Added
We believe that the advantage of our approach to combatting T cell-driven autoimmune disease is in the combination of highly selective delivery and precise gene silencing in T cells to drive potency while sparing broader immune cells, thus potentially expanding the therapeutic margin of safety, or index.
Removed
Our work in T cells initially focuses on in vivo reprogramming of this cell type to treat cancer and autoimmune diseases. Our HSC research is focused initially on in vivo gene editing of HSCs for hematologic disorders, prioritizing sickle cell disease and beta-thalassemia.
Added
We achieve selective delivery using our modular, redosable ctLNP delivery system, which is designed to reach cell type targets of interest selectively through active ligand-mediated uptake. We are leveraging our T cell-selective LNP to deliver siRNA, a cargo that can potently and precisely regulate protein expression in T cells without off-target effects.
Removed
Our work in hepatocytes prioritizes hemophilia A, a rare monogenic disease that results from mutations in a single gene, has significant unmet need, and clear biomarkers for development.
Added
The intracellular mechanism of action of siRNA means that our T cell-selective LNP-siRNA has the potential to reach targets inaccessible by other modalities, creating a large and new target space for autoimmune disease.
Removed
We plan to expand our portfolio to include programs for additional indications in other tissues, including retina, skeletal muscle, and to the central nervous system, or CNS, by developing discrete ctLNPs, each with a unique targeting ligand engineered to provide targeted delivery of mRNA and/or iqDNA to T cells, HSCs and hepatocytes or for ETAP programs.
Added
Selective and potent siRNA delivery to T cells opens a broad landscape of protein targets to address T cell-driven autoimmune disease indications, including targets that are undruggable or poorly drugged by conventional modalities.
Removed
In November 2023, following a review of strategic priorities and a determination by our management and board of directors to implement a strategic reorganization to invest in our ctLNP delivery system to develop wholly-owned programs for extrahepatic cell types and to develop our iqDNA platform for our lead program in hemophilia A and other programs, we announced a strategic reorganization, pursuant to which we undertook a RIF and implemented reductions in operational expenditures including cGMP readiness and manufacturing expenses.
Added
We intend to build a portfolio of therapeutic candidates for T cell-driven autoimmune indications, selecting those with a strong link to protein target biology, high unmet need, a clear clinical/regulatory pathway, and path to demonstrate clinical superiority.
Removed
For additional information on our collaboration with Moderna and the accounting thereunder, refer to Note 4, Collaboration and License Agreements.
Added
We are prioritizing protein target selection for these indications based on the following: - targets in T cells that are undruggable or poorly drugged with conventional modalities; - well-characterized biology; - superiority of mechanism of action (selective delivery and intracellular knockdown); and - clear target engagement in early clinical development.
Removed
In June 2020, we completed our IPO pursuant to which we issued and sold 12,105,263 shares of our common stock, including 1,578,947 shares sold by us pursuant to the full exercise of the underwriters’ option to purchase additional shares. We received net proceeds of $210.7 million, after deducting underwriting discounts and commissions and other offering expenses.
Added
We expect to announce the target and indication of our lead T cell-selective LNP-siRNA program for autoimmune disease by mid-year 2025.
Removed
In 115 Table of Contents January 2021, we issued and sold 9,200,000 shares of our common stock, including 1,200,000 shares sold by us pursuant to the full exercise of the underwriters’ option to purchase additional shares, in a follow-on public offering, resulting in net proceeds of $211.3 million after deducting underwriting discounts and commissions and other offering expenses.
Added
Following receipt of the complaint, we filed a counterclaim against the landlord asserting breach of contract and violation of Massachusetts General Law Chapter 93A.
Removed
In March 2023, in connection with the Share Purchase Agreement entered into with Moderna, we issued and sold 5,859,375 shares of our common stock to Moderna at a price of $6.14 per share for an aggregate purchase price of $36.0 million. Historically, we have incurred significant operating losses.
Added
On October 29, 2024, the Court determined that although we did not have the right to terminate the Seyon Lease, the Landlord’s subsequent termination was effective, and that we had alleged sufficient facts to state a claim for breach of contract and violation of Massachusetts General Law Chapter 93A by the Landlord.
Removed
Due to our history of cumulative net losses since inception and uncertainties surrounding our ability to generate future taxable income, we have recorded a full valuation allowance against our net deferred tax assets at each balance sheet date.

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Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

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Biggest changeITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK Interest Rate Market Risk We are exposed to market risk related to changes in interest rates. We had cash, cash equivalents and marketable securities of $264.4 million as of December 31, 2023. We did not record any impairment charges to our marketable debt securities during the year ended December 31, 2023.
Biggest changeITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK Interest Rate Market Risk We are exposed to market risk related to changes in interest rates. We had marketable securities of $108.9 million as of December 31, 2024. We did not record any impairment charges to our marketable securities during the year ended December 31, 2024.
As of December 31, 2023, a hypothetical increase in interest rates of 100 basis points across the entire yield curve on our holdings would have resulted in a $0.9 million decrease to the fair value of our holdings. We currently do not seek to hedge this exposure to fluctuations in interest rates.
As of December 31, 2024, a hypothetical increase in interest rates of 100 basis points across the entire yield curve on our holdings would have resulted in a $0.4 million decrease to the fair value of our holdings. We currently do not seek to hedge this exposure to fluctuations in interest rates.

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