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What changed in Entrada Therapeutics, Inc.'s 10-K — 2024 vs 2025

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Paragraph-level year-over-year comparison of Entrada Therapeutics, Inc.'s 2024 and 2025 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 2025 report.

+637 added−579 removedSource: 10-K (2026-02-26) vs 10-K (2025-02-27)

Top changes in Entrada Therapeutics, Inc.'s 2025 10-K

637 paragraphs added · 579 removed · 467 edited across 8 sections

Item 1. Business

Business — how the company describes what it does

161 edited+81 added−34 removed276 unchanged
Biggest changeWe have also submitted regulatory applications to initiate a Phase 1/2 MAD clinical study of ENTR-601-45 in the United Kingdom and Europe for patients living with DMD who are amenable to exon 45 skipping. • On February 3, 2025, we announced the receipt of authorization from the United Kingdom’s Medicines and Healthcare Products Regulatory Agency (“MHRA”) and Research Ethics Committee for its Clinical Trial of an Investigational Medicinal Product to initiate ELEVATE-44-201, a Phase 1/2 multiple ascending dose (“MAD”) clinical study of ENTR-601-44 for the potential treatment of Duchenne muscular dystrophy (“Duchenne” or “DMD”) in patients with a confirmed mutation in the DMD gene amenable to exon 44 skipping.
Biggest changeELEVATE-50-201 : The Company received regulatory authorization from the UK’s Medicines and Healthcare Products Regulatory Agency (“MHRA”) and Research Ethics Committee to initiate a Phase 1/2 MAD clinical study of ENTR-601-50 in ambulatory patients living with DMD who are amenable to exon 50 skipping.
As dose goes up there is a great opportunity to see an increase in efficacy • The renal excretion of the final metabolite also increases but in a non-linear fashion. For every doubling of the dose we see more than a doubling of the percentage of metabolite excreted. Furthermore, this difference increases as the dose goes up.
As dose increases, there is a great opportunity to see an increase in efficacy • The renal excretion of the final metabolite also increases but in a non-linear fashion. For every doubling of the dose we see more than a doubling of the percentage of metabolite excreted. Furthermore, this difference increases as the dose goes up.
Products that are granted a marketing authorization with the results of the pediatric clinical trials conducted in accordance with the PIP (even where such results are negative) are eligible for six months’ supplementary protection certificate extension. In the case of orphan medicinal products, a two-year extension of the orphan market exclusivity may be available.
Products that are granted a marketing authorization with the results of the pediatric clinical trials conducted in accordance with the PIP (even where such results are negative) may be eligible for six months’ supplementary protection certificate extension. In the case of orphan medicinal products, a two-year extension of the orphan market exclusivity may be available.
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 (1) a life-threatening or chronically debilitating condition affecting not more than five in ten thousand persons in the EU when the application is made, or (2) a life-threatening, seriously debilitating or serious and chronic condition in the EU and that without incentives it is unlikely that the marketing of the drug in the EU would generate sufficient return to justify the necessary investment in its development.
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 medicinal product by the European Commission if its sponsor can establish: that the product is intended for the diagnosis, prevention or treatment of (1) a life-threatening or chronically debilitating condition affecting not more than five in ten thousand persons in the EU when the application is made, or (2) a life-threatening, seriously debilitating or serious and chronic condition in the EU and that without incentives it is unlikely that the marketing of the drug in the EU would generate sufficient return to justify the necessary investment in its development.
Pursuant to Regulation (EC) No. 726/2004, the centralized procedure is compulsory for specific products, including for medicines produced by certain biotechnological processes, products designated as orphan medicinal products, advanced therapy medical products (gene therapy, somatic cell therapy and tissue-engineered medicines) and products with a new active substance indicated for the treatment of HIV, AIDS, cancer, neurodegenerative disorders, diabetes, auto-immune and other immune dysfunctions and viral diseases.
Pursuant to Regulation (EC) No. 726/2004, the centralized procedure is compulsory for specific products, including for medicines produced by certain biotechnological processes, products designated as orphan medicinal products, advanced therapy medicinal products (gene therapy, somatic cell therapy and tissue-engineered medicines) and products with a new active substance indicated for the treatment of HIV, AIDS, cancer, neurodegenerative disorders, diabetes, auto-immune and other immune dysfunctions and viral diseases.
We currently rely on third-party contract manufacturing organizations (“CMOs”), and suppliers for EEV peptides, including linkers, and nucleotides that comprise ENTR-601-44, ENTR 601-45, ENTR-601-50, ENTR-601-51, VX-670, our other potential therapeutic candidates, and the conjugation of these components, and we expect to continue to do so to support our IND-enabling studies and our clinical trials and commercial activities.
We currently rely on third-party contract manufacturing organizations (“CMOs”), and suppliers for EEV peptides, including linkers, and nucleotides that comprise ENTR-601-44, ENTR 601-45, ENTR-601-50, ENTR-601-51, ENTR-801, VX-670, our other potential therapeutic candidates, and the conjugation of these components, and we expect to continue to do so to support our IND-enabling studies and our clinical trials and commercial activities.
Many benefits accrue to sponsors of therapeutic candidates with PRIME designation, including but not limited to, early and proactive regulatory dialogue with the EMA, frequent discussions on clinical trial designs and other development program elements, and accelerated MAA assessment once a dossier has been submitted.
Many benefits accrue to sponsors of therapeutic candidates with PRIME designation, including but not limited to, early and proactive regulatory dialogue with the EMA, frequent discussions on clinical trial designs and other development program elements, and the possibility of accelerated MAA assessment once a dossier has been submitted.
Item 1. Business Overview We are a clinical-stage biopharmaceutical company aiming to transform the lives of patients by e stablishing a new class of medicines which engage intracellular targets that have long been considered inaccessible .
Item 1. Business Overview We are a clinical-stage biopharmaceutical company aiming to transform the lives of patients by e stablishing a new class of medicines that engage intracellular targets that have long been considered inaccessible .
The PRIority MEdicines (“PRIME”), scheme is intended to encourage drug development in areas of unmet medical need and provides accelerated assessment of products representing substantial innovation reviewed under the centralized procedure.
The PRIority MEdicines (“PRIME”) scheme is intended to encourage drug development in areas of unmet medical need and accelerated assessment of products representing substantial innovation reviewed under the centralized procedure.
Furthermore, in the eccentric force contractions (“ECC”) challenge to the gastronemius muscle, a dose dependent increase in resistance to membrane damage was observed following the tenth contraction, which was maintained until at least 8 weeks after the third Q6W dose of ENTR-601-45. 16 Table of Contents Data shown across 10 ECC contractions normalized into a percentage of the initial force before any ECC and as the percentage of force retained after the 10th contraction.
Furthermore, in the eccentric force contractions (“ECC”) challenge to the gastronemius muscle, a dose dependent increase in resistance to membrane damage was observed following the tenth contraction, which was maintained until at least 8 weeks after the third Q6W dose of ENTR-601-45. 18 Table of Contents Data shown across 10 ECC contractions normalized into a percentage of the initial force before any ECC and as the percentage of force retained after the 10th contraction.
The team is led by Dipal Doshi, our Chief Executive Officer, who brings over 20 years of leadership experience within life sciences companies; Nathan Dowden, our President and Chief Operating Officer, who has three decades of experience leading corporate strategy, portfolio management, business planning and operations; Natarajan Sethuraman, Ph.D., our President of Research and Development, who is an expert in large molecule therapeutic development and delivery platforms with over 30 years of experience across pharmaceutical and biotechnology companies; Kory Wentworth, our Chief Financial Officer, who has over 20 years of public accounting and global biopharmaceutical experience, and our General Counsel, Jared Cohen Ph.D., J.D., who has 20 years of both external and in-house experience at a range of mature and early stage biopharmaceutical companies.
The team is led by Dipal Doshi, our Chief Executive Officer, who brings over 20 years of leadership experience within life sciences companies; Nathan Dowden, our President and Chief Operating Officer, 23 Table of Contents who has three decades of experience leading corporate strategy, portfolio management, business planning and operations; Natarajan Sethuraman, Ph.D., our President of Research and Development, who is an expert in large molecule therapeutic development and delivery platforms with over 30 years of experience across pharmaceutical and biotechnology companies; Kory Wentworth, our Chief Financial Officer, who has over 20 years of global biopharmaceutical and public accounting experience, and our General Counsel, Jared Cohen Ph.D., J.D., who has 20 years of both external and in-house experience at a range of mature and early stage biopharmaceutical companies.
An applicant seeking approval to market and distribute a new drug or 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 (“GLP”) regulations, as applicable; 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; submission to the FDA of an IND, for human clinical testing, which must become effective before human clinical trials may begin; approval by an independent institutional review board (“IRB”), representing each clinical trial site before each clinical trial site may be initiated; performance of adequate and well-controlled human clinical trials, in accordance with current Good Clinical Practices (“GCP”), and any additional nonclinical studies required to establish the safety, efficacy, potency and purity of the product candidate for each proposed indication; preparation and submission to the FDA of a new drug application (“NDA”), or a Biologics License Application (“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 and to assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality and purity; 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 NDA or BLA; payment of user fees under the Prescription Drug User Fee Act (“PDUFA”); securing FDA approval of the NDA or BLA; and compliance with any post-approval requirements, including the potential requirement to implement a Risk Evaluation and Mitigation Strategy (“REMS”), and any post-approval studies or other post-marketing commitments required by the FDA.
An applicant seeking approval to market and distribute a new drug or biologic in the U.S. 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 (“GLP”) regulations, as applicable; 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; submission to the FDA of an IND, for human clinical testing, which must become effective before human clinical trials may begin; approval by an independent institutional review board (“IRB”), representing each clinical trial site before each clinical trial site may be initiated; performance of adequate and well-controlled human clinical trials, in accordance with current Good Clinical Practices (“GCP”), and any additional nonclinical studies required to establish the safety, efficacy, potency and purity of the product candidate for each 29 Table of Contents proposed indication; preparation and submission to the FDA of a new drug application (“NDA”), or a Biologics License Application (“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 and to assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality and purity; 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 NDA or BLA; payment of user fees under the Prescription Drug User Fee Act (“PDUFA”); securing FDA approval of the NDA or BLA; and compliance with any post-approval requirements, including the potential requirement to implement a Risk Evaluation and Mitigation Strategy (“REMS”), and any post-approval studies or other post-marketing commitments required by the FDA.
The GDPR is wide-ranging in scope and imposes numerous requirements on companies that process personal data, including requirements relating to ensuring an appropriate legal basis and/or condition applies to the processing of personal data, the processing of sensitive date (such as health data), where required by law obtaining consent of the individuals to whom the personal data relates, providing information to individuals regarding data processing activities, implementing safeguards to protect the security and confidentiality of personal data, providing notification of data breaches, conducting data protection impact assessments for high risk processing and taking certain measures when engaging third-party processors.
The GDPR is wide-ranging in scope and imposes numerous requirements on companies that process personal data, including requirements relating to ensuring an appropriate legal basis and/or condition applies to the processing of personal data, the processing of sensitive date (such as health data), where required by law obtaining consent of the individuals to whom the personal data relates, providing information to individuals regarding data processing activities, implementing safeguards to protect the security and confidentiality of personal data, providing notification of data breaches, conducting data protection impact assessments for high risk processing and taking 42 Table of Contents certain measures when engaging third-party processors.
Our future commercial success depends in part on our ability to: • obtain, maintain, enforce and defend patent and other intellectual property rights for our important technology, inventions and know-how; 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 21 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.
Our future commercial success depends in part on our ability to: • obtain, maintain, enforce and defend patent and other intellectual property rights for our important technology, inventions and know-how; 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.
In addition, the manufacturing of authorized products, for which a separate manufacturer’s license is mandatory, must also be conducted in strict compliance with the EMA’s GMP requirements and comparable requirements of other regulatory bodies in the EU, which mandate the methods, facilities and controls used in manufacturing, processing and packing of medical products to assure their safety and identity.
In addition, the manufacturing of authorized products, for which a separate manufacturer’s license is mandatory, must also be conducted in strict compliance with the EMA’s GMP requirements and comparable requirements of other regulatory bodies in the EU, which mandate the methods, facilities and controls used in manufacturing, processing and packing of medicinal products to assure their safety and identity.
Of these full-time employees, 144 employees are engaged in research and development. None of our employees are represented by labor unions or covered by collective bargaining agreements. We consider our relationship with our employees to be good. Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and new employees.
Of these full-time employees, 116 employees are engaged in research and development. None of our employees are represented by labor unions or covered by collective bargaining agreements. We consider our relationship with our employees to be good. Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and new employees.
These sanctions may include, but are not limited to, the FDA’s refusal to allow an applicant to proceed with 25 Table of Contents clinical testing, refusal to approve pending applications, license suspension, or revocation, withdrawal of an approval, warning letters, adverse publicity, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines and civil or criminal investigations and penalties brought by the FDA or the Department of Justice (“DOJ”), and other governmental entities, including state agencies.
These sanctions may include, but are not limited to, the FDA’s refusal to allow an applicant to proceed with clinical testing, refusal to approve pending applications, license suspension, or revocation, withdrawal of an approval, warning letters, adverse publicity, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines and civil or criminal investigations and penalties brought by the FDA or the Department of Justice (“DOJ”), and other governmental entities, including state agencies.
ENTR-601-45 The decision to initiate the ELEVATE-45 multiple-ascending dose trial is based in part on the clinical trial ENTR-601-44-101 described above, and in part on the strength of preclinical pharmacodynamic data indicating robust exon skipping, dystrophin production and functional correction in the del44hDMD. mdx mouse model.
ENTR-601-45 The decision to initiate the ELEVATE-45 multiple-ascending dose trial was based in part on the clinical trial ENTR-601-44-101 described above, and in part on the strength of preclinical pharmacodynamic data indicating robust exon skipping, dystrophin production and functional correction in the del44hDMD. mdx mouse model.
Nonetheless, we take steps to protect and preserve our trade secrets and other confidential and proprietary information and prevent the unauthorized disclosure of the foregoing, including by entering into non-disclosure and invention assignment agreements with parties who have access to our trade secrets or other confidential and proprietary information, such as employees, consultants, outside scientific collaborators, contract research and manufacturing organizations, sponsored researchers and other advisors, at the commencement of their 23 Table of Contents employment, consulting or other relationships with us.
Nonetheless, we take steps to protect and preserve our trade secrets and other confidential and proprietary information and prevent the unauthorized disclosure of the foregoing, including by entering into non-disclosure and invention assignment agreements with parties who have access to our trade secrets or other confidential and proprietary information, such as employees, consultants, outside scientific collaborators, contract research and manufacturing organizations, sponsored researchers and other advisors, at the commencement of their employment, consulting or other relationships with us.
Part I is assessed by a coordinated review by the competent authorities of all EU Member States in which an application for authorization of a clinical trial has been submitted (Member States concerned) of a draft report prepared by a Reference Member State. Part II is assessed separately by each Member State concerned.
Part I is assessed by a coordinated review by the competent authorities of all EU Member States in which an application for authorization of a clinical trial has been submitted (Member States concerned) of a draft report prepared by a reporting Member State. Part II is assessed separately by each Member State concerned.
Systemic manifestations such as fatigue, gastrointestinal (“GI”) complications, cataracts, incontinence and excessive daytime sleepiness greatly impact a patient’s quality of life. As a result, DM1 leads to physical impairment, activity limitations and decreased participation in social activities and work.
Systemic manifestations such as fatigue, gastrointestinal (GI) complications, cataracts, incontinence and excessive daytime sleepiness greatly impact a patient’s quality of life. As a result, DM1 leads to physical impairment, activity limitations and decreased participation in social activities and work.
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; • fines, warning letters or holds on post-approval clinical trials; 33 Table of Contents • 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; or • injunctions or the imposition of civil or criminal penalties.
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; • 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; or • injunctions or the imposition of civil or criminal penalties.
However, the term of U.S. patents may be extended or adjusted for delays incurred due to compliance with FDA requirements or by delays encountered during prosecution that are caused by the United States Patent and Trademark Office (“USPTO”).
However, the term of U.S. patents may be extended or adjusted for delays incurred due to compliance with FDA requirements or by delays encountered during prosecution that are caused by the U.S. Patent and Trademark Office (“USPTO”).
The FDCA requires that a sponsor who is planning to submit a marketing application for a product that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration submit an initial Pediatric Study Plan (“PSP”), within sixty days of an end-of-Phase 2 meeting or as may be agreed between the sponsor and FDA.
The FDCA requires that a sponsor who is planning to submit a marketing application for a product 31 Table of Contents that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration submit an initial Pediatric Study Plan (“PSP”), within sixty days of an end-of-Phase 2 meeting or as may be agreed between the sponsor and FDA.
In our preclinical studies, we observed that approximately 50% of the EEV-conjugated material escaped the endosome to reach the intracellular disease target as compared to the We believe our EEV Platform can offer meaningful advantages over existing therapeutic approaches, including broad potential therapeutic index, potential utility across multiple modalities, and potential applicability to a wide range of diseases.
In our preclinical studies, we observed that approximately 50% of the EEV- 10 Table of Contents conjugated material escaped the endosome to reach the intracellular disease target as compared to the We believe our EEV Platform can offer meaningful advantages over existing therapeutic approaches, including broad potential therapeutic index, potential utility across multiple modalities, and potential applicability to a wide range of diseases.
Moreover, because of the extensive time required for development, testing and regulatory review of a potential product, it is possible that before any of our therapeutic candidates can be commercialized, any related patent may expire or remain in force for only a short period following commercialization, thereby reducing any competitive advantage provided by the patent.
Moreover, because of the extensive time required for development, testing and regulatory review of a potential product, it is possible that before any of our therapeutic candidates can be commercialized, any related patent may expire or remain in force for only a short period following commercialization, thereby reducing any competitive advantage provided 26 Table of Contents by the patent.
As a result, increasingly high barriers are being erected to the entry of new products. Political, economic and regulatory developments may further complicate pricing negotiations and pricing negotiations may continue after reimbursement has been obtained. Reference pricing used by various European Union Member States, and parallel trade (arbitrage between low-priced and high-priced Member States), can further reduce prices.
As a result, increasingly high barriers are being erected to the entry of new products. Political, economic and regulatory developments may further complicate pricing negotiations and pricing negotiations may continue after reimbursement has been obtained. Reference pricing used by various EU Member States, and parallel trade (arbitrage between low-priced and high-priced Member States), can further reduce prices.
Individual states in the United States have also become increasingly active in passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain drug access and marketing cost disclosure and transparency measures, and designed to encourage importation from other countries and bulk purchasing.
Individual states in the U.S. have also become increasingly active in passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain drug access and marketing cost disclosure and transparency measures, and designed to encourage importation from other countries and bulk purchasing.
The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions. 29 Table of Contents If the FDA approves a new product, it may limit the approved indication(s) for use of the product. It may also require that contraindications, warnings, or precautions be included in the product labeling.
The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions. If the FDA approves a new product, it may limit the approved indication(s) for use of the product. It may also require that contraindications, warnings, or precautions be included in the product labeling.
Recently, many countries in the European Union have increased the amount of discounts required on pharmaceuticals and these efforts could continue as countries attempt to manage healthcare expenditures, especially in light of the severe fiscal and debt crises experienced by many countries in the European Union. The downward pressure on healthcare costs in general, particularly prescription products, has become intense.
Recently, many countries in the EU have increased the amount of discounts required on pharmaceuticals and these efforts could continue as countries attempt to manage healthcare expenditures, especially in light of the severe fiscal and debt crises experienced by many countries in the EU. The downward pressure on healthcare costs in general, particularly prescription products, has become intense.
All forms of DM1, except the late-onset form, 17 Table of Contents are associated with high levels of disease burden and in the most severe cases can be associated with premature mortality. Life expectancy ranges from 45 years to 60 years. Seventy percent of early mortality is caused by cardiorespiratory complications.
All forms of DM1, except the late-onset form, are associated with high levels of disease burden and in the most severe cases can be associated with premature mortality. Life expectancy ranges from 45 years to 60 years. Seventy percent of early mortality is caused by cardiorespiratory complications.
There is no obligation for a manufacturer to make its investigational products available to eligible patients as a result of the Right to Try Act. Compliance with CGMP Requirements 28 Table of Contents Before approving an NDA or BLA, the FDA will typically inspect the facility or facilities where the product is manufactured.
There is no obligation for a manufacturer to make its investigational products available to eligible patients as a result of the Right to Try Act. Compliance with CGMP Requirements Before approving an NDA or BLA, the FDA will typically inspect the facility or facilities where the product is manufactured.
Clock stops may extend the timeframe of evaluation of a MAA considerably beyond 210 days. Where the CHMP gives a positive opinion, the EMA provides the opinion together with supporting documentation to the European Commission, who make the final decision to grant a marketing authorization, which is issued within 67 days of receipt of the EMA’s recommendation.
Clock stops may extend the timeframe of evaluation of a MAA considerably beyond 210 days. Where the CHMP gives a positive opinion, the EMA provides the opinion together with supporting documentation to the European Commission, which makes the final decision to grant a marketing authorization, which is issued within 67 days of receipt of the EMA’s recommendation.
VX-670 is comprised of a PMO conjugated to an EEV (the same EEV used in Entrada's DMD programs), which we would expect to sterically block CUG repeats and relieve or prevent the sequestration MBNL1 while leaving DMPK mRNA unaffected and leaving healthy levels of DMPK intact.
VX-670 is comprised of a PMO conjugated to an EEV (the same EEV used in Entrada's DMD programs), which we would expect to sterically block CUG 20 Table of Contents repeats and relieve or prevent the sequestration MBNL1 while leaving DMPK mRNA unaffected and leaving healthy levels of DMPK intact.
Clinical trials are conducted under protocols detailing, among other things, the objectives of the trial, 26 Table of Contents inclusion and exclusion criteria, the parameters to be used in monitoring safety, and the effectiveness criteria to be evaluated. A protocol for each clinical trial and any subsequent protocol amendments must be submitted to the FDA as part of the IND.
Clinical trials are conducted under protocols detailing, among other things, the objectives of the trial, inclusion and exclusion criteria, the parameters to be used in monitoring safety, and the effectiveness criteria to be evaluated. A protocol for each clinical trial and any subsequent protocol amendments must be submitted to the FDA as part of the IND.
The conduct of such a clinical trial could be expensive and result in delays in our commercialization efforts. In the European Union, pricing and reimbursement schemes vary widely from country to country. Some countries provide that products may be marketed only after a reimbursement price has been agreed.
The conduct of such a clinical trial could be expensive and result in delays in our commercialization efforts. In the EU, pricing and reimbursement schemes vary widely from country to country. Some countries provide that products may be marketed only after a reimbursement price has been agreed.
However, the FDA-approved labels for all four drugs state that continued approval may be contingent upon the verification of a clinical benefit in confirmatory clinical trials. None of the products are approved by the European 11 Table of Contents Medicines Agency (“EMA”) due to insufficient evidence of clinical benefit.
However, the FDA-approved labels for all four drugs state that continued approval may be contingent upon the verification of a clinical benefit in confirmatory clinical trials. None of the products are approved by the European Medicines Agency (“EMA”) due to insufficient evidence of clinical benefit.
The BPCIA established a regulatory scheme authorizing the FDA to 32 Table of Contents approve biosimilars and interchangeable biosimilars. A biosimilar is a biological product that is highly similar to an existing FDA-licensed “reference product.” The FDA has issued multiple guidance documents outlining an approach to review and approval of biosimilars.
The BPCIA established a regulatory scheme authorizing the FDA to approve biosimilars and interchangeable biosimilars. A biosimilar is a biological product that is highly similar to an existing FDA-licensed “reference product.” The FDA has issued multiple guidance documents outlining an approach to review and approval of biosimilars.
A single UK-wide marketing authorization will be granted by the MHRA for all novel medicinal products to be sold in the UK, enabling products to be sold in a single pack and under a single authorization throughout the UK.
A single UK-wide marketing authorization will be granted by the MHRA for medicinal products to be sold in the UK, enabling products to be sold in a single pack and under a single authorization throughout the UK.
We believe our EEV Platform can enable the efficient intracellular delivery of highly targeted and potent therapeutics throughout the body. The cornerstone of our platform, our proprietary EEV peptides are based upon small 9 Table of Contents cyclic peptides of approximately 10 amino acid residues or fewer.
We believe our EEV Platform can enable the efficient intracellular delivery of highly targeted and potent therapeutics throughout the body. The cornerstone of our platform, our proprietary EEV peptides are based upon small cyclic peptides of approximately 10 amino acid residues or fewer.
The heightening compliance environment and the need to build and maintain robust and 34 Table of Contents secure systems to comply with different privacy compliance and/or reporting requirements in multiple jurisdictions could increase the possibility that we may fail to comply fully with one or more of these requirements.
The heightening compliance environment and the need to build and maintain robust and secure systems to comply with different privacy compliance and/or reporting requirements in multiple jurisdictions could increase the possibility that we may fail to comply fully with one or more of these requirements.
Even if any therapeutic candidates we may develop are approved, sales of such therapeutic candidates will depend, in part, on the extent to which third-party payers, including government health programs in the United States such as Medicare and Medicaid, commercial health insurers and managed care organizations, provide coverage and establish adequate reimbursement levels for, such therapeutic candidates.
Even if any therapeutic candidates we may develop are approved, sales of such therapeutic candidates will depend, in part, on the extent to which third-party payers, including government health programs in the U.S. such as Medicare and Medicaid, commercial health insurers and managed care organizations, provide coverage and establish adequate reimbursement levels for, such therapeutic candidates.
Intellectual Property We strive to protect our proprietary technology, inventions, improvements, platforms, program candidates, therapeutic 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 foreign jurisdictions.
Intellectual Property We strive to protect our proprietary technology, inventions, improvements, platforms, program candidates, therapeutic 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 U.S. and in foreign jurisdictions.
Importantly, a dedicated EMA contact and rapporteur from the Committee for Medicinal Products for Human Use (“CHMP”), or Committee for Advanced Therapies are appointed early in the PRIME scheme facilitating increased understanding of the product at the EMA’s committee level.
Importantly, a dedicated EMA contact and a rapporteur from the Committee for Medicinal Products for Human Use (“CHMP”) or the Committee for Advanced Therapies (“CAT”), as applicable, are appointed early in the PRIME scheme, facilitating increased understanding of the product at the EMA’s committee level.
For example, in the United States, a patent claiming a new chemical entity or 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 (the “Hatch-Waxman Act”) for up to five years beyond the normal expiration date of the patent.
For example, in the U.S., a patent claiming a new chemical entity or 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 (the “Hatch-Waxman Act”) for up to five years beyond the normal expiration date of the patent.
Third-party reimbursement and coverage may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in product development. In addition, any companion diagnostic tests require coverage and reimbursement separate and apart from the coverage and reimbursement for their companion 39 Table of Contents pharmaceutical or biological products.
Third-party reimbursement and coverage may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in product development. In addition, any companion diagnostic tests require coverage and reimbursement separate and apart from the coverage and reimbursement for their companion pharmaceutical or biological products.
For the purposes of accelerated approval, 30 Table of Contents a surrogate endpoint is a marker, such as a laboratory measurement, radiographic image, physical sign, or other measure that is thought to predict clinical benefit but is not itself a measure of clinical benefit.
For the purposes of accelerated approval, a surrogate endpoint is a marker, such as a laboratory measurement, radiographic image, physical sign, or other measure that is thought to predict clinical benefit but is not itself a measure of clinical benefit.
If reports of requested pediatric studies are submitted to and accepted by the FDA within the statutory time limits, whatever statutory or regulatory periods of exclusivity that cover the product are extended by six months. U.S.
If reports of requested pediatric studies are submitted to and accepted by the FDA within the statutory time limits, whatever statutory or regulatory periods of exclusivity that cover the product are extended by six months. 35 Table of Contents U.S.
Once renewed, the marketing authorization is valid for an unlimited period, unless the European Commission or the competent authority decides, on justified grounds relating to pharmacovigilance, to proceed with one additional five-year renewal period.
Once renewed, the marketing authorization is valid for an unlimited period, unless the European Commission or the applicable Member State competent authority decides, on justified grounds relating to pharmacovigilance, to proceed with one additional five-year renewal period.
Patent Term Restoration and Extension and Marketing Exclusivity 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 Hatch-Waxman Act, which permits a patent extension of up to five years for patent term lost during product development and FDA regulatory review.
Patent Term Restoration and Extension and Marketing Exclusivity In the U.S., 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 Hatch-Waxman Act, which permits a patent extension of up to five years for patent term lost during product development and FDA regulatory review.
We believe we are the first company to demonstrate evidence of delivery to satellite cells in preclinical models. Muscle satellite cells are a pool of quiescent muscle stem cells which are activated 12 Table of Contents upon injury to help repair or regenerate myofibers.
We believe we are the first company to demonstrate evidence of delivery to satellite cells in preclinical models. Muscle satellite cells are a pool of quiescent muscle stem cells which are activated upon injury to help repair or regenerate myofibers.
Among these patent families, we have 281 pending applications (including PCT, provisional and non-provisional applications) in the U.S. and Europe, as well as other countries of strategic value; and 83 granted patents in the U.S., Europe, China, India, Japan, and Hong Kong (including a total of 45 member state validations of three European patents).
Among these patent families, we have 266 pending applications (including PCT, provisional and non-provisional applications) in the U.S. and Europe, as well as other countries of strategic value; and 88 granted patents in the U.S., Europe, China, India, Japan, and Hong Kong (including a total of 45 member state validations of three European patents).
During the additional two-year period of market exclusivity, a generic or biosimilar MAA can be submitted and authorized, and the innovator’s data may be referenced, but no generic or biosimilar medicinal product can be marketed until the 36 Table of Contents expiration of the market exclusivity.
During the additional two-year period of market exclusivity, a generic or biosimilar MAA can be submitted and authorized, and the innovator’s data may be referenced, but no generic or biosimilar medicinal product can be marketed until the expiration of the market exclusivity.
We estimate that DMD occurs in approximately one in every 3,500 to 5,000 live male births and that the patient population is approximately 41,000 patients in the aggregate in the United States and Europe. Approximately 80% of patients have mutations amenable to exon skipping in the nucleus. Corticosteroids are the current standard of care.
We estimate that DMD occurs in approximately one in every 3,500 to 5,000 live male births and that the patient population is approximately 41,000 patients in the aggregate in the U.S. and Europe. Approximately 80% of patients have mutations amenable to exon skipping in the nucleus. Corticosteroids are the current standard of care.
As of January 1, 2021, the United Kingdom’s European Union (Withdrawal) Act 2018 incorporated the GDPR (as it existed on December 31, 2020 but subject to certain UK specific amendments) into UK law, referred to as the UK GDPR.
As of January 1, 2021, the UK’s European Union (Withdrawal) Act 2018 incorporated the GDPR (as it existed on December 31, 2020 but subject to certain UK specific amendments) into UK law, referred to as the UK GDPR.
DM1 is commonly estimated to affect approximately 110,000 people in the United States and Europe. The disease is typically categorized based on age of onset and severity of symptoms into various phenotypes: 75% classical (adult-onset in the second to fourth decade of life); 10% childhood; and 15% congenital.
DM1 is commonly estimated to affect approximately 110,000 people in the U.S. and Europe. The disease is typically categorized based on age of onset and severity of symptoms into various phenotypes: 75% classical (adult-onset in the second to fourth decade of life); 10% childhood; and 15% congenital.
In some cases, the FDA may approve an NDA or BLA for a product but require the sponsor to conduct additional clinical trials to further assess the product’s safety and effectiveness after approval. Such post-approval trials are typically 27 Table of Contents referred to as Phase 4 clinical trials.
In some cases, the FDA may approve an NDA or BLA for a product but require the sponsor to conduct additional clinical trials to further assess the product’s safety and effectiveness after approval. Such post-approval trials are typically referred to as Phase 4 clinical trials.
In the United States, a rare disease or condition is statutorily defined as a condition that affects fewer than 200,000 individuals in the United States or that affects 200,000 or more individuals in the United States and for which there is no reasonable expectation that the cost of developing and making available the biologic for the disease or condition will be recovered from sales of the product in the United States.
In the U.S., a rare disease or condition is statutorily defined as a condition that affects fewer than 200,000 individuals in the U.S. or that affects 200,000 or more individuals in the U.S. and for which there is no reasonable expectation that the cost of developing and making available the biologic for the disease or condition will be recovered from sales of the product in the U.S.
Pediatric Exclusivity Pediatric exclusivity is another type of non-patent marketing exclusivity in the United States and, if granted, provides for the attachment of an additional six months of marketing protection to the term of any existing regulatory exclusivity, including orphan exclusivity, for all formulations, dosage forms, and indications of the active moiety and, for drugs, patent terms.
Pediatric Exclusivity Pediatric exclusivity is another type of non-patent marketing exclusivity in the U.S. and, if granted, provides for the attachment of an additional six months of marketing protection to the term of any existing regulatory exclusivity, including orphan exclusivity, for all formulations, dosage forms, and indications of the active moiety and, for drugs, patent terms.
We make these reports available through our website as soon as reasonably practicable after we electronically file such reports with, or furnish such reports to, the SEC. You can review our electronically filed reports 41 Table of Contents and other information that we file with the SEC on the SEC’s web site at http://www.sec.gov.
We make these reports available through our website as soon as reasonably practicable after we electronically file such reports with, or furnish such reports to, the SEC. You can review our electronically filed reports and other information that we file with the SEC on the SEC’s web site at http://www.sec.gov.
A fifth drug, ataluren, was conditionally approved outside of the United States in certain territories for nonsense mutations in ambulatory patients with DMD aged five years and older. These therapies require weekly intravenous infusions which is suboptimal from a patient perspective.
A fifth drug, ataluren, was conditionally approved outside of the U.S. in certain territories for nonsense mutations in ambulatory patients with DMD aged five years and older. These therapies require weekly intravenous infusions which is suboptimal from a patient perspective.
We expect that additional United States federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that the United States federal government will pay for healthcare drugs and services, which could result in reduced demand for our drug candidates or additional pricing pressures.
We expect that additional U.S. federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that the U.S. federal government will pay for healthcare drugs and services, which could result in reduced demand for our drug candidates or additional pricing pressures.
The federal government has levied large civil and criminal fines against companies for alleged improper promotion and has also requested that companies enter into consent decrees or permanent injunctions under which specified promotional conduct is changed or curtailed.
The federal government has levied large civil and criminal fines against 37 Table of Contents companies for alleged improper promotion and has also requested that companies enter into consent decrees or permanent injunctions under which specified promotional conduct is changed or curtailed.
The responsibilities of the marketing organization would include developing educational initiatives with respect to approved products and establishing relationships with researchers and practitioners in relevant fields of medicine. Manufacturing and Supply We do not own or operate manufacturing facilities.
The responsibilities of the marketing organization would include developing educational initiatives with respect to approved products and establishing relationships with researchers and practitioners in relevant fields of medicine. 28 Table of Contents Manufacturing and Supply We do not own or operate our own manufacturing facilities.
In the United States, healthcare professionals are generally permitted to prescribe drugs for such off-label uses because the FDA does not regulate the practice of medicine. However, FDA regulations impose rigorous restrictions on manufacturers’ communications, prohibiting the promotion of off-label uses.
In the U.S., healthcare professionals are generally permitted to prescribe drugs for such off-label uses because the FDA does not regulate the practice of medicine. However, FDA regulations impose rigorous restrictions on manufacturers’ communications, prohibiting the promotion of off-label uses.
This provision has been transposed into the Human Medicines Regulations 2012 and so remains applicable in the UK despite its departure from the EU. Payments made to physicians in certain EU Member States must be publicly disclosed.
This provision has been transposed into the Human Medicines Regulations 2012 and so remains applicable in the UK despite its departure from the EU. 41 Table of Contents Payments made to physicians in certain EU Member States must be publicly disclosed.
In the United States and markets in other countries, patients who are prescribed treatments for their conditions and providers performing the prescribed services generally rely on third-party payers to reimburse all or part of the associated healthcare costs.
In the U.S. and markets in other countries, patients who are prescribed treatments for their conditions and providers performing the prescribed services generally rely on third-party payers to reimburse all or part of the associated healthcare costs.
European Union Member States may approve a specific price for a product or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the product on the market.
EU Member States may approve a specific price for a product or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the product on the market.
A sponsor who wishes to conduct a clinical trial outside the United States may, but need not, obtain FDA authorization to conduct the clinical trial under an IND. When a foreign clinical trial is conducted under an IND, all FDA IND requirements must be met unless waived.
A sponsor who wishes to conduct a clinical trial outside the U.S. may, but need not, obtain FDA authorization to conduct the clinical trial under an IND. When a foreign clinical trial is conducted under an IND, all FDA IND requirements must be met unless waived.
General Data Protection Regulation Once we begin processing of personal data regarding individuals in the European Union, including personal health data, our activities will be subject to the GDPR.
General Data Protection Regulation Once we begin processing of personal data regarding individuals in the EU, including personal health data, our activities will be subject to the GDPR.
Much like the Anti-Kickback Statue prohibition in the United States, the provision of benefits or advantages to physicians to induce or encourage the prescription, recommendation, endorsement, purchase, supply, order or use of medicinal products is also prohibited in the EU.
Much like the Anti-Kickback Statue prohibition in the U.S., the provision of benefits or advantages to physicians to induce or encourage the prescription, recommendation, endorsement, purchase, supply, order or use of medicinal products is also prohibited in the EU.
Government Regulation Government authorities in the United States, at the federal, state and local level and in other countries and jurisdictions, including the European Union, extensively regulate, among other things, the research, development, testing, manufacture, pricing, reimbursement, sales, quality control, approval, packaging, storage, recordkeeping, labeling, advertising, promotion, distribution, marketing, post-approval monitoring and reporting and import and export of drugs and biological products such as those we are developing.
Government Regulation Government authorities in the U.S., at the federal, state and local level and in other countries and jurisdictions, including the EU, extensively regulate, among other things, the research, development, testing, manufacture, pricing, reimbursement, sales, quality control, approval, packaging, storage, recordkeeping, labeling, advertising, promotion, distribution, marketing, post-approval monitoring and reporting and import and export of drugs and biological products, such as those we are developing.
Outside the United States, ensuring adequate coverage and payment for any therapeutic candidates we may develop will face challenges. Pricing of prescription pharmaceuticals is subject to governmental control in many countries.
Outside the U.S., ensuring adequate coverage and payment for any therapeutic candidates we may develop will face challenges. Pricing of prescription pharmaceuticals is subject to governmental control in many countries.
As of February 20, 2025 , our organization was comprised of 183 talented individuals with significant experience across discovery, preclinical research, manufacturing, clinical development and operations. We are supported by leading scientific and clinical experts in the fields of peptide chemistry, oligonucleotide and protein optimization, disease specific pathophysiology and clinical development.
As of February 19, 2026 , our organization was comprised of 152 talented individuals with significant experience across discovery, preclinical research, manufacturing, clinical development and operations. We are supported by leading scientific and clinical experts in the fields of peptide chemistry, oligonucleotide and protein optimization, disease specific pathophysiology and clinical development.
For more information, please see the section entitled “Risk Factors—Risks Related to Our Intellectual Property.” License Agreement with The Ohio State University On May 12, 2017, we entered into an option agreement with Ohio State Innovation Foundation (“OSIF”), an affiliate of The Ohio State University (“OSU”) responsible for the commercialization of technology developed at or created by or for OSU, in which the Company obtained an option (“OSIF Option Agreement”) to license all patents and patent applications involving technologies using cell-penetrating peptides arising out of or related to specified invention disclosures or through a sponsored research agreement executed with OSU on the same date (“OSU SRA”).
For more information, please see the section titled “ Risk Factors — Risks Related to Our Intellectual Property ” included elsewhere in this Annual Report. 27 Table of Contents License Agreement with The Ohio State University On May 12, 2017, we entered into an option agreement with Ohio State Innovation Foundation (“OSIF”), an affiliate of The Ohio State University (“OSU”) responsible for the commercialization of technology developed at or created by or for OSU, in which the Company obtained an option (“OSIF Option Agreement”) to license all patents and patent applications involving technologies using cell-penetrating peptides arising out of or related to specified invention disclosures or through a sponsored research agreement executed with OSU on the same date (“OSU SRA”).
In addition, once we begin to conduct business in the United Kingdom, we will be subject to stringent data protection laws that are in effect in the United Kingdom.
In addition, once we begin to conduct business in the UK, we will be subject to stringent data protection laws that are in effect in the UK.
Orphan drug exclusivity means that the FDA may not approve another sponsor’s marketing application for the same product for the same indication for seven years, except in certain 31 Table of Contents limited circumstances.
Orphan drug exclusivity means that the FDA may not approve another sponsor’s marketing application for the same product for the same indication for seven years, except in certain limited circumstances.
The UK GDPR and the UK Data Protection Act 2018 set out the United Kingdom’s data protection regime, which is independent from but aligned to the European Union’s data protection regime. Non-compliance with the UK GDPR may result in monetary penalties of up to £17.5 million or 4% of worldwide revenue, whichever is higher.
The UK GDPR and the UK Data Protection Act 2018 set out the UK’s data protection regime, which is independent from but aligned to the EU’s data protection regime. Non-compliance with the UK GDPR may result in monetary penalties of up to £17.5 million or 4% of worldwide revenue, whichever is higher.
The FDCA provides a five-year period of non-patent marketing exclusivity within the United States to the first applicant to gain approval of an NDA for a new chemical entity.
The FDCA provides a five-year period of non-patent marketing exclusivity within the U.S. to the first applicant to gain approval of an NDA for a new chemical entity.
Changes in the patent laws and rules, whether by legislation, judicial decisions or regulatory interpretation, in the United States and other jurisdictions may have uncertain affects that could improve or diminish our ability to protect our inventions and 22 Table of Contents obtain, maintain, defend and enforce our patent rights, and could therefore affect the value of our business in uncertain ways.
Changes in the patent laws and rules, whether by legislation, judicial decisions or regulatory interpretation, in the U.S. and other jurisdictions may have uncertain affects that could improve or diminish our ability to protect our inventions and obtain, maintain, defend and enforce our patent rights, and could therefore affect the value of our business in uncertain ways.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeAny of the above events could significantly harm our business, prospects, financial condition and results of operations and cause the price of our common stock to decline. We are an “emerging growth company”, and we cannot be certain if the reduced reporting requirements applicable to emerging growth companies will make our common stock less attractive to investors.
Biggest changeWe are an “emerging growth company” and a smaller reporting company and we cannot be certain if the reduced reporting requirements applicable to emerging growth companies and smaller reporting companies will make our common stock less attractive to investors. We are an “emerging growth company,” as defined in the Jumpstart Our Business Startups Act of 2012 (“JOBS Act”).
Furthermore, if we decide to submit an application for accelerated approval, there can be no assurance that such application will be accepted or that any approval will be granted on a timely basis, or at all.
Furthermore, if we decide to submit an application for accelerated approval, there can be no assurance that any such application will be accepted or that any approval will be granted on a timely basis, or at all.
Supreme Court’s July 2024 decision to overturn prior established case law giving deference to regulatory agencies’ interpretations of ambiguous statutory language has introduced uncertainty regarding the extent to which FDA’s regulations, policies and decisions may become subject to increasing legal challenges, delays, and/or changes.
Supreme Court’s July 2024 decision to overturn prior established case law giving deference to regulatory agencies’ interpretations of ambiguous statutory language has introduced uncertainty regarding the extent to which FDA’s regulations, policies and decisions may become subject to increasing legal challenges, delays, and/or changes.
Even if we are able to obtain a license, the license would likely obligate us to pay license fees or royalties or both, and the rights granted to us might be nonexclusive, which could result in our competitors gaining access to the same intellectual property.
Even if we are able to obtain a license, the license would likely obligate us to pay license fees or royalties or both, and the rights granted to us might be nonexclusive, which could result in our competitors gaining access to the same intellectual property.
Collaborations involving our research programs or any therapeutic candidates we may develop pose numerous risks to us, including the following: • collaborators would have significant discretion in determining the efforts and resources that they will apply to these collaborations; 64 Table of Contents • collaborators may not perform their obligations as expected; • collaborators may not pursue development and commercialization of any therapeutic 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 therapeutic candidate, repeat or conduct new clinical trials or require a new formulation of a therapeutic candidate for clinical testing; • collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with any therapeutic 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, causing the emphasis on our product development or commercialization program under such collaboration to be delayed, diminished or terminated; • collaborators with marketing and distribution rights to one or more products may not commit sufficient resources to the marketing and distribution of such product or products; • 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; • if a collaborator of ours is involved in a business combination, the collaborator might de-emphasize or terminate the development or commercialization of any therapeutic candidate licensed to it by us; • disputes may arise between the collaborators and us that result in the delay or termination of the research, development, or commercialization of any therapeutic 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 therapeutic candidates we may develop; • our collaborators’ business or operations could be disrupted due to reasons outside of our control, such as global health crises, macroeconomic conditions and geopolitical developments, which could have an adverse impact on their development and commercialization efforts or the prospects of our collaboration; and • collaboration agreements may not lead to development or commercialization of therapeutic candidates in the most efficient manner or at all.
Collaborations involving our research programs or any therapeutic candidates we may develop pose numerous risks to us, including the following: • collaborators would have significant discretion in determining the efforts and resources that they will apply to these collaborations; • collaborators may not perform their obligations as expected; • collaborators may not pursue development and commercialization of any therapeutic 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 therapeutic candidate, repeat or conduct new clinical trials or require a new formulation of a therapeutic candidate for clinical testing; • collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with any therapeutic 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; 68 Table of Contents • collaborators may be acquired by a third party having competitive products or different priorities, causing the emphasis on our product development or commercialization program under such collaboration to be delayed, diminished or terminated; • collaborators with marketing and distribution rights to one or more products may not commit sufficient resources to the marketing and distribution of such product or products; • 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; • if a collaborator of ours is involved in a business combination, the collaborator might de-emphasize or terminate the development or commercialization of any therapeutic candidate licensed to it by us; • disputes may arise between the collaborators and us that result in the delay or termination of the research, development, or commercialization of any therapeutic 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 therapeutic candidates we may develop; • our collaborators’ business or operations could be disrupted due to reasons outside of our control, such as global health crises, macroeconomic conditions and geopolitical developments, which could have an adverse impact on their development and commercialization efforts or the prospects of our collaboration; and • collaboration agreements may not lead to development or commercialization of therapeutic candidates in the most efficient manner or at all.
The federal False Claims Act also permits a private individual acting as a “whistleblower” to bring actions on behalf of the federal government alleging violations of the federal False Claims Act and to share in any monetary recovery; • the federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), which created new federal criminal statutes that prohibit a person from knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or obtain, by means of false or fraudulent pretenses, representations or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless of the payor (e.g., public or private) and knowingly and willfully falsifying, concealing or covering up by any trick or device a material fact or making any materially false, fictitious, or fraudulent statements or representations in connection with the delivery of, or payment for, healthcare benefits, 74 Table of Contents items or services relating to healthcare matters; similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; • HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (“HITECH”) and their respective implementing regulations, including the Final Omnibus Rule published in January 2013, which impose requirements on certain covered healthcare providers, health plans, and healthcare clearinghouses as well as their respective business associates, independent contractors or agents of covered entities, that perform services for them that involve the creation, maintenance, receipt, use, or disclosure of, individually identifiable health information relating to the privacy, security and transmission of individually identifiable health information.
The federal False Claims Act also permits a private individual acting as a “whistleblower” to bring actions on behalf of the federal government alleging violations of the federal False Claims Act and to share in any monetary recovery; • the federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), which created new federal criminal statutes that prohibit a person from knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or obtain, by means of false or fraudulent pretenses, representations or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless of the payor (e.g., public or private) and knowingly and willfully falsifying, concealing or covering up by any trick or device a material fact or making any materially false, fictitious, or 78 Table of Contents fraudulent statements or representations in connection with the delivery of, or payment for, healthcare benefits, items or services relating to healthcare matters; similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; • HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (“HITECH”) and their respective implementing regulations, including the Final Omnibus Rule published in January 2013, which impose requirements on certain covered healthcare providers, health plans, and healthcare clearinghouses as well as their respective business associates, independent contractors or agents of covered entities, that perform services for them that involve the creation, maintenance, receipt, use, or disclosure of, individually identifiable health information relating to the privacy, security and transmission of individually identifiable health information.
As our therapeutic candidates and discovery programs progress, we or others may determine: that certain of our risk allocation decisions were incorrect or insufficient; that we made platform level technology mistakes; that individual programs or our EEV science in general has technology or biology risks that were unknown or underappreciated; that our choices on how to develop our infrastructure to support our scale will result in an inability to manufacture our therapeutics for clinical trials or otherwise impair our manufacturing; or that we have allocated resources in such a way that large investments are not recovered and capital allocation is not subject to rapid re-direction.
As our therapeutic candidates and discovery programs progress, we or others may determine: that certain of our risk allocation decisions were incorrect or insufficient; that we made platform level technology mistakes; that individual programs or our science in general has technology or biology risks that were unknown or underappreciated; that our choices on how to develop our infrastructure to support our scale will result in an inability to manufacture our therapeutics for clinical trials or otherwise impair our manufacturing; or that we have allocated resources in such a way that large investments are not recovered and capital allocation is not subject to rapid re-direction.
Other events that may prevent successful enrollment, initiation or timely completion of clinical development include: • we may be unable to generate sufficient preclinical, toxicology or other in vivo or in vitro data to support the initiation of clinical trials; • delays in reaching a consensus with regulatory authorities on trial design; • delays in reaching agreement on acceptable terms with prospective clinical research organizations (“CROs”) and clinical trial sites; • delays in opening clinical trial sites or obtaining required institutional review board (“IRB”) or independent ethics committee approval, or the equivalent review groups for sites outside the United States, at each clinical trial site; • we may need to add new or additional clinical trial sites; • 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; • negative or inconclusive results observed in clinical trials, including failure to demonstrate statistical significance, safety, purity or potency, which could lead us, or cause regulators to require us, to conduct additional clinical trials or abandon product development programs; • positive results from our preclinical studies of our therapeutic candidates may not necessarily be predictive of the results from required later preclinical studies and clinical trials and positive results from such preclinical studies and clinical trials of our therapeutic candidates may not be replicated in subsequent preclinical studies or clinical trial results; • failure by us, any CROs we engage or any other third parties to adhere to clinical trial requirements; • failure to perform in accordance with applicable GCPs; • failure by investigators to adhere to clinical trial protocols leading to variable results; • delays in the testing, validation, manufacturing and delivery of any therapeutic candidates we may develop to the clinical sites, including delays by third parties with whom we have contracted to perform certain of those functions; • failure of our third-party contractors to comply with regulatory requirements or to meet their contractual obligations to us in a timely manner, or at all; • delays in having patients complete participation in a trial or return for post-treatment follow-up; • clinical trial sites or patients 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 associated with the therapeutic candidate that are viewed to outweigh its potential benefits; • occurrence of serious adverse events associated with a therapeutic 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; • the FDA, other regulatory authorities, or ethics committees may require us to submit additional data such as long-term toxicology studies or impose other requirements before permitting us to initiate a clinical trial; • 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 enrollment, initiation or timely completion of clinical development include: • we may be unable to generate sufficient preclinical, toxicology or other in vivo or in vitro data to support the initiation of clinical trials; • delays in reaching a consensus with regulatory authorities on trial design; • delays in reaching agreement on acceptable terms with prospective clinical research organizations (“CROs”) and clinical trial sites; • delays in opening clinical trial sites or obtaining required institutional review board (“IRB”) or independent ethics committee approval, or the equivalent review groups for sites outside the United States, at each clinical trial site; • we may need to add new or additional clinical trial sites; • 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; • negative or inconclusive results observed in clinical trials, including failure to demonstrate statistical significance, safety, purity or potency, which could lead us, or cause regulators to require us, to conduct additional clinical trials or abandon product development programs; • positive results from our preclinical studies of our therapeutic candidates may not necessarily be predictive of the results from required later preclinical studies and clinical trials and positive results from such preclinical studies and clinical trials of our therapeutic candidates may not be replicated in subsequent preclinical studies or clinical trial results; • failure by us, any CROs we engage or any other third parties to adhere to clinical trial requirements; • failure to perform in accordance with applicable GCPs; • failure by investigators to adhere to clinical trial protocols leading to variable results; • delays in the testing, validation, manufacturing and delivery of any therapeutic candidates we may develop to the clinical sites, including delays by third parties with whom we have contracted to perform certain of those functions; 53 Table of Contents • failure of our third-party contractors to comply with regulatory requirements or to meet their contractual obligations to us in a timely manner, or at all; • delays in having patients complete participation in a trial or return for post-treatment follow-up; • clinical trial sites or patients 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 associated with the therapeutic candidate that are viewed to outweigh its potential benefits; • occurrence of serious adverse events associated with a therapeutic 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; • the FDA, other regulatory authorities, or ethics committees may require us to submit additional data such as long-term toxicology studies or impose other requirements before permitting us to initiate a clinical trial; • 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.
For example: • others may be able to make products that are similar to our therapeutic candidate or utilize similar technology but that are not covered by the claims of the patents that we license or may own; • we might not have been the first to make the inventions covered by our current or future patent applications; • we might not have been the first to file patent applications covering our inventions; • others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our intellectual property rights; • it is possible that our current or future patent applications will not lead to issued patents; • any patent issuing from our current or future patent applications may be held invalid or unenforceable, including as a result of legal challenges by our competitors or other third parties; 89 Table of Contents • our competitors or other third parties might conduct research and development activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; • we have engaged in scientific collaborations in the past and will continue to do so in the future and our collaborators may develop adjacent or competing products that are outside the scope of our patents; • we may not develop additional proprietary technologies that are patentable; • the patents of others may harm our business; and • we may choose not to file for patent protection in order to maintain certain trade secrets or know-how, and a third party may subsequently file a patent application covering such intellectual property.
For example: 93 Table of Contents • others may be able to make products that are similar to our therapeutic candidate or utilize similar technology but that are not covered by the claims of the patents that we license or may own; • we might not have been the first to make the inventions covered by our current or future patent applications; • we might not have been the first to file patent applications covering our inventions; • others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our intellectual property rights; • it is possible that our current or future patent applications will not lead to issued patents; • any patent issuing from our current or future patent applications may be held invalid or unenforceable, including as a result of legal challenges by our competitors or other third parties; • our competitors or other third parties might conduct research and development activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; • we have engaged in scientific collaborations in the past and will continue to do so in the future and our collaborators may develop adjacent or competing products that are outside the scope of our patents; • we may not develop additional proprietary technologies that are patentable; • the patents of others may harm our business; and • we may choose not to file for patent protection in order to maintain certain trade secrets or know-how, and a third party may subsequently file a patent application covering such intellectual property.
To the extent that any disruption, data breach, or cybersecurity incident were to result in a loss of, or damage to, our data or applications, or those of our third-party CROs, vendors and other contractors and consultants, or inappropriate disclosure of confidential or proprietary information, we could incur liability and reputational damage and the further development and commercialization of ENTR-601-44, ENTR-601-45, ENTR-601-50, ENTR-601-51, our partnered candidate VX-670 or any future therapeutic candidates could be delayed.
To the extent that any disruption, data breach, or cybersecurity incident were to result in a loss of, or damage to, our data or applications, or those of our third-party CROs, vendors and other contractors and consultants, or inappropriate disclosure of confidential or proprietary information, we could incur liability and reputational damage and the further development and commercialization of ENTR-601-44, ENTR-601-45, ENTR-601-50, ENTR-601-51, ENTR-801, our partnered candidate VX-670 or any future therapeutic candidates could be delayed.
The FDA or comparable foreign regulatory authorities can delay, limit or deny approval of a therapeutic candidate for many reasons, including: • such authorities may disagree with the design or implementation of our or our current or future collaborators’ clinical trials; • negative or ambiguous results from our clinical trials or results may not meet the level of statistical significance required by the FDA or comparable foreign regulatory agencies for approval; • serious and unexpected drug-related side effects may be experienced by participants in our clinical trials or by individuals using drugs similar to our therapeutic candidates; • such authorities may not accept clinical data from trials which are conducted at clinical facilities or in countries where the standard of care is potentially different from that of the United States; 53 Table of Contents • we or any of our current or future collaborators may be unable to demonstrate that a therapeutic candidate is safe and effective, and that therapeutic candidate’s clinical and other benefits outweigh its safety risks; • such authorities may disagree with our interpretation of data from preclinical studies or clinical trials; • such authorities may not agree that the data collected from clinical trials of our therapeutic candidates are acceptable or sufficient to support the submission of an NDA or BLA or other submission or to obtain regulatory approval in the United States or elsewhere, and such authorities may impose requirements for additional preclinical studies or clinical trials; • such authorities may disagree regarding the formulation, labeling and/or the specifications of our therapeutic candidates; • approval may be granted only for indications that are significantly more limited than what we apply for and/or with other significant restrictions on distribution and use; • such authorities may find deficiencies in the manufacturing processes, approval policies or facilities of our third-party manufacturers with which we or any of our current or future collaborators contract for clinical and commercial supplies; • regulations of such authorities may significantly change in a manner rendering our or any of our potential future collaborators’ clinical data insufficient for approval; or • such authorities may not accept a submission due to, among other reasons, the content or formatting of the submission.
The FDA or comparable foreign regulatory authorities can delay, limit or deny approval of a therapeutic candidate for many reasons, including: • such authorities may disagree with the design or implementation of our or our current or future collaborators’ clinical trials; • negative or ambiguous results from our clinical trials or results may not meet the level of statistical significance required by the FDA or comparable foreign regulatory agencies for approval; • serious and unexpected drug-related side effects may be experienced by participants in our clinical trials or by individuals using drugs similar to our therapeutic candidates; • such authorities may not accept clinical data from trials which are conducted at clinical facilities or in countries where the standard of care is potentially different from that of the United States; • we or any of our current or future collaborators may be unable to demonstrate that a therapeutic candidate is safe and effective, and that therapeutic candidate’s clinical and other benefits outweigh its safety risks; • such authorities may disagree with our interpretation of data from preclinical studies or clinical trials; • such authorities may not agree that the data collected from clinical trials of our therapeutic candidates are acceptable or sufficient to support the submission of an NDA or BLA or other submission or to obtain regulatory approval in the United States or elsewhere, and such authorities may impose requirements for additional preclinical studies or clinical trials; • such authorities may disagree regarding the formulation, labeling and/or the specifications of our therapeutic candidates; • approval may be granted only for indications that are significantly more limited than what we apply for and/or with other significant restrictions on distribution and use; • such authorities may find deficiencies in the manufacturing processes, approval policies or facilities of our third-party manufacturers with which we or any of our current or future collaborators contract for clinical and commercial supplies; • regulations of such authorities may significantly change in a manner rendering our or any of our potential future collaborators’ clinical data insufficient for approval; or • such authorities may not accept a submission due to, among other reasons, the content or formatting of the submission.
Our future capital requirements will depend on many factors, including, but not limited to: • the type, number, scope, progress, expansions, results, costs and timing of our preclinical studies and any clinical trials of the therapeutic candidates that we are pursuing or may choose to pursue in the future; • the clinical development plans we establish for our therapeutic candidates; • the costs and timing of manufacturing for our therapeutic candidates and commercial manufacturing if any therapeutic candidate is approved; • the costs of establishing and maintaining clinical and commercial supply for the development and manufacture of our therapeutic candidates; • the costs, timing and outcome of regulatory review of our therapeutic candidates; • the terms and timing of establishing and maintaining collaborations, licenses and other similar arrangements; • the costs of obtaining, maintaining and enforcing our patents and other intellectual property rights; • our efforts to enhance operational systems and hire additional personnel to satisfy our obligations as a public company, including enhanced internal controls over financial reporting; • the costs associated with hiring additional personnel and consultants as our preclinical and clinical activities increase; • the achievement of milestones or occurrence of other developments that trigger payments under any collaboration agreements, if any; • the costs and timing of establishing or securing sales and marketing capabilities if any therapeutic candidate is approved; • subject to receipt of regulatory approval, revenue, if any, received from commercial sales of our therapeutic candidates; • our ability to achieve sufficient market acceptance, coverage and adequate reimbursement from third-party payors and adequate market share and revenue for any approved products; • the costs of preparing, filing and prosecuting patent applications, maintaining and protecting our intellectual property rights, including enforcing and defending intellectual property related claims; and • the ongoing costs of operating as a public company.
Our future capital requirements will depend on many factors, including, but not limited to: • the type, number, scope, progress, expansions, results, costs and timing of our preclinical studies and any clinical trials of the therapeutic candidates that we are pursuing or may choose to pursue in the future; • the clinical development plans we establish for our therapeutic candidates; • the costs and timing of manufacturing for our therapeutic candidates and commercial manufacturing if any therapeutic candidate is approved; • the costs of establishing and maintaining clinical and commercial supply for the development and manufacture of our therapeutic candidates; 47 Table of Contents • the costs, timing and outcome of regulatory review of our therapeutic candidates; • the terms and timing of establishing and maintaining collaborations, licenses and other similar arrangements; • the costs of obtaining, maintaining and enforcing our patents and other intellectual property rights; • our efforts to enhance operational systems and hire additional personnel to satisfy our obligations as a public company, including enhanced internal controls over financial reporting; • the costs associated with hiring additional personnel and consultants as our preclinical and clinical activities increase; • the achievement of milestones or occurrence of other developments that trigger payments under any collaboration agreements, if any; • the costs and timing of establishing or securing sales and marketing capabilities if any therapeutic candidate is approved; • subject to receipt of regulatory approval, revenue, if any, received from commercial sales of our therapeutic candidates; • our ability to achieve sufficient market acceptance, coverage and adequate reimbursement from third-party payors and adequate market share and revenue for any approved products; • the costs of preparing, filing and prosecuting patent applications, maintaining and protecting our intellectual property rights, including enforcing and defending intellectual property related claims; and • the ongoing costs of operating as a public company.
The rapid evolution of artificial intelligence will require the application of significant resources to design, develop, test and maintain our products and services to help ensure that artificial intelligence is implemented in accordance with applicable law and regulation and in a socially responsible manner and to minimize any real or perceived unintended harmful impacts.
The rapid evolution of AI will require the application of significant resources to design, develop, test and maintain our products and services to help ensure that artificial intelligence is implemented in accordance with applicable law and regulation and in a socially responsible manner and to minimize any real or perceived unintended harmful impacts.
We currently rely, and expect to continue to rely, on third parties with respect to many of these items, including contract manufacturing organizations (“CMOs”) for the manufacturing of any therapeutic candidates we test in preclinical or clinical development, as well as CROs for the conduct of our animal testing and research and CROs for the conduct of our planned clinical trials.
We currently rely, and expect to continue to rely, on third parties with respect to many of these items, including contract manufacturing organizations (“CMOs”) for the manufacturing of any therapeutic candidates we test in preclinical or clinical development, as well as contract research organizations (“CROs”) for the conduct of our animal testing and research and CROs for the conduct of our planned clinical trials.
The degree of market acceptance of our therapeutics will depend on a number of factors, including: • the demonstration of clinical efficacy and safety compared to other more-established products; • the indications for which our therapeutic candidates are approved; • the limitation of our targeted patient population and other limitations or warnings contained in any FDA-approved labeling; • the acceptance of a new drug for the relevant indication by healthcare providers and their patients; • the pricing and cost-effectiveness of our therapeutics, as well as the cost of treatment with our therapeutics in relation to alternative treatments and therapies; • our ability to obtain and maintain sufficient third-party coverage and adequate reimbursement from government healthcare programs, including Medicare and Medicaid, private health insurers and other third-party payors; • the willingness of patients to pay all, or a portion of, out-of-pocket costs associated with our therapeutics in the absence of sufficient third-party coverage and adequate reimbursement; • any restrictions on the use of our therapeutics, and the prevalence and severity of any adverse effects; • potential product liability claims; • the timing of market introduction of our therapeutics as well as competitive drugs; • the effectiveness of our or any of our current or potential future collaborators’ sales and marketing strategies; and • unfavorable publicity relating to the product.
The degree of market acceptance of our therapeutics will depend on a number of factors, including: • the demonstration of clinical efficacy and safety compared to other more-established products; • the indications for which our therapeutic candidates are approved; • the limitation of our targeted patient population and other limitations or warnings contained in any FDA-approved labeling; • the acceptance of a new drug for the relevant indication by healthcare providers and their patients; • the pricing and cost-effectiveness of our therapeutics, as well as the cost of treatment with our therapeutics in relation to alternative treatments and therapies; • our ability to obtain and maintain sufficient third-party coverage and adequate reimbursement from government healthcare programs, including Medicare and Medicaid, private health insurers and other third-party payors; 70 Table of Contents • the willingness of patients to pay all, or a portion of, out-of-pocket costs associated with our therapeutics in the absence of sufficient third-party coverage and adequate reimbursement; • any restrictions on the use of our therapeutics, and the prevalence and severity of any adverse effects; • potential product liability claims; • the timing of market introduction of our therapeutics as well as competitive drugs; • the effectiveness of our or any of our current or potential future collaborators’ sales and marketing strategies; and • unfavorable publicity relating to the product.
In addition, the loss of clinical trial data for ENTR-601-44, ENTR-601-45, ENTR-601-50, ENTR-601-51, our partnered candidate VX-670 or any other therapeutic candidates could result in delays in our marketing approval efforts and significantly increase our costs to recover or reproduce the data.
In addition, the loss of clinical trial data for ENTR-601-44, ENTR-601-45, ENTR-601-50, ENTR-601-51, ENTR-801, our partnered candidate VX-670 or any other therapeutic candidates could result in delays in our marketing approval efforts and significantly increase our costs to recover or reproduce the data.
The success of therapeutic candidates we may identify and develop will depend on many factors, including: • timely and successful completion of preclinical studies, including toxicology studies, biodistribution studies and minimally efficacious dose studies in animals, where applicable; • sufficiency of our financial and other resources to complete the necessary preclinical studies and clinical trials; • effective INDs or comparable foreign applications that allow commencement of our planned clinical trials or future clinical trials for any therapeutic candidates we may develop; • successful enrollment and completion of clinical trials, including under the FDA’s current Good Clinical Practices (“GCPs”), GLPs and any additional regulatory requirements from foreign regulatory authorities, such as the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Guideline for Good Clinical Practice ; • positive results from our current and future clinical trials that support a finding of safety and effectiveness and an acceptable risk-benefit profile in the intended populations; 46 Table of Contents • receipt of regulatory marketing approvals from applicable regulatory authorities; • establishment of arrangements with third-party manufacturers for clinical supply and, where applicable, commercial manufacturing capabilities; • establishment, maintenance, defense and enforcement of patent, trademark, trade secret and other intellectual property protection or regulatory exclusivity for any therapeutic candidates we may develop; • patient recruitment and enrollment; • commercial launch of any therapeutic candidates we may develop, if approved, whether alone or in collaboration with others; • acceptance of the benefits and use of our therapeutic candidates we may develop, including method of administration, if and when approved, by patients, the medical community and third-party payors; • our ability to compete effectively with other therapies and treatment options; • maintenance of a continued acceptable safety, tolerability and efficacy profile of any therapeutic candidates we may develop following approval; and • establishment and maintenance of healthcare coverage and adequate reimbursement by payors.
The success of therapeutic candidates we may identify and develop will depend on many factors, including: • timely and successful completion of preclinical studies, including toxicology studies, biodistribution studies and minimally efficacious dose studies in animals, where applicable; • sufficiency of our financial and other resources to complete the necessary preclinical studies and clinical trials; • effective INDs, CTAs or other comparable foreign applications that allow commencement of our planned clinical trials or future clinical trials for any therapeutic candidates we may develop; • successful enrollment and completion of clinical trials, including under the FDA’s current Good Clinical Practices (“GCPs”), GLPs and any additional regulatory requirements from foreign regulatory authorities, such as the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Guideline for Good Clinical Practice; • positive results from our current and future clinical trials that support a finding of safety and effectiveness and an acceptable risk-benefit profile in the intended populations; • receipt of regulatory marketing approvals from applicable regulatory authorities; • establishment of arrangements with third-party manufacturers for clinical supply and, where applicable, commercial manufacturing capabilities; • establishment, maintenance, defense and enforcement of patent, trademark, trade secret and other intellectual property protection or regulatory exclusivity for any therapeutic candidates we may develop; • patient recruitment and enrollment; • commercial launch of any therapeutic candidates we may develop, if approved, whether alone or in collaboration with others; • acceptance of the benefits and use of our therapeutic candidates we may develop, including method of administration, if and when approved, by patients, the medical community and third-party payors; • our ability to compete effectively with other therapies and treatment options; • maintenance of a continued acceptable safety, tolerability and efficacy profile of any therapeutic candidates we may develop following approval; and • establishment and maintenance of healthcare coverage and adequate reimbursement by payors.
In that event, we may be required to spend significant time and resources to redesign our therapeutic candidate or the method for manufacturing it or to develop or license replacement technology, all of which may not be feasible on a technical or commercial basis.
In that event, we may be required to spend time and resources to redesign our therapeutic candidate or the method for manufacturing it or to develop or license replacement technology, all of which may not be feasible on a technical or commercial basis.
For as long as we continue to be an emerging growth company, we intend to take advantage of exemptions from various reporting requirements that are applicable to other public companies that are not emerging growth companies, including: • being permitted to provide only two years of audited financial statements, in addition to any required unaudited interim financial statements, with correspondingly reduced “Management’s Discussion and Analysis of Financial Condition and Results of Operations” disclosure in our periodic reports; • not being required to comply with the auditor attestation requirements of Section 404 of the Sarbanes-Oxley Act of 2002, as amended (“Sarbanes-Oxley Act”); • not being required to comply with any requirement that may be adopted by the Public Company Accounting Oversight Board regarding mandatory audit firm rotation or a supplement to the auditor’s report providing additional information about the audit and the financial statements; • reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements; and 100 Table of Contents • exemptions from the requirements of holding nonbinding advisory stockholder votes on executive compensation and stockholder approval of any golden parachute payments not previously approved.
For as long as we continue to be an emerging growth company, we intend to take advantage of exemptions from various reporting requirements that are applicable to other public companies that are not emerging growth companies, including: • being permitted to provide only two years of audited financial statements, in addition to any required unaudited interim financial statements, with correspondingly reduced “Management’s Discussion and Analysis of Financial Condition and Results of Operations” disclosure in our periodic reports; • not being required to comply with the auditor attestation requirements of Section 404 of the Sarbanes-Oxley Act of 2002, as amended (“Sarbanes-Oxley Act”); • not being required to comply with any requirement that may be adopted by the Public Company Accounting Oversight Board regarding mandatory audit firm rotation or a supplement to the auditor’s report providing additional information about the audit and the financial statements; • reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements; and • exemptions from the requirements of holding nonbinding advisory stockholder votes on executive compensation and stockholder approval of any golden parachute payments not previously approved.
The use of certain artificial intelligence technology can give rise to intellectual property risks, including by disclosing or otherwise compromising our confidential or proprietary intellectual property, or by undermining our ability to assert or defend ownership rights in intellectual property created with the assistance of artificial intelligence tools.
The use of certain AI technology can give rise to intellectual property risks, including by disclosing or otherwise compromising our confidential or proprietary intellectual property, or by undermining our ability to assert or defend ownership rights in intellectual property created with the assistance of artificial intelligence tools.
If our operations are found to be in violation of any of the laws described above or any other governmental laws and regulations that may apply to us, we may be subject to 75 Table of Contents significant penalties, including administrative, civil and criminal penalties, damages, fines, disgorgement, the exclusion from participation in federal and state healthcare programs, individual imprisonment, reputational harm, and the curtailment or restructuring of our operations, as well as additional reporting obligations and oversight if we become subject to a corporate integrity agreement or other agreement to resolve allegations of non-compliance with these laws.
If our operations are found to be in violation of any of 79 Table of Contents the laws described above or any other governmental laws and regulations that may apply to us, we may be subject to significant penalties, including administrative, civil and criminal penalties, damages, fines, disgorgement, the exclusion from participation in federal and state healthcare programs, individual imprisonment, reputational harm, and the curtailment or restructuring of our operations, as well as additional reporting obligations and oversight if we become subject to a corporate integrity agreement or other agreement to resolve allegations of non-compliance with these laws.
Patient enrollment and trial competition may be affected by other factors including: 51 Table of Contents • clinicians’ and patients’ perceived risks and benefits of the therapeutic candidate under trial, particularly therapeutic candidates developed using a novel and unproven therapeutic approach, like our EEV therapeutic candidates in relation to available or investigational drugs; • size of the patient population, in particular for rare diseases such as the diseases on which we are initially focused, and process for identifying patients; • design of the trial protocol; • efforts to facilitate timely enrollment in clinical trials; • eligibility and exclusion criteria; • availability of competing therapies and clinical trials; • severity of the disease or disorder under investigation; • proximity and availability of clinical trial sites for prospective patients; • ability to obtain and maintain patient consent; • risk that enrolled patients will drop out before completion of the trial; • patient referral practices of physicians; and • ability to monitor patients adequately during and after treatment.
Patient enrollment and trial competition may be affected by other factors including: • clinicians’ and patients’ perceived risks and benefits of the therapeutic candidate under trial, particularly therapeutic candidates developed using a novel and unproven therapeutic approach, like our EEV therapeutic candidates in relation to available or investigational drugs; • size of the patient population, in particular for rare diseases such as the diseases on which we are initially focused, and process for identifying patients; • design of the trial protocol; • efforts to facilitate timely enrollment in clinical trials; • eligibility and exclusion criteria; • availability of competing therapies and clinical trials; • severity of the disease or disorder under investigation; • proximity and availability of clinical trial sites for prospective patients; • ability to obtain and maintain patient consent; • risk that enrolled patients will drop out before completion of the trial; • patient referral practices of physicians; and • ability to monitor patients adequately during and after treatment.
Additionally, if the results of future clinical trials are inconclusive or if there are safety concerns or serious adverse events associated with any therapeutic candidates we may develop, we may: • be delayed in obtaining marketing approval for therapeutic candidates, if at all; • obtain approval for indications or patient populations that are not as broad as intended or desired; • obtain approval with labeling that includes significant use or distribution restrictions or safety warnings; • be subject to changes in the way the product is administered; • be required to perform additional clinical trials to support approval or be subject to additional post-marketing testing requirements; • have regulatory authorities withdraw, or suspend, their approval of the product or impose restrictions on its distribution in the form of a modified risk evaluation and mitigation strategy; • be subject to the addition of labeling statements, such as warnings or contraindications; • be sued; or • experience damage to our reputation.
Additionally, if the results of future clinical trials are inconclusive or if there are safety concerns or serious adverse events associated with any therapeutic candidates we may develop, we may: • be delayed in obtaining marketing approval for therapeutic candidates, if at all; • obtain approval for indications or patient populations that are not as broad as intended or desired; • obtain approval with labeling that includes significant use or distribution restrictions or safety warnings; • be subject to changes in the way the product is administered; • be required to perform additional clinical trials to support approval or be subject to additional post-marketing testing requirements; • have regulatory authorities withdraw, or suspend, their approval of the product or impose restrictions on its distribution in the form of a modified risk evaluation and mitigation strategy; • be subject to the addition of labeling statements, such as warnings or contraindications; 54 Table of Contents • be sued; or • experience damage to our reputation.
Disputes may arise regarding intellectual property subject to a licensing agreement, including: 81 Table of Contents • the scope of rights granted and obligations imposed 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, therapeutic 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 • the priority of invention of patented technology.
Disputes may arise regarding intellectual property subject to a licensing agreement, including: • the scope of rights granted and obligations imposed 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, therapeutic 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 • the priority of invention of patented technology.
Our Bylaws provide that, unless we consent in writing to an alternative forum, the Court of Chancery of the State of Delaware is the sole and exclusive forum for any state law claims for (i) any derivative action or proceeding brought on our behalf, (ii) any action asserting a claim of breach of, or a claim based on, fiduciary duty owed by any of our current or former directors, officers, and employees to us or our stockholders, (iii) any action asserting a claim arising pursuant to any provision of the DGCL, our certificate of incorporation or our bylaws or (iv) any action asserting a claim that is governed by the internal affairs doctrine, in each case subject to the Court of Chancery having personal jurisdiction over the indispensable parties named as defendants therein (“Delaware Forum Provision”).
Our Bylaws provide that, unless we consent in writing to an alternative forum, the Court of Chancery of the State of Delaware is the sole and exclusive forum for any state law claims for (i) any derivative action or proceeding brought on our behalf, (ii) any action asserting a claim of breach of, or a claim based on, fiduciary duty owed by any of our current or 106 Table of Contents former directors, officers, and employees to us or our stockholders, (iii) any action asserting a claim arising pursuant to any provision of the DGCL, our certificate of incorporation or our bylaws or (iv) any action asserting a claim that is governed by the internal affairs doctrine, in each case subject to the Court of Chancery having personal jurisdiction over the indispensable parties named as defendants therein (“Delaware Forum Provision”).
Under existing U.S. environmental laws and regulations, current or previous owners or operators of real property and entities that disposed or arranged for the disposal of hazardous substances may be held strictly, jointly and 73 Table of Contents severally liable for the cost of investigating or remediating contamination caused by hazardous substance releases, even if they did not know of and were not responsible for the releases.
Under existing U.S. environmental laws and regulations, current or previous owners or operators of real 77 Table of Contents property and entities that disposed or arranged for the disposal of hazardous substances may be held strictly, jointly and severally liable for the cost of investigating or remediating contamination caused by hazardous substance releases, even if they did not know of and were not responsible for the releases.
All of these risks may relate to our current and future programs sharing similar science (including EEV science) and infrastructure, and in the event material decisions in any of these areas turn out to have been incorrect or under-optimized, we may experience a material adverse impact on our business and ability to fund our operations and we may never realize what we believe is the potential of EEV peptides.
All of these risks may relate to our current and future programs sharing similar science (including EEV science) and infrastructure, and in the event material decisions in any of these areas turn out to have been incorrect or under-optimized, we may experience a material adverse impact on our business and ability to fund our operations and we may never realize what we believe is the potential of our technology.
Regardless of merit or eventual outcome, liability claims may result in: • decreased demand for any therapeutic candidates we may develop; • injury to our reputation and significant negative media attention; • withdrawal of clinical trial participants and inability to continue clinical trials; • initiation of investigations by regulators; • significant costs to defend any related litigation; • substantial monetary awards to trial participants or patients; • product recalls, withdrawals or labeling, marketing or promotional restrictions; 59 Table of Contents • loss of revenue; • exhaustion of any available insurance and our capital resources; • decline in our stock price; • reduced resources of our management to pursue our business strategy; and • the inability to commercialize any therapeutic candidates we may develop.
Regardless of merit or eventual outcome, liability claims may result in: • decreased demand for any therapeutic candidates we may develop; • injury to our reputation and significant negative media attention; • withdrawal of clinical trial participants and inability to continue clinical trials; • initiation of investigations by regulators; • significant costs to defend any related litigation; • substantial monetary awards to trial participants or patients; • product recalls, withdrawals or labeling, marketing or promotional restrictions; • loss of revenue; • exhaustion of any available insurance and our capital resources; • decline in our stock price; • reduced resources of our management to pursue our business strategy; and • the inability to commercialize any therapeutic candidates we may develop.
Our approach to the discovery and development of therapeutic candidates based on our EEV Platform is unproven, and we do not know whether we will be able to conduct clinical studies on any of our therapeutic candidates beyond ENTR-601-44 and our partnered candidate VX-670, develop any therapeutic candidates that succeed in clinical development or produce products of commercial value.
Our approach to the discovery and development of therapeutic candidates that are based on our EEV Platform is unproven, and we do not know whether we will be able to conduct clinical studies on any of our therapeutic candidates beyond ENTR-601-44, ENTR-601-45 and our partnered candidate VX-670, develop any therapeutic candidates that succeed in clinical development or produce products of commercial value.
If we fail to comply with applicable regulatory requirements following approval of any therapeutic candidates we may develop, a regulatory agency may: • issue a warning letter asserting that we are in violation of the law; • seek an injunction or impose civil or criminal penalties or monetary fines; • suspend or withdraw regulatory approval; • suspend any ongoing clinical trials; • refuse to approve a pending NDA, BLA or comparable foreign regulatory filing, or supplements thereto submitted by us; • seize product; or • refuse to allow us to enter into supply contracts, including government contracts.
If we fail to comply with applicable regulatory requirements following approval of any therapeutic candidates we may develop, a regulatory agency may: 62 Table of Contents • issue a warning letter asserting that we are in violation of the law; • seek an injunction or impose civil or criminal penalties or monetary fines; • suspend or withdraw regulatory approval; • suspend any ongoing clinical trials; • refuse to approve a pending NDA, BLA or comparable foreign regulatory filing, or supplements thereto submitted by us; • seize product; or • refuse to allow us to enter into supply contracts, including government contracts.
It is not uncommon to observe results in clinical trials that are unexpected based on preclinical studies and early clinical trials, and many therapeutic candidates fail in clinical trials despite very promising early results. Unexpected observations or toxicities observed in our IND-enabling studies for example, could delay clinical trials for ENTR-601-50, ENTR-601-51 or our other development programs.
It is not uncommon to observe results in clinical trials that are unexpected based on preclinical studies and early clinical trials, and many therapeutic candidates fail in clinical trials despite very promising early results. Unexpected observations or toxicities observed in our IND-enabling studies for example, could delay clinical trials for ENTR-601-51, ENTR-801 or our other development programs.
A suspension or termination may be imposed due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols, inspection of the clinical trial operations or trial 50 Table of Contents site by the FDA or other regulatory authorities resulting in the imposition of a clinical hold, unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from using a product or treatment, failure to establish or achieve clinically meaningful trial endpoints, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial.
A suspension or termination may be imposed due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols, inspection of the clinical trial operations or trial site by the FDA or other regulatory authorities resulting in the imposition of a clinical hold, unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from using a product or treatment, failure to establish or achieve clinically meaningful trial endpoints, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial.
In addition, the U.S. government has the right, under certain limited circumstances, to require us to grant exclusive, partially exclusive, or non-exclusive licenses to any of these inventions to a third party if it determines that: (1) adequate steps have not been 82 Table of Contents taken to commercialize the invention; (2) government action is necessary to meet public health or safety needs; or (3) government action is necessary to meet requirements for public use under federal regulations (also referred to as march-in rights).
In addition, the U.S. government has the right, under certain limited circumstances, to require us to grant exclusive, partially exclusive, or non-exclusive licenses to any of these inventions to a third party if it determines that: (1) adequate steps have not been taken to commercialize the invention; (2) government action is necessary to meet public health or safety needs; or (3) government action is necessary to meet requirements for public use under federal regulations (also referred to as march-in rights).
We may engage in strategic transactions that could impact our liquidity, increase our expenses and present significant distractions to our management. 76 Table of Contents From time to time, we may consider strategic transactions, such as acquisitions of companies, asset purchases and out-licensing or in-licensing of intellectual property, products or technologies.
We may engage in strategic transactions that could impact our liquidity, increase our expenses and present significant distractions to our management. 80 Table of Contents From time to time, we may consider strategic transactions, such as acquisitions of companies, asset purchases and out-licensing or in-licensing of intellectual property, products or technologies.
Our approach to the discovery and development of therapeutic candidates based on our EEV Platform is unproven, and we do not know whether we will be able to develop any products of commercial value, or if competing technological approaches will limit the commercial value of our therapeutic candidates or render our EEV Platform obsolete.
Our approach to the discovery and development of therapeutic candidates that are based on our EEV Platform is unproven, and we do not know whether we will be able to develop any products of commercial value, or if competing technological approaches will limit the commercial value of our therapeutic candidates or render our EEV Platform obsolete.
We cannot be certain that, upon inspection, such regulatory authorities will determine that any of our clinical trials comply with the GCP requirements. In addition, our clinical trials must be conducted with biologic product produced under CGMP requirements and may require a large number of patients.
We cannot be certain that, upon inspection, such regulatory authorities will determine that any of our clinical trials comply with the GCP requirements. In addition, our clinical trials must be conducted with drug product produced under cGMP requirements and may require a large number of patients.
As an organization, the only clinical trial we have completed is our Phase 1 clinical trial of ENTR-601-44 in healthy volunteers in the UK, and we have not completed the clinical development of any therapeutic candidate nor have we 42 Table of Contents obtained any regulatory approvals, manufactured a commercial-scale product, or arranged for a third party to do so on our behalf, or conducted sales and marketing activities necessary for successful product commercialization.
As an organization, the only clinical trial we have completed is our Phase 1 clinical trial of ENTR-601-44 in healthy volunteers in the UK, and we have not completed the clinical development of any therapeutic candidate nor have we obtained any regulatory approvals, manufactured a commercial-scale product, or arranged for a third party to do so on our behalf, or conducted sales and marketing activities necessary for successful product commercialization.
In addition, Section 203 of the General Corporation Law of the State of Delaware (“DGCL”) prohibits a publicly-held Delaware corporation from engaging in a business combination with an interested stockholder, generally a person 101 Table of Contents which together with its affiliates owns, or within the last three years has owned, 15% of our voting stock, for a period of three years after the date of the transaction in which the person became an interested stockholder, unless the business combination is approved in a prescribed manner.
In addition, Section 203 of the General Corporation Law of the State of Delaware (“DGCL”) prohibits a publicly-held Delaware corporation from engaging in a business combination with an interested stockholder, generally a person which together with its affiliates owns, or within the last three years has owned, 15% of our voting stock, for a period of three years after the date of the transaction in which the person became an interested stockholder, unless the business combination is approved in a prescribed manner.
In addition to the factors discussed in this “Risk Factors” section and elsewhere in this Annual Report, these factors include: • the timing and results of INDs, preclinical studies and clinical trials of our therapeutic candidates or those of our competitors; • the success of competitive products or announcements by potential competitors of their product development efforts; • our decision to initiate a clinical trial, not to initiate a clinical trial or to terminate an existing clinical trial; • any delay in our regulatory filings for our therapeutic candidates and any adverse development or perceived adverse development with respect to the applicable regulatory authority’s review of such filings; • adverse developments concerning our potential future in-house manufacturing facilities or CMOs; • regulatory actions with respect to our therapeutics or therapeutic candidates or our competitors’ products or therapeutic candidates; • actual or anticipated changes in our growth rate relative to our competitors; • the size and growth of our initial target markets; • unanticipated serious safety concerns related to the use of our therapeutic candidates; • regulatory or legal developments in the U.S. and other countries; • developments or disputes concerning patent applications, issued patents or other proprietary rights; • significant lawsuits, including patent or stockholder litigation; • publication of research reports about us or our industry, or positive or negative recommendations or withdrawal of research coverage by securities analysts; • the recruitment or departure of key personnel; • announcements by us or our competitors of significant acquisitions, strategic collaborations, joint ventures, collaborations or capital commitments; • actual or anticipated changes in estimates as to financial results, development timelines or recommendations by securities analysts; • fluctuations in the valuation of companies perceived by investors to be comparable to us; • market conditions in the pharmaceutical and biotechnology sector; • changes in the structure of healthcare payment systems; • share price and volume fluctuations attributable to inconsistent trading volume levels of our shares; • our failure to meet the estimates and projections of the investment community or that we may otherwise provide to the public; • announcement or expectation of additional financing efforts; • sales of our common stock by us, our insiders or our other stockholders; • expiration of market stand-off or lock-up agreements; • the impact of any natural disasters or public health emergencies; • general economic, political, industry and market conditions such as recessions, interest rates, fuel prices, foreign currency fluctuations, tariffs (including tariffs that have been or may in the future be imposed by the United States or other countries), sanctions, trade protection measures or other trade barriers (including further legislation or actions taken by the United States or other countries that restrict trade), social, political and economic risks and acts of war (such as the ongoing conflict between Russia and Ukraine and the conflict in the Middle East) or terrorism; and • other events or factors, many of which are beyond our control.
In addition to the factors discussed in this “Risk Factors” section and elsewhere in this Annual Report, these factors include: • the timing and results of INDs, preclinical studies and clinical trials of our therapeutic candidates or those of our competitors; • the success of competitive products or announcements by potential competitors of their product development efforts; • our decision to initiate a clinical trial, not to initiate a clinical trial or to terminate an existing clinical trial; • any delay in our regulatory filings for our therapeutic candidates and any adverse development or perceived adverse development with respect to the applicable regulatory authority’s review of such filings; • adverse developments concerning our potential future in-house manufacturing facilities or CMOs; • regulatory actions with respect to our therapeutics or therapeutic candidates or our competitors’ products or therapeutic candidates; • actual or anticipated changes in our growth rate relative to our competitors; • the size and growth of our initial target markets; • unanticipated serious safety concerns related to the use of our therapeutic candidates; • regulatory or legal developments in the U.S. and other countries; • developments or disputes concerning patent applications, issued patents or other proprietary rights; • significant lawsuits, including patent or stockholder litigation; • publication of research reports about us or our industry, or positive or negative recommendations or withdrawal of research coverage by securities analysts; 101 Table of Contents • the recruitment or departure of key personnel; • announcements by us or our competitors of significant acquisitions, strategic collaborations, joint ventures, collaborations or capital commitments; • actual or anticipated changes in estimates as to financial results, development timelines or recommendations by securities analysts; • fluctuations in the valuation of companies perceived by investors to be comparable to us; • market conditions in the pharmaceutical and biotechnology sector; • changes in the structure of healthcare payment systems; • share price and volume fluctuations attributable to inconsistent trading volume levels of our shares; • our failure to meet the estimates and projections of the investment community or that we may otherwise provide to the public; • announcement or expectation of additional financing efforts; • sales of our common stock by us, our insiders or our other stockholders; • expiration of market stand-off or lock-up agreements; • the impact of any natural disasters or public health emergencies; • general macroeconomic, geopolitical, industry and market conditions such as recessions, interest rates, fuel prices, foreign currency fluctuations, tariffs (including tariffs that have been or may in the future be imposed by the United States or other countries), sanctions, trade protection measures or other trade barriers (including further legislation or actions taken by the United States or other countries that restrict trade), social, political and economic risks and military acts of war or terrorism; and • other events or factors, many of which are beyond our control.
In addition, because we have only completed a Phase 1 clinical trial for ENTR-601-44 and have not yet 47 Table of Contents completed any clinical trials with our other therapeutic candidates, we have only limited data assessing safety of our approach in humans, and there may be short-term or long-term effects from treatment with any therapeutic candidates that we develop that we cannot predict at this time.
In addition, because we have only completed a Phase 1 clinical trial for ENTR-601-44 and have not yet completed any clinical trials with our other therapeutic candidates, we have only limited data assessing safety of our approach in humans, and there may be short-term or long-term effects from treatment with any therapeutic candidates that we develop that we cannot predict at this time.
These changes include provisions that affect the way patent applications are prosecuted, redefine prior art, provide more efficient and cost-effective avenues for competitors to challenge the validity of patents, and enable third-party submission of prior art to the USPTO during patent prosecution and additional procedures to attack the validity of a patent at USPTO-administered post-grant proceedings, 84 Table of Contents including post-grant review, inter partes review, and derivation proceedings.
These changes include provisions that affect the way patent applications are prosecuted, redefine prior art, provide more efficient and cost-effective avenues for competitors to challenge the validity of patents, and enable third-party submission of prior art to the USPTO during patent prosecution and additional procedures to attack the validity of a patent at USPTO-administered post-grant proceedings, including post-grant review, inter partes review, and derivation proceedings.
Risks Related to Ownership of Our Common Stock We do not know whether an active, liquid and orderly trading market will develop for our common stock and as a result it may be difficult for our stockholders to sell their shares of our common stock.
Risks Related to Ownership of Our Common Stock We do not know whether an active, liquid and orderly trading market will be sustained for our common stock and as a result it may be difficult for our stockholders to sell their shares of our common stock.
Even if any of our current or future therapeutic candidates were to receive marketing approval or be commercialized for use in combination with other existing therapies, we would continue to be subject to the risks that the FDA, EMA or other comparable foreign regulatory authorities could revoke approval of the therapy used in combination with any of our therapeutic candidates, or safety, efficacy, manufacturing or supply issues could arise with these existing therapies.
Even if any of our current or future therapeutic candidates were to receive 63 Table of Contents marketing approval or be commercialized for use in combination with other existing therapies, we would continue to be subject to the risks that the FDA, EMA or other comparable foreign regulatory authorities could revoke approval of the therapy used in combination with any of our therapeutic candidates, or safety, efficacy, manufacturing or supply issues could arise with these existing therapies.
In addition, we may seek to obtain additional licenses from our licensors and, in connection with obtaining such licenses, we may agree to amend our existing licenses in a manner that may be more favorable to the licensors, including by agreeing to terms that could enable third parties, including our competitors, to receive licenses to a portion of the intellectual property that is subject to our existing licenses and to compete with any therapeutic candidates we may develop and our technology.
In addition, we may seek to obtain additional licenses from our licensors and, in connection with obtaining such licenses, we may agree to amend our existing licenses in 85 Table of Contents a manner that may be more favorable to the licensors, including by agreeing to terms that could enable third parties, including our competitors, to receive licenses to a portion of the intellectual property that is subject to our existing licenses and to compete with any therapeutic candidates we may develop and our technology.
Sales of these or other products that we may identify will depend substantially, both domestically and abroad, on the extent to which the costs of our therapeutics will be paid by health maintenance, managed care, pharmacy benefit and similar healthcare management 67 Table of Contents organizations, or reimbursed by government health administration authorities, private health coverage insurers and other third-party payors.
Sales of these or other products that we may identify will depend substantially, both domestically and abroad, on the extent to which the costs of our therapeutics will be paid by health maintenance, managed care, pharmacy benefit and similar healthcare management organizations, or reimbursed by government health administration authorities, private health coverage insurers and other third-party payors.
Certain market participants, including major institutional investors and capital providers, use third-party benchmarks and scores to assess companies’ ESG profiles in making investment or voting decisions. Unfavorable ESG ratings could lead to increased negative investor sentiment towards us, which could negatively impact our share price as well as our access to and cost of capital.
Certain market participants, including major institutional investors and capital providers, use third-party benchmarks and scores to assess companies’ ESG profiles in making investment or voting decisions. Unfavorable ESG 102 Table of Contents ratings could lead to increased negative investor sentiment towards us, which could negatively impact our share price as well as our access to and cost of capital.
Food and Drug Administration (“FDA”), the European Medicines Agency (“EMA”) or other comparable foreign regulatory authority guidelines and requirements, the quantity of production and the terms of our agreements with manufacturers; • expenditures that we will or may incur to acquire or develop additional therapeutic candidates and technologies or other assets; • the timing and outcomes of preclinical studies and clinical trials for ENTR-601-44, ENTR-601-45, ENTR-601-50, ENTR-601-51, our partnered candidate VX-670 and any therapeutic candidates from our discovery programs, or competing therapeutic candidates; • the need to conduct unanticipated clinical trials or trials that are larger or more complex than anticipated; • competition from existing and potential future products that compete with ENTR-601-44, ENTR-601-45, ENTR-601-50, ENTR-601-51, our partnered candidate VX-670 or any of our discovery programs, and changes in the competitive landscape of our industry, including consolidation among our competitors or partners; • any delays in regulatory review or approval of ENTR-601-44, ENTR-601-45, ENTR-601-50, ENTR-601-51, our partnered candidate VX-670 or therapeutic candidates from any of our discovery programs; • the level of demand for any of our therapeutic candidates, if approved, which may fluctuate significantly and be difficult to predict; • the risk/benefit profile, cost and reimbursement policies with respect to our therapeutic candidates, if approved, and existing and potential future products that compete with ENTR-601-44, ENTR-601-45, ENTR-601-50, ENTR-601-51, our partnered candidate VX-670 or any of our discovery programs; • our or our partners' ability to commercialize ENTR-601-44, ENTR-601-45, ENTR-601-50, ENTR-601-51, our partnered candidate VX-670 or therapeutic candidates from any of our discovery programs, if approved, inside and outside of the U.S., either independently or working with third parties; • our ability to establish and maintain collaborations, licensing or other arrangements; • our ability to adequately support future growth; • potential unforeseen business disruptions that increase our costs or expenses; • future accounting pronouncements or changes in our accounting policies; and • the changing and volatile United States and global economic and political environment.
Food and Drug Administration (“FDA”), the European Medicines Agency (“EMA”) or other comparable foreign regulatory authority guidelines and requirements, the quantity of production and the terms of our agreements with manufacturers; 48 Table of Contents • expenditures that we will or may incur to acquire or develop additional therapeutic candidates and technologies or other assets; • the timing and outcomes of preclinical studies and clinical trials for ENTR-601-44, ENTR-601-45, ENTR-601-50, ENTR-601-51, ENTR-801, our partnered candidate VX-670 and any therapeutic candidates from our discovery programs, or competing therapeutic candidates; • the need to conduct unanticipated clinical trials or trials that are larger or more complex than anticipated; • competition from existing and potential future products that compete with ENTR-601-44, ENTR-601-45, ENTR-601-50, ENTR-601-51, ENTR-801, our partnered candidate VX-670 or any of our discovery programs, and changes in the competitive landscape of our industry, including consolidation among our competitors or partners; • any delays in regulatory review or approval of ENTR-601-44, ENTR-601-45, ENTR-601-50, ENTR-601-51, ENTR-801, our partnered candidate VX-670 or therapeutic candidates from any of our discovery programs; • the level of demand for any of our therapeutic candidates, if approved, which may fluctuate significantly and be difficult to predict; • the risk/benefit profile, cost and reimbursement policies with respect to our therapeutic candidates, if approved, and existing and potential future products that compete with ENTR-601-44, ENTR-601-45, ENTR-601-50, ENTR-601-51, ENTR-801, our partnered candidate VX-670 or any of our discovery programs; • our or our partners' ability to commercialize ENTR-601-44, ENTR-601-45, ENTR-601-50, ENTR-601-51, ENTR-801, our partnered candidate VX-670 or therapeutic candidates from any of our discovery programs, if approved, inside and outside of the U.S., either independently or working with third parties; • our ability to establish and maintain collaborations, licensing or other arrangements; • potential unforeseen business disruptions that increase our costs or expenses; • future accounting pronouncements or changes in our accounting policies; and • the changing and volatile U.S. and global economic and political environment.
In addition, if our efforts in the United States and elsewhere are not successful, we may not be able to complete a clinical development program that enables the approval and marketing of ENTR-601-44 as planned, or at all. Furthermore, therapeutic candidates are subject to continued preclinical safety studies, which may be conducted concurrently with our clinical testing.
In addition, if our efforts in the United States and elsewhere are not successful, we may not be able to complete a clinical development program that enables the approval and marketing of our therapeutic candidates as planned, or at all. Furthermore, therapeutic candidates are subject to continued preclinical safety studies, which may be conducted concurrently with our clinical testing.
It is possible therefore, that there will be increased regulatory complexities in the UK and EU, which could disrupt the timing of any regulatory approvals that we may determine to pursue in these jurisdictions. The FDA, EMA and other comparable foreign regulatory authorities may not accept data from trials conducted in locations outside of their jurisdiction.
It is possible therefore, that there will be increased regulatory complexities in the UK and EU, which could disrupt the timing of any regulatory approvals that we may determine to pursue in these jurisdictions. 61 Table of Contents The FDA, EMA and other comparable foreign regulatory authorities may not accept data from trials conducted in locations outside of their jurisdiction.
Changes in either the patent laws or interpretation of patent laws in the United States and worldwide, including patent reform legislation such as the Leahy-Smith America Invents Act (the “Leahy-Smith Act”), could increase the uncertainties and costs surrounding the prosecution of any owned or in-licensed patent applications and the maintenance, enforcement or defense of any current in-licensed issued patents and issued patents we may own or in-license in the future.
Changes in either the patent laws or interpretation of patent laws in the United States and worldwide, including patent reform legislation such as the Leahy-Smith America Invents Act (the “Leahy-Smith Act”), could increase the 88 Table of Contents uncertainties and costs surrounding the prosecution of any owned or in-licensed patent applications and the maintenance, enforcement or defense of any current in-licensed issued patents and issued patents we may own or in-license in the future.
Given that our proprietary position is based, in part, on our know-how and trade secrets and despite our efforts to protect our trade secrets, a competitor’s discovery of our proprietary technology and confidential information or other unauthorized use or disclosure would impair our competitive position and may have a material adverse effect on our business, financial condition, results of operations and prospects.
Given that our 67 Table of Contents proprietary position is based, in part, on our know-how and trade secrets and despite our efforts to protect our trade secrets, a competitor’s discovery of our proprietary technology and confidential information or other unauthorized use or disclosure would impair our competitive position and may have a material adverse effect on our business, financial condition, results of operations and prospects.
In our planned clinical trials that will include a placebo group, some of the patients who end up receiving placebo may perceive that they are not receiving the therapeutic candidate being tested, and they may decide to withdraw from our clinical trials to pursue other alternative therapies rather than continue the trial with the perception that they are receiving placebo.
In our planned clinical trials that will include a placebo group, some of the patients who end up receiving placebo may perceive that they are not receiving the therapeutic candidate being tested, and they may decide to withdraw from our clinical trials to pursue other alternative therapies rather than continue the trial with 55 Table of Contents the perception that they are receiving placebo.
Further, because all of our therapeutic candidates and development programs are based on our EEV Platform, adverse developments with respect to one of our programs may have a significant adverse impact on the actual or perceived likelihood of success and value of our other programs. In addition, the biotechnology and biopharmaceutical industries are characterized by rapidly advancing technologies.
Further, because many of our therapeutic candidates and development programs are based on our EEV Platform, adverse developments with respect to one of these programs may have a significant adverse impact on the actual or perceived likelihood of success and value of our other programs. In addition, the biotechnology and biopharmaceutical industries are characterized by rapidly advancing technologies.
By way of example, the California Consumer Privacy Act (“CCPA”), which went into effect on January 1, 2020, established a comprehensive privacy framework for covered businesses by creating an expanded definition of personal information, establishing new data privacy rights for consumers in the State of California, and imposing special rules on the collection of consumer data from minors.
By way of example, the California Consumer Privacy Act (“CCPA”), which went into effect on January 1, 2020, established a comprehensive privacy framework for covered businesses by creating an expanded definition of personal information, data privacy rights for consumers in the State of California, and special rules on the collection of consumer data from minors.
These comprehensive privacy laws will, among other things, impact how regulated businesses collect and process personal sensitive data, conduct data protection assessments, transfer personal data to affiliates, and respond to consumer rights requests. Furthermore, in addition to comprehensive privacy laws, certain states have enacted laws which focus on certain specific types of information.
These comprehensive privacy laws will, among other things, impact how regulated businesses collect and 96 Table of Contents process personal sensitive data, conduct data protection assessments, transfer personal data to affiliates, and respond to consumer rights requests. Furthermore, in addition to comprehensive privacy laws, certain states have enacted laws which focus on certain specific types of information.
A failure of one or more clinical trials can occur at any stage of testing, which may result from a 49 Table of Contents multitude of factors, including, but not limited to, flaws in trial design, dose selection issues, patient enrollment criteria and failure to demonstrate favorable safety or efficacy traits.
A failure of one or more clinical trials can occur at any stage of testing, which may result from a multitude of factors, including, but not limited to, flaws in trial design, dose selection issues, patient enrollment criteria and failure to demonstrate favorable safety or efficacy traits.
The use of new and evolving technologies, such as artificial intelligence, in our offerings may result in spending material resources and presents risks and challenges that can impact our business including by posing security and other risks to our confidential information, proprietary information and personal information, and as a result we may be exposed to reputational harm and liability.
The use of new and evolving technologies, such as AI, in our offerings may result in spending material resources and presents risks and challenges that can impact our business including by posing security and other risks to our confidential information, proprietary information and personal information, and as a result we may be exposed to reputational harm and liability.
Recent volatility in capital markets and lower market prices for many securities may affect our ability to access new capital through sales of shares of our common stock or issuance of indebtedness, which may harm our liquidity, limit our ability to grow our business, pursue acquisitions or improve our operating infrastructure and restrict our ability to compete in our markets.
Recent volatility in capital markets and lower market prices for many securities may affect our ability to access new capital through sales of shares of our common stock or issuance of indebtedness, which may harm our liquidity, limit 100 Table of Contents our ability to grow our business, pursue acquisitions or improve our operating infrastructure and restrict our ability to compete in our markets.
Any therapeutic candidate for which we obtain marketing approval, if ever, along with the manufacturing processes, post-approval clinical data, labeling, advertising and promotional activities for such medicine, will be subject to 58 Table of Contents continual requirements of and review by the FDA and other regulatory authorities.
Any therapeutic candidate for which we obtain marketing approval, if ever, 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.
In the U.S., we also are required to register ongoing clinical trials and post the results of completed 61 Table of Contents clinical trials on a government-sponsored database, clinicaltrials.gov, within certain timeframes. Failure to do so can result in fines, adverse publicity and civil and criminal sanctions.
In the U.S., we also are required to register ongoing clinical trials and post the results of completed clinical trials on a government-sponsored database, clinicaltrials.gov, within certain timeframes. Failure to do so can result in fines, adverse publicity and civil and criminal sanctions.
These factors could include, among others, events such as liquidity constraints or failures, the ability to perform obligations under various types of financial, credit or liquidity agreements or arrangements, disruptions or instability in the financial 78 Table of Contents services industry or financial markets, or concerns or negative expectations about the prospects for companies in the financial services industry.
These factors could include, among others, events such as liquidity constraints or failures, the ability to perform obligations under various types of financial, credit or liquidity agreements or arrangements, disruptions or instability in the financial services industry or financial markets, or concerns or negative expectations about the prospects for companies in the financial services industry.
However, we may be unable to secure such licenses or otherwise acquire or in-license any compositions, methods of use, processes or 86 Table of Contents other intellectual property rights from third parties that we identify as necessary for our therapeutic programs and other proprietary technologies we may develop.
However, we may be unable to secure such licenses or otherwise acquire or in-license any compositions, methods of use, processes or other intellectual property rights from third parties that we identify as necessary for our therapeutic programs and other proprietary technologies we may develop.
Patent protection must ultimately be sought on a country-by- 83 Table of Contents country basis, which is an expensive and time-consuming process with uncertain outcomes. Accordingly, we may choose not to seek patent protection in certain countries, and we will not have the benefit of patent protection in such countries.
Patent protection must ultimately be sought on a country-by-country basis, which is an expensive and time-consuming process with uncertain outcomes. Accordingly, we may choose not to seek patent protection in certain countries, and we will not have the benefit of patent protection in such countries.
Also, current inflationary trends in the global economy may impact salaries and wages, costs of goods and transportation expenses, among other things, and recent and potential future disruptions in access to bank deposits or lending commitments due to bank failures may create market and economic instability.
Also, current inflationary trends in the global economy 103 Table of Contents may impact salaries and wages, costs of goods and transportation expenses, among other things, and recent and potential future disruptions in access to bank deposits or lending commitments due to bank failures may create market and economic instability.
Government authorities and third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular products. Increasingly, third-party payors are requiring that drug companies provide them with predetermined discounts from list prices and are challenging the prices charged for products.
Government authorities and third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular products. Increasingly, third-party payors are requiring that drug companies provide them with predetermined discounts 71 Table of Contents from list prices and are challenging the prices charged for products.
In addition, there 88 Table of Contents could be public announcements of the results of hearings, motions or other interim proceedings or developments, and if securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock.
In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments, and if securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock.
The stock market in general, and pharmaceutical and biotechnology companies in particular, have experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance of these companies. 96 Table of Contents Broad market and industry factors may negatively affect the market price of our common stock, regardless of our actual operating performance.
The stock market in general, and pharmaceutical and biotechnology companies in particular, have experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance of these companies. Broad market and industry factors may negatively affect the market price of our common stock, regardless of our actual operating performance.
However, we may not be granted an extension because of, for example, failing to exercise due diligence during the testing phase or regulatory review process, failing to apply within applicable deadlines, failing to apply prior to expiration of relevant patents or otherwise failing to satisfy applicable requirements.
However, we may not be granted 89 Table of Contents an extension because of, for example, failing to exercise due diligence during the testing phase or regulatory review process, failing to apply within applicable deadlines, failing to apply prior to expiration of relevant patents or otherwise failing to satisfy applicable requirements.
Any undesirable side effects or unexpected characteristics associated with our therapeutic candidates in clinical trials may lead us to elect to abandon their 52 Table of Contents development or limit their development to more narrow uses or subpopulations in which the undesirable side effects or other characteristics are less prevalent, less severe or more acceptable from a risk-benefit perspective, which may limit the commercial expectations for the therapeutic candidate if approved.
Any undesirable side effects or unexpected characteristics associated with our therapeutic candidates in clinical trials may lead us to elect to abandon their development or limit their development to more narrow uses or subpopulations in which the undesirable side effects or other characteristics are less prevalent, less severe or more acceptable from a risk-benefit perspective, which may limit the commercial expectations for the therapeutic candidate if approved.
Despite the time and expense invested in clinical development of therapeutic candidates, regulatory approval is never guaranteed. Neither we nor any current or future collaborator is permitted to market any of our therapeutic candidates in the United States until we receive approval from the FDA.
Despite the time and expense invested in clinical development of therapeutic candidates, regulatory approval is never guaranteed. 56 Table of Contents Neither we nor any current or future collaborator is permitted to market any of our therapeutic candidates in the United States until we receive approval from the FDA.
Certain features in our therapeutic candidates, including those related to large enzymes, antibodies and oligonucleotides, and their components, may result in foreseen and unforeseen risks that are active across some or all of our modalities. In addition, the biology risk across much of our development portfolio represents targets and pathways not clinically validated by one or more approved drugs.
Certain features in our therapeutic candidates, including those related to proteins and oligonucleotides, and their components, may result in foreseen and unforeseen risks that are active across some or all of our modalities. In addition, the biology risk across much of our development portfolio represents targets and pathways not clinically validated by one or more approved drugs.
We may in the future discover material weaknesses in our system of internal financial and accounting controls and procedures that could result in a material misstatement of our financial statements. Our internal control over financial reporting will not prevent or detect all errors and all fraud.
We may in the future discover material weaknesses in our system of internal financial and accounting controls and procedures that could result in a material misstatement of our financial statements. Our internal control over financial 107 Table of Contents reporting will not prevent or detect all errors and all fraud.
Risks Related to Commercialization of Our Therapeutic Candidates The commercial success of our therapeutic candidates will depend upon the degree of market acceptance of such therapeutic candidates by physicians, patients, healthcare payors and others in the medical community. 66 Table of Contents Our therapeutic candidates may not be commercially successful.
Risks Related to Commercialization of Our Therapeutic Candidates The commercial success of our therapeutic candidates will depend upon the degree of market acceptance of such therapeutic candidates by physicians, patients, healthcare payors and others in the medical community. Our therapeutic candidates may not be commercially successful.
Smaller or early stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. 68 Table of Contents Currently, patients with DMD are treated with corticosteroids to manage the inflammatory component of the disease. EMFLAZA (deflazacort) is an FDA-approved corticosteroid marketed by PTC Therapeutics, Inc. (“PTC”).
Smaller or early stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. Currently, patients with DMD are treated with corticosteroids to manage the inflammatory component of the disease. EMFLAZA (deflazacort) is an FDA-approved corticosteroid marketed by PTC Therapeutics, Inc.
For example, under Section 174 of the Internal Revenue Code of 1986, as amended (the “Code”), in taxable years beginning after December 31, 2021, expenses that are incurred for research and development in the U.S. will be capitalized and amortized, which may have an adverse effect on our cash flow.
For example, under Section 174 of the Internal Revenue Code of 1986, as amended, or the Code, in taxable years beginning after December 31, 2021, expenses that are incurred for research and development performed outside the U.S. will be capitalized and amortized, which may have an adverse effect on our cash flow.
The ability of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding levels, statutory, regulatory and policy changes, the FDA’s ability to hire and retain key personnel and accept the payment of user fees, and other events that may otherwise affect the FDA’s ability to perform routine functions.
The ability of the FDA and other comparable regulatory authorities to review and approve new products can be affected by a variety of factors, including government budget and funding levels, statutory, regulatory and policy changes, the FDA’s or other comparable regulatory authorities' ability to hire and retain key personnel and accept the payment of user fees, and other events that may otherwise affect the FDA’s or other comparable regulatory authorities' ability to perform routine functions.
Based on our current operating plans, we believe that our cash, cash equivalents and marketable securities as of December 31, 2024 will be sufficient to fund our operations into the second quarter of 2027. We have based this estimate on assumptions that may prove to be wrong, and we could use our capital resources sooner than we currently expect.
Based on our current operating plans, we believe that our cash, cash equivalents and marketable securities as of December 31, 2025 will be sufficient to fund our operations into the third quarter of 2027. We have based this estimate on assumptions that may prove to be wrong, and we could use our capital resources sooner than we currently expect.
In order to market and sell any therapeutic candidates we may develop in the EU and many other foreign jurisdictions, including the UK, we or our collaborators must obtain separate marketing approvals and comply with 57 Table of Contents numerous and varying regulatory requirements. The approval procedure varies among countries and can involve additional testing.
In order to market and sell any therapeutic candidates we may develop in the EU and many other foreign jurisdictions, including the UK, we or our collaborators must obtain separate marketing approvals and comply with numerous and varying regulatory requirements. The approval procedure varies among countries and can involve additional testing.
There can be no assurance that we will be able to successfully complete these types of negotiations and ultimately acquire the rights to the intellectual property surrounding the additional therapeutic candidates that we may seek to develop or market.
There can be no assurance that we will be able to successfully complete these types of negotiations and ultimately acquire the rights to the intellectual property surrounding the additional 95 Table of Contents therapeutic candidates that we may seek to develop or market.
Our vendors may in turn incorporate artificial intelligence tools into their own offerings, and the providers of these artificial intelligence tools may not meet existing or rapidly evolving regulatory or industry standards, including with respect to privacy and data security.
Our vendors may in turn incorporate AI tools into their own offerings, and the providers of these AI tools may not meet existing or rapidly evolving regulatory or industry standards, including with respect to privacy and data security.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeAs appropriate, we contractually require certain third-parties to certify that they have the ability to implement and maintain appropriate cybersecurity measures, consistent with applicable laws, and to promptly report any suspected cybersecurity incidents that may affect our company or our data. We face a number of cybersecurity risks in connection with our business.
Biggest changeAs part of our cybersecurity risk management program, we maintain processes related to third-party vendor cybersecurity risk management. As appropriate, we contractually require certain third-parties to certify that they have the ability to implement and maintain appropriate cybersecurity measures, consistent with applicable laws, and to promptly report any suspected cybersecurity incidents that may affect our company or our data.
Our Head of Information Technology (“IT”), who reports directly to our CFO, has primary responsibility for the day-to-day management of our cybersecurity risk management program. The individual currently operating as our Head of IT possesses approximately 20 years of experience with information technology and cybersecurity risk management programs.
Our Head of Information Technology (“IT”), who reports directly to our CFO, has primary responsibility for the day-to-day management of our cybersecurity risk management program. The individual currently operating as our Head of IT possesses over 20 years of experience with information technology and cybersecurity risk management programs.
Under the purview of our audit committee, our President and Chief Operating Officer, General Counsel, and Chief Financial Officer (“CFO”) (collectively, the “Risk and Compliance Committee”) are primarily responsible for assessing, managing and mitigating our critical risks from cybersecurity threats.
Under the purview of our audit committee, our President and Chief Operating Officer, Chief Financial Officer (“CFO”), General Counsel and Vice President of Quality (collectively, the “Risk and Compliance Committee”) are primarily responsible for assessing, managing and mitigating our critical risks from cybersecurity threats.
Although risks from cybersecurity threats have to date not materially affected us, and we do not believe they are reasonably likely to materially affect us, our business strategy, results of operations or financial condition, we have, from time to time, experienced threats and security incidents relating to our and our third party vendors’ information systems.
Although risks from cybersecurity threats have to date not materially affected us, and we do not believe they are reasonably likely to materially affect us, our business strategy, results of operations or financial condition, we have, from time to time, experienced threats and security 109 Table of Contents incidents relating to our and our third party vendors’ information systems.
For more information, please refer to Item 1A, “Risk Factors,” in this annual report on Form 10-K. Governance One of the key functions of our board of directors is informed oversight of our risk management process, including risks from cybersecurity threats. Our board of directors has delegated this cybersecurity risk management oversight function to our audit committee.
For more information, please refer to Item 1A, “Risk Factors,” in this Annual Report. Governance One of the key functions of our board of directors is informed oversight of our risk management process, including risks from cybersecurity threats. Our board of directors has delegated this cybersecurity risk management oversight function to our audit committee.
These cybersecurity risk assessments are designed to include identification of reasonably foreseeable internal and external cybersecurity risks, analysis on the likelihood and potential damage that could result from such risks, and feedback on the sufficiency of our existing procedures, systems, and safeguards to mitigate such cybersecurity risks. 104 Table of Contents As part of our cybersecurity risk management program, we maintain processes related to third-party vendor cybersecurity risk management.
These cybersecurity risk assessments are designed to include identification of reasonably foreseeable internal and external cybersecurity risks, analysis on the likelihood and potential damage that could result from such risks, and feedback on the sufficiency of our existing procedures, systems, and safeguards to mitigate such cybersecurity risks.
Added
We face a number of cybersecurity risks in connection with our business.

Item 2. Properties

Properties — owned and leased real estate

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Removed
We also continue to lease approximately 23,189 square feet of space at 6 Tide Street in Boston, Massachusetts, our previous headquarters. The lease expires in November 2025, subject to an option to extend the lease for three additional years.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Removed
On February 7, 2025, OSIF filed a complaint in the United States District Court for the Southern District of Ohio against us, alleging claims for breach of contract related to the License Agreement, by and between us and OSIF, dated as of December 14, 2018, as amended.
Removed
The dispute concerns our payment of sublicensing fees to OSIF arising from the Sublicense Agreement. The complaint seeks compensatory damages, pre-judgment and post-judgment interest, and attorneys' fees and costs, as well as an order for specific performance. We dispute OSIF’s claims and intend to vigorously 105 Table of Contents defend against the claims.
Removed
We and OSIF are in discussions concerning mediation of their disputes and, pending agreement on mediation procedures, plan to ask the Court to stay or extend deadlines in the litigation pending the parties’ mediation. Item 4. Mine Safety Disclosures Not applicable. 106 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 changeSecurities Authorized for Issuance Under Equity Compensation Plans The information required by Item 5 of Form 10-K regarding equity compensation plans is incorporated herein by reference to Item 12 of Part III of this Annual Report.
Biggest changeSecurities Authorized for Issuance Under Equity Compensation Plans The information required by Item 5 of Form 10-K regarding equity compensation plans is incorporated herein by reference to Item 12 of Part III of this Annual Report. Recent Sales of Unregistered Equity Securities None. Purchases of Equity Securities by the Issuer or Affiliated Purchasers None. Item 6. Reserved Not Applicable.
Holders of Our Common Stock As of February 20, 2025, there were approximately 20 stockholders of record of our common stock. The actual number of stockholders is greater than the number of record holders, and includes stockholders who are beneficial owners, but whose shares are held in street name by brokers and other nominees.
Holders of Our Common Stock As of February 19, 2026, there were approximately 12 stockholders of record of our common stock. The actual number of stockholders is greater than the number of record holders, and includes stockholders who are beneficial owners, but whose shares are held in street name by brokers and other nominees.
Removed
Recent Sales of Unregistered Equity Securities On December 7, 2022, the Company entered into a stock purchase agreement (the “Stock Purchase Agreement”) with Vertex Pharmaceuticals Incorporated (Vertex), pursuant to which Vertex agreed to purchase from the Company 1,618,613 shares (the “Shares”) of the Company’s common stock, par value $0.0001 per share, in a private placement transaction for an aggregate purchase price of approximately $26.3 million or $16.26 per share.
Removed
The purchase price per Share is equal to one hundred five percent (105%) of the daily volume-weighted average per share price of the Company’s common stock on the Nasdaq Global Market over the ten trading days ending on and including the last trading day prior to the execution of the Stock Purchase Agreement.
Removed
On February 8, 2023, following the expiration of the waiting period and clearance under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, the private placement transaction closed.
Removed
Use of Proceeds from Initial Public Offering of Common Stock In November 2021, the Company completed its initial public offering ( “ IPO ” ) in which the Company issued and sold 10,436,250 shares of its common stock, including 1,361,250 shares pursuant to the full exercise of the underwriters’ option to purchase additional shares, at a public offering price of $20.00 per share .
Removed
All of the shares of common stock issued and sold in our IPO were registered under the Securities Act pursuant to a registration statement on Form S-1, as amended (File No. 333-260160), which was declared effective by the Securities and Exchange Commission (the “SEC”) on October 28, 2021. Goldman Sachs & Co.
Removed
LLC, Cowen and Company, LLC and Evercore Group L.L.C. acted as joint book-running managers for the offering. The aggregate net proceeds received by the Company from the IPO were approximately $190.7 million , after deducting underwriting discounts and commissions of $14.6 million, and offering expenses payable by the Company of $3.4 million.
Removed
No offering expenses were paid directly or indirectly to any of our directors or officers (or their associates) or persons owning 10% or more of any class of our equity securities or to any other affiliates. There has been no material change in our planned use of the net proceeds from the offering as described in our final prospectus.
Removed
Purchases of Equity Securities by the Issuer or Affiliated Purchasers 107 Table of Contents None. Item 6. Reserved Not Applicable.

Item 7. Management's Discussion & Analysis

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

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Biggest changeResults of Operations Comparison of the years ended December 31, 2024 and 2023 Year ended December 31, (in thousands) 2024 2023 Change Collaboration revenue $ 210,782 $ 129,013 $ 81,769 Operating expenses: Research and development 125,306 99,884 25,422 General and administrative 38,465 32,291 6,174 Total operating expenses 163,771 132,175 31,596 Income (loss) from operations 47,011 (3,162) 50,173 Other income: Interest and other income 19,474 15,218 4,256 Total other income 19,474 15,218 4,256 Income before provision for income taxes $ 66,485 $ 12,056 $ 54,429 Provision for income taxes (859) (18,741) 17,882 Net income (loss) $ 65,626 $ (6,685) $ 72,311 Research and Development Expenses Year ended December 31, (in thousands) 2024 2023 Change Direct research and development expenses ENTR-601-44 $ 13,109 $ 10,043 $ 3,066 ENTR-601-45 8,584 9,782 (1,198) ENTR-601-50 10,851 3,016 7,835 ENTR-601-51 1,345 1,531 (186) Collaboration services 12,074 11,970 104 Other preclinical and discovery 7,926 6,712 1,214 Unallocated research and development expenses Personnel related (including stock-based compensation) 41,762 31,250 10,512 Facility related and other 29,655 25,580 4,075 Total research and development expenses $ 125,306 $ 99,884 $ 25,422 Research and development expenses were $125.3 million for the year ended December 31, 2024, compared to $99.9 million for the year ended December 31, 2023.
Biggest changeResearch and Development Expenses 116 Table of Contents Year ended December 31, (in thousands) 2025 2024 Change Direct research and development expenses ENTR-601-44 $ 24,340 $ 13,109 $ 11,231 ENTR-601-45 16,772 8,584 8,188 ENTR-601-50 7,694 10,851 (3,157) ENTR-601-51 8,622 1,345 7,277 Collaboration services 2,463 12,074 (9,611) Ocular programs 1,962 2,960 (998) Other preclinical and discovery 2,672 4,966 (2,294) Unallocated research and development expenses Personnel related (including stock-based compensation) 48,246 41,762 6,484 Facility related and other 29,498 29,655 (157) Total research and development expenses $ 142,269 $ 125,306 $ 16,963 Research and development expenses were $142.3 million for the year ended December 31, 2025, compared to $125.3 million for the year ended December 31, 2024.
Investing Activities Net cash used in investing activities was $27.8 million for the year ended December 31, 2024, and was driven by $437.7 million in purchases of marketable securities and $3.2 million in purchases of property and equipment , which were partially offset by $413.1 million from the maturities of marketable securities.
Net cash used in investing activities was $27.8 million for the year ended December 31, 2024, and was driven by $437.7 million in purchases of marketable securities and $3.2 million from purchases of property and equipment, which were partially offset by $413.1 million from the maturities of marketable securities.
While our significant accounting policies are described in more detail in Note 2 to our consolidated financial statements appearing elsewhere in this Annual Report, we believe that the following accounting policies are those most critical to the judgments and estimates used in the preparation of our consolidated financial statements.
While our significant accounting policies are described in more detail in Note 2, Summary of Significant Accounting Policies , to the consolidated financial statements appearing elsewhere in this Annual Report, we believe that the following accounting policies are those most critical to the judgments and estimates used in the preparation of our consolidated financial statements.
These expenses include: 109 Table of Contents • personnel-related expenses, including salaries, related benefits and stock-based compensation expense for individuals engaged in research and development functions; • expenses incurred in connection with our research programs and development of our therapeutic candidates and research programs, including under agreements with third parties, such as consultants, contractors and CROs to conduct preclinical studies and clinical trials; • the cost of developing and validating our manufacturing process for use in our preclinical studies and potential future clinical trials, including the cost of raw materials used in our research and development activities and engaging with third party CMOs; • costs incurred in connection with the performance of research and development activities under the Vertex Agreement; • the cost of laboratory supplies and research materials; • the costs of payments made under third-party licensing agreements and related future payments should certain development and regulatory milestones be achieved; and • facilities, depreciation and other direct and allocated expenses, including rent and other operating costs, incurred as a result of our research and development activities.
These expenses include: • personnel-related expenses, including salaries, related benefits and stock-based compensation expense for individuals engaged in research and development functions; • expenses incurred in connection with our research programs and development of our therapeutic candidates and research programs, including under agreements with third parties, such as consultants, contractors and CROs to conduct preclinical studies and clinical trials; • the cost of developing and validating our manufacturing process for use in our preclinical studies and potential future clinical trials, including the cost of raw materials used in our research and development activities and engaging with third party CMOs; • costs incurred in connection with the performance of research and development activities under the Vertex Agreement; • the cost of laboratory supplies and research materials; • the costs of payments made under third-party licensing agreements and related future payments should certain development and regulatory milestones be achieved; and • facilities, depreciation and other direct and allocated expenses, including rent and other operating costs, incurred as a result of our research and development activities.
Our future capital requirements will depend on many factors, including costs associated with: • the continuation of our current research programs and our preclinical development of therapeutic candidates from our current research programs; • seeking to identify additional research programs and additional therapeutic candidates; • advancing our existing and future therapeutic candidates into clinical development; • initiating preclinical studies and clinical trials for any therapeutic candidates we identify and develop or expand development of existing programs into additional indications; • maintaining, expanding, enforcing, defending and protecting our intellectual property portfolio and providing reimbursement of third-party expenses related to our patent portfolio; • timing of manufacturing for our therapeutic candidates and commercial manufacturing if any therapeutic candidate is approved; • establishing and maintaining clinical and commercial supply for the development and manufacture of our therapeutic candidates; • seeking regulatory and marketing approvals for any of our therapeutic candidates that we develop, if any; • seeking to identify, establish and maintain additional collaborations and license agreements, and the success of those collaborations and license agreements; • ultimately establishing a sales, marketing and distribution infrastructure to commercialize any platforms for which we may obtain marketing approval, either by ourselves or in collaboration with others; • generating revenue from commercial sales of therapeutic candidates we may develop for which we receive marketing approval; • hiring additional personnel including research and development, clinical and commercial personnel; • adding operational, financial and management information systems and personnel, including personnel to support our product development; • achieve sufficient market acceptance, coverage and adequate reimbursement from third-party payors and adequate market share and revenue for any approved products; • acquiring or in-licensing products, intellectual property and technologies; and • the ongoing costs of operating as a public company and recent increases in inflationary rates.
Our future capital requirements will depend on many factors, including costs associated with: • the continuation of our current research programs and our preclinical development of therapeutic candidates from our current research programs; • advancing our existing and future therapeutic candidates into clinical development; • initiating preclinical studies and clinical trials for any therapeutic candidates we identify and develop or expand development of existing programs into additional indications; • maintaining, expanding, enforcing, defending and protecting our intellectual property portfolio and providing reimbursement of third-party expenses related to our patent portfolio; • timing of manufacturing for our therapeutic candidates and commercial manufacturing if any therapeutic candidate is approved; • establishing and maintaining clinical and commercial supply for the development and manufacture of our therapeutic candidates; • seeking regulatory and marketing approvals for any of our therapeutic candidates that we develop, if any; • seeking to identify, establish and maintain additional collaborations and license agreements, and the success of those collaborations and license agreements; • ultimately establishing a sales, marketing and distribution infrastructure to commercialize any platforms for which we may obtain marketing approval, either by ourselves or in collaboration with others; • generating revenue from commercial sales of therapeutic candidates we may develop for which we receive marketing approval; • hiring additional personnel including research and development, clinical and commercial personnel, to meet our strategic goals; • adding operational, financial and management information systems and personnel, including personnel to support our product development; • achieving sufficient market acceptance, coverage and adequate reimbursement from third-party payors and adequate market share and revenue for any approved products; • acquiring or in-licensing products, intellectual property and technologies; and • the ongoing costs of operating as a public company and recent increases in inflationary rates.
The income tax expense recorded for the year ended December 31, 2024 was driven largely by the current tax liability associated with the $75.0 million payment for the achievement of the clinical advancement milestone for VX-670 and $1.7 million in related interest owed to taxing authorities pursuant to Section 453A.
The income tax expense recorded for the year ended December 31, 2024 was primarily driven by the current tax liability associated with the $75.0 million payment for the achievement of the clinical advancement milestone for VX-670 and $1.7 million in related interest owed to taxing authorities pursuant to Section 453A.
Item 7. MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS You should read the following discussion and analysis of our financial condition and results of operations together with our consolidated financial statements and related notes appearing elsewhere in this Annual Report on Form 10-K (Annual Report).
Item 7. MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS You should read the following discussion and analysis of our financial condition and results of operations together with our consolidated financial statements and related notes appearing elsewhere in this Annual Report on Form 10-K (“Annual Report”).
If we raise funds through collaborations or other similar arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or therapeutic candidates or grant licenses on terms that may not be favorable to us and/or may reduce the value of our common stock.
If we raise funds through collaborations or other similar arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or therapeutic candidates or grant licenses on terms that may not 120 Table of Contents be favorable to us and/or may reduce the value of our common stock.
Milestone payments under license agreements are accrued, with a corresponding expense being recognized, in the period in which the milestone is determined to be probable of achievement and the related amount is reasonably estimable. Our research and development costs are primarily devoted to supporting our neuromuscular program development and platform discovery efforts.
Milestone payments under license agreements are accrued, with a corresponding expense being recognized, in the period in which the milestone is determined to be probable of achievement and the related amount is reasonably estimable. 112 Table of Contents Our research and development costs are primarily devoted to supporting our neuromuscular program development and platform discovery efforts.
As part of the process of preparing our consolidated financial statements, we are required to make the following significant judgements and estimates to determine amounts to be recognized in collaboration revenue.
As part of the process of preparing our consolidated financial statements, we are required to make the following significant judgments and estimates to determine amounts to be recognized in collaboration revenue.
We estimate the fair value of stock options granted using the Black-Scholes option-pricing model (“Black-Scholes”) for stock option grants to both employees and non-employees. The fair value of the Company’s common stock is used to determine the fair value of RSUs and PSUs. The Company’s stock-based compensation awards are subject to service-based vesting conditions.
We estimate the fair value of stock options granted using the Black-Scholes option-pricing model (“Black-Scholes”) for stock option grants to both employees and non-employees. The fair value of the Company’s common stock is used to determine the fair value of RSUs 115 Table of Contents and PSUs. The Company’s stock-based compensation awards are subject to service-based vesting conditions.
This is due to the numerous risks and uncertainties associated with product development, including the following: • the scope, timing, rate of progress and expenses of our ongoing and potential future research activities, including preclinical and IND-enabling studies, clinical trials and other research and development activities we decide to pursue; 110 Table of Contents • the successful initiation, enrollment and completion of clinical trials under current good clinical practices; • the timing of filing and acceptance of INDs or comparable foreign applications that allow commencement of future clinical trials for our therapeutic candidates; • whether our therapeutic candidates show safety and efficacy in our clinical trials and an acceptable risk-benefit profile in the intended populations; • our ability to hire and retain key research and development personnel; • our ability to successfully develop, obtain regulatory and marketing approvals of our therapeutic candidates for the expected indications and patient populations; • our ability to establish and maintain agreements with third-party manufacturers for clinical supply for our clinical trials and commercial manufacturing, if our therapeutic candidates are approved; • commercializing therapeutic candidates, if and when approved, whether alone or in collaboration with others; • our ability to maintain a continued acceptable safety, tolerability and efficacy profile of our therapeutic candidates following approval; • our ability to establish new licensing or collaboration arrangements to support our potential therapeutic candidates on favorable business terms; • any decisions we make to discontinue, delay or modify our programs to focus on others; • obtaining, maintaining, protecting and enforcing patent and trade secret protection and regulatory exclusivity for our therapeutic candidates; and • obtaining and maintaining adequate coverage and reimbursement from third party payors.
This is due to the numerous risks and uncertainties associated with product development, including the following: • the scope, timing, rate of progress and expenses of our ongoing and potential future research activities, including preclinical and IND-enabling studies, clinical trials and other research and development activities we decide to pursue; • the successful initiation, enrollment and completion of clinical trials under current good clinical practices; • the timing of filing and acceptance of INDs or comparable foreign applications that allow commencement of future clinical trials for our therapeutic candidates; • whether our therapeutic candidates show safety and efficacy in our clinical trials and an acceptable risk-benefit profile in the intended populations; • our ability to hire and retain key research and development personnel; • our ability to successfully develop, obtain regulatory and marketing approvals of our therapeutic candidates for the expected indications and patient populations; • our ability to establish and maintain agreements with third-party manufacturers for clinical supply for our clinical trials and commercial manufacturing, if our therapeutic candidates are approved; • commercializing therapeutic candidates, if and when approved, whether alone or in collaboration with others; • our ability to maintain a continued acceptable safety, tolerability and efficacy profile of our therapeutic candidates following approval; • our ability to establish new licensing or collaboration arrangements to support our potential therapeutic candidates on favorable business terms; • any decisions we make to discontinue, delay or modify our programs to focus on others; • obtaining, maintaining, protecting and enforcing patent and trade secret protection and regulatory exclusivity for our therapeutic candidates; and • obtaining and maintaining adequate coverage and reimbursement from third party payors. 113 Table of Contents A change in the outcome of any of these variables with respect to the development of any of our therapeutic candidates could significantly change the costs and timing associated with the development of that therapeutic candidate.
Until such time, if ever, as we can generate substantial product revenue to support our cost structure, we expect to finance our cash needs through a combination of equity offerings, debt financings, license and collaboration agreements 117 Table of Contents and other similar arrangements.
Until such time, if ever, as we can generate substantial product revenue to support our cost structure, we expect to finance our cash needs through a combination of equity offerings, debt financings, license and collaboration agreements and other similar arrangements.
Based on our current operating plans, we believe that our cash, cash equivalents and marketable securities as of December 31, 2024 will be sufficient to fund our operations into the second quarter of 2027. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect.
Based on our current operating plans, we believe that our cash, cash equivalents and marketable securities as of December 31, 2025 will be sufficient to fund our operations into the third quarter of 2027. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect.
We expect that our research and development expenses will increase as we advance ENTR-601-44 and ENTR-601-45 through clinical trials, progress ENTR-601-50 and ENTR-601-51 through preclinical development and into clinical trials, and continue to perform discovery work for future product candidates.
We expect that our research and development expenses will increase as we advance ENTR-601-44 and ENTR-601-45 through clinical trials, ENTR-601-50 into clinical trials, ENTR-601-51 and our ocular programs through preclinical development and into clinical trials, and continue to perform discovery work for future product candidates.
At the end of each 112 Table of Contents subsequent reporting period, the Company re-evaluates the estimated variable consideration included in the transaction price and any related constraint, and if necessary, adjusts its estimate of the overall transaction price.
At the end of each subsequent reporting period, the Company re-evaluates the estimated variable consideration included in the transaction price and any related constraint, and if necessary, adjusts its estimate of the overall transaction price.
Revenue Recognition Substantially all of our revenue to date has been generated from the Vertex Agreement. We account for revenue pursuant to ASC Topic 606, "Revenue from Contracts with Customers" ("ASC 606").
Revenue Recognition 114 Table of Contents Substantially all of our revenue to date has been generated from the Vertex Agreement. We account for revenue pursuant to ASC Topic 606, "Revenue from Contracts with Customers" ("ASC 606").
Critical Accounting Policies and Significant Judgments and Estimates Our management’s discussion and analysis of financial condition and results of operations is based on our consolidated financial statements, which have been prepared in accordance with generally accepted accounting principles in the United States.
Critical Accounting Policies and Significant Judgments and Estimates Our management’s discussion and analysis of financial condition and results of operations is based on our consolidated financial statements, which have been prepared in accordance with generally accepted accounting principles in the U.S.
For additional details regarding our associated accounting policies of ASC 606, refer to Notes 2, Summary of Significant Accounting Policies, and 12, Collaboration and License Agreements , to the consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K.
For additional details regarding our associated accounting policies of ASC 606, refer to Notes 2, Summary of Significant Accounting Policies, and 12, Collaboration and License Agreements , to the consolidated financial statements appearing elsewhere in this Annual Report.
For additional information about our OSIF License Agreement and amounts that could become payable in the future under such agreements, see “Business—Intellectual property— License agreement with The Ohio State University” and Note 10 , Commitments and Contingencies, to our consolidated financial statements included elsewhere in this Annual Report.
For additional information about our OSIF License Agreement and amounts that could become payable in the future under such agreements, see “ Business—Intellectual property— License Agreement with The Ohio State University ” and Note 10 , Commitments and Contingencies, to our consolidated financial statements included elsewhere in this Annual Report.
If we fail to become profitable or are unable to sustain profitability on a continuing basis, we may be unable to continue our operations at planned levels and be forced to reduce or terminate our operations. As of December 31, 2024, we had cash, cash equivalents and marketable securities of $420.0 million .
If we fail to become profitable or are unable to sustain profitability on a continuing basis, we may be unable to continue our operations at planned levels and be forced to reduce or terminate our operations. As of December 31, 2025, we had cash, cash equivalents and marketable securities of $295.7 million.
As of December 31, 2024, we also had federal and state research and development tax credit carryforwards of $3.4 million and $1.5 million , respectively, which may be available to reduce future tax liabilities and expire at various dates beginning in 2039 and 2035, respectively.
As of December 31, 2025, we also had federal and state research and development tax credit carryforwards of $9.6 million and $5.3 million , respectively, which may be available to reduce future tax liabilities and expire at various dates beginning in 2039 and 2035, respectively.
In addition, as of December 31, 2024, we had state net operating loss carryforwards of $6.0 million , which may be available to offset future taxable income and expire at various dates beginning in 2036.
In addition, as of December 31, 2025, we had state net operating loss carryforwards of $192.9 million , which may be available to offset future taxable income and expire at various dates beginning in 2036.
As of December 31, 2024, we have not sold any shares of common stock under the ATM program. 115 Table of Contents In June 2024, we entered into a securities purchase agreement with a limited number of investors relating to a registered direct offering (the “June 2024 Offering”) of 3,367,003 shares of our common stock at a purchase price of $14.85 per share and, in lieu of common stock to certain investors who so chose, pre-funded warrants (the “Pre-Funded Warrants”) to purchase 3,367,003 shares of our common stock at a purchase price of $14.8499 per Pre-Funded Warrant, which represents the price per share at which the shares of common stock were sold to the investors in the June 2024 Offering, minus $0.0001, which is the exercise price of each Pre-Funded Warrant.
In June 2024, we entered into a securities purchase agreement with a limited number of investors relating to a registered direct offering (the “June 2024 Offering”) of 3,367,003 shares of our common stock at a purchase price of $14.85 per share and, in lieu of common stock to certain investors who so chose, pre-funded warrants (the “Pre-Funded Warrants”) to purchase 3,367,003 shares of our common stock at a purchase price of $14.8499 per Pre-Funded Warrant, which represents the price per share at which the shares of common stock were sold to the investors in the June 2024 Offering, minus $0.0001, which is the exercise price of each Pre-Funded Warrant.
The Company regularly evaluates and, when necessary, updates the costs associated with the remaining effort pursuant to the performance obligations under the Vertex Agreement. The Company estimates the amount of consideration to which it will be entitled in exchange for transferring the promised goods or services to a customer.
The Company regularly evaluates and, when necessary, updates the costs associated with the remaining effort pursuant to the performance obligations under the Vertex Agreement. The Company completed its research plan activities for VX-670 during 2025. The Company estimates the amount of consideration to which it will be entitled in exchange for transferring the promised goods or services to a customer.
Financing Activities Net cash provided by financing activities was $103.0 million for the year ended December 31, 2024, consisting of $99.6 million in net proceeds from sales of our common stock and pre-funded warrants, $2.8 million proceeds from stock option exercises and $0.6 million from the issuance of common stock under our 2021 Employee Stock Purchase Plan (the “ESPP”).
Net cash provided by financing activities wa s $103.0 million for the year ended December 31, 2024, consisting of $99.6 million in net proceeds from sales of our common stock and pre-funded warrants, $2.8 million of proceeds from stock option exercises and $0.6 million from the issuance of common stock under the ESPP.
The aggregate net proceeds from the sale of common stock and Pre-Funded Warrants in the June 2024 Offering were approximately $99.6 million, after deducting offering expenses payable by us. We will receive nominal proceeds, if any, from the exercise of the Pre-Funded Warrants.
The aggregate net proceeds from the sale of common stock and Pre-Funded Warrants in the June 2024 Offering were approximately $99.6 million, after deducting offering expenses payable by us.
Overview We are a clinical-stage biopharmaceutical company aiming to transform the lives of patients by e stablishing a new class of medicines which engage intracellular targets that have long been considered inaccessible .
Overview We are a clinical-st age biopharmaceutical company aiming to transform the lives of patients by establishing a new class of medicines that engage intracellular targets that have long been considered inaccessible.
Since our IPO, we have determined the fair market value of our common stock using the closing price of our common stock as reported on the Nasdaq Global Market on the date of grant.
We determine the fair market value of our common stock using the closing price of our common stock as reported on the Nasdaq Global Market on the date of grant.
The initial fixed rental rate is approximately $0.2 million per month and will increase 3% per annum thereafter. 6 Tide Street Lease We have a noncancellable operating lease of 23,189 square feet of office and laboratory space at 6 Tide Street in Boston, Massachusetts. The term for the lease will end on November 30, 2025.
The fixed rental rate is approximately $0.2 million per month for the remainder of the term. 6 Tide Street Lease We had a noncancellable operating lease of 23,189 square feet of office and laboratory space at 6 Tide Street in Boston, Massachusetts. The term for the lease ended on November 30, 2025.
General and Administrative Expenses General and administrative expenses consist primarily of salaries and personnel-related costs, including stock-based compensation, for our personnel in executive, legal, finance and accounting, corporate and business development, human resources and other administrative functions.
We may never succeed in obtaining regulatory approval for any of our therapeutic candidates. General and Administrative Expenses General and administrative expenses consist primarily of salaries and personnel-related costs, including stock-based compensation, for our personnel in executive, legal, finance and accounting, corporate and business development, human resources and other administrative functions.
General and Administrative Expenses General and administrative expenses for the year ended December 31, 2024 were $38.5 million , compared to $32.3 million for the year ended December 31, 2023.
General and Administrative Expenses General and administrative expenses for the year ended December 31, 2025 were $41.1 million , compared to $38.5 million for the year ended December 31, 2024.
For the year ended December 31, 2023, net cash provided by operating activities was $139.8 million , and was driven by our net loss of $6.7 million, net cash provided by changes in our operating assets and liabilities of $136.3 million , adjustments for non-cash expenses relating to stock-based compensation expense of $13.1 million and depreciation expense of $2.8 million, and adjustments for non-cash income related to net amortization of premiums and discounts of $5.7 million on marketable securities.
For the year ended December 31, 2024, net cash provided by operating activities was $41.6 million , and was driven by our net income of $65.6 million, net cash used in changes in our operating assets and liabilities of $118.9 million , adjustments for non-cash expenses relating to stock-based compensation expense of $17.9 million and depreciation expense of $3.8 million, and adjustments for non-cash income related to net amortization of premiums and discounts of $10.0 million on marketable securities.
Cash Flows The following table summarizes our cash flows for each of the periods presented: Year Ended December 31, (in thousands) 2024 2023 Net cash (used in) provided by operating activities $ (41,557) $ 139,803 Net cash used in investing activities (27,798) (138,395) Net cash provided by financing activities 102,964 21,037 Net increase in cash, cash equivalents and restricted cash $ 33,609 $ 22,445 Operating Activities For the year ended December 31, 2024, net cash used in operating activities was $41.6 million , and was driven by our net income of $65.6 million, net cash used in changes in our operating assets and liabilities of $118.9 million, adjustments for non-cash expenses relating to stock-based compensation expense of $17.9 million and depreciation expense of $3.8 million, and adjustments for non-cash income relating to accretion of premiums and discounts on marketable securities of $10.0 million .
Cash Flows The following table summarizes our cash flows for each of the periods presented: Year Ended December 31, (in thousands) 2025 2024 Net cash used in operating activities $ (128,512) $ (41,557) Net cash provided by (used in) investing activities 116,808 (27,798) Net cash provided by financing activities 887 102,964 Net (decrease) increase in cash, cash equivalents and restricted cash $ (10,817) $ 33,609 Operating Activities For the year ended December 31, 2025, net cash used in operating activities was $128.5 million , and was driven by our net loss of $143.8 million, net cash used in changes in our operating assets and liabilities of $4.7 million, adjustments for non-cash expenses relating to stock-based compensation expense of $19.6 million and depreciation expense of $4.1 million, and adjustments for non-cash income relating to accretion of premiums and discounts on marketable securities of $3.7 million .
Since inception, we have incurred significant net losses. As of December 31, 2024, we had an accumulated deficit of $129.3 million. We expect to generate operating losses and negative operating cash flows for the foreseeable future as we advance our platform and EEV therapeutic candidates.
Since our inception, we have incurred significant net losses. As of December 31, 2025, we had an accumulated deficit of $273.1 million. Other than the recognition of revenue related to collaboration payments, we expect to continue to generate operating losses and negative operating cash flows for the foreseeable future as we advance our platform and therapeutic candidates.
The increase of $6.2 million was primarily attributable to the following: • a $5.9 million increase in personnel-related costs, primarily as a result of the increase in headcount in our general and administrative function, inclusive of stock-based compensation expense of $10.1 million an d $6.9 million for the years ended December 31, 2024 and 2023, respectively.
The increase of $2.6 million was primarily attributable to an increase in professional services to support our growth, as well as an increase in personnel-related costs, inclusive of stock-based compensation expense of $10.9 million an d $10.1 million for the years ended December 31, 2025 and 2024, respectively.
IDB Sublease The Company subleases a portion of the office and laboratory space leased under the IDB Lease to a third-party. The term of the sublease commenced in April 2023. The sublease term is 3 years.
IDB Sublease We sublease a portion of the office and laboratory space leased under the IDB Lease to a third-party. The term of the sublease commenced in April 2023 and extends through August 2026.
Net cash used in investing activities was $138.4 million for the year ended December 31, 2023, and was driven by $407.2 million in purchases of marketable securities and $5.6 million from purchases of property and equipment, , which were partially offset by $274.4 million from the maturities of marketable securities.
Investing Activities Net cash provided by investing activities was $116.8 million for the year ended December 31, 2025, and was driven by $259.4 million of maturities of marketable securities, which were partially offset by $141.6 million in purchases of marketable securities and $1.0 million in purchases of property and equipment .
As of December 31, 2024, we had federal net operating loss carryforwards of $4.2 million , which may be available to offset future taxable income. None of our federal net operating loss carryforwards will expire, but all are limited in their usage to an annual deduction equal to 80% of annual taxable income.
None of our federal net operating loss carryforwards will expire, but all are limited in their usage to an annual deduction equal to 80% of annual taxable income.
Because of the numerous risks and uncertainties associated with research, development and commercialization of our candidates, we are unable to estimate the exact amount of our working capital requirements.
We have based this estimate on assumptions that may prove to be wrong, and we could utilize our available capital resources sooner than we expect. Because of the numerous risks and uncertainties associated with research, development and commercialization of our candidates, we are unable to estimate the exact amount of our working capital requirements.
License Agreements We have also entered into a license agreement (“OSIF License Agreement”) with Ohio State Innovation Foundation (“OSIF”), an affiliate of The Ohio State University (“OSU”), under which we are obligated to make specific milestone and royalty payments.
For additional information about our lease commitments, see Note 11, Leases , to our consolidated financial statements included elsewhere in this Annual Report. License Agreements We have a license agreement (“OSIF License Agreement”) with Ohio State Innovation Foundation (“OSIF”), an affiliate of The Ohio State University (“OSU”), under which we are obligated to make specific milestone and royalty payments.
Income Taxes The Company recorded income tax expense of $0.9 million for the year ended December 31, 2024 and income tax expense of $18.7 million for the year ended December 31, 2023.
Income Taxes The Company recorded income tax expense of $0.9 million for both the year ended December 31, 2025 and the year ended December 31, 2024. The income tax expense recorded for the year ended December 31, 2025 was primarily driven by adjustments made upon the finalization of tax returns.
Based on our current operating plans, we believe that our cash, cash equivalents and marketable securities as of December 31, 2024 will be sufficient to fund our operations into the second quarter of 2027. We have based this estimate on assumptions that may prove to be wrong, and we could utilize our available capital resources sooner than we expect.
Based on our 119 Table of Contents current operating plans, we believe that our cash, cash equivalents and marketable securities as of December 31, 2025 will be sufficient to fund our operations into the third quarter of 2027.
Interest and Other Income Total interest and other income was $19.5 million for the year ended December 31, 2024 , compared to $15.2 million of interest and other income for the year ended December 31, 2023. This increase is primarily driven by higher interest rates and larger investments in debt securities.
Interest and Other Income Total interest and other income was $15.1 million for the year ended December 31, 2025 , compared to $19.5 million of interest and other income for the year ended December 31, 2024.
In addition, we expect to incur additional costs associated with operating as a public company. Our operating expenses and future funding requirements are expected to increase substantially as we continue to advance our portfolio of programs.
Future Funding Requirements We expect to incur significant expenses and operating losses for the foreseeable future as we advance the preclinical and, if successful, the clinical development of our programs. Our operating expenses and future funding requirements are expected to increase substantially as we continue to advance our portfolio of programs.
Payments due upon cancellation consist only of payments for services provided or expenses incurred, including non-cancelable obligations of our service providers, up to the date of cancellation. 118 Table of Contents Emerging Growth Company and Smaller Reporting Company Status We are an “emerging growth company”, or “EGC”, under the Jumpstart Our Business Startups Act of 2012 (the “JOBS Act”).
Payments due upon cancellation consist only of payments for services provided or expenses incurred, including non-cancelable obligations of our service providers, up to the date of cancellation.
Since our inception, we have raised over $850.0 million of gross proceeds from sales of stock to leading biotechnology investors and from the Vertex Agreement. As of December 31, 2024, we had cash, cash equivalents and marketable securities of $420.0 million.
To finance our operations beyond that point we will need to raise additional capital, which cannot be assured. Sources of Liquidity Since our inception, we have raised over $850.0 million of gross proceeds from sales of stock to leading biotechnology investors and from the Vertex Agreement.
Since our inception, we have devoted substantially all our resources to research and development efforts relating to our EEV Platform, advancing development of our portfolio of programs and general and administrative support for these operations, including raising capital. We have raised over $850.0 million of gross proceeds from equity sales to leading biotechnology investors and from the Vertex Agreement.
The decrease was driven by changes in interest earned from debt securities and money market funds as well as a decrease in the amount of marketable securities held. 117 Table of Contents Liquidity and Capital Resources Overview Since our inception, we have devoted substantially all our resources to research and development efforts relating to our EEV Platform, advancing development of our portfolio of programs and general and administrative support for those operations, including raising capital.
For both periods, a significant portion of the taxable income related to the collaboration payments was offset by current year expenses and prior year accumulated losses. For additional details about the current year tax provision, refer to Note 9, Income Taxes , to the Consolidated Financial Statements appearing elsewhere in this Annual Report on Form 10-K.
For additional details about the current year tax provision, refer to Note 9, Income Taxes , to the consolidated financial statements appearing elsewhere in this Annual Report. As of December 31, 2025, we had federal net operating loss carryforwards of $178.3 million , which may be available to offset future taxable income.
In September 2023, we entered into a sales agreement (“Sales Agreement”) with Cowen and Company, LLC (“Cowen”) under which we may, from time to time, issue and sell shares of our common stock having aggregate sales proceeds of up to $150.0 million, in a series of one or more ATM equity offerings (the “2023 ATM Program”).
We will receive nominal proceeds, if any, from the exercise of the Pre-Funded Warrants. 118 Table of Contents In November 2025, the Company entered into a sales agreement (the "Sales Agreement"), with TD Securities (USA) LLC (f/k/a Cowen and Company, LLC), acting as the Company's agent and/or principal (the "Sales Agent"), with respect to an "at the market offering" program under which the Company may, from time to time, at its sole discretion, issue and sell shares of its common stock having an aggregate offering price of up to $150.0 million through the Sales Agent.
Based on the market value of our common stock held by our non-affiliates as of the last business day of the fiscal quarter ended June 30, 2024, we no longer qualify as a “smaller reporting company” as defined in the Exchange Act, effective December 31, 2024.
We are also a “smaller reporting company” because the market value of our stock held by non-affiliates was less than $250 million as of June 30, 2025.
Net cash provided by financing activities wa s $21.0 million for the year ended December 31, 2023, consisting of $19.4 million in net proceeds from sales of our common stock in connection with the Vertex Agreement, $1.2 million of proceeds from stock option exercises and $0.4 million from the issuance of common stock under the ESPP. 116 Table of Contents Funding Requirements We expect to incur significant expenses and operating losses for the foreseeable future as we advance the preclinical and, if successful, the clinical development of our programs.
Financing Activities Net cash provided by financing activities was $0.9 million for the year ended December 31, 2025, consisting of $0.4 million proceeds from stock option exercises and $0.5 million from the issuance of common stock under our 2021 Employee Stock Purchase Plan (the “ESPP”).
See “Management’s Discussion and Analysis of Financial Condition and Results of Operations—Liquidity and Capital Resources.” To finance our operations beyond that point we will need to raise additional capital, which cannot be assured. Components of Our Results of Operations Revenue Substantially all of our revenue to date has been derived from the Vertex Agreement.
Based on our current operating plans, we believe that our cash, cash equivalents and marketable securities as of December 31, 2025 will be sufficient to fund our operations into the third quarter of 2027. Components of Our Results of Operations Revenue Substantially all of our revenue to date has been derived from the Vertex Agreement.
Removed
We enter 2025 with significant momentum, including the planned initiation of our next clinical trial of ENTR-601-44, regulatory submissions under review for ENTR-601-45, and the ongoing progress of our VX-670 partnership with Vertex Pharmaceuticals Incorporated (“Vertex”). We plan to have four clinical programs in patients ongoing by the end of 2025, marking a new phase in the Company’s growth.
Added
Through proprietary, 111 Table of Contents versatile and modular approaches, we are advancing a robust development portfolio of genetic medicines for the potential treatment of neuromuscular and inherited retinal diseases, among others. In 2026, we expect to progress our ENTR-601-44 and ENTR-601-45 clinical trials, an EU filing for the ENTR-601-50 clinical trial, and regulatory submissions for ENTR-601-51.
Removed
This regulatory progress follows positive preliminary data in healthy volunteers from a Phase 1 clinical trial, ENTR-601-44-101, reported in 2024. Key business updates include: • In 2024, we submitted regulatory applications to initiate global Phase 1/2 MAD clinical studies in patients for ENTR-601-44 in the United States, United Kingdom and Europe.
Added
In addition, our VX-670 partnership with Vertex Pharmaceuticals Incorporated (“Vertex”) continues to progress, with dosing completion anticipated in mid-2026. We anticipate reporting on the results of two cohorts of patient data from our ENTR-601-44 program, and one from our ENTR-601-45 program during 2026. As of December 31, 2025, we had cash, cash equivalents and marketable securities of $295.7 million .
Removed
We have also submitted regulatory applications to initiate a Phase 1/2 MAD clinical study of ENTR-601-45 in the United Kingdom and Europe for patients living with DMD who are amenable to exon 45 skipping. • On February 3, 2025, we announced the receipt of authorization from the United Kingdom’s Medicines and Healthcare Products Regulatory Agency (“MHRA”) and Research Ethics Committee for its Clinical Trial of an Investigational Medicinal Product to initiate ELEVATE-44-201, a Phase 1/2 multiple ascending dose (“MAD”) clinical study of ENTR-601-44 for the potential treatment of Duchenne muscular dystrophy (“Duchenne” or “DMD”) in patients with a confirmed mutation in the DMD gene amenable to exon 44 skipping.
Added
Results of Operations Comparison of the years ended December 31, 2025 and 2024 Year ended December 31, (in thousands) 2025 2024 Change Collaboration revenue $ 25,421 $ 210,782 $ (185,361) Operating expenses: Research and development 142,269 125,306 16,963 General and administrative 41,050 38,465 2,585 Total operating expenses 183,319 163,771 19,548 (Loss) income from operations (157,898) 47,011 (204,909) Other income: Interest and other income 15,072 19,474 (4,402) Total other income 15,072 19,474 (4,402) (Loss) income before provision for income taxes $ (142,826) $ 66,485 $ (209,311) Provision for income taxes 924 859 65 Net (loss) income $ (143,750) $ 65,626 $ (209,376) Collaboration Revenue Collaboration revenue was $25.4 million for the year ended December 31, 2025 and $210.8 million for the year ended December 31, 2024.
Removed
We are on track to initiate ELEVATE-44-201 in the United Kingdom in the second quarter of 2025. • On February 24, 2025, we announced that the United States Food and Drug Administration (“FDA”) had lifted the clinical hold on the Investigational New Drug application (“IND”) for ENTR-601-44, and we received authorization to initiate ELEVATE-44-102, a Phase 1b MAD clinical study of ENTR-601-44 in adult DMD patients.
Added
The decrease of $185.4 million was primarily a result of fewer costs incurred for VX-670 during the year ended December 31, 2025 as compared to the year ended December 31, 2024, as we substantially completed our research plan activities for VX-670 during the first quarter of 2025.
Removed
The Company plans to initiate study enrollment in the first half of 2026. • Based on the positive preclinical data, we are on track to submit regulatory applications to initiate a clinical trial of our third Duchenne product candidate, ENTR-601-50, in patients who are exon 50 skipping amenable, in the fourth quarter of 2025. • In 2024, we selected ENTR-601-51 as our clinical candidate for our exon 51 program in patients who are exon 51 skipping amenable, and expect to submit global regulatory filings in 2026. • Our Vertex partnered candidate, VX-670, is in an ongoing global Phase 1/2 clinical trial, and in November 2024, Vertex announced completion of the Phase 1 SAD portion of the study and initiation of the Phase 2 MAD portion to evaluate both safety and efficacy. • We have also generated positive preclinical data from programs outside of our neuromuscular franchise, which include new moieties, and expect to share our first clinical candidate in ocular disease later in 2025. 108 Table of Contents We believe that the potential success of our early programs can translate into the efficient development of additional therapeutic candidates and allow us to build portfolios in neuromuscular disease and beyond.
Added
The increase of $17.0 million in research and development expenses was primarily attributable to: • an increase of $10.7 million in direct research and development expenses, driven by additional costs incurred related to the progress of our Duchenne programs, partially offset by fewer costs incurred related to our collaboration with Vertex; and • an increase of $6.3 million in unallocated research and development expenses driven by an increase in personnel costs of 6.5 million and a decrease in facilities related costs of 0.2 million.
Removed
A change in the outcome of any of these variables with respect to the development of any of our therapeutic candidates could significantly change the costs and timing associated with the development of that therapeutic candidate. We may never succeed in obtaining regulatory approval for any of our therapeutic candidates.
Added
Personnel costs are inclusive of stock-based compensation expense of $8.7 million and $7.8 million for the years ended December 31, 2025 and 2024, respectively.
Removed
The income tax expense recorded for the year ended 111 Table of Contents December 31, 2024 was driven largely by the current tax liability associated with the $75.0 million payment for the achievement of the clinical advancement milestone for VX-670 and $1.7 million in related interest owed to taxing authorities pursuant to Section 453A.
Added
As of December 31, 2025, we had cash, cash equivalents and marketable securities of $295.7 million.
Removed
The income tax expense recorded for the year ended December 31, 2023 was driven largely by the current tax liability associated with the tax recognition of the upfront payment received pursuant to the Vertex Agreement and the capitalization of research and development expenses under Section 174.
Added
During the year ended December 31, 2025, there have been no sales of common stock pursuant to the Sales Agreement.
Removed
As the Company progresses towards satisfaction of performance obligations under the Vertex Agreement, the estimated costs associated with the remaining effort required to complete the performance obligations in accordance with the research plans may change, which may materially impact revenue recognition.
Added
Reduction in Force On April 29, 2025, our board of directors approved a strategic plan, designed to increase the focus of our resources on our expanding portfolio of clinical candidates in DMD and key preclinical programs. In connection with the new strategic plan, we reduced our workforce by approximately 20% (the "Reduction").
Removed
Prior to our IPO, there was no public market for our common stock, and consequently, the estimated fair value of our common stock was determined by our board of directors as of the date of each option grant, with input from management, considering third-party valuations of our common stock as well as our board of directors’ assessment of additional objective and subjective factors that it believed were relevant and which may have changed from the date of the most recent third-party valuation through the date of the grant.
Added
As a result of the Reduction, we incurred charges of $1.9 million, primarily consisting of one-time severance payments and employee termination-related benefits during the year ended December 31, 2025. $1.7 million of the charge was recorded as research and development expenses and $0.2 million of the charge was recorded as general and administrative expenses.
Removed
These third-party valuations were performed in accordance with the guidance outlined in the American Institute of Certified Public Accountants’ Accounting and Valuation Guide, Valuation of Privately-Held-Company Equity Securities Issued as Compensation (“Practice Aid”).
Added
We do not expect to incur additional charges related to the Reduction. 121 Table of Contents Emerging Growth Company and Smaller Reporting Company Status We are an “emerging growth company”, or “EGC”, under the Jumpstart Our Business Startups Act of 2012 (the “JOBS Act”).
Removed
The Practice Aid identifies various available methods for allocating the enterprise value across classes of series of capital stock 113 Table of Contents in determining the fair value of our common stock at each valuation date.
Added
We may continue to be a smaller reporting company if either (i) the market value of our stock held by non-affiliates is less than $250 million or (ii) our annual revenue was less than $100 million during the most recently completed fiscal year and the market value of our stock held by non-affiliates is less than $700 million.
Removed
The increase of $25.4 million in research and development expenses was primarily attributable to: • an increase of $10.8 million in direct research and development costs primarily driven by additional activities performed to advance our DMD programs and discovery work for future product candidates; 114 Table of Contents • an increase of 10.5 million in personnel related costs driven by increased headcount in our research and development function, inclusive of stock-based compensation expense of $7.8 million and $6.2 million for the years ended December 31, 2024 and 2023, respectively; and • an increase of $4.1 million in facility related and other costs to support our expanding operations.
Added
If we are a smaller reporting company at the time we cease to be an emerging growth company, we may continue to rely on exemptions from certain disclosure requirements that are available to smaller reporting companies.
Removed
Provision for Income Taxes The Company recorded income tax expense of $0.9 million for the year ended December 31, 2024 and income tax expense of $18.7 million for the year ended December 31, 2023.

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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 As of December 31, 2024, we no longer qualify as a smaller reporting company.
Biggest changeItem 7A. Quantitative and Qualitative Disclosures About Market Risk We are a smaller reporting company as defined by Rule 12b-2 of the Exchange Act and are not required to provide the information required under this item. 122 Table of Contents
Removed
However, in accordance with Item 10(f)(2)(i) of Regulation S-K, we are permitted to apply the scaled disclosure requirements for smaller reporting companies in this Annual Report and are not required to provide the information required under this item.
Removed
We will be transitioning to the disclosure requirements applicable to non-smaller reporting companies beginning with our Quarterly Report on Form 10-Q for the fiscal quarter ending March 31, 2025 . 119 Table of Contents

Other TRDA 10-K year-over-year comparisons