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

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Paragraph-level year-over-year comparison of Voyager 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.

+690 added−590 removedSource: 10-K (2026-03-09) vs 10-K (2024-12-31)

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

690 paragraphs added · 590 removed · 462 edited across 7 sections

Item 1. Business

Business — how the company describes what it does

189 edited+85 added−74 removed244 unchanged
Biggest changeWe expect that our TRACER discovery platform, non-viral therapeutics platform, and preclinical programs will compete with a variety of therapies in development, including: ● Our anti-tau antibody and tau silencing gene therapy programs for AD will potentially compete with tau antibodies being developed by Lundbeck LLC , Merck & Co. , Inc. in collaboration with Teijin Limited, Eisai Co., Ltd., Janssen Pharmaceuticals, Inc., UCB S.A., Bristol-Myers Squibb Company in collaboration with Prothena Corporation plc , along with several other companies, as well as an antisense oligonucleotide program being developed by Ionis Pharmaceuticals, Inc. in collaboration with Biogen Inc. ; ● Our program for a monogenic form of ALS will potentially compete with tofersen being developed by Biogen Inc. , in collaboration with Ionis Pharmaceuticals, Inc. , and gene therapies being developed by Novartis Gene Therapies, Inc. and uniQure, Inc.; ● Our TRACER discovery platform will potentially compete with a variety of companies developing AAV capsids, including: 4D Molecular Therapeutics, Inc., Affinia Therapeutics Inc., Apertura Gene Therapy, LLC, Capsida Biotherapeutics, Inc., Capsigen Inc., Dyno Therapeutics, Inc., Kate Therapeutics Inc., Sangamo Therapeutics , Inc., and Shape Therapeutics Inc ; and ​ ● O ur non-viral therapeutics platform will potentially compete with a variety of companies developing non-viral shuttles for the delivery of genetic medicines to the CNS, including: ABL Bio, Inc. in collaboration with Sanofi S.A., Aliada Therapeutics, Inc.
Biggest changeWe expect that our TRACER discovery platform, non-viral therapeutics platform, and clinical and preclinical programs will compete with a variety of therapies in development, including: ● Our anti-tau antibody program for AD will potentially compete with tau antibodies being developed by Lundbeck LLC, Merck & Co., Inc. in collaboration with Teijin Limited, Eisai Co., Ltd., Janssen Pharmaceuticals, Inc., a subsidiary of Johnson & Johnson, UCB S.A., Bristol-Myers Squibb Company in collaboration with Prothena Corporation plc, along with several other companies; ● Our tau silencing gene therapy program for AD will potentially compete with an antisense oligonucleotide program being developed by Ionis Pharmaceuticals, Inc. in collaboration with Biogen Inc.; ● Our TDP-43 small molecule will potentially compete with a variety of companies developing small-molecules for TDP-43, including: Dewpoint Therapeutics, Inc., WaveBreak Therapeutics, LLC, Molefy Pharma SL, and various academic groups; ● Our TRACER discovery platform will potentially compete with a variety of companies developing AAV capsids, including: 4D Molecular Therapeutics, Inc., Affinia Therapeutics Inc., Apertura Gene Therapy, LLC, Capsida Biotherapeutics, Inc., Capsigen, Inc., Dyno Therapeutics, Inc., Kate Therapeutics Inc.
Subject to certain limitations and exceptions, we have agreed (a) during the Alexion Research Term, not to conduct any internal program or program on behalf of a third party that is directed to development or commercialization of any capsid candidates, or grant any third party or affiliate any right or license under our rights in such capsid candidates to exploit any therapeutic product, in combination with any Alexion Transgene, in any indication for therapeutic, diagnostic and prophylactic human and veterinary use; and (b) not to grant any third party or affiliate any right or license under our patents to exploit any licensed capsid in combination with any Alexion Transgene. ​ Financial ​ Prior to Pfizer’s transfer of its rights under the Alexion Agreement to Alexion, Pfizer paid us an upfront payment of $30.0 million in October 2021, and an additional fee of $10.0 million in connection with its exercise of an option.
Subject to certain limitations and exceptions, we have agreed (a) during the Alexion Research Term, not to conduct any internal program or program on behalf of a third party that is directed to development or commercialization of any capsid candidates, or grant any third party or affiliate any right or license under our rights in such capsid candidates to exploit any therapeutic product, in combination with any Alexion Transgene, in any indication for therapeutic, diagnostic and prophylactic human and veterinary use; and (b) not to grant any third party or affiliate any right or license under our patents to exploit any licensed capsid in combination with any Alexion Transgene. ​ Financial Terms ​ Prior to Pfizer’s transfer of its rights under the Alexion Agreement to Alexion, Pfizer paid us an upfront payment of $30.0 million in October 2021, and an additional fee of $10.0 million in connection with its exercise of an option.
From and after the first IND application filing for the Novartis HD Program, the parties have agreed that Novartis will assume sole responsibility for the development and 14 Table of Contents commercialization of Novartis HD Program Products, including all further preclinical and clinical development and any commercialization of the Novartis HD Program products and product candidates. ​ With respect to each of the Novartis SMA Program Products and Novartis HD Program Products, Novartis is obligated to use commercially reasonable efforts to develop and obtain regulatory approval for at least one of each such product in the United States and in certain other international markets specified in the 2023 Novartis Collaboration Agreement. ​ Intellectual Property ​ Under the terms of the 2023 Novartis Collaboration Agreement, each party owns the entire right, title, and interest in and to all patents or know-how controlled by such party and existing as of or before the 2023 Novartis Collaboration Agreement Effective Date, or invented, authored, discovered, developed, created or acquired solely by or on behalf of such party after the 2023 Novartis Collaboration Effective Date outside of its activities under the 2023 Novartis Collaboration Agreement. ​ We and Novartis have further agreed that all know-how created by either or both parties in the performance of the activities as undertaken pursuant to the performance of the Novartis HD Program plan or in the course of development, manufacture and commercialization of Novartis HD Program Products and all patent rights covering such know-how, or collectively, the 2023 Novartis Arising IP, is to be owned as follows: (i) we solely own all 2023 Novartis Arising IP comprised of know-how or other intellectual property rights related to any TRACER Capsid, including the use or manufacture of any TRACER Capsid, and that is created jointly by our representatives and representatives of Novartis or created solely by representatives of Novartis through the use of our confidential information; and (b) with respect to all other 2023 Novartis Arising IP, (i) we solely own all such 2023 Novartis Arising IP created solely by our representatives, (ii) Novartis solely owns all such 2023 Novartis Arising IP created solely by Novartis representatives; and (iii) the parties jointly own all such 2023 Novartis Arising IP created jointly by representatives of both Novartis and us. ​ Exclusivity ​ Subject to certain limitations and exceptions, we have agreed during the 2023 Novartis Collaboration Term not to (a) conduct any wholly-owned program or program on behalf of a third party that is directed to the development or commercialization of any capsids for use in any therapeutic product containing a capsid in combination with a payload designed to have therapeutic effect on the gene agreed between the parties as the target of the Novartis SMA Program when packaged into a capsid and delivered to the appropriate cells; (b) develop or commercialize any competing Novartis HD Program Product intended to have a therapeutic effect on genes agreed between the parties as the targets of the Novartis HD Program; or (c) grant any third party any right, license, option, covenant not to assert or similar right, under any patents or know-how controlled by us or our affiliates (excluding an acquiring entity) as of the 2023 Novartis Collaboration Agreement Effective Date or during the 2023 Novartis Collaboration Term, that would enable a third party to do any of the foregoing. ​ 15 Table of Contents Termination ​ Unless earlier terminated, with respect to any licensed product(s) under the 2023 Novartis Collaboration Agreement, on a country-by-country basis, the 2023 Novartis Collaboration Agreement expires upon the expiration of the last-to-expire royalty term with respect to such licensed product in such country in the territory, or the 2023 Novartis Collaboration Term.
From and after the first IND application filing for the Novartis HD Program, the parties have agreed that Novartis will assume sole responsibility for the development and commercialization of Novartis HD Program Products, including all further preclinical and clinical development and any commercialization of the Novartis HD Program products and product candidates. ​ With respect to each of the Novartis SMA Program Products and Novartis HD Program Products, Novartis is obligated to use commercially reasonable efforts to develop and obtain regulatory approval for at least one of each such product in the United States and in certain other international markets specified in the 2023 Novartis Collaboration Agreement. ​ Intellectual Property ​ Under the terms of the 2023 Novartis Collaboration Agreement, each party owns the entire right, title, and interest in and to all patents or know-how controlled by such party and existing as of or before the 2023 Novartis Collaboration Agreement Effective Date, or invented, authored, discovered, developed, created or acquired solely by or 13 Table of Contents on behalf of such party after the 2023 Novartis Collaboration Effective Date outside of its activities under the 2023 Novartis Collaboration Agreement. ​ We and Novartis have further agreed that all know-how created by either or both parties in the performance of the activities as undertaken pursuant to the performance of the Novartis HD Program plan or in the course of development, manufacture and commercialization of Novartis HD Program Products and all patent rights covering such know-how, or collectively, the 2023 Novartis Arising IP, is to be owned as follows: (a) we solely own all 2023 Novartis Arising IP comprised of know-how or other intellectual property rights related to any TRACER Capsid, including the use or manufacture of any TRACER Capsid, and that is created jointly by our representatives and representatives of Novartis or created solely by representatives of Novartis through the use of our confidential information; and (b) with respect to all other 2023 Novartis Arising IP, (i) we solely own all such 2023 Novartis Arising IP created solely by our representatives, (ii) Novartis solely owns all such 2023 Novartis Arising IP created solely by Novartis representatives; and (iii) the parties jointly own all such 2023 Novartis Arising IP created jointly by representatives of both Novartis and us. ​ Exclusivity ​ Subject to certain limitations and exceptions, we have agreed during the 2023 Novartis Collaboration Term not to (a) conduct any wholly-owned program or program on behalf of a third party that is directed to the development or commercialization of any capsids for use in any therapeutic product containing a capsid in combination with a payload designed to have therapeutic effect on the gene agreed between the parties as the target of the Novartis SMA Program when packaged into a capsid and delivered to the appropriate cells; (b) develop or commercialize any competing Novartis HD Program Product intended to have a therapeutic effect on genes agreed between the parties as the targets of the Novartis HD Program; or (c) grant any third party any right, license, option, covenant not to assert or similar right, under any patents or know-how controlled by us or our affiliates (excluding an acquiring entity) as of the 2023 Novartis Collaboration Agreement Effective Date or during the 2023 Novartis Collaboration Term, that would enable a third party to do any of the foregoing. ​ Termination ​ Unless earlier terminated, with respect to any licensed product(s) under the 2023 Novartis Collaboration Agreement, on a country-by-country basis, the 2023 Novartis Collaboration Agreement expires upon the expiration of the last-to-expire royalty term with respect to such licensed product in such country in the territory, or the 2023 Novartis Collaboration Term.
A company, institution, or organization which takes responsibility for the initiation and management of a clinical development program for such products, and for their regulatory approval, is typically referred to as a sponsor. ​ The process required by the FDA before a biological product may be marketed in the United States generally involves the following: ​ ● completion of nonclinical laboratory tests and animal studies according to the FDA’s GLPs and applicable requirements for the humane use of laboratory animals or other applicable regulations; ​ ● preparation of clinical trial material in accordance with cGMPs; ​ ● design of a clinical protocol and submission to the FDA of an application for an IND, which must become effective before human clinical trials may begin; ​ ● approval by an independent institutional review board, or IRB, or ethics committee representing each clinical trial site before each clinical trial may be initiated; ​ 33 Table of Contents ● performance of adequate and well-controlled human clinical trials according to the FDA’s good clinical practices, or GCPs, and any additional requirements for the protection of human research subjects and their health information, to establish the safety, purity, potency, and efficacy, of the proposed biological product for its intended use; ​ ● submission to the FDA of a BLA for marketing approval that includes substantive evidence of safety, purity, and potency from results of nonclinical testing and clinical studies, including payment of application user fees; ​ ● satisfactory completion of an FDA inspection prior to BLA approval of the manufacturing facility or facilities where the biological product is produced to assess compliance with cGMP, to assure that the facilities, methods and controls are adequate to preserve the biological product’s identity, strength, quality and purity; ​ ● potential FDA inspection of the nonclinical and clinical study sites that generated the data in support of the BLA; ​ ● potential FDA Advisory Committee meeting to elicit expert input on critical issues; ​ ● p ayment of user application and program fees pursuant to the Prescription Drug User Fee Act, or PDUFA; ​ ● FDA review and approval of the BLA , authorizing licensure of the biological product for marketing of the product in the US for one or more indications ; and ​ ● compliance with any post approval requirements, including the potential requirement to implement a Risk Evaluation and Mitigation Strategy, or REMS, and the potential requirement to conduct post approval studies. ​ Preclinical Studies ​ Before a sponsor begins testing a product candidate with potential therapeutic value in humans, the product candidate enters the preclinical testing stage.
A company, institution, or organization which takes responsibility for the initiation and management of a clinical development program for such products, and for their regulatory approval, is typically referred to as a sponsor. ​ The process required by the FDA before a biological product may be marketed in the United States generally involves the following: ​ ● completion of nonclinical laboratory tests and animal studies according to the FDA’s good laboratory practices, or GLPs, and applicable requirements for the humane use of laboratory animals or other applicable regulations; ​ ● preparation of clinical trial material in accordance with cGMPs; ​ ● design of a clinical protocol and submission to the FDA of an application for an IND, which must become effective before human clinical trials may begin; ​ ● approval by an independent institutional review board, or IRB, or ethics committee representing each clinical trial site before each clinical trial may be initiated; ​ ● performance of adequate and well-controlled human clinical trials according to the FDA’s good clinical practices, or GCPs, and any additional requirements for the protection of human research subjects and their health information, to establish the safety, purity, potency, and efficacy of the proposed biological product for its intended use; ​ ● submission to the FDA of a biologics license application, or BLA, for marketing approval that includes substantive evidence of safety, purity, and potency from results of nonclinical testing and clinical studies, including payment of application user fees; ​ ● satisfactory completion of an FDA inspection prior to BLA approval of the manufacturing facility or facilities where the biological product is produced to assess compliance with cGMP, to assure that the facilities, methods and controls are adequate to preserve the biological product’s identity, strength, quality and purity; ​ ● potential FDA inspection of the nonclinical and clinical study sites that generated the data in support of the BLA; ​ ● potential FDA Advisory Committee meeting to elicit expert input on critical issues; ​ ● p ayment of user application and program fees pursuant to the Prescription Drug User Fee Act, or PDUFA; ​ ● FDA review and approval of the BLA , authorizing licensure of the biological product for marketing of the product in the US for one or more indications ; and ​ ● compliance with any post approval requirements, including the potential requirement to implement a Risk Evaluation and Mitigation Strategy, or REMS, and the potential requirement to conduct post approval studies. ​ 32 Table of Contents Preclinical Studies ​ Before a sponsor begins testing a product candidate with potential therapeutic value in humans, the product candidate enters the preclinical testing stage.
The parties have further agreed that all know-how created by either or both parties in the performance of the activities as undertaken pursuant to a development plan during the 2023 Discovery Period or in the course of development, manufacture and commercialization of Collaboration Candidates or products and all patent rights covering such know-how, or collectively the 2023 Neurocrine Arising IP, is to be owned as follows: (a) we solely own all 2023 Neurocrine Arising IP created jointly by representatives of us and Neurocrine that constitutes capsid know-how and capsid patent rights, and 2023 Neurocrine Arising IP created solely by representatives of Neurocrine through the use of our confidential information, including unpublished sequence information for our capsids; and (b) with respect to all other 2023 Neurocrine Arising IP, (i) we solely own all such 2023 Neurocrine Arising IP created solely by our representatives, (ii) Neurocrine solely owns all such 2023 Neurocrine Arising IP created solely by Neurocrine representatives; and (iii) the parties jointly own all such 2023 Neurocrine Arising IP created jointly by representatives of both Neurocrine and us. 2023 Neurocrine Arising IP owned by us is included in the license granted from us to Neurocrine described above. ​ Exclusivity ​ During the term of the 2023 Neurocrine Collaboration Agreement, neither party nor any of its respective affiliates is permitted to directly or indirectly develop, manufacture or commercialize any other gene therapy product directed to a target under any 2023 Neurocrine Program, or grant any affiliate or third party a license or sublicense to enable any third-party to do so, subject to specified exceptions, including the parties’ conduct of certain basic research, provided that Neurocrine or its affiliates may develop competitive products that do not contain an adeno-associated virus as the viral vector. ​ Termination ​ Unless earlier terminated, the 2023 Neurocrine Collaboration Agreement expires on the later of (a) the expiration of the last to expire 2023 Royalty Term with respect to all 2023 Collaboration Products worldwide or (b) the expiration or termination of any 2023 Co-Co Agreement.
The parties have further agreed that all know-how created by either or both parties in the performance of the activities as undertaken pursuant to a development plan during the 2023 Discovery Period or in the course of development, manufacture and commercialization of Collaboration Candidates or products and all patent rights covering such know-how, or collectively 19 Table of Contents the 2023 Neurocrine Arising IP, is to be owned as follows: (a) we solely own all 2023 Neurocrine Arising IP created jointly by representatives of us and Neurocrine that constitutes capsid know-how and capsid patent rights, and 2023 Neurocrine Arising IP created solely by representatives of Neurocrine through the use of our confidential information, including unpublished sequence information for our capsids; and (b) with respect to all other 2023 Neurocrine Arising IP, (i) we solely own all such 2023 Neurocrine Arising IP created solely by our representatives, (ii) Neurocrine solely owns all such 2023 Neurocrine Arising IP created solely by Neurocrine representatives; and (iii) the parties jointly own all such 2023 Neurocrine Arising IP created jointly by representatives of both Neurocrine and us. 2023 Neurocrine Arising IP owned by us is included in the license granted from us to Neurocrine described above. ​ Exclusivity ​ During the term of the 2023 Neurocrine Collaboration Agreement, neither party nor any of its respective affiliates is permitted to directly or indirectly develop, manufacture or commercialize any other gene therapy product directed to a target under any 2023 Neurocrine Program, or grant any affiliate or third party a license or sublicense to enable any third party to do so, subject to specified exceptions, including the parties’ conduct of certain basic research, provided that Neurocrine or its affiliates may develop competitive products that do not contain an adeno-associated virus as the viral vector. ​ Termination ​ Unless earlier terminated, the 2023 Neurocrine Collaboration Agreement expires on the later of (a) the expiration of the last-to-expire 2023 Royalty Term with respect to all 2023 Collaboration Products worldwide or (b) the expiration or termination of any 2023 Co-Co Agreement.
ITEM 1. BUSINESS ​ We are a biotechnology company whose mission is to leverage the power of human genetics to modify the course of and ultimately cure neurological diseases. Our pipeline includes programs for Alzheimer’s disease, or AD; Friedreich’s ataxia, or FA; Parkinson’s disease; and multiple other diseases of the central nervous system, or CNS.
ITEM 1. BUSINESS ​ We are a biotechnology company whose mission is to leverage the power of human genetics to modify the course of and ultimately cure neurological diseases. Our pipeline includes programs for Alzheimer’s disease, or AD; Friedreich’s ataxia, or FA; Parkinson’s disease, or PD; and multiple other diseases of the central nervous system, or CNS.
In the event we exercise our 2023 Co-Co Option, the parties have also agreed that Neurocrine is entitled to receive (in addition to its 50% share of profits) 50% of our share of profits until our obligation to repay 50% of all development costs incurred by Neurocrine in connection with the GBA1 Program prior to such exercise have been paid off out of our 50% share of profits.
In the event we exercise our 2023 Co-Co Option, the parties have also agreed that Neurocrine is entitled to receive (in addition to its 50% share of profits) 50% of our share of profits until our obligation to repay 50% of all development costs incurred by Neurocrine in connection with the GBA1 Program prior to such exercise have been paid off.
In addition to other benefits, such as the ability to have greater interactions with the FDA, this designation enables a company to petition FDA to initiate review of sections of a NDA or BLA application before the application is complete, a process known as rolling review. ​ ● Breakthrough therapy designation .
In addition to other benefits, such as the ability to have greater interactions with the FDA, this designation enables a company to petition FDA to initiate review of sections of an NDA or a BLA application before the application is complete, a process known as rolling review. ​ ● Breakthrough therapy designation .
Alexion may also terminate the Alexion Agreement, in whole or in part, for any or no reason upon ninety days’ written notice to us. ​ Upon certain terminations for cause by Alexion, the license that we have granted to Alexion under the Alexion Agreement shall become irrevocable and perpetual, and all milestone payments and royalties that would have otherwise been payable by Alexion under such license had the Alexion Agreement remained in effect would be substantially reduced. ​ License Agreement with Touchlight IP Limited On November 3, 2022, we and Touchlight IP Limited, or Touchlight, entered into a license agreement, or the Touchlight License Agreement, to authorize historical use by us of a certain DNA preparation process, or the Subject DNA Preparation Process, and to authorize the prospective exploitation of TRACER Capsids created with the use of the Subject DNA Preparation Process. ​ 26 Table of Contents The terms of the Touchlight License Agreement include a one-time, non-refundable technology access fee of $5.0 million, paid to Touchlight during the fourth quarter of 2022. ​ The terms of the Touchlight License Agreement also include future milestone payments and low single-digit royalties payable to Touchlight by us if we or our program collaborators or licensees choose to utilize in a therapeutic product certain TRACER Capsids that were created with the historical use of the Subject DNA Preparation Process.
Alexion may also terminate the Alexion Agreement, in whole or in part, for any or no reason upon ninety days’ written notice to us. ​ Upon certain terminations for cause by Alexion, the license that we have granted to Alexion under the Alexion Agreement shall become irrevocable and perpetual, and all milestone payments and royalties that would have otherwise been payable by Alexion under such license had the Alexion Agreement remained in effect would be substantially reduced. ​ License Agreement with Touchlight IP Limited On November 3, 2022, we and Touchlight IP Limited, or Touchlight, entered into a license agreement, or the Touchlight License Agreement, to authorize historical use by us of a certain DNA preparation process, or the Subject DNA Preparation Process, and to authorize the prospective exploitation of TRACER Capsids created with the use of the Subject DNA Preparation Process. ​ The terms of the Touchlight License Agreement include a one-time, non-refundable technology access fee of $5.0 million, paid to Touchlight during the fourth quarter of 2022. ​ The terms of the Touchlight License Agreement also include future milestone payments and low single-digit royalties payable to Touchlight by us if we or our program collaborators or licensees choose to utilize in a therapeutic product certain TRACER Capsids that were created with the historical use of the Subject DNA Preparation Process.
Our principal executive offices are located at 75 Hayden Avenue, Lexington, MA. We lease our office and laboratory space, which consist of approximately 26,148 square feet located in Cambridge, Massachusetts and 93,449 square feet located in Lexington, MA. Our lease in Cambridge expires in 2026 and our lease in Lexington expires in 2031.
Our principal executive offices are located at 75 Hayden Avenue, Lexington, Massachusetts. We lease our office and laboratory space, which consist of approximately 26,148 square feet located in Cambridge, Massachusetts and 93,449 square feet located in Lexington, Massachusetts. Our lease in Cambridge expires in 2026 and our lease in Lexington expires in 2031.
Alexion is also required to use commercially reasonable efforts to commercialize each Alexion Licensed CNS Product in the United States and at least one Alexion Major Market Country where Alexion or its designated affiliates or sublicensees has received regulatory approval for such Alexion Licensed CNS Product, subject to certain limitations. ​ 25 Table of Contents Intellectual Property ​ Under the terms of the Alexion Agreement, each of the parties owns the entire right, title, and interest in and to all patents or know-how controlled by such party and existing as of or before the effective date of the Alexion Agreement, or invented, developed, created, generated or acquired solely by or on behalf of such party after such effective date. ​ Exclusivity ​ Subject to certain specified exceptions, any patents and know-how that are invented or otherwise developed jointly by or on behalf of the parties during the term of the Alexion Agreement and in the course of our and Alexion’s activities under the Alexion Agreement will follow inventorship under U.S. patent law.
Alexion is also required to use commercially reasonable efforts to commercialize each Alexion Licensed CNS Product in the United States and at least one Alexion Major Market Country where Alexion or its designated affiliates or sublicensees has received regulatory approval for such Alexion Licensed CNS Product, subject to certain limitations. ​ Intellectual Property ​ Under the terms of the Alexion Agreement, each of the parties owns the entire right, title, and interest in and to all patents or know-how controlled by such party and existing as of or before the effective date of the Alexion Agreement, or invented, developed, created, generated or acquired solely by or on behalf of such party after such effective date. ​ Exclusivity ​ Subject to certain specified exceptions, any patents and know-how that are invented or otherwise developed jointly by or on behalf of the parties during the term of the Alexion Agreement and in the course of our and Alexion’s activities under the Alexion Agreement will follow inventorship under U.S. patent law.
In cases where data from foreign clinical trials are intended to serve as the sole basis for marketing approval in the United States, the FDA will generally not approve the application on the basis of foreign data alone unless (i) the data are applicable to the U.S. population and U.S. medical practice; (ii) the trials were performed by clinical investigators of recognized competence and pursuant to GCP regulations; and (iii) the data may be considered valid without the need for an on-site inspection by the FDA, or if the FDA considers such inspection to be necessary, the FDA is able to validate the data through an on-site inspection or other appropriate means. ​ In addition, even where the foreign study data are not intended to serve as the sole basis for approval, the FDA will not accept the data as support for an application for marketing approval unless the study is well-designed and well-conducted in accordance with GCP requirements and the FDA is able to validate the data from the study through an onsite inspection if deemed necessary.
In cases where data from 35 Table of Contents foreign clinical trials are intended to serve as the sole basis for marketing approval in the United States, the FDA will generally not approve the application on the basis of foreign data alone unless (i) the data are applicable to the U.S. population and U.S. medical practice; (ii) the trials were performed by clinical investigators of recognized competence and pursuant to GCP regulations; and (iii) the data may be considered valid without the need for an on-site inspection by the FDA, or if the FDA considers such inspection to be necessary, the FDA is able to validate the data through an on-site inspection or other appropriate means. ​ In addition, even where the foreign study data are not intended to serve as the sole basis for approval, the FDA will not accept the data as support for an application for marketing approval unless the study is well-designed and well-conducted in accordance with GCP requirements and the FDA is able to validate the data from the study through an onsite inspection if deemed necessary.
The parties jointly own all rights, title and interest in and to all intellectual property rights made or invented jointly by employees or agents of both parties. ​ Exclusivity ​ During the term of the 2019 Neurocrine Collaboration Agreement, neither party nor any of its respective affiliates is permitted to directly or indirectly exploit any AAV-based gene therapy products directed to a target to which a 2019 Collaboration Product is directed, subject to specified exceptions, including the parties’ conduct of basic research activities. ​ Termination Unless earlier terminated, the 2019 Neurocrine Collaboration Agreement expires on the later of (a) the expiration of the last to expire 2019 Royalty Term with respect to a 2019 Collaboration Product in all countries in the relevant territory or (b) the expiration or termination of all 2019 Co-Co Agreements.
The parties jointly own all rights, title and interest in and to all intellectual property rights made or invented jointly by employees or agents of both parties. ​ Exclusivity ​ During the term of the 2019 Neurocrine Collaboration Agreement, neither party nor any of its respective affiliates is permitted to directly or indirectly exploit any AAV-based gene therapy products directed to a target to which a 2019 Collaboration Product is directed, subject to specified exceptions, including the parties’ conduct of basic research activities. 22 Table of Contents ​ Termination ​ Unless earlier terminated, the 2019 Neurocrine Collaboration Agreement expires on the later of (a) the expiration of the last to expire 2019 Royalty Term with respect to a 2019 Collaboration Product in all countries in the relevant territory or (b) the expiration or termination of all 2019 Co-Co Agreements.
Although the FDA has indicated that these and other guidance documents it previously issued are not legally binding, the guidance documents provide the FDA’s current thinking on, among other things: the proper preclinical assessment of gene therapies; the chemistry, manufacturing and control information that should be included in an IND application; the proper design of tests to measure product potency in support of an IND or BLA application; and measures to observe for potential delayed adverse effects in participants who have received investigational gene therapies with the duration of follow-up based on the potential for risk of such effects.
Although the FDA has indicated that these and other guidance documents it previously issued are not legally binding, the guidance documents provide the FDA’s current thinking on, among other things: the proper preclinical assessment of gene therapies; the chemistry, manufacturing and control information that should be included in an IND application; the proper design of tests to measure product potency in support of an IND or BLA application; and measures to observe for potential delayed 36 Table of Contents adverse effects in participants who have received investigational gene therapies with the duration of follow-up based on the potential for risk of such effects.
In November 2013, the federal Drug Supply Chain Security Act became effective in the United States, mandating an industry-wide, electronic, interoperable system to trace prescription drugs through the pharmaceutical distribution supply chain with a ten-year phase-in process. Manufacturers were required by November 2023 to have such systems and processes in place.
In November 2013, the federal Drug Supply Chain Security Act, or DSCSA, became effective in the United States, mandating an industry-wide, electronic, interoperable system to trace prescription drugs through the pharmaceutical distribution supply chain with a ten-year phase-in process. Manufacturers were required by November 2023 to have such systems and processes in place.
If a Collaboration Candidate fails to meet criteria established by the JSC and is removed from consideration to become a development candidate or is named a development candidate, then a new Collaboration Candidate may be nominated to be a potential development candidate to replace the Collaboration Candidate that has failed or succeeded such that not more than four potential development candidates per program are under consideration at any one time during the 2023 Discovery Period. ​ Manufacturing ​ The parties have agreed that the applicable development plans shall specify the allocation between us and Neurocrine of responsibilities for the manufacturing of Collaboration Candidates associated with the applicable 2023 Neurocrine Program during the 2023 Discovery Period.
If a Collaboration Candidate fails to meet criteria established by the JSC and is removed from consideration to become a development candidate or is named a development candidate, then a new Collaboration Candidate may be nominated to be a potential development candidate to replace the Collaboration Candidate that has failed or succeeded such that not more than four potential development candidates per program are under consideration at any one time during the 2023 Discovery Period. ​ ​ 18 Table of Contents Manufacturing ​ The parties have agreed that the applicable development plans shall specify the allocation between us and Neurocrine of responsibilities for the manufacturing of Collaboration Candidates associated with the applicable 2023 Neurocrine Program during the 2023 Discovery Period.
Neurocrine may terminate the 2023 Neurocrine Collaboration Agreement with respect to a given 2023 Collaboration Product by providing written notice of termination to us within thirty days after complete readout of any clinical trial if the results of such clinical trial fail to meet the pre-specified primary endpoint(s) set forth in the applicable protocol or if there is a safety finding during the clinical trial relating to such 2023 Collaboration Product that either (i) is substantially irreversible or not monitorable in 21 Table of Contents patients or (ii) results in Neurocrine’s decision to designate such 2023 Collaboration Product as a terminated product under the 2023 Collaboration Agreement.
Neurocrine may terminate the 2023 Neurocrine Collaboration Agreement with respect to a given 2023 Collaboration Product by providing written notice of termination to us within thirty days after complete readout of any clinical trial if the results of such clinical trial fail to meet the pre-specified primary endpoint(s) set forth in the applicable protocol or if there is a safety finding during the clinical trial relating to such 2023 Collaboration Product that either (i) is substantially irreversible or not monitorable in patients or (ii) results in Neurocrine’s decision to designate such 2023 Collaboration Product as a terminated product under the 2023 Collaboration Agreement.
The updates are intended to help pave the way for more efficient clinical trials to facilitate the development of medical products. The draft guidance is adopted from the International Council for Harmonisation’s recently updated E6(R3) draft guideline that was developed to enable the incorporation of rapidly developing technological and methodological innovations into the clinical trial enterprise.
The updates are intended to help pave the way for more efficient clinical trials to facilitate the development of medical products. The final guidance is adopted from the International Council for Harmonisation’s recently updated E6(R3) final guideline that was developed to enable the incorporation of rapidly developing technological and methodological innovations into the clinical trial enterprise.
None of these expedited programs, however, changes the standards for approval but each may help expedite the development or approval process governing product candidates. ● Fast Track Designation . Candidate products are eligible for Fast Track designation if they are intended to treat a serious or life-threatening condition and demonstrate the potential to address unmet medical needs for the condition.
None of these expedited programs, however, changes the standards for approval but each may help expedite the development or approval process governing product candidates. ● Fast Track Designation . Product candidates are eligible for Fast Track designation if they are intended to treat a serious or life-threatening condition and demonstrate the potential to address unmet medical needs for the condition.
Patents that grant from these pending provisional and non-provisional applications are generally expected to commence expiration in 2042, 2043, 2044, and 2045, subject to possible patent term extensions. ​ We also own one patent family pending in the United States and foreign jurisdictions directed to capsid variants generated using other methodologies.
Patents that grant from these pending provisional and non-provisional applications are generally expected to commence expiration in 2042, 2043, 2044, 2045, 2046, and 2047, subject to possible patent term extensions. ​ We also own one patent family pending in the United States and foreign jurisdictions directed to capsid variants generated using other methodologies.
Pursuant to mutually-agreed development plans, during the period beginning on the Neurocrine Effective Date and ending on the third anniversary of the Neurocrine Effective Date, which period may be extended upon mutual written agreement of us and Neurocrine, or the 2023 Discovery Period, and as overseen by the Joint Steering Committee that oversees our ongoing collaboration with Neurocrine, we are responsible for identifying capsids meeting target criteria, producing development candidates, and conducting other non-clinical activities regarding the 2023 Collaboration Products.
Pursuant to mutually-agreed development plans, during the period beginning on the Neurocrine Effective Date and ending on the third anniversary of the Neurocrine Effective Date, which period may be extended upon mutual written agreement of us and Neurocrine, or the 2023 Discovery Period, and as overseen by the Joint Steering Committee that oversees our ongoing collaboration with Neurocrine, we are responsible for identifying capsids meeting target criteria, producing development candidates, and conducting other non-clinical activities regarding the 2023 17 Table of Contents Collaboration Products.
Patents that grant from these patent families are generally expected to expire between 2025 and 2036, subject to possible patent term extensions. ​ We have exclusively licensed one family of patents and patent applications directed to AAV capsids from the University of Massachusetts. In this pending patent family, there are 14 granted patents and two pending patent applications.
Patents that grant from these patent families are generally expected to expire between 2026 and 2036, subject to possible patent term extensions. ​ We have exclusively licensed one family of patents and patent applications directed to AAV capsids from the University of Massachusetts. In this pending patent family, there are 14 granted patents and two pending patent applications.
In the event of a breach by us with respect to a 2019 Neurocrine Program, if such termination were to occur after a 2019 Transition Event, then (a) if a 2019 Co-Co Agreement is in effect with respect to such program, Neurocrine can terminate the 2019 Co-Co Agreement for such program and we would no longer have co-development and co-commercialization rights with respect to the 2019 Collaboration Product and (b) subject to any license agreements, Neurocrine would no longer have any obligations with respect to any 2019 Collaboration Products resulting from such program. 24 Table of Contents ​ Alexion Option and License Agreement (Formerly Pfizer Option and License Agreement) ​ Summary of Agreement ​ We are party to an option and license agreement, or the Alexion Agreement, with Alexion.
In the event of a breach by us with respect to a 2019 Neurocrine Program, if such termination were to occur after a 2019 Transition Event, then (a) if a 2019 Co-Co Agreement is in effect with respect to such program, Neurocrine can terminate the 2019 Co-Co Agreement for such program and we would no longer have co-development and co-commercialization rights with respect to the 2019 Collaboration Product and (b) subject to any license agreements, Neurocrine would no longer have any obligations with respect to any 2019 Collaboration Products resulting from such program. ​ Alexion Option and License Agreement (Formerly Pfizer Option and License Agreement) ​ Summary of Agreement ​ We are party to an option and license agreement, or the Alexion Agreement, with Alexion.
We additionally may rely on regulatory protection afforded through data exclusivity, market exclusivity and patent term extensions where available. ​ Our commercial success may depend in part on our ability to: obtain and maintain patent and other protections for commercially important technology, inventions and know-how related to our business; defend and enforce our patents; preserve the confidentiality of our trade secrets and know-how; and operate without infringing the valid and enforceable patents and intellectual property rights of third parties.
We additionally may rely on regulatory protection afforded through data exclusivity, market exclusivity and patent term extensions where available. 27 Table of Contents ​ Our commercial success may depend in part on our ability to: obtain and maintain patent and other protections for commercially important technology, inventions and know-how related to our business; defend and enforce our patents; preserve the confidentiality of our trade secrets and know-how; and operate without infringing the valid and enforceable patents and intellectual property rights of third parties.
During the product approval process, the FDA also will determine whether a REMS is necessary to assure the safe use of the product.
During the biological product approval process, the FDA also will determine whether a REMS is necessary to assure the safe use of the biological product.
Any advances in gene therapy technology made by a competitor may be used to develop therapies that could compete against any of our product candidates. ​ Many of our competitors, either alone or with their strategic partners, have substantially greater financial, technical and human resources than we do and significantly greater experience in the discovery and development of product candidates, obtaining FDA and other regulatory approvals of product candidates and commercializing those product candidates.
Any advances in gene therapy technology made by a competitor may be used to develop therapies that could compete against any of our product candidates. ​ Many of our competitors, either alone or with their strategic partners, have substantially greater financial, technical and human resources than we do and significantly greater experience in the discovery and development of product candidates, obtaining FDA and other regulatory approvals of product candidates and commercializing those 26 Table of Contents product candidates.
Huntington’s disease is an autosomal dominant disorder, which means that an individual is at risk of inheriting the disease if only one parent is affected. While the exact function of the HTT gene in healthy individuals is unknown, it is essential for normal development before birth.
HD is an autosomal dominant disorder, which means that an individual is at risk of inheriting the disease if only one parent is affected. While the exact function of the HTT gene in healthy individuals is unknown, it is essential for normal development before birth.
We are eligible to receive specified development, regulatory, and commercialization milestone payments of up to an aggregate of $125.0 million for the first Novartis Initial Licensed Product for each Initial Novartis Target for which a Novartis License Option has been exercised to achieve the corresponding milestone.
We are eligible to receive specified development, regulatory, and commercialization milestone payments of up to an aggregate of $125.0 million for the first Novartis Initial Licensed Product for the remaining Initial Novartis Target for which a Novartis License Option has been exercised to achieve the corresponding milestone.
Although we expect to rely on contract manufacturers, we have personnel with manufacturing and quality experience to oversee our contract manufacturers. ​ 28 Table of Contents Intellectual Property ​ Overview ​ We strive to protect the proprietary technology, inventions, and know-how to enhance improvements that are commercially important to the development of our business, including seeking, maintaining, and defending patent rights, whether developed internally or licensed from third parties.
Although we expect to rely on contract manufacturers, we have personnel with manufacturing and quality experience to oversee our contract manufacturers. ​ Intellectual Property ​ Overview ​ We strive to protect the proprietary technology, inventions, and know-how to enhance improvements that are commercially important to the development of our business, including seeking, maintaining, and defending patent rights, whether developed internally or licensed from third parties.
We agreed, were we to exercise the 2019 Co-Co Option, to enter into a cost- and profit-sharing arrangement with Neurocrine, or the 2019 Co-Co Agreement, and (a) jointly develop and commercialize 2019 Collaboration Products for the FA Program, or 2019 Co-Co Products, (b) share 22 Table of Contents in its costs, profits and losses, and (c) forfeit certain milestones and royalties on net sales in the United States during the effective period of the 2019 Co-Co Agreement.
We agreed, were we to exercise the 2019 Co-Co Option, to enter into a cost- and profit-sharing arrangement with Neurocrine, or the 2019 Co-Co Agreement, and (a) jointly develop and commercialize 2019 Collaboration Products for the FA Program, or 2019 Co-Co Products, (b) share in its costs, profits and losses, and (c) forfeit certain milestones and royalties on net sales in the United States during the effective period of the 2019 Co-Co Agreement.
Accelerated approval means that a product candidate may be approved on the basis of adequate and well controlled clinical trials establishing that the product candidate has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit, or on the basis of an effect on a clinical endpoint other than survival or irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity and prevalence of the condition and the availability or lack of alternative 42 Table of Contents treatments.
Accelerated approval means that a product candidate may be approved on the basis of adequate and well controlled clinical trials establishing that the product candidate has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit, or on the basis of an effect on a clinical endpoint other than survival or irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity and prevalence of the condition and the availability or lack of alternative treatments.
Under the 2023 Novartis Collaboration Agreement, we and Novartis have agreed to collaborate to develop AAV gene therapy products and product candidates intended for the treatment of Huntington’s disease, which we refer to as the Novartis HD Program. The Novartis HD Program is currently in preclinical development.
Under the 2023 Novartis Collaboration Agreement, we and Novartis have agreed to collaborate to develop AAV gene therapy products and product candidates intended for the treatment of HD, which we refer to as the Novartis HD Program. The Novartis HD Program is currently in preclinical development.
The royalties are subject to potential reductions in customary circumstances including patent claim expiration, payments for certain third-party licenses, and biosimilar market penetration, subject to specified limits. ​ Termination ​ Unless earlier terminated, the Alexion Agreement expires on the expiration of the last-to-expire royalty term with respect to all Alexion Licensed CNS Products in all countries.
The royalties are subject to potential reductions in customary circumstances including 24 Table of Contents patent claim expiration, payments for certain third-party licenses, and biosimilar market penetration, subject to specified limits. ​ Termination ​ Unless earlier terminated, the Alexion Agreement expires on the expiration of the last-to-expire royalty term with respect to all Alexion Licensed CNS Products in all countries.
Patents that grant from these families are generally expected to commence expiration in 2037, with some later filed applications commencing expiration in 2040, 2041, 2042, 2043, 2044, and 2045 all of which are subject to possible patent term extensions. ​ We own five pending patent families to RNA inhibitors for treating tauopathies with seven pending non-provisional patent applications and three pending provisional applications.
Patents that grant from these families are generally expected to commence expiration in 2037, with some later filed applications commencing expiration in 2040, 2041, 2042, 2043, 2044, and 2045 all of which are subject to possible patent term extensions. ​ We own five pending patent families to RNA inhibitors for treating tauopathies with 34 pending non-provisional patent applications.
Following the end of the 2023 Discovery Period, Neurocrine shall be responsible for the manufacturing of all Collaboration Candidates and products. ​ Financial Terms ​ Under the terms of the 2023 Neurocrine Collaboration Agreement, Neurocrine paid us an upfront payment of approximately $136.0 million and approximately $39.0 million as consideration for an equity purchase of 4,395,588 shares of our common stock in February 2023.
Following the end of the 2023 Discovery Period, which expired in February 2026, Neurocrine shall be responsible for the manufacturing of all Collaboration Candidates and products. ​ Financial Terms ​ Under the terms of the 2023 Neurocrine Collaboration Agreement, Neurocrine paid us an upfront payment of approximately $136.0 million and approximately $39.0 million as consideration for an equity purchase of 4,395,588 shares of our common stock in February 2023.
For example, with enactment of the Tax Cuts and Jobs Act of 2017, 46 Table of Contents or the TCJA, which was signed by President Trump on December 22, 2017, Congress repealed the “individual mandate.” The repeal of this provision, which requires most Americans to carry a minimal level of health insurance, became effective in 2019.
For example, with enactment of the Tax Cuts and Jobs Act of 2017, or the TCJA, which was signed by President Trump on December 22, 2017, Congress repealed the “individual mandate.” The repeal of this provision, which requires most Americans to carry a minimal level of health insurance, became effective in 2019.
Previously, such communications were permitted under FDA guidance, but this legislation explicitly provides protection to sponsors who convey certain information about products in development to payors, including unapproved uses of approved products. In addition, in January 2025, the FDA published final guidance outlining its policies governing the distribution of scientific information to healthcare providers about unapproved uses of approved products.
Previously, such communications were permitted under FDA guidance, but this legislation explicitly provides protection to sponsors who convey certain information about products in development to payors, including unapproved uses of approved products. 40 Table of Contents In addition, in January 2025, the FDA published final guidance outlining its policies governing the distribution of scientific information to healthcare providers about unapproved uses of approved products.
Moreover, FDORA established expedited procedures authorizing FDA to withdraw an accelerated approval if certain conditions are met, including where a required confirmatory study fails to verify and describe the predicted clinical benefit or where evidence demonstrates the product is not shown to be safe or effective under the conditions of use.
Moreover, FDORA established expedited procedures authorizing 42 Table of Contents FDA to withdraw an accelerated approval if certain conditions are met, including where a required confirmatory study fails to verify and describe the predicted clinical benefit or where evidence demonstrates the product is not shown to be safe or effective under the conditions of use.
If the executive officers are not able to resolve the matter, then (a) with respect to the FA Program, subject to specified exceptions, (i) Neurocrine has the right to resolve such matter prior to our exercise of the 2019 Co-Co Option with regard to an applicable 2019 Co-Co Product or if the 2019 Co-Co Option expires or goes unexercised and (ii) following the timely exercise by us of the 2019 Co-Co Option, depending on the subject of such matter, either Neurocrine, in certain instances, or the parties jointly or the JSC, in other instances, would have the right to resolve such matter, and (b) with respect to 2019 Discovery Programs, subject to specified exceptions, Neurocrine has the right to resolve such matter.
If the executive officers are not able to resolve the matter, then with respect to the FA Program, subject to specified exceptions, (i) Neurocrine has the right to resolve such matter prior to our exercise of the 2019 Co-Co Option with regard to an applicable 2019 Co-Co Product or if the 2019 Co-Co Option expires or goes unexercised and (ii) following the timely exercise by us of the 2019 Co-Co Option, depending on the subject of such matter, either Neurocrine, in certain instances, or the parties jointly or the JSC, in other instances, would have the right to resolve such matter.
Patents that grant from this patent family are generally expected to commence expiration in 2039, subject to possible patent term extensions. ​ Licensed Intellectual Property ​ We have obtained exclusive licenses and non-exclusive licenses to patents directed to both compositions of matter and methods of use. ​ We have licensed four families of patents and patent applications, in the field of gene therapy for human diseases, directed to RNAi constructs as vector payloads, their design and use in the treatment of neurological disorders from the University of Massachusetts.
Patents that grant from this patent family are generally expected to commence expiration in 2037, subject to possible patent term extensions. ​ Licensed Intellectual Property ​ We have obtained exclusive licenses and non-exclusive licenses to patents directed to both compositions of matter and methods of use. ​ We have licensed three families of patents and patent applications, in the field of gene therapy for human diseases, directed to RNAi constructs as vector payloads, their design and use in the treatment of neurological disorders from the University of Massachusetts.
Under the Prescription Drug User Fee Act, or PDUFA, each BLA must be accompanied by a significant user fee unless an exception or waiver applies, such as the first application filed by a small business or BLAs for product candidates designated as orphan drugs, unless the product candidate includes an indication that is not for a rare disease or condition.
Under the PDUFA, each BLA must be accompanied by a significant user fee unless an exception or waiver applies, such as the first application filed by a small business or BLAs for product candidates designated as orphan drugs, unless the product candidate includes an indication that is not for a rare disease or condition.
Pursuant to the Novartis Amendment, we agreed to amend the 2022 Novartis Option and License Agreement to incorporate the grant to Novartis of a direct license, or the Novartis Direct License, to a TRACER Capsid, or the Novartis Direct Licensed Capsid, for exclusive use with a certain gene, or the Novartis Direct License 16 Table of Contents Target, to develop and commercialize the Novartis Direct Licensed Capsid as incorporated into AAV gene therapy candidates comprised of the Novartis Direct Licensed Capsid and a payload directed to the Novartis Direct License Target, or Novartis Direct Licensed Products.
Pursuant to the Novartis Amendment, we agreed to amend the 2022 Novartis Option and License Agreement to incorporate the grant to Novartis of a direct license, or the Novartis Direct License, to a TRACER Capsid, or the Novartis Direct Licensed Capsid, for exclusive use with a certain gene, or the Novartis Direct License Target, to develop and commercialize the Novartis Direct Licensed Capsid as incorporated into AAV gene therapy candidates comprised of the Novartis Direct Licensed Capsid and a payload directed to the Novartis Direct License Target, or Novartis Direct Licensed Products.
From and after the first IND application filing for the Novartis HD Program, we and Novartis have agreed that Novartis will assume sole responsibility for the development and commercialization of gene therapy products and 13 Table of Contents product candidates under the Novartis HD Program, including all further preclinical and clinical development and any commercialization of the Novartis HD Program products and product candidates. ​ Collaboration Programs and Licensing Agreements 2023 Novartis Collaboration Agreement ​ On December 28, 2023, or the 2023 Novartis Collaboration Agreement Effective Date, we entered into the 2023 Novartis Collaboration Agreement, with Novartis to (a) provide rights to Novartis with respect to certain TRACER Capsids for use in the research, development, and commercialization by Novartis of AAV gene therapy products and product candidates, comprising such TRACER Capsids and payloads intended for the treatment of spinal muscular atrophy, or the Novartis SMA Program, and (b) collaborate to develop AAV gene therapy products and product candidates under the Novartis HD Program, in each case, leveraging TRACER Capsids and other intellectual property controlled by us. ​ Novartis SMA Program and Novartis HD Program Licenses ​ Under the terms of the 2023 Novartis Collaboration Agreement, we granted to Novartis and its affiliates: ​ ● a non-exclusive, non-transferable, non-sublicensable (except in limited circumstances for contractors), worldwide, royalty-free right and license under any patents or know-how controlled by us and related to the TRACER Capsids to evaluate the same for use in the development of a product or product candidate under the Novartis SMA Program, or a Novartis SMA Program Product, comprising such a TRACER Capsid and a payload selected by Novartis during the period beginning on the 2023 Novartis Collaboration Agreement Effective Date and ending on the third anniversary of the 2023 Novartis Collaboration Agreement Effective Date; ​ ● an exclusive (even as to us), sublicensable, non-transferable, worldwide, royalty-bearing right and license under any patents or know-how controlled by us and relating to the selected TRACER Capsids to exploit the same as incorporated into a Novartis SMA Program Product for all human and veterinary diagnostic, prophylactic and therapeutic uses during the 2023 Novartis Collaboration Term (as defined below); and ​ ● an exclusive (even as to us), non-transferable, sublicensable, worldwide, royalty-bearing right and license under any patents and know-how controlled by us and relating to the development of a product or product candidate under the Novartis HD Program, or a Novartis HD Program Product to exploit the same for all human and veterinary diagnostic, prophylactic and therapeutic uses during the 2023 Novartis Collaboration Term. ​ Governance ​ We and Novartis have agreed to manage the Novartis HD Program through a Joint Steering Committee until dissolved after the first IND application filing for a Novartis HD Program Product.
From and after the first IND application filing for the Novartis HD Program, we and Novartis have agreed that Novartis will assume sole responsibility for the development and commercialization of gene therapy products and product candidates under the Novartis HD Program, including all further preclinical and clinical development and any commercialization of the Novartis HD Program products and product candidates. ​ Collaboration Programs and Licensing Agreements ​ 2023 Novartis Collaboration Agreement ​ On December 28, 2023, or the 2023 Novartis Collaboration Agreement Effective Date, we entered into the 2023 Novartis Collaboration Agreement, with Novartis to (a) provide rights to Novartis with respect to certain TRACER Capsids for use in the research, development, and commercialization by Novartis of AAV gene therapy products and product candidates, comprising such TRACER Capsids and payloads intended for the treatment of spinal muscular atrophy, or the Novartis SMA Program, and (b) collaborate to develop AAV gene therapy products and product 12 Table of Contents candidates under the Novartis HD Program, in each case, leveraging TRACER Capsids and other intellectual property controlled by us. ​ Novartis SMA Program and Novartis HD Program Licenses ​ Under the terms of the 2023 Novartis Collaboration Agreement, we granted to Novartis and its affiliates: ​ ● a non-exclusive, non-transferable, non-sublicensable (except in limited circumstances for contractors), worldwide, royalty-free right and license under any patents or know-how controlled by us and related to the TRACER Capsids to evaluate the same for use in the development of a product or product candidate under the Novartis SMA Program, or a Novartis SMA Program Product, comprising such a TRACER Capsid and a payload selected by Novartis during the period beginning on the 2023 Novartis Collaboration Agreement Effective Date and ending on the third anniversary of the 2023 Novartis Collaboration Agreement Effective Date; ​ ● an exclusive (even as to us), sublicensable, non-transferable, worldwide, royalty-bearing right and license under any patents or know-how controlled by us and relating to the selected TRACER Capsids to exploit the same as incorporated into a Novartis SMA Program Product for all human and veterinary diagnostic, prophylactic and therapeutic uses during the 2023 Novartis Collaboration Term (as defined below); and ​ ● an exclusive (even as to us), sublicensable, non-transferable, worldwide, royalty-bearing right and license under any patents and know-how controlled by us and relating to the development of a product or product candidate under the Novartis HD Program, or a Novartis HD Program Product to exploit the same for all human and veterinary diagnostic, prophylactic and therapeutic uses during the 2023 Novartis Collaboration Term.
We are also eligible to receive (a) specified sales milestone payments of up to an aggregate of $400.0 million for the Novartis SMA Program and up to an aggregate of $375.0 million for the Novartis HD Program and (b) tiered, escalating royalties in the high single-digit to low double-digit percentages of annual net sales of the Novartis SMA Program Products and the Novartis HD Program Products.
We are also eligible to receive (a) specified sales milestone payments of up to an aggregate of $400.0 million for the Novartis SMA Program and up to an aggregate of $375.0 million for the Novartis HD Program and (b) tiered, escalating royalties in the high single-digit to low double-digit percentages of annual net sales of the Novartis SMA Program Products and the 14 Table of Contents Novartis HD Program Products.
In such event, the JSC shall determine whether such nominated Collaboration Candidate meets certain development criteria. There will be a maximum of four potential development candidates for which development is being performed under any 2023 Neurocrine Program at any given time during the 2023 Discovery Period.
In such event, the JSC shall determine whether such nominated Collaboration Candidate meets certain development criteria. There will be a maximum of four potential development candidates for which development is being performed under any 2023 Neurocrine Program at any given time during the 2023 Discovery Period, which expired in February 2026.
On December 9, 2024, with issuance of its 2025 Physician Fee Schedule final regulation, CMS finalized its rules governing the IRA inflation rebate programs. The legislation also requires manufacturers to pay rebates for drugs in Medicare Part D whose price increases exceed inflation.
On December 9, 2024, with issuance of its 2025 Physician Fee Schedule final regulation, CMS finalized its rules governing the IRA inflation rebate programs. 47 Table of Contents The legislation also requires manufacturers to pay rebates for drugs in Medicare Part D whose price increases exceed inflation.
With respect to both licensed and company-owned intellectual property, we cannot be sure that patents will be granted with respect to any of our pending patent applications or with respect to any patent applications filed by us in the future, nor can we be sure that any of our existing patents or any patents that may be granted to us in the future will be commercially useful in protecting our commercial products and methods of using or manufacturing the same. ​ We own at least 421 pending patent applications and at least 113 patents have issued in the United States and foreign jurisdictions.
With respect to both licensed and company-owned intellectual property, we cannot be sure that patents will be granted with respect to any of our pending patent applications or with respect to any patent applications filed by us in the future, nor can we be sure that any of our existing patents or any patents that may be granted to us in the future will be commercially useful in protecting our commercial products and methods of using or manufacturing the same. ​ We own at least 359 pending patent applications and at least 92 patents have issued in the United States and foreign jurisdictions.
Nonetheless, from a practical perspective, a sponsor’s failure to follow the FDA’s recommendations for design of a clinical program may put the program at significant risk of failure. 37 Table of Contents ​ Gene Therapy Products ​ We expect that the procedures and standards applied to gene therapy products will be applied to any gene therapy product candidates we may develop.
Nonetheless, from a practical perspective, a sponsor’s failure to follow the FDA’s recommendations for design of a clinical program may put the program at significant risk of failure. ​ Gene Therapy Products ​ We expect that the procedures and standards applied to gene therapy products will be applied to any gene therapy product candidates we may develop.
Friedreich’s ataxia is an autosomal recessive disorder, meaning that a person must obtain a defective copy of the FXN gene from both parents in order to develop the condition. One healthy copy of the FXN gene, or 50% of normal frataxin protein levels, is sufficient to prevent the disease phenotype.
FA is an autosomal recessive disorder, meaning that a person must obtain a defective copy of the FXN gene from both parents in order to develop the condition. One healthy copy of the FXN gene, or 50% of normal frataxin protein levels, is sufficient to prevent the disease phenotype.
On August 15, 2024, the HHS published the results of the first Medicare drug price negotiations for ten selected drugs that treat a range of conditions, including diabetes, chronic kidney disease, and rheumatoid arthritis. The prices of these ten drugs will become effective January 1, 2026.
On August 15, 2024, the HHS published the results of the first Medicare drug price negotiations for ten selected drugs that treat a range of conditions, including diabetes, chronic kidney disease, and rheumatoid arthritis. The prices of these ten drugs became effective January 1, 2026.
Subject to certain specified exceptions, any patents and know-how that are invented or otherwise developed jointly by or on behalf of the parties during the term of the 2022 Novartis Option and License Agreement and in the course of the parties’ activities under the 2022 Novartis Option and License Agreement will follow inventorship under U.S. patent law. ​ Exclusivity ​ Subject to certain limitations and exceptions, we have agreed (a) during the Novartis Research Term, not to conduct any internal program or program on behalf of a third party that is directed to the development or commercialization of any of our capsids, or grant any third party or affiliate any right or license under our rights in such capsids, to exploit any therapeutic product containing a capsid in combination with a payload designed to have therapeutic effect on any of the Novartis Licensed Targets; and (b) not to grant any third party or affiliate any right or license under our patents to exploit any Novartis Licensed Capsid for any of the Novartis Licensed Targets. ​ Termination ​ Unless earlier terminated, the 2022 Novartis Option and License Agreement expires on the expiration of the last-to-expire royalty term with respect to all Novartis Licensed Products in all countries.
Subject to certain specified exceptions, any patents and know-how that are invented or otherwise developed jointly by or on behalf of the parties during the term of the 2022 Novartis Option and License Agreement and in the course of the parties’ activities under the 2022 Novartis Option and License Agreement will follow inventorship under U.S. patent law. ​ 16 Table of Contents Exclusivity ​ Subject to certain limitations and exceptions, we agreed (a) during the Novartis Research Term, which expired in March 2025, not to conduct any internal program or program on behalf of a third party that is directed to the development or commercialization of any of our capsids, or grant any third party or affiliate any right or license under our rights in such capsids, to exploit any therapeutic product containing a capsid in combination with a payload designed to have therapeutic effect on any of the Novartis Licensed Targets; and (b) not to grant any third party or affiliate any right or license under our patents to exploit the Novartis Licensed Capsid for the Novartis Licensed Target. ​ Termination ​ Unless earlier terminated, the 2022 Novartis Option and License Agreement expires on the expiration of the last-to-expire royalty term with respect to all Novartis Licensed Products in all countries.
Violations may also result in injunctions and/or criminal prosecution or disqualification from federal grants. ​ 36 Table of Contents Clinical Studies Outside of the United States in Support of FDA Approval ​ In connection with the clinical development of our programs, we may conduct trials at sites outside of the United States.
Violations may also result in injunctions and/or criminal prosecution or disqualification from federal grants. ​ Clinical Studies Outside of the United States in Support of FDA Approval ​ In connection with the clinical development of our programs, we may conduct trials at sites outside of the United States.
The FDA will seek to ensure the sponsor of a breakthrough therapy product candidate receives intensive guidance on an efficient development program, involvement of senior managers and experienced staff on a proactive, collaborative and cross-disciplinary review and rolling review. ​ ● Priority review .
The FDA will seek to ensure the sponsor of a breakthrough therapy product candidate receives intensive guidance on an efficient development program, involvement of senior managers and experienced staff on a proactive, collaborative and cross-disciplinary review and rolling review. ​ 41 Table of Contents ● Priority review .
This group provides an independent recommendation as to whether or not a trial may move forward at designated checkpoints based on review of available data from the study, to which only the DMC maintains access.
This group provides an independent recommendation as to whether or not a trial may move forward at designated checkpoints based on review of available data from the study, to 33 Table of Contents which only the DMC maintains access.
Under the 2019 Neurocrine Collaboration Agreement, we agreed to collaborate on the conduct of four collaboration programs, which we refer to collectively as the 2019 Neurocrine Programs: the NBIb-1817 (VY-AADC) program for the treatment of Parkinson’s disease, or the VY-AADC Program; the FA Program; and other undisclosed programs, or the 2019 Discovery Programs.
Under the 2019 Neurocrine Collaboration Agreement, we agreed to collaborate on the conduct of four collaboration programs, which we refer to collectively as the 2019 Neurocrine Programs: the NBIb-1817 (VY-AADC) program for the treatment of PD, or the VY-AADC Program; the FA Program; and other undisclosed programs, or the 2019 Discovery Programs.
The final guidance calls 41 Table of Contents for such communications to be truthful, non-misleading and scientifically sound and to include all information necessary for healthcare providers to interpret the strengths and weaknesses and validity and utility of the information about the unapproved use of the approved product.
The final guidance calls for such communications to be truthful, non-misleading and scientifically sound and to include all information necessary for healthcare providers to interpret the strengths and weaknesses and validity and utility of the information about the unapproved use of the approved product.
As a result of the Novartis Amendment, the Novartis Direct License Target is now deemed a Licensed Target under the 2022 Novartis Option and License Agreement, as such term is defined therein, and the Novartis Direct License is subject to all other terms and conditions applicable to other licenses granted to Novartis under the 2022 Novartis Option and License Agreement.
As a result of the Novartis Amendment, the Novartis Direct License Target was deemed a Licensed Target under the 2022 Novartis Option and License Agreement, as such term is defined therein, and the Novartis Direct License became subject to all other terms and conditions applicable to other licenses granted to Novartis under the 2022 Novartis Option and License Agreement.
Litigation and legislation over the ACA are likely to continue, with unpredictable and uncertain results. Pharmaceutica l Price Reform The prices of prescription pharmaceuticals have also been the subject of considerable discussion in the United States.
Litigation and legislation over the ACA are likely to continue, with unpredictable and uncertain results. 46 Table of Contents Pharmaceutica l Price Reform The prices of prescription pharmaceuticals have also been the subject of considerable discussion in the United States.
The 2023 Co-Co Trigger Event is the date on which we receive topline data from the first clinical trial for a product candidate being developed for Parkinson’s disease pursuant to the GBA1 Program or if none, then another indication under the GBA1 Program. ​ Governance ​ Our research and development activities under the 2023 Neurocrine Collaboration Agreement are to be conducted pursuant to plans agreed to by the parties, on a 2023 Neurocrine Program-by-2023 Neurocrine Program basis, 19 Table of Contents and overseen by the JSC, which is composed of an equal number of representatives from each of us and Neurocrine.
The 2023 Co-Co Trigger Event is the date on which we receive topline data from the first clinical trial for a product candidate being developed for PD pursuant to the GBA1 Program or if none, then another indication under the GBA1 Program. ​ Governance ​ Our research and development activities under the 2023 Neurocrine Collaboration Agreement are to be conducted pursuant to plans agreed to by the parties, on a 2023 Neurocrine Program-by-2023 Neurocrine Program basis, and overseen by the JSC, which is composed of an equal number of representatives from each of us and Neurocrine.
These families of patents and patent applications are pending in the United States and internationally and comprise eight granted patents and one pending application. Patents have been granted in the United States.
These families of patents and patent applications are pending in the United States and internationally and comprise seven granted patents and one pending application. Patents have been granted in the United States.
On February 10, 2025, President Trump issued an Executive Order directing the Attorney General to review the guidelines and policies governing FCPA investigations and enforcement actions. Per the Executive Order, this review will result in new DOJ FCPA guidelines intended to enhance American economic competitiveness and to safeguard national security interests.
On February 10, 2025, President Trump issued an Executive Order directing the Attorney General to review the guidelines and policies governing FCPA investigations and enforcement actions. Per the Executive Order, this review will result in new DOJ FCPA guidelines intended to enhance American economic competitiveness and to safeguard 45 Table of Contents national security interests.
Further, the legislation subjects drug manufacturers to civil monetary penalties and a 47 Table of Contents potential excise tax for failing to comply with the legislation by offering a price that is not equal to or less than the negotiated “maximum fair price” under the law or for taking price increases that exceed inflation.
Further, the legislation subjects drug manufacturers to civil monetary penalties and a potential excise tax for failing to comply with the legislation by offering a price that is not equal to or less than the negotiated “maximum fair price” under the law or for taking price increases that exceed inflation.
If a working group or subcommittee cannot agree on a matter within its purview within a specified time, such matter is to be referred sequentially to the JSC and then the executive officers of the parties.
If a working group or subcommittee cannot agree 21 Table of Contents on a matter within its purview within a specified time, such matter is to be referred sequentially to the JSC and then the executive officers of the parties.
The primary endpoints for the trial were incidence of treatment-emergent adverse events and clinically relevant changes from baseline in vital signs, electrocardiograms, or ECGs, and clinical laboratory parameters. The secondary endpoints for the trial were various serum pharmacokinetic parameters, CSF concentrations of VY7523, and incidence, level, and characterization of treatment-emergent anti-drug antibodies, or ADAs.
The primary endpoints for the trial were incidence of treatment-emergent adverse events and clinically relevant changes from baseline in vital signs, electrocardiograms and clinical laboratory parameters. The secondary endpoints for the trial were various serum pharmacokinetic parameters, cerebrospinal fluid, or CSF, concentrations of VY7523, and incidence, level, and characterization of treatment-emergent anti-drug antibodies.
The regulatory requirements applicable to biological product development, approval and marketing are subject to change, and regulations and administrative guidance often are revised or reinterpreted by the agencies in ways that may have a significant impact on our business. ​ U.S. Government Regulation ​ U.S.
The regulatory requirements applicable to biological product development, approval and marketing are subject to change, and regulations and administrative guidance often are revised or reinterpreted by the agencies in ways that may have a significant impact on our business. ​ 31 Table of Contents U.S. Government Regulation ​ U.S.
Patents that grant from these patent families are generally expected to commence expiration in 2039, 2041, and 2042, subject to possible patent term extensions. ​ Trademark Protection ​ We have registered trademarks and service marks or pending trademarks and service mark applications in the United States and a number of other countries for the in the marks VOYAGER and VOYAGER (with design elements), which we presently use or may use in connection with our pharmaceutical research and development services and our biological preparations for gene therapy for the treatment of various diseases. ​ We also own registrations in the United States and United Kingdom, for the mark TRACER for services including, among others, “research and development of platform technologies for genetic delivery of therapies and pharmaceutical via adeno-associated virus (AAV) capsids.” 32 Table of Contents ​ In connection with the ongoing development and advancement of our products and services in the U.S. and in various international jurisdictions, we routinely seek to create protection for our marks and enhance their value by pursuing trademarks and service marks where available and when appropriate.
Patents that grant from these patent families are generally expected to commence expiration in 2039, 2041, and 2042, subject to possible patent term extensions. ​ Trademark Protection ​ We own registered trademarks and service marks, as well as pending trademarks and service mark applications in the United States and a number of other countries for the in the marks VOYAGER, VOYAGER (with design elements), VOYAGER THERAPEUTICS and VOYAGER THERAPEUTICS (with design elements), which we presently use or may use in connection with our pharmaceutical research and development services and our biological preparations for gene therapy for the treatment of various diseases. ​ We also own registrations in the United States and United Kingdom for the mark TRACER for services including, among others, “research and development of platform technologies for genetic delivery of therapies and pharmaceutical via adeno-associated virus (AAV) capsids.” ​ In addition, we have pending trademark and service mark applications in the United States for the marks VOYAGER NEUROSHUTTLE and NEUROSHUTTLE, which we presently use or may use in connection with biotechnology research services and pharmaceutical products and therapeutics for the treatment of diseases and disorders, among other uses. ​ In connection with the ongoing development and advancement of our products and services in the U.S. and in various international jurisdictions, we routinely seek to create protection for our marks and enhance their value by pursuing trademarks and service marks where available and when appropriate.
As a result, submission of an IND may not result in the FDA allowing clinical trials to commence. ​ 34 Table of Contents Following commencement of a clinical trial under an IND, the FDA may also place a clinical hold or partial clinical hold on that trial.
As a result, submission of an IND may not result in the FDA allowing clinical trials to commence. ​ Following commencement of a clinical trial under an IND, the FDA may also place a clinical hold or partial clinical hold on that trial.
HD Program (2023 Novartis Collaboration Agreement) Disease Overview ​ Huntington’s disease is a fatal, inherited neurodegenerative disease that results in the progressive decline of motor and cognitive functions and a range of behavioral and psychiatric disturbances. Huntington’s disease is caused by mutations in the huntingtin, or HTT, gene.
This program is progressing in preclinical development. ​ HD Program (2023 Novartis Collaboration Agreement) Disease Overview ​ Huntington’s disease, or HD, is a fatal, inherited neurodegenerative disease that results in the progressive decline of motor and cognitive functions and a range of behavioral and psychiatric disturbances. HD is caused by mutations in the huntingtin, or HTT, gene.
Our current AAV gene therapy manufacturing process is being transferred to our contract manufacturing organizations to enable clinical current good manufacturing practice, or cGMP manufacturing. ​ We presently contract with third parties for the manufacturing of our program materials. We currently have no plans to build our own clinical or commercial scale cGMP manufacturing capabilities.
Our current AAV gene therapy manufacturing process has been transferred to our contract manufacturing organizations to enable clinical current good manufacturing practice, or cGMP manufacturing. ​ We presently contract with third parties for the manufacturing of our program materials. We currently have no plans to build our own clinical or commercial scale cGMP manufacturing capabilities.
The Novartis Licensed Targets are distinct from targets in our wholly-owned and partnered pipeline. ​ Intellectual Property ​ Under the terms of the 2022 Novartis Option and License Agreement, each party owns the entire right, title, and interest in and to all patents or know-how controlled by such party and existing as of or before the 2022 Novartis Option and License Effective Date, or invented, developed, created, generated or acquired solely by or on behalf of such party after the 2022 Novartis Option and License Effective Date.
The remaining Initial Novartis Target is distinct from targets in our wholly-owned and partnered pipeline. ​ Intellectual Property ​ Under the terms of the 2022 Novartis Option and License Agreement, each party owns the entire right, title, and interest in and to all patents or know-how controlled by such party and existing as of or before the 2022 Novartis Option and License Effective Date, or invented, developed, created, generated or acquired solely by or on behalf of such party after the 2022 Novartis Option and License Effective Date.
If a CRL is issued, the sponsor will have one year to respond to the deficiencies identified by the FDA, at which time the FDA can deem the application withdrawn or, in its discretion, grant the sponsor an additional six-month 40 Table of Contents extension to respond.
If a CRL is issued, the sponsor will have one year to respond to the deficiencies identified by the FDA, at which time the FDA can deem the application withdrawn or, in its discretion, grant the sponsor an additional six-month extension to respond.
With the passage of the 21 st Century Cures Act, or the Cures Act, in December 2016, Congress authorized the FDA to accelerate review and approval of products designated as regenerative advanced therapies.
With the passage of the 21st Century Cures Act, or the Cures Act, in December 2016, Congress authorized the FDA to accelerate review and approval of products designated as regenerative advanced therapies.
We believe that we are in material compliance with applicable environmental laws 48 Table of Contents and that continued compliance therewith will not have a material adverse effect on our business. We cannot predict, however, how changes in these laws may affect our future operations.
We believe that we are in material compliance with applicable environmental laws and that continued compliance therewith will not have a material adverse effect on our business. We cannot predict, however, how changes in these laws may affect our future operations.
Such royalty percentages, for net sales in and outside the United States, range from (a) for the GBA1 Program, 20 Table of Contents the low double-digits to twenty and the high single-digits to mid-teens, respectively, and (b) for each 2023 Discovery Program, high single-digits to mid-teens and mid-single digits to low double-digits, respectively.
Such royalty percentages, for net sales in and outside the United States, range from (a) for the GBA1 Program, the low double-digits to twenty and the high single-digits to mid-teens, respectively, and (b) for each 2023 Discovery Program, high single-digits to mid-teens and mid-single digits to low double-digits, respectively.
In these two pending patent families directed to the TRACER discovery platform, there are one granted patent and 12 pending applications, which are generally expected to commence expiration in 2039 and 2041, respectively, subject to possible patent term extensions. ​ We also own 11 pending patent families comprising 87 pending U.S. and foreign applications and one granted U.S. patent, as well as one pending provisional application directed to capsid variants identified using the TRACER discovery platform showing improved properties over their wild-type AAV counterparts.
In these two pending patent families directed to the TRACER discovery platform, there are five granted patents and 10 pending applications, which are generally expected to commence expiration in 2039 and 2041, respectively, subject to possible patent term extensions. ​ We also own 12 pending patent families comprising 82 pending U.S. and foreign applications and five granted patents, as well as two pending provisional application directed to capsid variants identified using the TRACER discovery platform showing improved properties over their wild-type AAV counterparts.
Until the expiration of the Alexion Research Term, while we are not obligated to conduct additional research activities to identify additional TRACER Capsids that may be useful for AAV gene therapies for the treatment of rare neurological diseases, we have agreed to continue to disclose to Alexion, on a rolling basis, the performance characteristics identified for all such TRACER Capsids, if and when available.
Until the expiration of the Alexion Research Term, although we were not obligated to conduct additional research activities to identify additional TRACER Capsids that may have been useful for AAV gene therapies for the treatment of rare neurological diseases, we agreed to continue to disclose to Alexion, on a rolling basis, the performance characteristics identified for all such TRACER Capsids, if and when available.
In particular, information related to the product, patient population, phase of investigation, study sites and investigators and other aspects of the clinical trial is made public as part of the registration of the clinical trial. The NIH’s Final Rule on registration and reporting requirements for clinical trials became effective in 2017.
National Institutes of Health, or NIH. In particular, information related to the product, patient population, phase of investigation, study sites and investigators and other aspects of the clinical trial is made public as part of the registration of the clinical trial. The NIH’s Final Rule on registration and reporting requirements for clinical trials became effective in 2017.
Patents that grant from this patent family are expected to commence expiration in 2041, 2042, 2043, 2044, and 2045, subject to possible patent term extensions. ​ Huntington’s Disease ​ We own four pending patent families with 10 granted patents and 21 patent applications directed to pharmaceutical compositions and methods for targeting HTT for the treatment of Huntington’s disease.
Patents that grant from this patent family are expected to commence expiration in 2041, 2042, 2043, 2044, 2045, and 2046, subject to possible patent term extensions. ​ Huntington’s Disease ​ We own two pending patent families with two granted patents directed to pharmaceutical compositions and methods for targeting HTT for the treatment of Huntington’s disease.
In this event, the BLA must be resubmitted. ​ If the submission is accepted for filing, the FDA’s goal is to review the BLA, within ten months for a standard review, or, if the BLA relates to an unmet medical need in the treatment of a serious or life-threatening condition, perform a priority review, within six months.
If the submission is accepted for filing, the FDA’s goal is to review the BLA, within ten months for a standard review, or, if the BLA relates to an unmet medical need in the treatment of a serious or life-threatening condition, perform a priority review, within six months.
We co-own at least 33 pending patent applications and at least 13 patents have issued from these co-owned families in the United States and foreign jurisdictions. At least nine patent applications have been filed and are pending in the United States and foreign jurisdictions by or on behalf of universities which have granted us exclusive license rights to the technology.
We co-own at least 20 pending patent applications and at least 23 patents have issued from these co-owned families in the United States and foreign jurisdictions. At least six patent applications have been filed and are pending in the United States and foreign jurisdictions by or on behalf of universities which have granted us exclusive license rights to the technology.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeIf we or others later identify undesirable side effects caused by our product candidate, several potentially significant negative consequences could result, including: ● regulatory authorities may suspend or withdraw approvals of such product candidate; ​ ● regulatory authorities may require additional warnings on the label; ​ ● we may be required to change the way a product candidate is administered or conduct additional clinical trials; ​ ● we could be sued and held liable for harm caused to patients; and ​ ● our reputation may suffer. ​ Any of these events could prevent us from achieving or maintaining market acceptance of our product candidates and could significantly harm our business, prospects, financial condition and results of operations.
Biggest changeIf we or others later identify undesirable side effects caused by our product candidate, several potentially significant negative consequences could result, including: ● regulatory authorities may suspend or withdraw approvals of such product candidate; ​ 65 Table of Contents ● the FDA or regulatory authorities outside the U.S. may impose a clinical hold or partial clinical hold, which could cause us or our collaborators to have to stop, delay or restrict further development; ​ ● we or our collaborators may, even without a clinical hold, decide to interrupt, delay or halt existing non-clinical studies and clinical trials or stop development; ​ ● we may have difficulty enrolling patients in our clinical trials and completing such trials on the timelines we expect or at all, or we may have to conduct additional non-clinical studies or clinical trials as part of a development program; ​ ● regulatory authorities may require additional warnings on the label; ​ ● we or our collaborators may be required to change the way a product candidate is administered or conduct additional clinical trials; ​ ● we or our collaborators may not be able ultimately to demonstrate, to the satisfaction of regulatory authorities, that our product candidates are safe and that the benefits outweigh the safety risks, and the applicable regulatory authorities may not approve the product candidate; ​ ● we or our collaborators could be subject to regulatory investigations or government enforcement actions, or be sued and held liable for harm caused to individuals exposed to or taking our product candidate; and ​ ● our reputation may suffer. ​ Any of these events could prevent us from achieving or maintaining market acceptance of our product candidates and could significantly harm our business, prospects, financial condition and results of operations.
A clinical trial failure can occur at any stage of testing. Similarly, there may be delays or difficulties in our initiation of future clinical trials. Similarly, there may be delays or difficulties in our initiation of future clinical trials.
A clinical trial failure can occur at any stage of testing. Similarly, there may be delays or difficulties in our initiation of future clinical trials.
Under the PREA, an NDA, BLA or supplement to an NDA or BLA for certain drugs and biological products must contain data to assess the safety and effectiveness of the drug or biological product in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective, unless the sponsor receives a deferral or waiver from the FDA.
Under the PREA, an NDA, BLA or supplement to an NDA or a BLA for certain drugs and biological products must contain data to assess the safety and effectiveness of the drug or biological product in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective, unless the sponsor receives a deferral or waiver from the FDA.
In the United States, third-party payors, including government payors such as the Medicare and Medicaid programs, play an important role in determining the extent to which new drugs and biologics will be covered and reimbursed. The Medicare and Medicaid programs increasingly are used as models for how private payors and government payors develop their coverage and reimbursement policies.
In the United States, third-party payors, including government payors such as the Medicare and Medicaid programs, play an important role in determining the extent to which new drugs and biologics will be covered and reimbursed. Medicare and Medicaid programs increasingly are used as models for how private payors and government payors develop their coverage and reimbursement policies.
Other events that may prevent successful or timely completion of clinical development include: ● delays in reaching a consensus with regulatory authorities or collaborators on trial design, implementation, management , or other aspects of the clinical trial; ● delays in reaching agreement on acceptable terms with prospective CROs and clinical trial sites; ● delays in opening clinical trial sites or obtaining required IRB or independent ethics committee approval at each clinical trial site; ● as a result of a serious adverse event, or SAE, or after an inspection of our clinical trial operations or trial sites or the decision by us or our collaborators, or the requirement of regulators or IRBs to suspend or 61 Table of Contents terminate clinical research for various reasons, including noncompliance with regulatory requirements or a finding that the participants are being exposed to unacceptable health risks; ● failure by us, our collaboration partners, any CROs we engage, or any other third parties to adhere to clinical trial protocols or regulatory requirements; ● failure by us, our collaboration partners, any CROs we engage, or any other third parties to perform in accordance with the FDA’s good clinical practices, or GCPs, or applicable regulatory guidelines in the European Union; ● failure by physicians to adhere to delivery protocols leading to variable results; ● delays in the testing, validation, manufacturing and delivery of our product candidates to the clinical sites, including delays by third parties with whom we have contracted to perform certain of those functions; ● insufficient or inadequate supply or quality of our product candidates or other materials necessary to conduct clinical trials of our product candidates; ● 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 at a rate higher than we anticipate; ● selection of clinical endpoints that require prolonged periods of clinical observation or analysis of the resulting data; ● receipt of negative or inconclusive clinical trial results; ● occurrence of SAEs associated with the product candidate that are viewed to outweigh its potential benefits; ● occurrence of SAEs in trials of the same class of agents conducted by other sponsors; ● changes in regulatory requirements and guidance that require amending or submitting new clinical protocols; or ● the cost of clinical trials of our product candidates may be greater than we anticipate.
Other events that may prevent successful or timely completion of clinical development include: ● delays in reaching a consensus with regulatory authorities or collaborators on trial design, implementation, management , or other aspects of the clinical trial; ● delays in reaching agreement on acceptable terms with prospective CROs and clinical trial sites; ● delays in opening clinical trial sites or obtaining required IRB or independent ethics committee approval at each clinical trial site; ● as a result of a serious adverse event, or SAE, or after an inspection of our clinical trial operations or trial sites or the decision by us or our collaborators, or the requirement of regulators or IRBs to suspend or terminate clinical research for various reasons, including noncompliance with regulatory requirements or a finding that the participants are being exposed to unacceptable health risks; ● failure by us, our collaboration partners, any CROs we engage, or any other third parties to adhere to clinical trial protocols or regulatory requirements; ● failure by us, our collaboration partners, any CROs we engage, or any other third parties to perform in accordance with the FDA’s good clinical practices, or GCPs, or applicable regulatory guidelines in the European Union; ● failure by physicians to adhere to delivery protocols leading to variable results; 63 Table of Contents ● delays in the testing, validation, manufacturing and delivery of our product candidates to the clinical sites, including delays by third parties with whom we have contracted to perform certain of those functions; ● insufficient or inadequate supply or quality of our product candidates or other materials necessary to conduct clinical trials of our product candidates; ● 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 at a rate higher than we anticipate; ● selection of clinical endpoints that require prolonged periods of clinical observation or analysis of the resulting data; ● receipt of negative or inconclusive clinical trial results; ● occurrence of SAEs associated with the product candidate that are viewed to outweigh its potential benefits; ● occurrence of SAEs in trials of the same class of agents conducted by other sponsors; ● changes in regulatory requirements and guidance that require amending or submitting new clinical protocols; or ● the cost of clinical trials of our product candidates may be greater than we anticipate.
Our ability to generate future revenues from product sales depends heavily on our and our collaborators’ and licensors’ success in: ● completing preclinical and clinical development of our product candidates or product candidates incorporating our licensed capsids or other technologies and identifying new product candidates; ● seeking and obtaining regulatory and marketing approvals for product candidates for which we or they complete clinical development; ● launching and commercializing product candidates for which we or they obtain regulatory and marketing approval by establishing a sales, marketing and distribution infrastructure or, alternatively, collaborating with a commercialization partner; ● obtaining and maintaining adequate coverage and reimbursement by government and third-party payors for our product candidates if and when approved; ● maintaining and enhancing a sustainable, scalable, reproducible and transferable manufacturing process for our vectors and product candidates; ● establishing and maintaining supply and manufacturing relationships with third parties that have the financial, operating and technical capabilities to provide adequate products and services, in both amount and quality, to support clinical development and the market demand for our or their product candidates, if and when approved; ● obtaining an adequate level of market acceptance of our or their product candidates as viable treatment options; ● addressing any competing technological and market developments; ● implementing additional internal systems and infrastructure, as needed; ● negotiating favorable terms in any collaboration, option, licensing, or other arrangements into which we may enter and performing our obligations in such collaborations; 52 Table of Contents ● obtaining, maintaining, protecting, enforcing and expanding our portfolio of intellectual property rights, including patents, trade secrets and know-how; ● avoiding and defending against third-party claims of interference or infringement; and ● attracting, hiring and ret aining qualified personnel.
Our ability to generate future revenues from product sales depends heavily on our and our collaborators’ and licensors’ success in: ● completing preclinical and clinical development of our product candidates or product candidates incorporating our licensed capsids or other technologies and identifying new product candidates; ● seeking and obtaining regulatory and marketing approvals for product candidates for which we or they complete clinical development; ● launching and commercializing product candidates for which we or they obtain regulatory and marketing approval by establishing a sales, marketing and distribution infrastructure or, alternatively, collaborating with a commercialization partner; ● obtaining and maintaining adequate coverage and reimbursement by government and third-party payors for our product candidates if and when approved; ● maintaining and enhancing a sustainable, scalable, reproducible and transferable manufacturing process for our vectors and product candidates; 53 Table of Contents ● establishing and maintaining supply and manufacturing relationships with third parties that have the financial, operating and technical capabilities to provide adequate products and services, in both amount and quality, to support clinical development and the market demand for our or their product candidates, if and when approved; ● obtaining an adequate level of market acceptance of our or their product candidates as viable treatment options; ● addressing any competing technological and market developments; ● implementing additional internal systems and infrastructure, as needed; ● negotiating favorable terms in any collaboration, option, licensing, or other arrangements into which we may enter and performing our obligations in such collaborations; ● obtaining, maintaining, protecting, enforcing and expanding our portfolio of intellectual property rights, including patents, trade secrets and know-how; ● avoiding and defending against third-party claims of interference or infringement; and ● attracting, hiring and ret aining qualified personnel.
For example: ● others may be able to make antibody, gene therapy, or non-viral therapeutic products that are similar to our product candidates but that are not covered by the claims of the patents that we own, license or may access in the future; ● we, or our license partners or current or future collaborators, might not have been the first to make the inventions covered by the issued patent or pending patent application that we license or may own in the future; ● we, or our license partners or current or future collaborators, might not have been the first to file patent applications covering certain of our or their inventions; ● others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our owned or licensed intellectual property rights; 107 Table of Contents ● it is possible that our pending patent applications or those that we may own in the future will not lead to issued patents , or result in issued patents with a scope of protection that could be designed around or circumvented by our competitors ; ● issued patents that we hold rights to may be held invalid or unenforceable, including as a result of legal challenges by our competitors; ● our competitors 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 may not develop additional proprietary technologies that are patentable; ● the patents of others may have an adverse effect on our business; and ● we may choose not to file a patent for certain inventions, trade secrets or know-how, and a third party may subsequently file a patent covering such intellectual property.
For example: ● others may be able to make antibody, gene therapy, or non-viral therapeutic products that are similar to our product candidates but that are not covered by the claims of the patents that we own, license or may access in the future; ● we, or our license partners or current or future collaborators, might not have been the first to make the inventions covered by the issued patent or pending patent application that we license or may own in the future; ● we, or our license partners or current or future collaborators, might not have been the first to file patent applications covering certain of our or their inventions; ● others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our owned or licensed intellectual property rights; ● it is possible that our pending patent applications or those that we may own in the future will not lead to issued patents , or result in issued patents with a scope of protection that could be designed around or circumvented by our competitors ; ● issued patents that we hold rights to may be held invalid or unenforceable, including as a result of legal challenges by our competitors; 113 Table of Contents ● our competitors 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 may not develop additional proprietary technologies that are patentable; ● the patents of others may have an adverse effect on our business; and ● we may choose not to file a patent for certain inventions, trade secrets or know-how, and a third party may subsequently file a patent covering such intellectual property.
We expect that we will be subject to additional risks in commercializing our product candidates outside the United States, including: ● different regulatory requirements for approval of drugs and biologics in foreign countries; ● reduced or loss of protection under our intellectual property rights; ● unexpected changes in tariffs, trade barriers and regulatory requirements; ● economic weakness, including inflation, or political instability in particular foreign economies and markets; ● compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; ● foreign currency fluctuations, which could result in increased operating expenses and reduced revenues, and other obligations incident to doing business in another country; ● workforce uncertainty in countries where labor unrest is more common than in the United States; ● shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; 97 Table of Contents ● business interruptions resulting from geopolitical actions, including war and terrorism, from natural disasters including earthquakes, typhoons, floods and fires, or from economic, social, or political instability; and ● greater difficulty with enforcing our contracts in jurisdictions outside of the United States.
We expect that we will be subject to additional risks in commercializing our product candidates outside the United States, including: ● different regulatory requirements for approval of drugs and biologics in foreign countries; ● reduced or loss of protection under our intellectual property rights; ● unexpected changes in tariffs, trade barriers and regulatory requirements; ● economic weakness, including inflation, or political instability in particular foreign economies and markets; ● compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; ● foreign currency fluctuations, which could result in increased operating expenses and reduced revenues, and other obligations incident to doing business in another country; ● workforce uncertainty in countries where labor unrest is more common than in the United States; ● shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; 101 Table of Contents ● business interruptions resulting from geopolitical actions, including war and terrorism, from natural disasters including earthquakes, typhoons, floods and fires, or from economic, social, or political instability; and ● greater difficulty with enforcing our contracts in jurisdictions outside of the United States.
Restrictions under applicable federal and state healthcare laws and regulations include the following: ● the federal Anti-Kickback Statute prohibits, among other things, persons from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order or recommendation or arranging of, any good or service, for which payment may be made under a federal healthcare program such as Medicare and Medicaid; ● the federal False Claims Act imposes criminal and civil penalties, including through civil whistleblower or qui tam actions, against individuals or entities for, among other things, knowingly presenting, or causing to be presented, false or fraudulent claims for payment by a federal healthcare program or making a false statement or record material to payment of a false claim or avoiding, decreasing or concealing an obligation to pay money to the federal government, with potential liability including mandatory treble damages and significant per-claim penalties; ● the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters; ● HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, and its implementing regulations, also imposes obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information; ● the federal Physician Payments Sunshine Act requires applicable manufacturers of covered products to report payments and other transfers of value to physicians, other healthcare providers, and teaching hospitals; and ● analogous state and foreign laws and regulations, such as state anti-kickback, false claims, and transparency laws, may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers.
Restrictions under applicable federal and state healthcare laws and regulations include the following: ● the federal Anti-Kickback Statute prohibits, among other things, persons from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order or recommendation or arranging of, any good or service, for which payment may be made under a federal healthcare program such as Medicare and Medicaid; 91 Table of Contents ● the federal False Claims Act imposes criminal and civil penalties, including through civil whistleblower or qui tam actions, against individuals or entities for, among other things, knowingly presenting, or causing to be presented, false or fraudulent claims for payment by a federal healthcare program or making a false statement or record material to payment of a false claim or avoiding, decreasing or concealing an obligation to pay money to the federal government, with potential liability including mandatory treble damages and significant per-claim penalties; ● the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters; ● HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, and its implementing regulations, also imposes obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information; ● the federal Physician Payments Sunshine Act requires applicable manufacturers of covered products to report payments and other transfers of value to physicians, other healthcare providers, and teaching hospitals; and ● analogous state and foreign laws and regulations, such as state anti-kickback, false claims, and transparency laws, may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers.
Because we currently rely on certain third parties to manufacture all or part of our product candidates and to perform quality testing, and because we collaborate with various organizations and academic institutions for the advancement of our proprietary antibody program and gene therapy, vectorized antibody, and non-viral therapeutic platforms and programs, we must, at times, share our proprietary technology and confidential information, including trade secrets, with them.
Because we currently rely on certain third parties to manufacture all or part of our product candidates and to perform quality testing, and because we collaborate with various organizations and academic institutions for the advancement of our proprietary antibody program and gene therapy and non-viral therapeutic platforms and programs, we must, at times, share our proprietary technology and confidential information, including trade secrets, with them.
In the event we exercise our 2023 Co-Co Option, the parties have also agreed that Neurocrine is entitled to receive (in addition to its 50% share of profits) 50% of our share of profits until our obligation to repay 50% of all development costs incurred by Neurocrine in connection with the GBA1 Program prior to such exercise have been paid off out of our 50% share of profits.
In the event we exercise our 2023 Co-Co Option, the parties have also agreed that Neurocrine is entitled to receive (in addition to its 50% share of profits) 50% of our share of profits until our obligation to repay 50% of all development costs incurred by Neurocrine in connection with the GBA1 Program prior to such exercise have been paid off.
If we fail to comply with applicable regulatory requirements following approval of any of our product candidates, a regulatory authority may: ● issue a warning letter asserting that we are in violation of the law; ● seek an injunction or impose administrative, civil or criminal penalties or monetary fines; ● suspend or withdraw regulatory approval; 70 Table of Contents ● suspend any ongoing clinical trials; ● refuse to approve a pending BLA or comparable foreign marketing application, or any supplements thereto, submitted by us or our collaboration partners; ● restrict the marketing or manufacturing of the product; ● seize or detain the product or otherwise require the withdrawal of the product from the market; ● refuse to permit the import or export of products; 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 of our product candidates, a regulatory authority may: ● issue a warning letter asserting that we are in violation of the law; ● seek an injunction or impose administrative, civil or criminal penalties or monetary fines; ● suspend or withdraw regulatory approval; 72 Table of Contents ● suspend any ongoing clinical trials; ● refuse to approve a pending BLA or comparable foreign marketing application, or any supplements thereto, submitted by us or our collaboration partners; ● restrict the marketing or manufacturing of the product; ● seize or detain the product or otherwise require the withdrawal of the product from the market; ● refuse to permit the import or export of products; or ● refuse to allow us to enter into supply contracts, including government contracts.
In connection with our VY-HTT01 Program for the treatment of Huntington’s disease, for example, we were unable to successfully predict what the FDA would require and were unable to obtain a second pre-IND meeting with the FDA to discuss the product candidate’s regulatory pathway with the FDA.
In connection with our earlier VY-HTT01 Program for the treatment of Huntington’s disease, for example, we were unable to successfully predict what the FDA would require and were unable to obtain a second pre-IND meeting with the FDA to discuss the product candidate’s regulatory pathway with the FDA.
The success of our business depends upon our ability to identify, develop and commercialize product candidates generated through our proprietary antibody program and our gene therapy, vectorized antibody, and non-viral therapeutics platforms and programs. Research programs to identify new product candidates require substantial technical, financial and human resources.
The success of our business depends upon our ability to identify, develop and commercialize product candidates generated through our proprietary antibody program and our gene therapy and non-viral therapeutics platforms and programs. Research programs to identify new product candidates require substantial technical, financial and human resources.
Even if the FDA accepted such data, it could require us to modify our planned clinical trials to receive clearance to initiate such trials in the United States or to continue such trials once initiated. ​ Other risks inherent in conducting international clinical trials or using international trial sites include: ● foreign regulatory requirements, differences in healthcare services, and differences in cultural customs that could restrict or limit our ability to conduct our clinical trials; ● the administrative burden of complying with a variety of foreign laws, medical standards and regulatory requirements, including the regulation of pharmaceutical and biotechnology products and treatment; ● the failure of enrolled patients to adhere to clinical protocols or inadequate collection and assessment of clinical data as a result of differences in healthcare services or cultural customs; 58 Table of Contents ● foreign exchange fluctuations; ● diminished or loss of protection of intellectual property in the relevant jurisdiction; and ● political, economic, environmental, and health risks relevant to specific foreign countries, including risks related to natural disasters or disease outbreaks.
Even if the FDA accepted such data, it could require us to modify our planned clinical trials to receive clearance to initiate such trials in the United States or to continue such trials once initiated. ​ Other risks inherent in conducting international clinical trials or using international trial sites include: ● foreign regulatory requirements, differences in healthcare services, and differences in cultural customs that could restrict or limit our ability to conduct our clinical trials; ● the administrative burden of complying with a variety of foreign laws, medical standards and regulatory requirements, including the regulation of pharmaceutical and biotechnology products and treatment; ● the failure of enrolled patients to adhere to clinical protocols or inadequate collection and assessment of clinical data as a result of differences in healthcare services or cultural customs; ● foreign exchange fluctuations; ● diminished or loss of protection of intellectual property in the relevant jurisdiction; and ● political, economic, environmental, and health risks relevant to specific foreign countries, including risks related to natural disasters or disease outbreaks.
If we are unable to establish sales, medical affairs and marketing capabilities or enter into agreements with third parties to market and sell our product candidates, we may be unable to generate any product revenue.
If we are unable to establish sales, medical affairs, market access and marketing capabilities or enter into agreements with third parties to market and sell our product candidates, we may be unable to generate any product revenue.
A failure to obtain accelerated approval, review or approval for our product candidate would result in a longer time period to commercialization of such product candidate, could increase the cost of development of such product candidate and could harm our competitive position in the marketplace. 68 Table of Contents Even if we complete the necessary preclinical studies and clinical trials, the marketing approval process is expensive, time-consuming and uncertain and may prevent us from obtaining approvals for the commercialization of some or all of our product candidates.
A failure to obtain accelerated approval, review or approval for our product candidate would result in a longer time period to commercialization of such product candidate, could increase the cost of development of such product candidate and could harm our competitive position in the marketplace. 70 Table of Contents Even if we complete the necessary preclinical studies and clinical trials, the marketing approval process is expensive, time-consuming and uncertain and may prevent us from obtaining approvals for the commercialization of some or all of our product candidates.
To the extent that any disruption or security breach were to result in a loss of, or damage to, our data or applications, or inappropriate disclosure of confidential or proprietary information, or a loss of cash in response to ransom threats, we could incur liability, our competitive and financial position and the market perception of the effectiveness of our security measures could be harmed, our credibility could be damaged, and the further development and commercialization of our product candidates could be delayed. 114 Table of Contents ITEM 1B.
To the extent that any disruption or security breach were to result in a loss of, or damage to, our data or applications, or inappropriate disclosure of confidential or proprietary information, or a loss of cash in response to ransom threats, we could incur liability, our competitive and financial position and the market perception of the effectiveness of our security measures could be harmed, our credibility could be damaged, and the further development and commercialization of our product candidates could be delayed. 119 Table of Contents ITEM 1B.
Our amended and restated certificate of incorporation provides that, unless we consent in writing to an alternative forum, the Court of Chancery of the State of Delaware will be the sole and exclusive forum for (a) any derivative action or proceeding brought on our behalf, (b) any action asserting a claim of breach of a fiduciary duty owed by any of our directors, officers and employees to us or our stockholders, (c) any action asserting a claim arising pursuant to any provision of the Delaware General Corporation Law, our certificate of incorporation or our bylaws or (d) any action asserting a claim that is governed by the internal affairs doctrine, in each case subject to the Court of 112 Table of Contents Chancery having personal jurisdiction over the indispensable parties named as defendants therein.
Our amended and restated certificate of incorporation provides that, unless we consent in writing to an alternative forum, the Court of Chancery of the State of Delaware will be the sole and exclusive forum for (a) any derivative action or proceeding brought on our behalf, (b) any action asserting a claim of breach of a fiduciary duty owed by any of our directors, officers and employees to us or our stockholders, (c) any action asserting a claim arising pursuant to any provision of the Delaware General Corporation Law, our certificate of incorporation or our bylaws or (d) 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.
If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, 71 Table of Contents we may lose any marketing approval that we may have obtained and we may not achieve or sustain profitability, which would harm our business, financial condition, results of operations and prospects.
If we are slow or unable to adapt to changes in existing 73 Table of Contents requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may lose any marketing approval that we may have obtained and we may not achieve or sustain profitability, which would harm our business, financial condition, results of operations and prospects.
Regulatory requirements governing biological, gene therapy , and other non-viral therapeutic products have changed frequently and may continue to change in the future.
Regulatory requirements governing gene therapy , non-viral therapeutic , and other products have changed frequently and may continue to change in the future.
The 2023 Co-Co Trigger Event is the date on which we receive topline data from the first Phase 1 clinical trial in Parkinson’s disease for a product candidate being developed pursuant to the GBA1 Program. ​ In the future, we may seek to enter into collaborations regarding other of our product candidates with other entities to utilize their established marketing and distribution capabilities, but we may be unable to enter into such agreements on favorable terms, if at all.
The 2023 Co-Co Trigger Event is the date on which we receive topline data from the first Phase 1 clinical trial in PD for a product candidate being developed pursuant to the GBA1 Program. ​ In the future, we may seek to enter into collaborations regarding other of our product candidates with other entities to utilize their established marketing and distribution capabilities, but we may be unable to enter into such agreements on favorable terms, if at all.
We compete with many companies that currently have extensive, experienced and well-funded medical affairs, marketing and sales operations to recruit, hire, train and retain marketing and sales personnel. We also face competition in our search for third parties to assist us with the sales and marketing efforts of our product candidates.
We compete with many companies that currently have extensive, experienced and well-funded medical affairs, market access, marketing and sales operations to recruit, hire, train and retain personnel. We also face competition in our search for third parties to assist us with the sales and marketing efforts of our product candidates.
While we have not experienced 113 Table of Contents any such material system failure, accident or security breach to date, if such an event were to occur and cause interruptions in our operations or the operations of those third parties with which we contract, it could result in a material disruption of our development programs and our business operations, whether due to a loss of our trade secrets or other proprietary information or other similar disruptions, and could require a substantial expenditure of resources to remedy.
While we have not experienced any such material system failure, accident or security breach to date, if such an event were to occur and cause interruptions in our operations or the operations of those third parties with which we contract, it could result in a material disruption of our development programs and our business operations, whether due to a loss of our trade secrets or other proprietary information or other similar disruptions, and could require a substantial expenditure of resources to remedy.
If we or our manufacturers were to fail to comply with the FDA, EMA, or other regulatory authority, it could result in sanctions being imposed on us, including clinical holds, 80 Table of Contents fines, injunctions, civil penalties, delays, suspension or withdrawal of approvals, license revocation, seizures or recalls of product candidates or products, operating restrictions and criminal prosecutions, any of which could significantly and adversely affect supplies of our product candidates.
If we or our manufacturers were to fail to comply with the FDA, EMA, or other regulatory authority, it could result in sanctions being imposed on us, including clinical holds, fines, injunctions, civil penalties, delays, suspension or withdrawal of approvals, license revocation, seizures or recalls of product candidates or products, operating restrictions and criminal prosecutions, any of which could significantly and adversely affect supplies of our product candidates.
If any of our product candidates is approved but fails to achieve market acceptance among physicians, patients, or third-party payors, we will not be able to generate significant revenues from such product, which could harm our business, financial condition, results of operations and prospects. ​ The insurance coverage and reimbursement status of newly-approved products is uncertain.
If any of our product candidates is approved but fails to achieve market acceptance among physicians, patients, or third-party payors, we will not be able to generate significant revenues from such product, which could harm our business, financial condition, results of operations and prospects. ​ 97 Table of Contents The insurance coverage and reimbursement status of newly-approved products is uncertain.
We presently manufacture our AAV product candidates using a mammalian cell system. We are aware of third parties which also use this system in the manufacture of their products and who hold intellectual property on their AAV manufacturing systems.
We presently manufacture our AAV product candidates using a mammalian cell system. We are aware of third parties that also use this system in the manufacture of their products and who hold intellectual property on their AAV manufacturing systems.
We expect to experience pricing pressures in connection with the sale of any of our product candidates due to the trend toward managed healthcare, the increasing influence of health maintenance organizations and additional legislative changes. The downward pressure on 95 Table of Contents healthcare costs in general, particularly prescription drugs and surgical procedures and other treatments, has become intense.
We expect to experience pricing pressures in connection with the sale of any of our product candidates due to the trend toward managed healthcare, the increasing influence of health maintenance organizations and additional legislative changes. The downward pressure on healthcare costs in general, particularly prescription drugs and surgical procedures and other treatments, has become intense.
Even if resolved in our favor, litigation or other legal proceedings relating to intellectual property claims may cause us to incur significant expenses and could distract our technical and management personnel from their normal responsibilities. In addition, there could be 104 Table of Contents public announcements of the results of hearings, motions or other interim proceedings or developments.
Even if resolved in our favor, litigation or other legal proceedings relating to intellectual property claims may cause us to incur significant expenses and could distract our technical and management personnel from their normal responsibilities. In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments.
A competitor’s discovery of our trade secrets and/or know-how would impair our competitive position and have an adverse impact on our business, financial condition, results of operations and prospects. Risks Related to Ownership of Our Common Stock Sales of a substantial number of shares of our common stock in the public market could cause our stock price to fall.
A competitor’s discovery of our trade secrets and/or know-how would impair our competitive position and have an adverse impact on our business, financial condition, results of operations and prospects. 114 Table of Contents Risks Related to Ownership of Our Common Stock Sales of a substantial number of shares of our common stock in the public market could cause our stock price to fall.
In addition, if we make manufacturing or formulation changes to our product candidates, such as our previous transition to an HEK 293-based production system from a baculovirus/Sf9 AAV production system or as a result of unanticipated clinical trial results, we may need to conduct additional studies to bridge our modified product candidates to earlier versions.
In addition, if we make manufacturing or formulation changes to our product candidates, such as we did in connection with our previous transition to an HEK 293-based production system from a baculovirus/Sf9 AAV production system or as a result of unanticipated clinical trial results, we may need to conduct additional studies to bridge our modified product candidates to earlier versions.
Without an internal team or the support of a third party to perform marketing and sales functions, we may be unable to compete successfully against these more established companies. ​ 93 Table of Contents Our efforts to educate the medical community and third-party payors on the benefits of our product candidates may require significant resources and may never be successful.
Without an internal team or the support of a third party to perform marketing and sales functions, we may be unable to compete successfully against these more established companies. ​ Our efforts to educate the medical community and third-party payors on the benefits of our product candidates may require significant resources and may never be successful.
Our ability to develop a product candidate for any of our lead gene therapy or other biological therapy programs may take longer than we anticipate, or may not happen at all, and could require funding at a level higher than we expect. In addition, our product candidates, if approved, may not achieve commercial success.
Our ability to develop a product candidate for any of our lead gene therapy or other biological therapy programs may take longer than we anticipate, or may not happen at all, and 55 Table of Contents could require funding at a level higher than we expect. In addition, our product candidates, if approved, may not achieve commercial success.
As a result, increasingly high barriers are being erected to the entry of new products such as ours. The commercial success of any of our product candidates will depend upon its degree of market acceptance by physicians, patients, third-party payors and others in the medical community.
As a result, increasingly high barriers are being erected to the entry of new products such as ours. 99 Table of Contents The commercial success of any of our product candidates will depend upon its degree of market acceptance by physicians, patients, third-party payors and others in the medical community.
Nonetheless, the approval of a biosimilar to our product candidates would have a material adverse impact on our business due to increased competition and pricing pressure. 75 Table of Contents Risks Related to Third Parties To date, substantially all of our revenue has been derived from our ongoing collaborations and licensing agreements with Neurocrine, Novartis, and Alexion, and from our prior collaborations with Sanofi Genzyme, AbbVie Biotechnology Ltd and AbbVie Ireland Unlimited Company, or AbbVie.
Nonetheless, the approval of a biosimilar to our product candidates would have a material adverse impact on our business due to increased competition and pricing pressure. 78 Table of Contents Risks Related to Third Parties To date, substantially all of our revenue has been derived from our ongoing collaborations and licensing agreements with Neurocrine, Novartis, and Alexion, and from our prior collaborations with Sanofi Genzyme Corporation, AbbVie Biotechnology Ltd and AbbVie Ireland Unlimited Company.
Termination may also result in unfavorable terms associated with such termination or may result in obligations on our part to license or grant back intellectual property rights to prior licensors. 99 Table of Contents Furthermore, the research resulting in certain of our licensed patent rights and technology was funded by the U.S. government.
Termination may also result in unfavorable terms associated with such termination or may result in obligations on our part to license or grant back intellectual property rights to prior licensors. Furthermore, the research resulting in certain of our licensed patent rights and technology was funded by the U.S. government.
Various extensions may be available, but the life of a patent, and the protection it affords, is limited. Even if patents covering our product candidates are obtained, once the patent life has expired, we may be open to competition from competitive products, including generics or biosimilars.
Various extensions may be available, but the life of a patent, and the protection it affords, is limited. Even if patents covering our product candidates 112 Table of Contents are obtained, once the patent life has expired, we may be open to competition from competitive products, including generics or biosimilars.
In the United States, for example, the application user fee to obtain FDA review of a marketing application is more than $4.3 million and may be higher in the future.
In the United States, for example, the application user fee to obtain FDA review of a marketing application is more than $4.6 million and may be higher in the future.
Such an occurrence may cause our business, financial condition, results of operations and prospects to be harmed. 81 Table of Contents Additionally, if supply from any third-party manufacturers is delayed or interrupted, there could be a significant disruption in the supply of our clinical or commercial material.
Such an occurrence may cause our business, financial condition, results of operations and prospects to be harmed. Additionally, if supply from any third-party manufacturers is delayed or interrupted, there could be a significant disruption in the supply of our clinical or commercial material.
The U.S. government can exercise its march-in rights if it determines that action is necessary because we fail to achieve practical application of the government-funded technology, because action is necessary to alleviate health or safety needs, to meet requirements of federal regulations or to give preference to U.S. industry.
The U.S. government can exercise its march-in rights if it determines that action is 105 Table of Contents necessary because we fail to achieve practical application of the government-funded technology, because action is necessary to alleviate health or safety needs, to meet requirements of federal regulations or to give preference to U.S. industry.
For example, an April 2024 report from the Office of the United States Trade Representative identified a number of countries, including India and China, where challenges to the procurement and enforcement of patent rights have been reported. Several countries, 102 Table of Contents including India and China, have been listed in the report every year since 1989.
For example, an April 2024 report from the Office of the United States Trade Representative identified a number of countries, including India and China, where challenges to the procurement and enforcement of patent rights have been reported. Several countries, including India and China, have been listed in the report every year since 1989.
In addition, our trade secrets may otherwise become known or be independently discovered by competitors. 103 Table of Contents Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights, the outcome of which would be uncertain and could harm our business.
In addition, our trade secrets may otherwise become known or be independently discovered by competitors. Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights, the outcome of which would be uncertain and could harm our business.
Some of our clinical trials were conducted with small patient populations and were not blinded or placebo-controlled, making it difficult to predict whether the favorable results that we observed in such trials will be sustained or 57 Table of Contents repeated in larger and more advanced clinical trials.
Some of our clinical trials were conducted with small patient populations and were not blinded or placebo-controlled, making it difficult to predict whether the favorable results that we observed in such trials will be sustained or repeated in larger and more advanced clinical trials.
Even if we are able to demonstrate that any future SAEs are not product-related, and regulatory authorities do not order us to cease further development of our product candidates, such occurrences could affect patient recruitment or the ability of enrolled patients to complete the trial.
Even if we are able to demonstrate that any future side effects are not product-related, and regulatory authorities do not order us to cease further development of our product candidates, such occurrences could affect patient recruitment or the ability of enrolled patients to complete the trial.
Any of these occurrences may harm our ability to develop other product candidates and may harm our business, financial condition and prospects significantly. 63 Table of Contents Additionally, if any of our product candidates receives marketing approval, the FDA could require us to adopt a REMS to ensure that the benefits outweigh its risks.
Any of these occurrences may harm our ability to develop other product candidates and may harm our business, financial condition and prospects significantly. Additionally, if any of our product candidates receives marketing approval, the FDA could require us to adopt a REMS to ensure that the benefits outweigh its risks.
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 other jurisdictions. The provision of benefits or advantages to physicians is governed by anti-bribery laws of European Union Member States and the UK Bribery Act 2010.
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 other jurisdictions. The provision 92 Table of Contents of benefits or advantages to physicians is governed by anti-bribery laws of European Union Member States and the UK Bribery Act 2010.
Additionally, there may be significant delays in obtaining coverage and reimbursement for newly approved drugs and biologics, and coverage may be more limited than the purposes for which the drug is approved by the FDA or comparable foreign regulatory authorities. 94 Table of Contents There is significant uncertainty related to third-party coverage and reimbursement of newly approved products.
Additionally, there may be significant delays in obtaining coverage and reimbursement for newly approved drugs and biologics, and coverage may be more limited than the purposes for which the drug is approved by the FDA or comparable foreign regulatory authorities. There is significant uncertainty related to third-party coverage and reimbursement of newly approved products.
Any ruling of a similar scope in other countries could affect the scope of our 106 Table of Contents intellectual property rights. The ambiguities and changing law in all countries as to patenting genetic material may directly affect our ability to secure and/or maintain patent protection for our gene therapy products.
Any ruling of a similar scope in other countries could affect the scope of our intellectual property rights. The ambiguities and changing law in all countries as to patenting genetic material may directly affect our ability to secure and/or maintain patent protection for our gene therapy products.
Given that our proprietary position is based, in part, on our know-how and trade secrets, a competitor’s discovery of our 108 Table of Contents proprietary technology and confidential information or other unauthorized use or disclosure would impair our competitive position and may harm our business, financial condition, results of operations and prospects.
Given that our proprietary position is based, in part, on our know-how and 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 harm our business, financial condition, results of operations and prospects.
We are early in our development efforts. VY7523, our anti-tau antibody candidate, is currently in early-stage clinical trials, and all of our other active product candidates are currently in preclinical development.
We are early in our development efforts. VY7523, our anti-tau antibody candidate, is in early-stage clinical trials, and all of our other active product candidates, including VY1706, are currently in preclinical development.
In the event we are unable to achieve milestones necessary to demonstrate progress on our programs relevant to our ongoing collaborations with Neurocrine or Novartis, Neurocrine or Novartis may be unwilling to fund these programs at the desired levels or at all, which could require us to fund these programs to a greater extent than we have expected, to decline to pursue certain program objectives or to discontinue one or more of the programs.
In the event we are unable to achieve milestones necessary to demonstrate progress on our programs relevant to our ongoing collaborations with Neurocrine or Novartis or our collaboration programs are deprioritized by our collaborators, Neurocrine or Novartis may be unwilling to fund these programs at the desired levels or at all, which could require us to fund these programs to a greater extent than we have expected, to decline to pursue certain program objectives or to discontinue one or more of the programs.
Delay or failure to obtain, or unexpected costs in obtaining, the regulatory approval necessary to bring a potential product candidate to market could decrease our ability to generate sufficient product revenue, and our business, financial condition, results of operations and prospects may be harmed.
Delay or failure to obtain, or unexpected costs in obtaining, the regulatory approval necessary to bring a potential product candidate to market could 57 Table of Contents decrease our ability to generate sufficient product revenue, and our business, financial condition, results of operations and prospects may be harmed.
If another sponsor receives such approval before we do (regardless of our orphan drug designation), we may be precluded from receiving marketing approval for our product for the applicable exclusivity period. The applicable period is seven years in the United States and 10 years in the European Union.
If another sponsor receives such approval before we do (regardless of our orphan drug designation), we may be precluded from receiving marketing approval for our product for the applicable exclusivity period. The applicable period is seven years 66 Table of Contents in the United States and 10 years in the European Union.
These changes included aggregate reductions to Medicare payments to providers of up to 2% per fiscal year, which went into effect in 84 Table of Contents April 2013 and will remain in effect through 2032 under the Coronavirus Aid, Relief, and Economic Security Act, or the CARES Act.
These changes included aggregate reductions to Medicare payments to providers of up to 2% per fiscal year, which went into effect in April 2013 and will remain in effect through 2032 under the Coronavirus Aid, Relief, and Economic Security Act, or the CARES Act.
Thereafter, following the change in administrations, CMS issued a public statement on January 29, 2025, declaring that lowering the cost of prescription drugs is a top priority of the new administration and CMS is committed to considering opportunities to bring greater 86 Table of Contents transparency in the negotiation program.
Thereafter, following the change in administrations, CMS issued a public statement on January 29, 2025, declaring that lowering the cost of prescription drugs is a top priority of the new administration and CMS is committed to considering opportunities to bring greater transparency in the negotiation program.
Most of our product candidates are in preclinical development, and one is in early-stage clinical trials. Our current portfolio of product candidates is subject to change as we continue to conduct preclinical and clinical testing and to develop product candidates and prioritize or abandon product candidates based on 82 Table of Contents such results and other factors.
Most of our product candidates are in preclinical development, and one is in early-stage clinical trials. Our current portfolio of product candidates is subject to change as we continue to conduct preclinical and clinical testing and to develop product candidates and prioritize or abandon product candidates based on such results and other factors.
We are developing and implementing a corporate compliance program designed to ensure that we will market and sell any future products that we successfully develop from our product candidates in compliance with all applicable laws and regulations, but we cannot guarantee that this program will protect us from governmental investigations or 88 Table of Contents other actions or lawsuits stemming from a failure to be in compliance with such laws or regulations.
We are developing and implementing a corporate compliance program designed to ensure that we will market and sell any future products that we successfully develop from our product candidates in compliance with all applicable laws and regulations, but we cannot guarantee that this program will protect us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws or regulations.
If our licensors fail to maintain such patents, or lose rights to those patents or patent applications, the rights we have licensed may be reduced or eliminated and our right to develop and commercialize any of our products that are the subject of such licensed rights could be adversely affected.
If our licensors fail to maintain such patents, or lose rights to those patents or patent applications, the rights we have licensed may be reduced or eliminated and our right to develop and commercialize any 104 Table of Contents of our products that are the subject of such licensed rights could be adversely affected.
Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are typically not published until 18 months after filing or, in some cases, only 100 Table of Contents upon issuance or not at all.
Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are typically not published until 18 months after filing or, in some cases, only upon issuance or not at all.
Our estimates may prove to be incorrect, and new studies may change the estimated incidence or prevalence of 92 Table of Contents the diseases we seek to address.
Our estimates may prove to be incorrect, and new studies may change the estimated incidence or prevalence of 96 Table of Contents the diseases we seek to address.
Additionally, we could face heightened risks with respect to obtaining marketing authorization in the UK as a result of the withdrawal of the UK from the EU, commonly referred to as Brexit. The UK is no longer part of the European Single Market and EU Customs Union.
Additionally, we could face heightened risks with respect to obtaining marketing authorization in the United Kingdom as a result of the withdrawal of the United Kingdom from the European Union, commonly referred to as Brexit. The United Kingdom is no longer part of the European Single Market and EU Customs Union.
Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare (beginning in 2026), with prices that can be negotiated subject to a cap; imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation (first due in 2023); and replaces the Part D coverage gap discount program with a new discounting program (beginning in 2025).
Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare (beginning in 2026), with prices that can be negotiated subject to a cap; imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation; and replaces the Part D coverage gap discount program with a new discounting program.
Our inability to obtain access to a sufficient supply of these NHPs in a timely manner or at all may impair or delay our ability to complete preclinical studies to support capsid discovery efforts or IND applications or similar applications in other jurisdictions.
Our inability to obtain access to a sufficient supply of these 60 Table of Contents NHPs in a timely manner, or at all, may impair or delay our ability to complete preclinical studies to support capsid discovery efforts or IND applications or similar applications in other jurisdictions.
Applicable legislation in the EU also requires sponsors to either conduct clinical trials in a pediatric population in accordance with a Pediatric Investigation Plan approved by the Pediatric Committee of the European Medicines Agency, or EMA, or to obtain a waiver or deferral from the conduct of these studies by this Committee.
Applicable legislation in the EU also requires sponsors to either conduct clinical trials in a pediatric population in accordance with a Pediatric Investigation Plan approved by the Pediatric Committee of the EMA or to obtain a waiver or deferral from the conduct of these studies by this Committee.
This could result in a delay in approval, or rejection, of our marketing 69 Table of Contents applications by the FDA or comparable foreign regulatory authority, as the case may be, and may ultimately lead to the denial of marketing approval of one or more of our product candidates.
This could result in a delay in approval, or rejection, of our marketing applications by the FDA or comparable foreign regulatory authority, as the case may be, and may ultimately lead to the denial of marketing approval of one or more of our product candidates.
Moreover, an unsuccessful outcome in any clinical trial for which our collaborator, optionee, or licensee is responsible could be harmful to the public perception and prospects of our proprietary antibody program and gene therapy and vectorized antibody platforms. 76 Table of Contents Our relationship with any current or future collaborators, optionees, or licensees may pose several risks, including the following: ● collaborators, optionees, and licensees have significant discretion in determining the amount and timing of the efforts and resources that they will apply to these collaborations and option and license transactions; ● collaborators, optionees, or licensees may not perform their obligations as expected or desired; ● the preclinical studies and clinical trials conducted as part of these collaborations or by our licensees may not be successful; ● collaborators, optionees, or licensees may not pursue development and commercialization of any product candidates that achieve regulatory approval or may elect not to continue or renew development or commercialization programs based on preclinical study or clinical trial results, changes in the collaborators’, optionees’, or licensees’ strategic focus or available funding or external factors, such as an acquisition, which divert resources or create competing priorities; ● collaborators, optionees, or licensees may delay preclinical studies and clinical trials, provide insufficient funding for preclinical studies and clinical trials, stop a preclinical study or clinical trial or abandon a product candidate, repeat or conduct new preclinical studies or clinical trials or require a new formulation of a product candidate for preclinical studies or clinical trials; ● we may not have access to, or may be restricted from disclosing, certain information regarding product candidates being developed or commercialized under a collaboration or by a licensee and, consequently, may have limited ability to inform our stockholders about the status of such product candidates; ● collaborators, optionees, or licensees could independently develop, or develop with third parties, products that compete directly or indirectly with our product candidates if the collaborators, optionees, or licensees believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours; ● product candidates developed in collaboration with us or by a licensee may be viewed by our collaborators or licensees as competitive with their own product candidates or products, which may cause collaborators or licensees to cease to devote resources to the commercialization of our product candidates; ● a collaborator or licensee with marketing and distribution rights to one or more of our product candidates that achieve regulatory approval may not commit sufficient resources to the marketing and distribution of any such product candidate; ● disagreements with collaborators, optionees, or licensees, including disagreements over proprietary rights, contract interpretation or the preferred course of development of any product candidates, may cause delays or termination of the research, development or commercialization of such product candidates, may lead to additional responsibilities or expenses for us with respect to such product candidates (in the case of collaborations) or may result in litigation or arbitration, any of which would be time-consuming and expensive; ● in collaboration, licensing, and option arrangements where we have licensed intellectual property rights to collaborators, licensees, and optionees who have the right to control prosecution of the licensed intellectual property rights, disputes may arise with respect to the prosecution strategy for the relevant intellectual property rights, which may impair our ability to pursue our preferred prosecution strategy or achieve the desired protection from any relevant patents; 77 Table of Contents ● collaborators, optionees, or licensees may not properly maintain or defend our intellectual property rights or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential litigation; ● disputes may arise with respect to the ownership or inventorship of intellectual property developed pursuant to our collaborations or option and license transactions; ● collaborators, optionees, or licensees may infringe the intellectual property rights of third parties, which may expose us to litigation and potential liability; ● the terms of our collaboration or license agreement may restrict us from entering into certain relationships with other third parties, thereby limiting our options; and ● collaborations may be terminated for the convenience of the collaborator and, if terminated, we could be required to raise additional capital to pursue further development or commercialization of the applicable product candidates.
Our relationship with any current or future collaborators, optionees, or licensees may pose several risks, including the following: ● collaborators, optionees, and licensees have significant discretion in determining the amount and timing of the efforts and resources that they will apply to these collaborations and option and license transactions; ● collaborators, optionees, or licensees may not perform their obligations as expected or desired; 79 Table of Contents ● the preclinical studies and clinical trials conducted as part of these collaborations or by our licensees may not be successful; ● collaborators, optionees, or licensees may not pursue development and commercialization of any product candidates that achieve regulatory approval or may elect not to continue or renew development or commercialization programs based on preclinical study or clinical trial results, changes in the collaborators’, optionees’, or licensees’ strategic focus or available funding or external factors, such as an acquisition, which divert resources or create competing priorities; ● collaborators, optionees, or licensees may delay preclinical studies and clinical trials, provide insufficient funding for preclinical studies and clinical trials, stop a preclinical study or clinical trial or abandon a product candidate, repeat or conduct new preclinical studies or clinical trials or require a new formulation of a product candidate for preclinical studies or clinical trials; ● we may not have access to, or may be restricted from disclosing, certain information regarding product candidates being developed or commercialized under a collaboration or by a licensee and, consequently, may have limited ability to inform our stockholders about the status of such product candidates; ● collaborators, optionees, or licensees could independently develop, or develop with third parties, products that compete directly or indirectly with our product candidates if the collaborators, optionees, or licensees believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours; ● product candidates developed in collaboration with us or by a licensee may be viewed by our collaborators or licensees as competitive with their own product candidates or products, which may cause collaborators or licensees to cease to devote resources to the commercialization of our product candidates; ● a collaborator or licensee with marketing and distribution rights to one or more of our product candidates that achieve regulatory approval may not commit sufficient resources to the marketing and distribution of any such product candidate; ● disagreements with collaborators, optionees, or licensees, including disagreements over proprietary rights, contract interpretation or the preferred course of development of any product candidates, may cause delays or termination of the research, development or commercialization of such product candidates, may lead to additional responsibilities or expenses for us with respect to such product candidates (in the case of collaborations) or may result in litigation or arbitration, any of which would be time-consuming and expensive; ● in collaboration, licensing, and option arrangements where we have licensed intellectual property rights to collaborators, licensees, and optionees who have the right to control prosecution of the licensed intellectual property rights, disputes may arise with respect to the prosecution strategy for the relevant intellectual property rights, which may impair our ability to pursue our preferred prosecution strategy or achieve the desired protection from any relevant patents; ● collaborators, optionees, or licensees may not properly maintain or defend our intellectual property rights or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential litigation; ● disputes may arise with respect to the ownership or inventorship of intellectual property developed pursuant to our collaborations or option and license transactions; 80 Table of Contents ● collaborators, optionees, or licensees may infringe the intellectual property rights of third parties, which may expose us to litigation and potential liability; ● the terms of our collaboration or license agreement may restrict us from entering into certain relationships with other third parties, thereby limiting our options; and ● collaborations or licenses may be terminated for the convenience of the collaborator or licensee and, if terminated, we could be required to raise additional capital to pursue further development or commercialization of the applicable product candidates.
For example, we are no longer advancing VY9323, formerly the lead development candidate for our SOD1 silencing program for ALS, as a development candidate and are assessing alternate payloads for the program based on three-month data from a non-human primate GLP toxicology study suggesting that a different payload would be necessary to achieve the desired product profile for the program.
For example, we are no longer advancing VY9323, formerly the lead development candidate for our SOD1 silencing program for ALS, as a development candidate based on three-month data from a non-human primate GLP toxicology study suggesting that a different payload would be necessary to achieve the desired product profile for the program.
The European Commission’s proposal for revision of several legislative instruments related to medicinal products (including potentially reducing the duration of regulatory data protection and revising the eligibility for expedited pathways) was published on April 26, 2023.
The European Commission’s proposal for revision of several legislative instruments related to medicinal products (including potentially reducing the duration of regulatory data protection and revising the eligibility for expedited 77 Table of Contents pathways) was published on April 26, 2023.
While we believe that our gene therapy platform, vectorized antibody platform, non-viral therapeutics platform, product programs, product candidates and scientific expertise in the fields of proprietary antibodies, gene therapy, and 72 Table of Contents neuroscience provide us with competitive advantages, we face potential competition from various sources, including larger and better-funded pharmaceutical, specialty pharmaceutical and biotechnology companies, as well as from academic institutions, governmental agencies and public and private research institutions.
While we believe that our gene therapy platform, non-viral therapeutics platform, product programs, product candidates and scientific expertise in the fields of proprietary antibodies, gene therapy, and neuroscience provide us with competitive advantages, we face potential competition from various sources, including larger and better-funded pharmaceutical, specialty pharmaceutical and biotechnology companies, as well as from academic institutions, governmental agencies and public and private research institutions.
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.
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 69 Table of Contents clinical benefit.
Our program materials are manufactured using technically complex processes requiring specialized equipment and facilities, highly specific raw materials, cells, and reagents, and other production constraints. Several of these raw materials, cells, and reagents are provided by a limited number of suppliers.
Our program materials are manufactured using technically complex processes requiring specialized equipment and facilities, highly specific raw materials, cells, and reagents, and other production constraints. Several of these raw materials, cells, and reagents are provided by a limited 83 Table of Contents number of suppliers.
Our company has completed several transactions since its inception which resulted in an ownership change under Section 382 of the Code. In addition, future changes in our stock ownership, some of which are outside of our control, could result in ownership changes in the future.
Our company has 118 Table of Contents completed several transactions since its inception which resulted in an ownership change under Section 382 of the Code. In addition, future changes in our stock ownership, some of which are outside of our control, could result in ownership changes in the future.
The CPRA also created a new enforcement agency – the California Privacy Protection Agency – whose sole responsibility is to enforce the CPRA, which will further increase compliance risk. The CPRA may apply to some of our business activities. In addition to California, at least 18 other states have passed comprehensive privacy laws similar to the CCPA and CPRA.
The CPRA also created a new enforcement agency – the California Privacy Protection Agency – whose sole responsibility is to enforce the CPRA, which will further increase compliance risk. The CPRA may apply to some of our business activities. In addition to California, a number of other states have passed comprehensive privacy laws similar to the CCPA and CPRA.
Unlike most guidance documents issued by the FDA, the DAP guidance when finalized will have the force of law because FDORA specifically dictates that the form and manner for submission 59 Table of Contents of DAPs are specified in FDA guidance.
Unlike most guidance documents issued by the FDA, the DAP guidance when finalized will have the force of law because FDORA specifically dictates that the form and manner for submission of DAPs are specified in FDA guidance.
We may not prevail in any lawsuits that we initiate, and the damages or other remedies awarded, if any, may not be commercially meaningful. Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license.
We may not prevail in any 108 Table of Contents lawsuits that we initiate, and the damages or other remedies awarded, if any, may not be commercially meaningful. Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license.
Moreover, we may become party to, or be threatened with, adversarial proceedings or litigation regarding intellectual property rights with respect to our product candidates and technology, including ex parte re-examination, post-grant review and inter partes review before the USPTO or foreign patent offices.
Moreover, we may become party to, or be threatened with, adversarial proceedings or litigation regarding intellectual property rights with respect to our product candidates and technology, including ex parte re- 109 Table of Contents examination, post-grant review and inter partes review before the USPTO or foreign patent offices.
In July 2020, the European Court of Justice invalidated the Privacy Shield program, a voluntary self- 90 Table of Contents certification privacy protection mechanism that facilitated transfers of personal data from the European Union to the United States.
In July 2020, the European Court of Justice invalidated the Privacy Shield program, a voluntary self-certification privacy protection mechanism that facilitated transfers of personal data from the European Union to the United States.
For example, the clinical trial must be well-designed and conducted and performed by qualified investigators in accordance with ethical principles. The trial population must also adequately represent the U.S. population, and the data must be applicable to the U.S. population and U.S. medical practice in ways that the FDA deems clinically meaningful.
For example, the clinical trial must be well-designed and conducted and performed by qualified investigators in 59 Table of Contents accordance with ethical principles. The trial population must also adequately represent the U.S. population, and the data must be applicable to the U.S. population and U.S. medical practice in ways that the FDA deems clinically meaningful.
In some circumstances, particularly in-licenses with academic institutions, we may not have the right to control the preparation, filing and prosecution of patent applications, or to maintain, enforce or defend the patents, covering technology that we license from third parties.
In some circumstances, particularly in-licenses with academic institutions and our collaboration with Transition Bio, we may not have the right to control the preparation, filing and prosecution of patent applications, or to maintain, enforce or defend the patents, covering technology that we license from third parties.
A product candidate that has received an RMAT designation that is granted accelerated approval and is subject to post-approval requirements may fulfill such requirements through the submission of clinical evidence, clinical studies, patient registries, or other sources of real world evidence, such as electronic health records; the collection of larger confirmatory data sets; or post-approval monitoring of all patients treated with such therapy prior to its approval.
A product candidate that has received an RMAT designation that is granted accelerated approval and is subject to post-approval requirements may fulfill such requirements through the submission of clinical evidence, clinical studies, patient registries, or other sources of real world evidence, such as electronic health records; the collection of larger confirmatory data sets; or post-approval monitoring of all patients treated with such therapy prior to its approval. 68 Table of Contents RMAT designation is within the discretion of the FDA.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeAdditionally, the VP of IT has participated in Gartner cybersecurity programs and conferences and received training on combating cyber threats, including phishing, malware, and social engineering. 115 Table of Contents Employee Training and Technology-Based Safeguards We provide annual data protection and cybersecurity training for all personnel, including full-time, part-time, and temporary staff.
Biggest changeOur VP of IT has experience with compliance programs for cybersecurity-related regulations and standards. 120 Table of Contents Additionally, the VP of IT has participated in Gartner cybersecurity programs and conferences and received training on combating cyber threats, including phishing, malware, and social engineering.
Board and Audit Committee Oversight We do not believe that there are currently any known risks from cybersecurity threats that are reasonably likely to materially impact the company or its business strategy, operations, or financial condition. The Audit Committee provides direct oversight of cybersecurity risk and updates the Board of Directors on such matters.
Board and Audit Committee Oversight We do not believe that there are currently any known risks from cybersecurity threats that have materially affected or are reasonably likely to materially affect the company, including its business strategy, results of operations, or financial condition. The Audit Committee provides direct oversight of cybersecurity risk and updates the Board of Directors on such matters.
Our VP of IT brings over 15 years of experience in cybersecurity, including serving as Chief Information Security Officer for a multinational company in the specialty materials industry. Our VP of IT has experience with compliance programs for cybersecurity-related regulations and standards.
Our VP of IT brings over 15 years of experience in cybersecurity, including serving as Chief Information Security Officer for a multinational company in the specialty materials industry.
This program covers topics such as: ● Social engineering and phishing awareness , ● Password protection and mobile security , and ● Incident response and reporting.
Employee Training and Technology-Based Safeguards We provide annual data protection and cybersecurity training for all personnel, including full-time, part-time, and temporary staff. This program covers topics such as: ● Social engineering and phishing awareness , ● Password protection and mobile security , and ● Incident response and reporting.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeWhile the outcome of any such matters cannot be predicted with certainty, as of December 31, 2024, we were not party to any material pending proceedings. No material governmental proceedings are pending or, to our knowledge, contemplated against us.
Biggest changeWhile the outcome of any such matters cannot be predicted with certainty, as of December 31, 2025, we were not party to any material pending proceedings. No material governmental proceedings are pending or, to our knowledge, contemplated against us.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeThis number of holders of record also does not include stockholders whose shares may be held in trust by other entities. 116 Table of Contents ​ Dividends ​ We have not paid any cash dividends on our common stock since inception and do not anticipate paying cash dividends in the foreseeable future. ​ ITEM 6. RESERVED ​ ​
Biggest changeThis number of holders of record also does not include stockholders whose shares may be held in trust by other entities. ​ Dividends ​ We have not paid any cash dividends on our common stock since inception and do not anticipate paying cash dividends in the foreseeable future. ​ Stock Performance Graph ​ The following graph compares the cumulative annual stockholder return on our common stock over the period commencing December 31, 2020 and ending on December 31, 2025, to that of the total return for the Nasdaq Composite Index and the Nasdaq Biotechnology Index, assuming an investment of $100 on December 31, 2020.
Prior to this time, there was no public market for our common stock. ​ Stockholders ​ As of March 3, 2025, there were approximately 10 holders of record of our common stock.
Prior to this time, there was no public market for our common stock. ​ 121 Table of Contents Stockholders ​ As of March 2, 2026, there were approximately 10 holders of record of our common stock.
Added
In calculating cumulative total annual stockholder return, reinvestment of dividends, if any, is assumed. The indices are included for comparative purposes only. They do not necessarily reflect management’s opinion that such indices are an appropriate measure of the relative performance of our common stock and are not intended to forecast or be indicative of future performance of our common stock.
Added
The following graph and related information shall not be deemed “soliciting material” or be “filed” with the SEC, nor shall such information be incorporated by reference in any of our filings under the Securities Act, or the Exchange Act, whether made before or after the date hereof and irrespective of any general incorporation language in any such filing. ​ ​ ​ ITEM 6.

Item 7. Management's Discussion & Analysis

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

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Biggest changeWe anticipate that our expenses will increase substantially in the long term in connection with our ongoing activities, as we: ● conduct clinical trials in connection with our anti-tau antibody program; ● continue investing in our proprietary antibody program, non-viral therapeutics platform, gene therapy and vectorized antibody platforms and programs, and other research and development initiatives; ● continue investing in and supporting TRACER, our proprietary discovery platform to facilitate the selection of AAV capsids and our investment to discover TRACER Capsids with broad tropism in CNS and other tissues with cell-specific transduction properties for particular therapeutic applications; ● increase our investment in the discovery and development of modalities for receptor-mediated non-viral delivery of therapeutic payloads to the CNS; ● conduct joint research and development under our strategic collaborations for the research, development, and commercialization of certain of our pipeline programs, including our FA Program pursuant to our collaboration and license agreement with Neurocrine entered into in January 2019, or the 2019 Neurocrine Collaboration Agreement, our GBA1 Program , pursuant to our collaboration and license agreement with Neurocrine entered into in January 2023, or the 2023 Neurocrine Collaboration Agreement , and our Huntington’s disease program, or the Novartis HD Program, pursuant to our license and collaboration agreement with Novartis entered into in December 2023, or the 2023 Novartis Collaboration Agreement ; ● initiate additional preclinical studies and clinical trials for, and continue research and development of, our other programs; ● continue our process research and development activities, as well as establish our research-grade manufacturing capabilities; ● identify additional diseases for treatment with our AAV gene therapies and develop additional programs or product candidates; ● seek marketing and regulatory approvals for any of our product candidates that successfully complete clinical development; ● maintain, expand, protect and enforce our intellectual property portfolio; ● identify, acquire or in-license other product candidates and technologies; 118 Table of Contents ● expand our operational, financial and management systems and personnel, including personnel to support our clinical development, manufacturing and commercialization efforts; ● increase our clinical trial insurance coverage as we expand our clinical trials and increase our product liability insurance once we engage in commercialization efforts; and ● continue to operate as a public company.
Biggest changeWe expect to continue to incur significant expenses and operating losses for the foreseeable future in connection with our ongoing activities, as we: ● initiate and conduct clinical trials in connection with our tau silencing program, which we expect to initiate in the second half of 2026, and continue to conduct clinical trials in connection with our anti-tau antibody program; ● continue investing in our proprietary antibody program, non-viral therapeutics platform, gene therapy platforms and programs, and other research and development initiatives; 124 Table of Contents ● continue investing in NeuroShuttle, our proprietary non-viral delivery platform leveraging novel receptor-binding molecules to transport multiple modalities of neurotherapeutics across the blood-brain barrier ; ● continue investing in and supporting TRACER™ (Tropism Redirection of AAV by Cell-type-specific Expression of RNA), our proprietary discovery platform to facilitate the selection of adeno-associated virus, or AAV, capsids, which we refer to as TRACER Capsids, and our investment to discover TRACER Capsids with broad tropism in CNS and other tissues with cell-specific transduction properties for particular therapeutic applications; ● continue investing in our collaboration with Transition Bio to advance small molecules targeting TDP-43 to treat ALS and frontotemporal dementia with TDP-43 pathology; ● increase our investment in the discovery and development of additional modalities for receptor-mediated non-viral delivery of therapeutic payloads to the CNS, including but not limited to our alkaline phosphatase and other BBB-receptor ; ● conduct joint research and development under our strategic collaborations for the research, development, and commercialization of certain of our pipeline programs, including our Friedreich’s ataxia program, or the FA Program, pursuant to our collaboration and license agreement with Neurocrine entered into in January 2019, or the 2019 Neurocrine Collaboration Agreement, our glucosylceramidase beta 1 , or GBA1, gene therapy program for PD and other GBA1-mediated diseases, or the GBA1 Program, pursuant to our collaboration and license agreement with Neurocrine entered into in January 2023, or the 2023 Neurocrine Collaboration Agreement, and our Huntington’s disease program, or the Novartis HD Program, pursuant to our license and collaboration agreement with Novartis entered into in December 2023, or the 2023 Novartis Collaboration Agreement; ● initiate additional preclinical studies and clinical trials for, and continue research and development of, our other programs; ● continue our process research and development activities, as well as establish our research-grade manufacturing capabilities; ● identify additional diseases for treatment with our AAV gene and non-viral therapies and BBB-crossing technologies and develop additional programs or product candidates; ● seek marketing and regulatory approvals for any of our product candidates that successfully complete clinical development; ● maintain, expand, protect and enforce our intellectual property portfolio; ● identify, acquire or in-license other product candidates and technologies; ● expand our operational, financial and management systems and personnel, including personnel to support our clinical development, manufacturing and commercialization efforts; ● increase our clinical trial insurance coverage as we expand our clinical trials and increase our product liability insurance once we engage in commercialization efforts; and ● continue to operate as a public company. 125 Table of Contents Financial Operations Overview Revenue ​ To date, we have not generated any revenue from product sales and do not expect to generate any revenue from product sales for the foreseeable future.
The cash provided by operating activities for the year ended December 31, 2023, was primarily driven by our net income for the year ended December 31, 2023, of $132.3 million, stock-based compensation expense of $11.2 million, and an increase in deferred revenue of $9.4 million, offset by an increase in accounts receivable of $80.2 million due to the recording of the upfront payment under the 2023 Novartis Agreement.
The cash provided by operating activities for the year ended December 31, 2023, was primarily driven by our net income for the year ended December 31, 2023, of $132.3 million, stock-based compensation expense of $11.2 million, and an increase in deferred revenue of $9.4 million, partially offset by an increase in accounts receivable of $80.2 million due to the recording of the upfront payment under the 2023 Novartis Agreement.
We are a biotechnology company whose mission is to leverage the power of human genetics to modify the course of and ultimately cure neurological diseases. Our pipeline includes programs for Alzheimer’s disease, or AD; Friedreich’s ataxia, or FA; Parkinson’s disease; and multiple other diseases of the central nervous system, or CNS.
We are a biotechnology company whose mission is to leverage the power of human genetics to modify the course of and ultimately cure neurological diseases. Our pipeline includes programs for Alzheimer’s disease, or AD; Friedreich’s ataxia, or FA; Parkinson’s disease, or PD; and multiple other diseases of the central nervous system, or CNS.
Cash Flows from Financing Activities Net cash provided by financing activities was $114.0 million during the year ended December 31, 2024 primarily due to the $93.5 million in net proceeds from a public offering of common stock and warrants and $19.3 million in connection with the sale of common stock to Novartis in January 2024.
Net cash provided by financing activities was $114.0 million during the year ended December 31, 2024, primarily due to the $93.5 million in net proceeds from a public offering of common stock and warrants and $19.3 million in connection with the sale of common stock to Novartis in January 2024.
The cash used in investing activities for the year ended December 31, 2023 was primarily due to $224.0 million for purchases of marketable securities and $3.3 million for purchases of property and equipment, offset by $85.6 million from proceeds from maturities and sales of marketable securities.
The cash used in investing activities for the year ended December 31, 2023, was primarily due to $224.0 million for purchases of marketable securities and $3.3 million for purchases of property and equipment, partially offset by $85.6 million from proceeds from maturities and sales of marketable securities.
During the year ended December 31, 2023, we recognized collaboration revenue in connection with the following agreements: ● $79.0 million upon Novartis’ decision to exercise two of its license options under the 2022 Novartis Option and License Agreement, or Novartis License Options, along with the expiration of a third Novartis License Option, all of which were determined to be material rights in the 2022 Novartis Option and License Agreement ; ● $80.8 million under the 2023 Neurocrine Collaboration Agreement; ● $80.0 million under the 2023 Novartis Collaboration Agreement; ● $9.8 million under the 2019 Neurocrine Collaboration Agreement; and ● $0.4 million under other agreements. 122 Table of Contents Research and Development Expense Research and development expense increased by $35.2 million from $92.2 million for the year ended December 31, 2023, to $127.4 million for the year ended December 31, 2024.
During the year ended December 31, 2023, we recognized collaboration revenue in connection with the following agreements: ● $79.0 million upon Novartis’ decision to exercise two of its license options under the 2022 Novartis Option and License Agreement, or Novartis License Options, along with the expiration of a third Novartis License Option, all of which were determined to be material rights in the 2022 Novartis Option and License Agreement ; ● $80.8 million under the 2023 Neurocrine Collaboration Agreement; ● $80.0 million under the 2023 Novartis Collaboration Agreement; ● $9.8 million under the 2019 Neurocrine Collaboration Agreement; and ● $0.4 million under other agreements. 131 Table of Contents Research and Development Expense Research and development expense increased by $35.2 million from $92.2 million for the year ended December 31, 2023, to $127.4 million for the year ended December 31, 2024.
We use judgement in estimating the expected remaining costs to complete the research and development services for each performance obligation based on discussions with the Joint Steering Committee for the program and discussions with our collaboration partners. We evaluate the measure of progress each reporting period and, if necessary, adjust the measure and related revenue recognition.
We use judgment in estimating the expected remaining costs to complete the research and development services for each performance obligation based on discussions with the Joint Steering Committee for the program and discussions with our collaboration partners. We evaluate the measure of progress each reporting period and, if necessary, adjust the measure and related revenue recognition.
In a non-human primate, or NHP, study, a single 1.3E13 vector genomes per kilogram dose of VY1706 delivered intravenously resulted in reductions in tau mRNA levels of 50% to 73% across the cerebral cortex, including in areas of the brain where tau accumulates during progression of AD.
In a non-human primate, or NHP, study, a single 1.3E13 vector genomes per kilogram, or vg/kg, dose of VY1706 delivered intravenously resulted in reductions in tau mRNA levels of 50% to 73% across the cerebral cortex, including in areas of the brain where tau accumulates during the progression of AD.
Costs for certain activities, such as manufacturing, preclinical studies, and clinical trials, are generally recognized based on an evaluation of the progress to completion of specific tasks using information and data provided to us by our vendors and collaborators. Research and development activities are central to our business model.
Research and development costs are expensed as incurred. Costs for certain activities, such as manufacturing, preclinical studies, and clinical trials, are generally recognized based on an evaluation of the progress to completion of specific tasks using information and data provided to us by our vendors and collaborators. Research and development activities are central to our business model.
We utilize either the most likely amount method or expected amount method to estimate the amount expected to be received based on which method best predicts the amount expected to be received.
We utilize either the most likely amount method or expected value method to estimate the amount expected to be received based on which method best predicts the amount expected to be received.
We must develop assumptions that require judgment to determine the stand-alone selling price for each performance obligation identified in the contract. We utilize key assumptions to determine the stand-alone selling price for performance obligations, which may include other comparable transactions, pricing considered in negotiating the transaction and the estimated costs.
We must develop assumptions that require judgment to determine the stand-alone selling price for each performance obligation identified in the contract. We utilize key assumptions to determine the stand-alone selling price for performance obligations, which may include other comparable transactions, pricing considered in negotiating the transaction and the estimated costs of satisfying the performance obligation.
Our expenses will increase if: ● we are required by the FDA or the European Medicines Agency or other regulatory agencies to redesign or modify trials or studies or to perform trials or studies in addition to those currently expected; ● there are any delays in the receipt of regulatory clearance to begin our planned clinical programs; or ● there are any delays in enrollment of participants in or completing our clinical trials or the development of our product candidates . ​ General and Administrative Expenses ​ General and administrative expenses consist primarily of salaries and other related costs, including stock-based compensation, for personnel in executive, finance, accounting, information technology, business development, legal and human resource functions.
Our expenses will increase if: ● we are required by the FDA or the European Medicines Agency or other regulatory agencies to redesign or modify trials or studies or to perform trials or studies in addition to those currently expected; ● there are any delays in the receipt of regulatory clearance to begin our planned clinical programs; or ● there are any delays in site initiation, enrollment of participants in or completion of our clinical trials or the development of our product candidates . ​ General and Administrative Expenses ​ General and administrative expenses consist primarily of salaries and other related costs, including stock-based compensation, for personnel in executive, finance, accounting, information technology, business development, legal and human resource functions.
Debt financing and preferred equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, obtaining additional capital, acquiring or divesting businesses, making capital expenditures or declaring dividends. ​ If we raise additional funds through collaborations, strategic alliances, or option and license arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates or to grant licenses on terms that may not be favorable to us.
Debt financing and preferred equity financing, if available, may involve agreements that include covenants limiting or restricting our ability 135 Table of Contents to take specific actions, such as incurring additional debt, obtaining additional capital, acquiring or divesting businesses, making capital expenditures or declaring dividends. ​ If we raise additional funds through collaborations, strategic alliances, or option and license arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates or to grant licenses on terms that may not be favorable to us.
The terms of these arrangements typically include payment of one or more of the following: non-refundable, upfront fees; reimbursement of research and development costs; development, regulatory and commercial milestone payments; option exercise fees; and royalties on net sales of licensed products. ​ We estimate the transaction price based on the amount expected to be received for transferring the promised goods or services in the contract.
The terms of these arrangements typically include payment of one or more of the following: non- 127 Table of Contents refundable, upfront fees; reimbursement of research and development costs; development, regulatory and commercial milestone payments; option exercise fees; and royalties on net sales of licensed products. ​ We estimate the transaction price based on the amount expected to be received for transferring the promised goods or services in the contract.
Adequate additional financing may not be available to us on acceptable terms, or at all. ​ Until such time, if ever, as we can generate product revenues sufficient to achieve consistent profitability, we expect to finance our cash needs through a combination of equity offerings, debt financings, collaborations, strategic 126 Table of Contents alliances, and option and license arrangements.
Adequate additional financing may not be available to us on acceptable terms, or at all. ​ Until such time, if ever, as we can generate product revenues sufficient to achieve consistent profitability, we expect to finance our cash needs through a combination of equity offerings, debt financings, collaborations, strategic alliances, and option and license arrangements.
At this time, we cannot reasonably estimate or know the nature, timing and estimated costs of the efforts that will be necessary to complete the development of our product candidates. Because of the numerous risks and uncertainties associated with pharmaceutical product development, we are unable to accurately predict the timing or amount of increased expenses.
At 126 Table of Contents this time, we cannot reasonably estimate or know the nature, timing and estimated costs of the efforts that will be necessary to complete the development of our product candidates. Because of the numerous risks and uncertainties associated with pharmaceutical product development, we are unable to accurately predict the timing or amount of increased expenses.
Revenue is recognized using input-based measurements, which involves the measurement of progress toward each performance obligation based on the actual costs incurred compared to total projected costs.
Revenue is recognized using input-based measurements, which involves the measurement of progress toward each performance obligation based on the actual costs incurred compared to total expected costs.
The cash used in operating activities for the year ended December 31, 2024, was primarily driven by our net loss for the year ended December 31, 2024, of $65.0 million and a decrease in deferred revenue of $44.8 million due to revenue recognized under the 2019 Neurocrine Agreement and the 2023 Neurocrine Collaboration Agreement, offset by a decrease in accounts receivable of $78.6 million due to the collection of the upfront payment under the 2023 Novartis Agreement, and stock-based compensation expense of $14.8 million. ​ Net cash provided by operating activities was $77.9 million during the year ended December 31, 2023.
The cash used in operating activities for the year ended December 31, 2024, was primarily driven by our net loss for the year ended December 31, 2024, of $65.0 million and a decrease in deferred revenue of $44.8 million due to revenue recognized under the 2019 Neurocrine Agreement and the 2023 Neurocrine Collaboration Agreement, partially offset by a decrease in accounts receivable of $78.6 million due to the collection of the upfront payment under the 2023 Novartis Agreement, and stock-based compensation expense of $14.8 million.
The cash used in investing activities for the year ended December 31, 2024 was primarily due to $465.7 million for purchases of marketable securities and $3.5 million for purchases of property and equipment, offset by $374.3 million from proceeds from maturities and sales of marketable securities.
The cash used in investing activities for the year ended December 31, 2024, was primarily due to $465.7 million for purchases of 133 Table of Contents marketable securities and $3.5 million for purchases of property and equipment, partially offset by $374.3 million from proceeds from maturities and sales of marketable securities.
Our future capital requirements will depend on many factors, including: ​ ● the scope, progress, results, and costs of product discovery, preclinical studies and clinical trials for our product candidates , including our clinical trials to evaluate VY7523 ; ● the scope, progress, results, costs, prioritization, and number of our research and development programs; ● the progress and status of our strategic collaborations and option and license agreements and any similar arrangements we may enter into in the future, including any research and development costs for which we are responsible, future additional obligations that we may be committed to in connection with these agreements, and our receipt of any expense reimbursements, future milestone payments and royalties from our collaboration partners or licensors; ● the extent to which we are obligated to reimburse preclinical development and clinical trial costs, or the achievement of milestones or occurrence of other developments that trigger milestone and royalty payments, under any collaboration or license agreements to which we might become a party , such as the license agreement we entered into with Touchlight IP Limited in November 2022 ; ● the costs, timing and outcome of regulatory review of our product candidates; ● our ability to establish and maintain collaboration, distribution, or other marketing arrangements for our product candidates on favorable terms, if at all; ● the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending intellectual property-related claims; ● the extent to which we acquire or in-license other product candidates and technologies, including any intellectual property associated with such candidates or technologies, acquire or invest in other businesses, or out-license our product candidates, capsids or other technologies; ● the costs of advancing our manufacturing capabilities and securing manufacturing arrangements for pre-commercial and commercial production; ● the level of product sales by us or our collaborators from any product candidates for which we obtain marketing approval in the future; ● the costs of operating as a public company and maintaining adequate product, clinical trial, and directors’ and officers’ liability insurance coverage; and ● the costs of establishing or contracting for sales, manufacturing, marketing, distribution, and other commercialization capabilities if we obtain regulatory approvals to market our product candidates.
Our future capital requirements will depend on many factors, including: ​ ● the scope, progress, results, and costs of product discovery, preclinical studies and clinical trials for our product candidates, including our ongoing Phase 1 clinical trial to evaluate VY7523 and our planned Phase 1 clinical trial to evaluate VY1706; ● the scope, progress, results, costs, prioritization, and number of our research and development programs; ● the progress and status of our strategic collaborations and option and license agreements and any similar arrangements we may enter into in the future, including any research and development costs for which we are responsible, future additional obligations that we may be committed to in connection with these 134 Table of Contents agreements, including, for example, if we elect to exercise our rights for any of the three programs for which we retain opt-in rights, and our receipt of any expense reimbursements, future milestone payments and royalties from our collaboration partners or licensors; ● the extent to which we are obligated to reimburse preclinical development and clinical trial costs, or the achievement of milestones or occurrence of other developments that trigger milestone and royalty payments, under any collaboration or license agreements to which we might become a party, such as the license agreement we entered into with Touchlight IP Limited, or Touchlight, in November 2022, which we refer to as the Touchlight License Agreement, and the research collaboration, option and license agreement we entered into with Transition Bio in June 2025; ● the costs, timing and outcome of regulatory review of our product candidates; ● our ability to establish and maintain collaboration, distribution, or other marketing arrangements for our product candidates on favorable terms, if at all; ● the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending intellectual property-related claims; ● the extent to which we acquire or in-license other product candidates and technologies, including any intellectual property associated with such candidates or technologies, acquire or invest in other businesses, or out-license our product candidates, capsids or other technologies; ● the costs of advancing our manufacturing capabilities and securing manufacturing arrangements for pre-commercial and commercial production; ● the level of product sales by us or our collaborators from any product candidates for which we obtain marketing approval in the future; ● the costs of operating as a public company and maintaining adequate product, clinical trial, and directors’ and officers’ liability insurance coverage; and ● the costs of establishing or contracting for sales, manufacturing, marketing, distribution, and other commercialization capabilities if we obtain regulatory approvals to market our product candidates .
Furthermore, we expect to incur increasing costs associated with operating as a public company, executing financial statement controls, satisfying regulatory and quality standards, fulfilling healthcare compliance requirements, and maintaining product, clinical trial and directors’ and officers’ liability insurance coverage.
Furthermore, we expect to incur increasing costs associated with operating as a public company, satisfying regulatory and quality standards, fulfilling healthcare compliance requirements, and maintaining product, clinical trial and directors’ and officers’ liability insurance coverage.
If we are unable to raise capital or enter into business development transactions when needed or on acceptable terms, we could be forced to delay, reduce or eliminate our research and development programs or any future commercialization efforts. ​ As of December 31, 2024, we had cash, cash equivalents, and marketable securities of $ 332.4 million.
If we are unable to raise capital or enter into business development transactions when needed or on acceptable terms, we could be forced to delay, reduce or eliminate our research and development programs or any future commercialization efforts. ​ As of December 31, 2025, we had cash, cash equivalents, and marketable securities of $ 201.7 million.
Based upon our current operating plan, we expect that our existing cash, cash equivalents, and marketable securities at December 31, 2024, along with amounts expected to be received as reimbursement for development costs under our collaboration and license agreements with Neurocrine and Novartis and interest income, to be sufficient to meet our 125 Table of Contents planned operating expenses and capital expenditure requirements into mid-2027.
Based upon our current operating plan, we expect that our existing cash, cash equivalents, and marketable securities at December 31, 2025, along with amounts expected to be received as reimbursement for development costs under our collaboration and license agreements with Neurocrine and Novartis and interest income, to be sufficient to meet our planned operating expenses and capital expenditure requirements into 2028.
If our development efforts are successful, we may also generate revenue from product sales. ​ Expenses ​ Research and Development Expenses ​ Research and development expenses consist primarily of costs incurred for our research activities, including our program discovery efforts, and the development of our proprietary antibody, gene therapy, vectorized antibody, and non-viral therapeutic platforms and programs which include: ​ ● employee-related expenses including salaries, benefits, and stock-based compensation expense; ​ ● costs of funding research performed by third parties that conduct research and development, preclinical and clinical activities, manufacturing and production design on our behalf; ​ ● the cost of purchasing laboratory supplies and non-capital equipment used in designing, developing and manufacturing preclinical and clinical study materials; ● consultant fees; ● facility costs including rent, depreciation and maintenance expenses; ● the cost of securing and protecting intellectual property rights associated with our research and development activities; and ● fees for maintaining licenses under our third-party licensing agreements. 119 Table of Contents Research and development costs are expensed as incurred.
If our development efforts are successful, we may also generate revenue from product sales. ​ Expenses ​ Research and Development Expenses ​ Research and development expenses consist primarily of costs incurred for our research activities, including our program discovery efforts, and the development of our proprietary antibody, gene therapy, and non-viral therapeutic platforms and programs, which include: ​ ● employee-related expenses including salaries, benefits, and stock-based compensation expense; ​ ● severance benefits, including cash severance, temporary health care coverage, and transition support services related to restructurings, which were recognized in 2025; ​ ● costs of funding research performed by third parties that conduct research and development, preclinical and clinical activities, manufacturing and production design on our behalf; ​ ● the cost of purchasing laboratory supplies and non-capital equipment used in designing, developing and manufacturing preclinical and clinical study materials; ● consultant fees; ● facility costs including rent, depreciation and maintenance expenses; ● the cost of securing and protecting intellectual property rights associated with our research and development activities; ● fees for maintaining licenses under our third-party licensing agreements; and ● payments under our research and collaboration agreements.
Looking forward, we have the potential to earn up to $8.2 billion in milestone payments across the partnered portfolio, including $2.9 billion in potential development milestone payments, as well as royalties. ​ All of the gene therapies in our wholly-owned and collaborative pipeline leverage TRACER.
Looking forward, we have the potential to earn up to $6.8 billion in milestone payments across the partnered portfolio, including $2.4 billion in potential development milestone payments, as well as royalties. All of the gene therapies in our wholly-owned and collaborative pipeline are delivered intravenously leveraging TRACER capsids.
Changes in our estimates of the expected remaining costs to complete the research and development services for our performance obligations can result in significant changes to the amount of revenue we recognize each period. 121 Table of Contents Results of Operations Comparison of the years ended December 31, 2024 and 2023: The following table summarizes our results of operations for the years ended December 31, 2024 and 2023, respectively, together with the changes in those items in dollars: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended ​ ​ ​ ​ ​ December 31, ​ ​ ​ ​ ​ 2024 2023 Change ​ ​ ​ (in thousands) ​ Collaboration revenue ​ $ 80,001 $ 250,008 $ (170,007) ​ Operating expenses: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Research and development ​ 127,368 ​ 92,172 ​ 35,196 ​ General and administrative ​ 35,920 ​ 35,822 ​ 98 ​ Total operating expenses ​ 163,288 ​ 127,994 ​ 35,294 ​ Other income, net: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Interest income ​ 18,328 ​ 11,721 ​ 6,607 ​ Other income ​ 622 ​ 3 ​ 619 ​ Total other income, net ​ 18,950 ​ 11,724 ​ 7,226 ​ (Loss) income before income taxes ​ ​ (64,337) ​ ​ 133,738 ​ ​ (198,075) ​ Income tax provision ​ ​ 665 ​ ​ 1,408 ​ ​ (743) ​ Net (loss) income ​ $ (65,002) ​ $ 132,330 ​ $ (197,332) ​ Collaboration Revenue Collaboration revenue was $80.0 million and $250.0 million for the years ended December 31, 2024 and 2023, respectively.
Other income, net decreased during the year ended December 31, 2025, primarily related to interest income as our marketable securities decreased during the year ended December 31, 2025, as compared to the year ended December 31, 2024. ​ 130 Table of Contents Comparison of the years ended December 31, 2024 and 2023: ​ The following table summarizes our results of operations for the years ended December 31, 2024 and 2023, respectively, together with the changes in those items in dollars: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended ​ ​ ​ ​ December 31, ​ ​ ​ ​ 2024 ​ ​ ​ 2023 ​ ​ ​ Change ​ ​ (in thousands) Collaboration revenue ​ $ 80,001 ​ ​ ​ $ 250,008 ​ ​ ​ $ (170,007) Operating expenses: ​ ​ ​ ​ ​ ​ ​ ​ ​ Research and development ​ 127,368 ​ 92,172 ​ 35,196 General and administrative ​ 35,920 ​ 35,822 ​ 98 Total operating expenses ​ 163,288 ​ 127,994 ​ 35,294 Other income, net: ​ ​ ​ ​ ​ ​ ​ ​ ​ Interest income ​ 18,328 ​ 11,721 ​ 6,607 Other income ​ 622 ​ 3 ​ 619 Total other income, net ​ 18,950 ​ 11,724 ​ 7,226 (Loss) income before income taxes ​ ​ (64,337) ​ ​ 133,738 ​ ​ (198,075) Income tax provision ​ ​ 665 ​ ​ 1,408 ​ ​ (743) Net (loss) income ​ $ (65,002) ​ $ 132,330 ​ $ (197,332) Collaboration Revenue Collaboration revenue was $80.0 million and $250.0 million for the years ended December 31, 2024 and 2023, respectively.
Funding Requirements ​ Our expenses increased during the year ended December 31, 2024 as compared with the prior year as our development programs progressed and we increased headcount.
Funding Requirements ​ Our expenses increased during the year ended December 31, 2025, as compared with the prior year as our development programs progressed.
For additional information about our revenue recognition policy, see the section titled “Summary of significant accounting policies and basis of presentation.” ​ For the foreseeable future, we expect substantially all of our revenue will be generated from the 2019 Neurocrine Collaboration Agreement, the 2023 Neurocrine Collaboration Agreement, the 2023 Novartis Collaboration Agreement, the 2022 Novartis Option and License Agreement, and our option and license agreement with Alexion entered into on October 1, 2021, or the Alexion Agreement, and any other strategic collaborations and out-licensing arrangements we may enter into in the future.
For additional information about our revenue recognition policy, see the section titled “Summary of significant accounting policies and basis of presentation” in Note 2 to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K. ​ For the foreseeable future, we expect substantially all of our revenue will be generated from the 2019 Neurocrine Collaboration Agreement, the 2023 Neurocrine Collaboration Agreement, the 2023 Novartis Collaboration Agreement, the 2022 Novartis Option and License Agreement, and our option and license agreement with Alexion entered into on October 1, 2021, or the Alexion Agreement, and any other strategic collaborations and out-licensing arrangements we may enter into in the future.
All amounts for the year ended December 31, 2023, have been reclassified to conform to the current year’s presentation. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended ​ ​ ​ ​ ​ December 31, ​ ​ ​ ​ ​ 2024 2023 Change ​ ​ ​ (in thousands) ​ Internal research and development ​ $ 38,422 $ 27,860 ​ $ 10,562 ​ External research and development ​ 58,081 ​ 46,008 ​ 12,073 ​ Facilities and other ​ 30,865 ​ 18,304 ​ 12,561 ​ Total research and development expenses ​ $ 127,368 ​ $ 92,172 ​ $ 35,196 ​ ​ The increase in research and development expense for the year ended December 31, 2024 was primarily attributable to the following: ​ ● approximately $12.6 million for facility and other costs primarily related to our lease for additional laboratory and office space at 75 Hayden Avenue in Lexington, Massachusetts, which we took occupancy of on February 1, 2024, along with an impairment charge on our leased office and laboratory space in Cambridge, Massachusetts; ​ ● approximately $12.1 million for external research and development costs related to increased program-related spending; and ​ ● approximately $10.6 million for increased internal research and development costs associated with higher headcount in research and development functions as compared to the same period in the prior year . ​ General and Administrative Expense ​ General and administrative expense balance remained consistent for the year ended December 31, 2024, compared to December 31, 2023. ​ Other Income, Net Other income, net of approximately $19.0 million was recognized during the year ended December 31, 2024, as compared to $11.7 million during the year ended December 31, 2023.
All amounts for the year ended December 31, 2023, have been reclassified to conform to the current year’s presentation. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended ​ ​ ​ ​ December 31, ​ ​ ​ ​ 2024 ​ ​ ​ 2023 ​ ​ ​ Change ​ ​ (in thousands) Internal research and development ​ $ 38,422 ​ ​ ​ $ 27,860 ​ $ 10,562 External research and development: ​ ​ ​ ​ ​ ​ Anti-tau antibody program (VY7523) ​ ​ 15,647 ​ ​ 16,923 ​ ​ (1,276) SOD1 silencing gene therapy program ​ ​ 15,818 ​ ​ 6,251 ​ ​ 9,567 Tau silencing gene therapy program (VY1706) ​ ​ 7,455 ​ ​ 696 ​ ​ 6,759 Partnered programs ​ ​ 4,985 ​ ​ 7,650 ​ ​ (2,665) Other programs and platforms ​ ​ 14,176 ​ ​ 14,488 ​ ​ (312) Facilities and other ​ 30,865 ​ 18,304 ​ 12,561 Total research and development expenses ​ $ 127,368 ​ $ 92,172 ​ $ 35,196 ​ The increase in research and development expenses for the year ended December 31, 2024, was primarily attributable to the following: ​ ● approximately $12.6 million for facility and other costs primarily related to our lease for additional laboratory and office space at 75 Hayden Avenue in Lexington, Massachusetts, which we took occupancy of on February 1, 2024, along with an impairment charge on our leased office and laboratory space in Cambridge, Massachusetts; ​ ● approximately $12.1 million for external research and development costs related to increased program-related spending; and ​ ● approximately $10.6 million for increased internal research and development costs associated with higher headcount in research and development functions as compared to the same period in the prior year . ​ General and Administrative Expense ​ General and administrative expenses remained consistent for the year ended December 31, 2024, compared to December 31, 2023. ​ Other Income, Net Other income, net of approximately $19.0 million was recognized during the year ended December 31, 2024, as compared to $11.7 million during the year ended December 31, 2023.
Net cash used in investing activities was $7.3 million during the year ended December 31, 2022.
Net cash used in investing activities was $94.9 million during the year ended December 31, 2024.
The cash used in investing activities for the year ended December 31, 2022 was primarily due to $54.8 million for purchases of marketable securities and $2.5 million for purchases of property and equipment, offset by $50.0 million from proceeds from maturities and sales of marketable securities.
The cash provided by investing activities for the year ended December 31, 2025, was primarily due to $262.0 million in proceeds from maturities and sales of marketable securities, partially offset by $133.9 million in purchases of marketable securities and $2.6 million in purchases of property and equipment.
We expect our expenses to continue to increase as we continue the research and development of, conduct clinical trials of, and seek marketing approval for our product candidates including our Phase 1 MAD clinical trial to evaluate VY7523 in 2025, and as we continue to enter into or conduct activities in connection with our collaboration agreements.
We will continue to incur research and development expenses as we conduct clinical trials and seek marketing approval of our product candidates, and as we continue to enter into or conduct activities in connection with our collaboration agreements.
Net cash provided by financing activities was $1.1 million during the year ended December 31, 2022 primarily due to the proceeds from the exercise of stock options, and purchases by our employees of our common stock under our employee stock purchase plan.
Cash Flows from Financing Activities Net cash provided by financing activities was $0.8 million during the year ended December 31, 2025, primarily due to the $0.5 million in proceeds from the purchase of common stock under the employee stock purchase plan.
In total, these partnerships have delivered more than $500.0 million in non-dilutive funding to us to date, including upfront fees, development milestone payments, option exercise fees, license fees, and research and development expense reimbursement.
We have also licensed capsids to Alexion for one undisclosed rare neurological disease target and to Novartis for one undisclosed CNS target. In total, our partnerships have delivered more than $500.0 million in non-dilutive funding to us to date, including upfront fees, development milestone payments, option exercise fees, license fees, and research and development expense reimbursement.
Some of our programs are wholly-owned, and some are advancing with licensees and collaborators including Alexion, AstraZeneca Rare Disease, or Alexion; Novartis Pharma AG, or Novartis; and Neurocrine Biosciences, Inc., or Neurocrine.
Some of our programs are wholly-owned, and some are advancing with licensees and collaborators, including Alexion, AstraZeneca Rare Disease, or Alexion; Novartis Pharma AG, or Novartis; Neurocrine Biosciences, Inc., or Neurocrine; and Transition Bio, Inc., or Transition Bio. We are advancing our own proprietary pipeline of drug candidates for neurological diseases, with a focus on AD.
Milestone payments that are not within our control or the licensee’s control, such as regulatory approvals, are not considered probable of being achieved until those approvals are received. At the end of each reporting period, we re-evaluate the probability of achievement of such development milestones and any related constraint, and if necessary, adjust our estimate of the overall transaction price.
At the end of each reporting period, we re-evaluate the probability of achievement of such development and regulatory milestones and any related constraint, and if necessary, adjust our estimate of the overall transaction price.
The effects of material revisions in estimates, if any, will be reflected in the financial statements prospectively from the date of change in estimates. ​ While our significant accounting policies are described in more detail in the notes to our consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K, we believe that certain aspects of our accounting policy on revenue recognition require the most significant judgments and estimates in the preparation of our financial statements. 120 Table of Contents Revenue Recognition – ASC 606 ​ We recognize revenue in accordance with Financial Accounting Standards Board, or FASB, Accounting Standards Codification, or ASC, Topic 606 Revenue from Contracts with Customers, or ASC 606. ​ We enter into license, option, and collaboration agreements which are within the scope of ASC 606, under which we license or provide options to license certain of our product candidates and, in certain cases, perform research and development.
The effects of material revisions in estimates, if any, will be reflected in the financial statements prospectively from the date of change in estimates. ​ While our significant accounting policies are described in more detail in the notes to our consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K, we believe that certain aspects of our accounting policy on revenue recognition require the most significant judgments and estimates in the preparation of our financial statements.
TRACER is a broadly applicable, RNA-based screening platform that enables rapid discovery of AAV capsids with robust penetration of the blood-brain barrier, or BBB, and enhanced CNS tropism in multiple species, including NHPs. We are also developing a second non-viral therapeutics platform focused on non-viral receptor-mediated transport across the BBB.
TRACER is a broadly applicable, RNA-based screening platform that enables rapid discovery of AAV capsids with robust penetration of the blood-brain barrier, or BBB, and enhanced CNS tropism in multiple species, including NHPs. We subsequently utilized these BBB-penetrant capsids to identify the receptors by which the capsids enter the BBB.
For the year ended December 31, 2024, we recognized $49.7 million of collaboration revenue from the 2023 Neurocrine Collaboration Agreement, $15.0 million of collaboration revenue from an amendment, or the Novartis Amendment, to our option and license agreement with Novartis entered into in March 2022, or the 2022 Novartis Option and License Agreement, $10.4 million of collaboration revenue from the 2019 Neurocrine Collaboration Agreement, and $4.9 million of collaboration revenue from the 2023 Novartis Collaboration Agreement.
During the year ended December 31, 2024, we recognized collaboration revenue in connection with the following agreements: ● $49.7 million under the 2023 Neurocrine Collaboration Agreement; ● $15.0 million of collaboration revenue from the execution of the amendment to the 2022 Novartis Option and License Agreement, or the Novartis Amendment; ● $10.4 million under the 2019 Neurocrine Collaboration Agreement; and ● $4.9 million under the 2023 Novartis Collaboration Agreement. ​ ​ ​ ​ 129 Table of Contents Research and Development Expense Research and development expense increased by $7.3 million from $127.4 million for the year ended December 31, 2024, to $134.7 million for the year ended December 31, 2025.
Other income, net during the year ended December 31, 2024, was primarily related to interest income due to increased interest rates on increased balances of marketable securities, as our marketable securities increased during the year ended December 31, 2024, as compared to the year ended December 31, 2023. 123 Table of Contents Liquidity and Capital Resources ​ Sources of Liquidity ​ We have funded our operations primarily through private placements of redeemable convertible preferred stock, public offerings and private placements of our common stock, strategic collaborations and option and license arrangements, including our 2019 Neurocrine Agreement, 2023 Neurocrine Collaboration Agreement, 2022 Novartis Agreement, 2023 Novartis Collaboration Agreement, Alexion Agreement, and with our prior collaboration agreements. ​ As of December 31, 2024, we had cash, cash equivalents, and marketable securities of $332.4 million.
Other income, net during the year ended December 31, 2024, increased primarily related to interest income due to higher interest rates and as our marketable securities increased during the year ended December 31, 2024, as compared to the year ended December 31, 2023. ​ 132 Table of Contents Liquidity and Capital Resources ​ Sources of Liquidity ​ We have funded our operations primarily through private placements of redeemable convertible preferred stock, public offerings and private placements of our common stock, strategic collaborations and option and license arrangements, including our 2019 Neurocrine Collaboration Agreement, 2023 Neurocrine Collaboration Agreement, 2022 Novartis Agreement, 2023 Novartis Collaboration Agreement, Alexion Agreement, and with our prior collaboration agreements. ​ Cash Flows ​ The following table provides information regarding our cash flows: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended ​ ​ ​ December 31, ​ ​ ​ 2025 ​ ​ ​ 2024 ​ ​ ​ 2023 ​ ​ ​ ​ ​ (in thousands) ​ Net cash (used in) provided by: ​ ​ ​ ​ ​ ​ ​ ​ ​ Operating activities ​ $ (132,467) ​ $ (15,310) ​ $ 77,919 ​ Investing activities ​ 125,446 ​ (94,859) ​ (141,643) ​ Financing activities ​ 816 ​ 114,015 ​ 33,645 ​ Net (decrease) increase in cash, cash equivalents, and restricted cash ​ $ (6,205) ​ $ 3,846 ​ $ (30,079) ​ Cash Flows from Operating Activities Net cash used in operating activities was $132.5 million during the year ended December 31, 2025.
Net cash used in operating activities was $12.5 million during the year ended December 31, 2022.
Net cash provided by operating activities was $77.9 million during the year ended December 31, 2023.
For more information, refer to Note 7 to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K. ​ Off-Balance Sheet Arrangements ​ We did not have, during the periods presented, and we do not currently have, any off-balance sheet arrangements, as defined under applicable rules of the Securities and Exchange Commission, or the SEC. ​ Smaller Reporting Company Status ​ As of June 30, 2024, we ceased to qualify as a smaller reporting company, which requires us to comply with disclosure requirements that are applicable to other public companies that are not smaller reporting companies following the filing of our Annual Report on Form 10-K for the year ending December 31, 2024, and any portions of our definitive proxy statement relating to our 2025 Annual Meeting of Stockholders incorporated by reference therein. ​
For more information, refer to Note 7 to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K. ​ Off-Balance Sheet Arrangements ​ We did not have, during the periods presented, and we do not currently have, any off-balance sheet arrangements, as defined under applicable rules of the Securities and Exchange Commission, or the SEC. ​ ​
Despite reporting $132.3 million in net income for the year ended December 31, 2023, we have a history of incurring significant losses. We reported a net loss of $65.0 million for the year ended December 31, 2024, and we reported a net loss of $46.4 million for the year ended December 31, 2022.
Restructuring expenses are recorded as either research and development expense or general and administrative expense in the consolidated statements of operations and comprehensive loss. Despite reporting $132.3 million in net income for the year ended December 31, 2023, we have a history of incurring significant losses.
Other significant costs include corporate facility costs not otherwise included in research and development expenses, legal fees related to patent and corporate matters and fees for accounting and consulting services. ​ During the year ended December 31, 2024, our general and administrative expenses have remained consistent with the amount recorded in the same period in prior year. ​ Other Income, Net ​ Other income, net consists primarily of interest income on our marketable securities. ​ Critical Accounting Policies and Estimates ​ Our management’s discussion and analysis of our consolidated financial condition and results of operations are based on our consolidated financial statements, which have been prepared in accordance with U.S. generally accepted accounting principles.
Other Income, Net ​ Other income, net consists primarily of interest income on our marketable securities. ​ Critical Accounting Policies and Estimates ​ Our management’s discussion and analysis of our consolidated financial condition and results of operations are based on our consolidated financial statements, which have been prepared in accordance with U.S. generally accepted accounting principles.
We expect that Neurocrine will submit IND filings in 2025 for the two most advanced of these programs, a glucosylceramidase beta 1, or GBA1, gene therapy program for Parkinson’s disease and other GBA1-mediated diseases, or the GBA1 Program, and a frataxin, or FXN, gene therapy program for FA, or the FA Program.
Two of these programs are in collaboration with Neurocrine: a frataxin (FXN) gene therapy program for FA, which we refer to as the FA Program, and a glucosylceramidase beta 1, or GBA1, gene therapy program that will focus on Gaucher and PD, which we refer to as the GBA1 Program.
In addition to the Neurocrine collaborations, we have partnered with Novartis on TRACER Capsid-based gene therapies for spinal muscular atrophy 117 Table of Contents and Huntington’s disease. We have also licensed capsids to Novartis for three undisclosed CNS targets and to Alexion for one undisclosed rare neurological disease target.
Two of these three programs have development candidates selected and are advancing through preclinical toxicology studies. In addition to the Neurocrine collaborations, we have partnered with Novartis on TRACER Capsid-based gene therapies for spinal muscular atrophy and Huntington’s disease.
The cash used in operating activities for the year ended December 31, 2022 was primarily driven by operating expenses, net of stock-based compensation and depreciation, offset by an increase in deferred revenue partially driven by the upfront payment of $54.0 million from Novartis in connection with our entry into the 2022 Novartis Option and License Agreement during the year ended December 31, 2022. 124 Table of Contents Cash Flows from Investing Activities Net cash used in investing activities was $94.9 million during the year ended December 31, 2024.
The cash used in operating activities for the year ended December 31, 2025, was primarily driven by our net loss for the year ended December 31, 2025, of $119.7 million and a decrease in deferred revenue of $28.8 million due to revenue recognized under the 2019 Neurocrine Agreement, 2023 Neurocrine Collaboration Agreement, and 2023 Novartis Agreement, partially offset by stock-based compensation expense of $14.8 million. ​ Net cash used in operating activities was $15.3 million during the year ended December 31, 2024.
As of December 31, 2024, we had an accumulated deficit of $326.2 million. We expect to continue to incur significant expenses and operating losses for the foreseeable future.
We reported net losses of $119.7 million and $65.0 million for the years ended December 31, 2025 and 2024, respectively. As of December 31, 2025, we had an accumulated deficit of $445.9 million.
Our wholly-owned prioritized pipeline includes two tau targeting programs: VY7523 (which we formerly referred to as VY-TAU01), an anti-tau antibody for AD and VY1706, a tau silencing gene therapy for AD. The murine version of VY7523 reduced tau spread by more than 60% in preclinical studies.
Our wholly-owned prioritized pipeline includes two tau targeting programs: VY1706, a tau silencing gene therapy for AD, and VY7523, an anti-tau antibody for AD. VY1706 is a gene therapy that leverages an intravenously delivered TRACER Capsid containing a vectorized small interfering RNA specifically targeting tau mRNA.
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We are advancing our own proprietary pipeline of drug candidates for neurological diseases, with a focus on AD, and particularly on tau, which we view as a critically important AD target.
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We expect to complete a good laboratory practices, or GLP, toxicology study in the first quarter of 2026.
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We believe this trial has the potential to generate proof-of-concept data for slowing the spread of pathological tau via tau positron emission tomography imaging in the second half of 2026. VY1706 was selected as the development candidate for the tau silencing gene therapy in November 2024.
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Having had a Type C communication with the FDA in the first quarter of 2026, we anticipate the submission of an investigational new drug, or IND, application in the second quarter of 2026 and initiation of a clinical trial for the VY1706 program in the second half of 2026.
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We anticipate submission of an investigational new drug, or IND, for the VY1706 program in 2026. Our proprietary pipeline also includes early research initiatives to develop a vectorized anti-amyloid antibody for AD and a vectorized superoxide dismutase 1, or SOD1, knockdown gene therapy for SOD1 amyotrophic lateral sclerosis. We are also working with our collaboration partners on multiple programs.
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VY7523 is an IV-administered, recombinant, humanized IgG4 monoclonal antibody developed to inhibit the spread of pathological tau, which is closely correlated with disease progression and cognitive decline in AD. The murine version of VY7523 reduced tau spread by approximately 70% in preclinical studies.
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We are advancing seven gene therapy programs with Neurocrine. Development candidates were selected for three of these programs in 2024, resulting in milestone payments to us.
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We expect initial tau positron emission tomography, or PET, imaging data in the second half of 2026. Our proprietary pipeline also includes an early research initiative to develop a non-viral therapeutic that leverages our proprietary Voyager NeuroShuttle TM platform for the treatment of an undisclosed neurological disease.
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These two programs are particularly significant to us for two reasons: the subsequent clinical trials of these programs have the potential to establish human proof-of-concept for the TRACER Capsids, and we have the option to opt-in on co-development and co-commercialization in the United States. for both products.
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We paused investment in our apolipoprotein E, or APOE, gene therapy program to prioritize other programs. The decision is unrelated to data from the program, which have demonstrated dose-dependent APOE4 protein reduction and APOE2 protein expression in murine studies while maintaining total APOE at physiological levels.
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Financial Operations Overview Revenue ​ To date, we have not generated any revenue from product sales and do not expect to generate any revenue from product sales for the foreseeable future.
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In addition to our wholly-owned pipeline, we are advancing three programs with collaboration partners for which we retain options to participate in future development and commercialization.
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We are in the early stages of development of our product candidates. During the year ended December 31, 2024, our research and development expenses have increased as compared to the amounts recorded in the same period in the prior year.
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Neurocrine has stated that, pending successful FDA IND clearance, it intends to initiate a clinical trial with NBIB-’223 for FA in the second half of 2026. In preclinical studies, IV-administered NBIB-’223 resulted in protein expression in the brain and heart.
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As our research and development programs progress and as we identify product candidates and initiate preclinical studies and clinical trials, including our clinical trials to evaluate VY7523, we expect research and development costs to continue to increase.
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Neurocrine has informed us that it continues to progress the GBA1 Program in addition to three gene therapy programs for which we do not have opt-in rights.
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Based upon our current operating plan, we expect that our existing cash, cash equivalents, and marketable securities at December 31, 2024, along with amounts expected to be received as reimbursement for development costs under our collaboration and license agreements with Neurocrine and Novartis and interest income, to be sufficient to meet our planned operating expenses and capital expenditure requirements into mid-2027. ​ Cash Flows ​ The following table provides information regarding our cash flows: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended ​ ​ ​ December 31, ​ ​ ​ 2024 2023 2022 ​ ​ (in thousands) ​ Net cash (used in) provided by: ​ ​ ​ ​ ​ ​ ​ ​ ​ Operating activities ​ $ (15,310) ​ $ 77,919 ​ $ (12,509) ​ Investing activities ​ (94,859) ​ (141,643) ​ (7,339) ​ Financing activities ​ 114,015 ​ 33,645 ​ 1,110 ​ Net increase (decrease) in cash, cash equivalents, and restricted cash ​ $ 3,846 ​ $ (30,079) ​ $ (18,738) ​ Cash Flows from Operating Activities Net cash used in operating activities was $15.3 million during the year ended December 31, 2024.
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We maintain an option to co-develop and co-commercialize 40% of the FA Program and 50% of the GBA1 Program for PD in the U.S. 123 Table of Contents Our third opt-in program is our collaboration with Transition Bio to develop selective small molecules for the treatment of amyotrophic lateral sclerosis, or ALS, and frontotemporal dementia with TDP-43 pathology.
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We have an option for an exclusive license to the worldwide rights to develop and commercialize this program. In addition to the three partnered programs for which we retain opt-in rights, we have entered into multiple additional collaboration and licensing agreements with collaboration partners. We are collaborating with Neurocrine on three gene therapy programs against undisclosed targets.
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We have identified multiple receptors, including alkaline phosphatase, or ALPL, that are capable of transporting a large biologic molecule, such as a capsid, across the BBB. We have leveraged our knowledge of BBB receptors, discovered using TRACER, to develop a second delivery platform called Voyager NeuroShuttle TM .
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Voyager NeuroShuttle is a non-viral delivery platform leveraging novel receptor-binding molecules to transport multiple modalities of neurotherapeutics across the blood-brain barrier. The first NeuroShuttle within the platform leverages the ALPL receptor.
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During the third quarter of 2025, we shared the results of initial murine proof-of-concept studies of ALPL-VYGR-NeuroShuttle demonstrating in the study sustained brain expression over three weeks, compared to less than one week for transferrin receptor, or TfR, shuttles, with no impact on circulating reticulocytes or downstream measurements of anemia.
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In addition to the initial murine proof-of-concept data provided for the ALPL-VYGR-NeuroShuttle, a proof-of-concept study using anti-amyloid antibodies demonstrated that the ALPL-NeuroShuttle showed similar target engagement to a TfR shuttle.
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We initiated a discovery program using ALPL-VYGR-NeuroShuttle to target an undisclosed neurological disease. ​ During the year ended December 31, 2025, the restructurings in June 2025 and December 2025 resulted in restructuring expenses of $4.3 million.
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Employees impacted by the restructurings were eligible to receive one-time severance benefits, including cash severance, temporary health care coverage, and transition support services, subject to each employee entering into a separation agreement, which included a general release of claims against the company.
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For the year ended December 31, 2025, we recognized $30.5 million of collaboration revenue from the 2023 Neurocrine Collaboration Agreement, $5.9 million of collaboration revenue from the 2023 Novartis Collaboration Agreement, $3.5 million of collaboration revenue from the 2019 Neurocrine Collaboration Agreement, and $0.5 million of collaboration revenue from other agreements.
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We are in the early stages of development of our product candidates. We expect research and development expenses to decrease in the near term as a result of continued portfolio prioritization and alignment of operating expenditures with our current capital resources.
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Other significant costs include corporate facility costs not otherwise included in research and development expenses, legal fees related to patent and corporate matters, fees for accounting and consulting services, and one-time severance benefits, including cash severance, temporary health care coverage, and transition support services related to restructurings recognized in 2025.
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We expect general and administrative costs to decrease in the near term as a result of our continued disciplined expense management.
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Revenue Recognition – ASC 606 ​ We recognize revenue in accordance with Financial Accounting Standards Board, or FASB, Accounting Standards Codification, or ASC, Topic 606 Revenue from Contracts with Customers, or ASC 606. ​ We enter into license, option, and collaboration agreements which are within the scope of ASC 606, under which we license or provide options to license certain of our product candidates and, in certain cases, perform research and development.
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Milestone payments that are not within our control or the licensee’s control, such as regulatory approvals, are not considered probable of being achieved until those approvals are received.

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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 changeOur primary exposure to market risk is interest rate sensitivity, which is affected by changes in the general level of U.S. interest rates, particularly because our investments, including cash equivalents, are in the form of money market funds and marketable securities 127 Table of Contents and are invested in U.S. Treasury notes.
Biggest changeOur primary exposure to market risk is interest rate sensitivity, which is affected by changes in the general level of U.S. interest rates, particularly because our investments, including cash equivalents, are in the form of money market funds and marketable securities and are invested in U.S. Treasury or government obligations and corporate securities.
We do not believe that inflation had a material effect on our business, financial condition, or results of operations during the year ended December 31, 2024. ​ ITEM 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DAT A The financial statements required to be filed pursuant to this Item 8 are appended to this report.
We do not believe that inflation had a material effect on our business, financial condition, or results of operations during the year ended December 31, 2025. ​ 136 Table of Contents ITEM 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DAT A The financial statements required to be filed pursuant to this Item 8 are appended to this report.

Other VYGR 10-K year-over-year comparisons