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What changed in REGENXBIO Inc.'s 10-K — 2024 vs 2025

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

+647 added−527 removedSource: 10-K (2026-03-05) vs 10-K (2025-03-13)

Top changes in REGENXBIO Inc.'s 2025 10-K

647 paragraphs added · 527 removed · 433 edited across 7 sections

Item 1. Business

Business — how the company describes what it does

174 edited+79 added−32 removed233 unchanged
Biggest changeOur patent portfolio relating to ABBV-RGX-314 includes one issued U.S. patent that will expire in 2037, one pending PCT and seven PCTs that have entered national stage for which any issued U.S. or European patent would expire in 2037, 2038, 2039, 2040 or 2043, in each case without taking into account any possible patent term adjustment or extension. 16 Neuromuscular Diseases In addition to our NAV Technology Platform patents covering the NAV AAV8 vector and its manufacture, our patent portfolio includes more recent filings relating to RGX-202, the NAV AAV8 capsid carrying our microdystrophin construct used to treat Duchenne and the manufacture of RGX-202.
Biggest changeOur patent portfolio relating to RGX-121 includes one issued U.S. patent that will expire in 2034, one issued U.S. patent that will expire in 2038, one issued U.S. patent that will expire in 2039, one issued U.S. patent that will expire in 2040, one issued U.S. patent that will expire in 2042, one issued European patent that will expire in 2036, one pending PCT application and ten PCTs that have entered national stage for which any issued U.S. or European patents would expire in 2034, 2036, 2037, 2038, 2039, 2041 or 2042, in each case without taking into account any possible patent term adjustment or extension. 18 Table of Contents Manufacturing Our patent portfolio covers aspects of our manufacturing processes which support our ability to perform large scale manufacturing, increase yield and purity of AAV vector products and meet clinical supply requirements.
Wilson at Penn after September 2014 during the performance of a research program we sponsored; and • is owned by Penn; and • is necessary or useful for the practice of the licensed patent rights.
Wilson at Penn after September 2014 during the performance of a research program we sponsored; • is owned by Penn; and • is necessary or useful for the practice of the licensed patent rights.
In order to obtain coverage and reimbursement for any product that might be approved for sale, it may be necessary to conduct expensive pharmacoeconomic studies in order to demonstrate the medical necessity and cost-effectiveness of the products, in addition to the costs required to obtain regulatory approvals.
To obtain coverage and reimbursement for any product that might be approved for sale, it may be necessary to conduct expensive pharmacoeconomic studies in order to demonstrate the medical necessity and cost-effectiveness of the products, in addition to the costs required to obtain regulatory approvals.
Under this Minnesota license agreement, as amended, we receive an exclusive license under the licensed patent rights to make, have made, use, offer to sell or sell, offer to lease or lease, import or otherwise offer to dispose or dispose of products covered by the licensed patent rights in all fields of use in any country or territory in which a licensed patent has been issued and is unexpired or a licensed patent application is pending until November 2019, after which time the field of use would be limited to all fields of use using 15 our NAV Vectors in addition to certain additional indications and areas.
Under this Minnesota license agreement, as amended, we receive an exclusive license under the licensed patent rights to make, have made, use, offer to sell or sell, offer to lease or lease, import or otherwise offer to dispose or dispose of products covered by the licensed patent rights in all fields of use in any country or territory in which a licensed patent has been issued and is unexpired or a licensed patent application is pending until November 2019, after which time the field of use would be limited to all fields of use using our NAV Vectors in addition to certain additional indications and areas.
The grant of marketing authorization in the EU for products containing viable human tissues or cells such as gene therapy medicinal products is governed by Regulation (EC) No 1394/2007 on advanced therapy medicinal products, read in combination with Directive 2001/83/EC on the Community code relating to medicinal products for human use and Regulation (EC) No 726/2004 laying 26 down Community procedures for the authorization and supervision of medicinal products for human and veterinary use and establishing the EMA.
The grant of marketing authorization in the EU for products containing viable human tissues or cells such as gene therapy medicinal products is governed by Regulation (EC) No 1394/2007 on advanced therapy medicinal products, read in combination with Directive 2001/83/EC on the Community code relating to medicinal products for human use and Regulation (EC) No 726/2004 laying down Community procedures for the authorization and supervision of medicinal products for human and veterinary use and establishing the EMA.
Penn has the right to terminate: • with notice if we are late in paying money due under the license agreement; • with notice if we fail to achieve a diligence event on or before the applicable completion date or otherwise breach the license agreement; 14 • if we or our affiliates experience insolvency; or • if we commence any action against Penn to declare or render any claim of the licensed patent rights invalid or unenforceable.
Penn has the right to terminate: • with notice if we are late in paying money due under the license agreement; • with notice if we fail to achieve a diligence event on or before the applicable completion date or otherwise breach the license agreement; • if we or our affiliates experience insolvency; or • if we commence any action against Penn to declare or render any claim of the licensed patent rights invalid or unenforceable.
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. Equivalent laws have been adopted in other countries that impose similar obligations. 24 Other U.S.
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. Equivalent laws have been adopted in other countries that impose similar obligations. Other U.S.
Moreover, a payor’s decision to provide coverage for a drug product does not imply that an adequate reimbursement rate will be approved. 25 Third-party payors are increasingly challenging the price and examining the medical necessity and cost-effectiveness of medical products and services, in addition to their safety and efficacy.
Moreover, a payor’s decision to provide coverage for a drug product does not imply that an adequate reimbursement rate will be approved. Third-party payors are increasingly challenging the price and examining the medical necessity and cost-effectiveness of medical products and services, in addition to their safety and efficacy.
Biological Products Development Process 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, including evaluations of product chemistry, formulations, toxicity in animal studies in accordance with good laboratory practice (GLP) and applicable requirements for the humane use of laboratory animals or other applicable regulations; • submission to the FDA of an IND, which must become effective before human clinical studies may begin; • performance of adequate and well-controlled human clinical studies according to the FDA’s requirements for good clinical practice (GCP) and additional requirements for the protection of human research subjects and their health information, to establish the safety 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, as well as information on the chemistry, manufacturing and controls to ensure product identity and quality, and proposed labeling; • satisfactory completion of an FDA inspection 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 and, if applicable, the FDA’s current good tissue practice (GTP), for the use of human cellular and tissue products; • potential FDA inspection of the nonclinical and clinical study sites and the clinical study sponsor that generated the data in support of the BLA; and • FDA review and approval, or licensure, of the BLA.
Biological Products Development Process 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, including evaluations of product chemistry, formulations, toxicity in animal studies in accordance with good laboratory practice (GLP) and applicable requirements for the humane use of laboratory animals or other applicable regulations; • submission to the FDA of an IND, which must become effective before human clinical studies may begin; • performance of adequate and well-controlled human clinical studies according to the FDA’s requirements for good clinical practice (GCP) and additional requirements for the protection of human research subjects and their health information, to establish the safety and efficacy of the proposed biological product for its intended use; 20 Table of Contents • 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, as well as information on the chemistry, manufacturing and controls to ensure product identity and quality, and proposed labeling; • satisfactory completion of an FDA inspection 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 and, if applicable, the FDA’s current good tissue practice (GTP), for the use of human cellular and tissue products; • potential FDA inspection of the nonclinical and clinical study sites and the clinical study sponsor that generated the data in support of the BLA; and • FDA review and approval, or licensure, of the BLA.
Our Good Manufacturing Practices (cGMP) production facility, the REGENXBIO Manufacturing Innovation Center (RMIC), is located in our corporate headquarters in Rockville, Maryland. The RMIC has been designed to support clinical and future commercial production of AAV Therapeutics and has been in operation since mid-2022.
Our Good Manufacturing Practices (cGMP) production facility, the REGENXBIO Manufacturing Innovation Center (RMIC), is located in our corporate headquarters in Rockville, Maryland. The RMIC was designed to support clinical and future commercial production of AAV therapeutics and has been in operation since mid-2022.
Applications to the FDA are required before conducting clinical testing of biological products, and each clinical study protocol for a gene therapy product is reviewed by the FDA. 18 Within the FDA, the Center for Biologics Evaluation and Research (CBER) regulates gene therapy products as biological products.
Applications to the FDA are required before conducting clinical testing of biological products, and each clinical study protocol for a gene therapy product is reviewed by the FDA. Within the FDA, the Center for Biologics Evaluation and Research (CBER) regulates gene therapy products as biological products.
Our AAV Therapeutic Platform Discovery and Development of AAV Therapeutics We have a team of scientists and engineers dedicated to expanding the understanding and applications of AAV vectors, applying the differentiated capabilities of the NAV Technology Platform and exploring the potential to generate new, innovative AAV Therapeutics.
Our AAV Platform Discovery and Development We have a team of scientists and engineers dedicated to expanding the understanding and applications of AAV vectors, applying the differentiated capabilities of the NAV Technology Platform and exploring the potential to generate new, innovative AAV therapeutics.
To date, thousands of patients have been treated by REGENXBIO and our NAV Technology Licensees using NAV Vectors across clinical trials, managed access and commercial settings. 12 Our NAV Technology Licensees are shown below.
To date, thousands of patients have been treated by REGENXBIO and our NAV Technology Licensees using NAV Vectors across clinical trials, managed access and commercial settings. Our NAV Technology Licensees are shown below.
Clinical studies involve the administration of the biological product candidate to healthy volunteers or patients under the supervision of qualified investigators, generally physicians not employed by or under the study sponsor’s control.
Clinical studies involve the administration of the biological product candidate to healthy volunteers or patients under the supervision of qualified investigators, generally physicians not employed by the study sponsor or under the study sponsor's control.
Wilson, or other Penn researchers working under his direct supervision at Penn; and • is related to the AAV technology platform discovered by Dr. Wilson prior to September 2014; or • is related to the AAV technology platform discovered by Dr.
Wilson, or other Penn researchers working under his direct supervision at Penn; • is related to the AAV technology platform discovered by Dr. Wilson prior to September 2014 or discovered by Dr.
Under the license agreement, as amended, we were entitled to receive over $270 million in fees, development and commercial milestones. In addition, we are entitled to receive mid-single to low double-digit royalties on net sales for Zolgensma or any product developed for the treatment of SMA using the NAV AAV9 vector.
Under the license agreement, as amended, we were entitled to receive over $270 million in fees, development and commercial milestones. In addition, we are entitled to receive mid-single to low double-digit royalties on net sales of Zolgensma, Itvisma or any other product developed for the treatment of SMA using the NAV AAV9 vector.
Neurodegenerative Diseases In addition to our NAV Technology Platform patents covering the NAV AAV9 vector and the manufacture of NAV AAV9 vector used in our neurodegenerative disease program, our RGX-121 patent portfolio includes more recent filings that cover our clinical candidate vector, routes of administration used in our neurodegenerative disease clinical-stage program (intracisternal administration for intrathecal delivery, as well as lumbar puncture and intraventricular administration), formulations and clinical protocols.
Neurodegenerative Diseases In addition to our patents covering the manufacture of NAV AAV9 vector used in our neurodegenerative disease program, our RGX-121 patent portfolio includes more recent filings that cover our clinical candidate vector, routes of administration used in our neurodegenerative disease clinical-stage program (intracisternal administration for intrathecal delivery, as well as lumbar puncture and intraventricular administration), formulations and clinical protocols.
Federal Anti-Kickback Statute violations and certain marketing practices, including off-label promotion, also may implicate the FCA; • federal criminal laws that prohibit executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters; • the federal Physician Payment Sunshine Act, which requires certain manufacturers of drugs, devices, biologics and medical supplies to report annually to the Centers for Medicare & Medicaid Services (CMS) information related to payments and other transfers of value to physicians and teaching hospitals, and ownership and investment interests held by physicians and their immediate family members; • the Health Insurance Portability and Accountability Act of 1996 (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, which governs the conduct of certain electronic healthcare transactions and protects the security and privacy of protected health information; and • state and foreign law equivalents of each of the above federal laws, such as anti-kickback and false claims laws which may apply to: items or services reimbursed by any third-party payor, including commercial insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures; and state laws governing the privacy and security of health information in certain circumstances.
Federal Anti-Kickback Statute violations and certain marketing practices, including off-label promotion, also may implicate the FCA; • federal criminal laws that prohibit executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters; 26 Table of Contents • the federal Physician Payment Sunshine Act, which requires certain manufacturers of drugs, devices, biologics and medical supplies to report annually to the Centers for Medicare & Medicaid Services (CMS) information related to payments and other transfers of value to physicians and teaching hospitals, and ownership and investment interests held by physicians and their immediate family members; • the Health Insurance Portability and Accountability Act of 1996 (HIPAA) imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters; • regulations promulgated under HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, which govern the conduct of certain electronic healthcare transactions and protects the security and privacy of protected health information; and • state and foreign law equivalents of each of the above federal laws, such as anti-kickback and false claims laws which may apply to: items or services reimbursed by any third-party payor, including commercial insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures; and state laws governing the privacy and security of health information in certain circumstances.
Because this is a relatively new and expanding area of novel therapeutic interventions, there can be no assurance as to the length of the study period, the number of patients the FDA will require to be enrolled in the studies in order to establish the safety, efficacy, purity and potency of human gene therapy products, our ability to recruit sufficient numbers of study subjects for any trial, or that the data generated in these studies will be acceptable to the FDA to support marketing approval.
Because this is a relatively new and expanding area of novel therapeutics, there can be no assurance as to the length of the study period, the number of patients the FDA will require to be enrolled in the studies in order to establish the safety, efficacy, purity and potency of human gene therapy products, our ability to recruit sufficient numbers of study subjects for any trial, or that the data generated in these studies will be acceptable to the FDA to support marketing approval.
Competition We are aware of a number of companies focused on developing and commercializing gene therapies in various disease indications, including 4D Molecular Therapeutics, Inc., Adverum Biotechnologies, Inc., Amicus Therapeutics, Inc., Astellas Pharma, BioMarin Pharmaceutical, Inc., MeiraGTx Limited, Novartis AG, Passage Bio, Inc., PTC Therapeutics, Inc., Roche, Sanofi, Sarepta Therapeutics, Inc., Solid Biosciences, Inc., Taysha Gene Therapies, Inc., Tenaya Therapeutics, Inc., Ultragenyx Pharmaceutical Inc. and uniQure N.V., as well as a number of companies addressing other methods for modifying genes and regulating gene expression.
Competition We are aware of a number of companies focused on developing and commercializing gene therapies in various disease indications, including 4D Molecular Therapeutics, Inc., Amicus Therapeutics, Inc., Astellas Pharma, BioMarin Pharmaceutical, Inc., Lilly, MeiraGTx Limited, Novartis AG, Passage Bio, Inc., PTC Therapeutics, Inc., Roche, Sanofi, Sarepta Therapeutics, Inc., Solid Biosciences, Inc., Taysha Gene Therapies, Inc., Tenaya Therapeutics, Inc., Ultragenyx Pharmaceutical Inc. and uniQure N.V., as well as a number of companies addressing other methods for modifying genes and regulating gene expression.
Duchenne is estimated to occur in approximately one in every 3,500-5,000 live male births and has an estimated prevalence of more than 30,000 cases in the U.S., Europe and Japan. RGX-202 is designed to deliver a transgene for a novel microdystrophin that includes the functional elements of the C-Terminal (CT) domain found in naturally occurring dystrophin.
Duchenne is estimated to occur in approximately one in every 3,500-5,000 live male births and has an estimated prevalence of more than 30,000 cases in the U.S., Europe and Japan. 8 Table of Contents RGX-202 is designed to deliver a transgene for a novel microdystrophin that includes the functional elements of the C-Terminal (CT) domain found in naturally occurring dystrophin.
At dose level 2, 71% of patients were ERT-free at last time point, up to almost three years. In January 2025, we announced a strategic partnership with Nippon Shinyaku to develop and commercialize RGX-121 in the United States and Asia. For more information, refer to "Nippon Shinyaku Partnership for MPS Diseases" below.
At dose level 2, 71% of patients were ERT-free at last time point, up to almost three years. In January 2025, we announced a strategic partnership with Nippon Shinyaku to develop and commercialize RGX-121 and RGX-111 in the United States and certain countries in Asia. For more information, refer to "Nippon Shinyaku Partnership for MPS Diseases" below.
The expedited programs, in general, do not change the standards for approval. Rather, these programs are intended to expedite the development and approval process, but they do not necessarily accomplish that intent. Post-Approval Requirements Maintaining substantial compliance with applicable federal, state, and local statutes and regulations requires the expenditure of substantial time and financial resources.
The expedited programs, in general, do not change the standards for approval. Rather, these programs are intended to expedite the development and approval process, but they do not necessarily accomplish that intent. 24 Table of Contents Post-Approval Requirements Maintaining substantial compliance with applicable federal, state, and local statutes and regulations requires the expenditure of substantial time and financial resources.
Our NAV Technology Platform consists of exclusive rights to a large portfolio of AAV vectors (NAV Vectors), including commonly used AAV8 and AAV9. We believe this platform forms a strong foundation for our current clinical-stage programs and, with our ongoing research and development, we expect to continue to expand our platform and pipeline of potential AAV vector-based gene therapies.
Our NAV Technology Platform has consisted of exclusive rights to a large portfolio of AAV vectors (NAV Vectors), including commonly used AAV8 and AAV9. We believe this platform forms a strong foundation for our current clinical-stage programs and, with our ongoing research and development, we expect to continue to expand our platform and pipeline of potential AAV vector-based gene therapies.
However, there is no guarantee that a product will be considered by the EU’s regulatory authorities to be an innovative medicinal product which is eligible for the relevant periods of data and market exclusivity. Products authorized as “orphan medicinal products” in the EU are entitled to benefits additional to those granted in relation to innovative medicinal products.
However, there is no guarantee that the EU’s regulatory authorities will consider a product to be an innovative medicinal product which is eligible for the relevant periods of data and market exclusivity. Products authorized as “orphan medicinal products” in the EU are entitled to benefits additional to those granted in relation to innovative medicinal products.
During this period, applicants for approval of generics or biosimilars of these innovative products cannot rely on data contained in the marketing authorization dossier submitted for the innovative medicinal product to support their application. Innovative medicinal products for which marketing authorization is granted are also entitled to ten years of market exclusivity.
During this period, applicants for approval of generics or biosimilars of these innovative products cannot rely on data 28 Table of Contents contained in the marketing authorization dossier submitted for the innovative medicinal product to support their application. Innovative medicinal products for which marketing authorization is granted are also entitled to ten years of market exclusivity.
We emphasize an inclusive environment and equitable treatment as an important part of our company culture. Available Information Our principal offices are located at 9804 Medical Center Drive, Rockville, MD 20850, and our telephone number is (240) 552-8181. Our website address is www.regenxbio.com.
We emphasize an inclusive environment and equitable treatment as an important part of our company culture. 31 Table of Contents Available Information Our principal offices are located at 9804 Medical Center Drive, Rockville, MD 20850, and our telephone number is (240) 552-8181. Our website address is www.regenxbio.com.
Wilson (the 2014 SRA). 13 Our license agreement with Penn, as amended, provides us with an exclusive, worldwide license under certain patents and patent applications in order to make, have made, use, import, offer for sale and sell products covered by the claims of the licensed patents and patent applications as well as all patentable inventions (to the extent they are or become available for license) that: • were discovered by Dr.
Our license agreement with Penn, as amended, provides us with an exclusive, worldwide license under certain patents and patent applications in order to make, have made, use, import, offer for sale and sell products covered by the claims of the licensed patents and patent applications as well as all patentable inventions (to the extent they are or become available for license) that: • were discovered by Dr.
As of December 31, 2024, our NAV Technology Licensees are currently applying our NAV Technology Platform to a number of AAV Therapeutics over a broad range of therapeutic areas and disease indications.
As of December 31, 2025, our NAV Technology Licensees are currently applying our NAV Technology Platform to a number of AAV therapeutics over a broad range of therapeutic areas and disease indications.
Under the terms of the Penn license agreement, we issued equity to Penn and are also obligated to pay Penn: • up to $20.5 million upon the achievement of various development and sales-based milestones, of which $0.5 million have been paid to date; • low- to mid-single digit royalties on net sales of licensed pharmaceutical products sold by us or our affiliates; • low-single digit to low-double digit royalty percentages of net sales on licensed products intended for research purposes only; • low- to mid-double digit royalty percentage on royalties received from third parties on net sales of licensed pharmaceutical products by such third parties; • certain sublicense fees, of which $6.0 million remain outstanding as of December 31, 2024; and • reimbursements for ongoing patent prosecution and maintenance expenses.
Under the terms of the Penn license agreement, we issued equity to Penn and are also obligated to pay Penn: • up to $20.5 million upon the achievement of various development and sales-based milestones, of which $0.5 million have been paid to date; • low- to mid-single digit royalties on net sales of licensed pharmaceutical products sold by us or our affiliates; 15 Table of Contents • low-single digit to low-double digit royalty percentages of net sales on licensed products intended for research purposes only; • low- to mid-double digit royalty percentage on royalties received from third parties on net sales of licensed pharmaceutical products by such third parties; • certain sublicense fees, of which $3.0 million remain outstanding as of December 31, 2025; and • reimbursements for ongoing patent prosecution and maintenance expenses.
As of July 29, 2024, ABBV-RGX-314 at dose level 3 with short course prophylactic steroid eye drops continued to be well tolerated with no drug-related serious adverse events (SAEs) and no cases of intraocular inflammation, endophthalmitis, vasculitis, retinal artery occlusion, choroidal effusion, or hypotony. Mild episcleritis occurred in three patients, all resolved and completed treatment with topical steroids.
As of July 29, 2024, sura-vec at dose level 3 with short course prophylactic steroid eye drops continued to be well tolerated with no drug-related serious adverse events (SAEs) and no cases of intraocular inflammation, endophthalmitis, vasculitis, retinal artery occlusion, choroidal effusion, or hypotony. Mild episcleritis occurred in three patients, all resolved and completed treatment with topical steroids.
Equity ownership in certain NAV Technology Licensees has generated significant additional return for REGENXBIO shareholders, and we believe the acquisition of these NAV Technology Licensees in strategic transactions by biopharmaceutical companies is an important validation of the NAV Technology Platform. Zolgensma License In March 2014, we entered into an agreement with AveXis, Inc.
Equity ownership in certain NAV Technology Licensees has generated significant additional return for REGENXBIO stockholders, and we believe the acquisition of these NAV Technology Licensees in strategic transactions by biopharmaceutical companies is an important validation of the NAV Technology Platform. Novartis License for Zolgensma and Itvisma In March 2014, we entered into an agreement with AveXis, Inc.
Under the Breakthrough Therapy program, products intended to treat a serious or life-threatening disease or condition may be eligible for additional benefits when preliminary clinical evidence demonstrates that such product may have substantial improvement on one or more clinically significant endpoints over available therapies.
Under the Breakthrough Therapy program, products intended to treat a serious or life-threatening disease or condition may be eligible for additional benefits when preliminary clinical evidence indicates that such product may demonstrate substantial improvement on one or more clinically significant endpoints over available therapies.
To support future commercialization of ABBV-RGX-314, the cGMP material produced by our NAVXpress platform process has been incorporated in the ongoing pivotal trials, ATMOSPHERE and ASCENT, for the treatment of wet AMD using ABBV-RGX-314 delivered subretinally. These trials are expected to support global regulatory submissions, including with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).
To support future commercialization of sura-vec, the cGMP material produced by our NAVXpress platform process has been incorporated in the ongoing pivotal trials, ATMOSPHERE and ASCENT, for the treatment of wet AMD using sura-vec delivered subretinally. These trials are expected to support global regulatory submissions, including with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).
If approved, RGX-121 would be the first approved gene therapy and one-time treatment for MPS II. 10 RGX‑111 for the Treatment of MPS I RGX-111 is our investigational AAV Therapeutic for the treatment of MPS I, a rare disease caused by deficiency of IDUA, an enzyme required for the breakdown of polysaccharides in lysosomes.
If approved, RGX-121 is expected to be the first approved gene therapy and one-time treatment for MPS II. RGX‑111 for the Treatment of MPS I RGX-111 is our investigational AAV Therapeutic for the treatment of MPS I, a rare disease caused by deficiency of IDUA, an enzyme required for the breakdown of polysaccharides in lysosomes.
Our Investigational AAV Therapeutics As of December 31, 2024, in addition to the patents related to our NAV Technology Platform described above, our patent portfolio included a total of six issued U.S. patents, one issued European patent, two pending International Patent applications filed pursuant to the Patent Cooperation Treaty (PCTs) and 22 PCTs that have entered national stage relating to our product candidates, which are described below: Retinal Diseases In addition to our NAV Technology Platform patents covering the NAV AAV8 vector and manufacture of NAV AAV8 vectors used in our retinal disease programs, our patent portfolio includes more recent filings relating to our clinical candidate vectors, clinical protocols, routes of administration to the eye (subretinal and suprachoroidal), formulations and target diseases treated by our gene therapy vectors.
Our Investigational AAV Therapeutics As of December 31, 2025, in addition to the patents related to our NAV Technology Platform described above, our patent portfolio included a total of six issued U.S. patents, one issued European patent, one pending International Patent application filed pursuant to the Patent Cooperation Treaty (PCTs) and 23 PCTs that have entered national stage relating to our product candidates, which are described below: Retinal Diseases In addition to our patents covering the manufacture of NAV AAV8 vectors used in our retinal disease programs, our patent portfolio includes more recent filings relating to our clinical candidate vectors, clinical protocols, routes of administration to the eye (subretinal and suprachoroidal), formulations and target diseases treated by our gene therapy vectors.
AbbVie Eye Care Collaboration In September 2021, REGENXBIO and AbbVie announced a global strategic partnership to develop and commercialize ABBV-RGX-314, a potential one-time gene therapy for the treatment of wet AMD, DR and other chronic retinal diseases.
AbbVie Eye Care Collaboration In September 2021, REGENXBIO and AbbVie announced a global strategic partnership to develop and commercialize surabgene lomparvovec (sura-vec, ABBV-RGX-314), a potential one-time gene therapy for the treatment of wet AMD, DR and other chronic retinal diseases.
If the FDA concludes a REMS is needed, the sponsor of the BLA must submit a proposed REMS; the FDA will not approve the BLA without a REMS, if required. Before approving a BLA, the FDA will inspect the facilities at which the product is manufactured.
If the FDA concludes a REMS is needed, the sponsor of the BLA must submit a proposed REMS; the FDA will not approve the BLA without a REMS, if required. 22 Table of Contents Before approving a BLA, the FDA will inspect the facilities at which the product is manufactured.
A person or entity no longer needs to have actual knowledge of this statute or specific intent to violate it; • the federal False Claims Act (FCA), which prohibits, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment from Medicare, Medicaid or other federal healthcare programs that are false or fraudulent.
A person or entity need not have actual knowledge of this statute or specific intent to violate it; • the federal False Claims Act (FCA), which prohibits, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment from Medicare, Medicaid or other federal healthcare programs that are false or fraudulent.
In June 2022, we entered into a license agreement with Johns Hopkins University (JHU) for the exclusive rights to JHU's undivided interest in intellectual property jointly owned by JHU and us relating to suprachoroidal delivery of anti-VEGF vectors.
In June 2022, we entered into a license agreement with Johns Hopkins University (JHU) for the exclusive rights to JHU's undivided interest in intellectual property JHU and we jointly own relating to suprachoroidal delivery of anti-VEGF vectors.
In January 2024, we announced data from the AAVIATE trial demonstrating that patients treated with ABBV-RGX-314 continue to demonstrate stable BCVA and CRT at six months. In addition, a meaningful reduction in anti-VEGF treatment burden was observed following administration of ABBV-RGX-314.
In January 2024, we announced data from the AAVIATE trial demonstrating that patients treated with sura-vec continue to demonstrate stable BCVA and CRT at six months. In addition, a meaningful reduction in anti-VEGF treatment burden was observed following administration of sura-vec.
The Collaboration and License Agreement with Nippon Shinyaku (the Nippon Shinyaku Collaboration and License Agreement) became effective in March 2025. Under the terms of the Nippon Shinyaku Collaboration and License Agreement, we will receive an upfront payment of $110 million.
The Collaboration and License Agreement with Nippon Shinyaku (the Nippon Shinyaku Collaboration and License Agreement) became effective in March 2025. Under the terms of the Nippon Shinyaku Collaboration and License Agreement, we received an upfront payment of $110 million.
Although this approach has demonstrated improvements in survival, growth, cardiac and respiratory function, mobility and intellect, it is also associated with clinically relevant morbidity and an estimated 10% to 20% mortality.
Although this approach has demonstrated improvements in survival, growth, cardiac and respiratory function, mobility and intellect, it is also associated with clinically relevant morbidity and an 11 Table of Contents estimated 10% to 20% mortality.
We will lead the manufacturing of ABBV-RGX-314 for clinical development and U.S. commercial supply, and AbbVie will lead manufacturing of ABBV-RGX-314 for commercial supply outside the United States. Manufacturing expenses will be allocated between the parties in accordance with the terms of the AbbVie Collaboration and License Agreement and mutually agreed supply agreements.
We will lead the manufacturing of sura-vec for clinical development and U.S. commercial supply, and AbbVie will lead manufacturing of sura-vec for commercial supply outside the United States. Manufacturing expenses will be allocated between the parties in accordance with the terms of the AbbVie Collaboration and License Agreement and mutually agreed supply agreements.
Our patent portfolio relating to ABBV-RGX-314 supports our clinical development and our collaboration with AbbVie for the clinical development of ABBV-RGX-314. Our patent portfolio covers the use of ABBV-RGX-314 for the treatment of wet AMD through subretinal or suprachoroidal administration and for the treatment of DR through suprachoroidal administration; it also covers formulations and devices used for suprachoroidal administration.
Our patent portfolio relating to sura-vec supports our clinical development and our collaboration with AbbVie for the clinical development of sura-vec. Our patent portfolio covers the use of sura-vec for the treatment of wet AMD through subretinal or suprachoroidal administration and for the treatment of DR through suprachoroidal administration; it also covers formulations and devices used for suprachoroidal administration.
In August 2018, we entered into a license agreement with Emory University (Emory) for the exclusive rights to Emory’s undivided interest in intellectual property jointly owned by Emory and us relating to the delivery of AAV vectors to the CNS.
In August 2018, we entered into a license agreement with Emory University (Emory) for the exclusive rights to Emory’s undivided interest in intellectual property that we and Emory jointly own relating to the delivery of AAV vectors to the CNS.
Since our founding, we have built a team of experts in research and development, scalable manufacturing, and preclinical and clinical development, enabling us to have integrated, end-to-end capabilities. We believe AAV Therapeutics represent a simplified and efficient potential new class of innovative medicines.
Our internal pipeline is shown below. Since our founding, we have built a team of experts in research and development, preclinical and clinical development, scalable manufacturing and commercialization, enabling us to have integrated, end-to-end capabilities. We believe AAV therapeutics represent a simplified and efficient potential new class of innovative medicines.
Stable to improved visual acuity was observed, with a mean BCVA of +12 letters from baseline at four years for Cohort 3 patients and -5 letters from baseline at three years for Cohort 4 patients following ABBV-RGX-314 administration.
Stable to improved visual acuity was observed, with a mean BCVA of +12 letters from baseline at four years for Cohort 3 patients and -5 letters from baseline at three years for Cohort 4 patients following sura-vec administration.
Clinical Development of RGX-202 AFFINITY DUCHENNE ® is a multicenter, open-label Phase I/II/III trial of RGX-202 in ambulatory patients aged one and older. Patients receive a dose of 2x10 14 GC/kg.
Clinical Development of RGX-202 AFFINITY DUCHENNE ® is a multicenter, open-label Phase I/II/III trial evaluating two dose levels (1x10 14 GC/kg and 2x10 14 GC/kg) of RGX-202 in ambulatory patients aged one and older.
NAV Vectors have been extensively investigated in clinical trials registered in the National Institutes of Health (NIH) clinical trials database and are being used in one FDA-approved AAV Therapeutic in the United States (Novartis’ Zolgensma).
NAV Vectors have been extensively investigated in clinical trials registered in the National Institutes of Health (NIH) clinical trials database and are being used in two FDA-approved AAV therapeutics in the United States (Novartis’ Zolgensma and Itvisma).
Our NAV Technology Platform is being applied to a number of programs over a broad range of therapeutic areas and disease indications by our NAV Technology Licensees. These partnered programs include Novartis’ Zolgensma ® , a gene therapy for the treatment of spinal muscular atrophy (SMA), which was approved by the U.S.
Our NAV Technology Platform is being applied to a number of programs over a broad range of therapeutic areas and disease indications by our NAV Technology Licensees. These partnered programs include Novartis’ Zolgensma ® and Itvisma ® gene therapies for the treatment of spinal muscular atrophy (SMA), a debilitating and potentially deadly disease. Zolgensma was approved by the U.S.
Since our inception, we have built and advanced multiple promising AAV Therapeutics into late-stage clinical development. All of our AAV Therapeutics were built on our NAV Technology Platform.
Since our inception, we have built and advanced multiple promising gene therapies into late-stage clinical development. All of our gene therapies were built on our NAV Technology Platform.
We retain all rights to, and one hundred percent of any potential proceeds related to the sale of, the Priority Review Voucher for RGX-121 received upon approval.
We retain all rights to, and 100% of any potential proceeds related to the sale of, the Priority Review Voucher for RGX-121 received upon approval.
It is possible that the information that we post on our social media channels could be deemed material information. Therefore, we encourage investors, the media and others interested in our company to review the information that we post on our social media channels. 29
It is possible that the information that we post on our social media channels could be deemed material information. Therefore, we encourage investors, the media and others interested in our company to review the information that we post on our social media channels. 32 Table of Contents
In December 2020, we sold a portion of our royalty rights from the net sales of Zolgensma to entities managed by Healthcare Royalty Management, LLC (HCR) for a gross purchase price of $200 million.
In December 2020, we sold a portion of our royalty rights from the net sales of Zolgensma and Itvisma to entities managed by Healthcare Royalty Management, LLC (collectively and with other affiliated entities, HCR) for a gross purchase price of $200 million.
Clinical studies are conducted under protocols detailing, among other things, the objectives of the clinical study, dosing procedures, subject selection and exclusion criteria, and the parameters to be used to monitor subject safety, including stopping rules that assure a clinical study will be stopped if certain adverse events should occur.
Clinical studies are conducted under protocols detailing, among other things, the objectives of the clinical study, dosing procedures, subject selection and exclusion criteria, and the parameters to be used to monitor subject safety, often including stopping rules that ensure a clinical study or treatment of a specific patient will be stopped if certain adverse events occur.
The last to expire patent under the GSK license agreement, absent patent term extension, is January 2026. We may terminate this license agreement for any reason upon a specified number of days’ written notice.
The last to expire patent under the GSK license agreement, absent patent term 16 Table of Contents extension, was in January 2026. We may terminate this license agreement for any reason upon a specified number of days’ written notice.
However, there are some EU level legal frameworks that must be taken into account, including Directive 89/105/EEC (the Price Transparency Directive).
However, there are some EU level legal frameworks that must be considered, including Directive 89/105/EEC (the Price Transparency Directive).
In 2018, we amended the license to include additional intellectual property owned or in-licensed by us, including rights to the NAV Technology Platform beyond NAV AAV9, as well as additional AAV vectors we may discover or license for a certain period of time, for the treatment of SMA.
In 2018, we amended the license to include additional intellectual property owned or in-licensed by us including a patent family covering intrathecal treatment of SMA that expires in 2037, and including rights to the NAV Technology Platform beyond NAV AAV9, as well as additional AAV vectors we may discover or license for a certain period of time, for the treatment of SMA.
Accordingly, we cannot be sure that submission of an IND will result in the FDA allowing clinical studies to begin, or that, once begun, issues will not arise that suspend or terminate such studies.
Accordingly, we cannot be sure that submission of an IND will result in the FDA allowing clinical studies to begin, or that, once begun, issues will not arise that would lead to the FDA suspending or terminating such studies.
A new Regulation on HTA on EU level was adopted in December 2021: Regulation (EU) 2021/2282 on health technology assessment (the HTA Regulation) and applies from January 12, 2025. The HTA Regulation covers new medicines and certain new medical devices.
A new Regulation on HTA on EU level was adopted in December 2021: Regulation (EU) 2021/2282 on health technology assessment (the HTA Regulation) and has been applicable since January 12, 2025. The HTA Regulation covers new medicines and certain new medical devices.
In the UK, following implementation of the Windsor Framework (an agreement which made changes to the Northern Ireland Protocol), from January 1, 2025, medicinal products may be designated as an orphan drug in the UK and will be valid UK-wide if the medicine meets criteria similar to those set out in European legislation.
In the UK, following implementation of the Windsor Framework (an agreement which made changes to the Northern Ireland Protocol), from January 1, 2025, medicinal products may be designated as an orphan drug in the UK and will be valid UK-wide regardless of whether there is an EU orphan designation or EU authorization as an orphan medicinal product if the medicine meets certain criteria similar to those set out in European legislation.
As of January 1, 2021, the UK is a “third country” with respect to the EU (subject to the terms of the EU UK Trade Agreement), and EU law ceased to apply directly in the UK.
As a consequence of Brexit, the UK formally left the EU and as of January 1, 2021, the UK is a “third country” with respect to the EU (subject to the terms of the EU UK Trade Agreement), so that EU law ceased to apply directly in the UK.
Together, with our manufacturing and end-to-end capabilities, we are excited about the prospect of bringing these assets to commercial stage and continuing to leverage our NAV Technology Platform to generate additional promising AAV Therapeutics. Our NAV Technology Platform In 2009, we acquired exclusive rights to our NAV Technology Platform.
Together, with our in-house, U.S.-based manufacturing and end-to-end capabilities, we are excited about the prospect of bringing these assets to commercial stage and continuing to leverage our NAV Technology Platform to generate additional promising gene therapies. Our NAV Technology Platform In 2009, we acquired exclusive rights to our NAV Technology Platform.
Each protocol and any amendments to the protocol must be submitted to the FDA as 19 part of the IND. Clinical studies must be conducted and monitored in accordance with the FDA’s regulations imposing the GCP requirements, including the requirement that all research subjects provide informed consent.
Each protocol and any significant change to the protocol must be submitted to FDA as an amendment to the IND . Clinical studies must be conducted and monitored in accordance with the FDA’s regulations imposing the GCP requirements, including the requirement that all research subjects provide informed consent.
In our exploratory research, we work internally and through collaborations with external researchers to identify and optimize AAV Therapeutics based on AAV vector targeting, transgene optimization and evaluation of effective delivery devices. We then execute proof-of-concept research that informs the next steps in our pipeline strategy.
Our early evaluation of targets includes scientific rationale and cross-functional analysis of technical feasibility. In our exploratory research, we work internally and through collaborations with external researchers to identify and optimize AAV therapeutics based on AAV vector targeting, transgene optimization and evaluation of effective delivery devices. We then execute proof-of-concept research that informs the next steps in our pipeline strategy.
We have developed product formulations specific to our different delivery devices and routes of administration. We aim to ensure that our formulations are designed and assessed to ensure product stability can be maintained for numerous years and that our AAV Therapeutics can be exposed to a variety of handling and delivery procedures.
We aim to ensure that our formulations are designed and assessed to ensure product stability can be maintained for numerous years and that our AAV therapeutics can be exposed to a variety of handling and delivery procedures.
We also sublicense our NAV Technology Platform to third parties in order to develop and bring to market AAV Therapeutics for a range of severe diseases with significant unmet medical needs outside of our core disease indications and therapeutic areas. The Trustees of the University of Pennsylvania.
We currently use our NAV Technology Platform to develop treatments in the areas of retinal, neuromuscular and neurodegenerative diseases. We also sublicense our NAV Technology Platform to third parties in order to develop and bring to market AAV therapeutics for a range of severe diseases with significant unmet medical needs outside of our core disease indications and therapeutic areas.
We believe we have extensive human safety experience to support the development of our investigational AAV Therapeutics based on data from thousands of patients dosed with AAV Therapeutics derived from our NAV Technology Platform in more than 15 different clinical-stage programs and with one FDA approved product.
We believe we have extensive human safety experience to support the development of our investigational AAV therapeutics based on data from thousands of patients dosed with AAV therapeutics derived from our NAV Technology Platform in two FDA approved products and numerous clinical stage programs.
Post-approval clinical studies, sometimes referred to as Phase IV clinical studies, may be conducted after initial marketing approval. These clinical studies are used to gain additional experience from the treatment of patients in the intended therapeutic indication, particularly for long-term safety follow-up. In some cases, Phase IV studies may be required by the FDA as a condition of approval.
Post-approval clinical studies, sometimes referred to as Phase IV clinical studies, may be conducted after initial marketing approval. These clinical studies are used to gain additional experience from the treatment of patients in the intended therapeutic 21 Table of Contents indication, particularly for long-term safety follow-up.
Under the terms of the agreement, we are obligated to pay Emory an upfront fee, annual maintenance fees under certain circumstances, royalties on net sales, sublicense fees, and fees upon the achievement of various milestones for the first licensed product. Clearside Biomedical, Inc.
Under the terms of the agreement, we are obligated to pay Emory an upfront fee, annual maintenance fees under certain circumstances, royalties on net sales, sublicense fees, and fees upon the achievement of various milestones for the first licensed product. This patent estate is sublicensed to Novartis for the treatment of spinal muscular atrophy. Clearside Biomedical, Inc.
Under the terms of the agreement, we are obligated to pay JHU an upfront fee, royalties on net sales, minimum annual royalties, sublicense fees and fees upon the achievement of various milestones for the first two licensed products. Additionally, the Company is obligated to pay for certain costs incurred related to the maintenance of the licensed patents.
Under the terms of the agreement, we are obligated to pay JHU an upfront fee, royalties on net sales, minimum annual royalties, sublicense fees and fees upon the achievement of various milestones for the first two licensed products.
Similarly, an IRB can suspend or terminate approval of a clinical study at its institution if the clinical study is not being conducted in accordance with the IRB’s requirements or if the biological product has been associated with unexpected serious harm to patients. Human gene therapy products are a new category of therapeutics.
The IRB can suspend or terminate approval of a clinical study at its institution if the clinical study is not being conducted in accordance with the IRB’s requirements or if the biological product has been associated with unexpected serious harm to patients.
AAV Therapeutic Delivery Devices We believe that a critical component of AAV Therapeutic development is to deliver treatments safely, effectively and efficiently to the right part of the body. We leverage the differentiated characteristics of NAV Vectors to target different tissues and cells.
We believe this allows us to accelerate the process of developing AAV therapeutics. 5 Table of Contents AAV Therapeutic Delivery Devices We believe that a critical component of AAV Therapeutic development is to deliver treatments safely, effectively and efficiently to the right part of the body. We leverage the differentiated characteristics of NAV Vectors to target different tissues and cells.
By the time of death, most patients with CNS involvement are severely mentally handicapped and require constant care. MPS II is estimated to occur in approximately 1 in 100,000 to 1 in 170,000 births worldwide.
By the time of death, most patients with CNS involvement are severely mentally handicapped and require constant care. MPS II is estimated to occur in approximately 1 in 100,000 to 1 in 170,000 births worldwide. Based on global population, this equates to approximately 500 to 1,000 MPS II patients born each year worldwide.
The principal marketed anti-VEGF competition for DR without DME is Roche/Genentech (Lucentis) and Regeneron (Eylea, Eylea HD). Companies with products in development for the treatment of DR without DME include, but may not be limited to, Kodiak Sciences, Novartis, Ocular Therapeutix and Roche. • DMD.
Companies with products in development for the treatment of DR with DME include, but may not be limited to, 4D Molecular Therapeutics, Eyepoint, Kodiak Sciences, Merck, Oculis, and Roche. The principal marketed anti-VEGF competition for DR without DME is Roche/Genentech (Lucentis, Susvimo) and Regeneron (Eylea, Eylea HD).
In the future, we may apply for restoration of patent term for one of our currently owned or licensed patents to add patent life beyond its current expiration date, depending on the expected length of the clinical studies and other factors involved in the filing of the relevant BLA.
In the future, we may apply for restoration of patent term for one of our currently owned or licensed patents to add patent life beyond its current expiration date, depending on the expected length of the clinical studies and other factors involved in the filing of the relevant BLA. 25 Table of Contents A biological product can obtain pediatric market exclusivity in the United States.
This six-month exclusivity, which runs from the end of other exclusivity protection, may be granted based on the voluntary completion of a pediatric study in accordance with an FDA-issued “Written Request” for such a study.
Pediatric exclusivity, if granted in the case of a biologic approved under a BLA, adds six months to existing exclusivity periods. This six-month exclusivity, which runs from the end of other exclusivity protection, may be granted based on the voluntary completion of a pediatric study in accordance with an FDA-issued “Written Request” for such a study.
In Great Britain, gene therapy medicinal products are classified as advanced therapy medicinal products. In order to place an advanced therapy medicinal product on the Great Britain market, a person must hold a marketing authorization for the medicinal product. There are various routes to applying for a marketing authorization in Great Britain.
To place an advanced therapy medicinal product on the UK market, a person must hold a marketing authorization for the medicinal product. There are various routes to applying for a marketing authorization in the UK.
The sub-study evaluated subretinal delivery of ABBV-RGX-314 in patients who received ABBV-RGX-314 in the Phase I/IIa or bridging studies and elected to receive treatment in their second eye. As of September 11, 2024, ABBV-RGX-314 has been well tolerated in the treated second eye with no drug-related serious adverse events and no cases of intraocular inflammation observed.
The sub-study evaluated subretinal delivery of sura-vec in patients who received sura-vec in the Phase I/IIa or bridging studies and elected to receive treatment in their second eye. As of May 26, 2025, sura-vec was well tolerated in the treated second eye with no drug-related serious adverse events and no cases of intraocular inflammation observed.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeRisks Related to Manufacturing • Products intended for use in gene therapies are novel, complex and difficult to manufacture. • Delays in obtaining regulatory approval of our manufacturing process or disruptions in our manufacturing process may delay or disrupt our commercialization efforts. • Third parties we rely upon to conduct our product manufacturing may not perform satisfactorily. 30 • We are required to comply with ongoing manufacturing regulatory requirements.
Biggest changeRisks Related to Third Parties • If third parties do not meet our deadlines, our preclinical and clinical development programs could be delayed or unsuccessful. • If our licensing arrangements or collaborations are not successful, our business could be harmed. 33 Table of Contents Risks Related to Manufacturing • Products intended for use in gene therapies are novel, complex and difficult to manufacture. • Delays in obtaining regulatory approval of our manufacturing process and facility or disruptions in our manufacturing process and product testing may delay or disrupt our commercialization efforts. • Third parties we rely upon to manufacture and supply materials for our programs including ingredients and key components for our product candidates and to perform quality testing may not perform satisfactorily. • We are required to comply with ongoing manufacturing regulatory requirements and regulatory health authorities routinely conduct inspections of our product manufacturing and testing facilities that may result in findings that cause a delay or disrupt our drug development and commercialization efforts.
If we are unable to obtain regulatory approval for, or successfully commercialize , our lead product candidates, our business will be materially harmed. Our product candidates will require substantial clinical development and testing, manufacturing bridging studies and process validation and regulatory approval prior to commercialization.
If we are unable to obtain regulatory approval for, or successfully commercialize , our lead product candidates, our business will be materially harmed. Our product candidates require substantial clinical development and testing, manufacturing bridging studies and process validation and regulatory approval prior to commercialization.
The future regulatory and commercial success of these product candidates is subject to a number of risks, including the following: • we may not have sufficient financial and other resources or patient availability to complete the necessary clinical trials for our lead product candidates ; • we may not be able to provide evidence of quality, efficacy and safety for our lead product candidates ; 32 • we do not know the degree to which our lead product candidates will be accepted by patients, the medical community and third-party payors as a therapy for the respective diseases to which they relate, even if approved ; • the results of our clinical trials may not meet the level of statistical or clinical significance required by the FDA, EMA or comparable foreign regulatory bodies for marketing approval, and modifications to the design of our clinical trials could delay their enrollment, commencement or completion ; • subjects in our clinical trials may die or suffer other adverse effects for reasons that may or may not be related to our lead product candidates ; • subjects in clinical trials undertaken by our licensees or collaborators, or undertaken by others using AAV, may die or suffer other adverse effects for reasons that may or may not be related to our NAV Technology Platform or AAV ; • certain patients’ immune systems might prohibit the successful delivery of certain gene therapy products to the target tissue, thereby limiting the treatment outcomes ; • we may not successfully establish commercial manufacturing capabilities; • if approved for treatment of the expected conditions, our lead product candidates will likely compete with other treatments then available, including the off-label use of products already approved for marketing and other therapies currently available or which may be developed ; • our products and products developed by our licensees and collaborators may not maintain a continued acceptable safety profile following regulatory approval ; • we may not maintain compliance with post-approval regulation and other requirements ; and • we may not be able to obtain, maintain or enforce our rights under our licensed patents and other intellectual property rights .
The future regulatory and commercial success of these product candidates is subject to a number of risks, including the following: • we may not have sufficient financial and other resources or patient availability to complete the necessary clinical trials for our lead product candidates ; • we may not be able to provide evidence of quality, efficacy and safety for our lead product candidates ; • we do not know the degree to which our lead product candidates will be accepted by patients, the medical community and third-party payors as a therapy for the respective diseases to which they relate, even if approved ; • the results of our clinical trials may not meet the level of statistical or clinical significance required by the FDA, EMA or comparable foreign regulatory bodies for marketing approval, and modifications to the design of our clinical trials could delay their enrollment, commencement or completion ; • subjects in our clinical trials may die or suffer other adverse effects for reasons that may or may not be related to our lead product candidates ; • subjects in clinical trials undertaken by our licensees or collaborators, or undertaken by others using AAV, may die or suffer other adverse effects for reasons that may or may not be related to our NAV Technology Platform or AAV ; • certain patients’ immune systems might prohibit the successful delivery of certain gene therapy products to the target tissue, thereby limiting the treatment outcomes ; • we may not successfully establish commercial manufacturing capabilities for each of our products; • if approved for treatment of the expected conditions, our lead product candidates will likely compete with other treatments then available, including the off-label use of products already approved for marketing and other therapies currently available or which may be developed ; • our products and products developed by our licensees and collaborators may not maintain a continued acceptable safety profile following regulatory approval ; • we may not maintain compliance with post-approval regulation and other requirements ; and • we may not be able to obtain, maintain or enforce our rights under our licensed patents and other intellectual property rights .
We anticipate that our expenses will increase substantially if, and as, we: • continue our research studies and preclinical and clinical development of our product candidates, including our lead product candidates; • initiate additional preclinical studies and clinical trials for our lead product candidates and future product candidates, if any; • initiate additional activities relating to manufacturing, including building out additional laboratory and manufacturing capacity; • seek to identify additional product candidates; • prepare our BLA and MAA for our lead product candidates and seek marketing approvals for any of our other product candidates that successfully complete clinical trials, if any; • further develop our NAV Technology Platform; • establish a sales, marketing and distribution infrastructure to commercialize any product candidates for which we may obtain marketing approval, if any; 38 • maintain, expand and protect our intellectual property portfolio and enforce our intellectual property rights; and • acquire or in-license other product candidates and technologies.
We anticipate that our expenses will increase substantially if, and as, we: • continue our research studies and preclinical and clinical development of our product candidates, including our lead product candidates; • initiate additional preclinical studies and clinical trials for our lead product candidates and future product candidates, if any; • initiate additional activities relating to manufacturing, including building out additional laboratory and manufacturing capacity; • seek to identify additional product candidates; • prepare our BLA and MAA for our lead product candidates and seek marketing approvals for any of our other product candidates that successfully complete clinical trials, if any; • further develop our NAV Technology Platform; • establish a sales, marketing and distribution infrastructure to commercialize any product candidates for which we may obtain marketing approval, if any; • maintain, expand and protect our intellectual property portfolio and enforce our intellectual property rights; and • acquire or in-license other product candidates and technologies.
Our ability to generate future revenues from sales of our product candidates and in connection with sales of our licensees’ and collaborators’ products depends heavily on our, and our licensees’ and collaborators’, success in: • completing research studies and preclinical and clinical development of product candidates and identifying new gene therapy product candidates; • obtaining regulatory and marketing approvals for product candidates for which clinical trials are completed; • commercializing product candidates for which regulatory and marketing approval is obtained by establishing a sales force, marketing and distribution infrastructure or, alternatively, collaborating with a commercialization partner; • negotiating favorable terms in any collaboration, licensing or other arrangements into which we or our licensees and collaborators may enter and performing our obligations in such collaborations; • qualifying for adequate coverage and reimbursement by government and third-party payors for product candidates; • 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 can provide adequate, in both amount and quality, products and services to support clinical development and the market demand for product candidates, if approved; • obtaining market acceptance of product candidates as a viable treatment option; • competing effectively when other companies may develop products that are priced lower, reimbursed more favorably by government or other third-party payors, safer, more effective or more convenient to use than our products, if any, or our licensees’ and collaborators’ products; • implementing additional internal systems and infrastructure, as needed; • negotiating favorable terms in any collaboration, licensing or other arrangements into which we may enter and performing our obligations in such collaborations; • maintaining, protecting and expanding our portfolio of intellectual property rights, including patents, trade secrets and know-how; • avoiding and defending against third-party interference, infringement and other intellectual property related claims; and • attracting, hiring and retaining qualified personnel.
Our ability to generate future revenues from sales of our product candidates and in connection with sales of our licensees’ and collaborators’ products depends heavily on our, and our licensees’ and collaborators’, success in: • completing research studies and preclinical and clinical development of product candidates and identifying new gene therapy product candidates; • obtaining regulatory and marketing approvals for product candidates for which clinical trials are completed; • commercializing product candidates for which regulatory and marketing approval is obtained by establishing a sales force, marketing and distribution infrastructure or, alternatively, collaborating with a commercialization partner; • negotiating favorable terms in any collaboration, licensing or other arrangements into which we or our licensees and collaborators may enter and performing our obligations in such collaborations; • qualifying for adequate coverage and reimbursement by government and third-party payors for product candidates; • 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 can provide adequate, in both amount and quality, products and services to support clinical development and the market demand for product candidates, if approved; • obtaining market acceptance of product candidates as a viable treatment option; • competing effectively when other companies may develop products that are priced lower, reimbursed more favorably by government or other third-party payors, safer, more effective or more convenient to use than our products, if any, or our licensees’ and collaborators’ products; • implementing additional internal systems and infrastructure, as needed; • negotiating favorable terms in any collaboration, licensing or other arrangements into which we may enter and performing our obligations in such collaborations; 45 Table of Contents • maintaining, protecting and expanding our portfolio of intellectual property rights, including patents, trade secrets and know-how; • avoiding and defending against third-party interference, infringement and other intellectual property related claims; and • attracting, hiring and retaining qualified personnel.
Regardless of merit or eventual outcome, liability claims may result in: • decreased demand for our technology, including any product candidates that we may develop; • loss of revenue; 50 • substantial monetary awards to trial participants or patients; • significant time and costs to defend the related litigation; • withdrawal of clinical trial participants; • the inability to license our NAV Technology Platform or commercialize any product candidates that we may develop; and • injury to our reputation and significant negative media attention.
Regardless of merit or eventual outcome, liability claims may result in: • decreased demand for our technology, including any product candidates that we may develop; • loss of revenue; • substantial monetary awards to trial participants or patients; • significant time and costs to defend the related litigation; • withdrawal of clinical trial participants; • the inability to license our NAV Technology Platform or commercialize any product candidates that we may develop; and • injury to our reputation and significant negative media attention.
Risks Related to Our Financial Position We face significant competition in an environment of rapid technological change and there is a possibility that our competitors may achieve regulatory approval before us or develop products that are safer, less expensive or more convenient or effective than ours, which may harm our financial condition and our ability to successfully market or commercialize our product candidates.
Risks Related to Our Financial Position We face significant competition in an environment of rapid technological change and there is a possibility that our competitors may achieve regulatory approval before us or develop products that are safer, less expensive or more convenient or effective than ours, any of which may harm our financial condition and our ability to successfully market or commercialize our product candidates.
Liability may be established under the federal Anti-Kickback Statute without proving actual knowledge of the statute or specific intent to violate it; 49 • federal civil and criminal false claims laws and civil monetary penalty laws which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment or approval from Medicare, Medicaid or other government payors that are false or fraudulent.
Liability may be established under the federal Anti-Kickback Statute without proving actual knowledge of the statute or specific intent to violate it; • federal civil and criminal false claims laws and civil monetary penalty laws which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment or approval from Medicare, Medicaid or other government payors that are false or fraudulent.
Any current or future licensing agreements or future collaborations we enter into may pose additional risks, including the following: • subjects in clinical trials undertaken by our licensees and collaborators may suffer adverse effects, including death; • our licensees and collaborators 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 clinical trial results, changes in the licensees’ or collaborators’ strategic focus or available funding or external factors, such as an acquisition, that divert resources or create competing priorities; • we may not have access to, or may be restricted from disclosing, certain information regarding product candidates being developed or commercialized under a collaboration and, consequently, may have limited ability to inform our stockholders about the status of such product candidates; 41 • our licensees or collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our product candidates if the licensees or collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours; • product candidates developed in collaboration with us may be viewed by our licensees or collaborators as competitive with their own product candidates or products, which may cause licensees or collaborators to cease to devote resources to the commercialization of our product candidates; • a licensee or collaborator 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; • our licensees or collaborators may breach their reporting, payment, intellectual property or other obligations to us, which could prevent us from complying with our contractual obligations to our upstream licensors; • disagreements with licensees or collaborators, including disagreements over intellectual property and other proprietary rights, payment obligations, 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 for us with respect to such product candidates or may result in litigation or arbitration, any of which would be time-consuming and expensive and could potentially lessen the value of such agreements and collaborations; • our licensees or collaborators 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 of our other rights to intellectual property developed pursuant to our licensing agreements or collaborations; • depending on the terms of the licensing agreement, the licensee or collaborator may have sole discretion regarding material aspects of the development, marketing or sale of a product candidate; • our licensees or collaborators may infringe or otherwise violate the intellectual property rights of third parties, which may expose us to litigation and potential liability; and • licensing agreements or collaborations may be terminated for the convenience of the licensee or collaborator and, if terminated, we could be required to raise additional capital to pursue further development or commercialization of the applicable product candidates.
Any current or future licensing agreements or future collaborations we enter into may pose additional risks, including the following: • subjects in clinical trials undertaken by our licensees and collaborators may suffer adverse effects, including death; 46 Table of Contents • our licensees and collaborators 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 clinical trial results, changes in the licensees’ or collaborators’ strategic focus or available funding or external factors, such as an acquisition, that divert resources or create competing priorities; • we may not have access to, or may be restricted from disclosing, certain information regarding product candidates being developed or commercialized under a collaboration and, consequently, may have limited ability to inform our stockholders about the status of such product candidates; • our licensees or collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our product candidates if the licensees or collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours; • product candidates developed in collaboration with us may be viewed by our licensees or collaborators as competitive with their own product candidates or products, which may cause licensees or collaborators to cease to devote resources to the commercialization of our product candidates; • a licensee or collaborator 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; • our licensees or collaborators may breach their reporting, payment, intellectual property or other obligations to us, which could prevent us from complying with our contractual obligations to our upstream licensors; • disagreements with licensees or collaborators, including disagreements over intellectual property and other proprietary rights, payment obligations, 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 for us with respect to such product candidates or may result in litigation or arbitration, any of which would be time-consuming and expensive and could potentially lessen the value of such agreements and collaborations; • our licensees or collaborators 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 of our other rights to intellectual property developed pursuant to our licensing agreements or collaborations; • depending on the terms of the licensing agreement, the licensee or collaborator may have sole discretion regarding material aspects of the development, marketing or sale of a product candidate; • our licensees or collaborators may infringe or otherwise violate the intellectual property rights of third parties, which may expose us to litigation and potential liability; and • licensing agreements or collaborations may be terminated for the convenience of the licensee or collaborator and, if terminated, we could be required to raise additional capital to pursue further development or commercialization of the applicable product candidates.
To the extent that any disruption or security breach results in a loss of, or damage to, our trade secrets, data or applications, or inappropriate disclosure of confidential or proprietary information, we could incur liability, our competitive position could be harmed 51 and the further licensing of our NAV Technology Platform and development and commercialization of our product candidates could be delayed.
To the extent that any disruption or security breach results in a loss of, or damage to, our trade secrets, data or applications, or inappropriate disclosure of confidential or proprietary information, we could incur liability, our competitive position could be harmed and the further licensing of our NAV Technology Platform and development and commercialization of our product candidates could be delayed.
We currently do not have “key person” insurance on any of our employees. 48 Recruiting and retaining other qualified employees, consultants and advisors for our business, including scientific and technical personnel is, and will continue to be, critical to our success. There currently is a shortage of skilled individuals with substantial gene therapy experience.
We currently do not have “key person” insurance on any of our employees. Recruiting and retaining other qualified employees, consultants and advisors for our business, including scientific and technical personnel is, and will continue to be, critical to our success. There currently is a shortage of skilled individuals with substantial gene therapy experience.
Other than revenue in connection with sales of Zolgensma, we may generate only limited recurring revenue in the near term from our current NAV Technology Licensees and collaborators. We expect to continue to incur significant expenses and regularly incur operating losses for the foreseeable future. The net losses we incur may fluctuate significantly from quarter to quarter.
Other than revenue in connection with sales of Zolgensma and Itvisma, we may generate only limited recurring revenue in the near term from our current NAV Technology Licensees and collaborators. We expect to continue to incur significant expenses and regularly incur operating losses for the foreseeable future. The net losses we incur may fluctuate significantly from quarter to quarter.
If disputes over intellectual property that we have licensed prevent or impair our ability to maintain our current licensing arrangements on acceptable terms, we may be unable to successfully develop and commercialize the affected product candidates. 55 We may not be successful in obtaining necessary rights to our product candidates through acquisitions and in-licenses.
If disputes over intellectual property that we have licensed prevent or impair our ability to maintain our current licensing arrangements on acceptable terms, we may be unable to successfully develop and commercialize the affected product candidates. We may not be successful in obtaining necessary rights to our product candidates through acquisitions and in-licenses.
Regulatory authorities also may require additional trials if a new manufacturer is relied upon for commercial production. Switching manufacturers may involve substantial costs and could result in a delay in our desired clinical and commercial timelines. 44 Given the nature of biologics manufacturing, there is a risk of contamination during manufacturing.
Regulatory authorities also may require additional trials if a new manufacturer is relied upon for commercial production. Switching manufacturers may involve substantial costs and could result in a delay in our desired clinical and commercial timelines. Given the nature of biologics manufacturing, there is a risk of contamination during manufacturing.
Although we have generated significant revenues from licensing our NAV Technology Platform and our other intellectual property, such as our licensing pursuant to the AbbVie Collaboration and License Agreement and may do so under the Nippon Shinyaku Collaboration and License Agreement, we have never generated revenue from sales of our product candidates and may never do so in the future.
Although we have generated significant revenues from licensing our NAV Technology Platform and our other intellectual property, such as our licensing pursuant to the AbbVie Collaboration and License Agreement and Nippon Shinyaku Collaboration and License Agreement, we have never generated revenue from sales of our product candidates and may never do so in the future.
Changes in either the patent laws or interpretation of the patent laws in the United States and other countries may diminish the value of our patents or narrow the scope of our patent protection. 53 We may not be aware of all third-party intellectual property rights potentially relating to our technology and product candidates.
Changes in either the patent laws or interpretation of the patent laws in the United States and other countries may diminish the value of our patents or narrow the scope of our patent protection. We may not be aware of all third-party intellectual property rights potentially relating to our technology and product candidates.
Risks Related to Third Parties We rely on third parties to conduct aspects of our clinical trials and certain preclinical research development activities. If these third parties do not meet our deadlines or otherwise conduct the preclinical research and development activities and trials as required, our clinical and preclinical development programs could be delayed or unsuccessful.
Risks Related to Third Parties If the third parties we rely on to conduct aspects of our clinical trials and certain preclinical research development activities do not meet our deadlines or otherwise conduct the preclinical research and development activities and trials as required, our clinical and preclinical development programs could be delayed or unsuccessful.
The cGMP requirements govern quality control 43 of the manufacturing process and documentation policies and procedures. In complying with cGMP, we will be obligated to expend time, money and effort in production, record keeping and quality control to assure that the product meets applicable specifications and other requirements.
The cGMP requirements govern quality control of the manufacturing process and documentation policies and procedures. In complying with cGMP, we will be obligated to expend time, money and effort in production, record keeping and quality control to assure that the product meets applicable specifications and other requirements.
Such proceedings could result in the revocation or cancellation of or amendment to our patents in such a way that they no longer cover our NAV Technology 57 Platform or our product candidates. The outcome following legal assertions of invalidity and unenforceability is unpredictable.
Such proceedings could result in the revocation or cancellation of or amendment to our patents in such a way that they no longer cover our NAV Technology Platform or our product candidates. The outcome following legal assertions of invalidity and unenforceability is unpredictable.
We expect to require substantial future capital in order to complete research studies, preclinical and clinical development for our current product candidates and any future product candidates, and potentially commercialize these product candidates, if approved. We expect our spending levels to increase in connection with our preclinical and clinical trials of our product candidates.
We expect to require substantial future capital in order to complete research studies, preclinical and clinical development for our current product candidates and any future product candidates, and to commercialize these product candidates, if approved. We expect our spending levels to increase in connection with our preclinical and clinical trials of our product candidates.
In addition, there could be 56 public announcements of the results of hearings, motions or other interim proceedings or developments and if securities analysts or investors perceive these results to be negative, it could materially harm the price of our common stock.
In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments and if securities analysts or investors perceive these results to be negative, it could materially harm the price of our common stock.
Our net income or loss and other operating results may be affected by numerous factors, including: • any variations in the level of expenses related to our NAV Technology Platform, lead product candidates or future product candidates and technologies; • the addition or termination of any clinical trials and the timing and outcomes of clinical trials; • any regulatory or clinical developments affecting our lead product candidates, any future product candidates or our licensees’ product candidates; • our execution of any collaborative, licensing or similar arrangements and the timing of any payments we may make or receive under these arrangements; • changes in the competitive landscape of our industry, including consolidation among our competitors or partners; • the nature and terms of any stock-based compensation grants; • any intellectual property infringement lawsuits in which we may become involved; • our ability to adequately support future growth; • potential unforeseen business disruptions that increase our costs or expenses; • future accounting pronouncements or changes in our accounting policies; and • the changing and volatile global economic environment.
Our net income or loss and other operating results may be affected by numerous factors, including: • any variations in the level of expenses related to our NAV Technology Platform, lead product candidates or future product candidates and technologies; • the addition or termination of any clinical trials and the timing and outcomes of clinical trials; • any regulatory or clinical developments affecting our lead product candidates, any future product candidates or our licensees’ product candidates; • our execution of any collaborative, licensing or similar arrangements and the timing of any payments we may make or receive under these arrangements; • changes in the competitive landscape of our industry, including consolidation among our competitors or partners; • the nature and terms of any stock-based compensation grants; 65 Table of Contents • any intellectual property infringement lawsuits in which we may become involved; • our ability to adequately support future growth; • potential unforeseen business disruptions that increase our costs or expenses; • future accounting pronouncements or changes in our accounting policies; and • the changing and volatile global economic environment.
Lastly, certain patients’ immune systems might prohibit the successful delivery of certain gene therapy products to the target tissue, thereby limiting the treatment outcomes. 46 The insurance coverage and reimbursement status of newly approved products is uncertain.
Lastly, certain patients’ immune systems might prohibit the successful delivery of certain gene therapy products to the target tissue, thereby limiting the treatment outcomes. The insurance coverage and reimbursement status of newly approved products is uncertain.
We have historically financed our operations primarily through private and public offerings of our equity securities, collaborations and licensing rights to our NAV Technology Platform, including milestone payments and royalties from our NAV Technology Licensees.
We have historically financed our operations primarily through private and public offerings of our equity securities, collaborations and licensing rights to our NAV Technology Platform, including milestone payments and royalties from our NAV Technology Licensees and collaborators.
Events that may prevent successful or timely commencement and completion of preclinical and clinical development include: • delays in reaching a consensus with regulatory authorities on trial design; • delays in reaching agreement on acceptable terms with prospective CROs and clinical trial sites; • delays in opening clinical trial sites or obtaining required institutional review board or independent Ethics Committee approval at each clinical trial site; • delays in recruiting and enrolling suitable subjects to participate in our clinical trials, due to factors such as the size of the trial or subject population, process for identifying subjects, design or expansion of protocols, eligibility and exclusive criteria, perceived risks and benefits of the relevant product candidate or gene therapy generally, availability of competing therapies and trials, severity of the disease under investigation, need and length of time required to discontinue other potential therapies, availability of genetic testing, availability and proximity of trial sites for prospective subjects, ability to obtain subject consent and referral practices of physicians; • imposition of a clinical hold by regulatory authorities; • failure by us, any CROs we engage or any other third parties to adhere to clinical trial requirements; • failure to perform in accordance with GCP, or applicable regulatory guidelines in the European Union and other countries; • 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; • delays in having subjects complete participation in a trial or return for post-treatment follow-up; • clinical trial sites or subjects dropping out of a trial; • selection of clinical endpoints that require prolonged periods of clinical observation or analysis of the resulting data; • occurrence of serious adverse events associated with the product candidate that are viewed to outweigh its potential benefits; 34 • occurrence of serious adverse events in trials of the same class of agents conducted by other sponsors; or • changes in regulatory requirements and guidance that require amending or submitting new clinical protocols.
Events that may prevent successful or timely commencement and completion of preclinical and clinical development include: • delays in reaching a consensus with or changing requirements by regulatory authorities on trial design; • delays in reaching agreement on acceptable terms with prospective CROs and clinical trial sites; • delays in opening clinical trial sites or obtaining required institutional review board or independent Ethics Committee approval at each clinical trial site; • delays in recruiting and enrolling suitable subjects to participate in our clinical trials, due to factors such as the size of the trial or subject population, process for identifying subjects, design or expansion of protocols, eligibility and exclusive criteria, perceived risks and benefits of the relevant product candidate or gene therapy generally, availability of competing therapies and trials, severity of the disease under investigation, need and length of time required to discontinue other potential therapies, availability of genetic testing, availability and proximity of trial sites for prospective subjects, ability to obtain subject consent and referral practices of physicians; • imposition of a clinical hold by regulatory authorities in trials in addition to RGX-121 and RGX-111; • failure by us, any CROs we engage or any other third parties to adhere to clinical trial requirements; • failure to perform in accordance with GCP, or applicable regulatory guidelines in the European Union and other countries; • 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; • delays in having subjects complete participation in a trial or return for post-treatment follow-up; • clinical trial sites or subjects dropping out of a trial; • selection of clinical endpoints that require prolonged periods of clinical observation or analysis of the resulting data; • occurrence of serious adverse events associated with the product candidate that are viewed to outweigh its potential benefits; • occurrence of serious adverse events in trials of the same class of agents conducted by other sponsors; or • changes in regulatory requirements and guidance that require amending or submitting new clinical protocols.
Even with the requisite approvals from the FDA, the EMA and other regulatory authorities, the commercial success of our product candidates will depend, in part, on the acceptance of physicians, patients and health care payors of gene therapy products in general, and our product candidates in particular, as medically necessary, cost-effective and safe.
Even with the requisite approvals from the FDA, the EMA, European Commission and other regulatory authorities, the commercial success of our product candidates will depend, in part, on the acceptance of physicians, patients and health care payors of gene therapy products in general, and our product candidates in particular, as medically necessary, cost-effective and safe.
Our future success depends on our and our NAV Technology Licensees’ successful development and commercialization of viable gene therapy product candidates.
Our future success depends on our and our NAV Technology Licensees’ and collaborators’ successful development and commercialization of viable gene therapy product candidates.
Even if we obtain regulatory approval for our product candidates, we may be required by the FDA, the EMA or other regulatory bodies to conduct additional clinical trials to support approval of our product candidates for patients diagnosed with different mutations of the respective diseases to which our product candidates relate.
In addition, even if we obtain regulatory approval for our product candidates, we may be required by the FDA, the EMA or other regulatory bodies to conduct additional clinical trials to support approval of our product candidates for patients diagnosed with different mutations of the respective diseases to which our product candidates relate.
In previous clinical trials involving AAV vectors for gene therapy, some subjects experienced the development of a T-cell response, whereby after the vector is within the target cell, the cellular immune response system triggers the removal of transduced cells by activated T-cells.
In previous clinical trials involving AAV vectors for gene therapy, some subjects experienced the development of a T-cell response, whereby after the vector is within the target cell, the subject’s immune response system triggers the removal of transduced cells by activated T-cells.
Of the large number of biologics and drugs in development in the biopharmaceutical industry, only a small percentage result in the submission of a BLA to the FDA or marketing authorization application (MAA) to the EMA and even fewer are approved for commercialization.
Of the large number of biologics and drugs in development in the biopharmaceutical industry, only a small percentage result in the submission of a BLA to the FDA or marketing authorization application (MAA) to the EMA and even fewer are expected to be approved for commercialization.
Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish proprietary rights. We have raised significant capital through public offerings of our common stock in order to fund our operations, which has caused dilution to our stockholders.
Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish proprietary rights. We have raised significant capital through public offerings of our common stock to fund our operations, which has caused dilution to our stockholders.
In this regard, we are engaged in patent litigation with Sarepta Therapeutics, Inc. (Sarepta) arising from its use of cultured host cell technology, which we believe is claimed in a patent we licensed from Penn, to make gene therapy products to treat Duchenne muscular dystrophy and Limb-girdle muscular dystrophy, among other products. In January 2024, the U.S.
In this regard, we are engaged in patent litigation with Sarepta Therapeutics, Inc. (Sarepta) arising from its use of cultured host cell technology, which we believe is covered by a patent we licensed from Penn, to make gene therapy products to treat Duchenne muscular dystrophy and Limb-girdle muscular dystrophy, among other products. In January 2024, the U.S.
There can be no assurance that we or our NAV Technology Licensees will not experience problems or delays in developing current or future product candidates or that such problems or delays will not cause unanticipated costs, or that any such development problems can be solved.
There can be no assurance that we or our NAV Technology Licensees and collaborators will not experience problems or delays in developing current or future product candidates or that such problems or delays will not cause unanticipated costs, or that any such development problems can be solved.
Furthermore, even if we do receive regulatory approval to market our lead product candidates, any such approval may be subject to limitations on the indicated uses for which we may market the product.
Furthermore, even if we do receive regulatory approval to market our lead product candidates, any such approval may be subject to limitations on the indicated use or uses for which we may market the product.
We compete with many companies that currently have extensive, experienced and well-funded 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 marketing and sales operations to recruit, hire, train and retain marketing and sales personnel. We also face competition in our search for third parties 50 Table of Contents to assist us with the sales and marketing efforts of our product candidates.
Thus, if one of our licensed patents is eligible for patent term extension under the Hatch-Waxman Act, we may not be able to control whether a petition to obtain a patent term extension is filed, or obtained, from the U.S.
Thus, if one of our licensed patents is eligible for patent term extension under the Hatch-Waxman Act, we may not be able to control whether a petition to obtain a patent term extension is filed, or obtained, from the U.S. Patent and Trademark Office.
We currently rely and expect to continue to rely on third parties to conduct parts of our product manufacturing, and these third parties may not perform satisfactorily. We currently plan to have some of the material manufactured for our planned preclinical and clinical programs by third parties.
We currently rely and expect to continue to rely on third parties to conduct parts of our product manufacturing including key components, and these third parties may not perform satisfactorily. We currently plan to have some of the material manufactured for our planned preclinical and clinical programs by third parties.
As we advance our product candidates, we will be required to consult with these regulatory and advisory groups, and comply with applicable guidelines. If we fail to do so, we may be required to delay or discontinue development of certain of our product candidates.
As we advance our product candidates, we will be required to consult with these regulatory and advisory groups, and comply with applicable guidelines. If we fail to do so, we may be required to delay or discontinue development 35 Table of Contents of certain of our product candidates.
Any person or entity purchasing or otherwise acquiring any interest in any of our securities shall be deemed to have notice of and to have consented to this provision. The forum selection clauses in our restated certificate of incorporation may limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us, our directors, officers or other employees.
Any person or entity purchasing or otherwise acquiring any interest in any of our securities shall be deemed to have notice of and to have consented to this provision. 67 Table of Contents The forum selection clause in our restated certificate of incorporation may limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us, our directors, officers or other employees.
Risks Related to Our Intellectual Property • Our intellectual property rights may be limited by the terms and conditions of licenses granted to us by others. • We must obtain and maintain patent protection for our products and technology to protect our intellectual property rights. • Our reliance on third parties requires us to share our trade secrets, which increases the possibility that a competitor will discover them or that our trade secrets will be misappropriated or disclosed. • Our intellectual property licenses with third parties may be subject to disagreements. • We are required to comply with the agreements under which we license intellectual property rights from third parties. • We may not be successful in obtaining necessary rights to our product candidates through acquisitions and in-licenses. • We may not be able to protect our intellectual property rights in the United States and throughout the world. • Issued patents covering our NAV Technology Platform or our product candidates could be found invalid or unenforceable. • Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights. • We may be subject to intellectual property claims. • Changes in U.S. patent law could diminish the value of patents in general, thereby impairing our ability to protect our products. • We may be unable to obtain patent term extension and data exclusivity for our product candidates.
Risks Related to Our Intellectual Property • Our intellectual property rights may be limited by the terms and conditions of licenses granted to us by others. • We must obtain and maintain patent protection for our products and technology to protect our intellectual property rights. • Our reliance on third parties requires us to share our trade secrets, which increases the possibility that a competitor will discover them or that our trade secrets will be misappropriated or disclosed. • Our intellectual property licenses with third parties may be subject to disagreements. • We are required to comply with the agreements under which we license intellectual property rights from third parties. • We may not be successful in obtaining necessary rights to our product candidates through acquisitions and in-licenses. • We may not be able to protect our intellectual property rights in the United States and throughout the world. • Issued patents covering our NAV Technology Platform or our product candidates could be found invalid, unenforceable or found to lack patent eligibility by the courts or patent offices. • Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights. • We may be subject to intellectual property claims. 34 Table of Contents • Changes in U.S. patent law including appellate interpretation of patent eligibility in biotechnology could diminish the value of patents in general and biotechnology patents specifically, thereby impairing our ability to protect our products. • We may be unable to obtain patent term extension and data exclusivity for our product candidates.
Additionally, if the market opportunities for our lead product candidates or any future product candidates are smaller than we believe they are, our product revenues may be harmed and our business may suffer. We focus our research and product development on treatments for severe genetic and orphan diseases.
Additionally, if the market opportunities for our lead product candidates or any future product candidates are smaller than we believe they are, our product revenues may be harmed and our business may suffer. 51 Table of Contents We focus our research and product development on treatments for severe genetic and orphan diseases.
It is difficult to predict what the CMS, the agency responsible for administering the Medicare program, will decide with respect to coverage and reimbursement for fundamentally novel products such as ours, as there is little body of established practices and precedents for these types of products.
It is difficult to predict what the CMS, the agency responsible for administering the Medicare program, will decide with respect to coverage and reimbursement for fundamentally novel products such as ours, as there is not a large body of established practices and precedents for these types of products.
We or our collaborators may in the future become party to, or be threatened with, adversarial proceedings or litigation regarding intellectual property rights with respect to our product candidates and technology, including interference proceedings, post grant review and inter partes review before the USPTO.
We or our collaborators may in the future become party to, or be threatened with, adversarial proceedings or litigation 63 Table of Contents regarding intellectual property rights with respect to our product candidates and technology, including interference proceedings, post grant review and inter partes review before the USPTO.
The IRA also establishes a rebate obligation for drug manufacturers that increase prices of Medicare Part B and Part D covered drugs at a rate greater than the rate of inflation.
The IRA also establishes a rebate obligation for drug manufacturers that increase prices of 52 Table of Contents Medicare Part B and Part D covered drugs at a rate greater than the rate of inflation.
Competitors may use our technologies in jurisdictions where we have not obtained patent protection to develop their own products and, further, may export otherwise infringing products to territories where we have patent protection, but enforcement is not as strong as that in the United States.
Competitors may use our technologies in jurisdictions where we have not obtained patent protection to develop their own products and, further, may export 61 Table of Contents otherwise infringing products to territories where we have patent protection, but enforcement is not as strong as that in the United States.
For example, the IRA enacted in 2022, permits HHS to engage in price-capped negotiation to set the price of certain drugs and biologics reimbursed under Medicare Part B and Part D. The IRA contains statutory exclusions to the negotiation program, including for certain orphan designated drugs for which the only approved indication is for the orphan disease or condition.
For example, the IRA enacted in 2022, permits HHS to engage in price-capped negotiation to set the price of certain drugs and biologics reimbursed under Medicare Part B and Part D. The IRA contains statutory exclusions to the negotiation program, including for certain orphan designated drugs for which the only approved indications are for an orphan disease or condition.
Risks Related to Our Financial Position • We face significant competition and there is a possibility that our competitors may achieve regulatory approval before us or develop products that are safer, less expensive or more convenient or effective than ours. • We expect to regularly incur losses for the foreseeable future and may never again achieve or maintain profitability. • Failure to obtain additional funding when needed may force us to delay, limit or terminate certain of our licensing activities, product development efforts or other operations. • We have never generated revenue from sales of our product candidates and may never do so in the future.
Risks Related to Our Financial Position • We face significant competition and there is a possibility that our competitors may achieve regulatory approval before us or develop products that are safer, less expensive or more convenient or effective than ours. • We expect to regularly incur losses for the foreseeable future and may never again achieve or maintain profitability. • Our existing cash resources may not be sufficient to fund our operations for the next 12 months. • Failure to obtain additional funding when needed may force us to delay, limit or terminate certain of our licensing activities, product development efforts or other operations. • We have never generated revenue from sales of our product candidates and may never do so in the future.
We have incurred cumulative net losses and have had few profitable quarters since inception. We expect to regularly incur losses until we have successfully commercialized one or more product candidates and may never achieve or maintain profitability in the future. Since inception, we have incurred cumulative net losses.
We have incurred cumulative net losses since inception and expect to regularly incur losses until we have successfully commercialized one or more product candidates and may never achieve or maintain profitability in the future. Since inception, we have incurred cumulative net losses.
Patent and Trademark Office. 59 Risks Related to Ownership of Our Common Stock Our operating results may fluctuate substantially, which makes our future operating results difficult to predict and could cause the price of our common stock to fluctuate substantially. We expect our operating results to be subject to fluctuations.
Risks Related to Ownership of Our Common Stock Our operating results may fluctuate substantially, which makes our future operating results difficult to predict and could cause the price of our common stock to fluctuate substantially. We expect our operating results to be subject to fluctuations.
During the FDA review process, we will need to identify success criteria and endpoints such that the FDA will be able to subsequently evaluate the clinical efficacy and safety profile of our product candidates.
During the clinical development process, we will need to identify success criteria and endpoints for our clinical trials such that the FDA will be able to subsequently evaluate the clinical efficacy and safety profile of our product candidates.
We cannot assure you that our efforts to seek patent protection for our technology and products will not be negatively impacted by the decisions described above, rulings in other cases or changes in guidance or procedures issued by the USPTO.
We cannot provide any assurance that our efforts to seek patent protection for our technology and products will not be negatively impacted by the decisions described above, rulings in other cases or changes in guidance or procedures issued by the USPTO.
Issued patents covering our NAV Technology Platform or our product candidates could be found invalid or unenforceable if challenged in court. We may not be able to protect our trade secrets in court.
Issued patents covering our NAV Technology Platform or our product candidates could be found invalid or unenforceable if challenged in court and we may be unable to protect our trade secrets in court.
One customer accounted for approximately 98% of our total revenues for the year ended December 31, 2024. One customer accounted for approximately 95% of our total revenues for the year ended December 31, 2023. We expect future license and royalty revenue to be derived from a limited number of licensees and collaborators.
One customer accounted for approximately 98% of our total revenues for the year ended December 31, 2024. We expect future license, royalty and service revenues to continue to be derived from a limited number of licensees and collaborators.
Delay or failure to obtain, or unexpected costs in obtaining, the regulatory approval necessary to bring a potential product to market could decrease our ability to generate product revenue, and our business, financial condition, results of operations and prospects would be materially harmed. Our business depends substantially on the success of our lead product candidates.
Delay or failure to obtain, or unexpected costs in obtaining, the regulatory approval necessary to bring a potential product to market could decrease our ability to generate product revenue, and our business, financial condition, results of operations and prospects would be materially harmed.
We rely on additional third parties to manufacture ingredients of our product candidates and to perform quality testing, and reliance on these third parties entails risks to which we would not be subject if we manufactured the product candidates ourselves, including: • reduced control for certain aspects of manufacturing activities; • termination or nonrenewal of manufacturing and service agreements with third parties in a manner or at a time that is costly or damaging to us; • disruptions to the operations of our third-party manufacturers and service providers caused by conditions unrelated to our business or operations, including the bankruptcy of, or legal or regulatory actions against, the manufacturer or service provider; • reduced capacity of our third-party manufacturers and service providers caused by increased demand by their other customers; • discovery of data integrity issues with our third-party manufacturers and service providers which directly or indirectly impact our ability to use our product candidates; and • legal or regulatory actions against our third-party manufacturers and service providers which adversely affect our ability to use our product candidates.
We rely on additional third parties to manufacture ingredients of our product candidates and to perform quality testing, and reliance on these third parties entails risks to which we would not be subject if we manufactured the product candidates ourselves, including: • reduced control for certain aspects of manufacturing activities; • termination or nonrenewal of manufacturing and service agreements with third parties in a manner or at a time that is costly or damaging to us; • disruptions to the operations of our third-party manufacturers and service providers caused by conditions unrelated to our business or operations, including the bankruptcy of, or legal or regulatory actions against, the manufacturer or service provider; • reduced capacity of our third-party manufacturers and service providers caused by increased demand by their other customers; • discovery of data integrity issues with our third-party manufacturers and service providers which directly or indirectly impact our ability to use our product candidates; and • legal or regulatory actions against our third-party manufacturers and service providers which adversely affect our ability to use our product candidates. 49 Table of Contents FDA, EMA or other regulatory authority action could include injunction, recall, seizure or total or partial suspension of product manufacture or manufacturing authorization.
Accordingly, even if we are able to obtain the requisite financing to continue to fund our development programs, we cannot assure you that our lead product candidates will be successfully developed or commercialized.
Accordingly, even if we are able to obtain the requisite financing to continue to fund our development programs, we cannot provide any assurance that our lead product candidates will be successfully developed or commercialized.
Our NAV Technology Licensees and collaborators have multiple preclinical studies and clinical trials in progress. However, only one gene therapy product based on our licensing program, Novartis AG’s Zolgensma, has been approved or commercialized.
Our NAV Technology Licensees and collaborators have multiple preclinical studies and clinical trials in progress. However, only two gene therapy products based on our licensing program, Novartis AG’s Zolgensma and Itvisma, have been approved or commercialized.
If we were to lose the services of a significant number of employees, consultants or advisors, or those who sit in key positions, including scientific and technical roles, such loss could impede our ability to achieve our research, development, licensing and commercialization objectives.
In addition, our success depends in large part on the performance of our team. If we were to lose the services of a significant number of employees, consultants or advisors, or those who sit in key positions, including scientific and technical roles, such loss could impede our ability to achieve our research, development, licensing and commercialization objectives.
Our business could be negatively affected as a result of the actions of activist stockholders.
Our business could be negatively affected as a result of the actions of activist stockholders or stockholder litigation.
Risks Related to Ownership of Our Common Stock • Our operating results are difficult to predict and could cause the price of our common stock to fluctuate substantially. • Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish proprietary rights. 31 • Strategic partnerships and any other arrangements or acquisitions that we effect in the future may increase our capital requirements, dilute our stockholders, cause us to incur debt or assume contingent liabilities and subject us to other risks. • Provisions in our certificate of incorporation and bylaws might discourage, delay or prevent a change in control. • Our certificate of incorporation includes exclusive forum clauses for certain litigation. • Our business could be negatively affected as a result of the actions of activist stockholders.
Risks Related to Ownership of Our Common Stock • Our operating results are difficult to predict and could cause the price of our common stock to fluctuate substantially. • Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish proprietary rights. • Strategic partnerships and any other arrangements or acquisitions that we effect in the future may increase our capital requirements, dilute our stockholders, cause us to incur debt or assume contingent liabilities and subject us to other risks. • Provisions in our certificate of incorporation and bylaws might discourage, delay or prevent a change in control. • Our certificate of incorporation includes an exclusive forum clause for certain litigation. • Our business could be negatively affected as a result of the actions of activist stockholders or stockholder litigation. • If we are unable to maintain effective internal control over financial reporting, investors may lose confidence in the accuracy of our financial reports.
If the results of our planned clinical trials are inconclusive or if there are safety concerns or serious adverse events associated with our product candidates, we may: • receive a clinical hold for a particular product candidate, which, if not lifted, could require that we discontinue development of a product candidate; • be required to conduct additional studies or clinical trials with respect to a product candidate or for a potential indication, which may result in additional significant expense and delays in seeking regulatory approval; • be delayed in obtaining regulatory approval for our product candidates, if at all; • obtain approval for indications or patient populations that are not as broad as intended or desired; • obtain approval with labeling that includes significant use or distribution restrictions or safety warnings; • be subject to changes in the way the product is administered; • be required to perform additional clinical trials to support approval or be subject to additional post-marketing testing or other requirements; • have regulatory authorities withdraw, vary or suspend their approval of the product or impose restrictions on its distribution in the form of a modified risk evaluation and mitigation; • be subject to the addition of labeling statements, such as warnings or contraindications; • be sued; or • experience damage to our reputation.
If the results of our planned clinical trials are inconclusive or if there are safety concerns or serious adverse events associated with our product candidates, we may: • receive a clinical hold for a particular product candidate, in addition to RGX-111 and RGX-121, which, if not lifted, could require that we discontinue development of a product candidate; • be required to conduct additional studies or clinical trials with respect to a product candidate or for a potential indication, which may result in additional significant expense and delays in seeking regulatory approval; • be delayed in obtaining regulatory approval for our product candidates, if at all; • obtain approval for indications or patient populations that are not as broad as intended or desired; • obtain approval with labeling that includes significant use or distribution restrictions or safety warnings; • be subject to changes in the way the product is administered; • be required to perform additional clinical trials to support approval or be subject to additional post-marketing testing or other requirements; • have regulatory authorities withdraw, vary or suspend their approval of the product or impose restrictions on its distribution in the form of a modified risk evaluation and mitigation; • be subject to the addition of labeling statements, such as warnings or contraindications; • be sued; or • experience damage to our reputation. 39 Table of Contents Our NAV Technology Platform, our product candidates or our licensees’ or collaborators’ product candidates, and the process for administering such product candidates, may cause undesirable side effects or have other properties that could delay or prevent regulatory approval of product candidates, limit the commercial potential or result in significant negative consequences following any potential marketing approval.
Accordingly, in markets outside the United States, the reimbursement for our products may be reduced compared with the reimbursement in the United States and may be insufficient to generate commercially reasonable product revenues. 47 Moreover, increasing efforts by government and third-party payors in the United States and abroad to cap or reduce healthcare costs has led to increased pressure on the healthcare industry to reduce costs and may, in the future, cause such organizations to limit both coverage and the level of reimbursement for new products approved and, as a result, they may not cover or provide adequate payment for our product candidates.
Moreover, increasing efforts by government and third-party payors in the United States and abroad to cap or reduce healthcare costs has led to increased pressure on the healthcare industry to reduce costs and may, in the future, cause such organizations to limit both coverage and the level of reimbursement for new products approved and, as a result, they may not cover or provide adequate payment for our product candidates.
Infringement of these laws could result in substantial fines and imprisonment. Product liability lawsuits against us could cause us to incur substantial liabilities and could limit licensing of our NAV Technology Platform or commercialization of any product candidates that we may develop.
Product liability lawsuits against us could cause us to incur substantial liabilities and could limit licensing of our NAV Technology Platform or commercialization of any product candidates that we may develop.
The successful assertion of one or more large claims against us that exceed or are not covered by our insurance coverage or changes in our insurance policies, including premium increases or the imposition of large deductible or co-insurance requirements, could materially harm our business, financial condition, results of operations and prospects.
The successful assertion of one or more large claims against us that exceed or are not covered by our insurance coverage or changes in our insurance policies, including premium increases or the imposition of large deductible or co-insurance requirements, could materially harm our business, financial condition, results of operations and prospects. 57 Table of Contents Our customers are concentrated and therefore the loss of a significant customer may harm our business.
We will need to raise additional funding, which may not be available on acceptable terms, or at all. Failure to obtain this necessary capital when needed may force us to delay, limit or terminate certain of our licensing activities, product development efforts or other operations.
We will need to raise additional funding, which may not be available on acceptable terms, or at all, and failure to do so may force us to delay, limit or terminate certain of our licensing activities, product development and commercialization efforts or other operations.
If any such adverse events occur in our or third-party trials, our clinical trials could be suspended or terminated. 35 As a result of these concerns, we may decide, or the FDA, the European Commission, the EMA or other regulatory authorities could order us, to halt, delay or amend preclinical development or clinical development of our product candidates or we may be unable to receive regulatory approval of our product candidates for any or all targeted indications.
As a result of these concerns, we may decide, or the FDA, the European Commission, the EMA or other regulatory authorities could order us, to halt, delay or amend preclinical development or clinical development of our product candidates or we may be unable to receive regulatory approval of our product candidates for any or all targeted indications.
Our future capital requirements will depend on many factors, including: • the timing of enrollment, commencement and completion of our clinical trials; • the results of our clinical trials; • the results of our preclinical studies for our product candidates and any subsequent clinical trials; • the scope, progress, results and costs of drug discovery, laboratory testing, preclinical development and clinical trials for our product candidates; • the costs associated with building out additional laboratory and manufacturing capacity; • the costs, timing and outcome of regulatory review of our product candidates; • the impact of any government-imposed tariffs on cost of goods and services, particularly related to partnered product candidates; • the costs of future product sales, medical affairs, marketing, manufacturing and distribution activities for any of our product candidates for which we receive marketing approval; • revenue, if any, received from commercial sales of our products, should any of our product candidates receive marketing approval; • revenue received from commercial sales of Zolgensma and the timing and amount of Zolgensma royalties paid to HCR under our royalty purchase agreement; • revenue received from other commercial sales of our licensees’ and collaborators’ products, should any of their product candidates receive marketing approval, and other revenue received under our licensing agreements and collaborations; • the costs of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending any intellectual property-related claims; • our current licensing agreements or collaborations remaining in effect, including the AbbVie Collaboration and License Agreement relating to ABBV-RGX-314 and the Nippon Shinyaku Collaboration and License Agreement relating to RGX-121 and RGX-111, and our ability to timely achieve any milestones set forth in such agreements or collaborations; 39 • our ability to establish and maintain additional licensing agreements or collaborations on favorable terms, if at all; and • the extent to which we acquire or in-license other product candidates and technologies.
Our future capital requirements will depend on many factors, including: • the timing of enrollment, commencement and completion of our clinical trials; • the results of our clinical trials; • the results of our preclinical studies for our product candidates and any subsequent clinical trials; • the scope, progress, results and costs of drug discovery, laboratory testing, preclinical development and clinical trials for our product candidates; • delays or costs due to a clinical hold or CRL, including BLA resubmission; • whether we receive a priority review voucher (PRV) and are able to monetize or otherwise realize any potential value associated with such a voucher; • the value of any PRV received diminishes including any decreases due to demand for these vouchers; • the costs associated with building out additional laboratory and manufacturing capacity; • the costs, timing and outcome of regulatory review of our product candidates; • the impact of any government-imposed tariffs on cost of goods and services, particularly related to partnered product candidates; • the costs of future product sales, medical affairs, marketing, manufacturing and distribution activities for any of our product candidates for which we receive marketing approval; • revenue, if any, received from commercial sales of our products, should any of our product candidates receive marketing approval; • revenue received from commercial sales of Zolgensma and Itvisma, and the timing and amount of Zolgensma and Itvisma royalties paid to Healthcare Royalty Management, LLC (collectively and with other affiliated entities, HCR) under our royalty monetization agreements; 44 Table of Contents • revenue received from other commercial sales of our licensees’ and collaborators’ products, should any of their product candidates receive marketing approval, other revenue received under our licensing agreements and collaborations, and the timing and amount of any such revenues payable to HCR under our royalty monetization agreements; • the costs of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights including against Sarepta and defending any intellectual property-related claims; • our current licensing agreements or collaborations remaining in effect, including the AbbVie Collaboration and License Agreement relating to ABBV-RGX-314 and the Nippon Shinyaku Collaboration and License Agreement relating to RGX-121 and RGX-111, and our ability to timely achieve any milestones set forth in such agreements or collaborations; • our ability to establish and maintain additional licensing agreements or collaborations on favorable terms, if at all; and • the extent to which we acquire or in-license other product candidates and technologies.
Any potential acquisition or strategic partnership may entail numerous risks, including: • increased operating expenses and cash requirements; 60 • the assumption of additional indebtedness or contingent liabilities; • the issuance of our equity securities; • assimilation of operations, intellectual property and products of an acquired company, including difficulties associated with integrating new personnel; • the diversion of our management’s attention from our existing product programs and initiatives in pursuing such a strategic merger or acquisition; • retention of key employees, the loss of key personnel, and uncertainties in our ability to maintain key business relationships; • risks and uncertainties associated with the other party to such a transaction, including the prospects of that party and their existing products or product candidates and regulatory approvals; and • our inability to generate revenue from acquired technology and/or products sufficient to meet our objectives in undertaking the acquisition or even to offset the associated acquisition and maintenance costs.
Any potential acquisition or strategic partnership may entail numerous risks, including: • increased operating expenses and cash requirements; • the assumption of additional indebtedness or contingent liabilities; • the issuance of our equity securities; • assimilation of operations, intellectual property and products of an acquired company, including difficulties associated with integrating new personnel; • the diversion of our management’s attention from our existing product programs and initiatives in pursuing such a strategic merger or acquisition; • retention of key employees, the loss of key personnel, and uncertainties in our ability to maintain key business relationships; • risks and uncertainties associated with the other party to such a transaction, including the prospects of that party and their existing products or product candidates and regulatory approvals; and • our inability to generate revenue from acquired technology and/or products sufficient to meet our objectives in undertaking the acquisition or even to offset the associated acquisition and maintenance costs. 66 Table of Contents In addition, if we undertake acquisitions, we may issue dilutive securities, assume or incur debt obligations, incur large one-time expenses and acquire intangible assets that could result in significant future amortization expense.
The ability of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept the payment of user fees, and statutory, regulatory and policy changes. Average review times at the FDA have fluctuated in recent years as a result.
The ability and willingness of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept the payment of user fees, and statutory, regulatory and policy changes.
We have in the past, and in the future may, enter into licensing agreements or collaborations with third parties licensing parts of our NAV Technology Platform for the development of product candidates. If these licensing arrangements or collaborations are not successful, our business could be harmed.
We have in the past, and in the future may, enter into licensing agreements or collaborations with third parties licensing parts of our NAV Technology Platform for the development of product candidates which, if unsuccessful, could harm our business.
Future license and royalty revenue is uncertain due to the contingent nature of our licenses granted to third parties. Risks Related to Our Intellectual Property Our rights to license our NAV Technology Platform and to develop and commercialize our product candidates are subject, in part, to the terms and conditions of licenses granted to us by others.
Risks Related to Our Intellectual Property Our rights to license our NAV Technology Platform and to develop and commercialize our product candidates are subject, in part, to the terms and conditions of licenses granted to us by others.
If we license rights to product candidates, we may not be able to realize the benefit of such transactions if we are unable to successfully integrate the licensed product candidates with our existing operations. 42 If we are unable to reach agreements with suitable licensees or collaborators on a timely basis, on acceptable terms or at all, we may have to curtail the development of a product candidate, reduce or delay its development program, delay its potential commercialization, reduce the scope of any sales or marketing activities or increase our expenditures and undertake development or commercialization activities at our own expense.
If we are unable to reach agreements with suitable licensees or collaborators on a timely basis, on acceptable terms or at all, we may have to curtail the development of a product candidate, reduce or delay its development program, delay its potential commercialization, reduce the scope of any sales or marketing activities or increase our expenditures and undertake development or commercialization activities at our own expense.
Risk Factor Summary Risks Related to Our NAV Technology Platform and the Development of Our Product Candidates • It is difficult to predict the time and cost of development and of obtaining regulatory approval for our product candidates. • Our business depends substantially on the success of our lead product candidates. • We have limited clinical results for some of our product candidates. • Regulatory authorities may not consider the endpoints of our clinical trials to provide clinically meaningful results. • The results from our preclinical studies or clinical trials for our product candidates may not support as broad a marketing approval as we seek, and we may be required to conduct additional clinical trials or evaluate subjects for a follow-up period. • We may encounter substantial delays in our planned clinical trials, or we may fail to demonstrate safety and efficacy to the satisfaction of applicable regulatory authorities. • We may be negatively impacted if the results of our planned clinical trials are inconclusive or if there are safety concerns or serious adverse events associated with our product candidates. • Undesirable side effects may delay or prevent our product candidates and those of our licensees or collaborators from obtaining regulatory approval, limit their commercial potential or result in significant negative consequences following approval. • We cannot predict when, or if, we will obtain regulatory approval to commercialize a product candidate.
Risk Factor Summary Risks Related to Our NAV Technology Platform and the Development of Our Product Candidates • It is difficult to predict the time and cost of development and of obtaining regulatory approval for our product candidates. • Our business depends substantially on the success of our lead product candidates. • We have limited clinical results for some of our product candidates. • Regulatory authorities may not consider the endpoints of our clinical trials to provide clinically meaningful results. • The results from our preclinical studies or clinical trials for our product candidates may not support as broad a marketing approval as we seek, and we may be required to conduct additional clinical trials or evaluate subjects for a follow-up period. • Our planned clinical trials may be substantially delayed, or we may fail to demonstrate safety and efficacy to the satisfaction of applicable regulatory authorities. • The FDA’s clinical holds on RGX-111 and RGX-121 may delay development, increase costs, and adversely impact our business, financial condition and results of operations, or lead to the termination of one or both programs. • We received a Complete Response Letter from the FDA for the RGX-121 BLA, and it is uncertain when we may be able to resubmit the BLA, if at all, and the BLA may never be approved even after resubmission, which could adversely impact our business. • We may be negatively impacted if the results of our planned clinical trials are inconclusive or if there are safety concerns or serious adverse events associated with our product candidates. • Undesirable side effects may delay or prevent our product candidates and those of our licensees or collaborators from obtaining regulatory approval, limit their commercial potential or result in significant negative consequences following approval. • We cannot predict when, or if, we will obtain regulatory approval to commercialize a product candidate.
A competitor’s discovery of our trade secrets would impair our competitive position and harm our business. 54 Our intellectual property licenses with third parties may be subject to disagreements over contract interpretation, which could narrow the scope of our rights to the relevant intellectual property or technology, increase our financial or other obligations to our licensors or other parties, or decrease financial or other obligations of our licensees and collaborators.
Our intellectual property licenses with third parties may be subject to disagreements over contract interpretation, which could narrow the scope of our rights to the relevant intellectual property or technology, increase our financial or other obligations to our licensors or other parties, or decrease financial or other obligations of our licensees and collaborators.
If our operations are found to be in violation of any of the laws described above or any other government regulations that apply to us, we may be subject to penalties, including civil and criminal penalties, damages, fines, exclusion from participation in government health care programs, such as Medicare and Medicaid, reputational harm, public reprimands, third-party actions, such as cease and desist letters or injunctions, and the curtailment or restructuring of our operations, any of which could harm our ability to operate our business and our results of operations.
If our operations are found to be in violation of any of the laws described above or any other government regulations that apply to us, we may be subject to penalties, including civil and criminal penalties, damages, fines, exclusion from participation in government health care programs, such as Medicare and Medicaid, reputational harm, public reprimands, third-party actions, such as cease and desist letters or injunctions, and the curtailment or restructuring of our operations, any of which could harm our ability to operate our business and our results of operations. 55 Table of Contents The provision of benefits or advantages to physicians to induce or encourage the prescription, recommendation, endorsement, purchase, supply, order or use of medicinal products is prohibited in the European Union.
Despite our efforts to protect our trade secrets, our competitors may discover our trade secrets, either through breach of our agreements with third parties, independent development or publication of information by any of our third-party collaborators.
Despite our efforts to protect our trade secrets, our competitors may discover our trade secrets, either through breach of our agreements with third parties, independent development or publication of information by any of our third-party collaborators. A competitor’s discovery of our trade secrets would impair our competitive position and harm our business.
Even if we are successful in defending against such claims, litigation could result in substantial costs and be a distraction to management. 58 In addition, while it is our policy to require our employees and contractors who may be involved in the conception or development of intellectual property to execute agreements assigning such intellectual property to us, we may be unsuccessful in executing such an agreement with each party who, in fact, conceives or develops intellectual property that we regard as our own.
In addition, while it is our policy to require our employees and contractors who may be involved in the conception or development of intellectual property to execute agreements assigning such intellectual property to us, we may be unsuccessful in executing such an agreement with each party who, in fact, conceives or develops intellectual property that we regard as our own.
Even though we have obtained orphan drug exclusivity for certain product candidates, that exclusivity may not effectively protect the product candidate from competition because the FDA may subsequently approve another drug for the same condition if the FDA concludes that the latter drug is not the same drug or is clinically superior in that it is shown to be safer, more effective or makes a major contribution to patient care.
The availability of our competitors’ products could limit the demand, and the price we are able to charge, for any products that we may develop and commercialize. 42 Table of Contents Even though we have obtained orphan drug exclusivity for certain product candidates, that exclusivity may not effectively protect the product candidate from competition because the FDA may subsequently approve another drug for the same condition if the FDA concludes that the latter drug is not the same drug or is clinically superior in that it is shown to be safer, more effective or makes a major contribution to patient care.
Disruptions at the FDA and other agencies may also slow the time necessary for new product candidates to be reviewed and approved by necessary government agencies, which could adversely affect our business.
Average review times at the FDA have fluctuated in recent years as a result. Disruptions at the FDA and other agencies may also slow the time necessary for new product candidates to be reviewed and approved by necessary government agencies, which could adversely affect our business.
As we are developing novel treatments for diseases in which there is little clinical experience with new endpoints and methodologies, there is heightened risk that the FDA, the 33 EMA or other regulatory bodies may not consider the clinical trial endpoints that we select to provide clinically meaningful results (reflecting a tangible benefit to patients).
As we are developing novel treatments for diseases in which there is little clinical experience with new endpoints and methodologies, there is heightened risk that the FDA, the EMA or other regulatory bodies may not consider the clinical trial endpoints that we select to directly reflect how a treatment impacts a disease.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeIn the last three years, we have not identified any cybersecurity incidents which have materially affected, or are reasonably likely to materially affect, our business. For further information regarding cybersecurity risks, please refer to “Risk Factors – Risks Related to Our Business Operations” and other risks described in the “Risk Factors” section of this Annual Report on Form 10-K.
Biggest changeFor further information regarding cybersecurity risks, please refer to “Risk Factors – Risks Related to Our Business Operations” and other risks described in the “Risk Factors” section of this Annual Report on Form 10-K. 69 Table of Contents
ITEM 1C. CYBERSECURITY We regularly assess risks from cybersecurity threats; monitor our information systems for potential vulnerabilities; and test those systems pursuant to our cybersecurity policies, processes and practices. To protect our information systems from cybersecurity threats, we use various security tools that are designed to help identify, escalate, investigate, resolve and recover from security incidents in a timely manner.
ITEM 1C. CYBERSECURITY We regularly assess risks from cybersecurity threats, monitor our information systems for potential vulnerabilities and test those systems pursuant to our cybersecurity policies, processes and practices. To protect our information systems from cybersecurity threats, we use security tools that are designed to help identify, escalate, investigate, resolve and recover from security incidents in a timely manner.
We require annual information security training to be completed by our employees, and we maintain a limited cybersecurity liability insurance policy. 62 Our Senior Vice President of Information Technology (SVP, IT) is responsible for the establishment and maintenance of our cybersecurity program, as well as the assessment and management of cybersecurity risks.
We require annual information security training to be completed by our employees, and we maintain a limited cybersecurity liability insurance policy. Our Senior Vice President of Information Technology (SVP, IT) is responsible for the establishment and maintenance of our cybersecurity program, as well as the assessment and management of cybersecurity risks.
The output of this process is then integrated with our enterprise risk management (ERM) program. The ERM program is managed cross-functionally, with input from various senior management representatives across our business operations, and is used to assess risks to our business based on their potential likelihood and magnitude of impact.
The output of this process is then integrated within our enterprise risk management (ERM) program. The ERM program is managed cross-functionally, with input from various senior management representatives across our business operations, and is used to assess risks to our business based on their potential likelihood and magnitude of impact.
Our current SVP, IT has over 25 years of experience in information technology and possesses the requisite education, skills and experience expected of an individual assigned to these duties. We also engage third-party consultants and auditors to assess the effectiveness of our cybersecurity prevention and response systems and processes.
Our current SVP, IT has over 25 years of experience in information technology and possesses the requisite education, skills and experience expected of an individual assigned to these duties. We also engage third-party consultants and auditors on an annual basis to assess the effectiveness of our cybersecurity prevention and response systems and processes.
The Audit Committee of our Board of Directors oversees our ERM program regarding material risks arising from cybersecurity threats impacting our business. Management provides quarterly reporting on our material enterprise risks to the Audit Committee.
The Audit Committee of our Board of Directors oversees our ERM program, including with respect to material risks arising from cybersecurity threats impacting our business. Management provides quarterly reporting on our material enterprise risks to the Audit Committee.
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In the last three years, we have not identified any cybersecurity incidents which have materially affected, or are reasonably likely to materially affect, our business.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeITEM 3. LEGAL PROCEEDINGS From time to time, we are party to various lawsuits, claims or other legal proceedings that arise in the normal course of our business.
Biggest changeITEM 3. LEGAL PROCEEDINGS From time to time, we are party to various lawsuits, claims or other legal proceedings that arise in the normal course of our business. Please see Note 8, “Commitments and Contingencies—Litigation” to the accompanying audited consolidated financial statements for additional information. ITEM 4. MINE SAF ETY DISCLOSURES Not applicable. 70 Table of Contents PART II
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We do not believe that we are currently party to any pending legal actions that could reasonably be expected to have a material adverse effect on our business, financial condition, results of operations or cash flows. ITEM 4. MINE SAF ETY DISCLOSURES Not applicable. 63 PART II

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeMARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES Market Information Our common stock is traded on The Nasdaq Global Select Market under the symbol “RGNX.” Stock Performance Graph The graph set forth below compares the cumulative total stockholder return on our common stock between December 31, 2019 and December 31, 2024, with the cumulative total return of (a) the Nasdaq Composite Index and (b) the Nasdaq Biotechnology Index, over the same period.
Biggest changeITEM 5. MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES Market Information Our common stock is traded on The Nasdaq Global Select Market under the symbol “RGNX.” Holders As of February 27, 2026, there were five holders of record of our common stock.
We do not plan to pay dividends in the foreseeable future. ITEM 6. [RESERVED] 65
We do not plan to pay dividends in the foreseeable future. ITEM 6. [RESERVED] 71 Table of Contents
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The figures below assume an investment of $100 in our common stock, the Nasdaq Composite Index and the Nasdaq Biotechnology Index at the closing price on December 31, 2019 and assumes the reinvestment of dividends, if any. The comparisons shown in the graph below are based upon historical data.
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We caution that the stock price performance shown in the graph below is not necessarily indicative of, nor is it intended to forecast, the potential future performance of our common stock. Information used in the graph was obtained from the Nasdaq Stock Market LLC, a financial data provider and a source believed to be reliable.
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The Nasdaq Stock Market LLC is not responsible for any errors or omissions in such information.
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The following performance graph and related information shall not be deemed "soliciting material" or to be "filed" with the SEC, nor shall such information be incorporated by reference into any future filing under the Securities Act of 1933 or the Securities Exchange Act of 1934, each as amended, except to the extent that we specifically incorporate it by reference into such filing. $100 investment in stock or index December 31, 2019 December 31, 2020 December 31, 2021 December 31, 2022 December 31, 2023 December 31, 2024 REGENXBIO Inc. $ 100 $ 111 $ 80 $ 55 $ 44 $ 19 Nasdaq Composite $ 100 $ 145 $ 177 $ 119 $ 173 $ 224 Nasdaq Biotechnology $ 100 $ 126 $ 126 $ 114 $ 119 $ 118 64 Holders As of March 7, 2025, there were five holders of record of our common stock.

Item 7. Management's Discussion & Analysis

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

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Biggest changeThe decrease was primarily attributable to the following: • a decrease of $10.5 million in personnel-related costs for research and development personnel, including a $2.6 million decrease in stock-based compensation expense, primarily driven by the reduction in workforce associated with our corporate restructuring in the fourth quarter of 2023; • a decrease of $10.3 million in manufacturing expenses and other costs of clinical supply for our lead product candidates, largely driven by ABBV-RGX-314 and RGX-121 clinical supply costs; • a decrease of $6.2 million in preclinical activities and other early-stage research and development; and • a decrease of $6.1 million in costs for laboratories and facilities used by research and development personnel, including a $1.1 million decrease in depreciation expense allocated to research and development functions, primarily driven by a decrease in laboratory supplies and consumables.
Biggest changeThe increase was primarily attributable to the following: • an increase of $8.1 million in manufacturing-related expenses and other clinical supply costs for our lead product candidates, largely driven by manufacturing costs for ABBV-RGX-314, RGX-202 and RGX-121; • an increase of $5.8 million in personnel-related costs due to increased headcount of development personnel, net of a $2.0 million decrease in stock-based compensation expense; and • an increase of $5.7 million in costs associated with clinical trials and regulatory activities, largely driven by clinical trial expenses for RGX-202 pivotal trials.
We are also eligible to receive double-digit royalties on net sales of RGX-121 and RGX-111 by Nippon Shinyaku, subject to specified offsets and reductions. We also retain all rights to, and any proceeds related to the sale of, any priority review vouchers that may be issued upon the potential approvals of RGX-121 and RGX-111.
We are also eligible to receive double-digit royalties on net sales of RGX-121 and RGX-111 by Nippon Shinyaku, subject to specified offsets and reductions. We retain all rights to, and any proceeds related to the sale of, any priority review vouchers that may be issued upon the potential approvals of RGX-121 and RGX-111.
Investment Income Investment income consists of interest income earned and gains and losses realized from our cash and cash equivalents, marketable securities and non-marketable equity securities. Cash equivalents are comprised of money market mutual funds and highly liquid debt securities with original maturities of 90 days or less at acquisition. Marketable securities are comprised of available-for-sale debt securities.
Investment Income Investment income consists of interest income earned and gains and losses realized from our cash equivalents, marketable securities and non-marketable equity securities. Cash equivalents are comprised of money market mutual funds and highly liquid debt securities with original maturities of 90 days or less at acquisition. Marketable securities are comprised of available-for-sale debt securities.
License agreements generally have a term at least equal to the life of the underlying patents, but are terminable at the option of the licensee.
License agreements generally have a term at least equal to the life of the underlying patents, but are terminable at the option of the licensee.
If a licensee elects to terminate a license prior to the end of the license term, the licensed intellectual property is returned to us and any consideration recorded as accounts receivable or contract assets which is not contractually payable by the licensee is charged off as a reduction of license revenue in the period of the termination.
If a licensee elects to terminate a license prior to the end of the license term, the licensed intellectual property is returned to us and any consideration recorded as accounts receivable or contract assets which is not contractually payable by the licensee is charged off as a reduction of revenue in the period of the termination.
Collaborative Arrangements We evaluate our agreements with collaboration partners to determine whether they are within the scope of ASC 808, Collaborative Arrangements (ASC 808).
We evaluate our agreements with collaboration partners to determine whether they are within the scope of ASC 808, Collaborative Arrangements (ASC 808).
For transactions that are accounted for pursuant to ASC 808, an appropriate method of recognition and presentation is determined and consistently applied. For transactions that are accounted for pursuant to ASC 606, we apply the five-step model as described in our revenue recognition policies.
For transactions that are accounted for pursuant to ASC 606, we apply the five-step model as described in our revenue recognition policies. For transactions that are accounted for pursuant to ASC 808, an appropriate method of recognition and presentation is determined and consistently applied.
Because of the numerous risks and uncertainties associated with the development and commercialization of gene therapy product candidates, we are unable to estimate the total amount of operating expenditures and capital outlays necessary to complete the development of our product candidates.
Because of the numerous risks and uncertainties associated with the development and commercialization of gene therapy product candidates, we are unable to estimate the total amount of operating expenditures and capital outlays necessary to complete the development and commercialization of our product candidates.
Cash Flows from Financing Activities For the year ended December 31, 2024, our net cash provided by financing activities primarily consisted of $131.1 million in net proceeds received from the public offering of common stock and pre-funded warrants completed in March 2024, net of underwriting discounts and commissions and other offering expenses paid during the period, and $2.7 million in proceeds received from the exercise of stock options and issuance of common stock under our employee stock purchase plan.
For the year ended December 31, 2024, our net cash provided by financing activities primarily consisted of $131.1 million in proceeds received from the public offering of common stock and pre-funded warrants completed in March 2024, net of underwriting discounts and commissions and other offering expenses paid during the period, and $2.7 million in proceeds received from the exercise of stock options and issuance of common stock under our employee stock purchase plan.
Royalties on sales of licensed products, sales-based milestone payments, including milestones payable upon first commercial sales of licensed products, and sublicense fees based on the receipt of certain fees by licensees from any sublicensees are excluded from the transaction price of each license and recognized as revenue in the period that the related sales or sublicenses occur, provided that the associated license has been delivered to the licensee.
Royalties on sales of licensed products, sales-based milestone payments, including milestones payable upon first commercial sales of licensed products, and sublicense fees based on the receipt of certain fees by licensees from any sublicensees are excluded from the transaction price of each license and recognized as license and royalty revenue in the period that the related sales or sublicenses occur, provided that the associated license has been delivered to the licensee.
The following five steps are performed to determine the appropriate revenue recognition for arrangements within the scope 71 of ASC 606: (i) identify the contract(s) with a customer, (ii) identify the performance obligations in the contract, (iii) determine the transaction price, (iv) allocate the transaction price to the performance obligations in the contract and (v) recognize revenue when (or as) the entity satisfies the performance obligations.
The following five steps are performed to determine the appropriate revenue recognition for arrangements within the scope of ASC 606: (i) identify the contract(s) with a customer, (ii) identify the performance obligations in the contract, (iii) determine the transaction price, (iv) allocate the transaction price to the performance obligations in the contract and (v) recognize revenue when (or as) the entity satisfies the performance obligations.
Amounts received by us prior to the delivery of underlying performance obligations are deferred and recognized as 73 revenue upon the satisfaction of the performance obligations. Deferred revenue which is not expected to be recognized within 12 months from the reporting date is recorded as non-current on the consolidated balance sheets.
Amounts received by us prior to the delivery of underlying performance obligations are deferred and recognized as revenue upon the satisfaction of the performance obligations. Deferred revenue which is not expected to be recognized within 12 months from the reporting date is recorded as non-current on the consolidated balance sheets.
We are responsible for the manufacturing of RGX-121 and RGX-111 for clinical development and commercial supply, and manufacturing expenses will be allocated between the parties in accordance with the terms of the Nippon Shinyaku Collaboration Agreement. Nippon Shinyaku will be responsible, at its sole cost, for the commercialization of RGX-121 and RGX-111 in the licensed territories.
We are responsible for the manufacturing of RGX-121 and RGX-111 for clinical development and commercial supply, and manufacturing expenses will be allocated between the parties in accordance with the terms of the Nippon Shinyaku Collaboration Agreement. Nippon Shinyaku is responsible, at its sole cost, for the commercialization of RGX-121 and RGX-111 in the licensed territories.
Licenses may grant intellectual property rights for purposes of internal and preclinical research and development only, or may include the rights, or options to obtain future rights, to commercialize drug therapies for specific diseases using our NAV Technology Platform and other licensed rights.
Licenses may grant intellectual property rights for purposes of internal and preclinical research and development only, or may include the rights, or options to obtain future rights, to commercialize drug therapies for specific diseases using the NAV Technology Platform and other licensed rights.
(Nippon Shinyaku) for the development and commercialization of RGX-121 and RGX-111 (the Nippon Shinyaku Collaboration Agreement). Pursuant to the Nippon Shinyaku Collaboration Agreement, we are responsible for the development of RGX-121 and RGX-111 in the United States, and Nippon Shinyaku is responsible for development in licensed territories outside the United States.
Pursuant to the Nippon Shinyaku Collaboration Agreement, we are responsible for the development of RGX-121 and RGX-111 in the United States, and Nippon Shinyaku is responsible for development in licensed territories outside the United States.
Our lead programs and product candidates are described below: • ABBV-RGX-314: We are developing ABBV-RGX-314 (surabgene lomparvovec) in collaboration with AbbVie as a potential one-time treatment for chronic retinal conditions that cause total or partial vision loss, including wet age-related macular degeneration (wet AMD) and diabetic retinopathy (DR).
Our lead programs and product candidates are described below: • ABBV-RGX-314: We are developing ABBV-RGX-314 (surabgene lomparvovec, sura-vec) in collaboration with AbbVie as a potential one-time treatment for chronic retinal conditions that cause total or partial vision loss, including wet age-related macular degeneration (wet AMD) and diabetic retinopathy (DR).
Patients will receive a one-time, in-office injection of ABBV-RGX-314 at dose level 4 (1.5x10e12 GC/eye) with short course prophylactic steroid eye drops. • RGX-202: We are developing RGX-202 as an investigational AAV therapeutic for the treatment of Duchenne muscular dystrophy (Duchenne), using the NAV AAV8 vector to deliver a transgene for a novel microdystrophin that includes the functional elements of the C-Terminal domain as well as a muscle-specific promoter to support a targeted therapy for improved resistance to muscle damage associated with Duchenne.
Patients received a one-time, in-office injection of ABBV-RGX-314 at dose level 4 (1.5x10e12 GC/eye) with short course prophylactic steroid eye drops. • RGX-202: We are developing RGX-202 as an investigational AAV therapeutic for the treatment of Duchenne muscular dystrophy (Duchenne), using the NAV AAV8 vector to deliver a transgene for a novel microdystrophin that includes the functional elements of the C-Terminal domain as well as a muscle-specific promoter to support a targeted therapy for improved resistance to muscle damage associated with Duchenne.
The fair value of our common stock, as used as an input to determine the fair value of our stock option awards, is based on the closing price of our common stock on the date of the 74 grant.
The fair value of our common stock, as used as an input to determine the fair value of our stock option awards, is based on the closing price of our common stock on the date of the grant.
In December 2024, we entered into a Sales Agreement with Leerink Partners LLC (Leerink) pursuant to which we may offer and sell shares of our common stock having an aggregate offering price of up to $150.0 million from time to time through Leerink, acting as our sales agent (the Leerink ATM Program).
At-the-Market Offering Program In December 2024, we entered into a Sales Agreement with Leerink Partners LLC (Leerink) pursuant to which we may offer and sell shares of our common stock having an aggregate offering price of up to $150.0 million from time to time through Leerink, acting as our sales agent (the Leerink ATM Program).
For further information regarding the settlement agreement with Abeona and the allowance for credit losses, please refer to Note 10, “License and Collaboration Agreements – Settlement Agreement with Abeona Therapeutics” to the accompanying audited consolidated financial statements. We did not record any credit losses or recoveries during the year ended December 31, 2023. Investment Income .
For further information regarding the settlement agreement with Abeona and the allowance for credit losses, please refer to Note 10, “License and Collaboration Agreements—Settlement Agreement with Abeona Therapeutics” to the accompanying audited consolidated financial statements. We did not record any credit losses or recoveries during the year ended December 31, 2025. Investment Income.
Our license agreements are accounted for as contracts with customers within the scope of ASC 606, with the exception of transactions for which the counterparty is determined not to be a customer. At the inception of each license agreement, we determine the contract term for purposes of applying the requirements of ASC 606.
Our license and collaboration agreements are accounted for as contracts with customers within the scope of ASC 606, with the exception of transactions for which the counterparty is determined not to be a customer. At the inception of each agreement, we determine the contract term for purposes of applying the requirements of ASC 606.
Net cost reimbursement from AbbVie includes reimbursement of personnel and overhead costs attributable to the development of ABBV-RGX-314, the underlying costs of which are reported as unallocated expenses in the table above. We typically utilize our employee and infrastructure resources across our development programs.
In addition to reimbursement of direct development expenses, net cost reimbursement from AbbVie includes reimbursement of personnel and overhead costs attributable to the development of ABBV-RGX-314, the underlying costs of which are reported as unallocated expenses in the table above. We typically utilize our employee and infrastructure resources across our development programs.
Under the terms of the Nippon Shinyaku Collaboration Agreement, we will receive an up-front payment of $110.0 million from Nippon Shinyaku following the effective date of the agreement in March 2025 and we are eligible to receive up to $700.0 million from Nippon Shinyaku upon the achievement of specified development and sales-based milestones.
Under the terms of the Nippon Shinyaku Collaboration Agreement, we received an up-front payment of $110.0 million from Nippon Shinyaku following the effective date of the agreement in March 2025 and are eligible to receive up to $700.0 million from Nippon Shinyaku upon the achievement of specified development and sales-based milestones.
Cost of Revenues Our cost of revenues consists primarily of upstream fees due to our licensors as a result of revenue generated from the licensing of our NAV Technology Platform and other intellectual property rights, including sublicense fees and royalties on net sales of licensed products.
Cost of License and Royalty Revenues Our cost of license and royalty revenues consists primarily of upstream fees due to our licensors as a result of revenue generated from the licensing of our NAV Technology Platform and other intellectual property rights, including sublicense fees and royalties on net sales of licensed products.
We recognize royalty revenue from net sales of Zolgensma in the period in which the underlying products are sold by Novartis Gene Therapies, which in certain cases may require us to estimate royalty revenue for periods of net sales which have not yet been reported to us.
We recognize royalty revenue from net sales of Zolgensma and Itvisma in the period in which the underlying products are sold by Novartis Gene Therapies, which in certain cases may require us to estimate royalty revenue for periods of net sales which have not yet been reported to us.
Pursuant the Nippon Shinyaku Collaboration Agreement, we will receive an up-front payment of $110.0 million following the effective date of the agreement in March 2025 and are eligible to receive up to $700.0 million upon the achievement of specified development and sales-based milestones.
Pursuant the Nippon Shinyaku Collaboration Agreement, we received an up-front payment of $110.0 million following the effective date of the agreement in March 2025 and are eligible to receive up to $700.0 million upon the achievement of specified development and sales-based milestones.
Consideration payable to us under our license agreements may include: (i) up-front and annual fees, (ii) milestone payments based on the achievement of certain development and sales-based milestones, (iii) sublicense fees, (iv) royalties on sales of licensed products, (v) fees for services related to the development of licensed products and (vi) other consideration payable upon optional goods and services purchased by licensees.
Consideration payable to us under our license and collaboration agreements may include: (i) up-front and annual fees, (ii) milestone payments based on the achievement of certain development and sales-based milestones, (iii) sublicense fees, (iv) royalties on sales of licensed products, (v) fees for services related to the development and manufacturing of licensed products and (vi) other consideration payable upon optional goods and services purchased by licensees and collaborators.
The transaction price includes the fixed consideration payable to us during the contract term, as well as any variable consideration to the extent that it is probable that a significant reversal of revenue will not occur in the future.
The transaction price includes the fixed consideration payable to us over the contract term, as well as any variable consideration to the extent that it is probable that a significant reversal of revenue will not occur in the future.
As of December 31, 2024, no shares of common stock had been sold under the Leerink ATM Program. We intend to use proceeds obtained from the sale of shares under the Leerink ATM Program, if any, for general corporate purposes.
As of December 31, 2025, no shares of common stock had been sold under the Leerink ATM Program. We intend to use proceeds obtained from the sale of shares under the Leerink ATM Program, if any, for general corporate purposes.
For additional information regarding our collaborative arrangements, including our collaborations with AbbVie and Nippon Shinyaku, refer to Note 10, “License and Collaboration Agreements” to the accompanying audited consolidated financial statements. Accrued Research and Development Expenses We estimate our accrued research and development expenses as of each balance sheet date.
For additional information regarding our collaborative arrangements, including our collaborations with AbbVie and Nippon Shinyaku, refer to Note 10, “License and Collaboration Agreements” to the accompanying audited consolidated financial statements. 80 Table of Contents Accrued Research and Development Expenses We estimate our accrued research and development expenses as of each balance sheet date.
We recognized credit recoveries of $5.0 million during the year ended December 31, 2024 related to the full collection of amounts due under our settlement agreement with Abeona Therapeutics Inc. (Abeona), for which we had previously recorded an allowance for credit losses.
We recognized credit recoveries of $5.0 million during the year ended December 31, 2024 upon the full collection of amounts due under our settlement agreement with Abeona Therapeutics Inc. (Abeona), for which we had previously recorded an allowance for credit losses.
Licenses are generally terminable at the option of the licensee with advance notice to us. For each license granted, including licenses granted upon the exercise of license options, we evaluate these termination rights to determine whether a substantive termination penalty would be incurred by the licensee upon termination.
Licenses are generally terminable at the option of the licensee with advance notice to us. For each license granted, we evaluate these termination rights to determine whether a substantive termination penalty would be incurred by the licensee upon termination.
Overview of Our NAV Technology Platform In addition to our internal product development efforts, we also selectively license the NAV Technology Platform and other intellectual property rights to other leading biotechnology and pharmaceutical companies, which we refer to as NAV Technology Licensees.
NAV Technology Licensing Platform In addition to our internal product development efforts, we also selectively license the NAV Technology Platform and other intellectual property rights to other leading biotechnology and pharmaceutical companies, which we refer to as NAV Technology Licensees.
Consideration from licensees under our license agreements may include: (i) up-front and annual fees, (ii) milestone payments based on the achievement of certain development and sales-based milestones, (iii) sublicense fees, (iv) royalties on sales of licensed products, (v) fees for services related to the development of licensed products and (vi) other consideration payable upon optional goods and services purchased by licensees.
Consideration payable to us under our license and collaboration agreements may include: (i) up-front and annual fees, (ii) milestone payments based on the achievement of certain development and sales-based milestones, (iii) sublicense fees, (iv) royalties on sales of licensed products, (v) fees for services related to the development and manufacturing of licensed products and (vi) other consideration payable upon optional goods and services purchased by licensees and collaborators.
For a full discussion and analysis of financial condition and results of operations for the year ended December 31, 2023, including a year-over-year comparison to the year ended December 31, 2022, please read the “Management's Discussion and Analysis of Financial Condition and Results of Operations” section of our Annual Report on Form 10-K for the year ended December 31, 2023, which we filed with the SEC on February 27, 2024.
For a full discussion and analysis of financial condition and results of operations for the year ended December 31, 2024, including a year-over-year comparison to the year ended December 31, 2023, please read the “Management's Discussion and Analysis of Financial Condition and Results of Operations” section of our Annual Report on Form 10-K for the year ended December 31, 2024, which we filed with the SEC on March 13, 2025.
Our federal NOL carryforwards and a portion of our state NOL carryforwards as of December 31, 2024 may be carried forward indefinitely. The remaining portion of our state NOL carryforwards and our federal and state credit carryforwards as of December 31, 2024 expire at various dates between 2029 and 2044.
Our federal NOL carryforwards and a portion of our state NOL carryforwards as of December 31, 2025 may be carried forward indefinitely. The remaining portion of our state NOL carryforwards and our federal and state credit carryforwards as of December 31, 2025 expire at various dates between 2029 and 2045.
We have entered into a number of long-term operating leases for office, laboratory and manufacturing space in Rockville, Maryland, Washington, D.C. and New York, New York, as well as a number of laboratory and other equipment leases. As of December 31, 2024, we had recorded total lease liabilities of $82.0 million under our operating leases.
We have entered into a number of long-term operating leases for office, laboratory and manufacturing space in Rockville, Maryland, Washington, D.C. and New York, New York, as well as a number of laboratory and other equipment leases. As of December 31, 2025, we had recorded total lease liabilities of $73.5 million under our operating leases.
Development milestone payments are payable to us upon the achievement of specified development milestones. At the inception of each license agreement that contains development milestone payments, we evaluate whether the milestones are considered probable of achievement and estimate the amount to be included in the transaction price using the most likely amount method.
At the inception of each license agreement that contains development milestone payments, we evaluate whether the milestones are probable of achievement and estimate the amount to be included in the transaction price using the most likely amount method.
Off-Balance Sheet Arrangements We did not have any off-balance sheet arrangements during the periods presented, and we do not currently have, any off-balance sheet arrangements, as defined in the rules and regulations of the SEC. 81
Off-Balance Sheet Arrangements We did not have any off-balance sheet arrangements during the periods presented, and we do not currently have, any off-balance sheet arrangements, as defined in the rules and regulations of the SEC. 87 Table of Contents
Estimated royalties are reconciled to actual amounts reported in subsequent periods, and any differences are recognized as an adjustment to royalty revenue in the period the royalties are reported. We receive payments from licensees based on the billing schedules established in each license agreement.
Estimated royalties are reconciled to actual amounts reported in subsequent periods, and any differences are recognized as an adjustment to royalty revenue in the period the royalties are reported. We receive payments from licensees and collaborators based on the billing schedules established in the associated agreements.
Patients in this cohort will also receive short course prophylactic steroid eye drops. 66 DR and DME The ALTITUDE ® trial is a multi-center, open label, randomized, controlled, dose-escalation Phase II trial to evaluate the efficacy, safety and tolerability of ABBV-RGX-314 using suprachoroidal delivery for the treatment of DR.
Patients in this cohort received short course prophylactic steroid eye drops. 72 Table of Contents DR and DME The ALTITUDE ® trial is a multi-center, open label, randomized, controlled, dose-escalation Phase II trial to evaluate the efficacy, safety and tolerability of ABBV-RGX-314 using suprachoroidal delivery for the treatment of DR.
As of December 31, 2024, we had $6.0 million remaining payable to Penn under the Penn Letter Agreement, in addition to other amounts payable Penn under the Penn License.
As of December 31, 2025, we had $3.0 million remaining payable to Penn under the Penn Letter Agreement, in addition to other amounts payable under the Penn License.
Amounts recognized as revenue which have not yet been received from licensees, including unbilled royalties, are recorded as accounts receivable when our rights to the consideration are conditional solely upon the passage of time. Amounts recognized as revenue which have not yet been received from licensees are recorded as contract assets when our rights to the consideration are not unconditional.
Amounts recognized as revenue which have not yet been received from the customer are recorded as accounts receivable when our rights to the consideration are conditional solely upon the passage of time. Amounts recognized as revenue which have not yet been received from customers are recorded as contract assets when our rights to the consideration are not unconditional.
For the year ended December 31, 2024, our net cash used in operating activities of $173.1 million consisted of a net loss of $227.1 million, offset by adjustments for non-cash items of $48.4 million and favorable changes in operating assets and liabilities of $5.5 million.
Other changes in operating working capital occurred in the normal course of business. For the year ended December 31, 2024, our net cash used in operating activities of $173.1 million consisted of a net loss of $227.1 million, offset by adjustments for non-cash items of $48.4 million and favorable changes in operating assets and liabilities of $5.5 million.
Please refer to Note 6, “Leases” to the accompanying consolidated financial statements for further information regarding our lease commitments. Under the terms of our royalty purchase agreement with HCR, our future Zolgensma royalties, less amounts payable by us to certain licensors, will be payable to HCR up to a specified capped amount.
Please refer to Note 6, “Leases” to the accompanying consolidated financial statements for further information regarding our lease commitments. Under the terms of the 2020 Royalty Purchase Agreement, our Zolgensma and Itvisma royalties, less amounts payable by us to certain licensors, are payable to HCR up to a specified capped amount.
Royalty revenue to date consists primarily of royalties on net sales of Zolgensma, which is a licensed product under our license agreement with Novartis Gene Therapies for the development and commercialization of treatments for SMA.
Royalty revenue to date consists primarily of royalties on net sales of Zolgensma and Itvisma, which are licensed products under our license agreement with Novartis Gene Therapies for the development and commercialization of treatments for SMA.
Future license and royalty revenues are dependent on the successful development and commercialization of licensed products, which is uncertain, and revenues may fluctuate significantly from period to period.
Future revenues under our license and collaboration arrangements are dependent on the successful development and commercialization of licensed products, which is uncertain, and revenues may fluctuate significantly from period to period.
We intend to devote the majority of our current capital to preclinical research, clinical development, seeking regulatory approval of our product candidates and, if approved, commercialization of our product candidates, as well as additional capital expenditures needed to support these activities.
Future Liquidity and Ability to Continue as a Going Concern We intend to devote the majority of our current capital to preclinical research, clinical development, seeking regulatory approval of our product candidates and, if approved, commercialization of our product candidates, as well as additional capital expenditures needed to support these activities.
Our future capital requirements will depend on many factors, including: • the timing of enrollment, commencement and completion of our clinical trials; • the results of our clinical trials; • the results of our preclinical studies for our product candidates and any subsequent clinical trials; • the scope, progress, results and costs of drug discovery, laboratory testing, preclinical development and clinical trials for our product candidates; • the costs associated with building out additional laboratory and manufacturing capacity; • the costs, timing and outcome of regulatory review of our product candidates; • the impact of any government-imposed tariffs on cost of goods and services, particularly related to partnered product candidates; • the costs of future product sales, medical affairs, marketing, manufacturing and distribution activities for any of our product candidates for which we receive marketing approval; • revenue, if any, received from commercial sales of our products, should any of our product candidates receive marketing approval; • revenue received from commercial sales of Zolgensma and the timing and amount of Zolgensma royalties paid to HCR under our royalty purchase agreement; • revenue received from other commercial sales of our licensees’ and collaborators’ products, should any of their product candidates receive marketing approval, and other revenue received under our licensing agreements and collaborations; 80 • the costs of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending any intellectual property-related claims; • our current licensing agreements or collaborations remaining in effect, including the AbbVie Collaboration Agreement relating to ABBV-RGX-314 and the Nippon Shinyaku Collaboration Agreement relating to RGX-121 and RGX-111, and our ability to timely achieve any milestones set forth in such agreements or collaborations; • our ability to establish and maintain additional licensing agreements or collaborations on favorable terms, if at all; and • the extent to which we acquire or in-license other product candidates and technologies.
Our future capital requirements will depend on many factors, including: • the timing of enrollment, commencement and completion of our clinical trials; • the results of our clinical trials; • the results of our preclinical studies for our product candidates and any subsequent clinical trials; • the scope, progress, results and costs of drug discovery, laboratory testing, preclinical development and clinical trials for our product candidates; • delays or costs due to a clinical hold or CRL, including BLA resubmission; • whether we receive a PRV and are able to monetize or otherwise realize any potential value associated with such a voucher; • the value of any PRV received diminishes including any decreases due to demand for these vouchers; • the costs associated with building out additional laboratory and manufacturing capacity; • the costs, timing and outcome of regulatory review of our product candidates; • the impact of any government-imposed tariffs on cost of goods and services, particularly related to partnered product candidates; • the costs of future product sales, medical affairs, marketing, manufacturing and distribution activities for any of our product candidates for which we receive marketing approval; • revenue, if any, received from commercial sales of our products, should any of our product candidates receive marketing approval; • revenue received from commercial sales of Zolgensma and Itvisma, and the timing and amount of Zolgensma and Itvisma royalties paid to HCR under our royalty monetization agreements; • revenue received from other commercial sales of our licensees’ and collaborators’ products, should any of their product candidates receive marketing approval, other revenue received under our licensing agreements and collaborations, and the timing and amount of any such revenues payable to HCR under our royalty monetization agreements; • the costs of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights including against Sarepta and defending any intellectual property-related claims; • our current licensing agreements or collaborations remaining in effect, including the AbbVie Collaboration Agreement relating to ABBV-RGX-314 and the Nippon Shinyaku Collaboration Agreement relating to RGX-121 and RGX-111, and our ability to timely achieve any milestones set forth in such agreements or collaborations; • our ability to establish and maintain additional licensing agreements or collaborations on favorable terms, if at all; and • the extent to which we acquire or in-license other product candidates and technologies.
Fixed consideration under the license agreements may include up-front and annual fees payable during the contract term and fees for development services related to licensed products. Variable consideration under the license agreements may include development and sales-based milestone payments, sublicense fees and royalties on sales of licensed products.
Fixed consideration under the agreements may include up-front and annual fees payable to us over the contract term and fixed fees for development, manufacturing and other services. Variable consideration under the agreements may include development and sales-based milestone payments, payments for development, manufacturing and other services, sublicense fees and royalties on sales of licensed products.
Consideration contingent upon the exercise of options by a licensee is excluded from the transaction price and not accounted for as part of the license agreement until the option is exercised.
Consideration contingent upon the exercise of options by the customer is excluded from the transaction price and not accounted for as part of the arrangement until the option is exercised.
In November 2023, future development of RGX-111 was halted as a result of a strategic pipeline prioritization and corporate restructuring. Prior to that announcement, RGX-111 was demonstrated to be well tolerated and indicated encouraging biomarker and neurodevelopmental results in a Phase I/II study.
In November 2023, future development of RGX-111 was halted as a result of a strategic pipeline prioritization and corporate restructuring. Prior to that announcement, RGX-111 demonstrated to be well tolerated and indicated encouraging biomarker and neurodevelopmental results in a Phase I/II study. Efforts to continue development of RGX-111 as part of the strategic partnership with Nippon Shinyaku are ongoing.
For the year ended December 31, 2023, our net cash provided by investing activities consisted of $285.5 million in maturities of marketable debt securities and $2.0 million in proceeds received from uniQure upon the achievement of milestones associated with their acquisition of Corlieve, offset by $86.6 million used to purchase marketable debt securities and $10.0 million used to purchase property and equipment.
For the year ended December 31, 2024, our net cash provided by investing activities consisted of $290.2 million in maturities of marketable debt securities and $5.8 million in proceeds received from uniQure upon the achievement of milestones associated with their acquisition of Corlieve, offset by $190.1 million used to purchase marketable debt securities and $2.4 million used to purchase property and equipment.
Performance obligations under our license agreements may include (i) the delivery of intellectual property licenses, (ii) options granted to licensees to acquire additional licenses, to the extent the options represent material rights to the licensee, and (iii) research and development services to be performed by us related to licensed products.
Performance obligations under our license and collaboration agreements may include (i) the delivery of intellectual property licenses, (ii) development and manufacturing services to be performed by us related to licensed products and (iii) options granted to purchase additional goods and services, to the extent the options convey material rights.
Platform and early research reported in the table above includes direct costs not identifiable with a specific lead product candidate, including costs associated with our research and development platform used across programs, process and analytical development, early research and development for prospective product candidates and new technologies, and other costs in support of research and development activities. 70 Direct expenses related to the development of product candidates for which we have discontinued internal development are included in other product candidates in the table above.
Platform and early research reported in the table above includes direct costs not identifiable with a specific lead product candidate, including costs associated with our research and development platform used across programs, manufacturing support, process and analytical development, early research and development for prospective product candidates and new technologies, and other costs in support of research and development activities.
Licensing the NAV Technology Platform allows us to maintain our internal product development focus on our core disease indications and therapeutic areas while still expanding the NAV gene therapy pipeline, developing a greater breadth of treatments for patients, providing additional technological and potential clinical proof-of-concept for our NAV Technology Platform and creating potential additional revenue opportunities. 68 Financial Overview Revenues Our revenues to date consist primarily of license and royalty revenue resulting from the licensing of our NAV Technology Platform and other intellectual property rights.
Licensing the NAV Technology Platform allows us to maintain our internal product development focus on our core disease indications and therapeutic areas while still expanding the NAV gene therapy pipeline, developing a greater breadth of treatments for patients, providing additional technological and potential clinical proof-of-concept for our NAV Technology Platform and creating additional revenue opportunities.
If it is probable that a significant revenue reversal will not occur in the future, milestone payments are included in the transaction price and recognized as revenue upon the delivery of the license.
If it is probable that a significant revenue reversal will not occur in the future, milestone payments are included in the transaction price.
We are also recruiting patients in the AFFINITY BEYOND ® trial, an observational screening study. The primary objective is to evaluate the prevalence of AAV8 antibodies in patients with Duchenne up to 12 years of age.
Additional regulatory interactions with the FDA and the EMA are planned for 1H 2026. We are also recruiting patients in the AFFINITY BEYOND ® trial, an observational screening study. The primary objective is to evaluate the prevalence of AAV8 antibodies in patients with Duchenne up to 12 years of age.
Future costs of revenues are uncertain due to the nature of our license agreements and significant fluctuations in cost of revenues may occur from period to period. 69 Research and Development Expense Our research and development expenses consist primarily of: • salaries, wages and personnel-related costs, including benefits, travel and stock-based compensation, for our scientific personnel and others performing research and development activities; • costs related to executing preclinical studies and clinical trials; • costs related to acquiring, developing and manufacturing materials for preclinical studies and clinical trials; • fees paid to consultants and other third parties who support our product candidate development; • other costs in seeking regulatory approval of our product candidates; and • direct costs and allocated costs related to laboratories and facilities, depreciation expense, information technology and other overhead.
Research and Development Expense Our research and development expenses consist primarily of: • salaries, wages and personnel-related costs, including benefits, travel and stock-based compensation, for our scientific personnel and others performing research and development activities; • costs related to executing preclinical studies and clinical trials; • costs related to acquiring, developing and manufacturing materials for preclinical studies and clinical trials; 76 Table of Contents • fees paid to consultants and other third parties who support our product candidate development; • other costs in seeking regulatory approval of our product candidates; and • direct costs and allocated costs related to laboratories and facilities, depreciation expense, information technology and other overhead.
Topline data from these trials are expected to be shared in 2026. Suprachoroidal Delivery The AAVIATE ® trial is a multi-center, open label, randomized, controlled, dose-escalation Phase II trial to evaluate the efficacy, safety and tolerability of suprachoroidal delivery of ABBV-RGX-314 for the treatment of wet AMD.
Suprachoroidal Delivery The AAVIATE ® trial is a multi-center, open label, randomized, controlled, dose-escalation Phase II trial to evaluate the efficacy, safety and tolerability of suprachoroidal delivery of ABBV-RGX-314 for the treatment of wet AMD.
Subject to obtaining regulatory approval for our product candidates, we expect to incur significant commercialization expenses for product sales, marketing, manufacturing and distribution. Additionally, we expect to continue to incur capital expenditures associated with building out additional laboratory and manufacturing capacity to further support the development of our product candidates and potential commercialization efforts.
Additionally, we expect to continue to incur capital expenditures associated with building out additional laboratory and manufacturing capacity to further support the development of our product candidates and potential commercialization efforts.
Personnel costs including salaries, wages, benefits, bonuses and stock-based compensation expense, comprise a significant component of research and development and general and administrative expenses.
Operating Expenses Our operating expenses consist primarily of cost of license and royalty revenues, research and development expenses and general and administrative expenses. Personnel costs including salaries, wages, benefits, bonuses and stock-based compensation expense, comprise a significant component of research and development and general and administrative expenses.
As of December 31, 2024, our NAV Technology Platform was being applied in one commercial product, Zolgensma ® , and the preclinical and clinical development of a number of other licensed products.
As of December 31, 2025, our NAV Technology Platform was being applied in two commercial products, Zolgensma ® and Itvisma ® , and the preclinical and clinical development of various other licensed products.
As of December 31, 2024, we had federal net operating loss (NOL) carryforwards of $373.6 million, U.S. state NOL carryforwards of $408.9 million and federal and state research and development tax credit carryforwards of $87.2 million (net of unrecognized tax benefits of $0.1 million) which may be available to offset future income tax liabilities.
As of December 31, 2025, we had federal net operating loss (NOL) carryforwards of $754.4 million, U.S. state NOL carryforwards of $394.9 million and federal and state research and development tax credit carryforwards of $95.1 million which may be available to offset future income tax liabilities.
Investment income increased by $7.4 million, from $11.3 million for the year ended December 31, 2023 to $18.7 million for the year ended December 31, 2024. The increase was largely attributable to the achievement of milestones associated with the acquisition of our non-marketable equity securities of Corlieve Therapeutics SAS (Corlieve) by uniQure N.V. (uniQure) in July 2021.
Investment income decreased by $6.5 million, from $18.7 million for the year ended December 31, 2024 to $12.2 million for the year ended December 31, 2025. The decrease was primarily attributable to the achievement of milestones associated with the July 2021 acquisition of our non-marketable equity securities of Corlieve Therapeutics SAS (Corlieve) by uniQure N.V. (uniQure).
Milestone fees are payable to licensors upon our future achievement of certain development, regulatory and commercial milestones. Royalties are payable to licensors based on a percentage of net sales of licensed products. Patent maintenance costs are payable to licensors as reimbursement for the cost of maintaining licensed patents.
Royalties are payable to licensors based on a percentage of net sales of licensed products. Patent maintenance costs are payable to licensors as reimbursement for the cost of maintaining licensed patents.
As of December 31, 2024, the total amount of future Zolgensma royalties to be paid to HCR under the agreement was $95.6 million. We have no obligation to repay any amounts to HCR if total future Zolgensma royalty payments are not sufficient to repay these amounts.
As of December 31, 2025, the total amount of future royalties payable to HCR under the 2020 Royalty Purchase Agreement was $35.5 million. We have no obligation to repay any amounts to HCR if total future Zolgensma and Itvisma royalty payments from Novartis are not sufficient to repay these amounts.
At each reporting date, we re-evaluate the probability of achievement of each outstanding development milestone and, if necessary, adjust the transaction price for any milestones for which the probability of achievement has changed due to current facts and circumstances. Any such adjustments are recorded on a cumulative catch-up basis and recognized as revenue in the period of the adjustment.
At each reporting date, we re-evaluate the probability of achievement of each outstanding development milestone and, if necessary, adjust the transaction price for any milestones for which the probability of achievement has changed due to current facts and circumstances.
The transaction price for each license agreement is allocated to the underlying performance obligations based on their relative standalone selling prices and recognized as revenue when (or as) the performance obligations are satisfied.
The transaction price of our license and collaboration arrangements is allocated to the underlying performance obligations based on their relative standalone selling prices and recognized as revenue when (or as) the performance obligations are satisfied. Variable consideration payable based on services performed is allocated directly to the performance obligation for such services.
For the year ended December 31, 2023, our net cash used in operating activities of $218.4 million consisted of a net loss of $263.5 million and unfavorable changes in operating assets and liabilities of $10.9 million, offset by adjustments for non-cash items of $56.0 million.
For the year ended December 31, 2025, our net cash used in operating activities of $124.0 million consisted of a net loss of $193.9 million, offset by adjustments for non-cash items of $58.1 million and favorable changes in operating assets and liabilities of $11.8 million.
For additional information regarding the Nippon Shinyaku Collaboration Agreement, please refer to Note 10, “License and Collaboration Agreements—Nippon Shinyaku Collaboration and License Agreement” to the accompanying audited consolidated financial statements.
We recognized $84.7 million of revenue under the Nippon Shinyaku Collaboration Agreement during the year ended December 31, 2025. For additional information regarding the Nippon Shinyaku Collaboration Agreement, please refer to Note 10, “License and Collaboration Agreements—Nippon Shinyaku Collaboration and License Agreement” to the accompanying audited consolidated financial statements.
Income Taxes We account for income taxes in accordance with ASC 740, Income Taxes, which provides for deferred taxes using an asset and liability approach. We recognize deferred tax assets and liabilities for the expected future tax consequences of events that have been included in the consolidated financial statements or tax returns.
We recognize deferred tax assets and liabilities for the expected future tax consequences of events that have been included in the consolidated financial statements or tax returns.
In making this determination, we consider whether the options are priced at an incremental discount to the standalone selling price for the underlying licenses, goods or services, in which case the option is considered to be a material right to the licensee and is accounted for as a separate performance obligation under the current license agreement.
Options are evaluated at the inception of the agreement to determine whether they provide material rights to the customer. In making this determination, we consider whether the options are priced at an incremental discount to the standalone selling price of the underlying goods or services, in which case the option is considered to be a material right.
For additional information regarding the corporate restructuring, please refer to Note 14, “Restructuring” to the accompanying audited consolidated financial statements. Collaboration and License Agreement with AbbVie In September 2021, we entered into a collaboration and license agreement with AbbVie Global Enterprises Ltd. (AbbVie), a subsidiary of AbbVie Inc., to jointly develop and commercialize ABBV-RGX-314 (the AbbVie Collaboration Agreement).
AbbVie Collaboration for ABBV-RGX-314 In September 2021, we entered into a collaboration and license agreement with AbbVie Global Enterprises Ltd. (AbbVie), a subsidiary of AbbVie Inc., to jointly develop and commercialize ABBV-RGX-314 (as amended, the AbbVie Collaboration Agreement).
Our recent sources of liquidity include the following events and transactions: • In March 2024, we completed a public offering of 4,565,260 shares of our common stock at a price of $23.00 per share and 1,521,740 pre-funded warrants to purchase shares of our common stock at a price of $22.9999 per pre-funded warrant, which equaled the public offering price per share of the common stock less the $0.0001 exercise price of each pre-funded warrant.
We are also eligible to receive double-digit royalties on net sales of RGX-121 and RGX-111 by Nippon Shinyaku, subject to specified offsets and reductions. • In March 2024, we completed a public offering of 4,565,260 shares of our common stock at a price of $23.00 per share and 1,521,740 pre-funded warrants to purchase shares of our common stock at a price of $22.9999 per pre-funded warrant, which equaled the public offering price per share of the common stock less the $0.0001 exercise price of each pre-funded warrant.
In determining the appropriate interest rates for significant financing components, we evaluate the credit profile of the customer and prevailing market interest rates and select an interest rate in which we believe would be charged to the customer in a separate financing arrangement over a similar financing term.
In determining the appropriate interest rates for significant financing components, we evaluate the credit profile of the customer and prevailing market interest rates and select an interest rate in which we believe would be charged to the customer in a separate financing arrangement over a similar financing term. 78 Table of Contents We license our NAV Technology Platform and other intellectual property rights to other biotechnology and pharmaceutical companies, including collaborators for the joint development and commercialization of our product candidates.
Due to the contingent nature of the payments, the amounts and timing of payments to licensors under our in-license agreements are uncertain and may fluctuate significantly from period to period. 79 In March 2022, we entered into a letter agreement (the Penn Letter Agreement) with The Trustees of the University of Pennsylvania (Penn) to buy out our obligation to pay sublicense fees under our license agreement with Penn (the Penn License).
In March 2022, we entered into a letter agreement (the Penn Letter Agreement) with The Trustees of the University of Pennsylvania (Penn) to buy out our obligation to pay sublicense fees under our license agreement with Penn (the Penn License).
AFFINITY DUCHENNE ® is a multicenter, open-label Phase I/II/III trial to evaluate the safety, tolerability and clinical efficacy of a one-time intravenous dose of RGX-202 in patients with Duchenne aged one and older.
Other differentiating elements of RGX-202 include the proactive immune suppression regimen and in-house, state-of-the-art manufacturing that has demonstrated leading purity levels in Duchenne (>80% full capsids). AFFINITY DUCHENNE ® is a multicenter, open-label Phase I/II/III trial to evaluate the safety, tolerability and clinical efficacy of a one-time intravenous dose of RGX-202 in patients with Duchenne aged one and older.
The liability is amortized over the estimated life of the arrangement using the effective interest method. The total amount of royalty payments received by HCR under the agreement, less the net proceeds we received from the sale, is recorded as interest expense over the life of the arrangement.
The liabilities are amortized over the estimated life of the arrangements using the effective interest method. For arrangements in which there is no stated interest rate, the total amount of royalty and other payments paid to HCR under the arrangement, less the net proceeds we received from HCR, is recorded as interest expense over the life of the arrangement.
Additionally, we may never receive consideration in our license agreements that is contemplated on option fees, development and sales-based milestone payments, royalties on sales of licensed products or sublicense fees, given the contingent nature of these payments. Our revenues are concentrated among a low number of licensees and licenses are terminable at the option of the licensee.
Additionally, we may never receive consideration under our license or collaboration agreements that is contemplated on optional goods and services, development and sales-based milestones, royalties on sales of licensed products or sublicense fees, given the contingent nature of these payments.

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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 changeAs of December 31, 2024 and 2023, we had cash, cash equivalents and marketable securities of $244.9 million and $314.1 million, respectively. Our cash equivalents and marketable securities as of December 31, 2024 consisted of money market mutual funds, U.S. government and agency securities, certificates of deposit and corporate bonds.
Biggest changeAs of December 31, 2025 and 2024, we had cash, cash equivalents and marketable securities of $240.9 million and $244.9 million, respectively. Our cash equivalents and marketable securities as of December 31, 2025 consisted of money market mutual funds, U.S. government and agency securities and corporate bonds.
If market interest rates were to increase immediately and uniformly by 100 basis points, or one percentage point, from levels at December 31, 2024, we estimate that the increase would have resulted in a hypothetical decline of $0.8 million in the net fair value of our interest-sensitive securities as of December 31, 2024.
If market interest rates were to increase immediately and uniformly by 100 basis points, or one percentage point, from levels at December 31, 2025, we estimate that the increase would have resulted in a hypothetical decline of $0.8 million in the net fair value of our interest-sensitive securities as of December 31, 2025.
A similar increase in market interest rates as of December 31, 2023 would have resulted in an estimated hypothetical decline of $1.5 million in the net fair value of our interest-sensitive securities as of December 31, 2023.
A similar increase in market interest rates as of December 31, 2024 would have resulted in an estimated hypothetical decline of $0.8 million in the net fair value of our interest-sensitive securities as of December 31, 2024.

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