REGENXBIO Inc.
For the period ended Dec 31, 2025. Filed Mar 5, 2026.
View on SEC.govAbout this filing
A company's yearly report to the SEC, with audited financial statements. It is the fullest account a company gives of its business, its finances and the risks it sees.
FY2025 · Filed Mar 5, 2026
RGNX$7.62+3.3%Stored close · as of Nov 6, 2026
What changed in Risk Factors?
Read the current filingPrevious report: 10-K
Period ended 2024-12-31; filed 2025-03-13.
0000950170-25-038770
Item 1A. Risk FactorsCurrent report: 10-K
Period ended 2025-12-31; filed 2026-03-05.
0001193125-26-094013
Item 1A. Risk FactorsThe baseline is this issuer’s latest earlier reporting period of the same form that was filed before the current report. A previous 10-Q is a different quarter, not a year-over-year comparison. Amendments are excluded.
Compared 358 previous paragraphs and 386 current paragraphs.
300 unchanged; 55 reworded; 29 added; 1 removed; 2 previous and 2 current paragraphs rearranged.
Tables are not compared: 0 previous and 0 current tables excluded. Dates, whitespace, punctuation and numbering changes are ignored; changes to financial figures remain significant.
A changed paragraph is not evidence that risk increased or decreased. An unchanged paragraph does not establish that risk stayed the same.
Added paragraphs (29)
Current report
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.
Current report
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.
Current report
Our existing cash resources may not be sufficient to fund our operations for the next 12 months.
Current report
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.
Current report
Our business could be negatively affected as a result of the actions of activist stockholders or stockholder litigation.
Current report
If we are unable to maintain effective internal control over financial reporting, investors may lose confidence in the accuracy of our financial reports.
Current report
delays in reaching a consensus with or changing requirements by regulatory authorities on trial design;
Current report
The FDA’s clinical holds on RGX-111 and RGX-121 may delay development, impose additional regulatory requirements, increase costs and adversely impact our business, financial condition and results of operations, or lead to the termination of one or both programs.
Current report
In January of this year the FDA placed a clinical hold on the investigational new drug application(s) (“IND”) for RGX-111 and RGX-121, which was later identified as a partial clinical hold in FDA letters received February of this year. The clinical holds preclude the recruitment of new patients in the ongoing studies and any new dosing of any study subject pending our submission of additional information requested by the FDA. Under the clinical holds, certain aspects of the clinical investigation may continue including limited enrollment and continued monitoring. The FDA indicated that the clinical holds were imposed due to an unreasonable and significant risk of human illness or injury and the need for additional information to assess those risks to subjects.
Current report
We are working to address the FDA’s requests and intend to submit a complete response as soon as practicable. However, we cannot predict the timing or outcome of FDA’s review or the steps that may be required to lift the clinical holds on either RGX-111 or RGX-121. FDA will require additional information regarding safety assessment related to malignancy risk, longer-term follow up data and cross-program safety assessment. Our responses to the clinical hold deficiencies could be time-consuming and costly and may not ultimately satisfy FDA. The holds have already paused screening, enrollment, dosing and other study activities and may adversely impact investigator engagement, site readiness, patient retention and our relationships with regulators, partners and patient communities. If the holds are not lifted in a timely manner, or at all, or if additional safety signals emerge, our ability to resume development, obtain regulatory approvals and ultimately commercialize RGX-111 and/or RGX-121 could be materially impaired, which would adversely impact our business, financial condition, results of operations and prospects.
Current report
We received a Complete Response Letter from the FDA on our BLA for RGX-121, and if the resubmission of our BLA is not approved in accordance with our expected timeframe, our business could be materially and adversely affected.
Current report
In May 2025, the FDA accepted the BLA for RGX-121 for the treatment of patients with MPS II under the accelerated approval pathway. On February 7, 2026, we received the Complete Response Letter (“CRL”) from the FDA which stated that it had agreed to the study protocol in principle but outlined several reasons for not approving the gene therapy, including uncertainty regarding the identification of a target population with neuronopathic disease (vs. attenuated disease), the comparability of the natural history external control to the study population, and uncertainty that CSF HS D2S6 is a surrogate endpoint reasonably likely to predict clinical benefit. The CRL lists several potential paths forward, including a new study, treating additional patients and conducting longer-term follow up, and using an untreated control arm, all of which would be challenging in an ultra-rare disease population, like MPS II.
Current report
We plan to engage the FDA to discuss the CRL, including requesting a Type A meeting, as well as the planned BLA resubmission to provide additional evidence from global MPS II experts to further clarify the neuronopathic patient population and additional longer-term clinical data to support evidence of effectiveness. If we are unable to complete the BLA resubmission, or our resubmission does not address the deficiencies to the FDA’s satisfaction, our ability to commercialize RGX-121 will be further delayed, which could have a material adverse effect on our business, financial condition, and results of operations and may cause the market price of our common stock to decline.
Current report
We engage in formal and informal interactions with the FDA and other regulatory authorities throughout development to obtain feedback on clinical trial design, endpoints, manufacturing, and other regulatory matters. Although we may believe we have reached alignment with regulatory authorities on certain development plans or regulatory pathways, including as reflected in meeting minutes or written correspondence, such feedback and agreements are not binding and may be revised or reinterpreted. Any failure by such regulatory authorities to maintain or adhere to prior feedback or agreements could materially adversely affect our development timelines, regulatory strategy and investor confidence in approval predictability affecting our ability to raise additional capital.
Current report
In the European Union, companion diagnostics are subject to the European Union Regulation onin vitro diagnostic medical devices. This requires a conformity assessment of the companion diagnostic to be performed by a notified body, to demonstrate that it complies with the general safety and performance requirements of the Regulation. The notified body must consult with the EMA or a national regulatory authority in the EU to obtain an opinion on the suitability of the companion diagnostic for use with the medicinal product concerned. Following the successful completion of the conformity assessment procedure, the manufacturer may apply the CE mark to the companion diagnostic. Companies producing companion diagnostics are subject to various pre-market and post-market obligations in the EU, including the need to have a responsible person to oversee regulatory compliance. If the EMA determines that a companion diagnostic is required for a particular medicinal product, the EMA will not recommend approval of the medicinal product until the companion diagnostic has been CE marked.
Current report
Our existing cash resources may not be sufficient to fund our operations for the next 12 months.
Current report
Our existing cash, cash equivalents, and marketable securities may not be sufficient to fund our operating expenses and capital requirements for at least the next 12 months from the issuance date of our financial statements. As a result, there is substantial doubt about our ability to continue as a going concern. Drug development is a lengthy, expensive, and uncertain process, and our product candidates may fail at any stage of development. Our ability to continue as a going concern is dependent on the successful development, regulatory approval, and commercialization of our product candidates. Our financial statements include disclosures indicating that there is substantial doubt about our ability to continue as a going concern. This disclosure may adversely affect investor confidence, our stock price, and our ability to raise additional capital.
Current report
delays or costs due to a clinical hold or CRL, including BLA resubmission;
Current report
whether we receive a priority review voucher (PRV) and are able to monetize or otherwise realize any potential value associated with such a voucher;
Current report
the value of any PRV received diminishes including any decreases due to demand for these vouchers;
Current report
We rely on third-party suppliers, including sole-source suppliers, for materials and key components used in our preclinical and clinical studies and for potential commercial use. Clearside supplies the SCS Microinjector under an option and license agreement; however, in November 2025, Clearside filed for Chapter 11 bankruptcy protection and is seeking to sell substantially all of its assets, including the SCS Microinjector, through a court-supervised process, the outcome of which is uncertain. Any disruption in supply, failure of a purchaser to honor our contractual arrangements, or inability to secure continued supply or alternative delivery technology on commercially reasonable terms and in a timely manner could delay or prevent development or commercialization of product candidates that rely on this technology, including our sura-vec programs for Wet AMD and DR, and may adversely affect our business, financial condition, and results of operations.
Current report
Changes to tax legislation may adversely affect our business.
Current report
From time to time, the U.S. government may introduce new fiscal policies and tax laws or make substantial changes to existing tax legislation. These changes could have a material impact on our business and our customers’ business, results of operations, and financial condition. For example, in July 2025, the One Big Beautiful Bill Act (OBBBA) was signed into law, introducing significant tax changes. The OBBBA extends or makes permanent various tax provisions that were originally enacted in the 2017 Tax Cuts and Jobs Act and were set to expire at the end of 2025. The OBBBA features modified versions of individual and business tax relief proposals, and other new tax relief measures. In addition, it includes various revenue-raising measures, including changes to certain Inflation Reduction Act clean energy tax credits and various limits on business and individual tax deductions, that are intended to offset part of the cost of the legislation. We are currently evaluating the impact of the OBBBA on our business.
Current report
Our business could be negatively affected as a result of the actions of activist stockholders or stockholder litigation.
Current report
Additionally, we are subject to, and may in the future become subject to, legal proceedings, including securities class action litigation, stockholder derivative lawsuits and other claims that have arisen or may arise in the ordinary course of business. For example, in February 2026, a putative securities class action complaint was filed against us and certain of our current officers and directors. We believe we have meritorious defenses to the alleged claims and intend to vigorously defend against them. However, regardless of merit, litigation may be time-consuming and disruptive to our operations and cause significant expense and diversion of management attention. The outcome of any litigation is inherently uncertain, and if one or more legal matters are resolved against us for amounts above management's expectations, our business, financial condition, results of operations and prospects could be materially adversely affected. While we maintain insurance coverage for certain types of claims, such insurance coverage may be insufficient to cover all losses or all types of claims that may arise.
Current report
If we are unable to maintain effective internal control over financial reporting, investors may lose confidence in the accuracy of our financial reports.
Current report
As a public company, we are required to maintain internal control over financial reporting and to report any material weaknesses in such internal controls. Section 404 of the Sarbanes-Oxley Act (Section 404) requires that we evaluate and determine the effectiveness of our internal control over financial reporting and provide a management report on internal control over financial reporting. However, while we remain a non-accelerated filer, we will not be required to include an attestation report on internal control over financial reporting issued by our independent registered public accounting firm. We have not had, and do not expect to have, our independent registered public accounting firm attest to our management report on internal control over financial reporting as of December 31, 2025. Had our independent registered public accounting firm performed an evaluation of the effectiveness of our internal control over financial reporting in accordance with Section 404, it is possible that material weaknesses may have been identified.
Current report
If we have, or fail to identify, a material weakness in our internal control over financial reporting, we may not detect errors on a timely basis, the accuracy and timing of our financial reporting may be adversely affected and our financial statements may be materially misstated. In addition, our internal control over financial reporting will not prevent or detect all errors and fraud. Because of the inherent limitations in all control systems, no evaluation of controls can provide absolute assurance that misstatements due to error or fraud will not occur or that all control issues and instances of fraud will be detected.
Current report
If there are material weaknesses or failures in our ability to meet any of the requirements related to the maintenance and reporting of our internal controls, investors may lose confidence in the accuracy and completeness of our financial reports and that could cause the price of our common stock to decline. In addition, we could become subject to investigations by Nasdaq, the SEC or other regulatory authorities, which could require additional management attention and which could adversely affect our business.
Removed paragraphs (1)
Previous report
In the European Union, companion diagnostics are subject to the European Union Directive onin vitro diagnostic medical devices and its implementation in the European Union Member States. Recently revised European Union laws onin vitro diagnostics applied beginning in 2022, which provide for stricter requirements forin vitro diagnostic medical devices and impose additional obligations on manufacturers ofin vitro diagnostic medical devices that may impact the development and authorization of our product candidates in the European Union. For example, the new regulation extends the requirement for performance assessment procedures and requires greater involvement of notified bodies in the development ofin vitro diagnostic medical devices. This may result in additional regulatory and premarket requirements to market newin vitro diagnostic medical devices. Companies producingin vitro diagnostic medical devices will be required to have a responsible person to oversee regulatory compliance. In addition, the new regulation introduces risk classification ofin vitro diagnostic medical devices and significantly increases the number of products that will be subject to stricter regulation. It also introduces the requirement to involve a notified body in the conformity assessment procedure.
Reworded paragraphs (55)
Previous wording
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.
Current wording
Our planned clinical trials may be substantially delayed, or we may fail to demonstrate safety and efficacy to the satisfaction of applicable regulatory authorities.
Previous wording
Delays in obtaining regulatory approval of our manufacturing process or disruptions in our manufacturing process may delay or disrupt our commercialization efforts.
Current wording
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.
Previous wording
Third parties we rely upon to conduct our product manufacturing may not perform satisfactorily.
Current wording
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.
Previous wording
We are required to comply with ongoing manufacturing regulatory requirements.
Current wording
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.
Previous wording
Issued patents covering our NAV Technology Platform or our product candidates could be found invalid or unenforceable.
Current wording
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.
Previous wording
Our certificate of incorporation includes exclusive forum clauses for certain litigation.
Current wording
Our certificate of incorporation includes an exclusive forum clause for certain litigation.
Previous wording
Our gene therapy product candidates are based on a novel technology that makes it difficult to predict the time and cost of development and of subsequently obtaining regulatory approval. Only a few gene therapy products have been approved in the United States, the European Union or elsewhere.
Current wording
Our gene therapy product candidates are based on a novel technology that makes it difficult to predict the time and cost of development and of subsequently obtaining regulatory approval. Only a small number of gene therapy products have been approved in the United States, the European Union or elsewhere.
Previous wording
We have concentrated our research and development efforts on our proprietary AAV gene delivery platform (our NAV Technology Platform), and we have granted licenses to certain intellectual property related to our NAV Technology Platform to our NAV Technology Licensees. Our future success depends on our and our NAV Technology Licensees’ successful development and commercialization of viable gene therapy product candidates. 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. We also may experience unanticipated problems or delays in expanding our manufacturing capacity, and this may prevent us from completing our clinical trials, meeting the obligations of our collaborations or commercializing our products on a timely or profitable basis, if at all. For example, we, a partner or another group may uncover one or more previously unknown risks associated with AAV or our NAV Technology Platform, and this may prolong the period of observation required for obtaining regulatory approval, necessitate additional clinical testing or invalidate our NAV Technology.
Current wording
We have concentrated our research and development efforts on our proprietary AAV gene delivery platform (our NAV Technology Platform), and we have granted licenses to certain intellectual property related to our NAV Technology Platform to our NAV Technology Licensees and collaborators. Our future success depends on our and our NAV Technology Licensees’ and collaborators’ successful development and commercialization of viable gene therapy product candidates. 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. We also may experience unanticipated problems or delays in expanding our manufacturing capacity, and this may prevent us from completing our clinical trials, meeting the obligations of our collaborations or commercializing our products on a timely or profitable basis, if at all. For example, we, a partner or another group may uncover one or more previously unknown risks associated with AAV or our NAV Technology Platform, and this may prolong the period of observation required for obtaining regulatory approval, necessitate additional clinical testing or invalidate our NAV Technology.
Previous wording
In addition, the clinical trial requirements of the FDA, the EMA and other regulatory authorities and the criteria these regulators use to determine the quality, safety and efficacy of a product candidate vary substantially according to the type, complexity, novelty and intended use and market of such product candidates. The regulatory approval process for novel product candidates such as ours can be significantly more expensive and take longer than for other, better known or more extensively studied product candidates. Only a few gene therapy products have been approved in the United States, the European Union or elsewhere. It is difficult to determine how long it will take or how much it will cost to obtain regulatory approvals for our product candidates in the United States, the European Union or elsewhere, or how long it will take to commercialize our product candidates, if approved. Furthermore, approvals by one regulatory authority may not be indicative of what other regulatory authorities may require for approval, and approvals ofex vivo gene therapy products may not be indicative of what may be required for approval ofin vivo gene therapy products.
Current wording
In addition, the clinical trial requirements of the FDA, the EMA and other regulatory authorities and the criteria these regulators use to determine the quality, safety and efficacy of a product candidate vary substantially according to the type, complexity, novelty and intended use and market of such product candidates. The regulatory approval process for novel product candidates such as ours can be significantly more expensive and take longer than for product candidates from categories that are better known or that have been studied more extensively. Only a small number of gene therapy products have been approved in the United States, the European Union or elsewhere, including less than ten AAV-based gene therapies approved in the United States as of the end of 2025. It is difficult to determine how long it will take or how much it will cost to obtain regulatory approvals for our product candidates in the United States, the European Union or elsewhere, or how long it will take to commercialize our product candidates, if approved. Furthermore, approvals by one regulatory authority may not be indicative of what other regulatory authorities may require for approval, and approvals ofex vivo gene therapy products (such as autologous CAR T-cell therapies) may not be indicative of what may be required for approval ofin vivo gene therapy products (such as directly administered AAV-based gene therapies).
Previous wording
Our business depends substantially on the success of our lead product candidates. If we are unable to obtain regulatory approval for, or successfully commercialize, our lead product candidates, our business will be materially harmed.
Current wording
If we are unable to obtain regulatory approval for, or successfully commercialize, our lead product candidates, our business will be materially harmed.
Previous wording
Our product candidates will require substantial clinical development and testing, manufacturing bridging studies and process validation and regulatory approval prior to commercialization. Successful continued development and ultimate regulatory approval of our lead product candidates is critical for our future business success and our ability to generate product revenue. We have invested, and will continue to invest, a significant portion of our financial resources in the development of our lead product candidates. We will need to raise sufficient funds for, and successfully complete, our clinical trials of our lead product candidates in appropriate subjects. The future regulatory and commercial success of these product candidates is subject to a number of risks, including the following:
Current wording
Our product candidates require substantial clinical development and testing, manufacturing bridging studies and process validation and regulatory approval prior to commercialization. Successful continued development and ultimate regulatory approval of our lead product candidates is critical for our future business success and our ability to generate product revenue. We have invested, and will continue to invest, a significant portion of our financial resources in the development of our lead product candidates. We will need to raise sufficient funds for, and successfully complete, our clinical trials of our lead product candidates in appropriate subjects. The future regulatory and commercial success of these product candidates is subject to a number of risks, including the following:
Previous wording
we may not successfully establish commercial manufacturing capabilities;
Current wording
we may not successfully establish commercial manufacturing capabilities for each of our products;
Previous wording
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. 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. 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. If we or any of our future development partners are unable to develop, obtain regulatory approval for, or, if approved, successfully commercialize, our lead product candidates, we may not be able to generate sufficient revenue to continue our business.
Current wording
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. 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. 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. If we or any of our future development partners are unable to develop, obtain regulatory approval for, or, if approved, successfully commercialize, our lead product candidates, we may not be able to generate sufficient revenue to continue our business.
Previous wording
We have limited clinical results for some of our product candidates and success in preclinical studies or early clinical trials may not be indicative of results obtained in later trials.
Current wording
Clinical programs in rare diseases have limited datasets and success in preclinical studies or early clinical trials may not be indicative of results obtained in later trials.
Previous wording
Gene therapy development has inherent risks. Some of our lead product candidates have limited clinical and preclinical results and we may experience unexpected results in the future. We or any of our future development partners will be required to demonstrate through adequate and well-controlled clinical trials that our product candidates containing our proprietary vectors are safe and effective, with a favorable benefit-risk profile, for use in their target indications before we can seek regulatory approvals for their commercial sale. Drug development is a long, expensive and uncertain process, and delay or failure can occur at any stage of development, including after commencement of any of our clinical trials.
Current wording
Gene therapy development has inherent risks. Our lead product candidates in the rare disease space have limited clinical and preclinical results and we may experience unexpected results in the future. We or any of our future development partners will be required to demonstrate through adequate and well-controlled clinical trials that our product candidates containing our proprietary vectors are safe and effective, with a favorable benefit-risk profile, for use in their target indications before we can seek regulatory approvals for their commercial sale. Drug development is a long, expensive and uncertain process, and delay or failure can occur at any stage of development, including after commencement of any of our clinical trials.
Previous wording
The results of preclinical studies and early clinical trials are not always predictive of future results. Any product candidate we or any of our future development partners advance into clinical trials, including our lead product candidates, may not have favorable results in later clinical trials, if any, or receive regulatory approval. There is a high failure rate for drugs and biologic products proceeding through clinical trials. Data obtained from preclinical and clinical activities are subject to varying interpretations that may delay, limit or prevent regulatory approval. In addition, we may experience regulatory delays or rejections as a result of many factors, including due to changes in regulatory policy during the period of our product candidate development. Any such delays could materially harm our business, financial condition, results of operations and prospects.
Current wording
The results of preclinical studies and early clinical trials are not always predictive of future results. Preclinical studies have experimental and animal model limitations, may not detect or predict human adverse effects, and are not powered to detect rare events. Any product candidate we or any of our future development partners advance into clinical trials, including our lead product candidates, may not have favorable results in later clinical trials, if any, or receive regulatory approval. There is a high failure rate for drugs and biologic products proceeding through clinical trials. Data obtained from preclinical and clinical activities are subject to varying interpretations that may delay, limit or prevent regulatory approval. In addition, we may experience regulatory delays or rejections as a result of many factors, including due to changes in regulatory policy during the period of our product candidate development. Any such delays could materially harm our business, financial condition, results of operations and prospects.
Previous wording
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). In addition, the resulting clinical data and results may be difficult to analyze. Even if the FDA does find our success criteria to be sufficiently validated and clinically meaningful, we may not achieve the pre-specified endpoints to a degree of statistical significance. Further, even if we do achieve the pre-specified criteria, we may produce results that are unpredictable or inconsistent with the results of the non-primary endpoints or other relevant data. The FDA also weighs the benefits of a product against its risks, and the FDA may view the efficacy results in the context of safety as not being supportive of regulatory approval. The EMA and other regulatory authorities in the European Union and other countries may make similar comments with respect to these endpoints and data, which may jeopardize or preclude our ability to obtain regulatory approvals in the European Union and other jurisdictions.
Current wording
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. 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. In addition, we may not successfully achieve the statistical criteria to reflect what is clinically meaningful, or the resulting clinical data and results may be difficult to analyze. For example, even if we do achieve the pre-specified criteria, we may produce results that are unpredictable or inconsistent with the results of the non-primary endpoints or other relevant data. Further, we may be required to produce more data, including enhanced functional data, increased number of patients and/or data from untreated control arm patients to achieve FDA support. The FDA also weighs the benefits of a product against its risks, and the FDA may view the efficacy results in the context of safety as not being supportive of regulatory approval. The EMA and other regulatory authorities in the European Union and other countries may make similar comments with respect to these endpoints and data, which may jeopardize or preclude our ability to obtain regulatory approvals in the European Union and other jurisdictions.
Previous wording
While we believe our product candidates should be applicable for the treatment of patients with certain conditions, the results from our preclinical and planned clinical trials may not support as broad of a marketing approval as we seek. 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. This could result in significant cost increases and substantial delays in obtaining, or never obtaining, marketing approval for our product candidates to treat patients. The inability to market our product candidates to treat patients for the intended indications would materially harm our business, financial condition, results of operations and prospects.
Current wording
While we believe our product candidates should be applicable for the treatment of patients with certain conditions, the results from our preclinical and planned clinical trials may not support as broad of a marketing approval as we seek. This could result in significant cost increases and substantial delays in obtaining, or never obtaining, marketing approval for our product candidates to treat patients. 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 addition, we may be approved only for severe forms of a disease or condition. The inability to market our product candidates to treat patients for the intended indications would materially harm our business, financial condition, results of operations and prospects.
Previous wording
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.
Current wording
Our planned clinical trials may be substantially delayed, or we may fail to demonstrate safety and efficacy to the satisfaction of applicable regulatory authorities.
Previous wording
imposition of a clinical hold by regulatory authorities;
Current wording
imposition of a clinical hold by regulatory authorities in trials in addition to RGX-121 and RGX-111;
Previous wording
Any inability to successfully complete research studies and preclinical and clinical development could result in additional costs to us or impair our ability to generate revenues from product sales, regulatory and commercialization milestones and royalties. In addition, if we make manufacturing or formulation changes to our product candidates, we may need to conduct additional studies to bridge our modified product candidates to earlier versions. Clinical trial delays also could shorten any periods during which we may have the exclusive right to commercialize our product candidates, if approved, or allow our competitors to bring products to market before we do, which could impair our ability to successfully commercialize our product candidates, if approved, and may harm our business, financial condition, results of operations and prospects.
Current wording
Any inability to successfully complete research studies and preclinical and clinical development could result in additional costs to us or impair our ability to generate revenues from product sales, regulatory and commercialization milestones and royalties. In addition, if we make manufacturing or formulation changes to our product candidates, we may need to conduct additional studies to bridge our modified product candidates to earlier versions. Clinical trial delays also could shorten any periods during which we may have the exclusive right to commercialize our product candidates, if approved, or allow our competitors to bring products to market before we do, which could impair our ability to successfully commercialize our product candidates, if approved, and may harm our business, financial condition, results of operations and prospects. Furthermore, unpredictability in the regulatory environment and the regulatory requirements to obtain approval of our product candidates may adversely impact our ability to raise the capital needed to finance our operations.
Previous wording
receive a clinical hold for a particular product candidate, which, if not lifted, could require that we discontinue development of a product candidate;
Current wording
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;
Previous wording
There have been several significant adverse side effects in gene therapy treatments in the past, including reported cases of leukemia in trials using lentivirus vectors and death seen in trials sponsored by other companies using adenovirus vectors and AAV vectors, including NAV vectors. Gene therapy is still a relatively new approach to disease treatment and additional adverse side effects could be identified. There also is the potential risk of delayed adverse events following exposure to gene therapy products due to persistent biologic activity of the genetic material or other components of products used to carry the genetic material. Possible adverse side effects that could occur with treatment with gene therapy products include an immunologic reaction early after administration which could substantially limit the effectiveness of the treatment. 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. Furthermore, in clinical trials sponsored by other companies involving AAV vectors administered intravitreally for the treatment of retinal conditions, serious adverse reactions, such as panuveitis and loss of vision, have occurred. In addition to side effects caused by product candidates, the administration process or related procedures also can cause adverse side effects. If any such adverse events occur in our or third-party trials, our clinical trials could be suspended or terminated.
Current wording
There also is the potential risk of delayed adverse events following exposure to gene therapy products due to persistent biologic activity of the genetic material or other components of products used to carry the genetic material. Possible adverse side effects that could occur with treatment with gene therapy products include an immunologic reaction early after administration which could substantially limit the effectiveness of the treatment. 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. Approved labels for certain gene therapies state that AAV vector DNA can integrate into the host genome at low frequency and that such integration may carry a theoretical risk of malignancy, including hepatocellular carcinoma. Furthermore, in clinical trials sponsored by other companies involving AAV vectors administered intravitreally for the treatment of retinal conditions, serious adverse reactions, such as panuveitis and loss of vision, have occurred. In addition to side effects caused by product candidates, the administration process or related procedures also can cause adverse side effects. If any such adverse events occur in our or third-party trials, our clinical trials could be suspended or terminated. Additionally, if clinically meaningful AAV integration events or an increased incidence of cancer were observed in our studies or in the broader gene therapy field, the FDA or other regulatory authorities could impose additional requirements, place our clinical trials on hold, restrict dosing or patient populations, require enhanced warnings or other labeling limitations, or delay or deny approval of our product candidates. In the RGX-121 CRL, FDA noted that we should include a safety post marketing requirement in the resubmission.
Previous wording
Additionally, if any of our product candidates receives marketing approval, the FDA could require us to adopt a Risk Evaluation and Mitigation Strategy (REMS) and other regulatory authorities could impose other specific obligations as a condition of approval to ensure that the benefits of our product candidates outweigh their risks, which could delay approval of our product candidates. A REMS may include, among other things, a medication guide outlining the risks of the product for distribution to patients; a communication plan to health care practitioners or patients; and elements to assure safe use, which can severely restrict the distribution of a product by, for example, requiring that health care providers receive particular training and obtain special certification prior to prescribing and dispensing the product, limiting the healthcare settings in which the product may be dispensed and subjecting patients to monitoring and enrollment in a registry. If the FDA requires us to adopt a REMS for our products and we are unable to comply with its requirements, the FDA may deem our products to be misbranded and we may be subject to civil money penalties. The European Commission, the EMA and other regulatory authorities may, following grant of marketing authorization in their territory, impose similar obligations.
Current wording
Additionally, if any of our product candidates receives marketing approval, the FDA could require us to adopt a Risk Evaluation and Mitigation Strategy (REMS) and other regulatory authorities could impose other specific obligations as a condition of approval to ensure that the benefits of our product candidates outweigh their risks, which could delay approval of our product candidates. A REMS may include, among other things, a medication guide outlining the risks of the product for distribution to patients; a communication plan to health care practitioners or patients; and elements to assure safe use, which can severely restrict the distribution of a product by, for example, requiring that health care providers receive particular training and obtain special certification prior to prescribing and dispensing the product, limiting the healthcare settings in which the product may be dispensed and subjecting patients to monitoring and enrollment in a registry. If the FDA requires us to adopt a REMS program for our products and we are unable to comply with its requirements, the FDA may deem our products to be misbranded and we may be subject to civil money penalties. The European Commission, the EMA and other regulatory authorities may, following grant of marketing authorization in their territory, impose similar obligations.
Previous wording
We cannot commercialize a product candidate until the appropriate regulatory authorities have reviewed and approved the product candidate. Even if our product candidates meet their safety and efficacy endpoints in clinical trials, the regulatory authorities may not complete their review processes in a timely manner or we may not be able to obtain regulatory approval. 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. 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. In addition, government funding of other government agencies on which our operations may rely, including those that fund research and development activities, is subject to the political process, which is inherently fluid and unpredictable. Additional delays may result if an FDA Advisory Committee or other regulatory authority recommends non-approval or restrictions on approval. In addition, we may experience delays or rejections based on additional government regulation from future legislation or administrative action or based on changes in regulatory authority policy during the period of product development, clinical trials and the review process.
Current wording
We cannot commercialize a product candidate until the appropriate regulatory authorities have reviewed and approved the product candidate. Even if our product candidates meet their safety and efficacy endpoints in clinical trials, the regulatory authorities may not complete their review processes in a timely manner or we may not be able to obtain regulatory approval. 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. 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. In addition, government funding of other government agencies on which our operations may rely, including those that fund research and development activities, is subject to the political process, which is inherently fluid and unpredictable. Additional delays may result if an FDA Advisory Committee or other regulatory authority recommends non-approval or restrictions on approval. The FDA has recently delayed approvals or issued CRLs for a number of rare disease therapies, including those seeking accelerated approval. Heightened regulatory scrutiny may delay or prevent our ability to resolve the deficiencies identified in the RGX-121 CRL and obtain approval of our product candidates. In addition, we may experience delays or rejections based on additional government regulation from future legislation or administrative action or based on changes in regulatory authority policy during the period of product development, clinical trials and the review process.
Previous wording
Further, the regulatory authorities may require concurrent approval or the CE mark (a mandatory conformity assessment marking for certain products sold within the European Economic Area (the EEA)) of a companion diagnostic device, since it may be necessary to use FDA-cleared or FDA-approved, or CE-marked, diagnostic tests or diagnostic tests approved by other comparable foreign regulatory authorities to diagnose patients or to assure the safe and effective use of our product candidates in trial subjects. FDA refers to such tests asin vitro companion diagnostic devices. The FDA has articulated a policy position that, when safe and effective use of a therapeutic product depends on a diagnostic device, the FDA generally will require approval or clearance of the companion diagnostic device at the same time that the FDA approves the therapeutic product. The FDA’s guidance allows for two exceptions to the general rule of concurrent drug/device approval, namely, when the therapeutic product is intended to treat serious and life-threatening conditions for which no alternative exists, and when a serious safety issue arises for an approved therapeutic agent, and no FDA-cleared or FDA-approved companion diagnostic test is yet available. It is unclear how the FDA will apply this policy to our current or future gene therapy product candidates. Should the FDA deem genetic tests used for diagnosing patients for our therapies to bein vitro companion diagnostics requiring FDA clearance or approval, we may face significant delays or obstacles in obtaining approval of a BLA for our product candidates.
Current wording
Further, the regulatory authorities may require concurrent approval or the CE mark (a mandatory conformity assessment marking for certain products sold within the European Economic Area (the EEA)) of a companion diagnostic device, since it may be necessary to use FDA-cleared or FDA-approved, or CE-marked, diagnostic tests or diagnostic tests approved by other comparable foreign regulatory authorities to diagnose patients or to assure the safe and effective use of our product candidates in trial subjects. FDA refers to such tests asin vitro companion diagnostic devices. The FDA has articulated a policy position that, when safe and effective use of a therapeutic product depends on a diagnostic device, the FDA generally will require approval or clearance of the companion diagnostic device at the same time that the FDA approves the therapeutic product. The FDA’s guidance allows for an exception to the general rule of concurrent drug/device approval when the therapeutic product is intended to treat serious and life-threatening conditions for which no satisfactory alternative treatment exists and the benefits from the use of the therapeutic product are so pronounced as to outweigh the fact that no FDA-cleared or FDA-approved companion diagnostic test is yet available. It is unclear how the FDA will apply this policy to our current or future gene therapy product candidates. Should the FDA deem genetic tests used for diagnosing patients for our therapies to bein vitro companion diagnostics requiring FDA clearance or approval, we may face significant delays or obstacles in obtaining approval of a BLA for our product candidates. In this regard, in a 2024 case a U.S. District Court vacated FDA’s final rule to regulate laboratory developed test services, and FDA declined to appeal, creating uncertainty for FDA’s continued regulation of certain tests as companion diagnostics. Uncertainty about the legal status of certain companion diagnostics, including the possibility of additional law or further regulations or guidance from FDA, may create uncertainty that could lead to delay in the development and approval of our product candidates.
Previous wording
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.
Current wording
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.
Previous wording
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.
Current wording
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.
Previous wording
Since inception, we have incurred cumulative net losses. 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 devoted substantially all of our efforts to research and development, including preclinical and clinical development of our product candidates, and licensing our NAV Technology Platform, as well as to building out our team. We expect that it could be years before we commercialize most of ourproduct candidates, and we can provide no assurance that we will ever be able to do so. We license certain intellectual property related to our NAV Technology Platform to our NAV Technology Licensees and collaborators. 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. 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. We anticipate that our expenses will increase substantially if, and as, we:
Current wording
Since inception, we have incurred cumulative net losses. 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. We have devoted substantially all of our efforts to research and development, including preclinical and clinical development of our product candidates, and licensing our NAV Technology Platform, as well as to building out our team. We expect that it could be years before we commercialize most of ourproduct candidates, and we can provide no assurance that we will ever be able to do so. We license certain intellectual property related to our NAV Technology Platform to our NAV Technology Licensees and collaborators. 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. 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. We anticipate that our expenses will increase substantially if, and as, we:
Previous wording
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.
Current wording
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.
Previous wording
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. In addition, if we obtain marketing approval for any of our product candidates, we expect to incur significant expenses related to product sales, medical affairs, marketing, manufacturing and distribution. Accordingly, we will need to obtain substantial additional funding in connection with our continuing operations. If we are unable to raise capital when needed or on favorable terms, we could be forced to delay, reduce or eliminate certain of our licensing activities, our research and development programs or other operations.
Current wording
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, if we obtain marketing approval for any of our product candidates, we expect to incur significant expenses related to product sales, medical affairs, marketing, manufacturing and distribution. Accordingly, we will need to obtain substantial additional funding in connection with our continuing operations. Increased unpredictability in the regulatory environment and the regulatory requirements to obtain approval of our product candidates may adversely impact our ability to raise the capital needed to finance our operations. If we are unable to raise capital when needed or on favorable terms, we could be forced to delay, reduce or eliminate certain of our licensing activities, our research and development programs or other operations.
Previous wording
revenue received from commercial sales of Zolgensma and the timing and amount of Zolgensma royalties paid to HCR under our royalty purchase agreement;
Current wording
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;
Previous wording
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;
Current wording
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;
Previous wording
the costs of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending any intellectual property-related claims;
Current wording
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;
Previous wording
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.
Current wording
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.
Previous wording
We have generated significant revenues from licensing our NAV Technology Platform, including sublicense fees, milestone payments and royalties on net sales of a licensed product, Zolgensma, and licensing our intellectual property to AbbVie pursuant to the AbbVie Collaboration and License Agreement and may do so in the future pursuant to the Nippon Shinyaku Collaboration and License Agreement. However, our ability to generate revenue from sales of our internal product candidates will depend on our ability, alone or with partners, to successfully complete the development of, and obtain the regulatory approvals necessary to commercialize, our product candidates.
Current wording
We have generated significant revenues from licensing our NAV Technology Platform, including sublicense fees, milestone payments and royalties on net sales of licensed products, Zolgensma and Itvisma, and licensing our intellectual property to collaborators under our license and collaboration agreements with AbbVie and Nippon Shinyaku. However, our ability to generate revenue from sales of our internal product candidates will depend on our ability, alone or with partners, to successfully complete the development of, and obtain the regulatory approvals necessary to commercialize, our product candidates.
Previous wording
Many of these factors as they relate to our licensees’ and collaborators’ products, including Zolgensma, will be outside our control, and future revenues in connection with sales of such products may be precluded or limited by any of these factors.
Current wording
Many of these factors as they relate to our licensees’ and collaborators’ products, including Zolgensma and Itvisma, will be outside our control, and future revenues in connection with sales of such products may be precluded or limited by any of these factors.
Previous wording
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.
Current wording
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.
Previous wording
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.
Current wording
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.
Previous wording
Products intended for use in gene therapies are novel, complex and difficult to manufacture. We could experience production problems that result in delays in our development or commercialization programs, limit the supply of our products or otherwise harm our business.
Current wording
Products intended for use in gene therapies are novel, complex and difficult to manufacture, which could lead to production problems that result in delays in our development or commercialization programs, limit the supply of our products or otherwise harm our business.
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Current report — wording carried from elsewhere
There have been several significant adverse side effects in gene therapy treatments in the past, including reported cases of leukemia in trials using lentivirus vectors and death seen in trials sponsored by other companies using adenovirus vectors and AAV vectors, including NAV vectors. Gene therapy is still a relatively new approach to disease treatment and additional adverse side effects could be identified. Any such adverse safety events in our programs or in AAV gene therapy programs conducted by other companies may negatively impact the regulatory environment, public perception, and financing conditions for AAV-based therapies, which could significantly increase our associated expenses and negatively impact our ability to raise additional capital.
Current report — wording carried from elsewhere
Medicare Part B and Part D covered drugs at a rate greater than the rate of inflation. The inflation rebates may require us to pay rebates if we were to increase the cost of a covered Medicare Part B or Part D covered product faster than the rate of inflation. At this time, we are unable to predict how these recent legislative changes or any future legislation might affect our business. Moreover, reimbursement agencies in the European Union may be more conservative than CMS. It is difficult to predict what third-party payors will decide with respect to the coverage and reimbursement for our product candidates.
Rearranged previous paragraphs (2)
Previous report — wording carried elsewhere
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. 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
Previous report — wording carried elsewhere
Platform or our product candidates. The outcome following legal assertions of invalidity and unenforceability is unpredictable. With respect to the validity question, for example, we cannot be certain that there is no invalidating prior art, of which the patent examiner and we or our licensing partners were unaware during prosecution. If a defendant were to prevail on a legal assertion of invalidity or unenforceability, we could lose at least part, and perhaps all, of the patent protection on one or more of our product candidates. Such a loss of patent protection could materially harm our business.