VYGR 10-K & 10-Q changes, risk factors and insider trading

We are an early-stage biotechnology company and have not yet generated revenues from the sales of our product candidates. All of our product candidates are in the early stages of development. Investment in biotechnology companies is highly speculative because it entails substantial upfront capital expenditures and significant risk that any product candidates will fail to be safe and efficacious, obtain regulatory approval or become commercially viable. We have not yet demonstrated the ability to complete any clinical trials of our product candidates, obtain marketing approvals, manufacture a commercial-scale product or conduct sales and marketing activities necessary for successful commercialization. We continue to incur significant expenses related to research and development, and other operations in order to commercialize our product candidates. We have a history of incurring significant operating losses. We had a net loss of $119.7 million, net loss of $65.0 million, and net income of $132.3 million, and a net loss of $46.4 million for the years ended December 31, 2025, 2024, 2023, and 2022,2023, respectively. As of December 31, 2024,2025, we had an accumulated deficit of $326.2$445.9 million.

Even if one or more of the product candidates that we develop is approved for commercial sale, we anticipate incurring significant costs associated with commercializing any approved product candidate. Our expenses could increase beyond expectations if we are required by the FDA, EMA, or other regulatory authorities to redesign or modify preclinical studies or clinical trials or to perform preclinical studies or clinical trials in addition to those that we currently anticipate. Even if we are able to generate revenues from the sale of any approved products, we may not become profitable and may need to obtain additional funding to continue operations.operations and may we decide to discontinue commercial availability and/or voluntarily request the withdrawal of the new drug application, or NDA, for any of our products, which may raise additional potential risks and uncertainties. Any issues or hurdles related to our commercialization efforts may materially adversely affect our business, results of operations, financial condition and prospects and could lead us to make significant further changes to the scope and nature of our efforts.

Our operations have consumed significant amounts of cash since inception. As of December 31, 2024,2025, our cash, cash equivalents, and marketable securities were $332.4$201.7 million. Based upon our current operating plan, we expect that our existing cash, cash equivalents, and marketable securities atas of December 31, 20242025, along with amounts expected to be received as reimbursement for development costs under our collaboration and license agreements with Neurocrine and Novartis, and interest income, to be sufficient to meet our planned operating expenses and capital expenditure requirements into mid-2027.2028. We have based this estimate on assumptions that may prove to be wrong.

Identifying potential product candidates and conducting preclinical studies and clinical trials is a time-consuming, expensive, and uncertain process that takes years to complete. We may never generate the necessary data or results required to maintain the financial support of our collaborators or obtain marketing approval and achieve product sales. In the event we are unable to achieve milestones necessary to demonstrate progress on those programs, a current or future collaboration partner or licensor may be unwilling to fund these programs at the desired levelslevels, or at all, which could require us to fund these programs to a greater extent than we have expected, to decline to pursue certain program objectives or to discontinue one or more of the programs. Our ability to develop a product candidate for any of our lead gene therapy or other biological therapy programs may take longer than we anticipate, or may not happen at all, and could require funding at a level higher than we expect. In addition, our product candidates, if approved, may not achieve commercial success. Our product revenues, if any, and any commercial milestone payments or royalty payments under our collaboration or option and license agreements, will be derived from sales of products that may not be commercially available for many years, if at all. Accordingly, we will need to continue to rely on additional financing and business development transactions to achieve our business objectives. Adequate additional financing may not be available to us on acceptable terms, or at all.

Until such time, if ever, as we can generate product revenues sufficient to achieve consistent profitability, we expect to finance our cash needs through a combination of equity offerings, debt financings, collaborations, strategic alliances, and option and license arrangements. We do not have any committed external source of funds other than the amounts we are entitled to receive from our collaboration partners, Neurocrine and Novartis, and licensees for the reimbursement of certain research and development expenses, potential option exercises, the achievement of specified regulatory and commercial milestones, and royalty payments under the 2019 Neurocrine Collaboration Agreement, the 2023 Neurocrine Collaboration Agreement, and the 2023 Novartis Collaboration Agreement and the amounts we are entitled to receive from our licensees Alexion and Novartis for the achievement of specified development, regulatory, and commercialization milestones and royalty payments under the applicable option and license agreements. To the extent that we raise additional capital through the sale of equity or equity-linked securities, including convertible debt, our stockholders’ ownership interests will be diluted. For example, on November 10, 2025, we entered into a sales agreement with respect to an “at the market offering” program pursuant to which we may offer and sell shares of our common stock having an aggregate offering price of up to $100.0 million, from time to time through TD Securities (USA) LLC. Any significant sales of shares of our common stock pursuant to the sales agreement would result in dilution to our current stockholders. The amount of stockholder dilution through the sale of equity or equity-linked securities will be affected by the size of each securities offering and the offering price for the securities sold. The offering price will likely reflect the prevailing market price for our securities, with dilution increasing as the prevailing market price for our securities decreases. The terms of these securities may include liquidation or other preferences that adversely affect our existing stockholders’ rights as holders of our common stock. Debt financing and preferred equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, obtaining additional capital, acquiring or divesting businesses, making capital expenditures or declaring dividends. In addition, we may seek additional capital due to favorable market conditions or strategic considerations, even if we believe we have sufficient funds for our current or future operating plans. Our issuance of additional securities, whether equity or debt, or the possibility of such issuance, may cause the market price of our common stock to decline. Further, our existing stockholders may not agree with the terms of such financings.

Our operating history to date has been limited to building our team, business planning, raising capital, establishing our intellectual property portfolio, determining which neurological diseases to pursue, advancing our product candidatescandidates, including delivery and manufacturing and conducting preclinical studies and early-phase clinical trials. Consequently, any predictions about our future success or viability may not be as accurate as they could be if we had an operating history that included the late stage of clinical development, completion of clinical development, or commercialization of one or more product candidates. VY7523, our anti-tau antibody candidate, is in early-stage clinical trials, and.and all of our other active product candidates are currently in preclinical development.development, including VY1706, our tau silencing program.

In addition, we may encounter unforeseen expenses, difficulties, complications, delays and other known and unknown factors such as the regulatory setbacks that previously occurred in prior clinical programs,programs we have conductedconducted, such as those put on hold by the FDA.FDA, and the terminations, in part, of the 2019 Neurocrine Collaboration Agreement and the 2022 Novartis Option and License Agreement to date. These and other events that are part of our operating history may impact our ability to operate our business and to raise capital. All of our product candidates are in the early stages of development. To achieve our current goals, we will need to transition in the future from a company with a research and development focus to a company capable of supporting commercial activities. We may not be successful in such a transition.

We expect our financial condition and operating results to continue to fluctuate significantly from quarter-to-quarter and year-to-year due to a variety of factors, many of which are beyond our control as we advance more of our programs into the clinical stage. Accordingly, our stockholders should not rely upon the results of any quarterly or annual periods as indications of future operating performance.

Our AAV gene therapy, non-viral therapeutic, and other biological therapy product candidates are based on a proprietary technologytechnologies and, in several disease areas, unvalidated treatment approaches, which makesmake it difficult and potentially infeasible to predict the duration and cost of development of, and subsequently obtaining regulatory approval for, our product candidates.

AAV gene therapies are a relatively new technology. We cannot accurately predict when or if any of our product candidates will prove effective or safe in humans or whether these product candidates will receive marketing approval. Additionally, there can be no assurance that we will not experience problems or delays in the preclinical testing or development of our product candidates and that such problems or delays will not cause unanticipated costs, or that any such problems or delays can be solved in a timely or profitable basis, if at all. For example, we are no longer advancing VY9323, formerly the lead development candidate for our superoxide dismutase 1, or SOD1, silencing gene therapy program for amyotrophic lateral sclerosis, or ALS, as a development candidate and are assessing alternate payloads for the program based on three-month data from a non-human primate good laboratory practice, or GLP, toxicology study suggesting that a different payload would be necessary to achieve the desired product profile for the program. We also may experience unanticipated problems or delays in expanding our manufacturing capacity or outsourcing manufacturing activities to contract manufacturers.

The clinical trial requirements of the FDA, the EMA and other regulatory authorities and the criteria these regulators use to determine the safety and efficacy of a product candidate vary substantially according to the type, complexity, novelty and intended use and market of the product candidate. The regulatory approval process for novel product candidates such as gene therapies can be more expensive and take longer than for other,other better known or more extensively studied product candidates. Until August 2017, the FDA had never approved an AAV gene therapy product. Since that time, it has approved a limited number of gene therapy products. In Europe, a similarly limited number of AAV gene therapy products have been granted marketing authorization.

Regulatory requirements governing biological, gene therapy, non-viral therapeutic, and other non-viral therapeutic products have changed frequently and may continue to change in the future. Such requirements may lengthen the regulatory review process, require us to modify current studies or perform additional studiesstudies, or increase our development costs, which in turn may force us to delay, limit, or terminate certain of our programs.

All of our product candidates are in early stages of development, and the risk of failure is high. Clinical testing is expensive, is difficult to design and implement, can take many years to complete and is uncertain as to outcome. A failure of one or more clinical trials can occur at any stage of testing. Our product candidates may fail to show the desired safety and efficacy in preclinical testing or clinical development despite demonstrating promising results in earlier preclinical studies or clinical trials. In addition, the outcome of preclinical testing and early clinical trials may not be predictive of the success of later stage clinical trials. For example, despite data we believed was promising from the earlier PD-1101 Phase 1b clinical trial and from the separate PD-1102 Phase 1 clinical trial evaluating the delivery of VY-AADC (NBIb-1817), we and our strategic collaborator Neurocrine did not receive favorable data,data from, and were ultimately unable to complete, the RESTORE-1 Phase 2 clinical trial evaluating VY-AADC (NBIb-1817) for the treatment of Parkinson’s disease. Similarly, interim results generated from clinical trials do not necessarily predict final results, and results from one completed clinical trial may not be replicated in a subsequent clinical trial with a similar study design. Some of our clinical trials were conducted with small patient populations and were not blinded or placebo-controlled, making it difficult to predict whether the favorable results that we observed in such trials will be sustained or repeated in larger and more advanced clinical trials. Moreover, preclinical and clinical data are often susceptible to varying interpretations and analyses, and many companies that have believed their product candidates performed satisfactorily in preclinical studies and clinical trials have nonetheless failed to obtain marketing approval of their products.PD.

There is a high failure rate for product candidates proceeding through preclinical studies and clinical trials. A number of companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in late-stage clinical trials even after achieving promising results in early-stage clinical trials. If a larger population of patients does not experience positive results, if these results are not reproducible, or if our products show diminishing activity over time, our products may not receive approval from the EMA or the FDA. Data obtained from preclinical and clinical activities are subject to varying interpretations, which may delay, limit or prevent regulatory approval. In addition, we may encounter regulatory delays or rejections as a result of many factors, including changes in regulatory policy during the period of product development. Failure to confirm favorable results from earlier trials by demonstrating the safety and effectiveness of our products in late-stage clinical trials with larger patient populations could harm our business and we may never succeed in commercialization or generating product revenue.

We have conducted, and may in the future choose to conduct, one or more of our clinical trials outside the United States. To date, we have conducted clinical trials in the United States and Canada. We may in the future choose to conduct one or more of our clinical trials or include sites in current or future clinical trials outside the United States.

We are early in our development efforts. AllVY7523, our anti-tau antibody candidate, is in early-stage clinical trials, and all of our other active product candidatescandidates, including VY1706, are currently in preclinical developmentdevelopment. We or early-stageour clinical development. Wecollaborators may encounter substantial delays or difficulties in the commencement, enrollment or completion of our preclinical studies or clinical trials, or we or our collaborators may fail to demonstrate safety and efficacy sufficient to support further development or to satisfy the satisfaction of applicable regulatory authorities, any of which could prevent us or our collaborators from further developing or commercializing our current and future product candidates on a timely basis, if at all.

To conduct clinical trials, we must first complete preclinical testing and studies to support IND applications or similar applications in other jurisdictions. We cannot be certain of the timely completion or successful outcome of our preclinical testing and studies. Our ability to complete our preclinical testing and studies is contingent on, among other things, our ability to source animals and other supplies required for the conduct of such testing and studies. If we are unable to obtain such supplies, we may be unable to complete such preclinical testing and studies in a timely mannermanner, or at all. For example, some of our IND-enabling toxicology, capsid discovery, and other studies require certain NHPs that are customarily imported from outside the United States. Our inability to obtain access to a sufficient supply of these NHPs in a timely mannermanner, or at allall, may impair or delay our ability to complete preclinical studies to support capsid discovery efforts or IND applications or similar applications in other jurisdictions. We have previously encountered, and may encounter in the future, delays in obtaining a sufficient supply of such NHPs due to governmental or regulatory actions that result in importation restrictions in the United States or exportation restrictions in the country of origin. At times when the NHP supply in the United States has been constrained, we have conducted NHP studies at contract research facilities outside of the United States. When utilizing such facilities, we are required to observe export control regulations for the shipment of product candidates and their component materials and import control regulations for the shipment of samples to us for evaluation and storage. We may be required to incur delays or expenses in order to conduct our NHP studies in compliance with these regulations, and we may be subject to additional penalties, delays, or expenses if we fail to achieve compliance.

Additionally, we cannot predict if the FDA or similar regulatory authorities outside the United States will accept our planned clinical programs or if the outcome of our preclinical testing and studies will ultimately support the further development of our preclinical and clinical programs. In connection with our earlier VY-HTT01 Program for the treatment of Huntington’s disease, for example, we were unable to successfully predict what the FDA would require and were unable to obtain a second pre-IND meeting with the FDA to discuss the product candidate’s regulatory pathway with the FDA. As a result, in October 2020, the FDA notified us that the IND application for the planned Phase 1 and Phase 2 clinical trial to evaluate VY-HTT01 had been put on clinical hold.

In addition, the FDA’s and other regulatory authorities’ policies with respect to clinical trials may change and additional government regulations may be enacted. For example, in December 2022, with the passage of Food and Drug Omnibus Reform Act, known was FDORA, Congress required sponsors to develop and submit a diversity action plan, or DAP, for each Phase 3 clinical trial or any other “pivotal study” of a new drug or biological product. These plans are meant to encourage the enrollment of more diverse patient populations in late-stage clinical trials of FDA-regulated products. Specifically, action plans must include the sponsor’s goals for enrollment, the underlying rationale for those goals, and an explanation of how the sponsor intends to meet them. In addition to these requirements, the legislation directs the FDA to issue new guidance on DAPs. In June 2024, as mandated by FDORA, the FDA issued draft guidance outlining the general requirements for DAPs. Unlike most guidance documents issued by the FDA, the DAP guidance when finalized will have the force of law because FDORA specifically dictates that the form and manner for submission of DAPs are specified in FDA guidance. On January 27, 2025, in response to an Executive Order issued by President Trump on January 21, 2025, on Diversity, Equity and Inclusion programs, the FDA removed this draft guidance from its website. TheThereafter, implicationsfollowing litigation, the FDA was directed by a federal district court to restore the draft guidance to the FDA website. When the FDA did so, it stated that “information on this page may be modified and/or removed in the future subject to the terms of thisthe court’s order and implemented consistent with applicable law.” Accordingly, in light of these ongoing actions, there is considerable uncertainty surrounding the draft DAP guidance and how the FDA will consider diversity action areplans notin yetconnection known.with its review of BLAs.

We cannot guarantee that any clinical trials will be conducted as planned or completed on schedule, if at all. A clinical trial failure can occur at any stage of testing. Similarly, there may be delays or difficulties in our initiation of future clinical trials. Similarly, there may be delays or difficulties in our initiation of future clinical trials. For example, we no longer expect to file an IND or Canadian clinical trial application for VY9323, formerly the lead development candidate for our SOD1 silencing program for ALS, and are assessing alternate payloads for the program based on three-month data from a non-human primate GLP toxicology study suggesting that a different payload would be necessary to achieve the desired product profile for the program.

We also have very limited historical experience with clinical trials as a company. Identifying and qualifying patients to participate in clinical trials of our product candidates is critical to our success. We may not be able to identify, recruit and enroll a sufficient number of patients, or those with required or desired characteristics, to complete our clinical trials in a timely mannermanner, or at allall, pursuant to the requirements of the FDA, EMA, or other regulatory authorities. Patient enrollment and trial completion are affected by many factors including:

Any inability to successfully initiate or complete preclinical studies and clinical trials could result in additional costs and potential delays to us or impair our ability to generate revenues from product sales, regulatory and commercialization milestones and royalties. We do not know whether any of our preclinical studies or clinical trials will begin as planned, will need to be restructured, or will be completed on schedule, or at all. For example, ourthe decision to refocus ourthe Huntington’s disease program meansrequires wecompletion must conductof new preclinical studies, preparepreparation of a new IND, submit itsubmission to the FDA, and resolveresolution of any potential FDA objections before enrollingenrollment ourof the first patient in a new clinical trial. In addition, if we make manufacturing or formulation changes to our product candidates, such as we did in connection with our previous transition to an HEK 293-based production system from a baculovirus/Sf9 AAV production system or as a result of unanticipated clinical trial results, we may need to conduct additional studies to bridge our modified product candidates to earlier versions. Clinical trial delays also could shorten any periods during which we may have the exclusive right to commercialize our product candidates or allow our competitors to bring products to market before we do, which could impair our ability to successfully commercialize our product candidates and may harm our business, financial condition, results of operations and prospects.

Our product candidates may cause undesirable side effects or have other properties that could delay or prevent their further development or regulatory approval, limit their commercial potential or result in significant negative consequences following any potential marketing approval.

Our proprietary antibodiesantibodies, gene therapies and genenon-viral therapy product candidates may cause an immunologic reaction, or an immune response against the relevant product candidate. Other potential side effects associated with our gene therapy product candidates could include insertional oncogenesis, which is the process whereby the insertion of a functional gene near a gene that is important in cell growth or division results in uncontrolled cell division, which could potentially enhance the risk of malignant transformation. In past clinical trials that were conducted by others using non-AAV gene therapy vectors, several significant side effects were caused by gene therapy treatments, including reported cases of leukemia and death. For example, one of our competitors, Capsida Biotherapeutics, Inc., stated that it was not aware of significant safety signals in its preclinical program known as STXBP1, but its first patient dosed in its clinical program resulted in the death of a patient. Additionally, in a published review of patients with hepatocellular carcinomas, it was shown that a small subset contained an integrated genome sequence of wild-type AAV2, and it was suggested that AAV2 may be associated with insertional oncogenesis. If our vectors demonstrate a similar adverse effect, or other adverse effects, we may be required to halt or delay further clinical development of our product candidates or withdraw the product from the market post-approval. For example, in a recently published review of patients with hepatocellular carcinomas, it was shown that a small subset contained an integrated genome sequence of wild-type AAV2, and it was suggested that AAV2 may be associated with insertional oncogenesis.

In addition to sideSide effects could be caused by the product candidate,candidate or the administration process also could cause side effects.process. If in the future we are unable to demonstrate thatwhat caused such side effects were caused by the administration process or related procedures or are unable to modify the trial protocol adequately to address such side effects, the FDA, the European Commission, the EMA or other regulatory authorities could order us to cease further development of, or deny approval of, our product candidates for any or all targeted indications. For example, product candidates designed to “knock down” or reduce the expression of a gene or the production of its encoded protein could have effects on other parts of the body, or “off target” effects, that could result in unforeseen toxicity. Even if we are able to demonstrate that any future SAEsside effects are not product-related, and regulatory authorities do not order us to cease further development of our product candidates, such occurrences could affect patient recruitment or the ability of enrolled patients to complete the trial. Moreover, if we elect, or are required, to delay, suspend or terminate any clinical trial of any of our product candidates, the commercial prospects of such product candidates may be harmed and our ability to generate product revenues from any of these product candidates may be delayed or eliminated. Any of these occurrences may harm our ability to develop other product candidates and may harm our business, financial condition and prospects significantly.

Additionally, if any of our product candidates receives marketing approval, the FDA could require us to adopt a REMS to ensure that the benefits outweigh its risks. We believe that the likelihood of the FDA requiring a REMS may be higher for treatments with more invasive routes of administration such as directgene delivery through brain surgery.therapy. Such REMS may include, among other things, a medication guide outlining the risks of the product for distribution to patients and a communication plan to health care practitioners or the limitation of the use of the product to specifically trained neurosurgeons and/or certain centers. Furthermore, adverse events which were initially considered unrelated to the study treatment of the clinical trial may later be found to be caused by the study treatment. If we or others later identify undesirable side effects caused by our product candidate, several potentially significant negative consequences could result, including:

The FDA may also require that NDA or BLA submissions for our product candidates include pediatric data. Under the PREA, an NDA, BLA or supplement to an NDA or a BLA for certain drugs and biological products must contain data to assess the safety and effectiveness of the drug or biological product in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective, unless the sponsor receives a deferral or waiver from the FDA. Applicable legislation in the EU also requires sponsors to either conduct clinical trials in a pediatric population in accordance with a Pediatric Investigation Plan approved by the Pediatric Committee of the European Medicines Agency, or EMA,EMA or to obtain a waiver or deferral from the conduct of these studies by this Committee. For any of our product candidates for which we are seeking regulatory approval in the United States or the EU, we cannot guarantee that we will be able to obtain a waiver or alternatively complete any required studies and other requirements in a timely manner, or at all, which could result in associated reputational harm and subject us to enforcement action.

Further, our ability to develop and market new drug products may be impacted by litigation challenging the FDA’s approval of another company’s drug product. In April 2023, the U.S. District Court for the Northern District of Texas invalidated the approval by the FDA of mifepristone, a drug product which was originally approved in 2000 and whose distribution is governed by various measures adopted under a REMS. The Court of Appeals for the Fifth Circuit declined to order the removal of mifepristone from the market but did hold that plaintiffs were likely to prevail in their claim that changes allowing for expanded access of mifepristone, which the FDA authorized in 2016 and 2021, were arbitrary and capricious. In June 2024, the Supreme Court reversed that decision after unanimously finding that the plaintiffs (anti-abortion doctors and organizations) did not have standing to bring this legal action against the FDA. On October 11, 2024, the Attorneys General of three states (Missouri, Idaho and Kansas) filed an amended complaint in the district court in Texas challenging FDA’s actions. On January 16, 2025, the district court agreed to allow these states to file an amended complaint and continue to pursue this challenge. Thereafter, on September 30, 2025, the district court declined to dismiss the case and, instead, transferred it to the federal district court in the Eastern District of Missouri. Depending on the outcome of this litigation, our ability to develop new drug product candidates and to maintain approval of existing drug products could be delayed, undermined or subject to protracted litigation.

Disruptions inat the FDA and other government agencies caused byfrom funding shortagescuts, orpersonnel globallosses, healthregulatory concernsreform, government shutdowns and other developments could hinder theirour ability to hireobtain guidance from the FDA regarding our clinical development programs and retain key leadershipdevelop and othersecure personnelapproval orof otherwise prevent newour product candidates and services from being developed or commercialized in a timely manner, which couldwould negatively impact our business.

Disruptions at the FDA and other agencies may also slow the time necessary for new product candidates to be reviewed or approved by necessary government agencies, which would adversely affect our business. For example, overDuring the last several years, including for 35 days beginning on December 22, 2018,years the U.S. government has shut down several times and certain regulatory agencies, such as the FDA,FDA and the SEC, have had to furlough critical employees and stop critical activities. If a prolonged government shutdown occurs, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions,submissions whichand could have a material adverse effect onimpact our business.ability to access the public markets and obtain necessary capital to properly capitalize and continue our operations.

InAt addition,the same time, disruptions at the FDA and other government agencies may result from public health events similar to the COVID-19 pandemic. DuringFor example, during the COVID-19 pandemic, a number of companies announced receipt of complete response letters due to the FDA’s inability to complete required inspections for their applications. In the event of a similar public health emergency in the future, the FDA may not be able to continue its current pace and review timelines could be extended. Regulatory authorities outside the United States facing similar circumstances may adopt similar restrictions or other policy measures in response to a similar public health emergency and may also experience delays in their regulatory activities.

The biopharmaceutical industry is characterized by intense and dynamic competition to develop new technologies and proprietary therapies. Any product candidates that we successfully develop into products and commercialize may compete with existing therapies and new therapies that may become available in the future. While we believe that our gene therapy platform, vectorized antibody platform, non-viral therapeutics platform, product programs, product candidates and scientific expertise in the fields of proprietary antibodies, gene therapy, and neuroscience provide us with competitive advantages, we face potential competition from various sources, including larger and better-funded pharmaceutical, specialty pharmaceutical and biotechnology companies, as well as from academic institutions, governmental agencies and public and private research institutions.

Even if our competitors are unsuccessful in developing and commercializing their product candidates, their preclinical and clinical findings may lead us to conclude that our own similar product candidates are unlikely to achieve the desired performance characteristics. As a result, we may modify our development plans for, or discontinue further research and development of, such product candidates. For example, several of our competitors arehave conductingconducted clinical trials of anti-tau antisense oligonucleotide and antibody candidates with expected clinical data readouts in 2025 andor are conducting clinical trials with expected readouts in 2026. It is possible that we will modify our development plans for, or discontinue further research and development of, VY7523 or VY1706, the lead development candidate for our tau gene silencing gene therapy program,VY1706 if any of these clinical data readouts suggest that either candidate will likely fail to achieve the desired performance characteristics.

In addition, as a result of the expiration or successful challenge of our patent rights, we could face more litigation with respect to the validity and scope of patents relating to our competitors’ products. The availability of our competitors’ products could limit the demand,demand and the price we are able to charge,charge for any products that we may develop and commercialize. If we are not able to compete effectively against potential competitors, our business will not grow, and our financial condition and operations will be harmed.

Additionally, we could face heightened risks with respect to obtaining marketing authorization in the UKUnited Kingdom as a result of the withdrawal of the UKUnited Kingdom from the EU,European Union, commonly referred to as Brexit. The UKUnited Kingdom is no longer part of the European Single Market and EU Customs Union. As of January 1, 2025, the Medicines and Healthcare Products Regulatory Agency, or MHRA, is responsible for approving all medicinal products destined for the United Kingdom market (i.e., Great Britain and Northern Ireland). AtOn April 28, 2025, the United Kingdom Parliament adopted amendments to improve and strengthen the United Kingdom’s clinical trials regulatory regime; they are scheduled to take effect on April 28, 2026. These changes were needed since the current United Kingdom requirements are based upon the now-repealed EU Clinical Trials Directive (2001/20/EC), which has been replaced by the CTR. Since the United Kingdom left the EU prior to the date on which the CTR took effect, the United Kingdom legal framework did not benefit from the same time,revisions aas newoccurred international recognition procedure, or IRP, will apply, which intends to facilitate approval of pharmaceutical products in the UK. The IRP is open to applicants that have already received an authorization for the same product from one of the MHRA’s specified Reference Regulators, or RRs. The RRs notably include EMA and regulators in the EU/European Economic Area member states for approvals in theat EU centralized procedure and mutual recognition procedure as well as the FDA (for product approvals granted in the United States). However, the concrete functioning of the IRP is currently unclear. Any delay in obtaining, or an inability to obtain, any marketing approvals may force us or our collaborators to restrict or delay efforts to seek regulatory approval in the UK for our product candidates, which could significantly and materially harm our business.level.

In addition, foreign regulatory authorities may change their approval policies and new regulations may be enacted. For instance, the EU pharmaceutical legislation is currently undergoing a complete review process, in the context of the Pharmaceutical Strategy for Europe initiative, launched by the European Commission in November 2020. The European Commission’s proposal for revision of several legislative instruments related to medicinal products (including potentially reducing the duration of regulatory data protection and revising the eligibility for expedited pathways) was published on April 26, 2023. TheOn June 4, 2025, after almost two years of negotiations among the EU Member States, the Council of the European Union adopted its position on the proposed revisionsoverhaul remainof tothe beEU agreedgeneral andpharmaceutical adoptedlegislative byframework, which is known as the new Pharma Package. Thereafter, on December 11, 2025, the European Parliament and European Council andreached a provisional political agreement on the proposals may therefore be substantially revised before adoption,legislation, which is notexpected anticipatedto beforebe earlyadopted 2026.by mid-2026. The revisions may however have a significant impact on the pharmaceutical industry and our businessbusiness. They would, among other things, set a baseline period of eight years of data exclusivity and one year of market exclusivity with possible extensions for new indications up to a maximum of 11 years total. There will likely be a transition period of 24 months, with the changes taking effect in the long term.mid-2028.

We believe that any of the product candidates we develop as a biological product under a BLA should qualify for the 12-year period of exclusivity. However, there is a risk that this exclusivity could be shortened due to congressional action or otherwise, or that the FDA will not consider the subject product candidates to be reference products for competing products, potentially creating the opportunity for biosimilar competition sooner than anticipated. For example, in October 2025, the FDA issued draft guidance which proposes to eliminate the need for sponsors of biosimilar products to conduct comparative human clinical efficacy studies, allowing them to rely instead on analytical testing to demonstrate product differences from a reference product. Moreover, the extent to which a biosimilar, once approved, will be substituted for any one of the reference products in a way that is similar to traditional generic substitution for non-biological products will depend on a number of marketplace and regulatory factors that are still developing. Nonetheless, the approval of a biosimilar to our product candidates would have a material adverse impact on our business due to increased competition and pricing pressure.

To date, substantially all of our revenue has been derived from our ongoing collaborations and licensing agreements with Neurocrine, Novartis, and AlexionAlexion, and from our prior collaborations with Sanofi Genzyme,Genzyme Corporation, AbbVie Biotechnology Ltd and AbbVie Ireland Unlimited Company. If any ongoing or future collaboration, option and license, or license agreements were to be terminated, our business financial condition, results of operations and prospects could be harmed.

We are a biotechnology company whose mission is to leverage the power of human genetics to modify the course of and ultimately cure neurological diseases. Our pipeline includes programs for Alzheimer’s disease, or AD; Friedreich’s ataxia, or FA; Parkinson’s diseasedisease, or PD; and multiple other diseases of the central nervous system, or CNS. Many of our programs are derived from our TRACER™ (Tropism Redirection of AAV by Cell-type-specific Expression of RNA) adeno-associated virus, or AAV, capsid discovery platform, which we have used to generate novel capsids, or TRACER Capsids, and identify associated receptors to potentially enable high brain penetration with genetic medicines following intravenous, or IV, dosing. Some of our programs are wholly-owned, and some are advancing with licensees and collaboratorscollaborators, including Alexion, AstraZeneca Rare Disease, or Alexion; Novartis Pharma AG, or Novartis; and Neurocrine Biosciences, Inc., or Neurocrine.Neurocrine; and Transition Bio, Inc., or Transition Bio.

We are also workingcollaborating with our collaboration partnersNeurocrine on multiple programs. We are advancing seventhree gene therapy programs withagainst Neurocrine.undisclosed Developmenttargets. candidates were selected for threeTwo of these programs in 2024, resulting in milestone payments to us. We expect that Neurocrine will submit IND filings in 2025 for the two most advanced of these programs, a glucosylceramidase beta 1, or GBA1, gene therapy program for Parkinson’s disease and other GBA1-mediated diseases, or the GBA1 Program, and a frataxin, or FXN, gene therapy program for FA, or the FA Program. These two programs are particularly significant to us for two reasons: the subsequent clinical trials of thesethree programs have thedevelopment potentialcandidates to establish human proof-of-concept for the TRACER Capsids,selected and weare haveadvancing thethrough optionpreclinical totoxicology opt-in on co-development and co-commercialization in the United States. for both products.studies. In addition to the Neurocrine collaborations, we have partnered with Novartis on TRACER Capsid-based gene therapies for spinal muscular atrophy and Huntington’s disease. We have also licensed capsids to Novartis for three undisclosed CNS targets and to Alexion for one undisclosed rare neurological disease target and to Novartis for one undisclosed CNS target. In total, theseour partnerships have delivered more than $500.0 million in non-dilutive funding to us to date, including upfront fees, development milestone payments, option exercise fees, license fees, and research and development expense reimbursement. Looking forward, we have the potential to earn up to $8.2$6.8 billion in milestone payments across the partnered portfolio, including $2.9$2.4 billion in potential development milestone payments, as well as royalties.

All of the gene therapies in our wholly-owned and collaborative pipeline leverageare TRACER.delivered intravenously leveraging TRACER capsids. TRACER is a broadly applicable, RNA-based screening platform that enables rapid discovery of AAV capsids with robust penetration of the blood-brain barrier, or BBB, and enhanced CNS tropism in multiple species, including NHPs. We subsequently utilized these BBB-penetrant capsids to identify the receptors by which the capsids enter the BBB. We have identified multiple receptors, including alkaline phosphatase, or ALPL, that are alsocapable developingof transporting a secondlarge non-viralbiologic therapeuticsmolecule, platformsuch focusedas ona non-viral receptor-mediated transportcapsid, across the BBB.

Despite reporting $132.3 million in net income for the year ended December 31, 2023, we have a history of incurring significant losses. We reported a net losslosses of $119.7 million and $65.0 million for the yearyears ended December 31, 2024,2025 and we2024, reported a net loss of $46.4 million for the year ended December 31, 2022.respectively. As of December 31, 2024,2025, we had an accumulated deficit of $326.2$445.9 million. We expect to continue to incur significant expenses and operating losses for the foreseeable future. We anticipate that our expenses will increase substantially in the long termfuture in connection with our ongoing activities, as we:

To date, we have not generated any revenue from product sales and do not expect to generate any revenue from product sales for the foreseeable future. For the year ended December 31, 2024,2025, we recognized $49.7$30.5 million of collaboration revenue from the 2023 Neurocrine Collaboration Agreement, $15.0$5.9 million of collaboration revenue from anthe amendment, or the2023 Novartis Amendment, to our option and license agreement with Novartis entered into in March 2022, or the 2022 Novartis Option and LicenseCollaboration Agreement, $10.4$3.5 million of collaboration revenue from the 2019 Neurocrine Collaboration Agreement, and $4.9$0.5 million of collaboration revenue from theother 2023 Novartis Collaboration Agreement.agreements. For additional information about our revenue recognition policy, see the section titled “Summary of significant accounting policies and basis of presentation.presentation” in Note 2 to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K.

Research and development expenses consist primarily of costs incurred for our research activities, including our program discovery efforts, and the development of our proprietary antibody, gene therapy, vectorized antibody, and non-viral therapeutic platforms and programsprograms, which include:

Research and development activities are central to our business model. We are in the early stages of development of our product candidates. DuringWe the year ended December 31, 2024, ourexpect research and development expenses have increased as compared to the amounts recordeddecrease in the samenear periodterm inas thea priorresult year.of Ascontinued portfolio prioritization and alignment of operating expenditures with our researchcurrent andcapital development programs progress and as we identify product candidates and initiate preclinical studies and clinical trials, including our clinical trials to evaluate VY7523, we expect research and development costs to continue to increase.resources. At this time, we cannot reasonably estimate or know the nature, timing and estimated costs of the efforts that will be necessary to complete the development of our product candidates.

General and administrative expenses consist primarily of salaries and other related costs, including stock-based compensation, for personnel in executive, finance, accounting, information technology, business development, legal and human resource functions. Other significant costs include corporate facility costs not otherwise included in research and development expenses, legal fees related to patent and corporate matters andmatters, fees for accounting and consulting services.services, and one-time severance benefits, including cash severance, temporary health care coverage, and transition support services related to restructurings recognized in 2025. We expect general and administrative costs to decrease in the near term as a result of our continued disciplined expense management.

We estimate the transaction price based on the amount expected to be received for transferring the promised goods or services in the contract. The consideration may include fixed consideration and/or variable consideration. At the inception of each arrangement that includes variable consideration, we evaluate the amount of potential payment and the likelihood that the payments will be received. We utilize either the most likely amount method or expected amountvalue method to estimate the amount expected to be received based on which method best predicts the amount expected to be received. The amount of variable consideration which is included in the transaction price may be constrained, and is included in the transaction price only to the extent that it is probable that a significant reversal in the amount of the cumulative revenue recognized will not occur in a future period.

Our contracts often include development and regulatory milestone payments which are assessed under the most likely amount method and constrained if it is probable that a significant revenue reversal would occur. Milestone payments that are not within our control or the licensee’s control, such as regulatory approvals, are not considered probable of being achieved until those approvals are received. At the end of each reporting period, we re-evaluate the probability of achievement of such development and regulatory milestones and any related constraint, and if necessary, adjust our estimate of the overall transaction price. Given the nature of the milestone payments in our contracts with customers, most of the variable consideration is subject to a constraint that does not involve significant judgement.

We allocate the transaction price based on the estimated stand-alone selling price of each of the performance obligations. We must develop assumptions that require judgment to determine the stand-alone selling price for each performance obligation identified in the contract. We utilize key assumptions to determine the stand-alone selling price for performance obligations, which may include other comparable transactions, pricing considered in negotiating the transaction and the estimated costs.costs of satisfying the performance obligation. Additionally, in determining the standalone selling price for material rights, we utilize comparable transactions, industry standards for product development and clinical trial success probabilities and estimates of option exercise likelihood. We do not believe that reasonable changes in the assumptions used to determine stand-alone selling price for our performance obligations would materially impact the amount of revenue we recognize.

A significant portion of revenue recognized from the 2019 Neurocrine Collaboration Agreement and the 2023 Neurocrine Collaboration Agreement is related to performance obligations pursuant to which revenue is recognized using a proportional performance model. Revenue is recognized using input-based measurements, which involves the measurement of progress toward each performance obligation based on the actual costs incurred compared to total projectedexpected costs. We use judgementjudgment in estimating the expected remaining costs to complete the research and development services for each performance obligation based on discussions with the Joint Steering Committee for the program and discussions with our collaboration partners. We evaluate the measure of progress each reporting period and, if necessary, adjust the measure and related revenue recognition. Changes in our estimates of the expected remaining costs to complete the research and development services for our performance obligations can result in significant changes to the amount of revenue we recognize each period. In general, the uncertainty associated with expected costs to complete the research and development services for our performance obligations decreases as the remaining services near the end of their contractual term. As the research term for both collaboration agreements were near completion as of December 31, 2025, the uncertainty associated with expected costs was limited as of that date.

The increase in research and development expenseexpenses for the year ended December 31, 20242024, was primarily attributable to the following:

General and administrative expense balanceexpenses remained consistent for the year ended December 31, 2024, compared to December 31, 2023.

Other income, net of approximately $19.0 million was recognized during the year ended December 31, 2024, as compared to $11.7 million during the year ended December 31, 2023. Other income, net during the year ended December 31, 2024, wasincreased primarily related to interest income due to increasedhigher interest rates on increased balances of marketable securities,and as our marketable securities increased during the year ended December 31, 2024, as compared to the year ended December 31, 2023.

We have funded our operations primarily through private placements of redeemable convertible preferred stock, public offerings and private placements of our common stock, strategic collaborations and option and license arrangements, including our 2019 Neurocrine Collaboration Agreement, 2023 Neurocrine Collaboration Agreement, 2022 Novartis Agreement, 2023 Novartis Collaboration Agreement, Alexion Agreement, and with our prior collaboration agreements.

Net cash used in operating activities was $15.3$132.5 million during the year ended December 31, 2024.2025. The cash used in operating activities for the year ended December 31, 2024,2025, was primarily driven by our net loss for the year ended December 31, 2024,2025, of $65.0$119.7 million and a decrease in deferred revenue of $44.8$28.8 million due to revenue recognized under the 2019 Neurocrine Agreement and theAgreement, 2023 Neurocrine Collaboration Agreement, offset by a decrease in accounts receivable of $78.6 million due to the collection of the upfront payment under theand 2023 Novartis Agreement, andpartially offset by stock-based compensation expense of $14.8 million.

Net cash providedused byin operating activities was $77.9$15.3 million during the year ended December 31, 2023.2024. The cash providedused byin operating activities for the year ended December 31, 2023,2024, was primarily driven by our net incomeloss for the year ended December 31, 2023,2024, of $132.3$65.0 million, stock-based compensation expense of $11.2 million,million and ana increasedecrease in deferred revenue of $9.4$44.8 million,million due to revenue recognized under the 2019 Neurocrine Agreement and the 2023 Neurocrine Collaboration Agreement, partially offset by ana increasedecrease in accounts receivable of $80.2$78.6 million due to the recordingcollection of the upfront payment under the 2023 Novartis Agreement.Agreement, and stock-based compensation expense of $14.8 million.

Net cash usedprovided inby operating activities was $12.5$77.9 million during the year ended December 31, 2022.2023. The cash usedprovided inby operating activities for the year ended December 31, 20222023, was primarily driven by operating expenses,our net income for the year ended December 31, 2023, of $132.3 million, stock-based compensation expense of $11.2 million, and depreciation,an increase in deferred revenue of $9.4 million, partially offset by an increase in deferredaccounts revenuereceivable partiallyof driven$80.2 bymillion due to the recording of the upfront payment ofunder $54.0the million from2023 Novartis in connection with our entry into the 2022 Novartis Option and License Agreement during the year ended December 31, 2022.Agreement.

Net cash usedprovided inby investing activities was $141.6$125.4 million during the year ended December 31, 2023.2025. The cash usedprovided inby investing activities for the year ended December 31, 20232025, was primarily due to $224.0$262.0 million for purchases of marketable securities and $3.3 million for purchases of property and equipment, offset by $85.6 million fromin proceeds from maturities and sales of marketable securities.securities, partially offset by $133.9 million in purchases of marketable securities and $2.6 million in purchases of property and equipment.

Net cash used in investing activities was $7.3$94.9 million during the year ended December 31, 2022.2024. The cash used in investing activities for the year ended December 31, 20222024, was primarily due to $54.8$465.7 million for purchases of marketable securities and $2.5$3.5 million for purchases of property and equipment, partially offset by $50.0$374.3 million from proceeds from maturities and sales of marketable securities.

Net cash provided by financing activities was $1.1$0.8 million during the year ended December 31, 20222025, primarily due to the $0.5 million in proceeds from the exercisepurchase of stock options, and purchases by our employees of our common stock under ourthe employee stock purchase plan.

Our expenses increased during the year ended December 31, 20242025, as compared with the prior year as our development programs progressed and we increased headcount.progressed. We expect our expenses towill continue to increase as we continue theincur research and development of,expenses as we conduct clinical trials of, and seek marketing approval forof our product candidates including our Phase 1 MAD clinical trial to evaluate VY7523 in 2025,candidates, and as we continue to enter into or conduct activities in connection with our collaboration agreements. In addition, if we obtain marketing approval for any of our product candidates, we expect to incur significant expenses related to program sales, marketing, manufacturing and distribution to the extent that such sales, marketing and distribution are not the responsibility of potential collaborators. Furthermore, we expect to incur increasing costs associated with operating as a public company, executing financial statement controls, satisfying regulatory and quality standards, fulfilling healthcare compliance requirements, and maintaining product, clinical trial and directors’ and officers’ liability insurance coverage. We also anticipate the cost of goods and services and the levels of compensation paid to employees will increase due to inflationary conditions existing in the general economy. Accordingly, we will need to obtain substantial additional funding in connection with our continuing operations. If we are unable to raise capital or enter into business development transactions when needed or on acceptable terms, we could be forced to delay, reduce or eliminate our research and development programs or any future commercialization efforts.

As of December 31, 2024,2025, we had cash, cash equivalents, and marketable securities of $332.4$201.7 million. Based upon our current operating plan, we expect that our existing cash, cash equivalents, and marketable securities at December 31, 2024,2025, along with amounts expected to be received as reimbursement for development costs under our collaboration and license agreements with Neurocrine and Novartis and interest income, to be sufficient to meet our planned operating expenses and capital expenditure requirements into mid-2027.2028. Our future capital requirements will depend on many factors, including:

We are subject to a number of risks that could adversely affect our business, results of operationsoperations, financial condition and future prospects, including those identified in our Annual Report on Form 10-K for the fiscal year ended December 31, 2025, filed with the Securities and Exchange Commission on March 9, 2026. Any of the risks and uncertainties described in our Annual Report on Form 10-K could materially and adversely affect our business, financial condition, results of operations and future growth prospects, and such risks and uncertainties are not the only ones we face. Additional risks and uncertainties not presently known to us or that we presently deem less significant may also impair our business operations. Please see the discussion under the caption “Forward-Looking Statements” in this Quarterly Report on Form 10-Q for a discussion of some of the forward-looking statements that are qualified by these risk factors.

We are advancing our own proprietary pipeline of drug candidates for neurological diseases, with a focus on AD. Our wholly-owned prioritized pipeline includes two tau targeting programs: VY1706, a tau silencing gene therapy for AD, and VY7523, an anti-tau antibody for AD. VY1706 is a gene therapy that leverages an intravenously delivered TRACER Capsid containing a vectorized small interfering RNA specifically targeting tau mRNA. In a non-human primate, or NHP, study, a single 1.3E13 vector genomes per kilogram, or vg/kg, dose of VY1706 delivered intravenously resulted in reductions in tau mRNA levels of 50% to 73% across the cerebral cortex, including in areas of the brain where tau accumulates during the progression of AD. We completed investigational new drug-enabling good laboratory practices, or GLP, toxicology in the first quarter of 2026. Having had a Type C communication with the FDA in the first quarter of 2026, we anticipate completion of the investigational new drug, or IND, application process for the VY1706 program in the second quarter of 2026 and, subject to successful IND clearance, initiation of a clinical trial for the VY1706 program in the second half of 2026. VY7523 is an IV-administered, recombinant, humanized IgG4 monoclonal antibody developed to inhibit the spread of pathologicalextracellular tau, which is closely correlated with disease progression and cognitive decline in AD. VY7523 targets an epitope in the C-terminal region and is specific for pathological tau. The murine version of VY7523 reduced tau spread by approximately 70% in preclinical studies. VY7523 demonstrated an acceptable safety, tolerability, and immunogenicity profile as well as expected pharmacokinetic results in a Phase 1, single ascending dose clinical trial in healthy volunteers. In February 2025, we initiated a Phase 1 multiple ascending dose, or MAD, clinical trial of VY7523 in early AD patients. Enrollment in this MAD clinical trial was completed in the fourth quarter of 2025, and we expect initial tau positron emission tomographyPET imaging efficacy data in the secondfourth halfquarter of 2026.

In addition to our wholly-owned pipeline, we are advancing three programs with collaboration partners for which we retain options to participate in future development and commercialization. Two of these programs are in collaboration with Neurocrine: a frataxin (FXN) gene therapy program for FA, or the FA Program, and a glucosylceramidase beta 1 gene therapy program that will focus on Gaucher disease and PD, or the GBA1 Program. Neurocrine has stated that, pending successful FDA IND clearance, it intends to initiate a clinical trial with NBIB-’223 for the treatment of FA in the second half of 2026. In preclinical studies, IV-administered NBIB-’223 resulted in protein expression in the brain and heart, and GLP toxicology studies for NBIB-’223 are now complete. In May 2026, FDA granted orphan drug designation to NBIB-’223 for the treatment of FA. Neurocrine has informed us that it continues to progress the GBA1 Program in addition to three gene therapy programs for which we do not have opt-in rights. We maintain options to co-develop and co-commercialize the FA Program, under which profits and losses of the program would be allocated 60% to Neurocrine and 40% to us, and the GBA1 Program, under which profits and losses of the program would be allocated 50% to Neurocrine and 50% to us, in each case in the U.S.

We are collaborating with Neurocrine on three gene therapy programs against undisclosed targets. Two of these three programs have development candidates selected and are advancing through preclinical toxicology studies. In addition to the Neurocrine collaborations, we have partnered with Novartis on TRACER Capsid-based gene therapiestherapy programs for spinal muscular atrophy, or SMA, and Huntington’s disease, or HD. We have also licensed capsids to Novartis for one undisclosed CNS target and to Alexion for one undisclosed rare neurological disease target. In total, our partnerships have delivered more than $500.0 million in non-dilutive funding to us to date, including upfront fees, development milestone payments, option exercise fees, license fees, and research and development expense reimbursement. Looking forward, we have the potential to earn up to $6.8 billion in milestone payments across the partnered portfolio, including $2.4 billion in potential development milestone payments, as well as royalties.

All of the gene therapiestherapy product candidates in our wholly-owned and collaborative pipeline are delivered intravenously leveraging TRACER capsids.Capsids. TRACER is a broadly applicable, RNA-based screening platform that enables rapid discovery of AAV capsids with robust penetration of the blood-brain barrier, or BBB, and enhanced CNS tropism in multiple species, including NHPs. We subsequently utilized these BBB-penetrant capsids to identify the receptors by which the capsids enter the BBB. We have identified multiple receptors, including alkaline phosphatase, or ALPL, that are capable of transporting a large biologic molecule, such as a capsid, across the BBB.

We have leveraged our knowledge of BBB receptors, discovered using TRACER, to develop a second delivery platform called Voyager NeuroShuttleTM. Voyager NeuroShuttle is a non-viral delivery platform leveraging novel receptor-binding molecules to transport multiple modalities of neurotherapeutics across the BBB. The first NeuroShuttle within the platform leverages the ALPL receptor. During the third quarter of 2025, we shared the results of initial murine proof-of-concept studies of ALPL-VYGR-NeuroShuttle demonstrating in the study sustained brain expression over three weeks, compared to less than one week for transferrin receptor, or TfR, shuttles, with no impact on circulating reticulocytes or downstream measurements of anemia. In addition to the initial murine proof-of-concept data provided for the ALPL-VYGR-NeuroShuttle, a proof-of-concept study using anti-amyloid antibodies demonstrated that the ALPL-NeuroShuttleALPL-VYGR-NeuroShuttle showed similar target engagement to a TfR shuttle. We have initiated a discovery program using ALPL-VYGR-NeuroShuttle to target an undisclosed neurological disease.

The 2019 Neurocrine Collaboration Agreement provides for aggregate development milestone payments from Neurocrine to us for the gene therapy products, or the 2019 Collaboration ProductsProducts, under the FA Program of up to $195.0 million. We may be entitled to receive aggregate commercial milestone payments for each 2019 Collaboration Product of up to $275.0 million, for a total of up to $550.0 million under the FA Program. Neurocrine has also agreed to pay us royalties, based on future net sales of the 2019 Collaboration Products. Such royalty percentages, for net sales in and outside the United States, as applicable, range from the low-teens to high-teens and high-single digits to mid-teens, for the FA Program. For a further description of the 2019 Neurocrine Collaboration Agreement, refer to Note 9, Significant Agreements, to our consolidated financial statements included in our Annual Report on Form 10-K for the fiscal year ended December 31, 2025 under the caption “2019 Neurocrine Collaboration Agreement.”

We paid Transition Bio a low single-digit million dollarmillion-dollar upfront payment during the year ended December 31, 20242024, in connection with a prior agreement. During the fourth quarter of 2025, we paid Transition Bio an additional low single-digit million dollarmillion-dollar payment for the achievement of a research milestone. Transition Bio is eligible to receive potential research, development, commercial and net sales milestone payments totaling up to $500.0 million. Transition Bio is also eligible for high single-digit to low double-digit royalties on net sales during the royalty term of up to ten years. For a further description of the Transition Bio Agreement, refer to Note 9, Significant Agreements, to our consolidated financial statements included in our Annual Report on Form 10-K for the fiscal year ended December 31, 2025, under the caption “Other Agreements.”

We have a history of incurring significant losses. We reported a net loss of $27.9$52.4 million for the threesix months ended MarchJune 31,30, 2026, and a net loss of $119.7 million for the fiscal year ended December 31, 2025. As of MarchJune 31,30, 2026, we had an accumulated deficit of $473.8$498.3 million. We expect to continue to incur significant expenses and operating losses for the foreseeable future in connection with our ongoing activities, if and as we:

To date, we have not generated any revenue from product sales and do not expect to generate any revenue from product sales for the foreseeable future. For the three months ended MarchJune 31,30, 2026, we recognized $1.3 million of collaboration revenue from the 2023 Neurocrine Collaboration Agreement, $0.1$0.4 million of collaboration revenue from the 2019 Neurocrine Collaboration Agreement,Agreement and $1.2$2.8 million of collaboration revenue in connection with the 2023 Novartis Collaboration Agreement. For the threesix months ended MarchJune 31,30, 2025,2026, we recognized $4.5$1.3 million of collaboration revenue from the 2023 Neurocrine Collaboration Agreement, $0.5 million of collaboration revenue from the 2019 Neurocrine Collaboration Agreement, $1.2and $4.0 million of collaboration revenue in connection with the 2023 Novartis Collaboration Agreement, and $0.3 million of other collaboration revenue.Agreement.

We believe that several accounting policies are important to understanding our historical and future performance. We refer to these policies as critical because these specific areas generally require us to make judgments and estimates about matters that are uncertain at the time we make the estimate. There were no changes to our critical accounting policies during the three months ended MarchJune 31,30, 2026, as compared to those identified in our Annual Report on Form 10-K for the fiscal year ended December 31, 2025. It is important that the discussion of our operating results that follow be read in conjunction with the critical accounting policies disclosed in Item 7 “Management’s Discussion and Analysis of Financial Condition and Results of Operations – Critical Accounting Policies and Estimates” in our Annual Report on Form 10-K, as filed with the SEC on March 9, 2026.

Comparison of the three months ended MarchJune 31,30, 2026 and 2025

The following table summarizes our results of operations for the three months ended MarchJune 31,30, 2026,2026 and 2025:

Collaboration revenue was $2.6$3.2 million and $6.5$5.2 million for the three months ended MarchJune 31,30, 2026 and 2025, respectively. During the three months ended MarchJune 31,30, 2026, we recognized $1.3 million of collaboration revenue under the 2023 Neurocrine Collaboration Agreement, $0.1$0.4 million of collaboration revenue under the 2019 Neurocrine Collaboration Agreement,Agreement and $1.2$2.8 million of collaboration revenue under the 2023 Novartis Collaboration Agreement. During the three months ended MarchJune 31,30, 2025, we recognized $4.5$1.3 million of collaboration revenue under the 2023 Neurocrine Collaboration Agreement, $0.5$2.4 million of collaboration revenue under the 2019 Neurocrine Collaboration Agreement, $1.2$1.4 million of collaboration revenue under the 2023 Novartis Collaboration Agreement, and $0.3$0.1 million in other collaboration revenue.

The following table summarizes our research and development expenses for the three months ended MarchJune 31,30, 2026 and 2025:

Research and development expense was $24.6$22.0 million and $31.5$31.3 million for the three months ended MarchJune 31,30, 2026 and March 31, 2025, respectively. The $6.9$9.3 million decrease was primarily attributable to lower employee-related expenses and shared facilities and other costs due to thelower discontinuationheadcount ofresulting thefrom SOD1restructuring program,actions undertaken in 2025. The decrease was further attributable to reduced spend on the anti-tau antibody program (VY7523) as enrollment in planned clinical trials was completed, and lower employee-related expenses as we had lower headcount due to cost-cutting initiatives. The decrease was partially offset by an increase in the tau silencing gene therapy program (VY1706) in preparation for the planned clinical trial initiation.was completed as well as lower spend on other programs and platforms as a result of program prioritization.

Other income, net decreasedwas by $1.4$1.9 million fromand $3.7$3.3 million for the three months ended MarchJune 31,30, 20252026 toand $2.32025, respectively. The $1.3 million for the three months ended March 31, 2026. The decrease was primarily dueattributable to decreasedlower interest incomeearned on our marketable securities balances, as oura result of lower average marketable securities balance decreasedbalances during the three months ended MarchJune 31,30, 2026, as compared to the three months ended MarchJune 31,30, 2025.

In November 2025, we entered into a sales agreement with TD Securities (USA) LLC, as the sales agent, pursuant to which we maymay, from time to time, issue and sell shares of common stock withhaving an aggregate valueoffering price of up to $100.0 million inthrough an at-the-market offering,program, or the ATM Facility. WeDuring the six months ended June 30, 2026, we sold 630,5701,358,566 shares of our common stock under the ATM Facility during the three months ended March 31, 2026. These shares were sold at a weighted average price of $4.31 per share of $4.92 for aggregate net proceeds of $3.0$5.7 million, after deducting commissions and offering costs. As of MarchJune 31,30, 2026, $96.9$94.1 million remained available to be sold under the ATM Facility.

The following table provides information regarding our cash flows for the threesix months ended MarchJune 31,30, 2026,2026 and 2025:

Net cash used in operating activities was $33.4$59.3 million during the threesix months ended MarchJune 31,30, 2026, compared to $37.9$71.2 million during the threesix months ended MarchJune 31,30, 2025. The decrease in net cash used in operating activities is primarily attributed to a lower net loss. Net cash used in operating activities during the threesix months ended MarchJune 31,30, 2026, was primarily due to our net loss of $27.9$52.4 million, combined with changes in our working capital accounts, including decreases in accounts payable, accrued expenses and accountsoperating payablelease and deferred revenueliabilities during the threesix months ended MarchJune 31,30, 2026.

Net cash used in operating activities during the threesix months ended MarchJune 31,30, 2025, was primarily due to our net loss of $31.0$64.4 million, combined with changes in our working capital accounts, including a decreasedecreases in accounts payable, accrued expensesexpenses, operating lease liabilities and deferred revenue during the threesix months ended MarchJune 31,30, 2025.