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

Risks Related to Our Business and the Development of Our Clinical Product Candidates

We are dependent on the success of our lead clinical product candidate, AMT-130, for the treatment of Huntington’s disease. A failure of AMT-130 in clinical development, including inability to demonstrate sufficient safety or efficacy, or challenges associated with its regulatory approval, manufacturing or commercialization could adversely affect our business.

There are numerous factors that could impede or otherwise negatively impact our further development of AMT-130, including, but not limited to,to: potential patient safety issues; our failure to demonstrate sufficient clinical efficacy or durability of response data to warrant further development or accelerated or regular approval by the FDA, EMAEuropean Commission, MHRA or any other regulatory authority; ourshifting abilityFDA standards for an adequate and well-controlled trial in a rare disease population under clinical investigation; any inability to achieve alignment regarding an accelerated approval pathway for AMT-130 with FDA and other regulatory authorities on the primary statistical analysis plan and CMC requirements to support registrationFDA, and the timing of such regulatory alignment and other factors impacting our interactions with the FDA, which may be outside of our control; our ability to align on an approval pathway for AMT-130 with other regulatory agencies, such as the European Commission or MHRA; our current beliefs regarding the further development of and approval pathway for AMT-130, which are based on our interpretation of communications and interactions with the FDA to date, and the success of our efforts to address such communications and interactions; the results from future interim or topline data readouts from our Phase I/II trial,trials, including theas three-yearadditional follow-uppatient data frombecomes treated patients and safety and tolerability data from the third cohortavailable; any requirement for additional studies to obtain approval and for a Phase III confirmatory study; the timing and resources associated with our planned marketing applications; our ability to successfully commercialize AMT-130 should we choose to do so without a partner; challenges with potential development or commercial partners, should we choose to pursue further development or commercialization of AMT-130 with a partner; and our ability to fund the further development and commercialization of the AMT-130 program.

Any one or combination of these factors could force us to halt or discontinue the ongoing clinical trials of AMT-130 or related commercialization efforts.efforts or could prevent us from obtaining marketing approval within the predicted timeframes or at all. Certain of these risk factors are heightened in the context of drug development for rare diseases like Huntington’s disease and novel investigational products like gene therapies in which non-traditional study designs are utilized to demonstrate efficacy and safety, including open-label studies, single arm studies, studies utilizing active comparators or natural history data, biomarkers or other forms of surrogate endpoints, which may be utilized due to the challenges inherent in designing and conducting clinical trials for severe diseases that progress slowly and that affect small patient populations.

Notwithstanding alignment with FDA on key elements of the accelerated approval pathway, weWe cannot be certain that AMT-130, or any of our clinical product candidates, will be successful in clinical trials or ultimately receive regulatory approval. If we were required to,required, or if we chosechose, to,to discontinue development of AMT-130 or any other current or future product candidates,candidate, or if any of them were to fail to receive regulatory approval or achieve sufficient market acceptance, we could be prevented from or significantly delayed in achieving profitability and our business would be adversely affected.

Drug development is expensive, time-consuming, and uncertain as to the outcome. Our product candidates are in different stages of clinical or preclinical development, and there is a significant risk of failure or delay in each of these programs. We are currently conducting Phase I/II clinical trials in the U.S. and Europe for AMT-130, our investigational gene therapy for the treatment of Huntington’s disease. In JuneDecember 2024,2025, we announced that the FDA grantedconveyed Regenerativethat Medicinedata Advancedsubmitted Therapy (“RMAT”) designation for AMT-130 based onfrom the potentialPhase I/II studies of AMT-130 are currently unlikely to addressprovide the majorprimary unmetevidence medicalto needsupport amonga patientsBLA withsubmission. Huntington’sIn disease.March Following2026, ourfollowing initialreceipt of the final meeting minutes from the Type BA meeting withheld thein FDA,January 2026, we announced inthat Decemberthe 2024FDA stated that weit hadcannot reachedagree agreementthat withdata from the Phase I/II studies, compared to an external control, are sufficient to provide the primary evidence of effectiveness required to support a marketing application for AMT-130. The FDA onstrongly keyrecommended elementswe ofconduct ana acceleratedprospective, approvalrandomized, pathwaydouble-blind, forsham AMT-130surgery-controlled and have initiated BLA readiness activities based on this regulatory alignment.study. We are also advancing three other product candidates through Phase I/II(a) clinical development – AMT-260 for the treatment of mTLE, AMT-162 for the treatment of SOD1-ALS, andMTLE, AMT-191 for the treatment of Fabry disease.disease, and AMT-162 for the treatment of SOD1-ALS.

We have experienced clinical setbacks in the past and may experience setbacks in the future. For example, we experienced an immaterial but unexpected delay when our clinical trials of HEMGENIX® were placed on clinical hold by the FDA from December 2020 to April 2021 following a preliminary diagnosis of hepatocellular carcinoma in one patient. Similarly, we experienced an unexpected delay in the enrollment of our Phase Ib/II clinical trial of AMT-130 for the treatment of Huntington’s disease between July and October 2022 due to our voluntary postponement and comprehensive safety investigation into suspected unexpected serious adverse reactions in three patients. In addition, we have voluntarily paused enrollment in EPISOD1, our Phase I/II clinical trial of AMT-162, upon the recommendation of the IDMC following a September 2025 review of available preliminary data related to the safety and efficacy of AMT-162 in the context of a dose limiting toxicity, which resulted in a SAE determined to be related to AMT-162, that was observed in one patient in the second cohort. While enrollment is paused, we continue to collect and evaluate data from the five patients dosed in EPISOD1 to date. Per protocol, we have also paused dosing in the mid- and high-dose cohorts in our Phase I/II clinical trial of AMT-191 for the treatment of Fabry disease pending further evaluation following asymptomatic Grade 3 liver enzyme elevations observed in two patients in the mid-dose cohort, which were confirmed dose-limiting toxicity.

A failure of one or more clinical trials can occur at any stage and for a variety of reasons that we cannot predict with accuracy and that are out of our control. Events that may prevent successful or timely completion of clinical development, as well as clinical product candidate approval, include, but are not limited to:

Before obtaining marketing approval from regulatory authorities for the sale of our product candidates, we must conduct extensive clinical trials to demonstrate the safety and efficacy of our product candidates in humans. SuchWith such trials, regulatory review and approval take many years. Our clinical trials may never yield results that demonstrate that our product candidates are effective or safe in humans.humans and regulatory authorities may interpret our clinical trial results differently than we do. If the results of our clinical trials are inconclusive, or fail to meet the level of statistical significancecriteria required for regulatory approval, including the necessary level of statistical significance, or if there are safety concerns, concerns around efficacy or durability of response or other adverse events associated with our product candidates, we may:

Our ability to recruit and enroll patients for our clinical trials is heavily reliant on third parties. Clinical trial sites may not have the adequate infrastructure established to handle the administration of our gene therapy products, related surgeries or other means of product administration, or may have difficulty finding eligible patients to enroll into our clinical trials, which may delay or impede our planned trials and development timelines. In addition, neither we ornor any of our collaborators may not be able to identify and enroll sufficient eligible patients to participate in these trials as required by the FDA, the EMAEMA, the MHRA or other regulatory authorities. This may result in our failure to initiate or continue clinical trials for our product candidates or may cause us to abandon one or more clinical trials altogether. Because several of our programs are focused on the treatment of patients with rare or orphan or ultra-orphan diseases, our ability to enroll eligible patients in these trials may be limited or slower than we anticipate considering the small patient populations involved and the age range required for trial eligibility for certain indications. In addition, our potential competitors, including major pharmaceutical, specialty pharmaceutical and biotechnology companies, academic institutions and governmental agencies and public and private research institutions, may seek to develop competing therapies, which would further limit the small patient pool available for our studies. Patients may also be reluctant to enroll in clinical trials for gene therapy candidates where other therapeutic alternatives are available due to uncertainty aboutregarding the safety or effectiveness of gene therapies and the possibility that treatment with one gene therapy could preclude future gene therapy treatments due to the formation of antibodies following and in response to the treatment, or other unknown factors associated with novel therapeutics.

Our inability to successfully initiate or complete preclinical and clinical studies could result in additional costs to us or impair our ability to receive marketing approval, to generate revenues from product sales or from reaching certain development milestones,milestones or obtain regulatory approval. In addition, if we make manufacturing or formulation changes to our product candidates, including changes in the vector or manufacturing process used, we may need to conduct additional studies to bridge our modified product candidates to earlier versions. It is also possible that any such manufacturing or formulation changes may have an adverse impact on the performance of the product candidate.candidate or safety profile. Clinical trial delays could also 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 materially harm our business, financial condition, and results of operations.

Our product candidates may fail to show the required level of safety and efficacy in later stages of clinical development despite having successfully advanced through initial clinical studies. For example, theinterim, interimpreliminary or topline results from our ongoing clinical trials, including from the Phase I/II clinical trials of AMT-130, our clinical product candidate targeting Huntington’s disease, may not be predictive of the results of future interim analyses or later-stage trials. In some instances, there can be significant variability in safety or efficacy results between different clinical trials of the same product candidate due to numerous factors, including changes in trial procedures set forth in protocols, differences in the size and type of the patient populations, changes in and adherence to the clinical trial protocols and the rate of dropout among clinical trial participants. Moreover, should there be an issue with the design of any of our clinical trials, our results may be impacted. We may not discover such a flaw until the clinical trial is at an advanced stage. Changes to product candidates or how the results from our clinical trials are analyzed,analyzed and any external control to which the results are compared to, whether as a result of regulatory feedback or changes in clinical trial procedures and protocols, may also impact the results of subsequent analyses or studies.

A number of companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in later-stage clinical trials even after achieving promising results in early-stage clinical trials. If a larger population of patients does not experience positive results during our clinical trials, if the results are not reproducible or if our products show diminishing activity over time, our product candidates may not receive approval from the FDA, EMAEuropean Commission, the MHRA or comparable regulatory authorities, or may have conditional approvals revoked. Data obtained from preclinical and clinical activities may be subject to varying interpretations and analyses, which may delay, limit, or prevent regulatory approval. In addition, we may encounter regulatory delays or rejections due to shifting political priorities, resulting changes in regulatory agencies or other 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 later-stage clinical trials with larger patient populations could have a material adverse effect on our business, financial condition, and results of operations.

Additionally, we are currently conducting and may in the future conduct clinical trials that utilize an “open-label” trial design. An “open-label” clinical trial is one where both the patient and investigator know whether the patient is receiving the investigational therapeutic candidate (as opposed to an existing approved drug or placebo). Open-label trials typically test only the investigational therapeutic candidate and sometimes may do so at different dose levels. For example, our ongoing Phase I/II clinical trial of AMT-130 is designed as an open-label trial following a 12-month core study period during which certain patients received a sham surgical procedure. Certain of these patients crossed over to an arm allowing for treatment with AMT-130 and are now subject to long-term, unblinded follow-up monitoring for a period of five years. Open-label trials are subject to various limitations that may bias the interpretation of the data. Open-label trials may be subject to a “patient bias” where patients perceive their symptoms to have improved merely due to their awareness of receiving an experimental treatment. In addition, open-label trials may be subject to an “investigator bias” where those assessing and reviewing the physiological outcomes of the clinical trials are aware of which patients have received treatment and may interpret the information of the treated group more favorably given this knowledge. Accordingly, the results from our open-label trials, including early indications of potential efficacy, may not be predictive of future clinical trial results. Early evidence of slowing of disease progression in our AMT-130 clinical trial may not be predictive of continued evidence of potential efficacy as we continue to collect follow-up data from patients enrolled in the trial.

InterimInterim, topline or preliminary results from our clinical trials may change as more data become available, as such data are subject to regulatory audit and verification procedures, and/or regulatory review, which could result in material changes in the final results and conclusions.

From time to time, we publicly disclose interim, preliminarypreliminary, topline or other data from preclinical studies and clinical trials,trials. whichInterim and preliminary data are based on a preliminary and sometimes post hoc analysis of such data. WithAdditionally, with respect to interim and preliminary data, the results and related findings and conclusions are subject to change following a more comprehensive review of the data, the particular study, or trial. We also make assumptions, estimations, calculations, and conclusions as part of our preliminarypreliminary, interim or interimtopline analyses of data, and we may not have received or had the opportunity to evaluate all data at that time. AsInterim, a result, the interimpreliminary or preliminarytopline data that we report may differ from future results of the same studies, or different conclusions or considerations may qualify such results once additional data have been received and fully evaluated. Interim orand preliminary data also remain subject to regulatory audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published. As a result, preliminarypreliminary, interim or interimtopline data should be viewed with caution until the final data are available.

For example, in JulySeptember 2024,2025, we announced updated interimtopline data from ourthe ongoingpivotal Phase I/II clinical trialsstudy of AMT-130, along with our expectation that we will present additional clinical updates with respect to AMT-130 in the future.AMT-130. As part of the JulySeptember 20242025 update, we announcedannounced, among other things, a statistically significant, dose-dependent,significant slowing inof disease progression for patients receiving high-dose patientsAMT-130 dosedat with36 AMT-130,months as measured by cUHDRS,cUHDRS as well as a statistically significant reductionslowing of NfLdisease progression for patients receiving high-dose AMT-130 at 36 months as measured by TFC, in CSF.each Such measures of statistical significance were based on a post-hoc analysis of data from patients treated with AMT-130case, compared to a propensity score-weightedscore-matched external controlcontrol. cohort.Topline Interimor interim data from our clinical trials, including the AMT-130 trial,trials, and our analyses of that data are subject to the risk that one or more of our interim conclusions may materially change as more patient data become availableavailable, and as regulatory interactions focused on statistical analysis of the clinical data progress, among other factors. Significant differences between topline or interim data and subsequent data that become available could change the nature of our conclusions with respect to the safety and efficacy of our product candidates, which could adversely impact our business. Regulatory authorities may also interpret data differently than we do. In particular, in December 2025 we announced that the FDA conveyed that data submitted from the Phase I/II studies of AMT-130 are currently unlikely to provide the primary evidence to support a BLA submission. In March 2026, following receipt of the final meeting minutes from the Type A meeting held in January 2026, we announced that the FDA stated that it cannot agree that data from the Phase I/II studies, compared to an external control, are sufficient to provide the primary evidence of effectiveness required to support a marketing application for AMT-130. The FDA strongly recommended we conduct a prospective, randomized, double-blind, sham surgery-controlled study.

We have and may in the future disclose topline or interim results based on post-hoc analyses, the pooling of data from multiple studies, or using statistical assessments or comparisons, including comparisons to historical controls, which regulatory authorities may not agree with. TheIn FDAaddition, the FDA, EMA or MHRA may find that calculations of statistical significance using nominal p-values or any other statistical calculations are not sufficiently reliable or subject to certain statistical limitations and, as a result, determine that our preliminary results are insufficient evidence of clinical efficacy.

Accordingly, third parties, including regulatory agencies, may not accept or agree with our assumptions, estimates, calculations, conclusions, or analyses or may interpret or weigh the importance of data differently, which could negatively impact the value of the particular program, its prospects for approval and our business. In December 2024, followingNotwithstanding our initial Type B meeting, we announced that we had reached agreement with FDA on key elementsreceipt of anBreakthrough acceleratedTherapy approval pathwaydesignation for AMT-130, including that data from the ongoingAMT-130 Phase I/II studies of AMT-130, compared to a natural history external control, may serve as the primary basis for a BLA submission under FDA’s Accelerated Approval pathway. FDA also agreed that cUHDRS may be used as an intermediate clinical endpoint and that reductions in NfL measured in CSF may serve as supportive evidence of therapeutic benefit in the application for accelerated approval. Notwithstanding alignment with the agency on these elements,program, we may fail to continue to demonstrate clinical efficacy or durability of response data to warrant further development or approval, including accelerated approval by the FDA, EMAEuropean Commission, MHRA or any other regulatory authority.

In addition, the information we choose to publicly disclose regarding a particular study or clinical trial may be top-linetopline results based on what is typically extensive information, and others may not agree with what we determine is the material or otherwise appropriate information to include in our public disclosures. Any information we determine not to disclose may ultimately be deemed significant by others with respect to future decisions, conclusions, views, activities or otherwise regarding a particular product candidate or our business. If the preliminarypreliminary, interim or interimtopline data that we report differ from final results, or if others, including regulatory authorities, disagree with the conclusions reached, our ability to obtain approval for, and commercialize, product candidates may be harmed, which could seriously harm our business.

Data analyses conducted either on a post-hoc basis andor with a pre-specified statistical analysis plan using external, historical controls may not be accepted as a basis for regulatory approval.

We have in the past and may in the future undertake certain analyses to further understand the data and potential reasons for the study results, including retrospective, post-hoc, and subgroup analyses.analyses, which may make interpretation of the data more difficult. Because these analyses are not pre-planned and studies may not be adequately designed for these analyses, they may not be a reliable nor an acceptable basis for regulatory approval. For example, in conjunction with our July 2024 interim data update for AMT-130, we conducted a post-hoc analysis of clinical outcomes for the 21 treated patients at 24 months compared to an expanded, propensity-weighted external control consisting of 154 patients. Among other conclusions in this interim update, we reported, based on this analysis, a statistically significant, dose-dependent, slowing in disease progression measured by cUHDRS observed through 24 months in patients receiving the high dose of AMT-130. We also reported a statistically significant reduction of CSF NfL observed in patients treated with AMT-130.

Some of our favorable statistical data from these trials also are based on nominal p-values. Nominal p-values are subject to certain limitations, and because of these limitations, regulatory authorities may give less weight to nominal p-values, compared to standard p-values. As such, we anticipate proposing to the FDA a pre-specified statistical analysis to support a potential BLA submission. An unfavorable view of our proposed statistical analyses by regulatory authorities could negatively impact our ability to obtain, or the timing of, regulatory approval, which would have a material adverse effect on our revenue and adversely impact our business and financial results.

We are making use of experimental biological markers, or biomarkers, in an effort to facilitate our drug development and to optimize our clinical trials. Biomarkers are proteins or other substances whichthat can serve as an indicator of specific cell processes or as evidence of a patient’s biological response to drug product administration. For example, with respect to our ongoing clinical trials of AMT-130, we are measuring NfL in CSF as a potential indicator of neurodegeneration, as well as changes in total brain volume of patients treated with AMT-130.

While we believe that these biomarkers and data may serve useful purposes for us, including in the evaluation of whether our product candidates are having their intended effects through their assumed mechanisms of action,action and improving patient selection and monitoring patient compliance with trial protocols, these biomarkers and data have not been scientifically validated and are considered experimental as used in our trials. If our understanding and use of biomarkers is inaccurate or flawed, or if our reliance on specific biomarkers such as CSF NfL is otherwise misplaced, then we may fail to realize any benefits from using these data and may also be led to invest time and financial resources inefficiently in attempting to develop inappropriate drug candidates.

We seek to use our gene therapy technology platform to expand our product pipeline and to progress our product candidates through preclinical and clinical development ourselves or together with collaborators. To date, we have only been successful in obtaining regulatory approval for one product, HEMGENIX®,HEMGENIX, our gene therapy for the treatment of hemophilia B, which was approved for commercialization by the FDA and the EMAEuropean Commission in November 2022 and February 2023, respectively. AMT-130 is our investigational gene therapy candidate for the treatment of Huntington’s disease that utilizes our proprietary, gene-silencing miQURE® platform and incorporates an AAV vector carrying a miRNA specifically designed to silence the huntingtin gene and the potentially highly toxic exon 1 protein fragment, which is currently in ongoing Phase I/II studies in the U.S. and Europe. In addition to AMT-130, we are also developing other investigational gene therapies, including AMT-260 for the treatment of mTLE, AMT-162 for the treatment of SOD1-ALS andMTLE, AMT-191 for the treatment of Fabry disease.disease, and AMT-162 for the treatment of SOD1-ALS. Although we currently have a pipeline of programs at various stages of development, including an approved product for which commercialization has been exclusively out-licensed to CSL Behring, we may not be successful in identifying or developing additional products that are safe and effective. Even if we are successful in continuing to build our pipeline, the potential new product candidates that we identify may not be suitable for or may fail in clinical development.

More restrictive government regulation of gene therapies or negative public opinion may have an adverse effect on our business, financial condition, results of operations and prospects and may delay or impair the development and commercialization of our product candidates or demand for any products we may develop. For example, earlier gene therapy trials and approved gene therapy products have led to several well-publicized adverse events, including cases of leukemialeukemia, liver failure and death seen in other trials using other vectors.

Serious adverse events in our clinical trials, or other clinical trials involving gene therapy products or our competitors’ products, even if not ultimately attributable to the relevant product candidates, and the resulting publicity, could result in increased government regulation, unfavorable public perception, potential regulatory delays in the testing or approval of our product candidates, stricter labeling requirements for those product candidates that are approved and a decrease in demand for any products for which we obtain marketing approval. A small number of patients experienced serious adverse events during our clinical trials of AMT-060 (HEMGENIX®), etranacogene dezaparvovec (AMT-061), AMT-130, AMT-191, and AMT-130.AMT-162. However, adverse events in our clinical trials or those conducted by third parties (even if not ultimately attributable to our product candidates), and the resulting publicity, could result in delay, a hold or termination of our clinical trials, increased governmental regulation, unfavorable public perception, failure of the medical community to accept and prescribe gene therapy treatments, potential regulatory delays in the testing or approval of our product candidates, stricter labeling requirements for those product candidates that are approved and a decrease in demand for any such product candidates. If any of these events should occur, it may have a material adverse effect on our business, financial condition, and results of operations.

We face worldwide competition from larger pharmaceutical companies, specialty pharmaceutical companies and biotechnology firms, universities and other research institutions and government agencies that are developing and commercializing pharmaceutical products. Our key competitors focused on developing therapies in various indications, include among others, PTC Therapeutics,Novartis, Roche, Wave Life Sciences, AlnylumAlnylam Pharmaceuticals, Regeneron Pharmaceuticals, Skyhawk Therapeutics and SkyhawkSarepta Therapeutics (for Huntington’s disease), Neurona Therapeutics, EpilepsyGTx and CombigeneXenon Pharmaceuticals (for TLE), Biogen, Ionis,Ionis Pharmaceuticals, Neurimmune, Regeneron,Regeneron AlnylumPharmaceuticals, PharmaceuticalsAlnylam Pharmaceuticals, Coya Therapeutics, Amylyx Pharmaceuticals, NeuroSense Therapeutics, AL-S Pharma and Voyager Therapeutics (for ALS) and Amicus Therapeutics, Sanofi, Takeda, Chiesi, Idorsia, Sangamo Therapeutics, 4D Molecular Therapeutics, Skyline Pharmaceuticals and CANbridge (for Fabry disease).

Our commercial opportunity and/or the receipt of royalties from the sale of any approved products (should we chose to commercialize our products with a commercial partner) could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than the products that we develop. Our competitors also may obtain FDA, EMA,European Commission, MHRA or other regulatory approval for their products more rapidly than we do, which could result in our competitors establishing a strong market position before we are able to enter the market. A competitor approval may also prevent us from entering the market if the competitor receives any regulatory exclusivities that block our product candidates. Because we expect that gene therapy patients may generally require only a single administration, we believe that the first gene therapy product to enter the market for a particular indication will likely enjoy a significant commercial advantage and may also obtain market exclusivity under applicable orphan drug regimes.

Certain of our product candidates require medical devices for administration, such as AMT-130 and AMT-260, each of which requires a stereotactic, magnetic resonance imaging guided catheter.cannula. Other of our product candidates may also require the use of a companion diagnostic device to confirm the presence of specific genetic or other biomarkers. In addition, certain of our product candidates, includingsuch AMT-130 andas AMT-260, may require the use of immunosuppressive agents to reduce thepotential inflammatory responses associated with administration.

It is possible that our product candidates would be deemed to be combination products, potentially necessitating compliance with the FDA’s investigational device regulations or European or UK investigational medicinal product regulations, separate marketing application submissions or other approvals for the medical device component, a demonstration that our product candidates are safe and effective when used in combination with the medical devices, cross-labeling with the medical device, and compliance with certain of the FDA’sFDA’s, European or MHRA’s device regulations. If we are not able to comply with the FDA’sFDA’s, European or MHRA’s device regulations, if we are not able to effectively partner with the applicable medical device manufacturers, if we or any partners are not able to obtain any required FDAFDA, European or UK clearances or approvals of the applicable medical devices, or if we are not able to demonstrate that our product candidates are safe and efficacious when used with the applicable medical devices, we may be delayed in or may never obtain FDAFDA, European Commission or MHRA approval for our product candidates, which would materially harm our business.

The development and commercialization of our product candidates, including their design, testing, manufacture, safety, efficacy, purity, recordkeeping, labeling, storage, approval, advertising, promotion, sale, and distribution, are subject to comprehensive regulation by the FDA and other regulatory agencies in the U.S., the European Commission/EMA, MHRA and other regulatory agencies of the member states of the European Union,EU, and similar regulatory authorities in other jurisdictions. Failure to obtain marketing approval for a product candidate in a specific jurisdiction will prevent us from commercializing the product candidate in that jurisdiction and our ability to generate revenue willwould be materially impaired.

The process of obtaining marketing approval for our product candidates in the U.S., the EuropeanEU, Union,UK and other countries is expensive and may take many years, if approval is obtained at all. Changes in marketing approval policies during the development period, changes in or the enactment of additional statutes or regulations, reductions in staffing or other personnel limitations within a regulatory agency, orincluding staffing changes within the FDA’s Center for Biologics Evaluation and Research, changes in regulatory review for each submitted product application, changes in the regulatory philosophy or approach of regulatory authorities, or a federal government shutdown may cause delays in the approval or rejection of an application. Due toFollowing the recent2025 change in presidential administration in the U.S., we face substantial uncertainty regarding potential regulatory developments that may adversely affect our business, including those related to potential decreases in spending in the federal government, potential staffing reductions, or any other potential constraints on the FDA’s ability to engage in routine oversight and product review activities or(including itsreview abilityactivities for product candidates like AMT-130 that are subject to exerciseaccelerated approval pathways) or the manner in which it exercises its regulatory authority. There are also significant changes being debated in the EU that may impact the development or approval of our product candidates. Further, while these changes will not apply in the UK, certain provisions may apply to certain products depending on what basis they are placed on the market. Ongoing consultations in the UK, and changes introduced following Brexit, could materially impact the future regulatory regime that applies to products and the approval of product candidates in the UK, and could lead to greater divergence from EU legislation. Regulatory authorities may also be delayed in completing their review of any marketing applications or device clearances submitted by us or our partners. Regulatory authorities have substantial discretion in the approval process and may refuse to accept any application, may decide that our data are insufficient for approval, may require additional preclinical, clinical, or other studies and may not complete their review in a timely manner. Further, any marketing approval we ultimately obtain may be for only limited indications or be subject to stringent labeling or other restrictions or post-approval commitments that render the approved product not commercially viable.

BothThe theFDA, FDAEMA/European Commission, and the EMAMHRA have demonstrated caution in their regulation of gene therapy treatments, and ethical and legal concerns about gene therapy and genetic testing may result in additional regulations or restrictions on the development and commercialization of our product candidates that are difficult to predict. The FDA andFDA, the EMA and MHRA have issued various guidance documents pertaining to gene therapy products, which are and will be applicable to our product candidates. The close regulatory scrutiny of gene therapy products may result in delays and increased costs and may ultimately lead to the failure to obtain approval for any gene therapy product. Experiences with existing gene therapies, including any emergent adverse effects, could also impact how the FDA andFDA, the EMA and MHRA view our products and product candidates, making it harder to obtain or maintain regulatory approvals.

Regulatory requirements affecting gene therapy have changed frequently and continue to evolve, and agencies at both the U.S. federal and state level, as well as congressional committees and foreign governments, have sometimes expressed interest in further regulating biotechnology. In the U.S., there have been a number of changes relating to gene therapy development. By example, the FDA issued a number of guidance documents, and continues to issue guidance documents, on human gene therapy development, one of which was specific to human gene therapy for hemophilia, one that was specific to neurodegenerative diseases, and another of which was specific to rare diseases. Under proposed EU legislation, there is also a suggested amendment in relation to advanced therapy medicinal products to the effect that hospital pharmacies wouldcould be afforded greater flexibility to prepare product for dispensing onwithout the basis of the estimated prescriptions within that hospitalneed for theobtaining followinga 7marketing days rather than, as at present, in response to individual prescriptions.authorization.

The FDA, EMA, MHRA and other regulatory authorities will likely continue to revise and further update their approaches to gene therapies in the coming years. These regulatory agencies, committees and advisory groups and the new regulations and guidelines they promulgate may lengthen the regulatory review process, require us to perform additional studies, increase our development costs, lead to changes in regulatory positions and interpretations, delay or prevent approval and commercialization of our product candidates or lead to significant post-approval limitations or restrictions. Delay or failure to obtain, or unexpected costs in obtaining, the regulatory approval necessary to bring a potential product to market could decrease our ability to generate sufficient product revenues to maintain our business.

We may leverage certain specialized regulatory pathways and designations, such as the FDA’s accelerated approval pathwaypathway, RMAT designation and RMATBreakthrough Therapy designation, to develop our product candidates or to seek licensure. Even if one or more of our product candidates receives such a designation or is permitted to pursue such a pathway, we may be unable to obtain and maintain the benefits associated with such designations and pathways.

In May 2024 the FDA granted RMAT designation for AMT-130 based on AMT-130’s potential to address the major unmet medical need among patients with Huntington’s disease. The designation followed the FDA’s review of interim Phase I/II clinical data for AMT-130 and was based on an analysis comparing 24-month clinical data from the AMT-130 trials to a non-concurrent criteria-matched natural history cohort. In DecemberApril 2024, following our initial Type B meeting which was scheduled on the basis of our RMAT designation for AMT-130,2025, we announced that wethe FDA had reachedgranted agreementBreakthrough withTherapy FDAdesignation onto key elements of an accelerated approval pathway for AMT-130, as described under “Business— Recent Product Candidate Developments” in this Annual Report on Form 10-K.AMT-130. In the future, we may seek additional product designations intended to facilitate the development or regulatory review or approval process for our product candidates, such as fast-track designations, breakthroughBreakthrough therapyTherapy designation, RMAT designation, PRIME scheme access or priority review designation for our product candidates.

A fast-track product designation is designed to facilitate the clinical development and expedite the review of drugs intended to treat a serious or life-threatening condition and which demonstrate the potential to address an unmet medical need. A breakthrough therapy is defined as a drug that is intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition, where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. An RMAT designation is designed to accelerate approval timelines for regenerative advanced therapies. Priority review designation is intended to accelerate the FDA marketing application review timeframe for drug products that treat a serious condition and that, if approved, would provide a significant improvement in safety or effectiveness. PRIME is a scheme provided by the EMA, similar to the FDA’s breakthrough therapy designation, to enhance support for the development of medicines that target an unmet medical need.

For drugs and biologics that have beenreceived designatedspecial designations, such as fast track products,, RMATRMAT, (and Breakthrough Therapy designation in the case of AMT-130), or breakthrough therapies,AMT-130, or granted access to the PRIME scheme, more frequent interaction and communication between the regulatory agency and the sponsor of the trial can help to identify the most efficient path for clinical development. Sponsors of fast-track products, RMAT products, or breakthrough therapies may also be able to submit marketing applications on a rolling basis, meaning that the FDA may review portions of a marketing application before the sponsor submits the complete application to the FDA, if the sponsor pays the user fee upon submission of the first portion of the marketing application and the FDA approves a schedule for the submission of the remaining sections. For products that receive a priority review designation, the FDA’s marketing application review goal is shortened to six months, as opposed to ten months under standard review.

Biologics studied for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit over existing treatments may also receive accelerated approval by the FDA, meaning the agency may approve the product candidate based upon a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit. As part of our alignment with FDA in December 2024 on the accelerated approval pathway for AMT-130, the agency agreed that cUHDRS may be used as an intermediate clinical endpoint and that reductions in NfL measured in CSF may serve as supportive evidence of therapeutic benefit in the application for accelerated approval.

There is no guarantee that we would be able to obtain accelerated approval aseven FDAif maywe disagreeobtain with our interim endpointany or mayall findof thatthese suchdesignations endpointfor isa notgiven metproduct following subsequent clinical data.candidate. These designations and accelerated approval pathways may not lead to a faster development or regulatory review or approval process and may not increase the likelihood that our product candidates will receive marketing approval. Even thoughif we have alignedalign with the FDA on elements of the accelerated approval pathway for AMT-130, we may not ultimately be successful in obtaining marketing approval for AMT-130,AMT-130; or if we obtain such approval, we may be unsuccessful in meeting post-marketing compliance requirements, or fail to conduct required post-approval studies, or to confirm a clinical benefit during post-marketing studies, which could result in the FDA withdrawing our product from the market. In recent years, the accelerated approval pathway has come under significant FDA and public scrutinyscrutiny. and it is unclear how the incoming Trump Administration in the U.S. will address regulations related to accelerated approval pathways, if at all. Accordingly, it is uncertain whether theThe FDA may be more conservative in granting accelerated approval or, if granted, more apt to withdraw approval if clinical benefit is not confirmed. There is no guarantee that regulatory interactions with the FDA or comparable foreign authorities will result in our ability to avail ourselves of any specialized approval pathways for our product candidates.

Regulatory authorities in some jurisdictions, including the U.S.U.S., the EU, and the European Union,UK, may designate drugs for relatively small patient populations as orphan drugs. While certain of our product candidates, including AMT-130, AMT-191 and AMT-162 have received orphanOrphan drugDrug designation, there is no guarantee that we will be able to receive such designations in the future.future or that these designations will be maintained at the time of marketing authorization. The FDA may grant orphan designation to multiple sponsors for the same compound or active molecule and for the same indication. If another sponsor receives FDA approval for such product before we do, we would be prevented from launching our product in the U.S. for the orphan indication for a period of at least seven years unless we can demonstrate clinical superiority. There would be a similar impact in the EU and the UK.

Moreover, while orphanOrphan drugDrug designation neither shortens the development or regulatory review time, nor gives the product candidate advantages in the regulatory review or approval process, generally, if a product with an orphanOrphan drugDrug designation subsequently receives the first marketing approval for the relevant indication, the product is entitled to a period of market exclusivity, which precludes the FDA or the EMAEuropean and UK regulatory authorities from approving another marketing application for the same drug for the same indication for that period. The FDA and the EMA,European and UK regulatory authorities, however, may subsequently approve a similar drug (or same drug, in the case of the U.S.,U.S.), for the same indication during the first product’s market exclusivity period if the FDAFDA, EMA or the EMAMHRA concludes that the later drug is clinically superior in that it is shown to be safer or more effective or makes a major contribution to patient care. Orphan exclusivity in the U.S.U.S., EU and UK also does not prevent the FDA or European or UK regulatory authorities from approving another product that is considered to be the same as our product candidates for a different indication or a different product for the same orphan indication. If another product that is the same as ours is approved for a different indication, it is possible that third-party payorspayers will reimburse for products off-label even if not indicated for the orphan condition. Moreover, in the U.S. the exact scope of orphan drug exclusivity is currently uncertain and evolving due to a recent court decision.

Orphan drug exclusivity may be lost for a number of reasons, including, but not limited to if the FDAFDA, the EMA or the EMAMHRA determines that the request for designation was materially defective, or if the manufacturer is unable to assure sufficient quantity of the drug to meet the needs of patients with the rare disease or condition. The inability to obtain or failure to maintain adequate product exclusivity for our product candidates could have a material adverse effect on our business prospects, results of operations and financial condition.

Our focus on developing gene therapies makes it difficult to determine the availability and utility of the orphan drug regime to our product candidates. Regulatory criteria with respect to orphan products are evolving, especially in gene therapy. By example, in the U.S., whether two gene therapies are considered to be the same for the purpose of determining clinical superiority was updated via a final guidance document specific to gene therapies, and depends on a number of factors, including the expressed transgene, the vector, and other product or product candidate features. Depending on the products, whether two products are ultimately considered to be the same may be determined by the FDA on a case-by-case basis, making it difficult to make predictions regarding when the FDA might be able to make an approval of a product effective and whether periods of exclusivity will effectively block competitors seeking to market products that are the same or similar to ours for the same intended use. Accordingly, whether any of our gene therapies will be deemed to be the same as another product or product candidate is uncertain.

The FDA grants product sponsors certain periods of regulatory exclusivity, during which the agency may not approve, and in certain instances, may not accept, certain marketing applications for competing drugs. For example, in the U.S., biologic product sponsors may be eligible for twelve years of exclusivity from the date of approval, seven years of exclusivity for drugs that are designated to be orphan drugs, and/or a six-month period of exclusivity added to any existing exclusivity period for the submission of FDA requested pediatric data. While we intend to apply for all periods of market exclusivity that we may be eligible for, there is no guarantee that we will be granted any such periods of market exclusivity. By example, regulatory authorities may determine that our product candidates are not eligible for periods of regulatory exclusivity for various reasons, including a determination by the FDA that a BLA approval does not constitute a first licensure of the product. Additionally, under certain circumstances, the FDAFDA, European Commission, or MHRA may revoke the period of market exclusivity. Thus, there is no guarantee that we will be able to maintain a period of market exclusivity, even if granted. In the case of orphan designation, other benefits, such as tax credits and exemption from user fees may be available. If we are not able to obtain or maintain orphanOrphan drugDrug designation or any period of market exclusivity to which we may be entitled, we could be materially harmed, as we will potentially be subject to greater market competition and may lose the benefits associated with programs. It is also possible that periods of exclusivity will not adequately protect our product candidates from competition. For instance, even if we receive twelve years of exclusivity from the FDA, other applicants will still be able to submit and receive approvals for versions of our product candidates through a full BLA. It is also possible that periods of regulatory exclusivity may change. By example, the EU has proposed exclusivity changes, in the form of draft legislation, that would effectively shorten the periods of EU orphan market exclusivity and data exclusivity.

We and our commercial partner face uncertainty related to insurance coverage of, and pricing and reimbursement for, HEMGENIX® and otherour product candidates for which we may receive marketing approval.

We anticipate that the cost of treatment using our product candidates, if approved, will be significant. We expect that most patients and their families will not be capable of paying for our products themselves. There will be no commercially viable market for our product candidates without reimbursement from third partythird-party payers, such as government health administration authorities, private health insurers and other organizations. Even if there is a commercially viable market, if the level of third-party reimbursement is below our expectations, most patients may not be able to access treatment with our products and our potential revenues and gross margins will be adversely affected, and our business will be harmed.

The following Management’s Discussion and Analysis of Financial Condition and Results of Operations (“MD&A”) is intended to help the reader understand our results of operations and financial condition. This MD&A is provided as a supplement to, and should be read in conjunction with, our audited consolidated financial statements and the accompanying notes thereto and other disclosures included in this Annual Report on Form 10-K, including the disclosures under “Risk Factors.Factors”. Our consolidated financial statements have been prepared in accordance with generally accepted accounting principles in the U.S. (“U.S. GAAP”) and unless otherwise indicated are presented in U.S. dollars.

Except for the historical information contained herein, the matters discussed in this MD&A may be deemed to be forward-looking statements. Forward-looking statementstatements are only predictions based on management’s current views and assumptions and involve risks and uncertainties, and actual results could differ materially from those projected or implied. We make such forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. Words such as “may,” “expect,” “anticipate,” “estimate,” “intend,” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements.

We are a leader in the field of gene therapy, seeking to deliver to patients suffering from rare and other devastating diseases single treatments with potentially curative results. We are advancing a focused pipeline of innovative gene therapies, including our clinical candidates for the treatment of Huntington’s disease, amyotrophicMTLE, lateralFabry sclerosis caused by mutations in superoxide dismutase 1, refractory mesial temporal lobe epilepsy (“mTLE”),disease, and Fabry disease.SOD1-ALS.

AMT-130 is our novel gene therapy candidate for the treatment of Huntington’s disease, which utilizes our proprietary, gene-silencing miQURE platform and incorporates an AAV vector carrying a micro ribonucleic acid (“miRNA”) specifically designed to silence the huntingtin gene and the potentially highly toxic exon 1 protein fragment.

We are currently conducting the U.S. and European studies. We completed the enrollment of all 26 patients in the first two cohorts of our USU.S. study in March 2022 and the enrollment of 13 patients in the two cohorts of our European study in June 2023. As of FebruaryIn 2025, we havecompleted enrolledenrollment of all 12 patients intoin the third cohort, and we treated six patients with the high-dose of AMT-130 in a thirdfourth cohort to furtherevaluate investigatethe bothsafety dosesand efficacy of AMT-130 togetherin patients with perioperativelower immunosuppressionbaseline usingstriatal volumes compared to previous cohorts in the current,U.S. establishedPhase stereotacticI/II administration procedure.study.

Regulatory AlignmentUpdates

In August 2024,2025, we announced thatcompleted the firstenrollment patientof wasthree dosedcohorts inof athree patients each into our Phase I/IIaII clinical trial of AMT-191 for the treatment of Fabry disease. In February 2025, weWe announced thatinitial wedata completed the enrollment offrom the first cohort ofat thea clinicalscientific trialconference in September 2025 and thatadditional wepreliminary woulddata proceedat enrollinga thescientific secondconference cohortin ofFebruary the clinical trial.2026.

In OctoberSeptember 2024,2025, we announcedvoluntarily thepaused first patient was dosedenrollment in aEPISOD1, our Phase I/IIaII clinical trial of AMT-162 for the treatment of SOD1-ALS. InWe Januarycontinue 2025,to wecollect announcedand thatevaluate wedata completedfrom the enrollmentfive ofpatients thedosed firstin cohortEPISOD1 ofto the clinical trial and that we would proceed enrolling the second cohort of the clinical trial.date.

As of December 31, 2024,2025, we hadheld $367.5$622.5 million in cash and cash equivalents and investment securities (December 31, 20232024: $617.9$367.5 million cash and cash equivalents and investment securities). We had a net loss of $239.6$199.0 million in 2024the year ended December 31, 2025 and a net loss of $308.5$239.6 million and $126.8$308.5 million during the same periods in 20232024 and 2022,2023, respectively. As of December 31, 2024,2025, we had an accumulated deficit of $1,130.0$1,328.9 million (December 31, 20232024: $890.4$1,130.0 million).

SeeRefer to “Results of Operations” below for a discussion of the detailed components and analysis of the amounts above.

In preparing our consolidated financial statements in accordance with U.S. GAAP and pursuant to the rules and regulations promulgated by the SECSEC, we make assumptions, judgments and estimates that can have a significant impact on our net loss/income and affect the reported amounts of certain assets, liabilities, revenue and expenses, and related disclosures. On an ongoing basis, we evaluate our assumptions, estimates and judgments, including those related to what we believe to be our critical accounting policies. Refer to Note 2 “Summary of significant accounting policies” for a summary of our significant accounting policies.

We consider the following to be our critical accounting estimatesestimate in the year ended December 31, 20242025:

In July 20212021, (“Acquisitionin Date”),connection wewith acquiredthe uniQure France SAS (“Acquisition Date”) andAcquisition, we recorded contingent consideration related to amounts potentiallycontingently payable to uniQure France SAS’sFrance’s former shareholders. The amounts payable in accordance with the related share and purchase agreement (“SPA”) are contingent upon realizationthe achievement of certain milestones associated with AMT-260. Contingent consideration was measured at fair value atas of the Acquisitiondate Dateof the uniQure France Acquisition, with changes in fair value subsequently recognized in the consolidatedConsolidated statementsStatements of operationsOperations inand researchComprehensive Loss, within Research and development expenses.

Changes in the fair value of the contingent consideration canmay result from changes in the assumedassumptions achievementregarding the probability and timing of estimatedmilestone milestonesachievement, andas well as changes in the discount rate used to estimatein the fair valuevaluation of the liability:

The fair value of the contingent consideration liability as of December 31, 2025 was EUR 15.9 million ($18.7 million) and as of December 31, 2024 was EUR 10.5 million ($10.9 million). The increase was driven by changes to the discount rate and expected timing of future achievement of the related remaining milestones. If, as of December 31, 2023 was EUR 39.0 million ($43.0 million). The reduction was primarily driven by a EUR 26.8 million ($28.2 million) milestone payment we made in December 2024 related to2025, the first patient dosed in the AMT-260 clinical trial. If as of December 31, 2024, weCompany had assumed a 100% likelihood of AMT-260 advancing into a Phase III clinical study, then the fair value of the contingent consideration would have increased to EUR 33.751.4 million ($35.0$60.4 million). IfIf, as of December 31, 20242025 the Company had assumed that it would discontinue development of the AMT-260 program, then the contingent consideration would have been released to income.

We sold the exclusive global rights to HEMGENIX® to CSL Behring in 2021 (“License Sale”). We recognize license revenue in relation to the License Sale when it becomes probable that regulatory and sales milestone events will be achieved as well as when royalties on sales of HEMGENIX® have been earned. We recognized $10.1$15.9 million, $2.8$10.1 million and $100.0$2.8 million of license revenue for the years ended December 31, 2024, 2023 and 2022, respectively. We recognized $10.1 million and $2.8 million of license revenue in2025, 2024 and 20232023, respectively, related to royalty payments owed on HEMGENIX® sales, when earned. We recognized $100.0 million of license revenue in 2022 related to a milestone payment owed on the first sale of HEMGENIX® in the U.S. in 2023.

For a discussion of our risks, please see “Item 1A. Risk Factors” in our Annual Report on Form 10-K for the fiscal year ended December 31, 2025. ThereThe haveinformation beenpresented nobelow materialupdates, changesand toshould be read in conjunction with, the risk factors disclosed in our Annual Report on Form 10-K for the fiscalyear ended December 31, 2025. Except as presented below, there have been no material changes from the risk factors described in our Annual Report on Form 10-K for the year ended December 31, 2025.

In September 2025, we announced positive topline data from the three-year analysis of cohorts one and two of the ongoing Phase I/II studies of AMT-130 for the treatment of Huntington’s disease. We analyzed clinical outcomes for 29 patients treated with AMT-130 (n=17 high-dose; n=12 low-dose) of which 12 patients per dose group had attained 36 months of follow-up and were evaluated at that time point. Outcomes for each dose group were compared to a propensity score-matched external control drawn from the Enroll-HD natural history data set (n=940 for high-dose; n=626 for low-dose).

AMT-130 was generally well-tolerated in the Phase I/II studies, with a manageable safety profile at both doses. TheThere have been five drug-related serious adverse events (“SAEs”) reported across all cohorts, and the most common adverse events in the treatment groups were related to the administration procedure.

From November 2024 through April 2025, we held three Type B meetings with the U.S. Food and Drug Administration (the “FDA”). As part of these interactions, the FDA agreed that data from the ongoing Phase I/II studies, compared to a natural history external control, may serve as the primary basis of a Biologics License Application (“BLA”) submission under the FDA’s accelerated approval pathway. The FDA also agreed that cUHDRS may be used as an intermediate clinical endpoint and reductions in CSF NfL may serve as supportive evidence of therapeutic benefit in the application for such accelerated approval.

In October 2025, we met with the FDA at a pre-BLA meeting to discuss the application for AMT-130. In December 2025, we announced that in the final meeting minutes, the FDA conveyed that data submitted from the Phase I/II studies of AMT-130 arewere currently unlikely to provide the primary evidence to support a BLA submission.

In January 2026, we met with the FDA at a Type A meeting to discuss AMT-130. In March 2026, following receipt of the final meeting minutes from the Type A meeting, we announced that the FDA stated that it cannotcould not agree that data from the Phase I/II studies, compared to an external control, arewere sufficient to provide the primary evidence of effectiveness required to support a marketing application for AMT-130. The FDA strongly recommended we conduct a prospective, randomized, double-blind, sham surgery-controlled study.

In AprilMarch 2026, we announced that, following feedback fromheld a successful pre-submission meeting with the United Kingdom’s (“UK”) Medicines and Healthcare products Regulatory Agency (“MHRA”) regarding AMT-130, weand planthe toregulatory submitsubmission ais UKprogressing Marketingas Authorization Applicationplanned for AMT-130 in the third quarter of 2026.

We are conducting a Phase I/IIa clinical trial, GenTLE, of AMT-260 for the treatment of MTLE in the U.S. GenTLE consists of two parts. The first part is a multicenter, open-label trial with two dosing cohorts of at least six patients each to assess safety, tolerability, and initial efficacy of AMT-260 in patients with refractory MTLE. The second part is expected to be a randomized, controlled trial to generate proof of concept data.

In September 2025, we completed enrollment of the first three patients in the first cohort administering AMT-260 to patients with lesions in the non-dominant hemisphere of the brain. Following a review by the independent data monitoring committee (“IDMC”), we expanded the first cohort into MTLE in the dominant hemisphere and initiated a second cohort. We completed enrollment of six patients into the first cohort in 2025. We also initiated enrollment of a second cohort in 2025, which is expected to include an additional six patients.2025.

In FebruaryJune 2026, we announcedpresented updated preliminary data from the Phase I/II study of AMT-191 for Fabry disease. UpdatedThe preliminarydata, safetybased and exploratory efficacy data included the following, withon a March 15, 2026 data cutoff datedate, asincluded patient follow-up ranging from three months to more than 18 months and consisted of Januarythe 8, 2026following:

AMT-191 continued to show a manageable safety profile. No SAEs related to AMT-191 were observed at the 4x1013 gc/kg (“mid-dose”) and 2x1013 gc/kg (“low-dose”) doses. No additional SAEs were observed at the 6x1013 gc/kg (“high-dose”) dose beyond the fivethose previously reported in September 2025 in two patients. Per protocol, additional dosing in the mid- and high-dose cohorts has been paused pending further evaluation following asymptomatic Grade 3 liver enzyme elevations observed in two patients in the mid-dose cohort, which were confirmed dose-limiting toxicity.

As of MarchJune 31,30, 2026 and December 31, 2025, we had cash and cash equivalents and investment securities of $586.6$810.3 million and $622.5 million, respectively. We had a net loss of $53.5$81.1 million and $134.6 million in the three and six months ended MarchJune 31,30, 2026, compared to a net loss of $43.6$37.7 million and $81.4 million for the same periodperiods in 2025. As of MarchJune 31,30, 2026 and December 31, 2025, we had accumulated deficits of $1,382.5$1,463.5 million and $1,328.9 million, respectively. See “Results of Operations” below for a discussion of the detailed components and analysis of the amounts above.

In preparing our unaudited consolidated financial statements in accordance with U.S. GAAP and pursuant to the rules and regulations promulgated by the Securities and Exchange Commission (the “SEC”) we make assumptions, judgments and estimates that can have a significant impact on our net loss and affect the reported amounts of certain assets, liabilities, revenue and expenses, and related disclosures. We base our assumptions, judgments and estimates on historical experience and various other factors that we believe to be reasonable under the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities that are not clear from other sources. Actual results may differ from these estimates under different assumptions or conditions. In making estimates and judgments, management employs critical accounting policies. A summary of our critical accounting policies, as well as a discussion of our critical accounting estimates, are presented in our Annual Report. There were no material changes to our critical accounting policies during the threesix months ended MarchJune 31,30, 2026.

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

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

We recognize license revenues from CSL Behring related to royalty payments owed on HEMGENIX® sales, when earned. For the three months ended MarchJune 31,30, 2026 and 2025, we recognized $3.6$5.8 million and $1.6$5.3 million of license revenues, respectively.

R&D expenses for the three months ended MarchJune 31,30, 2026 were $29.2$34.0 million, compared to $36.1$35.4 million for the same period in 2025. Other research and development expenses are separately classified in the table below. These other expenses are not allocated to specific projects, as they are deployed across multiple projects under development.

In the three months ended MarchJune 31,30, 2026 and MarchJune 31,30, 20252025, we incurred costs ofrelated $2.8 million and $2.1 million respectively, forto the development of AMT-260. We incurred costsAMT-260 of $2.6$4.2 million and $2.0 million, respectively. The current year period included $3.7 million of clinical expenses and $0.3 million of CMC expenses, respectively, compared to $1.7 million and $0.2 million related to clinical trials and CMC development,million, respectively, compared to costs of $1.6 million and $0.4 million in the comparativeprior year period.

Amyotrophic Lateral Sclerosis caused by mutations in SOD1 (AMT-162) In the three months ended MarchJune 31,30, 2026 and MarchJune 31,30, 2025, we incurred $0.9costs related to the development of AMT-162 of $2.5 million and $1.8$1.1 millionmillion, ofrespectively. expenses,These respectively,costs were primarily in relationrelated to our Phase I/II clinical trial.

In the three months ended MarchJune 31,30, 2026 and MarchJune 31,30, 2025, we incurred $1.1costs related to research and technology projects of $1.9 million and $1.3$0.4 millionmillion, of costs, respectively, related to activities associated with product candidates for various other research programs and technology innovation projects.respectively.

Selling, general and administrative expenses for the three months ended MarchJune 31,30, 2026 were $20.1$17.4 million, compared to $10.9$13.5 million for the same period in 2025.

Our other non-operating items, net, for the three months ended MarchJune 31,30, 2026 and MarchJune 31,30, 2025 were as follows:

We recognize interest income associated with our cash and cash equivalents and investment securities. We recognized $5.2$5.1 million in interest income in the three months ended MarchJune 31,30, 2026, compared to $4.1$3.5 million in the same period in the2025. priorThe year.$1.5 Ourmillion interestincrease income increased by $1.1 million,was primarily due to increaseshigher inaverage amountsbalances of our investment securities held during the threecurrent monthsyear ended March 31, 2026,period, compared to the same period in the prior year.year period.

In May 2023, uniQure biopharma B.V. entered into an agreement (the “Royalty Financing Agreement”) with HemB SPV, L.P. to sell certain current and future royalties due to uniQure biopharma B.V. from CSL Behring from the net sales of HEMGENIX® pursuant to the CSL Behring Agreement. We recognized non-cash interest expenses related to the Royalty Financing Agreement of $12.6$13.0 million and $13.3$13.8 million in the three months ended MarchJune 31,30, 2026 and 2025, respectively.

We recognized interest expense related to the Hercules loan facility of $1.4 million and $1.8 million in the three months ended MarchJune 31,30, 2026,2026 and MarchJune 31,30, 2025, respectively,respectively. related to the Hercules loan facility. Our interest expense decreased byThe $0.4 million,million decrease was primarily due to improvedmore favorable terms following the amendment of the facility in September 2025 amendment2025, as well as a decrease in market interest rates.

WeIn issuedconnection pre-funded warrants as part ofwith our September 2025 follow-on public offering.offering, Wewe recognizeissued changespre-funded relatedwarrants tothat are classified as a liability recordedand in relation to this issuancemeasured at fair value.value each reporting period. We recognized a $3.8$16.0 million gainloss in the three months ended MarchJune 31,30, 20262026, relatedreflecting toan a decreaseincrease in the fair value of thethis liability related to pre-funded warrants,liability, compared to nil for the same period in 2025.

We recognized $0.5$1.8 million of deferred tax expense in the three months ended MarchJune 31,30, 2026, and $0.5$0.4 million of deferred tax expense for the same period in 2025.