NASDAQ: QURE

●We cannot predict when or if we will obtain marketing approval to commercialize our product candidates.

●Disruptions or changes at the FDA, or other government agencies, as a result of funding cuts, personnel losses, leadership changes, regulatory changes or regulatory reform, government shutdowns and other developments could hinder the timing of or our ability to obtain further guidance from the FDA regarding our clinical development programs and secure approval of our product candidates in a timely manner, which could adversely affect our business.

●The risks associated with the marketing approval process are heightened by the status of our products as gene therapies.

●We may leverage certain specialized regulatory pathways and designations, such as the FDA’s accelerated approval pathway, Regenerative Medicine Advance Therapy (“RMAT”) designation and Breakthrough 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.

●Negative public opinion and increased regulatory scrutiny of gene therapy and genetic research may damage the public perception of our product candidates or adversely affect our ability to conduct our business or obtain marketing approvals for our product candidates.

●Our business development and strategic initiatives, acquisitions, partnerships, collaborations or other transactions, may not achieve their intended benefits or goals and may result in additional risks to our business.

●We may not be successful in obtaining rights from external parties to new product candidates and key technologies, or in securing partnerships to support the development or commercialization of our product candidates.

●Gene therapies are complex, expensive and difficult to manufacture. Genezen Holdings Inc. and its subsidiary Genezen MA, Inc. (together “Genezen”) or any third-party manufacturer that we engage could experience capacity, production or technology transfer challenges that could result in delays in our development or commercialization schedules or otherwise adversely affect our business.

●The manufacturing of our products and product candidates is subject to significant government regulations and approvals. We currently rely and expect to continue to rely on third parties to manufacture our product candidates, and these third parties may not perform satisfactorily or may fail to comply with these regulations or maintain these approvals.

●We had net losses in the years ended December 31, 2025 and 2024, have incurred significant losses in previous years and expect to incur losses in the future, and may never achieve or maintain profitability.

●There may be future changes in legal and regulatory requirements or standards that may materially impact our results of operations.

●The market price of our ordinary shares has been and may in the future be volatile and fluctuate substantially.

●Our future success depends on our ability to retain key executives, technical staff, and other employees and to attract, retain and motivate qualified personnel.

●We face substantial competition, and others may discover, develop, or commercialize competing products before or more successfully than we do.

Part I

Unless the context requires otherwise, references in this report to “uniQure,” “Company,” “we,” “us” and “our” and similar designations refer to uniQure N.V. and our subsidiaries.

Item 1. Business.

Overview

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, refractory mesial temporal lobe epilepsy (“MTLE”), Fabry disease, and amyotrophic lateral sclerosis caused by mutations in superoxide dismutase 1 (“SOD1-ALS”).

Recent Product Candidate Developments

Huntington’s disease program (AMT-130)

In September 2025, we announced positive topline data from the pivotal Phase I/II study 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).

Topline 36-month efficacy results for patients receiving high-dose AMT-130 were as follows (data cutoff as of June 30, 2025):

●A statistically significant 75% slowing of disease progression as measured by composite Unified Huntington’s Disease Rating Scale (“cUHDRS”) (p=0.003), which met the primary endpoint of the study. Treated patients had a mean change in cUHDRS from baseline of -0.38 compared to a change of -1.52 for patients in the propensity score-matched external control.

●A statistically significant 60% slowing of disease progression as measured by Total Function Capacity (“TFC”) (p=0.033), which met a key secondary endpoint of the study. Treated patients had a mean change in TFC from baseline of -0.36 compared to a change of -0.88 for patients in the propensity score-matched external control.

●Favorable trends in other secondary endpoint measures of motor and cognitive function, including Symbol Digit Modalities Test (“SDMT”), Stroop Word Reading Test (“SWRT”) and Total Motor Score (“TMS”).

oAn 88% slowing of disease progression as measured by SDMT (p=0.057), with a mean change in SDMT from baseline of -0.44 compared to a change of -3.73 for patients in the propensity score-matched external control.

oA 113% slowing of disease progression as measured by SWRT (nominal p=0.002), with a mean change in SWRT from baseline of 0.88 compared to a change of -6.98 for patients in the propensity score-matched external control.

oA 59% slowing of disease progression as measured by TMS (nominal p=0.174), with a mean change in TMS from baseline of 2.01 compared to a change of 4.88 for patients in the propensity score-matched external control.

A mean reduction from baseline in cerebrospinal neurofilament light protein (“CSF NfL”) of -8.2% was observed at 36 months in the high-dose of AMT-130 of the Phase I/II studies. CSF NfL is a well-characterized, supportive biomarker of neurodegeneration. Elevation in CSF NfL has been shown to be strongly associated with greater clinical severity of Huntington’s disease.

We believe that the consistently favorable results in functional, motor and cognitive endpoints at 36 months observed in the high-dose group, compared to the variable trends observed in the low-dose group, reflect a dose-dependent response to AMT-130.

Various other supportive analyses of the results from the AMT-130 high-dose treatment group, including those using a propensity score-weighted external control and comparisons to the TRACK-HD and PREDICT-HD datasets, were consistent with the primary analysis.

AMT-130 was generally well-tolerated in the Phase I/II studies, with a manageable safety profile at both doses with no new drug-related serious adverse events (“SAEs”) observed since December 2022. The most common adverse events in the treatment groups were related to the administration procedure.

In 2025, we treated six patients with the high-dose of AMT-130 in a fourth cohort to evaluate the safety and efficacy of AMT-130 in patients with lower baseline striatal volumes compared to previous cohorts in the U.S. Phase I/II study.

In April 2025, we announced that the FDA granted Breakthrough Therapy designation to AMT-130 for the treatment of Huntington’s disease. The Breakthrough Therapy designation was supported by clinical data from the ongoing Phase I/II trials of AMT-130 for the treatment of Huntington’s disease showing the potential for meaningful slowing of disease progression. Breakthrough Therapy designation is intended to expedite the development and review of investigational therapeutic candidates that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s). In general, the preliminary clinical evidence should show a clear advantage over available therapy.

In addition to the Breakthrough Therapy designation, the FDA previously granted RMAT designation, Orphan Drug designation and Fast Track designation to AMT-130.

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 are 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 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 intend to continue engaging with the FDA regarding Phase III development considerations and plan to request a Type B meeting in the second quarter of 2026 to further discuss potential study design approaches.

Temporal lobe epilepsy program (AMT-260)

In May 2025, we presented initial safety and exploratory efficacy data from the first treated patient in our Phase I/IIa clinical trial (“GenTLE”) of AMT-260 for the treatment of MTLE in the United States (“U.S.”). As of the April 17, 2025 cutoff date, the patient showed a 92% reduction in seizure frequency observed through the first five months of follow-up with no serious safety events as of the data announcement.

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

Fabry disease program (AMT-191)

In February 2025, we announced a favorable recommendation from the IDMC following a review of safety data from the first two patients treated in the Phase I/II clinical trial of AMT-191 for the treatment of Fabry disease. The IDMC’s review did not identify any significant safety concerns and recommended proceeding with enrollment in the second cohort.

During 2025, we enrolled three patients in a second, lower dose cohort in our Phase I/II clinical trial of AMT-191 for the treatment of Fabry disease, as well as enrolled four patients in a third cohort.

In September 2025, we announced initial safety and exploratory efficacy data from the first cohort. The data presented in respect of the July 24, 2025 cutoff date, at which date all patients had less than three months of follow-up, was as follows:

●All patients in the first dose cohort showed sustained increases in α-galactosidase A (“α-Gal A”) enzyme activity, ranging from 27- to 208-fold above the mean normal range (1.38-8.66 nmol; mean normal of 3.57 nmol). All four patients were withdrawn from enzyme replacement therapy (“ERT”) and maintained stable plasma lyso-Gb3 levels through the cutoff date.

●AMT-191 showed a manageable safety profile. At the high dose, two SAEs unrelated to AMT-191 (stroke, diplopia), two related SAEs (chest pain, increased troponin), and one possibly related SAE (leptomeningeal enhancement) were observed in two patients. Additionally, one patient experienced an asymptomatic Grade 3 liver enzyme elevation that resolved with corticosteroid therapy. This event, classified as a dose-limiting toxicity per protocol, was not considered serious and did not require hospitalization. No loss of α-Gal A expression was observed in this patient.

In February 2026, we announced updated preliminary data from the Phase I/II study of AMT-191 for Fabry disease. Updated preliminary safety and exploratory efficacy data included the following, with a data cutoff date as of January 8, 2026:

●Dose-dependent elevations were observed across 11 patients in three dose levels with α-Gal A activity ranging from 0.34- to 82.2-fold above mean normal range (1.38-8.66 nmol; mean normal of 3.57 nmol) at the lowest dose, 1.6- to 312.52-fold at the mid dose, and 27.7- to 223.7-fold at the highest dose. These increases were durable for the measured time period ranging from the longest follow-up period of more than a year in a treated patient (high-dose cohort) to the shortest follow-up period of four-months in a treated patient (mid-dose cohort).

●Six of 11 dosed patients were withdrawn from ERT.

●Plasma lyso-Gb3 levels were stable post-dose across all dose cohorts, regardless of ERT status through the cutoff date.

AMT-191 continued to show a manageable safety profile. No SAEs related to AMT-191 were observed at the 4x1013 gc/kg and 2x1013 gc/kg doses. No additional SAEs were observed at the 6x1013 gc/kg dose beyond the five 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.

Amyotrophic Lateral Sclerosis (AMT-162)

In September 2025, we voluntarily paused enrollment of our Phase I/II multi-center, open-label trial of AMT-162 for the treatment of SOD1-ALS (“EPISOD1”) in the U.S. upon the recommendation of the IDMC following a 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 an SAE determined to be related to AMT-162, that was observed in one patient in the second cohort. We continue to collect and evaluate data from the five patients dosed in EPISOD1 to date.

Other Business Developments

Public Offerings

In January 2025, we received net proceeds of $70.1 million, after deducting underwriting discounts and commissions and other offering expenses payable by us, through a follow-on public offering of 4.4 million ordinary shares at a public offering price of $17.00 per ordinary share. In February 2025, we received an additional $10.4 million in net proceeds, after related offering expenses, upon the underwriters’ exercise of their option to purchase an additional 0.7 million ordinary shares at the public offering price.

In September 2025, we received net proceeds of $323.7 million, after deducting underwriting discounts and commissions and other offering expenses payable by us, through a follow-on public offering of 6.7 million ordinary shares at a public offering price of $47.50 per ordinary share, and, in lieu of ordinary shares to certain investors, pre-funded warrants to purchase 0.5 million of our ordinary shares at the public offering price per share less the $0.0001 per share exercise price of each pre-funded warrant.

Hercules Loan Amendment

In September 2025, we entered into a $175.0 million senior secured term loan facility (the “2025 Amended Facility”) with Hercules Capital, Inc. (“Hercules”). The 2025 Amended Facility consists of three tranches including a first tranche of $50.0 million replacing the debt outstanding as per the loan amendment date, an additional term loan tranche of $100.0 million, which can be drawn at our option, subject to the BLA approval of AMT-130 prior to June 2027, provided that confirmatory trials to the extent and in the manner required to support full approval (if applicable) remain ongoing or are being planned, and a third tranche of up to $25.0 million, subject to Hercules’ approval. All tranches have a floating interest rate of the greater of 9.45% and the prime rate plus 2.45%, reflecting a floating rate of 9.45% as of December 31, 2025. The tranches mature on October 1, 2030.

Our Mission and Strategy

Our mission is to deliver curative, one-time administered genomic medicines that transform the lives of patients. We aim to build an industry-leading, fully integrated, and global company that leverages its technology and proprietary manufacturing platform to deliver these medicines to patients with serious unmet medical needs. Our strategy to achieve this mission is to:

Advance the development and potential commercialization of AMT-130, a potential one-time gene-therapy approach for the treatment of Huntington’s disease. AMT-130 is the first AAV-based gene therapy for the treatment of Huntington’s disease to have entered into clinical development.

Advance our pipeline of clinical-stage gene therapy candidates and research programs. We have dosed patients in the clinical studies of our product candidates for the treatment of MTLE (AMT-260), Fabry disease (AMT-191), and SOD1-ALS (AMT-162). We intend to generate clinical data to assess the safety, tolerability and potential efficacy of these product candidates. We also continue to advance early-stage research candidates with a focus on gene therapies for severe diseases.

Develop next-generation delivery and cargo technologies. We are developing technologies that have the potential to augment the safety and efficacy of our product candidates and broaden the applicability of our gene therapies to a wider range of diseases and patients. These technologies include next-generation delivery approaches, such as smart AAV capsids potentially capable of improved central nervous system (“CNS”) transduction and crossing the blood-brain barrier after systemic delivery, as well as novel cargo technologies such as miQURE®, our one-time administered gene silencing platform, LinQURE®, a single AAV carrying multiple micro ribonucleic acids (“miRNAs”) designed to suppress different genes, and GoQURE® for simultaneous silencing of a disease gene and replacement with a healthy gene.

Central Nervous System Diseases

Huntington’s Disease

Huntington’s Disease and Market Background

Huntington’s disease is a severe genetic neurodegenerative disorder causing loss of muscle coordination, behavioral abnormalities and cognitive decline, often resulting in complete physical and mental deterioration over a 12 to 15-year period. The median survival time after onset is 15 to 18 years (range: 5 to >25 years). Huntington’s disease is caused by an inherited defect in a single gene that codes for a protein called Huntingtin (“HTT”). Approximately 75,000 people have Huntington’s disease in the U.S., European Union (“EU”), and United Kingdom (“UK”), with approximately 40,000 symptomatic Huntington’s disease patients in the U.S. In addition to this, there are hundreds of thousands of others at risk of inheriting the disease. Huntington’s disease mutation carriers can be identified decades before onset. There is currently no available therapy that can delay onset or slow progression of the disease. Although some symptomatic treatments are available, they are only transiently effective and are often associated with significant side effects.

Our Development of AMT-130 for Huntington’s Disease

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 a miRNA, specifically designed to silence the huntingtin gene and the potentially highly toxic exon 1 protein fragment.

Our goal for AMT-130 is to develop a gene therapy with the following profile:

(1)one-time administration of a disease-modifying therapy into the striatum, the area of the brain where Huntington’s disease is known to manifest;

(2)biodistribution of the therapy in both the deep and cortical structures of the brain via transport of the AAV vector and through secondary exosome-mediated delivery; and,

(3)safe, on-target and durable knockdown of HTT and exon 1 HTT.

We are currently conducting a multi-center randomized, controlled Phase I/II clinical trial for AMT-130 in the U.S. (the “U.S. study”), as well as an open-label Phase Ib/II study in Europe (the “European study”) with the same early-manifest criteria for Huntington’s disease as the U.S. study.

We completed the enrollment of all 26 patients in the first two cohorts of the U.S. study in March 2022 and the enrollment of 13 patients in the first two cohorts of the European study in June 2023. In the U.S. study, 26 patients with early manifest Huntington’s disease were randomized to treatment (six low-dose patients, 10 high-dose patients) or an imitation (sham) surgical procedure (10 patients). The U.S. study consists of a blinded 12-month core patient study period followed by an unblinded long-term follow-up period of five years. An additional four control patients crossed over to treatment. In the European study, 13 patients were enrolled and treated with AMT-130 (six low-dose patients and seven high-dose patients).

In 2023, we initiated patient dosing in a third cohort consisting of up to 12 patients to further investigate both doses of AMT-130 together with perioperative immunosuppression using the current, established stereotactic administration procedure. In February 2025, we completed enrollment of all 12 patients in the third cohort.

In 2025, we treated six patients with the high-dose of AMT-130 in a fourth cohort to evaluate the safety and efficacy of AMT-130 in patients with lower baseline striatal volumes compared to previous cohorts in the U.S. Phase I/II study.

Temporal Lobe Epilepsy Program (AMT-260)

Temporal Lobe Epilepsy Disease and Market Background

Temporal Lobe Epilepsy (“TLE”) affects approximately 0.5 million people in the U.S. alone, of which approximately 0.3 million U.S. patients are inadequately treated through anti-seizure medications and are considered refractory. 240,000 of U.S. refractory TLE patients have a lesion in the mesial temporal lobe (hippocampus), which is expressed as sclerosis, atrophy or scarring. MTLE is often caused by brain injury, infections or prolonged febrile seizures which can lead to hyperexcitability of the hippocampus and repeated seizures which can further damage the hippocampus over time. Refractory MTLE patients have a poor quality of life and a reduced lifespan. Surgical treatment for refractory patients is lobectomy or laser tissue ablation but only approximately 1% of eligible patients undergo surgery annually.

Our Development of AMT-260 for Temporal Lobe Epilepsy

In July 2021, we acquired uniQure France SAS (“uniQure France,” formerly Corlieve Therapeutics SAS) and its lead program, now known as AMT-260, to treat refractory MTLE. AMT-260 is being developed based on exclusive licenses to certain patents that uniQure France obtained following its formation in 2019 from two French research institutions.

AMT-260 is comprised of an AAV9 vector that locally delivers two engineered miRNAs designed to degrade the GRIK2 gene and suppress the aberrant expression of glutamate receptor subtype GLUK2 that is believed to trigger seizures in patients with refractory MTLE. The use of AAV9 to deliver any sequence that affects the expression of the GRIK2 gene in humans has been exclusively licensed from Regenxbio Inc. (“Regenxbio”).

We initiated a Phase I/IIa clinical trial that is being conducted in the U.S. and is intended to consist of two parts. The first active part of the clinical trial is a multicenter, open-label trial with two dosing cohorts of 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. The FDA-approved study protocol provides that the first three patients to be enrolled in the study are required to have Magnetic Resonance Imaging (“MRI”)-confirmed unilateral, hippocampal sclerosis.

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 positive review by the 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.

Amyotrophic Lateral Sclerosis (“ALS”)

ALS Disease and Market Background

ALS, commonly known as Lou Gehrig’s disease, is a progressive and fatal neuromuscular disease with the majority of ALS patients dying within 2 to 5 years of receiving a diagnosis. Familial ALS, a hereditary form of the disease, accounts for 5-10% of cases, whereas the remaining cases (sporadic ALS) have no clearly defined etiology. ALS affects persons of all races and ethnicities; however, persons of certain demographics (Caucasians, males, non-Hispanics and persons aged 60 years or older) and those with a family history of ALS are more likely to develop the disease.

ALS affects up to approximately 35,000 adults in the U.S. Evidence from prevalence studies suggests that prevalence and incident rates can vary significantly between regions and ethnicities. Most cases are sporadic (“sALS”) but approximately 10% are found to have a familial, i.e., dominant genetic causation (“fALS”). fALS can be caused by mutations in various genes including chromosome 9 open reading frame 72, SOD1, tyrosyl-DNA phosphodiesterase 2 and others.

One genetic mutation that causes ALS is pathogenic mutations in the superoxide dismutase enzyme 1 (“SOD1”). SOD1 is an enzyme that is responsible for catalyzing toxic superoxide to hydrogen peroxide and dioxygen. While the exact mechanism for the disease is not known, it is believed that a toxic gain of function in SOD1 results in oxidative stress and cell death of motor neurons. More than 100 pathogenic SOD1 have been identified. Mutations are concentrated in a few regions of the protein. Mutations can be both dominant and recessive. The most common mutations in the SOD1 gene are D90A, G93A, A4H and D46R.

Patients with different mutations progress at different rates. It is estimated that there are approximately 300 to 600 patients with SOD1-ALS in the U.S.

Our Development of AMT-162 for ALS – SOD1

In January 2023 we announced that we entered into a global licensing agreement with Apic Bio for a novel, one-time, intrathecally administered gene therapy for ALS caused by SOD1 mutations (formerly APB-102). The FDA cleared the Investigational New Drug (“IND”) application for APB-102 and granted it Orphan Drug and Fast Track designation. APB-102 is comprised of a recombinant AAVrh10 vector that expresses a miRNA designed to knock down the expression of SOD1 with the goal of slowing down or potentially reversing the progression of ALS in patients with SOD1 mutations. The FDA cleared the IND application for AMT-162 and has granted Orphan Drug and Fast Track Designation.

EPISOD1 is our Phase I/II multi-center, open-label trial of AMT-162 for the treatment of SOD1-ALS conducted in the U.S. consisting of three dose-escalating cohorts with up to four patients in each cohort. The trial is designed to explore the safety and tolerability of AMT-162 and assess exploratory signs of efficacy by measuring neurofilament light chain, a biomarker of neuronal damage, and SOD1 protein.

In September 2025, we voluntarily paused enrollment in EPISOD1 upon the recommendation of the IDMC following a 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 an SAE determined to be related to AMT-162, that was observed in one patient in the second cohort. We continue to collect and evaluate data from the five patients dosed in EPISOD1 to date.

Liver-directed diseases

Fabry disease program (AMT-191)

Fabry Disease and Market Background

Fabry disease is a progressive, inherited, multisystemic lysosomal storage disease characterized by specific neurological, cutaneous, renal, cardiovascular, cochleo-vestibular, and cerebrovascular manifestations. Fabry disease is caused by a defect in a gene that encodes for a protein called α-galactosidase A (“GLA”). The GLA protein is an essential enzyme required to breakdown globotriaosylsphingosine (“Gb3”) and lyso-globotriaosylsphingosine (“lyso-Gb3”). In patients living with Fabry disease, Gb3 and lyso-Gb3 accumulate in various cells throughout the body causing progressive clinical signs and symptoms of the disease. Current treatment options, which consist of bi-weekly intravenous enzyme replacement therapy, typically have no therapeutic benefit in patients with advanced renal or cardiac disease. Studies have also shown that a majority of male patients develop antibodies that inhibit the GLA protein and interfere with therapeutic efficacy.

Fabry disease has two major disease phenotypes: the type 1 “classic” and type 2 “later-onset” subtypes. Both lead to renal failure, and/or cardiac disease, and early death. Type 1 males have little or no functional a-Gal A enzymatic activity (<1% of normal mean) and marked accumulation of GL-3/Gb3 and related glycolipids in capillaries and small blood vessels which cause the major symptoms in childhood or adolescence. In contrast, males with the type 2 “later-onset” phenotype (previously called cardiac or renal variants) have residual a-Gal A activity, lack GL-3/Gb3 accumulation in capillaries and small blood vessels, and do not manifest the early manifestations of type 1 males. They experience an essentially normal childhood and adolescence. They typically present with renal and/or cardiac disease in the third to seventh decades of life. Most type 2 later-onset patients have been identified by enzyme screening of patients in cardiac, hemodialysis, renal transplant, and stroke clinics and recently by newborn screening. Fabry disease occurs in all racial and ethnic populations and affects males and females. It is estimated that type 1 classic Fabry disease affects at least one in 40,000 males and approximately one in 20,000 females. In the U.S., there may be approximately 7,000 type 1 Fabry patients. The type 2 later-onset phenotype is more frequent, and in some populations may occur as frequently as about 1 in 1,500 to 4,000 males.

Our Development of AMT-191 for Fabry Disease

AMT-191 is our investigational gene therapy candidate for the treatment of Fabry disease. AMT-191 is comprised of an AAV5 capsid that incorporates the GLA transgene and a proprietary, highly potent, liver-specific promoter. In 2023 we announced that the FDA had cleared the IND for AMT-191, and in 2024 we announced that the FDA granted Orphan Drug Designation and Fast Track Designation to AMT-191. We are conducting a Phase I/II clinical trial in the U.S. The multicenter, open-label clinical trial consists of three dose-ranging cohorts of three or more patients each to assess safety, tolerability, and efficacy of AMT-191 in patients with Fabry disease.

In February 2025, we announced the completion of enrollment in the first cohort of the Phase I/II trial. Additionally, the IDMC reviewed safety data from the initial two patients enrolled in the first cohort. The IDMC’s review did not identify any significant safety concerns and recommended proceeding with enrollment in the second cohort.

In 2025, we enrolled three patients in a second cohort and four patients in a third cohort in our Phase I/II clinical trial of AMT-191.

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.

Hemophilia B (HEMGENIX® or etranacogene dezaparvovec)

Hemophilia B Disease and Market Background

Hemophilia B is a rare, lifelong bleeding disorder caused by a single gene defect, resulting in insufficient production of factor IX, a protein primarily produced by the liver that helps blood clots form. Treatments for moderate to severe hemophilia B include prophylactic infusions of factor IX replacement therapy to temporarily replace or supplement low levels of blood-clotting factor and, while these therapies are effective, those with hemophilia B must adhere to strict, lifelong infusion schedules. They may also still experience spontaneous bleeding episodes as well as limited mobility, joint damage or severe pain as a result of the disease. For appropriate patients, HEMGENIX allows people living with hemophilia B to produce their own factor IX, which can lower the risk of bleeding.

CSL Behring collaboration

In June 2020, we entered into a commercialization and license agreement with CSL Behring LLC (the “CSL Behring Agreement”) pursuant to which CSL Behring LLC (“CSL Behring”) received exclusive global rights to HEMGENIX. The transaction became fully effective in May 2021. Unless earlier terminated as described below, the CSL Behring Agreement will continue on a country-by-country basis until expiration of the royalty term in a country. The royalty term expires in a country on the later of (a) 15 years after the first commercial sale of the product in such country, (b) expiration of regulatory exclusivity for the product in such country and (c) expiration of all valid claims of specific licensed patents covering the product in such country. Either we or CSL Behring may terminate the CSL Behring Agreement for the other party’s material breach if such breach is not cured within a specified cure period. In addition, if CSL Behring fails to commercialize the product in any of a group of major countries for an extended period of time following the first regulatory approval of the product in any of such group of countries (other than due to certain specified reasons) and such failure has not been cured within a specified cure period, then we may terminate the CSL Behring Agreement. CSL Behring may also terminate the CSL Behring Agreement for convenience.

We and CSL Behring also entered into a development and commercial supply agreement, pursuant to which, among other things, we agreed to supply the product to CSL Behring. We are contractually obligated to supply the product until such time that these capabilities are transferred to CSL Behring or its designated contract manufacturing organization. In September 2022, CSL Behring notified us of its intent to transfer manufacturing technology in the coming years related to HEMGENIX to a third-party contract manufacturer designated by CSL Behring. In addition, in July 2024, as part of the closing of the asset purchase agreement among our affiliates, uniQure Inc. and uniQure biopharma B.V. (“uniQure biopharma”), and Genezen Holdings Inc. and its subsidiary Genezen MA, Inc. (together “Genezen”) to sell certain assets and assume certain liabilities related to our former manufacturing facility and operations in Lexington, Massachusetts (the “Lexington Transaction”), we transferred the manufacturing and supply activities to Genezen such that Genezen manufactures and supplies CSL Behring’s commercial demand for HEMGENIX on our behalf.

New Technology Development

We are seeking to develop next-generation technologies with the goal of further improving the potential of AAV-based gene therapies to treat patients suffering from debilitating diseases. We are focused on innovative technologies across each of the key components of an AAV-based gene therapy, including: (i) the capsid, or the outer viral protein shell that encloses the target deoxyribonucleic acid (“DNA”); (ii) the cargo, including the transgene or therapeutic gene, and promoters, or the DNA sequence that drives or regulates the expression of the transgene; and (iii) administration techniques.

We dedicate significant effort to designing and screening novel AAV capsids with the potential for (i) higher biological potency; (ii) improved biodistribution including greater cell transduction and increased cellular specificity; (iii) enhanced safety; and (iv) manufacturing efficiency. We believe we have significant expertise in vector engineering and have created promising genetically engineered capsids using both rational and directed evolution approaches.

We have also demonstrated the ability to deliver engineered DNA constructs that can silence or suppress disease-causing genes. Our miQURE gene silencing platform, based on exclusively licensed technology from Cold Spring Harbor Laboratory (“CSHL”), is designed to degrade mutated genes without producing a “passenger strand” thereby mitigating potential off-target toxicity and induce silencing of the mutated gene in the entire target organ through secondary exosome-mediated delivery. miQURE-based gene therapy candidates, such as AMT-130, incorporate proprietary, therapeutic miRNA constructs that can be delivered using AAVs to potentially provide long-lasting activity. Preclinical studies of miQURE-based gene therapies have demonstrated several important advantages, including enhanced tissue-specificity, improved nuclear and cytoplasmic gene lowering and no off-target effects associated with impact to the cellular miRNA or messenger RNA transcriptome. The existing miQURE gene silencing strategy was expanded by linking several miRNA molecules in a single construct, resulting in the new linQURE platform.

Our Intellectual Property

We strive to protect the proprietary technologies that we believe are important to our business, including by seeking and maintaining patent protection in the U.S., Europe, and other jurisdictions for novel components of our gene therapies, the chemistries of and processes for manufacturing these gene therapies, the use of these components in gene therapies, our technology platform, and other inventions and technology. To the extent applicable, we also rely on trade secrets, know-how protection measures and monitoring of our proprietary information to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection.

We expect that our probability of success will be enhanced by our ability to obtain and maintain patent and other proprietary protection for commercially important technology, inventions and know-how related to our business, defend and enforce our patents, maintain our licenses to use intellectual property owned by third parties, preserve the confidentiality of our trade secrets and operate without infringing the valid and enforceable patents and other proprietary rights of third parties. We also rely on know-how, continuing technological innovation and in-licensing opportunities to develop, strengthen and maintain our proprietary position in the field of AAV-based gene therapies.

In some cases, we are dependent on the patented or proprietary technology of third parties to develop and commercialize our products. We must obtain licenses from such third parties on commercially reasonable terms, or our business could be harmed, possibly materially. For example, we license from third parties essential parts of the therapeutic gene cassettes as well as the principal AAV vectors we use and key elements of our manufacturing process. We anticipate that we will require licenses to additional technology in the future.

Because most patent applications throughout the world are confidential for 18 months after the earliest claimed priority date, and since the publication of discoveries in scientific and patent literature often lags actual discoveries, we cannot be certain that we were the first to invent or file applications for the inventions covered by our pending patent applications. Moreover, we may have to participate in post-grant proceedings in the patent offices of the U.S. or foreign jurisdictions, such as oppositions, reexaminations, or interferences, in which the patentability or priority of our inventions are challenged. Such proceedings could result in substantial cost, even if the eventual outcome is favorable to us. For more information regarding the risks related to our intellectual property, please see