AMT-130 / uniQure - LARVOL DELTA

uniQure Provides Regulatory Update on AMT-130 for Huntington’s Disease (GlobeNewswire) - "In the final meeting minutes, and consistent with uniQure’s November 3, 2025 press release, 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. uniQure is carefully evaluating the feedback and plans to urgently request a follow-up meeting with the FDA to take place in the first quarter of 2026."

FDA event • CNS Disorders • Huntington's Disease

Huntingtin protein in Health and Huntington's Disease: Molecular Mechanisms, Pathology and Therapeutic Strategies. (PubMed, Ageing Res Rev) - "The recent treatment approaches have also been explored by using molecular targets and diagnostic tools, including FANCD2 and FANCI-associated nuclease 1 (FAN1), which are genetic regulators of somatic CAG expansion; EPS8 dysregulation, which causes protein aggregation; and mismatch negativity (MMN), which is a brain response detected by EEG, a non-invasive biomarker for early cognitive impairment. These measures aim to slow down disease progression and improve the health and outcomes of patients."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Genetic Disorders • Huntington's Disease • Movement Disorders • Targeted Protein Degradation • FAN1 • FANCD2 • FANCI

Huntington's disease clinical trials update: October 2025. (PubMed, J Huntingtons Dis) - "In this edition of the Huntington's Disease Clinical Trials Update, we expand on the launch of the phase II/III clinical trial of SKY-0515 from Skyhawk Therapeutics and the phase I/II clinical trial of SPK-10001 from Spark Therapeutics. Further updates include recent developments in Roche's tominersen programme within GENERATION HD2, progress with votoplam (PTC518) in PIVOT-HD by PTC Therapeutics and developments in the collaborative PTC Therapeutics/Novartis programme. We also report positive topline data from uniQure's phase I/II clinical trial of AMT-130 after 36 months of follow-up. We additionally discuss regulatory developments regarding pridopidine following the negative PROOF-HD study. Finally, we provide an updated listing of all registered and ongoing clinical trials in Huntington's disease."

Journal • Huntington's Disease • Movement Disorders

uniQure Provides Regulatory Update on AMT-130 for Huntington’s Disease (GlobeNewswire) - "Though final meeting minutes have not yet been received, based on the discussions at the meeting, uniQure believes that the FDA currently no longer agrees that data from the Phase I/II studies of AMT-130 in comparison to an external control, as per the prespecified protocols and statistical analysis plans shared with the FDA in advance of the analyses, may be adequate to provide the primary evidence in support of a BLA submission. This is a key shift from prior communications with the FDA in multiple Type B meetings over the past year. Consequently, the timing of the BLA submission for AMT-130 is now unclear....uniQure expects to receive final minutes within 30 days of the meeting and plans to urgently interact with the FDA to find a path forward for the timely accelerated approval of AMT-130."

FDA filing • Huntington's Disease

CT-AMT-130-01: Safety and Proof-of-Concept (POC) Study With AMT-130 in Adults With Early Manifest Huntington's Disease (clinicaltrials.gov) - P1/2 | N=43 | Active, not recruiting | Sponsor: UniQure Biopharma B.V. | Recruiting ➔ Active, not recruiting

Enrollment closed • Huntington's Disease • Movement Disorders

uniQure Announces Closing of Upsized Public Offering and Full Exercise by Underwriters of Option to Purchase Additional Shares (UniQure Press Release) - "uniQure intends to use the net proceeds from this offering to fund its commercialization readiness activities, the potential commercial launch of AMT-130 and related commercialization activities, the development of its other clinical product candidates, business development initiatives and research projects, and for general corporate purposes."

Financing • Huntington's Disease

uniQure Announces Positive Topline Results from Pivotal Phase I/II Study of AMT-130 in Patients with Huntington’s Disease (GlobeNewswire) - "A statistically significant 75% slowing of disease progression as measured by 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....uniQure plans to submit a BLA in the first quarter of 2026, with anticipated U.S. launch later that year, pending approval."

P1/2 data • Huntington's Disease

Recent Company Developments and Updates (GlobeNewswire) - "Certain next steps and expected timing include: September 2025: Present topline, three-year data from the ongoing Phase I/II trials; Q3 2025: Initiate a fourth cohort evaluating high-dose AMT-130 in six patients with lower striatal volumes compared to those of patients enrolled in previous cohorts; Q4 2025: Hold pre-BLA meeting with FDA and complete PPQ campaign; Q1 2026: Submit BLA with a request for priority review designation....AMT-162 for the treatment of SOD1 amyotrophic lateral sclerosis (ALS) – The Company continues to enroll patients in the Phase I/II EPISOD1 study and expects to present initial data in the first half of 2026."

FDA filing • P1/2 data • Trial status • Amyotrophic Lateral Sclerosis • Huntington's Disease

CT-AMT-130-01: Safety and Proof-of-Concept (POC) Study With AMT-130 in Adults With Early Manifest Huntington's Disease (clinicaltrials.gov) - P1/2 | N=43 | Recruiting | Sponsor: UniQure Biopharma B.V. | Active, not recruiting ➔ Recruiting | Trial completion date: Jun 2029 ➔ Dec 2029

Enrollment open • Trial completion date • Huntington's Disease • Movement Disorders

uniQure aligns with FDA on Huntington’s therapy path (Investing.com) - "uniQure N.V...has announced progress in its regulatory discussions with the U.S. Food and Drug Administration (FDA) for AMT-130, a gene therapy candidate for Huntington’s disease. The company has aligned with the FDA on key aspects of its Biologics License Application (BLA) expected to be submitted in the first quarter of 2026. The recent Type B meetings with the FDA have resulted in agreement on several components of the statistical analysis plan and Chemistry, Manufacturing, and Controls (CMC) information to support the BLA for AMT-130. The FDA supports the use of the Unified Huntington’s Disease Rating Scale (cUHDRS) as an acceptable clinical endpoint for accelerated approval....The company also plans to submit updated statistical analysis and CMC plans to the FDA in the second quarter of 2025, followed by initiating a Process Performance Qualification (PPQ) run, presenting top-line Phase I/II data, and holding a pre-BLA meeting with the FDA later in the year. "

FDA event • FDA filing • Huntington's Disease

Combined Targeting of HTT , HTT1a and Somatic Instability in Huntington's Disease using LinQURE®: a Feasibility Study in Multiple HD Mouse Models (ASGCT 2025) - "Many therapies that are under development, including uniQure's clinical-stage candidate AMT-130, are designed to lower HTT levels, with the goal of slowing neurodegeneration...Such approaches hold major promise as potential next-generation gene therapies for HD. Disease Focus of Abstract:Central Nervous System Disorders"

Preclinical • CNS Disorders • Gene Therapies • Huntington's Disease • Movement Disorders • MSH3

uniQure Announces First Quarter 2025 Financial Results and Highlights of Recent Company Progress (GlobeNewswire) - P1/2 | N=37 | NCT04120493 | Sponsor: UniQure Biopharma B.V. | "Patients were blinded and randomized to receive either the high (n=6) or low dose (n=6) of AMT-130 in conjunction with an immunosuppression regimen. Key observations include: AMT-130 was generally well-tolerated at both dose levels; No treatment-related serious adverse events were reported; Three serious adverse events related to immunosuppression (mania, infection, and fever) were observed; all resolved fully with supportive care and; Perioperative changes in CSF NfL were consistent with previously reported observations, reinforcing their association with the surgical administration....In the third quarter of 2025, the Company expects to present data from its ongoing Phase I/II studies of AMT-130 in support of a potential BLA submission."

P1/2 data • Huntington's Disease

Huntington's disease clinical trials update: March 2025. (PubMed, J Huntingtons Dis) - "In this edition of the Huntington's Disease Clinical Trials Update, we expand on the ongoing phase I clinical trial of ALN-HTT02 from Alynlam Pharmaceuticals. We also report on the SAGE-718 (also known as dalzanemdor) program from Sage Therapeutics, with results of the phase II DIMENSION study and the recent termination of the open-label phase III PURVIEW study. Additionally, we discuss recent developments in the regulatory pathway for AMT-130, following discussions between uniQure and the U.S. Food and Drug Administration regarding key aspects of accelerated approval. Finally, we provide a comprehensive listing of all currently registered and ongoing clinical trials in Huntington's disease."

Journal • Huntington's Disease • Movement Disorders

uniQure Announces FDA Breakthrough Therapy Designation Granted to AMT-130 for the Treatment of Huntington’s Disease (GlobeNewswire) - "uniQure N.V...today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to AMT-130 for the treatment of Huntington’s disease, a rare, inherited neurodegenerative disorder for which there are currently no disease-modifying therapies available....The Breakthrough Therapy designation is supported by clinical data from the ongoing Phase I/II trials of AMT-130 for the treatment of Huntington’s disease....Additional regulatory update and guidance on the Biologics License Application submission expected in the second quarter of 2025."

Breakthrough therapy • FDA filing • Huntington's Disease

UniQure Shares Soar After Latest FDA Designation for Huntington's Disease Treatment (Market Watch) - "Gene therapy developer uniQure shares soared 46% in premarket trading after its treatment for Huntington's disease received breakthrough therapy designation from the Food and Drug Administration. Shares were trading around $13.70. The stock has doubled over the last year. The Netherlands-based company said the FDA's designation for AMT-130 is in addition to the regenerative medicine advanced therapy designation, orphan drug designation and fast track designation previously granted by the regulator."

Stock price • Huntington's Disease

CT-AMT-130-01: Safety and Proof-of-Concept (POC) Study with AMT-130 in Adults with Early Manifest Huntington's Disease (clinicaltrials.gov) - P1/2 | N=37 | Active, not recruiting | Sponsor: UniQure Biopharma B.V. | Recruiting ➔ Active, not recruiting

Enrollment closed • Huntington's Disease • Movement Disorders • NEFL

Huntington's Disease Clinical Trials Update: September 2024. (PubMed, J Huntingtons Dis) - "In this edition of the Huntington's Disease Clinical Trials Update, we expand on the ongoing extension study of PTC518 from PTC Therapeutics, including 12-month interim results from the parent study. We also discuss 24-month interim results from uniQure's AMT-130 program and 28-week follow-up results from Wave Life Sciences' SELECT-HD clinical trial of WVE-003. Additionally, we provide a comprehensive listing of all currently registered and ongoing clinical trials in Huntington's disease."

Journal • Review • Huntington's Disease • Movement Disorders

CT-AMT-130-01: Safety and Proof-of-Concept (POC) Study with AMT-130 in Adults with Early Manifest Huntington's Disease (clinicaltrials.gov) - P1/2 | N=37 | Recruiting | Sponsor: UniQure Biopharma B.V. | Active, not recruiting ➔ Recruiting

Enrollment open • Huntington's Disease • Movement Disorders • NEFL

uniQure Announces Alignment with FDA on Key Elements of Accelerated Approval Pathway for AMT-130 in Huntington’s Disease (GlobeNewswire) - "uniQure N.V...today announced that the company reached agreement with the U.S. Food and Drug Administration (FDA) on key elements of an Accelerated Approval pathway for AMT-130...'We have initiated BLA readiness activities and look forward to further engaging with the FDA in the first half of 2025 to discuss our statistical analysis plan and the technical CMC requirements.' As part of uniQure’s Regenerative Medicine Advanced Therapy (RMAT) Type B meeting held in late November, 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 for a BLA submission under the Accelerated Approval pathway...The FDA also agreed that cUHDRS may be used as an intermediate clinical endpoint and that reductions in neurofilament light chain (NfL) measured in cerebrospinal fluid (CSF) may serve as supportive evidence of therapeutic benefit in the application for accelerated approval."

FDA event • FDA filing • CNS Disorders • Huntington's Disease

CT-AMT-130-02: Safety and Efficacy of AMT-130 in European Adults with Early Manifest Huntington's Disease (clinicaltrials.gov) - P1/2 | N=14 | Active, not recruiting | Sponsor: UniQure Biopharma B.V. | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Huntington's Disease • Movement Disorders • CHI3L1 • GFAP • NEFL

uniQure Announces Third Quarter 2024 Financial Results and Highlights Recent Company Progress (GlobeNewswire) - "Advancing AMT-130 for the treatment of Huntington’s disease:...The Company will also discuss with the FDA a future communication plan that is expected to include additional sub-disciplinary meetings to take place in the first half of 2025...Patient dosing is ongoing in a third cohort of up to 12 patients to further evaluate both doses of AMT-130 together with an immunosuppression regimen, with a focus on evaluating near-term safety and tolerability. Enrollment in this third cohort is expected to be completed in the fourth quarter of 2024. The Company expects to provide an additional interim update from its ongoing Phase I/II clinical trials of AMT-130 in mid-2025."

Enrollment status • FDA event • P1/2 data • CNS Disorders • Huntington's Disease

Safety and Proof-of-Concept (POC) Study with AMT-130 in Adults with Early Manifest Huntington's Disease (clinicaltrials.gov) - P1/2 | N=36 | Active, not recruiting | Sponsor: UniQure Biopharma B.V. | Recruiting ➔ Active, not recruiting

Enrollment closed • Huntington's Disease • Movement Disorders • NEFL

Exon 1-targeting miRNA reduces the pathogenic exon 1 HTT protein in Huntington disease models. (PubMed, Brain) - "The effects were confirmed in primary Hu128/21 neuronal cultures. These results demonstrate that AAV5-miHTT gene therapy is an effective approach to lower both FL HTT and the pathogenic HTTexon1 levels, which could potentially have an additive therapeutic benefit compared to other HTT-targeting modalities."

Journal • CNS Disorders • Gene Therapies • Genetic Disorders • Huntington's Disease • Movement Disorders

uniQure Announces Positive Interim Data Update Demonstrating Slowing of Disease Progression in Phase I/II Trials of AMT-130 for Huntington’s Disease (GlobeNewswire) - P1/2 | N=26 | NCT04120493 | P1/2 | N=13 | NCT05243017 | Sponsor UniQure Biopharma B.V. | "uniQure N.V...today announced updated interim data including up to 24 months of follow-up data from 29 treated patients enrolled in the ongoing U.S. and European Phase I/II clinical trials of AMT-130 for the treatment of Huntington’s disease....A statistically significant, dose-dependent, slowing in disease progression measured by cUHDRS was observed through 24 months in patients receiving the high dose of AMT-130. At 24 months, the mean change in cUHDRS for patients receiving the high-dose of AMT-130 was -0.2 compared to -1.0 for patients in the propensity score-weighted external control, representing an 80% slowing of disease progression (p=0.007). At 24 months, the mean change in cUDHRS for patients receiving the low-dose of AMT-130 was -0.7 compared to -1.0 for patients in the propensity score-weighted external control..."

P1/2 data • CNS Disorders • Genetic Disorders • Huntington's Disease

uniQure Announces Positive Interim Data Update Demonstrating Slowing of Disease Progression in Phase I/II Trials of AMT-130 for Huntington’s Disease (GlobeNewswire) - "Based on the encouraging data from this interim analysis, uniQure anticipates the following next steps: In the second half of 2024, uniQure expects to hold a Type B, multi-disciplinary RMAT meeting with U.S. Food and Drug Administration (FDA) to present these updated data and discuss potential expedited clinical development pathways and accelerated approval. In the second half of 2024, uniQure expects to complete enrollment of the third cohort of the U.S. Phase I/II study exploring AMT-130 in combination with immunosuppression. In the first half of 2025, uniQure anticipates presenting safety data from this cohort. In mid-2025, uniQure expects to present another interim analysis from the ongoing Phase I/II studies of AMT-130. The data will include a 36-month comparison of treated patients to the propensity score-weighted external control."

FDA event • P1/2 data • Trial status • CNS Disorders • Genetic Disorders • Huntington's Disease