ifezuntirgene inilparvovec (AMT-130) / uniQure - LARVOL DELTA

uniQure Announces Additional Data from Ongoing Phase I/II Studies of ifezuntirgene inilparvovec (AMT-130) in Huntington’s Disease Showing Continued Slowing of Disease Progression (Yahoo Finance) - "In 12 high-dose patients at 48 months, both cUHDRS and TFC continued to demonstrate meaningful slowing of disease progression and clear dose-dependent response; the primary endpoint of cUHDRS showed 44% slowing of disease progression (non-significant p=0.144) and TFC showed a 61% slowing of disease progression (nominal p=0.008); Updated data reflecting all 15 high-dose patients showed substantial treatment effect on both cUHDRS and TFC at 36 months, the timepoint that is the regulatory anchor for the submitted BLA and the confirmatory study; the new analysis demonstrated 80% slowing of disease progression based on cUHDRS (nominal p=0.005) and 67% based on TFC (nominal p=0.011); Treatment effect at 48 months likely understated by substantial missing data and survivor bias in updated external control; post hoc analysis using prior external control showed slowing of disease of 54% on cUHDRS (nominal p=0.041) and 68% on TFC (nominal p=0.001) at 48 months."

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

MicroRNAs in polyglutamine diseases: Mechanistic insights, circulating biomarkers, and emerging microRNA-based therapeutic strategies. (PubMed, Neurobiol Dis) - P1/2 | "AAV5-miHTT has advanced to a first-in-human trial for Huntington's disease (NCT04120493)-a key milestone in clinical translation...Overcoming these barriers will require integrative approaches that combine single-cell transcriptomics, engineered delivery systems, machine learning, and longitudinally phenotyped clinical cohorts. This review integrates mechanistic insights, biomarker discovery, and therapeutic development to move miRNA-based strategies toward disease-modifying interventions for PolyQ disorders."

Biomarker • First-in-human • Journal • Review • Ataxia • CNS Disorders • Huntington's Disease • Metabolic Disorders • Movement Disorders • Muscular Atrophy • Psychiatry • ATXN3

uniQure Announces Submission of Biologics License Application for Ifezuntirgene Inilparvovec (AMT-130) in Huntington’s Disease (GlobeNewswire) - "Company also announces the submission of a Marketing Authorisation Application for ifezuntirgene inilparvovec in the U.K...Both submissions are supported by the three-year data analysis from the Phase I/II study, in which ifezuntirgene inilparvovec demonstrated a slowing of disease progression...The Company intends to present a four-year data analysis from the ongoing Phase I/II clinical studies before the end of the current third quarter."

FDA filing • MHRA filing • P1/2 data • CNS Disorders • Huntington's Disease

A Cost-Effectiveness Analysis for Treatments of Patients with Early Stage Huntington's Disease in the USA. (PubMed, Pharmacoecon Open) - "From a modified US societal perspective, this analysis suggests that AMT-130 may be cost-effective relative to SoC, whereas Tominersen exceeds the WTP threshold of $500,000 per QALY gained. Further evidence on long-term effectiveness and durability is needed to inform policy and reimbursement decisions."

HEOR • Journal • CNS Disorders • Huntington's Disease • Movement Disorders • Rare Diseases

uniQure N.V. stock surges on positive Phase 1/ 2 data for AMT-130 in Huntington's disease (AD HOC NEWS) - "The UHDR study evaluates AMT-130, uniQure's one-time gene therapy designed to lower mutant huntingtin protein levels in the brain. Interim analysis from low- and high-dose cohorts showed a 60% slowing in composite Unified Huntington's Disease Rating Scale scores versus natural history data at 24 months. High-dose patients demonstrated even stronger signals, with sustained motor function preservation....Analysts note the data de-risks the program, potentially paving way for Phase 3 initiation by late 2026."

New P3 trial • P1/2 data • CNS Disorders • Huntington's Disease

Recent Company Developments and Updates (GlobeNewswire) - "In September 2026, the Company plans to present data from its ongoing Phase I/II studies of AMT-130. The update is expected to include follow-up data on all patients treated with AMT-130 in the first two cohorts, including four years of follow-up on 24 patients (12 patients at the high-dose and 12 patients at the low dose). In March 2026, the Company held a successful pre-submission meeting with the United Kingdom’s (U.K.) Medicines and Healthcare products Regulatory Agency (MHRA) and the regulatory submission is progressing as planned for the third quarter of 2026."

MHRA filing • P1/2 data • CNS Disorders • Huntington's Disease

uniQure Announces Plan for BLA Submission for AMT-130 in Huntington’s Disease (UniQure Press Release) - "3-year analysis from the Phase I/II study can serve as the primary basis of a Biologics License Application for accelerated approval with FDA...In addition, the FDA seeks to align on the confirmatory study design prior to the BLA submission, including consideration of concurrent control on standard-of-care therapy instead of a sham procedure. FDA communicated that they would work as expeditiously as possible with uniQure on this effort. The Company is committed to conducting the confirmatory study without delay and expects to further align with the FDA on the details of such a study prior to BLA submission. The Company intends to submit the BLA in the third quarter of 2026....The Company expects to receive final minutes within 30 days of the recent Type B meeting."

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

Effect of immunosuppressive regimen on immunological parameters in participants receiving AMT-130, an investigational AAV-based gene therapy for Huntington’s disease (ASGCT 2026) - P1/2 | "Methods Cohort 3 evaluated two perioperative immunosuppressive regimens: preoperative dexamethasone monotherapy that was continued for one month post-operatively, or a triple-drug therapy consisting of preoperative rituximab, sirolimus, and dexamethasone, with the latter two continued for one month post-operatively. Immune suppression did not reduce the previously described post-operative peak in CSF Nf-L, suggesting the Nf-L increase results from the surgical procedure (ie, cannula placement) and may not be caused by AMT-130 or anti-AAV5 immune responses. Analysis of the risk-benefit profile does not support triple-drug immunosuppression but may support use of dexamethasone monotherapy during the administration of AMT-130."

Gene therapy • Bipolar Disorder • Cholestasis • CNS Disorders • Gene Therapies • Hepatology • Huntington's Disease • Infectious Disease • Mood Disorders • Movement Disorders • CHI3L1 • IFNG • NEFL

Focused Ultrasound as a Non-invasive Platform for the Striatal Delivery of AAV-Based Gene Therapies Targeting Msh3 in a Mouse Model of Huntington’s Disease (ASGCT 2026) - "Unfortunately, there are still no cures for Huntington’s disease and until the recent promising results from the uniQure’s AMT-130 clinical trial, HTT-lowering clinical trials have yielded limited success, highlighting the necessity for novel and alternative therapeutic strategies...Two-way ANOVA followed by Sidak’s multiple comparisons test. **** p"

Gene therapy • Non-invasive • Preclinical • CNS Disorders • Gene Therapies • Huntington's Disease • Infectious Disease • Movement Disorders • MLH1 • MSH3 • PMS1 • PMS2

Intraparenchymal delivery to the brain: Accelerating neurotherapeutics via a novel trajectory guide for minimally-invasive image-guided surgery (ASGCT 2026) - "Existing technologies require a lengthy (>90min) guide alignment period per catheter (Taha, B.R., 2021) and some protocols, like the recent AMT-130 Huntington’s trial, use six separate catheter alignments...Intraoperative image analysis occurred automatically with users only selecting a target point. Future work will validate these results in vivo with pre-clinical primate trials."

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

uniQure Announces Successful UK MHRA Pre-Submission Meeting for AMT-130 in Huntington’s Disease (The Manila Times) - "...plans to submit a Marketing Authorization Application (MAA) for AMT-130 for the treatment of Huntington’s disease in the third quarter of 2026...During the meeting, the Company and MHRA discussed the data package and manufacturing requirements to support a MAA submission for AMT-130. Following these discussions, the Company expects to submit a MAA based on the three-year analysis from the ongoing U.S. and European Phase I/II clinical trials."

MHRA filing • CNS Disorders • Huntington's Disease

In addition to the continued engagement with the MHRA, the Company has been granted a Type B meeting with the U.S. Food and Drug Administration in the second quarter of 2026. (The Manila Times) - "The Company expects to discuss key elements of a potential Phase III trial design and to receive feedback on the proposed statistical analysis plan for the four-year analysis expected in the third quarter of 2026. The Company is also actively pursuing additional regulatory pathways in international markets for potential registration of AMT-130 and expects to provide further updates in the second half of 2026."

FDA event • New P3 trial • Regulatory • CNS Disorders • Huntington's Disease

Discussant: AMT-130 Huntington’s Disease Gene Therapy: Clinical Study Outcomes at 3 Years (AAN 2026) - No abstract available

Clinical • Gene therapy • Gene Therapies • Huntington's Disease • Movement Disorders

Presenter: AMT-130 Huntington’s Disease Gene Therapy: Clinical Study Outcomes at 3 Years (AAN 2026) - P1/2 | "High-dose AMT-130 met its primary and a key secondary endpoint at 36 months compared with a well-matched NatHx cohort control, with positive trends seen on additional clinical and supportive measures."

Clinical • Gene therapy • Gene Therapies • Huntington's Disease • Movement Disorders

uniQure Provides Regulatory Update on AMT-130 for Huntington’s Disease (GlobeNewswire) - "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 uniQure conduct a prospective, randomized, double-blind, sham surgery-controlled study. uniQure intends to continue engaging with the FDA regarding Phase III development considerations and plans to request a Type B meeting in the second quarter of 2026 to further discuss potential study design approaches."

FDA event • Trial status • CNS Disorders • Huntington's Disease

uniQure Announces Type A Meeting Scheduled with FDA (GlobeNewswire) - "The Company expects to provide a regulatory update after the receipt of official meeting minutes."

FDA event • Huntington's Disease

AMT-130 gene therapy: a promising disease-modifying approach for Huntington's disease. (PubMed, Ann Med Surg (Lond)) - "While long-term efficacy and broader clinical validation are still required, AMT-130 shows strong potential to shift HD treatment from purely symptomatic care toward meaningful disease modification. Its success may also pave the way for microRNA-based therapies in other neurodegenerative disorders."

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

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