Uniqure N.v. · NASDAQ:QURE
Uniqure — 2026 HD Therapeutics Conference
33 slides from Uniqure's conference presentation, Feb 24, 2026
Slide 1: AMT-130: Propensity Score Adjustment Mitigates Potential Bias from Striatal Volume Absence in Enroll-HD
AMT-130: Propensity Score Adjustment Mitigates Potential Bias from Striatal Volume Absence in Enroll-HD David Margolin VP, Clinical Development 2026 HD Therapeutics Conference Charles – Huntington’s Disease Community Advocate
Slide 2: Disclaimer
Disclaimer This presentation may contain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical fact are forward-looking statements,
Slide 3: Author Disclosures
Author Disclosures David Margolin, Kenechi Ejebe, Wenfei Zhang, and Na Wang are employees of uniQure, Inc., and own stock or stock options Walid Abi-Saab is an employee of uniQure Switzerland GmbH and owns stock or stock options AMT-130 is an investigational agent currently being studied in the trea
Slide 4: AMT-130 Overview
AMT-130 Overview AMT-130 is an investigational gene therapy candidate for the treatment of Huntington’s disease1,2 AAV5 capsid Expression cassette miQURE® miHTT miRNA promoter polyA One-time administration via MRI-guided, convection- enhanced stereotactic neurosurgical delivery directly into the str
Slide 5: Study Design for AMT-130 Pivotal Phase I/II 3-year Analysis: High-Dose Cohort 1
AMT-130 data cutoff June 30, 2025 Study Design for AMT-130 Pivotal Phase I/II 3-year Analysis: High-Dose Cohort1 Baseline 1 year 2 year 3 year 4 year 5 year Time on study N = 17 dosed High-Dose AMT-130 Arm (study ongoing) n = 12 had 3 years of follow-up 10 (9) 7 (3) as of June 30, 2025 Key eligibili
Slide 6: Study Design for AMT-130 Pivotal Phase I/II 3-year Analysis: High-Dose Cohort 1
AMT-130 data cutoff June 30, 2025 Study Design for AMT-130 Pivotal Phase I/II 3-year Analysis: High-Dose Cohort1 Baseline 1 year 2 year 3 year 4 year 5 year Time on study N = 17 dosed High-Dose AMT-130 Arm (study ongoing) n = 12 had 3 years of follow-up 10 (9) 7 (3) as of June 30, 2025 Key eligibili
Slide 7: Study Design for AMT-130 Pivotal Phase I/II 3-year Analysis: External Comparator Cohort 1
AMT-130 data cutoff June 30, 2025 Study Design for AMT-130 Pivotal Phase I/II 3-year Analysis: External Comparator Cohort1 Baseline 1 year 2 year 3 year 4 year 5 year Time on study ENROLL-HD Matched External Control Arm (N = 940) n = 583 from Enroll-HD had 3 years of Propensity score matched to AMT-
Slide 8: Study Design for AMT-130 Pivotal Phase I/II 3-year Analysis: High-Dose Cohort 1
AMT-130 data cutoff June 30, 2025 Study Design for AMT-130 Pivotal Phase I/II 3-year Analysis: High-Dose Cohort1 Baseline 1 year 2 year 3 year 4 year 5 year Time on study N = 17 dosed n = 12 had 3 years of follow-up 10 (9) 7 (3) High-Dose AMT-130 Arm (study ongoing) as of June 30, 2025 ENROLL-HD Mat
Slide 9: Propensity Score Matching (PSM)
AMT-130 data cutoff June 30, 2025 Propensity Score Matching (PSM) Original, unadjusted population Clinical trial participants Real-world participants Abbreviations: PSM, propensity score matching Reference: Liau MYQ, et al. World J Methodol. 2024 Mar 20;14(1):90590. February 24, 2026 | 9
Slide 10: Propensity Score Matching (PSM)
AMT-130 data cutoff June 30, 2025 Propensity Score Matching (PSM) Original, unadjusted population PSM-adjusted population Adjustment summary Clinical trial Clinical trial participants participants Trial participants are matched to people with the most similar propensity score. PSM Modeling Individua
Slide 11: Demographics and Disease Characteristics
AMT-130 data cutoff June 30, 2025 Demographics and AMT-130 PSM External Control Disease Characteristics High-Dose (Enroll-HD) Mean (N = 17) (N = 940) Sex, Males (%) 47.1 55.6 Age, years 45.8 45.2 CAG repeats 42.4 42.8 CAP100 score 86.2 86.8 DCL = 3, 4 (%) 35.3, 64.7 30.5, 69.5 PIN Score 0.77 0.81 cU
Slide 12: Primary Endpoint: cUHDRS at 3 Years
AMT-130 data cutoff June 30, 2025 Primary Endpoint: cUHDRS at 3 Years cUHDRS LSM change from baseline at 3 years (±SE; MMRM) Enroll-HD PSM At 3 years: High-Dose External Control High-dose AMT-130 0.0 N = 17 N = 940 significantly reduced disease -0.38 progression by 75% based on -0.5 cUHDRS compared
Slide 13: Key Secondary Endpoint: TFC at 3 Years
AMT-130 data cutoff June 30, 2025 Key Secondary Endpoint: TFC at 3 Years TFC LSM change from baseline at 3 Years (±SE; MMRM) Enroll-HD PSM At 3 years: High-Dose External Control High-dose AMT-130 N = 17 N = 940 0.0 significantly reduced disease progression by 60% -0.36 based on TFC compared with -0.
Slide 14: Supportive Endpoint: Change in CSF NfL
AMT-130 data cutoff June 30, 2025 Supportive Endpoint: Change in CSF NfL CSF NfL mean change from baseline (±SE) 10 Mean CSF NfL were below 5 baseline at 2 and 3 years following administration of 0 Disease worsening high-dose AMT-130 NfL change -5 -8.2% -9.7% -10 In natural history studies, NfL incr
Slide 15: Overview of Adverse Events as of June 30, 2025 Data Cutoff
AMT-130 data cutoff June 30, 2025 Overview of Adverse Events as of June 30, 2025 Data Cutoff Low-dose High-dose Sham Surgery Dose-Blinded All AMT-130 AMT-130 AMT-130 (Cohort 3) (Cohorts 1, 2 and 3) (N = 10) (Cohort 1) (Cohort 2) (N = 12) (N = 45a) (N = 13a) (N = 20a) N % N % N % N % N % Any TEAEsb 1
Slide 16: Pivotal Phase I/II Study Summary
AMT-130 data cutoff June 30, 2025 Pivotal Phase I/II Study Summary • High-dose AMT-130 met primary and key secondary endpoints at 3 years Statistically significant 75% slowing of disease 1 progression based on cUHDRS Statistically significant 60% slowing of disease 2 progression based on TFC 3 Reduc
Slide 17: Pivotal Phase I/II Study Summary
AMT-130 data cutoff June 30, 2025 Pivotal Phase I/II Study Summary • High-dose AMT-130 met primary and key secondary endpoints at 3 years Statistically significant 75% slowing of disease 1 progression based on cUHDRS MRI data were not collected as part of ENROLL-HD protocol Statistically significant
Slide 18: TRACK-HD: Effect of Volumetric Criteria
TRACK-HD Effect of Volumetric Criteria Baseline Striatal Volume is a Predictor of Clinical Progression in TRACK-HD 105 participants from TRACK-HD with appropriate clinical criteria (DCL=4; TFC 9-13; ≥1 evaluable follow-up MRI scan) with 1–5 years of follow-up, stratified by baseline imaging Low stri
Slide 19: TRACK-HD and PREDICT-HD Participants Meeting AMT-130 Eligibility Criteria
TRACK-HD / TRACK-ON / PREDICT-HD Effect of Volumetric Criteria TRACK-HD and PREDICT-HD Participants Meeting Pivotal Phase I/II AMT-130 Clinical Eligibility Criteria, with/without Volumetric Criteria TRACK-HD/TRACK-ON and PREDICT-HD enrollees with HD N = 1,475 Did not meet AMT-130 eligibility criteri
Slide 20: TRACK-HD and PREDICT-HD Participants Meeting AMT-130 Eligibility Criteria
TRACK-HD / TRACK-ON / PREDICT-HD Effect of Volumetric Criteria TRACK-HD and PREDICT-HD Participants Meeting Pivotal Phase I/II AMT-130 Clinical Eligibility Criteria, with/without Volumetric Criteria TRACK-HD/TRACK-ON and PREDICT-HD enrollees with HD N = 1,475 Did not meet AMT-130 Did not meet AMT-13
Slide 21: Baseline Volumetric Criteria Predicts cUHDRS Decline in the Absence of Other Covariates
TRACK-HD / TRACK-ON / PREDICT-HD Effect of Volumetric Criteria Baseline Volumetric Criteria Predicts cUHDRS Decline in the Absence of Other Covariates Unweighted PS Weighted (Covariates: baseline age, sex, CAP100, DCL, TFC, TMS, SDMT, SWR) Volumetric criteria Volumetric criteria Volumetric criteria
Slide 22: Propensity Score Weighting (PSW)
TRACK-HD / TRACK-ON / PREDICT-HD Effect of Volumetric Criteria Propensity Score Weighting (PSW) Original, unadjusted population Clinical trial participants Real-world participants Abbreviations: PS, propensity score; PSW, propensity score weighting. February 24, 2026 | 22
Slide 23: Propensity Score Weighting (PSW)
TRACK-HD / TRACK-ON / PREDICT-HD Effect of Volumetric Criteria Propensity Score Weighting (PSW) PSW adjusted population Adjustment Original, unadjusted population summary Clinical trial Clinical trial participants participants People with more similar propensity scores get up-weighted, and people wi
Slide 24: Propensity Score Weighting (PSW)
TRACK-HD / TRACK-ON / PREDICT-HD Effect of Volumetric Criteria Propensity Score Weighting (PSW) PSW adjusted population Adjustment Original, unadjusted population summary Clinical trial Clinical trial participants participants People with more similar propensity scores get up-weighted, and people wi
Slide 25: Baseline Volumetric Criteria Are No Longer Predictive of cUHDRS Decline
TRACK-HD / TRACK-ON / PREDICT-HD Effect of Volumetric Criteria Baseline Volumetric Criteria Are No Longer Predictive of cUHDRS Decline When Propensity Score Adjustments Are Applied Unweighted PS Weighted (Covariates: baseline age, sex, CAP100, DCL, TFC, TMS, SDMT, SWR) Volumetric criteria Volumetric
Slide 26: Baseline Volumetric Criteria Are No Longer Predictive of TFC Decline
TRACK-HD / TRACK-ON / PREDICT-HD Effect of Volumetric Criteria Baseline Volumetric Criteria Are No Longer Predictive of TFC Decline When Propensity Score Adjustments are Applied Unweighted PS Weighted (Covariates: baseline age, sex, CAP100, DCL, TFC, TMS, SDMT, SWR) Volumetric criteria Volumetric cr
Slide 27: Study Design for AMT-130 Phase I/II Cohort 4: Lower Striatal Volume as Eligibility Criteria
AMT-130 Cohort 4 Study Design for AMT-130 Phase I/II Cohort 4: Lower Striatal Volume as Eligibility Criteria Baseline 1 year 2 year 3 year 4 year 5 year Time on study N=6 High Dose (study ongoing) Key eligibility criteria o Aged 25-65 years o Diagnostic confidence level: 3 or 4* o Total functional c
Slide 28: Study Design for AMT-130 Phase I/II Cohort 4: Lower Striatal Volume as Eligibility Criteria
AMT-130 Cohort 4 Study Design for AMT-130 Phase I/II Cohort 4: Lower Striatal Volume as Eligibility Criteria Baseline 1 year 2 year 3 year 4 year 5 year Time on study N=6 High Dose (study ongoing) Key eligibility criteria o Aged 25-65 years o Diagnostic confidence level: 3 or 4* o Total functional c
Slide 29: Baseline Demographics and Disease Characteristics Relevant to Eligibility: Cohort 4
AMT-130 Cohort 4 Baseline Demographics and Disease Characteristics Relevant to Eligibility: Cohort 4 Demographics and AMT-130 High-Dose Disease Characteristics Cohort 4 Mean or % (n=6) Sex, Males (%) 16.7 Age 43.7 CAG repeats 44.5 DCL = 3, 4 (%) 16.7, 83.3 TFC 12.0 Abbreviations: CAG, cytosine-adeni
Slide 30: Striatal Volume Summary Points
Striatal Volume Summary Points • Previous studies have indicated that striatal volume is predictive of decline, this was replicated in the TRACK-HD/TRACK-ON/PREDICT-HD combined cohort • However, propensity score analysis supported that other covariates can be substituted to adjust for the effect of
Slide 31: Clinical Trial Sites
Clinical Trial Sites CT-AMT-130-01 (US) CT-AMT-130-02 (UK, Poland) University of Alabama The University of Texas, Houston Activated Sites: Principal Investigator: Victor Sung, MD Principal Investigator: Erin Furr-Stimming, MD Cardiff University University of California, San Francisco Virginia Common
Slide 32: Thank YOU!
Acknowledgements AMT-130 Study Steering Committee: DSMB members Ralf Reilmann (co-chair), GHI, Muenster, Germany Vicki Wheelock (co-chair), UCDH, Sacramento, CA, USA uniQure and MedPace Clinical Studies Teams Samuel Frank, BIDMC, MA, USA Erin Furr-Stimming, UTH, Houston, TX, USA HD Community Jeff Lo
Slide 33: uniQure
uniQure