uniQure (QURE) Study Update summary

Program Overview and Objectives

• AMT-130 is a gene therapy in Phase I/II trials for early-to-moderate Huntington's disease, aiming to slow disease progression and improve quality of life.

• The therapy is administered once via MRI-guided neurosurgical delivery, with potential for long-term effects and early intervention.

• Direct brain delivery and a proprietary gene silencing platform target toxic exon-1 splice isoform and full-length mHTT.

Study Design and Patient Population

• Interim data presented from 29 patients in ongoing Phase I/II trials in the US, Europe, and UK, with 21 treated patients completing 24 months of follow-up.

• Patients have been followed for up to 3 years, with the majority reaching the 2-year mark, enabling robust post-hoc analyses.

• Propensity score methodology was used to compare AMT-130 treated patients to a well-matched external natural history cohort from TRACK-HD, TRACK-HD-ON, and PREDICT-HD studies (n=154).

• Baseline characteristics were well-matched between treated patients and controls.

Efficacy and Clinical Outcomes

• Statistically significant, dose-dependent slowing of disease progression observed at 24 months, as measured by cUHDRS.

• High-dose AMT-130 group showed an 80% reduction in the rate of disease progression compared to external controls (p=0.007); low-dose showed 30% slowing (p=0.21).

• High-dose patients remained essentially unchanged from baseline at 24 months, an unprecedented result in Huntington's disease.

• cUHDRS composite endpoint demonstrated greater sensitivity and reduced variability compared to individual subscales.

• High-dose AMT-130 showed favorable trends across individual cUHDRS components, including motor and cognitive measures.