uniQure (QURE) Study Update summary

Study design and patient population

• Interim data from two ongoing multi-center Phase I/II trials enrolled 29 AMT-130 treated patients (12 low dose, 17 high dose) and 10 controls, with 21 treated patients completing 24 months of follow-up.

• Patients received a single administration of AMT-130 via MRI-guided neurosurgical delivery and have been followed for up to 3 years, with most reaching the 2-year mark.

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

• Baseline characteristics were well-matched between treated patients and controls, enabling robust post-hoc analyses.

Efficacy and biomarker results

• High-dose AMT-130 showed an 80% reduction in the rate of disease progression on cUHDRS at 24 months compared to external controls (p=0.007), with dose-dependent effects; low-dose showed 30% slowing (p=0.21).

• Motor and cognitive function remained near baseline for high-dose patients over 24 months, with favorable trends across cUHDRS components.

• Statistically significant reduction in CSF neurofilament light chain (NfL), a biomarker of neurodegeneration, was observed at 24 months (p=0.02 vs. baseline), with mean CSF NfL levels for both doses below baseline, contrasting with a 26% increase in untreated patients.

• The reduction in NfL is unprecedented in Huntington’s disease trials and supports the disease-modifying potential of AMT-130.

Safety and tolerability

• AMT-130 was generally well tolerated at both doses, with a manageable safety profile and no new drug-related serious adverse events reported during up to three years of follow-up.

• Most common adverse events were procedural, such as headache and post-lumbar puncture syndrome.

• Plans are in place to evaluate immune suppression protocols in a new cohort to further optimize perioperative safety.