uniQure (QURE) Study Update summary

Regulatory alignment and accelerated approval pathway

• Achieved alignment with the FDA on an accelerated approval pathway for AMT-130 in Huntington's disease, avoiding the need for an additional registration trial and reducing time to potential licensure by about five years.

• FDA agreed that data from ongoing phase I/II studies, using a natural history external control, may serve as the primary basis for a BLA application.

• cUHDRS accepted as an intermediate clinical endpoint, with CSF NfL reduction as supportive evidence.

• RMAT designation granted in May 2024, enabling more frequent regulatory interactions and recognizing potential to address unmet needs.

• Next FDA engagement planned for H1 2025 to finalize statistical analysis and CMC requirements.

Clinical data and study progress

• Phase I/II studies showed statistically significant, dose-dependent, and durable slowing of disease progression at 24 months, based on cUHDRS, compared to external controls.

• Statistically significant reduction in CSF neurofilament light chain levels at 24 months supports therapeutic effect.

• 24 subjects with two-year data (12 high dose, 12 low dose) included in regulatory briefing.

• Enrollment in Cohort 3 (immunosuppression safety) nearly complete; 45 patients expected to be dosed by Q1 2025.

• Initial safety update from Cohort 3 and three-year update on 21 patients from Cohorts 1 and 2 expected in 2025.

Study design and interim results

• Two multi-center, dose-escalating Phase I/II studies are ongoing in the US and Europe, exploring safety, tolerability, and efficacy of AMT-130.

• US study enrolled 26 early manifest Huntington's patients; European study enrolled 13, with a third cohort enrolling 12 more.

• Treated patients received a single administration of AMT-130 via MRI-guided neurosurgical delivery to the striatum.

• Long-term follow-up of treated patients is planned for five years.