uniQure (QURE) Status Update summary

Regulatory alignment and FDA guidance

• Achieved alignment with the FDA on key components of the primary statistical analysis plan and CMC requirements for AMT-130, supporting a BLA submission in Q1 2026.

• FDA supports an accelerated approval pathway for AMT-130 in Huntington's disease, with agreement on using cUHDRS as the registrational endpoint and Enroll-HD as the primary external control dataset.

• FDA agreed that validation of the AMT-130 manufacturing process can leverage prior HEMGENIX experience, with additional full-scale GMP batches and a single PPQ batch.

• No specific p-value or effect size threshold required by the FDA; focus is on consistency and robustness of results.

• Enroll-HD database approved as the primary external control for efficacy analysis, with TRACK-HD and PREDICT-HD used for sensitivity analyses.

Clinical and statistical analysis plan

• Primary efficacy analysis will compare three-year change in cUHDRS in high-dose patients to a propensity score-adjusted external control from Enroll-HD.

• Sensitivity analyses will use both propensity score weighting and matching, with supplemental analyses to assess robustness.

• Enroll-HD offers a large, contemporaneous dataset with over 33,000 patients, enhancing statistical power and matching quality.

• Previous data showed an 80% reduction in cUHDRS decline at high dose over two years; similar trends expected at three years.

• Phase I/II studies involve multi-center, dose-escalating trials in the US and Europe, with 26 US and 13 EU patients enrolled.

Manufacturing and commercial readiness

• AMT-130 manufacturing process is highly homologous to HEMGENIX, using the same facility, personnel, and quality systems.

• Process performance qualification for AMT-130 expected to take four to five months, leveraging HEMGENIX experience.

• Routine site inspections may occur, but no new inspection is specifically triggered by AMT-130.

• Commercial preparations focus on medical education, market access, treatment center onboarding, and patient mapping.