uniQure (QURE) investor relations material

Study design and endpoints

• Pivotal Phase I/II trial of AMT-130 in Huntington's disease, with high- and low-dose arms, conducted in the U.S. and Europe, using single MRI-guided neurosurgical administration.

• Outcomes compared to propensity score-matched external controls from the Enroll-HD dataset; prespecified statistical analysis plan aligned with FDA guidance.

• Primary endpoint: change in cUHDRS at 36 months; key secondary endpoint: TFC at 36 months.

• 29 patients received AMT-130 (17 high dose, 12 low dose), with 12 per group reaching 36 months of follow-up.

• FDA agreed to cUHDRS as a registrational endpoint and supported use of external controls.

Key efficacy and biomarker results

• High-dose AMT-130 achieved a statistically significant 75% slowing of disease progression by cUHDRS at 36 months (p=0.003), meeting the primary endpoint.

• Statistically significant 60% slowing of decline in TFC at 36 months (p=0.033), indicating preserved independence.

• Favorable trends in additional clinical subdomains: SDMT (88% slowing, p=0.057), SWRT (113% slowing, p=0.002), TMS (59% slowing, p=0.174).

• CSF neurofilament light chain (NfL) levels remained below baseline at 36 months, supporting reduced neurodegeneration.

• Low-dose group showed biological activity but less robust, dose-dependent effects.

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 since December 2022.

• Most adverse events were related to the procedure and resolved with standard care; common events included headache and procedural pain.

• Short course of steroids identified as optimal immunosuppression; triple immunosuppression not favored.

• Long-term safety data (36 months) support a favorable risk-benefit profile.