uniQure (QURE) Study update summary

Study design and endpoints

• Phase I/II study evaluated high- and low-dose AMT-130 in Huntington’s disease, with cUHDRS and TFC assessed at 36 and 48 months against propensity score-matched ENROLL-HD external controls.

• The first two cohorts included 29 patients (17 high dose, 12 low dose); 51 patients were dosed across all cohorts. Secondary endpoints included SDMT, SWRT and TMS.

Efficacy at 36 months

• In an expanded analysis, all 15 high-dose patients reaching month 36 showed 80% cUHDRS slowing (nominal P=0.005) and 67% TFC slowing (nominal P=0.011) versus ENROLL-HD B.

• The original 12-patient analysis versus ENROLL-HD A showed 75% cUHDRS slowing (P=0.003) and 60% TFC slowing (P=0.033); these data supported regulatory submissions.

• Secondary endpoints showed favorable trends, including 59% slowing on total motor score and >120% slowing on SDMT and Stroop, with nominally significant P values; SDMT and SWRT also showed significant slowing.

• Dose-dependent response was consistent with a treatment effect.

Efficacy at 48 months

• In 12 high-dose patients versus updated ENROLL-HD B controls, cUHDRS slowing was 44% (P=0.144; not statistically significant) and TFC slowing was 61% (P=0.008).

• Post hoc comparison with ENROLL-HD A showed 54% cUHDRS slowing (nominal P=0.041) and 68% TFC slowing (nominal P<0.001).

• High-dose patients consistently outperformed low-dose patients on cUHDRS and TFC; the high-dose cUHDRS effect was one point favorable versus low dose across 48 months, while low-dose cUHDRS declined ~2 points over four years.

• At 48 months, secondary endpoints showed significant slowing on SWRT (P=0.006) and modest effects on SDMT and TMS.

• ENROLL-HD B controls had survivor bias and >50% missingness at year four, and declined more slowly than ENROLL-HD A; these limitations may understate progression and treatment effect.