uniQure N.V. announced updated interim data including up to 24 months of follow-up data from 29 treated patients enrolled in the ongoing U.S. and European Phase I/II clinical trials of AMT-130 for the treatment of Huntington?s disease. For the first time, uniQure conducted a statistical analysis of clinical outcomes for the 21 treated patients at 24 months compared to an expanded, propensity-weighted external control (n=154) developed in collaboration with the Cure Huntington?s Disease Initiative (CHDI) using data from the TRACK-HD, TRACK-ON and PREDICT-HD natural history studies. The external control includes patients that met the Phase I/II clinical trial eligibility criteria, and whose data contributions were statistically weighted using propensity scoring to closely match the baseline characteristics of patients treated with AMT-130.

Disease-related outcomes for these well-balanced cohorts were then compared after 24 months follow-up. A statistically significant, dose-dependent, slowing in disease progression measured by cUHDRS was observed through 24 months in patients receiving the high dose of AMT-130. At 24 months, the mean change in cUHDRS for patients receiving the high-dose of AMT-130 was -0.2 compared to -1.0 for patients in the propensity score-weighted external control, representing an 80% slowing of disease progression (p=0.007).

At 24 months, the mean change in cUDHRS for patients receiving the low-dose of AMT-130 was -0.7 compared to -1.0 for patients in the propensity score-weighted external control, representing a 30% slowing of disease progression (p=0.21). cUHDRS has been demonstrated to be the most sensitive measurement of clinical progression in Huntington?s disease patients. Trends in measurements of motor and cognitive function showed near-baseline stability throughout the 24 months of follow-up in patients receiving the high dose of AMT-130.

A statistically significant reduction of NfL in cerebrospinal fluid (CSF) was observed in patients treated with AMT-130. Patients treated with AMT-130 had a mean reduction in CSF NfL of 11% compared to baseline (p=0.02) at 24 months. Mean CSF NfL levels for both high and low doses were below baseline at 24 months.

CSF NfL is a well-characterized biomarker of neurodegeneration that has been shown to be strongly associated with the clinical severity of Huntington?s disease. An independent natural history study demonstrated a 26% increase in CSF NfL at 24 months in patients with early manifest Huntington?s disease (n=19). Based on data observed to date, AMT-130 remains generally well-tolerated, with a manageable safety profile at both doses.

There were no new AMT-130-related serious adverse events reported. Next Steps: ?Based on the encouraging data from this interim analysis, uniQure anticipates the following next steps: In the second half of 2024, uniQure expects to hold a Type B, multi-disciplinary RMAT meeting with U.S. Food and Drug Administration (FDA) to present these updated data and discuss potential expedited clinical development pathways and accelerated approval. In the second half of 2024, uniQure expects to complete enrollment of the third cohort of the U.S. Phase I/II study exploring AMT-130 in combination with immunosuppression.

In the first half of 2025, uniQure anticipates presenting safety data from this cohort. In mid-2025, uniQure expects to present another interim analysis from the ongoing Phase I/II studies of AMT-130. The data will include a 36-month comparison of treated patients to the propensity score- weighted external control.