uniQure N.V. announced initial observations on the first four patients enrolled in the lower-dose cohort of its ongoing Phase I/II clinical trial of AMT-130 for the treatment of Huntington’s disease. Two of the four enrolled patients received AMT-130, and two patients experienced an imitation (sham) surgery in this randomized, blinded clinical trial being conducted in the United States. One-Year Observations on AMT-130: The first four patients were a heterogeneous group representing a spectrum of Stage I-II early manifest disease with 41-44 CAG repeats, baseline Total Functional Capacity scores of 10-13 and Total Motor Scores of 7-23. AMT-130 was generally well tolerated in the treated patients at the lower dose of 6x1012 vector genomes (vg). There have been no serious adverse events (SAEs) to date related to AMT-130 in these patients. NfL increased as expected immediately following the AMT-130 surgical procedure and returned to baseline in the two treated patients. NfL remained relatively constant in the two untreated control patients. Structural magnetic resonance imaging did not reveal any clinically meaningful safety findings in either treated or control patients at one year of follow-up. Measurements of total and mutant HTT protein in the cerebral spinal fluid of the four patients were highly variable and inconclusive. The safety profile of AMT-130 in the low-dose cohort to date supports continued enrollment of patients in the higher-dose cohort of 6x1013 vg. Nineteen patients have been enrolled in the clinical trial to date, including 9 of 16 in the higher-dose cohort. A clinical update on the low-dose cohort of ten patients, largely focused on safety, is expected in the second quarter of 2022 after patient unblinding. Full safety and efficacy data from the first two cohorts in the Phase I/II clinical trial are expected in the first half of 2023 after all patients in the higher-dose cohort have achieved one year of follow-up. Planned Expansion of Phase I/II Studies of AMT-130: The U.S. Phase I/II clinical trial of AMT-130 for the treatment of Huntington’s disease is exploring the safety, tolerability, and efficacy signals in a planned 26 total patients with early manifest Huntington’s disease split into a 10 patient, low-dose cohort followed by a 16 patient, higher-dose cohort; patients will be randomized to treatment with AMT-130 or an imitation (sham) surgery. The multi-center trial consists of a blinded 12-month core study period followed by unblinded long-term follow-up for five years. A total of 16 patients in the clinical trial will receive a single administration of AMT-130 through MRI-guided, convection-enhanced stereotactic neurosurgical delivery directly into the striatum (caudate and putamen). uniQure also plans to initiate a third cohort in the ongoing U.S. Phase I/II clinical trial in the second half of 2022 that will explore the use of alternative stereotactic navigation systems to simplify placement of catheters for infusions of AMT-130. This will be explored in two steps and include up to 18 additional randomized patients who will receive the higher dose of 6x1013 vg. The European, open-label Phase Ib/II study of AMT-130 will enroll 15 patients with early manifest Huntington’s disease across two dose cohorts. Screening has been initiated, and the first procedures in the lower-dose cohort are expected to be complete in early 2022. Together with the U.S. study, the European study is intended to establish safety, proof of concept, and the optimal dose of AMT-130 to take forward into Phase III development or into a confirmatory study should an accelerated registration pathway be feasible. AMT-130 is uniQure’s first clinical program focusing on the central nervous system (CNS) incorporating its proprietary miQURE® platform.