Objective: To investigate safety and tolerability of repeated subcutaneous (s.c.) doses of HER-096 in subjects with Parkinson’s disease.

Background: HER-096 is a retro-inverso isomerized peptide derived from the C-terminal domain of the human CDNF protein. HER-096 is metabolically stable, penetrates the blood-brain barrier and has shown robust neuroprotective and neurorestorative effects in a preclinical model of Parkinson’s disease (PD). In a randomized, double-blind, placebo-controlled Phase 1a study, single ascending s.c. doses of HER-096 were found to be well tolerated by healthy volunteer subjects.

Method: This Phase 1b study is a randomized, double-blind, placebo-controlled study assessing safety, tolerability and pharmacokinetics (PK) of s.c. HER-096, including extensive exploratory biomarker analyses. The first part of the study extends the Phase 1a cerebrospinal fluid (CSF) PK analysis in elderly healthy volunteers (n=8) to a 300 mg dose level. In the second part of the study, subjects with PD (n=24) receive repeated 200 or 300 mg s.c. doses of HER-096 or placebo (randomized in a 2:1 ratio), twice a week for four weeks. The primary endpoint is safety (incidence, type and severity of treatment-emergent adverse events, including injection-related events). PK properties of HER-096 are assessed as secondary endpoints. Exploratory biomarker endpoints include digital motor scores for bradykinesia and dyskinesia based on the Parkinson’s Kinetigraph (PKG^®), and changes in preselected biomarkers in blood, CSF and urine in relation to HER-096 exposure. In addition, untargeted proteomic, transcriptomic and metabolomic assays on blood, CSF and urine samples are included.

Results: Topline data from the Phase 1b study are expected to be available in September 2025. Single dose PK data so far show that HER-096, at 200-300 mg s.c. doses, provides pharmacologically relevant CSF concentrations (range: 15-179 ng/ml) and has an extended CSF half-life compared to plasma.

Conclusion: Single ascending s.c. doses of HER-096 were safe and well tolerated in the previous Phase 1a study. Combined CSF PK data from the Phase 1a and 1b studies suggest the expected level of CSF exposure in humans at the tested dose levels, in line with available preclinical PK/PD data. Topline safety data and available biomarker data from the repeated dose part of the study will be reported at the meeting.

« Back to 2025 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/a-phase-1b-study-to-investigate-safety-and-tolerability-of-repeated-subcutaneous-doses-of-her-096-in-subjects-with-parkinsons-disease/