Category: Parkinson’s Disease: Clinical Trials
Objective: The aim of this study was to investigate safety, tolerability and biomarker responses of repeated subcutaneous (s.c.) doses of HER-096 in subjects with Parkinson’s disease (PD).
Background: HER-096 is a brain-penetrating modified peptide derived from the C-terminal domain of the human CDNF protein. In preclinical models of Parkinson’s disease, HER-096 has shown disease-modifying potential through restoration of Unfolded Protein Response signaling and improved mitochondrial function.
Method: This Phase 1b study was a randomized, double-blind, placebo-controlled study assessing safety, tolerability and pharmacokinetics (PK) of s.c. HER-096, including extensive exploratory biomarker analyses. Subjects with PD (n=24) received 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 was safety and tolerability. Plasma and CSF PK were assessed as secondary endpoints. Exploratory biomarker endpoints included changes in preselected biomarkers in blood and CSF. In addition, untargeted proteomic and metabolomic assays on blood, CSF and extracellular vesicle samples were included.
Results: Repeated doses of HER-096 were safe and well tolerated. Majority of reported adverse events were related to the injection site, and were transient and mostly mild. There were no serious adverse events, dose-limiting toxicities or discontinuations with subjects receiving HER-096 injections. Plasma PK profile in PD patients was comparable to healthy volunteers (Phase 1a study). Mean CSF levels of HER-096 8 h after the last dose were 81+/-21 and 143+/-41 ng/ml in 200 and 300 mg groups, respectively. After 28-day dosing, both targeted and untargeted biomarker assessments indicated a biological response to HER-096 dosing, including biomarkers that are connected to the mechanism of action of HER-096 (proteostasis and mitochondria). There was notable pathway level concordance in biomarker responses across different sample types (plasma, CSF, EV) and technologies.
Conclusion: The primary endpoint of safety and tolerability was met. Plasma and CSF PK profiles support moving to Phase 2 with the current dose levels and dosing frequency. Exploratory biomarker data revealed changes in biomarkers related to e.g. proteostasis and mitochondria, indicating biological response to treatment in PD patients.
To cite this abstract in AMA style:
K. Holmström, K. Jääskeläinen, N. Kulesskaya, A. Ludwig, J. Koskinen, A. Vuolanto, A. Domanska, M. Engström, S. Määttänen, P. Vainio, M. Scheinin, C. Videbaek, Z. Lovro, F. Scheperjans, J. Rinne, H. Huttunen. A Phase 1b Study to Investigate Safety, Tolerability and Biomarker Responses of Repeated Subcutaneous Doses of HER-096 in Subjects with Parkinson’s Disease [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/a-phase-1b-study-to-investigate-safety-tolerability-and-biomarker-responses-of-repeated-subcutaneous-doses-of-her-096-in-subjects-with-parkinsons-disease/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/a-phase-1b-study-to-investigate-safety-tolerability-and-biomarker-responses-of-repeated-subcutaneous-doses-of-her-096-in-subjects-with-parkinsons-disease/