Gain Therapeutics has announced positive topline results from its Phase 1 clinical trial evaluating GT-02287, a novel, orally administered small molecule therapy targeting glucocerebrosidase (GCase) for the treatment of Parkinson's disease. The study, which enrolled 72 healthy volunteers, demonstrated that GT-02287 was safe and generally well-tolerated, with evidence of CNS exposure and target engagement, paving the way for a Phase 1b trial in Parkinson's patients.
Phase 1 Trial Results
The Phase 1 trial assessed the safety, tolerability, and pharmacokinetics of GT-02287 in healthy volunteers up to 64 years of age. The results indicated that single and multiple doses of GT-02287 were safe and generally well-tolerated, even at the highest planned dose levels. Notably, approximately 15% of the participants were over the age of 50. Unblinded data confirmed the absence of discontinuations or serious adverse events. Furthermore, GT-02287 was detected in the cerebrospinal fluid (CSF), and peripheral target engagement was demonstrated, suggesting the drug's ability to reach the brain and interact with its intended target.
Upcoming Phase 1b Trial in Parkinson's Patients
Building on these promising Phase 1 results, Gain Therapeutics plans to initiate a Phase 1b trial in patients with Parkinson's disease in Q4 2024. The primary goal of this trial is to evaluate the safety and tolerability of GT-02287 in this patient population and to obtain proof of mechanism based on relevant biomarkers. Data from this trial is anticipated by mid-2025. According to Jonas Hannestad, M.D., Ph.D., Chief Medical Officer of Gain, this trial aims to demonstrate safety and tolerability in Parkinson's disease patients and to confirm the drug's mechanism of action through biomarker analysis.
GT-02287: A Novel Approach to Parkinson's Treatment
GT-02287 is designed to address Parkinson's disease, particularly in patients with or without a GBA1 mutation. Mutations in the GBA1 gene are the most common genetic abnormality associated with Parkinson's disease. The drug functions as an allosteric protein modulator, restoring the function of the lysosomal enzyme GCase, which becomes misfolded and impaired due to GBA1 mutations or other age-related stress factors. Preclinical studies in Parkinson's disease models have shown that GT-02287 can restore GCase enzymatic function, reduce aggregated α-synuclein, decrease neuroinflammation and neuronal death, increase dopamine levels, and improve both motor function and cognitive performance. Additionally, GT-02287 has been shown to significantly reduce plasma neurofilament light chain (NfL) levels, an emerging biomarker for neurodegeneration.
Preclinical Evidence Supports Cognitive Benefits
Compelling preclinical data in mouse models of GBA1-PD, including findings presented at FENS Forum 2024, demonstrated improvements in cognitive performance, in addition to motor performance, following GT-02287 administration. These findings suggest that GT-02287 has the potential to slow the progression of Parkinson's disease. Support for Gain’s Parkinson’s disease program has been provided by The Michael J. Fox Foundation for Parkinson’s Research (MJFF), The Silverstein Foundation for Parkinson’s with GBA, and the Eurostars-2 joint program with co-funding from the European Union Horizon 2020 research and Innosuisse – Swiss Innovation Agency.
Gene Mack, Interim CEO and current CFO of Gain, expressed enthusiasm about the promising profile of GT-02287, particularly highlighting the CNS exposure and target engagement observed in the Phase 1 trial.
