Gain Therapeutics Inc. (GANX:NASDAQ) has commenced its Phase 1b clinical trial for GT-02287, a promising therapeutic candidate for Parkinson's disease (PD). The open-label trial, initiated following regulatory approval in Australia, will assess the safety and tolerability of GT-02287 over a three-month dosing period in patients with either idiopathic or GBA1-associated PD. Enrollment is anticipated to conclude by Spring 2025, with initial results expected mid-year.
The Phase 1b trial builds upon encouraging outcomes from a prior Phase 1 study involving healthy volunteers. In this earlier trial, GT-02287 exhibited a favorable safety profile and demonstrated significant engagement with the glucocerebrosidase (GCase) enzyme, a key biomarker in Parkinson's disease. According to a company news release, GT-02287 led to a statistically significant increase in GCase activity, exceeding a 50% improvement. Dr. Jonas Hannestad, Chief Medical Officer of Gain, noted the high level of interest from investigators and potential participants in Australia, a region historically underrepresented in PD clinical trials.
Preclinical Evidence
Preclinical data further support GT-02287's potential as a disease-modifying therapy. The compound, a brain-penetrant allosteric modulator, has shown efficacy in restoring GCase enzymatic function, reducing neuroinflammation, and improving motor and cognitive performance in preclinical models of PD. GT-02287 has garnered financial support from organizations such as the Michael J. Fox Foundation and The Silverstein Foundation.
Trial Design and Endpoints
The Phase 1b trial will evaluate the safety and tolerability of GT-02287 at a dose of 13.5 mg/kg/day over three months in patients with GBA1-PD or idiopathic Parkinson's disease. Secondary endpoints include assessing pharmacokinetics, GCase modulation, levels of GCase substrates, and other relevant biomarkers in plasma and cerebrospinal fluid. The trial is being conducted across seven sites in major metropolitan areas of Australia.
GT-02287: Mechanism of Action
GT-02287 is an orally administered, brain-penetrant small molecule designed to restore the function of the lysosomal enzyme glucocerebrosidase (GCase). GCase becomes misfolded and impaired due to mutations in the GBA1 gene, the most common genetic abnormality associated with Parkinson's disease, or other age-related stress factors. By restoring GCase function, GT-02287 aims to reduce aggregated α-synuclein, neuroinflammation, and neuronal death, potentially slowing or stopping the progression of Parkinson's disease.
Market Opportunity
Parkinson's disease remains the second most common neurodegenerative disease after Alzheimer's, with current treatments primarily addressing symptoms rather than the underlying disease mechanisms. Gain Therapeutics believes that GT-02287, with its novel mechanism of action targeting GCase dysfunction, is uniquely positioned in the Parkinson's treatment landscape. The company anticipates multiple milestones in 2025, including interim results from the Phase 1b trial and preparation for Phase 2 trials in the U.S. and EU.
