Gain Therapeutics Completes Dosing in Phase 1 MAD Study of GT-02287 for Parkinson’s

Gain Therapeutics Inc., a clinical-stage biotechnology company, has announced the completion of the highest planned dose levels for the multiple ascending dose (MAD) portion of its Phase 1 study involving its lead drug candidate, GT-02287. This milestone was met without any discontinuations or serious adverse events. The study's topline data is set to be released in August, with a full safety analysis and plasma pharmacokinetics to be presented at a future congress.

According to Gain's Executive Chairman, Khalid Islam, Ph.D., the successful completion of the single ascending dose (SAD) and MAD portions in 72 healthy subjects—with no serious adverse events or discontinuations—reinforces the potential of GT-02287 as a transformative therapy for Parkinson’s disease. The company aims to initiate a clinical trial for Parkinson’s disease patients by the fourth quarter of 2024.

The MAD part of the Phase 1 study began in February, completing four cohorts with 32 healthy volunteers undergoing daily oral dosing for 14 days. GT-02287 was well tolerated, with no safety signals detected. Adverse events were mostly mild (90%) and moderate (10%), with no Grade 3 or higher events recorded. The favorable safety profile and the range of plasma exposures achieved bolster the drug's best-in-class potential.

The primary goal of this Phase 1 trial, involving both single and multiple ascending doses, was to evaluate the safety and tolerability of GT-02287 when administered orally once daily in healthy adults. The secondary goal was to assess the pharmacokinetics of both SAD and MAD dose levels to determine the recommended doses for further clinical development in Parkinson’s patients. The SAD part concluded in April with positive results and no serious adverse events. It involved 40 healthy participants across five separate cohorts, all of which completed the planned dose levels without any premature discontinuations or safety signals.

GT-02287 has shown promise in restoring the function of the lysosomal enzyme glucocerebrosidase (GCase), which often becomes misfolded and dysfunctional due to mutations in the GBA1 gene. This gene mutation is a common genetic risk factor for Parkinson’s disease. Preclinical data in mouse models of GBA1-PD, presented at the FENS Forum 2024, indicated that GT-02287 improved both cognitive and motor performance. This suggests the drug could potentially slow the progression of Parkinson’s disease.

GT-02287 is an allosteric protein modulator designed to restore the function of the lysosomal enzyme GCase, which is impaired due to GBA1 gene mutations. In preclinical models, the drug improved motor function, cognitive performance, and reduced neurodegeneration markers. The drug also significantly decreased plasma neurofilament light chain levels, an emerging biomarker for neurodegeneration.

Gain Therapeutics' lead program in Parkinson’s disease has received funding support from The Michael J. Fox Foundation for Parkinson’s Research, The Silverstein Foundation for Parkinson’s with GBA, and the Eurostars-2 program, co-funded by the European Union Horizon 2020 research and Innosuisse – Swiss Innovation Agency.

Gain Therapeutics Inc. is at the forefront of developing next-generation allosteric therapies. The company’s Magellan™ drug discovery platform leverages AI-supported structural biology, proprietary algorithms, and supercomputer-powered models to identify novel allosteric binding sites on disease-implicated proteins. This unique approach speeds up the discovery of novel, allosteric small molecule modulators that can restore or disrupt protein function, enabling the development of innovative treatments for neurodegenerative diseases, rare genetic disorders, and oncology.