Gain Therapeutics, Inc. announced the last healthy subject in the multiple ascending dose (MAD) part of its Phase 1 study has completed the highest planned dose levels. No discontinuations or serious adverse events were reported. After database lock, topline data from this Phase 1, randomized, double-blind, placebo-controlled study is expected to be released in August, and full safety analysis and plasma pharmacokinetics are expected to be presented at a future congress.

The MAD part of the Phase 1 study was initiated in February, and all four MAD cohorts have completed daily oral dosing for 14 days. GT-02287 was well tolerated up to and including the highest planned dose level, and no safety signals have been detected in the 32 healthy volunteers who participated in the MAD part. Of the adverse events that occurred, 90% were mild and 10% were moderate with no Grade 3 or higher events reported.

The favorable safety and tolerability profile and the appropriate range of plasma exposures achieved after oral administration further bolster GT-02287?s best-in-class potential. The primary objective of this Phase 1 clinical trial with single- and multiple ascending doses was to evaluate the safety and tolerability of GT-02287 administered orally once daily in healthy adults. The secondary objective was to evaluate the pharmacokinetics of SAD and MAD dose levels to identify recommended doses for further clinical development in people with Parkinson?s disease.

The SAD part of the Phase 1 clinical trial concluded in April with positive results and no serious adverse events. The SAD part of the Phase 1 clinical trial enrolled 40 healthy participants across five separate cohorts ? all of which were completed at the planned dose levels with no premature discontinuations or safety signals.

GT-02287 has been shown to restore the function of the lysosomal enzyme glucocerebrosidase (GCase), which becomes misfolded and dysfunctional due to GBA1 gene mutations, the most common genetic risk factor for the development of Parkinson?s disease. Compelling preclinical data in mouse models of GBA1-PD, including that presented at FENS Forum 2024 in June describing improvement in cognitive performance in addition to motor performance after administration of GT-02287, suggests that GT-02287 may have the potential to slow the progression of Parkinson?s disease. Gain Therapeutics?

lead drug candidate, GT-02287, is in clinical development for the treatment of Parkinson?s disease. The orally administered, brain-penetrant small molecule is an allosteric protein modulator that restores the function of the lysosomal protein enzyme glucocerebrosidase (GCase) which becomes misfolded and impaired due to mutations in the GBA1 gene, the most common genetic abnormality associated with PD, or other age-related stress factors. In preclinical models of PD, GT-02287 restored GCase enzymatic function, reduced aggregated a-synuclein, neuroinflammation and neuronal death, increased dopamine levels and improved motor function and cognitive performance.

Additionally, GT-02287 significantly reduced plasma neurofilament light chain (NfL) levels, an emerging biomarker for neurodegeneration. Gain?s lead program in Parkinson?s disease has been awarded funding support from The Michael J. Fox Foundation for Parkinson?s Research (MJFF) and The Silverstein Foundation for Parkinson?s with GBA, as well as from the Eurostars-2 joint program with co-funding from the European Union Horizon 2020 research and Innosuisse ? Swiss Innovation Agency.