Gain Therapeutics, a clinical-stage biotechnology company leading the discovery and development of the next generation of allosteric small molecule therapies, announces positive results from the single ascending dose (SAD) part of its Phase 1 study. GT-02287 was generally well tolerated up to and including the highest planned dose level, and there were no serious adverse events. The good safety and tolerability profile and the appropriate range of plasma exposure levels achieved after oral administration further bolster GT-02287’s best and first-in-class potential.

The Phase 1 clinical trial is a single center, randomized, double-blind, placebo-controlled, single- and multiple ascending dose (SAD/MAD) study to evaluate the safety and tolerability of GT-02287 administered orally once daily in healthy adults. The secondary objective is to evaluate the pharmacokinetics of SAD and MAD dose levels to identify a maximum tolerated dose (MTD) and identify recommended doses for further clinical development in the setting of GBA1 Parkinson’s disease. 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. The MAD part of the Phase 1 trials was initiated in February in parallel to the last SAD cohorts after approval from the Bellberry Human Research Ethics Committee (HREC) in Australia – a decision based on a review of the safety and tolerability profile observed in the SAD cohorts.

“We are encouraged by the promising data observed to date with GT-02287,” commented Gain CEO Matthias Alder. “The SAD data support further development of GT-02287 and we remain on track with our previous guidance to complete the multiple ascending dose (MAD) part of this Phase 1 clinical trial in Q2”.

“Current therapies only treat symptoms whereas GT-02287 has the potential to slow or stop disease progression in PD by treating the underlying cause of the disease. We expect to initiate a first-in-patient cohort in the Phase 1 clinical trial in the second half of 2024 that can provide proof of mechanism in patients with PD based on relevant biomarkers and potentially other exploratory measures,” added Gain Chief Medical Officer Jonas Hannestad.

GT-02287 has been shown to restore the function of the lysosomal enzyme glucocerebrosidase (GCase), which becomes misfolded and dysfunctional due to a GBA1 gene mutation, the most common genetic risk factor for the development of Parkinson’s disease. Compelling preclinical data presented at WORLDSymposium™ earlier in February 2024 demonstrated that treatment with GT-02287 restored motor function and substantially reduced plasma levels of the emerging neurodegeneration biomarker NfL. Based on these data, GT-02287 may have the potential to slow the progression of Parkinson’s disease.