Gain Therapeutics (GANX) Study Update summary

Study design and patient population

• Phase 1b open-label study of GT-02287 in Parkinson's disease enrolled 21 patients, with 19 completing 90 days and 15 entering an extension phase.

• Participants were enrolled across seven sites in Australia, with the study focusing on safety, tolerability, and biomarker analysis, particularly in CSF.

• Patients were not excluded based on GBA mutation status or baseline glucosylsphingosine levels, which were measured for exploratory analyses.

• GT-02287 is an orally administered, brain-penetrant allosteric enzyme modulator targeting GCase dysfunction in PD.

• Study extension allows up to 12 months of treatment for further outcome assessment.

Clinical outcomes

• After 90 days, patients showed an average improvement of 2.2 points on the combined MDS-UPDRS Part II and III scores.

• Among 13 of 15 evaluable patients, a greater improvement of around four points was observed, suggesting possible outliers.

• Anecdotal improvements were noted in balance, gait, and sense of smell, with stabilization in MDS-UPDRS scores.

• No changes in dopamine administration were required during the study period.

Biomarker findings

• GT-02287 led to an 81% average reduction in CSF glucosylsphingosine (GluSph) after 90 days, indicating increased GCase activity in the brain.

• Reduction in GluSph is a first-ever observation for a GCase modulator in PD patients, suggesting potential to impact disease progression.

• Decreases in CSF glucosylsphingosine correlated with improvements in UPDRS scores at the patient level.

• Glucosylsphingosine is considered a superior biomarker to glucosylceramide for monitoring GCase pathway engagement and disease activity.

• Reductions in glucosylsphingosine were also observed in blood, though CSF is preferred for CNS disease monitoring.