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 for up to 12 months.

• The trial was conducted across seven sites in Australia, focusing on safety, tolerability, and clinical outcomes after three months of dosing.

• Exclusion criteria for MDS-UPDRS analysis included alpha-synuclein negative status and off-state measurements.

• The extension phase will provide longer-term data, with final results expected around September.

Clinical outcomes and efficacy signals

• After 90 days, patients showed an average improvement of 2.2 points in combined MDS-UPDRS Part II and III scores among 15 analyzed patients.

• 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, indicating effects are not due to symptomatic treatment.

• The improvement aligns with expectations for a disease-modifying therapy at this early stage.

Biomarker findings and mechanistic insights

• GT-02287 demonstrated 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.

• Reduction in CSF glucosylsphingosine was observed in all patients with elevated baseline levels after 90 days.

• Decreases in glucosylsphingosine correlated with improvements in UPDRS scores, suggesting a link between biomarker response and clinical benefit.

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