Gain Therapeutics (GANX) Study Update summary

Study design and patient population

• Phase 1b open-label study enrolled 21 Parkinson's patients across seven sites in Australia, with 19 completing the first 90 days and 15 entering an extension phase.

• All patients received GT-02287 for 90 days, with an optional extension allowing up to 12 months of treatment.

• Four patients were excluded from MDS-UPDRS analysis due to baseline or measurement criteria.

• The study focused on safety, tolerability, clinical outcomes, and biomarker changes, particularly in CSF.

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

Clinical outcomes and UPDRS scores

• Average improvement of 2.2 points in combined MDS-UPDRS Part II and III scores after 90 days among 15 analyzed patients.

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

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

• No changes in dopamine administration were required for any subjects during the study.

• Stabilization of UPDRS scores at 90 days is seen as an early sign of disease modification.

Biomarker findings and mechanistic insights

• Phase 1b study showed 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.

• Decrease in CSF glucosylsphingosine observed in patients with elevated baseline levels after 90 days.

• Reduction in glucosylsphingosine correlates with improvements in UPDRS scores at the patient level.

• Glucosylsphingosine is considered a superior biomarker to glucosylceramide for monitoring treatment response.