Objective: To evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the brain-penetrant glucocerebrosidase (GCase) modulator GT-02287 in people with Parkinson’s disease with and without a GBA1 pathogenic variant.

Background: In Phase 1 in healthy volunteers, GT-02287 was safe and well tolerated, produced therapeutic plasma and CSF levels, and increased GCase activity in dry blood spots. An open-label Phase 1b study of GT-02287 in people with PD in Australia started recruitment in February 2025 and is expected to be completed by the end of 2025.

Method: This study aims to enroll 15-20 participants 30-85 years of age who have been diagnosed with PD within the last 7 years and who are treatment-naïve or on a stable dose of dopaminergic therapy. Sites are using their local databases and networks to find potential participants, most of whom will have idiopathic PD. In addition, Gain Therapeutics has partnered with Shake It Up Australia Foundation and the Queensland Institute for Medical Research to leverage the >10,000 Australia Parkinson’s Genetics Study nationwide cohort to recruit participants with GBA-PD. All participants receive oral GT-02287 13.5 mg/kg once daily for 90 days. The incidence, nature, and severity of adverse events, and the incidence of clinically significant changes in vital signs, laboratory tests, physical examinations, body weight, and 12-lead ECGs are used to evaluate safety and tolerability, the primary endpoint. Secondary and exploratory endpoints include levels of GT-02287 in plasma and CSF, and target-engagement and disease biomarkers in blood and CSF, including GCase activity, glucosylsphingosine and glucosylceramide, inflammatory markers, mitochondrial DNA, neurofilament light chain, and aggregated, phosphorylated, and total α-synuclein.

Results: As of March 2025, four participants had enrolled in the study (two with idiopathic PD and two with GBA-PD). Interim safety, tolerability, PK, and biomarker data will be presented at the MDS conference in October 2025.

Conclusion: GT-02287 is a GCase-targeting small molecule that successfully completed Phase 1 in healthy volunteers and that is currently being evaluated in people with PD. Based on the genetic association of GBA1 variants with PD and extensive preclinical data demonstrating that GT-02287 modulates molecular pathways implicated in PD, this novel compound has the potential to slow disease progression in GBA1-PD and possibly in idiopathic PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/gt-02287-in-parkinsons-disease-interim-data-from-a-phase-1b-study/