Objective: To evaluate the long-term safety, tolerability, and PK of the oral, brain-penetrant glucocerebrosidase (GCase) modulator GT-02287 in people with Parkinson’s disease.

Background: Preclinical evidence has demonstrated that GT-02287 corrects molecular pathway abnormalities that contribute to the pathogenesis and progression of PD, indicating that GT-02287 has the potential to slow disease progression. After a Phase 1 study in healthy volunteers, an open-label Phase 1b study in people with PD was initiated. The Phase 1b study consists of two parts: Part 1 with dosing for 90 days (data presented previously), and Part 2, a 9-month optional extension available to participants who completed Part 1 (data presented here).

Method: Individuals 30-85 years of age who had been diagnosed with PD within the last 7 years and who were either treatment-naïve or on a stable dose of dopaminergic therapy were eligible. All participants received oral GT-02287 13.5 mg/kg/day and could reduce the dose to 11 mg/kg/day for inadequate tolerability. Adverse events, vital signs, laboratory tests, physical examinations, body weight, and 12-lead ECGs were used to evaluate safety and tolerability. Secondary and exploratory endpoints included pharmacokinetics, clinical scales (MDS-UPDRS, etc.), and plasma and CSF biomarkers (sphingolipids, neurofilament, inflammatory markers, and α-synuclein).

Results: 21 participants enrolled in the study. Dosing in Part 1 was complete in November of 2025, and Part 1 data were presented at the AD/PD conference in March 2026. Of the 19 participants who completed dosing in Part 1, 16 chose to continue dosing in Part 2. As of March 2026, all 16 participants had completed at least 5 months of dosing (3 months in Part 1 and 2 months in Part 2). No new safety signals were apparent at this time, and the transient elevations in liver enzymes that occurred in several participants in Part 1 did not occur again. MDS-UPDRS scores were stable or had decreased in most participants by Day 90, and this trajectory appears to continue in Part 2. Complete safety, tolerability, clinical, and biomarker data for Part 2 will be presented here.

Conclusion: GT-02287 has successfully completed a Phase 1 study in healthy volunteers and a Phase 1b study in people with PD. A randomized, placebo-controlled Phase 2 trial is being planned.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/long-term-open-label-data-on-the-gcase-modulator-gt-02287-in-people-with-parkinsons-disease/