Announcement • Jul 16
Gain Therapeutics Announces Clinical Progress and Operational Update for Rexaceract and GT-04686
Gain Therapeutics, Inc. provided an operational update regarding its lead drug candidate, rexaceract, formerly known as GT-02287, a disease modifying therapy for Parkinson’s disease. The company achieved critical inflection points related to the clinical development of rexaceract. The immediate focus remains the clinical development of rexaceract to address the unmet need in Parkinson’s disease, as the company endeavors to create a new backbone of therapy that slows or stops the progression of symptoms. The results from the Phase 1b study of rexaceract and open-label extension continue to support the hypothesis for the drug candidate and its mechanism of action, and safety and tolerability have been observed through five months of treatment. All 16 participants who entered the ongoing Phase 1b extension study remained on study at Day 150, and following the most recent review on July 6, 2026, an independent Data Monitoring Committee recommended the study continue without modification. Longer term outcomes in this dosing extension are anticipated to read out in October 2026. Data from Part 1 and Part 2 of the study includes the first 90 days administration of rexaceract, during which reduction in cerebrospinal fluid (CSF) levels of glucosylsphingosine (GluSph) in patients with elevated levels at baseline correlated with an early clinical benefit. That response is largely maintained after at least five months of administration, while the entire cohort of 16 patients can be categorized as non-progressors at both three and five months regardless of baseline characteristics. The company looks forward to the next updates at 270 days and 360 days, which will occur over the summer and at the conclusion of the study in October 2026. With Investigational New Drug (IND) authorization in hand, the clinical team is working to commence a Phase 2 study in people with Parkinson’s disease, anticipated to start in the third quarter of 2026. The FDA’s decision to authorize the IND application follows positive Phase 1 results in both healthy volunteers and people with Parkinson’s disease, in which rexaceract was well-tolerated and demonstrated both biomarker and clinical evidence of activity. Following the recent acceptance of “rexaceract” as the International Nonproprietary Name (INN) for GT-02287, all references made to GT-02287 within the program will transition to this established nonproprietary name. The planned Phase 2 study of rexaceract is expected to enroll participants with early Parkinson’s disease across sites in the United States, Australia, and Europe. The Clinical Advisory Board and experienced consultants have informed key protocol decisions, including patient selection, endpoint development, and statistical planning. After 90 days of treatment with rexaceract in participants with elevated baseline levels of GluSph in CSF at baseline, GluSph decreased by an average of 81%. Elevated GluSph, a hallmark of GCase dysfunction, has been shown to increase the aggregation of a-synuclein as well as to impair mitochondrial function and other intracellular processes in neurons. In individuals with high levels of CSF GluSph at baseline, levels of DOPA decarboxylase (DDC) decreased following 90 days of treatment with rexaceract. After 150 days of treatment, participants with elevated baseline GluSph demonstrated greater clinical benefit than those with low baseline levels, with a difference of 4.8 points in the sum of MDS-UPDRS Part II and III scores. Stabilization or improvement of MDS-UPDRS scores has been observed across the overall study population. Gain Therapeutics has also been advancing a second product candidate, GT-04686, and recently presented preclinical evidence of its activity in both in vitro and in vivo models. Results showed an increase in GCase activity and lipid substrate depletion in patient fibroblasts harboring both mutated and wildtype GBA1, as well as restoration of motor and non-motor function in an animal model of Parkinson’s disease. GT-04686 is a structurally distinct allosteric GCase chaperone and will be the next program in the pipeline advancing towards clinical development. Current activities are focused on optimizing the program and generating the data necessary to support IND-enabling studies, including refinement of the target product profile, preclinical pharmacology, manufacturing readiness, and development planning. These efforts are intended to position GT-04686 for a successful transition into formal IND-enabling development and, ultimately, clinical evaluation. Rexaceract is an orally administered, brain-penetrant small molecule that restores the function of the lysosomal enzyme GCase which becomes misfolded and impaired due to mutations in the GBA1 gene or other age-related stress factors. In preclinical models of Parkinson’s disease, rexaceract restored GCase enzymatic function, reduced endoplasmic reticulum stress, lysosomal and mitochondrial pathology, aggregated a-synuclein, neuroinflammation and neuronal death, as well as plasma neurofilament light chain (NfL) levels, a biomarker of neurodegeneration. In rodent models of both GBA1-PD and idiopathic PD, rexaceract was shown to rescue deficits in motor function and gait and prevent the development of deficits in complex behaviors such as nesting. Compelling preclinical data in models of both GBA1-PD and idiopathic PD, demonstrating a disease-modifying effect after administration of rexaceract, suggest that rexaceract may have the potential to slow or stop the progression of Parkinson’s disease. Results from a Phase 1 study of rexaceract in healthy volunteers demonstrated favorable safety and tolerability, plasma and CNS exposures in the projected therapeutic range, and target engagement with an increase in GCase activity among those receiving rexaceract at clinically relevant doses. Rexaceract is currently being evaluated in a Phase 1b clinical trial for the treatment of Parkinson’s disease with or without a GBA1 mutation. The primary endpoint of the trial, which enrolled participants across seven sites in Australia, is to evaluate the safety and tolerability of rexaceract after three months of dosing in people with Parkinson’s disease. The Phase 1b study extension allows participants to continue to be treated with rexaceract for up to a total of 12 months. Gain’s lead program in Parkinson’s disease has been awarded funding support early in its development from The Michael J. Fox Foundation for Parkinson’s Research (MJFF) and The Silverstein Foundation for Parkinson’s with GBA, as well as from the Eurostars-2 joint program with co-funding from the European Union Horizon 2020 research and Innosuisse – Swiss Innovation Agency.
