Gain Therapeutics has set its sights on proving the effectiveness of its Parkinson’s disease therapy next year after the brain-penetrant small molecule demonstrated “peripheral target engagement” in a phase 1 trial.
The trial of 72 healthy volunteers aged up to 64 years assessed single and multiple oral doses of the allosteric protein modulator, dubbed GT-02287. The study showed no discontinuations or serious events, according to the biotech, which concluded the drug was “safe and generally well tolerated up to and including the highest planned dose levels across all age groups.”
GT-02287 is designed to restore the function of a lysosomal protein enzyme called glucocerebrosidase. This enzyme can become misfolded and impaired due to mutations in the GBA1 gene, which is the most common genetic abnormality associated with Parkinson’s.
As well as being safe, today’s phase 1 data showed that GT-02287 was found to be present in the cerebrospinal fluid of patients and the drug showed peripheral target engagement, the company noted.
“The favorable safety and tolerability profile at oral dose levels that resulted in therapeutic plasma levels, CNS exposure, and target engagement further strengthens GT-02287’s potential to be a lead treatment for Parkinson’s disease in patients with or without a GBA1 mutation,” Gain said in the Aug. 29 release.
Back in June, Gain unveiled preclinical data showing mice that received GT-02287 built nests that looked similar to those of healthy animals, while the nests of mice that didn’t receive treatment were poorly constructed. GT-02287 was also shown to reduce plasma neurofilament light chain levels, considered a biomarker for neurodegeneration.
Gain didn’t dive deep into its human data until later in the year, but executives said today that their first clinical findings justified initiating a phase 1b trial of GT-02287 in patients with Parkinson’s by the end of 2024 in order to demonstrate that the drug’s mechanism works according to key biomarkers. The aim is for that trial to read out by mid-2025.
“We are enthusiastic about the promising profile of GT-02287, particularly with the added observation of CNS exposure and target engagement,” Gain’s chief financial officer and interim CEO Gene Mack said in today’s release.
“We’re proud to be executing on our near-term clinical milestones and look forward to presenting the full data and advancing GT-02287 further in the clinic with the goal of improving the lives of people with Parkinson’s disease,” Mack added.
Allosteric modulators like GT-02287 are drugs that bind to a protein’s surface, changing the formation of the protein’s binding site. But biotechs working with this drug class have struggled to show success against Parkinson’s in later-stage studies.
In April, Sage Therapeutics’ NMDA receptor positive allosteric modulator dalzanemdor failed a phase 2 Parkinson’s study, while Addex Therapeutics blamed COVID-related recruitment issues for halting a phase 2b/3 Parkinson’s trial of its metabotropic glutamate receptor subtype 5 negative allosteric modulator back in 2022.