Maze Therapeutics, a biopharmaceutical company focused on developing precision medicines using human genetics, has announced positive results from the Phase 1 clinical trial of MZE829 in healthy volunteers. MZE829 is an oral small molecule that inhibits APOL1, which Maze is exploring as a treatment for APOL1 kidney disease (AKD), a form of chronic kidney disease affecting over one million patients in the U.S. APOL1 is a protein linked to genetic variants (G1 and G2) that increase the risk of progressive kidney diseases, particularly in individuals of West African descent. MZE829 was discovered through Maze’s innovative platform, Maze Compass™.
The first-in-human Phase 1 randomized, placebo-controlled trial for MZE829 was designed to assess its safety, pharmacokinetics (PK), food effects, and potential drug interactions in healthy volunteers, enrolling 111 participants. Results showed that MZE829 was well tolerated, with single doses up to 480 mg and multiple doses up to 350 mg, all associated with mild treatment-related adverse events and no severe incidents. The drug exhibited dose-proportional PK with low variability and a half-life of approximately 15 hours, allowing for once-daily dosing. The study also indicated that MZE829 could potentially be administered alongside standard treatments for APOL1 kidney disease (AKD), such as cyclosporine and tacrolimus.
Dr. Harold Bernstein, president of R&D and chief medical officer at Maze, expressed satisfaction with the trial’s positive results, highlighting MZE829’s tolerability and the established dosing regimen for the upcoming Phase 2 trial in AKD patients. He noted that, based on its mechanism and genetic data from the Compass platform, MZE829 could benefit a significant number of AKD patients. The Phase 2 trial aims to include a diverse patient population to identify who may benefit most from the treatment.
The Phase 2 trial will use an open-label basket design, targeting various clinical phenotypes and moderate to severe AKD cases based on proteinuria levels. It will specifically include patients with two copies of the high-risk APOL1 alleles (G1 and G2) and will assess efficacy through uACR reduction across a broad AKD population. The company expects to start the Phase 2 trial in Q1 2025.
About Maze Therapeutics
Maze Therapeutics is a clinical-stage biopharmaceutical company focused on leveraging human genetics to develop innovative small molecule precision medicines for common diseases, particularly in renal, cardiovascular, and metabolic areas, including obesity. The company utilizes its Compass platform to gain insights into genetic variants associated with diseases and their biological pathways. Maze’s pipeline includes two lead programs, MZE829 and MZE782, both representing novel precision medicine approaches for chronic kidney disease.
