Maze Therapeutics Announces Positive Phase 1 Results for MZE829 in APOL1 Kidney Disease

Maze Therapeutics, a biopharmaceutical company focused on creating precision medicines for common diseases through human genetics, has announced promising results from its Phase 1 clinical trial of MZE829. The trial involved healthy volunteers and aimed to explore the safety, pharmacokinetics, food effects, and potential drug interactions of MZE829, an oral inhibitor of APOL1. This compound is being developed as a potential treatment for APOL1 kidney disease (AKD), a subset of chronic kidney disease that affects over a million individuals in the United States.

APOL1 kidney disease is linked to genetic variants of the APOL1 gene, specifically the G1 and G2 variants, which increase the risk of kidney diseases in individuals of West African ancestry. MZE829 was developed using Maze’s proprietary platform, Maze Compass™, which integrates genetic insights to identify promising drug candidates.

The Phase 1 trial, which was randomized, placebo-controlled, and involved single and multiple ascending doses, included 111 participants. The results were positive, showing that MZE829 was well tolerated at single doses up to 480 mg and multiple doses up to 350 mg. All treatment-related adverse events were mild, with no severe or serious adverse events reported. The pharmacokinetics of MZE829 indicated dose-proportional behavior with low variability, and the half-life of about 15 hours supports once-daily dosing. Furthermore, the trial suggested that MZE829 could be used alongside standard AKD treatments like cyclosporine and tacrolimus without adverse interactions.

Dr. Harold Bernstein, President of R&D and Chief Medical Officer at Maze Therapeutics, expressed satisfaction with the trial's outcomes, highlighting the establishment of a dosing regimen suitable for Phase 2 trials. He emphasized the potential of MZE829, based on its APOL1 targeting mechanism and genetic data from the Compass platform, to benefit a large population of AKD patients. The upcoming Phase 2 trial aims to include a diverse group of AKD patients to understand better who might benefit from MZE829. The trial will focus on patients with two copies of the high-risk APOL1 alleles (G1 and G2) and will measure efficacy through reductions in urine albumin-to-creatinine ratio (uACR) across a broad spectrum of AKD patients.

Maze Therapeutics plans to initiate the Phase 2 trial in the first quarter of 2025. This trial will use an open-label basket design to include various clinical phenotypes and disease severities, categorized by proteinuria levels.

Maze Therapeutics is leveraging its genetic-based platform to develop treatments for several conditions, with a particular focus on renal, cardiovascular, and metabolic diseases, including obesity. Their pipeline features leading programs like MZE829 and MZE782, both of which are novel precision medicine approaches targeting chronic kidney disease.