Maze Therapeutics, a clinical-stage biopharmaceutical company focused on leveraging human genetics to create innovative small molecule precision medicines for common diseases, has announced promising results from the Phase 1 clinical trial of its drug candidate MZE829 in healthy volunteers. MZE829 is an oral small molecule inhibitor of APOL1 that Maze is developing as a potential treatment for APOL1 kidney disease (AKD), a form of chronic kidney disease that affects over one million patients in the United States alone.
APOL1 is a protein encoded by the APOL1 gene, with genetic variants (G1 and G2) linked to an increased risk of various progressive kidney diseases, particularly in individuals of West African descent. MZE829 was discovered through insights from Maze’s proprietary platform, Maze Compass™.
The first-in-human Phase 1 trial was a randomized, placebo-controlled study assessing the safety, pharmacokinetics (PK), food interactions, and potential drug interactions of MZE829 in 111 healthy volunteers. Results indicated that MZE829 was well tolerated, with single doses up to 480 mg and multiple doses up to 350 mg showing only mild treatment-related adverse events; no severe or serious adverse events were reported. The pharmacokinetics demonstrated dose proportionality and low variability, with a half-life of approximately 15 hours, suggesting that MZE829 can be administered once daily. The trial also explored potential drug interactions, showing that MZE829 could be safely combined with standard treatments for AKD, such as cyclosporine and tacrolimus.
Dr. Harold Bernstein, M.D., Ph.D., president of R&D and chief medical officer of Maze, expressed his satisfaction with the trial results, stating, “We are very pleased with the positive outcome of our Phase 1 trial of MZE829, demonstrating its tolerability and establishing the dosing regimen that we plan to take into our Phase 2 trial in patients with AKD. Given its mechanism targeting APOL1 and the genetic data derived from our Compass platform, we believe that MZE829 has the potential to address a significant patient population with AKD. Therefore, we aim to enroll a diverse group of patients with varying characteristics in our Phase 2 trial to fully represent the spectrum of AKD and determine which patients may benefit from MZE829.”
The upcoming Phase 2 clinical trial is expected to adopt an open-label basket design, encompassing a range of clinical phenotypes and moderate to severe disease stages based on proteinuria levels. It will include AKD patients with two copies of the high-risk APOL1 alleles (G1 and G2) and evaluate efficacy through reductions in urinary albumin-to-creatinine ratio (uACR) across a broad AKD population. Maze anticipates initiating the Phase 2 trial in the first quarter of 2025.
