Maze Therapeutics Begins Phase 2 Trial of MZE829 for APOL1 Kidney Disease

SOUTH SAN FRANCISCO, CA, USA, February 07, 2025 – Maze Therapeutics, Inc., a company in the clinical stage specializing in biopharmaceuticals and working with human genetics to develop innovative small molecule precision medicines, has started dosing patients in its Phase 2 clinical trial named the HORIZON Study. This trial focuses on MZE829, an oral small molecule APOL1 inhibitor aimed at treating patients with APOL1 kidney disease (AKD), a variant of chronic kidney disease that affects over a million people in the United States.

The HORIZON Study heralds a significant step forward in the treatment of AKD. Harold Bernstein, M.D., Ph.D., who serves as the president, R&D, and chief medical officer of Maze, expressed enthusiasm about the trial’s potential. He highlighted the broad patient criteria of the HORIZON Study, which includes a variety of AKD characteristics beyond those typically considered in existing studies. This approach aims to validate the concept of MZE829 and refine patient selection for subsequent pivotal trials. MZE829 holds promise as a disease-modifying therapy, potentially meeting an urgent need in the treatment of kidney diseases.

The trial is designed as a Phase 2, open-label basket study. It will enroll AKD patients who carry two high-risk APOL1 alleles, G1 and G2, grouping them based on clinical phenotype and proteinuria levels, and will also include patients with type 2 diabetes. The diverse characteristics of AKD that the trial will focus on include patients with severe disease and nephrotic range proteinuria, like those with focal segmental glomerulosclerosis (FSGS), as well as those with lower proteinuria levels and hypertensive nephropathy, and patients with proteinuria in the context of diabetic kidney disease. This study is particularly notable for being the first to involve a small molecule APOL1 inhibitor in diabetic AKD patients.

In August 2024, Maze initiated a multicenter observational study to identify Black and African American individuals carrying the APOL1 G1 and G2 mutations, aiming to explore biomarkers in proteinuric kidney disease. The HORIZON Study’s primary goal is the reduction of proteinuria, measured by the percentage of subjects achieving a 30% or greater decrease from baseline in the urinary albumin-to-creatinine ratio (uACR) by week 12. According to published literature, this reduction threshold is expected to provide meaningful clinical benefits. uACR is a crucial metric for measuring proteinuria across various stages of glomerular kidney disease, especially in hypertension and diabetes contexts, and has been used to assess cardiovascular disease risk. Maze anticipates obtaining potential proof of concept interim data by the first quarter of 2026.

Maze Therapeutics is committed to using human genetics to create precision medicines for renal, cardiovascular, and related metabolic diseases, such as obesity. The company's development pipeline is powered by its Compass platform, which provides insights into genetic variants and their connections to biological pathways impacting specific patient populations. Maze’s lead programs, MZE829 and MZE782, epitomize a novel approach to precision medicine for patients with these diseases.