Maze Therapeutics Initiates Phase 2 Trial of MZE829 for APOL1 Kidney Disease
核心洞察
Maze Therapeutics has dosed the first patient in its Phase 2 HORIZON study, evaluating MZE829 for APOL1 kidney disease (搜索) (AKD).
The HORIZON trial is an open-label, basket design study including AKD patients with varying degrees of proteinuria and diabetic AKD.
The primary endpoint is a 30% or greater reduction in proteinuria, measured by urinary albumin-to-creatinine ratio (uACR) at week 12.
Maze Therapeutics has commenced its Phase 2 HORIZON study, marking a significant step in the development of MZE829, an oral apolipoprotein L1 (搜索) (APOL1) inhibitor, for the treatment of APOL1 kidney disease (搜索) (AKD). The first patient has been dosed in this trial, which aims to evaluate the safety and efficacy of MZE829 across a broad spectrum of AKD patients.
The HORIZON study is designed as an open-label, basket trial, enrolling patients with two high-risk APOL1 alleles (G1, G2). Participants will be stratified based on proteinuria levels and clinical phenotype, encompassing individuals with severe nephrotic range proteinuria, such as those with focal segmental glomerulosclerosis (搜索) (FSGS), as well as those with lower proteinuria levels, hypertensive nephropathy (搜索), and diabetic kidney disease (搜索). Notably, this trial is the first to include diabetic AKD subjects in its small molecule APOL1 inhibitor research.
The trial's primary endpoint is the reduction of proteinuria, specifically measured by a 30% or greater decrease from baseline in the urinary albumin-to-creatinine ratio (uACR) at week 12. uACR is recognized as a sensitive proteinuria measure, particularly in hypertension and diabetes, and is linked to cardiovascular disease risk assessment. Interim proof-of-concept data is anticipated in the first quarter of 2026.
MZE829: A Potential Disease-Modifying Therapy
MZE829 represents a novel, small molecule precision medicine approach for patients with AKD. Harold Bernstein, M.D., Ph.D., president, R&D, and chief medical officer of Maze, stated, “We are excited to announce the initiation of our HORIZON Study for MZE829, a Phase 2 clinical trial with a novel, potential new medicine that could disrupt current treatment for AKD.” He further emphasized the trial's design to include a broad spectrum of patients, reflecting the diverse characteristics of AKD, aiming to demonstrate proof of concept and refine patient selection for future pivotal trials.
Addressing Unmet Needs in AKD
AKD, a subset of chronic kidney disease (搜索), affects over one million individuals in the United States. The HORIZON study seeks to address a critical unmet need in kidney disease treatment by evaluating MZE829 across a wider population than previous studies. Maze Therapeutics also initiated a clinical observational trial in August 2024 to detect black and African American subjects carrying the high-risk APOL1 alleles and to investigate kidney disease biomarkers in these populations.
Maze Therapeutics is also advancing MZE782 for phenylketonuria (搜索) (PKU), a genetic metabolic disease, for which the biotech has an ongoing Phase I study and plans to run a parallel mid-stage trial.
IPO and Financial Strategy
Maze Therapeutics recently priced an upsized IPO at $16 per share, raising $140 million. The company intends to use the proceeds to support the development of MZE829 and MZE782, as well as other programs in cardiovascular, renal, and metabolism indications.