Maze Therapeutics has reported positive results from its Phase 1 clinical trial of MZE829, an oral small molecule inhibitor of APOL1, being developed as a potential treatment for APOL1 kidney disease (AKD). The Phase 1 trial, which enrolled 111 healthy volunteers, demonstrated that MZE829 was well-tolerated and exhibited dose-proportional pharmacokinetics, supporting a once-daily dosing regimen. These findings pave the way for a Phase 2 clinical trial in patients with AKD, planned for the first quarter of 2025.
Phase 1 Trial Details
The Phase 1 randomized, placebo-controlled, single and multiple ascending dose trial evaluated the safety, pharmacokinetics (PK), food effect, and potential drug interactions of orally administered MZE829. Participants received single doses up to 480 mg and multiple doses up to 350 mg. The results indicated that all treatment-related adverse events were mild, with no severe or serious adverse events reported. The observed half-life of approximately 15 hours supports once-daily dosing. Drug interaction evaluations suggest MZE829 can be administered with standard AKD treatments like cyclosporine and tacrolimus.
Targeting APOL1 in Kidney Disease
APOL1 kidney disease (AKD) affects over one million people in the United States, particularly those of West African ancestry who carry genetic variants (G1 and G2) of the APOL1 gene. These variants increase the risk of progressive kidney diseases. MZE829, identified using Maze's Compass platform, is designed to inhibit APOL1, addressing a genetically validated driver of AKD.
Planned Phase 2 Trial
The company plans to initiate a Phase 2 open-label basket trial in Q1 2025. This trial will include AKD patients with two copies of the high-risk APOL1 alleles (G1 and G2) and will assess efficacy using uACR reduction across a broad AKD population, encompassing a range of clinical phenotypes and moderate to severe forms of the disease, as determined by proteinuria levels.
Management Commentary
"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," said Harold Bernstein, M.D., Ph.D., president, R&D, and chief medical officer of Maze. "Based on its mechanism targeting APOL1, as well as genetics data derived through our Compass platform, we believe that MZE829 has the potential to address a large population of patients with AKD. As such, we intend to enroll patients with a wide array of characteristics into our Phase 2 trial to reflect the full spectrum of AKD patients and determine which patients may benefit from treatment with MZE829."
