Maze Therapeutics announced positive topline Phase 2 HORIZON results for MZE829, an oral small-molecule dual-mechanism APOL1 inhibitor, reporting a 35.6% mean reduction in urinary albumin-to-creatinine ratio (uACR) at week 12 in broad APOL1-mediated kidney disease patients, with 50% of patients achieving greater than 30% reduction.
In a predefined subgroup, patients with focal segmental glomerulosclerosis showed a 61.8% mean reduction in uACR, and non-diabetic AMKD patients had a 48.6% mean reduction. Fifteen patients were enrolled in the safety analysis, and 12 were evaluable for efficacy, with most patients subnephrotic at baseline.
MZE829 was generally well tolerated, with no serious or severe treatment-related adverse events reported; the most common treatment-related adverse events were headache and diarrhea (two patients each), and one patient discontinued early due to mild nausea.
The open-label Phase 2 basket study had primary endpoints of safety and tolerability and secondary endpoints including pharmacokinetics and uACR reduction, and patients remained on stable background therapies such as SGLT2 inhibitors and GLP-1 receptor agonists. The company expects to continue enrollment and advance MZE829 into a pivotal program and will host a conference call to discuss the data.
