Maze Therapeutics has revealed positive outcome from the Phase I clinical trial in healthy volunteers assessing oral MZE829, being developed to potentially treat apolipoprotein L1 (APOL1) kidney disease (AKD).
MZE829, a small molecule inhibitor of APOL1, is being developed by Maze as a potential therapy for AKD, which is said to predominantly affect individuals of West African descent.
The genetic variants of the APOL1 gene, known as G1 and G2, have been linked to an increased risk of progressive kidney diseases.
The randomised, first-in-human, placebo-controlled, single and multiple ascending dose trial enrolled total of 111 participants.
It assessed the safety, pharmacokinetics (PK), food effect, and possible drug interactions of MZE829 when administered orally to healthy subjects.
The results from the trial indicated that MZE829 was well tolerated, with the highest single doses at 480mg and multiple doses up to 350mg.
Furthermore, all treatment-linked adverse events seen in the trial were mild in nature without any severe or serious adverse events observed.
Pharmacokinetic analysis showed dose-proportional results with low variability across doses and the half-life of approximately 15 hours suggest that MZE829 could be administered once daily.
MZE829 also showed potential when used in combination with standard care medicines for AKD, such as cyclosporine and tacrolimus.
Maze R&D president and chief medical officer Harold Bernstein said: “We are very pleased with the positive outcome of our Phase I trial of MZE829, demonstrating its tolerability and establishing the dosing regimen that we plan to take into our Phase II trial in patients with AKD.
“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.”
Based on the latest findings, the company is preparing for the Phase II clinical trial, which is expected to begin in the first quarter of 2025.
The Phase III trial will adopt an open-label basket design to encompass a variety of clinical phenotypes and disease severities, as indicated by proteinuria levels.
