Maze Therapeutics announces results from Phase 1 trial of MZE782

Maze Therapeutics (MAZE) announced positive clinical results from the Phase 1 healthy volunteer study of MZE782, an oral small molecule targeting the solute transporter, SLC6A19. MZE782 has potential to be a best-in-class therapy for patients with PKU, an inherited metabolic disorder, and a first-in-class therapy for patients with CKD. MZE782 produced dose-dependent increases in 24-hour urinary excretion of the neutral amino acids Phe and Gln across both SAD and MAD cohorts, confirming target engagement and SLC6A19 inhibition. A 39-fold increase in urinary Phe excretion over 24 hours was observed with a single dose of 960 mg of MZE782. A 42-fold increase in urinary Phe excretion over 24 hours on Day 7 was observed in the 240 mg twice-daily dose cohort. A 55-fold increase in urinary Gln excretion over 24 hours was observed with a single dose of 960 mg of MZE782. A 68-fold increase in urinary Gln excretion over 24 hours on Day 7 was observed in the 240 mg twice-daily dose cohort. All participants in the MAD cohorts of the Phase 1 study were assessed for changes in eGFR. MZE782 demonstrated a dose-dependent initial eGFR dip over seven days of dosing that was similar in magnitude to what has been observed in patients initiating SGLT2 and RAAS inhibitors. With other renoprotective therapies, this initial dip is correlated to a slower rate of eGFR decline and better preservation of kidney function over longer periods of time in CKD patients.