Maze Therapeutics Announces Positive First-in-Human Results from Phase 1 Trial of MZE782, Establishing Proof of Mechanism for a Potent, Oral SLC6A19 Inhibitor with Potential to Treat Phenylketonuria (PKU) and Chronic Kidney Disease (CKD)

Core Insights - Maze Therapeutics announced positive Phase 1 clinical results for MZE782, indicating its potential as a best-in-class therapy for phenylketonuria (PKU) and a first-in-class therapy for chronic kidney disease (CKD) [1][2] Study Design - The Phase 1 trial was a randomized, double-blind, placebo-controlled study involving 112 healthy adult volunteers, assessing single ascending doses (SAD) and multiple ascending doses (MAD) of MZE782 [3][4] - SAD doses ranged from 30 to 960 mg, while MAD doses ranged from 120 to 240 mg twice daily and 120 to 720 mg once daily [3] Safety and Tolerability Profile - MZE782 was well tolerated across all doses, with no serious adverse events reported [5][6] - Mild treatment-related adverse events included headache (4%) and diarrhea (2%) in the SAD cohort, with no adverse events in the MAD cohort [6] Pharmacokinetics - MZE782 demonstrated a favorable plasma pharmacokinetic profile, with consistent absorption and a half-life of 11 hours [7] - Steady-state was achieved by Day 3, supporting a once- or twice-daily dosing regimen for Phase 2 trials [7] Pharmacodynamics - MZE782 produced dose-dependent increases in urinary excretion of phenylalanine (Phe) and glutamine (Gln), confirming target engagement [8][9] - A 42-fold increase in urinary Phe excretion was observed in the 240 mg twice-daily dose cohort after seven days [9] Estimated Glomerular Filtration Rate (eGFR) - MZE782 showed a dose-dependent initial eGFR dip similar to SGLT2 inhibitors, suggesting a potential beneficial effect on kidney physiology [9] - The combined 240 mg BID cohorts demonstrated a change of -11.5 mL/min/1.73m² after seven days, compared to -2.5 mL/min/1.73m² in the placebo cohort [9] Next Steps - The company plans to initiate two Phase 2 proof-of-concept trials for MZE782 in 2026, focusing on plasma Phe reduction in PKU and proteinuria reduction in CKD [10] Company Overview - Maze Therapeutics is a clinical-stage biopharmaceutical company focused on developing small molecule precision medicines for kidney and metabolic diseases, utilizing its Compass platform [15]