Maze Therapeutics (MAZE) investor relations material

Study background and objectives

• MZE-782 is an oral SLC6A19 inhibitor developed for PKU and CKD, targeting genetically validated pathways to address unmet needs in patients not responsive to current therapies.

• The Phase I trial was randomized, double-blind, placebo-controlled, enrolling 112 healthy adults in single, multiple ascending, and food effect cohorts.

• Primary objective was to evaluate safety and tolerability; secondary endpoints included PK, PD (urinary phenylalanine and glutamine excretion), food effect, and eGFR.

• Doses ranged from 30 to 960 mg (SAD) and up to 720 mg (MAD), with food effect evaluated at 480 mg and absorption assessed with high- and low-fat meals.

Safety and tolerability

• MZE-782 was well tolerated at all dose levels, with no serious or severe adverse events and no discontinuations due to treatment-related adverse events.

• Only mild, non-dose-related treatment-related adverse events (headache, diarrhea) occurred in SAD cohorts.

• No clinically relevant changes in vital signs, laboratory tests, or ECGs were observed.

Pharmacokinetics and pharmacodynamics

• Linear PK observed with a tmax of 6 hours and an 11-hour half-life, supporting once or twice daily dosing; steady state achieved by day three.

• Dose-dependent increases in urinary phenylalanine (up to 42-fold) and glutamine (up to 68-fold) excretion at day seven, exceeding results from competing SLC6A19 inhibitors.

• Even lower doses exceeded the 10-fold threshold linked to meaningful plasma phenylalanine reduction in PKU.