Maze Therapeutics (MAZE) 3rd Annual Guggenheim Healthcare Innovation Conference summary

APOL1 study and mechanism

• HORIZON enrolled more than 50 patients across three cohorts, exceeding the prior 30–45 target; enrollment was fairly evenly distributed across FSGS, non-diabetic and diabetic patients.

• Greater disease awareness, community engagement, site adjustments and interim data supported faster enrollment; these tactics may help shorten pivotal-study timelines.

• 829 binds a different APOL1 pore site than compounds described in literature; preclinical work suggests it both blocks pores and disrupts their assembly, with greater potency in a proteinuria model.

• The 2027 data will assess uACR across the three cohorts; a reduction of at least 30% across patients, on standard of care including SGLT2 inhibitors, is a stated benchmark.

• The 12–13-week uACR response continued to deepen; dosing with or without food can increase exposure, and the protocol was amended to allow both conditions.

APOL1 market and regulatory outlook

• Recent findings suggest APOL1 inhibitors may benefit a broader population, with or without diabetes, potentially reaching hundreds of thousands of patients.

• PARASOL analysis found proteinuria correlated with eGFR outcomes in non-diabetic patients, potentially supporting accelerated approval; possible pivotal endpoints include proteinuria, eGFR slope or a combination.

• Further agency engagement will evaluate whether proteinuria alone could support accelerated approval, based on the analysis and emerging clinical data.

• Differentiation measures include proteinuria reduction versus other programs and safety/tolerability; 829 has shown uACR declines on standard of care, including SGLT2 inhibitors.

PKU program

• The MZE782 SLC6A19 inhibitor phase II proof-of-concept study is placebo-controlled, with low- and high-dose arms and exploration of combination treatment with a BH4 agonist.

• Preclinical potency and ADME, plus phase I urinary phenylalanine biomarker increases of 40–50 times baseline across QD and BID doses, support a potential differentiated profile.

• 2027 data are expected to test whether treatment lowers plasma phenylalanine and helps patients reach the 360 micromolar threshold used to consider leaving a medical diet.