Maze Therapeutics (MAZE) Citigroup’s Biopharma Back to School Summit 2026 summary

Pipeline and near-term priorities

• Three wholly owned small-molecule programs in clinical development, built using a human-genetics-based discovery platform; focus on precision medicines for kidney and metabolic diseases.

• MZE829 HORIZON Phase II data expected by year-end 2026 or early 2027; a pivotal program is planned to start in H1 2027.

• MZE782 Phase II in PKU began in August 2026, with top-line data guided for 2027; a Phase II CKD study is planned to begin in H1 2027.

MZE829 for APOL1-mediated kidney disease

• APOL1 high-risk variants predominantly affect people of West African descent; two copies can drive earlier, faster CKD progression and dialysis up to 10 years earlier. No approved AMKD treatments.

• Of ~6 million U.S. residents with two high-risk variants, ~15%-20% may develop CKD and AMKD; estimates include ~1 million with CKD and ~250,000 potentially able to benefit from an APOL1 inhibitor.

• March 2026 interim HORIZON results in 12 evaluable patients showed 36% average UACR reduction; 6 of 12 had reductions of at least 30%. FSGS patients averaged 62%, with 3 of 4 responding.

• HORIZON is an open-label Phase II basket study in proteinuria CKD patients with two APOL1 high-risk variants, across FSGS, diabetic and non-diabetic/non-FSGS segments; 10-15 patients per segment expected by year-end 2026 or early 2027, inclusive of reported patients.

• MZE829 has a dual mechanism: blocks APOL1 pore formation and disrupts pore assemblies. Pivotal design will reflect final HORIZON results, FDA discussions and potential PARASOL recommendations on surrogate endpoints.

• A 30% proteinuria reduction is a commonly cited activity threshold; a 20% reduction may still be meaningful, particularly in complex diabetic CKD. Two of five diabetic patients had 35% and 47% reductions on top of background GLP-1 or SGLT2 treatment.

MZE782 for PKU and CKD

• MZE782 inhibits SLC6A19, reducing phenylalanine absorption or reabsorption into blood and promoting urinary clearance independently of PAH; ~60,000 PKU patients are estimated in key geographies, with ~two-thirds on an onerous diet or untreated.

• In a 2025 Phase I study of 100+ healthy volunteers, MZE782 was well tolerated and increased urinary phenylalanine excretion up to 40-fold; the 240 mg BID dose achieved 42-fold, regardless of fed or fasted state.

• CIPheR Phase II tests 120 mg BID, 240 mg BID, and 240 mg BID with a BH4 agent; monotherapy eligibility threshold is 600, versus 360 for combination. The study will assess plasma phenylalanine reduction and safety; data are guided for 2027.

• Combination testing seeks to determine how far phenylalanine can fall below 360, a key threshold for diet liberalization. Co-formulation with BH4 is not a current focus; next steps will follow Phase II results.

• No neutral-amino-acid excretion-related issues or adverse events emerged in Phase I; available data from a similar mechanism and Hartnup syndrome patients were also cited as reassuring.