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Maze Therapeutics January 2026 Harnessing the power of human genetics to transform the lives of patients
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Forward-Looking Statements This presentation contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. All statements other than statements of historical fact are statements that could be deemed forward-looking statements, including, without limitation, statements concerning the company’s future plans and prospects, any expectations regarding the safety, efficacy, or mechanism of action of MZE829, MZE782 and other candidates under development, the ability of MZE829 to treat APOL1-mediated Kidney Disease (AMKD) or other indications, the ability of MZE782 to treat Chronic Kidney Disease (CKD), Phenylketonuria (PKU) or other indications, the market size of AMKD, CKD and PKU, the planned design and timing of the company’s clinical trials, data results and further development of MZE829, MZE782 and other therapeutic candidates, the ability of the Compass platform to accelerate innovation and expand the company's pipeline, potential pipeline expansion, and the sufficiency of the company’s cash and cash equivalents to fund its operating expenses and capital expenditure requirements. In addition, when or if used in this presentation, the words “may,” “could,” “should,” “anticipate,” “believe,” “estimate,” “expect,” “intend,” “plan,” “predict” and similar expressions and their variants, as they relate to the company may identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Although the company believes the expectations reflected in such forward-looking statements are reasonable, the company can give no assurance that such expectations will proveto be correct. Readers are cautioned that actual results, levels of activity, safety, performance or events and circumstances could differ materially from those expressed or implied in the company’s forward-looking statements due to a variety of factors, including risks and uncertainties related to the company’s ability to advance MZE829, MZE782 and its other therapeutic candidates, obtain regulatory approval of and ultimately commercialize the company’s therapeutic candidates, the timing and results of preclinical studies and clinical trials, the company’s ability to fund development activities and achieve development goals, its ability to protect its intellectual property, general business and economic conditions, and risks related to the impact on its business of macroeconomic conditions, including inflation, volatile interest rates, tariffs, instability in the global banking sector, and public health crises. Further information on potentialrisk factors that could affect the company’s business and its financial results are detailed under the heading “Risk Factors” included in the company’s annual and quarterly reports and other filings filed from time to time with the SEC. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. These forward-looking statements speak only as of the date of this presentation and Maze undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof. This presentation also contains estimates and other statistical data made by independent parties and by the company relating to its industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions, and estimates of the company’s future performance and the future performance of the markets in which the company operates are necessarily subject to a high degree of uncertainty and risk. 2
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Maze Therapeutics: Harnessing the power of human genetics to transform the lives of patients 3 Cutting-Edge Genetics Kidney & Metabolic Disease Mid-clinical-stage biopharma Novel small molecule precision medicines Expected cash runway into 2028
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Focused Pipeline in Kidney & Metabolic Diseases 4 Program Target Indication Target Validation Lead Optimization IND-Enabling Phase 1 Phase 2 Phase 3 Anticipated Catalysts MZE829 APOL1 APOL1-mediated Kidney Disease (AMKD) Report topline PoC Phase 2 data by end of Q1 2026 MZE782 SLC6A19 Phenylketonuria (PKU) Initiate Phase 2 by mid-2026 Chronic Kidney Disease (CKD) Initiate Phase 2 in 2H 2026 Research & Discovery Multiple Kidney & Metabolic Diseases, including obesity MZE001 / S606001 GYS1 Pompe Disease Phase 2 enrolling Phase 2 ready Phase 2 ready Phase 2 ready Expect operating capital into 2028 based on the current business plan
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APOL1-Mediated Kidney Disease (AMKD) Proof-of-Concept Data by End of Q1 2026 MZE829 5
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MZE829: Precision Medicine with Dual Mechanism and Broad Potential in AMKD Clinically-validated target to address a disease that disproportionally affects people of African ancestry Oral Therapy to Treat the Underlying Cause of APOL1 -mediated Kidney Disease - Clinically-validated target with high unmet need - Maze was the first to elucidate the function of APOL1 as a pore through insights from variant functionalization - Precision medicine for at least 250,000 individuals and potentially >1M patients in the U.S. 1 Phase 2 Basket Design Enables Multiple Registration Strategies - Potential to use proteinuria as an approvable Phase 3 endpoint in patients with FSGS - PARASOL Project will extend its efforts to investigate potential clinical trial endpoints for AMKD - Study ongoing to demonstrate clinical PoC in both diabetic and non -diabetic patients 6 1. 2017-2020 NHANES; Grams et al. (2016) JASN 27:2842-50; Friedman et al. (2011) JASN 22:2098-105; Nadkarni et al. (2018) NEJM 379:2571-2 FSGS: Focal Segmental Glomerulosclerosis PARASOL: Proteinuria and GFR as Clinical Trial Endpoints in Focal Segmental Glomerulosclerosis MZE829: Differentiated Dual -Mechanism APOL1 Inhibitor with Best -in-Class Potential - Inhibits both pore formation and channel function - Preclinical data show increased potency Phase 1 Profile Supports Phase 2 Dose Selection - Dose-proportional PK and 250 mg selected for Phase 2 - Well-tolerated with no significant AEs or SAEs at single doses up to 480 mg & multiple doses up to 350 mg
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MZE829: Addressing Critical Needs in AMKD 7 Accelerated Progression: Dialysis initiation ~10 years earlier than non-APOL1 CKD patients2 Suboptimal Outcomes with SoC: Patients with AMKD progress rapidly to ESKD despite treatment with available therapies3 Earlier Disease Onset: APOL1 high-risk variants linked to CKD onset before age 501 Disease Burden MZE829 Opportunity Dual APOL1 Inhibition: Disrupts channel function by inhibiting pore assembly and blocking ion flux for broader disease modulation Long-Term Impact: Potential to delay progression to ESKD Best-in-class Potential: Selective APOL1 inhibitor with potential to modify disease course 1. Freedman BI et al. APOL1 renal-risk variants are associated with earlier onset of end-stage kidney disease and with faster progression of nephropathy in African Americans. Kidney Int. 2015;87(1):120-129. 2. Freedman BI, Cohen AH. Hypertension-attributed nephropathy: what’s in a name? Nat Rev Nephrol. 2016;12(1):27-36. 3. Nadkarni GN et al. APOL1 genotype and risk of kidney disease progression and mortality: A prospective cohort study. Lancet. 2022;399(10343):2031–2039. SoC: standard of care; ESKD: end-stage kidney disease
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Broad AMKD Represents Significant Need 8 At least 250,000 Estimated AMKD patients in U.S. Hypertensive Non-Diabetics Diabetics Other CKD (e.g. SLE, HIVAN) FSGS MZE829 Phase 2 topline PoC data in initial broad AMKD patients by end of Q1 2026 No approved therapies currently exist for AMKD despite its prevalence and severity SLE = systemic lupus erythematosus HIVAN = HIV-associated nephropathy, FSGS = Focal Segmental Glomerulosclerosis
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MZE829 Dual Mechanism: Disrupts APOL1 Pore Assembly and Inhibits Pore Function 9 APOL1 Driven Podocyte Death and Kidney Damage MZE829 Dual Mechanism of Action Glomerular Podocyte APOL1 pore APOL1 monomer Na+, K+, Ca2+, H+ APOL1 pore APOL1 monomer MZE829 blocks pore function MZE829 blocks pore formation1 2Toxic APOL1 pores are increased in podocytes Increased number of toxic pores disrupts podocyte function and leads to podocyte death MZE829 Glomerular Podocyte
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MZE829: Solid Phase 1 Results Support Advancement into Phase 2 • Favorable Safety Profile: Well-tolerated with no SAEs and mild, self-limited AEs reported at single doses up to 480 mg and multiple doses up to 350 mg QD for 7 days in 111 healthy adult volunteers • Predictable Pharmacokinetics (PK): Dose-proportional increases in plasma levels, consistent single- and multiple-dose PK and ~15-hour half-life supports once-daily dosing • Minimal DDI Risk: No clinically meaningful impact on CYP3A4 inhibition or induction, supporting broad potential use • Phase 2 Dose Selected: 250 mg QD chosen for Phase 2 based on predicted therapeutic exposure (EC90-95) with safety margin 10 0 24 48 72 96 120 144 168 192 216 240 264 288 1 10 100 1000 10000 Time (hr) MZE829 Plasma Concentration (ng/mL) 60 mg 120 mg 240 mg 350 mg 480 mg 0 24 48 72 96 120 0.1 1 10 100 1000 10000 Time (hr) MZE829 Plasma Concentration (ng/mL) 20 mg 60 mg 120 mg 240 mg 480 mg (split dose) 0 24 48 72 96 120 144 168 192 216 240 264 288 1 10 100 1000 10000 Time (hr) MZE829 Plasma Concentration (ng/mL) 60 mg 120 mg 240 mg 350 mg Single Ascending Doses Multiple Ascending Doses Phase 1 FIH Exposures & Predicted Response1 1. ASN 2024: Mouse BAC-tg model with overlay of MZE829 human steady-state exposures observed in Phase 1 FIH: first-in-human; SAE: serious adverse event; DDI: drug-drug interaction; QD: once-daily
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MZE829 Phase 2 HORIZON Study Topline proof-of-concept data in initial broad AMKD patients expected by the end of Q1 2026 Patient Timeline Treatment Period 12 weeks Follow-up 4 weeks Screening Up to 6 weeks Study Elements uACR and Disease Severity • MZE829 once-daily 250 mg oral • Open-label, basket study • APOL1- mediated CKD with diabetes • APOL1- mediated CKD without diabetes • Severe FSGS without diabetes* • All patients enrolled will have two copies of the risk variants • Patients will be on stable backgroundCKD regimen (RAASi +/- other SoC e.g., SGLT2i, MRA, etc.) for at least 8 weeks prior to study • In-clinic/home-health visits every ~4 weeks • T arget enrollment for Q1 2026 data disclosure: Broad AMKD patients (with and without diabetes) • Endpoints: • Primary: safety, tolerability • Secondary: uACR, PK • Exploratory: uPCR, quality of life, biomarkers, eGFR 11 uACR mg/g <30 300 NORMAL to MILD MODERATE SEVERE HORIZON cut-off for broad AMKD ≥2000 nephrotic range * FSGS enrollment cutoff is uPCR greater than or equal to 1500 mg/g 3000+ Stable SoC required for at least 8 weeks pre-treatment
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≥30% average uACR reduction in broad AMKD is broadly accepted as clinically meaningful and would demonstrate clinical PoC Percent Change in uACR Broad AMKD Patients ≥30% average reduction in uACR would be clinically meaningful Illustrative uACR Reduction Graph Used in practice (e.g., KDIGO guidelines 2) Validated surrogate endpoint for CKD drug development across multiple programs Correlated with eGFR slope improvement and 10-year delay to ESKD 1 ≥30% uACR Reduction PARASOL: Evaluating as surrogate endpoint for AMKD3 12 ≥30% reduction in uACR in broad AMKD patients would demonstrate Clinical PoC and inform potential advancement into Phase 2b/3 planning 1. Carroll KJ, et al. ERA-EDTA Congress 2021, MO246; 3 2. CKD Evaluation and Management – KDIGO 3. https://www.is-gd.org/parasol
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MZE782 13 Phenylketonuria (PKU) Phase 2 initiation by mid-2026
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MZE782: Oral Therapy with the Potential to Transform PKU Management 1. Trefz, F K et al. “Significance of genotype in tetrahydrobiopterin-responsive phenylketonuria.” Journal of inherited metabolic disease vol. 32,1 (2009): 22-6. 2. Longo, Nicola et al. “Long-term safety and efficacy of sapropterin: the PKUDOS registry experience.” Molecular genetics and metabolism vol. 114,4 (2015): 557-63. 3. National PKU Alliance (NPKUA).https://npkua.org. 4. Bilder DA et al. Neuropsychiatric comorbidities in adults with phenylketonuria: A retrospective cohort study. Mol Genet Metab. 2013;108(3):155–160.14 Strict Dietary Burden: Lifelong low-Phe diet is difficult to maintain3 Neuropsychiatric Burden: Fluctuating Phe levels can impair brain function4 Limited Efficacy of PAH Activators: Only 10 - 20% of patients with classic PKU respond to treatment1, 2 Disease Burden MZE782 Opportunity Convenient, Well-Tolerated Oral Therapy: Oral dosing may improve adherence and patient acceptance Potential for Diet Liberalization: May reduce dependence on strict low-Phe diets, improving quality of life and adherence Applicability Across PKU Spectrum: Designed to benefit patients with classic, moderate and mild forms of the disease
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PKU Represents Significant Need 15 Benefit from enzyme substitution therapy Benefit from oral therapies Potential Additional Opportunity for MZE782 • Patients who are not well controlled by current therapies • Previously untreated patients including classical PKU • Patients who have failed on current therapies . Note: Chart represents approximate breakdown of US patients No treatment or medical diet alone At least 60,000 Estimated PKU patients in key geographies
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MZE782: Substrate Reduction Therapy for PKU 16 Leveraging Maze’s expertise in developing oral substrate reduction therapies Phe breakdown via PAH Reduced activity of PAH Reduced activity of PAH Phe uptake in gut Kidney Phe uptake Normal PKU Treatment with MZE782 Potential for MZE782 to Work Across Entire Spectrum of Patients with PKU
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Strong Phase 1 Data supportive of advancement into Ph 2 17 Study Design • Randomized, double-blind, placebo-controlled study evaluating single ascending doses and multiple ascending doses of orally administered MZE782 in 112 healthy adult volunteers Dosing • The single ascending doses, or SAD, ranged from 30 mg to 960 mg and the multiple ascending doses, or MAD, with dosing once or twice daily for seven days, ranged from 120 mg to 240 mg twice daily and 120 mg to 720 mg once daily Safety & Tolerability • MZE782 was well tolerated with an excellent safety profile at all dose levels evaluated Pharmacokinetics • MZE782 has linear PK across single doses of 30-960 mg with half-life ~11 hrs • Supportive of a once- or twice-daily dosing regimen to be evaluated in Phase 2. Urinary Phe • Consistent increases in urinary excretion of Phe observed with increasing doses and plasma exposures to MZE782 ‒ Up to 42X increase in urinary Phe at Day 7 Food Effect • Moderate positive food effect observed only with single doses of MZE782 • When MZE782 administered twice daily, steady state plasma exposures similar with or without food administration
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Placebo 120 QD 120 BID 720 QD 240 BID 240 BID Fed Placebo 120 QD 120 BID 720 QD 240 BID 240 BID Fed Placebo 120 QD 120 BID 720 QD 240 BID 240 BID Fed 0 5 10 15 20 25 30 35 40 45 50 55 60 65 12 17 28 42 39 13 24 38 55 48 10 11 27 27 33 Dose Groups Urine Phe - Change from Baseline Ratio (0-24h) 1 1 1 MZE782 Clinical Study Showed Phe Excretion Exceeding 40-Fold; expected to initiate PKU Phase 2 by mid-2026 N=6 treated with MZE782 per cohort Geometric Mean ± GSD values are plotted. Amount excreted (Ae) in urine polled over specified time interval. Baseline is defined as the day before treatment (Day -1). Ratio=Ae post-dose/Ae at baseline. Ratio of 1 indicates no change. >1 indicates increase, <1 indicates decrease. e.g., Ratio of 10 indicates 10x increase over baseline. 18 Up to 39x increase in urinary L-phenylalanine excretion over 24h following MZE782 administration Day 1 Day 3 Day 7 Urine Phe - Change from Baseline Ratio (0-24h) Multiple Ascending Dose Up to 42x increase in urinary L-phenylalanine excretion on Day 7 of MZE782 administration Dose Groups (mg) Placebo 30 60 4x30 120 240 480 960 0 5 10 15 20 25 30 35 40 45 50 55 60 65 9 8 15 23 39 Dose Groups Urine Phe - Change from Baseline Ratio (0-24h) 1 2 Urine Phe - Change from Baseline Ratio (0-24h) Day 1 10x Fold Threshold Single Ascending Dose Dose Groups (mg) 5
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MZE782 19 Chronic Kidney Disease (CKD) Phase 2 initiation in 2H 2026
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MZE782: Addressing Persistent Gaps in CKD Treatment 1. Centers for Disease Control and Prevention (CDC). Chronic Kidney Disease in the United States, 2021. 2. Curovic et al. Diabetes Care 46:593, 2023. 3. Mende CW (2022) Chronic Kidney Disease and SGLT2 inhibitors: A Review of the Evolving Treatment Landscape. Adv Ther 39:148-164. 4. INVOKANA (canagliflozin) and FARXIGA (dapagliflozin) drug labels. DKA: diabetic ketoacidosis; UTI: urinary tract infection20 Inadequate response in a large subset of patients; ~25% of patients respond inadequately to SGLT2i therapies2 SGLT2i treatment associated with increased risk of DKA and UTIs, which may limit uptake or lead to discontinuation3, 4 CKD is often diagnosed late with patients unaware of their condition until later stages of the disease1 Disease Burden MZE782 Opportunity Add-On Therapy: Add-on potential to improve outcomes in combination with SoC and potentially reduce side effects Targeted Innovation: SLC6A19 inhibition offers a new mechanism in all CKD populations Monotherapy Potential: T o reduce proteinuria and slow progression to ESKD in patients inadequately controlled on SoC
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Demonstrated In Vivo Proof of Concept for SLC6A19 Inhibition in a Preclinical Model • First in vivo PoC of reduction in proteinuria with pharmacologic SLC6A19 inhibition in aristolochic acid injury (AAI) model • Demonstrates complementary effect with SGLT2 inhibition • Consistent with genetically- informed hypotheses that SLC6A19 inhibition could result in kidney benefit Study ID: MZS-I023-25-021, week 1.5 KIM-1 = Kidney Injury Molecule-1, a protein biomarker that is specifically elevated in the urine and blood of individuals with kidney injury; PoC: proof of concept21 Mean + SEM Ordinary one-way ANOVA (vs. AAI Control) **** p<0.0001 *** p<0.0005 SLC6A19 inhibition protects against albuminuria (UACR) and proximal tubule damage (KIM-1) through a potentially independent mechanism compared to SGLT2 inhibition
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Initial eGFR Dip on SGL T2i Therapy Predicts Slower Chronic eGFR Decline in CKD 1. Bailey, Clifford J et al. “Renal Protection with SGLT2 Inhibitors: Effects in Acute and Chronic Kidney Disease.” Current diabetes reports vol. 22,1 (2022): 39-52. doi:10.1007/s11892-021-01442-z 2. Holtkamp, Frank A et al. “An acute fall in estimated glomerular filtration rate during treatment with losartan predicts a slower decrease in long-term renal function.”Kidney internationalvol. 80,3 (2011): 282-7. doi:10.1038/ki.2011.79 3. Meraz-Muñoz, Alejandro Y et al. “eGFR Decline after SGLT2 Inhibitor Initiation: The Tortoise and the Hare Reimagined.” Kidney360 vol. 2,6 1042-1047. 26 Mar. 2021, doi:10.34067/KID.000117202122 Strengthens rationale for MZE782 to potentially improve CKD outcomes Typical eGFR Trajectory1 Initial Dip Slower rate of decline following initial dip Initial eGFR dip is a transient hemodynamic effect seen with renoprotective therapies2,3 Observed with approved CKD therapies, including SGLT2 inhibitors2,3 Moderate initial dip associated with slower chronic eGFR decline and better long -term kidney outcomes 2,3 Provides a pharmacodynamic readthrough supporting potential efficacy in CKD
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MZE782: Preliminary Clinical Data Support Potential Protective Mechanism in CKD; expected to start CKD Phase 2 by 2H 2026 23 Observed “dip” in eGFR generally consistent with exposure-response N=4 Matched Placebo N=12 240 mg BID (fed + fasted) ΔeGFR for Empagliflozin (SGLT2i) 25 mg QD1 Early data appear to have comparable effect to other reno-protective therapies eGFR derived using the 2021 CKD-EPI Creatinine Equation; . † Baseline eGFR = mean of the 3 pre-dose measurements ; 1Range of placebo-adjusted and non-adjusted % change from baseline eGFR (“eGFR dip”) at 4 weeks’ treatment with empagliflozin 25 mg QD on background ramipril in patients without significant renal impairment provided for approximate reference (Lytvyn Y, 2022). Dapagliflozin significantly lowers renal glucose threshold and reabsorptive capacity (TmG), driving glucosuria in both healthy and T2D subjects (DeFronzo et al., Diabetes Care 2013). 240 mg BID vs. Matched Placebo Treatment (7 Days) No Treatment Exposure Response: eGFR Change vs. MZE782 Exposure 0 -5 -15 -10 50,000 150,000100,000 200,000 Day 7 AUC₀₋₂₄ (h*ng/mL)
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Research & Discovery 24 Kidney & Metabolic Diseases
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GENETIC PRECISION Focus on genetically- validated targets (APOL1, SLC6A19) MECHANISTIC MODULATION Understanding variant function in context of disease pathophysiology ORAL THERAPIES Best / first in class potential small molecule programs SMARTER DEVELOPMENT Biomarker-based trials; proven regulatory path Unlocking Precision Pathways in Kidney & Metabolic Disease Maze is built to turn complex genetics into targeted, oral medicines that change the course of disease VARIANT DISCOVERY VARIANT FUNCTIONALIZATION SMALL MOLECULE DISCOVERY PRECISION CLINICAL TRIAL DESIGN 25
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Navigating the Path to Precision Medicine • Proprietary Compass platform translates human genetics into precision therapies through variant discovery and functionalization to small molecule discovery and development 26 Compass platform accelerates precision medicine innovation through genetic insights, fueling an expanding pipeline in kidney & metabolic diseases, including obesity Early Research Programs Maze Compass Platform Pipeline Expansion Opportunities • Driving lifecycle expansion and the identification of potential new indications, including broader CKD populations for MZE829 (APOL1) and optimized use of MZE782 (SLC6A19) in CKD and PKU • Uncovering new kidney and metabolic disease candidates through Compass-driven insights across our pre-clinical program initiatives
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Expected Key Catalysts Financial Position By end of Q1 2026: Report MZE829 Phase 2 topline, PoC data in initial broad AMKD patients Mid-2026: Initiate MZE782 Phase 2 PoC trial in PKU 2H 2026: Initiate MZE782 Phase 2 PoC trial in CKD $383.9 million cash, cash equivalents and marketable securities as of September 30, 2025 Completed PIPE financing in September 2025, raising approximately $150M in gross proceeds, providing operating capital into 2028 based on current business plan Eligible for development, regulatory and commercial milestones and royalties from partnered programs Key Near-T erm Catalysts & Financials Multiple paths to patients across AMKD, PKU and CKD, enabled by near-term data 27
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Maze Therapeutics January 2026 Harnessing the power of human genetics to transform the lives of patients
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Phase 1 Data in Healthy Volunteers MZE782 – Appendix 29
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MZE782: Phase 1 SAD and MAD Healthy Volunteer Trial 1. 30 mg tablet strength used (120 mg tablet strength in other cohorts) 2. Doses administered with standard meal (versus fasting in prior MAD cohorts) 3. Dose administered with high-fat meal 4. Dose administered with low-fat meal 5. No placebo-treated participants Randomized, Double-blind, Placebo-controlled SAD and MAD in 112 Healthy Adult Volunteers Single Ascending Dose (SAD) N = 56 Multiple Ascending Dose (MAD) N = 40; 7 days 120 mg QD 720 mg QD 240 mg BID 240 mg BID2 120 mg BID 30 mg1 960 mg 240 mg 4x30 mg1 480 mg 60 mg1 120 mg Dosing: • 8 individuals per cohort randomized 6:2 (MZE782:Placebo) Endpoints: • Primary: Safety and tolerability • Secondary: PK, urinary excretion of Phe and Gln, food effect • Exploratory: eGFR 480 mg Single Dose Preliminary Food Effect3 N = 8 Multiple Dose Crossover Food Effect4 N = 8 480 mg5 30
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SAD/MAD Demographics MZE782 (n = 86) Placebo (n = 26) Total (n = 112) Gender, n (%) Female 40 (46.5) 9 (34.6) 49 (43.8) Male 46 (53.5) 17 (65.4) 63 (56.3) Age, years, median (range) 36.5 (20, 61) 40.0 (20, 60) 38.0 (20, 61) Ethnicity, n (%) Hispanic or Latino 37 (43.0) 7 (26.9) 44 (39.3) Non-Hispanic or Latino 49 (57.0) 19 (73.1) 68 (60.7) Race, n (%) White 51 (59.3) 16 (61.5) 67 (59.8) Black or African American 26 (30.2) 9 (34.6) 35 (31.3) Asian 3 (3.5) 1 (3.8) 4 (3.6) Native Hawaiian or Pacific Islander 1 (1.2) 0 (0) 1 (0.9) American Indian or Alaska Native 1 (1.2) 0 (0) 1 (0.9) Mixed/Other 4 (4.7) 0 (0) 4 (3.6) Well-Balanced and Comparable Between Placebo and Treatment Arms 31
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MZE782: Safety & T olerability • No SAEs • No severe AEs • 3 TRAEs: all mild in severity • No dose-dependent pattern in TRAEs • No TRAEs leading to discontinuation • No clinically relevant changes in vital signs, laboratory tests and ECGs SAE: Serious Adverse Event; AE: Adverse Event; TRAE: Treatment Related Adverse Event MZE782 Well-Tolerated Across All Doses Evaluated TRAEs by Preferred Term: SAD Cohorts MZE782 (n=56) Placebo (n=16) Headache 2 (4%) 0 Diarrhea 1 (2%) 0 TRAEs by Preferred Term: MAD Cohorts MZE782 (n=30) Placebo (n=10) None - - 32
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Treatment-Related Adverse Events (TRAEs) PFE: Preliminary food effect; CFE: Crossover food effect 1. Values in columns represent # of participants with reported TRAE 2. 30-mg tablet strength utilized in these cohorts 3. All MAD cohorts administered fasted except this 240 mg BID cohort that was administered with standard meal SAD Cohort TRAE1 30 mg2 (N=6) 60 mg2 (N=6) 120 mg (N=6) 4 x 30 mg2 (N=6) 240 mg (N=6) 480 mg (N=6) 480 mg (N=6) PFE 480 mg (N=8) CFE 960 mg (N=6) Placebo (N=16) Headache 1 - - - - - - 1 - - Diarrhea - 1 - - - - - - - - MAD Cohort TRAE1 120 mg QD (N=6) 120 mg BID (N=6) 240 mg BID (N=6) 720 mg QD (N=6) 240 mg BID3 (N=6) Placebo (N=10) Any - - - - - - 33
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Treatment-Emergent Adverse Events (TEAEs) Not Related to MZE782 PFE: Preliminary food effect; CFE: Crossover food effect 1. Values in columns represent # of participants with reported TEAE 2. 30-mg tablet strength utilized in these cohorts 3. All MAD cohorts administered fasted except this 240 mg BID cohort that was administered with standard meal SAD Cohort TEAE1 30 mg2 (N=6) 60 mg2 (N=6) 120 mg (N=6) 4 x 30 mg2 (N=6) 240 mg (N=6) 480 mg (N=6) 960 mg (N=6) 480 mg (N=6) PFE Placebo (N=16) Venipuncture Site Pain 1 Device Site Rash 1 URI 1 Viral Infection 1 Headache 1 Light Sensitivity 1 Ventricular extrasystoles 1 MAD Cohort TEAE1 120 mg QD (N=6) 120 mg BID (N=6) 240 mg BID (N=6) 720 mg QD (N=6) 240 mg BID3 (N=6) 480 mg (N=8) CFE Placebo (N=10) Rhinorrhea 1 Epistaxis 1 Diarrhea 1 1 Abdominal Pain 1 1 Headache 1 Anxiety 1 Somnolence 1 34
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MZE782: Favorable PK Profile With Single and Multiple Dosing N=6 per cohort Mean ± SD are plotted. PK samples were collected for up to 168h postdose in SAD and 96h post last dose in MAD (Day 7). Linear PK across single doses (30 to 960 mg) with t½ ~11 hours Single Ascending Dose Multiple Ascending Dose Multiple dose PK consistent with single dose and accumulation consistent with t½ 0 24 48 72 96 120 144 168 192 216 240 264 288 1 10 100 1000 10000 Time (hr) MZE782 Plasma Concentration (ng/mL) 120 mg QD 120 mg BID 240 mg BID 720 mg QD 35
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MZE782: Dose-Dependent Glutamine Excretion Exceeding 60-Fold N=6 treated with MZE782 per cohort Geometric Mean ± SD values are plotted. Amount excreted (Ae) in urine polled over specified time interval. Baseline is defined as the day before treatment (Day -1). Ratio=Ae post-dose/Ae at baseline. Ratio of 1 indicates no change. >1 indicates increase, <1 indicates decrease. e.g., Ratio of 10 indicates 10x increase over baseline. Up to 55x increase in urinary L-glutamine excretion over 24h following MZE782 administration Up to 68x increase in urinary L-glutamine excretion on Day 7 of MZE782 administration Urine Gln - Change from Baseline Ratio (0-24h) Day 1 Single Ascending Dose Placebo 30 60 4x30 120 240 480 960 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 15 19 17 28 35 55 Dose Groups Urine Gln - Change from Baseline Ratio (0-24h) 1 4 Dose Groups (mg) Urine Gln - Change from Baseline Ratio (0-24h) Multiple Ascending Dose Day 1 Day 3 Day 7 Placebo 120 QD 120 BID 720 QD 240 BID 240 BID Fed Placebo 120 QD 120 BID 720 QD 240 BID 240 BID Fed Placebo 120 QD 120 BID 720 QD 240 BID 240 BID Fed 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 29 37 52 68 50 28 43 50 64 50 20 24 39 40 37 Dose Groups Urine Gln - Change from Baseline Ratio (0-24h) 1 1 1 Dose Groups (mg) 36