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Biomea Fusion Corporate Presentation 1ST QUARTER 2026
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LEGAL DISCLAIMER & FORWARD-LOOKING STATEMENTS Certain statements in this presentation and the accompanying oral commentary are forward-looking statements. These statements relate to future events or the future business and financial performance of Biomea Fusion, Inc. (the “Company”) and involve known and unknown risks, uncertainties, and other factors that may cause the actual results, levels of activity, performance or achievements of the Company or its industry to be materially different from those expressed or implied by any forward-looking statements. In some cases, forward-looking statements can be identified by terminology such as “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “potential” or other comparable terminology. All statements other than statements of historical fact could be deemed forward-looking, including any projections of financial information or profitability, the initiation, timing and results of pending or future preclinical studies and clinical trials, the actual or potential actions of the Food and Drug Administration (FDA), the status and timing of ongoing research, development and corporate partnering activities, any statements about historical results that may suggest trends for the Company's business; any statements of the plans, strategies, and objectives of management for future operations and any statements of expectation or belief regarding future events, potential markets or market size, or technology developments. The Company has based these forward-looking statements on its current expectations, assumptions, estimates, and projections. While the Company believes these expectations, assumptions, estimates and projections are reasonable, such forward-looking statements are only predictions and involve known and unknown risks and uncertainties, many of which are beyond the Company's control. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our most recent annual report on Form 10-K filed with the Securities and Exchange Commission (the SEC), as well as discussions of potential risks, uncertainties, and other important factors in our other subsequent filings with the SEC. The forward-looking statements in this presentation are made only as of the date hereof. Except as required by law, the Company assumes no obligation and does not intend to update these forward- looking statements or to conform these statements to actual results or to changes in the Company's expectations. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our 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 our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk.
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Biomea Fusion (NASDAQ:BMEA) is a diabetes and obesity medicines company developing oral small molecules with the potential to restore beta cell function and reduce body weight while providing convenient, patient-friendly treatment options . Potentially first-in-class investigational selective menin inhibitor ICOVAMENIB Next-generation, investigational oral GLP- 1 receptor agonist BMF-650 Transformative Oral Therapies for Metabolic Disease • SMALL MOLECULE • ORAL • TARGET: OBESITY 3 • S MALL MOLECULE • ORAL • T ARGET : DIABETES
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STUDY NAME INDICATION PRE-CLINICAL PHASE I PHASE II PHASE III NEXT MILESTONE COVALENT-111 Type 2 Diabetes 52-week follow-up data presented Oct/Dec 2025 COVALENT-211 Type 2 Diabetes Insulin-Deficient Patients Commencement of Phase IIb (First patient enrollment planned 1Q 2026) COV ALENT-212 T ype 2 Di abetes Patients not controlled on GLP-1-based therapies Commencement of Phase I I (First patient enrollment planned 1Q 2026) GLP-131 Obesi ty Phase I wei ght reduction data expected 2Q 2026 ICOVAMENIB ICOVAMENIB ICOVAMENIB BMF-650 (study completed) (study initiated) (study initiated) (study enrolling) Biomea Pipeline Biomea Fusion retains full worldwide rights across all its programs 4
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ICOVAMENIB Potential First -in-Class Oral Menin Inhibitor Target: DIABETES
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Current Type 2 Diabetes Therapies do not Address the Root Cause of Diabetes - All are Targeting the Symptoms of Hyperglycemia 6 • Existing Type 2 Diabetes therapies primarily address downstream metabolic symptoms • Icovamenib is a first-in- class menin inhibitor, targeting a previously unaddressed pathway
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Mean Time to Loss of Glucose Control (HbA1c>7%) Impact of tirzepatide on HbA1c: Sustained Reduction During Treatment, Rebound After Discontinuation Nathan, et al. N Engl J Med 2022;387:1063-107 Kubota M, et al. Cureus. 2023 Oct 4;15(10) Current Type 2 Diabetes Therapies Require Chronic Treatment and Typically Do not Maintain Long-term Glucose Control Despite over 60 approved therapies in the US for Type 2 Diabetes, 50% of people with diabetes remain poorly controlled, highlighting the urgent need for novel, durable therapies to improve long -term outcomes 7
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Progressive Decline in Beta-Cell Mass and Function is the Root Cause of Diabetes Adapted from Lebovitz H. Diabetes Rev. 1999;7:139-153. 8
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ICOVAMENIB Addressing Diabetes at the Root Cause Level Icovamenib is a potentially first -in-class investigational oral therapy designed to be taken for 12 weeks to restore the body’s natural insulin production by regenerating beta cells - offering the potential for durable, disease-modifying benefits for diabetes patients. ONCE-DAILY ORAL THERAPY GENERALLY FAVORABLE SAFETY-PROFILE OBSERVED TO DATE NON-CHRONIC 9
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High Unmet Need in Patients with Diabetes 1.Zohu Lancet 2024; 404: 2077-93 (adjusted by company to account for Severe Insulin-deficient patients and those failing a GLP-1 based therapy) 2.Fendo 2022 doi: 10.3389/fendo.2022.927661 https://doi.org/10.1371/journal.pone.0304036 $20b Estimated U.S./EU revenue potential (based on 10% penetration, at 10k p.a.) 80m Type 2 Diabetes US/EU diagnosed patients approx. 20m Addressable U.S./EU target patients 1 60+ All approved Type 2 Diabetes therapies are chronic agents, none address the root cause of the disease 15-25% Type 2 Diabetes patients are severely insulin- deficient. This group has the highest failure rate among all diabetes subgroups 2 TARGET POPULATION FOR ICOVAMENIB ICOVAMENIB 10
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Karnik SK, et al. Science. 2007;318:806-809 • 2007 Stanford study found menin regulates islet growth during pregnancy 1 • Elevated prolactin (during pregnancy and breastfeeding) lowers menin, promoting beta cell growth 1 • Nursing mice show higher beta cell mass than mice separated from their offspring immediately postpartum 2 • In humans, lactation lowers the lifetime maternal T2D risk by up to 50% 3-5 • Reduced Type 2 Diabetes risk persists for up to 30 years postpartum 5 Menin is Naturally Inhibited During Pregnancy & Breastfeeding Allowing for Beta Cell Regeneration & Reduced Diabetes Risk Menin inhibition with icovamenib may phenocopy the marked reduction in Type 2 Diabetes incidence observed during pregnancy and after breastfeeding 1. Karnik SK et al._2007_Science_Menin controls growth of pancreatic beta-cells in pregnant mice and promotes gestational diabetes mellitus. 2. Hens JR et al. Protective Effects Of Lactation On Maternal Metabolism. J Endocrine Soc, Volume 7, Issue Supplement_1, Abst ract citation ID: bvad114.737, Diabetes And Glucose Metabolism, THU302, October–November 2023. 3. Kim SY_2018_KJFM_Breastfeeding can reduce the risk of developing diabetes. 4. Pinho‐Gomes A -C et al ._2021_Di abetes Obes M etab_A ssoci ati on of l actati on w i th maternal ri sk of ty pe 2 di abetes - A sy stemati c rev i ew and meta -anal y si s of observ ati onal studi es. 5. Gunderson EP et al._2018_JAM A Int M ed_Lactation duration and progression to diabetes in women across the childbearing year s - The 30- y ear CARDIA s tudy 11
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Increased beta cell mass and function Increased insulin synthesis and secretion DUAL EFFECT BETA CELL QUANTITY & FUNCTION GLP-1 RECEPTOR EXPRESSION I ncreased GL P -1 receptor expression and GLP -1 rel ease; enhanced i ncreti n ef f ect Enhanced weight loss with preservation of lean muscle ma s s in pre clinica l s tudie s combining icovamenib with a GLP-1RA ORAL NON -CHRONIC GENERALLY WELL TOLERATED COMPLIMENTARY TO OTHER AGENTS USED ICOVAMENIB Mechanism of Action of Icovamenib – a Selective and Partial Menin Inhibitor ORAL DIFFERENTIATING FEATURES 12
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52-Week Results COVALENT-111 Phase II Study Icovamenib in Type 2 Diabetes – All Comers Reported in 4Q 2025 ICOVAMENIB
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Increased beta cell mass and function Increased insulin synthesis and secretion DUAL EFFECT BETA CELL QUANTITY & FUNCTION GLP-1 RECEPTOR EXPRESSION I ncreased GL P -1 receptor expression and GLP -1 rel ease; enhanced i ncreti n ef f ect Enhanced weight loss with preservation of lean muscle ma s s in pre clinica l s tudie s combining icovamenib with a GLP-1RA ORAL NON -CHRONIC GENERALLY WELL TOLERATED COMPLIMENTARY TO OTHER AGENTS USED ICOVAMENIB Mechanism of Action of Icovamenib – a Selective and Partial Menin Inhibitor ORAL DIFFERENTIATING FEATURES 14
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ICOVAMENIB | COVALENT -111 COVALENT-111 Trial Design Phase 2a Randomized, Double-Blind, Placebo-controlled Study in Participants with T2D, All Comers 3:1 N=216 Planned Participants Eligibility Criteria • Adults (18-65 years) with T2D (<7 years) • HbA1c 7.0-10.5% • BMI 25-40 kg/m2 • Treated with up to 3 antidiabetic agents (excluding insulin and SFUs) • N=72 participants per arm (3:1 ratio, Icovamenib: PBO) icovamenib x12 wks 100 mg (QD) 15 BID: twice daily BMI: Body Mass Index HbA1c: glycated hemoglobin PBO: Placebo QD: daily SFUs: sulfonylureas T2D: Type 2 Diabetes
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Arm A, B, and C primary analysis: Change in HbA1c Prespecified subgroup analysis to include assessment of HbA1c change within each T2D subgroup: • Severe I nsul i n Def i ci ent Di abetes • Mild Age-Rel ated Di abetes • Mild Obe s ity Dia be te s • Severe I nsul i n Resi stant Di abetes Subgroup analysis based on algorithm e s ta blis he d pe r Ahlqvis t e t a l. (Lancet Diabetes Endocrinol. 2018;6:361-369) ICOVAMENIB | COVALENT -111 COVALENT-111 Statistical Analysis Plan Read Out of Insulin-Deficient & Insulin Resistant Subgroups at Weeks 26 and 52 16
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*Per the COVALENT-111 Protocol the population analyzed includes only subjects who received ≥80% of their planned dosing. A clini cal hold interrupted the dosing. Patients were also excluded if they had significant protocol deviation. DEMOGRAPHICS AND BASELINE CHARACTERISTICS WERE WELL MATCHED BETWEEN ICOVAMENIB- AND PLACEBO-TREATED PARTICIPANTS Baseline Demographics & Characteristics Per Protocol Population* on 1 or More Antihyperglycemic Agents at Baseline (N=163) ICOVAMENIB | COVALENT -111 Parameter Mean (SD) or % Arm A icovamenib (8 wks 100mg QD) (N=45) Arm B icovamenib (12 wks 100 mg QD) (N=36) Arm C icovamenib (8 wks 100 mg QD then 4 wks of 100 mg BID) (N=33) Combined Arms icovamenib (N=114) Combined Arms placebo (N=49) Age (yr) 55 (7) 56 (6) 51 (10) 54 (8) 55 (7) Duration of T2D Diagnosis (yr) 4.3 (1.8) 4.7 (1.8) 4.2 (2.2) 4.4 (1.9) 4.3 (2.0) Sex (% Female) (31) (56) (36) (40) (43) HbA1c % (SD) 8.3 (1.1) 8.3 (1.0) 8.0 (0.8) 8.2 (1.0) 8.3 (1.0) Fasting C-peptide (ng/mL) 3.4 (1.2) 3.8 (1.5) 3.7 (1.8) 3.6 (1.5) 3.5 (1.4) BMI (kg/m2) 30.9 (4.7) 32.7 (4.5) 32.4 (4.9) 31.9 (4.7) 32.6 (4.2) BMI <30 kg/m2 (%) (49) (22) (30) (35) (27) BMI ≥30 kg/m2 (%) (51) (75) (70) (64) (73) 17
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MOST PARTICIPANTS WERE TREATED WITH METFORMIN MONOTHERAPY, WITH APPROXIMATELY 20% TREATED WITH SGLT2I, 10% WITH DPP4I, AND 10% WITH GLP -1 BASED MEDICINES Antihyperglycemic Agents at Baseline Per Protocol Population on 1 or More Antihyperglycemic Agents at Baseline (N=163) ICOVAMENIB | COVALENT -111 Parameter Arm A icovamenib (8 wks 100mg QD) (N=45) Arm B icovamenib (12 wks 100 mg QD) (N=36) Arm C icovamenib (8 wks 100 mg QD then 4 wks of 100mg BID) (N=33) Combined Arms icovamenib (N=114) Combined Arms placebo (N=49) Number of T2D Medications, n (%) 1 39 (87) 23 (64) 23 (70) 85 (75) 41 (84) 2 4 (9) 11 (31) 7 (21) 22 (19) 6 (12) 3 2 (4) 2 (6) 3 (9) 7 (6) 2 (4) Metformin Monotherapy, n (%) 36 (80) 18 (50) 22 (67) 76 (67) 38 (78) SGLT2i, n (%) 6 (13) 12 (33) 8 (24) 26 (23) 7 (14) DPP4i, n (%) 3 (7) 4 (11) 3 (9) 10(9) 2 (4) GLP-1 based medicines, n (%) 3 (7) 3 (8) 5 (15) 11 (10) 4 (8) 18
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SIDD = Severe Insulin-Deficient Diabetes MARD = Mild Age-Related Diabetes MOD = Mild Obesity-Related Diabetes SIRD = Severe Insulin-Resistant Diabetes T2D Subtype at Baseline Per Protocol Population on 1 or More Antihyperglycemic Agents at Baseline (N=163) ICOVAMENIB | COVALENT -111 Parameter Arm A icovamenib (8 wks 100mg QD) (N=45) Arm B icovamenib (12 wks 100 mg QD) (N=36) Arm C icovamenib (8 wks 100 mg QD then 4 wks of 100 mg BID) (N=33) Combined Arms icovamenib (N=114) Combined Arms placebo (N=49) SIDD, n (%) 11 (24) 6 (17) 4 (12) 21 (18) 12 (24) MARD, n (%) 11 (24) 6 (17) 5 (15) 22 (19) 8 (16) MOD, n (%) 21 (47) 22 (61) 22 (67) 65 (57) 24 (49) SIRD, n (%) 2 (4) 2 (6) 2 (6) 6 (5) 5 (10) 19
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All presented data utilized a while-on-treatment esti mand w i th mi x ed model repeated measures (M M RM ) anal y si s and w as censored f o r use of rescue medication, defined as any modification in anti -diabetic therapy . Change in HbA1c from Baseline through Week 52 – All Subtypes ICOVAMENIB | COVALENT -111 Across treatment durations (Arm A = 8 weeks 100 mg, Arm B = 12 weeks 100 mg, Arm C = 8 weeks 100 mg 4 weeks at 200 mg) per protocol participants taking one or more antihyperglycemic medications at baseline -0.5% threshold for clinical significance CMS Clinical Endpoints Review (2024) 20 TREATMENT OFF-TREATMENT
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12 Weeks of Dosing (Arms B & C) Delivered Lasting Benefit Through 52 Weeks for Severe Insulin-Deficient Diabetes Patients - 9 Months After Last Dose ICOVAMENIB | COVALENT -111 PRIMARY TARGET POPULATION FOR ICOVAMENIB Arm B: 12 weeks of dosing 100 mg QD; Arm C: 8 weeks of 100 mg QD + 4 weeks of 100 BID Arm A was excluded from this analysis because it included only 8 weeks of dosing which the company is not planning to pursue. -0.5% threshold for clinical significance CMS Clinical Endpoints Review (2024) INITIAL TARGET POPULATION FOR ICOVAMENIB 21 TREATMENT OFF-TREATMENT
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Icovamenib increased Insulin Secretion as Measured by C-peptide Index All severe insulin-deficient participants (All Arms A, B, C) ICOVAMENIB | COVALENT -111 PRIMARY TARGET POPULATION FOR ICOVAMENIB 0.7 0.8 0.9 1.0 1.1 1.2 1.3 1.4 1.5 0 12 52 Fold Change in C-peptide index Weeks Icovamenib (N=21) Placebo (N=12) 29% 2% 22 TREATMENT OFF-TREATMENT
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• Dosing timing relative to food can impact icovamenib’s pharmacokinetics (PK) • In a ‘Food Effect Study’ icovamenib achieved optimal PK exposure when administered within 30 minutes after a meal • These findings inform the dosing strategy for Phase II studies Higher HbA1c Reduction was Associated with Higher Icovamenib Exposure Week 52, All Dosing Arms (N=114), HbA1c Reduction vs. Icovamenib Exposure (Mean AUC) ICOVAMENIB | COVALENT -111 23
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Increased beta cell mass and function Increased insulin synthesis and secretion DUAL EFFECT BETA CELL QUANTITY & FUNCTION GLP-1 RECEPTOR EXPRESSION I ncreased GL P -1 receptor expression and GLP -1 rel ease; enhanced i ncreti n ef f ect Enhanced weight loss with preservation of lean muscle ma s s in pre clinica l s tudie s combining icovamenib with a GLP-1RA ORAL NON -CHRONIC GENERALLY WELL TOLERATED COMPLIMENTARY TO OTHER AGENTS USED ICOVAMENIB Mechanism of Action of Icovamenib – a Selective and Partial Menin Inhibitor ORAL DIFFERENTIATING FEATURES 24
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Post-hoc Analysis: Patients on a GLP-1 Based Therapy at Enrollment (n=11, All Obese Patients) Showed Durable & Clinically Meaningful Response 9 Months After Last Dose ICOVAMENIB | COVALENT -111 -0.5% threshold for clinical significance CMS Clinical Endpoints Review (2024) INITIAL TARGET POPULATION FOR ICOVAMENIB Treatment Off-Treatment 25
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Disclaimer: The data presented above are based on cross-study comparisons and are not based on any head- to-he a d clinica l tria ls . Cross -study compar i sons ar e i nher entl y l i mi ted and may suggest mi sl eadi ng si mi l ar i ti es and di f f er ences. The values shown in the cross -study comparisons are directional and may not be directly comparabl e. THERAPY DOSING REGIMEN ADMINISTRATION ROUTE OBSERVATION PERIOD MEAN HbA1c REDUCTION (PLACEBO ADJ. %) Icovamenib (menin inhibitor) 12 weeks Oral Week 52 -1.5% to -1.8% (100 mg) Ozempic (GLP-1 Agonist) Mounjaro (GLP-1/GIP Agonist) Jardiance (SGLT2 Inhibitor) Januvia (DPP4 Inhibitor) Chronic dosing Chronic dosing Chronic dosing Chronic dosing Injectable Injectable Oral Oral Week 30 Week 40 Week 24 Week 24 -1.2 (0.5mg) -1.4 (1mg) -1.8 (5mg) -1.7 (15mg) -0.7 (10mg) -0.9 (25mg) -0.8 (100mg) Ozempic FDA Label; Mounjaro FDA Label; Jardiance FDA Label; Januvia FDA Label Short Treatment with Icovamenib Delivered HbA1c Reductions Comparable to Chronic Injectable & Oral Standards of Care Comparing icovamenib to currently approved type 2 diabetes agents with chronic dosing ICOVAMENIB | COVALENT -111 26
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Overview of Treatment Emergent Adverse Events (TEAEs) Through 52 Weeks (Safety Population, N=267) Data are n (%) TEAE = Treatment Emergent Adverse event. SAE = Serious Adverse Event. *Arm A had an SAE of atrial fibrillation, unrelated to study treatment and occurred during the treatment period. *Arm C had an SAE of COVID-19. Unrelated to study treatment and occurred during the treatment period. *Placebo Arm had an SAE of nephrolithiasis. Unrelated to study treatment and occurred during the treatment period. Parameter Arm A icovamenib (N=67) Arm B icovamenib (N=67) Arm C icovamenib (N=67) Combined Arms icovamenib (N=201) Combined Arms placebo (N=66) Patients with ≥1 TEAE, N (%) 19 (28) 22 (33) 14 (21) 55 (27) 18 (27) Treatment-Related SAEs, N (%) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) SAEs*, N (%) 1 (1) 0 (0) 1 (1) 2 (1) 1 (1) Treatment Discontinuation due to TEAE, N (%) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Study Discontinuation due to TEAE, N (%) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Deaths, N (%) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) ICOVAMENIB | COVALENT -111 27
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Treatment Emergent Adverse Events (TEAEs) Occurring in ≥5% in Any Study Arm and TEAEs Reported for ALT and/or AST Elevations (Safety Population, N=267) Data are n (%) of TEAE with ≥5% frequency in any arm. ALT (alanine aminotransferase) or AST (aspartate aminotransferase) increase irrespective of incidence %. Diarrhea: In the icovamenib arms, all 7 events were Grade 1. Nausea: In the icovamenib arms, 6 of 7 events were Grade 1, and 1 event was Grade 2. In the placebo arm, the 1 event was Grade 1. Hyperglycemia: In the icovamenib arms, 2 of 8 events were Grade 1, and 6 events was Grade 2. In the placebo arm, all 3 events were Grade 2. Headache: In the icovamenib arms, 4 of the 5 events were Grade 1, and 1 event was Grade 2. In the placebo arm, 1 of the 2 events was Grade 1, and 1 event was Grade 2. ALT increase: In the icovamenib arms, 4 of the 5 events were Grade 1 and 1 event was Grade 2. AST increase: In the icovamenib arms, all 4 events were Grade 1. Parameter Arm A icovamenib (N=67) Arm B icovamenib (N=67) Arm C icovamenib (N=67) Combined Arms icovamenib (N=201) Combined Arms placebo (N=66) Diarrhea, N (%) 4 (6) 2 (3) 1 (1) 7 (4) 0 Nausea, N (%) 2 (3) 3 (4) 2 (3) 7 (4) 1 (2) Hyperglycemia, N (%) 2 (3) 5 (7) 1 (1) 8 (4) 3 (5) Headache, N (%) 0 4 (6) 1 (1) 5 (3) 2 (3) ALT increase, N (%) 3 (4) 0 2 (3) 5 (3) 0 AST increase, N (%) 3 (4) 0 1 (1) 4 (2) 0 Resolution of ALT/AST w/o interruption in study treatment, % 100 100 100 100 N/A ICOVAMENIB | COVALENT -111 28
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Menin Inhibition Potentially Leads to Increased Clinical Benefit Key Findings Through Week 52 After Only a Short Treatment Course • COVALENT-211 PHASE IIB IN SEVERE INSULIN DEFICIENT T2D, FIRST PATIENT PLANNED FOR ENROLLMENT IN 1Q 2026. • COVALENT-212 PHASE II T2D PATIENTS NOT CONTROLLED ON GLP-1 BASED THERAPIES. FIRST PATIENT PLANNED FOR ENROLLMENT IN 1Q 2026. Durable Clinical Activity in Insulin Deficient T2D Durable Clinical Activity in T2D Not Controlled on GLP-1-based Therapies Favorable Safety Higher exposure aligned with deeper HbA1c reductions. Data supports also potential for exposure improvements 1.2% mean HbA1c reduction (p=0.01) maintained through Week 52 after only 12 weeks of dosing 1.3% mean HbA1c reduction (p=0.05) maintained through Week 52 after only 12 weeks of dosing Generally well tolerated, no treatment-related serious adverse events NEXT STEPS: ICOVAMENIB 29
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ICOVAMENIB | COVALENT -211 A Phase II Trial of Icovamenib in Insulin Deficient Participants with Type 2 Diabetes Who Are Not Achieving Glycemic Targets N=60 2:1 randomization Objectives To demonstrate that icovamenib 100 mg once daily for 12 weeks is superior to placebo for glycemic control at Week 26 and Week 52 Endpoints • Mean change in HbA1c from baseline at Week 26 and 52 • Mean change in fasting plasma glucose (FPG) from baseline at Week 26 • Safety • Adult participants with Type 2 Diabetes who were treated with 1-3 antidiabetic medications • HbA1c 7.5%-10.5% • BMI ≤ 32 kg/m2 • Background therapy maintained unless rescue required Inclusion Criteria 30
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ICOVAMENIB | COVALENT -212 A Phase II Trial of Icovamenib in Participants with Type 2 Diabetes Who Are Not Achieving Glycemic Targets While Using GLP-1-Based Therapy N=60 2:1 randomization Endpoints Inclusion CriteriaObjectives • Adult participants with T2D who are not achieving glycemic targets despite GLP-1-based therapy • HbA1c ≥7.5% and ≤9.5% • BMI 25 to 40 kg/m2 • Background therapy maintained unless rescue required 31 T o demonstrate that icovamenib 100 mg once daily for 12 weeks is superior to placebo for glycemic control at Week 26 and W eek 52 • Mean change in HbA1c from baseline at Week 26 and 52 • Mean change in fasting plasma glucose (FPG) f rom basel i ne at W eek 26 • Saf ety
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ICOVAMENIB Preclinical Study Results Icovamenib in Combination with GLP-1 Based Therapies
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ICOVAMENIB | PRECLINICAL Icovamenib Downregulated Menin Protein Levels and Proliferated Beta Cells In Preclinical Human Islet Experiments Post Icovamenib Treatment Beta Cells Proliferate Post Icovamenib Treatment Menin Levels are Downregulated 33
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Icovamenib Enhanced GLP-1 Receptor & Insulin Expression (8 mM glucose)Cadaver derived human islets Gene expression & Protein analysis GLP-1 Receptor Insulin GLP-1 Receptor Insulin ICOVAMENIB WITH GLP-1RA Post Icovamenib Treatment Increased Gene Expression GLP-1 Receptor and Insulin Post Icovamenib Treatment Increased Protein Levels of GLP-1 Receptor and Insulin 34
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APPETITE SUPPRESSION BODY WEIGHT REDUCTION OBSERVED SUPERIOR APPETITE SUPPRESSION WITH ABOUT 10% GREATER BODY WEIGHT REDUCTION THAN LOW-DOSE SEMAGLUTIDE ALONE THE OBSERVED BODY WEIGHT LOSS WAS PRIMARILY DUE TO FAT MASS REDUCTION WITH COMPLETE PRESERVATION OF LEAN MASS Combination Treatment of Icovamenib & Low-dose Semaglutide Reduced Food Intake & Body Weight ICOVAMENIB WITH GLP-1RA 35
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BODY WEIGHT FAT MASS Combination of Icovamenib & Low Dose Semaglutide Selectively Promoted Fat Loss with Complete Lean Mass Preservation in ZDF Rats LEAN MASS ICOVAMENIB WITH GLP-1RA 36
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Next-Generation Oral GLP -1 Receptor Agonist BMF-650 Preclinical Results & Clinical Overview Target: OBESITY
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Improved PK Profile Greater oral exposure with lower variability observed in preclinical studies Generally Favorable Safety Profile Better tolerability associated with higher plasma protein binding in preclinical models Patient Friendly Design Oral delivery with the potential for simplified dose escalation Differentiated properties exhibited by BMF-650 • Only 3 of 10 patients remain on GLP-1 therapy at one year due to tolerability, GI effects and complexity of use. • A therapy with a greater therapeutic window can allow effective dosing with improved tolerability. • An oral agent with improved tolerability could potentially expand the long-term use. “Why is a greater therapeutic window important?” Designed to Deliver Strong Efficacy with Improved Oral Tolerability A Next-Generation Oral GLP-1 Receptor Agonist BMF-650 1.Khan, et al. JAM A 2024 doi:10.1001/jama.2024.22284. 1 38
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CYNOMOLGUS MONKEY PO PK CYNOMOLGUS MONKEY PK DAY 6 BMF -650 SPRAGUE-DAWLEY RAT PO PK SPRAGUE-DAWLEY RAT PK DAYS 1, 7 BMF -650 Continuous Exposure after multiple days * d6 of 6 days of daily PO dosing; d6# after 6 additional days of PO dosing at indicated dose level. ** hr*ng/mL PO =per oral Dose Proportionate Exposure Pharmacokinetics of BMF-650 Showed Very Good Preclinical Bioavailability with Low Inter-Individual Variability BMF-650 showed 2 - to 3 -fold greater oral bioavailability in comparison to orforglipron BMF-650 showed 2 - to 3 -fold greater oral bioavailability in comparison to orforglipron BMF-650 | PRECLINICAL 39
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BMF-650, 10 mg/kg BMF-650, 30 mg/kg VEHICLE Preclinical Weight-Loss Study in Obese Cynomolgus Monkeys PRE-STUDY: 14 DAYS STUDY: 28 DAYS GROUP 1 (n=5) GROUP 2 (n=5) GROUP 3 (n=5) STUDY OVERVIEW STUDY DESIGN • 14-day acclimation; 3 groups (n=5) • QD dosing via oral gavage for 28 days • BMF-650: 10 or 30 mg/kg, or vehicle ASSESSMENTS • Food provided as breakfast, fruit snack, and dinner; intake tracked • Body weight & physicals recorded daily • Lab values measured on days -5, 13, 20, 29 • Study captured daily food intake & weight change BMF-650 | PRECLINICAL 40
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Disclaimer: No head-to-head studies of BM F -650 and CT -996 have been conducted. Comparing results from different preclinical studies may be unreliable due to differences in study designs, study endpoints, and other parameters. BMF-650 BODY WEIGHT CHANGE Oral BMF-650 Weight Loss Study in Obese Cynomolgus Monkeys Weight loss in cross-study comparison with CT-996 (Roche/Carmot), while not head-to-head appeared favorable CT-996 BODY WEIGHT CHANGE Literature data; Carmot Therapeutics (now part of the Roche group), ADA 2024. BMF-650 | PRECLINICALBMF-650 | PRECLINICAL 41
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BODY WEIGHT CHANGE (individual obese monkey) Mean reduction in BW (Day 29) Vehicle -3.4% BMF-650 10 mg/kg-12.3% BMF-650 30 mg/kg-15.2% Oral BMF-650 Demonstrated Strong Dose Dependent Body Weight Reduction in Obese Cynomolgus Monkeys BMF-650 | PRECLINICAL 42
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WEEK 1 2 3 4 EMESIS 16%* 4.2% 4.2% 1.4% *One monkey (#3) accounted for 8 of the 18 total events • BMF-650 generally well tolerated with no elevations of AST or ALT • With 420 dosing occurrences (280 active/140 placebo) there were only a total of 18 (6.4%) events of emesis in the active group • Most events occurred early, with a marked decline after the first week • Study was run without a titration scheme, once daily dosing over 28 days Oral BMF-650 Generally Well Tolerated in 28 Day Preclinical Animal Study Low rate of emesis events, mostly in one animal, that decreased rapidly over time BMF-650 | PRECLINICAL (Events per 70 weekly dosing occurrences) SAFETY SUMMARY 43
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10 mg (fasted) 25 mg (fed)25 mg (fasted) 50 mg (fasted) 100 mg (fed)100 mg (fasted) 200 mg (fasted) Design BMF-650 | GLP-131 A Randomized, Double-blind, Placebo-controlled, FIH Study of an Oral Non-peptide GLP-1 Receptor Agonist Part 1 is a single ascending dose (SAD) study and Part 2 is a multiple ascending dose (MAD) study. Single Ascending Dose (SAD) Multiple Ascending Dose (MAD) Objectives Safety and tolerability, PK, and food effect Safety and tolerability, and efficacy (weight-loss) Eligibility Healthy overweight or obese patients (BMI 25.0–40.0 kg/m²) Healthy overweight or obese patients (BMI 30.0–45.0 kg/m²) 10 mg → 25 mg → 50 mg → 100 mg COHORT 1 2 3 4 BMF-650 active drug placebo 25 mg → 50 mg → 100 mg → 200 mg 25 mg → 75 mg → 150 mg → 300 mg 50 mg → 100 mg → 200 mg → 400 mg 7 DAYS → 7 DAYS → 7 DAYS → 21 DAYS 5 cohorts N=40 N=40 x 4 cohorts x Body weight vs. Baseline recorded at Day 28 and Day 42 44
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BMF-650 Allowance for Intellectual Property of BMF-650 Received BMF-650 Intellectual Property: Our US and PCT applications for BMF-650 are published and proceeding through examination We received allowance in mid December 2025 for our US patent application covering BMF-650 Additional details, including the list of allowed claims, are available through the U.S. Patent and Trademark Office (USPTO). 45
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BMF-650 | GLP-131 Phase I study currently enrolling • Phase I study in obese, otherwise healthy volunteers is currently enrolling • 28-day weight reduction data anticipated in 2Q 2026 CLINICAL STUDY Oral BMF-650 Preclinically Demonstrated a Strong Profile with Consistent Exposure & Weight Loss Effect Intrinsic potency Robust appetite suppression and weight reduction in primate models Projected clinical dose aligned with other leading oral GLP-1 agents Generally well tolerated with no safety concerns identified to date Superior oral bioavailability observed vs. orforglipron (across species) Similar to the broader orforglipron chemotype 46
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ICOVAMENIB COVALENT-211 Phase IIb Insulin Deficient T2D Patients First Patient Enrollment Panned in 1Q 2026 + Evaluate icovamenib in Insulin Deficient T2D Patients + GLP-131 Phase I Obesity Study Evaluate Safety of BMF- 650 and 28-Day Weight Reduction in Obese Patients + Study Enrollment Completion Expected 2Q 2026 + BMF-650 COVALENT-121 Food Effect Study Optimize Dosing Criteria + Started September 2025 + COVALENT-212 Phase II T2D Patients not controlled on GLP -1 based therapies Evaluate icovamenib added to GLP-1 based Therapies in T2D + First Patient Enrollment Panned in 1Q 2026 + ICOVAMENIB Advancing Multi Program Clinical Pipeline Through 2026 ICOVAMENIB WITH GLP -1RA Completed in December 2025 + 47
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Initiate GLP -131 Phase I Study COV-211 Phase IIb First Patient Enrollment Planned (Insulin -Deficient Diabetes) 3Q 2025 GLP-131 Phase I 28-Day Weight Loss Study Results Expected COV-111 T2D All Comers 52-Week Topline Data COV-212 Phase II First Patient Enrollment Planned (Diabetes Not Controlled on GLP -1 Based Therapies) COV-121 Food Effect Study Results 1H 2026 BMF-650 COVALENT-111 Icovamenib Phase II in T2D Patients All Comers, Topline 52 -Week Data Presented October 2025 COVALENT-121 Icovamenib Food Effect Study Completed December 2025 COVALENT-211 Icovamenib Phase II in Insulin -Deficient T2D Patients COVALENT-212 Icovamenib Phase II (GLP-1 combo) in T2D Patients not Controlled on GLP -1 Based Therapies GLP-131 BMF-650 Phase I in Obese otherwise Healthy Volunteers 4Q 2025 Timeline Overview of Key Program Activities ICOVAMENIB 48
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Ralph DeFronzo, M.D. ENDOCRINOLOGIST, PROFESSOR OF MEDICINE UTHSCSA Melanie Davies, M.D. DIABETOLOGIST, PROFESSOR OF DIABETES MEDICINE AT THE UNIVERSITY OF LEICESTER “Icovamenib's recent data has shown an impressive restoration of beta cell function as demonstrated by significant elevations in C-peptide even after the treatment period ended. This data validates the mechanism of action of this menin inhibitor as a disease modifying agent and helps address the poor adherence and persistence commonly seen in type 2 diabetes.” Steve Edelman, M.D. ENDOCRINOLOGIST, PROFESSOR OF MEDICINE UCSD / VA SAN DIEGO “The icovamenib data looks exciting. The data presented today help to confirm icovamenib’s mechanism of action. We have not previously seen data like this with any antihyperglycemic agent. As more trials are conducted, I believe that inhibition of menin may lead to benefits across all subtypes of diabetes. I applaud Biomea for developing a potential new treatment option that may be disease modifying for patients with diabetes.” “Great foray into precision medicine. We need to be addressing patients in a much more individualized manner. By addressing insulin-deficient diabetes patients with icovamenib, we have seen post treatment that the beta cell pool is being restored and producing a higher level of insulin, as measured by C- peptide. This indicates a fundamental and potentially lasting impact on the disease and validates the mechanism of action of menin inhibition.” Key Opinion Leader Highlight Icovamenib’s Potential to Redefine Diabetes Care 49
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Alice Cheng, M.D. ENDOCRINOLOGIST, ASSOCIATE PROFESSOR OF MEDICINE UNIVERSITY OF TORONTO “Icovamenib is a very interesting molecule that acts quite differently than anything I have seen before. We are observing glucose controlled and beta cell-specific proliferation and an increase in stimulated C-peptide secretion leading to patient benefits that continued after the icovamenib dosage ended. I am very excited to further explore the many opportunities that the covalent inhibition of menin will provide to patients.” Rohit Kulkarni, M.D., Ph.D. PROFESSOR OF MEDICINE AT HARVARD MEDICAL SCHOOL Julio Rosenstock, M.D. DIRECTOR VELOCITY CLINICAL RESEARCH AT MEDICAL CITY DALLAS AND CLINICAL PROFESSOR OF MEDICINE, UNIV. OF TEXAS SOUTHWESTERN MEDICAL CENTER “The icovamenib data are quite interesting because of the continued effects despite having stopped it. Usually, one would expect to see the HbA1c levels climb towards baseline when the medication is stopped, but with icovamenib, the HbA1c levels decreased, which is quite intriguing and unprecedented.” “We do not have an agent today that addresses one of the root cause of diabetes - beta cell dysfunction - icovamenib would be the first. Patients are achieving lasting benefits without continuous chronic dosing, suggesting that icovamenib may be disease modifying. I am very impressed.” Key Opinion Leader Highlight Icovamenib’s Potential to Redefine Diabetes Care 50
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THANK YOU For questions or inquiries, please reach out to Meichiel Weiss at ir@biomeafusion.com www.biomeafusion.com