Slides
Page 1
Biomea Fusion Corporate Presentation 4TH QUARTER 2025
Page 2
Legal Disclaimer & Forward-looking Statement 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. 2
Page 3
Biomea Fusion 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. >800m PEOPLE WORLDWIDE LIVING WITH DIABETES 1 20-40% OF T2D PATIENTS WORLDWIDE HAVE SEVERE BETA CELL DYSFUNCTION 3-5 1b PEOPLE GLOBALLY ARE CLASSIFIED AS OBESE 2 >$100b PROJECTED INCRETIN THERAPY MARKET BY 2030 6 First-in-class small molecule menin inhibitor taken for just 12 weeks to durably restore the body's natural insulin production by regenerating pancreatic beta cells. Target - Diabetes ICOVAMENIB Next-generation, oral GLP- 1 Receptor Agonist Target - Obesity (Appetite & Glycemic Control) BMF-650 3 Transformative Oral Therapies for Metabolic Disease 1. Zhou. Lancet 2024; 404: 2077–93. 2. World Health Organization 3. Ahlqvist et al Diabetes 2020;69:2086–2093. 4. Mohan V. Diabetes Care 2025;48:153–163. 5. Song A. et al. Front Endocrinol. 2022;13:978612. 6.Goldman Sachs Research 2023; Grandview Research. 2023.
Page 4
TWO PHASE II STUDIES STARTING IN 4Q25 ICOVAMENIB • Short-course therapy • Increase of beta cell mass • Restoration of beta cell function • Durable HbA1c improvements • Potential synergy when combined with GLP-1 therapies • Phase IIa study complete First-in-Class Oral Menin Inhibitor (Selective & Partial Menin Inhibition) • Improved PK and tolerability • Potential for a more patient friendly profile vs. orforglipron • Reduction of appetite and improvement in glucose PHASE I STUDY ENROLLMENT ONGOING DATA EXPECTED 1H 2026 Next-Generation Oral GLP-1 Receptor Agonist (Appetite & Glycemic Control) 4 BMF-650
Page 5
STUDY INDICATIONS PRE-CLINICAL PHASE I PHASE II PHASE III NEXT MILESTONE COVALENT-111 T2D – All Comers 52-week follow-up data presented October 2025 COVALENT-211 T2D – Insulin- Deficient Patients Commencement of Phase IIb (planned start 4Q 2025) COVALENT-212 T2D – Patients not controlled on GLP-1 based therapies Commencement of Phase II (planned start 4Q 2025) GLP-131 Obesity/T2D Phase I data expected 1H 2026 ICOVAMENIB ICOVAMENIB ICOVAMENIB BMF-650 (study completed) (study planned) (study planned) (enrolling) 5 Biomea Pipeline Biomea Fusion retains full worldwide rights across all programs
Page 6
ICOVAMENIB First-in-Class Oral Menin Inhibitor Selective & Partial Menin Inhibition
Page 7
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 pups immediately postpartum 2 • In humans, lactation lowers the lifetime maternal T2D risk by up to 50% 3-5 • Protection from occurrence of T2D increases with the duration of lactation; ≥3 months provides benefit, ≥6 months strongest 3-5 • Reduced T2D risk persists for up to 30 years postpartum 5 7 Menin is Inhibited by Prolactin During Pregnancy & Breastfeeding Allowing for Beta Cell Regeneration & Reduced Diabetes Risk Menin inhibition with icovamenib may phenocopy the marked reduction in T2D incidence observed 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, Abstract 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_Diabetes Obes Metab_Association of lactation with maternal risk of type 2 diabetes - A systematic review and meta-analysis of observational studies. 5. Gunderson EP et al._2018_JAMA Int Med_Lactation duration and progression to diabetes in women across the childbearing years - The 30-year CARDIA study
Page 8
Increased beta cell mass and function Increased insulin synthesis and secretion DUAL EFFECT BETA CELL QUANTITY & FUNCTION GLP-1 RECEPTOR EXPRESSION Increased GLP-1 receptor expression and incretin effect Enhanced weight loss with preservation of lean muscle mass in preclinical studies combining icovamenib with a GLP-1RA ORAL Short duration dosing with sustained effect NON -CHRONIC Favorable safety profile observed to date WELL TOLERATED Mechanism orthogonal and complementary to other metabolic agents COMBINATION -READY 8 ICOVAMENIB Mechanism of Action of Icovamenib Convenient once-daily oral therapy ORAL DIFFERENTIATING FEATURES
Page 9
Icovamenib Increases Beta Cell Quantity, Function & GLP-1 Receptor Expression Following a Short Treatment Period Stages of Beta Cell Proliferation (After Icovamenib Treatment) 9
Page 10
18% OF PEOPLE IN US WITH T2D 44% OF PEOPLE IN ASIA-PAC WITH T2D Type 2 Diabetes is a Heterogeneous Disease – Two Core Drivers INSULIN RESISTANCE Severe insulin- deficient diabetes Mild age-related diabetes Mild obesity- related diabetes Severe insulin resistant diabetes MEDIAN HOMA -B 49% MEDIAN HOMA -B 64% MEDIAN HOMA -B 74% MEDIAN HOMA -B 101% MEDIAN HbA1c 8.3% MEDIAN HbA1c 7.0% MEDIAN HbA1c 7.2% MEDIAN HbA1c 7.0% INSULIN DEFICIENCY 39% OF PEOPLE IN US WITH T2D 22% OF PEOPLE IN US WITH T2D 15% OF PEOPLE IN US WITH T2D Ahlqvist et al. Lancet Diabetes Endocrinol 2018; 6: 361–69 Analysis from two independent 4,000 patient studies, (ADOPT and RECORD) MEDIAN BMI MEDIAN BMI MEDIAN BMI MEDIAN BMI29 KG/M 2 29 KG/M 2 36 KG/M 2 34 KG/M 2 PRIMARY TARGET POPULATION FOR ICOVAMENIB 10 Patients with insulin-deficient T2D are most likely to benefit from a beta cell regenerating therapy like icovamenib PRIMARY ISSUE: LOW INSULIN PRODUCTION PRIMARY ISSUE: IMPAIRED INSULIN ACTION
Page 11
High Unmet Need in Patients with Severe Insulin-Deficient Type 2 Diabetes 11 1.Zohu Lancet 2024; 404: 2077-93 (adjusted by company to account for Severe Insulin-deficient patients) 2.Fendo 2022 doi: 10.3389/fendo.2022.927661 https://doi.org/10.1371/journal.pone.0304036 $14b Estimated U.S./EU revenue potential (based on 10% penetration, at 10k) 80m Type 2 Diabetes US/EU diagnosed patients 14m Addressable U.S./EU target patients 1 60+ Approved T2D therapies, all chronic agents, none address the root cause of the disease 18-44% Of all T2D patients are severely insulin- deficient, this group has the highest failure rate among all T2D subgroups 2 PRIMARY TARGET POPULATION FOR ICOVAMENIB
Page 12
52-Week Results COVALENT-111 Phase II Study Icovamenib in Type 2 Diabetes ICOVAMENIB
Page 13
ICOVAMENIB | COVALENT -111 COVALENT-111 Trial Design Phase 2a Randomized, Double-Blind, Placebo-controlled Study in Participants with T2D 13 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)
Page 14
Arm A, B, and C primary analysis: change in HbA1c Prespecified subgroup analysis to include assessment of HbA1c change within each T2D subgroup: • Severe Insulin Deficient Diabetes • Mild Age Related Diabetes • Mild Obesity Diabetes • Severe Insulin Resistant Diabetes Subgroup analysis based on algorithm established per Ahlqvist et al. (Lancet Diabetes Endocrinol. 2018;6:361-369) ICOVAMENIB | COVALENT -111 14 COVALENT-111 Statistical Analysis Plan Read Out of Insulin-Deficient & Insulin Resistant Subgroups at Weeks 26 and 52
Page 15
*Per the COVALENT-111 Protocol the population analyzed includes only subjects who received ≥80% of their planned dosing. A clinical 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 15 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)
Page 16
MOST PARTICIPANTS TREATED WITH METFORMIN MONOTHERAPY, WITH APPROXIMATELY 20% TREATED WITH SGLT2I, 10% WITH DPP4I, AND 10% WITH GLP -1 BASED MEDICINES 16 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)
Page 17
SIDD = Severe Insulin-Deficient Diabetes MARD = Mild Age-Related Diabetes MOD = Mild Obesity-Related Diabetes SIRD = Severe Insulin-Resistant Diabetes 17 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) INITIAL TARGET POPULATION FOR ICOVAMENIB
Page 18
All presented data utilized a while-on-treatment estimand with mixed model repeated measures (MMRM) analysis and was censored for use of rescue medication, defined as any modification in anti-diabetic therapy. 18 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) Treatment Off-Treatment
Page 19
19 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 Treatment Off-Treatment
Page 20
20 12 Weeks of Dosing (Arm B) Delivered Most Improved Results Through 52 Weeks for Severe Insulin-Deficient Diabetes Patients 9 Months After Last Dose ICOVAMENIB | COVALENT -111 Arm B: 12 weeks of dosing 100 mg QD -0.5% threshold for clinical significance CMS Clinical Endpoints Review (2024) INITIAL TARGET POPULATION FOR ICOVAMENIB Treatment Off-Treatment
Page 21
Food type and timing of dosing relative to food impact icovamenib’s pharmacokinetics. Food-effect study data expected 4Q 2025 to optimize dosing instructions, which we expect will further improve exposure and improve consistency of outcome across patients. 21 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
Page 22
Increased beta cell mass and function Increased insulin synthesis and secretion DUAL EFFECT BETA CELL QUANTITY & FUNCTION GLP-1 RECEPTOR EXPRESSION Increased GLP-1 receptor expression and incretin effect Enhanced weight loss with preservation of lean muscle mass in preclinical studies combining icovamenib with a GLP-1RA ORAL Short duration dosing with sustained effect NON -CHRONIC Favorable safety profile observed to date WELL TOLERATED Mechanism orthogonal and complementary to other metabolic agents COMBINATION -READY 23 ICOVAMENIB Mechanism of Action of Icovamenib Convenient once-daily oral therapy ORAL DIFFERENTIATING FEATURES
Page 23
22 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
Page 24
Disclaimer: The data presented above are based on cross-study comparisons and are not based on any head-to-head clinical trials. Cross-study comparisons are inherently limited and may suggest misleading similarities and differences. The values shown in the cross-study comparisons are directional and may not be directly comparable. 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 24 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
Page 25
25 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. Subject required hospitalization and was discharged in 3 days. Subject continued in the study. *Arm C had an SAE of COVID-19. Unrelated to study treatment and occurred during the treatment period. Subject required hospitalization and was discharged in 3 days. Subject continued in the study. *Placebo Arm had an SAE of nephrolithiasis. Unrelated to study treatment and occurred during the treatment period. Subject required hospitalization and was discharged in 3 days. Subject continued in the study. 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
Page 26
26 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 and ALT or AST increase irrespective of incidence; Safety population TEAE, treatment-emergent adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase. 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, 6 of 8 events were Grade 2, and 2 events was Grade 1. 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
Page 27
*Hypoglycemic adverse event occurred outside of the 12-week treatment window. 27 Subjects with Treatment Emergent Adverse Events of Hypoglycemia (Safety Population, N=267) ICOVAMENIB | COVALENT -111 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) Grade 1, N (%) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Grade 2, N (%) 0 (0) 1 (1)* 0 (0) 1 (0.5)* 0 (0) Grade 3, N (%) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)
Page 28
28 Durable Efficacy in Insulin Deficient T2D Key Findings Through Week 52 After a Short Treatment Course Per Protocol Participants taking one or more antihyperglycemic medications at baseline COVALENT-211 PHASE IIB IN SEVERE INSULIN DEFICIENT T2D, FIRST PATIENT IN 1Q 2026 COVALENT-212 PHASE II T2D PATIENTS NOT CONTROLLED ON GLP-1 BASED THERAPIES. FIRST PATIENT IN 1Q 2026 Durable Efficacy in T2D not controlled on GLP -1 based Therapies Menin Inhibition leads to increased clinical Benefit Favorable Safety 1.5% mean HbA1c reduction (p=0.01) maintained through Week 52 1.3% mean HbA1c reduction (p=0.05) through Week 52 after only 12 weeks of dosing Higher exposure aligned with deeper HbA1c reductions. Data supports also potential for exposure improvements Well tolerated, no treatment-related serious adverse events. NEXT STEPS: ICOVAMENIB | COVALENT -111
Page 29
ICOVAMENIB Preclinical Study Results Icovamenib in Combination with GLP-1 Based Therapies
Page 30
INCREASED GENE EXPRESSION 30 Icovamenib Enhances 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 INCREASE IN PROTEIN LEVELS
Page 31
APPETITE SUPPRESSION BODY WEIGHT REDUCTION 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 31 Combination Treatment of Icovamenib & Low-dose Semaglutide Reduces Food Intake & Body Weight ICOVAMENIB WITH GLP-1RA
Page 32
BODY WEIGHT FAT MASS 32 Combination of Icovamenib & Low Dose Semaglutide Selectively Promotes Fat Loss with Complete Lean Mass Preservation in ZDF Rats LEAN MASS ICOVAMENIB WITH GLP-1RA
Page 33
Next-Generation Oral GLP-1 Receptor Agonist for Obesity • Preclinical studies show strong appetite suppression and progressive weight reduction in obese primates • Phase I study in obese healthy volunteers currently enrolling • Initial 28-day weight reduction data in obese, otherwise healthy volunteers expected in first half of 2026 BMF-650
Page 34
FAVORABLE SAFETY PROFILE PATIENT FRIENDLY DESIGN IMPROVED PK PROFILE Greater oral exposure with lower variability observed in preclinical studies Better tolerability associated with higher plasma protein binding in preclinical models Oral delivery with the potential for simplified dose escalation 34 Differentiated properties exhibited by BMF-650 compared to orforglipron. Only 3 of 10 patients remain on GLP-1 therapy at one year due to tolerability, GI effects and complexity of use. An oral agent with improved tolerability could 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 1.Khan, et al. JAMA 2024 doi:10.1001/jama.2024.22284. 1 BMF-650
Page 35
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 35 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
Page 36
BMF-650, 10 mg/kg BMF-650, 30 mg/kg VEHICLE 36 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
Page 37
Disclaimer: No head-to-head studies of BMF-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 37 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 appears favorable CT-996 BODY WEIGHT CHANGE Literature data; Carmot Therapeutics (now part of the Roche group), ADA 2024. BMF-650 | PRECLINICALBMF-650 | PRECLINICAL
Page 38
BODY WEIGHT CHANGE (INDIVIDUAL) Mean reduction in BW (Day 29) Vehicle -3.4% BMF-650 10 mg/kg -12.3% BMF-650 30 mg/kg -15.2% 38 Oral BMF-650 Demonstrates Strong Dose Dependent Body Weight Reduction in Obese Cynomolgus Monkeys BMF-650 | PRECLINICAL
Page 39
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 39 BMF-650 Was Well Tolerated in 28 Day Preclinical 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
Page 40
Phase I study enrolling • Phase I study currently enrolling • 28 Day Weight Reduction in obese otherwise healthy Volunteers anticipated in 1H 2026 NEXT STEPS 40 BMF-650 Demonstrated a Strong Preclinical Profile with Consistent Oral 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 Superior oral bioavailability vs. orforglipron (across species) BMF-650 is similar to the broader orforglipron chemotype BMF-650 | GLP-131
Page 41
ICOVAMENIB COVALENT-211 Phase IIb Insulin Deficient T2D Initiation expected 4Q 25+ Evaluate icovamenib in insulin deficient patients + GLP-131 Phase I Obesity Study Evaluate safety of BMF-650 and 28 day weight reduction in obese patients + Study enrolling, completion expected 1H 26 + 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 therapy in T2D + Initiation expected 4Q 25+ 41 ICOVAMENIB Advancing Multi Program Clinical Pipeline Through 2025 & 2026 ICOVAMENIB WITH GLP -1RA Completion expected December 2025 +
Page 42
Initiate GLP -131 Phase I Study Initiate COV -211 Phase IIb (Insulin-Deficient Diabetes) 3Q 2025 Phase I 28-Day Weight Loss COV-111* 52-Week Topline Data Initiate COV -212 Phase II (T2D not controlled on GLP -1 based therapy) COV-121 Food Effect Study 1H 2026 BMF-650 COVALENT-111 Phase II in T2D Patients * 52 -Week Data Presented October 2025 COVALENT-121 Icovamenib Food Effect Study started September 2025; expected completion December 2025 COVALENT-211 Phase II in Severe Insulin -Deficient T2D Patients COVALENT-212 Phase II (GLP-1 combo) in T2D Patients Uncontrolled on GLP -1 Based Therapies 4Q 2025 42 Clinical Pipeline & Key Program Activities Overview 12 month-snapshot ICOVAMENIB
Page 43
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.” 44 KOLs Highlight Icovamenib’s Potential to Redefine Diabetes Treatment
Page 44
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.” 45 KOLs Highlight Icovamenib’s Potential to Redefine Diabetes Treatment
Page 45
THANK YOU For questions or inquiries, please reach out to Meichiel Weiss at ir@biomeafusion.com www.biomeafusion.com