Slides
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TECH Biomea Fusion Corporate Presentation 3Q 2026 biomea FUSION ™
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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, including our expected cash runway, the initiation, timing and results of pending or future preclinical studies and clinical trials, the actual or potential actions of the U.S. 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
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Transforming diabetes and obesity with novel oral medicines 3 ICOVAMENIB Potential first-in-class oral small molecule targeting menin - the control switch to beta cell restoration Restores functional beta-cell mass and improve endogenous insulin production in both type 1 and type 2 diabetes Critical unmet need: In type 1 diabetes, there are no approved therapies that directly restore or preserve beta-cell function, and patients rely on lifelong insulin therapy.1 In type 2 diabetes, approximately 1/3 of all diabetes patients fail standard of care and progress to insulin dependence driving complications such as kidney disease, nerve damage, vision loss, and cardiovascular issues.2-4 In obesity and overweight individuals, current therapies have substantially improved weight loss, but may also result in loss of lean muscle mass, raising concerns about preservation of physical function and quality of life.5 BMF-650 Next-generation oral GLP-1 receptor agonist Designed for consistent exposure, higher bioavailability and improved tolerability with scalable weight reduction Critical unmet need: Real world evidence indicates that up to 70% of patients on currently available GLP-1 based therapies drop out within the first year due to gastrointestinal adverse events and other tolerability considerations.4 Biomea Fusion founded in 2017 (public in 2021; NASDAQ: BMEA ) Clinical-stage company advancing two differentiated metabolic investigative programs 1.www.breakthrought1d.org Scherer et al., Scientific Reports, 2020; 2. Nichols et al., Diabetes Care, 2015; 3.UKPDS Group. Lancet, 1998; 4. Prime Therapeutics & Magellan Rx Management, 2023 real-world claims analysis. 5. Neeland IJ, et al. Changes in lean body mass with glucagon-like peptide-1-based therapies and mitigation strategies. Diabetes Obes Metab. 2024. Biomea funded through key clinical readouts for icovamenib and BMF-650 into 2Q of 2027
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Investment Thesis 4 Biomea is building a leading metabolic disease company with two differentiated programs and multiple near-term catalysts. First-in-class beta cell restorative therapy in diabetes Potential best-in-class oral GLP-1 receptor agonist in obesity Multiple Phase II readouts over the next 12 months Experienced leadership team with a clear vision and execution plan Cash runway through key upcoming value inflection read outs
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PROGRAM INDICA TION PHASE I PHASE II PHASE III Biomea pipeline Biomea Fusion retains full worldwide rights across all programs and is currently funded through major catalysts into 2Q 2027 UPCOMING MILESTONES ICOVAMENIB Potential first-in- class oral menin inhibitor BMF-650 Potential best-in- class oral GLP-1 RA (study enrolling) GLP-131 (study enrolling) COVALENT-211 (study enrolling) COVALENT-212 Phase II 26-week data (primary endpoint) anticipated 4Q 2026 Phase II 26-week data (primary endpoint) anticipated 4Q 2026 Phase I 28-day weight reduction data anticipated in 3Q 2026 Type 2 diabetes Patients with insulin deficiency (~7M U.S. Patients) 1 Patients not controlled on GLP-1 based therapies Type 2 diabetes (15-45% U.S. Patients on GLP-1RA) 2,3 Obesity (>100M U.S. Patients) 5 1.International Diabetes Federation. IDF Diabetes Atlas www.diabetesatlas.org (Based on company calculations) 2.NHANES analyses of glycemic control among U.S. adults with diabetes (JAMA; Diabetes Care); 3.SUSTAIN, AWARD, and SURPASS clinical trial programs for GLP-1 receptor agonists 4.Mayer-Davis et al., NEJM / CDC updates 5.National Center for Health Statistics August 2023. Accessed J une 10 , 2026 5 OPAL Study Obesity/Overweight Sponsored by Leicester Diabetes Center Phase II initiation anticipated in 2H 2026 (>190M U.S. Patients) 5 ICOVAMENIB with low dose Semaglutide
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1 in 3 Americans will develop diabetes during their lifetime In the U.S. 80% of people with diabetes will die from diabetes.1 Premature mortality caused by diabetes results in an estimated 12-14 years of life lost.2 Diabetes creates one of the largest economic burdens on the U.S. health care system. $1 out of every $4 in U.S. health care costs is being spent on caring for people with diabetes3. There are over 60+ approved type 2 diabetes therapies, but these therapies struggle to address the root cause of the disease. In the US today, ~38 Million adults have diabetes, and 97.6 Million have prediabetes3 Over 800 million adults globally are living with diabetes4 1. Tabish Int J Health Sci. 2007 Jul;1(2):V–VIII. 2. National library of Medicine 1(2); 2007 Jul PMC3068646 3. CDC National Diabetes Statistics Report accessed January 2025 4. Zohu Lancet 2024; 404: 2077–93 6 Today diabetes remains poorly controlled in 50% of patients treated with standard of care agents4
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The Opportunity 7 Growing market with large unmet need Diabetes >38M People living with diabetes in U.S.1 >35M People with T2D in U.S.2 1:3 People in U.S. with T2D using Insulin3 25% Of U.S. healthcare dollars go to treat those with diabetes4 Obesity >190M People in U.S. are obese or overweight5 100M + People in U.S. are obese5 5M+ People in U.S. discontinue GLP-16 Large unmet need for durable, well-tolerated therapies 1. CDC, Natl. Diabetes Stat. Rep., 2022 2. ADA, Standards of Care in Diabetes, Diabetes Care, 2024 3. Li J Diabetes Complications 2012;26(1):17-22 4. CDC Health and Economic Benefits of Diabetes Interventions 5. CDC National Health and Nutrition Examination Survey 6. IQVIA prescription data Addressing root biology has the potential to address patient outcomes
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Icovamenib aims to delay need for insulin therapy and reduce complications and disease burden Early-Stage Mid-Stage Late-Stage Lifestyle Metformin GLP-1 / SGLT2 ± Other Add-Ons Persistent HbA1c elevation despite optimized therapy Basal Insulin ± Intensification Macrovascular disease Coronary artery disease Chronic kidney disease Severe autonomic neuropathy Retinopathy Stroke β-cell stress Insulin deficiency/resistance Metabolic dysregulation Microvascular disease Diabetes nephropathy (early) Peripheral neuropathy Autonomic neuropathy (early) In the U.S., >50% of patients with diabetes remain above HbA1c targets ≥7%1 Depending on the GLP-1 RA agent, 15-45% do not achieve HbA1c < 7% in clinical trials2 1.NHANES analyses of glycemic control among U.S. adults with diabetes (JAMA; Diabetes Care); 2.SUSTAIN, AWARD, and SURPASS clinical trial programs for GLP-1 receptor agonists 8 icovamenib
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Potential first-in-class menin inhibitor for diabetes – PRECLINICAL RESULTS ICOVAMENIB
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• Physiologic states such as pregnancy and lactation suppress menin, enabling beta-cell expansion and increased insulin output • Preclinical and human data consistently link reduced menin signaling to improved beta-cell mass and function. First in a 2005 paper in Proceedings of the National Academy of Sciences (PNAS) by Satyajit K. Karnik et al. titled “ Menin regulates pancreatic islet growth by promoting histone methylation and expression of genes encoding p27^Kip1 and p18^INK4c” • Icovamenib has been shown to directly inhibit menin, aiming to pharmacologically replicate a naturally occurring, validated biologic process 10 Karnik SK, et al. Science. 2007;318:806-809 Menin is naturally inhibited during pregnancy and breastfeeding - allowing for adaptive beta cell mass increase & reduced diabetes risk
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“We conclude that during pregnancy, placental hormones act through the prolactin receptor to increase beta cell mass by up regulating beta cell proliferation by engaging Jak2, Akt, menin/p18, and p21.” Hughs et al. Endocrinology, March 2011, 152(3):847–855 “This quantitative morphological study shows a marked enlargement of the islets of Langerhans in pregnant women.” F. A. Van Assche et al. British Jornal of Obstetrics and Gynaecology, 1978 November 11 Beta Cells Proliferation During Pregnancy
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“In nondiabetic obesity, an expansion in beta cell mass occurs to provide sufficient insulin and to prevent hyperglycemia. This expansion is at least in part due to beta cell proliferation. Linnmann et al. American Society for Nutrition. Adv. Nutr. 5: 278– 288, 2014 Insulin Positive Beta-Cell Volume (ml) 12 Beta Cells Proliferation in Obesity
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IMPROVED BETA CELL MASS & FUNCTION FOR TYPE 1 AND TYPE 2 DIABETES Icovamenib promotes selective and partial reduction in menin levels Induction of beta cell proliferation Increased expression of • GLP-1 • GLP-1 receptor IMPROVED INCRETIN EFFECTS Icovamenib’s mechanism of action ICOVAMENIB | MOA 13 Lowering menin levels releases the break on beta cell proliferation and GLP-1 and GLP-1 receptor expression Decrease in blood glucose (HbA1c) Increase in insulin/C-peptide Synergistic with GLP-1 based therapies Potential for lean mass/muscle preservation Potential for weight loss Improved beta cell function Pancreatic islet Decrease in blood glucose (HbA1c) 13
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Menin is a scaffold protein, encoded by the gene MEN1, that has been recognized for its role in Type 2 Diabetes Mellitus (T2DM) as a key regulator of beta-cell proliferation. Men1 knockout mice demonstrate increased beta-cell mass generation (Yang et al., 2010) and menin inhibition has previously been shown to improve glycemic control in high fat induced diabetic mice (Ma et al., 2021). Men1-excised mice do not develop hyperglycemia in a Streptozotocin-(STZ) induced rat model, which is a model for impaired beta- cell function and insulin production, demonstrating the role of menin in glycemic control. Men1-excised mice did not develop hyperglycemia in the STZ model, which was observed in the control group MEN1 excision prevents development of STZ-induced hyperglycemia Potential for menin inhibition demonstrated by beta cell ablation diabetes model in MEN1-excised mice 14 Control Men1-excised Yang, et al. 2010
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ORAL GLUCOSE TOLERANCE TEST (DAY 17) 15 Icovamenib significantly reduced blood glucose in STZ rats (a model in which only insulin decreases blood glucose levels) STZ TREATMENT TYPICALLY RESULTS IN ~50% BETA CELL LOSS 0 15 30 60 90 120 0 200 400 600 800 Minutes Blood Glucose (mg/dL) Mean ± SEM Vehicle Pioglitazone (30 mg/kg) BMF-219 (175mg/kg) * * * * * * p<0.05 vs Vehicle Icovamenib (175mg/kg) (insulin desensitizer) (menin inhibitor) STZ=Streptozotocin, an antibiotic that produces pancreatic islet beta cell destruction and is widely used experimentally to produce a model in diabetes Butler, et al. (EASD) Diabetologia 65 (Suppl 1), 1–469 (2022) presentation #197 ICOVAMENIB | PRECLINICAL
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ICOVAMENIB | PRECLINICAL 16 ICOVAMENIB | PRECLINICAL Icovamenib downregulated menin protein levels & promoted beta cell proliferation in ex vivo human islet cultures MENIN LEVELS DOWNREGULA TED Standard Glucose (5.5 mM) High Glucose (8 mM) ICOVAMENIB CONDITIONALL Y PROMOTED BET A CELL PROLIFERATION ONL Y UNDER HYPERGL YCEMIC CONDITIONS Frias, et al. (WCIRDC) Metabolism,Vol153, Supplement,2023,#88Somanath, et al. (EASD) Diabetologia 68 (Suppl 1), 1–754 (2025). Oral presentation #66
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ICOVAMENIB | PRECLINIAL Icovamenib enhanced GLP-1 receptor & insulin expression in human islets ICOVAMENIB | PRECLINICAL Cadaver derived human islets • Gene expression & Protein analysis • Glucose Stimulated Insulin Secretion -/+ Semaglutide Culture 7 days under glucotox conditions (8mM glucose) 17 ICOVAMENIB INCREASED GLP-1 RECEPTOR AND INSULIN PROTEIN LEVELS GLP-1 Receptor Insulin ICOVAMENIB ENHANCES THE RESPONSIVENESS OF HUMAN ISLETS TO GLP-1 RECEPTOR AGONISTS Balakrishnan, et al. (WCIRDC) Supplement,2025,156226. Oral presentation Glucose stimulated insulin secretion Somanath, et al. (EASD) Diabetologia 68 (Suppl 1), 1–754 (2025). Oral presentation #66
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Combination treatment of icovamenib & low-dose semaglutide improved glycemic control in ZDF rats ICOVAMENIB WITH GLP-1RA 0 5 10 15 20 25 30 35Blood glucose (mmol/L) day 21 day 28 TZP/Sema Group 1 (semaglutide) Group 2 (icovamenib +semaglutide) ✱✱✱✱ ✱✱✱✱ day -3 day 15 Fasting Blood Glucose† 50% lower p <0.0001 HbA1c day -3 day 15 day 28 day 39 5 10 15 9.9 9.8 8.6 7.59.8 9.4 9.6 8.79.9 9.8 8.6 7.59.8 9.4 9.6 8.7 HbA1c (%) ✱ ✱✱ >2% lower from baseline p <0.01p <0.05 Plots represent mean ± SEM Dots represent data for individual animal † 6hr fasting on days -3 and 21, overnight fasting on days 15 and 28. Group 1 (n=10) vehicle vehicle + semaglutide Day 0 Day 14 Day 28 Group 2 (n=10) Day 0 Day 14 Day 28 icovamenib + semaglutideicovamenib male ZDF rats 12 to 13 weeks age semaglutide low dose, 5 nmol/kg, s.c. QD icovamenib, 200 mg/kg, p.o. QD 18 60% lower Somanath, et al. (ADA) Diabetes 2025;74 (Supplement_1):870-P
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Combination Treatment of Icovamenib & Low-dose Semaglutide Reduces Food Intake & Body Weight ICOVAMENIB WITH GLP-1RA SUPERIOR APPETITE SUPPRESSION WITH ABOUT 10% GREA TER BODY WEIGHT REDUCTION THAN LOW-DOSE SEMAGLUTIDE ALONE THE OBSERVED BODY WEIGHT REDUCTION WAS PRIMARIL Y DUE TO FA T MASS LOSS WITH PRESERVA TION OF LEAN MASS APPETITE SUPPRESSION BODY WEIGHT REDUCTION 19 Somanath, et al. (ADA) Diabetes 2025;74 (Supplement_1):870-P
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20 Icovamenib enhanced intracellular proglucagon expression in a human colon L-cell model ICOVAMENIB IN COLON CELLS Tanataweethum, N. et al. (ADA) Diabetes 2026; 75 (Supplement_1): 2871–LB
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21 Icovamenib Induced Myogenic Effects in Human Skeletal Myoblast-derived Myotubes ICOVAMENIB IN MYOTUBES Tanataweethum, N. et al. (ADA) Diabetes 2026; 75 (Supplement_1): 2871–LB
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Icovamenib promoted lipolysis in primary human adipocytes 22 ICOVAMENIB IN ADIPOCYTES Tanataweethum, N. et al. (ADA) Diabetes 2026; 75 (Supplement_1): 2871–LB
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Icovamenib promoted effects indicative of lipolysis and fat browning in primary human adipocytes Enhanced Glycerol Release Upregulation of thermogenic and lipolytic genes Human White Adipocytes (differentiated from primary subcutaneous preadipocytes) Human Brown Adipocytes (differentiated from primary subcutaneous preadipocytes) *differentiation media (D7 to D14) Pre-adipocytes Pre-adipocytes PPIA (Cyclophilin A) was used as housekeeping gene for normalization of data 23 ICOVAMENIB IN ADIPOCYTES Tanataweethum, N. et al. (ADA) Diabetes 2026; 75 (Supplement_1): 2871–LB
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Potential first-in-class menin inhibitor for diabetesdiabetes – CLINICAL RESULTS in Type 1 Diabetes ICOVAMENIB | COVALENT-112
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Current T1D therapies are designed to preserve and protect icovamenib is developed to RESTORE beta cell function 25 1.Zarei M et al. Diabetes Epidemiology and Management 2025;17, 2. Diabetes Care 2025. 3. NIDDK. Diabetes in America, 2024 1 2 3
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DRUG Mean C-PEPTIDE AUC VS PLACEBO Ustekinumab ATG (TrialNet) MELD-ATG Most therapies in development for stage 3 T1D show limited and non-durable C-peptide impact *Ladarixin and Diamyd, both Immune modulating, not mentioned here as they demonstrated no meaningful difference compared to placebo Nature Medicine 2024 vol 30, 2657–2666 Diabetes Care 2018 Jul 16;41(9):1917–1925 26 DRUG Mean C-PEPTIDE AUC VS PLACEBO Teplizumab (Tzield) Baricitinib SAB-142 SAB Bio website corporate presentation (March 10, 2026) https://www.sab.bio/ ESPE Yearbook of Paediatric Endocrinology (2024) 21 10.2 N Engl J Med 2023;389:2140-2150 DRUG Mean C-PEPTIDE AUC VS PLACEBO Verapamil Rituximab NEJM. 2009 361:2143–2152 Nature. 2018 Aug;24(8):1108-1112 Lancet 2025 Sep 27;406(10510):1375-1388
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COVALENT-112 (NCT06152042) was a Phase 2 trial designed to examine beta cell function (as measured by C- peptide change and the change of exogenous insulin usage) and glucose and lipid metabolism in participants with T1D treated with standard of care insulin and icovamenib. SCREENING: 5 WEEKS DOSING PERIOD: 12 WEEKS Icovamenib 200 mg QD Icovamenib 100 mg QD ARM A N = 10 ARM B N = 10 FOLLOW-UP: 40 WEEKS ARM A N = 10 ARM B N = 10 Cohort 1 T1D diagnosed within 3 years with a C-peptide ≥0.2 nmol/L Cohort 2 T1D diagnosed between 3-15 years with a C-peptide ≥0.08 nmol/L Study enrollment and dosing were interrupted in May 2024 due to an FDA clinical hold, which was subsequently resolved, but reduced the number of patients enrolled and followed through to the 52-week readout. Icovamenib 200 mg QD 27 Icovamenib 100 mg QD ICOVAMENIB | COVALENT-112 Study design
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52% mean increase from baseline 12 WEEKS TREATMENT 52% mean increase in C-peptide during the 12 weeks treatment period of icovamenib Data represents post-hoc analysis of patients who received per statistical analysis plan, 80% of planned doses 1 Historical control in T1D patients (n=1549) C-peptide declining over first 7 years at 47% yearly.Diabetes Care. 2018 Jun 7;41(7):1486–1492 * 4-hour Mixed Meal Tolerance Test (MMTT) 1.21 +0.7 P<0.001 (n=5) (n=3) 28 Cohort 1 (< 3 years since diagnosis) ICOVAMENIB | COVALENT-112 1.4 2.1 1.4 1.3 0.0 0.5 1.0 1.5 2.0 2.5 Baseline Week 4 Week 8 Week 12 Mean C-peptide AUC (nmol/L)* 200mg icovamenib 100mg icovamenib Historical Control1 (n=6) (n=5) (n=5) (n=3) (n=6) (n=5) Frias, J. (ADA) Diabetes 2026; 75 (Supplement_1): 2858–LB.
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0.6% reduction in mean HbA1c from baseline 12 WEEKS TREATMENT 0.6% mean reduction in HbA1c during the 12 weeks treatment period of icovamenib 29 ICOVAMENIB | COVALENT-112 7.7 7.3 7.0 7.5 8.0 8.5 9.0 Baseline Week 4 Week 8 Week 12 Mean HbA1c (%) 200mg icovamenib 100mg icovamenib (n=4) (n=3) (n=4) (n=5) (n=5) (n=4) (n=4) (n=4) Frias, J. (ADA) Diabetes 2026; 75 (Supplement_1): 2858–LB.
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Baseline C-peptide levels sustained through week 52 with minimal decline (only -7.1%) observed post 12 weeks of 200mg daily icovamenib 30 -7% -32% 12 WEEKS TREATMENT Data represents post-hoc analysis of patients who received per statistical analysis plan, 80% of planned doses 1 Historical control in T1D patients (n=1549) C-peptide declining over first 7 years at 47% yearly.Diabetes Care. 2018 Jun 7;41(7):1486–1492 * 4-hour Mixed Meal Tolerance Test (MMTT) -47%1 40 WEEKS OFF TREATMENT (n=4) (n=5) Change in mean C-peptide AUC at Week 52 vs baseline 0 0.5 1 1.5 2 2.5 Baseline 4 8 12 16 26 52 Mean C-peptide AUC (nmol/L)* Weeks 200mg icovamenib 100mg icovamenib (n=6) (n=5) Demographics (means) | n=6 Age: 28 years Sex: 67% female BMI: 25 kg/m 2 Disease course: 2.4y HbA1c: 7.4% Fasting Plasma Glucose: 178 mg/dL Fasting C-Peptide: 0.7 ng/mL Demographics (means) | n=5 Age: 31 years Sex: 40% female BMI: 24 kg/m 2 Disease course: 2.1y HbA1c: 8.3% Fasting Plasma Glucose: 155 mg/dL Fasting C-Peptide: 0.8 ng/mL Cohort 1 (< 3 years since diagnosis) ICOVAMENIB | COVALENT-112 Frias, J. (ADA) Diabetes 2026; 75 (Supplement_1): 2858–LB.
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Cytokine profiling of cohort 1 (<3 years since T1D diagnosis) participants receiving 200mg icovamenib 31 Week 12 Week 26 Week 52 pg/mL change status pg/mL change status pg/mL change status Il-1β 1.07 0.40 Non-Inflammatory 1.00 0.27 Non-Inflammatory 0.70 -0.27 Non-Inflammatory IL-2 3.43 -0.83 Non-Inflammatory 3.57 -1.20 Non-Inflammatory 1.20 -3.23 Non-Inflammatory IL-6 3.27 0.70 Non-Inflammatory 0.53 -1.70 Non-Inflammatory 0.53 -1.70 Non-Inflammatory IL-8 6.57 0.77 Non-Inflammatory 7.17 -0.07 Non-Inflammatory 5.37 -1.18 Non-Inflammatory IL-10 1.30 -0.03 Non-Inflammatory 1.33 0.00 Non-Inflammatory 1.30 -0.03 Non-Inflammatory IFN-γ - - Non-Inflammatory - - Non-Inflammatory - - Non-Inflammatory TNF-α 7.53 -0.17 Non-Inflammatory 7.73 -1.35 Non-Inflammatory 4.07 -5.33 Non-Inflammatory • All cytokines remained classified as Non-Inflammatory from baseline through Week 52, indicating no evidence of systemic immune activation in participants receiving 200 mg icovamenib • Small Week 12 increases in IL-1β, IL-6, and IL-8 were transient and not associated with increases in IL-2 or TNF-α • By Week 52, most pro-inflammatory cytokines were stable or decreased from baseline • The increase in C-peptide was not accompanied by a measurable systemic inflammatory cytokine response but rather led to a stabilization and mild reduction of inflammatory markers over time Mean values were assessed for all patients for each cytokine (n=3) relative to baseline. ICOVAMENIB | COVALENT-112 Frias, J. (ADA) Diabetes 2026; 75 (Supplement_1): 2858–LB.
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32 Favorable 52-week safety profile ICOVAMENIB | COVALENT-112 Cohort 1 Cohort 2 Arm A 100 mg QD (N = 8) Arm B 200 mg QD (N = 9) Cohort 1 Total (N = 17) Arm A 100 mg QD (N = 9) Arm B 200 mg QD (N = 10) Cohort 2 Total (N = 19) Patients with ≥1 TEAE, N (%) 3 (38) 0 (0) 3 (18) 1 (11) 3 (30) 4 (21) Treatment-Related SAEs, N (%) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) SAEs* , N (%) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Treatment Discontinuation due to TEAE, N (%) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Study Discontinuation due to TEAE, N (%) 0 0 0 0 0 0 Deaths, N (%) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Diarrhea, N (%) 1 (13) 0 1 ( 6) 1 (11) 0 1 ( 5) Nausea, N (%) 1 (13) 1 (11) 2 (12) 1 (11) 1 (10) 2 (11) Hyperglycemia, N (%) 0 0 0 0 1 (10) 1 ( 5) Headache, N (%) 1 (13) 0 1 ( 6) 0 1 (10) 1 ( 5) AST/ALT increase, N (%) 3 (38 2 (22) 5 (29) 1 (11) 7 (70) 8 (42) Resolution of ALT/AST w/o interruption in study treatment, % 100 100 100 100 80 90 Frias, J. (ADA) Diabetes 2026; 75 (Supplement_1): 2858–LB.
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33 Optimal dose and target population identified for T1D phase 2 program ICOVAMENIB | COVALENT-112
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Immune Suppressant (JAK inhibitor) 6 Months Primary endpoint C-peptide AUC Off Therapy Icovamenib 100>>>200 mg QD (n=32) Placebo (n=8) 15 Months Secondary endpoint C-peptide AUC Month 0 Month 3 Month 6 Month 9 Month 12 Month 15 icovamenib 200 mg QD (n=8) (n=8) (n=8) (n=8) Icovamenib + Immune Suppressant (JAK inhibitor) 34 Icovamenib 200 mg QD (n=8) SCREENING: XX DA YS TREA TMENT : 6 MONTHS BLINDED/FOLLOW UP: ADD 6 MONTHS BLINDED/FOLLOW UP: ADD 3 MONTHS Active (n=32) Placebo (n=8) Proposed phase 2 trial design for T1D clinical trial* Inclusion Criteria • Adult participants with T1D diagnosed within 3 years with a C-peptide ≥0.2 nmol/L • Background therapy maintained unless rescue required 12 Months Secondary endpoint C-peptide AUC *Subject to regulatory and investigator alignment, and feedback from applicable health authorities.
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Study investigators * Primary Investigator Peter Gottlieb, MD Professor of Pediatrics and Medicine | Barbara Davis Center, University of Colorado • Professor of Pediatrics and Medicine and holds the Orr Family Endowed Chair in Adult Diabetes at the Barbara Davis Center, one of the world’s leading centers for Type 1 diabetes research and clinical care. • Long-standing member of Type 1 Diabetes TrialNet and chairs its Collaborative Mechanistic Studies Panel, helping drive pivotal immunotherapy trials across all stages of T1D. • With 190+ publications, his work focuses on T- and B-cell–driven autoimmunity. Sub-Investigators Jason Gaglia, MD, MMSc Ass. Professor | Joslin Diabetes Center, Harvard Medical School Worlds leading diabetes center (36,000 patients annually, 150 MDs/PhDs) David Baidal, MD Ass. Professor | Diabetes Research Institute, University of Miami Miller School of Medicine Ralph A. DeFronzo, MD Professor and Chief of the Diabetes Division | UT Health of San Antonio 35*Subject to regulatory and investigator alignment, and feedback from applicable health authorities.
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G. Alexander “Zan” Fleming, MD FOUNDER & EXECUTIVE CHAIRMAN, KINEXUM FORMER FDA SENIOR MEDICAL OFFICER AND DIVISION LEADER FOR METABOLIC & ENDOCRINE DRUGS, INVOLVED IN THE REVIEW OF LANDMARK DIABETES AND METABOLIC THERAPIES INCLUDING METFORMIN, THE FIRST RAPID- ACTING INSULIN ANALOGS, EARL Y STATINS, AND PP AR AGONISTS Efforts to intervene against type 1 diabetes (T1D) have historically focused on preserving remaining insulin secretion in people just diagnosed with T1D. These icovamenib data are unique in showing increased C-peptide- reflected insulin secretion in patients with established T1D during dosing and persistence of this effect after treatment was stopped. In people with established T1D, endogenous insulin secretion progressively declines to very low levels. Any evidence of improvement in endogenous insulin secretion—even among a few T1D individuals—is unprecedented and of immense biologic and clinical significance. These findings warrant rigorous and longer-term evaluation. KOL perspectives across clinical significance, biology, and future development in T1D The new data presented today with icovamenib in patients with type 1 diabetes suggest a potential new therapeutic avenue in a disease where fundamental unmet need has long persisted. To date, approved therapies have not directly addressed the progressive loss of functional beta cells that underlies diabetes. Biomea has made critical progress in identifying and characterizing this molecule, which has demonstrated the ability to reduce menin protein levels and activate pathways associated with beta cell function. Today's icovamenib type 1 data further validates and deepens our understanding of icovamenib's mechanism of action. Congratulations to the Biomea team on reaching this important therapeutic milestone. What stands out to me in the icovamenib diabetes data is not only the emerging signal of biological activity, but also the safety profile observed to date with using icovamenib in diabetes studies. That combination is important, because safety ultimately determines whether rational combination strategies can be explored as the program moves forward. Looking ahead, future studies will be critical in determining whether the improvements observed in beta cell function of these Type 1 diabetes patients can be maintained over time, particularly in the presence of ongoing immune activity. It will also be important to understand whether combination approaches—including immunomodulatory therapies— are needed and can further enhance or stabilize the observed effects. These are key questions that will inform the long term clinical potential of this approach. Rohit Kulkarni, MD, PhD PROFESSOR OF MEDICINE, HARVARD MEDICAL SCHOOL | SENIOR INVESTIGATOR & SECTION CO- HEAD (ISLET CELL & REGENERATIVE BIOLOGY), JOSLIN DIABETES CENTER David Baidal, MD ASSISTANT PROFESSOR DIABETES RESEARCH INSTITUTE, UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE 36
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Alice Cheng, MD ENDOCRINOLOGIST , ASSOCIATE PROFESSOR OF MEDICINE UNIVERSITY OF TORONTO The icovamenib data in Type 1 diabetes naturally makes us pause and reflect on what it could ultimately mean for people living with Type 1 diabetes. While these early findings require confirmation, they suggest a different way of thinking about treatment, one that extends beyond glucose management and begins to engage underlying disease biology. For younger individuals in particular, the possibility of preserving or improving endogenous beta cell function over time could have meaningful implications for lifelong disease burden. Results like these invite consideration of how the treatment landscape in Type 1 diabetes may evolve if such approaches prove durable and safe. KOL perspectives across clinical significance, biology, and future development in T1D The icovamenib data in type 1 diabetes are encouraging, this is particularly interesting as icovamenib targets a pathway that has not been meaningfully explored in this disease. Despite advances in insulin delivery and glucose monitoring, disease-modifying options remain limited for patients. These findings support the need for focused, proof-of-concept studies in well-characterized patient populations to better understand this signal, its durability, and the underlying biology. An important next step will be examining the interplay between beta cell effects and the autoimmunity inherent in type 1 diabetes, and whether combination approaches with immunomodulatory therapies could further enhance or stabilize these beta cell effects. While insulin therapy is life saving for people with Type 1 diabetes, chronic exogenous insulin use is not without consequence. Over time, it is associated with well recognized iatrogenic risks, including hypoglycemia, diabetic ketoacidosis, weight gain, lipohypertrophy, and increased cardiovascular burden. Targeting menin with icovamenib represents a fundamentally new therapeutic approach in diabetes. Rather than simply replacing insulin, it seeks to improve endogenous beta cell function. The early results we are seeing in Type 1 diabetes are highly encouraging. I am excited to explore longer dosing periods to fully assess the potential of enabling patients to regain their own beta cell–mediated glucose control which is something no current therapy has been able to achieve. If this approach is confirmed, this could represent a meaningful step towards allowing patients to live their daily lives with greater physiological stability and far less constant fear of their disease. Jason Gaglia, MD, MMSc ASSISTANT PROFESSOR OF MEDICINE, HARVARD MEDICAL SCHOOL | STAFF PHYSICIAN, JOSLIN DIABETES CENTER — ONE OF THE WORLD'S LEADING DIABETES CENTERS Ralph DeFronzo, MD ENDOCRINOLOGIST , PROFESSOR OF MEDICINE UTHSCSA 37
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Potential first-in-class menin inhibitor for diabetes – CLINICAL RESULTS in Type 2 Diabetes ICOVAMENIB | PRECLINICALICOVAMENIB | COVALENT-111
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IMPROVED BETA CELL MASS & FUNCTION FOR TYPE 1 AND TYPE 2 DIABETES Icovamenib promotes selective and partial reduction in menin levels Induction of beta cell proliferation Increased expression of • GLP-1 • GLP-1 receptor IMPROVED INCRETIN EFFECTS Icovamenib’s mechanism of action ICOVAMENIB | MOA 39 Lowering menin levels releases the break on beta cell proliferation and GLP-1 and GLP-1 receptor expression Decrease in blood glucose (HbA1c) Increase in insulin/C-peptide Synergistic with GLP-1 based therapies Potential for lean mass/muscle preservation Potential for weight loss Improved beta cell function Pancreatic islet Decrease in blood glucose (HbA1c) Lowering menin levels releases the break on beta cell proliferation
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*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. 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) 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) 40 Frias, et al. Metabolism, Volume 177, Supplement,2025
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Icovamenib increased beta cell quantity, function & GLP-1 receptor expression following a short treatment period BUILDING OF THE BET A CELL POOL MA TURA TION OF BET A CELL POOL DECREASE IN BET A CELL MASS INSULIN DEPENDENCE Use of icovamenib for patients failing standard of care ICOVAMENIB Diagnosis of Type 2 Diabetes Use of standard of care agents Dosing 12 weeks 1/3 of Type 2 Diabetes patients end up on insulin Follow-up period additional 14 weeks Long-term follow-up period additional 26 weeks 41 FURTHER DECREASE IN BET A CELL MASS INSULIN DEPENDENCE Improved beta cell mass and function C-peptide HbA1c ICOVAMENIB | PRECLINICALICOVAMENIB | COVALENT-111 Note: To our knowledge, none of the menin/MLL inhibitors exploring menin for cancer indications have yet been able to advance to diabetes clinical trials
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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. 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 42 -0.6 -0.5 -0.4 -0.3 -0.2 -0.1 0.0 0.1 0.2 0 8 12 26 36 42 52 Mean Change HbA1c (%) Weeks Pooled Placebo (N=49) Arm A (N=45) Arm B (N=36) Arm C (N=33) Frias, et al. Metabolism, Volume 177, Supplement,2025 -0.5% threshold for clinical significance CMS Clinical Endpoints Review (2024) TREA TMENT OFF-TREA TMENT
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-2.0 -1.5 -1.0 -0.5 0.0 0.5 1.0 0 8 12 26 36 42 52 Mean Change HbA1c (%) Week Pooled Placebo (N=12) icovamenib (N=10) -0.5% threshold for clinical significance CMS Clinical Endpoints Review (2024) TREA TMENT OFF-TREA TMENT -0.5 -0.8 -1.2 P=0.01 -0.3 0.1 0.3 12 weeks of dosing (arms B&C) delivered lasting benefit through 52 weeks for severe insulin-deficient diabetes patients Arm A was excluded from this analysis because it included only 8 weeks of dosing which the company is not planning to pursue. 43 INITIAL TARGET POPULA TION FOR ICOVAMENIB ICOVAMENIB | PRECLINICALICOVAMENIB | COVALENT-111 Frias, et al. Metabolism, Volume 177, Supplement,2025
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Icovamenib increased insulin secretion as measured by C-peptide index in severe insulin-deficient patients (arms B&C) 0.7 0.8 0.9 1.0 1.1 1.2 1.3 1.4 1.5 1.6 0 12 52 Fold Change in C-peptide Index Weeks Icovamenib (N=10) Placebo (N=12) TREA TMENT OFF-TREA TMENT 2% 24% 44 Data censored at onset of rescue medication, defined as any modification in antihyperglycemic therapy ICOVAMENIB | PRECLINICALICOVAMENIB | COVALENT-111
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IMPROVED BETA CELL MASS & FUNCTION Icovamenib promotes selective and partial reduction in menin levels Induction of beta cell proliferation Increased expression of • GLP-1 • GLP-1 receptor Icovamenib’s mechanism of action ICOVAMENIB | PRECLINICAL 45 Lowering menin levels releases the break on beta cell proliferation and GLP-1 and GLP-1 receptor expression Decrease in blood glucose (HbA1c) Increase in insulin/C-peptide Pancreatic islet IMPROVED INCRETIN EFFECTS Synergistic with GLP-1 based therapies Potential for lean mass/muscle preservation Potential for weight loss Improved beta cell function Decrease in blood glucose (HbA1c)
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Patients on a GLP-1 based therapy at enrollment showed durable & clinically meaningful response in reduction of blood sugar (HbA1c) 46 -2.0 -1.5 -1.0 -0.5 0.0 0.5 1.0 1.5 0 8 12 52 Mean Change HbA1c (%) Weeks Pooled Placebo (N=4) icovamenib (N=12) -1.2 P=0.05 -0.5% threshold for clinical significance CMS Clinical Endpoints Review (2024) TREA TMENT OFF-TREA TMENT 0.6 -0.7 -0.3 0.1 1.1 ICOVAMENIB | PRECLINICALICOVAMENIB | COVALENT-111 Frias, et al. Metabolism, Volume 177, Supplement,2025
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Icovamenib increased insulin secretion as measured by C-peptide index in GLP-1 RA treated patients – 9 months post last dose 0.4 0.6 0.8 1.0 1.2 1.4 1.6 0 12 52 Fold Change in C-peptide Index Weeks Icovamenib (N=11) Placebo (N=4) 47 35% -4% Data censored at onset of rescue medication, defined as any modification in antihyperglycemic therapy TREA TMENT OFF-TREA TMENT ICOVAMENIB | PRECLINICALICOVAMENIB | COVALENT-111
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48 Favorable 52-week safety profile Data are n (%) TEAE = Treatment Emergent Adverse event. SAE = Serious Adverse Event. Data are n (%) of TEAE with ≥5% frequency in any arm. ALT (alanine aminotransferase) or AST (aspartate aminotransferase) increase irrespective of incidence %. *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. 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. All incidences of ALT and AST elevations resolved without interruption. 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) 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 treatment interruption (%) 100 100 100 100 N/A Deaths, N (%) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) ICOVAMENIB | COVALENT-111 Note: In AML studies icovamenib demonstrated a well-tolerated safety profile across all dose levels, with up to 500 mg QD / 325 mg BID, and dose durations extending over 1 year Frias, et al. Metabolism, Volume 177, Supplement,2025
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*Icovamenib data are from a Phase II study in selected populations: insulin deficient diabetes patients and GLP-1 inadequate res ponders. Di scl ai mer : The data pr esented abov e ar e based on cr oss -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 dosing Oral Week 52 (COVALENT-111) -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 52 (SUSTAIN 8) Week 40 (SURPASS 1) Week 52 (Extension study) Week 52 (Sitagliptin) -1.5 (1mg) -1.9 (5mg) -2.1 (15 mg) -0.6 (10mg) -0.6 (25mg) -0.5 (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 49 ICOVAMENIB | COVALENT-111
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Potential first-in-class oral menin inhibitor for diabetes – ONGONG STUDIES in Diabetes ICOVAMENIB
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Phase IIa key derisking-insights: Optimal dose selected, 100 mg Food Effect Study confirmed optimal PK exposure of icovamenib within 30 minutes after a meal 12-week treatment observed to drive durable and lasting effects, no chronic treatment required Strong clinical activity in insulin-deficient and GLP-1 inadequate responder populations Treatment-emergent AEs comparable to placebo Optimal dose, dose-duration, target population identified for phase IIb program ICOVAMENIB 51 COVALENT-211 Phase II trial in type 2 insulin deficient diabetes patients failing standard of care • Adult participants with T2D who were treated with 1-3 antidiabetic medications • HbA1c 7.5%-10.5% and BMI ≤ 32 kg/m2 • Background therapy maintained unless rescue required COVALENT-212 Phase II trial in type 2 diabetes patients failing standard of care while on a GLP-1 RA • Adult participants with T2D who are not achieving glycemic targets despite GLP-1-based therapy • HbA1c ≥7.5% and ≤9.5% and BMI 25 to 40 kg/m2 • Background therapy maintained unless rescue required Direct application in Phase II Studies
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ICOVAMENIB | COVALENT-211 A Phase II trial of icovamenib in T2D insulin deficient participants who are not achieving glycemic targets Objectives Endpoints Placebo 100 mg QD Icovamenib 100 mg QDARM A (n=40) ARM B (n=20) Stable Background Therapy SCREENING: 28 DAYS TREATMENT : 12 WEEKS FOLLOW-UP: 52 WEEKS Week 26: Primary endpoint Week 52: Secondary endpoint Inclusion Criteria 52 FOLLOW-UP: 26 WEEKS • 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 To demonstrate that icovamenib 100 mg once daily for 12 weeks is superior to placebo for glycemic control at Week 26 and Week 52 • Mean change in HbA1c from baseline at Week 26 and 52 • Mean change in fasting plasma glucose (FPG) from baseline at Week 26 • Safety Objectives Endpoints Inclusion Criteria
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ICOVAMENIB | COVALENT-212 Phase II trial of icovamenib in participants with T2D who are not achieving glycemic targets while using GLP-1-based therapy Objectives Endpoints Placebo 100 mg QD Icovamenib 100 mg QDARM A (n=40) ARM B (n=20) Background Therapy: Stable GLP-1-based-therapy Inclusion Criteria SCREENING: 28 DAYS TREATMENT : 12 WEEKS FOLLOW-UP: 52 WEEKS Week 26: Primary endpoint Week 52: Secondary endpoint FOLLOW-UP: 26 WEEKS 53 • 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 To demonstrate that icovamenib 100 mg once daily for 12 weeks is superior to placebo for glycemic control at Week 26 and Week 52 • Mean change in HbA1c from baseline at Week 26 and 52 • Mean change in fasting plasma glucose (FPG) from baseline at Week 26 • Safety Objectives Endpoints Inclusion Criteria
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-1.2 -1.0 0.3 0.2 Applying enrollment criteria of COVALENT-211 (red) vs published results in SIDDs dosed in COVALENT-111 (blue) TREA TMENT OFF-TREA TMENT -1.5 -1.0 -0.5 0.0 0.5 0 12 26 52 Mean Change HbA1c (%) Weeks 54
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An investigational next-generation oral GLP-1 receptor agonist for obesity - PRECLINICAL RESULTS and - CLINICAL OVERVIEW BMF-650
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BMF-650: A potential best-in-class oral GLP-1 receptor agonist THE CURRENT GLP-1 MARKET BMF-650 is designed to be the oral GLP-1 RA patients can start, stay on, and have long term benefits from 1.Real-world evidence across multiple GLP-RA studies (e.g. N Engl J Med 2021.385.896-907. JAMA Netw Open 2022.5e223433; Diabetes Obe Metab. 2023.25.1254-1264 Needle burden Inconvenient Injection site reactions Some patients averse to injections BMF-650 Designed for sustainable weight loss management Next Generation Oral GLP-1 RA Oral administration Convenience without injections Tw o-step titration Faster path to maintenance dose Designed for improved GI tolerability Potential for better tolerability and adherence Built to improve persistence Helping more patients stay on therapy THE POJECTED IMPACT Weight Loss Management Better tolerability will lead to continuous weight management Better Patient Experience Simpler regimen and fewer GI side effects Higher P ersistence More patients stay on therapy and reach therapeutic benefit Long-term Health Benefits Sustained weight management supports cardiometabolic health Chronic therapy in mind Designed for sustainable weight loss management Long, complex titration (typically 4- 8+ steps, which can take 3-9 months depending on product) High rates of GI side effects Many do not reach maintenance dose High discontinuation rates 7 out of 10 Patients discontinue GLP-1 therapy due to side effects1 Injectable GLP-1 RAs First Generation Oral GLP-1 RAs BMF-650 56
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• Good potency on-target to achieve more efficient drug titration • No off-target concerns from counter-screening assays BMF-650 showed favorable in vitro on-target activity and off- target selectivity Compound GLP-1 human EC50 β-arrestin1 EC50 β-arrestin2 EC50 25 °C 37 °C BMF-650 8.6 nM 2.6 nM > 10 µM > 10 µM orforglipron 2.6 nM 0.1 nM > 10 µM > 10 µM BMF-650 | PRECLINICAL 57
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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 58 BMF-650 | PRECLINICAL
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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 up to ~15% body weight reduction after 28-days BMF-650 demonstrated robust, dose dependent weight loss in obese 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 59 0 1 2 3 4 5 6 7 8 9 1011121314151617181920212223242526272829 -20 -15 -10 -5 0 Day % Change from baseline Vehicle BMF-650 10mpk BMF-650 30mpk Day 8 -2.3% -4.8% -7.5% Day 15 -2.7% -7.5% -10.7% Day 22 -2.8% -10.2% -13.5% Day 29 -3.4% -12.3% -15.2% Body Weight Change from Baseline Wang, et al. Obesity 2025: 33 Sup 2 Poster #085
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BODY WEIGHT CHANGE (individual obese monkey) Mean reduction in body weight (Day 29) Vehicle -3.4% BMF-650 10 mg/kg -12.3% BMF-650 30 mg/kg -15.2% Oral BMF-650 demonstrates strong dose dependent body weight reduction in obese cynomolgus monkeys 60 BMF-650 | PRECLINICAL Wang, et al. Obesity 2025: 33 Sup 2 Poster #085
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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, Phase I 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 ef fect Safety and tolerability , and ef ficacy (weight -l oss) 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 50 mg → 100 mg → 200 mg → 200 mg 75 mg → 150 mg → 300 mg → 300 mg 75 mg → 200 mg → 400 mg → 400 mg 7 DAYS → 7 DAYS → 7 DAYS → 21 DAYS 5 cohorts N=40 N=50 x 5 cohorts x Body weight at Day 29 and Day 43 versus Baseline 61 5 200 mg → 400 mg
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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 BMF-650 | PRECLINICAL (Events per 70 weekly dosing occurrences) SAFETY SUMMARY 62 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
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Key Milestones - Overview 3Q 2026 4Q 2026 1Q 2027 2Q 2027 3Q 2027 4Q 2027 BMF-650 ICOVAMENIB PLANNED T1D – IST | Phase 2 Study | n=40 | Enrollment anticipated to start 1Q 27 PLANNED T1D LEICESTER DIABETES CENTER | Phase 2 Study | n=36 | Enrollment anticipated to start 1Q 27 LEICESTER DIABETES CENTER in Obesity | Phase 2 Study | n=64 | Start: 3Q 2026 | Enrollment anticipated to start 3Q 26 COVALENT-211 in insulin deficient T2D | Phase 2 Study | n=60 | Start: 2Q 2026 COVALENT-212 in GLP-1 uncontrolled T2D | Phase 2 Study | n=60 | Start: 2Q 2026 GLP-131 in Obesity | Phase I | 28-day weight loss BMF-650 Phase 2 Initiation depending on Phase I results T2D FDA End of Phase 2 Meeting and Phase 3 Initiation T1D FDA End of Phase 2 Meeting and Phase 3 Initiation Icovamenib in Type 1 Diabetes Icovamenib in Obesity Icovamenib in Type 2 Diabetes - Insulin deficient - GLP-1 uncontrolled BMF-650 Obesity and weight management Current Cash Position Runway into 2Q 2027 63
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THANK YOU (NASDAQ: BMEA) For questions or inquiries, please reach out to Meichiel Weiss at ir@biomeafusion.com www.biomeafusion.com
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Slowing the clock on diabetes Turning a healthcare crisis into a huge opportunity The problem: Diabetes is a global healthcare crisis, with over 800 million people affected worldwide. The disease is expanding at an estimated ~4% annually. In the United States, one in every four healthcare dollars is spent on people living with diabetes, totaling over $400 billion per year. More than 100 million Americans have prediabetes; approximately 40% will progress to diabetes, and ~60% are diagnosed only after reaching late-stage disease. The economic impact: Late-stage diabetes drives over 50% of healthcare related costs due to complications such as kidney failure, cardiovascular disease, amputations and visual loss. With late-stage diabetes the healthcare system is burden by additional $15,000 - $20,000 per patient. Assuming 10m US diabetes patients are in late stage, delaying the progression could save the system $150-200billion. Our breakthrough: We are developing a novel mechanism of action developed to restore beta-cell function and slow the progression of hyperglycemia. By rebuilding a functional beta-cell pool, the body may regain the ability to regulate its own insulin production. The true burden of diabetes is not early disease, but late-stage progression with irreversible organ damage. Slowing that clock by even a few years could generate societal returns exceeding the annual economic output of the entire pharmaceutical sector. Icovamenib would delay the need for unwieldy and often unreliable insulin therapy for years! Our vision: Keeping diabetes patients durably controlled, preventing progression to late-stage disease and avoiding the devastating complications that drive cost, morbidity, and mortality.
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Placebo icovamenib 100 mg QD 200 mg QD (weeks 1 ➔ 8) (months 2 ➔ 6) ARM A (n=24) N=36 RANDOMIZED 2:1 icovamenib Active Drug Placebo MMTT + Proteomics + Biobanking Primary Outcome MMTT = Mixed Meal Tolerance Test QD = Once Daily Primary Outcome = Change in C-peptide ARM B (n=12) NEW Biomea sponsored T1D study planned for 2026* Long term dosing of icovamenib in T1D to show continuous C-peptide increase icovamenib 200 mg QD (months 2 ➔ 6) SCREENING & CONSENT BASELINE DAT A COLLECTION TREATMENT : MONTHS 0 ➔ 6 TREA TMENT : MONTHS 6 ➔ 12 SAFETY MONITORING: 6 MONTHSINTERIM ANAL YSIS *Subject to regulatory and investigator alignment, and feedback from applicable health authorities.