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Transforming diabetes and obesity with novel oral medicines Biomea
Fusion founded in 2017 (public in 2021; NASDAQ: BMEA ) Clinical-stage company advancing two differentiated metabolic investigative programs ICOVAMENIB Potential first-in-class oral menin inhibitor - the control switch to beta cell restoration
Restores functional beta-cell mass to address disease biology in type 2 diabetes Increased insulin production and synergy with GLP-1 shown in preclinical models Durable HbA1c reduction and C-peptide increase through 52 weeks after a
12-week course in the first Phase II trial in T2D patients failing standard of care Two Phase II studies underway with 26 weeks primary endpoint data anticipated in 4Q 2026 with the potential to address over 10M U.S. T2D diabetes patients
Critical unmet need: 1/3 of all diabetes patients fail standard of care and progress to insulin dependence 1-3 driving complications such as kidney disease, nerve damage, vision loss, and cardiovascular issues. BMF-650 Next-generation oral GLP-1
receptor agonist Designed for consistent exposure, higher bioavailability and improved tolerability with scalable weight reduction Improved bioavailability, better plasma protein binding, greater oral exposure with lower variability
Demonstrated weight reduction and generally well tolerated in preclinical models Phase I clinical study in obese healthy volunteers ongoing with 28-day weight reduction data anticipated in 2Q 26, aiming to address over 100M U.S. obese
patients Critical unmet need: Real world evidence indicates that up to 70% of patients on currently available GLP-1 based therapies drop out 4 within the first year due to gastrointestinal adverse events and other tolerability considerations. Biomea
funded through key clinical readouts for icovamenib and BMF-650 into Q1 of 2027. 3 1.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.
Biomea Fusion pipeline - targeting diabetes & obesity Biomea
Fusion retains full worldwide rights across all programs Program Indications Pre-clinical Phase I Phase II Phase III Key Catalysts Phase II 26-week data Type 2 diabetes (study initiated) ICOVAMENIB COVALENT-211 (primary endpoint) Patients with
Insulin- deficiency anticipated 4Q 2026 Type 2 diabetes Phase II 26-week data ICOVAMENIB (study initiated) COVALENT-212 Patients not controlled on (primary endpoint) GLP-1-based therapies anticipated 4Q 2026 52-week follow-up data Type 2 diabetes
(study completed) COVALENT-111 presented 4Q 2025 Patients - all comers ICOVAMENIB Type 1 diabetes 52-week follow-up data (study completed) COVALENT-112 Patients - all comers expected in Q2 2026 Phase I weight reduction BMF-650 (study
enrolling) GLP-131 Obesity data expected Q2 2026 4
ICOVAMENIB Severe insulin-deficient diabetes patients after 12-weeks of
dosing Potential first-in-class menin inhibitor aimed to restore functional beta-cells Aims to serve a significant unmet need for millions of diabetes patients failing on standard of care Icovamenib is developed to: GLP-1 RA uncontrolled diabetes
patients after 12 weeks of dosing Employ and enhance body's natural response to + hyperglycemia as evidenced in pregnancy Conditionally drive beta-cell proliferation and activity + only in presence of high glucose levels Enhance GLP-1 efficacy
by upregulating GLP-1 + receptors on the beta-cell surface Post-hoc analysis of patients on GLP-1 based therapy not achieving stable HbA1c <7% Target beta-cell restoration and potentially delay at enrollment (9 months after last dose) + or
prevent onset of end-stage disease Early signs of clinical activity with 12 weeks of dosing 5 in diabetes patients failing standard of care therapies
Two transformative phase II trials ongoing Near term readouts expected
in 4Q 2026 ICOVAMENIB Two Phase II trials underway Phase IIa completed and proposed mechanism supported COVALENT-211 Persistent 52-week HbA1c reduction Insulin-deficient T2D failing standard of care after 12 weeks of treatment
Enrollment ongoing 26-week topline data expected 4Q 2026 Increased C-peptide OFF DRUG in both responding patient populations validating mechanism of action of COVALENT-212 restored beta-cell mass T2D inadequately controlled on GLP-1
therapy Go-forward regimen generally well- Enrollment ongoing tolerated 26-week topline data expected 4Q 2026 6
Diabetes patients are poorly controlled with over 7M US patients
currently needing insulin as a last resort Icovamenib targets beta-cell restoration and may delay or prevent onset of end-stage disease 1 38M of people with diabetes will die from the disease 4 PEOPLE IN THE US WITH DIABETES The end-stage in the
evolution of diabetes is insulin-dependence, which 80% drives complications such as kidney disease, nerve damage, vision loss, and cardiovascular issues. 35M 5 PEOPLE IN US WITH T2D 2 of life lost from diabetes 12-14 Diabetes today remains poorly
controlled in 50% of patients treated 3 with standard of care agents The burden to the healthcare system is years immense. There is no current therapy except for insulin replacement 7M PEOPLE IN US WITH T2D 6 USING INSULIN Approved therapies are not
adequately resolving the growing problem of type 2 diabetes. 60+ No current therapy restores beta-cell function 1.Tabish Int J Health Sci. 2007 Jul;1(2):V-VIII. 4. CDC, Natl. Diabetes Stat. Rep., 2022 2.National library of Medicine 1(2); 2007
Jul PMC3068646 5. ADA, Standards of Care in Diabetes, Diabetes Care, 2024 3.Zohu Lancet 2024; 404: 2077-93 6. Ahlqvist, Lancet Diabetes Endocrinol., 2018 7
BMF-650 Oral GLP-1 RA developed for improved patient friendly
tolerability ~15% Body Weight Reduction Aims to serve a significant unmet need with millions of in 28-day Obese Monkey Study obese Americans dropping off the available GLP-1 1 RAs agents within the first year BMF-650 is developed to: Built on the
orforglipron scaffold with key structural + improvements Greater oral exposure and bioavailability with lower + variability observed in preclinical models Higher plasma protein binding supporting better + tolerability Potential for simplified dose
escalation schedule + with generally well-tolerated safety profile 8 1. Prime Therapeutics & Magellan Rx Management, 2023 real-world claims analysis.
ICOVAMENIB Biology, mechanism of action & preclinical
ICOVAMENIB | PRECLINICAL Icovamenib's mechanism of action
IMPROVED BETA CELL MASS & FUNCTION Induction of beta Increase in insulin cell proliferation Decrease in blood glucose Pancreatic islet Icovamenib promotes selective and partial reduction in menin levels Lowering menin levels releases the break
on beta cell proliferation and GLP-1 and IMPROVED INCRETIN EFFECTS GLP-1 receptor expression Synergistic with GLP-1 based therapies Improved beta cell function Increased expression of Decrease in blood glucose GLP-1 GLP-1 receptor
Potential for weight loss Potential for lean mass/muscle preservation 10
ICOVAMENIB | PRECLINICAL Icovamenib increased beta cell quantity,
function & GLP-1 receptor expression following a short treatment period Improved beta cell mass and function BUILDING OF THE ICOVAMENIB MATURATION OF BETA CELL POOL BETA CELL POOL Dosing Follow-up period Long-term follow-up 12 weeks additional
14 period additional 26 Use of icovamenib weeks weeks for patients failing standard of care INSULIN FURTHER DECREASE INSULIN DECREASE IN BETA DEPENDENCE IN BETA CELL MASS DEPENDENCE CELL MASS Diagnosis of Type 2 Diabetes 1/3 of Type 2 Diabetes
patients Use of standard of end up on insulin care agents 11
ICOVAMENIB | PRECLINICAL ICOVAMENIB | PRECLINICAL Icovamenib
downregulated menin protein levels & promoted beta cell proliferation in ex vivo human islet cultures ICOVAMENIB CONDITIONALLY PROMOTED BETA CELL PROLIFERATION MENIN LEVELS DOWNREGULATED ONLY UNDER HYPERGLYCEMIC CONDITIONS Standard Glucose (5.5
mM) High Glucose (8 mM) 12
ICOVAMENIB | PRECLINICAL ICOVAMENIB | PRECLINIAL Icovamenib enhanced
GLP-1 receptor & insulin expression and demonstrated potential synergy in combination with semaglutide ex vivo Culture 7 days under glucotox conditions (8mM glucose) Cadaver derived Gene expression & Protein analysis human islets
Glucose Stimulated Insulin Secretion -/+ Semaglutide (200nM) ICOVAMENIB INCREASED GLP-1 RECEPTOR ICOVAMENIB IN COMBINATION WITH SEMAGLUTIDE AND INSULIN EXPRESSION INCREASED GLUCOSE-STIMULATED INSULIN SECRETION GLP-1 Receptor Insulin 13
ICOVAMENIB WITH GLP-1RA Combination treatment of icovamenib &
low-dose semaglutide reduced food intake & body weight APPETITE SUPPRESSION BODY WEIGHT REDUCTION SUPERIOR APPETITE SUPPRESSION WITH ABOUT 10% GREATER BODY WEIGHT REDUCTION THAN LOW-DOSE SEMAGLUTIDE ALONE THE OBSERVED BODY
WEIGHT REDUCTION WAS PRIMARILY DUE TO FAT MASS LOSS WITH PRESERVATION OF LEAN MASS 14
ICOVAMENIB Potential first-in-class oral menin inhibitor clinical study
ICOVAMENIB | COVALENT-111 Baseline demographics & characteristics
Per Protocol Population* on 1 or More Antihyperglycemic Agents at Baseline (N=163) Arm C Arm A Arm B Combined Arms Combined Arms icovamenib Parameter icovamenib icovamenib (8 wks 100 mg QD then 4 icovamenib placebo (8 wks 100mg QD) (12 wks 100 mg
QD) Mean (SD) or % wks of 100 mg BID) (N=114) (N=49) (N=45) (N=36) (N=33) 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) 2 BMI (kg/m ) 30.9 (4.7) 32.7 (4.5) 32.4 (4.9) 31.9 (4.7) 32.6 (4.2) 2 BMI <30 kg/m (%) (49) (22) (30) (35) (27) 2
BMI 30 kg/m (%) (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) *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 16 had significant protocol deviation.
ICOVAMENIB | COVALENT-111 Change in HbA1c from baseline through week 52
- all subtypes 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 0.2 TREATMENT
OFF-TREATMENT 0.1 Pooled Placebo (N=49) 0.0 Arm A (N=45) Arm B (N=36) -0.1 Arm C (N=33) -0.2 -0.3 -0.4 -0.5% threshold for clinical significance -0.5 CMS Clinical Endpoints Review (2024) -0.6 0 8 12 26 36 42 52 Weeks 17 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. Mean Change HbA1c (%)
ICOVAMENIB | COVALENT-111 Higher HbA1c reduction was associated with
higher icovamenib exposure Week 52, All Dosing Arms (N=114), HbA1c Reduction vs. Icovamenib Exposure (Mean AUC) Dosing timing relative to food will 184 0.5% impact icovamenib's pharmacokinetics (PK) 207 1.0% In a
Food Effect Study' icovamenib achieved optimal PK exposure when administered within 30 minutes after a 218 1.5% meal These findings now inform the dosing strategy for the ongoing Phase II studies 273 2.0 0 50 100
150 200 250 300 PK (Mean AUC) 18 Reduction HbA1c % at Week 52
ICOVAMENIB 12 weeks of dosing (arms B&C) delivered lasting benefit
through 52 weeks for severe insulin-deficient diabetes patients 1.0 INITIAL TARGET TREATMENT OFF-TREATMENT POPULATION FOR ICOVAMENIB 0.5 0.3 Pooled Placebo (N=12) 0.1 icovamenib (N=10) 0.0 -0.3 -0.5 -0.5% threshold for clinical significance -0.5 CMS
Clinical Endpoints Review (2024) -0.8 -1.0 -1.2 P=0.01 -1.5 -2.0 0 8 12 26 36 42 52 Week 19 Arm A was excluded from this analysis because it included only 8 weeks of dosing which the company is not planning to pursue. Mean Change HbA1c
ICOVAMENIB Icovamenib increased insulin secretion as measured by
C-peptide index in severe insulin-deficient patients (arms B&C) 1.6 TREATMENT OFF-TREATMENT Icovamenib (N=10) 1.5 Placebo (N=12) 1.4 1.3 24% 1.2 1.1 2% 1.0 0.9 0.8 0.7 0 12 52 Weeks 20 Data censored at onset of rescue medication, defined as any
modification in antihyperglycemic therapy Fold Change in C-peptide Index
ICOVAMENIB Patients on a GLP-1 based therapy at enrollment showed
durable & clinically meaningful response in reduction of blood sugar (HbA1c) 1.5 TREATMENT OFF-TREATMENT 1.1 1.0 0.6 0.5 Pooled Placebo (N=4) 0.1 icovamenib (N=12) 0.0 -0.3 -0.5% threshold for clinical significance -0.5 CMS Clinical Endpoints
Review (2024) -0.7 -1.2 P=0.05 -1.0 -1.5 -2.0 0 8 12 52 Weeks 21 Mean Change HbA1c (%)
ICOVAMENIB Icovamenib increased insulin secretion as measured by
C-peptide index in GLP-1 RA treated patients - 9 months post last dose 1.6 TREATMENT OFF-TREATMENT 35% 1.4 Icovamenib (N=11) Placebo (N=4) 1.2 -4% 1.0 0.8 0.6 0.4 0 12 52 Weeks 22 Data censored at onset of rescue medication, defined as any
modification in antihyperglycemic therapy Mean Change HbA1c (%)
ICOVAMENIB | COVALENT-111 Favorable 52-week safety profile Arm A Arm B
Arm C Combined Arms Combined Arms Parameter icovamenib icovamenib icovamenib icovamenib placebo (N=67) (N=67) (N=67) (N=201) (N=66) Patients with 1 TEAE, N (%) 19 (28) 22 (33) 14 (21) 55 (27) 18 (27) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)
Treatment-Related SAEs, N (%) SAEs*, N (%) 1 (1) 0 (0) 1 (1) 2 (1) 1 (1) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Treatment Discontinuation due to TEAE, N (%) Study Discontinuation due to TEAE, N (%) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 3 (4) 0 2 (3) 5 (3) 0 ALT
increase, N (%) 3 (4) 0 1 (1) 4 (2) 0 AST increase, N (%) 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) 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