Biomea Fusion, Inc. · NASDAQ:BMEA

Biomea Fusion — EASD Annual Meeting 2022

23 slides from Biomea Fusion's conference presentation, Sep 22, 2022

1. Slide 1: Oral long-acting menin inhibitor normalizes type 2 diabetes in two rat models

   Presentation # 197 Oral long-acting menin inhibitor normalizes type 2 diabetes in two rat models *Thomas Butler, Sanchita Mourya, Weiqun Li, Tenley Archer, Taisei Kinoshita, Mini Balakrishnan, Priyanka Somanath EASD Annual Meeting 2022 Oral Presentation Golgi Hall Session: OP 33 Therapy outside the

2. Slide 2: Our understanding of diabetes has evolved

   Our understanding of diabetes has evolved; Progression of type 1 and type 2 diabetes are both driven by beta cell loss Progression of Type 2 Diabetes “Understanding of Diabetes has evolved” Pipeline-in-a-Pill – Single Agent for Multiple Indications MLL Fusion & NPM1 Driven Tumors Initial clinical va

3. Slide 3: Menin: A key checkpoint for beta cell homeostasis

   Menin: A key checkpoint for beta cell homeostasis; an important target for type 1 and type 2 diabetes • Menin functions in a histone Menin Activation methyltransferase protein complex containing MLL • This complex promotes Suppress Beta Cell trimethylation of histone H3 on Homeostasis lysine 4 (H3K4

4. Slide 4: BMF-219, A potent & selective covalent menin inhibitor

   BMF-219, A potent & selective covalent menin inhibitor BMF-219 exerts transient changes in Menin Protein menin Menin Half Life Varies By Compartment S C Half Life in Cytoplasm: <1hr Half Life in Nucleus: 6-8 hrs Menin’s half-life in nucleus is MEN1 Gene Expression Decreases most relevant for w/ BMF-

5. Slide 5: Zucker Diabetic Fatty Rat – A model of insulin resistance

   Zucker Diabetic Fatty Rat –A model of insulin resistance THE ZDF RAT Study Design Day • The ZDF rat is a model of pancreatic exhaustion, thus mimicking some aspects of human diabetes. Treatment groups (n=10/group): 1. Vehicle • Pioglitazone and metformin provide therapeutic efficacy in 2. BMF-219 17

6. Slide 6: BMF-219 significantly reduces blood glucose by OGTT in ZDF rats

   BMF-219 significantly reduces blood glucose by Oral Glucose Tolerance Test (OGTT) in ZDF rats OGTT, Day 15 A 600 * p<0.05 vs Vehicle ** p<0.01 vs Vehicle OGTT, Area Under the Curve (AUC) Blood Glucose (mg/dL) *** p<0.001 vs Vehicle 80000 *** p<0.001 vs Vehicle Mean  SEM 400 54% reduction 60000 ** *

7. Slide 7: BMF-219 reduces blood glucose, insulin, and c-peptide levels in ZDF Rats

   BMF-219 significantly reduces blood glucose, insulin, and c-peptide levels in ZDF Rats (After 2 Weeks of Dosing) Blood Glucose (4hr fasting) Insulin (4hr fasting) * p<0.05 ** p<0.01 400 10 *** p<0.0001 Serum insulin (ng/mL) Blood glucose (mg/dL) 8 300 Mean ± SEM ** 6 * 200 * 4 *** ** 100 2 0 0 Non-f

8. Slide 8: BMF-219 increases insulin sensitivity in ZDF rats

   BMF-219 increases insulin sensitivity in ZDF rats A HOMA-IR (4hr fasting) B HOMA-IR (non-fasting) 150 400 *** p<0.001 vs Vehicle *** p<0.001 vs Vehicle 300 100 (ng/mL) 200 *** *** 50 *** *** 100 *** *** 0 0 Day 1 Day 8 Day 14 Measurement of HOMA-IR in rats treated with BMF-219 for 16 Days 8

9. Slide 9: BMF-219 reduces blood lipemic levels and reduces body weight at day 17

   BMF-219 significantly reduces blood lipemic levels and reduces body weight at day 17 Cholesterol * p<0.05 Body Weight (g) ** p<0.01 250 600 Serum Cholesterol (mg/dL) * p<0.05 vs Vehicle *** p<0.0001 200 ** p<0.01 vs Vehicle 550 * Body weight (g) Mean ± SEM 150 ** 500 100 450 50 0 400 350 Triglycerid

10. Slide 10: BMF-219 displays durable glycemic control during drug washout

    BMF-219 displays durable glycemic control during drug washout, two weeks after the last dose After 2-week Drug Washout OGTT, Day 29 800 Blood Glucose (mg/dL) 600 Mean  SEM OGTT AUC on day 29 400 100000 * * 80000 *p<0.05 vs Vehicle 75% glycemic control * 200 * maintained on day 29 * * 60000 * post-d

11. Slide 11: BMF-219 maintains impact on glucose, insulin and c-peptide during washout

    BMF-219 maintains a strong impact on blood glucose, insulin and c- peptide levels during drug washout, two weeks after the last dose Day 31: After 2-week Drug Washout Blood Glucose (4hr fasting) Insulin (4hr fasting) C-peptide (4hr fasting) * p<0.05 600 ** p<0.01 *** p<0.0001 Blood glucose (mg/dL) 1

12. Slide 12: BMF-219 increases β-islets in pancreas sections of ZDF diabetic model

    BMF-219 increases β-islets in pancreas sections of ZDF diabetic model A. Vehicle; Day 31 B. Pioglitazone; Day 17 D. BMF-219; Day 31 C. BMF-219; Day 17 A) Vehicle-treated animal, Day 31. Beta islets display low congregation and growth, while alpha cells dominate. B) Pioglitzaone-treated animal, Day 1

13. Slide 13: BMF-219 increases β-islets in pancreas sections of ZDF diabetic model

    BMF-219 increases β-islets in pancreas sections of ZDF diabetic model Quantitative Analysis of pancreatic +2.0% islet tissue cross sections shows BMF-219 treated animals show novel effects in Beta Cell Area growth and maintenance. BMF-219 was able to maintain Beta Cell function and prevent Beta Cell

14. Slide 14: BMF-219 demonstrates strong β-cell activity, supporting quantitative analysis

    BMF-219 demonstrates strong β-cell activity, supporting quantitative analysis HOMA-Beta, a measurement of Beta Cell Function, was analyzed using 4-hr fasting glucose and insulin levels in animal plasma. BMF-219 displayed a significant level of Beta Cell function compared to vehicle at Day 31 in an N

15. Slide 15: Streptozotocin (STZ) Rat, A type 2 diabetes model of beta cell loss

    Streptozotocin (STZ) Rat, A type 2 diabetes model of beta cell loss MEN1 Excision Prevents Development of STZ-induced Hyperglycemia ▪ Menin is a scaffold protein, encoded by the gene MEN1, that has been recently recognized for its role in Type 2 Diabetes Mellitus (T2DM) as a key regulator of b-cell

16. Slide 16: STZ Rat Model - Study Design

    STZ Rat Model- Study Design The Streptozotocin (STZ)-Induced Rat Model Study Design Only direct insulin injection shows an effect in this model with high fat diet STZ treatment typically results in ~50% Beta Cell Loss 16

17. Slide 17: BMF-219 reduced blood glucose by OGTT in an STZ-induced rat model

    BMF-219 significantly reduced blood glucose by Oral Glucose Tolerance Test (OGTT) in an STZ-induced rat model Oral Glucose Tolerance Test (Day 17) Non-Fasting Glucose STZ + HFD model Non-fasting Glucose Vehicle 800 Pioglitazone (30 mg/kg) 800 BMF-219 (175mg/kg) Blood Glucose (mg/dL) MeanSE (mg/dL)

18. Slide 18: BMF-219 demonstrates recovery of β-cell activity

    BMF-219 demonstrates recovery of β-cell activity HOMA-Beta, a measurement of Beta Cell Function, was analyzed using 4-hr fasting glucose and insulin levels in animal plasma. BMF-219 displayed a significant level of Beta Cell function compared to vehicle at Day 17 in a Beta +96% Cell Type 2 Diabetes

19. Slide 19: BMF-219 reduces blood lipemic levels and body weight in STZ rats

    BMF-219 significantly reduces blood lipemic levels and body weight in STZ rats Body Weight 550 Total Cholesterol Triglyceride 500 150 (at Day 17) 250 (at Day 17) Serum Cholesterol (mg/dL) Serum Triglyceride (mg/dL) 450 Mean ± SEM 200 400 BW (g) Mean ± SEM Mean ± SEM 100 350 * 150 * 300 7% reduction

20. Slide 20: BMF-219 in ex-vivo Human Islet Microtissue (Sneak Peak)

    BMF-219 in ex-vivo Human Islet Microtissue (Sneak Peak) 20

21. Slide 21: Human Donor Islets (Ex-Vivo): Statistically significant increase in beta cells

    Human Donor Islets (Ex-Vivo): Statistically significant increase in beta cells with BMF-219 Solvent BMF-219 BMF-219 (Conc. 1) (Conc. 2) Threshold 375 Threshold 325 21 21 Do Not Copy

22. Slide 22: Conclusions & Next Steps

    Conclusions & Next Steps ▪ BMF-219 was tested in two type 2 diabetic in-vivo models at clinically relevant exposures. BMF-219 treatment in STZ-induced diabetic rat model: ➢ Improved glucose metabolism (OGTT AUC reduction 41%, p<0.05) and reduction in blood lipemic levels and body weight. Minimal eff

23. Slide 23: Thank You

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