Slide 1: BMF-219: A Novel Therapeutic Agent to Reestablish Functional Beta Cells
BMF-219: A Novel Therapeutic Agent to Reestablish Functional Beta Cells and Provide Long-Term Glycemic Control Juan Pablo Frias, Sanchita Mourya, Brian Munneke, Mini Balakrishnan, Priyanka Somanath, Thomas Butler All authors are employees of Biomea Fusion CONFIDENTIAL
Slide 2: Background
Background • Menin is a scaffold protein with multiple functions, including the regulation of gene transcription and cellular signaling • Through interacting with its binding partners, menin acts as an important regulator of glycemic control, whereby inhibition of menin activity enhances beta cell p
Slide 3: Aims
Aims • To assess the effects of BMF-219 in human donor islet microtissues • To assess the safety and efficacy of BMF-219 100 mg once daily for 4 weeks at Week 26 (22 weeks after final dose) Page 3
Slide 4: Ex-vivo human islet microtissues: Study design
BMF-219 – Human islet microtissues Ex-vivo human islet microtissues: Study design Cadaver-derived human islets (without diabetes) • BMF-219, harmine, or vehicle control for 1-3 weeks (+/- washout) • Assayed under standard (5.5 mM) and high (8.0 mM) glucose Islet aggregation 1 week 2 weeks • Beta cel
Slide 5: Human islet microtissues: Beta cell proliferation (Donor 1)
BMF-219 – Human islet microtissues Human islet microtissues: Beta cell proliferation (Donor 1) Proliferating beta cells as a fraction of total beta cells Standard glucose High glucose Day 14, high glucose Proliferating β-cell Fraction Day 14 Day 21 Day 14 Day 14 Day 21 Day 14 2.5 + washout + washout
Slide 6: Human islet microtissues: Beta cell proliferation (Donor 2)
BMF-219 – Human islet microtissues Human islet microtissues: Beta cell proliferation (Donor 2) Proliferating beta cells as a fraction of total beta cells Standard glucose High glucose Day 14, High glucose Proliferating β-cell Fraction Day 14 Day 21 Day 14 Day 21 0.3 * EdU+ NKX6.1+ / NKX6.1+ % 0.2 0.
Slide 7: Human islet microtissues: Beta cell insulin content
Donor 2 Donor 1 Total Insulin Content (ng/MT) Total Insulin Content (ng/MT) 10 20 30 0 10 20 30 0 DMSO DMSO 0.075 μM Biomea 0.3 μM Day 14 0.15 μM Harmine *** Day 14 BMF-219 – Human islet microtissues 10 μM BMF-219 0.3 μM DMSO Harmine 10 μM *** Biomea DMSO 0.3 μM Day 21 Harmine *** 0.075 μM 10 μM Sta
Slide 8: Human islets: CCNA2 and PbK gene expression
BMF-219 – Impact on beta cell proliferation gene expression Human islets: CCNA2 and PbK gene expression CCNA2 gene expression PbK gene expression BMF-219 BMF-219 BMF-219 (10nM) (30nM) (100nM) • BMF-219 resulted in increased CCNA2 and PbK expression, similar to literature results from menin knockdown
Slide 9: Key eligibility criteria and study design
Covalent-111 Study Key eligibility criteria and study design COVALENT-111 T2D MAD Cohorts Eligibility Criteria • T2D, age 18-65 yr 50 mg QD, without food x 4 weeks • Duration of diabetes 15 yr or less • HbA1c 7.0-10.0%, inclusive 100 mg QD, without food • Treated with diet/exercise ± up to 3 x 4 wee
Slide 10: Study objectives of T2D multiple ascending dose cohorts
Covalent-111 Study Study objectives of T2D multiple ascending dose cohorts Primary Objective: To assess the safety and tolerability of multiple ascending oral doses of BMF-219 Key Secondary Objectives: ▪ To determine the pharmacokinetics following multiple ascending doses of BMF-219 ▪ To determine t
Slide 11: Baseline characteristics and demographics
Covalent-111 Study Baseline characteristics and demographics BMF-219 100mg QD BMF-219 100mg QD without food with food Placebo (n=10) (n=10) (n=6) Age (year, min-max) 52 (38-63) 51 (35-60) 46 (31-61) Sex (n, M/F) 6/4 7/3 6/0 Duration of diabetes (year, min-max) 4.2 (0.5-9.0) 8.7 (4.0-14.0) 4.2 (1.0,
Slide 12: Greater BMF-219 exposure resulted in greater reduction in HbA1c at Week 26
COVALENT-111 Study Greater BMF-219 exposure at Week 4 resulted in greater reduction in HbA1c at Week 26 100 mg QD without food 100 mg QD with food BMF-219 mean AUClast at Week 4 Change in HbA1c at Week 26 0.3 ± 1.7 0.1 ± 1.1 300 0 224 ± 2.5 AUClast (ng*hr/mL) Change in HbA1C (%) 200 -0.5 -0.5 ± 1.1
Slide 13: Glycemic results summary at Week 26
COVALENT-111 Study Glycemic results summary at Week 26 BMF-219 100mg QD BMF-219 100mg QD without food with food Placebo (n=10) (n=10) (n=6) Mean change in HbA1c -0.5% 0.1% 0.3% Placebo adjusted mean change in HbA1c -0.8% -0.2% - Percent of participants with ≥1.0% reduction in HbA1c 20% 20% 0% Percen
Slide 14: % increase in HOMA-B and C-peptide AUC in responders
COVALENT-111 Study % increase in HOMA-B and C-peptide AUC in responders Patients with HbA1c reduction ≥0.5% at Week 26 and baseline HOMA-B <200 % change HOMA-B % change C-peptide AUC CONFIDENTIAL Page 14
Slide 15: Case Study 1: 45-year-old man with 9-year history of T2D
COVALENT-111 Study Case Study 1: 45-year-old man with 9-year history of T2D • 45-year-old man with 9-year history of T2D • BMF-219 100 mg once daily with food for 4 weeks • Metformin 500 mg BID • CGM at Week 26 with >75% TIR70-180 mg/dL • HbA1c 8.4%; FPG 216 mg/dL; BMI 29.6 kg/m2 • No tolerability i
Slide 16: Case Study 1: 45-year-old man with 9-year history of T2D
COVALENT-111 Study Case Study 1: 45-year-old man with 9-year history of T2D • 45-year-old man with 9-year history of T2D • BMF-219 100 mg once daily with food for 4 weeks • Metformin 500 mg BID • CGM at Week 26 with >75% TIR70-180 mg/dL • HbA1c 8.4%; FPG 216 mg/dL; BMI 29.6 kg/m2 • No tolerability i
Slide 17: Case Study 2: 29-year-old man with 4-year history of T2D
COVALENT-111 Study Case Study 2: 29-year-old man with 4-year history of T2D • 29-year-old man with 4-year history of T2D • BMF-219 200 mg once daily without food for 4 weeks • Metformin and empagliflozin • CGM at Week 21 with ~90% TIR70-180 mg/dL • HbA1c 9.5%; FPG 146 mg/dL; BMI 25.6 kg/m2 • No tole
Slide 18: Case Study 2: 29-year-old man with 4-year history of T2D
COVALENT-111 Study Case Study 2: 29-year-old man with 4-year history of T2D • 29-year-old man with 4-year history of T2D • BMF-219 200 mg once daily without food for 4 weeks • Metformin and empagliflozin • CGM at Week 21 with ~90% TIR70-180 mg/dL • HbA1c 9.5%; FPG 146 mg/dL; BMI 25.6 kg/m2 • No tole
Slide 19: Safety and tolerability
COVALENT-111 Study Safety and tolerability • BMF-219 was generally well tolerated and safe • There were no severe or serious adverse events reported • No dose discontinuations or modifications • No symptomatic or clinically significant hypoglycemia • All patients completed 4 weeks of dosing and foll
Slide 20: Summary and Conclusions
Summary and Conclusions • In ex-vivo cultured human islet microtissues, BMF-219 enhanced beta cell proliferation and increased beta cell insulin content in a glucose-dependent manner • In patients with T2D, 4 weeks of BMF-219 100 mg once-daily resulted in clinically meaningful improvements in glycem
Slide 21: Thank you
Thank you biomea We Aim to Cure FUSION