Biomea Fusion presents follow-up data on Phase II study COVALENT-111

Biomea Fusion announced the poster presentation of long-term 26 weeks follow-up data from the first two cohorts of adults with type 2 diabetes enrolled in the ongoing Phase II clinical study, COVALENT-111, and data from preclinical ex-vivo human islet experiments of BMF-219, the company’s investigational oral covalent menin inhibitor. Clinical Update for COVALENT-111 at WCIRDC 2023: Efficacy Data: 26 Week Glycemic Data: At Week 26, 22 weeks after the last dose of BMF-219, participants in 100 mg BMF-219 QD cohort saw an improved placebo adjusted mean reduction in HbA1c of 0.8%; Participants in 100 mg BMF-219 QD cohort saw an improved placebo adjusted mean reduction in HbA1c of 0.2% at Week 26; 20% of patients from the 100mg dose cohorts displayed a reduction in HbA1c of 1% or more, compared to 0% of patients for placebo at Week 26; After only four weeks of dosing and 22 weeks off treatment, participants in BMF-219 100 mg QD without food cohort demonstrated an 80% response rate – with any reduction in HbA1c. 26 Week Pharmacokinetic Data: Cohort 3 resulted in approximately 2.7-fold higher BMF-219 exposure than Cohort 2; Higher exposure resulted in greater reduction in HbA1c. Increase in mean HOMA-B and AUC C-peptide in Responders at Week 26: After 4 weeks of once daily BMF-219, responders with baseline HOMA-B less than200 (upper limit of normal) across both cohorts, achieved a greater increase from baseline in placebo-adjusted HOMA-B and stimulated C-peptide AUC at Week 26. Safety Data: Generally well-tolerated with no severe or serious adverse events; No symptomatic or clinically significant hypoglycemia; No dose discontinuation or modification. Preclinical Ex-Vivo Human Islet Data: BMF-219 was observed to upregulate the expression of key cell-cycle proteins, PbK and CCNA2, in a glucose-dependent fashion. When not sequestered to menin, PbK expression was known to be upregulated by JunD, which is a glucose-sensitive menin binding partner. Dependent on dose concentration and also dependent on dose duration, BMF-219 was observed to increase beta cell mass and function, as well as promote controlled proliferation and enhance insulin content in beta cells. Proliferation was observed only under elevated glucose conditions, which mimics diabetic levels, and with continuous drug exposure. Next Steps and Updates with BMF-219: BMF-219 in Type 1 and Type 2 Diabetes: Complete dose escalation for all dose levels in COVALENT-111; Initiate dose expansion portion of COVALENT-111 with longer durations of treatment at two dose levels including 100 mg and 200 mg; Explore utility of BMF-219 in type 1 diabetes and initiate enrollment of COVALENT-112 trial