Biomea Fusion (BMEA) Status Update summary

Key milestones and scientific findings

• Identified menin as a suppressor of GLP-1 receptor expression, with icovamenib inhibition enhancing GLP-1 pathway function and insulin secretion in preclinical models.

• Preclinical studies show icovamenib combined with GLP-1-based therapies significantly increases insulin secretion in human islets, supporting a synergistic mechanism.

• BMF-650, a next-generation oral GLP-1 receptor agonist, demonstrated higher bioavailability, smoother pharmacokinetics, and superior glucose-stimulated insulin secretion compared to orforglipron in preclinical studies.

• BMF-650 showed strong appetite suppression and improved glucose control in cynomolgus monkeys, supporting its potential for diabetes and obesity treatment.

• Combination of icovamenib and GLP-1-based therapies could shift treatment paradigms by enhancing efficacy and reducing side effects.

Clinical development and trial updates

• COVALENT-211 Phase II trial is planned for 2025 to test icovamenib and GLP-1-based therapy combination, focusing on glycemic efficacy and persistence after GLP-1 discontinuation.

• COVALENT-111 readout expected in December, targeting dose selection and biomarker identification for late-stage development in type 2 diabetes patients.

• Combination therapy aims to enable lower GLP-1 dosing, improved tolerability, and greater persistence, with icovamenib as a finite therapy to build beta cell mass.

• Translational studies are ongoing to confirm upregulation of GLP-1 receptor after icovamenib treatment.

• Biomarker strategies in upcoming trials will focus on beta cell function, C-peptide secretion, and patient stratification by beta cell deficiency and insulin resistance.

Strategic and operational outlook

• Resource allocation will balance diabetes and oncology programs, leveraging partnerships and capital investments to support multiple late-stage data readouts.

• Major data releases expected in Q4 and Q1, with presentations planned at key diabetes and metabolic disease conferences.

• IND filing for BMF-650 targeted for the second half of 2025, with ongoing GLP-TOX and in vivo efficacy studies.

• Appetite suppression and safety data for BMF-650 will be further evaluated in longer-term preclinical and clinical studies.

• Investor update webcast and presentation were made available, with a replay accessible online.