Biomea Fusion (BMEA) investor relations material

Study background, design, and objectives

• COVALENT-111 was a randomized, double-blind, placebo-controlled phase II trial in adults with type 2 diabetes, including all subtypes, focusing on safety, tolerability, and efficacy endpoints.

• Participants had HbA1c 7.0–10.5%, BMI 25–40 kg/m², and were on up to three antidiabetic agents (excluding insulin and sulfonylureas).

• Three dosing arms were evaluated: 8 weeks, 12 weeks, and 8 weeks plus 4 weeks higher dose, with 3:1 randomization to active drug vs. placebo.

• Subgroup analyses included severe insulin-deficient (SIDD), mild age-related (MARD), mild obesity-related (MOD), and severe insulin-resistant (SIRD) diabetes.

• The study aimed to identify patient subtypes most likely to benefit from menin inhibition and determine optimal dosing.

Key efficacy findings

• Icovamenib produced sustained, clinically meaningful HbA1c reductions at 52 weeks, with the greatest effect in SIDD patients (up to 1.8% reduction, p=0.01) and those failing GLP-1 therapy (up to 1.8% placebo-adjusted reduction).

• Durable efficacy was observed nine months post-dosing, suggesting restoration of beta cell function.

• Greater drug exposure correlated with greater HbA1c reduction; food type and timing impacted pharmacokinetics, prompting a dedicated food effect study.

• Icovamenib’s efficacy in SIDD was comparable to top-performing, chronically dosed diabetes agents, despite short-duration dosing.

Mechanism of action and clinical implications

• Icovamenib is an oral, selective covalent inhibitor of menin, a regulator of beta cell quantity and function.

• Menin inhibition may enable proliferation and reactivation of healthy, insulin-producing beta cells and upregulate GLP-1 receptor expression.

• The dual mechanism may improve glucose control, insulin production, and potentially support weight loss and muscle preservation.

• Combination with GLP-1 receptor agonists produced marked HbA1c reductions in insulin-resistant patients.

• Icovamenib’s non-chronic, episodic dosing and sustained effect differentiate it from current chronic therapies.