Biomea Fusion presented compelling new data at the 85th Scientific Sessions of the American Diabetes Association (ADA) demonstrating the potential of icovamenib, its investigational oral menin inhibitor, to enhance existing diabetes treatments while addressing key limitations of current therapies. The data, presented June 20-23, 2025 in Chicago, highlights icovamenib's ability to work synergistically with GLP-1 receptor agonists while preserving lean muscle mass.
Enhanced Efficacy in Combination Therapy
In preclinical studies using a Zucker Diabetic Fatty (ZDF) rat model of type 2 diabetes, icovamenib combined with low-dose semaglutide (0.02 mg/kg) demonstrated superior metabolic benefits compared to semaglutide alone. The combination therapy achieved 60% lower fasting blood glucose and 50% lower glucose oral glucose tolerance test area under the curve. HbA1c declined by more than 1% by day 28 and more than 2% by day 39, while insulin sensitivity improved with a 75% lower HOMA-IR, a marker of insulin resistance.
The combination also produced a 2-fold increase in C-peptide to glucose ratio, indicating enhanced beta cell function, and achieved 10% greater body weight reduction than low-dose semaglutide alone. Critically, the observed weight loss was primarily due to fat mass reduction with complete preservation of lean mass.
Muscle-Protective Effects
A separate preclinical study evaluated icovamenib's direct effects on muscle tissue using ex vivo human myotube cultures. In iPSC-derived 3D-engineered human myotubes, icovamenib treatment promoted healthy myotube morphology and diminished drug-induced atrophy caused by activin A or dexamethasone, suggesting muscle health supporting effects.
"The studies presented at ADA demonstrate that icovamenib enhanced glycemic control and drove additional weight loss when used in combination with GLP-1 therapies, while fully preserving lean mass," said Ramses Erdtmann, President and Chief Operating Officer of Biomea Fusion. "We believed these attributes set icovamenib apart in the diabetes landscape and support its potential to transform care for millions of patients."
Durable Clinical Benefits
The Phase II COVALENT-111 trial provided 26-week follow-up data demonstrating the durability of icovamenib's effects after short-course treatment. In severely insulin-deficient patients, icovamenib achieved a 1.0% placebo-adjusted mean HbA1c reduction and a 55% increase in C-peptide at week 26, three months after the last dose. Notably, over half of the C-peptide improvement occurred during the off-treatment period, indicating a durable effect on endogenous insulin production.
Short-course dosing of 8 or 12 weeks led to sustained HbA1c reductions through week 26 across the broader study population. Changes in HbA1c correlated significantly with changes in C-peptide, supporting the proposed mechanism of action to restore beta-cell function.
In patients inadequately controlled on baseline GLP-1 receptor agonist therapy, adding icovamenib to the GLP-1 therapy resulted in up to an additional 1.0% mean HbA1c reduction.
Safety Profile
Icovamenib demonstrated a favorable safety profile across all dosing arms in the clinical trial, with a low incidence of treatment-emergent adverse events, no clinically significant elevations in ALT or AST, and no study drug discontinuations or trial discontinuations due to adverse events.
Mechanism of Action
Icovamenib works by inhibiting menin, a protein thought to act as a brake on beta cell turnover and growth. The inhibition of menin could lead to the regeneration of normal, healthy beta cells. Beta cells in the pancreas are responsible for insulin synthesis and secretion, and their diminished function is a core component of diabetes pathophysiology.
The combination approach may allow for lower doses of GLP-1-based therapies to achieve glycemic and weight loss targets while improving tolerability, offering a compelling rationale for clinical evaluation of icovamenib-based combination regimens. As a potentially first disease-modifying therapy for both type 1 and type 2 diabetes, icovamenib could become an important addition to the diabetes treatment landscape pending successful completion of clinical studies and regulatory approval.
