Biomea Fusion has announced ‘compelling’ results from in vivo studies of icovamenib in combination with semaglutide. Icovamenib is an investigational, orally bioavailable, potent, and selective covalent inhibitor of menin. The molecule was built using Biomea Fusion’s FUSION System and is designed to regenerate insulin-producing beta cells with the aim to cure diabetes. Icovamenib’s proposed mechanism of action in diabetes is to enable the proliferation, preservation and reactivation of a patient’s own healthy, functional, insulin-producing beta cells.
This preclinical study evaluated the efficacy of icovamenib, an investigational covalent menin inhibitor, in combination with a GLP-1 receptor agonist (i.e., semaglutide) to assess key metabolic parameters in animal models including: improvements in C-peptide index, a marker of insulin secretion and glucose regulation, blood glucose, HbA1c, insulin resistance (HOMA-IR) and beta cell function (HOMA-B), changes in body weight and composition, including fat and lean mass, and appetite suppression.
Menin is thought to act as a brake on beta cell turnover and growth, supporting the notion that inhibition of menin could lead to the regeneration of normal, healthy beta cells. Based on these and other scientific findings, Biomea is exploring the potential for icovamenib-mediated menin inhibition as a viable therapeutic approach to potentially halt or reverse progression of T2D.
Biomarkers were analysed at multiple time points throughout a 28-day period. The study was conducted in two groups, one group of 10 Zucker Diabetic Fatty (ZDF) rats dosed with icovamenib (day 1 through day 28) in combination with semaglutide (day 14 through day 28) and a second group of 10 ZDF rats dosed with semaglutide alone (day 14 through day 28). ZDF rat is a type 2 diabetes animal model of insulin resistance.
Highlights from the study include:
A 60% reduction in fasting blood glucose level was observed with combination therapy compared to semaglutide alone.
A 50% reduction in area under the curve (AUC) was observed during the Oral Glucose Tolerance Test (OGTT) with combination therapy versus semaglutide alone, indicating improved glucose metabolism (p<0.0001).
HbA1c reduction on Day 28 was greater with the combination therapy (>1%) compared to semaglutide alone (p<0.05).
Insulin resistance as measured by HOMA-IR was reduced by 75% with combination therapy compared to semaglutide alone (p<0.001).
Combination treatment also improved beta-cell function as measured by HOMA-B.
Combination therapy reduced body weight by 11.5% and fat mass by 29.5% compared to semaglutide alone.
A 43% increase in lean mass compared to semaglutide alone was also observed with combination therapy.
Icovamenib in combination with semaglutide was well tolerated across multiple time points.
“We believe these preclinical results underscore the potential of icovamenib to transform diabetes treatment when combined with GLP-1-based therapies,” said Juan Pablo Frias, Biomea Fusion’s Chief Medical Officer. “Our studies demonstrated that icovamenib not only increased the C-peptide index but also amplified key benefits of GLP-1 therapies, including improved glycaemic and body weight control. Importantly, this synergy may enable lower doses of GLP-1 therapies to achieve glycaemic and weight loss targets, potentially reducing side effects and improving tolerability. We are very encouraged by these preclinical results and look forward to further assessing this combination in clinical trials to potentially address unmet needs of people living with type 2 diabetes.”
As the potentially first disease-modifying therapy for T1D and T2D, the company believes icovamenib could become an important addition and complement to the diabetes treatment landscape once it has successfully completed its ongoing clinical studies.
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