Biomea Fusion Unveils Preclinical Data on Icovamenib Boosting GLP-1 Therapies; Introduces BMF-650

Biomea Fusion, Inc., a biopharmaceutical company, has presented promising preclinical data for its diabetes and obesity treatments. The company is focused on developing oral covalent small molecules to treat diabetes, obesity, and genetically defined cancers. They recently shared data on two key products, icovamenib (BMF-219) and BMF-650, highlighting their potential in enhancing therapy outcomes for diabetes.

The preclinical studies of icovamenib demonstrated its ability to boost the efficacy of GLP-1-based therapies, such as tirzepatide and semaglutide. These therapies are commonly used to manage diabetes by increasing insulin secretion. The combination of icovamenib with these therapies resulted in significant insulin secretion under hyperglycemic conditions. The improvement was dose-dependent, suggesting that icovamenib could potentially double the insulin response achieved by GLP-1-based therapies alone.

Menin, a protein involved in beta-cell proliferation and GLP-1 receptor expression, plays a crucial role in this process. According to Juan Pablo Frias, MD, Chief Medical Officer at Biomea Fusion, icovamenib’s combination with tirzepatide or semaglutide enhanced the responsiveness of human islets to GLP-1 therapy, leading to substantial insulin secretion. These findings suggest that icovamenib could offer a promising approach to improving glycemic control in diabetic patients.

In addition to icovamenib, Biomea Fusion is developing BMF-650, an investigational next-generation oral small-molecule GLP-1 receptor agonist (GLP-1 RA). BMF-650 has shown positive early preclinical activity, including enhanced glucose-stimulated insulin secretion, reduced blood glucose levels, and appetite suppression in cynomolgus monkeys. These results highlight BMF-650's potential as a treatment for diabetes and obesity.

The preclinical studies conducted by Biomea Fusion evaluated BMF-650's properties compared to a leading oral GLP-1 RA. BMF-650 exhibited higher bioavailability and a more consistent pharmacokinetic profile, which may translate to improved tolerability and support successful dose escalation in patients. The human dose is estimated to be around 100 mg once daily. In human donor islet studies, BMF-650 significantly enhanced glucose-stimulated insulin secretion, and in cynomolgus monkey studies, it showed significant improvements in glucose control.

Appetite suppression studies revealed that BMF-650, when administered daily, significantly reduced food intake during peak drug concentration, with sustained effects throughout the day over a six-day study period. These findings suggest that BMF-650 has the potential to be an effective oral treatment for both diabetes and obesity.

Thomas Butler, CEO and Chairman of the Board at Biomea Fusion, stated that the preclinical findings support the potential of icovamenib as a combination agent for GLP-1-based therapies. By reducing the required dosage of GLP-1 RA, icovamenib may improve efficacy, tolerability, and patient adherence, leading to longer-lasting benefits. Butler also expressed excitement about BMF-650, which has shown superior insulin secretion, better glucose control, a smoother pharmacokinetic profile, and higher bioavailability compared to a leading GLP-1 RA in preclinical studies. The appetite suppression results are particularly promising, indicating a new and impactful profile that could benefit patients with obesity.

Biomea Fusion plans to initiate a Phase II study, COVALENT-211, in 2025 to evaluate the combination of icovamenib with a GLP-1-based therapy. The company aims to continue developing its pipeline of next-generation covalent-binding small-molecule medicines designed to maximize clinical benefits for patients.

Obesity is a chronic disease requiring long-term management and is associated with various severe health complications, including type 2 diabetes, cardiovascular diseases, and certain cancers. The CDC estimates that over 40% of adults in the U.S. are obese, posing a significant burden on public health. Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of medications that mimic the effects of native GLP-1, playing a vital role in glucose homeostasis and appetite regulation. These agents have shown robust clinical efficacy in improving glycemic control and promoting weight loss.

Biomea Fusion continues to leverage its proprietary FUSION™ System to discover, design, and develop next-generation covalent-binding small-molecule medicines aimed at curing diseases and improving patient outcomes.