Biomea Fusion announced promising preclinical results for BMF-650, its investigational oral GLP-1 receptor agonist, demonstrating significant weight loss and appetite suppression in obese non-human primates. The 28-day study in cynomolgus monkeys showed dose-dependent effects that compared favorably to published data from competing oral GLP-1 candidates, positioning the drug for clinical development later this year.
Robust Weight Loss in Primate Model
The preclinical study evaluated 15 obese cynomolgus monkeys randomized into three groups receiving either vehicle control, BMF-650 at 10 mg/kg, or BMF-650 at 30 mg/kg administered orally once daily for 28 days. The results demonstrated clear dose-dependent effects on both food intake and body weight.
Daily food intake was dramatically reduced in treated animals, dropping to an average of 35g/day in the 10 mg/kg group and 16g/day in the 30 mg/kg group, compared to 109g/day in the vehicle control group. This pronounced appetite suppression translated into substantial weight loss, with the respective dose groups achieving 12% and 15% average weight reduction from baseline over the 28-day treatment period.
"These new findings are especially relevant given the functional similarities between monkey and human GLP-1 receptors," said Thorsten Kirschberg, Executive Vice President of Chemistry at Biomea and program lead for BMF-650. "These data disclosed today further support our goal of developing a next-generation oral GLP-1 receptor agonist with enhanced pharmacokinetic properties, specifically a more consistent plasma exposure and improved bioavailability, while preserving the potent metabolic effects observed with injectable therapies."
Enhanced Pharmacokinetic Profile
BMF-650 belongs to the orforglipron chemotype class and is designed with improved pharmacokinetic properties to enhance oral bioavailability and achieve less variability compared to current GLP-1 receptor agonists. In preclinical studies, BMF-650 demonstrated a favorable pharmacokinetic profile with higher bioavailability and less inter-individual variability compared to published third-party preclinical data on another oral GLP-1 RA.
The drug showed robust glycemic control and appetite suppression in multiple preclinical models, resulting in pronounced and dose-dependent weight reduction. BMF-650 significantly enhanced glucose-stimulated insulin secretion in both human donor islets and in vivo in non-human primates, while demonstrating robust glucose-lowering activity.
Safety and Tolerability Profile
The preclinical data indicated that BMF-650 was generally well tolerated throughout the study period, with no aminotransferase elevations observed. The safety profile showed no concerns outside of the observed class effects typical of GLP-1 receptor agonists.
Biomea's development strategy focuses on achieving steady plasma levels and increased drug exposure to support a potential best-in-class profile among oral small-molecule GLP-1 therapies. The enhanced pharmacokinetic properties may support improved tolerability and more effective dose escalation in clinical settings compared to current GLP-1 receptor agonists.
Clinical Development Timeline
BMF-650 is currently advancing through IND-enabling studies, with submission of an Investigational New Drug application on track for the second half of 2025. Following IND clearance, Biomea anticipates initiating a Phase I trial in obese, otherwise healthy volunteers in late 2025.
The company plans to present a full set of preclinical data for BMF-650 at an upcoming medical conference. Kirschberg noted that "the pronounced and consistent appetite suppression and weight loss observed in primates, together with earlier data on glucose-lowering and oral bioavailability, provide strong support for advancing BMF-650 into clinical development."
Addressing the Obesity Epidemic
The development of BMF-650 addresses a significant unmet medical need, as obesity affects over 40% of adults in the United States according to the Centers for Disease Control and Prevention. Globally, over 650 million adults are living with obesity, with numbers steadily rising. Obesity is associated with diminished life expectancy and severe health complications including type 2 diabetes, cardiovascular diseases, chronic kidney disease, certain cancers, and chronic inflammation.
GLP-1 receptor agonists have demonstrated robust clinical efficacy in improving glycemic control, promoting weight loss, and enhancing insulin sensitivity in individuals with type 2 diabetes and obesity. However, current therapies are primarily injectable formulations, creating an opportunity for oral alternatives that could improve patient compliance and treatment outcomes.
