Biomea Fusion Releases Preclinical Data With BMF-219 in Diabetes

Biomea Fusion, Inc. recently announced BMF-219 displayed remarkable activity in both the Zucker Diabetic Fatty (ZDF) Rat and the Streptozotocin-Induced Diabetes (STZ) animal models of type 2 diabetes.

Loss of functional Beta-cell mass is a core component of the natural history in both types of diabetes — type 1 diabetes (mediated by autoimmune dysfunction) and type 2 diabetes (mediated by metabolic dysfunction). Beta-cells are found in the pancreas and are responsible for the synthesis and secretion of insulin. Insulin is a hormone that helps the body use glucose for energy and helps control blood glucose levels. In patients with diabetes, Beta-cell mass and function are diminished, leading to insufficient insulin secretion and hyperglycemia. Menin is thought to act as a brake on Beta-cell turnover / Beta-cell growth, supporting the notion that inhibition of menin could lead to the regeneration of normal healthy Beta-cells. Notably, it has previously been shown that knocking out the gene responsible for the creation of menin (MEN1) has been observed to produce profound glycemic control in diabetic animal models. Based on these and other scientific findings, Biomea explored the potential for menin inhibition as a viable therapeutic approach to permanently halt or reverse progression of type 2 diabetes.

Focusing on the hallmark of type 2 diabetes, Beta-cell dysfunction and loss of Beta-cell mass, Biomea conducted both the ZDF and the STZ experiments to measure the potential impact of BMF-219 for the treatment of type 2 diabetes. In both models, BMF-219 was able to normalize glucose levels in the majority of animals after just two weeks of treatment. Notably, the majority of the effect was maintained despite complete washout of BMF-219. Together, Biomea believes these results indicate the clinical potential for a novel menin inhibitor as a ground-breaking treatment for type 2 diabetes. Detailed reviews of both studies will be submitted to an upcoming scientific conference. The company intends to hold a meeting with regulators this quarter to discuss plans for a Phase 1/2 study.

“While the importance of menin in Beta-cell biology has been studied for some time, the normalization of insulin and glucose levels and potential repopulation of Beta-cells with a menin inhibitor in two distinct models is very unusual and noteworthy,” said Rohit Kulkarni MD, PhD, Senior Investigator and Margaret A Congleton Professor; Section Head, Islet Cell and Regenerative Biology; and Professor of Medicine, Harvard Medical School. “I am looking forward to engaging with the Biomea team to support the clinical development of this exciting compound for the treatment of diabetes.”

“We are a patient focused organization and we ‘aim to cure.’ As we reviewed the literature originally, we saw the relevance of menin in metabolic diseases and were compelled to explore the potential of our irreversible menin inhibitor for the benefit of patients,” said Tom Butler, CEO and Chairman of Biomea Fusion. “We have now engaged in the standard preclinical models to validate diabetic treatments and are excited with the responses we have observed. We have shown that the use of Biomea’s irreversible menin inhibitor BMF-219 has a significant impact on the progression of diabetes in several animal models. In our studies we were able to demonstrate a normalization of glucose levels and a reversal of hyperglycemia through the anticipated repopulation of Beta-cells, which is not easy to achieve. Most notably, the effect was sustained over the study period even without further dosing of BMF-219. We are now preparing the IND to support initiation of clinical trials to explore the potential benefits of BMF-219 for diabetic patients.”

Biomea Fusion is a biopharmaceutical company focused on the discovery and development of irreversible small molecules to treat patients with genetically defined cancers and metabolic diseases. An irreversible small molecule is a synthetic compound that forms a permanent bond to its target protein and offers a number of potential advantages over conventional reversible drugs, including greater target selectivity, lower drug exposure, and the ability to drive a deeper, more durable response. The company is utilizing its proprietary FUSION discovery platform to advance a pipeline of irreversible treatments against key oncogenic drivers of cancer and metabolic diseases. Biomea Fusion’s goal is to utilize its capabilities and platform to become a leader in developing irreversible small molecules in order to maximize the clinical benefit when treating various cancers and metabolic diseases.