Biomea Fusion, Inc. announced that in 2022 it plans to initiate clinical studies to dose its irreversible covalent menin inhibitor, BMF-219, in up to seven different cancer indications as well as in diabetes. Biomea is also confirming the preclinical development timeline of its second program, which the company is on track to announce in the first half of 2022 with an Investigational New Drug application (IND) planned within 12 months of candidate selection. BMF-219 is designed to be a highly selective, orally bioavailable small-molecule irreversible inhibitor of menin.

Menin, a protein involved in transcriptional regulation, impacting cell cycle control, apoptosis, and DNA damage repair, plays a direct role in oncogenic signaling in multiple cancers. The menin complex plays a critical role in MYC-dependent oncogenic signaling, whereby menin enhances MYC-mediated transcription to promote cancer progression. Inhibition of menin is a novel approach to cancer treatment.

Nonclinical studies of BMF-219 have shown sustained potent abrogation of menin-dependent oncogenic signaling and pathway control in vitro and in vivo. BMF-219 demonstrated consistent on-target inhibition with a strong anti-proliferative effect on various menin-dependent acute myeloid leukemia (AML) cell lines; diffuse large B-cell lymphoma (DLBCL) cell lines representing categories of Double/Triple Hit Lymphoma (DHL/THL) and Double Expressor Lymphoma (DEL); and multiple myeloma (MM) cell lines harboring diverse mutational backgrounds, including MYC dysregulation. BMF-219 also exhibited high potency in vitro KRAS-driven cancer cell models.

MYC, which exerts much of its oncogenic activity through interaction with menin, is a major downstream effector of the KRAS pathway. As previously announced, BMF-219 was also able to normalize glucose levels in both diabetic preclinical models studied with the glucose tolerance and homeostasis effect maintained despite complete washout of BMF-219.