On October 14, 2022 Biomea Fusion, Inc. ("Biomea") (Nasdaq: BMEA), a biopharmaceutical company focused on the discovery and development of covalent small molecules to treat patients with genetically defined cancers and metabolic diseases, reported that the U.S. Food and Drug Administration (FDA) has cleared Biomea’s IND application to begin a Phase I/Ib trial of BMF-219, a selective, covalent menin inhibitor in patients with unresectable, locally advanced, or metastatic NSCLC, CRC, and PDAC with an activating KRAS mutation (Press release, Biomea Fusion, OCT 14, 2022, View Source [SID1234622111]).
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"We are very excited to open this particular IND as we now look to validate the preclinical potential of BMF-219 in patients across several solid tumor types who have a KRAS mutation, which currently is associated with a very poor survival prognosis," said Thomas Butler, Biomea’s CEO and Chairman of the Board. "In January 2022, we mapped out perhaps one of the more aggressive clinical development plans among peer companies to initiate clinical studies of BMF-219 in up to seven tumor types by the end of 2022. I am so incredibly proud of our team’s extraordinary efforts to deliver on this plan, motivated by the persistent and significant unmet needs of numerous cancer patients."
Mr. Butler continued, "I would like to thank the FDA for their extraordinary effort clearing our IND on-time, and also our contract research organizations, our consultants, our investors, and of course TEAM FUSION for their commitment, guidance, and support in generating another broad and promising IND package for BMF-219."
KRAS is the most frequently mutated isoform amongst RAS oncogenes in human solid tumors, with high prevalence in NSCLC, CRC, and pancreatic cancer. With only one approved therapy targeting KRAS G12C for locally advanced or metastatic NSCLC, KRAS-driven tumors continue to represent a significant unmet medical need. A targeted pan-KRAS inhibitor has the potential to treat 25-35% of NSCLC, 35-45% of CRC, and approximately 90% of PDAC patients.
Menin is a scaffold protein and a required co-factor of oncogenic transcriptional proteins with functional interactions that are critical for the development of various cancers. As previously reported by Biomea Fusion, KRAS-mutant NSCLC, CRC, and PDAC cell lines and ex vivo preclinical models were highly sensitive to BMF-219. In preclinical models, high potency of BMF-219 was observed amongst various KRAS-mutant solid tumor cell lines, but not KRAS wild type, suggesting that BMF-219 broadly inhibited mutant KRAS in these tumor models. As a covalent menin inhibitor, BMF-219 has manifested advantages over the commercially KRAS-targeted inhibitor LUMIKRAS in multiple pre-clinical studies due to the independence of KRAS’ phosphorylation state within G12C tumors, and more broadly the ability to target multiple activating KRAS mutations.
About COVALENT–102
COVALENT-102 is an open-label, multi-cohort, multicenter, Phase I/Ib dose finding study evaluating the safety, tolerability, and clinical activity of escalating doses of oral BMF-219 administered to patients with unresectable, locally advanced, or metastatic NSCLC, CRC, and PDAC with a KRAS mutation.
About Non-Small Cell Lung Cancer (NSCLC)
NSCLC is the most common form of lung cancer, representing approximately 82% of all lung cancer cases or approximately 200,000 cases in the U.S. each year (Source: NCI SEER Data). Additionally, the five-year survival rate of NSCLC is approximately 25%. While lung cancer is the third most common form of cancer in the U.S. based on incidence, it contributes to the highest number of annual cancer deaths in the U.S. KRAS is the most frequently mutated oncogene in NSCLC, occurring in approximately 30% of patients. There remains a great unmet need for targeted therapies to address all KRAS driver mutations and avoid known mechanisms of resistance.
About Colorectal Cancer (CRC)
CRC is the fourth most common form of cancer and the second leading cause of cancer death in the U.S., representing approximately 150,000 cases in the U.S. each year (Source: NCI SEER Data). These cancers start in the rectum or the colon and can be diagnosed/identified early, even potentially as noncancerous polyps. The five-year survival rate of CRC is approximately 65%. Among other mutations, KRAS mutations occur in approximately 40% of patients with CRC. These mutations can not only help predict the absence of response to anti-EGFR therapy, but also result in poorer overall survival. Therefore, there’s a growing unmet need for personalized therapies for patients with KRAS-mutant colorectal cancer.
About Pancreatic Cancer (PDAC)
Pancreatic cancer is a relatively rare form of cancer in the U.S., representing approximately 60,000 cases in the U.S. each year (Source: NCI SEER Data). Pancreatic cancer is an aggressive cancer with a very low five-year survival rate of approximately 11%, indicating that there is a large unmet need. 80% of patients are diagnosed at an advanced stage, contributing to the low survival rate. KRAS mutations are found in nearly all pancreatic cancer patients and are considered as a driver of the malignant process in most of those patients.