Biomea Fusion Doses First Patient in Phase I/Ib Clinical Trial (COVALENT-102) of BMF-219 in KRAS Mutant Solid Tumors

  • BMF-219 is the first menin inhibitor to be clinically studied in patients with KRAS-mutated non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC)
  • A pan-KRAS inhibitor targeting multiple KRAS mutations (including G12C, G12D and G12R, among others) has the potential to treat 25-35% of NSCLC patients, 35-45% of CRC patients, and approximately 90% of PDAC patients
  • BMF-219 is now in clinical development across eight liquid and solid tumor types, as well as for patients with type 2 diabetes

REDWOOD CITY, CA, USA I January 17, 2023 I 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, today announced that the first patient has been dosed in COVALENT-102, the company’s Phase I/Ib trial of BMF-219, an oral, selective, covalent menin inhibitor in patients with KRAS-mutated unresectable, locally advanced, or metastatic NSCLC, CRC, and PDAC.

“We are eager to explore the potential of BMF-219 as a pan-KRAS inhibitor in patients with three of the most prominent KRAS-mutant solid tumor types, including those with tumors that have failed to respond to investigational and approved mutation-specific KRAS inhibitors,” said Steve Morris, M.D., Biomea’s Chief Medical Officer. “As a covalent menin inhibitor, we believe BMF-219 has critical advantages over late stage, mutation-specific inhibitors of KRAS including independence on the KRAS activation state, reduced likelihood for acquisition of resistance mutations, and its potential to address multiple activating KRAS mutations.”

KRAS is the most frequently mutated isoform amongst RAS oncogenes in human solid tumors, with high prevalence in NSCLC, CRC, and PDAC. KRAS G12C, KRAS G12D and KRAS G12V are among the most common KRAS mutations. However, there are numerous other known activating KRAS mutations. With only two approved therapies both targeting only KRAS G12C for locally advanced or metastatic NSCLC, KRAS-driven tumors continue to represent a significant unmet medical need.

As a covalent menin inhibitor, BMF-219 has manifested a differentiated profile over the commercially approved KRAS-targeted inhibitors LUMAKRAS (sotorasib) and KRAZATI (adagrasib) in multiple pre-clinical studies. As previously reported by Biomea, KRAS-mutant NSCLC, CRC, and PDAC cell lines and ex vivo patient specimens were highly sensitive to BMF-219 in preclinical models. The higher levels of activity of BMF-219 were observed among various KRAS-mutant solid tumor cell lines, but not KRAS wild type, suggesting that BMF-219 broadly inhibited mutant KRAS in these tumor models. A targeted pan-KRAS inhibitor has the potential to treat a large number of NSCLC, CRC, and PDAC patients.

About COVALENT–102
COVALENT-102 is an open-label, multi-cohort, multicenter, Phase I/Ib dose escalation and expansion study evaluating the safety, tolerability, and optimal biologic dose of BMF-219 administered orally to adult patients with KRAS-mutated unresectable, locally advanced or metastatic NSCLC, CRC, and PDAC. Additional information about the Phase I/Ib clinical trial of BMF-219 can be found at ClinicalTrials.gov using the identifier NCT05631574.

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). 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 remains a significant 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.

About Biomea Fusion
Biomea Fusion is a clinical stage biopharmaceutical company focused on the discovery and development of covalent small molecules to treat patients with genetically defined cancers and metabolic diseases. A covalent small molecule is a synthetic compound that forms a permanent bond to its target protein and offers a number of potential advantages over conventional non-covalent 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™ System to advance a pipeline of covalent-binding therapeutic agents 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 covalent small molecules in order to maximize the clinical benefit when treating various cancers and metabolic diseases.

SOURCE: Biomea Fusion

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