Patient Information
Learn about Menin and Oncology
Menin dysregulation is implicated in a wide rage of human pathologies, which menin inhibition can impact. Menin is a protein involved in transcriptional regulation, impacting cell cycle control, apoptosis, and DNA damage repair. It 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. The oncoprotein MYC is a master regulator of gene transcription and a potent driver of transformation. In non-transformed cells, MYC-regulated transcription is highly controlled; however, in many human cancers, MYC is dysregulated, often through constitutive and elevated MYC expression, which enables MYC to initiate and/or sustain tumor growth.
Nonclinical studies of Biomea’s covalent menin inhibitor, icovamenib, have shown sustained potent abrogation of menin-dependent oncogenic signaling and pathway control in vitro and in vivo. The covalent menin inhibitor icovamenib 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. Icovamenib also exhibited high potency in 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.
Acute Myeloid Leukemia
AML is the most common form of acute leukemia in adults and represents the largest number of annual leukemia deaths in the U.S. and Europe. AML originates within the white blood cells in the bone marrow and can rapidly move to the blood and other parts of the body, including the lymph nodes, spleen, and central nervous system. Approximately 20,000 people in the U.S are diagnosed with AML each year, and the five-year overall survival rate in adults is roughly 29% (Source: NCI SEER Data). Among patients with relapsed/refractory disease, the need is greatest, as the overall survival is approximately 3 to 9 months. It is estimated that upwards of 45% of AML patients have menin dependent genetic drivers (MLL-r or NPM1). ALL is a less common leukemia, with approximately 6,000 new cases in the U.S. each year and a higher five-year survival rate of nearly 70% (Source: NCI SEER Data). Between 10-15% of adult ALL patients and 60-70% of pediatric ALL patients have MLL-r translocations.
Diffuse Large B-Cell Lymphoma
Diffuse Large B-cell lymphoma is an aggressive (fast-growing) Non-Hodgkin lymphoma that affects B-lymphocytes, one type of white blood cell that make antibodies to fight infections and are an important part of the lymphatic system. In roughly ~30% of DLBCL patients, a cancer-causing gene, Myc, in combination with other genes, BCL2, drive the growth of the disease. These subset of DLBCL is known as Double Hit (DHL), Triple Hit (THL), or Double Expressor (DEL) lymphomas.
Multiple Myeloma
Multiple myeloma is a cancer of white blood cells, called a plasma cell, which normally help you fight infections by making antibodies that recognize and attack germs. In multiple myeloma, cancerous plasma cells accumulate in the bone marrow and crowd out healthy blood cells. In roughly 50% to 70% of MM patients, a cancer-causing gene, Myc, drives the growth of the disease. For Myc to drive MM it needs to interact with menin. MM is a cancer of plasma cells, which make antibodies (immunoglobulins) and are mainly located in the bone marrow. As cancerous cells migrate from the bone marrow, organ damage due to excess immunoglobulins in bones and blood and weakening of bones are common features. Approximately 35,000 people in the U.S. are diagnosed with MM each year and the 5-year relative survival rate is ~56% (Source: NCI SEER Data). Among patients with relapsed or refractory disease, the need is greatest, with overall survival as low as 6 months in some patients. Additionally, it is estimated that more than 60% of MM patients have menin dependent genetic drivers (MYC addicted or driven) and that these drivers are more common in the relapsed or refractory setting.
RAS Driven Solid Tumors
RAS genes (HRAS, KRAS, and NRAS) comprise the most frequently mutated oncogene family in human cancer. With the highest RAS mutation frequencies seen with the top three causes of cancer deaths in the United States (lung, colorectal, and pancreatic cancer).KRAS mutations are present in approximately 25% of tumors, making them one of the most common gene mutations linked to cancer. They are frequent drivers in lung, colorectal and pancreatic cancers. RAS exerts it oncogenic propertied via MYC, which is dependent on menin interaction.
Non-Small Cell Lung Cancer
NSCLC is the most common form of lung cancer, representing ~84% 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 ~25%. While lung cancer is the 3rd most common form of cancer in the U.S. based on incidence, lung cancer contributes to the highest number of annual cancer deaths in the U.S.. KRAS is the most frequent oncogene in NSCLC, occurring in ~30% of patients with NSCLC.
Pancreatic Cancer
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 ~11%, indicating that there is a large unmet need. It is rarely diagnosed early, contributing to the low survival rate. Among patients with pancreatic cancer, RAS mutations (including KRAS) occur in up to approximately 98% of patients.
Colorectal Cancer
CRC is the fourth most common form of cancer 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 50% of patients with CRC.
