On March 16, 2020 Bridge Medicines and The Rockefeller University reported an exclusive license agreement to develop novel inhibitors of ENL-YEATS for the treatment of acute leukemias such as Acute Myelogenous Leukemia (AML) and potentially solid tumors (Press release, Bridge Medicines, MAR 16, 2020, View Source [SID1234555625]).
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ENL-YEATS is an epigenetic "reader" protein that emerged from breakthrough science conducted in the laboratory of Lasker Award winner C. David Allis, Ph.D. The work was led by scientist Liling Wan, Ph.D., who was a postdoctoral fellow in the Allis lab at the time. Dr. Allis is the Joy and Jack Fishman Professor, Laboratory of Chromatin Biology and Epigenetics; Dr. Wan was recently appointed Assistant Professor of Cancer Biology and Assistant Investigator of the Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania.
Epigenetic pathways have been shown to regulate cancer cell proliferation and growth, which have recently proven to be successful drug targets. Drs. Wan and Allis found that ENL-YEATS was essential for leukemogenesis and leukemia maintenance by assuring transcription of several oncogenes, including MYC, a regulator gene.
The researchers also discovered a role for ENL-YEATS in Wilms Tumor, a rare kidney cancer found in children, suggesting that ENL-YEATS may be a driver in tumor types beyond acute leukemias.
The Tri-Institutional Therapeutics Discovery Institute, Inc. (Tri-I TDI) advanced the pioneering discoveries from the Allis Laboratory into early-stage drug molecules. Tri-I TDI’s mission is to work with innovative scientists at its founding institutions, The Rockefeller University, Memorial Sloan Kettering Cancer Center, and Weill Cornell Medicine, in a close collaboration with Takeda Pharmaceutical Company Ltd, to accelerate the discovery of new drug molecules.
For this ENL-YEATS program, the scientists at Tri-I TDI, in collaboration with Drs. Wan and Allis, were able to synthesize promising, patented, new molecules that may represent future new drug products. Bridge Medicines will further develop and advance these molecules through preclinical and clinical trials in an effort to bring a new treatment to patients.
"The ENL-YEATS discovery is a major scientific advancement in the area of cancer treatment, and we are thrilled to bring this important program into our portfolio," said Bill Polvino, CEO of Bridge Medicines. "We are encouraged by the promising data developed by these premier academic scientists and look forward to rapidly accelerating the development of this program, in keeping with our mission of translating brilliant discoveries into innovative medicines."
Dr. Allis added, "The ENL-YEATS program offers great promise and hope for patients with AML and Wilms Tumor. We are gratified to have Bridge Medicines partner with us in advancing this program and look forward to seeing it develop into a successful epigenetic therapy to combat these and potentially other diseases."
About AML
Acute Myeloid Leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood, interfering with normal blood cells. AML progresses rapidly and is typically fatal within weeks or months if left untreated. Current standard of care is chemotherapy, followed by radiation therapy or stem cell transplant. In 2015, AML affected about one million people and resulted in 147,000 deaths globally, and accounts for about 1.8% of cancer deaths in the United States.
About Wilms Tumor
Wilms Tumor, also known as nephroblastoma, is a cancer of the kidneys that typically occurs in children. It is named after Max Wilms, a German surgeon (1867-1918) who first described it. Approximately 650 cases are diagnosed in the U.S., annually. The majority of cases occur in children with no associated genetic syndromes; however, a minority of children with Wilms Tumor have a congenital abnormality.