CAMBRIDGE, Mass., June 26, 2013 /PRNewswire/ -- Epizyme, Inc., (NASDAQ: EPZM) a clinical stage biopharmaceutical company creating innovative personalized therapeutics for patients with genetically defined cancers, announced today the publication of data on the company's clinical candidate EPZ-5676, a potent and selective small-molecule inhibitor of DOT1L, a histone methyltransferase (HMT). DOT1L is implicated in acute leukemias in which the MLL gene is rearranged (MLL-r) . This research, published in the journal Blood, provides a detailed preclinical characterization of EPZ-5676, which Epizyme is developing for the treatment of MLL-r leukemia. The paper expands on data reported by the same authors in a poster at the December 2012 American Society of Hematology (ASH) annual meeting.
Key results presented in this paper include:
- detailed characterization of the correlation between DOT1L inhibition, methylation of the DOT1L target (H3K79), reversal of leukemogenic gene expression and anti-proliferative effects specific to MLL-r leukemia
- sustained tumor growth inhibition in animal models of MLL-r leukemia, including durable effects after drug dosing is discontinued- development of a quantitative PK/PD relationship - development of an assay to assess methylation of H3K79 status in non-invasive, surrogate tissues such as bone marrow and peripheral blood mononuclear cells "This paper provides a clear and comprehensive description of the preclinical characterization of EPZ-5676 that paved the way for this drug becoming the first HMT inhibitor to our knowledge to enter human clinical trials. The work is illustrative of the discovery efforts ongoing at Epizyme that are fueling the clinical development of multiple drugs against the HMT target class," said Robert A. Copeland, Ph.D., Executive Vice President and Chief Scientific Officer of Epizyme. The paper titled, "Potent Inhibition of DOT1L as Treatment for MLL-Fusion Leukemia," was authored by Roy M. Pollock, Scott R. Daigle, Edward J. Olhava and colleagues at Epizyme, and is available online here. About EPZ-5676 Epizyme initiated a Phase I study in September 2012 to evaluate the safety, pharmacokinetics and pharmacodynamics of escalating doses of EPZ-5676. An expansion cohort of patients with genetically defined MLL-r leukemia is anticipated in the second half of 2013. Epizyme retains all U.S. rights to EPZ-5676 and has granted Celgene an exclusive license to EPZ-5676 outside of the United States. In partnership with Abbott, Epizyme is developing a companion diagnostic for this program. About Mixed Lineage Leukemia (MLL-r) MLL-r leukemia is an aggressive subtype of two of the most common forms of acute leukemia, acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), and is caused by a chromosomal translocation involving the MLL gene. Based on published research, the five-year overall survival rate for adult patients with the MLL-r subtype of AML ranges from approximately 5 to 24 percent. MLL-r also occurs in an infant/pediatric population, which has a similarly poor prognosis. At this time, there are no approved therapies specifically indicated for MLL-r leukemia.