Epizyme Announces Publication of Preclinical Data Demonstrating Clinical Candidate EPZ-6438 as Potent and Selective Inhibitor of EZH2 in Genetically Defined Non-Hodgkin Lymphoma

CAMBRIDGE, Mass., Feb. 21, 2014 /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 from preclinical studies of the company's clinical candidate EPZ-6438 (E7438), a potent and selective small-molecule inhibitor of EZH2, a histone methyltransferase (HMT). Oncogenic mutations in EZH2 occur in a subset of patients with non-Hodgkin lymphoma (NHL), implicating EZH2 as a therapeutic target in these patients. This research, published online today and in the April issue of the journal Molecular Cancer Therapeutics, provides a preclinical description of EPZ-6438, which Epizyme is developing in partnership with Eisai for the treatment of EZH2 mutant-bearing NHL. The paper expands on data reported by the same authors in a poster presentation at the December 2012 American Society of Hematology (ASH) annual meeting.

"This paper provides a comprehensive description of the preclinical characterization of EPZ-6438 that paved the way for this drug to enter human clinical trials in 2013," said Robert A. Copeland, Ph.D., executive vice president and chief scientific officer, Epizyme. "It is the first and only EZH2 inhibitor in clinical development to our knowledge. The work is illustrative of the ongoing discovery efforts at Epizyme that are fueling the clinical development of multiple drugs against the HMT target class."

Key results published in Molecular Cancer Therapeutics include:

• Detailed characterization of the correlation between EZH2 inhibition, methylation of the EZH2 target (H3K27), reversal of lymphomagenic gene expression and antiproliferative effects specific to EZH2 mutant-bearing NHL cell lines.
• Sustained tumor growth inhibition in animal models of EZH2 mutant-bearing NHL, including durable effects after drug dosing is discontinued.
• Development of an assay to assess methylation of H3K27 in tumor, bone marrow, peripheral blood mononuclear cells and other surrogate tissues.
• Determination of a quantitative PK/PD relationship using this assay.

The paper titled, "Selective Inhibition of EZH2 by EPZ-6438 Leads to Potent Antitumor Activity in EZH2 Mutant Non-Hodgkin Lymphoma," was authored by Sarah Knutson and colleagues at Epizyme and Eisai, and is available online here.

About Epizyme, Inc.
Epizyme, Inc. is a clinical stage biopharmaceutical company creating personalized therapeutics for patients with genetically defined cancers. Epizyme has built a proprietary product platform that the company uses to create small molecule inhibitors of a 96-member class of enzymes known as histone methyltransferases, or HMTs. HMTs are part of the system of gene regulation, referred to as epigenetics, that controls gene expression. Genetic alterations can result in changes to the activity of HMTs, making them oncogenic (cancer-causing). By focusing on the genetic drivers of cancers, Epizyme's targeted science seeks to match the right medicines with the right patients for a personalized approach to cancer treatment.

For more information, visit www.epizyme.com and connect with us on Twitter at @EpizymeRx.

About EPZ-6438
Epizyme is developing EPZ-6438, a small molecule inhibitor of EZH2 created with our proprietary product platform, for the treatment of non-Hodgkin lymphoma patients who have an oncogenic (cancer-causing) point mutation in EZH2. In many human cancers, misregulated EZH2 enzyme activity results in misregulation of genes that control cell proliferation—without these control mechanisms, cancer cells are free to grow rapidly.

In June 2013, Epizyme initiated a Phase 1/2 clinical trial of EPZ-6438 in patients with advanced solid tumors or with relapsed or refractory B-cell lymphoma. This program is currently in the dose escalation phase. The company believes EPZ-6438 is the second HMTi to enter human clinical development (following Epizyme's DOT1L inhibitor, EPZ-5676). Additional information about this program, including clinical trial information, may be found here: http://clinicaltrials.gov/ct2/show/NCT01897571?term=7438&rank=1

Epizyme granted Eisai a worldwide license to EPZ-6438 (Eisai refers to this therapeutic candidate as E7438), subject to Epizyme's right to opt in for co-development, co-commercialization and profit share arrangement with Eisai in the United States. Epizyme is working with Roche and Eisai to develop a companion diagnostic to identify patients with non-wild type EZH2, where EZH2 contains point mutations. Additional information about these partnerships may be found here: http://www.epizyme.com/about-us/partnerships/

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SOURCE Epizyme, Inc.