Epizyme, Inc. to Present Pre-Clinical Data on DOT1L and EZH2 Inhibitor Programs at the 55th ASH Annual Meeting

CAMBRIDGE, Mass., Nov. 7, 2013 /PRNewswire/ -- Epizyme, Inc. (NASDAQ: EPZM), a clinical stage biopharmaceutical company creating innovative personalized therapeutics for patients with genetically defined cancers, will present pre-clinical data on EPZ-5676 and EPZ-6438, the Company's DOT1L and EZH2 clinical programs, at the 55th Annual Meeting of the American Society of Hematology (ASH) in New Orleans on December 7-10, 2013.

"EPZ-5676, our DOT1L inhibitor, and EPZ-6438, our EZH2 inhibitor, are currently being developed as single-agent treatments based on the durable tumor regressions seen in pre-clinical studies," said Robert A. Copeland, Ph.D., executive vice president and chief scientific officer, Epizyme. "Two of our ASH presentations highlight the synergistic efficacy we have demonstrated in pre-clinical combination studies with each of our clinical candidates in specific genetically defined tumors. These data point us towards the potential use of our therapeutic candidates in combination treatment settings. Additionally, we are pleased to present data at ASH highlighting the opportunity to pursue a second genetically defined cancer, MLL-PTD, with EPZ-5676. MLL-PTD represents a distinct genetically defined acute leukemia in addition to our current clinical focus on MLL-r."

EPZ-5676, an inhibitor of the histone methyltransferase (HMT) DOT1L, is being developed as a treatment for patients with acute leukemias with rearrangements of the MLL gene (MLL-r). In the fourth quarter of 2013, Epizyme plans to announce top-line dose escalation data from the ongoing Phase 1 clinical study and, based on this data, initiate an expansion cohort stage that will be limited to patients with MLL-r.

EPZ-6438 is an inhibitor of the HMT EZH2 being developed as a treatment for non-Hodgkin lymphoma patients with oncogenic point mutations in EZH2. A Phase 1/2 clinical study was initiated in June 2013 and is ongoing. With partner Eisai, Epizyme plans to initiate the Phase 2 stage of this study in 2014 after completion of the dose escalation stage. This Phase 2 stage will be limited to patients with non-Hodgkin lymphoma with oncogenic point mutations in EZH2. Epizyme and partner Eisai are exploring plans for clinical trials in patients with INI1-deficient tumors, including synovial sarcoma, after completion of the ongoing Phase 1 study.

Abstracts to be presented by Epizyme at ASH 2013 include:

DOT1L Inhibitor EPZ-5676 Displays Synergistic Antiproliferative Activity in Combination with Standard of Care Drugs or DNA Hypomethylating Agents in MLL-Rearranged Leukemia Cells (Abstract #3930)

• Monday, December 9, 6:00 – 8:00 p.m.
• Hall E (Ernest N. Morial Convention Center) Poster Session

Myeloid Leukemia Cells with MLL Partial Tandem Duplication are Sensitive to Pharmacological Inhibition of the H3K79 Methyltransferase DOT1L (Abstract #1256)

• Saturday, December 7, 5:30 – 7:30 p.m.
• Hall E (Ernest N. Morial Convention Center) Poster Session

EZH2 Inhibitor EPZ-6438 Synergizes With Anti-Lymphoma Therapies in Preclinical Models  (Abstract #4416)

• Monday, December 9, 6:00 – 8:00 p.m.
• Hall G (Ernest N. Morial Convention Center) Poster Session

Protein Methyltransferase Inhibitors as Personalized Cancer Therapeutics (Abstract #SCI-21)

• Saturday, December 7, 2:00 – 3:30 p.m.
• Rooms 243-245 (Ernest N. Morial Convention Center) Poster Session

Other noteworthy Epizyme presentations:

Scientific Spotlight Sessions: Epigenetic Mechanisms and DOT1L in MLL-Rearranged Leukemia

Development and Clinical Translation of Small Molecule DOT1L Inhibitors for MLL-Rearranged Leukemias

• Robert Gould, Ph.D., chief executive officer, Epizyme
• Monday, December 9, 2:45 – 4:15 p.m.
• Great Hall (Ernest N. Morial Convention Center)
• Oral presentation

Ad Hoc Scientific Committee on Epigenetics and Genomics: Histone Modifications in Normal and Malignant Hematopoiesis

Protein Methyltransferase Inhibitors as Personalized Cancer Therapeutics

• Robert A. Copeland, Ph.D., executive vice president and chief scientific officer, Epizyme
• Saturday, December 7, 2:00 – 3:30 p.m.
• Rooms 243-245 (Ernest N. Morial Convention Center)
• Sunday, December 8, 9:30 – 11:00 a.m.
• Rooms 343-345 (Ernest N. Morial Convention Center)
• Oral session/discussion

Continuing Conversation on Histone Modifications in Normal and Malignant Hematopoiesis: Strategies to Address the Next Questions

• Robert A. Copeland, Ph.D., executive vice president and chief scientific officer, Epizyme
• Sunday, December 8, 11:15 a.m. – 12:15 p.m.
• Room 333 (Ernest N. Morial Convention Center)
• Oral session/discussion

About EPZ-5676
Epizyme is developing EPZ-5676, a small molecule inhibitor of DOT1L created with Epizyme's proprietary product platform, for the treatment of acute leukemias in which the MLL gene is rearranged due to a chromosomal translocation (MLL-r). Due to the translocation, DOT1L is recruited to specific locations in the chromosome where it would not normally be present. As a result, DOT1L causes inappropriate methylation at these locations, which results in the increased expression of genes causing leukemia.

In September 2012, Epizyme initiated a Phase 1 clinical study with EPZ-5676. The company believes EPZ-5676 is the first HMTi to enter human clinical development. In the fourth quarter of 2013, Epizyme plans to announce top-line dose escalation data from the ongoing Phase 1 clinical study and, based on this data, initiate an expansion cohort stage that will be limited to patients with MLL-r. Additional information about this ongoing Phase 1 study can be found here: http://clinicaltrials.gov/show/NCT01684150.

Epizyme retains all U.S. rights to EPZ-5676 and has granted Celgene an exclusive license to EPZ-5676 outside of the United States. Epizyme has partnered with Abbott to develop a companion diagnostic to identify MLL-r patients. Additional information about these partnerships may be found here: www.epizyme.com/about-us/partnerships/.

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, a Phase 1/2 clinical study of EPZ-6438 was initiated in patients with advanced solid tumors or with relapsed or refractory B-cell lymphoma. This study is currently in the dose escalation stage. With partner Eisai, Epizyme plans to initiate the Phase 2 stage of this study in 2014 after completion of the dose escalation stage. The Phase 2 stage will be limited to patients with non-Hodgkin lymphoma with oncogenic point mutations in EZH2. Epizyme and partner Eisai are exploring plans for clinical trials in patients with INI1-deficient tumors, including synovial sarcoma, after completion of the ongoing Phase 1 study. The company believes EPZ-6438 is the second HMTi to enter human clinical development (following Epizyme's DOT1L inhibitor, EPZ-5676). Additional information about the ongoing Phase 1/2 study can 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: www.epizyme.com/about-us/partnerships/.

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.

Cautionary Note on Forward-Looking Statements
Any statements in this press release about future expectations, plans and prospects for the Company, including statements about the Company's strategy, future operations, clinical development of the Company's therapeutic candidates, expectations regarding the sufficiency of the Company's cash balance to fund operating expenses and capital expenditures, milestone or royalty payments from the Company's collaborators, the Company's anticipated milestones and future expectations and plans and prospects for the Company and other statements containing the words "anticipate," "believe," "estimate," "expect," "intend," "may," "plan," "predict," "project," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the uncertainties inherent in the initiation of future clinical trials, expectations of expanding ongoing clinical trials, availability and timing of data from ongoing clinical trials, expectations for regulatory approvals, development progress of the Company's companion diagnostics, availability of funding sufficient for the Company's foreseeable and unforeseeable operating expenses and capital expenditure requirements, other matters that could affect the availability or commercial potential of the Company's therapeutic candidates or companion diagnostics and other factors discussed in the "Risk Factors" section of the Company's 10-Q filed with the Securities and Exchange Commission on October 23, 2013. In addition, the forward-looking statements included in this press release represent the Company's views as of the date hereof. The Company anticipates that subsequent events and developments will cause the Company's views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing the Company's views as of any date subsequent to the date hereof.

SOURCE Epizyme, Inc.