Inc. (NASDAQ: EPZM), a clinical stage biopharmaceutical company
creating innovative personalized therapeutics for patients with
genetically defined cancers, reported pre-clinical data and early
clinical observations from an ongoing Phase 1 trial, being conducted in
collaboration with Eisai, the Institut Gustave Roussy, and the Institut
Bergonie, of EZH2 inhibitor EPZ-6438 (E7438) in patients with advanced
solid tumors and B-cell lymphomas. These data were presented today by
Robert Copeland, Ph.D., Chief Scientific Officer, Epizyme, during an
oral session on novel therapeutics in lymphoma at the American Society
of Hematology (ASH) meeting on Lymphoma Biology, held August 10-13 in
Colorado Springs, Colorado. The presentation is available on the Epizyme
website at http://www.epizyme.com/?p=1053.
"EPZ-6438 is the first EZH2 inhibitor to enter the clinic. We are very
pleased to see that the maximum tolerated dose has not been reached and
that there was a clear PK and PD dose relationship through the first
three cohorts that have been evaluated," said Robert Gould, Ph.D., Chief
Executive Officer, Epizyme. "Additionally, we saw two objective
responses among NHL patients enrolled in the first three cohorts of the
Phase 1 dose escalation study. We plan to present more complete Phase 1
results at a scientific conference later in 2014. Pending review of
those results, we expect to initiate two Phase 2 studies in 2014: one in
NHL and one in INI1-deficient tumors, such as malignant rhabdoid tumors."
Pre-clinical data have shown the utility of single-agent EZH2 inhibitors
in both EZH2 mutant and EZH2 wild type germinal center (GC) NHL models.
Data presented today showed that in pre-clinical studies in GC NHL cell
lines, combining EPZ-6438 with CHOP, a chemotherapy cocktail regimen
that is a standard of care in NHL, resulted in strong synergy of
lymphoma cell killing. When EPZ-6438 was combined with each individual
component of the CHOP regimen, the synergy was greatest with prednisone,
the corticosteroid component of CHOP. Prednisone greatly enhanced the
potency of EPZ-6438 for killing EZH2 mutant-bearing lymphoma cell lines,
and broadened the activity of EPZ-6438 to all GC NHL cell lines,
regardless of EZH2 mutational status. Combining EPZ-6438 with
dexamethasone, another corticosteroid, yielded similar synergistic
results. Synergy was also observed in both EZH2 mutant and wild type
cell lines when EPZ-6438 was combined with B-cell signaling pathway
agents and BCL2 antagonists.
Early Clinical Observations
The primary objective of the ongoing Phase 1 dose escalation study is to
evaluate the safety and tolerability of EPZ-6438 and determine the
maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D); the
secondary objectives are to determine pharmacokinetics (PK) and
pharmacodynamics (PD) of EPZ-6438. The study to date consists of five
dosing cohorts, with evaluation of doses f 100 mg to 1600 mg BID,
orally administered in 28-day cycles without a drug holiday in patients
with advanced solid tumors or with relapsed or refractory B-cell
lymphoma. Three of five dosing cohorts (100, 200 and 400 mg) have been
completed with 12 evaluable patients dosed, four of whom were NHL
patients. Dose cohorts evaluating 800 mg and 1600 mg are ongoing.
Early clinical observations from the three completed cohorts include:
About EZH2 Cancers
EZH2 is a histone methyltransferase (HMT) that is increasingly
understood to play a potentially oncogenic role in a number of cancers.
These include germinal center (GC) non-Hodgkin lymphomas, INI1-deficient
cancers such as synovial sarcoma and malignant rhabdoid tumors, and a
range of other solid tumors.
Epizyme and its partner Eisai are developing EPZ-6438, a small molecule
inhibitor of EZH2 created with Epizyme's proprietary product platform,
for the treatment of non-Hodgkin lymphoma patients. 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.
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/
In June 2013, Epizyme and Eisai initiated a Phase 1/2 clinical trial of
EPZ-6438 (E7438) in patients with advanced solid tumors or B-cell
lymphomas. This program is currently in the dose escalation phase.
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
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 Epizyme, Inc. 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: uncertainties inherent in the
initiation of future clinical studies or expansion of ongoing clinical
studies, availability and timing of data from ongoing clinical studies,
whether interim results from a clinical trial such as the results
reported in this release will be predictive of the final results of the
trial or results of early clinical studies will be indicative of the
results of future 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
Quarterly Report on Form 10-Q filed with the Securities and Exchange
Commission in May 2014. 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
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