Epizyme Publishes Landmark Data on Personalized Therapeutics for Lymphomas
- Unprecedented Demonstration of Selective Killing of Lymphoma
Cells with EZH2 Mutation -
Published in Nature Chemical Biology
- Sheds Light on Biological Understanding of Treatments for
Genetically Defined Cancers -
CAMBRIDGE, Mass., Oct. 1, 2012 /PRNewswire/ -- Epizyme, Inc., a
company leading the creation of a new class of personalized
therapeutics for patients with genetically defined cancers,
announced today the publication of breakthrough research in the
treatment of genetically defined lymphomas, in the journal Nature
Chemical Biology.
Epizyme's landmark research demonstrates for the first time that a potent, small molecule inhibitor selectively kills lymphoma cells bearing genetic mutations in EZH2, a histone methyltransferase (HMT). HMTs are an important epigenetic target class, with genetic alterations strongly associated with the development of several types of cancer. Cancers with genetic alterations of EZH2 require EZH2 enzymatic activity for proliferation, suggesting that EZH2 is a driving oncogene in these cancers.
"This publication shows that Epizyme's proprietary EZH2 inhibitor EPZ5687 selectively kills lymphoma cells bearing change-of-function mutations in EZH2 by permeating cells and selectively inhibiting H3K27 methylation, without an effect on any other histone methyl marks," said Kevin Kuntz, Ph.D., Associate Director of Chemistry, Epizyme and a corresponding author of the paper. "This paper demonstrates Epizyme's leadership in translating breakthroughs in biological understanding into personalized therapeutics for genetically defined cancers."
Key findings from the paper include:
Epizyme's HMT inhibitor (HMTi), EPZ5687, selectively kills tumor
cells bearing a genetic mutation in EZH2 with minimal effects on
cells that do not bear the mutation.
EPZ5687 is a potent inhibitor of EZH2 (Ki of 24 nM) with greater
than 500-fold selectivity compared to other HMTs.
EZH2 inhibition with EPZ5687 directly correlates with specific
tumor cell killing through the selective reduction of methylation
of the EZH2 substrate, histone H3 at lysine 27 (H3K27).
EZH2 is a driving oncogene, as cancers with genetic
change-of-function alterations of EZH2 (e.g., Tyr641 or Ala677
mutations) require EZH2 enzymatic activity for proliferation.
"These results provide compelling support for the hypothesis that
the change-of-function mutations in EZH2 in a set of patients with
non-Hodgkin's lymphoma are oncogenic, playing a driving role in the
development of cancer in these patients. The dependency of these
cancers on altered EZH2 activity suggests the potential of EZH2
inhibitors as personalized cancer therapeutic agents," said Eric
Hedrick, M.D., Chief Medical Officer, Epizyme.
The paper titled, "A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells," was authored by Sarah K. Knutson, Tim J. Wigle and colleagues at Epizyme, and is available online.
About Epizyme
Epizyme is leading the creation of small molecule histone
methyltransferase inhibitors (HMTi), a new class of personalized
therapeutics for patients with genetically defined cancers. Genetic
alterations in HMTs, a family of epigenetic enzymes, drive multiple
human diseases. Our approach represents the future of healthcare by
matching better medicines with the right patients.
Epizyme has benchmark partnerships with Celgene, GSK and Eisai and receives funding and strategic support from the Multiple Myeloma Research Foundation (MMRF) and the Leukemia & Lymphoma Society (LLS). For more information, visit www.epizyme.com.
Media Contact
Amanda Sellers
Spectrum
202.955.6222 ext. 2597
asellers@spectrumscience.com
SOURCE Epizyme, Inc.
Web Site: http://www.epizyme.com
Posted: October 2012
