Pharmion and MethylGene Announce Collaboration to Develop Sirtuin Inhibitors as Anti-Cancer Agents

BOULDER, Colo. and MONTREAL, Aug. 20 PharmionCorporation (Nasdaq: PHRM) and MethylGene Inc. (TSX: MYG) today announced aresearch collaboration for the development of novel small molecule inhibitorstargeting sirtuins, a separate and distinct class of histone deacetylaseenzymes (Class 3 HDACs) implicated in cell survival and death.

Pharmion and MethylGene's Class I specific HDAC inhibitor, MGCD0103, hasdemonstrated efficacy in a number of tumor types, and the sirtuins representpotentially attractive novel cancer targets within a related family ofenzymes. Sirtuins (including SIRT1) have been shown to deacetylate histoneproteins and numerous transcription factors, leading to promotion of normalcell survival and aberrant gene silencing in cancer cells. Inhibition ofsirtuins allows reexpression of silenced tumor suppressor genes, leading toreduced growth of cancer cells, and anti-cancer effects have been observedwith SIRT1 inhibitors in vitro and in vivo. As yet, no sirtuin inhibitorshave entered the clinic. Synergies in gene reexpression have been demonstratedby combining SIRT1 inhibition with either standard cytotoxics or otherepigenetic modifying drugs, including inhibitors of DNA methylation andhistone deacetylation. Two epigenetic therapy combinations are already underactive investigation in Phase 2 studies combining Pharmion's Vidaza, a DNAhypomethylating agent, with Pharmion and MethylGene's HDAC inhibitor,MGCD0103. The parties intend to explore combinations with resultinganti-sirtuins as well.

This agreement expands the January 2006 license and collaborationagreement between Pharmion and MethylGene for the research, development andcommercialization of MethylGene's oncology HDAC inhibitors, led by MGCD0103currently in Phase 2 clinical trials. Sirtuin inhibitors, the third epigeneticmodality to be explored for anticancer activity by Pharmion, and the second incollaboration with MethylGene, are expected to be studied both as monotherapyand combination therapy in the treatment of cancer once a clinical candidateis identified. MethylGene has already identified a series of potent leadcompounds, and Pharmion expects to file an initial Investigational New Drug(IND) application within the next 24 to 30 months.

"Sirtuins represent a new component of epigenetic tumor suppressor genesilencing that may potentially link some epigenetic changes associated withaging with those found in cancer, and, in particular, SIRT1 has emerged as akey contributor to the epigenetic silencing of genes that drivetumorigenesis," said Stephen B. Baylin, MD, Professor of Medicine andOncology, Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity School of Medicine in Baltimore, Maryland.

"By extending our collaboration with MethylGene to develop inhibitors ofsirtuins, we are extending our leadership position in the development ofepigenetic therapies, taking advantage of our translational medicine expertisein the preclinical and clinical development of these agents, and continuingthe build out of our focused oncology pipeline," said Patrick J. Mahaffy,President and Chief Executive Officer of Pharmion. "With the recent survivaldata demonstrated by Vidaza in higher-risk MDS, epigenetic therapies arerapidly emerging as an important component of cancer therapy and we believethat the sirtuins represent important new targets in the epigenetic field."

"Sirtuins are an area of increasing interest to us due to their potentialbroad application in epigenetic regulation of disease. This collaboration,focused in cancer, enhances the joint vision of our companies to be activelyinvolved in this important area of cancer research," said Donald F. Corcoran,President and Chief Executive Officer of MethylGene. "In addition, we arepleased to be collaborating on this project with Pharmion, as together ourCompanies have demonstrated a strong synergistic working rela