MethylGene Reports Scientific Progress in Two Anticancer Programs - DNA Methyltransferase and Histone Deacetylase: Two Enzyme Targets for Cancer Inhibition.

Business Editors/Health/Medical Writers

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MONTREAL--(BUSINESS WIRE)--Jan. 8, 2003

MethylGene Inc., a private Canadian drug discovery and development company, discloses new scientific data on its cancer targets DNA methyltransferases (DNMT) and histone deacetylases (HDAC) in two scientific publications and at the Gordon Research Conference on Cancer Genetics and Epigenetics in Ventura, California (January 5-10, 2003) at which Dr. MacLeod, Director of Biology, will be giving a talk entitled: "Epigenetic Regulators as Novel Cancer Targets."

Both MethylGene cancer targets regulate gene expression and specifically turn off tumor suppressor genes which are natural brakes against cancer. "From an anti-cancer therapeutic standpoint, we understand how the inactivation of tumor suppressor genes can be reversed by inhibiting the DNMT and HDAC enzymes," said Dr. Jeffrey Besterman, Senior Vice President, Research and Development. "Our scientific data further strengthens MethylGene's leadership position on these two important cancer targets."

In humans, there are three different isoforms of DMNT: DNMT1, DNMT3a, and DMNT3b. In a scientific publication entitled "DNA methyltransferase-1 (DNMT1) is required to maintain CpG methylation and tumor suppressor silencing in human cancer cells" in the January 2003 issue of Nature Genetics (Nat. Genet. 2003, 33, 61-65), MethylGene discloses the role of the DNMT1 isoform in tumor cell oncogenesis. The paper describes the Company's findings on the role of DNMT1 and DNMT3b in cancer cell survival.

The latest results reinforce the belief that inhibitors of the DNA methyltransferase family of enzymes may be useful anti-cancer therapies. MethylGene has designed small molecule inhibitors that are selective for individual DNMT isoforms. Its leading drug candidate, MG98, which inhibits the production of DNMT1, is currently in Phase I trials for solid and hematological tumors.

The field of inhibiting HDACs has emerged as a novel human anticancer strategy and MethylGene has developed multiple series of small molecule inhibitors of HDACs, including sulfonamide hydroxamic acids and anilides, as described in the Company's recently accepted chemistry paper entitled "Development of potential antitumor agents. Synthesis and biological evaluation of a new set of sulfonamide derivatives as histone deacetylase inhibitors," which will be published in the Journal of Medicinal Chemistry (tentative issue date: February 27, 2003). These inhibitors preferentially inhibit cancer cell proliferation, cause cancer cell cycle arrest, and induce apoptosis. In subsequent work, yet to be published, the Company has designed and synthesized new chemical series possessing improved pharmacological properties, including oral activity. MethylGene anticipates an IND filing at the end of 2003.

About MethylGene

MethylGene Inc. is a privately held Canadian biopharmaceutical company focused on the discovery and development of novel and proprietary medicines for the treatment of cancer and infectious diseases. The Company has built strong core competencies in pharmaceutical research, particularly in functional genomics, rational drug design, and medicinal chemistry. MG98, the lead anti-cancer compound is currently in human clinical trials. MG98 is partnered with MGI Pharma Inc. for North American rights, and with British Biotech plc for European rights. The Company has research and development programs to develop small molecule inhibitors against DNA methyltransferases, histone deacetylases, beta-lactamases, and several other enzyme targets in a collaboration with ChemBridge Research Laboratories. For more information about MethylGene, please visit www.methylgene.com.

This press release may contain forward-looking statements pertaining to MethylGene Inc. Such statements are subject to certain risk factors and uncertainties, particularly those inherent in the process of discovering, researching, developing and commercializing drugs that can be proven to be safe and effective for use as human therapeutics and the endeavor of building a business around such potential products. As a result, the reader is cautioned that actual results could differ materially from those projected or assumed around this release.