MethylGene Presents Phase I Data for its Novel Antifungal Agent, MGCD290, at the 49th Annual ICAAC Meeting

MONTREAL, QUEBEC--(Marketwire - September 15, 2009) - MethylGene Inc. (TSX: MYG) today disclosed Phase I and preclinical data for MGCD290, an oral, small molecule, Hos2 fungal inhibitor. In preclinical studies, MGCD290 potentiates and broadens the spectrum of activity of azole antifungal agents against multiple human fungal pathogens including azole-resistant clinical isolates. MethylGene is currently evaluating MGCD290 in Phase I clinical trials in adult healthy volunteers as a single agent and in combination with fluconazole. The data were presented in a poster session and an oral presentation at the 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Annual Meeting in San Francisco, California.

Poster M-1029: Multiple Phase I Studies in Healthy Subjects Demonstrate Safety and Pharmacokinetics of MGCD290, an Oral Fungal Hos2 Inhibitor + / - Fluconazole

Favorable Phase I data from three MGCD290 clinical studies were reported. All studies were performed in healthy adult volunteers and were double-blind, placebo-controlled and randomized. The objectives of the Phase I studies were to determine the tolerability and pharmacokinetics of MGCD290 when administered alone and in combination with fluconazole. All studies remain blinded.

The first two studies were sequential single ascending-dose (SAD) studies with MGCD290 administered alone (Trial 290-001) and in combination with fluconazole (Trial 290-002). Dose levels of MGCD290 for study 290-001 ranged from 100mg to 1000mg and for study 290-002, doses of MGCD290 were 300mg and 450mg in combination with 400mg of fluconazole. In study 290-001, 42 subjects received MGCD290 and no clinically significant adverse events were observed at any dose level evaluated. Maximal plasma concentrations were observed two hours after oral administration with a mean elimination half-life of eight hours. In study 290-002, no clinically significant adverse events were observed and MGCD290 with fluconazole was well-tolerated without apparent drug-drug interactions.

The third study (Trial 290-003) is an ongoing multiple ascending-dose (MAD) study evaluating the daily dosing of MGCD290 for two weeks at dose levels of 100mg, 180mg, 360mg and 540mg. Data for the first three cohorts in this study were reported. A fourth study (Trial 290-004), a MAD study evaluating daily dosing of MGCD290 for two weeks in combination with 400mg of fluconazole, is planned.

Oral Presentation Session M-1919: MGCD290, A Novel Small Molecule, Modulates Azole Antifungal Activity through Specific Inhibition of the Histone Deacetylase Hos2.

Fungi and fungal pathogens have multiple forms of the fungal histone deacetylase (HDAC) enzyme: Rpd3, Hos1, Hos2, Hda1 and Hos3. To determine the HDAC target of MGCD290, yeast knockouts of each homologue were performed and the sensitivity to azoles was determined. An HDAC knockout that was hypersensitive to azoles became a candidate target of MGCD290.

The deletion of the HOS2 gene, but not other fungal HDAC genes, decreased the minimal inhibitory concentration (MIC) of azoles (fluconazole, voriconazole and itraconazole) required to inhibit fungal growth. The synergy between MGCD290 and the azoles was abolished only in the HOS2 deletion mutant, and the deletion of this gene was sufficient to sensitize yeast to azoles. The deletion of the other homologues produced no change or only a very modest increase in azole susceptibility when compared to the deletion of Hos2. Hos2, therefore, appears to be the target of MGCD290.

About MethylGene

MethylGene Inc. (TSX: MYG) is a publicly-traded, clinical stage, biopharmaceutical company focused on the discovery, development and commercialization of novel therapeutics with a focus on cancer. The Company's product candidates include: MGCD265, an oral, multi-targeted kinase inhibitor targeting the c-Met, VEGF, Ron and Tie-2 receptor tyrosine kinases that is in Phase I and Phase II clinical trials for cancers; MGCD290, a fungal Hos2 inhibitor being developed for use in combination with fluconazole for serious fungal infections that is in Phase I clinical studies; and MGCD0103, an oral, isoform-selective HDAC inhibitor which has been in multiple clinical trials for solid tumors and hematological malignancies and is licensed to Taiho Pharmaceutical Co. Ltd for certain Asian countries. A fourth compound discovered using MethylGene's HDAC platform, EVP-0334 - a potential cognition enhancing agent, is in a Phase I study sponsored by EnVivo Pharmaceuticals Inc. MethylGene also has a funded collaboration with Otsuka Pharmaceutical Co. Ltd. for applications in ocular diseases using the Company's proprietary kinase inhibitor chemistry. Please visit our website at www.methylgene.com.

Certain statements contained in this news release, other than statements of fact that are independently verifiable at the date hereof, may constitute forward-looking statements. Such statements, based as they are on the current expectations of management of MethylGene, inherently involve numerous risks and uncertainties, known and unknown, many of which are beyond MethylGene's control. These risks and uncertainties could cause future results, performance or achievements to differ significantly from the results, performance or achievements expressed or implied by such forward-looking statements. Such results, performance or achievements include, but are not limited to, the timing and effects of regulatory action; the continuation of collaborations; the results of clinical trials; the timing of enrollment or completion of clinical trials; the success, efficacy or safety of MGCD0103, MGCD265 or MGCD290; the ability to scale up, formulate and manufacture sufficient GMP, clinical or commercialization quantities of MGCD0103, MGCD265 or MGCD290, and the relative success or the lack of success in developing and gaining regulatory approval and/or market acceptance for any compound or new product including MGCD0103, MGCD265 or MGCD290. Such risks include, but are not limited to, the impact of general economic conditions, economic conditions in the pharmaceutical industry, changes in the regulatory environment in the jurisdictions in which MethylGene does business, stock market volatility, fluctuations in costs, expectations with respect to our intellectual property position and our ability to protect our intellectual property and operate our business without infringing upon the intellectual property rights of others, changes in the competitive landscape including changes in the standard of care for the various indications in which MethylGene is involved, and changes to the competitive environment due to consolidation, as well as other risks, which you are urged to read, as described in MethylGene's Annual Information Form for the fiscal year ending December 31, 2008, under the heading 'risk factors and all other documents filed by the Company that can be found at www.sedar.com. Consequently, actual future results may differ materially from the anticipated results expressed in the forward-looking statements. The reader should not place undue reliance on the forward-looking statements included in this presentation. These statements speak only as an update on the date they are made and MethylGene is under no obligation to revise such statements as a result of any event, circumstance or otherwise except in accordance with law.