MethylGene Inc.

MethylGene Inc.

October 22, 2008 07:30 ET

MethylGene Presents Preclinical Biomarker Data For MGCD265 at the 20th EORTC-NCI-AACR Symposium

- MGCD265 shown to inhibit the activity of its targets in preclinical studies - Collection and analysis of biomarker data in MGCD265 Phase I trials ongoing

MONTREAL, QUEBEC--(Marketwire - Oct. 22, 2008) - MethylGene Inc. (TSX:MYG) today disclosed preclinical biomarker data for its kinase inhibitor, MGCD265, in a poster session at the 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Geneva.

MGCD265 is an oral, small molecule, multi-targeted kinase inhibitor that targets c-Met, VEGFR1, VEGFR2, VEGFR3, Tie-2 and Ron receptor tyrosine kinases. These kinases play key roles in tumor development, tumor survival and angiogenesis. MGCD265 is currently in two Phase I clinical trials in solid tumor cancers. To monitor MGCD265's biological activity in Phase I clinical trials, pharmacodynamic markers were determined from plasma samples and tumor tissue in mice bearing human xenograft tumors.

In a poster entitled "Preclinical Pharmacodynamic Markers of MGCD265, a Potent Orally Active c-Met / VEGFR Multi-targeted Kinase Inhibitor in Phase I Clinical Trials," (poster #81) results demonstrated that MGCD265 has anti-tumor activity not only in c-Met driven human xenograft models, but also in non c-Met driven models.

In c-Met driven cancers, MGCD265 showed activity in a gastric model with an amplified c-Met gene and in a glioblastoma model that is autocrine for hepatocyte growth factor (HGF), the growth factor that binds to and activates c-Met. In non c-Met-driven xenograft models, including breast, lung and colorectal cancers, MGCD265's anti-tumor activity suggests that this multi-targeted compound is also capable of inhibiting tumor growth through the inhibition of its VEGFR and Tie-2 targets. This broad activity may allow for MGCD265 to be developed against c-Met driven and/or VEGFR-driven tumor types.

MGCD265 inhibited c-Met phosphorylation in vivo as well as the activation of Erk and Akt downstream signaling pathways. This inhibition correlated with potent in vivo MGCD265-mediated inhibition of tumor cell proliferation and the induction of apoptosis. In addition, MGCD265 downregulated genes involved in angiogenesis. Moreover, results demonstrated that MGCD265 decreased the levels of the tumor-derived angiogenic factors, VEGF and HGF, in the plasma. MGCD265 was also shown to inhibit the circulating level of tumor-derived shed-c-Met (c-Met ectodomain), which has been associated with increased malignancy. Therefore, the concentrations of VEGF, HGF and shed-c-Met in plasma may be novel biomarkers for MGCD265 clinical activity in patients with solid tumor cancers. These pharmacodynamic parameters are being collected and analyzed in the ongoing MGCD265 Phase I clinical trials.

About MethylGene

MethylGene Inc. (TSX:MYG) is a publicly-traded, clinical stage, biopharmaceutical company focused on the discovery, development and commercialization of novel therapeutics for cancer. The Company's product candidates include: MGCD265, an oral, multi-targeted kinase inhibitor targeting the c-Met, Tie-2, Ron and VEGF receptor tyrosine kinases which is in Phase I clinical trials for solid tumor cancers; MGCD290, a fungal Hos2 (HDAC) inhibitor used in combination with azoles for fungal infections which is also in a Phase I clinical trial; 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 Celgene Corporation and Taiho Pharmaceutical. In addition, MethylGene's preclinical programs include: a kinase inhibitor program for ocular diseases and a sirtuin inhibitor program for cancer. MethylGene's development and commercialization partners include Celgene Corporation, Taiho Pharmaceutical Co. Ltd., Otsuka Pharmaceutical Co. Ltd. and EnVivo Pharmaceuticals. Please visit our website at

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, 2007, under the heading 'risk factors,', and all other documents filed by the Company that can be found at 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.

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