MethylGene Presents Preclinical Data for MGCD265 (A Multi-Targeted Met Kinase Inhibitor) at the American Association for Cancer Research(AACR) Annual Meeting

MONTREAL, QUEBEC--(Marketwire - April 20, 2010) - MethylGene Inc. (TSX: MYG)

- MGCD265 in Combination with Tarceva® (erlotinib) overcomes resistance to EGFR inhibition and achieves greater anti-tumor responses than either agent alone -

- MGCD265 demonstrates potent inhibitory activity against clinically relevant Met mutants -

MethylGene Inc. (TSX: MYG) today disclosed preclinical data during two presentations for its proprietary multi-targeted (Met) kinase inhibitor, MGCD265, at the AACR 101st Annual meeting held in Washington, DC.

MGCD265 is an oral multi-targeted receptor tyrosine kinase inhibitor currently in multiple clinical trials. MGCD265 targets Met and blocks Met activities which contribute to cancer development and progression such as cell proliferation, motility, angiogenesis and tumor cell survival.

In a poster presentation entitled “Potent Preclinical Antitumor Activity of MGCD265, an Orally Active Met/VEGFR Multi-targeted Kinase Inhibitor in Phase II Clinical Development, in Combination with an EGFR Inhibitor,” (poster #3612) results demonstrate that the combination of MGCD265 and erlotinib achieves greater anti-tumor responses compared to the antitumor activity of either agent alone. This combination is of particular interest since accumulating evidence indicates that Met tyrosine kinase receptor and EGFR are co-expressed and functionally cooperate in cancer cells. Moreover, Met activation either through gene amplification or in a ligand-dependent manner has been described as a mechanism of resistance to EGFR inhibitors. Therefore, blocking Met offers a compelling rationale to overcome resistance to EGFR inhibitors.

Preclinical studies in this presentation demonstrate in a non-small cell lung cancer (NSCLC) model that MGCD265 reverses resistance to EGFR inhibitors caused by Met activation, resulting in improved inhibition of cell proliferation. MGCD265 also downregulates the expression of EGFR ligands. Importantly, the combination of MGCD265 and erlotinib causes improved anti-tumor responses compared to the administration of either agent alone. This is demonstrated in multiple xenograft tumor models, including NSCLC, breast and gastric carcinoma models. Moreover, this combination results in better tumor growth inhibition in a NSCLC model that expresses an EGFR mutant resistant to EGFR inhibition (T790M). This combination is well tolerated in these in vivo human xenograft efficacy models and does not result in drug-drug interactions. These studies provide support for the development of MGCD265 in combination with EGFR inhibitors.

The Company’s second poster presentation, “MGCD265, an Orally Active Met/VEGFR Multi-targeted Kinase Inhibitor in Phase II Clinical Development, Potently Inhibits Clinically Relevant Met Mutants,” (poster #3609) demonstrates the potent inhibitory effects of MGCD265 on several clinically relevant Met missense mutants, including mutants causative of hereditary papillary renal cell carcinoma (HPRCC). These results are significant since several Met selective inhibitors are inactive against several of these tyrosine kinase domain Met mutants. MGCD265 is also potent at inhibiting juxtamembrane and extracellular domain Met mutants observed in NSCLC and small cell lung cancer (SCLC). In a xenograft model overexpressing one such juxtamembrane domain mutant (R988C), MGCD265 abrogates tumor growth promoted by the overexpression of this mutant Met, and this tumor growth inhibition correlated with concomitant pharmacodynamic inhibition of mutant Met protein phosphorylation. Thus, MGCD265 inhibits signaling through both wild type and mutant forms of Met and may benefit patients with cancers in which Met is activated due to missense mutations.

“The preclinical data reported today further expands on the functionality and potential benefits of MGCD265,” said Donald F. Corcoran, President and Chief Executive Officer of MethylGene, Inc. “MGCD265 is currently completing two Phase I clinical studies and has begun Phase II development. Human clinical data previously reported demonstrated early signs of activity, with several patients treated with MGCD265 having stable disease and one patient experiencing tumor shrinkage. We anticipate additional clinical data to be presented at the ASCO Annual Meeting in June. This preclinical data further supports the biological underpinnings and potential benefits of MGCD265, especially in regards to mutant Met-driven tumor, restoration of sensitivity to EGFR inhibitors due to resistance and clinical testing in non-small cell lung cancer patients.”

MGCD265 is currently completing two Phase I dose escalating trials (Trials 101 and 102) and a Phase II program (Trial 103) has commenced to determine the maximum tolerated dose of MGCD265 in combination with Tarceva® (an EGFR inhibitor) or Taxotere®, two approved agents used to treat NSCLC patients. The second stage of this trial is expected to be a randomized trial with one of these agents in combination with MGCD265 in NSCLC patients.

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 Met, VEGF, Ron and Tie-2 receptor tyrosine kinases that is in multiple clinical trials for cancer; MGCD290, a fungal Hos2 inhibitor for use in combination with fluconazole for serious fungal infections which is nearing completion of Phase I clinical studies; and mocetinostat (MGCD0103), an oral, isoform-selective HDAC inhibitor for cancer which has been in multiple Phase II clinical trials and is licensed to Taiho Pharmaceutical Co. Ltd in certain Asian countries. A fourth compound discovered using MethylGene’s HDAC platform, EVP-0334 - a potential cognition enhancing agent, is in Phase I trials 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 MGCD265, MGCD290 or mocetinostat (MGCD0103); the ability to scale up, formulate and manufacture sufficient GMP, clinical or commercialization quantities of MGCD265, MGCD290 or mocetinostat, 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 MGCD265, MGCD290 or mocetinostat.

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, 2009, 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.


Contacts:
Rx Communications Group, LLC
Rhonda Chiger
917-322-2569
rchiger@rxir.com

MethylGene Inc.
Donald F. Corcoran
President & CEO
514-337-3333 ext. 373
mctavishk@methylgene.com

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