MethylGene Inc.
TSX : MYG

MethylGene Inc.

November 17, 2009 12:30 ET

MethylGene Reports Favorable Phase I Data for MGCD265 in Solid Tumors at the AACR-NCI-EORTC International Conference

Compound is well tolerated with signs of activity and pharmacodynamic effect Three clinical trials ongoing

MONTREAL, QUEBEC--(Marketwire - Nov. 17, 2009) - MethylGene Inc. (TSX:MYG) today reported preliminary Phase I data for MGCD265 in a poster session at the 2009 AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference in Boston.

MGCD265 is an oral, small molecule multi-targeted kinase inhibitor for cancer that targets the Met, VEGF, Ron and Tie-2 receptor tyrosine kinases thereby inhibiting multiple pathways involved in tumor growth, metastasis and angiogenesis. The objective of this Phase I dose-escalation trial (Trial 265-102) is to evaluate the maximum-tolerated dose, safety, pharmacodynamics (PD) and pharmacokinetics (PK) of MGCD265 when administered orally to patients with advanced metastatic or unresectable solid tumors that were refractory to standard therapy. The starting dose for the trial was 24mg/m2 of MGCD265 administered daily every other week for a 28-day cycle. This trial is a companion to Trial 265-101 which is evaluating MGCD265 administered daily without interruption.

Preliminary results from Trial 265-102

MGCD265 capsules are well tolerated with signs of activity and pharmacodynamic effect.

To date, 20 patients have been enrolled in Trial 265-102 and have received doses of MGCD265 ranging from 24 mg/m2 to 340 mg/m2 with the maximum tolerated dose still to be determined. No dose-limiting toxicities have been observed. The Company has also introduced a tablet form, which will provide improved manufacturing of MGCD265 finished form.

Preliminary efficacy data indicate six patients with stable disease (30 percent of patients enrolled) per RECIST criteria, including one patient with a rare and aggressive form of bladder cancer, classified histologically as sarcomatoid, who was treated with MGCD265 for 12 cycles (approximately one year). This patient's cancer had previously progressed after three different courses of chemotherapy (chemo-resistant). Sarcomatoid tumors exhibit features of EMT (epithelial to mesenchymal transition), a process in which Met is known to play a role. An archived tumor biopsy obtained from this patient prior to MGCD265 treatment demonstrated Met expression and phosphorylation, and FISH analysis showed polysomy of chromosome 7 resulting in multiple copies of the Met gene. In a post-treatment tumor sample, a decrease in the level of phospho-Met was seen as well as a decrease in intact vascular structures using endothelial cell labeling with anti-CD31. These data suggest that treatment with MGCD265 resulted in long-term stable disease (10 cycles) and that the compound is inhibiting its targets in this patient. Also of note, a patient with medullary thyroid cancer experienced tumor shrinkage of 10 percent.

Across the study, MGCD265 appears to have a good safety profile at the doses administered with only grade two or less drug-related adverse events reported in the 20 treated patients. The most frequently reported drug-related grade two adverse event was diarrhea which occurred in two patients. This favorable safety profile may provide an opportunity to further investigate MGCD265 in combination with chemotherapy and as maintenance therapy.

"We continue to be encouraged by the activity, safety and pharmacodynamic characteristics of MGCD265," said Donald F. Corcoran, President and Chief Executive Officer of MethylGene. "We have not yet identified the maximum tolerated dose and we continue to evaluate MGCD265 in our Phase I trials while progressing the compound into Phase II trials including our ongoing trial in combination with Tarceva® and docetaxel."

MethylGene will continue its two ongoing Phase I trials and has initiated its Phase II program with MGCD265 in combination with Tarceva® (erlotinib) and docetaxel, focused on non-small cell lung cancer (NSCLC) patients. MethylGene has demonstrated good preclinical in vivo efficacy and tolerability of MGCD265 in combination with both agents. The Tarceva® combination may be of particular interest, as it has been shown that Met and EGFR functionally cooperate. The simultaneous inhibition of Met and EGFR has demonstrated enhanced anti-tumor activities in multiple in vivo models. Importantly, Met amplification has been described as a mechanism of resistance to EGFR inhibitors in NSCLC patients; therefore, blocking Met offers a compelling rationale to overcome resistance to EGFR inhibitors, such as Tarceva®, in the clinic. The Company also expects to commence another Phase II trial in breast cancer or bladder cancer.

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 mocetinostat (MGCD0103), an oral, isoform-selective HDAC inhibitor for cancers 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 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.

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