MethylGene Inc.

MethylGene Inc.

November 18, 2010 07:30 ET

MethylGene Presents Encouraging Clinical Data for MGCD265 in Solid Tumor Cancers at the 22nd EORTC-NCI-AACR Annual Meeting

MONTREAL, QUEBEC--(Marketwire - Nov. 18, 2010) - MethylGene Inc. (TSX:MYG) today disclosed safety and efficacy clinical data for MGCD265 in two poster presentations at the 22nd EORTC-NCI-AACR Symposium held in Berlin, Germany. Data was presented for the Company's two-arm trial (Trial 103) in which MGCD265 is administered in combination with either docetaxel or erlotinib in solid tumor patients. MGCD265 is a proprietary oral multi-targeted receptor tyrosine kinase inhibitor.

Poster Presentations

MGCD265, an Orally Active Met/VEGFR Multi-targeted Kinase Inhibitor, in Combination with Docetaxel: Clinical and Preclinical Experience (Trial MGCD265-103). Abstract #396.

In the docetaxel arm of Trial 265-103 (MGCD265 in combination with full-dose docetaxel), 18 patients with advanced solid malignancies have been enrolled. MGCD265 is administered orally daily in combination with docetaxel once every 21 days (one cycle) in patients with advanced solid malignancies. Twice per day (BID) dosing of MGCD265 has been initiated. The maximum-tolerated dose (MTD) has been reached and the Company is defining the recommended Phase 2 dose. Five patients have been on the study for more than four months. Of these, four non-small cell lung cancer (NSCLC) patients have experienced stable disease for durations ranging from 8 to 13 months. One NSCLC patient achieved a confirmed partial response and the other three patients all had tumor shrinkage accompanying their stable disease.

"The preliminary data with MGCD265 and docetaxel in this small set of non-small cell lung cancer patients is intriguing," stated Dr. Alan Sandler, Professor of Medicine and Division Chief, Division of Hematology & Medical Oncology; and DeArmond Chair for Clinical Cancer Research, Oregon Health & Science University. "Docetaxel is a common treatment for NSCLC patients and these patients often exhibit Met expression. Therefore, combining docetaxel with a Met-inhibiting agent to treat NSCLC is an interesting therapeutic path that I believe should be explored."

Preclinical xenograft studies described in the poster indicate that the combination of MGCD265 with docetaxel achieved greater antitumor responses than treatment with either agent alone. In patients, MGCD265 has been combined with a full dose of docetaxel (75mg/m2) and is well tolerated with no drug-drug interactions observed from preliminary pharmacokinetic evaluations. Overall, pharmacodynamic changes demonstrated that plasma levels of HGF (the ligand for Met) decreased significantly and that plasma levels of VEGF (the ligand for VEGFR) increased significantly, which suggests that MGCD265 is effectively covering its Met and VEGFR targets.

MGCD265, an Orally Active Met/VEGFR Multi-targeted Kinase Inhibitor, in Combination with Erlotinib: Clinical and Preclinical Experience (Trial MGCD265-103). Abstract #395.

In the erlotinib arm of Trial 265-103 (MGCD265 in combination with full-dose erlotinib), 27 patients have been enrolled and dose escalation continues. Both of the agents are administered orally daily to patients with advanced solid malignancies for 21–day cycles. BID dosing for MGCD265 has been initiated. Twelve patients have been on study for more than four months. Of these, one gastric cancer (linitis plastica) patient is currently experiencing stable disease for 11 cycles. After two cycles of treatment, CT scans confirmed a near complete resolution of ascites and a decrease in the thickness of the gastric wall. The most frequent MGCD265-related toxicities in both arms of Trial 265-103 are fatigue and diarrhea, consistent with ongoing single agent studies of MGCD265.

"Gastric cancer remains a significant worldwide problem, accounting for approximately 800,000 deaths annually. Unfortunately, standard therapies provide only modest benefit, and as such, new therapies are desperately needed," commented Dr. Amita Patnaik, Associate Director of Clinical Research at South Texas Accelerated Research Therapeutics (START) in San Antonio, Texas. "The preliminary activity seen in gastric cancer with the combination of MGCD265 and erlotinib is very exciting and certainly warrants further investigation."

Preclinical data for MGCD265 in combination with erlotinib in xenograft models indicated greater anti-tumor activity of the combination compared to either agent alone. The combination was well-tolerated in animals with no drug-drug interaction. In patients, MGCD265 was combined with a full dose of erlotinib (150mg) and is well tolerated with no drug-drug interaction observed from preliminary pharmacokinetic evaluations.

About MGCD265

MGCD265 is a novel, orally active small molecule inhibitor that targets a unique spectrum of receptor tyrosine kinases: Met, VEGFR 1, 2, and 3, Tie-2 and Ron. These kinases play key roles in tumor development, survival and metastasis as well as the inappropriate formation of blood vessels (angiogenesis) that nourish the tumor. MGCD265 is nearing completion of three Phase 1, single-agent and combination clinical trials (with erlotinib and docetaxel) in solid tumors. MGCD265 has an excellent safety profile, either alone or in combination, and has shown preliminary signs of clinical activity. 

About the Met Target

The Met receptor is a protein that is found on the cell's surface. When not properly regulated (i.e. over active) it plays a key role in the growth, metastasis and survival of various types of cancers. Met is also involved in angiogenesis and is most strongly associated with major cancers such as non-small cell lung, gastric, colorectal and breast carcinomas.

About MethylGene

MethylGene Inc. (TSX:MYG) is a publicly-traded, clinical stage biopharmaceutical company focused on the 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 fungal infections which has completed Phase 1 clinical studies; and mocetinostat (MGCD0103), an oral, isoform-selective HDAC inhibitor for cancer which has been in multiple Phase 2 clinical trials and is currently in a Phase 2 trial in refractory or relapsed follicular lymphoma. Mocetinostat 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 for neurodegenerative diseases has successfully completed Phase 1 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

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, as described in MethylGene's Annual Information Form for the fiscal year ending December 31, 2009, under the heading "Risk Factors" which you are urged to read 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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