MethylGene Presents Encouraging Clinical and Preclinical Data for MGCD265 at the American Society of Clinical Oncology 2010 Annual Meeting

MONTREAL, QUEBEC--(Marketwire - June 07, 2010) - MethylGene Inc. (TSX: MYG) today disclosed preliminary clinical and preclinical data for MGCD265 in poster presentations at the American Society of Clinical Oncology (ASCO) 2010 Annual Meeting held in Chicago, IL. In addition, the Company is providing a preliminary update on Trial 103 (the first stage of the Phase II program) in which MGCD265 is administered in combination with either erlotinib (Tarceva®) or docetaxel (Taxotere®) in solid tumor patients. MGCD265 is a proprietary 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.

"The data, to date, from MGCD265 clinical trials are promising with early signs of activity and an excellent safety profile," said Donald F. Corcoran, President and Chief Executive Officer of MethylGene. "Patients in these studies were heavily pretreated and it is encouraging to see prolonged disease stabilization in patients receiving MGCD265. We will continue to evaluate MGCD265 with a focus on completing Trial 103 in preparation for a blinded, randomized Phase II trial in non-small cell lung cancer patients (Trial 104)."

ASCO Presentations

MGCD265-101: Daily Administration of MGCD265 to Patients with Solid Tumors in a Dose-Escalation Phase I Study, Abstract #3106

To date, 30 heavily pretreated patients have been treated in this ongoing Phase I study evaluating MGCD265 in patients with advanced metastatic or unresectable malignancies. Twenty-two of these patients were evaluable for efficacy. MGCD265 was administered to adult patients as a single agent orally once per day for 21 days (one cycle) at doses ranging from 24mg/m2 to 300mg/m2. All of the patients treated with MGCD265 had previously received prior therapy of which 70% received more than two therapies and 47% received prior radiation therapy.

Ten patients (45%) of the 22 patients evaluable for efficacy as of the cut-off date achieved stable disease according to RECIST criteria of which five patients (23%) remain(ed) on study for four cycles or more (treatment durations range(d) from 84 to 168 days - one patient with colorectal cancer who has been on study for over 120 days is still ongoing). These patients had two to four prior therapies and consisted of patients with rectal, colorectal, thymic, cecal and squamous cell carcinoma of the thymus. The observed dose limiting toxicities included elevated lipase (n equal 1 at a dose of 250mg/m2 capsules) and hypertension (n equal 1 at a dose of 300mg/m2 capsules) in the 30 patients treated to date. The maximum tolerated dose (MTD) has not yet been reached and enrollment using twice-daily (BID) tablet dosing is commencing. Of note, significant expression of Met, P-Met and polysomy of chromosome 7 (indicating multiple copies of the Met gene) were observed in available archived tumor tissues from four of the five patients exhibiting stable disease. The overall pharmacodynamic changes detected in plasma upon MGCD265 treatment indicate: a decrease in HGF levels, an increase in s-Met levels (in Cycle 2) and an increase in VEGF levels. These preliminary data indicate that daily administration of MGCD265 is well tolerated with early signs of activity in patients with advanced malignancies.

MGCD265-102: A Phase I Study of Oral Administration of MGCD265 in Patients with Advanced Malignancies, Abstract #3108

This ongoing study includes data from 35 pretreated patients who were administered MGCD265 orally, as a single agent on an intermittent basis of one week on and one week off for 28 days (one cycle), in adult patients with advanced malignancies. The preliminary data indicate that MGCD265 appears to be active and well tolerated. The most frequent treatment-related adverse events reported to date were diarrhea (n equal 2), nausea (n equal 2) and fatigue (n equal 2). No serious MGCD265-related adverse events have been reported. The MTD has not been reached and enrollment using BID tablet dosing is ongoing.

Ten patients (33%) of the 30 patients evaluable for efficacy achieved stable disease as of the cut-off date according to RECIST criteria and four patients (13%) remain(ed) on study for four cycles or more (treatment durations ranged from 161 to 330 days - one patient with papillary renal carcinoma who has been on study for over 210 days is still ongoing). Two of these patients experienced minor tumor shrinkage. Analysis of archived tumor tissues from two patients (papillary renal cell carcinoma and sarcomatoid bladder cancer) with prolonged stable disease (approximately 8 to 10 cycles) demonstrated significant expression of Met, P-Met and polysomy of chromosome 7 (indicating multiple copies of the Met gene). A post-treatment biopsy from the patient with sarcomatoid bladder cancer indicated a decrease in the level of Met and P-Met and a change in vascular structures following MGCD265 treatment. To date, these preliminary data indicate that MGCD265 appears to be well tolerated with early signs of activity in patients with advanced malignancies. In addition, tumor biopsy material obtained from two patients indicated that patients who benefited from prolonged stable disease had pharmacodynamics (PD) which appear consistent with the proposed mechanism of action for MGCD265.

Potent Preclinical Anti-tumor Activity of MGCD265, an Oral Met/VEGFR Kinase Inhibitor in Clinical Development, in Combination with Taxanes or Erlotinib, Abstract #e13595 (publication in ASCO Proceedings)

In these preclinical studies, MGCD265 was administered in combination with docetaxel, paclitaxel (taxanes) or erlotinib (EGFR inhibitor) in multiple mouse xenograft models including non-small cell lung cancer (NSCLC) models. MGCD265 targets Met which may be over-expressed or mutated in NSCLC and its activation has been identified as a molecular mechanism through which tumors evade the specific inhibition of EGFR.

Results from these preclinical studies demonstrated that MGCD265 combined with docetaxel or paclitaxel achieved greater anti-tumor response than either agent alone and without overt toxicity in lung, breast, gastric, prostate carcinomas and glioblastoma. MGCD265 combined with docetaxel also resulted in a greater reduction of tumor vasculature. Favorable anti-tumor activity with the absence of overt toxicity was also demonstrated when MGCD265 was combined with erlotinib in several xenograft models including breast, gastric and NSCLC carcinomas and a NSCLC model that expressed an EGFR mutation (T790M) which appears to be a predominant mechanism for the development of resistance to erlotinib. In addition, MGCD265 combined with any of the three agents did not result in any drug-drug interactions. These studies help support the selection of erlotinib and docetaxel in an ongoing combination clinical trial (Trial 103, see preliminary results below).

Preliminary Clinical Trial Update

MGCD265-103: Daily Administration of MGCD265 in Combination with docetaxel or erlotinib

To date, 34 patients have been enrolled in Trial 103, a dose-escalating clinical study combining MGCD265 with either erlotinib or docetaxel. MGCD265 is administered orally, every day for 21 days (one cycle) in patients with advanced solid malignancies. Fifteen patients have been enrolled on the docetaxel arm with MGCD265 (doses up to 144mg/m2) and up to full doses of docetaxel (75mg/m2). A total of 19 patients have been enrolled on the erlotinib arm with MGCD265 (doses up to 144mg/m2) and up to full doses of erlotinib (150mg). In both arms, MGCD265 and the combinations have been well tolerated. The MTD has not been reached in either arm and dose escalation continues. BID tablet dosing is expected to be introduced soon.

On the docetaxel arm, five patients (33%) have been treated for more than four cycles and eight patients are ongoing. Interestingly, among the ongoing patients are four metastatic Stage IV NSCLC patients. These patients had previously received three to six prior therapies, including treatment with a taxane, and were all smokers. The current treatment duration of these four patients ranges from 16 to 38 weeks with tumor shrinkage reported. These patients exceed the time to disease progression (TTP) of approximately 12 weeks reported for second-line NSCLC patients treated with docetaxel as described in the Taxotere® label (TAX317 study). The current progression-free survival (PFS) mean and median for these four patients is 26 and 25 weeks, respectively. Pharmacokinetic data indicate no drug-drug interaction. Preliminary plasma pharmacodynamic analysis for patients where plasma samples were available indicates significant modulation of HGF, the ligand for Met (decreased in seven out of ten patients), and VEGF (increased in 8 of 10 patients). In summary, preclinical xenograft data and preliminary clinical data, especially in advanced NSCLC patients, indicate the potential for increased benefit in combining MGCD265 with docetaxel. In addition, plasma markers show significant modulation when these two drugs are combined.

In the erlotinib arm of the trial, six patients (32%) have been treated for at least four cycles and six patients are ongoing. One of these ongoing patients appears to have experienced significant clinical benefit. One dose-limiting toxicity has been experienced (n equal 1, diarrhea). Preliminary PD analysis in patients for which plasma samples were available indicates significant modulation of HGF (decreased in 9 of 12 patients) and VEGF (increase in 6 of 12 patients). In summary, enhanced tumor activity has been observed when MGCD265 was combined with erlotinib in human xenograft models, including a NSCLC model resistant to EGFR inhibitors. Preliminary clinical findings to date suggest that MGCD265 can be safely combined with erlotinib and preliminary signs of activity and plasma PD changes have been observed.

The Company's current goal is to identify the MTD for each combination in preparation for a randomized, placebo control, double-blind MGCD265 Phase II clinical trial (Trial 104) in refractory NSCLC patients with the selected comparator agent (erlotinib or docetaxel). The Company expects to provide additional data for Trial 103 at an appropriate scientific venue later this year.

It is estimated by the American Cancer Society (Cancer Facts & Figures, 2009) there will be 222,520 new cases of lung cancer in the U.S. in 2010 of which approximately 85% are classified clinically as NSCLC. Lung cancers are the leading cause of cancer-related deaths in the U.S. (28% of all cancers) in men and women. The five-year survival rate for NSCLC for all stages is estimated at 17%. Both erlotinib and docetaxel are approved for single-agent use as a second-line therapy 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 has completed 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 currently in a Phase II 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, 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, 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 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.