MethylGene Inc.
TSX : MYG

MethylGene Inc.

December 07, 2006 11:00 ET

MethylGene Initiates Phase II Clinical Trial with its Proprietary HDAC Inhibitor, MGCD0103, in High-Risk Myelodysplastic Syndromes 'MDS' and Acute Myelogenous Leukemia 'AML'

MONTREAL, QUEBEC--(CCNMatthews - Dec. 7, 2006) - MethylGene Inc. (TSX:MYG), along with its partner Pharmion Corporation (NASDAQ:PHRM) today announced the initiation of a Phase II clinical trial with its isotype-specific histone deacetylase (HDAC) inhibitor product candidate, MGCD0103, in patients with high-risk myelodysplastic syndromes (MDS) or relapsed or refractory acute myelogenous leukemia (AML). Specific patient populations include elderly patients who have previously untreated disease or adult patients who have relapsed or refractory disease.

This open-label, single-agent trial (Trial 007) will enroll up to 82 patients and be conducted at leading cancer centers in North America. MGCD0103 will be given orally, three times per week for four weeks (one cycle) without interruption at a flat-dose of 110 mg. This dose was determined based on safety and efficacy data from the companies' Phase I hematologic malignancy study (Trial 003). Key objectives of the study will be to determine the efficacy of MGCD0103 as a treatment option for these patients. Secondary objectives include determining the safety profile, as well as assessing biomarkers and predictive markers for MGCD0103. The trial is expected to last up to 24 months.

High-risk MDS and AML arise through several cellular events, including mutation and/or epigenetic silencing of tumor suppressor genes. The HDAC-dependent repression of transcription (common in the pathway to development of leukemia) is believed to be an important target for HDAC inhibitors. Therefore, it is hypothesized that specifically inhibiting those HDACs involved in transcription with MGCD0103 may restore normal cell function and inhibit tumor growth with fewer side effects than non-selective HDAC inhibitors.

"We previously reported encouraging results from our Phase I MDS/AML trial - four of nine patients, at the highest dose tested, had reductions in bone marrow blasts, including three complete bone marrow responses," said Mr. Donald F. Corcoran, President and Chief Executive Officer of MethylGene. "With that promising data, we are now progressing MGCD0103 into additional Phase II trials with a goal to demonstrate the activity and safety of MGCD0103 in patients afflicted with these cancers."

"This is a time of significant advance in the use of epigenetic therapies for the treatment of many hematological malignancies," said Dr. Hagop Kantarjian, Professor of Medicine and Chairman of the Department of Leukemia at the MD Anderson Medical Center. "We are particularly enthusiastic about the potential of MGCD0103, a potent and targeted histone deacetylase inhibitor, in the treatment of AML and MDS."

About MGCD0103, an Oral HDAC Inhibitor

MGCD0103 is a rationally designed, oral, isotype-specific histone deacetylase (HDAC) inhibitor. In addition to the clinical trial noted above, MethylGene and Pharmion continue to enroll patients in a Phase I single-agent trial evaluating MGCD0103 on a twice weekly oral schedule (Trial 004); a Phase I/II combination trial with the demethylating agent Vidaza® (azacitidine for injectable suspension, marketed by Pharmion) in patients with advanced myelodysplastic syndromes (MDS) or acute myelogenous leukemia (AML) (Trial 005); a Phase I/II trial in combination with Gemzar® in solid tumors and pancreatic cancer (Trial 006); a Phase II single-agent trial in patients with high-risk myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML) (Trial 007); a Phase II single-agent trial in patients with refractory or relapsed diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (Trial 008); and a Phase II single-agent trial in patients with refractory or relapsed Hodgkin's lymphoma (Trial 010). The Companies previously completed enrollment in three Phase I trials (Trials 001, 002, 003) with MGCD0103 in solid tumors or MDS/AML and expect to embark on additional single-agent and/or combination trials in solid and hematological cancers during the first half of 2007.

About Myelodysplastic Syndromes (MDS) and Acute Myelogenous Leukemia (AML)

Myelodysplastic syndromes are a serious and life-threatening group of diseases in which the bone marrow does not function normally, resulting in the production of malformed or immature blood cells. The disease begins when something causes a defect to occur in the genetic material (chromosomes) of one of the stem cells in the bone marrow. That stem cell in turn produces cells that carry the defect. The defective cells eventually predominate in the bone marrow and overwhelm healthy blood cells. These defective cells are less able to produce functioning blood cells, which results in low cell counts (cytopenias) in the bloodstream.

Without enough healthy blood cells - red, white and platelets - people with MDS are at risk for a variety of symptoms and complications including anemia, weakness, fatigue, infection and bleeding. Bone marrow failure results in death from bleeding and infection in the majority of patients, while transformation from MDS to acute myelogenous leukemia (AML) occurs in up to 40 percent of patients. The highest incidence of MDS is in patients over 60 years of age.

According to the Aplastic Anemia and MDS International Foundation, approximately 10,000-30,000 new cases of MDS are diagnosed each year in the United States, although it is difficult to accurately determine the incidence because MDS is not a disease for which the Centers for Disease Control and Prevention (CDC) mandates reporting of cases.

About MethylGene

MethylGene is a publicly-traded biopharmaceutical company focused on the discovery, development and commercialization of novel therapeutics in cancer. Two cancer product candidates are currently in clinical development: MGCD0103, partnered with Pharmion Corporation and Taiho Pharmaceutical Co., Ltd., and MG98, partnered with MGI Pharma, Inc. MethylGene has an exclusive license agreement with Merck & Co. for the development and commercialization of small molecule beta-lactamase inhibitors to overcome antibiotic resistance. MethylGene has partnered its non-oncology HDAC program for neurodegenerative diseases with EnVivo Pharmaceuticals. MethylGene has a portfolio of preclinical programs for its multi-targeted kinase and histone deacetylase (HDAC) inhibitors for both oncology and non-oncology indications, and continues to seek partnering opportunities in these areas. 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 MG98; 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 and MG98. 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 2005, under the heading "risk factors," 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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