MethylGene Inc.
TSX : MYG

MethylGene Inc.

June 05, 2006 15:30 ET

MethylGene Reports Positive Interim Results from Two Clinical Programs at the American Society of Clinical Oncology Conference, ASCO

MONTREAL, QUEBEC--(CCNMatthews - June 5, 2006) -

Interim Data From HDAC Inhibitor, MGCD0103, Includes Three Leukemia Patients Exhibiting Complete Bone Marrow Responses

MethylGene Inc. (TSX:MYG) today announced interim data for its lead oncology product candidate, MGCD0103, an oral, non-hydroxamate, isotype-selective histone deacetylase (HDAC) inhibitor at the American Society of Clinical Oncology (ASCO) 2006 Annual Meeting held in Atlanta. The interim data was presented on two studies evaluating MGCD0103 in leukemia / myelodysplastic patients and in solid tumors. Of particular interest, three of nine evaluable patients, at the two highest doses, achieved a complete bone marrow response in a Leukemia / Myelodysplastic Syndrome (MDS) trial. In a separate solid tumor study, five patients experienced stable disease.

"We have seen clear marrow responses in patients with highly refractory acute myelogenous leukemia. These are very exciting findings for this rationally designed oral drug with excellent pharmacokinetic and pharmacodynamic characteristics. Additionally, this agent has a manageable safety profile," stated Dr. G. Garcia-Manero, MD, Associate Internist and Associate Professor of Medicine, The University of Texas MD Anderson Cancer Center and a Principal Investigator of the MGCD0103 Leukemia / MDS trial.

Data from a second product candidate, MG98, a demethylating agent, were also disclosed. MG98 was administered in combination with interferon alpha on two dosing schedules (continuous infusion and an intermittent dosing regimen) to patients with renal cell cancer. A total of 19 patients have been enrolled in the study. Results to date show that five patients on the continuous infusion schedule achieved stable diseases and another two had unconfirmed partial responses. Three patients on the intermittent dosing regimen achieved stable diseases and another patient had a partial response.

Clinical Trial Details

In the symposium "Myelodysplastic Syndromes: Breakthroughs in Treatment," one of the Principal Investigators participating in MethylGene's clinical trial, Dr. G. Garcia-Manero, MD, presented, "Clinical Activity and Safety of the Histone Deacetylase Inhibitor MGCD0103, Results of a Phase I Study in Patients with Leukemia or Myelodysplastic Syndromes (MDS)" (Abstract # 6500). This Phase I, open label, dose escalation study has the objective of determining the maximum tolerated dose and the pharmacokinetic (PK) and pharmacodynamic (PD) properties of MGCD0103 as an oral monotherapy administered three-times weekly to patients with hematologic malignancies. Data on 23 patients enrolled as of May 2006 were presented. The maximum tolerated dose of this schedule was exceeded at 80 mg/m2 with nausea, vomiting, diarrhea, and/or fatigue as dose-limiting toxicities. Two patients with refractory AML and one patient with advanced MDS achieved complete bone marrow responses (bone marrow blast incidences were less than 5%). Both pharmacokinetic evaluations and the measurement of HDAC activity in peripheral white cells demonstrated a dose-dependent effect. Thus far, the data presented suggest that MGCD0103 was well tolerated at doses below 80 mg/m2 when given three-times weekly to leukemia / MDS patients. Importantly, the meaningful clinical activity in patients was consistent with dose dependent inhibition of the HDAC target.

In the symposium "Epigenetic Targeting As a Novel Anticancer Intervention," one of the Principal Investigators participating in MethylGene's clinical trial, Dr. M. A. Carducci, MD, Associate Professor in Oncology and Urology, Johns Hopkins Medical Institutions, presented "Phase I Study of Isotype-selective Histone Deacetylase (HDAC) Inhibitor MGCD0103 Given as a Three-Times Weekly Oral Dose in Patients with Advanced Solid Tumors" (Abstract # 3007). This Phase I, open-label, dose-escalation study has the objective of determining the safety, tolerability, pharmacokinetics and pharmacodynamics of MGCD0103 as an oral monotherapy administered three-times weekly to advanced solid tumor patients. Data on 28 patients enrolled as of May 2006 were presented. The maximum tolerated dose and the recommended Phase II dose have not yet been determined. The most common toxicity reported was Grade 1-3 fatigue. Three patients with kidney cancer, one patient with non-small cell lung cancer and one patient with colon cancer experienced stable disease. The half-life of MGCD0103 was 9 hours, consistent with previous studies. In conclusion, MGCD0103 was tolerated, has acceptable pharmacodynamic and pharmacokinetic properties, and has demonstrated prolonged stable disease in some patients.

As abstract entitled, "A Dose and Schedule Optimizing Evaluation of MG98 given as either a 2 hour IV infusion twice weekly or as a 7 day continuous infusion in combination with interferon alpha (INF) in nephrectomized patients with advanced RCC (Abstract # 14557)," highlighted that a MG98/Interferon alpha combination had clinical activity and acceptable safety in kidney cancer patients. The objective of this study was to determine the optimal dosing regimen, maximum tolerated dose, safety, tolerability, PK and the degree of inhibition of the target enzyme's expression levels. As of May 2006 nineteen patients have been evaluated, 10 on a continuous infusion schedule and nine on an intermittent schedule. On the continuous infusion schedule two doses were explored. A maximum tolerated dose was reached at 125 mg/m2 MG98/12 MIU of interferon. Five stable diseases and two unconfirmed partial responses were observed on this schedule with fatigue, nausea, anorexia and vomiting identified as dose limiting toxicities. On the intermittent schedule, three doses have been explored. The maximum tolerated dose was reached at 200 mg/m2 MG98/12 MIU of interferon with gastrointestinal / constitutional symptoms identified as dose limiting toxicities. Three stable diseases and one partial response were observed on this schedule. The data from this study support the conclusion that MG98 in combination with interferon alpha exhibits clinical activity with an acceptable safety profile.

Additional Clinical Trials

In addition to the clinical trials evaluating MGCD0103 noted above, MethylGene is currently enrolling patients in a Phase I monotherapy trial in hematological malignancies on a twice weekly oral schedule and a Phase I/II combination trial with Vidaza®, a demethylating agent (azacitidine, marketed by Pharmion Corp.), in patients with advanced MDS or AML. In the Phase I portion of this trial, MGCD0103 is administered orally, three-times per week in combination with standard Vidaza treatment. In the second quarter of 2006, together with its partners Pharmion Corporation and Taiho Pharmaceutical, the Company expects to begin a Phase I/II combination trial with an undisclosed chemotherapeutic and later in 2006 anticipates embarking on additional Phase II monotherapy trials. The Company expects to begin several Phase I/II MG98 combination trials with targeted agents in renal cell cancer patients in the second half of 2006.

About MethylGene

MethylGene is a publicly-traded biopharmaceutical company focused on the discovery, development and commercialization of novel therapeutics in cancer and infectious diseases. We intend to exploit our HDAC inhibitor technology in other diseases, such as diabetes, inflammation, fungal infections and neurodegenerative disorders. Two cancer product candidates are currently in clinical trials: 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. 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.

Contact Information

  • MethylGene Inc.
    Andrea Gilpin, Ph.D, MBA
    Director, Investor Relations
    (514) 337-3333 ext. 416
    gilpina@methylgene.com