MethylGene Inc. (TSX: MYG) today disclosed preclinical data for MGCD290, a fungal Hos2 inhibitor to be used in combination with azoles for the treatment of fungal infections. MethylGene is currently evaluating MGCD290 in a Phase I clinical trial. The data were presented in two poster sessions at the joint 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) / Infectious Disease Society of America (IDSA) 46th Annual Meeting in Washington, DC.
Poster M-2123: In Vivo Properties of MGCD290, an Antifungal Hos2 Histone Deacetylase (HDAC) Enzyme Inhibitor
In this preclinical study, immunocompromised CD-1 mice were inoculated intravenously with a fluconazole-resistant clinical isolate of Candida albicans. Fluconazole and MGCD290, alone or in combination, were administered orally once per day starting 16 hours post-infection.
Infection with the fluconazole-resistant clinical isolate C. albicans resulted in a survival rate of 0 percent in vehicle treated animals. A 15mg/kg dose of fluconazole alone or a 20mg/kg dose of MGCD290 alone resulted in a survival rate of 10 percent or less. With the addition of 20mg/kg of MGCD290 to 15mg/kg of fluconazole, the survival rate increased to 50 percent. Furthermore, a 90 percent survival rate was achieved with the combination of 20mg/kg of MGCD290 and 45 mg/kg of fluconazole, whereas treatment with 45mg/kg of fluconazole alone achieved a survival rate of only 40 percent. In a murine infection model using fluconazole-sensitive C. albicans, the combination treatment also increased survival beyond the activity achieved by fluconazole or MGCD290 alone. In addition, pharmacokinetic and toxicology studies indicated that MGCD290 was well tolerated at multiples of the efficacious dose and no drug-drug interactions with fluconazole were observed.
Poster M-2129: Combination Testing of MGCD290, a Fungal Histone Deacetylase Inhibitor, with Azole Antifungals Against a Large Collection of Clinical Fungal Isolates
The synergistic in vitro activity of MGCD290 when administered with the antifungal agents fluconazole, posaconazole and voriconazole against a diverse collection of fungal clinical isolates, including azole-resistant yeasts and molds was demonstrated. MGCD290 synergized with azoles against most clinical fungal isolates, including organisms intrinsically resistant to azoles, such as Mucor and Fusarium.
Ninety-one clinical isolates were tested, including Candida, Aspergillus, Zygomycetes, Cryptococcus, Rhodotorula, Fusarium, Trichosporon and Scedosporium species. Importantly, MGCD290 synergized with fluconazole in 87 percent of Candida clinical isolates (two-thirds of which were fluconazole-resistant) and in 60 percent of Aspergillus clinical isolates (all of which were fluconazole-resistant). Overall, MGCD290 demonstrated synergy with fluconazole against 60 percent of all clinical isolates, with posaconazole against 51 percent of clinical isolates and with voriconazole against 53 percent of clinical isolates.
MGCD290 is an orally available, small molecule inhibitor that targets the fungal Hos2 enzyme. This compound was designed to be used in combination with azoles, a widely-prescribed class of drugs for the treatment of fungal infections. MGCD290 appears to potentiate and broaden the antifungal spectrum of azole activity against human fungal pathogens, including azole-resistant isolates.
The demand for more effective antifungals is driven by a rising incidence of invasive fungal infections in immunocompromised patients such as surgical patients, organ transplant patients and cancer patients undergoing chemotherapy or bone marrow transplants. Due to these more aggressive medical interventions, the frequency of invasive fungal infections has increased in this expanding patient population. Current antifungal agents are limited by an inadequate spectrum of activity, toxicities, drug-drug interactions and drug resistance. Emerging infections caused by certain Candida and Aspergillus species are particularly difficult to treat in immunocompromised patients and are associated with significant morbidity and mortality.
MethylGene Inc. (TSX: MYG) is a publicly-traded, clinical stage, biopharmaceutical company focused on the discovery, development and commercialization of novel therapeutics for cancer. The Company’s product candidates include: MGCD265, an oral, multi-targeted kinase inhibitor targeting the c-Met, Tie-2, Ron and VEGF receptor tyrosine kinases which is in Phase I clinical trials for solid tumor cancers; MGCD290, a fungal Hos2 (HDAC) inhibitor used in combination with azoles for fungal infections which is also in a Phase I clinical trial; and MGCD0103, an oral, isoform-selective HDAC inhibitor which has been in multiple clinical trials for solid tumors and hematological malignancies and is licensed to Taiho Pharmaceutical. MethylGene’s development and commercialization partners include Taiho Pharmaceutical Co. Ltd., Otsuka Pharmaceutical Co. Ltd. and EnVivo Pharmaceuticals. 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, 2007, 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.
Contacts: Rx Communications Group, LLC Rhonda Chiger Investor Relations 917-322-2569 [email protected] MethylGene Inc. Donald F. Corcoran President & CEO 514-337-3333 ext. 373 [email protected]www.methylgene.com.
SOURCE: MethylGene Inc.