MethylGene: azoles kill more drug-resistance fungus with addition of MG3290

By Angela McDaniels

Seattle, Dec. 16 - MethylGene Inc. said preclinical study results demonstrate that a lower dose of azoles, common antifungal drugs, is needed to treat infections when combined with MG3290, the company's isotype-selective histone deacetylase (HDAC) inhibitor.

During in vivo and in vitro studies, MethylGene said it found that:

• MethylGene's HDAC inhibitor enhances the azole susceptibility of otherwise drug-resistant fungi.

• MG3290, when co-administered with ketoconazole, significantly decreases the extent of fungal infection and increases animal survival in a dose-dependent manner.

• The development of resistance to azole anti-fungal drugs may occur by an HDAC mediated mechanism.

• MethylGene's inhibitors may be more selective for fungal HDACs than for the human ones, an important therapeutic prerequisite.

The data was presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy in Washington, D.C.

"We believe that our compounds specifically target fungal HDACs. This means that we may be able to develop a therapeutic allowing current azoles to be more effective," president and chief executive officer Donald F. Corcoran said in a company news release.

"These experiments further validate our approach of discovering and developing novel HDAC isotype-selective inhibitors. We continue to aggressively push this program forward with the goal of identifying a clinical candidate over the next 12 to 18 months."

Serious infections with yeasts and other fungi often occur in hospital settings as a complication in immunocompromised patients, the company said. Resistance to azole anti-fungal medications and resistance is an increasing problem.

Infections caused by candida and aspergillus are especially common and difficult to manage medically. Aspergillosis has a high mortality rate and is an underserved market, the company said. In 2004, the market of systemic anti-fungal drugs was estimated to be $5 billion worldwide with azole sales being a major contributor to that market.

MethylGene is a biopharmaceutical company based in Montreal that develops therapeutics for cancer and infectious diseases.

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