BioWorld International Correspondent

PARIS - Mutabilis, developing new drugs to fight nosocomial infections, raised €8 million in its second funding round.

The financing was led by Auriga Partners, of Paris, one of two first-time investors, along with the French bank Crédit Lyonnais. The venture capital funds that provided Mutabilis with its initial funding of €2.2 million in mid-2002 - Bioam (managed by Biogestion SA), Axa Private Equity and Inserm-Transfert, all of Paris - also participated.

Founded in 2001 and based in Paris, Mutabilis now has funds to continue its drug discovery activities for the next three years. Its priorities are to strengthen its work force, especially in the area of medicinal chemistry, with a goal to initiate clinical trials in 2007.

CEO Stéphane Huguet told BioWorld International that the company employs 14 staff members and plans to expand its work force to 20 by early 2005. Mutabilis is housed in the Necker Medical School in central Paris, but Huguet said it would move to independent premises at the Biocitech biotechnology research and business park in the Paris suburb of Romainville in the fourth quarter.

Mutabilis is conducting research into antibacterial agents to identify and develop anti-infective molecules that can selectively prevent bacteria from multiplying and spreading through the bloodstream and extracellular fluids, while at the same time allowing useful bacteria to proliferate in sites that are their natural home, such as the skin and the intestines. It said those compounds have therapeutic potential for treating nosocomial (hospital-acquired) infections that are resistant to existing anti-infective drugs.

The company stressed the difference between its "anti-virulence" approach and antibiotics, which are designed to eliminate bacteria wherever they are found. It said the indiscriminate elimination of bacteria is responsible for many cases of resistance to antibiotics and has created an environment that is favorable to the development of nosocomial infections.

The company's virulence-based approach combines genomics with the physiopathological analysis of bacterial infections. The first step is identifying genes that code for factors needed for bacterial dissemination into the host and for the virulence factors that are common to pathogenic strains. Next is validating those factors as new targets for inhibition, and then developing them as antibacterial compounds.

Mutabilis said virulence-based drugs wouldn't kill the bacteria that compose normal flora. They would be active against multi-resistant strains, and by being more specific and not targeting essential functions, they would be less likely to induce resistance.

Mutabilis focuses on gene products necessary for bacterial dissemination into the host. By using whole-genome mutagenesis, Mutabilis has identified and patented several enzymes as targets for that approach. Its ongoing drug discovery programs are aimed at finding small-molecule inhibitors of validated targets.

"We have already shown proof of concept for this antivirulence approach using mutant bacteria," Huguet said. "By targeting just the bacteria responsible for an infection, while leaving unharmed the intestinal flora and bacteria living in natural sites, Mutabilis' technology aims to allow widespread use of anti-infective agents in situations where physicians cannot today use antibiotics because of the development of bacterial resistance."

Huguet said the company's virulence program was aimed at developing two sets of products, one targeting infections caused by Gram-positive pathogens and the other infections caused by Gram-negative pathogens. It aims to discover and patent one Gram-negative and one Gram-positive specific new chemical entity and take the two molecules into Phase I trials by 2007.

Also, Mutabilis is developing a prophylactic vaccine against the pathogen Escherichia coli. The vaccine would prevent certain nosocomial infections of the gastrointestinal tract in patients with various types of immunodeficiency, as well as the prevention of severe urinary tract infections. That type of vaccine could be combined with vaccines against other bacteria that cause nosocomial infections.

To finance its activities from 2007 on, including the clinical development of its two drug candidates, Huguet said Mutabilis has the choice of either arranging a third private financing or partnering with a larger biopharmaceutical company.

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