Replidyne's Investigational Antibacterial Agent REP3123 Prevents Sporulation In Clostridium Difficile

Main Category: GastroIntestinal / Gastroenterology
Also Included In: Infectious Diseases / Bacteria / Viruses;  Clinical Trials / Drug Trials;  Pharma Industry / Biotech Industry
Article Date: 20 Sep 2007 - 0:00 PDT

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Replidyne, Inc. (Nasdaq: RDYN) announced that in preclinical studies, its antibacterial candidate REP3123 is shown to inhibit growth and prevent spore-forming of the Gram-positive Clostridium difficile (C. difficile) bacterium without inhibiting other key organisms that are essential for normal intestinal functioning. C. difficile-associated disease (CDAD), a major cause of morbidity among the elderly and hospitalized patients, is acquired by ingesting spores present in the environment that then grow and multiply in the gut. In preclinical studies, REP3123 was superior to two agents widely used to treat C. difficile infections, vancomycin and metronidazole, in preventing the organism from forming spores. The study results suggest that REP3123 has the potential to reduce the presence of spores in the intestine, subsequently preventing dissemination into the environment, thereby potentially reducing outbreak and relapse rates.

These results will be presented on Thursday, September 20, 2007 at 10:00 AM in Room E253D by Ian A. Critchley, Ph.D., Executive Director, Microbiology at Replidyne during poster session 229 titled, "New Agents Active Against Clostridium difficile" at the 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy held at the McCormick Place conference center in Chicago.

REP3123 is a new narrow spectrum antibacterial agent that in vitro prevents the growth of C. difficile by inhibiting an essential enzyme in the bacterial cell called methionyl tRNA synthetase, which blocks the organism from synthesizing proteins. Methionyl tRNA synthetase is a novel target that has not been previously exploited by antibiotics and REP3123 shows no cross-resistance to currently marketed antibacterial agents. To determine the ability of REP3123 to prevent sporulation of C. difficile, four clinical isolates were studied including two epidemic BI/NAP1/027 strains identified in recent outbreaks in Quebec, Canada. The BI/NAP1/027 outbreak strains produce greater amounts of toxins A and B, have increased sporulation capacity, and cause more severe disease and increased morbidity and mortality. All bacterial strains were grown in the presence of low concentrations (sub-minimum inhibitory concentrations or MICs) of either REP3123, vancomycin or metronidazole. Spores were quantified after 96 hours of drug exposure. All four strains of C. difficile varied in their ability to produce spores under the conditions evaluated in this study. At 0.5 times the MIC, REP3123 was the most effective agent at preventing the production of spores in all strains (equal to or less than 1% of spores after 96 hours of treatment). In contrast, sub-MICs of metronidazole promoted spore formation in three strains and vancomycin promoted sporulation in two strains. The ability of REP3123 to inhibit sporulation was concentration-dependent, with no spores detected at concentrations of 0.5 times the MIC. The FDA has not approved REP3123 for marketing in this or any other indication.

"CDAD is a challenging disease for many reasons, including the difficulty associated with eradication of Clostridium difficile and its spores from the environment," explained Stuart Johnson, M.D., Associate Professor of Medicine, Stritch School of Medicine, Loyola University and the Hines VA Medical Center in Chicago. "These results demonstrating that REP3123 has a direct impact on inhibiting spore-formation of C. difficile bacteria are highly promising and clinically relevant."

"Through a novel mechanism of action that inhibits growth and targets both sporulation and toxin production, REP3123 could be a future treatment option that tackles the main challenges associated with treating CDAD: high rates of relapse and new outbreaks," stated Kenneth J. Collins, Replidyne's President & CEO. "We are excited by the potential of REP3123 and look forward to its further development."

About Clostridium difficile

C. difficile is a Gram-positive anaerobic bacterium that causes C. difficile-associated disease (CDAD). According to the Centers for Disease Control and Prevention, CDAD is on the rise worldwide, both in terms of number of cases and severity of the disease. Most cases of CDAD occur in a hospital setting due to increased use of antibiotics and other chemotherapeutics that disrupt normal intestinal flora, an ageing population, and difficulty of eradicating C. difficile spores. However, more recently, CDAD has been acquired in the community setting where several outbreaks with increased mortality have occurred. The emergence of an epidemic, hypervirulent C. difficile strain (BI/NAP1, 027) that produces high levels of toxins poses a real threat to public health and demands improved infection control as well as novel treatment options.

About Replidyne, Inc.

Replidyne is a biopharmaceutical company focused on discovering, developing, in-licensing and commercializing innovative anti-infective products. Replidyne's lead product, faropenem medoxomil, is a novel oral, community antibiotic, expected to be appropriate for use as a first-line antibiotic for treatment of respiratory and skin infections in adult and pediatric patients. Replidyne's second drug candidate, REP8839, is a topical anti-infective product candidate in development for the treatment of skin and wound infections, including methicillin-resistant S. aureus (MRSA) infections. Replidyne's investigational antibacterial agent REP3123 targets Gram-positive C. difficile bacteria and related diseases. In preclinical studies, REP3123 has been show to inhibit growth, toxin production and spore-forming in C. difficile bacteria. Replidyne is also pursuing the development of other novel anti-infective programs based on its in-house discovery research.

Safe Harbor

This press release contains plans, intentions, objectives, estimates and expectations that constitute forward-looking statements about Replidyne, Inc. that involve significant risks and uncertainties. Actual results could differ materially from those discussed due to a number of factors including, the success and timing of pre-clinical studies and clinical trials; the Company's ability to obtain a new partner for faropenem on acceptable terms; the Company's ability to obtain and maintain regulatory approval of product candidates and the labeling under any approval that may be obtained; plans to develop and commercialize product candidates; the loss of key scientific or management personnel; the size and growth of the potential markets for the Company's product candidates and the Company's ability to serve those markets; regulatory developments in the U.S. and foreign countries; the rate and degree of market acceptance of any future products; the accuracy of Company estimates regarding expenses, future revenues and capital requirements; the Company's ability to obtain and maintain intellectual property protection for our product candidates; the successful development of the Company's sales and marketing capabilities; the success of competing drugs that are or become available; and the performance of third party manufacturers. These and additional risks and uncertainties are described more fully in the Company's most recent Form 10-Q filed with the SEC under the Securities Exchange Act of 1934. Copies of filings made with the SEC are available through the SEC's electronic data gather analysis and retrieval system (EDGAR) at http://www.sec.gov. All forward-looking statements made in the press release are made as of the date hereof and the Company assumes no obligation to update the forward-looking statements in the document.

Replidyne, Inc.
http://www.replidyne.com