Replidyne, Inc.'s Investigational Antibacterial Agent REP3123 Prevents Toxin Production in Clostridium difficile
LOUISVILLE, Colo., Sept. 19 /PRNewswire-FirstCall/ -- Replidyne, Inc. announced today that in preclinical studies, its antibacterial candidate REP3123 is shown to stop the production of destructive intestinal toxins caused by Clostridium difficile (C. difficile) bacteria. C. difficile-associated disease (CDAD), an inflammatory condition caused by potentially lethal toxins that enter and then kill healthy cells in the gut, is a major cause of morbidity among elderly and hospitalized patients. The study results suggest that REP3123 inhibits growth and blocks the production of these disease-causing toxins potentially reducing the severity of, and even preventing, CDAD.
These results will be presented on Thursday, September 20, 2007 at 10:00 AM in Room E253D by Urs Ochsner, Ph.D., Principal Scientist, 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. When tested in high density cultures, REP3123 inhibited toxin production at low concentrations (< 1 ug/mL) for all C. difficile strains tested. In contrast, widely used agents such as vancomycin and metronidazole did not reduce toxin production in these high density cultures even at drug concentrations well above those required to inhibit growth of the bacteria. The levels of toxins were monitored by immunoassays using antibodies that specifically recognize two disease-causing factors, toxin A and toxin B. The dramatic reduction in the deleterious effects of the toxins was directly demonstrated by the gold standard cytotoxicity assay, which uses human fibroblasts to confirm the ability of REP3123 to block toxin production. The FDA has not approved REP3123 for marketing in this or any other indication.
"CDAD is a challenging disease because of the difficulty in managing patients with severe manifestations as well as the problem of recurrence in those patients who recover from the initial episode. As the disease is primarily toxin-mediated, new therapies that act by means other than simply eradicating the bacteria may be very helpful and should be studied," stated Stuart Johnson, M.D., Associate Professor of Medicine, Stritch School of Medicine, Loyola University and the Hines VA Medical Center in Chicago. "The finding that REP3123 has a direct impact on inhibiting toxin production of C. difficile bacteria is very important and equally as exciting."
"C. difficile-associated diseases have become a serious health matter in both the hospital and community settings," stated Kenneth J. Collins, Replidyne President & CEO. "These results, along with the sporulation-inhibition findings also reported today, are very encouraging and we look forward to the further development of REP3123."
About Clostridium difficile
C. difficile is a Gram-positive anaerobic bacterium that causes C. difficile-associated disease (CDAD). 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.
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.
CONTACT: Sabrina B. Oei, Dir. Investor & Public Relations of Replidyne,+1-303-996-5535
Web site: http://www.replidyne.com/