SAN FRANCISCO, Sept. 12, 2012 (GLOBE NEWSWIRE) -- ICAAC 2012 -- Trius Therapeutics, Inc. (Nasdaq:TSRX), a biopharmaceutical company focused on the discovery, development and commercialization of innovative antibiotics for life-threatening infections, today announced preclinical studies related to a new class of broad-spectrum, gram-negative antibacterial agents that are directed against novel targets Gyrase B (GyrB) and ParE. Trius scientists and research collaborators are presenting the results at the 52 nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) meeting being held in San Francisco from September 9-12, 2012. Fourteen posters and one podium presentation related to the company's GyrB/ParE preclinical program are being featured, including both in vivo and in vitro studies.
Currently there are no antibiotics in clinical use that inhibit both GyrB and ParE—two microbial enzymes essential for the replication of bacteria. As a result of the crisis of increasing bacterial resistance, there is an urgent need for new antibiotics, especially those active against common clinical infections caused by gram-negative pathogens. However, the development pipeline of gram-negative agents to replace resistant therapies is limited. Treatment of gram-negative bacterial infections can be difficult, because of the pathogen's double cell membrane, efflux pumps and ability to quickly mutate to develop resistance. As of 2011, the Centers for Disease Control and Prevention estimates that roughly 1.7 million hospital-associated infections, from all types of bacteria, cause or contribute to 99,000 deaths each year.
The data abstracts examine the effect of Trius' antibacterial agents against a panel of gram-positive and gram-negative pathogens. The results show significant potency in treating challenging gram-negative bacteria associated with hospital-acquired infections, such as Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumonias, and biodefense pathogens such as Yersinia pestis (plague), Francisella tularensis, Burkholderia mallei and Burkholderia pseudomallei.As reported in the presentations, Trius' antibacterial agents exhibit bactericidal (bacteria-killing) activity, low minimum inhibitory concentrations (MICs), and reduced emergence of bacterial resistance versus comparators such as ciprofloxacin. The compounds' dual-targeting mechanism may impair bacteria's ability to develop resistance, as suggested by previous studies. 1,2 These dual-inhibitor agents also avoid cross-resistance with established antibiotic classes, including the fluoroquinolones. This is consistent with the fact that the compounds bind to different subunits of DNA gyrase and topoisomerase IV than current antibiotics, such as fluoroquinolones. "The preclinical studies demonstrate potent activity against gram-negative pathogens, supporting the continued development of broad-spectrum antibiotics targeting GyrB and ParE," said Jeff Stein, President and Chief Executive Officer at Trius Therapeutics. "Since the discovery of quinolones in the 1960s, we believe this is the first new chemical class of antibiotics with potent activity against a wide range of gram-positive and gram-negative bacteria. The emergence of multi-drug resistant infections underscores the need for unique antibacterial agents. Based on the encouraging results, we look forward to submitting an Investigational New Drug (IND) application and anticipate initiating a Phase 1 trial in 2013."