Rib-X Pharmaceuticals, Inc., a development-stage company focused on the discovery, development and commercialization of novel antibiotics for the treatment of acute-care antibiotic-resistant infections, announced that one of its discovery-stage programmes has yielded several computationally designed series of chemically unique compounds demonstrating efficacy in the treatment of infection in animal models.
The R?-04 discovery programme is focused on the development of novel classes of antibiotics active against serious, rapidly emerging multi-drug resistant Gram-negative bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii. The company has built five chemical scaffolds, some of which have demonstrated activity against both Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Data from an earlier, related programme will be presented during a poster session at the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in San Francisco.
"In less than one year, our structure and computationally driven research engine has engineered a variety of new lead scaffolds that appear to exhibit promising activity in mice, good drug-like properties and good safety in early tests, in addition to varied profiles against MDR Gram-negative pathogens in vitro ," said Susan Froshauer, Ph. D., President and CEO of Rib-X Pharmaceuticals. "The success we've seen to date with our later clinical stage antibiotic compounds, radezolid and delafloxacin, along with the immense progress made on the R?-04 programme, underscores the strength and diversity of the growing Rib-X pipeline."
The R?-04 programme employs a de novo approach to develop novel antibiotics that are active against Gram-negative bacteria. This program exploits the peptidyl transferase region of the 50S subunit, which is the catalytic region of the ribosome and the binding site of many chemically distinct classes of antibiotics, including oxazolidinones (e.g., linezolid), lincosamides (e.g., clindamycin), phenyl propanoids (e.g., chloramphenicol), pleuromutilins (e.g., retapamulin) macrolides/ketolides (e.g., azithromycin) and sparsomycin. Rib-X has created five completely novel series of compounds targeting two novel sites that show good antibacterial activity against a number of clinically important multi-drug resistant Gram-negative pathogens.