Rib-X Pharmaceuticals, Inc., a development-stage antibiotics company with a broad product pipeline based on its innovative discovery platform, today announced the presentation of positive preclinical data for radezolid at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) conference.
Radezolid is a novel oxazolidinone that was designed, using Rib-X’s proprietary discovery process, to have a broader spectrum of coverage and increased activity against Gram-positive organisms as compared to other oxazolidinones.
According to details from the poster presentations, radezolid demonstrated its ability to attain antibacterial levels, reduce bacterial burden and prevent bacterial rebound in a preclinical study of methicillin-resistant Staphylococcus aureus (MRSA) infection, as well as its ability to overcome the main cause of linezolid resistance.
“Enhanced Oxazolidinones Modulate the Binding of P-site tRNA Substrate to the 50S Ribosomal Subunit.”
“The results of these studies are consistent with prior studies of radezolid, which demonstrated that the drug concentrates in immune cells and is preferentially delivered to the site of infection,” said Scott Hopkins, M.D. the Chief Medical Officer at Rib-X. “We also confirmed, using our X-ray crystal structure analysis, that radezolid targets ribosomal binding sites that are uncovered by linezolid. These attributes offer several potential therapeutic benefits, including enhanced MRSA coverage and greater potency than linezolid with broader spectrum of activity.”
“Radezolid was shown to be safe and effective with a once-daily oral dosing regimen in two completed Phase 2 studies and we believe that the positive profile that Rib-X has illustrated for radezolid positions it well as a best-in-class oxazolidinone with enhanced coverage, safety and dosing. The next key step for the development of radezolid is the initiation of the Phase 1 study with intravenous formulation later this year,” said Mark Leuchtenberger, President and Chief Executive Officer at Rib-X.
The first study compared in vivo cell and plasma concentrations of radezolid and linezolid in a common preclinical mammalian model of MRSA infection. Results demonstrated that radezolid concentrations within cells reached a steady state within the first 24 hours and that this level was maintained through 96 hours, even as concentrations in the plasma decreased upon therapy withdrawal.
Importantly, no bacterial rebound was observed in cells treated with radezolid. In comparison, linezolid concentrations in the cells decreased with the plasma concentrations upon therapy withdrawal and bacterial levels rebounded accordingly.
Radezolid’s ability to accumulate specifically within infected cells and maintain antibacterial levels without fluctuations in drug level may reduce the potential for drug failure and the development of bacterial resistance.
The poster presentation “Evaluation of Radezolid against a Methicillin-Resistant Staphylococccus aureus Rat Granuloma Pouch Infection” was authored by A. Marra, E. Bortolon, D. Molstad, Y. Wu, H. Jing, and E. Burak.
The second study shows that radezolid is effective against linezolid-resistant bacteria featuring CFR-methylated ribosomes and offers atomic-level insights into why this is the case. The poster presentation “Radezolid Overcomes CFR-Mediated Linezolid-Resistance by Efficiently Inhibiting Protein Synthesis on CFR-Methylated Ribosomes” was authored by F. Franceschi, J. DeVito, J. Dalton, J. Remy, E. Skripkin, J. Ippolito, and E. Duffy.
Additionally, Rib-X will present at ICAAC on September 13, 2010 a poster presentation “Enhanced Oxazolidinones Modulate the Binding of P-site tRNA Substrate to the 50S Ribosomal Subunit.” This poster demonstrates clearly the power of their structure-based approach in designing novel antibiotics, including radezolid.
Source : Rib-X Pharmaceuticals, Inc.