       RadezolidRadezolid—a next-generation, IV/oral oxazolidinone designed to meet the need for a potent antibiotic with a safety profile permitting long-term treatment of resistant infections, including MRSA.
Development Stage
Description
Radezolid is a novel oxazolidinone designed using Rib-X's proprietary drug discovery process. Oxazolidinones are a class of synthetic antimicrobial agents which inhibit protein synthesis within bacterial targets. Radezolid was specifically designed to have a broader spectrum of coverage, enhanced potency and improved safety compared to other oxazolidinones. While not yet tested for long-term use in humans, we have completed a 90-day animal toxicology study of radezolid which showed that radezolid was safely tolerated for the full 90 days at the maximum dose, which dose was 12 times greater than the efficacious dose used in humans for shorter-term studies. In preclinical and clinical studies, radezolid has been shown to concentrate in immune cells and to have preferential delivery to sites of infection. Radezolid has also demonstrated the ability to attain antibacterial levels, reduce bacterial burden and prevent bacterial rebound in methicillin-resistant Staphylococcus aureus (MRSA) infection and has been shown to overcome linezolid resistance.
Status
Radezolid successfully completed two Phase 2 studies and a Phase 1 intravenous (IV) toleration study to enable IV/oral switch for upcoming Phase 3 studies. The Phase 1 study was completed in the second half of 2011. In both oral Phase 2 studies, radezolid was shown to be safe and effective with a once-daily dosing regimen. We expect future clinical development of radezolid to involve an additional Phase 2 study in acute bacterial skin and skin structure infections with the IV formulation and a long-term Phase 1 safety study with the oral formulation.
Recent Data
At ICAAC 2010, data were presenteddemonstrating 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. 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. A second study showed that radezolid is effective against most forms of linezolid-resistant bacteria including the CFR mutants and offers atomic-level insights into why this is the case.
At ECCMID 2011, data were presented comparing the potency of radezolid to that of the only marketed oxazolidinone, linezolid, and another investigational oxazolidinone, torezolid, against a collection of Gram-positive bacteria with genetically defined mechanisms of oxazolidinone resistance, including target-based resistance and CFR mutants. While radezolid and torezolid both demonstrated enhanced activity against the collection's 90 strains compared to linezolid, radezolid demonstrated two- to 16-fold greater potency against the resistant strains in this panel compared to torezolid.
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