Rib-X presented data demonstrating potent activity against multi-drug resistant Gram-negative and Gram-positive bacteria for its clinical candidates, radezolid and delafloxacin, and for its preclinical development program, RX-04 features pipeline candidates at a recent conference.
The company described the efficacy of sample compounds from each of the three families of protein synthesis inhibitors from the RX-04 program when tested in three in vivo models of Gram-negative and Gram-positive infections. Bacterial burden reduction in all three models was exhibited with at least one compound, and a number of compounds were highly effective in the two Gram-negative infection models.
Rib-X also presented data confirming the novel classes directly impact ribosome function and exert their antibacterial activity by interfering with protein synthesis.
The inhibition of protein synthesis via different mechanisms is a common antibacterial strategy; however, Rib-X’s proprietary knowledge of the ribosome allowed the identification of a site for de novo design that has not been exploited by marketed ribosome inhibitors and is remote from sites of known target-based resistance.
The RX-04 program resulted in multiple series of compounds with activity against Gram-positive and Gram-negative infections resistant to most antimicrobial agents currently used in the clinic.
Delafloxacin was shown to be superior to multiple antibiotics currently used as standards of care for the treatment of MRSA infections, including levofloxacin.
Radezolid demonstrated 2 to 16-fold greater potency compared to torezolid against a collection of Gram-positive bacteria with genetically defined mechanisms of oxazolidinone resistance, including CFR mutants.
Release Date: May 9, 2011
Filed Under: Drug Discovery