CBR-2092, a rifamycin-quinolone hybrid antibiotic, has been evaluated in two Phase 1 human studies.  Based on data from animal models, CBR-2092 represents a unique agent for the treatment of a variety of staphylococcal infections that are recalcitrant to current antibiotic therapy including infections of indwelling medical devices. 

R-3-[(4-{1-[l-(3-Carboxy-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4H-quinolizine-8-yl)-pyrrolidin-3-yl-cyclopropyl]-methylamino}-piperidin-1-ylimino)-methylenyl]-rifamycin SV 

CBR-2092 is being developed for the treatment of serious or life-threatening bacterial infections including pathogens that have developed or acquired resistance to commonly used antibiotics. Key target pathogens for CBR-2092 include members of the staphylococci, streptococci and pneumococci genera that exhibit resistance or reduced susceptibility to currently marketed antibacterial agents. Potential uses in the hospital setting include treatment of complicated skin and skin structure infections and other acute infectious disease syndromes, including those mediated by multi-drug resistant (MDR) pathogens. 

CBR-2092 has activity in vitro against both rapidly dividing cells in planktonic culture and also against non-dividing populations in the stationary phase of growth. In addition, CBR-2092 exhibits significant activity in vitro against bacteria growing in the biofilm state that has been associated with a number of persistent and latent infections in humans. CBR-2092 exhibits promising activity in animal models of biofilm-associated foreign body infections, and the agent may have clinical utility in the treatment of indwelling medical device related infections for which existing therapeutic options are limited (Waldvogel and Bisno (Eds), 2000).  Additional biofilm-associated infections for which CBR-2092 may have clinical utility include infective endocarditis, necrotizing fasciitis, muscle skeletal infections, and osteomyelitis (Pace, Rupp et al. (Eds), 2006).

Profile of CBR-2092

In Vitro

In Vivo

CBR-2092 exhibits dose-dependent and predictable intravenous PK properties: 

• AUC0-24 hrs was identified as the PK-PD parameter best correlated with efficacy

CBR-2092 exhibits efficacy in rodent models of skin and soft tissue infections: 

• Efficacy equivalent to, or improved over, SSTI comparator agents.

 CBR-2092 exhibits efficacy in a rabbit model of MRSA endocarditis:

• Efficacy endpoints superior to vancomycin and rifampin+quinolone cocktails

• No resistance development observed for CBR-2092

CBR-2092 exhibits efficacy in models of biofilm-associated device infections:

• Models:
  • Mouse catheter implant model
  • Rat central venous catheter infection model

• Efficacy profile of CBR-2092 superior to all tested comparators

• No resistance development observed for CBR-2092

Clinical Studies

Following successful completion of IND-enabling activities, an IND application for CBR-2092 was submitted in May 2006 and Phase 1 studies were initiated in June 2006.  The first-in-human study (CBR-2092-001) evaluated the safety, tolerability and pharmacokinetics of single intravenous doses of CBR-2092 in the 10 to 400 milligram range.  CBR-2092 was judged to be generally safe and well tolerated and the corresponding study report is available to interested parties under CDA.  A second Phase 1 study (CBR-2092-002) was completed in which the safety, tolerability and pharmacokinetics of multiple intravenous doses of CBR-2092 was evaluated.  In this study, subjects received up to thirty doses of 50, 100 or 300 milligrams of CBR-2092 over a period of 17 days with q12 hour dose administration on days 3 to 16.