CRS3123 for C. difficile Overview

Clostridium difficile infection (CDI) is a gastrointestinal condition caused by toxin-producing strains of C. difficile bacteria. CDI symptoms range from severe diarrhea to toxic megacolon. C. difficile forms spores that are very difficult to eliminate from the hospital environment, leading to infection of hospitalized patients. Emergence of hypervirulent and drug-resistant strains of C. diff has resulted in an alarming increase in incidence and mortality of CDI in the past 15 years, especially among elderly patients. C. difficile is found in abundance in the environment, so exposure to this resilient, spore-forming pathogen can be presumed to be both continuous and unavoidable. Under normal circumstances, healthy gut microbiota keeps C. diff growth in check. Disruption of gut microbiota due to exposure to broad spectrum antibiotics or chemotherapy predisposes the patient to CDI. Vancomycin and fidaxomicin are the only approved antibiotics for C. diff treatment. Paradoxically, vancomycin is also one of the broad-spectrum antibiotics that is known to induce CDI due to disruption of normal gut microbiota.

About CRS3123

CRS3123 is a small molecule protein synthesis inhibitor that acts on the novel target methionyl-tRNA synthetase (MetRS). CRS3123 has numerous potential advantages over current CDI therapies.

• Highly potent against all clinical isolates of C. difficile;
• Narrow spectrum for C. difficile, which may substantially reduce the disruption of normal intestinal microbiota compared to current therapies;
• Inhibition of toxin production, potentially leading to lower morbidity and mortality, and faster resolution of symptoms;
• Inhibition of sporulation, potentially leading to lower rates of transmission and recurrence;
• Novel mechanism of action, which means that its use will not compromise the utility of systemic antibiotics (eg. vancomycin).