The focus of our research and discovery efforts is on identifying and engineering lysins which selectively kill specific species of Gram-negative bacteria. Emerging strains of multi-drug resistant (MDR) Gram-negative pathogens that are resistant to all or nearly all available antibiotics are considered to be urgent or serious health threats by global health authorities. We believe that lysins which target Gram-negative pathogens have the potential to be important therapeutics to combat antimicrobial resistance due to their novel mechanism of action and therapeutic profile, which is complimentary to conventional antibiotics. We have initially focused on Pseudomonas aeruginosa (P. aeruginosa) and identified candidates with potent in vitro activity against P. aeruginosa and continue to screen and characterize candidates targeted against additional gram-negative pathogens such as Escherichia coli, Enterobacter cloacea, and Klebsiella pneumoniae. In March 2017, ContraFect was awarded a $2.1 million grant from the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) to support the development of lysins to treat infections caused by P. aeruginosa.
Infections caused by MDR Gram-negative pathogens result in greater all-cause mortality, in-hospital mortality and length of hospitalization. For example, MDR P. aeruginosa infections increase in-hospital mortality by more than 5x and length of hospitalization by more than 2x compared to susceptible isolates. Like CF-301, Gram-negative targeted lysins should act faster than and synergistically with SOC antibiotics, have a specific spectrum of activity that spares the healthy microbiome, and rapidly clear biofilms.
Pseudomonas aeruginosa (P. aeruginosa)
Invasive P. aeruginosa infections, including ventilator associated pneumonia, blood stream infections, complicated urinary tract infections, and infections following surgery carry some of the highest risks of mortality among hospital acquired infections. An estimated 51,000 healthcare-associated P. aeruginosa infections occur in the United States each year.
P. aeruginosa is also the most common pathogen isolated from adults with cystic fibrosis, the most common cause of respiratory failure in cystic fibrosis and responsible for the deaths of the majority of these patients.
The Enterobacteriaceae family of gram-negative bacteria includes Klebsiella pneumoniae (K. pneumoniae), Enterobacter species (Enterobacter e.g. Enterobacter cloacae) and Escherichia coli (E.coli), all of which can cause serious, life-threatening infections, and have demonstrated concerning resistance patterns.
For example, K. pneumoniae are common causes of serious, potentially life-threatening pneumonia, complicated urinary tract and intra-abdominal infections in hospital settings, particularly in intensive care units and among vulnerable patients with impaired immune systems, diabetes or alcohol-use disorders. The mortality rates for hospital-acquired pneumonia due to K. pneumoniae can exceed 50% in vulnerable patients.
CF-301 is a lysin being studied for the treatment of Staph aureus bacteremia, including endocarditis, caused by MRSA or MSSA.View CF-301 »