CF-370 is an engineered lysin therapeutic candidate with potent activity against Pseudomonas aeruginosa (“P. aeruginosa”). As native lysins are typically unable to penetrate the outer membrane of gram-negative bacteria and consequently unable to work in vitro in human blood or in animal models, CF-370, to our knowledge, represents the first lysin to bypass the outer membrane of P. aeruginosa and to enable potent activity in human serum. Furthermore, CF-370 has exhibited the hallmark in vitro features of the lysin class, including rapid and potent bactericidal activity, synergy with a broad range of standard of care agents and the eradication of biofilms in preclinical studies.
The activity of CF-370 was studied against multi-drug resistant P. aeruginosa in multiple preclinical animal models. In a rabbit pneumonia model, CF-370 was well-tolerated and conferred a survival advantage to animals with 100% survival compared to only 40% survival among vehicle control animals. In animals receiving either meropenem or CF-370 alone, the mean bacterial lung counts decreased by 1.5-2log10 CFU/g versus pretreatment or vehicle-treated controls (p≤0.0016). CF-370 (10 mg/kg) in addition to meropenem was synergistic, with bacterial counts in all target tissues decreasing by an additional 2log10 CFU/g versus meropenem or CF-370 alone (p≤0.02). In a rabbit infective endocarditis model, CF-370 administered as either a single dose or in multiple doses was again well-tolerated. Activity against cardiac vegetations, with dense biofilm, the 3 days of CF-370 dosing at 10 mg/kg in addition to meropenem provided >2-log CFU reduction vs meropenem alone (p=0.0007). In other target organs – kidney, spleen and lungs – CF-370, at all doses, in addition to meropenem provided significantly more killing than meropenem alone, from 0.6 to 2.2log10 additional CFU reduction (p≤0.0053).
In July 2020, ContraFect was awarded a grant from the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) to support the development of CF-370 to treat infections caused by P. aeruginosa for funding up to $18.9 million.
Rapid Action of Cf-370
We utilized scanning electron microscopy to capture the rapid bactericidal activity of CF-370 against P. aeruginosa.
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.
For all of these reasons, P. aeruginosa is considered a critical priority by the World Health Organization and a serious threat by the Centers for Disease Control and Prevention.
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