ContraFect 370
ContraFect 370
OVERVIEW
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.
