ContraFect has been awarded to $18.9 million by the nonprofit investment group CARB-X to advance CF-370 as a potential treatment for Pseudomonas aeruginosa infections. These bacteria and the thick layer of biofilm they produce are a major cause of pulmonary exacerbations in cystic fibrosis (CF) patients.
CARB-X, which stands for Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator, launched in 2016 as a global partnership working to accelerate development of new antibiotics to address the rising challenge of drug-resistant bacteria.
The funding includes an initial commitment of $4.9 million, plus up to $14 million pending the attainment of milestones.
It follows two additional CARB-X grants recently given to ContraFect: a $3.4 million investment in the company’s lysin program (which includes CF-370) to treat antibiotic-resistant P. aeruginosa infections, and up to $6.9 million in funding to support studies in therapeutic peptides — amurins — against antibiotic-resistant bacterial infections with ESKAPE pathogens.
“We thank CARB-X for their support over the past three years which brought our Gram-negative lysin discovery program to this important milestone and underscores the power of our productive public-private partnership,” Cara Casino, MD, executive vice president of Research & Development and chief medical officer of ContraFect, said in a press release.
“We look forward to progressing CF-370 through [investigational new drug] enabling activities towards the clinic with CARB-X’s support,” she added.
ContraFect is focused on developing a new class of biological agents called direct lytic agents, which include two kinds of viral derived products — lysins and amurins. Essentially, lysins such as CF-370 are enzymes that bind to and digest the bacterial wall, rapidly killing these pathogens.
Unlike common antibiotics, which require bacterial cell division or metabolism to be effective, lysins are seen to require only contact with the bacterial cell wall to eliminate pathogens. This makes lysins up to 18 times faster than standard antibiotics at killing bacteria, the company reports on its website.
These agents are also said to be able to clear biofilms produced by bacteria; these films form a protective layer that keeps antibiotics and immune components from reaching the bacteria. ContraFect also states that lysins have low propensity for acquired resistance and work in synergy with common antibiotics.
The main goal of its lysin program is to develop lysins against the ESKAPE pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. This series of resistant bacteria pose the largest threats to patients.
ContraFect’s lead candidate, exebacase, is a lysin product that targets S. aureus, including resistant strains of these bacteria, and is being developed for bacteria in the blood (bacteremia), including those causing heart infections, and joint infections caused by prosthetics.
CF-370 is the company’s second lysin candidate, being developed for another of these ESKAPE pathogens, P. aeruginosa. The compound was selected for development based on its potent activity against these bacteria and its biofilms in the lab, signs of safety in animal models, and its favorable manufacturing process.
CF-370 “is the first lysin to demonstrate potent in vivo antibacterial activity against a resistant Gram-negative pathogen when administered intravenously to treat systemic infection,” Casino said.
“The promising data from animal models support the potential therapeutic utility of CF-370 for the treatment of serious infections caused by P. aeruginosa, including hospital-acquired and ventilator-associated pneumonias and pulmonary exacerbations of cystic fibrosis,” she added.
Of note, P. aeruginosa is the most common pathogen isolated from adults with CF and a major cause of respiratory failure in these patients.
Amurins, in turn, are small peptides that have antimicrobial properties. Like lysins, they can be directed to specific bacterial species — also with a specific focus on ESKAPE pathogens — while leaving the “good” bacteria unharmed.
Amurins can kill bacteria through a variety of mechanisms, but all are signaling molecules that interfere with the normal physiological functions of bacteria. They can also clear biofilms and be used along with standard antibiotics.
“As a leader in bringing new potential medical modalities to combat lethal and highly-resistant bacterial pathogens, it is important that we were recognized by CARB-X for the significant progress we have made with an investigative therapy for invasive Pseudomonas infections, which have some of the highest rates of mortality among hospital acquired infections,” said Roger J. Pomerantz, MD, ContraFect’s president, CEO, and chairman.
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