ContraFect will receive funding from the Cystic Fibrosis Foundation to conduct preclinical research about the potential of direct lytic agents, an alternative to conventional antibiotics, to treat lung infections caused by Gram negative antibiotic-resistant bacteria, including Pseudomonas aeruginosa.
While antibiotics have had a profound impact on the eradication of otherwise deadly infections, their overuse has fostered the spread of antibiotic-resistant bacteria.
Pseudomonas aeruginosa is one of the most critical bacteria affecting cystic fibrosis (CF) patients. In some cases, the bacteria can become resistant to the body’s immune system and to the action of antibiotics.
ContraFect direct lytic agents, or DLAs, are a next generation of antimicrobial therapeutics. DLAs include both lysins and amurin peptides and cause the rapid death of bacteria — much faster than conventional antibiotics. Both agents destroy the bacterial cell wall.
“We are thrilled to announce this agreement with the Cystic Fibrosis Foundation to examine our DLAs as novel potential therapeutic modalities for CF lung infections,” Cara Cassino, MD, said in a press release. Cassino is executive vice president of research and development and chief medical officer of ContraFect.
“Individuals living with CF are frequently burdened with life-threatening lung infections resulting from highly drug-resistant Gram-negative bacterial pathogens, including but not limited to Pseudomonas aeruginosa and there is an urgent need for new treatment approaches,” Cassino said.
Lysins are proteins derived from naturally occurring bacteriophages (viruses that infect bacteria). Lysins are lytic agents, as they can kill bacteria by breaking down a key component in the structure of the bacterial cell wall. According to ContraFect, once the cell wall is breached, the bacteria disintegrates rapidly.
Amurin peptides, a small-class of peptides (short chains of aminoacids, the building blocks of proteins), were shown to effectively kill several Gram-negative bacteria, including Pseudomonas aeruginosa, in lab studies. Moreover, these peptides strenghten the action of standard-of-care antibiotics, making them particularly suitable for CF patients infected with antibiotic-resistant bacteria.
The new funding will support lab tests with: ContraFect’s CF-370, a lab-made lysin targeting Pseudomonas aeruginosa, and also with amurin peptides targeting bacterial strains isolated from CF patients at different stages of disease.
These lab results will be a steppingstone for future clinical development of CF-370 and/or amurin peptides as potential alternative therapies for CF patients with lung infections.
Previous preclinical data in rabbit pneumonia models infected with resistant P. aeruginosa showed that single doses of CF-370 alone extended the animal’s survival and reduced the bacterial burden in the lung, kidney and spleen when compared to control (untreated) animals.
The data also showed that CF-370 in combination with the antibiotic meropenem led to a marked reduction in the bacterial burden compared to CF-370 alone.
In these animal models, CF-370 was well-tolerated with no adverse clinical consequences and no deaths reported.
“We believe that our DLA approach has promise to address these infections and provide meaningful therapeutic benefit to these patients,” said Cassino. “The opportunity to develop DLAs in CF highlights the broad therapeutic potential of our novel approach, as we continue to identify and evaluate additional new target diseases.”
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