Overview

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 grant from the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) to support the development of lysins to treat infections caused by P. aeruginosa. In January 2019, CARB-X increased the amount of the grant by $2.3 million.

Market Need

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.

Gram-negative Pathogens

Antibiotic resistance is a growing threat to public health and to the provision of health care worldwide. Infections caused by antibiotic-resistant pathogens substantially increase the burden of both healthcare-associated infections and community-acquired infections. Infections caused by drug-resistant Gram-negative pathogens result in greater all-cause mortality, in-hospital mortality and length of hospitalization. For example, drug-resistant P. aeruginosa infections increase in-hospital mortality by more than 5x and length of hospitalization by more than 2x compared to susceptible isolates.

Several factors have contributed to the emergence and spread of antibiotic resistance worldwide, including inappropriate antibiotic usage, extensive use in agricultural and veterinary sectors, aging populations, increasing numbers of immunocompromised individuals, growing global travel and migration from countries that have higher levels of antibiotic-resistant pathogens, and an inadequate number of new antibiotics in the development pipeline. We aim to address this deficiency with our novel, differentiated lysins targeting Gram-negative pathogens. Similar to exebacase, our Gram-negative targeted lysins should act faster than and synergistically with standard-of-care antibiotics, have a potent, yet specific, spectrum of activity that spares the healthy gastrointestinal microbiome, and rapidly clear biofilms.

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Exebacase (CF-301)

Exebacase is a novel, investigational  lysin with potent activity against Staph aureus, including MRSA strains. Exebacase is being studied in clinical trials as a treatment for patients with Staph aureus bacteremia, including endocarditis.

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Amurins

We have discovered a new class of direct lytic agents, antimicrobial peptides, that have potent in vitro activity across a wide range of resistant Gram-negative pathogens.

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