Traditional broad-spectrum antibiotics have for most of the last century exhibited extraordinary limb- and life-saving effects. However, two major, unintended adverse consequences of their use are now apparent:
- Rampant spread of broad drug resistance among bacteria
- Damage to the host’s microbiota, damage that may have lasting effects.
Both of these adverse consequences represent rapidly increasing areas of unmet medical need and expansive opportunities for approaches that deal with the underlying causes.
Pylum has developed Avidocin proteins designed to prevent and treat, for example, C. difficile infections. Avidocin proteins are engineered R-type bacteriocins, naturally occurring defensive proteins of bacteria, that target a specific strain of bacteria. Preclinical studies have shown mice inoculated with C. difficile spores and treated orally with Avidocin proteins remained uninfected, and the healthy gut bacteria of Avidocin protein-treated mice were not detectably disturbed. Studies also showed that rare C. difficile mutants that were selected in vitro for resistance to Avidocin proteins are compromised in their ability to grow and spread or cause disease. Avidocin proteins may be efficacious prophylactically to prevent colonization by C. difficile in high risk patients, to prevent the outgrowth of C. difficile causing life-threatening colitis in known asymptomatic carriers of C. difficile exposed to broad spectrum antibiotics, or to prevent recurrent C. difficile infections in previously cured patients.
Pylum plans to complete preclinical studies and submit an IND application for the management of C. difficile infections with Avidocin proteins.
Clostridioides difficile infection is one of the highest priority nosocomial infections. It lengthens hospital stays, raises the risk of mortality, and increases costs. Approximately one-quarter of people who have treatment for a C. difficile infection will have another. After three or more infections, 50% of those patients will have yet another infection. Initial infections can be treated with broad-spectrum antibiotics, but this increases the likelihood of recurrence.
Avidocin proteins specifically ablate the C. difficile bacteria, including antibiotic-resistant strains. Published murine in vivo data showed that the orally delivered C. difficile Avidocin killed the most toxigenic clinical isolates while leaving the gut flora unharmed. Unlike vancomycin and Fidaxomicin, frontline treatments for C. difficile infections, our C diff candidate did not disrupt colonization resistance or increase susceptibility to infection with C. difficile or vancomycin-resistant Enterococci (VRE) infection after treatment.
In addition to our C diff program, Pylum has more than 20 additional candidate molecules that have been cloned, engineered, expressed, purified, and in vitro validated for killing efficiency of specific pathogenic strains including L. monocytogenes, A. baumannii, MRSA, VRE, P. aeruginosa, Shigella spp, and Salmonella spp. These candidates help reduce the business risk by creating multiple opportunities with Orphaned Drug Designations