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.