SBIR-STTR Award

The rapid development and spread of microbial antibiotic resistance have rendered many previously potent antibiotics useless. P. aeruginosa is one of the most common gram-negative bacteria implicated in nosocomial infection and the second most common pathogen implicated in ventilator-associated pneumonia. The excessive use of antibiotics during treatment further accelerates development of multidrug-resistant (MDR) P. aeruginosa strains, leading to the ineffectiveness of the empirical antibiotic therapy against this microorganism. Zymeron is developing a new generation of host defensing peptide (HDP) mimetics as antibiotic candidates for the treatment of MDR P. aeruginosa infections. Our preliminary results indicate that synthetic mimetics of core pharmacophore pattern offer the advantages of protease resistance, reduced cytotoxicity, and good chemical stability over natural HDP. With further structural optimization, the Phase I results will demonstrate the efficacy of promising lead compounds against clinical isolates of MDR P. aeruginosa strains and the minimal toxicity in cell-based assays for the further preclinical development of peptidomimetics as antibiotic drug candidates for the treatment of P. aeruginosa Infections.

The management of infection caused by multidrug-resistant (MDR) Pseudomonas aeruginosa is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria. P. aeruginosa is one of the most common gram-negative bacteria implicated in nosocomial infection and the second most common pathogen implicated in ventilator-associated pneumonia (VAP). The excessive use of antibiotics during treatment further accelerates the spread of MDR P. aeruginosa strains, leading to the ineffectiveness of the empirical antibiotic therapy against this microorganism. Zymeron is developing a new generation of host defensing peptide (HDP) mimetics as antibiotic candidates for the treatment of MDR P. aeruginosa infections. The Phase I results demonstrated that the in vitro efficacy of the lead compounds is more potent or comparable to that of comparator antibiotics against 100 clinical isolates of MDR P. aeruginosa and show broad-spectrum activity against other priority gram-negative pathogens while being non-toxic to mammalian cell-lines. With further structural optimization of the promising lead compounds, the Phase II results will demonstrate the pharmacokinetic and safety profile in vivo, and efficacy in appropriate animal model for the advanced preclinical development of peptidomimetics as antibiotic drug candidates approved by FDA for the treatment of P. aeruginosa Infections.