SBIR-STTR Award

Multi-drug resistant (MDR) biofilms are perhaps the most difficult bacterial infections to fight. They require novel antibiotics that operate through new mechanisms which overcome the biofilm environment. We have discovered a class of antibiotics that are novel and have new targets which appear to evade resistance development. One example is already in the clinic to systemically treat Staphyloccal infections, including methicillin-resistant S. aureus. In addition, we have shown compounds in this series are active against bacterial and fungal biofilms. This STTR aims to identify a number of lead candidates with single micromolar activity against A. baumanni, S. epidermidis, E. faecalis, P. aeruginosa, E. coli and their drug/multi-drug resistance strains in Phase I. Active compounds that meet criteria for further evaluation (including those that have been shown previously to be active against drug-resistant S. aureus) will then be tested and optimized in Phase II to treat MDR biofilm infections.

Keywords:
Multi-Drug Resistant Antibiotics, Novel Mechanism Of Action, Biofilm Disruption, Rapid Biocidal Action, Small Molecule Mimics Of Antimicrobial Peptides (Smamps)

Multi-drug resistant (MDR) biofilms are one of the most difficult bacterial infections to treat. Current antibiotics are increasingly unable to cure these infections; underscoring the need to develop new antibiotics that operate through novel mechanisms which overcome the biofilm environment. PolyMedix has discovered a novel class of antibiotics, SMAMPS (small mimics of antimicrobial peptides), that work through a mechanism which appears to evade resistance development and is not depended on bacterial growth. One SMAMP is currently in human clinical trials to treat nosocomial infections, including methicillin-resistant S. aureus. During the Phase I STTR, potently active lead compounds were identified against pathogens associated with biofilm-embedded infections. Resistance to other antibiotics did not influence susceptibility to the PMX mimetics. Rapid killing kinetics and a low risk for the development of resistance are hallmark features of PMX mimetics and underscore their potential as novel antimicrobial agents suitable for further development for treatment of infections complicated by biofilm formation. This Phase II STTR aims to identify SMAMPs that are potently active in in vitro and in vivo biofilm infection models and possess pharmaceutical qualities suitable for further development.

Keywords:
Biofilm Infections, Drug Resistant Infections, Novel Compounds, Novel Mechanism Of Action, Biocidal,