Cell-penetrating antimicrobial therapeutics for treatment of complicated skin and soft tissue infections

Abstract In the United Statesskin and soft tissue infectionsSSTIsare one of the most common indications for antibiotic treatmentrepresentingof hospital admissions andmillion doctor visits a yearSSTIs range from selflimiting furuncles and cellulitis to life threatening sepsis and tissue necrosisRecent studies suggest more thanof all SSTIs were caused by staphylococcal or streptococcal speciesin particularmethicillin resistant staphylococcus aureusMRSAWe have engineered a novel class of cell penetrating antimicrobial therapeuticscalled CAHPswhich demonstrate broad spectrum activity against clinically relevant Gramand Grampathogenswhile exhibiting minimal toxicity in human cellsThese compounds have been shown to penetrate infected target cellsbreakdown established bacterial biofilms of Category B and C pathogensand to act as anti inflammatory agentsIdentifying a CAPH lead candidate as a novel therapeutic agent for the treatment ofinitiallycutaneous infections addresses a highly unmet medical needUltimatelyits use can be expanded into a broad spectrum antimicrobial therapeuticsThe initial product will be an IV formulation that can be administered in community and nosocomial settingsAn IV formulation is preferable for treating systemic cSSTIsespecially if hospital acquiredand could later also be supplemented with a topical product for use in both communal and hospital settingsThe Phase I portion of this proposal will involve characterization of the current prelead candidates for their antimicrobial potency and in vitro toxicity as well as for their pharmacokinetic characteristicsThe most promising candidate will be tested in in vivo efficacy models of systemic and topical infections and assessed for its exploratory safety profileThe end result of this work will be a novelfirst in class antibacterial drug candidate for treatment if SSTIs ready for preclinical development activities leading to the opening of an INDWe have assembled a team of expert advisors and collaborators to ensure successful completion of this research plan