Development of a Designer Proline-rich antimicrobial peptide Chaperone protein inhibitor (DPC) for treating multi-drug resistant bacteremia

Bloodstream infectionsBSIscaused by Gram negative bacterial pathogens are associated with significant morbidity and mortality due to the antibiotic resistant nature of the pathogensInfections caused by multi drug resistantMDRbacterial pathogens result in substantial health and economic impact due to the lack of effective therapeutic optionsThis lack of treatment options is particularly relevant for MDR Gram negative pathogenssuch as Pseudomonas aeruginosa and Acinetobacter baumanniiwhich have shown a great propensity to challenge the clinical care of patients suffering from such infectionsArrevus is developing a novel approach to addressing Gram negative MDR infections through the use of Designer Proline rich Antimicrobial peptide Chaperone protein inhibitorsDPCsderived from insectswhich serve as inhibitors to one of the critical bacterial proteins responsible for bacterial protein foldingDnaKAs an adjuvant therapy to current antibioticsDPCs have the potential to provide a much improved treatment option for MDR Gramnegative bacterial infectionsPreliminary studies have displayed the potential of ARVthe lead DPCas an antibiotic potentiating agent against MDR Gram negative bacterial pathogensOur efforts have shown thatARVvia an intramuscular route is effective against MDR Abaumannii in a bacteremia modelARVenhances the activity of colistin and imipenemARVhas a favorable preliminary safety profileandARVenhances the effects of legacy antimicrobials through a novel mechanism of actionCollectivelythese data support the continued development of AVRthrough a Fast Track program that is geared toward characterizing the therapeutic potential and safety profile of ARVin order to construct a target product profileTPPThis overall goal will be met through the execution of the following aimsPhase I Specific Aims areTo define the spectrum of activity of ARVTo evaluate the efficacy of intravenous dosing of ARVfor the treatment of Gram negative BSIsThe measures of success to advance to Phase II areIdentification of an optimal antibiotic for use as a co treatment with ARVagainst Gram negative pathogensandDetermination of the efficacy of ARVwhen delivered intravenously in a Gram negative BSI mouse modelPhase II Specific Aims areTo characterize the pharmacological properties and therapeutic activity of ARVTo obtain a preliminary safety profile of ARVThe measure of success for Phase II is to complete key pharmacological and safety assessments to craft the TPP The prevalence of Gram negative bloodstream infections is in the riseand these infections are increasingly difficult to treat with existing antibiotics due to antibiotic resistanceArrevus is developing a new class antimicrobial peptides derived from insects that act via a novel mode of action to enhance the ability of antibiotics to treat infections caused by Gram negative antibiotic resistant bacteria