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

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41AI136072-01
Agency Tracking Number: R41AI136072
Amount: $300,000.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIAID
Solicitation Number: PA16-303
Timeline
Solicitation Year: 2016
Award Year: 2018
Award Start Date (Proposal Award Date): 2018-01-23
Award End Date (Contract End Date): 2018-12-31
Small Business Information
2 DAVIS DR
Research Triangle Park, NC 27709-0003
United States
DUNS: 080059821
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 CARL KRAUS
 (347) 334-2687
 ckraus@arrevus.com
Business Contact
 ROBERT HOUSE
Phone: (347) 334-2687
Email: rhouse@arrevus.com
Research Institution
 NORTHWESTERN UNIVERSITY AT CHICAGO
 
750 N LAKE SHORE DR
CHICAGO, IL 60611-3152
United States

 Nonprofit college or university
Abstract

Project SummaryOver $billion is spent annually in the US treating chronicnon healing woundsmany of which face lifethreatening complications due to infectionsWound infections are difficult to treat due to the frequency of
antibiotic resistance as well as the formation of biofilmsa community of bacteria covered by an extracellular
polymeric substanceBiofilm related infections can result in a substantial increase in bacterial tolerance and
resistance to antibiotics compared to their planktonic phenotypeGiven the issues of resistancethe complex
nature of biofilmsand poor clinical outcomes associated with chronic woundsit is urgent that alternative
treatments be developed to address the bacterial protective mechanisms that maintain these difficult to treat
infectionsArrevus is pioneering a novel approach to provide an effective treatment option for chronic wound infections
through the development of Designer Proline rich Antimicrobial peptide Chaperone protein inhibitorsDPCsARVArrevuslead DPCkills bacteria in two distinct waysiby disrupting the bacterial lipid membrane
and iiby selectively inhibiting the chaperone protein DnaKDnaK is a ubiquitously expressed and highly
conserved prokaryotic heat shock protein critical for bacterial survival in stress conditions and is associated with
bacterial biofilm formationPreliminary studies show that ARVhas anti infective capabilities both alone
and in combination with other small molecule antibioticscan re sensitize multidrug resistantMDRbacteria
to antibioticsdoes not exhibit off target binding to the human homologHspandhas reduced bacterial
load and enhanced healing in several wound infection modelsIn this Phase I STTRArrevus will obtain proof of concept data to support the use of ARVas a
therapeutic option for treating multidrug resistant wound infectionsIn Aimwe will evaluate the in vitro efficacy
of ARValone and in combination with clinically relevant antibiotics against MDR Saureus and Paeruginosatwo microbes commonly associated with wound infectionsIn AimAwe will determine the
antimicrobial efficacyand in AimBwe will determine the anti biofilm activityIn Aimwe will assess the antibiofilm and antimicrobial capabilities of ARValone and in combination with a clinically utilized antibiotic
using the rabbit ear wound modelin collaboration with Robert GalianoM DNorthwestern UniversityThe
rabbit ear model is clinically relevant and will allow us to determine the anti biofilm properties of ARValoneAimAand in combination with a synergistic antibiotic determined in AimAimBSuccessful completion of the proposed studies will provide the necessary efficacy data to support further
development of ARVas a therapeutic agent for treating wound infections in Phase IIDevelopment of an
ARVantibiotic treatment for chronic wound infections has the potential to provide an alternative strategy
to address these hard to treat infections and enhance patient outcomes Project Narrative
Chronic wounds are a significant healthcare burden and often complicated by infectious agents which can
develop antibiotic resistance or form biofilmsBoth antibiotic resistance and biofilm formation complicate wound
treatment and healingleading to poor clinical outcomesArrevus 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
wound infections caused by Gram negative and Gram positive antibiotic resistant bacteria

* Information listed above is at the time of submission. *

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