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

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41AI140782-01
Agency Tracking Number: R41AI140782
Amount: $295,171.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIAID
Solicitation Number: PA17-303
Timeline
Solicitation Year: 2017
Award Year: 2018
Award Start Date (Proposal Award Date): 2018-06-08
Award End Date (Contract End Date): 2020-05-31
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: (301) 928-8409
Email: rhouse@arrevus.com
Research Institution
 WASHINGTON UNIVERSITY
 
CAMPUS BOX 1054
SAINT LOUIS, MO 63130-4862
United States

 Nonprofit College or University
Abstract

Urinary tract infectionsUTIsare one of the most common hospital acquired infections and are often caused by
multi drug resistantMDRbacterial pathogensMDR bacterial pathogens are associated with significant
morbidity and mortalitycreating enormous healthcare and economic burdens due to variations in disease natural
histories as well as the lack of effective therapeutic optionsTreatment option limitations are particularly relevant
for MDR Gram negative pathogenssuch as Escherichia coli and Klebsiella pneumoniaewhich have shown a
great propensity to challenge the clinical care of patientsArrevus is developing a novel approach to addressing
complicated UTIs caused by MDR Enterobacteriaceae through the use of Designer Proline rich Antimicrobial
peptide Chaperone protein inhibitorsDPCsderived from insects and selectively modifiedacting 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 thatDPCs enhance antibiotic
activityDPCs reduce bacterial burden in a UTI modelARVhas a favorable preliminary safety profileARVprovides an enhancement of the effects of antimicrobial agents through a novel MOAandARVhas demonstrable activity in murine MDR Gram negative bacteremia modelsCollectivelythese data
support the continued development of AVRthrough an STTR Phase I program targeting proof of concept
data for the use of ARVin the treatment of complicated UTIsThe proposed Phase I program will involve in vitro assessmentsincluding minimum inhibitory concentration
assays and checkerboard assaysto characterize the activity of ARVwith and without legacy antibiotics
against uropathogens and the evaluation of the potential of resistance development to ARVAimSuccessful completion of Aimwill identify an optimal ARVantibiotic pairingThis optimal combination will
then be assessed in a mouse UTI model against several uropathogensAimARVactivity will be
assessed alone and in combination with the antibiotic identified in Aimin order to determine bacterial burden
reductionThis Phase I program will provide the necessary proof of concept data to support further development
of ARVin a Phase II program that will center on extensive in vivo efficacy studies and preliminary safety
studies Urinary tract infections create significant healthcare and economic burdensand the impact of these infections
is increasing 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

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

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