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

> **NIH NIH R42** · ARREVUS, INC. · 2020 · $672,647

## Abstract

Bloodstream infections (BSIs) caused by Gram-negative bacterial pathogens are associated with significant
morbidity and mortality due to the antibiotic-resistant nature of the pathogens. Infections caused by multi-drug
resistant (MDR) bacterial pathogens result in substantial health and economic impact due to the lack of
effective therapeutic options. This lack of treatment options is particularly relevant for MDR Gram-negative
pathogens, such as Pseudomonas aeruginosa and Acinetobacter baumannii, which have shown a great
propensity to challenge the clinical care of patients suffering from such infections. Arrevus is developing a
novel approach to addressing Gram-negative MDR infections through the use of Designer Proline-rich
Antimicrobial peptide Chaperone protein inhibitors (DPCs) derived from insects, which serve as inhibitors to
one of the critical bacterial proteins responsible for bacterial protein folding, DnaK. As an adjuvant therapy to
current antibiotics, DPCs have the potential to provide a much-improved treatment option for MDR Gram-
negative bacterial infections.
Preliminary studies have displayed the potential of ARV-1501, the lead DPC, as an antibiotic potentiating agent
against MDR Gram-negative bacterial pathogens. Our efforts have shown that: 1) ARV-1501 via an
intramuscular route is effective against MDR A. baumannii in a bacteremia model; 2) ARV-1501 enhances the
activity of colistin and imipenem; 3) ARV-1501 has a favorable preliminary safety profile; and 4) ARV-1501
enhances the effects of legacy antimicrobials through a novel mechanism of action. Collectively, these data
support the continued development of AVR-1501 through a Fast-Track program that is geared toward
characterizing the therapeutic potential and safety profile of ARV-1501 in order to construct a target product
profile (TPP). This overall goal will be met through the execution of the following aims:
Phase I Specific Aims are: 1) To define the spectrum of activity of ARV-1501. 2) To evaluate the efficacy
of intravenous dosing of ARV-1501 for the treatment of Gram-negative BSIs. The measures of success to
advance to Phase II are 1) Identification of an optimal antibiotic for use as a co-treatment with ARV-1501
against Gram-negative pathogens; and 2) Determination of the efficacy of ARV-1501 when delivered
intravenously in a Gram-negative BSI mouse model.
Phase II Specific Aims are: 1) To characterize the pharmacological properties and therapeutic activity
of ARV-1501. 2) To obtain a preliminary safety profile of ARV-1501. The measure of success for Phase II
is to complete key pharmacological and safety assessments to craft the TPP.

## Key facts

- **NIH application ID:** 9859340
- **Project number:** 5R42AI136065-03
- **Recipient organization:** ARREVUS, INC.
- **Principal Investigator:** Bryan Hoang
- **Activity code:** R42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $672,647
- **Award type:** 5
- **Project period:** 2018-02-05 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9859340

## Citation

> US National Institutes of Health, RePORTER application 9859340, Development of a Designer Proline-rich antimicrobial peptide Chaperone protein inhibitor (DPC) for treating multi-drug resistant bacteremia (5R42AI136065-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9859340. Licensed CC0.

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