# Development of a Designer Proline-rich antimicrobial peptide Chaperone protein inhibitor (DPC) for treating sepsis

> **NIH NIH R41** · ARREVUS, INC. · 2020 · $299,999

## Abstract

PROJECT SUMMARY
 Sepsis is a life-threatening syndrome that involves a systemic inflammatory response that is initiated by an
infection. There are an estimated 1.5 million of cases annually in the US with 250,000 resulting in death. The
number of cases and associated deaths is expected to increase given the rising at-risk population of elderly
individuals and the compounding challenge of antibiotic resistance. Treatment of sepsis involves antimicrobial
therapy in addition to several supportive care measures to address the complications of the systemic
inflammatory response. In order to effectively and appropriately address the pathophysiological aspects of
sepsis, a treatment must provide antimicrobial activity in addition to immunomodulatory properties. It is
imperative that efforts to identify new and effective treatment strategies for sepsis shift from the traditional
antibiotic development programs that focus solely on antimicrobial activity and turn toward strategies that
address both antimicrobial and immunomodulatory aspects of the disease.
 Arrevus is developing a novel approach to addressing sepsis using Designer Proline-rich Antimicrobial
peptide Chaperone protein inhibitors (DPCs), derived from insects and selectively modified, acting 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 multi-drug
resistant (MDR) bacterial infections. Preliminary studies have displayed the potential of ARV-1502, the lead
DPC, as an effective antimicrobial agent against MDR bacterial pathogens in addition to providing
immunomodulatory effects. Specifically, our efforts have shown that: 1) DPCs show efficacy against MDR
pathogens (both gram-negative and gram-positive) alone and in combination with traditional antibiotics; 2)
DPCs offer a novel and specific bacterial target; 3) ARV-1502 has demonstrated immunomodulatory
properties; and 4) ARV-1502 exhibits a favorable safety profile. Collectively, these data support the continued
development of ARV-1502 through an STTR Phase I program targeting proof-of-concept data for the use of
ARV-1502 in the treatment of sepsis.
 In this Phase I proposal, we will build upon significant preliminary data to demonstrate proof-of-concept for
the use of ARV-1502 for treating sepsis through two aims. In Aim 1, we will characterize the effect of ARV-
1502 treatment on host innate and adaptive immunity using peripheral blood monocytes and T-cells from
sepsis patients. In Aim 2, we will assess the in vivo efficacy of ARV-1502 in murine sepsis models to improve
survival (in aim 2A using a near-lethal sepsis model) and host protective immunity (in aim 2B using a
survivable murine sepsis model in which animals survive the initial infection but are immunosuppressed). The
overall goal of this Phase I program is to generate initial proof-of-concept data and to ass...

## Key facts

- **NIH application ID:** 10007300
- **Project number:** 1R41AI149809-01A1
- **Recipient organization:** ARREVUS, INC.
- **Principal Investigator:** Carl Neil Kraus
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $299,999
- **Award type:** 1
- **Project period:** 2020-05-21 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10007300

## Citation

> US National Institutes of Health, RePORTER application 10007300, Development of a Designer Proline-rich antimicrobial peptide Chaperone protein inhibitor (DPC) for treating sepsis (1R41AI149809-01A1). Retrieved via AI Analytics 2026-06-16 from https://api.ai-analytics.org/grant/nih/10007300. Licensed CC0.

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