# Development of a Novel Chemokine Receptor Antagonist as a Treatment for Opioid Use Disorder

> **NIH NIH R44** · CREATIVE BIO-PEPTIDES, INC. · 2022 · $1,123,774

## Abstract

7. Project Summary
Over 2.1 million Americans suffer from opioid use disorder (OUD) resulting in 47,000 deaths annually. Individuals
seeking treatment must deal with limited access to qualified healthcare professionals, as well as barriers to
getting medication assisted treatment (MAT). Common MAT treatments utilizing buprenorphine often require
patients to experience withdrawal symptoms for several days prior to MAT initiation. Further, the stigma of OUD
treatment, which could be reduced if patients received ambulatory care, acts as an additional hindrance to access
and treatment. There is a paucity of options available for these individuals and the medical staff who treat them,
as methadone, buprenorphine and naloxone, the standards of care, are often not successful in achieving
treatment goals. Emerging evidence demonstrates that brain chemokine receptors control dopamine reward
pathways and influence behavioral effects of drug abuse which can be blunted by chemokine receptor
antagonists. CBP proposes to expand MAT capabilities for OUD with RAP-103, a small orally stable chemokine
receptor antagonist peptide that block’s opioid acquisition, maintenance, and withdrawal. Our evidence indicates
that RAP-103 has significant safety and efficacy advantages as a non-opioid for MAT use that blocks opioid self-
administration in fixed-ratio tests that show reduction in total opioid consumed and in progressive-ratio
experiments that show greatly reduced motivation to maintain opioid use. Additionally RAP-103 mitigates signs
of naloxone induced opioid withdrawal in a rodent model of morphine dependence. In this project, our objective
is to further demonstrate the feasibility of RAP-103 as a MAT agent and to progress to human testing. We intend
to do this by optimizing the lowest dose at which RAP-103 mitigates opioid self-administration in progressive-
ratio experiments in male and female rats. In view of the unique mechanism of RAP-103 action via chemokine
receptor antagonism we will identify chemokine and cytokine changes in mesolimbic (VTA and nucleus
accumbens) brain reward areas to provide a mechanism for how RAP-103 may mitigate the rewarding effects of
opioids and other drugs of abuse. CBP has been conducting pre-clinical pharmacokinetic and toxicokinetic safety
testing toward fulfilling requirements for filing an IND and conducting first-in-human safety testing. CBP has
assembled a team of experienced MAT clinician/researchers to plan a clinical development program for an OUD
use. We propose to conduct the additional pre-clinical safety tests that would support filing of an IND for an OUD
treatment use of RAP-103 at the end of the program. CBP will advance clinical development of RAP-103 as a
MAT for OUD with goals to provide safer treatment with no abuse risk, improve patient access, adherence,
tolerance and treatment. The superior safety profile (no respiratory depression and abuse or diversion potential),
reduced motivation to maintain opioid ...

## Key facts

- **NIH application ID:** 10492608
- **Project number:** 5R44DA050349-03
- **Recipient organization:** CREATIVE BIO-PEPTIDES, INC.
- **Principal Investigator:** Michael R Ruff
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,123,774
- **Award type:** 5
- **Project period:** 2019-09-30 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10492608

## Citation

> US National Institutes of Health, RePORTER application 10492608, Development of a Novel Chemokine Receptor Antagonist as a Treatment for Opioid Use Disorder (5R44DA050349-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10492608. Licensed CC0.

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