# Development of a Novel Chemokine Receptor Antagonist Peptide as a Non-Opioid Treatment for Relief of Chronic Pain

> **NIH NIH R44** · CREATIVE BIO-PEPTIDES, INC. · 2021 · $2,999,505

## Abstract

7. Project Summary
In response to RFS-NS-20-11, Creative Bio-Peptides, Inc. will develop the multi-chemokine receptor antagonist
peptide R103 to provide a non-opioid, potentially disease modifying treatment for neuropathic pain conditions.
We have completed proof-of-concept (POC) animal studies in neuropathic pain by partial nerve ligation and
diabetes. We will conduct a further POC study of R103 benefit in chemotherapy-induced peripheral neuropathy
(CIPN), a dose-limiting side effect of many anticancer drugs that can affect 68% or more of cancer patients. We
will also establish a neuroprotective mechanism for R103 pain effects. Additional chronic pain patients that may
benefit from R103 include those with spinal cord injury, chronic low-back pain, and post-herpetic neuralgia. Our
initial target patient population are the 2.5 million Americans with diabetic peripheral neuropathy (DPN), the most
common chronic neuropathic pain condition. Chemokines, molecules of the innate immune system that mediate
inflammation, acting through receptors such as CCR2, CCR5, and CCR8 promote pain by multiple mechanisms
that cause sustained excitability of primary nociceptive neurons, desensitize endogenous opioid anti-pain effects,
activate microglia and astrocytes, and cause peripheral monocyte infiltration into CNS. Blocking multiple
chemokine receptors that establish and sustain chronic pain with the multi-chemokine receptor antagonist (CRA)
R103 is a new and largely untested non-opioid approach to pain treatment. Substantial independent research
by others shows the value of CRA’s in diverse chronic pain conditions. R103 is a preferred CRA because of its
ease of dosing, rapid entry into the CNS, lack of toxicity and side effects, and potential to treat the defining
pathology of neuropathic pain, axonal degeneration. Unlike current FDA approved chemokine antagonists
(Plerixafor®, Selzentry®) which have significant safety concerns (allergic risks, need to be injected, “black-box”
warning for hepatotoxicity), R103 is safe and targets multiple chemokine receptors (CCR2/CCR5/CCR8)
implicated in persistent pain states. The program we propose will result in an IND for DPN and CINP use and
fast-track human phase 1 studies with exploratory patient efficacy cohorts. We will assess any respiratory
depression with R103, an FDA mandate for pain drugs. We will conduct scale-up peptide manufacture and
complete IND-enabling pre-clinical safety and PK/PD studies. We will schedule a pre-IND meeting with the FDA
to establish a regulatory approval plan and secure an IND for first-in human studies. The studies in the
proposal support expanding the IND to treat other neuropathies, like CIPN, and eventually neuralgias, and back
pain.

## Key facts

- **NIH application ID:** 10138162
- **Project number:** 1R44NS120541-01
- **Recipient organization:** CREATIVE BIO-PEPTIDES, INC.
- **Principal Investigator:** Michael R Ruff
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,999,505
- **Award type:** 1
- **Project period:** 2021-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10138162

## Citation

> US National Institutes of Health, RePORTER application 10138162, Development of a Novel Chemokine Receptor Antagonist Peptide as a Non-Opioid Treatment for Relief of Chronic Pain (1R44NS120541-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10138162. Licensed CC0.

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