# Completion of IND-package for a novel, non-narcotic painkiller

> **NIH NIH R44** · BLUE THERAPEUTICS, INC. · 2020 · $1,776,585

## Abstract

Project Summary
Opioids like morphine and hydrocodone are generally the most effective therapeutics for treatment of moderate
to severe pain. However, their use is limited by serious side effects - tolerance, constipation, respiratory
depression, physical dependence and high addictive potential. The frequency of clinical pain, coupled with a
lack of alternative therapeutic options has led to a national health crisis centered on prescription opioid abuse.
Alternative pain relievers with the analgesic potency of conventional opioids, but devoid of narcotic side effects
are an immediate need. The goal of this project is to develop and commercialize an alternative to
conventional opioid analgesics with reduced side effects and without the addictive properties common
to mu-opioid agonists. Our lead molecule, Blue181 is a highly selective agonist for a novel CNS target that
is a potent analgesic without apparent addictive potential, tolerance, or physical dependence. We started the
pre-clinical development of Blue181 using a combination of federal and private funds to scale up and develop
an industrial synthetic process for generating large amounts of Blue181 and shown that Blue181 does not
produce respiratory depression, reduction of GI transit, inhibition of hERG in the therapeutic range, or genetic
toxicity. We also have a preliminary understanding of the pharmacokinetic profile of Blue181. We will now
finish all the remaining IND-enabling studies targeting an initial indication of IV postoperative pain for Blue181.
We will continue our efforts on developing an FDA-compliant process for preparation of Blue181 in the
kilogram scale that would be amenable for later cGMP synthesis and prepare a CMC package for IND filing.
We will also perform studies to further delineate the PK and metabolic profile of Blue181 and determine the no-
observable-adverse-effects-level (NOAEL) in the toxicity species. Finally, we will finish safety pharmacology
studies (pulmonary toxicity and cardiotoxicity) and GLP toxicity in two species. At the end of the project period,
Blue181 will be an IND-ready asset and can be advanced into Phase 1 human trials.

## Key facts

- **NIH application ID:** 9889914
- **Project number:** 5R44DA041912-04
- **Recipient organization:** BLUE THERAPEUTICS, INC.
- **Principal Investigator:** Ajay S Yekkirala
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,776,585
- **Award type:** 5
- **Project period:** 2016-08-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9889914

## Citation

> US National Institutes of Health, RePORTER application 9889914, Completion of IND-package for a novel, non-narcotic painkiller (5R44DA041912-04). Retrieved via AI Analytics 2026-05-30 from https://api.ai-analytics.org/grant/nih/9889914. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*