# Development of SBS-226, a MOR agonist / DOR antagonist, for OUD

> **NIH NIH UG3** · SPARIAN BIOSCIENCES, INC. · 2024 · $3,957,359

## Abstract

ABSTRACT
 Opioid use disorder (OUD) is a chronic disorder characterized by the repeated,
compulsive use of opioid drugs with a detrimental impact to one’s physical, social, and
psychological wellbeing. The use of prescription opiates is often necessary to control moderate
to severe levels of pain. However, about 10% of patients prescribed an opiate for a medical
condition are at risk for developing OUD. Opiate Use Disorder is a global problem but is at crisis
levels in the U.S with significant mortality. It is estimated in this country that about ~11M misuse
opioids, ~5.6M people have OUD and close to 80K died from opioid related overdoses. Sadly, the
COVID epidemic has worsened the epidemic by increasing risk factors for OUD and occurred at
a time when fentanyl has flooded the supply. Current treatments are primarily buprenorphine and
methadone. Despite treatment options, OUD is difficult to effectively treat long-term due to
access, stigma, and efficacy of the compounds.
 Mitragyna speciosa, a plant commonly known as kratom, has anecdotally been used for
treatment of opiate withdrawal and OUD. The naturally occurring active substance is believed to
be mitragynine and the 7- OH mitragynine (7OH) metabolite which act through the mu opioid
receptor. An active metabolite of mitragynine, 7OH mitragynine, demonstrates MOR agonist
properties such as analgesia, tolerance, physical dependence, and reinforcing effects. In contrast,
an analog of mitragynine named 9-methoxy corynantheidine pseudoindoxyl (9CP) has a very
different receptor binding profile and in vivo properties. 9CP is an partial agonist at MOR and it is
also a delta opioid receptor (DOR) antagonist. Unlike the natural products found in kratom, when
studied in mice under acute dosing 9CP is non-addictive, and demonstrates far less respiratory
depression, tolerance, and signs of physical dependence than morphine. Most importantly, in
mice, 9CP can ameliorate naloxone-precipitated withdrawal in morphine-dependent mice.
 Sparian has created a series of 9CP analogs and screened them across CMC, ADME,
and PK properties and identified a lead candidate – SBS-226. Therefore, as an innovative
pharmacological approach, we propose the development of SBS-226 as a novel selective, potent
and non-addictive chemical entity utilizing mixed MOR agonism/DOR antagonism for the
treatment of OUD. In the present application, we propose a full IND-enabling development plan
and Phase 1 clinical trial.

## Key facts

- **NIH application ID:** 10915840
- **Project number:** 1UG3DA059278-01A1
- **Recipient organization:** SPARIAN BIOSCIENCES, INC.
- **Principal Investigator:** Jeffrey Reich
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $3,957,359
- **Award type:** 1
- **Project period:** 2024-09-30 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10915840

## Citation

> US National Institutes of Health, RePORTER application 10915840, Development of SBS-226, a MOR agonist / DOR antagonist, for OUD (1UG3DA059278-01A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/10915840. Licensed CC0.

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