UG3DA059278

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

Sparian Biosciences

TO SUPPORT BASIC AND CLINICAL NEUROSCIENCE, BIOMEDICAL, BEHAVIORAL AND SOCIAL SCIENCE, EPIDEMIOLOGIC, HEALTH SERVICES AND HEALTH DISPARITY RESEARCH. TO DEVELOP NEW KNOWLEDGE AND APPROACHES RELATED TO THE PREVENTION, DIAGNOSIS, TREATMENT, ETIOLOGY, AND CONSEQUENCES OF DRUG ABUSE AND ADDICTION, INCLUDING HIV/AIDS. TO SUPPORT RESEARCH TRAINING AND RESEARCH SCIENTIST DEVELOPMENT. TO SUPPORT DISSEMINATION OF RESEARCH FINDINGS. SMALL BUSINESS INNOVATION RESEARCH (SBIR) LEGISLATION IS INTENDED TO EXPAND AND IMPROVE THE SBIR PROGRAMS TO EMPHASIZE AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF TECHNOLOGY DEVELOPED THROUGH FEDERAL SBIR RESEARCH AND DEVELOPMENT, INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN THE SBIR PROGRAM. THE LEGISLATION INTENDS THAT THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.279 - Drug Abuse and Addiction Research Programs

National Institute on Drug Abuse (NIDA) [HHS - NIH]

New York, New York 100144606 United States

Single Zip Code

Development of Medications to Prevent and Treat Opioid and/or Stimulant Use Disorders and Overdose (UG3/UH3 - Clinical Trial Optional) (PAR-22-200)

Amendment Since initial award the total obligations have increased 101% from $3,957,359 to $7,941,988.