Development of cebranopadol, a potent dual mop/NOP agonist, for the treatment of opioid use disorder (OUD)
Active Cooperative Agreement Awarded Last action
- Award ID
- UG3DA059285
- Recipient
-
Adneuris Therapeutics Inc. UEI LKW7MCDM3GG5 Part of Tris Pharma Inc.
- Awarding agency
-
National Institute on Drug Abuse
National Institutes of Health, Department of Health and Human Services
- Obligated
- $16,642,955
Award facts
- Assistance listing
- 93.279 Drug Use and Addiction Research Programs
- Completion date 80% complete
- Originally
- Place of performance
- New Jersey, USA
Award details come from USAspending.gov.
Description
- Abstract
- /summary the U.S. Is experiencing a crisis of opioid misuse, addiction, and overdose; in the most recent year, there were over 100,000 drug-related overdose deaths, 75% of which involved opioids. Current pharmacotherapies for opioid use disorder (OUD) target MU opioid peptide (mop) receptors, one of five classes of opioid receptors. These therapies include the full mop agonist methadone, the partial mop agonist buprenorphine, and the mop antagonist naltrexone. There are several drawbacks in using these medications to treat OUD, which include the potential for abuse, development of physical dependence, and risk of overdose, particularly for methadone and buprenorphine. Buprenorphine and naltrexone also trigger severe withdrawal symptoms. There is thus an urgent need for an improved therapeutic for the treatment of OUD. Cebranopadol (TRN-228) is a first-in-class synthetic drug developed for its dual-action mechanism in treating pain, mediated by high affinity and potency for both mop and nociceptin/orphanin FQ receptor (NOP). NOP receptor activation has been associated with reduced development of tolerance, abuse-related behavior, addiction, and physical dependence. In this UG3/UH3 proposal, park therapeutics is developing TRN-228 as a first-in-class dual mop/NOP agonist that can be used as a safe and effective treatment for OUD. Preliminary nonclinical and clinical data indicate that cebranopadol has low potential for abuse and physical dependence and produces milder respiratory depression compared to pure mop agonists such as morphine and oxycodone. TRN-228 also decreases morphine, heroin, and cocaine self-administration in rats and did not induce withdrawal when given to opioid-dependent rats. The UG3 phase of this proposal will test whether oral TRN-228 is a safe and potentially effective alternative treatment for OUD, based on the following specific aims: 1) determining the effects of TRN-228 on intravenous fentanyl self-administration and fentanyl-induced respiratory depression in opioid-dependent rats, 2) determining the IV abuse potential of TRN-228, and 3) assessing the ability of TRN-228 to suppress withdrawal. Upon meeting the UG3 go/no-go milestones, park will progress to the UH3 phase which will demonstrate the therapeutic efficacy of TRN-228 in decreasing opioid use with low risk of withdrawal or abuse, which will be accomplished by 4) determining the effects of TRN-228 on fentanyl-induced respiratory depression in opioid-tolerant participants and 5) evaluating the ability of TRN-228 to block the subjective effects of hydromorphone. These studies will significantly advance the field by establishing the safety and preliminary efficacy of TRN-228. Successful completion of these aims will guide future efforts to establish a clinical program for FDA approval.
Transactions
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| Amendment | $3,324,591 | |
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| Amendment | $3,329,591 | |
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| Original award | $3,329,591 |
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Quick answers
Who received award UG3DA059285?
UG3DA059285 was awarded to Adneuris Therapeutics Inc. by National Institute on Drug Abuse (National Institutes of Health) on August 15, 2023.
How much is award UG3DA059285 worth?
$16,642,955 has been obligated on UG3DA059285.
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