This Project Grant award, provided by the National Institute on Drug Abuse (NIDA) under the Drug Use and Addiction Research Programs (CFDA 93.279), will fund a mechanistic study to investigate how targeting the orexin system affects symptoms related to neurofunctional domains associated with opioid use disorder (OUD) and insomnia. The total award amount is $2,285,443 and the project period runs from September 30, 2024 to July 31, 2029. The study, led by Virginia Commonwealth University, will...
This federal Project Grant award from the National Institute on Drug Abuse (NIDA), under the Drug Use and Addiction Research Programs (CFDA 93.279), is funding the development of a novel epigenetic regulator as a potential treatment for opioid use disorder (OUD). The grantee, Epivario Inc., a for-profit biotechnology research organization, will screen a new class of ACSS2 inhibitors and evaluate their efficacy in preclinical animal models of OUD. Specifically, the $275,253 award will support...
The National Institute on Drug Abuse (NIDA) awarded a $11,872,077 Cooperative Agreement (CFDA 93.279 - Drug Use and Addiction Research Programs) to Sparian Biosciences Inc. (doing business as Palion Therapeutics) to develop SBS-226, a novel chemical entity that acts as a mu-opioid receptor agonist and delta-opioid receptor antagonist, for the treatment of opioid use disorder (OUD). The project aims to advance SBS-226 through IND-enabling studies and a Phase 1 clinical trial. Sparian...
This Cooperative Agreement award from the National Institute on Drug Abuse (NIDA), under the Drug Use and Addiction Research Programs (CFDA 93.279), provides $19,302,777 to Nirsum Laboratories, Inc. to accelerate the development of NRS-033, a long-acting injectable medication for opioid use disorder (OUD). The key products and services to be delivered under this award include late-stage chemistry, manufacturing, and controls (CMC) for the active pharmaceutical ingredient (API) and drug...
This $385,000 Project Grant award from the National Institute on Drug Abuse (NIDA) under the Drug Use and Addiction Research Programs (CFDA 93.279) aims to advance integrated treatment for co-occurring opioid use disorder (OUD) and alcohol use disorder (AUD) in real-world settings. The key objectives are to: Assess the effectiveness of integrated treatment approaches, including first-line medications and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), for patients with co-occurring OUD...
This Cooperative Agreement award from the National Institute on Drug Abuse (NIDA), under the Drug Use and Addiction Research Programs (CFDA 93.279), provides $4,710,576 to Mebias Discovery Inc. to develop a new chemical entity, MEB-1170, as a maintenance medication for the treatment of opioid use disorder (OUD). The project aims to evaluate the efficacy of MEB-1170 in reducing fentanyl self-administration and its safety profile, including its ability to avoid respiratory depression and...
This Project Grant award of $398,137 from the National Institute on Drug Abuse (NIDA), under the Drug Use and Addiction Research Programs (CFDA 93.279), aims to develop high-precision epigenetic therapeutics for opioid use disorder (OUD). The grantee, Boston Interactome LLC, will apply a mammalian cell-based compound screening platform to identify functional modulators of the neuronal G9A complex, which regulates DFosB expression under chronic opioid exposure. The efficacy and specificity of the...
The National Institute on Drug Abuse (NIDA), through the Drug Use and Addiction Research Programs (CFDA 93.279), awarded a $23,579,701 Cooperative Agreement to Ensysce Biosciences, Inc. to continue the clinical development of PF614-MPAR, an opioid product with overdose protection. PF614-MPAR is a combination product that includes a trypsin-activated abuse-resistant oxycodone prodrug (PF614) and the trypsin inhibitor nafamostat, which provides overdose protection. The goal of this award is to...
This federal Project Grant award from the National Institute on Drug Abuse (NIDA), under the Drug Use and Addiction Research Programs (CFDA 93.279), provides $722,876 to New York University School of Medicine to conduct a 5-year study characterizing complex opioid use disorder (OUD) care trajectories and outcomes following acute service utilization. The research aims to: 1) characterize real-world OUD treatment trajectories in the year following hospital encounters among treatment-naive...
This Project Grant award from the National Institute on Drug Abuse (NIDA), under the Drug Use and Addiction Research Programs (CFDA 93.279), provides $798,828 to Dark Matter Therapeutics, Inc. to discover novel small molecule therapeutics for the safe and effective treatment of opioid use disorder (OUD). The project aims to leverage artificial intelligence (AI) to develop a drug discovery strategy that integrates target-based and phenotype-based methodologies. Specifically, the AI platform M3.AI...
CLINICAL EVALUATION OF C4X3256, A NON-OPIOID, HIGHLY-SELECTIVE OREXIN-1 RECEPTOR ANTAGONIST FOR THE TREATMENT OF OPIOID USE DISORDER - OPIOID USE DISORDER (OUD) AND ITS CONSEQUENCES ARE A MAJOR PUBLIC HEALTH CONCERN AND HAVE RECENTLY BEEN DECLARED A NATIONAL PUBLIC HEALTH EMERGENCY. DESPITE THE AVAILABILITY OF MEDICATIONS TO TREAT OUD, THERE IS A NEED FOR IMPROVED TREATMENT MODALITIES THAT INVOLVE OTHER MECHANISMS OF ACTION. CURRENT PHARMACOLOGIC TREATMENT OPTIONS ALL TARGET THE MU-OPIOID RECEPTOR, EITHER AS A FULL AGONIST (METHADONE), PARTIAL AGONIST (BUPRENORPHINE), OR ANTAGONIST (NALTREXONE). WHILE THESE MEDICATIONS HAVE DEMONSTRATED EFFICACY AND SAFETY, THEY ALSO HAVE LIMITATIONS. FULL AND PARTIAL AGONISTS HAVE ABUSE LIABILITY, AND SIGNIFICANT LEVELS OF MISUSE, ABUSE, AND DIVERSION HAVE BEEN OBSERVED IN THE US AND INTERNATIONALLY (LOFWALL 2014; YOKELL 2012). THIS HAS RESULTED IN RESTRICTIONS ON ACCESS DUE TO A LACK OF WAIVERED PRESCRIBERS AND PATIENT LIMITS ON PRESCRIBING FOR BUPRENORPHINE AND DISPENSING THROUGH FEDERALLY REGULATED OPIOID TREATMENT PROGRAMS REQUIRING DAILY OBSERVED BUPRENORPHINE. IN ADDITION, THERE ARE CONCERNS ABOUT METHADONE OVERDOSE. NALTREXONE REQUIRES ABSTINENCE FROM OPIOIDS PRIOR TO INITIATION OF TREATMENT, WHICH IS A BARRIER TO TREATMENT FOR MANY PATIENTS. OF THE 2.1 MILLION PEOPLE SUFFERING FROM OUD IN THE US, ONLY 20% SEEM TO RECEIVE ANY FORM OF TREATMENT AND MANY OF THOSE WHO ARE TREATED WITH THESE MEDICATIONS DO NOT ACHIEVE ABSTINENCE FROM OPIOID USE AND FAIL TO ACHIEVE RECOVERY (SALONER 2015). THUS, THERE IS A NEED FOR ADDITIONAL PHARMACOLOGIC TREATMENT OPTIONS, PARTICULARLY FOR MEDICATIONS WITHOUT ABUSE LIABILITY AND THAT DO NOT REQUIRE COMPLETION OF WITHDRAWAL FROM OPIOIDS PRIOR TO TREATMENT. NONCLINICAL STUDIES SUPPORT A ROLE FOR THE OREXIN SYSTEM IN DRUG SEEKING, AS COMPOUNDS THAT SELECTIVELY BLOCK SIGNALING AT THE OREXIN-1 RECEPTOR (OX1R) REDUCE SEEKING OF MULTIPLE DRUGS OF ABUSE (JAMES 2017). C4X3256, A NON-OPIOID, HIGHLY-SELECTIVE OX1R ANTAGONIST HAS BEEN SHOWN TO HAVE A LONG RESIDENCE TIME AT THE OX1R, AND ALSO REDUCE INTRAVENOUS SELF- ADMINISTRATION AND CUE-INDUCED REINSTATEMENT IN ANIMAL MODELS OF NICOTINE ADDICTION, SUGGESTING IT COULD BE A TREATMENT FOR A RANGE OF ADDICTION RELATED BEHAVIORS. STUDIES PROPOSED IN THE APPLICATION WILL MOVE C4X3256 FROM PRECLINICAL DEVELOPMENT THROUGH PHASE I TESTING, INCLUDING UP TO 7 DAYS DOSING IN HEALTHY VOLUNTEERS AND UP TO 28 DAYS DOSING IN SUBJECTS WITH OUD. THE CURRENT TOXICOLOGY STUDIES WILL SUPPORT THE ADMINISTRATION OF C4X3256 TO HUMAN VOLUNTEERS FOR 4 WEEKS. ADDITIONAL TOXICOLOGY STUDIES ARE PROPOSED TO ALLOW FOR EXTENDED DOSING DURATION IN PHASE II AND FOR WOMEN OF CHILDBEARING POTENTIAL TO PARTICIPATE IN PHASE II OUTPATIENT TRIALS. THUS, THE CLINICAL, PRECLINICAL AND SUPPORTING PHARMACEUTICAL DEVELOPMENT STUDIES PROPOSED WILL ALLOW C4X3256 TO MOVE TO PHASE II STUDIES.