This Project Grant award from the National Institute on Drug Abuse (NIDA), under the federal Drug Use and Addiction Research Programs (CFDA 93.279), aims to identify small molecule compounds that can bind to the GPR26 receptor and potentially treat opioid use disorders (OUDs) without directly targeting opioid receptors. The $399,884 award to Jillion Therapeutics Inc. will utilize DNA-encoded library (DEL) screening technology to test over 125 million proprietary compounds for high-affinity...
This $399,483 federal Project Grant award from the National Institute on Drug Abuse (NIDA) under the Drug Use and Addiction Research Programs (CFDA 93.279) aims to generate synergy between artificial intelligence (AI) and DNA-encoded library (DEL) technologies to identify novel multivalent compounds for treating substance use disorders (SUDs). The key objectives are to: 1) use DEL screening to identify compounds that target the opioid receptor delta (OPRD1) and dopamine receptor D3 (DRD3) to...
This Project Grant award from the National Institute on Drug Abuse (NIDA) under the Drug Use and Addiction Research Programs (CFDA 93.279) provides $275,253 to Epivario Inc. to develop a novel epigenetic regulator as a treatment for opioid use disorder (OUD). The award supports screening of next-generation compounds targeting the metabolic enzyme ACSS2, which has been shown to play a key role in the encoding of drug-related memories. This research aims to identify a potent ACSS2 inhibitor that...
This Project Grant award of $847,000 from the National Institute on Drug Abuse (NIDA) under the Drug Use and Addiction Research Programs (CFDA 93.279) supports research to investigate the neuropeptide S receptor 1 (NPSR1) as a potential target for reducing opioid self-administration and relapse in opioid use disorder. The research aims to evaluate whether NPSR1 agonism can alleviate the anxious phenotype observed during opioid withdrawal, which contributes to the intensified motivation to seek...
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 $398,137 to Boston Interactome LLC to develop high-precision epigenetic therapeutics for opioid use disorder (OUD). The project aims to identify small-molecule compounds that can selectively modulate the G9A protein complex, which regulates the expression of DFosB in the brain during chronic opioid exposure. The work will involve a...
The National Institute on Drug Abuse (NIDA) awarded Attune Neurosciences, Inc. a $399,739 Project Grant under the Drug Use and Addiction Research Programs (CFDA 93.279) to develop a wearable, head-worn low-intensity focused ultrasound (LIFU) device for enhancing sleep in individuals with substance use disorder (SUD), including opioid use disorder (OUD). The 9-month Phase I SBIR project aims to reconfigure Attune's existing LIFU device to create a more compact, user-friendly form factor, followed...
This Project Grant award from the National Institute of Biomedical Imaging and Bioengineering (NIBIB), under the "Discovery and Applied Research for Technological Innovations to Improve Human Health" (CFDA 93.286) program, aims to develop bioresorbable microdevices that can deliver intermittent sub-perceptual doses of 5HT2A agonists, such as psilocybin, to mitigate depression associated with opioid use disorder. The $306,556 award to Interval Therapeutics LLC will be used to produce...
The National Institute on Drug Abuse (NIDA) awarded a $19,302,777 Cooperative Agreement (CFDA 93.279 - Drug Use and Addiction Research Programs) to Nirsum Laboratories, Inc. to accelerate the development of NRS-033, a novel medication for the treatment of opioid use disorder (OUD). The project aims to advance late-stage chemistry, manufacturing, and controls (CMC), conduct registration-enabling non-clinical studies, establish quality systems, and engage with the FDA to expedite NRS-033 into...
This Project Grant award, funded by the National Institute on Drug Abuse (NIDA) under the Drug Use and Addiction Research Programs (CFDA 93.279), supports preclinical research to investigate the potential of targeting the neuropeptide S (NPS) receptor as a treatment for opioid use disorder. The $419,876 award, with a performance period from September 2024 to August 2026, aims to conduct proof-of-concept studies to determine whether NPS receptor-targeted molecules can reduce oxycodone taking...
This $397,829 Project Grant award from the National Institute on Drug Abuse (NIDA), under the Federal Drug Use and Addiction Research Programs (CFDA 93.279), supports the development of an AI platform to accelerate the discovery of therapeutics for substance use disorders (SUDs). The key objectives of this 1-year project are to: 1) create curated datasets and machine learning models to expedite drug discovery tasks, 2) identify mechanistic targets for GLP-1 receptor agonist pathways that can...
DETERMINATION OF ROUTE OF ADMINISTRATION AND CARDIAC SAFETY OF A NOVEL PSYCHOPLASTOGEN FOR THE TREATMENT OF SUDS - ABSTRACT DELIX THERAPEUTICS IS DEVELOPING PSYCHOPLASTOGENS, COMPOUNDS THAT PROMOTE RAPID AND SUSTAINED NEUROPLASTICITY. THIS NEW CLASS OF COMPOUNDS WAS IDENTIFIED BY DELIX FOUNDER, PROFESSOR DAVID OLSON (UC DAVIS). DLX-007 IS A NOVEL, POTENT PSYCHOPLASTOGEN DESIGNED AND INSPIRED BY KNOWN PSYCHOPLASTOGENS IBOGAINE AND 5-MEO-DMT. SIMILAR TO THESE CLINICALLY EFFECTIVE COMPOUNDS, DLX-007 PROMOTES STRUCTURAL AND FUNCTIONAL NEURAL PLASTICITY IN CIRCUITS RELEVANT FOR THE TREATMENT OF SUBSTANCE USE DISORDERS (SUDS) WITH DEMONSTRATED EFFICACY FOR A VARIETY OF SUBSTANCES IN PRECLINICAL MODELS INCLUDING OPIOID USE DISORDER (OUD). IN ADDITION TO REDUCING HEROIN- CONSUMPTION AND PRODUCING ANTIDEPRESSANT-LIKE EFFECTS IN RODENT, DLX-007 AVOIDS MANY OF THE SAFETY CONCERNS ABUNDANT TO IBOGAINE. DLX-007 HAS COMPLETED GLP IND-ENABLING STUDIES, SHOWING A GOOD SAFETY PROFILE AND DESIRED EFFECT IN RELEVANT PRECLINICAL MODELS OF OUD. IN ORDER TO FURTHER ADVANCE THE DEVELOPMENT OF DLX-007 AND POSITION IT FOR TRANSITION TO HUMAN TRIALS, DELIX PROPOSES TO ESTABLISH THE IDEAL ADMINISTRATION PROFILE, WHILE MAINTAINING ACCEPTABLE CARDIOTOXIC SAFETY, FOR THE TREATMENT OF HUMANS. IN THIS PROPOSAL, WE WILL FIRST ASSESS THE IDEAL ROUTE OF ADMINISTRATION BY ESTABLISHING THE PHARMACOKINETIC (PK) PARAMETERS OF INTRAMUSCULAR ADMINISTRATION IN THREE PRECLINICAL SPECIES, MODELLING THE PREDICTED HUMAN PK AND COMPARING THOSE RESULTS TO PREVIOUSLY OBTAINED PK PARAMETERS FOR INTRAVENOUS AND ORAL ADMINISTRATION. SECONDLY, WE WILL USE A STATE-OF-THE-ART CARDIOVASCULAR SAFETY ASSAY TO VALIDATE AND EXPAND THE COMPARATIVE IMPROVEMENTS OUR COMPOUND HAS IN RELATION TO IBOGAINE'S NOTORIOUS CARDIO-SAFETY PROFILE. THIS PROPOSAL INTRODUCES A NOVEL TREATMENT PARADIGM FOR SUD, NAMELY, LEVERAGING STRUCTURAL PLASTICITY. DELIX'S DLX-007 IS A HIGH POTENTIAL THERAPEUTIC FOR OUD, PRESERVING ITS NEUROPLASTIC PROMOTING CHARACTERISTICS AND BEHAVIORAL EFFICACY OF IBOGAINE BUT WITHOUT THE HALLUCINOGENIC LIABILITIES AND REDUCED CARDIOTOXIC LIABILITIES. DLX- 007 TREATMENT MAY REVERSE OPIOID-INDUCED STRUCTURAL CHANGES AND ITS CLINICAL DEVELOPMENT COULD ENHANCE THE THERAPEUTIC ARSENAL FOR TREATING OUD, IN PARTICULAR BECAUSE IT PROVIDES A NON-OPIOID RECEPTOR-BASED THERAPEUTIC THAT MIGHT BE CAPABLE OF REVERSING THE UNDERLYING DISEASE NEUROPATHOLOGY LONG-TERM. DUE TO DLX-007'S IMPROVED SAFETY PROFILE RELATIVE TO ITS PARENT COMPOUND, WE ANTICIPATE THAT DLX-007 MAY ALSO HAVE BROAD THERAPEUTIC POTENTIAL FOR TREATING MULTIPLE SUDS IN ADDITION TO OTHER NEUROPSYCHIATRIC AND NEURODEGENERATIVE DISORDERS CHARACTERIZED BY DENDRITIC SPINE AND SYNAPSE LOSS IN THE PFC AND ITS DOWNSTREAM TARGETS.