Ensysce Biosciences (La Jolla, California) has received a USD 5.28 million U01 cooperative agreement from the National Institute on Drug Abuse to continue clinical development of PF614-MPAR, an oxycodone prodrug designed to prevent overdose when patients take more than a prescribed dose. The award, the third-year continuation of a non-competing NIDA grant, funds a multi-ascending dose study across 25 mg, 50 mg and 100 mg strengths, positioning the program toward a New Drug Application. Ensysce Biosciences is led on this grant by principal investigator Lynn Kirkpatrick.
PF614-MPAR combines two proprietary mechanisms: a trypsin-activated prodrug (TAAP) that releases oxycodone only after enzymatic conversion in the gut, and a co-formulated trypsin inhibitor, nafamostat (MPAR), that blocks that conversion when doses exceed prescribed levels. Unlike existing abuse-deterrent opioid formulations, which primarily resist crushing or injection but do not address simple overconsumption of intact tablets, this chemistry-based approach specifically targets swallowing excess pills — reported as one of the most common forms of prescription opioid abuse. A completed Phase I study established the 25 mg dose and demonstrated proof-of-concept overdose protection when supratherapeutic amounts were administered.
The continuation funding reflects sustained NIH interest, through its Medication Development Research program, in pharmacologic countermeasures to opioid overdose beyond naloxone rescue and tamper-resistant formulations. For Ensysce, the grant extends a multi-year federal funding relationship supporting a lead pipeline asset, with three INDs already filed covering PF614 alone, the trypsin inhibitor alone, and the combination product. Whether the multi-dose safety data support an eventual FDA filing remains to be established in the studies this award funds.
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