Ensysce Biosciences, a clinical-stage pharmaceutical company, is making strides in developing safer pain relief options with reduced potential for opioid abuse and overdose. In a recent shareholder letter, CEO Dr. Lynn Kirkpatrick highlighted the progress of their two clinical programs, centered around the TAAP™ (Trypsin-Activated Abuse Protection) and MPAR® (Multi-Pill Abuse Resistance) platforms.
The company's lead product, PF614, is a TAAP™ extended-release oxycodone designed to resist tampering and reduce abuse via non-oral routes. The second drug candidate, PF614-MPAR, combines PF614 with a trypsin inhibitor for oral-overdose protection. Both programs aim to address the critical healthcare issues of opioid safety and access to pain medication in the U.S.
PF614 Phase 3 Trial Set to Begin in Q2 2025
Ensysce completed an End of Phase 2 meeting with the FDA, receiving feedback on the design of their Phase 3 clinical program for PF614. The Phase 3 study, titled "A Multicenter, Randomized, Double-Blind, Placebo- and Active-Controlled Study to Evaluate the Efficacy and Safety of PF614 for the Treatment of Moderate to Severe Pain after Abdominoplasty," will evaluate PF614 against placebo for pain relief in patients undergoing abdominoplasty surgery. Enrollment is expected to begin in the second quarter of 2025.
Results from the two-part PF614‑102 study, published in Clinical and Translational Science, demonstrated a clear dose relationship between PF614 and oxycodone release and established bioequivalence between PF614 and OxyContin, potentially allowing for a streamlined 505(b)(2) regulatory pathway.
PF614-MPAR Advances with Breakthrough Therapy Designation
PF614-MPAR received Breakthrough Therapy designation from the FDA, which expedites the development and review of drugs intended to treat serious conditions with substantial improvement over available therapies. The FDA also provided additional regulatory guidance for the PF614-MPAR non-clinical program, facilitating its progression toward a new drug application (NDA) submission.
A Phase 1b study, PF614-MPAR-102, is underway to evaluate the pharmacokinetics of oxycodone and PF614 when co-administered with nafamostat. This study will examine the full commercial dose range of PF614-MPAR to verify overdose protection and effective oxycodone delivery. Initial dosing of subjects occurred in November, following a $14 million grant from the NIH.
OUD Program Focuses on Safer Treatment Options
Ensysce's Opioid Use Disorder (OUD) program has selected PF9001 as its lead drug candidate. PF9001 utilizes the TAAP™ and MPAR® technology to provide a safer treatment option for opioid overuse and addiction, with a lower potential for cardiovascular side effects compared to traditional methadone treatments.
Strategic Partnerships and Manufacturing
To support commercial-scale production, Ensysce has established strategic partnerships to strengthen its manufacturing capabilities. PF614 drug substance is currently being produced for clinical trial use and will see commercial scale-up in 2025 through Purisys LLC. A partnership with a specialty drug product manufacturer will provide clinical trial material, drug products for regulatory submissions, and initial commercial batches of PF614 and PF614-MPAR.
With these advancements, Ensysce Biosciences aims to play a key role in providing safer pain medication options and addressing the prescription drug abuse crisis in the U.S.
