Ensysce Biosciences Achieves Major Milestone with Initiation of Enrollment in Pivotal Phase 3 Trial of PF614, Its Next-Generation Opioid

Rhea-AI Summary

Ensysce Biosciences (NASDAQ:ENSC) announced the enrollment of the first patient in its pivotal Phase 3 trial of PF614 on December 9, 2025. The study, PF614-301, is a multicenter, randomized, double‑blind, placebo‑ and active‑controlled trial evaluating PF614 for moderate to severe pain after abdominoplasty.

The trial will test twice‑daily dosing intended to provide consistent post‑surgical analgesia while incorporating an innovative chemical mechanism designed to reduce abuse and overdose risk. Initial sites include CenExel JBR in Salt Lake City and CenExel Atlanta under principal investigators Dr. Todd Bertoch and Dr. Jessica McCoun.

Positive

• First patient enrolled in pivotal Phase 3 PF614-301
• Study is multicenter, randomized, double‑blind, placebo‑ and active‑controlled
• Trial tests twice‑daily dosing aimed at smoother blood‑drug levels
• PF614 includes an innovative chemical abuse‑reducing mechanism

Negative

• None.

Key Figures

Trial phase Phase 3 Pivotal PF614-301 trial for moderate to severe post-abdominoplasty pain

Market Reality Check

$1.60 Last Close

Volume Volume 68,390 vs 20-day average 85,010 – trading below typical activity ahead of this news. normal

Technical Price $1.60 is trading below the $2.45 200-day moving average, indicating a weak longer-term trend into this milestone.

Peers on Argus

Among key biotech peers, several names are down (ARTL -4.26%, PLRZ -3.91%, TTNP -3.96%), while SILO is up 3.27%. With ENSC down 2.44% pre-news and no peers in momentum scanners, moves appear more stock-specific than a uniform sector shift.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Dec 02	IP/patent update	Positive	-4.6%	New U.S. patent allowance extending MPAR® overdose protection coverage to <b>2042</b>.
Nov 20	Regulatory feedback	Positive	-12.0%	FDA agreed with PF614 manufacturing approach, supporting commercial-scale production.
Nov 17	Financing	Negative	-4.8%	Closed <b>$4.0M</b> convertible preferred financing with up to <b>$20.0M</b> total capacity.
Nov 14	Earnings/operations	Negative	-4.8%	Q3 2025 results showed low cash and ongoing losses alongside PF614-301 trial initiation.
Oct 10	Conference update	Positive	-3.4%	PAINWeek 2025 symposium highlights on TAAP™ and MPAR® safer pain-management platforms.

Pattern Detected

Recent ENSC news, even when operationally positive, has often been followed by negative price reactions, suggesting a pattern of selling into good news.

Recent Company History

Over the last six months, Ensysce reported IP strengthening for MPAR®, FDA support for PF614 manufacturing, multiple financings, and ongoing outreach around its TAAP™ and MPAR® platforms. Notably, a pivotal PF614-301 Phase 3 initiation was highlighted in Q3 2025 results on Nov 14. Despite these milestones and funding steps (including a $4M convertible preferred deal and broader patent protection through 2042), the stock saw negative reactions to most announcements, underscoring sentiment or dilution concerns around otherwise constructive updates.

Market Pulse Summary

The stock is dropping -12.5% following this news. A negative reaction despite a clear clinical milestone would fit a recent pattern where ENSC sold off on positive operational updates. Prior IP, FDA, and trial news often coincided with declines, reflecting dilution concerns and balance-sheet risk. With the stock already below the $2.45 200-day moving average and a history of capital raises, weakness around this Phase 3 enrollment update could reflect skepticism about funding the full program rather than the asset’s promise alone.

Key Terms

phase 3 medical

"pivotal Phase 3 clinical trial of PF614, its lead product candidate."

Phase 3 is the late-stage clinical testing step for a new drug or medical treatment, where the product is given to large groups of patients to confirm effectiveness, monitor side effects, and compare it to standard care. Successful Phase 3 results are often the final scientific hurdle before regulators decide on approval and market launch—like passing a final exam before graduation—and can sharply change a company's valuation and future revenue prospects.

randomized medical

"A Multicenter, Randomized, Double-Blind, Placebo- and Active-Controlled Study"

Randomized means participants or units in a study are assigned to different groups by chance rather than by choice, like flipping a coin to decide who gets a new treatment and who gets a comparison. For investors, randomized designs matter because they reduce bias and make results more trustworthy, so outcomes from randomized studies carry more weight when assessing regulatory approval, commercial prospects, and the risk that trial results will change a company’s valuation.

double-blind medical

"A Multicenter, Randomized, Double-Blind, Placebo- and Active-Controlled Study"

A double-blind process means that neither the people conducting an activity nor the people involved know certain key details, such as who is receiving a treatment or a placebo. This approach helps prevent bias from influencing the results, making the outcome more trustworthy. For investors, it ensures that decisions or judgments are based on unbiased information rather than preconceived opinions or expectations.

placebo-controlled medical

"Randomized, Double-Blind, Placebo- and Active-Controlled Study to Evaluate the Efficacy"

"Placebo-controlled" describes a testing method where one group receives the actual treatment or intervention, while another group receives a harmless, inactive version called a placebo. This approach helps determine whether the real treatment has genuine effects beyond psychological expectations. For investors, understanding this ensures confidence that reported benefits are real and not influenced by bias or false perceptions.

AI-generated analysis. Not financial advice.

~ Engineered to Deliver Potent Pain Relief with Unique, Built-In, Abuse Protection ~

SAN DIEGO, CA / ACCESS Newswire / December 9, 2025 / Ensysce Biosciences, Inc. (NASDAQ:ENSC) ("Ensysce" or the "Company"), a clinical-stage pharmaceutical company pioneering novel solutions for severe pain with built-in abuse and overdose protection, today announced that the first patient has been enrolled in the Company's pivotal Phase 3 clinical trial of PF614, its lead product candidate.

This landmark study, PF614-301, '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'," is designed to demonstrate PF614's ability to provide strong, consistent post-surgical pain relief while incorporating an innovative chemical mechanism intended to reduce the risk of abuse. The trial will also evaluate PF614's potential to provide a smoother, safer treatment of severe acute pain using twice daily dosing with reduced highs and lows in blood drug concentration, an approach which is seen as beneficial by leaders in the field.

Enrollment has commenced at CenExel JBR in Salt Lake City, Utah, under the leadership of Dr. Todd Bertoch, and CenExcel Atlanta under the leadership of Dr. Jessica McCoun, both recognized expert in anesthesiology and pain medicine and the study's Principal Investigators.

"This is a significant milestone for Ensysce and for the millions of patients who depend on opioid analgesia during recovery from serious surgery." said Dr. Lynn Kirkpatrick, CEO of Ensysce. "Initiation of our pivotal Phase 3 program moves us one step closer to redefining pain care. We aim to show that PF614 can reliably deliver the level of pain control patients need, while its built-in protective features help safeguard against the dangers of abuse. We believe PF614 represents a next generation of safety for opioid therapy and this Phase 3 trial marks a significant step on our pathway to commercialization."

About Ensysce Biosciences

Ensysce Biosciences is a clinical-stage pharmaceutical company disrupting the pain treatment landscape with its proprietary Trypsin-Activated Abuse Protection (TAAP™) and Multi-Pill Abuse Resistance (MPAR^®) platforms. By engineering opioids with intrinsic safeguards against tampering, misuse, and overdose, Ensysce aims to offer safer, life-saving options for patients in need of powerful pain relief. Learn more at: www.ensysce.com

Forward-Looking Statements

Statements contained in this press release that are not purely historical may be deemed to be forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995 and other federal securities laws. Without limiting the foregoing, the use of words such as "may," "intends," "can," "might," "will," "expect," "plan," "possible," "believe" and other similar expressions are intended to identify forward-looking statements. The product candidates discussed are in clinic and not approved and there can be no assurance that the clinical programs will be successful in demonstrating safety and/or efficacy, that Ensysce will not encounter problems or delays in clinical development, or that any product candidate will ever receive regulatory approval or be successfully commercialized. All forward-looking statements are based on estimates and assumptions by Ensysce's management that, although Ensysce believes to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that Ensysce expected. In addition, Ensysce's business is subject to additional risks and uncertainties, including among others, the initiation and conduct of preclinical studies and clinical trials; the timing and availability of data from preclinical studies and clinical trials; expectations for regulatory submissions and approvals; potential safety concerns related to, or efficacy of, Ensysce's product candidates; the availability or commercial potential of product candidates; the ability of Ensysce to fund its continued operations, including its planned clinical trials; the dilutive effect of stock issuances from our fundraising; and Ensysce's and its partners' ability to perform under their license, collaboration and manufacturing arrangements. These statements are also subject to a number of material risks and uncertainties that are described in Ensysce's most recent quarterly report on Form 10-Q and current reports on Form 8-K, which are available, free of charge, at the SEC's website at www.sec.gov. Any forward-looking statement speaks only as of the date on which it was made. Ensysce undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required under applicable law.

Ensysce Biosciences Company Contact:
Lynn Kirkpatrick, Ph.D.
Chief Executive Officer
(858) 263-4196

Ensysce Biosciences Investor Relations Contact:
Shannon Devine
MZ North America
Main: 203-741-8811
ENSC@mzgroup.us

SOURCE: Ensysce Biosciences Inc.

View the original press release on ACCESS Newswire

FAQ

What did Ensysce (ENSC) announce on December 9, 2025 about PF614?

Ensysce announced the first patient enrollment in its pivotal Phase 3 trial PF614-301 for post‑abdominoplasty pain.

What is the design of the ENCS PF614 Phase 3 trial PF614-301?

PF614-301 is a multicenter, randomized, double‑blind, placebo‑ and active‑controlled study evaluating efficacy and safety.

Which sites began enrollment for ENCS PF614-301 and who are the investigators?

Enrollment began at CenExel JBR (Salt Lake City) under Dr. Todd Bertoch and CenExel Atlanta under Dr. Jessica McCoun.

How does PF614 aim to reduce abuse risk for ENCS (ENSC)?

PF614 incorporates an innovative chemical mechanism intended to reduce abuse and overdose risk, per the announcement.

What pain condition is ENCS testing PF614 for in Phase 3 PF614-301?

The trial evaluates PF614 for moderate to severe pain after abdominoplasty (post‑surgical pain).

What dosing regimen is being tested in Ensysce's PF614 Phase 3 trial?

The study tests a twice‑daily dosing approach intended to provide smoother, consistent analgesia.