Ensysce Biosciences Provides Enrollment Update on Pivotal Phase 3 Trial of PF614, Its Next-Generation Opioid for Severe Acute Pain

Rhea-AI Summary

Ensysce Biosciences (NASDAQ:ENSC) announced it has enrolled 50% of subjects targeted for interim review in the pivotal Phase 3 PF614-301 trial as of January 28, 2026. Enrollment began in late December 2025 across three U.S. sites, with interim data expected after the planned review.

PF614 is a twice-daily, activation‑dependent opioid candidate engineered for extended pain relief with built-in abuse and tamper protection.

Positive

• 50% enrollment of interim-review subjects achieved
• Three U.S. sites actively enrolling patients
• PF614 uses proprietary activation technology limiting tampering
• Twice-daily dosing designed for consistent post-surgical pain control

Negative

• No efficacy or safety results available yet for PF614
• Enrollment began in late December 2025, leaving 50% of interim cohort to recruit
• Trial currently limited to three U.S. sites, constraining geographic enrollment diversity

Key Figures

Enrollment milestone: 50% of subjects Clinical sites: 3 U.S. sites Dosing schedule: Twice-daily dosing

3 metrics

Enrollment milestone 50% of subjects Target enrollment reached for interim Phase 3 PF614 review

Clinical sites 3 U.S. sites PF614-301 trial locations in Utah, Georgia, and Texas

Dosing schedule Twice-daily dosing PF614 regimen for post-abdominoplasty pain relief

Market Reality Check

Price: $0.8469 Vol: Volume 89449 is below 20-...

normal vol

$0.8469 Last Close

Volume Volume 89449 is below 20-day average of 126021 ahead of this positive trial update. normal

Technical Shares at 0.8469, trading below 200-day MA of 1.99 and 88.93% below 52-week high.

Peers on Argus

Peer biotech moves are mixed: ARTL up 4.6%, SILO up 1.34%, while PLRZ, TTNP, and...

1 Up

Peer biotech moves are mixed: ARTL up 4.6%, SILO up 1.34%, while PLRZ, TTNP, and NCNA are down between 3.96% and 5.75%, suggesting ENSC’s action is stock-specific rather than a sector-wide trend.

Previous Clinical trial Reports

5 past events · Latest: Dec 09 (Positive)

Same Type Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Dec 09	Phase 3 initiation	Positive	-11.3%	First patient enrolled in pivotal PF614-301 Phase 3 trial.
Jul 16	Phase 3 launch	Positive	+2.4%	Launch of pivotal PF614-301 study for post-surgical pain relief.
Aug 27	NIH grant award	Positive	+47.1%	Award of <b>$14M</b> NIH/NIDA grant for PF614-MPAR clinical work.
Jul 09	Data presentation	Positive	+5.6%	IASP symposium and presentation of PF614 and PF614-MPAR clinical data.
May 20	Trial collaboration	Positive	+18.4%	Collaboration with Quotient Sciences to advance PF614-MPAR Phase 1b study.

Pattern Detected

Clinical-trial and development milestones have often produced sizable moves, mostly positive, but with at least one sharp negative reaction despite constructive trial progress.

Recent Company History

Over the past two years, Ensysce has repeatedly highlighted clinical progress for PF614 and PF614‑MPAR. Milestones include initiating pivotal Phase 3 PF614-301, securing a $14M NIH/NIDA grant for PF614‑MPAR, and advancing a Phase 1b overdose-protection study. These events frequently triggered double‑digit single‑day moves, mostly upward. Today’s enrollment‑update announcement fits this pattern of clinical development steps aimed at validating PF614’s efficacy and abuse‑deterrent profile.

Historical Comparison

clinical trial

+16.9 %

Average Historical Move

Historical Analysis

Across 5 clinical-trial releases, ENSC moved an average of 16.95%, showing that PF614 and PF614‑MPAR updates have historically driven pronounced single-day volatility.

Typical Pattern

Clinical news shows progression from PF614 Phase 3 study launch and first-patient enrollment to NIH-funded PF614‑MPAR work and ongoing Phase 1b overdose-protection trials, reflecting steady advancement of the pain and safety platform.

Market Pulse Summary

This announcement marks PF614’s pivotal Phase 3 trial reaching 50% of subjects needed for interim re...

Analysis

This announcement marks PF614’s pivotal Phase 3 trial reaching 50% of subjects needed for interim review, indicating rapid enrollment across 3 U.S. sites. It follows earlier milestones such as trial initiation and NIH-backed work on the PF614‑MPAR platform. Investors typically focus on whether upcoming interim data confirm meaningful post-surgical pain relief with abuse-deterrent features, while also weighing the company’s small capitalization and previously disclosed going-concern risks.

Key Terms

phase 3, clinical trial, randomized, double-blind, placebo-controlled, extended-release

4 terms

phase 3 medical

"pivotal Phase 3 clinical trial of PF614, the Company's next-generation opioid"

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.

clinical trial medical

"pivotal Phase 3 clinical trial of PF614, the Company's next-generation opioid"

A clinical trial is a carefully controlled study in which a new medicine, medical device, or treatment is tested on people to see if it is safe and effective. For investors it matters because trial results determine whether a product can win regulatory approval and reach patients, much like a road test decides if a new car can be sold; positive or negative results can sharply change a company’s prospects and stock value.

randomized, double-blind, placebo-controlled medical

"a multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy"

A "randomized, double-blind, placebo-controlled" process is a method used to test the effectiveness of a new treatment or intervention. Participants are randomly assigned to different groups, with one receiving the real treatment and the other a fake version, called a placebo. Neither the participants nor the researchers know who is receiving which, which helps ensure unbiased results. For investors, this rigorous approach increases confidence that the findings are accurate and not influenced by guesswork or bias.

extended-release medical

"while enabling extended-release pain control. This approach is intended to address"

Extended-release is a drug formulation designed to release its active ingredient slowly over an extended period so the medicine stays at steadier levels in the body and usually needs to be taken less often—think of a timed-release coffee versus sipping many short espressos. Investors care because extended-release versions can improve patient adherence, reduce side effects, and create product differentiation that supports higher pricing, longer commercial lifecycles, and clearer revenue visibility, while also attracting specific regulatory and manufacturing considerations.

AI-generated analysis. Not financial advice.

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

SAN DIEGO, CA / ACCESS Newswire / January 28, 2026 / 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 it has enrolled 50% of subjects targeted for interim review in its pivotal Phase 3 clinical trial of PF614, the Company's next-generation opioid candidate engineered to deliver powerful pain relief with built-in abuse protection..

Enrollment began in late December 2025 and is progressing rapidly across three U.S. clinical sites: CenExel JBR (Salt Lake City, Utah); CenExel Atlanta (Decatur, Georgia); and ERG-HD Research, LLC (Houston, Texas). The study is being led by Dr. Todd Bertoch, Dr. Jessica McCoun, and Dr. D'Aunno, recognized experts in anesthesiology and pain management.

The pivotal PF614-301 trial is a multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of PF614 for the treatment of moderate to severe pain following abdominoplasty. The study is designed to demonstrate PF614's ability to deliver consistent, clinically meaningful post-surgical pain relief using twice-daily dosing.

PF614 leverages Ensysce's proprietary chemical activation technology, which is designed to keep the opioid inactive until swallowed, limiting the impact of tampering and dose manipulation while enabling extended-release pain control. This approach is intended to address one of the central challenges in modern pain care: delivering opioid-level efficacy while reducing the risks of abuse and misuse.

"This milestone reflects the strength of our execution to provide better options to treat severe acute pain," said Dr. Lynn Kirkpatrick, Chief Executive Officer of Ensysce. "Patients recovering from major surgery still require opioid level analgesia for effective pain control. PF614 is designed to deliver that level of relief reliably and predictably while incorporating intrinsic safeguards that are absent from conventional opioids. Achieving this enrollment milestone in the early stages of this Phase 3 program brings us meaningfully closer to delivering interim data and advancing what we believe could be a new standard in acute pain management. We are pleased to share this encouraging study update."

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

View the original press release on ACCESS Newswire

FAQ

What enrollment milestone did Ensysce (ENSC) report on January 28, 2026?

Ensysce reported it has enrolled 50% of subjects targeted for interim review in the PF614 Phase 3 trial. According to the company, enrollment started in late December 2025 and is progressing across three U.S. clinical sites.

Which clinical trial is Ensysce (ENSC) advancing with PF614 and what is its design?

PF614-301 is a multicenter, randomized, double-blind, placebo-controlled Phase 3 trial for post-abdominoplasty pain. According to the company, the study evaluates twice-daily PF614 for moderate to severe post-surgical pain and includes an interim review.

How does PF614 aim to reduce abuse risk compared to conventional opioids?

PF614 uses chemical activation technology to keep the opioid inactive until swallowed, limiting tampering and dose manipulation. According to the company, this design aims to enable extended-release analgesia while reducing misuse risk.

Where is Ensysce (ENSC) conducting PF614 enrollment and who leads the study?

Enrollment is occurring at three U.S. sites: Salt Lake City, Decatur (Atlanta), and Houston. According to the company, the trial is led by recognized anesthesiology and pain management investigators including Drs. Bertoch, McCoun, and D'Aunno.

What next steps and timelines did Ensysce (ENSC) indicate after reaching 50% enrollment?

Reaching 50% enrollment brings the trial closer to the planned interim review and data readout, but no interim date was provided. According to the company, achieving this milestone advances progress toward interim data and subsequent development steps.