Ensysce Biosciences Issues Annual Shareholder Letter

Rhea-AI Summary

Ensysce Biosciences (NASDAQ:ENSC) issued its 2025 annual shareholder letter outlining clinical, regulatory, IP and financing progress. Key 2025 achievements include initiation of the pivotal PF614-301 Phase 3 trial with enrollment started at two sites, FDA alignment on PF614 commercial manufacturing and CMC strategy, and advancement of PF614-MPAR under Breakthrough Therapy pathway. The company secured additional capital including a November 2025 $4M convertible preferred financing enabling access to up to $20M over 24 months and continued non-dilutive support from NIDA totaling over $25M for MPAR programs. A new MPAR patent allowance extends protection through 2042. Anticipated 2026 priorities include continued Phase 3 enrollment, further FDA interactions, MPAR labeling work, and PF9001 IND-enabling activities.

Positive

• Pivotal PF614-301 Phase 3 enrollment initiated (Dec 9, 2025)
• FDA alignment on PF614 commercial CMC and starting materials
• MPAR patent allowance extends protection through 2042
• Access to up to $20M financing over 24 months plus >$25M NIDA grants

Negative

• November 2025 $4M convertible preferred has $2.50 fixed conversion price and 50% warrant coverage (potential dilution)

News Market Reaction

+10.64%

10 alerts

+10.64% News Effect

+7.9% Peak in 23 hr 21 min

+$368K Valuation Impact

$4M Market Cap

0.2x Rel. Volume

On the day this news was published, ENSC gained 10.64%, reflecting a significant positive market reaction. Argus tracked a peak move of +7.9% during that session. Our momentum scanner triggered 10 alerts that day, indicating notable trading interest and price volatility. This price movement added approximately $368K to the company's valuation, bringing the market cap to $4M at that time.

Data tracked by StockTitan Argus on the day of publication.

Key Figures

NIDA grant installment: $5 million Total NIDA funding: Over $25 million Next NIDA installment: $5 million +5 more

8 metrics

NIDA grant installment $5 million Second installment of second multi‑year NIDA grant (June 2025)

Total NIDA funding Over $25 million Cumulative non‑dilutive funding for PF614‑MPAR program to date

Next NIDA installment $5 million Third installment expected June 2026 under current grant

MPAR patent term Through 2042 New U.S. MPAR® patent Notice of Allowance in November 2025

Recent financing $4 million Convertible preferred financing completed November 2025

Total capital access Up to $20 million Capital accessible over 24 months from November 2025 financing

Conversion price $2.50 per share Fixed conversion price for preferred shares in November 2025 deal

Warrant coverage 50% Coverage on November 2025 convertible preferred financing

Market Reality Check

Price: $0.8419 Vol: Volume 52,168 is about 0....

low vol

$0.8419 Last Close

Volume Volume 52,168 is about 0.12x the 20‑day average 446,979, showing muted pre‑news activity. low

Technical Shares at $0.94 are well below the $2.15 200‑day MA and 90.18% under the $9.57 52‑week high, despite the positive strategic update.

Peers on Argus

ENSC was up 2.17% pre‑news while peers were mixed: PLRZ +54.92%, NCNA +1.11%, an...

1 Down

ENSC was up 2.17% pre‑news while peers were mixed: PLRZ +54.92%, NCNA +1.11%, and several others down ~4–5%, indicating stock‑specific dynamics rather than a unified biotech move.

Historical Context

5 past events · Latest: Dec 09 (Positive)

Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Dec 09	Phase 3 enrollment	Positive	-11.3%	First patient enrolled in pivotal PF614‑301 Phase 3 pain trial.
Dec 02	IP expansion	Positive	-4.6%	New MPAR® patent Notice of Allowance extending protection through 2042.
Nov 20	FDA feedback	Positive	-12.0%	FDA agreed with PF614 manufacturing approach, enabling commercial‑scale path.
Nov 17	Financing secured	Positive	-4.8%	$4M convertible preferred financing unlocking up to $20M total capital.
Nov 14	Earnings update	Negative	-4.8%	Q3 2025 results with low cash and ongoing losses despite grant funding.

Pattern Detected

Recent ENSC news has often been clinically or strategically positive but followed by negative 24‑hour price reactions, suggesting a pattern of bearish or skeptical market responses to good news.

Recent Company History

Over the last few months, ENSC has reported multiple milestones, including initiation of the pivotal PF614‑301 Phase 3 trial (July 2025) and FDA alignment on PF614 manufacturing (Nov 20, 2025). It also expanded MPAR® patent protection to 2042 and secured a $4.0M financing with up to $20.0M potential. Despite these developments, each event saw negative 24‑hour price reactions, contrasting the constructive operational and regulatory trajectory highlighted again in the new shareholder letter.

Market Pulse Summary

The stock surged +10.6% in the session following this news. A strong positive reaction aligns with t...

Analysis

The stock surged +10.6% in the session following this news. A strong positive reaction aligns with the shareholder letter’s emphasis on Phase 3 execution for PF614, extended MPAR® patent protection to 2042, and access to up to $20 million in capital. However, ENSC has previously sold off after constructive updates, and recent financings with $2.50 conversion terms and 50% warrant coverage highlight dilution risk that could cap sustained upside.

Key Terms

phase 3, breakthrough therapy designation, 505(b)(2) registration pathway, notice of allowance, +4 more

8 terms

phase 3 medical

"PF614-301 Phase 3 Trial Enrollment Underway, Advancing Toward Market Launch"

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.

breakthrough therapy designation regulatory

"PF614-MPAR under Breakthrough Therapy designation from the FDA"

A breakthrough therapy designation is a regulatory fast-track given to a drug or treatment that shows early signs of providing a major improvement over existing options for a serious condition. Think of it as a VIP lane that can speed up development and more intensive guidance from regulators, which matters to investors because it can shorten time to market, reduce development risk and potentially increase a company’s value — though it does not guarantee approval.

505(b)(2) registration pathway regulatory

"support for a streamlined 505(b)(2) registration pathway"

A 505(b)(2) registration pathway is a U.S. FDA drug-approval route that lets a company rely partly on existing clinical studies or the agency’s prior findings instead of repeating every test. Think of it as using an earlier set of blueprints tomodify a product—such as a new dose, form, or combination—so development can be faster and cheaper, which matters to investors because it can lower costs, shorten time-to-market, and still carries regulatory and commercial risk.

notice of allowance regulatory

"the U.S. Patent and Trademark Office issued a Notice of Allowance"

A notice of allowance is an official confirmation from a patent office that a patent application has met all necessary requirements and is approved for granting. It signals that the invention is likely to receive legal protection soon, which can be important for investors considering the value and exclusivity of a new product or technology. Think of it as a green light indicating that the invention is on track to become legally protected.

composition-of-matter regulatory

"This patent includes both composition-of-matter and method-of-use claims"

A composition-of-matter is a legal description of a specific chemical or biological substance or mixture—think of it as the exact recipe and ingredients that make up a drug, material, or chemical product. For investors, ownership of a composition-of-matter patent can act like a locked recipe that keeps competitors out, protecting future sales and profit margins and reducing the risk that a product will be easily copied.

method-of-use regulatory

"includes both composition-of-matter and method-of-use claims"

A method-of-use is a legal description of how a medicine, medical device, or technology is intended to be used to treat a specific condition or achieve a particular result. Think of it as the recipe for applying a product rather than the product itself; it can be protected by patents or regulatory approvals. Investors watch method-of-use protections because they can extend exclusive rights, affect future sales, create licensing opportunities, or trigger litigation that changes a product's commercial value.

ind-enabling activities regulatory

"Advancement of PF9001 toward IND-enabling activities"

IND-enabling activities are the lab tests, animal studies and manufacturing checks a company performs to demonstrate a new drug is reasonably safe and can be produced reliably before filing an Investigational New Drug (IND) application to begin human trials. For investors these steps are a key milestone because completing them reduces safety and regulatory risk, requires substantial time and funding, and signals that a program is ready to move from early development into clinical testing—like building a foundation before constructing a house.

contract research organization technical

"we partnered with Rho, Inc., a leading contract research organization (CRO)"

A contract research organization (CRO) is an outside company hired to run medical and scientific work for drug, device or biotech developers—like an experienced project manager and lab team that companies rent instead of building in-house. Investors care because CROs influence development speed, quality and cost: delays or successes in trials affect client spending, regulatory risk and ultimately revenues for both the sponsor and the CRO.

AI-generated analysis. Not financial advice.

• PF614-301 Phase 3 Trial Enrollment Underway, Advancing Toward Market Launch

• FDA Aligned with ENSC Manufacturing Path for PF614, Enabling Commercial Scale Up

• MPAR® Patent Protection Extended Through 2042

• Up to $20 Million in Funding Secured to Advance Late-Stage Programs

SAN DIEGO, CALIFORNIA / ACCESS Newswire / January 5, 2026 / Ensysce Biosciences, Inc. (NASDAQ:ENSC) ("Ensysce" or "Company"), a clinical-stage pharmaceutical company developing innovative solutions for severe pain relief while reducing the potential for opioid abuse and overdose, today issued its 2025 annual letter to shareholders from Chief Executive Officer, Dr. Lynn Kirkpatrick.

Dear Fellow Shareholders,

2025 was a year of meaningful execution and strategic advancement for Ensysce. I would like to thank our shareholders for your continued support as we advance our mission to deliver safer, more responsible opioid analgesics without compromising access to effective pain relief. Over the past year, we made substantial progress across clinical development, regulatory alignment, intellectual property, and financing- strongly positioning the Company for 2026 and beyond.

Our efforts in 2025 were centered on advancing our clinical programs built on Ensysce's proprietary TAAP™ (Trypsin-Activated Abuse Protection) and MPAR® (Multi-Pill Abuse Resistance) technology platforms. Together, these platforms are designed to fundamentally improve the safety profile of opioid medications by addressing both abuse and overdose risk while preserving therapeutic efficacy.

TAAP™ Program Update: PF614

Our lead clinical candidate, PF614, is an extended-release oxycodone analgesic incorporating TAAP™ technology. PF614 potentially represents a new class of opioid and is designed to activate only when swallowed and exposed to trypsin in the small intestine, rendering it highly resistant to tampering and reducing the potential for abuse through non-oral routes of administration.

In July 2025, we reached a major milestone with the initiation of our pivotal PF614-301 Phase 3 clinical trial, 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 Following Abdominoplasty." This study is designed to assess PF614's ability to deliver effective post-surgical pain relief via steady analgesia, while addressing key safety concerns associated with traditional opioids.

To ensure rigorous trial execution, we partnered with Rho, Inc., a leading contract research organization (CRO) with extensive experience in central nervous system (CNS) and pain studies. On December 9, 2025, we initiated subject enrollment at two clinical sites, with additional sites expected to follow. We anticipate providing enrollment and progress updates during the first half of 2026 as we advance our Phase 3 program.

Importantly, in November 2025 we received highly constructive written feedback from the U.S. Food and Drug Administration (FDA) regarding our commercial manufacturing strategy for PF614. The Agency agreed with our proposed regulatory starting materials, drug substance specifications, and overall chemistry, manufacturing and controls (CMC) approach. This alignment provides a clear and direct path to commercial-scale manufacturing. We have initiated drug substance manufacturing activities with Purisys, LLC, a subsidiary of Noramco, and are working closely with our drug product manufacturing partner, Galephar, to support NDA registration readiness.

MPAR® Program Update: PF614-MPAR

Our second clinical candidate, PF614-MPAR, combines PF614 with our proprietary MPAR® overdose protection technology. PF614-MPAR is engineered to "switch off" opioid release in an overdose scenario, offering a potentially life-saving advance for patients who require opioid-strength analgesia. We believe PF614-MPAR is the only oral opioid analgesic designed with built-in overdose protection if taken in amounts greater than a prescribed dose.

This program continues to receive strong support from the National Institute on Drug Abuse (NIDA). In June 2025, Ensysce received the second $5 million installment of its second multi-year NIDA grant, bringing total non-dilutive funding for this program to over $25 million to date. The current grant extends through 2027, with a third $5 million installment expected in June 2026.

Key MPAR® program developments during 2025 included:

• Continued advancement of PF614-MPAR under Breakthrough Therapy designation from the FDA

• Encouraging feedback from the FDA regarding overdose protection labeling and support for a streamlined 505(b)(2) registration pathway

• Progress in our PF614-MPAR-102 clinical study supported by multi-year NIDA funding, which continues to generate important data to support regulatory discussions

• Collaborative work with the FDA on a scientific whitepaper that articulates the rationale behind overdose protection labeling

In September 2025, we presented updates on both PF614 and PF614-MPAR at PainWeek 2025, the world's largest pain management conference. Our standing-room-only symposium, "Pain Management, Re-Invented: A New Era for Analgesia," featured leading experts in pain medicine and highlighted Ensysce's vision for opioids that treat severe pain while actively protecting patients with increased safety features built into the medications.

Opioid Use Disorder Program Update

In parallel, we continued advancing our opioid use disorder (OUD) program as a natural extension of our mission. In 2025, we identified PF9001 as our lead OUD candidate. PF9001 leverages both TAAP™ and MPAR® technologies and is designed to limit abuse, reduce cardiovascular risk, and incorporate built-in overdose protection.

This program is supported by another multi-year grant through the HEAL (Helping to End Addiction Long-term) program and with encouragement from NIDA. As opioid addiction continues to impact millions of individuals, we believe Ensysce can contribute a differentiated and safer therapeutic approach in this critical area of unmet medical need.

Expanding Intellectual Property Portfolio

In November 2025, the U.S. Patent and Trademark Office issued a Notice of Allowance for a new MPAR® patent, extending intellectual property protection through 2042. This patent includes both composition-of-matter and method-of-use claims, representing the strongest form of patent protection available. This milestone significantly enhances the long-term value of the MPAR® platform and reinforces the differentiated nature of our technology.

Strengthened Financial Position to Advance Late-Stage Clinical Programs

Throughout 2025, Ensysce was able to attract a number of investments that have allowed the Company to continue progressing its major program toward its pivotal studies. Most recently, in November 2025, we completed an additional $4 million convertible preferred financing, opening up access to up to $20 million in total capital over the course of the following 24 months. This capital supports the execution of our PF614 Phase 3 program and extends our operating runway.

The financing structure includes a fixed conversion price of $2.50 per share, subject to adjustment, and 50% warrant coverage, reflecting continued investor confidence and alignment with upcoming clinical and regulatory milestones. This financing, added to our continued grant support by NIDA, provides ENSC the ability to continue to progress its critical programs in 2026.

Looking Ahead

As we enter 2026, Ensysce is positioned for continued momentum. Key anticipated milestones include:

• Continued enrollment and execution of the PF614-301 Phase 3 trial

• Advancement of PF614-MPAR under Breakthrough Therapy designation

• Additional FDA interactions supporting commercial manufacturing readiness

• Further data generation to support overdose-protection labeling for MPAR products

• Advancement of PF9001 toward IND-enabling activities

We remain committed to advancing the next generation of powerful analgesics that address the severest of pain while incorporating safeguards aligned with modern public health priorities.

Subsequent to Year End: January 7, 2025 Shareholder Meeting

Finally, I would like to advise that our 2025 Annual Shareholders meeting will be held January 7, 2026. We thank our shareholders for their engagement and encourage you to vote through to the 7^th in support of the Company's strategic priorities.

On behalf of the entire Ensysce team, thank you for your continued confidence in our science, our strategy, and our mission. The progress achieved in 2025 has laid a strong foundation for the year ahead, and we look forward to sharing additional milestones as we continue to build long-term value.

Sincerely,
Dr. Lynn Kirkpatrick
Chief Executive Officer
Ensysce Biosciences, Inc.

About Ensysce Biosciences

Ensysce Biosciences is a clinical-stage company with a goal of disrupting the analgesic landscape by introducing a new class of highly novel opioids for the treatment of severe pain. Leveraging its Trypsin-Activated Abuse Protection (TAAP™) and Multi-Pill Abuse Resistance (MPAR®) platforms, the Company is developing unique, tamper-proof treatment options for pain that minimize the risk of both drug abuse and overdose. Ensysce's products are anticipated to provide safer options to treat patients suffering from severe pain and assist in preventing deaths caused by medication abuse. For more information, please visit 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, possible NASDAQ delisting, 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; continuation of government funding; 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, 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 progress did ENSC report for the PF614 Phase 3 trial on January 5, 2026?

Ensysce reported initiation of the pivotal PF614-301 Phase 3 study with subject enrollment started at two sites on Dec 9, 2025.

What did the FDA agree with regarding PF614 manufacturing for ENSC (ENSC)?

The FDA provided written feedback agreeing with the proposed regulatory starting materials, drug substance specifications, and overall CMC approach for PF614.

How much funding has ENSC secured to advance late-stage programs as of Jan 5, 2026?

Ensysce completed a $4M convertible preferred financing in Nov 2025 enabling access to up to $20M over 24 months and has received over $25M in NIDA grant funding for MPAR programs.

What IP protection did ENSC announce on Jan 5, 2026 for MPAR technology?

The U.S. Patent and Trademark Office issued a Notice of Allowance for an MPAR patent, extending intellectual property protection through 2042.

What is PF614-MPAR and what regulatory support does it have for ENSC (ENSC)?

PF614-MPAR combines PF614 with MPAR overdose-protection technology; it holds Breakthrough Therapy designation and has received encouraging FDA feedback on labeling and a 505(b)(2) pathway.

When is Ensysce's 2025 annual shareholder meeting scheduled?

The shareholder meeting is scheduled for January 7, 2026.