ENSC

Acquisition of Cy Biopharma Completed, Adding CY200 for Complex Regional Pain SyndromeUp to $77 million in new funding with the acquisition of Cy BiopharmaCompany to host a Corporate Update Call on Tuesday, August 18, 2026, at 11:00 a.m. ET SAN DIEGO, CA / ACCESS Newswire / August 13, 2026 / Ensysce Biosciences, Inc. (NASDAQ:ENSC) ("Ensysce" or the "Company"), a clinical-stage biotechnology company developing novel neuroplastogenic therapies beyond mood disorders, with an initial focus on complex pain, today reported financial and operational results for the second quarter ended June 30, 2026. On August 6, 2026, we completed the acquisition of Cy Biopharma, Inc. ("Cy Biopharma") with private placement financings of $38.6 million, adding CY200, an Orphan Drug-designated candidate for Complex Regional Pain Syndrome (CRPS), to be our lead pipeline asset. We now have cash runway into late 2027, and a second financing tranche of up to $38.6 million, triggered upon achievement of certain clinical milestones, would carry the company into 2028. The acquisition was a stock-for-stock merger that brought in $17.1 million in cash from Cy Biopharma's pre-acquisition convertible note financing. Concurrent with the acquisition, Ensysce entered into a definitive agreement for the sale of Series C non-voting convertible preferred stock in a private placement financing with gross proceeds to the Company of approximately $21.5 million before deducting transaction expenses. The private placement financing was led by Ally Bridge Group and included participation from Perceptive Advisors, Dellora Investments, Ikarian Capital and Adage Capital Partners, L.P. Complex Regional Pain Syndrome (CRPS) Program Update With the acquisition of Cy Biopharma, the Company added CY200, a clinical-stage neuroplastogenic candidate for the treatment of CRPS Type 1, which has received U.S. FDA Orphan Drug Designation. CRPS is among the most severe chronic pain disorders, with few effective treatment options and significant physical, psychological, and socioeconomic burden, and there is currently no approved therapy for the condition. Rather than managing symptoms alone, CY200 is designed to address the underlying neurobiology of CRPS. The Company intends to apply proceeds from the private placement financings primarily to advance CY200 through a randomized Phase 2 trial evaluating efficacy, safety and tolerability for symptom alleviation in participants with CRPS Type 1, and to prepare for registrational development. "Cy Biopharma's neuroplastogenic approach to complex pain was the most compelling strategic opportunity we explored, and we believe this acquisition represents a significant value creation opportunity for Ensysce stockholders. The concurrent private placement financing was intentionally sized to support our immediate strategic objectives while maintaining financial discipline and allow us to progress our lead candidate in a pain market valued over $1 billion for which there is currently no approved therapy," said Dr. Lynn Kirkpatrick, Chief Executive Officer of Ensysce. "During the second quarter of 2026 we also advanced the clinical development of PF614-MPAR, the first opioid engineered with built-in overdose protection. To support this clinical development, we were awarded the third year of funding under a $15.1 million grant from the National Institute on Drug Abuse (NIDA), completing the award, a powerful vote of confidence from a leading federal agency that has backed this program with two major awards totaling over $26 million over six years." TAAPTM and MPAR® (Opioid Abuse Deterrent and Overdose Protection Programs) Update Trypsin‑Activated Abuse Protection (TAAP™) PF614 represents what we believe could be a next‑generation extended‑release oxycodone with built‑in abuse protection. PF614 remains inactive until it is swallowed and exposed to trypsin in the small intestine, where it "switches on" to release oxycodone in a controlled manner, providing what we believe is improved safety. Development of PF614 continues with the pivotal PF614-301 Phase 3 clinical trial, a multicenter, randomized, double-blind, placebo-controlled study evaluating PF614 for the treatment of moderate to severe pain following abdominoplasty. PF614-MPAR is a combination product that integrates both the TAAP™ and MPAR® (Multi-Pill Abuse Resistance) technologies to deliver effective opioid analgesia with the added benefit of built-in oral overdose protection, and has received FDA's Breakthrough Therapy designation. Ensysce has continued to enroll subjects in the PF614-MPAR-102 study, supported by the NIDA grant, reflecting ongoing external validation of the program's potential impact. As of June 30, 2026, $5.3 million of funding remained available through May 2027 under the grant. Ensysce also strengthened its intellectual property position for MPAR® during the quarter. In May 2026, the Taiwan Intellectual Property Office issued a patent titled "Compositions Comprising Enzyme-Cleavable Prodrugs and Controlled Release Nafamostat and Methods of Use Thereof," extending MPAR® patent protection through 2042 in that jurisdiction and expanding on U.S. Patent No. 12,599,578, which issued April 14, 2026. Q2 2026 Financial Results Cash - Cash and cash equivalents were $0.7 million as of June 30, 2026, compared to $4.3 million as of December 31, 2025. The decrease reflects $5.5 million of cash used in operating activities during the first six months of 2026, partially offset by $1.8 million of net proceeds from a preferred stock financing. Following quarter-end, the acquisition of Cy Biopharma and related financings provided cash of approximately $31 million, net of transaction expenses. Federal Grants - Funding under federal grants totaled $1.2 million for the second quarter of 2026 compared to $1.4 million in the comparable year ago quarter. This $0.2 million decrease is primarily due to the timing of research activities eligible for funding under the MPAR grant. Research & Development Expenses - R&D expenses were $2.5 million for the second quarter of 2026 compared to $1.9 million for the same period in 2025, representing an increase of $0.5 million. The increase was primarily the result of external research and development costs related to increased clinical activity for PF614. General & Administrative Expenses - G&A expenses were $1.3 million in the second quarter of 2026 and $1.2 million for the second quarter of 2025, representing an increase of $0.1 million. Other Income (Expense) - Total other income (expense) was income of $5,514 for the second quarter of 2026 compared to income of $16,998 in the same period of 2025. Total other income (expense) for the quarters ended June 30, 2026 and June 30, 2025, consisted primarily of interest income from cash and cash equivalents. Net Income (Loss) - Net loss attributable to common stockholders for the second quarter of 2026 was $2.6 million compared to a net loss of $1.7 million for the second quarter of 2025. As a clinical stage biotech company, our continued research and development efforts toward regulatory approvals for our product candidates are expected to result in losses for the foreseeable future. Results for periods after June 30, 2026, will reflect the acquisition of Cy Biopharma and related transaction expenses, and are therefore not comparable to the periods presented. Corporate Update Conference Call CEO, Dr. Lynn Kirkpatrick, President, James Morrison, and Cy Biopharma CMO, Professor Richard Langford, will host a conference call on Tuesday, August 18, 2026, at 11:00 a.m. ET to provide a corporate update, including the recently completed acquisition of Cy Biopharma. Date: Tuesday, August 18, 2026 Time: 11:00 a.m. ET U.S. Dial-in: 1-877-407-9716 International Dial-in: 1-201-493-6779 Webcast: https://viavid.webcasts.com/starthere.jsp?ei=1772527&tp_key=742e115fc1 Please dial in at least 10 minutes before the start of the call to ensure timely participation. A playback of the call will be available through Friday, September 18, 2026. To listen, call 1-844-512-2921 within the United States and Canada or 1-412-317-6671 when calling internationally. Please use the replay access ID 13762262. About Ensysce Biosciences Ensysce Biosciences is a clinical-stage biotechnology company developing novel neuroplastogenic therapies using psychedelics that go beyond mood disorders and address the root cause of chronic pain through central nervous system modulation. The company is also developing a new class of highly novel opioids for the treatment of severe pain while minimizing the risk of both drug abuse and overdose. For more information, please visit www.ensysce.com. Definitions CRPS: complex regional pain syndrome - a severe chronic pain disorder for which there is currently no approved therapy. TAAP™: trypsin activated abuse protection - designed to protect against prescription drug abuse. MPAR®: multi-pill abuse resistance - designed to protect against abuse and accidental overdose. 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 DevineMZ North AmericaMain: [email protected] Ensysce Biosciences, Inc.Condensed Consolidated Statements of Operations(Unaudited) Ensysce Biosciences, Inc.Condensed Consolidated Statements of Cash Flows(Unaudited) Ensysce Biosciences, Inc.Condensed Consolidated Balance Sheets(Unaudited) SOURCE: Ensysce Biosciences, Inc. View the original press release on ACCESS Newswire

~ IRB Approval Secured for PF614-MPAR-102 Part 3 ~ ~ Clinical Peer-Reviewed Data Published for First Overdose Protected Opioid PF614-MPAR®; Patent Estate Expanded ~ ~ Company Launches Formal Review of Strategic Alternatives ~ SAN DIEGO, CA / ACCESS Newswire / May 15, 2026 / Ensysce Biosciences, Inc. (NASDAQ:ENSC) ("Ensysce" or the "Company"), a clinical-stage pharmaceutical company pioneering next-generation pain and central nervous system therapeutics engineered to minimize abuse and overdose risk, today reported financial and operational results for the first quarter ended March 31, 2026. "The first quarter of 2026 delivered meaningful operational and clinical momentum across our pipeline, underscoring the strength of our strategy and the discipline of our execution," said Dr. Lynn Kirkpatrick, Chief Executive Officer of Ensysce. We achieved 50% of the interim enrollment target in our pivotal PF614-301 Phase 3 trial, published the first peer-reviewed clinical data validating our MPAR® overdose-protection technology, and expanded our patent estate across both our opioid and ADHD programs. Together these milestones reinforce what we believe is the next evolution of opioid safety." Dr. Kirkpatrick continued, "Following quarter-end, we closed a second financing tranche under an existing facility and secured IRB approval to initiate Part 3 of PF614-MPAR-102, the final stage of that study. Advancing this program strengthens the clinical evidence supporting a product we believe can fundamentally reshape how overdose risk is managed. In parallel, our Board has initiated a formal review of strategic alternatives, including potential partnerships and licensing opportunities, to accelerate the development of our TAAP™ and MPAR® platforms and unlock additional shareholder value." TAAP™ (Opioid Abuse Deterrent Program) Update PF614 is the Company's lead product candidate and represents what we believe could be a next‑generation extended‑release oxycodone with built‑in abuse protection. Developed using our proprietary Trypsin‑Activated Abuse Protection (TAAP™) technology, PF614 remains inactive until it is swallowed and exposed to trypsin in the small intestine, where it "switches on" to release oxycodone in a controlled manner. This targeted activation is designed to deliver effective pain relief while significantly reducing the potential for manipulation or non‑oral abuse. By making the active drug inaccessible until it reaches the digestive tract, TAAP™ aims to provide a safer opioid option for patients with severe pain who require opioid‑strength therapy. The Company believes this approach has the potential to meaningfully differentiate PF614 within the multi‑billion‑dollar pain management market and address longstanding concerns around tampering and misuse. In January, Ensysce announced that it had enrolled 50% of the subjects targeted for interim review in its pivotal PF614-301 Phase 3 clinical trial, a multicenter, randomized, double-blind, placebo-controlled study evaluating PF614 for the treatment of moderate to severe pain following abdominoplasty. Enrollment, which began in late December 2025, progressed across two U.S. clinical sites; CenExel JBR (Salt Lake City, Utah) and CenExel Atlanta (Decatur, Georgia), under principal investigators Dr. Todd Bertoch and Dr. Jessica McCoun, recognized experts in anesthesiology and pain management. The study is designed to demonstrate PF614's ability to deliver consistent, clinically meaningful post-surgical pain relief using twice-daily dosing while leveraging its built-in abuse protection chemistry. Achieving the interim enrollment milestone in the early stages of the program brings Ensysce meaningfully closer to delivering interim data and advancing what the Company believes could be a new standard in acute pain management. MPAR® (Opioid Abuse Deterrent and Overdose Protection Program) Update PF614-MPAR is the Company's next-generation combination product that integrates both the TAAP™ and MPAR® (Multi-Pill Abuse Resistance) technology to deliver effective opioid analgesia with the added benefit of built-in oral overdose protection. By pairing the PF614 prodrug with a trypsin inhibitor, PF614-MPAR is designed to "switch off" opioid release when supratherapeutic doses are taken, offering a differentiated safety profile aimed at reducing overdose risk while maintaining therapeutic efficacy for patients with severe pain. Initial clinical data from the PF614-MPAR-101 study demonstrated that the MPAR® mechanism performed as intended at a 25 mg dose, providing the desired overdose protection. These results supported the FDA's decision to grant Breakthrough Therapy designation in January 2024, a key regulatory milestone that underscores the potential for PF614-MPAR to address a significant unmet need in opioid safety. In March, Ensysce announced the publication of the first peer-reviewed clinical manuscript describing its MPAR® overdose protection technology in the January/February 2026 issue of the Journal of Opioid Management. The paper, "Formulation and a Phase 1 Clinical Study of PF614-MPAR, an Oxycodone Prodrug with Oral Opioid Overdose Protection," reported that PF614-MPAR achieved appropriate opioid plasma levels under normal dosing conditions while preventing large increases in exposure at supratherapeutic doses- reinforcing the potential for a fundamentally new safety paradigm in opioid analgesia. Following quarter end, in April 2026, Ensysce received Institutional Review Board (IRB) approval to initiate Part 3 of the PF614-MPAR-102 study, the final stage in evaluating the MPAR® overdose-protection technology. Part 3 is designed to further characterize PF614-MPAR‘s protective effect across multiple dosing scenarios, building on the previously published data demonstrating that the product delivers therapeutic plasma levels under normal use while significantly limiting additional opioid exposure when higher-than-prescribed doses are taken. The study continues with support from the National Institute on Drug Abuse (NIDA), reflecting ongoing external validation of the program's potential impact. ADHD Program Update Ensysce is leveraging its TAAP™ and MPAR® platforms beyond pain management to develop what could become the first abuse-deterrent, overdose-protected stimulant therapies for attention-deficit/hyperactivity disorder (ADHD). The Company's ADHD pipeline includes PF8026, a novel immediate-release amphetamine prodrug, and PF8001, an extended-release candidate. In January 2026, Ensysce received a Notice of Allowance from the European Patent Office for a patent covering PF8026, with both composition-of-matter and method-of-use claims. This strengthens the Company's intellectual property position and supports long-term value creation as it allows advancement of safer stimulant options for a large and growing market. The need for innovation in ADHD therapeutics is significant. In 2023, approximately 3.9 million people aged 12 or older misused prescription stimulants, highlighting the limitations of current treatments and the urgency for products engineered to resist common routes of abuse and incorporate overdose protection mechanisms. By applying TAAP™ and MPAR® to stimulant medications, Ensysce has the ability to address this unmet need and expand its platform into another major therapeutic category with substantial commercial potential. Opioid Use Disorder (OUD) Program Update Beyond its pain management portfolio, Ensysce is advancing treatments for opioid use disorder (OUD) aimed at reducing cravings, lower relapse risk, and improving long-term patient outcomes while maintaining patient safety and quality of life. The Company has selected PF9001 as its lead OUD candidate and is evaluating it as a potential next-generation alternative to methadone, with the added advantage of built-in overdose protection, reduced cardiovascular risk and convenient oral delivery profile. The PF9001 program has been supported by a multi-year HEAL (Helping to End Addiction Long-Term) grant and in collaboration with NIDA. This program support provides both scientific validation and non‑dilutive funding, reinforcing the potential of PF9001 to address critical gaps in current OUD treatment options and expand the application of Ensysce's TAAP™ and MPAR® technologies into another major public health challenge. Q1 2026 Financial Results Cash - Cash and cash equivalents were $0.7 million as of March 31, 2026, compared to $4.3 million as of December 31, 2025. Subsequent to March 31, 2026, on April 7, 2026, the Company closed a second tranche of $2.0 million in convertible preferred stock financing under its previously announced November 2025 commitment for up to $20 million over 24 months. Federal Grants - Funding under federal grants totaled $1.0 million for the first quarter of 2026 compared to $1.3 million in the comparable year ago quarter. This $0.3 million decrease is primarily due to the timing of research activities eligible for funding under the MPAR grant. Research & Development Expenses - R&D expenses were $3.3 million for the first quarter of 2026 compared to $1.9 million for the same period in 2025, representing an increase of $1.4 million. The increase was primarily the result of external research and development costs related to Phase 3 clinical trial activity for PF614. General & Administrative Expenses - G&A expenses were $1.2 million in the first quarter of 2026 and $1.4 million for the first quarter of 2025, representing a decrease of $0.2 million. Net Income (Loss) - Net loss attributable to common stockholders for the first quarter of 2026 was $3.6 million compared to a net loss of $1.9 million for the first quarter of 2025. As a clinical stage biotech company, our continued research and development efforts toward regulatory approvals for our product candidates are expected to result in losses for the foreseeable future. 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. Definitions TAAP™: trypsin-activated abuse protection - designed to protect against prescription drug abuse. MPAR®: multi-pill abuse resistance - designed to protect against abuse and accidental overdose. 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 annual report on Form 10-K 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 [email protected] Ensysce Biosciences, Inc. Condensed Consolidated Statements of Operations (Unaudited) Ensysce Biosciences, Inc. Condensed Consolidated Statements of Cash Flows (Unaudited) Ensysce Biosciences, Inc. Condensed Consolidated Balance Sheets (Unaudited) SOURCE: Ensysce Biosciences View the original press release on ACCESS Newswire

~ Fourth Quarter Highlighted by Clinical and Regulatory Milestones Positioning PF614 for Late-Stage Advancement ~ SAN DIEGO, CA / ACCESS Newswire / March 30, 2026 / Ensysce Biosciences, Inc. (NASDAQ:ENSC) ("Ensysce" or the "Company"), a clinical-stage pharmaceutical company developing innovative solutions for novel therapeutics while reducing the potential for abuse and overdose, today reported financial and operational results for the fourth quarter and full year ended December 31, 2025. "2025 was a year of meaningful progress for Ensysce, marked by significant clinical advancement, productive regulatory engagement, and continued strengthening of our intellectual property portfolio," said Dr. Lynn Kirkpatrick, Chief Executive Officer of Ensysce Biosciences. "We initiated our Phase 3 trial for PF614 and had constructive dialogue with the FDA supporting our manufacturing pathway." Dr. Kirkpatrick continued, "Enrollment in the PF614-301 Phase 3 study has progressed rapidly, while PF614-MPAR remains on an accelerated development path under Breakthrough Therapy designation. In parallel, we have advanced commercial manufacturing readiness for PF614 and have generated additional data supporting overdose-protection labeling for our MPAR platform. Beyond our late-stage programs, we strengthened the long-term value of our technology platforms through expanded patent protection and pipeline growth, including the advancement of PF9001 for opioid use disorder (OUD) and leveraging our TAAP™ and MPAR® technologies for additional indications such as attention deficit hyperactivity disorder (ADHD)." Program Updates TAAPTM (Opioid Abuse Deterrent) Program Update Ensysce's lead drug candidate, PF614, is a Trypsin-Activated Abuse Protection (TAAPTM) extended-release oxycodone designed to deliver effective pain relief while incorporating built-in abuse protection. Through proprietary chemical modification of oxycodone, PF614 remains pharmacologically inactive until swallowed and exposed to trypsin in the small intestine, where it is activated to release oxycodone. This mechanism is designed to preserve therapeutic efficacy while significantly reducing the potential for tampering and abuse. In December 2025, Ensysce announced the enrollment of the first patient in its pivotal Phase 3 clinical trial (PF614-301) evaluating PF614 for the treatment of moderate-to-severe post-surgical pain following abdominoplasty. The multicenter, randomized, double-blind, placebo-controlled study is designed to assess whether PF614 can deliver potent and consistent analgesia while leveraging its unique chemical design to mitigate the risk of opioid misuse. Clinical sites currently enrolling patients include CenExel JBR in Salt Lake City, Utah, and CenExcel Atlanta under experienced principal investigators in anesthesiology and pain medicine. Enrollment in PF614-301 represents a major milestone in Ensysce's strategy to introduce a next generation of safer opioid medicines and advance PF614 toward regulatory submission and potential commercialization. MPAR® (Opioid Abuse Deterrent and Overdose Protection) Program Update PF614-MPAR combines Ensysce's TAAP™ chemistry with its proprietary MPAR® (Multi-Pill Abuse Resistance) overdose-protection technology, designed to actively limit opioid release when multiple pills are consumed beyond prescribed doses. PF614-MPAR incorporates a trypsin inhibitor that automatically reduces opioid activation in overdose situations, effectively acting as a chemical "off-switch." Clinical data from the PF614-MPAR-101 study demonstrated that the MPAR® technology functioned as designed, providing overdose protection at a 25 mg dose. These results supported the FDA's Breakthrough Therapy designation granted in January 2024. In November 2025, the FDA provided encouraging feedback regarding the development pathway for PF614-MPAR, including support for pursuing overdose-protection labeling and the potential use of a streamlined 505(b)(2) regulatory pathway, which could accelerate development and market entry. The FDA and Ensysce are collaborating on a framework to define and communicate the safety benefits of overdose-protection opioids, including development of a scientific whitepaper on overdose protection. This milestone, backed by multi-year grants from the National Institute on Drug Abuse (NIDA), marks a significant step toward transforming opioid safety and redefining pain management. Opioid Use Disorder (OUD) Program Update In addition to its pain management portfolio, Ensysce is developing treatments for opioid use disorder (OUD) designed to reduce cravings and relapse risk while maintaining patient safety and quality of life. The Company selected PF9001 as its lead OUD candidate and is evaluating the compound as a potential next-generation methadone alternative with built-in overdose protection, reduced cardiovascular risk and an oral delivery profile. This program was supported by a multi-year HEAL (Helping to End Addiction Long-Term) grant and in collaboration with NIDA. Intellectual Property Expansion In December 2025, the U.S. Patent and Trademark Office allowed a new patent covering Ensysce's MPAR® technology, further strengthening the Company's intellectual property protection through 2042. The patent, titled "Compositions Comprising Enzyme-Cleavable Prodrugs and Controlled Release Nafamostat and Methods of Use Thereof," includes both composition-of-matter and method-of-use claims. Ensysce is also exploring the application of MPAR technology beyond opioids, including potential programs in amphetamines for ADHD and methadone for OUD. In early January, Ensysce announced that the European Patent Office provided Notice of Allowance in December 2025, for the issuance of a Patent 'Compositions Comprising Enzyme-Cleavable Amphetamine Prodrugs and Inhibitors Thereof' for PF8026 protected by the TAAPTM and MPAR® technologies. These two issuances expand the potential reach of Ensysce's platforms across multiple therapeutic areas where abuse and overdose risk remain significant clinical challenges. Fourth Quarter and Full Year 2025 Financial Results Cash - Cash and cash equivalents were $4.3 million as of December 31, 2025, compared to $3.5 million as of December 31, 2024. Cash used in operating activities totaled $7.8 million in 2025 compared to $7.5 million in 2024. Federal Grants - Funding under federal grants totaled $1.9 million for the fourth quarter of 2025 compared to $1.3 million in the comparable year ago quarter. For the full year, funding from federal grants totaled $5.1 million in 2025, compared to $5.2 million in 2024. The differences are due to the timing of research activities eligible for funding under the OUD and MPAR grants, as decreases in funding under the OUD grant that ended in August 2024 were offset by increases in funding under the MPAR grant which began in September 2024. Research & Development Expenses - R&D expenses were $3.6 million for the fourth quarter of 2025 compared to $3.8 million for the same period in 2024. Research and development expenses were $10.4 million for the year ended December 31, 2025, compared to $7.2 million for the year ended December 31, 2024, respectively, representing an increase of $3.2 million. The increase was primarily the result of external research and development costs related to increased clinical and pre-clinical programs for PF614 and PF614-MPAR. General & Administrative Expenses - G&A expenses were $1.1 million in the fourth quarter of 2025, consistent with $1.1 million for the fourth quarter of 2024. For 2025, G&A expenses were $4.9 million, representing an increase of $0.2 million compared to $4.7 million for 2024. Other Income (Expense) - Total other income (expense) was income of $13,856 for the fourth quarter of 2025 compared to income of $12,054 in the same period of 2024. For 2025, total other income (expense), net was income of $64,759 compared to expense of $1.3 million for 2024. Other income and expense for the year ended December 31, 2025, consisted primarily of interest income from cash and cash equivalents. Other income and expense for the year ended December 31, 2024, consisted primarily of interest expense associated with the amortization of the original issue discount and the debt issuance costs associated with convertible notes issued in 2023. Net Income (Loss) - Net loss attributable to common stockholders for the fourth quarter of 2025 was $2.8 million compared to a net loss of $3.6 million for the fourth quarter of 2024. For 2025, net loss was $10.2 million compared to $8.0 million for 2024. As a clinical stage biotech company, our continued research and development efforts toward regulatory approvals for our product candidates are expected to result in losses for the foreseeable future. About Ensysce Biosciences Ensysce Biosciences is a clinical-stage pharmaceutical company dedicated to disrupting the analgesic landscape through the development of a new class of safer opioid medicines for the treatment of severe pain. Leveraging its proprietary Trypsin-Activated Abuse Protection (TAAP™) and Multi-Pill Abuse Resistance (MPAR®) platforms, Ensysce is advancing tamper-resistant therapeutic options designed to minimize the risk of opioid abuse and oral overdose while preserving strong analgesic efficacy. For more information, visit www.ensysce.com. Definitions TAAP™: trypsin activated abuse protection - designed to protect against prescription drug abuse. MPAR®: multi-pill abuse resistance - designed to protect against abuse and accidental overdose. 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 annual report on Form 10-K 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 [email protected] Ensysce Biosciences, Inc. Condensed Consolidated Statements of Operations Ensysce Biosciences, Inc. Condensed Consolidated Statements of Cash Flows Ensysce Biosciences, Inc. Condensed Consolidated Balance Sheets (Unaudited) SOURCE: Ensysce Biosciences, Inc. View the original press release on ACCESS Newswire

~ Third Quarter Highlighted by Initiation of Phase 3 Study of PF614, Underscoring Progress Toward Market Readiness and Commitment to Novel Opioid Solutions ~ ~ Further Program Advancement Supported by Preferred Stock Financing ~ SAN DIEGO, CA / ACCESS Newswire / November 14, 2025 / Ensysce Biosciences, Inc. (NASDAQ:ENSC) ("Ensysce" or the "Company"), a clinical-stage pharmaceutical company pioneering next-generation severe pain therapeutics designed to minimize abuse and overdose risk, today reported financial and operational results for the third quarter ended September 30, 2025. Dr. Lynn Kirkpatrick, Chief Executive Officer of Ensysce, commented, "It has been another highly productive quarter as we navigate tumultuous times in drug development. Our team continued meaningful progress throughout the third quarter as we advanced what we consider a new evolution in opioid therapeutics, focused on delivering safer, highly efficacious options for severe pain management using our innovative platforms." She continued, "The initiation of our pivotal Phase 3 PF614-301 trial in July marks a major milestone in our mission to transform pain management. This study is designed to demonstrate PF614's ability to provide effective pain relief while supporting safe transitions to non-opioid care. Our alliance with Rho, Inc. ensures rigorous execution as we work to unlock significant long-term value through innovation in opioid safety." Dr. Kirkpatrick added, "We are also buoyed by encouragement from the U.S. Food and Drug Administration ("FDA") for our PF614-MPAR program, with Breakthrough Therapy designation, including working to align on overdose protection labeling and a regulatory pathway forward. This milestone reinforces our mission and commitment to transform opioid safety through scientific innovation, and we are proud to be working collaboratively with the FDA to ensure the full benefits of our technology reach the patients for which they are intended." "Looking ahead, we believe Ensysce is positioned to launch the next-generation opioid analgesia. Our strategy integrates scientific rigor, responsible development, and continued collaboration with National Institute on Drug Abuse ("NIDA") and FDA to address the dual challenges of pain and abuse. Our current investors have continued to support this development path through a convertible preferred stock financing and we appreciate the opportunity to move forward with our programs buoyed by their commitment to our mission. Each milestone brings us closer to redefining how severe pain can be treated - with efficacy, safety, and accountability at the core." Dr. Kirkpatrick concluded. TAAPTM (Opioid Abuse Deterrent Program) Update The Company's lead product, PF614, is a Trypsin-Activated Abuse Protection (TAAPTM) extended-release oxycodone and a potential "next generation" analgesic to treat severe pain. PF614's TAAPTM chemical modification of oxycodone renders it inactive until it is swallowed and exposed to the body's own trypsin in the small intestine to activate or "switch on" to release oxycodone. The TAAPTM technology is designed to control release when administered orally, be highly resistant to tampering, and reduce abuse, with a goal of providing what the Company believes is a safer opioid product for those suffering from severe pain who require opioid-strength analgesia. In July, Ensysce announced the initiation of its pivotal PF614-301 clinical trial, designed to evaluate the efficacy of PF614 in managing moderate to severe post-surgical pain following abdominoplasty. The study seeks to validate PF614's ability to deliver effective pain relief while reducing the risk of opioid abuse and supporting a safer transition to non-opioid outpatient care. To conduct the trial, Ensysce engaged Rho, Inc., a clinical research organization with extensive experience in central nervous system ("CNS") and pain-related studies. This initiation of services represents a significant milestone in Ensysce's mission to introduce a safer class of opioids and transform the future of pain management. MPAR® (Opioid Abuse Deterrent and Overdose Protection Program) Update PF614-MPAR is a combination product of the TAAPTM and MPAR® (Multi-Pill Abuse Resistance) technology to treat severe pain with the added benefit of oral overdose protection. PF614-MPAR combines prodrug PF614 with a trypsin inhibitor to reduce or "switch off" the release of the opioid in an overdose situation. Data from the initial clinical trial PF614-MPAR-101, demonstrating that the MPAR® technology worked as designed to provide the desired overdose protection to PF614-MPAR at a 25 mg dose, led to the FDA's Breakthrough Therapy designation in January 2024. In July, Ensysce received encouraging feedback from the FDA regarding the development of PF614-MPAR. The FDA supported Ensysce's pursuit of overdose protection labeling and confirmed the potential for a streamlined 505(b)(2) regulatory pathway, which could accelerate market entry. PF614-MPAR is engineered to activate overdose protection automatically when doses exceed prescribed limits. The FDA and Ensysce are aligned on a collaborative approach to ensure the drug's full safety benefits are recognized, including the creation of a whitepaper on overdose protection. This milestone, backed by multi-year NIDA grants, marks a significant step toward transforming opioid safety and redefining pain management. Opioid Use Disorder (OUD) Program Update In addition to its pain management pipeline, Ensysce is advancing innovative treatments for opioid use disorder (OUD), including novel compounds designed to reduce cravings and prevent relapse without compromising quality of life. Leveraging its proprietary TAAP™ and MPAR® technologies, the Company is developing what may be a safer methadone alternative. In 2024, Ensysce selected PF9001 as its lead OUD candidate, evaluating it for oral delivery, reduced cardiovascular risk, and built-in overdose protection. Supported by a multi-year HEAL (Helping to End Addiction Long-Term) grant, with encouragement from NIDA, the program is progressing toward non-clinical studies to support a future Investigational New Drug (IND) application. Q3 2025 Financial Results Cash - Cash and cash equivalents were $1.7 million as of September 30, 2025, compared to $3.5 million as of December 31, 2024. In November 2025, the Company completed a convertible preferred stock offering with gross proceeds of $4 million, with potentially $16 million of additional funding available through future tranches over the next 24 months. Federal Grants - Funding under federal grants totaled $0.5 million for the third quarter of 2025, compared to $3.4 million in the same quarter of 2024. The $2.9 million decrease is primarily due to the timing of research activities eligible for funding under the MPAR grant which began in September 2024. The 2024 period included significant funding under the OUD grant with research activity following the selection of a lead product candidate in June 2024. Research & Development Expenses - R&D expenses were $3.0 million for the third quarter of 2025 compared to $1.7 million for the same period in 2024. The increase was primarily the result of external research and development costs related to increased clinical and pre-clinical activity for PF614 and PF614-MPAR in the 2025 period. General & Administrative Expenses - G&A expenses were $1.3 million for the third quarter of 2025, relatively in line with $1.1 million during the same year ago period. Other Income (Expense) - Total other income (expense) was income of $11,967 for the third quarter of 2025 compared to income of $17,023 in the same period of 2024. Net Income (Loss) - Net loss attributable to common stockholders for the third quarter of 2025 was $3.7 million compared to a gain of $0.7 million for the third quarter of 2024. As a clinical-stage biotech company, the Company's continued research and development efforts toward regulatory approvals for its product candidates are expected to result in losses for the foreseeable future. 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. Definitions TAAP™: trypsin activated abuse protection - designed to protect against prescription drug abuse. MPAR®: multi-pill abuse resistance - designed to protect against abuse and accidental overdose. 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; 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 [email protected]   Ensysce Biosciences, Inc. Condensed Consolidated Statements of Operations (Unaudited) Ensysce Biosciences, Inc. Condensed Consolidated Statements of Cash Flows (Unaudited) Ensysce Biosciences, Inc. Condensed Consolidated Balance Sheets (Unaudited) SOURCE: Ensysce Biosciences View the original press release on ACCESS Newswire

Initiates Critical Milestone, Launching Phase 3 Trial of PF614 to Advance Next-Generation Opioid Therapy Toward Regulatory Approval Receives $5.3 Million Installment from NIDA To Support Overdose Protection Program Accelerates PF614-MPAR-102 Study with Full Enrollment of Part 2 SAN DIEGO, CA / ACCESS Newswire / August 13, 2025 / Ensysce Biosciences, Inc. (NASDAQ:ENSC) ("Ensysce" or the "Company"), a clinical-stage pharmaceutical company developing innovative solutions for severe pain relief while reducing the potential for opioid abuse and overdose, today reported financial and operational results for the second quarter ended June 30, 2025. Dr. Lynn Kirkpatrick, Chief Executive Officer of Ensysce, commented, "Momentum continued in the second quarter as we forged ahead progressing, what we believe will be the next evolution in opioid therapeutics: safety features built in to help guard against both misuse and overdose. The initiation of our pivotal Phase 3 trial for PF614 marks a major achievement for Ensysce and a critical step toward achieving our clinical and commercial strategy. This study is designed to validate PF614's ability to deliver what we believe will be superior pain relief for post-surgical pain with built-in abuse deterrence, reinforcing our commitment to developing safer opioid therapies. As we advance to seeking regulatory approval, PF614 has the potential to reshape the opioid treatment landscape and create long-term value for both patients and shareholders." Dr. Kirkpatrick added, "Fully enrolling Part 2 of our PF614-MPAR-102 study marks another important step in progressing this product with built in overdose-protection. With continued financial support from NIDA and the FDA's Breakthrough Therapy designation, we are accelerating the development of what could be a game-changing solution for those in severe pain, one that not only has superior efficacy but is designed to prevent unintentional overdose." "With the significant advancements made to date, we believe Ensysce is well-positioned to disrupt the opioid analgesic market with our lead candidates, PF614 and PF614-MPAR. Our approach leverages innovative chemistry to create opioid therapies that maintain strong efficacy while incorporating built-in safeguards against abuse and overdose. As we progress through the second half of the year, we are executing on a clear path of clinical and regulatory milestones across our TAAP™, MPAR®, and overdose use disorder (OUD) programs. With the opioid crisis continuing to take a devastating toll, our mission remains focused on saving lives and transforming how patients with pain and addiction are treated," Dr. Kirkpatrick concluded. TAAPTM (Opioid Abuse Deterrent Program) Update The Company's lead product, PF614, is a Trypsin-Activated Abuse Protection (TAAPTM) extended-release oxycodone and a potential "next generation" analgesic to treat severe pain. PF614's TAAPTM chemical modification of oxycodone renders it inactive until it is swallowed and exposed to the body's own trypsin in the small intestine to activate or "switch on" to release oxycodone. The TAAPTM technology is designed to control release when administered orally, be highly resistant to tampering, and reduce abuse, with a goal of providing a safer opioid product for those suffering from severe pain who require opioid-strength analgesia. In July, Ensysce announced the initiation of its pivotal PF614-301 study evaluating PF614, to manage and moderate severe post-surgical pain after abdominoplasty. The study aims to demonstrate PF614's effectiveness in pain relief while minimizing the risk of abuse and supporting a safer transition to non-opioid outpatient care. Ensysce has engaged Rho, Inc., a clinical research organization with deep expertise in central nervous system (CNS) disorders and pain studies, to conduct the trial. The collaboration marks a major step toward redefining pain therapy with a safer class of opioids. MPAR® (Opioid Abuse Deterrent and Overdose Protection Program) Update PF614-MPAR is a combination product of the TAAPTM and MPAR® (Multi-Pill Abuse Resistance) technology to treat severe pain with the added benefit of oral overdose protection. PF614-MPAR combines prodrug PF614 with a trypsin inhibitor to reduce or "switch off" the release of the opioid in an overdose situation. Data from the initial clinical trial PF614-MPAR-101, demonstrating that the MPAR® technology worked as designed to provide the desired overdose protection to PF614-MPAR at a 25 mg dose, led to the FDA's Breakthrough Therapy designation in January 2024. During the second quarter of 2025, the Company completed enrollment for Part 2 of its PF614-MPAR-102 study, to examine how food affects its MPAR technology, and is awaiting final data. The study is continuing with the third part of the trial through end of year and the Company is continuing to complete non-clinical studies required to support its use for chronic pain. PF614-MPAR, which combines Ensysce's TAAP™ and MPAR® technologies, has received FDA Breakthrough Therapy designation for its potential to prevent overdose while maintaining pain relief. Supported by a multi-year grant from the National Institute on Drug Abuse (NIDA), the program is advancing toward a new class of opioids designed to reduce the risks of abuse and overdose, a major step toward transforming pain management. OUD Program Update In addition to its pain management pipeline, Ensysce is advancing innovative treatments for opioid use disorder, including novel compounds designed to reduce cravings and prevent relapse without compromising quality of life. Leveraging its proprietary TAAP™ and MPAR® technologies, the Company is developing what may be a safer methadone alternative. In 2024, Ensysce selected PF9001 as its lead OUD candidate, evaluating it for oral delivery, reduced cardiovascular risk, and built-in overdose protection. Supported by a multi-year HEAL (Helping to End Addiction Long-Term) grant from NIDA, the program is progressing toward non-clinical studies to support a future Investigational New Drug (IND) application. In a key milestone during the quarter, Ensysce also received a Notice of Allowance from the U.S. Patent and Trademark Office for a patent covering the composition and use of PF9001, further strengthening its intellectual property position in the OUD space. Q2 2025 Financial Results Cash - Cash and cash equivalents were $2.2 million as of June 30, 2025, compared to $3.5 million as of December 31, 2024. During the quarter, the Company was awarded the second $5.3 million installment of a $15 million, three-year grant from the National Institute on Drug Abuse (NIDA)1. These funds are available for reimbursement of research and development expenses under the MPAR program through May 2026. Federal Grants - Funding under federal grants totaled $1.4 million for the second quarter of 2025, compared to $0.2 million in the same quarter of 2024. The $1.2 million difference is due to the timing of research activities eligible for funding, with increased clinical activities in 2025 for the PF614-MPAR-102 study under the MPAR grant which began in September 2024. Research & Development Expenses - R&D expenses were $1.9 million for the second quarter of 2025 compared to $0.9 million for the same period in 2024. The increase was primarily the result of external research and development costs related to PF614-MPAR, with increased pre-clinical and clinical activity in the 2025 period. General & Administrative Expenses - G&A expenses were constant at $1.2 million in the second quarter of both 2025 and 2024. Other Income (Expense) - Total other income (expense) was income of $16,998 for the second quarter of 2025 compared to expense of $12,351 in the same period of 2024. Net Income (Loss) - Net loss attributable to common stockholders for the second quarter of 2025 was $1.7 million compared to a net loss of $2.0 million for the second quarter of 2024. As a clinical-stage biotech company, the Company's continued research and development efforts toward regulatory approvals for its product candidates are expected to result in losses for the foreseeable future. ¹The research is supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number UO1DA059791. 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. Definitions TAAP™: trypsin activated abuse protection - designed to protect against prescription drug abuse. MPAR®: multi-pill abuse resistance - designed to protect against abuse and accidental overdose. 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 [email protected] Ensysce Biosciences, Inc. Condensed Consolidated Statements of Operations (Unaudited) Ensysce Biosciences, Inc. Condensed Consolidated Statements of Cash Flows (Unaudited) Ensysce Biosciences, Inc. Condensed Consolidated Balance Sheets (Unaudited) SOURCE: Ensysce Biosciences View the original press release on ACCESS Newswire

Receives U.S. Patent for Groundbreaking Treatment for Opioid Use Disorder Clinical Trial on Novel Analgesic, PF614-MPAR, Demonstrates Overdose Protection SAN DIEGO, CA / ACCESS Newswire / May 13, 2025 / Ensysce Biosciences, Inc. (NASDAQ:ENSC) ("Ensysce" or the "Company"), a clinical-stage pharmaceutical company developing innovative solutions for severe pain relief while reducing the potential for opioid abuse and overdose, today reported financial and operational results for the first quarter ended March 31, 2025. Dr Lynn Kirkpatrick, Chief Executive Officer of Ensysce, commented, "We are pleased with the meaningful strides the Company has continued to make in the first quarter to deliver what we believe are the ‘Next Generation' opioid analgesics with both abuse and overdose protection. Included in our recent accomplishments was the receipt of a Notice of Allowance from the U.S. Patent and Trademark Office for our lead opioid use disorder (OUD) drug candidate, PF9001. This patent adds to our portfolio of over 100 patents that span 25 countries around the world for our TAAP and MPAR® technologies in the pain and attention deficit disorder space. PF9001 is designed to have several advantages over current methadone therapy including overdose protection from our MPAR technology and reduced cardiotoxicity, which is a serious side effect seen with medications used today. We believe our approach to OUD therapy utilizing our novel TAAP and MPAR technologies will improve outcomes for patients through an increase in treatment adherence as well as provide much easier access to these critical therapies for those who struggle with this disorder." Dr. Kirkpatrick continued, "Additionally in April, we were pleased to announce completion of another critical milestone in the development of our opioid overdose protection. Part 1 of our PF614-MPAR-102 clinical study finished enrollment and confirmed protection from the risk of overdose when PF614-MPAR at any dose level is consumed accidentally or deliberately. We look forward to enrolling Parts 2 and 3 of the study which will continue to examine other properties of PF614-MPAR to support its use to treat severe pain when other analgesics are ineffective." "We believe Ensysce is set to disrupt the analgesic opioid market with our lead products PF614 and PF614-MPAR. Our mission has been to use "clever chemistry" to deliver a novel opioid analgesic featuring both abuse and overdose protection while retaining opioid-grade efficacy. As we approach the second half of the year, we have set in place plans for clinical and regulatory progress and look forward to continuing to provide updates on our TAAP, MPAR and OUD programs. The opioid crisis continues to claim close to 100,000 lives annually in the U.S. alone. Ensysce aims to not only save lives, but to reshape the way society approaches pain and addiction." TAAP TM (Opioid Abuse Deterrent Program) Update The Company's lead product, PF614, is a Trypsin-Activated Abuse Protection (TAAP TM ) extended-release oxycodone and a potential "next generation" analgesic to treat severe pain. PF614's TAAP TM chemical modification of oxycodone makes it inactive until it is swallowed and exposed to the body's own trypsin in the small intestine to activate or "switch on" to release oxycodone. The TAAP TM technology is designed to control release when administered orally, be highly resistant to tampering, and reduce abuse, with a goal of providing what the Company believes is a safer opioid product for those suffering with severe pain who require opioid-strength analgesia. Having received FDA feedback on the Phase 3 design for the PF614-301 clinical study, entitled "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", in December 2024, the Company has continued to perfect its study plans, working towards initiating the trial in mid-year 2025, and will continue to provide updates as the program develops. MPAR® (Opioid Abuse Deterrent and Overdose Protection Program) Update PF614-MPAR is a combination product of the TAAP TM and MPAR® (Multi-Pill Abuse Resistance) technology to treat severe pain with the added benefit of oral overdose protection. PF614-MPAR combines prodrug PF614 with a trypsin inhibitor to reduce or "switch off" the release of the opioid in an overdose situation. Data from the initial clinical trial PF614-MPAR-101, demonstrating that the MPAR® technology worked as designed to provide the desired overdose protection to PF614-MPAR at a 25 mg dose, led to the FDA's Breakthrough Therapy designation in January 2024. During the second quarter of 2025, the Company announced the completion of Part 1 of its second clinical trial, PF614-MPAR-102, that evaluated higher doses of PF614-MPAR for overdose protection. This Part of the study confirmed the earlier data from PF614-MPAR-101, showing that MPAR® technology can reduce risk from excessive doses when consumed accidentally or deliberately. The Company has now progressed to Part 2 of the three-part study and will examine whether there are any food effects on this MPAR® technology. The aggregate data will allow the Company to focus on perfecting a final drug product to move into commercialization and will be discussed with the FDA in an upcoming regulatory meeting. Opioid Use Disorder (OUD) Program Update In addition to pain management, Ensysce is advancing treatments for opioid use disorder, including innovative compounds that we believe will reduce cravings and block relapse without impairing quality of life. The Company has used its TAAP and MPAR® technology to provide what could be a safer methadone analogue to treat OUD. In 2024, a lead OUD drug candidate PF9001 was selected and has been evaluated for oral delivery, the potential for reduced cardiovascular side effects and overdose protection. The intent of the program is to provide a safer product to treat OUD, and to make OUD treatment more accessible to those who need it. The program, supported by a multi-year Helping to End Addiction Long-Term (HEAL) award, is planned to continue to non-clinical studies to support submission of an Investigational New Drug application in the future. In another milestone for this program, the Company announced in April it had secured patent protection for the OUD platform. A Notice of Allowance from the U.S. Patent and Trademark Office was issued for a patent entitled: Enzyme-Cleavable Methadone Prodrugs and Methods of Use Thereof¹ which includes both composition of matter and method of use claims for PF9001. Q1 2025 Financial Results Cash - Cash and cash equivalents were $3.1 million as of March 31, 2025, compared to $3.5 million as of December 31, 2024. Subsequent to the end of the quarter, the Company received gross proceeds of $2.2 million, prior to deducting placement agent fees and offering expenses, from the exercise of warrants originally issued in March 2025. Federal Grants - Funding under federal grants totaled $1.3 million for the first quarter of 2025 compared to $0.3 million in the comparable year ago quarter. The $1.0 million difference is due to the timing of research activities eligible for funding, with increased activities under the MPAR grant which began in September 2024. Research & Development Expenses - R&D expenses were $1.9 million for the first quarter of 2025 compared to $0.8 million for the same period in 2024. The increase was primarily the result of external research and development costs related to PF614-MPAR, with increased pre-clinical activity in the 2025 period. General & Administrative Expenses - G&A expenses were consistent at $1.4 million in the first quarter of both 2025 and 2024. Other Income (Expense) - Total other income (expense) was income of $21,939 for the first quarter of 2025 compared to expense of $1.3 million in the same period of 2024. Other expense for the 2024 period consisted primarily of interest expense associated with the amortization of the original issue discount and debt issuance costs for convertible notes issued in 2023. Net Income (Loss) - Net loss attributable to common stockholders for the first quarter of 2025 was $1.9 million compared to a net loss of $3.1 million for the first quarter of 2024. As a clinical stage biotech company, our continued research and development efforts toward regulatory approvals for our product candidates are expected to result in losses for the foreseeable future. ¹The research covered by this patent was supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number UG3DA050271. 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. Definitions TAAP™: trypsin activated abuse protection - designed to protect against prescription drug abuse. MPAR®: multi-pill abuse resistance - designed to protect against abuse and accidental overdose. 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; 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 annual report on Form 10-K 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 DevineMZ North AmericaMain: [email protected]   Ensysce Biosciences, Inc.Condensed Consolidated Statements of Operations(Unaudited) Ensysce Biosciences, Inc.Condensed Consolidated Statements of Cash Flows(Unaudited) Ensysce Biosciences, Inc.Condensed Consolidated Balance Sheets(Unaudited) SOURCE: Ensysce Biosciences View the original press release on ACCESS Newswire