Oxycodone

Secures Strategic Partnership for the Development and Commercial Launch of PF614 and PF614-MPAR Groundbreaking Trial on PF614-MPAR Generates Positive Interim Results SAN DIEGO, CALIFORNIA / ACCESS Newswire / March 10, 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 fourth quarter and full year ended December 31, 2024. Dr. Lynn Kirkpatrick, Chief Executive Officer of Ensysce, commented, "Our team continued to make significant strides in the fourth quarter to deliver what we believe are the ‘Next Generation' opioid analgesics with both abuse and overdose protection. We received feedback from the FDA on our PF614 phase 3 study design and are now taking steps to prepare for the expected start of enrollment of this clinical study in the second quarter of 2025. We are finalizing the selection of clinical sites and an experienced team to execute our PF614 phase 3 trial to remain on track to submit our PF614 New Drug Application in 2026." Dr. Kirkpatrick continued, "Additionally, we are pleased with the continued positive results from our PF614-MPAR-102 study, showing PF614-MPAR provides overdose protection across our planned dosage range, when a greater-than-prescribed dose is consumed at one time. This second study of our overdose protection MPAR technology is continuing to evaluate subjects at higher dose limits in part 1 of the three-part study. The clinical trial is supported by our multi-year award from the National Institute on Drug Abuse and will continue to enroll subjects for parts 2 and 3 over the next year. Furthermore, in January, we entered into a highly valuable strategic partnership for the manufacture and commercial launch of both our PF614 and PF614-MPAR drug products. I'm pleased that Ensysce concluded 2024 and entered 2025 in a very favorable position. We are encouraged by the FDA's recent focus on commercialization of new drug products that address and treat pain. With the "clever chemistry" of our lead products PF614 and PF614-MPAR, Ensysce is planning to disrupt the analgesic market, offering novel protection against overdose and abuse with opioid-grade efficacy." TAAPTM (Opioid Abuse Deterrent Program) Update Our 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 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 Company's TAAPTM technology is designed to control release, be highly resistant to tampering, and reduce abuse, with a goal of providing what the company believes is a safer effective opioid product for those suffering with severe pain who require opioid-strength analgesia. During the fourth quarter, the Company announced its strategic partnership with a leading specialty drug manufacturer to push manufacture of PF614 to commercial launch and for the development of a PF614-MPAR final drug product. This collaboration establishes readiness and a shared commitment to achieving swift regulatory approval with efficient development of the initial commercial supply of the Company's highly innovative drug products, PF614 and PF614-MPAR. MPAR® (Opioid Abuse Deterrent and Overdose Protection Program) Update PF614-MPAR, the Company's second product to treat severe pain with the added benefit of oral overdose protection, is a combination product of the TAAPTM prodrug PF614 with a trypsin inhibitor. MPAR® (Multi-Pill Abuse Resistance) reduces or "switches off" the release of the opioid only in an overdose situation, by blocking the first step of the trypsin activation process, providing an additional layer of protection to Ensysce's TAAP™ medications. Data from the clinical trial, PF614-MPAR-101, demonstrating that the MPAR® technology worked as designed to provide overdose protection, led to the FDA's Breakthrough Therapy designation in January 2024. During the fourth quarter, the Company initiated a second clinical trial with PF614-MPAR, PF614-MPAR-102, to evaluate higher dosages of PF614-MPAR. In January, the Company announced interim data from PF614-MPAR-102 that showed a 100 mg dosage form of PF614-MPAR provided overdose protection when a greater-than-prescribed dose is consumed at one time. The study continues to examine the protection provided when 5 times the 100 mg dose unit is consumed, studying potential food effects, and conducting a multiple ascending dose study with the final PF614-MPAR combination. Thus far, adverse events have been limited, we believe verifying the favorable safety profile of PF614 and PF614-MPAR as a novel class of opioids to treat severe pain. Opioid Use Disorder (OUD) Program Update Using its TAAP technology, the Company created a pipeline of methadone analogues to treat OUD, and in 2024 selected its lead OUD drug candidate PF9001. The intent of the program is to reduce both the abuse profile and the cardiovascular side effects associated with traditional methadone OUD treatments, 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 continuing non-clinical studies to support moving into IND enabling work in the coming year. Q4 & Full Year 2024 Financial Results Cash - Cash and cash equivalents were $3.5 million as of December 31, 2024, compared to $4.2 million as of September 30, 2024 and $1.1 million as of December 31, 2023. For the year, cash from financing activities of $9.9 million exceeded cash used in operations of $7.5 million. Federal Grants - Funding under federal grants totaled $1.3 million for the fourth quarter of 2024 compared to $0.5 million in the comparable year ago quarter. For the full year of 2024, funding from federal grants was $5.2 million compared to $2.2 million for the full year of 2023. The increased funding in 2024 is largely attributable to a $14 million multi-year award from the National Institute on Drug Abuse (NIDA) to support the MPAR clinical program. The remaining cash funding under the MPAR grant is $1.6 million for the period through May 31, 2025, with an additional $9.0 million of funding available for the following two years. Research & Development Expenses - R&D expenses were $3.8 million for the fourth quarter of 2024 compared to $2.2 million for the same period in 2023. The increase was due to heightened activity for the MPAR and OUD programs in 2024. For the full year, R&D expenses were $7.2 million compared to $7.6 million for 2023. The full year decrease was primarily the result of reduced costs related to clinical and pre-clinical programs for PF614 as activity in 2024 transitioned to preparation for a Phase 3 trial. General & Administrative Expenses - G&A expenses were $1.1 million in the fourth quarter of 2024, compared to $1.4 million for the fourth quarter of 2023. For 2024, G&A expenses were $4.7 million, representing a decrease of $0.6 million compared to $5.4 million for 2023. The decrease was primarily a result of reduced stock-based compensation expenses in 2024. We expect future general and administrative expenses to approximate current levels. Other Income (Expense) - Total other income (expense) was income of $12,054 for the fourth quarter of 2024 compared to expense of $0.3 million in the same period of 2023. For 2024, total other income (expense), net was an expense of $1.3 million compared to income of $0.1 million for 2023. The changes in other expenses were primarily the result of interest expense associated with the amortization of the original issue discount and the debt issuance costs for the 2023 Notes and represented a net change in other income and expense of $1.3 million compared to 2023. Net Income (Loss) - Net loss attributable to common stockholders for the fourth quarter of 2024 was $3.6 million compared to a net loss of $3.5 million for the fourth quarter of 2023. For 2024, net loss was $8.0 million compared to $10.6 million for 2023. 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; 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: 203-741-8811ENSC@mzgroup.us Ensysce Biosciences, Inc.Condensed Consolidated Statements of Operations 2021 2020 2021 2020 Three Months Ended December 31, Year Ended December 31, 2024 2023 2024 2023 $ 1,303,659 $ 515,032 $ 5,210,031 $ 2,230,520 3,802,630 2,232,760 7,219,437 7,587,473 1,077,505 1,437,957 4,720,728 5,361,234 4,880,135 3,670,717 11,940,165 12,948,707 (3,576,476 ) (3,155,685 ) (6,730,134 ) (10,718,187 ) 12,054 (348,676 ) (1,256,875 ) 91,912 $ (3,564,422 ) $ (3,504,361 ) $ (7,987,009 ) $ (10,626,275 ) - 66 (216 ) 264 $ (3,564,422 ) $ (3,504,295 ) $ (7,987,225 ) $ (10,626,011 ) $ (2.90 ) $ (16.94 ) $ (11.45 ) $ (70.40 ) Ensysce Biosciences, Inc.Condensed Consolidated Statements of Cash Flows 2021 2020 Year Ended December 31, 2024 2023 $ (7,502,700 ) $ (10,779,982 ) 9,881,173 8,755,884 2,378,473 (2,024,098 ) 1,123,604 3,147,702 $ 3,502,077 $ 1,123,604 Ensysce Biosciences, Inc.Condensed Consolidated Balance Sheets December 31, December 31, 2024 2023 Assets Current assets: Cash and cash equivalents $ 3,502,077 $ 1,123,604 Prepaid expenses and other current assets 1,842,605 1,165,264 Total current assets 5,344,682 2,288,868 Other assets 252,550 419,217 Total assets $ 5,597,232 $ 2,708,085 Liabilities and stockholders' deficit Current liabilities: Accounts payable $ 1,357,079 $ 1,936,007 Accrued expenses and other liabilities 548,458 542,260 Notes payable and accrued interest 301,660 854,697 Total current liabilities 2,207,197 3,332,964 Long-term liabilities 10,096 26,388 Total liabilities 2,217,293 3,359,352 Stockholders' deficit 3,379,939 (651,267 ) Total liabilities and stockholders' equity $ 5,597,232 $ 2,708,085 Released March 10, 2025

Tris Pharma has been touting cebranopadol as offering a potential solution to the opioid crisis.\n Tris Pharma’s opioid alternative has scored a third win in a trio of clinical trials, providing the biotech with the data needed to take the pain relief drug to the FDA this year.The latest readout saw cebranopadol, a dual nociceptin/orphanin FQ peptide (NOP) receptor and µ-opioid peptide (MOP) receptor agonist, tested in a phase 3 trial of patients who have undergone toe surgery.The study achieved its primary endpoint of showing a statistically significant reduction in pain intensity measured each hour over 48 hours compared to placebo. Specifically, a once-daily 400-µg dose of cebranopadol resulted in a mean 56.1-point reduction in this pain measurement compared to placebo, giving a p-value of less than 0.001.A total of 57.5% of patients receiving cebranopadol didn’t require an additional “rescue medication” of a common analgesic, such as ibuprofen, over seven days compared to 28.4% of those on placebo, the biotech noted.A separate arm of the study involved patients receiving the common opioid oxycodone four times a day. The mean pain relief experienced by these patients was also less than the cebranopadol cohort, the company said.Tris’ drug also showed a favorable safety profile, with nausea being the most common adverse event and no serious adverse events reported in the trial. Today’s readout rounds off a trio of clinical proof points for cebranopadol this year, which Tris has been touting as offering a potential solution to the opioid crisis. January saw the biotech demonstrate a statistically significant reduction in pain intensity in patients who had undergone cosmetic surgery on their abdomen. Days later, the company pointed to data from a phase 1 trial of a crushed, nasal insufflation dose of cebranopadol to show that it was less likely to be abused than oxycodone.“With our phase 3 program for cebranopadol in the treatment of moderate-to-severe acute pain complete, we now have a comprehensive data package that will be submitted to the FDA as the basis for potential approval,” Tris’ CEO Ketan Mehta said in the March 6 release. “If approved, cebranopadol has the potential to redefine the standard of care for acute pain management, offering a first-in-kind treatment option for patients in need.”At the J.P. Morgan Healthcare Conference in San Francisco in January, Tris Chief Business Officer James Hackworth, Ph.D., told Fierce that the biotech believes cebranopadol’s mechanism is “unique.”While cebranopadol stimulates the MOP receptor in the same way that opioids do, its ability to also stimulate the NOP receptor avoids the other effects that have contributed to opioids’ addictiveness, he explained.Tris isn\'t the only company looking for a new way to treat pain after the the FDA recently approved Vertex Pharmaceuticals’ NaV1.8 pain signal inhibitor Journavx. But Hackworth told Fierce at JPM that he sees Vertex’s offering as “more complementary” than competitive to cebranopadol.