Methadone Hydrochloride

BXCL501 demonstrated clinical benefits and favorable tolerability pro treatment of opioid withdrawal symptoms Results from this NIDA-funded study support potential future development of BXCL501 in opioid withdrawal Opioid use disorder is a global health crisis, affecting approximately 5.9 million adults in the U.S. NEW HAVEN, Conn., March 05, 2026 (GLOBE NEWSWIRE) -- BioXcel Therapeutics, Inc. (Nasdaq: BTAI), a biopharmaceutical company built on artificial intelligence (“AI”) to develop transformative medicines in neuroscience, today announced positive topline results from a Phase 2 investigator-sponsored trial (IST) evaluating BXCL501 for the treatment of opioid withdrawal symptoms in adults with opioid use disorder (OUD) undergoing a methadone taper. The study suggested that BXCL501 may be as effective as or superior to lofexidine (Lucemyra ® ) for reducing the symptoms of opioid withdrawal during methadone taper, while having a more convenient dosing regimen and demonstrating a favorable tolerability profile. In this study, BXCL501 had similar or lower overall rates of cardiovascular (CV) effects than lofexidine. Specifically, the most common CV adverse event for Lucemyra, orthostatic hypotension, was significantly lower for the 180 µg twice daily (BID) BXCL501 dose group (18% vs 50% lofexidine, p<0.05) and remained lower in the highest 240 µg BID BXCL501 dose group (37%) over the seven-day dosing period. There were no reports of sedation or somnolence in the BXCL501 treatment arms (5% reported sedation in the lofexidine arm). These results support potential future development of BXCL501 in opioid withdrawal. These findings build on the earlier Company-sponsored Phase 1b/2 study, RELEASE, 1 which established the tolerability pro selected BXCL501 doses in opioid-dependent patients and extend those results into a clinically distinct setting that included a methadone taper and an active comparator. The results are consistent with the mechanism of action of BXCL501 (alpha 2-adrenergic receptor agonism), as locus coeruleus drives various opioid withdrawal symptoms. 2 These results strengthen the growing body of evidence supporting BXCL501 across multiple potential indications, reinforcing its potential as a “pipeline within a product.” These findings build on positive results from Phase 3 pivotal studies evaluating BXCL501 for the treatment of acute agitation associated with bipolar disorder and schizophrenia, as well as Alzheimer’s disease. For this National Institute on Drug Abuse (NIDA)-funded study, BioXcel Therapeutics supplied BXCL501. This study was planned as a 4-arm trial: BXCL501 180 µg BID or 240 µg BID, placebo, and lofexidine 0.54 mg QID as a positive control. It enrolled participants who were predominantly exposed to fentanyl and included a high proportion of participants exposed to fentanyl adulterated or associated with xylazine (FAAX), which has been designated as an emerging threat by the White House Office of National Drug Control Policy. 3 The trial was completed after 80 patients were enrolled. Key takeaways from the study include: BXCL501 240 µg BID reduced opioid withdrawal symptoms compared to placebo during a seven-day methadone taper, as measured by the Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop). After receiving BXCL501 240 µg, patients experienced a greater than 30% reduction in SOWS-Gossop scores, with peak symptom improvement observed on days 3 and 4. The reduction in withdrawal symptoms with BXCL501 numerically exceeded that observed with lofexidine 0.54 mg administered four times daily. BXCL501 demonstrated a favorable tolerability profile, with rates of key adverse events (including dizziness, orthostatic hypotension, bradycardia and insomnia) comparable to or lower than those reported for lofexidine in the Lucemyra ® (lofexidine) FDA label. “As we continue to face a worldwide crisis encompassing a large patient population suffering from opioid use disorder, these results showcase an encouraging therapeutic milestone demonstrating the significant potential of BXCL501 as a therapy for meaningfully reducing opioid withdrawal symptoms,” said Dr. Sandra Comer, Principal Investigator of the study and Professor of Neurobiology in the Department of Psychiatry at Columbia University. “Opioid withdrawal remains a significant burden on the healthcare system and patients, and despite available therapies, there is still a substantial unmet need for safe and more effective treatment options that can help patients successfully transition to other medications such as buprenorphine or naltrexone for long-term benefits.” Notably, OUD remains a critical global health crisis, with an estimated 36 to 61 million people worldwide living with opioid dependence. 4 Approximately 85% of chronic opioid users experience at least one withdrawal episode every six months, suggesting that 30 to 50 million individuals globally may require withdrawal management each year. In the United States alone, approximately 5.9 million people have diagnosed OUD, and about 8.9 million report annual opioid misuse. 5 Despite this substantial need, only about 25% of individuals with a substance use disorder receive specialized treatment, highlighting a significant treatment gap. 6 Currently approved options for opioid withdrawal management are limited, and tolerability challenges may affect adherence, underscoring the potential importance of BXCL501’s differentiated pro a non-opioid, orally dissolving thin film formulation of dexmedetomidine administered twice daily. Another potential advantage of BXCL501 is that it may be particularly well-suited for treating withdrawal from opioids adulterated with xylazine. About BioXcel Therapeutics, Inc. BioXcel Therapeutics, Inc. (Nasdaq: BTAI) is a biopharmaceutical company built on artificial intelligence (“AI”) to develop transformative medicines in neuroscience. Its wholly owned subsidiary, OnkosXcel Therapeutics, is focused on the development of medicines in immuno-oncology. The Company’s drug re-innovation approach leverages existing approved drugs and/or clinically validated product candidates together with big data and proprietary machine learning algorithms to identify new therapeutic indications. For more information, please visit bioxceltherapeutics.com . About BXCL501 Outside of its approved indication by the U.S. Food and Drug Administration as IGALMI ® (dexmedetomidine) sublingual film, BXCL501 is an investigational proprietary, orally dissolving film formulation of dexmedetomidine, a selective alpha-2 adrenergic receptor agonist. BXCL501 is under investigation by BioXcel Therapeutics for the acute treatment of agitation associated with Alzheimer’s dementia and for the acute treatment of agitation associated with bipolar I or II disorder or schizophrenia in the at-home setting. The safety and efficacy of BXCL501 for these investigational uses have not been established. BXCL501 has been granted Breakthrough Therapy designation by the FDA for the acute treatment of agitation associated with dementia and Fast Track designation for the acute treatment of agitation associated with schizophrenia, bipolar disorders, and dementia. Forward-Looking Statements This press release includes “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. We intend such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act of 1933, as amended and Section 21E of the Securities Exchange Act of 1934, as amended. All statements contained in this press release other than statements of historical fact should be considered forward-looking statements, including, without limitation, statements related to: potential future development of BXCL501 in opioid withdrawal; BXCL501’s potential as a “pipeline within a product”; the potential of BXCL501 to serve as a safe and effective treatment option that can help patients successfully transition to other medications. When used herein, words including “anticipate,” “believe,” “can,” “continue,” “could,” “designed,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “might,” “plan,” “possible,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, though not all forward-looking statements use these words or expressions. In addition, any statements or information that refer to expectations, beliefs, plans, projections, objectives, performance or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking. All forward-looking statements are based upon the Company’s current expectations and various assumptions. The Company believes there is a reasonable basis for its expectations and beliefs, but they are inherently uncertain. The Company may not realize its expectations, and its beliefs may not prove correct. Actual results could differ materially from those described or implied by such forward-looking statements as a result of various important factors, including, without limitation: its limited operating history; its incurrence of significant losses; its need for substantial additional funding and ability to raise capital when needed; the impact of the reprioritization; its significant indebtedness, ability to comply with covenant obligations and potential payment obligations related to such indebtedness and other contractual obligations; the Company has identified conditions and events that raise substantial doubt about its ability to continue as a going concern; its limited experience in drug discovery and drug development; risks related to the TRANQUILITY program; its dependence on the success and commercialization of IGALMI ® , BXCL501, BXCL502, BXCL701 and BXCL702 and other product candidates; the number of episodes of agitation and the size of the Company’s total addressable market may be overestimated, and approval that the Company may obtain may be based on a narrower definition of the patient population; its lack of experience in marketing and selling drug products; the risk that IGALMI ® or the Company’s product candidates may not be accepted by physicians or the medical community in general; the Company still faces extensive and ongoing regulatory requirements and obligations for IGALMI ® ; the failure of preliminary data from its clinical studies to predict final study results; failure of its early clinical studies or preclinical studies to predict future clinical studies; its ability to receive regulatory approval for its product candidates; its ability to enroll patients in its clinical trials; undesirable side effects caused by the Company’s product candidates; its novel approach to the discovery and development of product candidates based on EvolverAI; the significant influence of and dependence on BioXcel LLC; its exposure to patent infringement lawsuits; its reliance on third parties; its ability to comply with the extensive regulations applicable to it; impacts from data breaches or cyber-attacks, if any; risks associated with the increased scrutiny relating to environmental, social and governance (ESG) matters; risks associated with federal, state or foreign health care “fraud and abuse” laws; and its ability to commercialize its product candidates, as well as the important factors discussed under the caption “Risk Factors” in its Annual Report on Form 10-K for the fiscal year ended December 31, 2024, as such factors may be updated from time to time in its other filings with the SEC, which are accessible on the SEC’s website at and the Investors section of the Company’s website at. These and other important factors could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While the Company may elect to update such forward-looking statements at some point in the future, except as required by law, it disclaims any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing the Company’s views as of any date subsequent to the date of this press release. Contact Information: Corporate/Investors Russo Partners Nic Johnson nic.johnson@russopartnersllc.com 1.303.482.6405 Media Russo Partners David Schull david.schull@russopartnersllc.com 1.858.717.2310 Source: BioXcel Therapeutics, Inc. References Jones et al., Am J Drug Alcohol Abuse. 2023 49(1):109–122 Ivanov and Aston-Jones, Journal of Neurophysiology 2001 85:6, 2388-2397

~ Phase 1 Data Published in Journal of Opioid Management Validates First-in-Class Overdose-Limiting Opioid Technology of PF614-MPAR ~ SAN DIEGO, CA / ACCESS Newswire / March 3, 2026 / Ensysce Biosciences, Inc. (NASDAQ:ENSC) ("Ensysce" or the "Company"), a clinical-stage pharmaceutical company pioneering next-generation pain and central nervous system therapeutics designed to minimize risk of abuse and overdose, today announced the publication of the first clinical manuscript describing its MPAR® (Multi-Pill Abuse Resistance) overdose protection technology. The paper, titled "Formulation and a Phase 1 Clinical Study of PF614-MPAR, an Oxycodone Prodrug with Oral Opioid Overdose Protection," appears online in the Journal of Opioid Management Jan/Feb 2026 issue. PF614-MPAR is the first opioid candidate specifically designed to provide active protection against oral overdose-a limitation not addressed by currently marketed abuse-deterrent formulations. MPAR® technology is engineered to maintain therapeutic opioid exposure when taken as prescribed while automatically limiting additional opioid release when excessive numbers of pills are consumed. Data presented in the publication demonstrate that PF614-MPAR achieved appropriate opioid plasma levels under normal dosing conditions, while preventing large increases in opioid delivery when supratherapeutic doses were administered. These findings support the potential for a fundamentally new safety paradigm in opioid analgesia. MPAR® previously received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) in January 2024 based on this clinical evidence and the technology is protected by a growing intellectual property portfolio extending through 2042. "This peer-reviewed publication marks a defining milestone not only for Ensysce, but for the field of pain medicine," said Dr. Lynn Kirkpatrick, Chief Executive Officer of Ensysce. "CDC data projects that almost 80,000 people die every year from opioid overdose of which prescription opioids factor into 12.4% of these deaths 1 . These numbers, which amount to 30 deaths per day, are still considered a major health crisis. Importantly, to combat against overdose, MPAR® introduces a new class of chemically programmed opioids designed to protect patients even when dosing errors or misuse occur." The clinical work reported in this publication allowed for the optimization of the MPAR® formulation and the confirmation that the overdose-limiting mechanism functions as intended in humans. The continued support from the National Institute on Drug Abuse 2 helped enable this study and the ongoing second clinical trial evaluating the MPAR® technology. Beyond opioid analgesics, Ensysce is advancing MPAR® across additional therapeutic categories-including amphetamines and methadone-with the goal of developing safer treatments for pain, attention-deficit/hyperactivity disorder (ADHD), and opioid use disorder. ¹ 2 Research supporting this patent was funded by the National Institute on Drug Abuse of the National Institutes of Health under Award Number DA047682. 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 . 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 . Any forward-looking statement speaks only as of the date on which it was made. Ensysce undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required under applicable law. Ensysce Biosciences Company Contact: Lynn Kirkpatrick, Ph.D. Chief Executive Officer (858) 263-4196 Ensysce Biosciences Investor Relations Contact: Shannon Devine MZ North America Main: 203-741-8811 ENSC@mzgroup.us SOURCE: Ensysce Biosciences View the original press release on ACCESS Newswire