Naltrexone

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

Bringing medical advances from the lab to the clinic. （👆，征战罕见病，我们一起努力。） 根据卫健委公布的罕见病目录（共两批，207种），美国Healsan恒祥医学科技将持续对所有罕见病进行解读和大数据分析，以其能够为从事罕见病研究的生物制药公司、医生科学家及患者提供一些有用的信息。 编者按：他们的起步往往比别人更艰难：从小频繁崴脚、跑步跑不快；随着年龄增长，小腿肌肉逐渐萎缩，双腿细如“鹤腿”，足弓高高隆起，甚至连扣纽扣、握笔都成了奢望…… 这就是腓骨肌萎缩症（Charcot-Marie-Tooth Disease，简称CMT），全球最常见的遗传性周围神经病。自1886年被首次命名以来，近130多年的时间里，全球没有任何一款经FDA批准的针对性疾病修饰药物（DMT）。患者只能依靠康复训练、矫形器甚至骨科手术来延缓残疾的步伐。 然而，医学的齿轮正在加速转动。站在2026年的春天，回顾过去六年的研发狂奔，我们终于听到了破冰的碎裂声。从首个进入NDA（新药上市申请）讨论阶段的靶向药，到2026年初刚刚公布惊艳数据的First-in-class小分子，再到中国医保与本土研发的协同发力，CMT的治疗版图正在发生剧变。 本文将为您全景拆解2020-2026全球CMT新药研发现状及中国市场的准入破局，为制药企业寻找罕见病蓝海提供极具价值的洞察，也为在黑夜中坚守的患者点亮一盏长明灯。一、 基因里的“断电”危机：为什么CMT新药如此难开发？ 要理解目前制药界的管线布局，首先要看懂CMT的致病根源。CMT并非单一疾病，而是一组由超过100个不同基因突变引起的庞大家族，发病率约为1/2500。 脱髓鞘型（如最常见的CMT1A型）：主要由PMP22基因重复引起。包裹在神经外面的“绝缘层”（髓鞘）被破坏，导致神经电信号传导变慢。 轴突型（如CMT2型）：神经内部的“导线”（轴突）直接发生病变，导致信号无法传导到远端肌肉。 新药研发的“死亡之谷”：由于CMT进展极为缓慢，传统的临床试验很难在短时间内（通常是1-2年）用常规量表观察到显著的症状改善；此外，致病基因的高度异质性，意味着很难有一款药能“包治百病”。这也是过去几十年大量药企折戟沉沙的原因。二、 2020-2026 全球破冰期：距离FDA首批新药仅一步之遥 尽管目前FDA尚未正式批准任何一款CMT专属药物，但近六年的管线进展已呈现出“井喷”态势。针对不同分型的“精准打击”疗法，正陆续交出令人振奋的临床答卷。1. 2026年最新高光：Ignaseclant (NMD670) 惊艳突围 对于制药界和患者而言，2026年2月的最新消息无疑是一针强心剂。丹麦创新药企 NMD Pharma 宣布其核心管线 Ignaseclant (原名NMD670) 在针对CMT1型和2型的Phase 2a期临床试验中取得了积极的Topline结果。 机制突破：这是一款First-in-class的骨骼肌特异性氯离子通道1（ClC-1）小分子抑制剂。它不纠正基因，而是直接作用于神经肌肉接头（NMJ），通过增强肌肉对微弱神经信号的响应能力，直接改善患者的肌肉力量和抗疲劳能力。 临床表现：数据表明，患者在肌肉力量和功能表现上获得了“临床意义上的显著改善”，且安全性极佳。该药物已在2025年1月顺利获得FDA授予的孤儿药资格（ODD），是目前泛CMT亚型中最具潜力的广谱改善药物。2. “里程碑”的冲刺：Govorestat (AT-007) 剑指首款获批 针对一种特定亚型：CMT-SORD（山梨醇脱氢酶缺乏所致的CMT），美国Applied Therapeutics公司走在了最前列。 研发进展：CMT-SORD患者体内积累了大量有毒的糖类物质“山梨醇”，导致神经损伤。Govorestat 是一款醛糖还原酶抑制剂。在2025年的周围神经学会（PNS）年会上，其为期12至24个月的Phase 2/3期试验数据显示，该药能显著减缓MRI下的疾病进展，并改善临床评估结果。 FDA动态：公司已在2025年秋季与FDA进行了关键会议，正式探讨提交新药上市申请（NDA）的路径。它极有可能成为人类历史上首个获FDA批准的CMT靶向药物。3. 经典管线的坚守：PXT3003 的重塑与中国连结 提到CMT1A型（占所有CMT患者的50%以上），法国Pharnext公司开发的 PXT3003 是绕不开的重头戏。 “鸡尾酒”疗法：这是一种由巴氯芬、纳曲酮和D-山梨醇组成的低剂量复方口服液，旨在通过多靶点协同下调有毒蛋白PMP22的过度表达。 曲折与希望：过去几年中，PXT3003经历了Phase 3期试验（PREMIER）的数据风波，FDA要求其提供更稳健的数据。尽管欧美上市之路略显坎坷，但其前期展现的安全性与延缓疾病进展的潜力依然备受瞩目。值得注意的是，中国天士力医药已在此前通过合资形式拿下了PXT3003在大中华区的开发和商业化权益，这也意味着一旦该药在海外获批，中国患者将有望同步受益。4. 前沿基因与干细胞技术：彻底治愈的曙光 (2024-2025突破) 近两年，核酸药物和细胞疗法为CMT带来了“治本”的希望，并密集获得FDA的孤儿药认定： ASO基因静默：Vanda Pharmaceuticals的 VCA-894A 是一种新型反义寡核苷酸（ASO），专门针对导致CMT2S型的特定隐蔽剪接位点突变。该药于2024年初获批IND，标志着CMT进入了个性化基因靶向时代。 RNA调控机制：ReviR Therapeutics的 RTX-117 在2025年获得FDA孤儿药资格，通过激活eIF2B来恢复蛋白翻译，从根本上纠正病理生理学。 干细胞再生：韩国ENCell的 EN001（间充质干细胞疗法）也在2025年3月斩获FDA孤儿药认定，它能靶向受损神经，分泌再生因子并促进髓鞘再形成。三、 中国破局：政策托底、医保护航与本土研发布局 对于中国数以十万计的CMT患者来说，如何负担未来可能的高昂药费？如何度过当前的“无药”空窗期？过去的几年，国家给出了一张充满温度的答卷。1. 政策与医保的底座：从罕见病目录到“惠民保” “官方认证”的护身符：早在2018年，腓骨肌萎缩症就被国家五部委正式列入《第一批罕见病目录》。这为CMT在中国的流行病学登记、快速通关审批以及医保倾斜奠定了至关重要的法律基础。 当前医保报销现状：由于全球尚无特效药，目前中国基本医保对CMT的覆盖主要体现在对症治疗与并发症管理上。例如，用于营养神经的甲钴胺、维生素B族，以及缓解神经痛的加巴喷丁、普瑞巴林等均在国家医保目录内；针对足下垂、严重高足弓进行的骨科矫形手术，大部分费用也可通过基本医保报销。 “惠民保”的精准补漏：2023-2026年间，全国各地的城市定制型商业医疗保险（惠民保）迎来了升级。越来越多城市的惠民保将罕见病患者必需的基因检测（WES/WGS全外显子/全基因组测序）以及定制化踝足矫形器（AFO）纳入了补充报销范围，极大地减轻了患者确诊与康复的经济负担。2. 蓄势待发的中国力量 除了前文提到的天士力提前布局PXT3003外，国内资本与创新药企也正积极介入。例如，针对导致神经病变的HDAC6靶点，韩国宗根堂（Chong Kun Dang）研发的小分子CKD-510已展现出对CMT的潜力，并被诺华以13亿美元的重金买断全球权益。这一标杆事件极大地刺激了中国本土 Biotech（如诸多聚焦神经退行性疾病的初创公司）加速在离子通道、ASO及基因编辑管线上的跟进。可以说，针对CMT的“中国造”原创新药，正在水面下暗流涌动。四、 结语：给制药同仁的冲锋号，给患者的定心丸 致患者朋友：医学是严谨的，目前的现实是，我们依然没有等来能彻底“治愈”CMT的神奇药丸。但请您一定看到：最黑暗的130年已经过去。2026年，多款新药已经杀入三期临床的决赛圈，基因疗法和靶向小分子正在实验室里为你重塑健康的神经。 请务必保持积极的康复锻炼，穿戴好矫形器保护你的关节，避免过度肥胖和使用神经毒性药物。保护好现在的肌肉功能，就是为了在不久的将来，能够以最好的状态迎接新药的降临。 致制药同仁与临床医生：CMT这块曾经被认为是“硬骨头”的罕见病领域，随着致病机制的完全破译以及FDA在临床终点（如肌力改善量表、特定生物标志物）上越来越灵活的指导原则，正演变为下一个百亿级别的孤儿药蓝海。谁能率先在广谱神经肌肉接头功能改善，或者在特定基因型ASO疗法上取得中美双报的成功，谁就能在这一赛道建立绝对的护城河。 本公众号由美国Healsan (恒祥医学科技)运营。投稿及商务联系微信号：healsan 提供特惠码MELT99，可以获得优惠。 美国Healsan专长于Healsan医学大数据分析（Healsan™）、及基于大数据的Hanson临床科研服务（HansonCR™）和医学编辑服务（MedEditing™）。主要为医生科学家、生物制药公司和医院科研处等提供文献计量分析和SCI论文润色、编辑、选刊等服务，成为诸多机构的“临床科研外挂”。 网址： https://healsan.com/ （👆，征战罕见病，我们在行动！） ▼ Healsan医路成长更多免费资源： （点击👆图片，进入自己感兴趣的专辑。或点击“资源”，浏览本公众号所有资源）