δ opioid receptor x κ opioid receptor

ZURICH, SWITZERLAND / ACCESSWIRE / October 21, 2024 / NLS Pharmaceutics Ltd. (NASDAQ:NLSP)(NASDAQ:NLSPW) (“NLS” or the “Company”), a Swiss clinical-stage biopharmaceutical company dedicated to developing therapies for rare and complex central nervous system disorders, is pleased to announce that its Japanese patent application No. 2020-513594 has been granted. The patent covers the use of Mazindol ER (extended-release) for the treatment of heroin dependence, providing a new therapeutic strategy for opioid use disorder. “The development of mazindol as a treatment for substance use disorder could represent a significant breakthrough, offering new hope for patients battling addiction. It is crucial we align our strategy with the evolving landscape of pharmaceutical innovation in this area.” said Alex Zwyer, Chief Executive Officer of NLSP. “This application highlights the continued commitment from NLS to pioneer therapeutic approaches to address significant unmet medical needs.” Key Highlights of this Patent Mazindol ER for Heroin Dependence : Mazindol, a tetracyclic compound with unique pharmacological properties, has shown promising in vivo results in reducing heroin dependence by modulating neurotransmitter systems involved in reward signaling and addiction pathways. The patent protects the use of Mazindol ER as a treatment for opioid addiction, specifically targeting heroin, one of the most potent and addictive opioids. Mechanism of Action : Unlike traditional opioid agonists and antagonists, Mazindol works by indirectly modulating the reward systems of the brain, targeting opioid receptors such as μ-opioid, κ-opioid, and δ-opioid receptors. By influencing these receptors, Mazindol reduces cravings and compulsive drug-seeking behaviors, helping to mitigate the effects of opioid use disorder without inducing the same level of dependence associated with other treatments. Focus on Long-Term Efficacy : The patent includes claims for the sustained-release formulation of Mazindol, which allows for a steady release of the drug over time, improving patient compliance and reducing the risk of relapse. This extended-release formulation is designed to maintain therapeutic levels of the drug in the bloodstream for prolonged periods, providing more consistent symptom management for individuals recovering from heroin addiction. Scientific Basis Opioid Use Disorder (OUD), particularly heroin addiction, poses a significant public health challenge worldwide. Heroin binds strongly to opioid receptors in the brain, leading to intense euphoria followed by physical dependence and withdrawal symptoms. Traditional treatments often rely on opioid substitution therapies, which can carry their own risks of dependence. Mazindol offers an innovative, non-opioid approach that addresses the brain’s addiction circuitry, potentially reducing the risk of relapse and improving recovery outcomes. The unique effect of Mazindol on heroin dependence lies in its ability to regulate the meso-corticolimbic system, which includes the ventral tegmental area (VTA) and nucleus accumbens-key regions in the brain’s reward circuitry. By normalizing these pathways, Mazindol helps reduce the compulsive behaviors associated with opioid use disorder, offering hope for individuals struggling with heroin addiction. Appeal Decision in Japan NLS Pharmaceutics successfully appealed the original rejection of its patent application, receiving a favorable decision from the Japan Patent Office (JPO) on October 2, 2024. The granted patent, which includes eight claims, provides robust protection for Mazindol ER and its specific use in treating opioid dependence, particularly heroin addiction. This decision reflects an innovative contribution to addiction medicine and positions Mazindol ER as a potentially transformative treatment for heroin dependence in Japan and beyond. About NLS Pharmaceutics Ltd. NLS Pharmaceutics Ltd. is a global development-stage biopharmaceutical company working with internationally recognized scientists and world-class partners to develop innovative therapies for patients with rare and complex central nervous system disorders. Headquartered in Switzerland and founded in 2015, NLS is led by an experienced management team with a track record of successfully developing and commercializing product candidates. For more information, visit . Safe Harbor Statement This press release contains forward-looking statements pursuant to U.S. Federal securities laws. For example, NLS discusses potential benefits of its products and the granted patent. Forward-looking statements are based on the current expectations of NLS management and are subject to numerous factors and uncertainties that could cause actual results to differ. These factors include technology changes, delays or obstacles in launching clinical trials, and the non-approval of NLS products by regulatory agencies. NLS undertakes no obligation to update any forward-looking statements to reflect events or circumstances after the date of this release unless required by law. Detailed risk information is included in NLS’s filings with the U.S. Securities and Exchange Commission (SEC), available at . Contact: Investor Relations Contact InvestorRelations@nls-pharma.com SOURCE: NLS Pharmaceutics AG View the original press release on accesswire.com

MONMOUTH JUNCTION, N.J.--( BUSINESS WIRE )--Tris Pharma, Inc. (Tris), a commercial-stage biopharmaceutical company focused on attention deficit hyperactivity disorder (ADHD), pain, addiction and neurological disorders, today announced that the company will present data from its first-in-class, late-stage investigational pain therapy with a novel mechanism of action, cebranopadol, at the upcoming International Association for the Study of Pain (IASP) 2024 World Congress on Pain, taking place August 5-9, 2024, in Amsterdam. “I am inspired to see the rise in interest, funding and research into the development of novel treatment options for the millions of people who suffer daily from debilitating pain that impacts their quality of life,” said Ketan Mehta, founder and CEO at Tris Pharma. “Our team has been working with urgency to advance cebranopadol, a first-in-class investigational pain therapy with a novel mechanism of action, through clinical studies with the goal of offering physicians an effective treatment option that they can confidently prescribe and patients feel is safe. We look forward to collaborating with the pain community at IASP 2024 and sharing our latest findings.” Cebranopadol is the first and only dual nociceptin/orphanin FQ peptide (NOP) receptor and µ-opioid peptide (MOP) receptor (dual-NMR) agonist in development to treat moderate-to-severe pain. Dual-NMR agonist compounds have the potential to deliver gold-standard pain relief with a strong safety profile because they mimic the body’s natural pain-modulation processes by synergizing the analgesic and safety characteristics of the NOP receptor with the analgesic advantages of the MOP receptor. Tris Pharma plans to share important news regarding its Phase 3 clinical trials in the near future. Symposium Highlighting Novel Pain Mechanism Tris Pharma will host a symposium featuring a series of presentations focused on dual-NMR agonists, a promising new mechanism of action in treating pain, and its potential to overcome the shortfalls of opioids for moderate-to-severe pain. The symposium will be presented as part of the congress by leading scientists with extensive experience in the research and development of novel pain therapies. Details of the symposium are as follows: Symposium: Break the Mold in Pain Biology: The Promise of a New Mechanism that May Overcome the Shortfalls of Current Moderate to Severe Pain Medications Presenters: Charles E. Argoff, MD, Albany Medical College; Roberto Ciccocioppo, PhD, University of Camerino; Jeffrey Gudin, MD, University of Miami Miller School of Medicine Location: RAI Amsterdam Convention Centre, Elicium I Date and Time: August 6, 12:45 – 1:45 p.m. CEST At IASP 2024 Tris Pharma will be present at Booth #316 where company executives will be available to provide additional information and data presented at the congress. About Cebranopadol (TRN-228) Cebranopadol is the first and only investigational dual nociceptin/orphanin FQ peptide (NOP) receptor and µ-opioid peptide (MOP) receptor (dual-NMR) agonist for the treatment of moderate-to-severe pain, as well as opioid use disorder (OUD). Cebranopadol offers a first of its kind and novel mechanism of action that takes advantage of the inherent properties of the NOP receptor, which has demonstrated both the potential to lessen the risk of misuse while still providing effective pain relief, and the potential to block drugs of abuse from producing drug-seeking behaviors. The FDA has granted Fast Track Designation to cebranopadol for chronic low back pain. Cebranopadol’s profile has been well-characterized in pain management studies, and if approved, it could become the first and only pain-relief therapy with the demonstrated ability to provide efficacy equivalent to opioids with significantly less risk for misuse or risk of physical dependence, addiction or overdose. About Tris Pharma Tris Pharma is a privately held, innovation-driven biopharmaceutical company that is applying its drug development capabilities and proprietary technologies to transform the treatment of ADHD, pain and neurological disorders, including addiction and diseases of the central nervous system. Tris is an established commercial organization with a robust portfolio of best-in-class ADHD products and a promising pipeline of differentiated, near-term drug candidates. More information is available at www.trispharma.com and on LinkedIn @ TrisPharma .

▎药明康德内容团队编辑随着生物技术领域不断实现突破性进展，医药行业对2024年上半年可能涌现的医学创新充满期待。最近，行业媒体BioPharma Dive发布了一篇文章，从诸多前景广阔的研发项目中挑选出了10项有可能在今年上半年对整个行业产生显著影响的临床试验进行了专题报道。这些试验覆盖了广泛的研发领域，从革命性的基因疗法到前沿癌症治疗，它们不仅代表了医药研发的最新成就，更有望为全球患者带来生命的转机。在本文中，药明康德内容团队将结合公开资料，与读者分享这些值得关注的临床试验。图片来源：123RF值得关注的十项临床试验研发公司：Vertex Pharmaceuticals疗法名称：VX-548适应症：急性疼痛疗法类型：小分子药物临床试验注册号：NCT05558410，NCT05553366试验阶段：3期临床试验VX-548是Vertex公司研发的一种口服选择性NaV1.8抑制剂，与其它NaV离子通道相比，它对NaV1.8具有高度选择性。NaV1.8是在外周神经系统的痛觉信号传导中起到关键性作用的电压门控钠通道，是经过遗传学验证的疼痛治疗靶点。Vertex的策略是通过选择性抑制NaV1.8，开发新的药物类型。与阿片类药物相比，这类药物可能在提供更好镇痛效果的同时，避免上瘾等副作用。VX-548已获美国FDA授予快速通道资格与突破性疗法认定，用于治疗中度至重度急性疼痛。2023年12月公布的2期临床试验结果显示，经过12周的VX-548治疗，疼痛性糖尿病外周神经病变（DPN）患者在数字疼痛评定量表（NPRS）评估的每日疼痛强度每周平均值这一主要终点上均显示出具有统计学意义和临床重要性的降低。然而，在疼痛药物的研究领域，由于试验目的依赖于主观测量，且易受到安慰剂效应的影响，这使得研究成果的评估变得尤为复杂。一些专家认为需要更多的数据来验证其潜力。2024年初，Vertex公司将公布两项安慰剂对照研究以及一项单臂试验的结果，这些研究针对的是不同形式的急性疼痛，以探究VX-548的有效性和安全性。VX-548用于治疗慢性疼痛的后期研究将随后进行。研发公司：Alnylam Pharmaceuticals疗法名称：Vutrisiran（商品名：Amvuttra）适应症：转甲状腺素蛋白介导（ATTR）淀粉样变性心肌病疗法类型：小干扰RNA临床试验注册号：NCT04153149试验阶段：3期临床试验Amvuttra是一种在研、皮下给药的RNAi治疗药物，开发用于治疗ATTR淀粉样变性，包括遗传性ATTR和野生型ATTR淀粉样变性，通过靶向和沉默特定的mRNA，阻断野生型和变体转甲状腺素蛋白的产生。这款疗法通过Alnylam公司的增强稳定化学（ESC）-GalNAc偶联递送平台设计，增加了其治疗效力和代谢稳定性，允许以每季度的频率进行皮下注射，并具有减少至每半年注射一次的潜力。Amvuttra获得欧盟与美国在治疗转甲状腺素蛋白介导淀粉样变性的孤儿药资格，并在2022年6月获得美国FDA批准治疗遗传性ATTR淀粉样变性成人患者的多发性神经病变。目前，Alnylam公司正积极寻求监管机构批准其药物Amvuttra，用于治疗ATTR淀粉样变性心肌病，该公司正在进行的关键性3期Helios-B试验的结果将是获得批准的重要依据。Helios-B是一项大规模的3期、随机、双盲、安慰剂对照、多中心研究，旨在评估Amvuttra治疗ATTR淀粉样变性心肌病患者的疗效和安全性。这项试验已经进行了超过4年，足以证明Amvuttra是否能有效延长患者生命并减少住院的需要。Alnylam公司预计，这项研究将在今年年初公布其结果。研发公司：罗氏（Roche）旗下基因泰克（Genentech）疗法名称：Tiragolumab适应症：肺癌疗法类型：抗体临床试验注册号：NCT04294810试验阶段：3期临床试验Tiragolumab是一种新型免疫检查点抑制剂，该单克隆抗体靶向TIGIT且具完整的Fc区域。TIGIT是一种新型的抑制性免疫检查点，主要在T细胞和自然杀伤（NK）细胞表面表达，它可以抑制人体对癌症的免疫反应。TIGIT通路与PD-L1/PD-1通路互补，因此tiragolumab和Tecentriq双重阻断可能有助于克服免疫抑制并恢复免疫应答。当前，tiragolumab正在一项名为Skyscraper-01的3期临床研究中进行测试，以检验其联合Tecentriq与安慰剂联合Tecentriq相比，作为既往未接受过治疗的局部晚期、不可切除或转移性PD-L1高表达非小细胞肺癌（NSCLC）患者一线疗法的疗效和安全性，这些患者没有表皮生长因子受体（EGFR）突变或ALK易位。该试验初步分析结果显示，使用组合疗法患者的总生存期（OS）呈现改善趋势，但数据尚未成熟，未达统计学显著差异。业界分析师表示，这一发现为TIGIT靶向药物带来了希望，也让人们更加期待预计将于2024年初公布的最终结果。研发公司：Amylyx Pharmaceuticals疗法名称：AMX0035（商品名：Relyvrio）适应症：肌萎缩侧索硬化（ALS）疗法类型：小分子药物临床试验注册号：NCT05021536试验阶段：3期临床试验AMX0035是两种药物苯丁酸钠（sodium phenylbutyrate）和牛磺酸二醇（taurursodiol）的复方制剂，旨在跳过神经系统的复杂性，直接延缓神经细胞的死亡。在神经退行性疾病中，神经细胞的线粒体和内质网经常会出现异常。线粒体是细胞的“能量中心“，而内质网则是多种蛋白折叠的“厂房”，这两类细胞器的失常会导致蛋白折叠错误，能量代谢异常等问题，引起神经细胞的死亡。Amylyx公司的设想是，通过苯丁酸钠和牛磺酸二醇这两种药物改善细胞内线粒体和内质网的健康状态，从而延缓神经细胞的死亡。去年9月，美国FDA批准了AMX0035上市，用于治疗ALS，其依据是一项针对大约140名患者进行的研究，该研究发现AMX0035对疾病进展和存活率具有统计显著的益处。在获批之前，Amylyx公司已经启动了另一项规模更大的试验Phoenix，以证实之前的结果。Phoenix研究是一项3期、随机、双盲、安慰剂对照、多中心试验，旨在评估为期48周的AMX0035与安慰剂治疗对比，在治疗成年ALS患者方面的安全性和有效性。这项研究预计将于2024年3月结束，其最终的试验结果备受业界的关注。研发公司：强生（Johnson＆Johnson）疗法名称：Aticaprant（JNJ-67953964）适应症：抑郁症疗法类型：小分子药物临床试验注册号：NCT05455684试验阶段：3期临床试验Aticaprant（JNJ-67953964）是一种每日一次的选择性和短效kappa-阿片受体（KOR）拮抗剂，对μ阿片受体（MOR）和δ阿片受体（DOR）具有明显的选择性。KOR是一种参与多种神经系统功能的蛋白质，包括压力、疼痛以及情绪调节。目前，aticaprant正在一项随机、双盲、多中心、平行组、安慰剂对照研究中进行测试，以评估其作为辅助疗法用于中重度快感缺乏（ANH+）且对当前抗抑郁疗法反应不佳的抑郁症患者的辅助治疗。该试验目前仍处于招募（recruiting）状态，预计将于2024年6月初步完成。研发公司：吉利德科学（Gilead Sciences）疗法名称：Sacituzumab govitecan（商品名：Trodelvy）适应症：肺癌疗法类型：抗体偶联药物临床试验注册号：NCT05089734试验阶段：3期临床试验Trodelvy是一种靶向Trop-2的抗体偶联药物，Trop-2是一种在多种肿瘤类型中高度表达的细胞表面抗原。Trodelvy的设计将拓扑异构酶抑制剂SN-38通过一款可水解的连接子与单克隆抗体连接在一起。这种独特的组合将强效活性递送到表达Trop-2的细胞和微环境。目前，Trodelvy已在美国获批三项适应症，分别为三阴性乳腺癌，HR+/HER2-乳腺癌和尿路上皮癌。除以上获批适应症以外，Trodelvy还被开发用于其他潜在的用途，例如用于治疗转移性NSCLC、转移性小细胞肺癌、头颈癌和子宫内膜癌。吉利德科学于2021年11月启动了一项针对铂类化疗和抗PD-1/PD-L1免疫疗法治疗后病情进展的晚期或转移性NSCLC患者的开放标签、全球性、多中心、随机3期研究，以比较Trodelvy与多西他赛在这些患者中的疗效。该试验预计将于2024年5月初步完成。研发公司：赛诺菲（Sanofi）疗法名称：Tolebrutinib（曾用名SAR442168）适应症：多发性硬化疗法类型：小分子药物临床试验注册号：NCT04410978，NCT04410991试验阶段：3期临床试验Tolebrutinib是一款能够穿过血脑屏障的口服鲁顿氏酪氨酸激酶（BTK）抑制剂。BTK是B细胞受体信号通路的关键组成部分。BTK对各种免疫细胞的发育和功能都很重要，包括B淋巴细胞和巨噬细胞。通过抑制BTK，可调节与大脑和脊髓神经炎症相关的适应性和先天性免疫细胞。这款BTK抑制剂在治疗多发性硬化患者的2b期临床试验中已经达到主要和次要终点，显著降低患者大脑中与多发性硬化相关的病变。图片来源：123RF赛诺菲目前正在开展多项关键的3期临床试验，旨在评估其药物在治疗多种类型的多发性硬化患者中的疗效。特别值得关注的是GEMINI-1和GEMINI-2两项试验，它们专注于复发性多发性硬化患者，比较了tolebrutinib与市场上已有药物teriflunomide（商业名：Aubagio）的疗效和安全性。这两项3期随机、双盲研究预计将在2024年中期发布初步试验结果。这些结果将为我们提供关于tolebrutinib作为多发性硬化潜在治疗选择的重要信息，对于赛诺菲和整个医药界来说，都具有重要意义。研发公司：辉瑞（Pfizer）疗法名称：PF-06939926适应症：杜氏肌营养不良症（DMD）疗法类型：基因疗法临床试验注册号：NCT04281485试验阶段：3期临床试验PF-06939926是辉瑞旗下一款在研静脉注射基因疗法。它将由人类肌肉特异性启动子控制的“迷你”抗肌萎缩蛋白（mini-dystrophin）转基因装在腺相关病毒9（AAV9）载体中。AAV9病毒载体具有向肌肉组织靶向递送转基因的能力。这款在研疗法已经被FDA授予孤儿药资格、罕见儿科疾病药物认定和快速通道资格。既往发布的1b期研究结果显示，9名6至12岁的DMD患者接受了PF-06939926的治疗。治疗12个月后，患者显示出持久和具有统计学意义的显著改善，包括微型抗肌萎缩蛋白表达的持续水平，以及NorthStar门诊评估量表（NSAA）得分的改善。目前，PF-06939926正在一项随机、双盲、安慰剂对照、3期临床试验中接受测试，该研究旨在评估这项基因疗法对于年龄在4至8岁的DMD男孩的安全性和有效性。根据试验设计，三分之二的受试者将接受基因治疗。而其余被分配到安慰剂组的受试者将有机会在研究的第二年初接受同样的基因治疗。研究的主要结果分析计划在52周时进行，所有受试者都将在接受基因治疗后继续接受为期5年的随访。辉瑞公司表示，他们决定在获得明确结果之前不寻求药物的快速批准，他们认为后期研究能提供更加清晰和确凿的答案。预计这项具有重大意义的研究将在2024年发布其最终结果。研发公司：Moderna疗法名称：mRNA-1083适应症：流感，COVID-19疗法类型：mRNA疫苗临床试验注册号：NCT06097273试验阶段：3期临床试验Moderna公司正在开发一种名为mRNA-1083的新型mRNA疫苗，旨在同时对抗流感和COVID-19。得益于mRNA技术的多功能性和适应性，这种疫苗有潜力快速调整以匹配每年流行的主要病毒株。鉴于目前流感疫苗的有效率仅在40%到60%之间，这项创新有望改进流感疫苗的预防效率。在一项1/2期随机、观察者盲法的研究中，mRNA-1083在针对流感和COVID-19的免疫原性方面表现出色，与市场上已获批准的单适应症疫苗相比具有更强的效果。同时，该疫苗在安全性方面的表现也被认为是可接受的。基于这些初步结果，Moderna公司进一步发起了一项针对年龄≥50岁健康成人的3期随机、观察者盲法、活性对照临床研究。该研究旨在全面评估mRNA-1083疫苗的安全性、反应原性和免疫原性，并将其与同时接种流感和COVID-19疫苗的活性对照组进行比较。根据公开资料，预计该3期试验的结果可能将在2024年上半年公布。研发公司：Beam Therapeutics疗法名称：BEAM-101适应症：镰状细胞贫血病疗法类型：单碱基编辑疗法临床试验注册号：NCT05456880试验阶段：1/2期临床试验BEAM-101是Beam Therapeutics公司在研的一种单碱基编辑疗法，它通过在体外对患者的造血干细胞进行基因组改造，使其模仿遗传性持续性胎儿血红蛋白症个体中的单核苷酸多态性，来缓解导致镰刀状细胞贫血症的遗传突变的不良影响。该疗法整合了基因编辑和细胞疗法，在2021年11月获得了FDA的IND批准。目前，Beam Therapeutics正在进行一项开放标签、单臂、多中心、1/2期临床研究，以评估在重症镰状细胞贫血病患者中应用BEAM-101的安全性和有效性。Beam公司预计将于明年分享首批接受治疗的患者的初步数据。这些即将公布的数据对于验证碱基编辑技术的临床应用至关重要，特别是考虑到迄今为止，只有Verve Therapeutics公布了碱基编辑技术在临床试验中的应用结果。因此，Beam Therapeutics的这一研究将成为碱基编辑技术在临床应用方面的一个重要里程碑。结语随着2024年上半年的到来，医药与生物技术行业正迎来关键时期。这10项临床试验尤为引人注目，它们涵盖了基因疗法、mRNA疫苗及无成瘾性止痛药等多个领域，不仅代表着科学创新的成功转化，同时也承载着全球无数患者的希望。这些试验有潜力解决关键的未竟医疗需求，塑造行业的未来走向。随着这些试验的稳步推进，业界正热切期待它们带来的成果。这些成果不仅预示着治疗领域的突破性进步，还有望开启新的治疗时代。大家都在看▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料：[1] 10 clinical trials to watch in the first half of 2024，Retrieved January 3, 2024, from 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