Zervimesine

编者按：中枢神经系统（CNS）疾病由于病理机制复杂，且药物入脑受到血脑屏障（BBB）的限制，一直被认为是药物研发领域的重大挑战。在这一领域，小分子疗法展现出一定的优势，并在CNS疾病治疗中发挥着重要作用。当前CNS领域已有多款小分子药物获监管机构批准上市，此外全球范围内还有数百项小分子新药管线正在针对CNS疾病开展临床研究。作为医药创新的赋能者，药明康德已构建起完善的CNS能力体系，覆盖从早期筛选到IND申报的全流程。凭借丰富经验与深厚积累，药明康德致力于加速全球合作伙伴的CNS药物研发进程，助力客户早日将创新疗法带给患者。 在医药领域，CNS药物研发一直被视为最具挑战性的领域之一。其主要障碍在于BBB——这一高度选择性的生理“守门人”仅允许分子量约在400–600 Da以下的脂溶性分子被动扩散进入大脑。正因如此，药物在脑内的递送效率往往受限，导致疗效不足；如果提高用药剂量，药物在其他器官和组织中的非靶向分布又会引发更多副作用。 尽管困难重重，但监管机构已在CNS领域先后批准多款小分子药物的临床批件或上市，凸显了小分子疗法在CNS治疗中的重要作用。凭借较低的分子量，它们更容易穿透BBB；再加上固有的药代动力学优势以及较高的口服生物利用度，使小分子药物成为CNS疾病治疗的重要选择。除已上市的疗法外，目前还有数百项CNS疾病小分子新药管线处于临床开发阶段，涵盖帕金森病、阿尔茨海默病、肌萎缩侧索硬化症（ALS）等一系列重大疾病。 图片来源：123RF 2025年小分子新药治疗CNS疾病迎新进展 2025年以来，治疗CNS疾病的小分子新药管线取得一系列新的临床进展，适应症涵盖帕金森病、阿尔茨海默病、ALS、癫痫、精神分裂症、脑卒中等等。 其中，有药物向监管机构递交上市申请，有望在不久的将来造福患者。比如，9月，艾伯维（AbbVie）宣布已向FDA提交在研小分子tavapadon的新药申请（NDA），用于帕金森病治疗。Tavapadon是一种新型选择性多巴胺D1/D5受体部分激动剂，被开发为每日一次口服疗法。通过选择性地激活黑质纹状体通路上的D1/D5多巴胺受体，tavapadon有可能提供适当的多巴胺信号平衡以改善运动控制，同时避免D2/D3过度刺激，这被认为是当前多巴胺激动剂许多副作用的原因。 多款新药治疗阿尔茨海默病（AD）、痴呆等神经退行性疾病迎来新进展。比如，7月，Cognition Therapeutics公司公布其在研小分子药物zervimesine（CT1812）在针对路易体痴呆（DLB）患者的临床试验中取得积极结果。分析显示，该疗法使DLB患者在认知指标上改善91%。Zervimesine是一款在研每日一次口服的sigma-2受体（S2R）调节剂，可穿越血脑屏障，用于治疗中枢神经系统疾病。 再如，9月，Anavex Life Sciences公布了其用于治疗早期AD的在研小分子药物blarcamesine的2b/3期研究最新结果。在主要认知终点ADAS-Cog13（阿尔茨海默病研究中用于测量认知功能和追踪疾病进展的标准化神经心理学测试）上，与安慰剂相比，blarcamesine治疗48周后认知下降减少了 84.7%。Blarcamesine是一款每日口服一次的小分子SIGMAR1激活剂。SIGMAR1是在自噬过程中起到重要作用的膜蛋白。通过激活SIGMAR1，blarcamesine可以诱导自噬作用，清除细胞中积累的错误折叠蛋白，改善细胞的健康和生存。 同月，Galimedix Therapeutics宣布，其在研口服小分子GAL-101的1期临床试验顺利完成。该产品耐受性良好，临床安全性确立，未观察到淀粉样蛋白成像异常（ARIA）或其他严重不良事件（SAEs）。与临床前研究结果一致，GAL-101能够有效穿越血脑屏障，其药代动力学（PK）特征也为推动其口服剂型进入阿尔茨海默病2期临床试验提供了有力支持。GAL-101通过靶向错误折叠β淀粉样蛋白（Aβ）单体，阻止有毒Aβ寡聚体和原纤维的形成。 除此之外，其余在CNS疾病领域取得新进展的小分子新药还包括： 12月，Praxis Precision Medicines宣布，其在研小分子药物relutrigine在EMBOLD研究注册队列中取得积极结果，该研究纳入了携带SCN2A和SCN8A基因变异的发育性和癫痫性脑病（DEEs）患者。基于积极的疗效结果，独立数据监查委员会已建议提前因疗效原因终止试验。Praxis公司正在计划该产品向FDA递交新药申请（NDA）事宜。Relutrigine的作用机制为优先抑制持续性钠电流，而这一电流已被证实是严重DEEs患者癫痫发作症状的重要驱动因素。 再如，11月，Spinogenix公布了在研小分子疗法SPG302首次用于ALS患者的一项2a期临床试验的积极顶线结果。分析显示，在治疗结束时，82%的SPG302组患者表现为功能下降速度稳定或改善；与PRO-ACT数据库的历史对照相比，这些患者在6个月随访中平均功能下降速度降低约76%。SPG302是一款每日一次口服小分子药物，有望恢复突触功能，从而有潜力稳定甚至逆转认知及运动功能的下降。突触是神经元之间的关键连接，使人能够思考、规划、记忆和控制运动。 同月，拜耳（Bayer）宣布其在研小分子口服FXIa抑制剂asundexian于全球3期临床研究中取得积极主要结果。该研究在接受抗血小板治疗、发生过非心源性缺血性卒中或高危短暂性脑缺血发作的患者中开展，结果显示，每日一次50 mg asundexian较安慰剂在联合抗血小板治疗背景下可显著降低缺血性卒中风险。拜耳计划与全球监管机构开展沟通，为后续上市许可申请的提交做准备。Asundexian具有用于非心源性缺血性卒中患者卒中预防的潜力。 11月，纽欧申医药在研小分子药物——新型选择性M4毒蕈碱型乙酰胆碱受体正向变构调节剂 (M4 PAM) NS-136完成针对精神分裂症患者的2期临床试验的首例患者给药。靶向M4受体的正向变构调节是一种创新作用机制，具有治疗涵盖精神分裂症、阿尔兹海默病的精神症状或激越症状在内的多种精神疾病的潜力。纽欧申医药和丽珠医药正在共同开发的高选择性小分子KCNQ2/3激活剂NS-041也在今年迎来一系列进展：7月，该产品针对局灶性癫痫患者的2期临床研究完成首例患者给药；12月，该产品治疗抑郁症的临床研究申请在中国获批，将开展2期临床研究。NS-041通过调节神经元兴奋性发挥抗癫痫作用，同时通过调节中脑腹侧被盖区多巴胺神经元的兴奋性，从而改善相关抑郁症状。 10月，挚盟医药宣布其用于治疗ALS的新一代钾离子通道开放剂CB03-154已正式启动2/3期临床试验，针对ALS适应症；9月，该产品还在中国获批开展针对癫痫的2期临床试验。CB03-154为一款新一代KCNQ2/3钾离子通道开放剂。钾离子（K+）通道是分布广、种类多的一类离子通道，主要参与调节神经元的兴奋性及动作电位发放的频率和振幅，其功能失调与癫痫、ALS、重度抑郁等多种中枢神经系统疾病相关。 2月，InFlectis BioScience宣布在一项临床2a期试验中，其在研口服小分子疗法IFB-088具有良好安全性，并展现用以治疗延髓性肌萎缩侧索硬化症（bulbar-onset ALS）的初步潜在疗效。在意向治疗（ITT）人群中，根据ALS功能评分量表（ALSFRS）的评估显示，IFB-088组患者表现出较低的功能衰退趋势。本次临床试验还证实，IFB-088治疗延髓性肌萎缩侧索硬化症的机制涉及综合应激反应和氧化应激通路。IFB-088能够选择性地抑制eIF2α的去磷酸化，从而可增强综合应激反应，为细胞提供对抗各种应激（包括神经退行性疾病标志——内质网应激）的保护屏障。 除了上述进展，2025年以来，全球CNS疾病小分子新药管线还迎来其它一系列新进展，此处不再一一列举。 一体化CRDMO赋能平台助力合作伙伴加速创新疗法研发 在这一持续发展的领域中，药明康德始终坚持赋能全球合作伙伴，凭借一体化、端到端的CRDMO赋能平台，致力于加速全球合作伙伴的CNS药物研发进程，加速创新疗法的落地。 针对CNS新药研发领域的特殊挑战，药明康德建立了多项CNS专属的药物代谢与药代动力学（DMPK）能力。例如，其“漏斗（Funnel）”体外检测模型展现出高度准确性，能够有效区分可穿透血脑屏障的药物与因被动扩散能力不足或受外排转运蛋白影响而无法进入的药物，帮助合作伙伴快速识别潜力候选疗法，从而高效推进研发进程。 除了早期筛选，药明康德还为合作伙伴提供多样化的定制化研究策略，包括脑室内或鞘内给药、微透析技术、在啮齿类和大型动物模型中进行脑脊液连续采样、精确解剖和分离近20种不同脑区组织，以及利用全身自显影（QWBA）全面展示药物在脑内的分布。这些能力不仅应用于小分子药物，也广泛支持蛋白质、寡核苷酸等大分子药物，从早期筛选直至IND申报。 小分子药物近期在CNS治疗领域的进展，充分展现了科学创新与产业协作的力量。展望未来，药明康德将继续凭借一体化、端到端的CRDMO赋能平台，加速全球合作伙伴的突破性疗法的研发生产，支持CNS药物研发进步，造福全球患者。 免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「医药观澜」微信公众号回复“转载”，获取转载须知。

- Type C Meeting with U.S. Food and Drug Administration (FDA) Scheduled for Second Half of January -PURCHASE, N.Y., Dec. 03, 2025 (GLOBE NEWSWIRE) -- Cognition Therapeutics, Inc., (the “Company” or “Cognition”) (NASDAQ: CGTX), a clinical-stage company developing drugs that treat neurodegenerative disorders, announced that its expanded access program has reached full enrollment. Each of the individuals enrolled in the program are being treated with 100 mg of oral zervimesine daily for up to one year. The program was made possible through a generous donation from the family of a participant in the Phase 2 SHIMMER study of zervimesine (CT1812) in dementia with Lewy bodies (DLB). “We are grateful to the family who made it possible to provide expanded access to zervimesine for people who were in the Phase 2 DLB study,” stated Lisa Ricciardi, president and CEO of Cognition Therapeutics. “The efforts of our dedicated investigators and our clinical operations team made it possible to complete enrollment in only three months.” “The speed with which the program was enrolled is also a testament to the high level of interest among patients with DLB,” added Lawrence S. Honig, MD, PhD, professor of neurology at Columbia University Irving Medical Center and an investigator in the program. “The ability to provide our patients with a medication that they feel is making a meaningful difference in their lives is incredibly rewarding. I look forward to working with Cognition on the next phase of clinical development for zervimesine.” Having reached alignment with FDA on a registrational program for Alzheimer’s disease, Cognition Therapeutics is now pursuing similar input from the agency on DLB. The Company's request for a Type C meeting has been accepted by the U.S. Food and Drug Administration (FDA) and the meeting scheduled for the second half of January. The Type C meeting will focus on the proposed design of a Phase 3 program for zervimesine in this patient population. Meeting minutes are expected to follow the Type C meeting. About the Expanded Access ProgramThe COG1202 expanded access program is an open-label program for eligible SHIMMER participants who completed the Phase 2 study as well as additional patients with a diagnosis of mild-to-moderate DLB who meet the enrollment criteria. Dr. James E. Galvin, MD, MPH, director of the Comprehensive Center for Brain Health at the University of Miami Miller School of Medicine is acting as lead investigator for the multi-center, open-label program. As an investigational medicine, zervimesine has not been approved by regulatory authorities. Therefore, the safety and efficacy of zervimesine have not been fully characterized and there may be risks associated with its use. More information is available on clinicaltrials.gov under study identifier NCT06961760. About Zervimesine (CT1812)Zervimesine (CT1812) is an investigational, oral, once-daily pill in development for the treatment of CNS diseases such as Alzheimer’s disease and dementia with Lewy bodies (DLB). While these diseases have different symptoms, both are associated with the buildup of certain proteins in the brain – Aβ and ɑ-synuclein. As these proteins bind to receptors on the surface of neurons, they can damage and ultimately destroy the neurons. This results in a progressive loss in a person’s ability to learn, recall memories, move efficiently, or communicate. These diseases progress relentlessly and ultimately result in death. Zervimesine has been shown to interrupt the toxic effects of Aβ and ɑ-synuclein, which may slow progression of disease and improve the lives of those suffering from Alzheimer’s and DLB. Zervimesine has been generally well tolerated in clinical studies to date. The USAN Council has adopted zervimesine as the United States Adopted Name (USAN) for CT1812. About Cognition Therapeutics, Inc. Cognition Therapeutics, Inc., is a clinical-stage biopharmaceutical company discovering and developing innovative, small molecule therapeutics targeting age-related degenerative disorders of the central nervous system. We recently completed Phase 2 studies of our lead candidate, zervimesine (CT1812) in dementia with Lewy bodies (DLB), mild-to-moderate Alzheimer’s disease and geographic atrophy secondary to dry AMD. The Phase 2 START Study (NCT05531656) in early Alzheimer’s disease is ongoing. We believe zervimesine can regulate pathways that are impaired in these diseases through its interaction with the sigma-2 receptor, a mechanism that is functionally distinct from other approaches for the treatment of degenerative diseases. More about Cognition Therapeutics and our pipeline can be found at https://cogrx.com. Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. All statements contained in this press release or made during the conference, other than statements of historical facts or statements that relate to present facts or current conditions, including but not limited to, statements regarding our product candidates, including zervimesine (CT1812), and any expected or implied benefits or results, including that initial clinical results observed with respect to zervimesine will be replicated in later trials and our clinical development plans, including statements regarding our clinical studies of zervimesine, any analyses of the results therefrom and our expectations regarding the development programs for zervimesine, are forward-looking statements. These statements, including statements relating to the timing and expected results of our clinical trials involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance, or achievements to be materially different from any future results, performance, or achievements expressed or implied by the forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “might,” “will,” “should,” “expect,” “plan,” “aim,” “seek,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “forecast,” “potential” or “continue” or the negative of these terms or other similar expressions. We have based these forward-looking statements largely on our current expectations and projections about future events and financial trends that we believe may affect our business, financial condition, and results of operations. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, some of which cannot be predicted or quantified and some of which are beyond our control. Factors that may cause actual results to differ materially from current expectations include, but are not limited to: competition; our ability to secure new (and retain existing) grant funding; our ability to grow and manage growth, maintain relationships with suppliers and retain our management and key employees; our ability to successfully advance our current and future product candidates through development activities, preclinical studies and clinical trials and costs related thereto; uncertainties inherent in the results of preliminary data, pre-clinical studies and earlier-stage clinical trials being predictive of the results of early or later-stage clinical trials; the timing, scope and likelihood of regulatory filings and approvals, including regulatory approval of our product candidates; changes in applicable laws or regulations; the possibility that we may be adversely affected by other economic, business or competitive factors, including ongoing economic uncertainty; our estimates of expenses and profitability; the evolution of the markets in which we compete; our ability to implement our strategic initiatives and continue to innovate our existing products; our ability to defend our intellectual property; the impacts of ongoing global and regional conflicts on our business, supply chain and labor force; and the risks and uncertainties described more fully in the “Risk Factors” section of our annual and quarterly reports filed with the Securities & Exchange Commission and are available at www.sec.gov. These risks are not exhaustive and we face both known and unknown risks. You should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur, and actual results could differ materially from those projected in the forward-looking statements. Moreover, we operate in a dynamic industry and economy. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties that we may face. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Contact Information:Cognition Therapeutics, Inc.info@cogrx.comMike Moyer (investors)LifeSci Advisorsmmoyer@lifesciadvisors.com This press release was published by a CLEAR® Verified individual.