CT-1812

新药研发“死亡谷”又有项目被埋了。 最近一个月，多款靶向治疗阿尔茨海默病的创新药披露最新进展，喜忧参半。 近期披露进展的阿尔茨海默病新药 其中，Simufilam和AL002针对的靶点较为新颖。 细丝蛋白A（FLNA）本是细胞内正常存在的一种支架蛋白，在Aβ蛋白的毒性形式Aβ42影响下可发生错构，从而转变为Aβ蛋白的“帮凶”，导致磷酸化tau蛋白和炎症因子产生，使大脑神经元受损；髓样细胞触发受体（TREM2）是一种跨膜蛋白，参与调控大脑的小胶质细胞的吞噬作用和炎症反应。在病理状态下，TREM2无法与Aβ蛋白结合，导致小胶质细胞无法清除Aβ蛋白，使大脑神经元受损。因而，靶向FLNA和TREM2被认为是治疗阿尔茨海默病的可行策略。 遗憾的是，Simufilam和AL002双双失败，而且结果相当惨烈，无论是主要终点还是次要终点、生物标志物相关终点均未达到。 III期ReThink-ALZ研究结果显示，相比于安慰剂组，Simufilam组患者的阿尔茨海默病评定量表-认知功能子量表（ADAS-Cog12）评分（+2.8分 vs +3.2分，Δ=-0.39分，P=0.43）和阿尔茨海默病协作研究-日常生活能力量表（ADCS-ADL）评分（-3.3分 vs -3.8分，Δ=0.51分，P=0.40）并未显著改善。 II期INVOKE-2研究结果显示，相比于安慰剂组，AL002组患者的临床痴呆评定量表总和（CDR-SB）分数未显著改善。 而Blarcamesine和CT1812针对的靶点已经被研究得较为透彻。 σ1受体（σ1R）是一种位于内质网线粒体相关膜表面的分子伴侣蛋白，参与记忆功能发挥和神经保护等过程；σ2受体（σ2R）是一种内质网驻留膜蛋白，参与Aβ低聚物清除和神经元细胞的凋亡过程；毒蕈碱乙酰胆碱受体（mAChR）可与神经递质乙酰胆碱结合，帮助机体发挥学习和记忆功能。研究表明，Aβ蛋白会对这些受体介导的生理过程产生负面影响，导致阿尔茨海默病的发生发展，因而靶向激活σ1R、拮抗σ2R和激活mAChR具备治疗阿尔茨海默病的潜力。 作为σ1R/mAChR激动剂的Blarcamesine和作为σ2R拮抗剂的CT1812确实通过了临床研究的考验。 II/III期AD-004研究结果显示，相比于安慰剂组，Blarcamesine组患者的ADAS-Cog13评分显著改善（Δ=-2.027，P=0.008）。 II期SHINE研究结果显示，在意向性治疗（ITT）人群中，CT1812组与安慰剂组患者的ADAS-Cog11评分暂无显著性差异（P=0.30）。不过，在磷酸化tau-217蛋白水平低于中位数（1.0pg/mL）的人群中，相比于安慰剂组，CT1812组患者的ADAS-Cog11评分显著改善（P=0.06）。 基于上述结果，两款药物的下一步开发计划均已明朗——Anavex Life Sciences向欧洲药品监督管理局提交了Blarcamesine用于治疗阿尔茨海默病的上市申请，Cognition Therapeutics将与FDA讨论CT1812的注册性III期临床试验设计方案。 Copyright © 2024 PHARMCUBE. All Rights Reserved. 欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。 免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

– Topline results in second dementia indication expected to be reported in December 2024 – PURCHASE, N.Y., Nov. 26, 2024 (GLOBE NEWSWIRE) -- Cognition Therapeutics, Inc., (NASDAQ: CGTX), a clinical-stage company developing drugs that treat neurodegenerative disorders, announced that the last patient has completed their final clinic visit in the Phase 2 SHIMMER study of CT1812 in patients with mild-to-moderate dementia with Lewy bodies (DLB). The Company anticipates that topline results will be available in December 2024. “We would like to extend our appreciation to the patients and caregivers who participated in our study, without whom we would not have been able to accomplish this goal. In addition, we would like to thank our investigators, our partners at the National Institute of Aging and the Lewy Body Dementia Association (LBDA) and the greater DLB awareness community for their tireless commitment,” stated Anthony Caggiano, M.D., Ph.D., Cognition’s chief medical officer and head of R&D. Lisa Ricciardi, Cognition’s president and CEO, concluded, “We look forward to reviewing the results of this study to enhance our understanding of CT1812’s tolerability profile and identify signals of efficacy across measures of cognition and function.” About Dementia with Lewy Bodies (DLB)Dementia with Lewy bodies is the second most common cause of dementia, affecting an estimated 1.4 million Americans. The disease is believed to be caused by a buildup of the protein α-synuclein, which aggregates in Lewy bodies, which are found within brain neurons. DLB is referred to as a “whole-body” disease, as it disrupts biological processes affecting autonomic, digestive, cognitive, and motor systems. Varied initial symptoms may include day-to-day fluctuations in alertness level, hallucinations, delusions, movement disorders and REM sleep disorder (acting out dreams while sleeping). Only a few symptomatic treatments for DLB are approved and currently there are no disease-modifying therapeutics. About the SHIMMER StudyThe SHIMMER study is a double-blind, placebo-controlled Phase 2 clinical trial that enrolled 130 adults with mild-to-moderate DLB. Participants were evenly randomized to receive either placebo or one of two oral once-daily doses of CT1812 (100 mg or 300 mg) for six months. Participants are assessed throughout the study using the Montreal Cognitive Assessment (MoCA) and Mini Mental State Examination (MMSE), which track cognitive performance; the Clinician Assessment of Fluctuation (CAF) to measure the frequency and duration of cognitive fluctuations; and the MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III, an objective assessment of parkinsonism. The SHIMMER study is supported by a grant award from the National Institute on Aging of the National Institutes of Health (NIH) totaling approximately $30 million and is being conducted in collaboration with James E. Galvin, MD, MPH, director of the Comprehensive Center for Brain Health at the University of Miami Miller School of Medicine and the Lewy Body Dementia Association (LBDA). The SHIMMER study is being conducted at over 30 sites in the United States, many of which are LBDA centers of excellence. About CT1812 CT1812 is an experimental orally delivered small molecule oligomer antagonist that penetrates the blood-brain barrier and binds selectively to the sigma-2 (σ-2) receptor complex, which is involved in the regulation of key cellular processes. These processes are disrupted by toxic interaction with Aβ or α-synuclein oligomers, oxidative stress and other disease drivers. The ensuing damage to sensitive synapses can progress to a loss of synaptic function, which manifests as cognitive impairment and disease progression. Participants are currently being recruited in the START study (NCT05531656) of CT1812 in adults with early Alzheimer’s disease; and the MAGNIFY study (NCT05893537) in adults with geographic atrophy (GA) secondary to dry age-related macular degeneration. Enrollment has completed in the SHIMMER study (NCT05225415) in adults with dementia with Lewy bodies and the SHINE study (NCT03507790) in mild-to-moderate Alzheimer’s disease. 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 and retina. We currently are investigating our lead candidate CT1812 in clinical programs in Alzheimer’s disease, dementia with Lewy bodies (DLB) and dry age-related macular degeneration (dry AMD). We believe CT1812 and our pipeline of σ-2 receptor modulators can regulate pathways that are impaired in these diseases that are 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 StatementsThis 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, 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 CT1812 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 the 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; our ability to maintain the listing of our common stock on the Nasdaq Global Market; 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.comCasey McDonald (media)Tiberend Strategic Advisors, Inc.cmcdonald@tiberend.comMike Moyer (investors)LifeSci Advisorsmmoyer@lifesciadvisors.comThis press release was published by a CLEAR® Verified individual.