Donepezil Hydrochloride

ZUNVEYL Launch Momentum: Completed the second quarter of commercialization, generating approximately $2.8 million in total revenue for the quarter. Significant Growth: 102% quarterly increase in pharmacy orders, with record prescription volumes achieved each month during the quarter. Expanding Prescriber Base: Q3 prescribers surpassed 500 , representing 55% growth over the prior quarter. Disciplined Expense Management: Full-year operating spend guidance reduced to $28–30 million ; the Company expects operating profitability in 2027 . Strong Balance Sheet: $35.4 million in cash and cash equivalents as of September 30, 2025, excluding the October capital raise, which added $37.8 million in net proceeds , resulting in total pro forma non-GAAP cash and cash equivalents of approximately $73.2 million . VANCOUVER, British Columbia & GRAPEVINE, Texas--(BUSINESS WIRE)--Alpha Cognition Inc. (Nasdaq: ACOG) (“Alpha Cognition” or the “Company”) today announced its financial results for the third quarter ended September 30, 2025, and provided an operational update. “Our performance this quarter reinforces our belief in the strength of our long term care focused call strategy and reflects disciplined execution across the organization,” said Michael McFadden, Chief Executive Officer of Alpha Cognition. “Momentum for ZUNVEYL continues to build as we deepen engagement with LTC providers. During the quarter, we grew revenues, managed expenses, and increased our focus on the psychiatrists and medical directors. Clinician feedback continues to validate our belief that ZUNVEYL will become an important therapeutic option in the long-term care segment.” Recent Business and Operational Highlights Third Quarter 2025 Financial Results Conference Call Information Following the release, management will host a conference call to discuss financial and operational results in greater detail. About Alpha Cognition Inc. Alpha Cognition Inc. is a commercial stage, biopharmaceutical company dedicated to developing treatments for patients suffering from neurodegenerative diseases, such as Alzheimer’s disease and Cognitive Impairment with mild Traumatic Brain Injury (“mTBI”), for which there are currently no approved treatment options. ZUNVEYL is a patented drug approved as a new generation acetylcholinesterase inhibitor for the treatment of Alzheimer’s disease, with expected minimal gastrointestinal side effects. ZUNVEYL’s active metabolite is differentiated from donepezil and rivastigmine in that it binds neuronal nicotinic receptors, most notably the alpha-7 subtype, which is known to have a positive effect on cognition. ALPHA-1062 is also being developed in combination with memantine to treat moderate to severe Alzheimer’s dementia, and as an intranasal formulation for Cognitive Impairment with mTBI. INDICATION AND USAGE ZUNVEYL is a cholinesterase inhibitor indicated for the treatment of mild to moderate dementia of the Alzheimer’s type in adults. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS ZUNVEYL is contraindicated in patients with known hypersensitivity to benzgalantamine, galantamine, or to any inactive ingredients in ZUNVEYL. Serious skin reactions have occurred. WARNINGS AND PRECAUTIONS Serious Skin Reactions: Serious skin reactions (Stevens-Johnson syndrome and acute generalized exanthematous pustulosis) have been reported in patients receiving galantamine (the active metabolite of ZUNVEYL tablets). If signs or symptoms suggest a serious skin reaction, use of this drug should not be resumed, and alternative therapy should be considered. Anesthesia: See Drug Interactions Section Cardiovascular Conditions: Cholinesterase inhibitors, including ZUNVEYL, have vagotonic effects on the sinoatrial and atrioventricular nodes, leading to bradycardia and AV block. Bradycardia and all types of heart block have been reported in patients taking cholinesterase inhibitors, both with and without known underlying cardiac conduction abnormalities. Therefore, all patients should be considered at risk for adverse effects on cardiac conduction. Patients treated with galantamine up to 24 mg/day using the recommended dosing schedule showed a dose-related increase in risk of syncope. Gastrointestinal Conditions: Cholinesterase inhibitors, including ZUNVEYL, may increase gastric acid secretion. Patients should be monitored closely for active or occult gastrointestinal bleeding, especially those with a history of ulcer disease or those receiving concurrent nonsteroidal anti-inflammatory drugs (NSAIDs). Clinical studies of galantamine have shown no increase, relative to placebo, in the incidence of either peptic ulcer disease or gastrointestinal bleeding. Galantamine has been shown to produce nausea, vomiting, diarrhea, anorexia, and weight loss. Monitor the patient's weight during therapy with ZUNVEYL. Genitourinary Conditions: Although this was not observed in clinical trials with galantamine, cholinesterase inhibitors, including ZUNVEYL, may cause bladder outflow obstruction. Neurological Conditions: Cholinesterase inhibitors are believed to have some potential to cause generalized convulsions. Seizure activity may also be a manifestation of Alzheimer's disease. Patients with Alzheimer's disease should be monitored closely for seizures while taking ZUNVEYL. Pulmonary Conditions: Cholinesterase inhibitors, including ZUNVEYL, should be prescribed with care to patients with a history of severe asthma or obstructive pulmonary disease. Monitor for respiratory adverse reactions. ADVERSE REACTIONS The most common adverse reactions with galantamine tablets (≥5%) were nausea, vomiting, diarrhea, dizziness, headache, and decreased appetite. DRUG INTERACTIONS Use with Anticholinergics: Galantamine has the potential to interfere with the activity of anticholinergic medications. Use with Cholinomimetics and Other Cholinesterase Inhibitors: A synergistic effect is expected when cholinesterase inhibitors are given concurrently with succinylcholine, other cholinesterase inhibitors, similar neuromuscular blocking agents or cholinergic agonists such as bethanechol. USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data may cause fetal harm. Hepatic Impairment: In patients with moderate hepatic impairment, a decrease in clearance of galantamine was observed; therefore, a dosage adjustment is recommended. Use of ZUNVEYL in patients with severe hepatic impairment is not recommended. Renal Impairment: In patients with a creatinine clearance of 9 to 59 mL/min, an increase in exposure of galantamine was observed; therefore, a dosage adjustment is recommended. Use of ZUNVEYL in patients with creatinine clearance less than 9 mL/min is not recommended. These are not all of the possible side effects of ZUNVEYL. You can report side effects to the FDA. Visit www.fda.gov/MedWatch or call 1‑800‑FDA‑1088. Please click here for Full Prescribing Information. Forward-looking Statements This news release includes forward-looking statements within the meaning of applicable securities laws. Except for statements of historical fact, any information contained in this news release may be a forward‐looking statement that reflects the Company’s current views about future events and are subject to known and unknown risks, uncertainties, assumptions and other factors that may cause the actual results, levels of activity, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements. In some cases, you can identify forward‐looking statements by the words “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “project,” “potential,” “target,” “seek,” “contemplate,” “continue” and “ongoing,” or the negative of these terms, or other comparable terminology intended to identify statements about the future. Although the Company believes to have a reasonable basis for each forward-looking statement, we caution you that these statements are based on a combination of facts and factors currently known by us and our expectations of the future, about which we cannot be certain. The Company cannot assure that the actual results will be consistent with these forward-looking statements. These forward-looking statements are subject to certain risks, including risks regarding our ability to raise sufficient capital to implement our plans to commercialize ZUNVEYL, risks regarding the efficacy and tolerability of ZUNVEYL, risks related to ongoing regulatory oversight on the safety of ZUNVEYL, risk related to market adoption of ZUNVEYL, risks related to the Company’s intellectual property in relation to ZUNVEYL, risks related to the commercial manufacturing, distribution, marketing and sale of ZUNVEYL, risks related to product liability and other risks as described in the Company’s filings with Canadian securities regulatory authorities and available at www.sedar.com and the Company’s filings with the United States Securities and Exchange Commission (the “SEC”), including those risk factors under the heading “Risk Factors” in the Company’s most recent Annual Report on Form 10-K filed with the SEC on March 31, 2025 and the Company’s other filings with the SEC available at www.sec.gov. These forward‐looking statements speak only as of the date of this news release and the Company undertakes no obligation to revise or update any forward‐looking statements for any reason, even if new information becomes available in the future, except as required by law.

一、神经退行性疾病详细介绍 神经退行性疾病是一类因神经元结构或功能逐渐丧失而导致的慢性、进行性神经系统疾病，主要影响老年人，常见类型包括： 1. 阿尔茨海默病（AD）：最常见的痴呆类型，占病例的60%-80%，以β-淀粉样蛋白沉积、tau蛋白缠结和神经元丢失为特征，表现为记忆力减退、认知功能障碍和行为异常 。 2. 帕金森病（PD）：第二大神经退行性疾病，因黑质多巴胺能神经元死亡导致，症状包括震颤、肌强直、运动迟缓等，50岁后发病率显著上升 。 3. 肌萎缩侧索硬化症（ALS）：运动神经元进行性退化，导致肌肉无力、吞咽困难，最终呼吸衰竭，平均生存期3-5年 。 4. 额颞叶痴呆（FTLD）：以额叶和颞叶萎缩为特征，表现为行为异常、语言障碍，多见于60岁以下人群。 5. 亨廷顿病（HD）：遗传性疾病，由HTT基因突变导致，表现为舞蹈样动作、认知衰退和精神症状。 病理机制：衰老、基因突变、蛋白质稳态失衡（如Aβ、α-突触核蛋白异常积累）、线粒体功能障碍和神经炎症是核心因素。例如，AD中的β-淀粉样蛋白沉积引发神经炎症，破坏神经元网络；PD中的α-突触核蛋白聚集导致多巴胺能神经元死亡 。 治疗现状：目前缺乏根治方法，主要依赖对症治疗。例如，AD使用胆碱酯酶抑制剂改善认知，PD通过多巴胺替代疗法缓解症状。新兴技术如基因治疗（如CRISPR修复突变）、干细胞疗法（如iPS细胞分化为多巴胺神经元）和AI药物设计正在临床试验中，但尚未广泛应用。 二、全球神经退行性疾病基本现状与未来趋势 1. 中国 现状： 老龄化加速，神经退行性疾病负担全球最重。预计2050年帕金森病患者将达1050万，占全球41.6%，年龄标准化患病率全球第一（583例/10万人） 。 阿尔茨海默病患者超1000万，且以每年30万速度递增。 治疗以仿制药为主（如左旋多巴、多奈哌齐），但本土创新崛起，如睿健医药、神济昌华通过AI+化学诱导平台开发帕金森病细胞疗法，恒瑞医药布局PROTAC技术。 政策支持：将阿尔茨海默病纳入医保特殊病种，“十四五”规划推动基因编辑、干细胞等技术研发。 未来趋势： 人口老龄化持续加剧，预计2050年60岁以上人口占比超35%，疾病负担将进一步加重。 精准医疗与创新药研发加速，如间充质干细胞治疗AD和PD的临床试验已启动（中部战区总医院），计划2028年完成随访。 整合医学模式兴起，强调早期筛查（如血液生物标志物检测）和社区支持，降低家庭照料压力。 2. 日本 现状： 全球老龄化最严重国家，65岁以上人口占比超32%，神经退行性疾病患者数量庞大。家族性阿尔茨海默病（FAD）患者约100人，发病早、进展快。 再生医学全球领先，京都大学iPS细胞研究所利用患者iPS细胞生成多巴胺神经元治疗PD，2024年临床试验显示5/7患者运动功能改善。 药物再利用策略突破，如帕金森病药物溴氪被发现可减少FAD患者β-淀粉样蛋白沉积，2025年进入III期临床试验。 未来趋势： 依托iPS细胞技术推进个性化治疗，计划2028年将PD细胞疗法商业化。 扩大临床试验规模，如溴氪针对FAD的III期试验覆盖全国多家医院，目标2028年获批。 应对老龄化挑战，开发远程监测和居家护理技术，缓解医疗资源压力。 3. 美国 现状： 神经退行性疾病医疗支出全球最高，2021年痴呆症相关费用达3550亿美元，预计2050年将超1万亿美元。 研发投入领先，NIH 2026财年为阿尔茨海默病研究拨款39亿美元，重点支持生物标志物发现、基因治疗和生活方式干预 。 药物审批加速，如Aβ单抗药物Aducanumab和Lecanemab获批上市，虽疗效有限但推动行业信心 。 未来趋势： 加大罕见病研究，如NIH通过《加速获得ALS关键治疗法案》资助Clene Inc.的CNM-Au8疗法，2025年进入扩大准入阶段。 人工智能深度应用，如谷歌Isomorphic Labs利用AI设计药物，首款针对神经退行性疾病的候选分子计划2025年底进入临床。 整合公私合作，如NIH与药企联合开展“阿尔茨海默病预防计划”，探索早期干预策略 。 4. 加拿大 现状： 人口老龄化显著，65岁以上人口占比19%，预计2050年达25%。阿尔茨海默病患者超74万，护理资源紧张。 长期护理体系依赖公共资金，如魁北克省CHSLD机构提供免费医疗服务，但非医疗费用需个人承担，低收入家庭负担沉重。 研究聚焦数据共享，如安大略省ONDRI项目整合5种神经退行性疾病数据，推动早期诊断和个性化治疗 。 未来趋势： 联邦与省协作推进全国痴呆战略，如2019年拨款5000万加元支持社区服务，但各省政策差异大（如安大略省ALS护理资源不足） 。 基因治疗突破，如SickKids医院针对罕见病SPG50的单患者基因疗法显著延缓病情，为超罕见病治疗提供范式 。 技术赋能护理，如紧急呼叫手环、远程医疗等降低居家养老风险，但护工短缺问题亟待解决。 5. 欧盟 现状： 神经退行性疾病患者超1500万，医疗支出占GDP的1.2%，东欧国家资源匮乏（如罗马尼亚每10万人仅1.3名神经科医生） 。 政策协调与数据共享：EPND平台整合60多个队列的12万患者数据，加速生物标志物发现；NEURONET促进18个IMI项目协同，推动药物研发 。 药物审批高效，集中审批程序（CP）覆盖创新药和先进疗法，如基因治疗药物Zolgensma快速获批，但成员国间可及性差异显著（如保加利亚MS药物覆盖率84%，罗马尼亚仅60%）。 未来趋势： 深化跨国合作，如JPND联合24国制定战略研究议程，2025年启动精准医疗项目，探索多组学驱动的治疗方案 。 应对区域差异，通过“健康联盟”计划向东欧国家提供技术援助，扩大移动记忆团队和远程诊断覆盖 。 伦理与监管并重，如EMA建立基因治疗长期随访机制，确保安全性和疗效。 三、全球共同挑战与解决方案 1. 老龄化加剧：2050年全球60岁以上人口将达21亿，神经退行性疾病患者数量预计翻倍。需加强公共卫生干预，如推广健康生活方式（运动、地中海饮食）以降低风险 。 2. 研发瓶颈：传统药物研发周期长、成功率低。AI、基因编辑和再生医学（如iPS细胞）是破局关键，需国际协作共享数据和资源（如EPND、JPND） 。 3. 医疗资源不均：发达国家与发展中国家、城乡之间差距显著。需建立全球卫生援助机制，推广低成本筛查工具（如基于智能手机的认知测试） 。 4. 护理负担沉重：全球超5000万家庭照料者面临心理和经济压力。政策应支持喘息服务、远程护理和社区支持网络。 四、总结 神经退行性疾病是全球老龄化背景下最严峻的公共卫生挑战之一。中国、日本、美国、加拿大和欧盟在疾病负担、研发投入和政策应对上各具特点，但共同趋势是： 技术驱动创新：AI、基因编辑、干细胞疗法重塑治疗格局。 精准医疗兴起：基于生物标志物的早期诊断和个性化治疗成为焦点。 全球协作深化：数据共享、跨国研究和伦理框架构建加速进展。 未来，需整合医学、技术和社会资源，实现从症状管理向疾病修正的跨越，改善患者生活质量并减轻社会负担。