Benfotiamine

“源头创新+科学家IP+炙手可热的阿尔茨海默（AD）领域”怎么也是一个至少早期融资亿元的组合。然而，2008年就开始做研发，标榜全球独一无二的AD诊断和新药研发体系的日馨医药，怎么就凉了呢？“8月份跟我‘打保票’的合作，还没走完合同，这个人年底就离职了”一位曾准备与日馨医药有一笔合作的业内人士对E药经理人表示。日前，有媒体实地探访了日馨医药上海研发中心，发现早已“人去楼空”，现场一位工作人员表示，公司全面停运的状态已经持续了好几个月。与此同时，天眼查也显示，日馨医药曾因未按时履行法律义务而被法院强制执行的记录有88条，并且该公司被法院列为限制高消费企业，该公司的法人戴卫东已被列入失信名单。曾经高喊“源头创新”的“阳面”与如今人走茶凉的“背面”形成了鲜明对比。日馨医药曾一度标榜公司致力于阿尔茨海默病新药的“源头创新”，主要产品脱胎于创始人钟春玖团队公开发表的研究成果，在2022年3月就获批了临床III期。标榜源头创新却未曾有过专业医药界投资者进驻，源头创新产品也从未被浪潮推向台前，更脱离现实的是，这样一家Biotech的法人与管理者都不具备医药产业背景，种种疑问或许就是如今日馨医药人走茶凉的问题底牌。一场关于“源头创新”的祛魅曾经有多辉煌，现在就有多迷茫。据悉，日馨医药创立于2008年，标榜“源头创新”，其联合创始人、首席科学家钟春玖曾在多次公开演讲中表示公司依托于“脑能量（葡萄糖）代谢障碍”假说，创建了全球独有的、具有完全自主知识产权的AD创新药研发体系和临床前评价平台、新型诊断研究体系。同时也是他的团队在2000年左右就首先发现了这一假说，并在之后发现TDP/TPK是阿尔茨海默病关键病理损害因子和可干预靶标。钟春玖曾在接受媒体采访时表示，AD危险因子通过诱发疾病的关键致病基因——硫胺素焦磷酸激酶（TPK）表达抑制，引起二磷酸硫胺素减少，导致脑葡萄糖代谢障碍、Aβ沉积、神经纤维缠结、神经炎症和脑萎缩等，从而导致疾病的发生发展。TPK表达缺陷小鼠模型是AD研究史上唯一一个能全面反映人类AD疾病所有重要病理生理特征的动物模型。根据目前最新的公开信息，日馨医药依托于这一假说有5个候选新药进入IND的不同阶段，其中RX01针对轻、中度阿尔茨海默病患者，已经完成中国I/II期临床研究，证明安全有效，此外还有RX08、RX04、RX07和RX16开展了临床前研究，皆是针对阿尔茨海默病。同时，该公司还在研发用于早期和精准诊断的试剂盒。钟春玖曾对媒体透露，截至2021年，日馨医药的研发投入已经超过2亿元，预计未来III期试验仍将花费1.5亿美元左右。不过有意思的是，在国家药品审评中心CDE网站上所公式的登记号为CXHB2200004的苯磷硫胺片，申请人是上海日馨医药科技股份有限公司，治疗中度阿尔茨海默病，而注册分类却为2.4类（含有已知活性成份的新适应证的制剂）。从管理层来看，天眼查数据显示，日馨医药的三位大股东（持股超过5%）分别是上述科学家创始人钟春玖，持股33.45%；董事长、法人戴卫东，持股19.33%；以及董事叶小忠，持股11.2%。除了钟春玖是复旦大学附属中山医院官网公示的神经内科主任医师，教授，博士生导师，戴卫东和叶小忠都来自上海国民实业集团，而这一集团的投资范围包括家具、物业、汽车、新能源，与制药关联微弱。值得注意的是，在2016年之后，戴卫东才正式成为日馨医药的法人，在此之前，日馨医药还发生过两次法人变更，分别是2009年由叶小忠变更为钟珍，2011年，由钟珍变更为钟春玖，2016年再次变更为戴卫东。而钟春玖不仅担任日馨医药的首席科学家，还同时在复旦大学附属中山医院担任神经内科主任医师、教授、博士生导师。2021年，日馨医药还曾提交IPO辅导申请，想要在科创板上市，不过最终仅仅止步于辅导备案阶段。还有消息称，日馨医药的投资人在2022年6月就已经撤资。这两个时间点其实颇为“微妙”，2021年正是渤健的颠覆性AD新药Aduhelm获的FDA批准，而该药物获批后屡经波折，适应证被FDA由“用于所有阿尔兹海默症患者”修改为用于轻症患者。2022年，支撑“β淀粉样蛋白假说”的学术论文又被质疑存在学术不端行为。AD领域的种种争议或许间接加剧了日馨医药在资本市场上举步维艰的境况。现如今，打开日馨医药的官网www.raising-pharma.com，会被提示“没有找到站点”，显然从技术端来看，已经停止运营。科学家创业的“危险”不过，令人生疑的是，在AD新药研发上取得巨大成功的礼来、诺和诺德都曾受到资本追捧，礼来的市值已经位列纯制药企业第一，诺和诺德市值也超过了体量是其数倍的强生，为何偏偏日馨医药在资本层面碰壁？其实从日馨医药的管理结构上就不难回答。一般意义上，有产业经验的资本+科学家+职业经理人被认为是科学家创业的最优组合，资本对于产业风向的判断和职业经理人的企业管理运营经验恰恰是帮助科学家进行创新成果转化成产品的关键因素，同时这两者也能够弥补科学家所不具备的产品市场化能力和企业管理能力。从这一角度来看，日馨医药遇“滑铁卢”的主因之一或许正是关键因素“三缺二”，仅有钟春玖提出的源头创新理论作为支撑，后续无论是资本方还是运营者都缺乏医药行业的相关经验。美国一项公开调查显示，美国由高校教授创业并领导的公司失败率高达96%-97%，成功率相当于天使投资成功率。西湖大学校长施一公也曾调侃：“压死骆驼的最后一根稻草，是鼓励科学家创业。”当然，科学家创业也不乏成功的范例。百济神州就是 “科学家+职业经理人+全程支持的产业投资人”相辅相成的典型。其创始人之一王晓东就是一位优秀的科学家，32岁建立自己的实验室，发现了细胞程序性死亡的凋亡通路，41岁当选美国院士，2003年归国创立北京生命科学研究所。另一位创始人欧雷强则是专业的职业经理人，不仅曾担任多家制药企业高管，还创立了保诺科技，期间积累了丰富的产业内管理经验、资源和人脉，成为他后来与王晓东携手打造百济神州的基础，再加上之后全程投资百济神州的高瓴资本，投资人的坚持不懈、职业经理人的丰富经验、科学家的创新能力对于今天成为中国“创新一哥”的百济神州来说缺一不可。而新冠疫情期间炙手可热的mRNA新冠疫苗明星公司Moderna更是诠释了科学家如何“科学地创业”。创立Moderna的想法其实来自于创始人之一干细胞科学家Derrick Rossi，但是由于技术商业化能力不足，所以通过另一位兼具科学和产业经验的科学家Robert Langer找到了著名生物医疗风投机构以及初创企业孵化器 Flagship Pioneering的创始人兼CEO Noubar Afeyan，最终打造出了受世界瞩目的Moderna。可见，成功的科学家创业并非天方夜谭，失败的“矛头”也不在于科学家本身。正如创业圈著名的木桶理论，好技术固然重要，但技术、市场、产品、财务、管理缺一不可。另一方面，一位投资人曾告诉E药经理人，科学家的研究成果向产品转化中较难的地方就是思维的转变。研究思维和商业思维是完全不一样的思维方式，管理实验室和管理企业也完全不同。具体到流程上，从实验室产品到能批量生产还有巨大的鸿沟，到了商业化对于创始人又是一道巨大的坎，一方面是商业化意识的不足，一方面是商业化能力的不足。“越早期的公司存在的问题越多，所有事情都需要从零做起，包括股权架构、运营管理、财务法务等等。”一位业内投资人对E药经理人表示，“这就需要有经验的投资机构去做投后服务，来帮助企业进入到正常运行状态。”不过也可以看到，越来越多的兼具科学家与职业经理人的源头创新公司正在吸引国内的投资者们的注意。例如目前为止国内一级市场A轮融资最高的公司炎明生物，今年7月完成了7亿元A轮融资，由国投创业领投、国风投基金联合领投，太平医疗健康基金、国寿科创基金、荷塘创投基金跟投。创始人邵峰兼具中国科学院院士、北生所科研副所长等多个头衔，另一位创始人邓天敬曾担任保诺科技CEO，炎明生物的产品也脱胎于邵峰团队“Gasdermin D（GSDMD）是细胞焦亡的执行者”这一研究成果。再比如上半年获得超亿元Pre-A+轮融资的神曦生物，创始人兼首席科学顾问陈功是国际著名的再生医学专家，是国际上最早在成年哺乳类动物上运用大脑内源性星形胶质细胞原位直接转分化为功能性神经元的先驱者之一。董事长尹旭东曾是诺华集团中国总裁，高管团队也都来自诺华、辉瑞、AZ等MNC。回到日馨医药，或许更容易理解它如今的境况，明显缺少医药行业经验的管理者，与饱受争议的AD“源头创新”领域，双双踩到了如今资本寒冬环境下捂紧钱袋子的投资人们的雷点，融资环境好还有“投机者”买单，市场下行周期或许只能在“被筛掉的项目”中。参考资料：https://baijiahao.baidu.com/s?id=1775905979976165375&wfr=spider&for=pchttps://mp.weixin.qq.com/s/qkpN1WPklVy5SCnXcoiU9Ahttps://mp.weixin.qq.com/s/aZIy31oHvzERjOMiW6sfUg登记邮箱信息订阅E药经理人信息服务扫描二维码精彩推荐CM10 | 集采 | 国谈 | 医保动态 | 药审 | 人才 | 薪资 | 榜单 | CAR-T | PD-1 | mRNA | 单抗 | 商业化 | 国际化 ｜ 猎药人系列专题启思会 | 声音·责任 | 创百汇 | E药经理人理事会 | 微解药直播 | 大国新药 | 营销硬观点 | 投资人去哪儿 | 分析师看赛道 | 药事每周谈 | 医药界·E药经理人 | 中国医药手册创新100强榜单 | 恒瑞 | 中国生物制药 | 百济 | 石药 | 信达 | 君实 | 复宏汉霖 ｜翰森 | 康方生物 | 上海医药 | 和黄医药 | 东阳光药 |  荣昌 | 亚盛医药 | 齐鲁制药 | 康宁杰瑞 | 贝达药业 | 微芯生物 | 复星医药 ｜再鼎医药跨国药企50强榜单 | 辉瑞 | 艾伯维 | 诺华 | 强生 | 罗氏 | BMS | 默克 | 赛诺菲 | AZ | GSK | 武田 | 吉利德科学 | 礼来 | 安进 | 诺和诺德 | 拜耳 | 莫德纳 | BI | 晖致 | 再生元

July 7, 2022 13:10 UTC WHITE PLAINS, N.Y.--(BUSINESS WIRE)-- The Burke Neurological Institute (BNI) has received a five year award expected to total $45 million from the National Institutes of Health (NIH) to launch a large-scale, multi-center clinical trial to evaluate benfotiamine, a synthetic precursor of thiamine (vitamin B1), as a potentially effective therapy for mild Alzheimer’s disease (AD) or mild cognitive impairment (MCI). This follow-up trial will expand on previous work completed at BNI, suggesting that high levels of benfotiamine significantly slowed the rate of functional decline in participants with mild cognitive impairment or early AD. This press release features multimedia. View the full release here: Gary Gibson, Ph.D, Burke Neurological Institute; Weill Cornell Medicine (Photo: Business Wire) “It is gratifying to see research which the Alzheimer’s Drug Discovery Foundation initially identified as promising and supported in a pilot study continue to be pushed forward with funding from the NIH’s National Institute on Aging,” said Dr. Howard Fillit, Co-Founder and Chief Science Officer of the Alzheimer’s Drug Discovery Foundation (ADDF). “With the improved biomarkers that have been developed since the pilot, this next phase will provide a deeper understanding of how benfotiamine works in the brain. Novel approaches that target the many biological factors which contribute to Alzheimer’s, like metabolic dysfunction, are essential to finding effective treatments for this disease.” Dysfunction in the brain’s ability to metabolize glucose is a known marker of AD and other dementias and can begin decades before a person has clinical symptoms or memory loss. Previous work by Burke Neurological Institute/Weill Cornell Medicine researcher Dr. Gary E. Gibson, who will also be a leader of the upcoming clinical trial, suggested that reduction in glucose metabolism is due to a decline in thiamine-dependent processes. Using multiple experimental models, he and others have shown that increasing thiamine to very high levels via benfotiamine was protective against Alzheimer’s-like symptoms. Dr. Gibson noted, “I am particularly excited about this trial because it will determine how relevant these decades of research are to the treatment of Alzheimer’s disease. If our hypothesis is correct, we will advance an exciting investigative clinical treatment pathway relevant for millions of patients, and with potential advantages in safety and value.” These foundational experiments led to a recent pilot study, published in the Journal of Alzheimer’s Disease in 2020 and carried out by Dr. Gibson along with research partners at Weill Cornell Medicine, Burke Rehabilitation Institute, and Columbia University Irving Medical Center. The study suggested a slowed rate of cognitive decline in 35 participants with mild MCI or early AD who took 300-mg benfotiamine pills twice daily, and the treatment was completely safe. The larger upcoming clinical trial will be carried out in collaboration with leading researchers in AD and related dementias; Dr. Howard Feldman, director of the Alzheimer’s Disease Cooperative Study (ADCS) at the University of California, San Diego and Dr. Jose Luchsinger, investigator at Columbia University Irving Medical Center. “We are excited to receive this funding which will enable the further testing of benfotiamine through to its clinical proof of concept, including adaptively testing for the optimal dose and treatment response across clinical and biomarker measures,” said Dr Feldman. Dr. Luchsinger stated “I have been conducting research to understand the metabolic contributions to AD for 20 years and believes that understanding the role of thiamine in AD is an important step in this field.” Enrolling roughly 400 patients in up to 50 US-based clinical trial sites, with study coordination by the ADCS, will support the new study to be among the first to select patients and follow progression over 18 months, using several measures, including cognitive tests and blood markers that signal AD and MCI status and progression. The trial will provide a larger and more robust evaluation of benfotiamine’s potential use in treating AD by following cognitive measures as well as a number of blood markers that reflect the brain’s glucose use, neuron loss, inflammation, and even aspects of brain pathology. These promising blood markers to track AD progression have themselves been under investigation for many years and represent the cumulative work of researchers across the globe. Additional academic institutions partnering with BNI to support this trial include the University of Gothenberg (Gothenberg, Sweden), the University of Cambridge (Cambridge, United Kingdom) and Georgetown University (Washington, DC). BNI is also pleased to collaborate with C2N Diagnostics (St. Louis, MO), a company focused on advanced brain health diagnostics. There is enormous unmet need regarding both treatment and prevention of AD in the growing and aging population. More than six million Americans are living with AD, which is forecasted to rise to nearly 13 million by 2050. Globally, the prevalence of AD is projected to rise from 57 million to 153 million in 2050. There is no true cure for the disease and no effective treatments exist. Clinical trials over the last decade have frequently failed, and the most recently approved therapy has been met with controversy regarding efficacy, safety, value and pricing. Treatments for AD and MCI that are effective, safe, and affordable are critically needed across the globe. Enrollment of trial participants is expected to begin in the first quarter of 2023. The Phase II randomized controlled trial of benfotiamine in early Alzheimer's Disease is funded by NIH grant R01AG076634. The content of this press release is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. About Alzheimer’s Disease Cooperative Study: The Alzheimer’s Disease Cooperative Study (ADCS) is an academic research organization located at UC San Diego which is dedicated to developing treatments for those at risk or affected by Alzheimer’s disease. For upwards of 30 years, with funding including the National Institute on Aging, it has been a field leader in progressing potential new treatments through innovation in clinical trials with design, methods, and analytics. It has a trials coordinating center in San Diego and a network of participating sites across the United States. About Alzheimer’s Drug Discovery Foundation Founded in 1998 by Leonard A. and Ronald S. Lauder, the Alzheimer's Drug Discovery Foundation (ADDF) is dedicated to rapidly accelerating the discovery of drugs to prevent, treat and cure Alzheimer's disease. The ADDF is the only public charity solely focused on funding the development of drugs for Alzheimer's, employing a venture philanthropy model to support research in academia and the biotech industry. Through the generosity of its donors, the ADDF has awarded more than $209 million to fund over 690 Alzheimer's drug discovery programs, biomarker programs and clinical trials in 19 countries. To learn more, please visit: . About Burke Neurological Institute The Burke Neurological Institute is based in White Plains, NY, and was established in 1978 by Dr. Fletcher McDowell as a research institute dedicated to finding cures for chronic neurological disabilities. The Institute transforms groundbreaking research into clinical treatments so that people can see, talk, and walk again. Their goal is to combine the most rigorous, contemporary brain science with heartfelt compassionate care to innovate and develop novel cures for stable disability in those afflicted with neurological conditions such as stroke, traumatic brain injury or spinal cord injury. Burke Neurological Institute is an academic affiliate of Weill Cornell Medicine.