Encoded Therapeutics, Inc.

Venrock has added half a billion dollars to its healthcare investing strategy, the firm confirmed to Endpoints News on Wednesday. It comes on top of its $650 million 10th fund — which goes toward both tech and healthcare — that the firm revealed during the 2024 JPM Healthcare Conference in January. A regulatory document outlining a $500 million fund was filed on Wednesday. “We can confirm this $500M fund is separate from the $650M fund announced in January,” a Venrock spokesperson said in an email to Endpoints. “This is a new pool of capital, though not a new strategy; it will invest in certain investment opportunities alongside existing Venrock Healthcare Capital Partner funds.” The filing lists Venrock investors Bong Koh and Nimish Shah, both of whom are focused on crossover and public investing in biotech and pharma, according to the firm’s website. Koh jokingly refers to himself as “team bag carrier” on his LinkedIn profile: “While their bags are heavy and have odd odors, [it] is a real priviledge [sic] that they trust me to be a good steward of their bags.” Venrock Healthcare has been active recently. Alongside Wellington Management, it led the $215 million Series B for obesity biotech Metsera last week. It’s also an investor in Jade Biosciences, a Paragon Therapeutics spinout that disclosed a reverse merger on Oct. 31. Venrock is also an investor in a preclinical growth factor startup called Cavalry Biosciences , ADC startup MBrace Therapeutics, CNS gene therapy maker Encoded Therapeutics and multiple other startups.

正文共：2386字 1图 预计阅读时间：5分钟 由于患者招募困难，卫材终止了一项三期临床试验。 美东时间2024年11月17日，知名行业媒体《Endpoints News》发文称，卫材终止了旗下Lorcaserin（氯卡色林）用于辅助治疗Dravet综合征的三期MOMENTUM 1研究（NCT04572243）。 根据美国临床试验数据库（ClinicalTrials.gov）查询，目前MOMENTUM 1研究已处于终止状态，并提示该状态并非由于任何安全性或有效性原因导致。 关于Dravet综合征 Dravet综合征（Dravet syndrome ，DS），为婴儿期起病的难治性癫痫综合征，由法国医生Charlotte Dravet在1978年首次报道，既往又称婴儿严重肌阵挛癫痫。 DS是一种罕见的癫痫性脑病，根据国外文献报道DS患病率为1/40000~1/20000（也有文献报道为发病率为1/15700~1/40900）占3岁以内婴幼儿癫痫的8%。2018年，该疾病被列入国家第一批罕见病目录（编号：105号）。 DS发病主要由遗传因素决定，其主要致病基因为钠离子通道α1亚单位基因SCN1A突变，此外如SCN1B、GABRG2等基因也可能与Dravet综合征有关。 目前，DS暂无治愈方法，治疗主要是对症支持治疗，旨在减少癫痫发作的频率和强度。常用药物包括丙戊酸、司替戊醇、芬氟拉明、药用级大麻二酚、托吡酯等。 其中，芬氟拉明作为一种5-HT2C受体激动剂，最早（1973年）被批准用于减肥，1997年因严重心脏毒性而停用。后来其较低剂量被重新启用，治疗一些癫痫性脑病：2020 年，美国和欧盟先后批准芬氟拉明作为DS治疗的添加药物。 相同命运的氯卡色林 此次，卫材终止的氯卡色林与芬氟拉明同为5-羟色胺（5-HT，又称血清素）受体激动剂。 其研发历程也颇为相似。氯卡色林原研为Arena，2012年获FDA批准上市用于减肥治疗，商品名Belviq。后因市场表现一般，Arena于2017年将其权益卖给了卫材。 值得一提的是，基于芬氟拉明的前车之鉴。FDA在批准Belviq时要求生产商开展一项随机、双盲、安慰剂对照的上市后研究，以评估氯卡色林的心血管风险。这项研究有12000例参与者，为期5年，于2018年6月结束。 因此，氯卡色林是完成FDA要求的长期心脏安全研究的第一种新型减肥药物。只不过，FDA在对其安全性数据进行审查时发现，服用氯卡色林的患者被确诊为癌症的人数更多（462， 7.7% vs 423, 7.1%）。 2020年1月，FDA要求Belviq，Belviq XR从美国市场撤市。这对卫材而言，称得上无妄之灾。尽管癌症风险增高的原因还不明确，FDA也无法断定氯卡色林就是直接的致癌原因，但撤市已成定局。 后者激流勇进，前者寸步难行 芬氟拉明在肥胖症失利之后，在癫痫性脑病中“复活”。那么氯卡色林，理应也可走通这条路径。 2020年，卫材在与FDA协商后启动了氯卡色林治疗DS的三期MOMENTUM 1研究。当时目标是在美国招募58名受试者，如今4年过去，卫材还在招募在面临招募困境。 根据《Endpoints News》报道，卫材一位的发言人通过电子邮件表示，“随着其他经FDA批准的疗法可用于治疗这一复杂的疾病（DS），招募患者进行试验性治疗变得极其困难。” 目前，针对DS的治疗涌现了各种新型治疗方式，包括但不限于：Stoke的反义寡核苷酸（ASO），STK-001；Longboard的5-HT2C受体超激动剂Bexicaserin；Encoded的AAV9介导的候选基因调控疗法，ETX101。 其中，Bexicaserin已进入临床三期阶段。它虽然与氯卡色林、芬氟拉明同为5-HT2C受体激动剂，但却显示出对5-HT2C受体的选择性增加。 具体而言，5-HT2受体次家族有A、B、C三种亚型，研究发现，中枢5-羟色胺主要通过作用于脑内5-羟色胺2C受体（5-HT2C）起到调节食欲的作用，这也是其减重的原因。 而5-HT2A与5-HT2B激动，可能导致致幻活性与心脏毒性相关不良反应。芬氟拉明与右芬氟拉明的退市，便与同时激动5-HT2B导致的肺动脉高压和心脏瓣膜异常有关。 至于氯卡色林，今年4月是我国列入第二类精神药品目录。此前（2013年），该药物已被FDA列入《管制物质法案》附表Ⅳ管理。 以目前的科研水平结合当前商业价值，几经波折的氯卡色林，或许不值得继续投入资源。 参考资料： 1.Eisai terminates Phase 3 trial of Dravet drug, citing recruitment challenges（Endpoints News） 2.clinicaltrials.gov 3.Dravet 综合征诊断与治疗的中国专家共识（癫痫杂志） 4.Wirrell E C, Laux L, Donner E, et al. Optimizing the Diagnosis and Management of Dravet Syndrome: Recommendations From a North American Consensus Panel[J]. Pediatric Neurology,2017,68:18-34 5.田小娟，张月华. Dravet综合征治疗和预后研究进展[J]. 中国实用儿科杂志,2017(10):789-793 6.新列管药“氯卡色林”的由来（中国禁毒报） 7.其他公开资料 封面图来源：pixabay 主管说没有预算，这个局怎么破？这里可以24小时免费观看FDA、EMA培训录像，自己不断成长，还不麻烦公司！~ 2024-11-17 第四届佛山创新药论坛圆满落幕，行业领袖共绘“BD出海与投融资”新未来 2024-11-16 FDA要变天！特朗普正式提名罗伯特·肯尼迪领导卫生与公众服务部 2024-11-15 版权声明/免责声明 本文为原创文章。 本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。 文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。 如有任何问题，请与我们联系。 衷心感谢! 药时代官方网站:www.drugtimes.cn 联系方式: 电话:13651980212 微信:27674131 邮箱:contact@drugtimes.cn 点击查看更多精彩！

ORLANDO, Fla.--( BUSINESS WIRE )--Encoded Therapeutics Inc., a clinical-stage biotechnology company developing genetic medicines for severe central nervous system (CNS) disorders, announced today that it will present new preclinical data on ETX201, an AAV9-based vectorized miRNA approach designed to reduce the expression of the UBE3A-ATS and unsilence paternal UBE3A expression for the treatment of Angelman syndrome. At the Foundation for Angelman Syndrome Therapeutics (FAST) 17 th Annual Global Science Summit in Orlando, FL, Encoded will present data showing that ETX201 was well tolerated in non-human primates (NHPs) with broad expression across multiple brain regions following a single intracerebroventricular administration. ETX201 miRNA transcript was also detectable in the cerebrospinal fluid. Knockdown of the UBE3A antisense transcript (UBE3A-ATS) was observed, in addition to widespread paternal UBE3A upregulation across the cortex and hippocampus -- critical, disease-relevant brain regions important for learning, memory, and cognitive functioning. “ Our approach restores expression of the UBE3A gene by unsilencing the paternal allele and represents an important step towards addressing the underlying cause of Angelman syndrome with a potentially durable, one-time therapy,” said Stephanie Tagliatela, co-founder and Chief Scientific Officer of Encoded. “ These data validate our vectorized miRNA technology and provide strong rationale for exploring its application for common CNS diseases.” FAST Global Science Summit Presentation Details: Title: ETX201: An experimental vectorized miRNA-based approach for the treatment of Angelman syndrome Presenter: Sirika Pillay, Ph.D., Director of Molecular and Cellular Pharmacology, Encoded Therapeutics Date & Time: Saturday, November 9, at 9:50-10:10 a.m. ET About Angelman Syndrome Angelman syndrome is a severe and lifelong neurodevelopmental disorder that is estimated to affect approximately 1 in 12,000 to 1 in 20,000 people globally. It is caused by loss of function in the maternally inherited copy of the UBE3A gene, which plays a critical role in the development and function of the nervous system. As a result of this deficiency, individuals with Angelman syndrome experience a range of challenges, including cognitive impairment, developmental delays, lack of speech, movement disorders (such as ataxia and tremors), seizures, as well as sleeping and feeding problems. While affected individuals typically have a normal lifespan, they are unable to live independently; they require substantial support throughout their lives, relying on caregivers and family for assistance with daily activities. Despite its significant impact, there are currently no approved therapies specifically designed to treat Angelman syndrome. About ETX201 ETX201 is a vectorized microRNA (miRNA) designed to unsilence the paternal copy of UBE3A , which is naturally silenced in neurons by the UBE3A antisense transcript (UBE3A-ATS). ETX201 expresses a miRNA that targets the UBE3A-ATS to knock down its expression and is delivered using a clinically-validated adeno-associated virus serotype 9 (AAV9) vector. This potential one-time treatment approach aims to consistently and durably restore UBE3A expression and address the spectrum of symptoms associated with Angelman syndrome by targeting the underlying cause of the disease. About Encoded Therapeutics Encoded Therapeutics is a clinical-stage genetic medicines company developing potentially disease-modifying therapies to improve the lives of people with severe CNS disorders. Our proprietary vector engineering approach combines novel regulatory elements and payloads with AAV vectors to unlock innovative solutions for debilitating, intractable CNS conditions. At the forefront is our flagship clinical program, ETX101 for Dravet syndrome, which targets the underlying cause of the disorder to enable highly selective upregulation of SCN1A for potentially long-lasting benefit. In parallel, we are advancing a pipeline of potentially best-in-class programs to address significant unmet needs across both rare and common CNS conditions. Harnessing our proprietary technology platform and expertise, we can efficiently advance programs from discovery through clinical development. Encoded is committed to pioneering breakthrough treatments for CNS disorders. For more information, please visit www.encoded.com .