CRISPR Therapeutics AG

▎Armstrong 从2017年首款CAR-T疗法获批以来，FDA累计已经批准6款CAR-T疗法，分别是诺华的Kymriah、传奇/强生的Carvykti、吉利德的Yescarta和Tecartus、百时美施贵宝的Breyanzi和Abecma。2024年上半年，6款CAR-T疗法合计销售额20亿美元，预计全年将超过40亿美元。 CAR-T疗法在血液瘤取得了里程碑般的临床突破，但复杂的个体化制备过程和高额的制备成本，严重限制了CAR-T疗法的普及，在支付天花板较低的国内市场就更是如此。在这种背景下，通用型CAR-T替代自体CAR-T的系统性优势就尤为明显，可以批量化制备，成本更低且患者无需等待。 然而尽管优势明显潜力巨大，通用型CAR-T疗法的道路却充满挫折，这其中宿主抗移植物反应 （HvGR）是亟待解决的痛点，它会导致通用型CAR-T缓解持久度差的问题。具体而言，通用型CAR-T由于采用了异体来源的T细胞，给药治疗后会引起患者的T细胞、NK细胞攻击异体的CAR-T细胞，导致通用型CAR-T被排异，从而影响疗效。 多家生物技术公司通过结合多种不同策略来尝试攻克HvGR，目前仍在探索中。大多公司的uCAR T品种选择先从CD19这个靶点开始，可能是因为外周血B细胞表达CD19，有利于促进扩增。 截至目前，全球范围内有多家Biotech聚焦开发通用型CAR-T疗法。 附表 全球范围内布局通用型CAR-T疗法的代表企业 Caribou Biosciences通过逐步优化，目前主要形成了5种编辑策略，包括敲除TCR、B2M、PD-1，B2M基因中特异性插入B2M-HLA-E肽融合基因，削弱T细胞和NK细胞的识别和排斥。 尽管采用更大剂量的清淋预处理方案（环磷酰胺【60毫克/千克/天，连续2天】和氟达拉滨【25毫克/平方米/天，连续5天】），Caribou Biosciences的首发管线CB-010在B-NHL上取得了94%的ORR和69%的CR，但是仍有多例患者在6个月之内复发，表明该通用型CAR-T的缓解持久性仍然需要更好的解决。 Sana Biotechnology也是通用型CAR-T领域的主要玩家，首发管线SC291处于1期临床阶段。 SC291的初步临床数据来看，4例可评估患者2例达到CR，1例达到PR，1例SD，但其中PR和SD的患者均很快出现复发和/或疾病进展。另外，因为观察时间太短，疗效持续时间尚不得而知。另外，还有也没有看到其uCAR T的扩增数据，不知是否可以有效抵抗宿主免疫细胞的排异。 还有CRISPR Therapeutics的通用型CD19 CAR-T，其通用型的CTX110的数据来看，整体CR率较低，DoR应该也不如自体CAR-T。 从早期的扩增数据来看，CAR拷贝数的峰值相对自体CAR-T也较低。 Poseida的通用型BCMA CAR-T敲除了B2M、TCR，目前处于1b期临床阶段。 P-BCMA-ALLO1的CR相比于同类竞品仍然比较低，且mDoR只有不到8个月（232天），而自体的Abecma和Carvykti分别为11.0个月和21.8个月。 此外，Allogene的通用型BCMA CAR-T疗法ALLO-715也表现出类似的特点，在3.2X108剂量组中，24个患者的CAR-T中位峰值只有6419拷贝/ug gDNA，扩增远低于自体CAR-T，mDoR为8.3个月，与Poseida类似，但均远低于自体CAR-T。 可以看到，各家Biotech的通用型CAR-T往往表现出疗效较弱、持久性差、容易复的问题。虽然采用了一系列避免HvGR的策略，整体上看持久性仍然是一个巨大的挑战。 国内biotech也在通用型CAR-T领域不断耕耘和探索，比如，近期邦耀生物在Cell期刊发表了通用型CAR-T治疗自免疾病的IIT临床数据，治疗3例硬皮病(一种自身免疫性疾病）患者，并取得初步疗效。科济药业也将在今年ASH会议上披露其通用型CAR-T候选产品CT0590的初步临床数据，意味着可能在通用型CAR-T技术上已经取得了一些进展。根据公开信息，科济药业的THANK-uCAR为一种差异化的通用型CAR-T技术。常规通用型CAR-T会普遍敲除B2M，以克服宿主T细胞对通用型CAR-T的HvGR，但B2M的敲除会引起宿主NK细胞对通用型CAR-T的HvGR，THANK-uCAR技术，采用同时表达NKG2A CAR的方式杀伤激活的NK细胞，从而减少NK细胞对通用型CAR T的杀伤。 总结 CAR-T作为活的药物，是一种革命性的疗法，可能一针可以治愈疾病，不仅可用于肿瘤，还可望用于自身免疫性疾病等，但因自体CAR-T高昂生产成本等挑战，限制了其广泛应用。通用型CAR-T的技术突破将让这些问题迎刃而解，惠及广大患者。针对通用型CAR-T的关键挑战---HvGR，科济药业发展了THANK-uCAR技术，利用NKG2A CAR与B2M敲除的组合，同时减免宿主T细胞和NK细胞对uCAR T细胞的杀伤，进而促使uCAR T的扩增，其临床疗效值得期待。 Armstrong技术全梳理系列 GPRC5D靶点全梳理； CD40靶点全梳理； CD47靶点全梳理； 补体靶向药物技术全梳理； 补体药物：眼科治疗的重要方向； Claudin 6靶点全梳理； Claudin 18.2靶点全梳理； 靶点冷暖，行业自知； 中国大分子新药研发格局； 被炮轰的“me too”； 佐剂百年史； 胰岛素百年传奇； CUSBEA：风雨四十载； 中国新药研发的焦虑； 中国生物医药企业的研发竞争； 中国双抗竞争格局； 中国ADC竞争格局； 中国双抗技术全梳理； 中国ADC技术全梳理； Ambrx技术全梳理； Vir Biotech技术全梳理； Immune-Onc技术全梳理； 亘喜生物技术全梳理； 康哲药业技术全梳理； 科济药业技术全梳理； 恺佧生物技术全梳理； 同宜医药技术全梳理； 百奥赛图技术全梳理； 腾盛博药技术全梳理； 创胜集团技术全梳理； 永泰生物技术全梳理； 中国抗体技术全梳理； 德琪医药技术全梳理； 德琪医药技术全梳理2.0； 和铂医药技术全梳理； 荣昌生物技术全梳理； 再鼎医药技术全梳理； 药明生物技术全梳理； 恒瑞医药技术全梳理； 豪森药业技术全梳理； 正大天晴技术全梳理； 吉凯基因技术全梳理； 基石药业技术全梳理； 百济神州技术全梳理； 百济神州技术全梳理第2版； 信达生物技术全梳理； 信达生物技术全梳理第2版； 中山康方技术全梳理； 复宏汉霖技术全梳理； 先声药业技术全梳理； 君实生物技术全梳理； 嘉和生物技术全梳理； 志道生物技术全梳理； 道尔生物技术全梳理； 尚健生物技术全梳理； 康宁杰瑞技术全梳理； 科望医药技术全梳理； 科望医药技术全梳理2.0； 岸迈生物技术全梳理； 礼进生物技术全梳理； 康桥资本技术全梳理； 余国良的抗体药布局； 荃信生物技术全梳理； 安源医药技术全梳理； 三生国健技术全梳理； 仁会生物技术全梳理； 乐普生物技术全梳理； 同润生物技术全梳理； 宜明昂科技术全梳理； 派格生物技术全梳理； 迈威生物技术全梳理； Momenta技术全梳理； NGM技术全梳理； 普米斯生物技术全梳理； 普米斯生物技术全梳理2.0； 三叶草生物技术全梳理； 贝达药业抗体药全梳理； 泽璟制药抗体药全梳理； 恒瑞医药抗体药全梳理； 齐鲁制药抗体药全梳理； 石药集团抗体药全梳理； 豪森药业抗体药全梳理； 华海药业抗体药全梳理； 科伦药业抗体药全梳理； 百奥泰技术全梳理； 凡恩世技术全梳理。

Wholly owned first-in-class program anticipated to enter clinical trials in first half of 2025 THOUSAND OAKS, Calif., Oct. 30, 2024 /PRNewswire/ -- Capsida Biotherapeutics ("Capsida") today announced the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to Capsida for CAP-002. CAP-002 is the company's lead investigational gene therapy for the treatment of developmental and epileptic encephalopathy (DEE) due to syntaxin-binding protein 1 (STXBP1) mutations. CAP-002 is a novel, first-in-class IV-administered gene therapy using one of Capsida's proprietary engineered capsids designed to achieve brain-wide neuronal expression of the STXBP1 protein while significantly detargeting the liver. CAP-002 is currently in IND-enabling studies. "FDA's granting Orphan Drug Designation signals the significant potential that CAP-002 demonstrates based upon our preclinical data," said Peter Anastasiou, Chief Executive Officer of Capsida Biotherapeutics. "There are no disease-modifying therapies available for STXBP1 developmental and epileptic encephalopathy and CAP-002 could be the first, bringing hope for patients and families affected by this devastating disorder." The STXBP1 protein is present in every neuron in the brain and is essential for normal neurotransmission. A mutation in the STXBP1 gene is associated with treatment-resistant seizures, severe developmental delay and intellectual disability, motor abnormalities, and sudden unexpected death in epilepsy (SUDEP). Preclinical pharmacology studies have established the potential to treat and even fully correct the disease through gene supplementation. These studies demonstrated rescue of these neurological phenotypes was dependent on supplementation of STXBP1 in neurons throughout the brain at levels not achievable by wild-type serotypes, such as AAV9. Capsida conducted these studies with a proprietary murine disease model in collaboration with Mingshan Xue, Ph.D., associate professor of neuroscience and molecular and human genetics at Baylor College of Medicine, as well as a member of the Cain Foundation Laboratories and the Duncan Neurological Research Institute at Texas Children's Hospital. "Receiving Orphan Drug Designation moves us one step closer to our goal of transforming the lives of people living with STXBP1 developmental and epileptic encephalopathy," said Swati Tole, M.D., Chief Medical Officer at Capsida. "We are committed to advancing CAP-002, with our IND filing in the first half of 2025, and bringing novel gene therapies to people with high unmet medical needs." The FDA's Orphan Drug Designation is intended to encourage the development of treatments for rare diseases, defined as those affecting fewer than 200,000 people in the United States. Orphan Drug Designation may shorten the clinical development path through closer FDA collaboration and potential qualification for expedited development programs. This designation also provides the company with certain benefits, including tax credits for qualified clinical trials, exemption from user fees, and potential seven-year market exclusivity upon FDA approval. About STXBP1 Developmental and Epileptic Encephalopathy Developmental and epileptic encephalopathy caused by STXBP1 mutations is estimated to affect up to one in 26,000 children globally. It is associated with treatment resistant seizures, severe developmental delay and intellectual disability, motor abnormalities, and sudden unexpected death in epilepsy (SUDEP). There are no approved treatments. About Capsida Biotherapeutics Capsida Biotherapeutics is a fully integrated gene therapy company with a central nervous system (CNS) pipeline consisting of disease modifying and potentially curative treatments for rare and more common diseases across all ages. Capsida's intravenously (IV) administered gene therapies utilize proprietary engineered capsids that enable high transduction levels to desired tissues and cells, while limiting tropism to non-target organs, such as the liver. Capsida has three wholly owned programs, including a potential -first-in-class treatment for STXBP1 developmental and epileptic encephalopathy and a best-in-class treatment Parkinson's disease associated with GBA mutations, both of which are in IND-enabling studies and on track to enter the clinic in the first half of 2025. In addition to its wholly owned programs, the Company has validating CNS partnerships with AbbVie, Lilly, CRISPR Therapeutics, and the AbbVie partnership was expanded to include ophthalmology disorders. Capsida was founded in 2019 by lead investors Versant Ventures and Westlake Village BioPartners and originated from groundbreaking research in the laboratory of Viviana Gradinaru, Ph.D., a neuroscience professor at Caltech. Visit us at . SOURCE Capsida Biotherapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Pfizer, Sanofi and others report Q3 beats; AbbVie, Roche and Novartis strike big deals; the 2024 presidential election looms; and BioSpace takes a look back at 10 years of NextGen, our annual pick of young biotechs to watch. > Listen on Spotify > Listen on Apple Podcasts > Listen on Amazon Music > Listen on iHeart Earnings heat up as Pfizer got a much-needed Q3 beat amidst criticism from activist investor Starboard Value. Novartis and Sanofi are among others that have outpaced Wall Street expectations this quarter, as Eli Lilly, Merck, AbbVie, Amgen, Biogen, GSK, Bristol Myers Squibb and Takeda are all reporting today and tomorrow. The past week has also seen a pack of deals, with AbbVie ’s $1.4 billion buy of Aliada Therapeutics, Roche ’s potential $1 billion deal with Dyno Therapeutics and Novartis ’ up to $2.1 billion commitment to Monte Rosa’s molecular glue degraders. With less than a week until Election Day, we unpack what biopharma might expect under a Trump or Harris administration. We also take a look back at 10 years of BioSpace ’s NextGen list of top up-and-coming startups. A lot have been bought out by bigger companies—some for big money—while some, such as CRISPR Therapeutics, continue to operate independently. Finally, we took a close look at questions stemming from Sarepta ’s new data for Duchenne muscular dystrophy gene therapy Elevidys, and separately but not unrelatedly, at the FDA’s accelerated approval pathway.