evoncabtagene pazurgedleucel

同写意20岁庆！第五届全球生物医药前沿技术大会报名开启！“意”同创新，穿越周期。7月中旬，苏州金鸡湖畔，让我们与“新药写意人”一起为中国医药创新“同写意”！5月初，阿斯利康宣布完成对法国基因疗法公司Cellectis高达1.4亿美元的增值投资，再次将Cellectis带到了众人眼前。如果用一条曲线来描绘Cellectis的发展之路，走势可以说是陡峭的。Cellectis成立于1999年，最初专注于基因编辑技术的开发。通过引入曾经风光一时的第二代基因编辑技术TALEN，研究通用型CAR-T疗法受到追捧。但没两年，CRISPR技术横空出世，风靡整个生物界。TALEN迅速被CRISPR光芒掩盖，而将TALEN作为核心技术的Cellectis不出意外地没落了，一度濒临破产。不过，作为通用型CAR-T细胞研发的先行者，Cellectis又神奇地翻过了崎岖的山头。2015年，Cellectis一款通用型CAR-T产品成功救治一名患白血病的1岁小女孩，患儿获得了CR且5年未复发，引起极大关注。Cellectis绝处逢生，并在当年成功登录美国纳斯达克。好景不长，这款救起Cellectis的产品后继无力，曾经看好它们的公司也在不同程度上“撤退”。2022年，Cellectis带着UCART20x22重新进入业界视野。当年8月，它宣布FDA已批准一项IND申请，以启动对复发或难治性非霍奇金淋巴瘤患者的临床试验，2023年披露的数据非常亮眼，但也没能拯救日渐低迷的市值。自上市以来，Cellectis市值蒸发超过90%。截至5月10日收盘，其市值为2.20亿美元。从二级市场的反应来看，大家显然对Cellectis技术和产品的未来有些担忧，毕竟数据再好，没有一款上市产品是个不争的事实，且通用CAR-T暴露出来的极大的安全风险问题，以及CRISPR技术的“碾压”，无疑给Cellectis施加了多重压力。在获得阿斯利康投资前，Cellectis手上的现金流已经难以支撑公司继续走下去。1一眼定余生Cellectis的核心技术是转录激活子样效应子核酸酶——TALEN（transcription activator-like effector nuclease），也称为第二代基因编辑技术，在2011年引入自爱荷华州立大学和明尼苏达大学。图源：Cellectis官网TALEN技术诞生于2009年，彼时，在第一代基因编辑技术锌指核酸酶技术（ZFN）的垄断和技术局限性下，科学家们在基因编辑领域已经困扰多年。该技术基于一类从转录激活因子样效应物（TALEs）衍生的蛋白质，这种用于基因编辑的核酸酶结构是一种融合蛋白，一部分来自转录激活物类似的特殊效应器TALE，另一部分是可以与II型限制性内切酶的核酸酶域相融合的部分，可以定位在特异的DNA序列上。TALENs结构示意图TALEN具有的高精度和设计简便性，一出现便迅速霸榜基因编辑领域，直接取代了ZFN，收获一众“粉丝”。2011年，Nature Methods将TALEN技术列为年度技术，Science紧随其后，2012年将之列入年度十大科技突破，针对该文的评论更是给予它基因组的巡航导弹技术的美誉。很快，各大生物公司相继推出自己的TALEN产品。Addgene机构出售单个TALEN质粒，Golden Gate拥有TALEN 2.0试剂盒（来自Dan Voytas实验室），Life Technologies可提供定制TALEN——GeneArt Precision TAL。Cellectis的子公司Cellectis Plant Sciences和Cellectis Bioresearch也分别推出了开发农业用途的TALEN，以及出售定制和预制的酶。Cellectis则致力于将TALEN应用到研发通用型CAR-T产品中。但操作繁琐、实用性受限（没有为可能寻找的所有基因序列创造核酸酶，且可能无法做到）和脱靶等问题阻止着TALEN技术的进一步提高，也限制了其应用和推广。更致命的是，CRISPR出现了。拥有诺贝尔奖加成的CRISPR操作简便、周期短、成本低，目前已成为主流的基因编辑工具。被追捧的永远只有第一名，但Cellectis很专一，依然继续在研究TALEN这把“剪刀”。2“通用”难成药去年底，全球首款CRISPR基因编辑疗法Casgevy获得FDA批准治疗镰状细胞病，再次将CRISPR推上流量顶峰。随着CRISPR基因编辑技术的热度越来越高，属于Cellectis的光环也越来越淡。不过Cellectis执着于TALEN的原因也很简单，他看好这项技术在通用型CAR-T中的前景。2015年，在合作产品UCAR-T19（通用CD19 CAR-T）的临床试验中，1岁小女孩Layla Richards被成功救治，Cellectis因此收获了无数鲜花和掌声，也肯定了自己的努力方向。但短暂的流量过后，Cellectis陷入了长久的沉寂。之后的时间里，这家公司的通用型CAR-T频繁爆出严重的安全事件，3年内经历了2次“死亡危机”。2017年，在Cellectis针对母细胞浆样树突状细胞瘤和急性髓细胞性白血病患者开展的I期临床试验中，一名患者在接受UCRAT123治疗的第8天经历了5级CRS和4级CLS（毛细血管渗漏综合征），并在第9天死亡。第二次的死亡事件发生在2020年，另一款通用型CAR-T（UCAR-TCS1A）的临床试验中。一名多发性骨髓瘤患者接输注UCAR-T CS1A出现CRS，并在治疗25天后死于心脏骤停。通用型CAR-T的安全性问题并不是个例，除了Cellectis之外，Allogene、CRISPR Therapeutics等头部通用型CAR-T企业也经历了不同程度的安全性事件。2022年，来自Celyad Oncology的一款同种异体CAR-T疗法CYAD-101-002的Ib期临床试验收到了两起死亡案例报告，决定自愿暂停临床试验。2021年，一位患者在接受Allogene旗下的同种异体CAR-T候选药物ALLO-501A治疗后，出现1级CRS和2级ICANS两种不良反应，在为评估全血细胞减少症而进行的骨髓活检中检测到了染色体异常，这一现象或许会导致患者发生癌症风险。刚声名鹊起的CRISPR Therapeutics也未能幸免。2020年，一位患者在接受其通用型CAR-T细胞疗法CTX110治疗52天后死亡。当然，也不都是坏消息。2022年底，来自Atara的Ebvallo （tabelecleucel）获EC批准在欧盟上市。作为全球唯一一款UCAR-T疗法，Ebvallo还是带给了业界不少信心。3合作焕发新生？Cellectis如今的股价已经跌到地板，阿斯利康增持之前，现金流也已捉襟见肘。与略显窘迫的现状不同的是，这家法国公司也曾是业界眼中的“香饽饽”。在UCART19成功救治白血病女孩的前一年，施维雅（Servier）和辉瑞就对这家法国生物技术公司抛出橄榄枝，分别用1000万美元、8000万美元的预付款开始了一段相伴之路。辉瑞更在后来收购了Cellectis少部分股份，并在2015年初被传闻考虑收购该公司。值得一提的是，与Cellectis合作开发通用型实体瘤的Allogene，在当时也拥有一部分开发和商业化UCART19的独家权利。不过，UCART19的成果表现有限，施维雅更是于2022年直接退出了该项目。在癌症患者中，CAR-T细胞疗法有严重的副作用，可能导致致命的CRS和神经毒性。但在自身免疫性疾病中，这些似乎是可管理的。去年底，Nature报告了CAR-T治疗自身免疫性疾病取得的突破。根据美国血液学会会议上公布的数据，CAR-T疗法让15名患有自身免疫性疾病的患者重获新生。阿斯利康也许正是看中了Cellectis技术在自身免疫性疾病中的可能性。此番布局CAR-T赛道，从Cellectis角度来说，Baird分析师Jack Allen的评价是“交易的完成是积极的”，因为这至少维持Cellectis运营到2026年。Cellectis也不需要使用自己的资金来开发交易中涉及的药物。早在2023年11月，Cellectis就与阿斯利康达成合作协议，得到后者2.45亿美元投资。当时Cellectis的股票大涨约180%。此次阿斯利康的增资之后，Cellectis一共交出了44%的股份，30%的投票权以及两个董事会席位。目前，Cellectis有三个全资拥有的CAR-T候选项目正在针对血癌进行临床开发，预计2024年将分享每个项目的最新数据。Cellectis的目标是确定针对CD22和CD20xCD22的CAR-T细胞疗法的二期推荐剂量，并分享其CD123资产的双剂量数据。Cellectis CAR-T疗法在研管线，图源：Cellectis官网自免之外，Cellectis也在寻找新的化合机会。2021年，Cellectis和Cytovia Therapeutics两次宣布合作，用于开发TALEN基因编辑的iPSC衍生NK细胞（iNK）和CAR-NK细胞，以最大限度地降低脱靶效应的风险并释放NK细胞的全部潜力，进行细胞治疗。这家法国企业成立的时间不短，但一直在大幅的起落之间穿行，前路依然扑朔迷离，期待他的坚守能够换来成功。参考文献：1、AstraZeneca ups stake in Cellectis in latest cell therapy bet；biopharmadive2、阿斯利康“搭救”通用CAR-T先驱；药渡3、基因编辑III TALENs；万悟Ethereal4、基因组编辑三大利器：TALEN、ZFN和CRISPR/Cas；癌图腾5、Nature报告：“一切都消失了！”CAR-T治疗红斑狼疮、重症肌无力等自身免疫性疾病取得突破性效果更多优质内容，欢迎关注↓↓↓

The emerging pipeline of CAR-T in NHL includes late-stage, mid-stage, and early-stage drugs in different lines of therapies and different indications, mainly including B- cell Lymphoma such as DLBCL, FL, MCL, MZL, CLL/SLL, and others, with one of them being developed for a T-cell Lymphoma, PTCL. LAS VEGAS, April 15, 2024 /PRNewswire/ -- DelveInsight's CAR T-Cell Therapy for Non-Hodgkin's Lymphoma Market Insights report includes a comprehensive understanding of current treatment practices, CAR T-Cell Therapy for NHL emerging drugs, market share of individual therapies, and current and forecasted market size from 2019 to 2032, segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain), and the United Kingdom, and Japan]. Key Takeaways from the CAR T-Cell Therapy for Non-Hodgkin's Lymphoma Market Report According to DelveInsight's analysis, the market size for CAR T-Cell therapy for NHL reached USD 1,200 million in 2023 across the US. DelveInsight's analysis reveals that the total incident cases of selected indications for CAR-T in NHL in the 7MM comprised ~155,200 in 2023. Leading CAR T-Cell therapy for NHL companies such as Allogene Therapeutics, Novartis, Miltenyi Biomedicine, Mustang Bio, CRISPR Therapeutics, 2seventy Bio, Imugene, and others are developing novel CAR T-Cell therapies for NHL drugs that can be available in the CAR T-Cell therapy for NHL market in the coming years. Other promising CAR T-Cell therapies for NHL in the pipeline include Cemacabtagene Ansegedleucel, Rapcabtagene Autoleucel, Zamtocabtagene Autoleucel, MB-106, CTX110, BBT369, Azercabtagene Zapreleucel , and others. BREYANZI is poised to dominate the CAR-T market in NHL in the forthcoming years, with potential approvals anticipated across two indications: CLL/SLL, follicular lymphoma and MCL. Notably, it has already secured approval for DLBCL in 3L+, 2L+ TE, and NTE. Novartis is progressing with its additional CD-19 CAR-T therapy, Rapcabtagene autoleucel, with expectations of a significantly reduced turnaround time for availability compared to KYMRIAH. Companies are leveraging the strength of dual and triple targeting in CAR-T therapies. Miltenyi Biomedicine, ImmPACT Bio, 2seventy bio, and Novartis are developing CD19/20 Bispecific CAR-T, CD79a/CD20 Bispecific CAR-T, and CD2xCD3xCD19 CAR-T, enhancing treatment efficacy by targeting multiple antigens simultaneously. Discover which therapies are expected to grab the major CAR T-Cell therapy for NHL market share @ CAR T-Cell Therapy for NHL Market Report CAR T-Cell Therapy for Non-Hodgkin's Lymphoma Overview CAR-T cell therapy represents a groundbreaking advancement in cancer immunotherapy, especially for specific types of NHL that have shown resistance to traditional therapies. Through the manipulation of genetically modified T cells, this state-of-the-art treatment boosts the immune system's capacity to locate and eliminate cancerous cells. Essentially, CAR-T cell therapy modifies a patient's T cells genetically to carry chimeric antigen receptors (CARs) on their surface. These engineered CARs are tailored to identify and attach to particular proteins found on cancer cells' surfaces, thereby directing the immune system to effectively combat the malignancy. CAR T-Cell Therapy for Non-Hodgkin's Lymphoma Epidemiology Segmentation In 2023, DLBCL had the highest number of cases among all selected indications for CAR-T therapy, followed by Follicular lymphoma. The total incident cases of MZL in the 7MM were around 13,800 in 2023 and are projected to increase during the forecasted period. The CAR T-Cell therapy for NHL market report proffers epidemiological analysis for the study period 2019–2032 in the 7MM segmented into: Total Incident Cases of Selected Indications for CAR-T in NHL (Mantle cell lymphoma, DLBCL, Follicular lymphoma, Marginal Zone Lymphoma, Primary mediastinal large B-cell lymphoma, Chronic lymphocytic leukemia/small-cell lymphocytic lymphoma) and Total Indication-wise Eligible Cases of CAR-T in NHL. CAR T-Cell Therapy for Non-Hodgkin's Lymphoma Treatment Market The treatment landscape for NHL is complex, influenced by factors such as the type of NHL, the stage of the disease, the patient's overall health, and their preferences. CAR-T cell therapy has emerged as a promising option within this landscape, especially for aggressive B-cell NHLs that have not responded to standard treatments. Previously, such cases posed significant challenges, often resulting in poor outlooks despite attempts with salvage chemotherapy and autologous stem cell transplants. However, the introduction of CAR-T cell therapy has drastically changed this scenario, showing impressive response rates and the potential for long-lasting remissions even in patients with advanced disease after multiple prior treatments. The approval of various CAR-T therapies for NHL by the FDA highlights the importance of this advancement. YESCARTA, KYMRIAH, BREYANZI, and TECARTUS have all proven effective across different types of NHL, including DLBCL, follicular lymphoma, and mantle cell lymphoma. Ongoing research aims to improve CAR-T cell therapy for NHL further, seeking to increase effectiveness, decrease side effects, and expand the range of target antigens beyond CD19. Additionally, studies are looking into the combined use of CAR-T cell therapy with other treatments like checkpoint inhibitors or targeted therapies, with the ultimate goal of optimizing treatment outcomes for NHL patients. To know more about CAR T-Cell therapy for Non-Hodgkin's Lymphoma treatment guidelines, visit @ CAR T-Cell Therapy for Non-Hodgkin's Lymphoma Management Emerging CAR T-Cell Therapies for NHL and Key Companies Cemacabtagene Ansegedleucel: Allogene Therapeutics Rapcabtagene Autoleucel: Novartis Zamtocabtagene Autoleucel: Miltenyi Biomedicine MB-106: Mustang Bio CTX110: CRISPR Therapeutics BBT369: 2seventy Bio Azercabtagene Zapreleucel: Imugene Learn more about the FDA-approved CAR T-Cell therapy for NHL @ Drugs for CAR T-Cell Therapy for NHL Treatment CAR T-Cell Therapy for Non-Hodgkin's Lymphoma Market Dynamics The dynamics of the CAR T-Cell therapy for the NHL market are expected to change in the coming years. The market for CAR T-cell therapy in NHL is characterized by a surge in research and development activities, as pharmaceutical companies race to bring new therapies to the market. With several CAR T-cell therapies receiving FDA approval, competition among manufacturers is intense, driving innovation and investment in the field. As a result, we witness a dynamic landscape with ongoing clinical trials, collaborations, and strategic partnerships aiming to expand the reach and efficacy of CAR T-cell therapies for NHL. Moreover, the market dynamics of CAR T-cell therapy for NHL are influenced by patient accessibility and reimbursement challenges. Despite the remarkable efficacy of these therapies, their high cost poses a significant barrier to widespread adoption. Healthcare systems and insurers grapple with the economic implications of CAR T-cell therapy, leading to negotiations on pricing and reimbursement models. Efforts are underway to make these life-saving treatments more accessible to patients, including discussions on value-based pricing and outcome-based reimbursement. As the field continues to evolve, the CAR T-cell therapy for NHL market dynamics will be shaped by a delicate balance between the clinical benefits of CAR T-cell therapy and the economic considerations surrounding its widespread implementation in the treatment of Non-Hodgkin's lymphoma. Scope of the CAR T-Cell Therapy for Non-Hodgkin's Lymphoma Market Report Therapeutic Assessment: CAR T-Cell Therapy for Non-Hodgkin's Lymphoma current marketed and emerging therapies CAR T-Cell Therapy for Non-Hodgkin's Lymphoma Market Dynamics: Key Market Forecast Assumptions of Emerging CAR T-Cell Therapy for Non-Hodgkin's Lymphoma Drugs and Market Outlook Competitive Intelligence Analysis: SWOT analysis, Conjoint Analysis and Market entry strategies Unmet Needs, KOL's views, Analyst's views, CAR T-Cell Therapy for Non-Hodgkin's Lymphoma Market Access and Reimbursement Discover more about CAR T-Cell therapy for NHL drugs in development @ CAR T-Cell Therapy for Non-Hodgkin's Lymphoma Clinical Trials Table of Contents Related Reports CAR T-Cell Therapy for Non-Hodgkin's Lymphoma Pipeline CAR T-Cell Therapy for Non-Hodgkin's Lymphoma Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key CAR T-Cell therapy for NHL companies, including Allogene Therapeutics, Novartis, Miltenyi Biomedicine, Mustang Bio, CRISPR Therapeutics, 2seventy Bio, Imugene, among others. CAR T-Cell Therapy Market CAR T-Cell Therapy Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key CAR T-cell therapy companies, including CytoAgents, Genentech, Incyte Corporation, Caribou Biosciences, Chimeric Therapeutics, Allogene Therapeutics, Kyverna Therapeutics, iCell Gene Therapeutics, Synthekine, Janssen Research & Development, SecuraBio, ImmPACT Bio, A2 Biotherapeutics, Gracell Biopharmaceuticals, Wugen, Sana Biotechnology, Oncternal Therapeutics, Vor Biopharma, CARsgen Therapeutics, Autolus Limited, Arcellx, Kite, Novartis, Lyell Immunopharma, ImmPACT Bio, Tmunity Therapeutics, Poseida Therapeutics, Precigen, AffyImmune Therapeutics, 2seventy bio, Takeda, Cartesian Therapeutics, Cabaletta Bio, Legend Biotech, Miltenyi Biomedicine, Beam Therapeutics, among others. CAR T-Cell Therapy Competitive Landscape CAR T-cell Therapy Competitive Landscape – 2024 report provides comprehensive insights about the pipeline and current landscape, pipeline and marketed drug profiles, and the key CAR T-cell therapy companies, including Alnylam Pharmaceuticals, JW Therapeutics, Gilead Sciences, Janssen Pharmaceuticals, Innovent Biologics, Sorrento Therapeutics, Cartesian Therapeutics, CASI Pharmaceuticals, Juventas Cell Therapy, Novartis, Poseida Therapeutics,Shanghai Unicar-Therapy Bio-medicine Technology, Sinobioway Cell Therapy, Tessa Therapeutics, Wuhan Bio-Raid Biotechnology, Miltenyi Biomedicine, Bristol-Myers Squibb, Autolus Limited, Beijing Immunochina Medical Science and Technology, Carsgen Therapeutics, Cellular Biomedicine Group, Chongqing Precision Biotech, Eureka Therapeutics, Formula Pharmaceuticals, Guangzhou Bio-gene Technology, Hebei Senlang Biotechnology, Mustang Bio, MolMed, Aurora BioPharma, Atara Biotherapeutics, Autolus, Bellicum Pharmaceuticals, Kecellitics Biotech Company, Yake Biotechnology, Minerva Biotechnologies, Allogene Therapeutics, PersonGen BioTherapeutics (Suzhou), Precision BioSciences, Pregene (ShenZhen) Biotechnology Company, Shanghai GeneChem, Shanghai Longyao Biotechnology, Shenzhen BinDeBio, among others. CAR T-Cell Therapy for Multiple Myeloma Market CAR T-Cell Therapy for Multiple Myeloma Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key CAR T-cell therapy for multiple myeloma companies, including Cartesian Therapeutics, Arcellx, Novartis, Bristol-Myers Squibb, CARsgen Therapeutics, Poseida Therapeutics, Juno Therapeutics, CRISPR Therapeutics, bluebird bio, Cellectis SA, Caribou Biosciences, Luminary Therapeutics, Celyad Oncology, Allogene Therapeutics, Gadeta, Nanjing IASO Biotherapeutics, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP