This is a single arm, open-label, multi-center, Phase 1 study to determine the safety and tolerability of an experimental therapy called NKX019 (allogeneic CAR NK cells targeting CD19) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) or B cell acute lymphoblastic leukemia (B-ALL)

开始日期2021-08-20

申办/合作机构

Nkarta, Inc.

100 项与 NKX-019 相关的临床结果

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100 项与 NKX-019 相关的转化医学

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100 项与 NKX-019 相关的专利（医药）

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项与 NKX-019 相关的新闻（医药）

2024-04-16

·E药经理人

这一全能技术赛道遭赛诺菲、强生“抛弃”，新贵百亿市值跌去90%，会“暴雷”吗？

赛诺菲25亿收购“分道扬镳”，强生220亿合作“打水飘”，Biotech新贵市值跌去90%，当资本冷却，技术却迟迟未变现，NK细胞疗法或成2024年又一个“被打脸”的前沿技术领域？撰文| Erin编辑| 彡氜2023年，强生的一笔“合作终止”将NK细胞疗法遇到的困境推至台前。近日，曾被赛诺菲“捧在手心”的NK细胞疗法明星公司Kiadis Pharma也被“断崖式分手”，甚至直接被关停。回顾2023年以来，NK细胞疗法领域步步坠入“黑暗”，被强生“抛弃”的Fate Therapeutics裁员60%、市值跌去90%；以“IPSC”为证券简称的Century Therapeutics市值一度不足1亿美元；Catamaran Bio更是因融资难走向破产……MNC麾下公司沦为弃子、独立的Biotech难以为继，“one cell，many fates”仍然悬挂在Fate Therapeutics官网主页。曾经的登高望远，如今必须回归到如何走好脚下的路，被关停的Kiadis Pharma绝非第一例，或许仍有更多NK细胞疗法公司在勉强度日。另外，当与之竞争的技术路线CAR-T细胞疗法的价格已经被印度药企“打到”3亿美元，还在临床早期的CAR-NK研发者们又将如何应对原来许诺的成本优势逼近的压力？Kiadis为何沦为赛诺菲“弃子”“尽管我们竭尽全力探索出售等潜在的撤资方案，但最后还是不得已关停了Kiadis业务。”斥资超3亿欧元，收入囊中三年，临床研发虽时有进展，但面对增长的压力，NK细胞疗法公司Kiadis Pharma最终还是沦为了大药企赛诺菲的“弃子”。为什么被放弃？赛诺菲在接受外媒采访时道出了原因：“研发成本高于其他治疗领域，而临床试验成功的概率却很低。”原因很赤裸，赛诺菲财报中的数据也更醒目：公司2023年无形资产减值超8亿欧元，主要受到NK Cell和PRO-XTEN技术平台相关的项目战略调整的影响。事实上，虽然Kiadis Pharma如今变成了“牛夫人”，但在三年前还是赛诺菲的“小甜甜”。两家公司的结缘其实可以追溯到2020年，Kiadis Pharma由于在T细胞疗法领域受挫，从而将重点转向了旗下子公司CytoSen Therapeutics的NK细胞平台。转型后的Kiadis Pharma，很快就吸引到了赛诺菲的目光。同年7月，赛诺菲提出以1750万欧元的预付款与其合作开发NK细胞疗法K-NK004，并与赛诺菲重磅产品CD38单抗艾沙妥昔单抗联合，一同“抢占”另一家老牌巨头强生的达雷妥尤单抗在多发性骨髓瘤的市场。这也被视作赛诺菲“高调”入局NK细胞疗法领域的开端。或许是被寄予厚望，仅三个月后，Kiadis Pharma直接被赛诺菲斥资超3亿欧元收入囊中。当时的赛诺菲全球研发主管 John Reed表示，“Kiadis的K-NK细胞技术平台将在治疗血液和实体瘤方面具有广泛的应用，并能与赛诺菲的免疫肿瘤学管线产生协同效应。”当时，Kiadis的NK细胞疗法核心管线是K-NK002，其急性髓系白血病 (AML)和骨髓增生异常综合征的临床已经进入到II期；还有一款K-NK003作为后续产品治疗复发或难治性 AML则进行到临床I期；而被赛诺菲看上的K-NK004项目仍处在临床前阶段。此外，Kiadis还有一款治疗新冠的NK细胞疗法KNK-ID-101正在1/2a 期临床试验中。Kiadis也在探索实体瘤NK细胞疗法的开发。横跨血液肿瘤、实体瘤、传染病等多个领域的开发，再加上当时大火的“新冠概念”，多个标签叠加的冲击让赛诺菲迅速“上头”，买下Kiadis也在情理之中。赛诺菲对NK细胞疗法的投入，不止于此。2022年，赛诺菲还与CRISPR先驱、诺贝尔奖得主Jennifer Doudna创建的Scribe Therapeutics达成合作，意在利用CRISPR基因组编辑技术改造创新NK细胞疗法以对抗肿瘤。这笔合作首付款2500万美元，总额高达10亿美元。这笔交易让Kiadis，不再孤单。然而，Kiadis很难想象，曾经的核心管线K-NK003（SAR44541）到了2024年还在临床早期，并且将因撤资而终止，Kiadis本身也因赛诺菲的优先级调整而被迫“消失”。其实从赛诺菲本身来讲，是无奈之举，也是理性之举。根据赛诺菲财报，2023年总收入430.70亿欧元（约471亿美元），同比增长5.3%，其中，制药业务收入378.90亿欧元（约414亿美元），同比增长5.1%。而收入首破百亿美元大关的度普利尤单抗占据了近乎三分之一的销售额，除此之外，尚没有下一款销售额超20亿美元的药品。也即，赛诺菲的制药产品中，“能打的”重磅“炸弹”药物如今只有度普利尤单抗。赛诺菲的压力可想而知，不论是拓展一些潜力产品，还是减少一些非潜力产品。除了关停Kiadis，赛诺菲也在上周剥离了另一无形资产减值的项目Amunix，该公司也是其在2021年12月以约10亿美元收购的公司。而早在3月份，赛诺菲还关停了一家位于英国剑桥的研究机构，并裁员90人，该机构也是赛诺菲曾通过收购Kymab公司获得。事实上，早在2023年10月，赛诺菲发布三季度财报之际，其首席执行官Paul Hudson就重提了“Play to Win”战略，配合此战略，赛诺菲不仅推出了管线优先级调整和成本削减计划，预计到2025年底节省约20亿欧元，还释放了分拆消费者保健业务的信号。包括本次关停Kiadis等业务在内，其实也是这一计划的落地举措。推荐阅读 * 干细胞的“无根”狂想曲，从全球顶尖再生医学公司卖保健品说起……* 一针25万，CAR-T破冰价来了？MNC先后关停，NK细胞疗法爆雷了吗？赛诺菲并非第一例被NK细胞疗法“伤到”的MNC，强生在2023年就曾与iPSC平台新贵Fate Therapeutics“分手”。强生与Fate Therapeutics合作于2020年，总额高达31亿美元，这笔合作主要是利用Fate Therapeutics的iPSC产品平台和杨森专有的肿瘤抗原binders创建新型CAR-NK和CAR-T细胞候选产品，用于血液系统恶性肿瘤和实体瘤。根据当时的新闻稿，二者的“分手”虽然主要是源于Fate Therapeutics拒绝了强生的续约条款，但背后的原因可能是合作的主要产品CAR-NK细胞候选产品FT555进度不及预期，Fate Therapeutics迫于压力以及大药企“及时止损”的续约条款，最终选择了终止合作。两则大药企接连“失利”的消息可能还带有部分内部调整的因素，但2023年以来，带有NK细胞疗法标签的Biotech持续走低的股价、大幅裁员，甚至破产，都在宣告这一前沿领域正在走向洗牌。曾以“IPSC”为证券简称的Century Therapeutics也在2023年初宣布裁员90%；专注在CAR-NK细胞疗法的Biotech公司Catamaran Bio在今年初宣布破产；曾被称为“NK第一股”的NantKwest，在与ImmunityBio合并后，如今股价也不及最高峰时的一半；Fate Therapeutics自与强生分手后，股价一路走低，市值最高曾达百亿美金，如今已跌去90%……总结NK细胞疗法走到如今局面的原因，或许就是“理想很丰满，现实很骨感”。NK细胞疗法在早期被认为能有效克服CAR-T细胞疗法来源受限、制备成本高、细胞因子风暴(CRS)副作用等难题。简单来讲，NK细胞被称作自然杀伤细胞，是人体健康的“第一道防线”。与获得性免疫细胞T细胞相比，NK细胞不需要被激活就能直接“上阵杀敌”，反应更灵敏，“杀敌”范围更广。因此，CAR-NK细胞疗法可以弥补CAR-T疗法的相关劣势。不仅可以在治疗过程中避免CRS和神经毒性等副作用的风险，还能可以更好地避免肿瘤逃逸。而NK细胞是非特异性免疫细胞，来源广泛，使低成本、规模化生产“通用型”CAR-NK异体细胞治疗产品成为可能。不仅如此，NK细胞疗法还被认为能够在神经系统疾病、传染性疾病、抗衰老、自免疾病等多个领域具有广阔前景。如果以“NK cell”为关键词在clinicaltrials.gov上搜索，全球约有超过740项临床项目登记在册。登高望远虽然前景广阔，但脚下的路如何走下去仍然是NK细胞疗法亟待突破的困境。去年在《Nature Biotechnology》上的一篇文章显示，NK细胞疗法的开发迟迟未有突破性进展的原因在于其扩增难题。研究者曾希望通过基因改造来使其能像T细胞一样扩增，但这又会遭遇与T细胞疗法一样的毒性难题。赛诺菲与Kiadis如今的结局或许也可以佐证，基因编辑也未能突破NK细胞疗法的困境。可以看到，如今全球进展较快的NK细胞疗法：来自Celularity公司的CYNK-001、Fate Therapeutics的FT576、Nkarta Therapeutic的NKX019等都仍在临床早期阶段，在神经系统疾病、传染性疾病、抗衰老、自免疾病等多元领域的应用更是尚未兑现。不过，NK细胞疗法也并非就此落寞，赛诺菲在NK细胞疗法上的期待也未消失，毕竟其在2023年初加码的Innate Pharma，在昨天刚刚宣布，其与赛诺菲合作研发的SAR443579（IPH6101）进入到了II期临床。在国内，曾经的NK细胞疗法明星公司英百瑞、博生吉等虽然逐渐低调，但2024年最新一则NK细胞疗法公司的融资消息——先博生物完成2亿元A+轮融资，与2年前英百瑞“高调”的2.3亿元A轮融资相比，如今其实也并未落下。回复“CXO”，了解电子期刊详情精彩推荐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 | 出海启思会 | 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｜亚虹医药跨国药企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

细胞疗法免疫疗法并购财报

2024-04-16

·Firstwordpharma

With new name and fresh funds, Cullinan dives into autoimmune diseases

The oncology-to-autoimmune pipeline gained a new convert on Tuesday. Cullinan Therapeutics is at least the sixth company so far this year to announce plans to test a CD19-directed therapy in lupus – the majority being current or castoff cancer programmes. Formerly Cullinan Oncology, the biotech said it has ended a Phase I trial assessing its CD19xCD3 bispecific T cell engager in B cell non-Hodgkin lymphoma (B-NHL), and will instead launch a new study of the compound, CLN-978, to treat systemic lupus erythematosus (SLE). It plans to submit a trial application to the FDA in the third quarter. Cullinan CEO Nadim Ahmed told FirstWord the move into autoimmune diseases was driven in part by the opportunity to offer a disease-modifying treatment across a range of conditions with unmet need. “More recently, lymphoma has become an area of much more competitive intensity and as such, the unmet need across lymphoma has reduced,” he added.The company will continue to move forward its pipeline of five clinical immuno-oncology programmes while it brings on autoimmune disease experts. Expanding into the new disease space makes sense for Cullinan, Ahmed said, because “the biology of oncology and immunology has continued to converge. Therefore, expanding our presence into immunology is a very natural adjacency for us as a company and represents an excellent strategic fit.”To fund the additional disease focus, Cullinan raised $280 million on Tuesday, including the sale of pre-funded warrants for $6 million and a $274 million private placement, both at $19 per share. New and existing investors participated in the PIPE, including Adage Capital Partners, Avidity Partners, Blue Owl Healthcare Opportunities, Boxer Capital, Braidwell, BVF Partners, Foresite Capital Management, an affiliate of Deerfield Management, Invus, OrbiMed, Paradigm BioCapital, Rock Springs Capital, RTW Investments, Surveyor Capital, and Venrock Healthcare Capital Partners.Joining the CD19 crowdEncouraged by data published in NEJM this February, which suggested that CD19-targeted cell therapy could lead to sustained remission for patients with several autoimmune diseases, Cullinan joins the ranks of half a dozen other biotechs testing their CD19 mettle in lupus. Most recently, Eliem Therapeutics acquired Tenet Medicine and its anti-CD19 antibody that’s Phase II-ready for SLE, the same day that Century Therapeutics announced it would also test its CD19-targeting iNK cell therapy – currently in the clinic for B-cell malignancies – in patients with SLE.Last month, Nkarta deprioritised development of its CAR-NK cell therapy NKX019 in acute myeloid leukaemia (AML), and will instead prioritise an upcoming trial in lupus nephritis (LN). Caribou Biosciences and Allogene both announced plans this year to study their respective allogeneic CD19-directed CAR-T programmes in lupus. And Kyverna Therapeutics, which has already begun Phase II testing of its CD19 CAR-T in lupus nephritis, among other autoimmune diseases, is a prime example of growing investor appetite – the biotech raised a $319-million IPO in February, so far the year’s second-largest. For more insight into the firm’s autoimmune strategy, see ViewPoints: Kyverna CEO outlines next steps for autoimmune CAR-T pipeline.While the early data supporting a CD19 approach in lupus is based on a CAR-T, Ahmed said its T cell engager could offer safety and dosing advantages over the cell therapy – for which approved treatments carry a class-wide boxed warning for secondary malignancies – while still providing a powerful immune system reset. “As a potential first-in-class opportunity, CLN-978 is differentiated from CAR-T based on off-the-shelf convenience and patient-friendly subcutaneous administration with the potential to deliver potent disease-modifying effects with a favourable safety profile,” he said. According to Cullinan, CAR-T therapy may also be a logistically challenging therapy for lupus patients, given its requirement for lymphodepleting chemotherapy and its complex manufacturing processes, which can limit patient access.

细胞疗法临床1期免疫疗法IPO临床2期

2024-04-05

·Firstwordpharma

Caribou to test off-the-shelf CAR-T in lupus

Caribou Biosciences is the latest cell therapy developer to jump on the autoimmunity hype train. The company said the FDA has cleared a safety trial of its allogeneic CD19-targeting CAR-T cell therapy in certain patients with lupus, with the study expected to kick off by year-end. The Phase I GALLOP trial will enrol patients with lupus nephritis (LN) and extrarenal lupus (EL) to receive CB-010. The cell therapy is engineered with Caribou’s Cas9 CRISPR hybrid RNA-DNA (chRDNA) technology to have a PD-1 knockout, which is intended to reduce CAR-T cell exhaustion.The study will employ partial human leukocyte antigen (HLA) matching between patients and iterations of the donor-derived off-the-shelf cell therapy, which Caribou said may improve clinical outcomes based on data from the ANTLER study, an ongoing Phase I trial of CB-010 to treat relapsed/refractory B cell non-hodgkin lymphoma. HLAs act “as our body’s identity card to know one’s ‘self’ from ‘not self,’” said Mehdi Hamadani, an investigator for ANTLER. “In stem cell transplants, it has been shown that a close HLA match between patients and donors significantly reduces the rejection of the therapy. This same logic can be applied to allogeneic CAR-T cells as well, so that the activity of the therapy persists long enough to target and destroy the diseased cells.”Caribou’s move to test CB-010 in lupus follows a larger trend from biotechs and large pharmas alike to explore the potential of certain cancer cell therapies to treat autoimmune diseases. Partially fueling the movement is early clinical data from a team of German scientists that found a CD19 CAR-T led to over two years of remission for patients with systemic lupus erythematosus (SLE). Vasileios Kyttaris, rheumatology specialist and assistant professor of medicine at Beth Israel Deaconess Medical Center, told FirstWord that lupus patients would need to experience, at a minimum, two to four years of drug-free remission for the intensive therapy to catch on. The relatively new space is also attracting investor interest. Kyverna Therapeutics successfully spun its autoimmune cell therapy pipeline into what is so far the year’s second biggest IPO. “Two years ago, it wasn’t clear that targeting CD19 for autoimmune disease would create such a big buzz. People are now starting to take notice,” chief executive Peter Maag told FirstWord in an interview last month. For more, see ViewPoints: Kyverna CEO outlines next steps for autoimmune CAR-T pipeline.Other cell therapy modalities are also following suit. Last month, Nkarta said it would halt most development activities for its allogeneic CAR-NK cell therapy NKX019 in cancer and instead focus on autoimmune diseases, and LN in particular.

细胞疗法临床1期免疫疗法

100 项与 NKX-019 相关的药物交易

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研发状态

适应症	最高研发状态	国家/地区	公司
CD19阳性B细胞急性淋巴细胞白血病	临床1期	澳大利亚更多	Nkarta, Inc. 更多
大B细胞淋巴瘤	临床1期	澳大利亚更多	Nkarta, Inc. 更多
套细胞淋巴瘤	临床1期	美国更多	Nkarta, Inc. 更多
小淋巴细胞淋巴瘤	临床1期	澳大利亚更多	Nkarta, Inc. 更多
B细胞恶性肿瘤	临床1期	澳大利亚更多	Nkarta, Inc. 更多

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05020678 (Corporate Publications) 人工标引	临床1期	非霍奇金淋巴瘤	19	NKX019	繭艱窪夢襯觸繭顧選夢(鏇遞鏇夢蓋廠醖衊淵夢) = Neutrophil count decreased (63%); Platelet count decreased (42%); Febrile neutropenia (26%); Anemia (21%); WBC count decreased (16%); Lymphocyte count decreased (11%) 餘餘鑰鑰積艱簾築構構 (醖窪鏇簾窪顧糧鏇醖壓 )	积极	2022-12-05