Spanlecortemlocel (Magenta Therapeutics)

前言        风干两年的咸鱼，下了油锅居然还蹦跶一下，这种奇事还真就发生了。2023年1月25日，Magenta Therapeutics宣布，由于一名患者在服用药物后死亡，研究暂停，并重新评估药物安全性。2月2日，Magenta宣布要对战略替代方案进行全面审查。隔天，Magenta股票居然大涨51.66%。即便如此，现在它的市值也不到巅峰时的一个零头。01撞到头破血流才停下的临床试验Magenta这款可能导致了患者死亡的MGTA-117，是一款ADC药物，靶点为CD117，主要作用于骨髓中的造血干细胞和癌细胞。该药物正在急性髓系白血病和髓系综合性复发患者中进行剂量递增试验。MGTA-117的I/II期临床试验一波三折，过强的毒性已经早早为悲剧埋下伏笔。一开始，MGTA-117的IND申请就被FDA打回。FDA要求Magenta开发额外的生物测定方法，用于安全检测和剂量递增试验设计。2021年9月，临床暂停解除，但随着试验阶段进行，剂量不断提升，又出事了。2022年12月，MGTA-117连续出现两起4级呼吸系统严重不良反应事件。这一消息导致MGTA股价大跌50%。Magenta决定停止该队列（队列4）用药，但依旧根据队列3为新患者用药。尽管队列3的药物剂量少于队列4，但2022年1月25日，又有一名患者出现了呼吸衰竭与心脏骤停的5级严重不良反应，最终导致患者死亡。Magenta表示，该事件可能与MGTA-117有关，试验暂停。图片来源：雪球02墙外开花的亮眼产品Magenta这家公司诞生伊始，本和ADC没啥关系，他们的核心领域一度是干细胞疗法。Magenta推出的第一款干细胞治疗产品MGTA-456 ，是一种经过扩增的 cd34+ 细胞治疗产品，可用于快速诱导并维持造血干细胞的植入。根据Magenta在2020年公布的一项2期临床数据，该产品在神经和认知功能方面具有临床意义和持久的益处，并可解决脑肾上腺脑营养不良症(CALD)患儿的脑炎症。Magenta借助MGTA-456画了个大饼，让不少投资机构吃撑了。Magenta2018年上市时可谓是众星捧月，Atlas venture、Third Rock等知名投资公司领投。不幸的是，2020年6月，MGTA-456由于患者入组困难、新冠影响与临床试验设计等原因研究终止。另一款与MGTA-456相似的干细胞疗法MGTA-145接过MGTA-456的接力棒，成为了Magenta的主要管线。Magenta目前的管线布局如果只有这两款产品，Magenta恐怕只是一家平平无奇的小biotech，在医药行业群星中，只能当一个小小的背景板。但有野心的Magenta没有止步于此，“罪魁祸首”MGTA-117诞生了。干细胞移植需要对患者进行清髓，清除患者体内原有的干细胞。传统清髓手段主要依靠化疗，而Magenta另辟蹊径，希望通过ADC药物MGTA-117耗尽血液或骨髓中表达CD117的靶细胞，让患者无需化疗即可完成清髓。就这样，一家研究干细胞疗法的公司也搞起了ADC。在2019年12月9日的美国血液学会年会（ASH）上，美国国立卫生研究院分子和临床血液学部主任John Tisdale博士的口头报告专门强调了MGTA-117的研究进展，表明“这是一次非常成功的试验，人类首次在不使用放、化疗的情况下，通过ADC的手段，成功将基因修饰细胞移植到非人灵长类动物中。”03Magenta为什么这么头铁2021年3月，Magenta公布了2020年财报，一年亏损七千多万美元，现金流只能维持到2023年。这一消息让投资者望风而逃，一年时间，股价从最高值14.2美元跌到4.4美元左右。Magenta也成为了2022医药行业裁员大潮中的一朵小浪花。2022年4月，Magenta宣布裁员14%，并暂停MGTA-145计划在健康受试者中进行的临床试验。自此Magenta的核心管线停摆，ADC产品MGTA-117成为了Magenta最后的希望。MGTA-117的成败直接关系到整个公司的命运。也许这就是在出现了严重不良反应之后，MGTA-117的临床研究仍没有停止的原因。最终，患者死亡事件为这家公司的结局标上句点。最后的赌博全盘皆输，资本不相信眼泪，留给Magenta的时间不多了。Magenta的结局，很可能是被收购，或者与其他公司合并。即便是乐观估计，恐怕也得卖掉自己的管线。也可能是由于卖身传闻，投资者才纷纷涌入，致使股价大涨。投资者们希望会出现溢价收购的情况，此刻购入或许只是为了抄底，赌一把可以在Magenta后续战略调整中抢到点残羹冷炙罢了，并非真的看好这家公司。Magenta这次股价大涨，不过是从0.56美元的低价涨到0.85美元，勉强追回2022年12月患者发生4级严重不良反应事件后的股价而已。咸鱼没有翻身，只是被油锅煎得翘了起来。03小结有破釜沉舟般的勇气， 不撞南墙不回头，是科学界成功的要素之一。近些年杀出重围的传奇biotech们，多少都有一些这样的特质。但他们是坚信自己的产品能成功，而不是拒绝接受已经失败的事实。像Magenta这样不能“力拔山兮”却“气盖世”，连壮烈自刎留个体面的机会都没有了。临死前最后的回光返照，只是投机客的引渡冥灯，悲兮悲兮。参考资料https://endpts.com/magenta-halts-stem-cell-work-and-may-sell-itself-following-patient-death-clinical-hold/https://endpts.com/patient-death-spurs-trial-halt-for-magenta-therapeutics/magenta官网消息其他网络公开资料封面图来源：pixabay推荐阅读正月十五猜灯谜！全是新药专题，您能猜中几道？～~ 附：十五家药企、机构之精美元宵节海报！~~专栏 | 知名投资专家柳达：化学药的开发有无范式？卖了8年的PD-1，还能保持20%的增长率，它是怎么做到的？这款药被2022版上海市新冠病毒感染诊疗规范推荐，临床价值在哪里？罗氏2022，营收近700亿美元！新增长抵消新冠影响诺和诺德2022财报公布：全年销售额大涨25%，GLP-1产品拉动整架马车点击这里，报名创新药BD高阶研讨会【上海站】！

It’s been a pretty good year for mergers and acquisitions in the biopharma industry. But the landscape for IPOs has been excellent as well, particularly in Massachusetts, which has recorded 13 IPOs since the beginning of the year. It’s been a pretty good year for mergers and acquisitions in the biopharma industry, with Takeda Pharmaceutical buying Shire for $62.2 billion, and the year starting with Sanof i buying Bioverativ for $11.6 billion and then Ablynx for $4.8 billion. Celgene acquired Juno Therapeutics for $9 billion, shortly after buying Impact Biomedicines for $1.1 billion. But the landscape for initial public offerings (IPOs) has been excellent as well, particularly in Massachusetts, which has recorded 13 IPOs since the beginning of the year, raising a combined $1.3 billion. This exceeds by money raised the record in 2014, when 17 Massachusetts biotechs raised $1.2 billion, and the year’s only half over. And there are three biotech companies in Massachusetts that have filed to go public, but hadn’t done so yet. One of those includes Rubius Therapeutics . The list of Massachusetts biotech companies with IPOs so far this year is listed below. #1. Cue BioPharma . Headquartered in Cambridge, Mass., Cue focuses on injectable biologics engineered to modulate the immune system to treat cancer, chronic infectious diseases and autoimmune disorders. Its IPO on January 2 raised $66 million. #2. Unum Therapeutics . Also based in Cambridge, Unum is also working in the immuno-oncology space, developing therapies based on an antibody-coupled T cell receptor. It is differentiated from CAR-T or TCR by not being restricted to a particular target and may have applications in a broad range of cancer types. The company’s IPO raised $69 million on March 29. #3. Scholar Rock . Of course, based in Cambridge, Scholar Rock is focused on the biology of growth factor activation, targeting growth factors in the disease microenvironment. This has applications in neuromuscular disorders, cancer, fibrosis, and anemia. It raised $75 million on May 24. #4. R estorBio . Headquartered in Boston, RestorBio is focusing on aging-related diseases. Its lead program, RTB101, focuses on the mechanistic target of rapamycin (mTOR) pathway, an evolutionarily conserved pathway that regulates aging. On January 26, the company raised $85 million. #5. Evelo Biosciences . Located in Cambridge, Evelo Biosciences focuses on monoclonal microbials for oncology and inflammatory diseases. Its lead product is EDP1066, currently in a clinical trial in inflammatory diseases, such as psoriasis, atopic dermatitis, and ulcerative colitis/Crohn’s colitis. On May 9, the company raised $85 million. #6. AvroBio . Headquartered in Cambridge, AvroBio is focused on lentiviral-based gene therapies for rare diseases. Its lead gene therapy is AVR-RD-01 for Fabry disease. It also has three more gene therapies for other lysosomal storage disorders. On June 21 it raised $99 million. #7. Neon Therapeutics . Located in—you guessed it—Cambridge, Neon is working on directing the immune system using neoantigens to treat cancer. Neoantigens are specific genetic mutations that are common in cancer. The company’s June 27 IPO raised $100 million. #8. Magenta Therapeutics . Magenta is based in Cambridge and is developing therapeutics for bone marrow transplant for patients with autoimmune diseases, blood cancers and genetic diseases. The company’s most advanced clinical product is MGTA-456, a cell therapy in a Phase II clinical trial in patients with inherited metabolic diseases. Magenta raised $100 million on June 21. #9. Surface Oncology . Based in Cambridge, Surface Oncology, not surprisingly given its name, focuses on cancer. The differentiating factor is its focus on the tumor microenvironment. On June 12, it i nitiated a Phase I clinical trial of SRF373, a fully human antibody targeting CD73, the second of its immunotherapies to advance into this clinic this year. On April 19, its IPO raised $108 million. #10. Translate Bio . Headquartered in Lexington, Mass., Translate focuses on messenger RNA (mRNA) to treat diseases caused by protein or gene dysfunction. On June 11, it signed a deal with Sanofi Pasteur to develop up to five undisclosed infectious disease pathogens. The company raised $122 million on June 28. #11. Solid Biosciences . Based in Cambridge, Solid is focused on a gene therapy for Duchenne muscular dystrophy (DMD). On June 18, the U.S. Food and Drug Administration (FDA) lifted a clinical hold on the company’s IGNITE DMD Phase I/II clinical trial of SGT-001 for DMD, acknowledging the company had addressed all the questions the agency had in its clinical hold. The company raised $125 million on January 26. #12. Homology Medicines . Headquartered in Bedford, Mass., Homology is a genetic medicines company focused on rare genetic diseases. Its proprietary platform utilizes its human hematopoietic stem cell-derived adeno-associated virus vectors (AAVHSCs) to deliver genetic medicines either through a gene therapy or nuclease-free gene editing modality for a variety of genetic disorders. Its IPO on March 28 raised $144 million. #13. Kiniksa Pharmaceuticals. Kiniksa has headquarters in Hamilton, Bermuda and Lexington, Mass. The company’s pipeline includes rilonacept for recurrent pericarditis, mavrilimumab for giant cell arteritis, KPL-716 for prurigo nodularis/atopic dermatitis, KPL-045 for T-cell dependent and B-cell-mediated indications, and KPL-404 for the same as KPL-045. On May 24, its IPO raised $153 million.