As al lo gene ic cell ther a py ap proach es flour ish, Cen tu ry loads up $160M to scale iP SC plat form for CAR-T, CAR-NK

当al lo基因ic细胞向py ap推进面粉时,岑图瑞投入1.6亿美元用于CAR-T、CAR-NK的iP SC平台

2021-03-04 03:30:13 ENDPOINTS NEWS

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La­lo Flo­res is con­fi­dent he’s found the way for­ward in cell ther­a­py. The feel­ing, to be sure, is not ex­clu­sive. Thanks to splashy com­pa­nies like Al­lo­gene, Lyell and Arti­va, bio­phar­ma is well aware of the promis­es of al­lo­gene­ic ther­a­pies as next-gen­er­a­tion al­ter­na­tives to the au­tol­o­gous CAR-Ts that have al­ready made it to the mar­ket. But few­er are talk­ing about a fin­er dis­tinc­tion with­in that al­lo­gene­ic group: Where do you find the cells to en­gi­neer and turn in­to a fi­nal off-the-shelf prod­uct? While most have opt­ed for donor cells, Cen­tu­ry Ther­a­peu­tics — where Flo­res is CEO — is bank­ing on in­duced pluripo­tent stem cells. Al­most two years af­ter launch­ing with $250 mil­lion in cash and three em­ploy­ees, it’s col­lect­ed $160 mil­lion to fu­el the now 100-per­son team’s dash to the clin­ic. In par­al­lel with all the ad­vances in cell en­gi­neer­ing over the years, there’s been a sim­i­lar evo­lu­tion in the sci­ence of re­pro­gram­ming skin or blood cells in­to an em­bry­on­ic-like state and coax­ing them in­to T or NK cells. Fate Ther­a­peu­tics, a J&J-part­nered pi­o­neer now in the clin­ic, has done much to ed­u­cate the field about it, and more re­cent­ly we’ve seen star­tups like Notch emerge; Cen­tu­ry wants to join them in the lead­ing spot, Flo­res said. The room for im­prove­ment, af­ter all, is sig­nif­i­cant. Even in the few lym­phoma in­di­ca­tions where Kym­ri­ah and Yescar­ta have been ap­proved, not all pa­tients achieve a com­plete re­sponse and many who do would re­lapse. “So clear­ly what that means is that there was not enough pres­sure on the tu­mor, there were enough cells that sur­vived that treat­ment […] and that’s the rea­son pa­tients re­lapse,” Flo­res said. “Our goal at Cen­tu­ry is to in­crease the dura­bil­i­ty of the re­spons­es.” Cen­tu­ry is “plat­form ag­nos­tic” and there­fore de­vel­op­ing both CAR-T and CAR-NKs cre­at­ed with its iP­SCs. The lead pro­gram is a CD19 CAR-T that they hope to steer in­to a hu­man tri­al by 2022. In ad­di­tion to the anti­gen tar­gets, the biotech has de­vised a com­bi­na­tion of three ge­net­ic ed­its to pre­vent im­mune re­jec­tion of the ther­a­peu­tic cells — open­ing up the pos­si­bil­i­ty to dose sev­er­al times un­til the pa­tient re­sponds. With each new pro­gram, once they fi­nal­ize all the mod­i­fi­ca­tions Cen­tu­ry would iso­late a sin­gle clone to start what they call a mas­ter cell bank. “It may take you a cou­ple of years to get to that point,” Flo­res said. “But once you have a mas­ter cell bank, that is the be­gin­ning of your man­u­fac­tur­ing process. And from there it on­ly takes you 30 days to make a man­u­fac­tur­ing run that will sup­ply thou­sands of dos­es.” Ul­ti­mate­ly, he en­vi­sions Cen­tu­ry’s ther­a­pies to be stored as a frozen prod­uct in hos­pi­tals. The pre­clin­i­cal pipeline goes af­ter a slate of hema­to­log­i­cal ma­lig­nan­cies as well as sol­id tu­mors like glioblas­toma, where they would de­ploy a bis­pe­cif­ic CAR. The sub­stan­tial back­ing from Ver­sant and Bay­er in its Se­ries B has helped Flo­res re­cruit a ex­perts in pro­tein en­gi­neer­ing, gene edit­ing and man­u­fac­tur­ing, with him man­ag­ing the head­quar­ters in Philadel­phia, R&D chief Hyam Lev­it­sky lead­ing a team in Seat­tle and the group that was for­mer­ly Em­pir­i­ca Ther­a­peu­tics set­ting up a third of­fice in Cana­da af­ter Cen­tu­ry ac­quired the Uni­ver­si­ty of Toron­to spin­out. More re­cent­ly, it’s leased the space for an man­u­fac­tur­ing fa­cil­i­ty in New Jer­sey, just 45 min­utes from the HQ, adding in-house ca­pac­i­ty to com­ple­ment the ex­ist­ing pro­duc­tion un­der a part­ner­ship with Fu­ji­film Cel­lu­lar Dy­nam­ics. “Each time you de­vel­op a prod­uct, you be­gin the whole process of learn­ing how to scale up man­u­fac­tur­ing,” he said. “Go­ing to this jour­ney, there’s many learn­ings and it’s re­al­ly im­por­tant to cap­ture all those learn­ings with­in your own em­ploy­ees, your own sci­en­tists, or with­in your close part­ner as we have in FC­DI.” They could be tak­ing those learn­ings to Nas­daq soon. Though Flo­res notes Cen­tu­ry now has two to three years of run­way, the Se­ries C syn­di­cate — Fi­deli­ty, the Fed­er­at­ed Her­mes Kauff­man Funds, RA Cap­i­tal, Lo­gos Cap­i­tal, Or­biMed, Mar­shall Wace, Qatar In­vest­ment Au­thor­i­ty, Avid­i­ty Part­ners, and Oc­ta­gon Cap­i­tal — fea­tures well-known crossover play­ers with whom he will be ex­plor­ing an IPO. In what could be an early shot in the battle against drugmakers that whiff on confirmatory studies to support accelerated approvals, the FDA ordered Bristol Myers Squibb late last year to give up Opdivo’s approval in SCLC. Now, Merck is next on the firing line — are we seeing the FDA buckling down on post-marketing offenders? Merck has withdrawn its marketing approval for PD-(L)1 inhibitor Keytruda in metastatic small cell lung cancer as part of what it describes as an “industry-wide evaluation” by the FDA of drugs that do not meet the post-marketing checkpoints on which their accelerated nods were based, the company said Monday. The global pandemic may have roiled economies, killed hundreds of thousands and throttled entire industries, but the only effect it had on biopharma venture investing was to help turbocharge the field to giddy new heights. Below you’ll find the new top 100 venture investors in the industry, ranked by the number of deals they were publicly involved in, as tracked by DealForma chief Chris Dokomajilar. The numbers master then calculated the estimated amount of money they put into each deal — divvying up the cash by the number of players — to indicate how they managed their syndicates. CRLs. 483s. CBER, CDER and RWE. For biopharma professionals, these acronyms command attention because of the fundamental role FDA plays in drug development. Now Endpoints is doubling down on regulatory coverage, and launching a weekly report focusing on developments out of White Oak, with analysis and insight into what it all means. Coverage will be led by our new senior editor, Zachary Brennan. He joins Endpoints from POLITICO, where he covered pharma. Prior to that he was the managing editor for Regulatory Focus, a news publication from the Regulatory Affairs Professionals Society. One of Europe’s most high-profile biopharma investors is getting $540 million to invest in new crossover deals for late-stage companies. The Paris-based VC says the fresh Sofinnova Crossover Fund raise positions them as the “largest crossover investor in Europe dedicated to late-stage biopharma and medtech investments.” They got a leg up in France after winning a special “Tibi” designation from the French government, giving them access to a pool of €6 billion that helped them gain an edge with institutional investors. Since they were founded close to 50 years ago, the venture group has backed more than 500 companies and currently has more than €2 billion under management. GlaxoSmithKline and Vir Biotechnology were hopeful that one of their partnered antibodies would carve out a win after getting the invite to a major NIH study in hospitalized Covid-19 patients. But just like Eli Lilly, the pair’s drug couldn’t hit the mark, and now they’ll be left to take a hard look at the game plan. The NIH has shut down enrollment for GSK and Vir’s antibody VIR-7831 in its late-stage ACTIV-3 trial after the drug showed negligible effect in achieving sustained recovery in hospitalized Covid-19 patients, the partners said Wednesday. A little more than a week after BrainStorm acknowledged that regulators at the FDA had informed them that the biotech needed more data before it could expect to gain an approval for its ALS treatment NurOwn — while still touting a “clear signal” of efficacy and not ruling out an application — the agency has decided to clarify the record in a most unusual statement. The FDA statement amounts to a straight slap own, offering a different set of efficacy numbers from the company’s public presentation last November and ruling out any chance of statistical significance. The outsourcing market for cell and gene therapies has stayed red-hot in recent months as some of the biggest CDMOs — and even major drugmakers — are diving in. Now, a Swiss CDMO wants a bigger piece of the action, and it’s looking to set up shop in Novartis’ fledgling life sciences hub in Stein. Celonic plans to build a 91,500-square-foot manufacturing center focused on cell and gene therapies, next-gen vaccines and other “innovative” drugs as part of a two-part expansion at Novartis’ Rhine Valley hub, the CDMO said last week. Over the last decade, drugmakers have proven JAK inhibitors can treat a smattering of immune-related diseases ranging from rheumatoid arthritis to Covid-19. Now Eli Lilly has pulled out a new one. Lilly and its biotech partner Incyte announced Wednesday that their JAK inhibitor baricitinib effectively regrew patients’ hair in a Phase III trial for alopecia areata, an autoimmune condition that can cause sudden, severe and patchy hair loss. Lilly didn’t break down the results from the 546-patient trial, but the primary endpoint was improvement on a standard score for alopecia symptoms. Janux Therapeutics had kept a relatively low profile since being founded back in 2017 but burst onto the scene late last year when Merck plunked down more than $1 billion in promised milestones for its T cell engagers. Now, less than three months later, the small biotech has clinched its first round of private funding led by some prominent backers. As it prepares its first programs for INDs, Janux completed a $56 million Series A on Wednesday morning, with Jay Lichter’s Avalon Ventures joining forces with new investors OrbiMed and RA Capital Management to fund the company. Janux will use the cash to primarily advance its T cell engagers targeting PSMA and TROP2, which are expected to hit the clinic in the first and second quarters of 2022, respectively.
La lo Flo-res相信他在牢房里找到了路。 当然,这种感觉并不明显。多亏了Allo-Gene、Lyell和Arti-Va这样的知名公司,Bio-Pharma很清楚Allo-Geneic There-a Pies作为Au-Tol-O-Gous Car的下一代企业的前景,这些企业已经准备好进入市场。但是,很少有人在谈论与这个有限基因集团的一个潜在的差异:你从哪里找到细胞来进行消化,然后转到一个独立的现成产品中去呢? 尽管大多数人都选择了供体细胞,但弗洛雷斯担任首席执行官的一些人却在依靠引进的多基因干细胞。 在两年多的时间里,以2.5亿美元的现金和三个项目投入了1.6亿美元,以支持现在的100人团队向临床冲刺。 与这些年来细胞免疫的所有变化一样,在将皮肤或血细胞转化为细胞样状态并诱导其转化为T细胞或NK细胞的科学中也存在着一种类似的发展趋势。Fate Thera Peutics,一个现在在临床的J&J部分的Pio-neer,已经做了很多关于它的领域的教育,更多的是我们看到像Notch这样的明星出现;弗洛雷斯说:“Centu-ry希望和他们一起成为领头羊。” 改善的空间,除了所有,是签署的,如果我不能。即使是在少数几个已经被证明是正确的,也不是所有的人都实现了完全的再认识,而且很多做到了的人也会再认识。 弗洛雷斯说:“很明显,这意味着没有足够的压力,有足够的细胞来维持治疗[…]。这就是原因。”“我们在Centu-ry的目标是增加我们的硬脑膜。” CENtu-RY是“Plat-Form Ag-Nos”,因此CAR-T和CAR-NKs都与它的IP SCs相结合。主导项目是一辆CD19汽车-T,他们希望在2022年前转向一辆Hu-Man Trial。 在反基因的作用下,生物技术已经设计出了三个基因的组合,以预先排出细胞的免疫反应--将细胞开放几次,直到细胞的反应。 对于每一个新的程序,一旦他们建立了所有的模型,就会产生一个错误的克隆,开始他们所谓的大规模细胞库。 弗洛雷斯说:“你可能需要几年的时间才能达到这个目的。”“但一旦你有了一个大规模的细胞库,那就是你的男人转变过程。从那以后,你要花30天的时间去做一个能给你带来好处的人。“ 最后,他的馅饼将作为冷冻产品存放在寄存的地方。前临床管道去了一个石板上的血细胞和解决像胶质瘤,在那里,他们会制造一个双PE的汽车。这位来自Versant和Bayer的副总裁帮助Flores重新组建了一位项目工程师,gene Editing和Man Fac,他在费城担任首席执行官,研发总监Hyam Levit Sky领导了一个团队,在Cana设立了三分之一业务的团队请求Toron的Uni-sit退出。 更重要的是,它为一个在新的工厂工作的人租赁了空间,离总部只有45分钟的路程,增加了内部包装,以与Fuji-Film Cel-lar Dy-namics合作。 他说:“你每完成一项生产,你就经历了学习如何扩大生产规模的整个过程。”“到了今天,我们会学到很多东西,我们必须把这些东西用自己的方法、自己的科学,或者用我们在FC中所学到的接近的部分来完成。” 他们可能很快就会把这些学到的东西拿到NAS DAQ上。尽管有两三年的经营之路,但Cen'tu're Sen'di'del'ty、Fed'er'at Her'mes Kauff'man Funds、RA'cap'i'tal、Lo'gos Cap'i'tal、or'bimed、Mar'shallwace、Catal'in'mentau'thor'i'ty、Avid'i'ty Parter'ners、Oc'ta'gonCap'i'tal都是知名的跨界投资者,他将与他们进行IPO。 去年年底,FDA命令百时美施贵宝放弃Opdivo在SCLC的审批,这可能是对那些利用验证性研究来支持加速审批的制药商的一次早期打击。现在,默克是下一个上火线的--我们看到FDA对上市后违法者的严厉打击了吗? 默克公司周一表示,该公司已经撤回了对转移性小细胞肺癌的PD-(L)1抑制剂Keytruda的上市批准,作为FDA对不符合上市后检查点的药物进行“全行业评估”的一部分。 这场全球大流行可能扰乱了经济,夺走了数十万人的生命,扼杀了整个行业,但它对生物制药风险投资的唯一影响是帮助该领域达到令人眩晕的新高度。 根据DealForma首席执行官Chris Dokomajilar的记录,以下是业内前100名风险投资家的排名,根据他们公开参与的交易数量排名。然后,数字大师计算出他们投入每笔交易的估计金额--按玩家人数分配现金--以表明他们是如何管理自己的辛迪加的。 CRLS.483s.CBER、CDER和RWE。对于生物制药专业人员来说,这些首字母缩略词之所以引起注意,是因为FDA在药物开发中起着重要作用。现在Endpoints正在加倍扩大监管覆盖范围,并推出一份关注White Oak公司发展的周报,并对这一切意味着什么进行分析和洞察。 报道将由我们新的高级编辑Zachary Brennan领导。他加入了POLITICO的端点,在那里他报道了制药。在此之前,他是管理事务专业人士协会的新闻刊物《管理焦点》的执行编辑。 欧洲最受瞩目的生物制药投资者之一将获得5.4亿美元,投资于新的跨界交易,为处于后期阶段的公司投资。 这家总部位于巴黎的风投公司表示,新的Sofinnova跨界基金融资使他们成为“欧洲最大的跨界投资者,致力于后期生物制药和医疗技术投资”。 他们在法国获得了法国政府颁发的“Tibi”特许权,从而获得了60亿欧元的资金池,帮助他们在机构投资者中获得了优势。自50年前成立以来,这家风险集团已经支持了500多家公司,目前管理着超过20亿欧元的资金。 葛兰素史克公司和Vir Biotechnology公司在接到NIH一项针对住院Covid-19患者的重大研究的邀请后,希望他们合作的抗体之一能够赢得胜利。但就像礼来一样,这对组合的药物不能击中目标,现在他们将被留在认真看比赛计划。 合作伙伴周三表示,NIH已经停止了GSK和Vir的抗体VIR-7831在其晚期Active-3试验中的注册,因为该药物在实现住院的Covid-19患者的持续康复方面显示出可忽略不计的效果。 一周多一点后,BrainStorm公司承认FDA的监管机构已经通知他们,该生物技术公司需要更多的数据才能获得ALS治疗NurOwn的批准--同时仍在吹捧疗效的“明确信号”,并不排除申请--该机构决定在一份最不寻常的声明中澄清记录。 FDA的声明完全是对自己的一记耳光,它提供的药效数据与该公司去年11月的公开声明不同,并且排除了任何统计意义的可能性。 近几个月来,细胞和基因疗法的外包市场一直处于火热状态,因为一些最大的CDMO(甚至是主要的制药商)纷纷涉足。现在,一家瑞士CDMO想要分得更大的一杯羹,它正打算在诺华公司位于斯坦因的新生生命科学中心开店。 CDMO上周表示,赛隆公司计划在诺华莱茵河谷中心分两部分进行扩建,计划建设一个占地9.15万平方英尺的制造中心,专注于细胞和基因疗法、下一代疫苗和其他“创新”药物。 过去十年,制药商已经证明JAK抑制剂可以治疗从类风湿性关节炎到COVID-19等一小部分免疫相关疾病。现在礼来又拿出了一个新的。 礼来及其生物技术合作伙伴Incyte周三宣布,他们的JAK抑制剂baricitinib在一项针对斑秃的III期试验中有效地修复了患者的头发。斑秃是一种会导致突然、严重和斑片状脱发的自身免疫性疾病。礼来没有对546名患者的试验结果进行分析,但主要终点是脱发症状标准评分的改善。 Janux Therapeutics自2017年成立以来一直保持着相对低调的姿态,但去年年底,默克公司斥资逾10亿美元,承诺为其T细胞参与器提供一系列里程碑项目,这让Janux Therapeutics突然崭露头角。现在,不到三个月后,这家小型生物技术公司已经获得了由一些知名支持者牵头的第一轮私人融资。 Janux在为INDs准备第一个项目的同时,于周三上午完成了5600万美元的a轮融资,由Jay Lichter的Avalon Ventures联合新的投资者OrbiMed和RA Capital Management为该公司提供资金。Janux公司将利用这笔资金主要推进针对PSMA和TROP2的T细胞接合器,预计将分别于2022年第一季度和第二季度投入临床应用。

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