Ianalumab

当下，自身免疫赛道成为了商业化端群雄逐鹿、研发端龙争虎斗的新高地。 撰文| 润屿 撰文| 顿河 芳晨 刚过去的5月，数笔大并购带来了一个极为关键的信号：药企“诸神之战”，已正式转移至了自免领域。 全球营收NO.1的强生“提刀”杀入，不到半个月时间狂掷152亿收购自免资产。渤健完成超10亿美元并购，目的在于用一个在肿瘤界必争的靶点CD38，去开发自免适应证。 2023年畅销药TOP10排位赛上，销售额排名前六的产品中，有一半来自自免领域，强生、赛诺菲与艾伯维之间暗流涌动。礼来等MNC正探索PD-1在自免领域的价值，CAR-T也开始拥抱自免赛道、“自免CAR-T第一股”已以较大募资规模登陆纳斯达克…… 从MNC的明争暗逐，到资本的看好，自免已成为众兵家必争之地。而在这场大战中，最精彩的莫过于：艾伯维、赛诺菲、强生、诺华都在称自己为“自免一哥”。 到底谁是真正的“一哥”？“四强”纷纷把拿手好戏搬上了舞台。 “一哥”之辩  自免舞台，“四强”登场，率先开启了一场口头上的“博弈”。 刚刚先后以8.5亿美元现金和12.5亿美元收购了两家自免Biotech的强生，直接点燃导火索，称最新收购的自免产品与赛诺菲/再生元的度普利尤单抗，以及与艾伯维乌帕替尼比起来，或更具独特优势，且能治疗更多适应证。 赛诺菲、艾伯维表面淡定，但或许内心在想：你的自免业务只是曾经辉煌，但现在，请在自免板块收入上先打败我再说。 谈到自免领域收入，艾伯维率先会心一笑。即使药王修美乐专利到期，但2023年仍旧无人超越它在自免领域的吸金能力。艾伯维的“出战”语录是：请记住，我只培养冠军。曾经的修美乐可以统领一个时代，现在的Skyrizi（瑞莎珠单抗）和乌帕替尼，是绝对的种子选手。“自免一哥”非我莫属。 但听到艾伯维的这一番发言，赛诺菲不干了：别老药新药一起算，全球TNF-α抑制剂整体销售已经疲软，度普利尤单抗才是自免新靶点核心药物中最畅销的。而且不是我骄傲，度普利尤单抗是我们推出的第一个免疫学药物，如此成绩，不配一个“一哥”头衔？ 这时，在一角坐观竞争的诺华站了起来：能担“一哥”者，考验的是破冰的胆量和能力。司库奇尤单抗一路用“头对头”试验，PK掉了其他银屑病玩家。关键是，我还能在一度“冰封”的中国自免创新药市场，把这一产品卖到最好，让中国的自免赛道被点燃。前者修美乐没能做起来，而后续进入中国的自免新药复刻我的曲线。另外，我们的自免管线数量布局，也是数一数二的。 整体来看，艾伯维、强生、诺华、赛诺菲的强劲增长动力，均以自免药物为支撑，而四家MNC在自免领域各有优势。 但从自免业务收入、上市药物销售额、研发布局力度和丰富度、以及技术积累与积淀等各个细分维度来看，“自免一哥”在各自的语境里，早已称王。 难分伯仲 论当下自免业务整体收入，艾伯维还是妥妥的“一哥”。2023年，一款老药修美乐，加上“双子星”——乌帕替尼和Skyrizi，三个产品创造了260亿美元的营收。即使赛诺菲和诺华两者自免业务（按主要产品来算）合力对打还是打不过。 但论单个产品收入，最亮眼的不是艾伯维，反倒是赛诺菲。 赛诺菲IL-4R产品度普利尤单抗，是全球首个治疗中重度特应性皮炎（AD）的生物制剂。2023年，度普利尤单抗大卖115.57亿美元，在十大畅销药中排名第五。这款药的存在，首先证明了IL-4Rα单抗在中重度AD系统治疗靶向药中最具综合优势，无论是能覆盖的人群、2型炎症，还是安全性；再是凭一举之力奠定了赛诺菲在自免领域的地位。最关键的，这款药是新靶点自免药物中，目前最畅销的一款。 论积淀，强生是 “老大哥”。手握四张“王牌”的强生，其自免创新产品商业化之旅比艾伯维早了好几年。TNF-a抑制剂英夫利昔单抗是全球上市最早的两大自免产品之一，另外，还有百亿美元炸弹乌司奴单抗、Tremfya（古塞奇尤单抗）和Simponi（戈利木单抗）三大自免产品。2023年，尽管强生最大的产品亮点已转移至肿瘤领域，然而从营收贡献来看，自免仍是其第一大业务板块，总收入在180亿美元。 论自免领域研发战略布局最妥当、产品接力节奏最为紧密的，是诺华。 在全球，诺华司库奇尤单抗是销售额达50亿美元的重磅炸弹，在银屑病治疗领域，该产品通过一连串的“头对头”临床试验，PK掉了一众对手。海外多项头对头临床试验数据显示，IL-17 单抗产品司库奇尤单抗，优于辉瑞/安进的依那西普（TNF-α 单抗）和强生乌司奴单抗（IL-12/23 单抗）。 目前，司库奇尤单抗治疗化脓性汗腺炎（HS）适应证在美国FDA及欧盟均已获批；重磅在研BTK抑制剂remibrutinib关于治疗慢性自发性荨麻疹（CSU）患者的III期临床试验在近日公布了积极数据，诺华打算自今年下半年开始向全球监管单位提交remibrutinib用于CSU的批准申请；在干燥综合征领域，诺华抗B细胞活化因子受体（BAFF-R）全人源单克隆抗体Ianalumab（VAY736）也是目前全球进展最快，且唯一进入临床III期的靶向BAFF-R抑制剂。 而论管线布局，“自免”标签最鲜明的，是艾伯维和赛诺菲。前者梦想囊获自免多个子赛道“大满贯”，后者紧握手里的自免王牌，正在筹谋一盘自免大棋。 但两者夯实自免领域实力的路径和阶段都不一样。 艾伯维继续坚持采用“爆款策略”，当修美乐遭遇专利悬崖危机时，已巧妙找到了接下来的高增长引擎：口服JAK1抑制剂乌帕替尼和IL-23单抗Skyrizi（瑞莎珠单抗），艾伯维预计两者2027年合计收入将达到270亿美元。尤其是Skyrizi，有望成为第二个百亿“药王”，自2019年全球首次获批之后，基本上以50%左右的年增长率迅速放量。两大产品的适应证布局与拓展之快，而且艾伯维对其进行了银屑病和特应性皮炎等多个大适应证的“头对头”研究，并挑战成功。 赛诺菲尚且还在度普利尤单抗大单品“上分”时代。但2024年及未来，赛诺菲将聚焦于自免领域展开布局版图。 “一哥”之战背后 产品PK，市场之争，“一哥”之战背后，整个自免赛道被赋予了前所未有的“生命力”。 2023年，从所有畅销药营收来看，自免领域创新药的销售体量，已十分接近于肿瘤领域。但不论从患者规模、用药周期，还是从渗透率来讲，自免都还是一个等待被挖掘的超级蓝海赛道，有着广泛未被激活的市场需求，这一赛道几乎占据了所有能够诞生重磅炸弹药物的必备因素：患者基数大、生存期长、用药时间长，一个领域包含百余种不同疾病。 而且难得的是，尽管TNF-α抑制剂一类自免药物销售增速集体趋缓，但近7年，以IL-23、IL-17、JAK、IL4/13 等新靶点重磅药物，其销售集体以高增长态势，展现出了自免赛道独特的“魅力”，且为中国的自免市场引入活力与生机。 典型如诺华的司库奇尤单抗。兴业证券显示，司库奇尤单抗在诺华的强力推动下，在国内2020年、2021年、2022年的销售额分别约5亿元、15亿元和45亿元，占据了国内银屑病生物制剂的主要市场份额，国内银屑患者对于IL-17单抗熟悉度最高。 而“自免四强”在激烈竞争过程中，其实机遇和危机并存，“青黄不接”等风险正倒逼他们通过并购、BD等方式，打造更多自免后备军和全新想象力，这再度为自免行业的快速发展，带来了“刺激”。 强生是最典型的例子，作为业内“老大哥”，他同时面临着核心产品专利到期、FIC产品在遭遇“头对头”挑战后棋逢对手等问题。但在本月，强生已经在焦虑之下，彰显了大闯自免新路的决心。 2023年，强生自免板块业务占比有所下滑。英夫利昔单抗销售额降幅尤其严重；古赛奇尤单抗身处于IL-23抑制剂这一天花板自免赛道，但作为全球首款IL-23单抗药物，其在2023年增速放缓；乌司奴单抗终于突破百亿美元门槛，但其在美国的主要专利正式在2023年到期。 作为核心自免上市产品最丰富、积淀最深的MNC，强生有些急于找回自免高地。于是，2024年，强生的新突破口，定在了进军中重度特应性皮炎和中重度哮喘治疗领域，同时，发挥其打造双抗产品的优势。 5月17日，强生收购自免双抗疗法公司 Proteologix，囊获一款靶向 IL-13 和 TSLP 的双抗，用于治疗中重度特应性皮炎和中重度哮喘，以及另一款靶向 IL-13 和 IL-22 的双抗产品，也用于治疗中重度特应性皮炎。5 月 28 日，强生再度宣布收购另一家自免Biotech，后者的核心资产仍旧双抗药物，适应证同样面向特应性皮炎。 但双抗自免产品，能行吗？还需要最终验证。 另外，努力打造下一个“药王”的艾伯维，同样也有些焦虑。 艾伯维营收主要来源于五大疾病领域，但自免占据了绝对的收入大头。虽然Skyrizi和乌帕替尼大有修美乐接班者之势，但要实现自免“全满贯”，还得继续填补后备力量，同时坚守好爆款专利。 今年以来，艾伯维不止一次与免疫治疗公司达成合作，寻找FIC产品。 回复“V”，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

Novartis secured 79.6 percent acceptance by MorphoSys shareholders during the initial acceptance period, reaching the minimum 65% acceptance thresholdSettlement of the shares tendered during the initial acceptance period is expected to occur on 23 May 2024Additional statutory acceptance period is expected to end on 30 May 2024 at 24:00 hours CESTTransaction strengthens the Novartis pipeline in oncology, adding pelabresib, a late-stage BET inhibitor for myelofibrosis and tulmimetostat, an early-stage investigational dual inhibitor of EZH2 and EZH1 for solid tumors or lymphomas Basel, 16 May 2024 – Today, Novartis BidCo AG, an (indirect) wholly owned subsidiary of Novartis AG, announced the result of its voluntary public takeover offer (the “Offer”) for the shares of MorphoSys AG (“MorphoSys”), including all shares represented by MorphoSys American Depositary Shares (“ADS”). As of the expiry of the acceptance period at 24:00 hours CEST on 13 May 2024, the Offer has been accepted by approximately 79.6 percent of the total share capital of MorphoSys, including purchases by Novartis BidCo AG outside the Offer for approximately 11.6 percent of the share capital. All conditions of the Offer, including the minimum acceptance threshold of 65%, were fulfilled by the end of the acceptance period. The settlement of the shares tendered during the initial acceptance period is scheduled for 23 May 2024. The statutory two-week additional acceptance period for the Offer will commence on 17 May 2024 and end on 30 May 2024 at 24:00 hours CEST and 18:00 hours EDT (also on 30 May 2024). During this time, shareholders who have not tendered their MorphoSys shares, including shares represented by MorphoSys ADS, can still accept the Offer.With all offer conditions fulfilled, Novartis can now begin the necessary steps to progress the integration of MorphoSys, including full access to pelabresib (CPI-0610), a novel BET inhibitor in combination with ruxolitinib for patients with myelofibrosis. The integration also allows full access to tulmimetostat (CPI-0209), an early-stage investigational dual inhibitor of EZH1 and EZH2 currently being tested in patients with solid tumors or lymphomas, as well as a broad portfolio of partnered assets, some of which are in partnership with Novartis, including ianalumab (VAY736). In the context of the integration Novartis continues to progress the workstreams for implementation of both a delisting of MorphoSys and a domination and profit and loss transfer agreement with MorphoSys. Georgeson is acting as information agent for Novartis for the Offer. Deutsche Bank is acting as share tender agent and The Bank of New York Mellon is acting as ADS tender agent for the Offer. The offer document for the Offer and additional information are available at www.novartis.com/investors/morphosys-acquisition. A takeover offer hotline for retail shareholders is available between 9:00-18:00 hours CEST from Monday through Friday at +49 89 38038187 (for German callers) and +44 203 005 6716 (for international callers). A takeover offer hotline for ADS holders is available between 9:00-23:00 hours EDT from Monday through Friday and 12:00-18:00 hours EDT on Saturdays at +1 (866) 356-7344 (for U.S. callers) and +1 (781) 236-4704 (for callers outside the U.S.). Additional Information and Where to Find it This communication is neither an offer to purchase nor a solicitation of an offer to sell shares of MorphoSys. The final terms and further provisions regarding the Offer are available in the offer document published by Novartis BidCo AG (formerly known as Novartis data42 AG) (the “Bidder”). The offer document has been approved by the BaFin and has been filed with the U.S. Securities and Exchange Commission (the “SEC”). The solicitation and offer to buy shares of MorphoSys is only being made pursuant the offer document. In connection with the Offer, the Bidder and Novartis AG have filed Tender Offer Statement on Schedule TO with the SEC (together with the offer document, an Offer to Purchase including the means to tender and other related documents, the “Offer Documents”), the management board and supervisory board of MorphoSys have issued a joint reasoned statement in accordance with sec. 27 of the German Securities Acquisition and Takeover Act and MorphoSys has filed a Solicitation/Recommendation Statement on Schedule 14D-9 with the SEC (together with the joint reasoned statement, the “Recommendation Statements”). THE MORPHOSYS SHAREHOLDERS AND OTHER INVESTORS ARE URGED TO READ THE OFFER DOCUMENTS AND THE RECOMMENDATION STATEMENTS BECAUSE THEY CONTAIN IMPORTANT INFORMATION WHICH SHOULD BE READ CAREFULLY BEFORE ANY DECISION IS MADE WITH RESPECT TO THE OFFER. The Offer Documents and the Recommendation Statements will be distributed to all stockholders of MorphoSys in accordance with German and U.S. securities laws. The Tender Offer Statement on Schedule TO and the Solicitation/Recommendation Statement on Schedule 14D-9 are available for free at the SEC’s website at www.sec.gov. Additional copies may be obtained for free by contacting the Bidder or MorphoSys. Free copies of these materials and certain other offering documents are available on the Bidder’s website at www.novartis.com/investors/morphosys-acquisition or by contacting the Bidder’s investor relations department at +41 61 324 7944. In addition to the Offer to Purchase, including the means to tender and certain other Offer Documents, as well as the Solicitation/Recommendation Statement, MorphoSys and the Bidder will file other information with the SEC. Filings by Novartis AG and the Bidder with the SEC are also available for free to the public from commercial document-retrieval services and at the website maintained by the SEC at www.sec.gov. In order to reconcile certain areas where German law and U.S. law conflict, Novartis AG and the Bidder have requested and received no-action and exemptive relief from the SEC to conduct the Offer in the manner described in the offer document. Acceptance of the Offer by stockholders residing outside Germany and the U.S. may be subject to further legal requirements. With respect to the acceptance of the Offer outside Germany and the U.S., no responsibility is assumed for the compliance with such legal requirements applicable in the respective jurisdiction. DisclaimerThis press release contains forward-looking statements concerning Novartis AG, the Bidder, MorphoSys and the Offer that involve substantial risks and uncertainties. Forward-looking statements include any statements containing the words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “goal,” “may,” “might,” “plan,” “predict,” “project,” “seek,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue” and similar expressions. In this communication, forward-looking statements include statements about the parties’ ability to satisfy the conditions to the consummation of the Offer; statements about the expected timetable for the consummation of the Offer; the plans, objectives, expectations and intentions of Novartis AG and the Bidder; and the financial condition, results of operations and business of MorphoSys and Novartis AG. The forward-looking statements contained in this communication represent the judgment of the Bidder and Novartis AG as at the date of this communication and involve known and unknown risks and uncertainties, which might cause the actual results, financial condition and liquidity, performance or achievements of Novartis AG, or industry results, to be materially different from any historic or future results, financial conditions and liquidity, performance or achievements expressed or implied by such forward-looking statements. In addition, even if the results, performance, financial condition and liquidity of Novartis AG, and the development of the industry in which it operates are consistent with such forward-looking statements, they may not be predictive of results or developments in future periods. Those risks and uncertainties that could cause the actual results to differ from expectations contemplated by forward-looking statements include, among other things: uncertainties as to the timing of the Offer; uncertainties as to how many of the MorphoSys stockholders will tender their stock in the Offer; the possibility that competing offers will be made; the possibility that various conditions for the Offer may not be satisfied or waived, including that a governmental entity may prohibit, delay or refuse to grant approval for the consummation of the Offer; the effects of the Offer on relationships with employees, other business partners or governmental entities; that the Bidder and Novartis AG may not realize the potential benefits of the Offer; transaction costs associated with the Offer; that expectations may be incorrect; the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission, as well as the Solicitation/Recommendation Statement on Schedule 14D-9 to be filed by MorphoSys and the Tender Offer Statement on Schedule TO and related Offer Documents to be filed by the Bidder and Novartis AG. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements. These forward-looking statements speak only as of the date of publication of this communication. The Bidder, Novartis AG and MorphoSys expressly disclaim any obligation to update any such forward-looking statements in this communication to reflect any change in its expectations with regard thereto or any change in events, conditions or circumstances on which any such statement is based or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements, unless specifically required by law or regulation. About Novartis Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide. Reimagine medicine with us: Visit us at https://www.novartis.com and connect with us on LinkedIn, Facebook, X/Twitter and Instagram. Novartis Media RelationsE-mail: media.relations@novartis.com Central North America Anja von Treskow +41 79 392 9697 Michael Meo +1 862 274 5414 Anna Schäfers +41 79 801 7267 Marlena Abdinoor +1 617 335 9525 SwitzerlandSatoshi Sugimoto +41 79 619 2035 Novartis Investor RelationsCentral investor relations line: +41 61 324 7944E-mail: investor.relations@novartis.com Central North America Isabella Zinck +41 61 324 7188 Sloan Simpson +1 862 345 4440 Nicole Zinsli-Somm +41 61 324 3809 Jonathan Graham +1 201 602 9921 Imke Kappes +41 61 324 8269 Parag Mahanti +1 973 876 4912