ABBV-668

尽管在千亿美元免疫赛道持续领跑于一众竞争对手，龙头地位无人能撼动，但“免疫王者”艾伯维仍然没有懈怠——持续打造免疫领域“冠军选手”，在赢取免疫赛场“大满贯”征途中，仍不断培养“冠军选手”或“归化”“种子选手”。艾伯维俨然已经成为免疫赛道的“六边形战士”，多维防御竞争对手发起的一波又一波的挑战。就在3月25日，艾伯维宣布和Landos Biopharma签订最终协议，艾伯维将潜在斥资超过2亿美元收购Landos——一家专注为自身免疫性疾病患者开发口服疗法的临床阶段的生物公司。Landos的主打项目NX-13是一款潜在“first-in-class”口服NLRX1激动剂，旨在治疗溃疡性结肠炎（UC），目前已进入临床2期阶段。这也是新年伊始，艾伯维在免疫领域的第二个大动作。而1个月前的2月28日，艾伯维和免疫治疗公司OSE Immunotherapeutics 宣布达成战略合作伙伴关系，共同开发 OSE-230──一种旨在解决严重慢性炎症性疾病的单克隆抗体。与此同时，刚刚结束的2024美国皮肤科学会年会和2024欧洲克罗恩病和结肠炎组织年会上，艾伯维也有大动作——公布了乌帕替尼在皮科和消化领域的研究进展，均引人瞩目。频频出手的艾伯维，再度吸引了业内的目光。作为免疫赛道的“六边形战士”，艾伯维如同乒乓赛场的中国队，一直以擅长培育“冠军选手”著称，不仅拥有“冠军选手”修美乐、还有“种子选手”Skyrizi和乌帕替尼，共同“征战”免疫领域不同赛场赢取“大满贯”，同时在“梯队建设”上，也不断完善“后备人才”方阵。竞争对手短时间内要威胁艾伯维的免疫王者位置实在不易。01“冠军选手”接力从修美乐，到“双子星”Skyrizi和乌帕替尼，艾伯维在培养“冠军选手”和“种子选手”的能力上，一直为业界瞩目。2023年，艾伯维的3款自免产品均进入免疫赛道产品销量前十，也是唯一一家3款免疫产品全部进入销量前十的药企。其中，已蝉联11年“药王”的修美乐以144.04亿美元的销量，再度问鼎2023免疫赛道药王。“种子选手”Skyrizi和乌帕替尼分别以77.63亿美元和39.69亿美元，分列免疫赛道产品销量的第四和第七位。一方面，艾伯维通过持续对修美乐进行创新挖潜，把修美乐这一“药王”级的创新药价值做到极致的；另一方面，艾伯维着力打造具有接棒修美乐能力的“种子选手”，无论是自己“培养”的选手乌帕替尼，还是“归化”选手Skyrizi，均成长速度惊人，已可独挡一面。Skyrizi和乌帕替尼已连续8个季度增长超过50%，从2019年时候的两者合计收入4亿美元，迅速增长至2023年的合计117亿美元。根据Evaluate Pharma的最新预测，2024年Skyrizi销量将接近100亿美元，有望成为艾伯维培育的第二个百亿“药王”。艾伯维预计两者2027年合计收入将达到270亿美元，为艾伯维继续在免疫赛道驰骋提供了充足的动力。虽然其他头部药企不乏自家的“优秀选手”，也不断发起对艾伯维免疫王者地位一波又一波的挑战。然而，从整体表现来看，艾伯维去年凭借整体优势，轻松赢下了王者之战——其免疫管线营收261.36亿美元，比排名第二的强生高出80多亿美元，并远远超过排在第三和第四位的赛诺菲和诺华的营收总和。02免疫赛场“大满贯”在免疫赛场，艾伯维一直展示着自己的统治力。从TNF-α到白介素抑制剂、JAK抑制剂，从皮科到消化、免疫等不同子领域，布局于不同靶点的3个“冠军选手”和“种子选手”，让艾伯维在“大满贯”的路上，一路生花。在TNF-α抑制剂中，艾伯维的修美乐一直占据第一把交椅，涵盖三大主流自身免疫疾病领域多个适应症，包括类风湿关节炎、银屑病关节炎、强直性脊柱炎、克罗恩病、溃疡性结肠炎等。这个初代“冠军选手”，在20年时间里，为艾伯维带来的收入累计超过2000亿美元。乌帕替尼是一款每日口服一次的JAK1选择性小分子抑制剂，艾伯维将其视为修美乐的继任者之一。乌帕替尼也不负众望，在美国和中国一举拿下7个适应症。除去适应症的拓展，艾伯维也一直在深挖乌帕替尼的潜力。在2024美国皮肤科学会年会和2024欧洲克罗恩病和结肠炎组织年会上，艾伯维分别公布了乌帕替尼在相关领域的最新进展，无不体现出“种子选手”的实力。另一款“种子选手”Skyrizi是一种白细胞介素-23(IL-23)抑制剂。目前，Skyrizi已有斑块型银屑病、银屑病关节炎和克罗恩病3个适应症在美国获批。Skyrizi也有望被引入中国。在一场与乌司奴单抗的PK中（克罗恩病患者中的头对头研究），无论是在临床缓解，还是内镜缓解率上，Skyrizi都赢得了更好的表现。03完备的“梯队建设”凭借初代“冠军选手”打下的江山，艾伯维不断培养出接棒的“种子选手”，在免疫赛场上不断荣誉加身。不过这些并没有让艾伯维沉浸在过去的成绩里，如何赢得未来，才是艾伯维考虑的。有着完备的体系和底蕴，在培养“后备力量”上，艾伯维显然得心应手。艾伯维两款完全自研的免疫学产品Lutikizumab和ABBV-668均已进入2期临床。在今年1月，Lutikizumab治疗成人中重度化脓性汗腺炎的2期临床取得积极结果，基于此，艾伯维进一步将Lutikizumab推进到3期临床。ABBV-668是艾伯维开发的苏氨酸蛋白激酶（RIPK）抑制剂，2期临床也有望在明后两年内完成。除了自己培养，凭借多年赛道深耕的阅历和眼光，艾伯维也在不断“归化”“种子选手”，撬动高价值产品，从而重塑和巩固自身实力，比如最成功的“归化选手”Skyrizi。就在本周，艾伯维和Landos Biopharma达成协议，艾伯维潜在斥资超过2亿美元收购Landos。其主打产品NX-13是一款潜在“first-in-class”口服NLRX1激动剂。收购完成后，艾伯维将获得更多治疗免疫系统相关疾病的药物，有望进一步扩充其“种子选手”阵营。此外，今年年初，艾伯维接连宣布与OSE Immunotherapeutics和Tentarix Biotherapeutics达成合作。与OSE Immunotherapeutics的合作，让艾伯维获得了一款严重慢性炎症性疾病在研新药OSE-230的开发、生产以及商业化全球独家许可权利。与Tentarix biotheraptics的合作，将把艾伯维在肿瘤学和免疫学方面的专业知识与Tentarix的专有Tentacles平台相结合。虽然千亿美元免疫赛道强者众多，目前处在一个新老交替、列强纷争的时代。但凭借“冠军选手”和“种子选手”的表现，艾伯维在免疫赛场的统治力仍将持续。艾伯维已然认识到“梯队建设”的重要性，从自研创新到收购引入，艾伯维早已布局未来“新生力量”，将六维雷达图边框“拉满”，“六边形战士”的统治地位难以被撼动。

AbbVie already has blockbuster drugs for ulcerative colitis, but that isn’t stopping the pharmaceutical giant from trying to expand its scope in this disease. To that end, the company is acquiring Landos Biopharma, a clinical-stage biotech whose lead asset brings a different approach to treating this prevalent inflammatory disorder of the gut. According to deal terms announced Monday deal, AbbVie will pay $20.42 for each share of Blacksburg, Virginia-based Landos, which represents a 155% premium to the biotech’s closing stock price on Friday. Landos’s drug, named NX-13, is a small molecule designed to target and activate the NOD-like receptor X1, or NLRX1. This receptor is associated with the modulation of inflammatory proteins involved in ulcerative colitis and Crohn’s disease. As a once-daily oral drug, NX-13 would provide a more convenient dosing alternative to many inflammatory bowel disorder drugs that are administered as injections or infusions, including some products currently marketed by AbbVie. In a Phase 1b test enrolling patients with active ulcerative colitis, the Landos drug posted results showing it was safe and well tolerated across a range of doses. Furthermore, the results showed signals of clinical improvement. Results were published last November in the Journal of Crohn’s and Colitis. A placebo-controlled Phase 2 proof-of-concept clinical trial is underway testing two doses of the drug. The study has a targeted enrollment of 80 patients who have moderate-to-severe ulcerative colitis. Preliminary data are expected in the fourth quarter of this year. “With this acquisition, we aim to advance the clinical development of NX-13, a differentiated, first-in-class, oral asset with the potential to make a difference in the lives of people living with ulcerative colitis and Crohn’s disease,” AbbVie’s Roopal Thakkar, senior vice president, chief medical officer, global therapeutics, said in a prepared statement. AbbVie brings several different approaches to the intestinal inflammation, irritation, and ulcers caused by ulcerative colitis. Humira an antibody drug designed to bind to and block tumor necrosis factor alpha, a protein associated with several inflammatory disorders. Rinvoq, approved for both Crohn’s disease and ulcerative colitis, belongs to a class of drugs that block a different set of inflammatory proteins called Janus kinases. The antibody drug Skyrizi blocks IL-23, a signaling protein associated with inflammation. Skyrizi, whose approved indications include the treatment of Crohn’s disease, is currently under regulatory review for ulcerative colitis. The AbbVie pipeline includes ABBV-668, a RIPK1 inhibitor currently in Phase 2 testing in ulcerative colitis. AbbVie also holds an option to a biologic drug that Calibr, a division of Scripps Research, is developing for inflammatory bowel disease. This program is in Phase 1 testing. Founded in 2017, Landos was one of the first startups in Xontogeny, an accelerator run by Chairman and CEO Chris Garabedian, a biotech industry veteran. While the per share price of AbbVie’s Landos acquisition is a premium to its closing stock price last Friday as well as its $16 per share IPO price in 2021, the biotech’s shares have not traded anywhere near that price for more than two years. Last May, the company completed a 1-for-10 reverse stock split that consolidated shares in order to boost the stock price to maintain compliance with the Nasdaq’s listing requirements. On a split-adjusted basis, the per-share acquisition price is still below Landos’s IPO price. However, Landos shareholders could receive more. The deal includes a contingent value right that will pay up to $11.14 per share, adding $75 million to the purchase price. That additional payment is tied to the achievement of a clinical development milestone. In a regulatory filing, Landos said the milestone is the start of Phase 3 testing of NX-13 or any other drug candidate addressing the NRLX1 pathway for the treatment of ulcerative colitis. This study must start before March 31, 2029, according to the agreement. In research note sent to investors on Monday research, Leerink Partners analyst Thomas Smith wrote that Landos is a logical strategic fit for AbbVie, providing the pharma giant with optionality in its inflammatory bowel disorder pipeline for a relatively modest upfront cash payment. While acknowledging some overlap with AbbVie’s Rinvoq, Skyrizi, and Humira as well as the clinical-stage assets for inflammatory bowel disease, Smith said Leerink believes there is high probability of the acquisition closing and low risk of opposition from the Federal Trade Commission.