Risankizumab-RZAA

iStock, Artem_Egorov With immunology and inflammation blockbusters like AbbVie’s Skyrizi and Rinvoq reeling in nearly $7 billion combined in the third quarter, the pipeline-in-a-product strategy has never been more attractive. Last year, biotech executive and entrepreneur Andrew Pannu told BioSpace that immunology and inflammation could be a particularly attractive therapeutic space because of its “pipeline-in-a-product” potential. It’s a playbook many biopharma companies—including Novartis and Vertex—appear increasingly keen to operate by. In one of 2024’s biggest acquisitions—and Vertex’s largest-ever—the Boston-based pharma subsumed immunotherapy player Alpine Immune Sciences and its lead asset povetacicept for $4.9 billion. A dual antagonist of the BAFF and APRIL cytokines for autoimmune and inflammatory diseases, povetacicept is currently being studied in Phase III and Phase II/III trials for IgA nephropathy (IgAN) and primary membranous nephropathy, respectively, and Vertex said in a press release last month that it has “pipeline-in-a-product potential across a range of B cell–mediated diseases.” This is also a strategy echoed in the immunology and inflammation (I&I) space by Novartis, which recently presented Phase III data for ianalumab in Sjögren’s disease at the American College of Rheumatology Convergence congress. If approved, it would be the first targeted treatment for this common rheumatic autoimmune disease. But Novartis isn’t stopping there. Ianalumab, a B cell–depleting antibody that, like povetacicept, targets the BAFF receptor, is also in mid- to late-stage development for systemic lupus erythematosus (SLE), lupus nephritis and systemic sclerosis as well as earlier-stage development for three hematological indications. “We’ve had this common theme around saying that when we understand a drug and its mechanism of action, we will evaluate it in multiple indications simultaneously,” Shreeram Aradhye, president of development and chief medical officer at Novartis, told BioSpace last month. The company took the same approach, Aradhye said, with remibrutinib, which was approved by the FDA in September as Rhapsido, the first BTKi drug for chronic spontaneous urticaria (CSU). Elsewhere in the pipeline, the company is also studying remibrutinib in pediatric chronic spontaneous urticaria, hidradenitis suppurativa, multiple sclerosis and food allergy, among other indications. “Having an asset where we understand the mechanism of action, making sure that we garner its full value by evaluating it in multiple places where it could help in ambitious parallel programs that are being run, has also worked out well for us,” Aradhye said. Biogen, too, has spent big money to expand its presence in I&I. In May 2024, the big biotech snapped up Human Immunology Biosciences , aka HI-Bio, for up to $1.8 billion. At the center of the deal was felzartamab, whose mechanism of selectively depleting CD38+ cells could give Biogen “applicability across a range of immune-mediated diseases,” BMO Capital Markets analysts wrote in a note to investors at the time. With the global immunology market projected to exceed $257 billion by 2032, it’s no wonder so many companies are looking to optimize their shots on goal. Proof Is in the Market If I&I–focused companies need additional incentive to embark on this strategy, they need look no further than AbbVie. In the third quarter, the company’s two-headed immune blocking behemoth—made up of Skyrizi and Rinvoq—brought in nearly $7 billion combined, accounting for almost half of AbbVie’s income for the quarter. Together, the two drugs cover a host of immune-mediated diseases. Skyrizi is indicated for plaque psoriasis, psoriatic arthritis, Crohn’s disease and ulcerative colitis, while Rinvoq is approved to treat rheumatoid arthritis, atopic dermatitis and ankylosing spondylitis. Rinvoq’s reach could soon expand further, with recent successful Phase III data in alopecia areata and vitiligo . And of course, Skyrizi and Rinvoq are successors of AbbVie’s Humira—which long held the title of the world’s top-selling drug. The blockbuster held FDA approvals in upwards of 15 autoimmune and inflammatory diseases since its initial greenlight for rheumatoid arthritis in 2002 . In an interview with BioSpace , Graig Suvannavejh, managing director of Equity Research at Mizuho Securities, pointed to another prime example of I&I single product success: Sanofi and Regeneron’s Dupixent . A dual inhibitor of IL-4 and IL-13 signaling, Dupixent is approved in the U.S. to treat eight inflammation-driven diseases, including atopic dermatitis, chronic obstructive pulmonary disease and asthma. In the third quarter, Sanofi reported €4.2 billion ($4.8 billion), the first time the antibody has exceeded the €4 billion mark in a single quarter. Earnings AbbVie’s Immunology Dyad Dominates Again in Q3 Skyrizi and Rinvoq made nearly $7 billion combined, almost half of the company’s income for the quarter alone. October 31, 2025 · 2 min read · Dan Samorodnitsky Build a ‘Better Mousetrap’ While the pipeline-in-a-product strategy is leveraged across other therapeutic spaces—think Keytruda in oncology—I&I presents a unique opportunity, experts told BioSpace . “The key thing about immunology is that a lot of these diseases . . . they present with very, very different symptomatology, and what the cause of the disease is and what autoantibodies involved are all different, but there are centralized mechanisms that you can leverage with a single product,” said Myles Minter, biotech analyst and partner at William Blair. A company can prove safety in one indication, he continued, “and then expedite the development as a pipeline in a product in subsequent indications.” Further, Minter said, once these pathways are established, the opportunity exists to improve upon original drugs with next-generation models. “You’ve also got this pathway that’s been set by predecessor compounds, that the biology actually plays out. It’s just, can you do it in a better way? And that’s where we’re seeing all these next-generation therapies come through.” Minter offered the example of Roche’s Rituxan (rituximab), first approved for non-Hodgkin lymphoma in 1997, and for a variety of other cancers and inflammatory diseases since. Minter described Rituxan as “quite a brutal therapy.” He explained, “It will deplete your B cells, but it is efficacious when it works.” Now, on the B cell modulation side, Vertex and other companies are focused on candidates such as povetacicept that inhibit BAFF and APRIL—two targets expressed on the various B cells responsible for autoantibody production in many autoimmune diseases. Novartis’s ianalumab also targets the BAFF receptor. It’s a strategy that has worked before. Suvannavejh pointed out that Humira was not the first drug to block tumor necrosis factor (TNF)—it was just the most effective. Humira was preceded in the market by J&J’s Remicade and Amgen’s Enbrel, “but . . . it’s really Abbott and then AbbVie that kind of perfected the model, and I think they just had a better mousetrap for blocking TNF alpha.” The range of diseases that can be targeted in I&I is also quite broad, Minter noted. “Inflammation and immunology spans a lot of different indications, and it gives you an option to go either after very prevalent diseases,” such as atopic dermatitis and plaque psoriasis. “Or you can go into increasingly rare disease opportunities,” where he sees Vertex and Biogen heading with their respective pipelines. Of course, no matter how plentiful the opportunities—or the company’s cash on hand—it is important to be “somewhat capital efficient,” Minter said. “You can’t just put a drug into every single indication that comes in your head and do it all at once.” On that note, there are key indications the biggest players are prioritizing. Minter highlighted IgAN, the lead indication for povetacicept. Novartis won FDA approval last year for Fabhalta, the first complement inhibitor for the reduction of proteinuria in primary IgAN . Suvannavejh, meanwhile, pointed to atopic dermatitis, rheumatoid arthritis, psoriasis, asthma, chronic obstructive pulmonary disease (COPD) and ulcerative colitis. For Suvannavejh, the common theme between Humira and Dupixent and similar drugs is that they broadly target common pathways of inflammation across the skin, gastrointestinal and other organ systems. “There are X number of cellular cytokines and mediators of inflammation, and if you can find that widget that can block inflammation, then you have the potential of working in lots of different conditions,” he said, “because inflammation is everywhere.” Business 5 Biotechs Taking the Pipeline-in-a-Product Approach to Drug Development The platform strategy of using one molecule to target an underlying biological pathway to address many different diseases can be a goldmine for smaller companies. But it also has a unique set of challenges. August 20, 2025 · 10 min read · Tristan Manalac

作者 | 草履虫 编辑 | 郑瑶 据公开资料，2025年第二季度，全球生物医药行业一级市场融资事件数同比下降41.1%，融资总额同比下降28.3%，不少明星项目也陷入“B轮死”的尴尬。 然而，真正的猎手善于在寂静中寻找机会，将子弹射向那些能穿越周期、定义未来的硬核地带。 01肿瘤：放弃重磅炸弹，聚焦技术平台 2025年，推动药企收购或BD交易的动因已从追求短期收入增长的“重磅炸弹”药物，转向构建长期技术能力的平台型资产。 这一转变背后的原因显而易见。一方面，大型药企需要抵御即将到来的专利悬崖风险；另一方面，监管机构日益认可那些具备灵活性与可扩展性的技术平台——这类平台更适用于联合疗法开发及适应性临床试验设计。 与传统单一资产开发相比，技术平台具有“一对多”优势。多特异性支架、ADC连接子、RNA引导递送及降解剂化学等技术，能够为产品线注入可衍生出多个研发项目的潜力。 诺华自2017年起通过收购Advanced Accelerator Applications和Endocyte等企业，快速建立核药领先地位，打造“诊断-治疗”一体化生态。2024年5月，其以10亿美元预付款收购Mariana Oncology，进一步强化布局。 目前，诺华多款核药已实现商业化突破，Lutathera 2024年全球销售额达7.24亿美元，并已在中国提交临床申请；Pluvicto在2025年上半年销售额达8.25亿美元，同比增长26%。 平台化策略正在成为应对专利悬崖的利器。 其中，大幅缩短药物发现周期，降低研发成本的AI驱动药物发现平台备受青睐。 2025年，默克宣布与加拿大AI制药公司Variational AI达成协议，潜在交易总价值达3.49亿美元，默克将利用其AI药物发现平台设计和优化针对两个未公开靶点的小分子候选药物。 2025年，晶泰科技与DoveTree达成一项高达59.9亿美元的超级合作，专注于发现和开发新型小分子药物，该合作直接推动了公司2025年上半年的业绩爆发，彰显了AI驱动药物发现平台的巨大商业潜力。 此外，精准靶向技术是另一个资本重点布局领域。放射性配体疗法（RLT）作为精准靶向的代表，正迎来快速发展期。一篇发表在Nature Reviews Drug Discovery上的文章显示，目前全球有超过60个RLT管线处于临床开发阶段（图1）。 图1.临床阶段放射配体疗法中使用的放射性同位素；图片来源：Nature Reviews Drug Discovery 下一代RLT技术正在向多元化方向发展。在放射性同位素方面，除了已广泛应用的Lu-177外，Actinium-225和Lead-212等新型同位素显示出更好的疗效和安全性（图1）。在靶向配体方面，工程蛋白和抗体衍生物正在超越传统抗体，实现更好的肿瘤靶向性。 值得注意的是，2025年，跨境并购成为肿瘤领域的显著特征，跨境合作能够利用不同市场间的估值差异实现战略收益。同时，通过获取不同地区的监管经验和市场入口，并加速全球同步申报的进程。 德国BioNTech公司收购中国的普米斯生物与德国的CureVac公司、阿斯利康收购瑞士的EsoBiotec公司、大鹏药品收购Araris Biotech AG公司，每一笔交易都凸显出全球药企正积极布局，以获取临床试验渠道、生产基地以及区域性监管等优势，同时也反映了市场对跨境技术整合的高度认可。 02自免：新靶点、新形式、新适应症多线推进 自免市场是仅次于肿瘤的第二大市场。据Frost & Sullivan数据统计，2022年全球自免市场规模为1323亿美元，到2030年，全球自免市场将达1767亿美元，其中生物药市场为1450亿美元，占比高达82.1%。 图2.自免市场规模（亿美元）及增速（%）；图片来源：华创证券研报 市场的支付能力已经过验证，在2024年全球十大畅销药中，自免药物占据三席，数量上超过了肿瘤药物。赛诺菲的度普利尤单抗、艾伯维的利生奇珠单抗和强生的乌司奴单抗，这三款“百亿美元俱乐部”成员，共同勾勒出一个高价值、高增长且需求持续旺盛的市场轮廓。 当前，自免领域最引人注目的技术趋势是T细胞衔接器（TCE）的崛起。其通过“双靶点桥接”，一端靶向B细胞表面抗原，另一端结合T细胞表面的CD3分子，精准激活人体自身免疫系统来清除致病细胞。 相较于传统药物无差别地抑制免疫系统，TCE能更精确地靶向异常活化的B细胞；与依赖毒性载荷的ADC药物相比，TCE依靠激活T细胞，理论上具有更好的安全性；相比流程复杂、价格高昂的CAR-T疗法，TCE作为一种现货型药物，成本更低，更易于推广。 巨大的治疗潜力使TCE成为MNC争相布局的战略要地。2025年6月，和铂医药将其BCMAxCD3双特异性TCEHBM7020授权给日本大冢制药，HBM7020具备非对称结构，能够有效解决轻链错配挑战，展现出了良好的安全性与成药性。 2024年11月，维立志博与风险投资公司Aditum Bio宣布成立新药研发公司 Oblenio Bio，维立志博将其CD19/BCMA/CD3三特异性TCE LBL-051授权给OblenioBio，共同推进项目开发。 另外，为构建长期竞争力并规避同质化风险，资本在自免领域的布局正沿着靶点创新、形式优化、适应症拓展三个方向深化。 当前TCE的靶点主要集中在CD19、BCMA等成熟靶点上，未来的突破有赖于向新靶点拓展，借鉴CAR-T疗法在肿瘤领域的经验，CD22、BAFF-R等靶点也具备向自免领域转化的潜力。 此外，药物形式正超越传统的双抗，向三抗甚至多抗TCE演进，以期通过多靶点协同提升疗效并克服耐药性。嘉和生物将其CD3/CD20双抗GB261授权给TRC，其“非对称”结构设计是通过降低CD3端亲和力，减少细胞因子风暴（CRS）发生率，同时保留抗体依赖的细胞介导的细胞毒作用；与此同时，自免药物的研发不再局限于类风湿关节炎、银屑病等传统领域，正迅速覆盖更多未被满足的临床需求。 科伦博泰与和铂医药将联合开发的TSLP抗体HBM9378授权给Windward，用于治疗哮喘和慢性阻塞性肺疾病（COPD），通过拓展呼吸系统等新的自免疾病领域来挖掘市场潜力，交易金额达9.7亿美元。 03GLP-1：挖掘细分领域，追求差异化创新 目前，减重市场已形成诺和诺德与礼来双巨头垄断格局，市占率接近97%。投资人正将目光从同质化竞争转向差异化创新，聚焦于口服制剂、超长效技术、多靶点药物、组合疗法及适应症拓展等细分方向（图4）。 提高患者用药便利性与依从性，是GLP-1药物迭代的重要方向。目前，主流研发聚焦于“口服制剂”与“超长效制剂”。口服GLP-1药物主要包括小分子与多肽两类。礼来的Orforglipron在全球口服小分子中进展最快，预计今年年底递交上市申请（图3），国内企业如恒瑞医药、华东医药、闻泰科技等也在该领域积极布局，部分管线已进入临床中后期，展现出较强的出海潜力。 图3.主要GLP-1小分子专利结构；图片来源：华泰证券研报 在长效化方面，司美格鲁肽与替尔泊肽已实现每周给药，而下一代”超长效制剂”则致力于将给药周期延长至每两周甚至每月一次。安进的Maridebart cafraglutide（MarITide）作为每月一次给药的GLP-1/GIP双靶点药物，二期数据显示其52周减重效果可达约20%，且安全性良好。 此外，随着市场对减重效果要求的提升，单一GLP-1靶点已难以满足“高质量减重”的需求。“多靶点激动剂”通过协同激活或抑制多个代谢相关受体，实现“抑制食欲+加速代谢+器官保护”的协同机制，在减重效果与代谢综合改善方面显著优于单靶点药物。 图4.MNC下一代减重药物管线布局；图片来源：开源证券研报 礼来的替尔泊肽（GLP-1/GIP）与Retatrutide（GLP-1/GIP/GCGR）、信达生物的玛仕度肽（GLP-1/GCGR）等是其中的代表。 此外，GLP-1与FGF21的联用也在探索用于改善血脂异常和治疗MASH等适应症，华东医药的GLP-1/GCGR/FGF21三靶点药物DR10624即为FIC布局。 “组合疗法”是另一大创新方向，旨在实现“减脂增肌+代谢修复”。GLP-1类药物在减重的同时常伴随肌肉流失，而联用ActRII（激活素受体II）或MSTN（肌肉生长抑制素）靶点药物，有望在减重的同时保留甚至增加瘦体重。礼来通过收购Versanis获得了ActRIIA/B单抗Bimagrumab，其与GLP-1联用的临床试验正在进行中。 国内来凯医药在ActRII靶点布局领先，其LAE102已进入临床阶段。此外，GLP-1与胰淀素（AMYR）类似物或外周限制性CB1拮抗剂的联用，也在探索增强疗效与改善安全性的潜力。 04结语 在肿瘤、自免与GLP-1的深水区，技术平台、精准免疫与差异化疗法正悄然重塑全球医药领域未来。 参考资料： [1] https://www.nature.com/articles/d41573-025-00096-w [2]华创证券研报、华泰证券研报、开源证券研报 [3]各企业官网及各种公开资料等 END 内容沟通：Xinmeitizhongxin- 商务合作：13810647732