Tulisokibart

编者按：过去10余年间，美国FDA批准了10多款炎症性肠病（IBD）创新疗法。作为医药和生命科学产业创新的赋能者，药明康德很高兴能为多款IBD疗法赋能，助力这些创新疗法的问世，造福病患。与此同时，产业界正在不断寻求新型疗法，持续改善患者的生活质量。药明康德也将持续为合作伙伴提供从研究、开发到生产的全链条服务，加速IBD新药从实验室到临床的研发进程。炎症性肠病（简称IBD）领域在过去一年诞生了多项高额授权合作及交易。比如：2024年7月，礼来（Eli Lilly and Company）以总额约32亿美元收购Morphic Holding，并获得后者主打项目MORF-057（一款选择性口服小分子α4β7整合素抑制剂）用以开发治疗IBD；2024年6月，艾伯维（AbbVie）与明济生物达成一项总额约17.1亿美元的合作，共同开发处于临床前阶段的下一代TL1A抗体FG-M701，用于治疗IBD。同一年，艾伯维还先后收购Celsius Therapeutics和Nimble公司，前者主打项目为一款TREM1靶向抗体，拟开发治疗IBD；后者主打项目同样是一款IBD领域新药，为口服肽类IL-23受体抑制剂。IBD成为新药研发领域的焦点，源于其持续加重的疾病负担。根据全球疾病负担估计，全球有超过680万人受到IBD困扰。IBD属于炎症性慢性自身免疫性疾病，最常见的类型包括克罗恩病和溃疡性结肠炎。国际权威期刊Nature今年5月发表的文章指出，IBD疾病的流行范围正在蔓延，已成为一场全球性的健康挑战。IBD以肠道慢性炎症为特征，患者长期遭受腹痛、腹泻、直肠出血、疲劳和体重下降等症状的困扰，长期炎症还可引发纤维化等并发症，甚至可能发展为肠癌。由于发病机制复杂，这类疾病至今没有治愈手段。IBD患者常常面临着反复发作的症状，病程长且反复，带来长期的痛苦，因此IBD也有“绿色癌症”之称。自从上世纪40年代IBD疗法首次出现突破以来，业界已通过多种糖皮质激素、免疫抑制剂以及近些年的新型小分子药物缓解IBD症状，极大改善了患者的生存状况。尤其进入20世纪80年代末，靶向促炎细胞因子——肿瘤坏死因子（TNF）的单克隆抗体首次获批用于治疗克罗恩病，开启了靶向生物制剂的治疗时代。目前，用于IBD治疗的生物制剂主要包含TNF抑制剂、整合素抑制剂以及白细胞介素（IL）抑制剂等。最近十年，新型小分子药物不断涌现，为IBD治疗提供了新的选择。其中，Janus激酶（JAK）抑制剂和鞘氨醇-1-磷酸（S1P）受体调节剂是发展较为迅速的两类小分子药物。目前已有泛JAK抑制剂和选择性JAK1抑制剂获批，用于溃疡性结肠炎或克罗恩病的治疗。S1P受体调节剂是另一类小分子IBD疗法，已获批的S1P受体调节剂通过切断淋巴细胞前往炎症部位的道路，有效缓解溃疡性结肠炎。注：根据公开资料梳理，为不完全统计临床需求催生更多新兴疗法受限于IBD复杂的发病机制，大多数患者仍无法通过现有药物实现持久的疾病缓解。Pharmaceuticals杂志今年1月综述指出，临床及真实世界数据显示，单一药物的有效率很少超过60%。这一现状促使科学界在优化现有疗法的同时，持续探索IBD炎症机制，开拓新靶点和新型治疗手段。根据公开资料梳理，目前全球有100多款在研新药正在临床阶段探索治疗IBD的疗效和安全性。这些临床在研管线以抗体和小分子药物为主，且不断涌现出新靶点和新机制药物。在小分子药物领域，除了JAK、SIP等已经过临床验证的靶点，还包括TYK2、PDE4、RIPK1、NLRX1、miR-124等靶点的管线。例如Abivax公司在研的obefazimod正在开展溃疡性结肠炎3期临床研究。它能够增强炎症反应天然调节剂microRNA-124的表达，进而抑制许多炎症反应介导物的生产，有望成为一种利用人体自然调节机制调节慢性炎症患者免疫反应的新兴疗法。在抗体类在研IBD药物领域，除了已经临床验证的IL-12/23、α4β7整合素外，还涵盖多种新兴靶点如TL1A、TREM1、CCR9、PSGL-1、IL7R、OSMRβ、NKG2D等。比如TL1A靶点领域近年来诞生了多项高额授权合作。在这一靶点领域，赛诺菲（Sanofi）与梯瓦（Teva）共同开发的duvakitug、罗氏（Roche）在研的afimkibart（RO7790121）、默沙东（MSD）在研的tulisokibart等均已进入3期临床研究阶段。产业携手，突破IBD新药研发挑战，为IBD患者带来新的希望然而，IBD新药研发仍然面临诸多挑战。《自然》子刊Nature Reviews Drug Discovery去年发表综述指出，IBD新药研发在靶点识别、临床前研究、临床试验中的各个环节均面临较大的挑战。比如在靶点识别方面，IBD发病机制的多层级、复杂性，使得目前仍缺乏可预测治疗反应的生物标志物；在临床前研究方面，目前的实验模型仍然存在局限性；在临床试验中，受试者筛选的复杂性、研究设计的复杂性、临床研究终点的不确定性等诸多因素，都使得临床试验的成功率不高。面对挑战，产业界正通过全球生态圈合作，加速研发突破，致力于为患者带来更好的治疗方案。其中，合同研发和生产机构（CXO）在其中发挥着重要作用。作为创新的推动者、客户信赖的合作伙伴以及全球健康产业的重要贡献者，药明康德通过独特的CRDMO业务模式，不断降低研发门槛，助力客户提升研发效率，为患者带来更多突破性的治疗方案。例如，在IBD候选新药筛选环节，药明康德持续为合作伙伴提供基于DNA编码化合物库（DNA encoded library, DEL）技术的筛选服务，助力高效、可靠地发现具治疗潜力的IBD新型分子。在今年4月发表的一项研究中，药明康德助力研究者筛选出了具有IBD治疗潜力的BET蛋白抑制剂候选分子，有望带来更高效安全的疗法。再以药理药效研究为例，根据公开信息，药明康德生物学业务平台在IBD新药临床前药理药效研究方面提供一站式服务，助力客户加速新药研发进程。为助力生物医药领域合作伙伴在IBD领域的新药开发，该平台以不同诱导方式构建了多种类型的IBD体内药理药效模型来模拟临床不同的场景。同时，在多个热门靶点（如JAK抑制剂、TNF-α抗体、S1P1受体抑制剂、IL-6/18抗体等）上进行了模型的药理药效验证。随着生物科技的进步以及对IBD发病机理的探索，将推动这一治疗领域的持续发展，为IBD患者带来治愈的希望。学术界的研究也指出，对于IBD的未来管理，预防是关键。多样化的预防策略能极大减轻IBD在全球范围内日益增长的健康负担。随着新疗法的不断涌现和研究的深入，我们期待看到更多有效的IBD治疗选择。我们同样期待，药明康德通过一体化、端到端的CRDMO平台，能够助力全球合作伙伴为包括IBD在内的自身免疫性疾病带来更多创新治疗选择。推荐阅读停药后有望长期缓解！《自然》子刊：这些自身免疫性疾病患者，更适合CAR-T疗法“首例”患者已恢复正常生活！《柳叶刀》：CAR-T治疗自身免疫疾病再获突破《柳叶刀》重磅：首个！CAR-T细胞疗法成功治愈这种自身免疫性疾病！参考资料（可上下滑动查看）[1] Hracs, L., Windsor, J.W., Gorospe, J. et al. (2025) Global evolution of inflammatory bowel disease across epidemiologic stages. Nature. doi: 10.1038/s41586-025-08940-0.[2]Honap S, Jairath V, Danese S, Peyrin-Biroulet L. (2024) Navigating the complexities of drug development for inflammatory bowel disease. Nat Rev Drug Discov. doi:10.1038/s41573-024-00953-0[3]Petronio L, Dal Buono A, Gabbiadini R, Migliorisi G, Privitera G, Ferraris M, Loy L, Bezzio C, Armuzzi A. (2025)Drug Development in Inflammatory Bowel Diseases: What Is Next? Pharmaceuticals (Basel).doi: 10.3390/ph18020190.[4] Yeo-Jin Jeong et al., KB-0118, A novel BET bromodomain inhibitor, suppresses Th17-mediated inflammation in inflammatory bowel disease. Biomedicine & Pharmacotherapy, DOI: 10.1016/j.biopha.2025.117933. [5]多重机制减轻炎症！全球数百万人深受困扰，这种慢性疾病有望迎来全新抑制剂. Retrieved Apr 7，2025, From https://mp.weixin.qq.com/s/7fR51PV5Zx3ZD4tZM26BaQ[6]“绿色癌症”的药物研究进展及相关动物模型. Retrieved Nov 18，2024, From https://mp.weixin.qq.com/s/5nhJbUQpp7elicgH6Qfn-g版权说明：本文欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权或其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。分享，点赞，在看，传递医学新知

iStock, Prostock-Studio R&D spending across the global pharmaceutical sector climbed 1.5% in 2024, according to unreleased data from Evaluate Pharma. Even with strong macro headwinds —inflation, rising costs, geopolitical tensions —the global pharmaceuticals industry continued to pump more money into R&D investments in 2024. That’s according to data from analyst firm Evaluate Pharma, which in an email gave BioSpace a sneak peek at their World Preview 2025 report, set to be published in June 2025. Pharma R&D spending in 2024 grew by 1.5%, a relatively modest jump by the industry’s own standards, considering that from 2022 to 2023, budgets soared 11.5%. Still, R&D spending last year was staggering: drugmakers the world over pumped nearly $288 billion into research and development. “R&D is central to refreshing product portfolios, which have a natural lifecycle owing to patents and exclusivity periods,” Daniel Chancellor, VP of thought leadership at Norstella, Evaluate’s parent company, told BioSpace . “Without reinvestment into R&D (or business development), revenues are increasingly at risk of competition and will inevitably decline.” This is why Evaluate estimates that the industry will continue to grow their R&D budgets through the end of the decade—which, as per its yet-to-be-released data, could reach just under $340 billion by 2030—even as the political and economic environment grows increasingly unwelcoming. “R&D spending will continue to grow, thankfully because industry revenue growth is robust,” Chancellor assured BioSpace . He qualified this assertion, however, by noting that Evaluate “expects R&D margins to decline” as companies continue to enact “cost containment measures” to surmount the increasing number of external challenges to their businesses. These challenges include tariffs, drug pricing and the cost of capital. In the context of these high-level barriers, Guglielmo Bruni Roccia, senior pharmaceutical industry analyst at BMI, a Fitch Solutions company, offered a more pessimistic view of R&D spending patterns in the coming years. President Donald Trump’s Most Favored Nation drug pricing policy , for example, “could result in compression of U.S. revenues, which would in turn reduce available R&D funding,” Roccia told BioSpace . “With constrained revenue streams, we expect pharmaceutical companies will likely prioritize R&D projects with greater certainty of profitability and where they have a greater competitive advantage,” he added. Still, there is reason to be optimistic. Experts who spoke with BioSpace pointed to the industry’s spending spree, particularly in manufacturing , as a promising signal. “Infrastructure investments enhance R&D capabilities, indicating a complementary rather than competitive relationship,” Roccia explained, noting that a manufacturing push “will support and potentially boost R&D activities rather than hinder them.” Norstella’s Chancellor agreed, adding that “these new facilities will rely on the success of R&D to produce the drugs of tomorrow, as well as meeting demand for current portfolios.” Dealmaking appears to be continuing at pace, as well. Despite an increasingly tricky political thicket , the first quarter witnessed a rush of M&A and licensing deals, with the industry earmarking some $40 billion for business development initiatives. This bodes well for the industry, since deals contributed heavily to the encouraging R&D trend in 2024. All top spenders in this list are anchored by a major contract at least hundreds of millions of dollars in value, bolstered by additional spending to beef up their pipelines. Below, BioSpace looks at the pharma industry’s most prolific investors in R&D and how they are using these budgets to advance their business. Merck Reigns Even After Scaling Back R&D Spend: $17.9 billion YoY Change: -41% In 2023, Merck went on an expensive deal-making spree. The pharma acquired immune specialist Prometheus Biosciences for $10.8 billion , licensed three of Daiichi Sankyo’s antibody-drug conjugates for $4 billion upfront and inked a potential $2.55 billion molecular glue deal with Proxygen, among other transactions. With a particularly bloated R&D purse in 2023, the 41% decrease in spending last year is more of a rightsizing of Merck’s budget than a steep scale-back. Indeed, the company still came out ahead of its Big Pharma peers with a hefty $17.94 billion investment, corresponding to 28% of its total revenue. “With the looming loss of exclusivity of Merck’s Keytruda, Merck has ramped up R&D efforts to address the nearly $30 billion revenue gap left by the drug,” Ophelia Chan, senior business fundamentals analyst at GlobalData, told BioSpace. “It’s worth keeping a close eye on [Merck’s] pipeline, which includes around 20 potential new blockbuster candidates that could collectively generate over $50 billion in the future,” Chan added. Among them is ifinatamab deruxtecan, an antibody-drug conjugate (ADC) that targets B7-H3, a transmembrane protein over expressed in various cancers. Merck is running the Phase III IDeate-Esophageal01 study to test the ADC in advanced or metastatic esophageal squamous cell carcinoma. Ifinatamab deruxtecan is also being proposed for heavily pretreated advanced small cell lung cancer, for which it is in late-stage development . Merck is also testing tulisokibart (MK-7240), which was picked up in the $10.8 billion acquisition of Prometheus Biosciences, in multiple inflammatory diseases . Phase II data, published in the New England Journal of Medicine in September 2024, showed that a higher percentage of ulcerative colitis patients treated with the anti-TL1A antibody achieved clinical remission versus placebo. Tulisokibart is in Phase III development for ulcerative colitis and Crohn’s disease. Merck CEO Robert Davis told investors in February that he expects blockbuster opportunities from the pharma’s ophthalmology business, which received a $1.3 billion boost last year with the May acquisition of the eye specialist EyeBio. The centerpiece of the acquisition is the trispecific antibody Restoret being assessed for diabetic macular edema (DME) and neovascular age-related macular degeneration (AMD). In September 2024, Merck kicked off the Phase IIb/III trial for Restoret in DME. The study, dubbed BRUNELLO , is set to complete by the end of 2027. Johnson & Johnson Strong in Cancer and Immuno—but not Neuro R&D Spend: $17.2 billion YoY Change: 14.2% J&J started 2024 by renewing its focus on its three main priority therapeutic areas—“oncology, immunology and neuroscience,” CEO Joaquin Duato told investors during the pharma’s full-year 2023 earning call—and the pharma’s R&D spending last year largely reflected this. For instance, J&J paid $2 billion to acquire Ambrx in January 2024. The bet builds out the pharma’s portfolio of ADCs, which in recent years have become a major focus in cancer therapy. In addition, J&J last year made two hefty investments into its immuno business: the $850 million acquisition of Proteologix and its pipeline of anti-inflammatory dermatology assets, and a $1.25 billion payment to Numab Therapeutics for its bispecific antibody for atopic dermatitis. All told, J&J spent more than $17.2 billion on R&D last year, accounting for over 19% of its total revenue. This sum also covers its medtech investments. Even as these deals helped J&J populate its early- and mid-stage pipelines, the pharma last year likewise pushed its late-stage assets forward. In immuno, for instance, the company in August 2024 sought approval for its monoclonal antibody nipocalimab in myasthenia gravis, which was ultimately granted in April to be marketed as Imaavy. Notably, neuroscience was a weak point for J&J’s 2024 R&D agenda. In October 2024, the pharma pruned its early- and mid-stage neuro pipeline, leaving the investigational human orexin-2 receptor blocker seltorexant on the cutting room floor. J&J had been studying seltorexant for agitation and aggression in Alzheimer’s disease. The company also axed a Phase II ion channel blocker for bipolar depression and a Phase I Parkinson’s disease therapy. J&J seems set on changing that this year, however, starting 2025 strong with the massive $14.6 billion acquisition of Intra-Cellular Therapies. Roche’s Mixed Year for Cancer R&D Spend: CHF 13 billion ($15.8 billion) YoY Change: 1% During its full-year 2024 business report in February 2024, Roche leaders recognized that sales were stagnating, driven largely by tanking demand for its COVID-19 products and currency difficulties at the time. The company identified dealmaking as one of its care strategies to revitalize growth. Still, unlike Merck and J&J, which enacted substantial changes to their budgets, Roche’s R&D spending in 2024 remained largely flat year-on-year. The Swiss company poured just over CHF 13 billion ($15.8 billion) in its R&D and business development efforts last year, a slight 1% increase from 2023. 2024 also posed formidable challenges to Roche’s R&D efforts in cancer. In July 2024, for instance, the company’s anti-TIGIT antibody tiragolumab failed to significantly improve progression-free survival in the Phase II/III SKYSCRAPER-06 study in NSCLC, forcing Roche to discontinue that trial. A few months later, in November, tiragolumab again delivered disappointing NSCLC outcomes . Perhaps reflecting these difficulties in oncology development, Roche in April 2024 axed three early-stage cancer assets, including camonsertinib, which it was testing for solid tumors. In August, Roche closed down the cancer immunology unit of its subsidiary Genentech, with a spokesperson at the time pointing to “shifts in the science of immuno-oncology” as the reason for the shake-up. Despite some obstructions in oncology, Roche in 2024 saw notable progress in its obesity portfolio, anchored by the assets it obtained from its $2.7 billion acquisition of Carmot Therapeutics in December 2023. Last May, the pharma announced that Carmot’s CT-388, a dual GLP-1/GIP receptor agonist, could lower bodyweight by 18.8% versus placebo at 24 weeks. Roche followed this up with a July 2024 readout for another Carmot asset, the oral GLP-1 receptor agonist CT-996. Phase I data at the time showed that the pill can cut weight by 6.1% versus placebo after four weeks. Roche’s standout deal last year was the November 2024 acquisition of Poseida Therapeutics for $1 billion upfront. Roche and Poseida are long-time partners , and the acquisition strengthens their CAR T collaboration, targeting multiple myeloma and B cell lymphomas, among other blood cancers. With more than half of the year left to go, it remains unclear how Roche’s R&D budget will change in 2025—though it’s unlikely that the pharma will go on a big spending spree soon. During its full-year business report in February, CEO Thomas Schinecker said that Roche will remain “ disciplined ” with dealmaking this year, focusing only on assets that make strong financial sense for the company. AstraZeneca Upped Investment to Buff Pipeline R&D Spend: $13.6 billion YoY Change: 25% AstraZeneca opened 2024 with a commitment to “investing in new technologies and new products to shape the future of medicine,” CEO Pascal Soriot said in February 2024 during the pharma’s full-year 2023 earnings call. A month later, in March, AstraZeneca made good on this commitment by inking two high-ticket acquisitions to build out its late-stage pipeline. The first of these deals is with Amolyt Pharma, which the pharma acquired for $800 million upfront . A few days later, AstraZeneca dropped $2 billion to acquire Fusion Pharmaceuticals. From Amolyt, AstraZeneca received the hypoparathyroidism candidate eneboparatide, which recently aced a Phase III trial , along with other assets being developed for rare diseases. Meanwhile, Fusion gave AstraZeneca its radiopharma pipeline, anchored by FPI-2265, an actinium-225 radioconjugate therapy being proposed for the treatment of metastatic castration-resistant prostate cancer. AstraZeneca last year also poured money into the opposite end of its pipeline, expanding its early-stage portfolio with a $19 million deal with Nona Biosciences in May 2024 for several preclinical monoclonal antibodies for cancer. That same month, AstraZeneca started putting bets in the lucrative obesity arena by paying $80 million to support Versant Ventures startup SixPeaks, which will work on next-generation, muscle-preserving weight-loss drugs. One of AstraZeneca’s most closely watched assets is its Daiichi Sankyo-partnered antibody-drug conjugate Dato-DXd. Despite winning FDA approval earlier this year for breast cancer under the brand name Datroway, the molecule ran into a rough patch last year, failing two Phase III trials in September—one in breast cancer and another in non-small cell lung cancer . Elsewhere in AstraZeneca’s cancer pipeline, the AKT blocker Truqap in November 2024 delivered a late-stage victory , significantly improving radiographic progression-free survival in certain types of prostate cancer. In April, however, Truqap stumbled in a Phase III prostate cancer, pushing the pharma to axe the Phase III CAPItell-280 study. AstraZeneca appears to be sustaining the pace of its R&D spending into the new year. In March alone, for instance, the pharma put $1 billion on the line to acquire EsoBiotec and its cell therapy pipeline, and signed two agreements with South Korea’s Alteogen to collaborate on subcutaneous cancer therapies. All told, AstraZeneca’s payments to Alteogen could total $1.35 billion . AbbVie Makes Strong Neuro Push R&D Spend: $12.8 billion YoY Change: 60% Of all the companies on this list, AbbVie saw the biggest increase in its R&D spending, soaring 60% year-on-year to hit nearly $12.8 billion. Likely the biggest contributing factor is the pharma’s $8.7 billion acquisition of Cerevel Therapeutics in December 2023. The star of this buyout was the next-generation antipsychotic agent emraclidine, which ultimately failed a pair of Phase II trials, forcing investors to question AbbVie’s neuro strategy. The Cerevel acquisition wasn’t a complete wash for AbbVie, however. In September 2024, just a month after closing the transaction, the pharma notched a late-stage clinical win in Parkinson’s disease with tavapadon. Beyond Cerevel, AbbVie sustained its neuro push in 2024, linking up with Gilgamesh Pharmaceuticals in May 2024 for $65 million upfront and up to $1.95 billion in option and milestone fees. The partnership is focused on developing psychedelic therapies for psychiatric indications. Outside of neuro, AbbVie in 2024 leaned further into its main area of expertise—immunology —putting up $250 million to acquire Massachusetts biotech Celsius Therapeutics and its investigational antibody for inflammatory bowel diseases. Oncology also saw a lot of progress for AbbVie last year, including a slew of positive readouts in ovarian cancer, non-small cell lung cancer and other solid tumors at ESMO 2024. A few months later, in December, the pharma likewise released data supporting the use of its bispecific T cell–engaging antibody epcoritamab as a monotherapy or as part of a combination regimen in patients with diffuse large B cell lymphoma. Despite being among pharma’s top R&D spenders, AbbVie doesn’t seem to be resting on its laurels. Already, the company has made several deals this year that could top $1 billion. In January, AbbVie teamed up with Neomorph to develop molecular glue degraders, putting up to $1.64 billion on the line for this partnership.