Ribociclib Succinate

编者按ESMO TAT ASIA2025年7月18-20日，欧洲肿瘤内科学会靶向抗癌亚洲大会（ESMO TAT Asia）于中国香港召开。ESMO TAT聚焦抗癌药物开发的不同关键相关方，涵盖医药创新、数字化转型、科研方法、商业洞察、行业监管、公共政策等多个方面，旨在深化工业界、学术界、临床界与监管机构的通力合作，推动抗癌药物科研进展。会上，EVER-132-002研究披露中国人群数据，为临床带来了更为坚实的循证基础。《肿瘤瞭望》特别邀请中山大学肿瘤防治中心王树森教授梳理EVER-132-002研究从全球到中国的数据表现，解读该研究对临床实践带来了深远意义。EVER-132-002中国亚组数据2025 ESMO TAT Asia汇总了183项主题汇报，推动了行业进步。在乳腺癌领域，针对Trop-2靶点的精准治疗发展备受关注。此前，基于TROPiCS-02研究[1]、EVER-132-002研究[2]，全球首个靶向Trop-2的抗体偶联药戈沙妥珠单抗（SG）已获批用于晚期激素受体（HR）阳性、人表皮生长因子受体2（HER2）阴性乳腺癌患者，为临床带来了新的选择。此次ESMO TAT Asia会上，由中山大学肿瘤防治中心王树森教授为第一作者、中国医学科学院肿瘤医院徐兵河院士作为通讯作者，更新了EVER-132-002研究中，中国人群数据，结果显示戈沙妥珠单抗较医生选择的化疗（TPC）改善我国患者中位无进展生存期（PFS）和中位总生存期（OS），疗效与安全性表现与全人群一致，从而进一步夯实了循证基础和临床实践信心。01EVER-132-002研究，为亚洲HR+/HER2-晚期乳腺癌带来新策略ESMO TAT ASIAEVER-132-002研究是一项针对既往2-4次化疗经治的HR+/HER2-转移性乳腺癌的Ⅲ期、多中心、随机对照研究，共入组331例亚裔患者（中国大陆约70%），约50%的患者接受过CDK4/6i治疗。将患者按1:1随机分组后分别予以戈沙妥珠单抗或TPC治疗，结果显示：戈沙妥珠单抗与TPC的盲法独立中央审查（BICR）评估的mPFS为4.3个月vs 4.2个月（HR, 0.67; 95%CI 0.52-0.87; P=0.0028），戈沙妥珠单抗6个月、9个月和12个月PFS率均较TPC显著改善近2倍，展现了持续获益；两组mOS分别为21.0个月vs.15.3个月（HR,0.64; 95%CI 0.47-0.88; P=0.0061），证实了戈沙妥珠单抗在亚洲人群的PFS与OS双重获益，与全球多中心研究TROPiCS-02保持一致。EVER-132-002研究的BICR PFS和OS亚组分析显示，无论CDK4/6i经治与否，相较于TPC，戈沙妥珠单抗均可改善患者的PFS（经治 HR 0.56；未经治 HR 0.79）和OS（经治 HR 0.50；未经治 HR 0.77）。与之类似，无论是HER2 IHC0还是HER2低表达，戈沙妥珠单抗同样较TPC取得了PFS（零表达HR 0.59；低表达HR 0.74）和OS（零表达HR 0.65, 低表达HR 0.61）获益[3]。安全性方面，戈沙妥珠单抗的表现与既往研究相似，以血液学毒性、腹泻为主，未发生间质性肺炎、眼毒性等需要特殊关注的不良反应，临床管理经验成熟，安全可控。戈沙妥珠单抗治疗相关不良事件导致停药的比例为3%，患者耐受性好。此外，在五水平五维健康量表（EQ-5D-5L）评分和生活质量视觉模拟量表（EQ-VAS）评分方面，戈沙妥珠单抗在治疗结束时较基线下降幅度均小于TPC，确证了其生活质量优势[2,4]。02中国人群数据公布，再次夯实循证基础ESMO TAT ASIA2025年ESMO TAT Asia年会上，EVER-132-002研究中国大陆人群数据正式披露[5]。该研究中，中国大陆患者约占70%，其中有118例纳入戈沙妥珠单抗组，114例纳入TPC组，约有90%存在基线内脏转移，约43%的患者为CDK4/6i经治，约56%的患者在转移阶段既往接受过2线化疗。此次披露的数据显示，中位随访13.6个月，戈沙妥珠单抗较TPC改善了BICR评估的mPFS，为5.5个月 vs 4.1个月，HR 0.622（95%CI: 0.457-0.846）；研究者评估的mPFS为5.7个月 vs 4.1个月，HR 0.550（95%CI: 0.411-0.736）；且各亚组获益一致。从绝对值上看，戈沙妥珠单抗为中国人群带来的PFS获益较整体人群具有优势的趋势。EVER-132-002研究中国大陆人群PFS在OS方面，戈沙妥珠单抗较TPC同样取得了有临床意义的改善，为20.5个月 vs 15.1个月，HR 0.583（95%CI: 0.401-0.847）,降低了41.7%的死亡风险，较全人群降低死亡风险程度具有更大获益的趋势。亚组分析显示，年龄＜65岁、基线ECOG评分1分、HER2 低表达、存在内脏转移、转移性阶段前序化疗3-4线患者、CDK4/6i经治患者显示了更大的OS获益趋势。EVER-132-002研究中国大陆人群OS及亚组分析安全性方面，戈沙妥珠单抗在中国大陆人群的表现与全人群表现一致，以血液学毒性、腹泻为主，因治疗相关不良事件导致停药的比例为3.4%，未见治疗相关死亡事件，具有较好的耐受性和可控的安全性。EVER-132-002研究中国大陆人群安全性表现03从全球到中国，戈沙妥珠单抗谱写HR+/HER2-晚期乳腺癌治疗新格局ESMO TAT ASIAHR+/HER2-乳腺癌约占所有乳腺癌70%，是最常见的乳腺癌亚型[6]。对于此类患者而言，内分泌治疗联合CDK4/6i是一线标准治疗方案，中位PFS为23.8个月~33.6个月[7,8]，而绝大多数患者都会面临内分泌耐药，后续治疗尚无标准方案。目前内分泌耐药后的HR+/HER2-晚期乳腺癌有部分靶向治疗药物可供选择，但需要患者具有相应靶向基因突变，且大多仅见PFS获益，OS获益有限。在此背景下，ADC为临床带来了新的选择。Trop-2约在85%~90%的乳腺癌中存在过表达[9]，在TNBC与激素受体阳性（HR+）亚型中过表达比例最高[10]。以戈沙妥珠单抗为代表的新一代 ADC、具备优化的结构特点，通过旁观者效应发挥更大的肿瘤杀伤作用，使用Trop-2 ADC 治疗无需进行相关检测，临床实践中更为便捷。戈沙妥珠单抗作为全球首个、亦是中国首个获批的靶向Trop-2 ADC，基于TROPiCS-02研究和EVER-132-002研究的数据表现，成为了当前在内分泌耐药治疗中唯一获得PFS、OS双重显著获益的Trop-2 ADC，获得了国内外指南的一致高级别推荐。在国际上，《美国国立综合癌症网络(NCCN)乳腺癌临床实践指南2025 v4》推荐对于内脏危象或内分泌难治的晚期复发HR+/HER2-患者，可二线优选戈沙妥珠单抗（Category 1, preferred）[11]。《欧洲肿瘤内科学会（ESMO）转移性乳腺癌在线指南（2025 v1.2）》建议对于内分泌难治且经化疗后进展的HR+/HER2-晚期乳腺癌人群，可选择戈沙妥珠单抗（Ⅰ，B，MCBS 4 分）[12]。在中国，《中国临床肿瘤学会（CSCO）乳腺癌诊疗指南2025》[13]推荐戈沙妥珠单抗用于CDK4/6i经治HR+/HER2低表达晚期乳腺癌患者，（II 级推荐、证据级别为1A）；《中国抗癌协会与中华医学会肿瘤学分会乳腺癌诊治指南与规范(2025年版精要本)》[14]推荐在HR+/HER2-晚期乳腺癌的二线治疗中，若既往使用过CDK4/6i，且经过至少1次化疗，可将戈沙妥珠单抗作为“考虑”方案。《中国晚期乳腺癌规范诊疗指南（2024版）》对于CDK4/6i经治的HR+/HER2-乳腺癌患者，推荐戈沙妥珠单抗作为二线及其后治疗策略（推荐，I A）[15]。此次EVER-132-002研究中国人群的数据披露，将进一步夯实其在HR+/HER2-乳腺癌应用的地位，为其推荐级别的提升提供更为坚实的循证医学证据。《中国晚期乳腺癌规范诊疗指南（2024版）》推荐的HR+/HER2-晚期乳腺癌治疗方案目前，戈沙妥珠单抗已在我国相继获批用于晚期三阴性乳腺癌二线治疗人群和HR+/HER2-晚期乳腺癌内分泌耐药且化疗经治人群的适应症。随着临床研究的逐步深入，戈沙妥珠单抗在乳腺癌应用的布局也在逐步完善。在mTNBC方面，戈沙妥珠单抗一线应用的两项全球多中心研究——ASCENT-03（SG较化疗一线显著改善mPFS[16]）和 ASCENT-04（SG+帕博利珠单抗 vs 化疗+帕博利珠单抗 mPFS 11.2个月 vs 7.8个月, HR 0.65, P=0.0009[17]）均已获得阳性结果。在HR+/HER2- mBC 方面，全球、多中心、开放标签的Ⅲ期ASCENT-07研究，将针对未经化疗的内分泌经治HR+/HER2-晚期乳腺癌患者，继续探索戈沙妥珠单抗单药前线治疗对比化疗的疗效与安全性，该结果预计年内公布，值得期待[18]。作为Trop-2 ADC的引领者，戈沙妥珠单抗将不断开拓引领，持续开发新的循证医学证据，为内分泌耐药的HR+/HER2-乳腺癌患者带来更多治疗希望！参考文献上下滑动查看更多内容[1] Rugo HS, Bardia A, Marmé F, et al. Sacituzumab Govitecan in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer. J Clin Oncol. 2022;40(29):3365-3376. doi:10.1200/JCO.22.01002[2] Xu B, Wang S, Yan M, et al. Sacituzumab govitecan in HR+HER2- metastatic breast cancer: the randomized phase 3 EVER-132-002 trial. Nat Med. 2024 Oct 1. doi: 10.1038/s41591-024-03269-z.[3] Joohyuk Sohn, Shusen Wang, Binghe Xu, et al. 2024 SABCS P2-09-25: Subgroup Analyses From the Phase 3 EVER-132-002 Study of Asian Patients With HR+/HER2- Metastatic Breast Cancer. 2024 SABCS abs#1993[4] Dai M S, et al. Health-Related Quality of Life (HRQOL) in the Ever-132-002 Study of Sacituzumab Govitecan (SG) VS Treatment of Physician's Choice (TPC) in Asian Patients with HR+/HER2- MBC.GBCC 2024.[5] Shusen Wang, Min Yan, et al. Sacituzumab govitecan (SG) vs treatment of physician’s choice (TPC) in Chinese patients (pts) with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2–) metastatic breast cancer (mBC): subanalysis of the results from the phase 3 EVER-132-002 study. 2025 ESMO TAT Asia Poster #14eP.[6] Clarke CA, Keegan TH, Yang J, et al. Age-specific incidence of breast cancer subtypes: understanding the black-white crossover. J Natl Cancer Inst. 2012;104(14):1094-1101. doi:10.1093/jnci/djs264[7] Tripathy D, Im SA, Colleoni M, et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 2018;19(7):904-915. doi:10.1016/S1470-2045(18)30292-4[8] Slamon DJ, Neven P, Chia S, et al. Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer. N Engl J Med. 2020;382(6):514-524. doi:10.1056/NEJMoa1911149[9] Izci H, Punie K, Waumans L, et al. Correlation of TROP-2 expression with clinical-pathological characteristics and outcome in triple-negative breast cancer. Sci Rep. 2022;12(1):22498. Published 2022 Dec 28. doi:10.1038/s41598-022-27093-y[10] Neelima Vidula, Christina Yau, Hope S. Rugo. Trop2 gene expression (Trop2e) in primary breast cancer (BC): Correlations with clinical and tumor characteristics. Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017) 1075-1075.[11] NCCN Guidelines 2025.v4 Invasive Breast Cancer. Available at: https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf[12] ESMO Metastatic Breast Cancer Living Guidelines, v1.2 April 2025. Available at: https://www.esmo.org/living-guidelines/esmo-metastatic-breast-cancer-living-guideline/hr-positive-her2-negative-metastatic-breast-cancer/hr-positive-her2-negative-metastatic-breast-cancer/de-novo-mbc-or-recurrence-12-months-after-the-end-of-adjuvant-et-et-sensitive-naive/sub-diagrams/hr-her2-mbc-pd-not-candidate-for-et-targeted-therapy[13] 中国临床肿瘤学会指南工作委员会.中国临床肿瘤学会（CSCO）乳腺癌诊疗指南(2025). 2025年CSCO指南会.[14] 《中国抗癌协会与中华医学会肿瘤学分会乳腺癌诊治指南与规范》编撰秘书处, 中国抗癌协会与中华医学会肿瘤学分会乳腺癌诊治指南与规范(2025年版精要本). -上海: 复旦大学出版社. 2024年12月.[15] 国家肿瘤质控中心乳腺癌专家委员会, 中国抗癌协会乳腺癌专业委员会, 中国抗癌协会肿瘤药物临床研究专业委员会. 中国晚期乳腺癌规范诊疗指南（2024版）[J]. 中华肿瘤杂志, 2024, 46(12): 1079-1106.[16] Gilead Sciences, Inc. ASCENT-03: Trodelvy® Demonstrates Highly Statistically Significant & Clinically Meaningful Improvement in Progression Free Survival in Patients With First-line Metastatic Triple-Negative Breast Cancer Who Are Not Candidates for Checkpoint Inhibitors. Available at: https://www.gilead.com/news/news-details/2025/ascent-03-trodelvy-demonstrates-highly-statistically-significant--clinically-meaningful-improvement-in-progression-free-survival-in-patients-with-first-line-metastatic-triple-negative-breast[17] Sara M. Tolaney, et al. Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC): Primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study. 2025 ASCO LBA 109.[18] Hope Rugo, et al. ASCENT-07: A phase 3, randomized, open-label study of sacituzumab govitecan versus treatment of physician’s choice in patients with HR+/HER2– inoperable, locally advanced, or metastatic breast cancer post-endocrine therapy. 2023 SABCS.Abstract PO1-05-09.王树森 教授中山大学肿瘤防治中心乳腺癌单病种首席专家香港大学临床肿瘤学系荣誉教授主任医师、博士生导师中国临床肿瘤协会(CSCO）乳腺癌专家委员会副主任委员中国研究型医院协会乳腺癌专业委员会副主任委员 中国抗癌协会乳腺癌专业委员会常务委员  广东省临床医学学会乳腺癌专委会主任委员广东省癌症中心乳腺癌诊疗质量控制专家委员会主任委员广东省胸部肿瘤防治研究会乳腺癌专业委员会主任委员 现在主要从事乳腺癌内科的精准治疗、化疗、内分泌治疗及靶向治疗。主持国自然重点项目1项、面上项目1项，省科技厅项目3项，获国家科技重大专项资助1项。主编教材《临床肿瘤学（clinical oncology）》，参编教材或专著多部。作为主要执笔人或参与者制定了多项国家级的乳腺癌诊疗相关指南。在国内外期刊以第一作者或通讯作者发表论文多篇， 其中近年以来以第一作者或通讯作者于JAMA、JCO、STTT、CANCER COMMUNICATIONS 等杂志发表SCI论文多篇。作为主要研究者牵头发起多中心临床研究30多项，其中包括I期临床试验6项目，Ⅱ、Ⅲ期大型多中心临床试验多项。（来源：《肿瘤瞭望》编辑部）声 明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

In May 2025, a new wave of capital and technological resonance swept across the global biotechnology sector. Industry giants such as CSPC Pharmaceutical Group, Sanofi, and Eli Lilly accelerated their deployment of next-generation therapies through multibillion-dollar deals. From AI-driven targeted protein degradation (TPD) and RNA editing to in vivo CAR-T therapies, and from oral small-molecule drugs to non-opioid analgesics, the industry is fiercely competing around three central themes: “conquering previously undruggable targets,” “breaking traditional R&D bottlenecks,” and “reshaping the treatment paradigm for chronic diseases and cancer.” 1. CSPC Eyes $5 Billion Global Collaboration: EGFR-ADC Licensing and AI-Driven Drug Discovery Platform for Global Expansion On May 30, 2025, CSPC Pharmaceutical Group announced that it is in discussions with several independent third parties regarding three potential transactions. These involve its self-developed epidermal growth factor receptor antibody-drug conjugate (EGFR-ADC) and other innovative therapeutics developed via its proprietary technology platform. The deals cover development, manufacturing, and commercialization rights, with a potential total value of up to $5 billion, including upfront payments, R&D milestone payments, and commercial milestone payments. A key asset in the negotiations is CSPC’s EGFR-ADC, a drug built on precise conjugation of monoclonal antibodies and cytotoxic agents. EGFR (epidermal growth factor receptor) is overexpressed in various solid tumors, such as non-small cell lung cancer and colorectal cancer. The ADC specifically targets and binds to EGFR on tumor cell surfaces, delivering a highly potent payload (e.g., a topoisomerase or tubulin inhibitor) directly into the cancer cells to induce apoptosis. Compared to traditional chemotherapy, EGFR-ADC significantly reduces systemic toxicity while expanding the therapeutic window. CSPC's technology platform also includes an AI-powered drug discovery system, which simulates target-ligand interactions to accelerate screening and optimization of small-molecule candidates, particularly for developing oral therapies for chronic diseases, such as autoimmune disorders. Another licensed product, liposomal irinotecan injection, uses liposomal encapsulation to prolong drug half-life, increase local tumor concentration, and overcome resistance—offering new hope for hard-to-treat cancers like pancreatic cancer. 2. Sanofi Acquires DR-0201 for $1.9 Billion: Advancing Deep B Cell Depletion Therapy and Redefining Autoimmune Disease Treatment On May 27, 2025, Sanofi announced the acquisition of DR-0201 (now renamed SAR448501) in a deal valued at $1.9 billion. DR-0201 is a bispecific myeloid cell engager (MCE) developed by clinical-stage biopharma company Dren Bio. The acquisition was executed through the purchase of Dren Bio’s affiliate Dren 0201, Inc. for an upfront payment of $600 million, with potential additional payments of up to $1.3 billion tied to development and commercialization milestones. As a potential first-in-class therapy, DR-0201 is designed to achieve deep B cell depletion to treat autoimmune diseases such as systemic lupus erythematosus (SLE), addressing the unmet need for patients resistant to current therapies. The transaction significantly strengthens Sanofi’s global leadership in immunology and adds a critical asset to its next-generation immunotherapeutics pipeline. The core mechanism of DR-0201 lies in its dual-targeting design. One arm binds to phagocytic receptors (e.g., Dectin-1) on myeloid cells such as dendritic cells and macrophages, while the other targets the CD20 antigen on B cells. This bispecific configuration activates myeloid cell phagocytosis to induce deep clearance of B cells. Unlike conventional CD20 monoclonal antibodies, DR-0201 targets multiple B cell subtypes, including plasma cells, offering more comprehensive suppression of pathogenic B-cell-driven immune responses. In autoimmune diseases, B cells not only produce autoantibodies but also exacerbate inflammation via antigen presentation and cytokine secretion. DR-0201’s deep depletion of B cells helps reset the adaptive immune system, providing durable remission for patients with refractory disease. Preclinical and Phase I trials have shown promising safety and efficacy across indications such as non-Hodgkin’s lymphoma, Sjögren’s syndrome, and polymyositis, without inducing cytokine release syndrome or neurotoxicity—common side effects seen with other immunotherapies. This acquisition is strategically significant for Sanofi: First, DR-0201 substantially enhances Sanofi’s immunology pipeline, particularly in autoimmune indications. Although Sanofi’s flagship drug Dupixent leads the market, its core patents will expire in 2031, and new-generation therapies are urgently needed to maintain leadership. DR-0201 is well-positioned to become the "next immunology blockbuster" for difficult-to-treat diseases like lupus, while also paving the way for label expansions into COPD, chronic spontaneous urticaria, and more. Second, by acquiring Dren Bio’s platform technology, Sanofi reinforces its capabilities in developing myeloid cell-targeting agonists and phagocytosis-based therapies—with applications in oncology, infectious diseases, and metabolic disorders. Maintaining Dren Bio as an independent entity promotes synergy in pipeline development (e.g., selective pathogenic cell clearance programs) and accelerates translational research. For Dren Bio, this deal provides strong financial backing ($600M upfront + $1.3B in milestones) to focus on other candidates, such as novel bispecifics or small molecules targeting myeloid cells. Additionally, Sanofi’s global commercialization infrastructure and clinical development expertise will support efficient advancement of DR-0201 into Phase II/III trials and beyond. 3. Eli Lilly Acquires SiteOne for $1 Billion to Advance Non-Opioid Pain Therapies and Accelerate Pipeline Diversification On May 27, 2025, Eli Lilly and Company announced the completion of its $1 billion acquisition of clinical-stage biotech firm SiteOne Therapeutics. The deal centers on SiteOne’s lead asset STC-004, a non-opioid oral analgesic targeting the Nav1.8 sodium ion channel, which is currently in Phase II clinical trials. The transaction includes an upfront payment estimated at $300–400 million, with an additional $700 million tied to regulatory and commercial milestones. This acquisition marks a strategic expansion of Lilly’s pain management portfolio and reflects its intent to reduce dependency on its blockbuster diabetes and obesity franchise (e.g., GLP-1 receptor agonist tirzepatide) by capturing opportunities in the rapidly growing non-opioid analgesics market. STC-004 is a highly selective Nav1.8 inhibitor, designed to modulate voltage-gated sodium channels (VGSCs) involved in pain transmission. Nav1.8 is predominantly expressed in nociceptive neurons of the peripheral nervous system (e.g., dorsal root ganglia), playing a critical role in transmitting pain signals. Unlike traditional opioids, which act on central nervous system (CNS) receptors and are associated with addiction and respiratory depression, STC-004 blocks the sodium ion influx via Nav1.8, effectively interrupting pain signaling at the peripheral level—providing relief without CNS-related risks. Compared to Vertex Pharmaceuticals’ approved Nav1.8 inhibitor Journavx (suzetrigine), which was authorized for acute pain but showed limited superiority over opioids in Phase III trials, STC-004 offers key advantages: greater selectivity, oral convenience, and reduced resistance risk. Its optimized molecular structure enhances Nav1.8 targeting while minimizing off-target effects, potentially expanding its therapeutic window. Beyond STC-004, SiteOne's platform also includes other sodium channel inhibitors (e.g., Nav1.7, Nav1.9), laying the groundwork for multi-target pain therapies in the future. 4. AI-Driven Molecular Glue Discovery: VantAI Expands Collaboration with Blueprint Medicines to Target “Undruggable” Proteins On May 20, 2025, VantAI and Blueprint Medicines announced an expanded partnership, building on their initial 2022 collaboration. The extended agreement focuses on developing induced proximity therapeutics, including molecular glues and heterobifunctional degraders, aimed at modulating historically undruggable targets. This effort will leverage VantAI’s new AI foundation model Neo-1 to accelerate rational molecular design. Under the terms, VantAI is eligible to receive up to $1.67 billion in potential milestone payments, including $1.4 billion in commercial milestones and $270 million in R&D/regulatory milestones, along with tiered royalties on future product sales. This collaboration deepens both companies' positions in the targeted protein degradation (TPD) space and demonstrates how AI can overcome traditional drug discovery constraints. For VantAI, the deal validates its integrated AI drug discovery platform, combining NeoLink’s structural proteomics with the Neo-1 foundation model. The partnership provides long-term financial support and accelerates real-world application of VantAI’s AI in drug design. The launch of Neo-1 represents a paradigm shift—transforming molecular glue development from serendipitous discovery to rational design. Blueprint’s reputation lends credibility to VantAI’s technology, while collaboration around undruggable targets will help build data and experience critical for VantAI’s internal pipeline, including proprietary glue programs. For Blueprint Medicines, this marks a pivotal extension of its precision medicine strategy. By integrating VantAI’s AI capabilities, Blueprint can rapidly identify and optimize molecular glue candidates for complex disease drivers, dramatically shortening development timelines. The companies plan to focus on oncology and hematology targets, such as transcription factors and key signaling nodes—areas where Blueprint's current pipeline (e.g., Kisqali, Ayvakit) leaves strategic gaps. The partnership will also advance engineered protein-protein interface (PPI) technologies, enabling Blueprint to differentiate its TPD programs from competitors like Arvinas and C4 Therapeutics. Long-term, this alliance positions Blueprint to build a next-generation pipeline for undruggable targets, strengthening its global leadership in oncology and rare disease therapeutics. 5. AstraZeneca Acquires EsoBiotec for $1 Billion: Transforming In Vivo CAR-T Therapy and Accelerating the “Third Wave” of Cell Therapy On May 20, 2025, AstraZeneca announced the acquisition of EsoBiotec, a pioneering in vivo cell therapy company, in a transaction valued at $1 billion. AstraZeneca will pay $425 million upfront, with additional milestone payments of up to $575 million tied to development and regulatory achievements. At the core of the deal is EsoBiotec’s proprietary Engineered Nanobody Lentiviral Platform (ENaBL), which uses highly targeted lentiviral vectors to deliver gene payloads directly to immune cells such as T cells inside the patient’s body, enabling in vivo reprogramming without ex vivo manipulation. This technology could address major limitations of conventional CAR-T therapies, including long manufacturing cycles, high costs, and safety concerns—opening a new frontier in treating cancer and autoimmune diseases. The ENaBL platform leverages lentiviral vector-mediated gene delivery. Its mechanism includes: ·Targeted cell recognition via engineered nanobodies displayed on the lentivirus surface (e.g., anti-CD3, anti-CD8, or anti-TCR nanobodies), ensuring precise binding to T cells; ·Efficient gene integration, with viral payloads encoding chimeric antigen receptors (CARs) or immune modulators that integrate into host T cell genomes, enabling stable long-term expression; ·Functional T cell activation in vivo, allowing patients’ T cells to express CARs and actively target tumor or autoreactive cells. Unlike traditional CAR-T therapies, which require leukapheresis, genetic editing, and reinfusion, ENaBL enables systemic administration via intravenous injection. Additionally, the platform incorporates features such as CD47 gene insertion (to evade macrophage clearance) and MHC-I knockout (to reduce immunogenicity), improving both efficacy and safety. This approach can reduce the treatment timeline from weeks to minutes, significantly lower production costs, and eliminate the need for lymphodepletion preconditioning—a key advantage in expanding access to cell therapy. 6. Eli Lilly Invests $1.3 Billion in Rznomics: Advancing RNA Editing for Genetic Hearing Loss On May 15, 2025, South Korea–based Rznomics announced a global R&D collaboration and licensing agreement with Eli Lilly, valued at over $1.3 billion, including undisclosed upfront payments and future milestone-based and revenue-sharing components. The collaboration focuses on developing RNA editing therapies for hereditary sensorineural hearing loss, using Rznomics’ proprietary trans-splicing ribozyme platform. Rznomics will lead early-stage research, while Lilly will oversee late-stage development and global commercialization. The deal marks Lilly’s strategic expansion into RNA editing therapeutics, aiming to address unmet needs in hearing loss and beyond. Rznomics’ platform is based on group I intron-derived trans-splicing ribozymes, which enable precise RNA editing via two consecutive transesterification reactions. The mechanism includes: ·Target recognition and cleavage, where the ribozyme’s Internal Guide Sequence (IGS) forms a complementary P1 helix with the target RNA (5′-GN′N′N′N′N′-3′), and an exogenous guanosine acts as a nucleophile to cleave at the 5′ splice site, exposing a 3′-OH uridine; ·RNA replacement and ligation, in which the ribozyme undergoes conformational change, and its conserved ωG residue replaces the exogenous guanosine to ligate a therapeutic RNA sequence to the cleaved target RNA; ·Dynamic regulation and safety, enabled by RNA-sensing riboswitches, which balance therapeutic gene expression with endogenous RNA levels, avoiding overexpression. Additionally, the use of DNA vectors allows for stable and durable RNA modulation without genomic integration, minimizing genotoxic risk. The platform offers three distinct advantages: ·A dual-function, single-molecule system (silencing pathogenic RNA while promoting therapeutic gene expression), ·Dynamic expression control (for personalized therapy), ·Long-lasting safety profile (no genome editing required). While currently in preclinical development for genetic hearing loss, the technology holds potential across metabolic, neurological, and genetic disorders. This collaboration represents a transformational milestone for Rznomics, marking its emergence from a domestic biotech into a global RNA therapeutics leader. The $1.3 billion deal, including milestones, ensures robust funding for platform development and clinical translation. Eli Lilly’s involvement provides high-level validation, strengthening Rznomics’ credibility in capital markets and with potential partners, and attracting future investment. Lilly’s commercialization capabilities are expected to accelerate time to market, with the hearing loss therapy potentially becoming the first RNA editing drug based on trans-splicing ribozymes to receive approval—possibly before 2030. 7. Novo Nordisk and Septerna Enter $2.2 Billion Collaboration to Redefine Oral Weight Loss Drug Development On May 14, 2025, Novo Nordisk, a global leader in pharmaceuticals, announced an exclusive worldwide collaboration and licensing agreement with U.S.-based biotechnology company Septerna, with a total deal value of up to $2.2 billion. The partnership focuses on the development of oral small-molecule drugs targeting obesity, type 2 diabetes, and other cardiometabolic diseases. The deal includes over $200 million in upfront and near-term milestone payments, with the remaining value to be realized through development, commercialization milestones, and royalties on product sales. The collaboration will initiate four discovery programs, targeting key G protein–coupled receptor (GPCR) pathways, including GLP-1, GIP, and glucagon receptor (GCGR). By combining Novo Nordisk’s scientific leadership in metabolic diseases with Septerna’s proprietary GPCR drug discovery platform, the companies aim to accelerate the development of next-generation oral weight management therapies. Novo Nordisk will lead global development and commercialization post-IND, while Septerna will co-lead early-stage research and share in global profits for selected programs. At the core of Septerna’s innovation is its Native Complex Platform™, which overcomes longstanding challenges in GPCR drug discovery. This proprietary technology isolates GPCRs from cellular membranes and reconstitutes them into native-like complexes, incorporating ligands, signaling proteins, and lipid bilayers that mimic the natural membrane environment. This approach preserves the native structure, function, and dynamics of GPCRs, addressing the common issue of receptor instability in traditional in vitro assays. Leveraging this platform, Septerna can screen billions of small molecules to identify precise binding sites on validated targets such as GLP-1 and GIP receptors—including novel allosteric pockets. The platform supports multiple pharmacological modes of action, including agonists, antagonists, and allosteric modulators, enabling comprehensive control over GPCR signaling. The resulting oral small-molecule candidates offer high selectivity, potency, and favorable drug-like properties, directly modulating GPCR pathways to regulate metabolism, energy balance, and appetite—offering long-acting therapeutic options for obesity and diabetes. Summary The global surge in biotechnology financing in May 2025 underscores three major industry trends: breakthrough technologies are reigniting investor interest, therapeutic paradigms are rapidly evolving, and global competition is reshaping industry alliances. Amid this wave, Eli Lilly’s strategic expansion into non-opioid analgesics and RNA editing therapies reflects a dual-track approach toward chronic and rare diseases, while Novo Nordisk’s investment in oral small molecules complements its GLP-1-based franchise and exemplifies a broader industry shift toward multi-target, multi-mechanism, and multimodal strategies, especially as companies approach patent cliffs. Meanwhile, China’s innovation-driven biotech firms, such as CSPC, are increasingly entering strategic partnerships and acquisition agreements with Western pharmaceutical giants like Novo Nordisk and Sanofi. These moves signal a transition from “point-to-point competition” to a deeper integration of technology sovereignty and ecosystem alliances, reshaping the global biotechnology landscape. How to get the latest progress on drug deals? If you would like to access the latest transaction event information, you can click on the 'Deal' module from the homepage of the Synapse database. Within the Deal module, you can search for global pharmaceutical transaction information using labels such as Drugs, Organization, Target, Drug Type, Deal Date.  Furthermore, you can obtain the original link to the transaction coverage by clicking on the "Deal Name." In the analysis view, you can see the most active assignors, assignees, popular targets, and other dimensions of analysis, as well as the distribution of research and development statuses at the time of the transaction, to help you better understand the search results. The Synapse database also supports the ability to view current transactions from the dimension of "drugs" (by selecting "drugs" from the "Adjust Dimension" dropdown menu above). Targeting transactions involving renowned pharmaceutical companies that are of interest to the industry, such as Merck, Roche, etc., Synapse has identified a group of "leading companies" through drugs that have achieved global sales exceeding 1 billion US dollars in 2022. Transactions involving drugs from these leading companies can be filtered by clicking on the "Leading Company" tag on the left-hand side. In addition to the drug transaction module, you can also view related transaction history on the drug detail page and the institution detail page. Click on the image below to explore new pharmaceutical funding transactions!