Sanyou Biopharmaceuticals Co., Ltd.

作者：戴珊珊 周昀茜美工：何国红 罗真真排版：马超01 引言值此三优生物医药十周年之际，我们见证了肿瘤精准医疗的飞速发展。从传统的细胞毒化疗药物到靶向治疗的兴起，从免疫检查点抑制剂的问世到ADC（抗体-药物偶联物）的创新应用，肿瘤治疗正在经历着革命性的变化。本文将聚焦于发病率和致死率相对较高的六大恶性肿瘤——肺癌，乳腺癌、结直肠癌，前列腺癌，胃癌，肝癌，介绍其治疗现状以及在研靶点，为行业专业人士提供全面的靶点开发参考。02 肺癌：精准治疗与免疫革新的前沿阵地肺癌长期位列全球发病率与致死率首位，2022年全球肺癌新发病例248万，死亡182万[1]  。肺癌治疗已进入精准医学时代。目前已形成EGFR/ALK靶向药物、PD-1/PD-L1免疫检查点抑制剂和抗体药物偶联物（ADC）三足鼎立的治疗格局。奥希替尼、帕博利珠单抗等药物显著改善患者生存，而T-DXd、DS-1062等新一代ADC为难治性患者带来新希望[2,3]。在研靶点与创新方向：1）免疫检查点：除PD-1/PD-L1外，CTLA-4、TIGIT、LAG-3等成为联合治疗新选择；2）ADC靶点：C-MET、DLL3、TROP2、CEACAM5、B7-H3等在NSCLC和SCLC中显示显著疗效；3）双特异性抗体：PD-1 × VEGF（ivonescimab）、DLL3 × CD3（tarlatamab）等代表免疫治疗新模式；4）新型靶向药物：KRAS G12C抑制剂等为更多患者提供治疗机会。▲ 图1 基于insight数据库统计肺癌靶点分布图03 乳腺癌：全球女性健康的重大挑战乳腺癌是女性最常见的恶性肿瘤，2022年全球肺癌新发病例229万，死亡67万，预计2040年将增至约300万例[4] 。乳腺癌治疗早期以手术为主，结合新辅助治疗；晚期采用分型指导的全身治疗策略[5] 。治疗模式从单药向精准联合、从晚期向早期辅助延伸。三大亚型展现不同的治疗特点和疗效进展：1）HER2阳性领域，曲妥珠单抗（trastuzumab）仍是核心基础治疗药物，DS-8201等新一代ADC进一步提升了治疗效果[6] ，国产RC48等也显示出良好的疗效[7] ；2）HR+/HER2-领域，CDK4/6抑制剂显著改善了患者生存获益[8] ；3）TNBC领域，TROP2-ADC联合免疫治疗为患者带来治疗突破[9] 。在研靶点与创新方向：1）新型ADC靶点：TROP2、HER3、NECTIN-4、B7-H3、LIV-1等；2）PI3K/AKT通路：alpelisib在PIK3CA突变患者中显效；3）新一代内分泌药物：口服SERD如camizestrant；4）免疫检查点：PD-1/PD-L1、CLTA-4在TNBC中显示潜力；5）表观遗传调节：KMT2C、FOXM1等新靶点。▲ 图2 基于insight数据库统计乳腺癌靶点分布图04 结直肠癌：从传统治疗到精准分子分型结直肠癌是全球第三大高发癌种，仅次于肺癌和乳腺癌。2022年全球新发超190万例，死亡约90万例[1] 。手术切除为早期CRC一线方案，辅助和新辅助化疗根据危险因素分层应用。转移性CRC标准治疗包括基于RAS/BRAF/MSI分型的化疗联合靶向药物（EGFR、VEGF单抗），HER2和BRAF突变亚群也可选择相应靶向。MSI-H/dMMR亚型对免疫检查点抑制剂（PD-1/PD-L1或CTLA-4）响应显著，但仅约5% mCRC患者属于该亚型，其余大多数MSS/pMMR患者对免疫单药疗效有限[10] 。在研靶点与创新方向：1）已上市靶点持续拓展，EGFR、VEGF：EGFR单抗（西妥昔单抗、帕尼单抗）及VEGF单抗（贝伐珠单抗）在RAS/BRAF分型亚组中优化组合，HER2/BRAF靶向药不断纳入新版指南；2）c-MET、CEACAM5、TROP2、CDH17等新兴抗体药物偶联物（ADC）赛道快速推进，部分已进入注册阶段；3）LAG3、TIGIT、CLDN18.2、DLL3、B7-H3等成为双特异性抗体和ADC创新热点，特别是在MSS/pMMR人群联合免疫方向取得进展；4）分层诊疗理念下，mCRC分子分型指导多靶点精准联合（如BRAF/EGFR、HER2/PI3K等新组合），推动生存获益持续提升。▲ 图3 基于insight数据库统计结直肠癌靶点分布图05 前列腺癌：雄激素依赖向个体化精准治疗演进前列腺癌是全球第四大高发癌症，男性第二大恶性肿瘤。2022年前列腺癌新发病例146万，死亡40万人[1,11] 。前列腺癌早期多通过根治性手术和/或放疗治疗。中晚期及转移性病例以内分泌去势（ADT）联合AR抑制剂（阿比特龙、恩扎卢胺等）为标准一线方案，药物耐受性高、副作用相对较轻。去势抵抗后常加用多西他赛等化疗，伴DNA修复缺陷者可用PARP抑制剂奥拉帕利。核素靶向药物、免疫检查点抑制剂、肿瘤疫苗等多线治疗也在逐步应用[12] 。在研靶点与创新方向：1）PSMA：前列腺特异性膜抗原，Lu-177-PSMA-617已获批，多个PSMA-ADC在研；2）AR：雄激素受体仍是核心靶点，新一代AR拮抗剂持续开发；3）GNRHR：促性腺激素释放激素受体，多个激动剂和拮抗剂在研；4）PD-1/PD-L1：免疫检查点，已批准抗体数量最多；5）PARP：聚腺苷二磷酸核糖聚合酶，在BRCA突变患者中显效；6）新兴靶点探索，包括DLL3、STEAP1、TROP2等。▲ 图4 基于insight数据库统计前列腺癌靶点分布图06 胃癌：精准亚型与新靶点带动创新胃癌是全球第五大癌症，2022年全球新发超96万例，死亡约66万例[13] 。胃癌精准治疗格局已基本确立。HER2阳性患者以曲妥珠单抗联合化疗为标准一线治疗[14] ，同时FDA/EMA已批准PD-L1阳性者加用帕博利珠单抗形成三联疗法。德曲妥珠单抗作为新一代HER2-ADC药物，已获批用于二线及后线治疗，显著改善生存获益。2024年12月新上市的佐妥昔单抗成为首个CLDN18.2靶向药物，针对HER2阴性、CLDN18.2阳性患者提供新的治疗选择。在研靶点与创新方向：1）CLDN18.2领域竞争激烈，除已获批的zolbetuximab外，超过100款相关药物在研，包括ADC、双特异性抗体和CAR-T疗法；2）TROP2-ADC领域，sacituzumab tirumotecan等药物展现良好前景；3）新免疫检查点方面，TIGIT抑制剂domvanalimab在EDGE-Gastric研究中显示抗肿瘤活性，STAR221 III期试验正在验证其疗效[13] ；4）新兴靶点探索，包括C-MET、TROP2、MSLN等；5）已上市靶点持续拓展，包括VEGFR2、FGFR2等。▲ 图5 基于insight数据库统计胃癌靶点分布图07 肝癌：免疫组合引领的治疗新格局肝癌是全球第六大癌症和第三大癌症死因，2022年新发病例约90万，死亡病例超过75万，其中中国占全球发病和死亡人数的一半以上，主要危险因素包括乙型肝炎病毒感染、丙型肝炎病毒感染、酒精性肝病和非酒精性脂肪性肝炎。肝细胞癌一线治疗现已步入多元化时代。索拉非尼和仑伐替尼（多靶点TKI）为晚期首选，阿替利珠单抗联合贝伐珠单抗免疫组合（IMbrave150方案）跃升为主要标准。二线包括瑞戈非尼、卡博替尼和拉姆西单抗等TKI，以及免疫检查点抑制剂纳武利尤单抗、帕博利珠单抗。创新药物如靶向VEGF/FGFR的多靶点抑制剂和联合免疫治疗也被广泛应用[15] 。在研靶点与创新方向：1）GPC3成为ADC与CAR-T疗法的重要靶点，已有突破性疗效报道；2）TGF-β通路相关抑制剂（如galunisertib）、TIGIT、LAG-3等新型免疫检查点在持续探索中；3）FGFR4、MET、AXL、PI3K/AKT/mTOR、Wnt/β-catenin等信号轴的新一代小分子抑制剂正在开发；4）肿瘤微环境调控、肠道菌群干预和溶瘤病毒疗法等新方向亦为创新热点[16] 。▲ 图6 基于insight数据库统计肝癌靶点分布图08 总结与展望：协同创新，引领未来肿瘤治疗进入了一个新时代。免疫检查点抑制剂、ADC药物和靶向治疗的快速发展，正在改写多种肿瘤的治疗指南。未来的突破将更多地来自于：◆ 创新靶点的发现：持续挖掘如DLL3、TROP2、B7-H3、GPC3、STEAP1、CDH17等新兴靶点的潜力；◆ 联合用药的智慧：“ADC+免疫”、“双抗+ADC”等联合策略将成为研发主流；◆ 三个体化精准医疗：基于生物标志物的深度分析，为每位患者匹配最优治疗方案。三优生物将继续秉持科学严谨、勇于创新的精神，与全球同道携手，共同推动抗体药物研发，为攻克癌症贡献我们的智慧与力量。注：本文内容基于最新发表的科学文献和临床研究数据，旨在为医药行业专业人士提供参考。具体治疗方案应遵循相关临床指南和专业医师建议。Sanyou 10th Anniversary | Six Major Malignant Tumor Targets Overview01 IntroductionOn the occasion of the 10th anniversary of Sanyou Biopharmaceuticals, we have witnessed the rapid evolution of precision oncology. From traditional cytotoxic chemotherapies to the rise of targeted therapies-and from the advent of immune checkpoint inhibitors to the innovative applications of antibody-drug conjugates (ADCs)-the landscape of cancer treatment is undergoing revolutionary change. This article focuses on high-incidence and high-mortality cancers-lung, breast, colorectal, prostate, and gastric-summarizing the current treatment patterns and landscape of investigational targets, providing industry professionals with a comprehensive reference for target development.02 Lung Cancer: Frontier of Precision Therapy and Immunological RevolutionLung cancer has long ranked first globally in incidence and mortality, with 2.48 million new cases and 1.82 million deaths in 2022[1] . Lung cancer therapy has entered the precision medicine era, now dominated by EGFR/ALK-targeting drugs, PD-1/PD-L1 immune checkpoint inhibitors, and ADCs. Osimertinib and pembrolizumab have significantly improved patient survival, while next-generation ADCs such as T-DXd and DS-1062 offer new hope for refractory cases[2,3] .Emerging Targets & Innovations:(1) Immune checkpoints: In addition to PD-1/PD-L1, new avenues include CTLA-4, TIGIT, LAG-3, enabling combination therapies;(2) ADC targets: C-MET, DLL3, TROP2, CEACAM5, B7-H3 have shown significant efficacy in NSCLC and SCLC;(3) Bispecific antibodies: PD-1×VEGF (ivonescimab), DLL3×CD3 (tarlatamab), representing new models of immunotherapy;(4) Novel targeted drugs: KRAS G12C inhibitors, MET antibodies, HER3-ADC provide more options to patients.▲ Fig.1 Mapping of lung cancer target distribution derived from Insight Database03 Breast Cancer: A Major Challenge to Women’s Health WorldwideBreast cancer is the most common cancer among women, with 2.29 million new cases and 666,103 deaths worldwide in 2022, projected to rise to 3 million cases by 2040[4] . Early-stage treatment emphasizes surgery with neoadjuvant therapy; advanced stages adopt subtype-guided systemic strategies[5] . Treatments have shifted from monotherapy to precise combinations and from late- to early-stage interventions.The three major subtypes demonstrate different treatment characteristics and therapeutic advances:(1) In the HER2-positive domain, trastuzumab remains the core foundational therapy, with next-generation ADCs such as DS-8201 further improving treatment outcomes[6] , while domestic drugs like RC48 also demonstrate good efficacy[7] ;(2) In the HR+/HER2- domain, CDK4/6 inhibitors significantly improve patient survival benefits[8] ;(3) In the TNBC domain, TROP2-ADC combined with immunotherapy brings therapeutic breakthroughs for patients[9] .Emerging Targets & Innovations:(1) Novel ADC targets: TROP2, HER3, NECTIN-4, B7-H3, LIV-1; (2) PI3K/AKT pathway: Alpelisib is effective in PIK3CA mutant patients; (3) Nextgen endocrine drugs: Oral SERD agents such as camizestrant;(4) Immune checkpoints: PD-1/PD-L1, CLTA-4 show promise in TNBC;(5) Epigenetics: KMT2C, FOXM1 and other new targets.▲ Fig.2  Mapping of Breast cancer target distribution derived from Insight Database04 Colorectal Cancer: From Traditional Therapy to Precision Molecular StratificationColorectal cancer is the third most common cancer worldwide, following lung and breast-with over 1.9 million new cases and 904,019 deaths in 2022[1] . Surgical resection remains the mainstay for early CRC, with adjuvant/neoadjuvant chemotherapy applied based on risk stratification. Metastatic CRC is treated with chemotherapy plus targeted drugs (EGFR, VEGF antibodies) guided by RAS/BRAF/MSI subtyping; HER2 and BRAF mutant subsets also have matching options. The MSI-H/dMMR subtype responds well to immune checkpoint inhibitors but accounts for only ~5% of metastatic CRC. Most MSS/pMMR patients show limited benefit from monotherapy[10] .Emerging Targets & Innovations: (1) Extension of existing targets: EGFR and VEGF monoclonal antibodies continue in combination regimens for RAS/BRAF subtypes, with HER2 and BRAF targeting steadily adopted in guidelines;(2) New ADC tracks such as c-MET, CEACAM5, TROP2, CDH17 are progressing rapidly, with some reaching registration phase;(3) Double-specific antibodies and ADCs focusing on LAG3, TIGIT, CLDN18.2, DLL3, B7-H3 are innovative hotspots, especially in combined immunotherapy for MSS/pMMR patients;(4) Under molecular stratification, multi-targeted precise combos (e.g., BRAF/EGFR, HER2/PI3K) continue to push survival benefit upward.▲ Fig.3 Mapping of colorectal cancer target distribution derived from Insight Database05 Prostate Cancer: From Androgen Dependence to Personalized Precision TherapyProstate cancer is the fourth most common cancer globally and the second leading cancer among men, with 1.46 million new cases and 397,430 deaths in 2022[1,11] . Early-stage prostate cancer is primarily treated with radical surgery and/or radiotherapy. Advanced/metastatic cases are treated with androgen deprivation therapy (ADT) plus AR inhibitors (abiraterone, enzalutamide), offering high tolerability and mild side effects. With castration resistance, docetaxel or other chemotherapy and PARP inhibitors (e.g., olaparib) are added where DNA repair defects are present. Radionuclide therapies, immune checkpoint inhibitors, and cancer vaccines are also gradually being adopted[12] .Emerging Targets & Innovations:(1) PSMA: Lu-177-PSMA-617 is approved; several PSMA-ADC drugs are in development;(2) AR: Androgen receptor remains core, with next-gen antagonists under active development;(3) GNRHR: Gonadotropin-releasing hormone receptor agonists/antagonists;(4) PD-1/PD-L1: The most widely approved checkpoint antibodies; (5) PARP: Highly effective in BRCA-mutant cohorts;(6) Exploring novel targets such as DLL3, STEAP1, TROP2.▲ Fig.4 Mapping of Prostate cancer target distribution derived from Insight Database06 Gastric Cancer: Precision Subtyping and Novel Targets Drive InnovationGastric cancer is the fifth most common globally, with over 968,784 new cases and 660,175 deaths in 2022[13] . The standard of care for HER2-positive patients is trastuzumab plus chemotherapy as first-line therapy[14] , with FDA/EMA now approving pembrolizumab for PD-L1-positive patients to form triple combinations. Next-generation HER2-ADC (trastuzumab deruxtecan) is approved for second- and later-line treatment. Zolbetuximab, approved in December 2024, is the first CLDN18.2-targeted therapy for HER2-negative/CLDN18.2-positive patients.Emerging Targets & Innovations:(1) Intense competition in CLDN18.2, with over 100 related agents under development (including ADCs, bispecifics, and CAR-T) besides approved zolbetuximab;(2) TROP2-ADC agents such as sacituzumab tirumotecan show promise;(3) Immune checkpoints: TIGIT inhibitor domvanalimab has shown anti-tumor activity in the EDGE-Gastric trial, with the Phase III STAR221 study ongoing[13] ;(4) New targets such as C-MET, TROP2, and MSLN are under active exploration;(5) Extension of existing targets: VEGFR2, FGFR2.▲ Fig.5 Mapping of Gastric cancer target distribution derived from Insight Database07 Liver Cancer: A New Treatment Paradigm Led by Immune CombinationLiver cancer is the sixth most common and third most deadly cancer worldwide-with about 968,784 new cases and over 758,725 deaths in 2022. Over half of these occur in China, with main risk factors including hepatitis B and C infection, alcoholic liver disease, and non-alcoholic steatohepatitis. First-line therapy for hepatocellular carcinoma is now diverse: sorafenib and lenvatinib (multi-targeted TKIs) as traditional standards for the advanced stage, while the combination of atezolizumab and bevacizumab (IMbrave150) has become a major new standard. Second-line options include regorafenib, cabozantinib, ramucirumab, and immune checkpoint inhibitors (nivolumab, pembrolizumab). Next-generation TKIs targeting VEGF/FGFR and combination immunotherapies are widely used[15] .Emerging Targets & Innovations:(1) GPC3 is a pivotal target for both ADC and CAR-T, with breakthrough efficacy reported;(2) TGF-β pathway inhibitors (like galunisertib), TIGIT, LAG-3 (novel checkpoint targets) are under active exploration;(3) Inhibitors targeting FGFR4, MET, AXL, PI3K/AKT/mTOR, and Wnt/β-catenin pathways are advancing;(4) Tumor microenvironment modulation, gut microbiome intervention, and oncolytic virus therapies are promising new directions[16] .▲ Fig.6 Mapping of Liver cancer target distribution derived from Insight Database08 Conclusion & Outlook: Synergistic Innovation Leading the WayCancer treatment has entered a new era. Immune checkpoint inhibitors, ADCs, and targeted treatments are rapidly rewriting clinical guidelines. Future breakthroughs will increasingly come from:◆ Discovery of innovative targets: Continued exploration of new targets such as Claudin 18.2, TROP2, B7-H3, and CDH17;◆ Combination wisdom: Strategies such as “ADC plus immunotherapy” and “bispecific plus ADC” will become R&D mainstream;◆ Personalized precision medicine: Deep biomarker analysis enables optimal treatment for each patient.SanyouBio will continue to uphold scientific rigor and innovative spirit, working in concert with global peers to advance antibody drug development and contribute our wisdom and strength to conquering cancer.Note: This content is based on the latest published scientific literature and clinical research data, and is intended as a reference for medical industry professionals only. Specific treatment decisions should follow current clinical guidelines and the recommendations of professional physicians.▍参考文献[1] BRAY F, LAVERSANNE M, SUNG H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J/OL]. CA: A Cancer Journal for Clinicians, 2024, 74(3): 229-263. DOI:10.3322/caac.21834.[2] ZHAO S, ZHAO H, YANG W, et al. The next generation of immunotherapies for lung cancers[J/OL]. Nature Reviews Clinical Oncology, 2025: 1-25. DOI:10.1038/s41571-025-01035-9.[3] ZHOU F, GUO H, XIA Y, et al. The changing treatment landscape of EGFR-mutant non-small-cell lung cancer[J/OL]. Nature Reviews Clinical Oncology, 2025, 22(2): 95-116. DOI:10.1038/s41571-024-00971-2.[4] ARNOLD M, MORGAN E, RUMGAY H, et al. Current and future burden of breast cancer: Global statistics for 2020 and 2040[J/OL]. The Breast, 2022, 66: 15-23. DOI:10.1016/j.breast.2022.08.010.[5] GRADISHAR W J, MORAN M S, ABRAHAM J, et al. Breast Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology[J/OL]. Journal of the National Comprehensive Cancer Network, 2024, 22(5): 331-357. DOI:10.6004/jnccn.2024.0035.[6] LI R, HUA M, LI J, et al. The safety of trastuzumab deruxtecan (DS‐8201) with a focus on interstitial lung disease and/or pneumonitis: A systematic review and single‐arm meta‐analysis[J/OL]. Cancer, 2024, 130(17): 2968-2977. DOI:10.1002/cncr.35349.[7] HONG X, CHEN X, WANG H, et al. A HER2‐targeted Antibody‐Drug Conjugate, RC48‐ADC, Exerted Promising Antitumor Efficacy and Safety with Intravesical Instillation in Preclinical Models of Bladder Cancer[J/OL]. Advanced Science, 2023, 10(32): 2302377. DOI:10.1002/advs.202302377.[8] MORRISON L, LOIBL S, TURNER N C. The CDK4/6 inhibitor revolution-a game-changing era for breast cancer treatment[J/OL]. Nature Reviews Clinical Oncology, 2024, 21(2): 89-105. DOI:10.1038/s41571-023-00840-4.[9] BARDIA A, HURVITZ S A, TOLANEY S M, et al. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer[J/OL]. New England Journal of Medicine, 2021, 384(16): 1529-1541. DOI:10.1056/nejmoa2028485.[10] MORRIS V K, KENNEDY E B, BAXTER N N, et al. Treatment of Metastatic Colorectal Cancer: ASCO Guideline[J/OL]. Journal of Clinical Oncology, 2023, 41(3): 678-700. DOI:10.1200/jco.22.01690.[11] HAN B, ZHENG R, ZENG H, et al. Cancer incidence and mortality in China, 2022[J/OL]. Journal of the National Cancer Center, 2024, 4(1): 47-53. DOI:10.1016/j.jncc.2024.01.006.[12] RAYCHAUDHURI R, LIN D W, MONTGOMERY R B. Prostate Cancer[J/OL]. JAMA, 2025, 333(16): 1433-1446. DOI:10.1001/jama.2025.0228.[13] SUNDAR R, NAKAYAMA I, MARKAR S R, et al. Gastric cancer[J/OL]. The Lancet, 2025, 405(10494): 2087-2102. DOI:10.1016/s0140-6736(25)00052-2.[14] BANG Y J, CUTSEM E V, FEYEREISLOVA A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial[J/OL]. The Lancet, 2010, 376(9742): 687-697. DOI:10.1016/s0140-6736(10)61121-x.[15] LIVER E A for the S of the, SANGRO B, ARGEMI J, et al. EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma[J/OL]. Journal of Hepatology, 2025, 82(2): 315-374. DOI:10.1016/j.jhep.2024.08.028.[16] ZHENG J, WANG S, XIA L, et al. Hepatocellular carcinoma: signaling pathways and therapeutic advances[J/OL]. Signal Transduction and Targeted Therapy, 2025, 10(1): 35. DOI:10.1038/s41392-024-02075-w.推荐阅读创新前沿｜2025ADC热门靶点与技术创新启示三优十周年｜AI-STAL篇-千亿高等电点单域抗体库6类分子形式之环状多肽分子产生系统解决方案轻松玩转三优oneClick+线上9大云程序6类分子形式之mRNA分子产生系统解决方案三重好礼相送暨四种抗体制备解决方案全新上线三优生物单域抗体产生系统解决方案三优生物双抗参比品网站SY-BsAb正式上线三优ADC药物研发系统解决方案三优生物oneClick+平台再次上新三优磁阵列全人源小鼠抗体发现平台重磅发布三优超万亿全人单克隆抗体产生平台盘点三优磁阵列全人源小鼠抗体发现平台隆重上线共同轻链抗体产生之超万亿共轻库盘点三优生物73种全系列双抗参比品全新上线关于三优生物三优生物是一家以“让天下没有难做的创新生物药”为使命，以超万亿分子库和人工智能技术双驱的生物医药智能高新技术企业。公司以智能超万亿分子库为核心，打造了干湿结合、国际领先的创新生物药临床前智能化及一体化研发平台，通过“新药发现、临床前研究、智能化药物研发及前沿科学研究”等四个维度加速全球新药发现及靶标深度研究。公司总部位于中国上海，在美国、欧洲等地设有子公司，现有投产及布局的研发及GMP场地20000多平方米。公司为合作伙伴提供“差异化CRO、整合型CDO、协同型CPO、特色CRS”于一体的“创新生物药4C综合业务”。公司已建立全球营销网络，已与全球1200多家药企、生技公司等建立了良好的合作关系；已完成了1200多个新药发现及开发服务项目；已完成了50多个合作研发项目，其中9个合作项目已完成临床申报。公司已获得国家高新技术、上海市专精特新、上海市小巨人和上海“张江之星”企业认定。

作者：唐立成美工：何国红 罗真真排版：马超抗体偶联药物（ADC）领域正经历着前所未有的繁荣与动荡。2025年，全球进入临床阶段的ADC药物已突破200个，涵盖50余个靶点，其中10个核心靶点集中了超40%的研发管线。截至当前，全球已获批ADC药物总数已达17款（详见表1）。中国药企在这一领域频频有精彩表现——百利天恒的EGFR/HER3双抗ADC在关键III期临床告捷，成为全球首个取得突破的双抗ADC；信诺维的Claudin18.2 ADC以15亿美元授权安斯泰来后快速推进至III期临床；而复宏汉霖的PD-L1 ADC则领跑全球，率先进入国际多中心II期研究。▲ 表1 全球ADC获批药物详情表01 全球ADC临床管线全景分析抗体偶联药物（ADC）的临床开发呈现指数级增长态势。截至2025年7月，全球处于临床阶段的ADC药物约230个，涵盖从I期到III期的全阶段布局。这些药物在靶点选择上呈现明显的“靶点聚集效应”：HER2、TROP2、EGFR、Claudin18.2四大靶点占据主导地位，合计占比超过50%。▲ 图1 全球ADC热门靶点热门靶点背后的科学逻辑驱动了这一分布格局：HER2：作为经典肿瘤驱动基因，在乳腺癌、胃癌等多种实体瘤中高表达，其内化效率高的特性使其成为ADC的理想靶标。目前已有三款HER2 ADC（T-DM1、DS-8201、RC48）获批上市，临床验证降低了研发风险。TROP2：在三阴性乳腺癌等缺乏有效治疗手段的癌种中广泛表达，成为解决未满足临床需求的突破口。吉利德的Trodelvy获批后，其市场表现证明了该靶点的商业价值。EGFR：在非小细胞肺癌、头颈癌等多种肿瘤中过表达，得利于百利天恒的EGFR/HER3双抗ADC药物BL-B01D1的推动，EGFR双抗ADC管线迎来大爆发。Claudin18.2：具有高度组织特异性（主要在胃黏膜），在70%-80%的胃癌患者中表达，被视为胃癌靶向治疗的“圣杯”。但其在正常组织中的低水平表达也为安全性埋下隐患。02 热门靶点的临床进展与技术迭代01HER2靶点：后DS-8201时代的破局尝试HER2 ADC领域目前正经历技术代际更替，作为一个已有三款ADC药物上市的成熟靶点，HER2仍有不少挖掘潜力。第三代ADC药物DS-8201在2024年全球年销突破40亿美元，涵盖乳腺癌、胃癌、肺癌等五大癌种，堪称ADC界的“天花板”。DS-8201凭借高DAR值（~8）和可裂解连接子技术，在乳腺癌治疗中取得突破，但其引发的间质性肺病（ILD）风险和耐药问题催生了新一代研发策略。▲ 图2 国内外HER2 ADC产品对比除了高歌猛进的好消息，也有坏消息传来。就在2025年5月，曾经视为HER2 ADC又一款明星潜力药物的BB-1701被百力司康的合作伙伴卫材宣布终止双方高达20亿美元的合作，原因是合作伙伴卫材主导的试验显示ORR仅14.3%，相比百力司康自主试验（206试验）的患者客观缓解率（ORR）21.4%，最佳缓解率（BRR）32.1%相差甚远。02Claudin18.2靶点：从折戟案例中寻找出路Claudin18.2 ADC的研发之路布满荆棘。全球12个进入临床阶段的该靶点ADC中，7个在Ⅱ期遭遇安全性问题，石药集团的SYSA1801（EO-3021）是最新折戟案例。但同时，也有不少管线表现出很大的潜力。信达生物的IBI343在2025年6月的ASCO报道了其治疗晚期胰腺癌的I期临床研究优异数据。确认的客观缓解率（cORR）为22.7%，疾病控制率（DCR）为81.8%，中位无进展生存期（PFS）为5.4个月，中位总生存期（OS）为9.1个月。≥3级恶心、呕吐的发生率均为0。信达生物在今年6月底刚刚开启了一项IBI343针对胰腺癌的III期临床试验。信诺维的XNW27011也展现出很好的安全性。在I期剂量递增研究中，4.8 mg/kg以下剂量未观察到≥3级治疗相关不良事件，未出现间质性肺病或神经毒性。其采用的可裂解连接子技术增强了肿瘤微环境中的药物释放效率，即使在CLDN18.2低表达患者中也观察到疗效。此外还有恒瑞医药的SHR-A1904、康诺亚的CMG-901、德琪医药的ATG022等多款已进入临床的CLDN18.2 ADC颇具潜力。03PD-L1靶点：免疫调节型ADC的崛起复宏汉霖的HLX43开创了免疫调节型ADC新赛道。该药物通过双重抗肿瘤机制发挥作用：一方面通过经典ADC途径精准杀伤肿瘤细胞；另一方面通过阻断PD-L1激活免疫应答。在2025年ASCO年会上公布的I期数据显示，其对不同PD-L1表达状态的NSCLC患者均有效，包括EGFR突变型、脑转移患者等难治人群。HLX43的高DAR值设计（≈8）突破了传统ADC的载荷限制，但同时也带来安全性挑战。其全球多中心II期研究将重点评估这一设计在更大患者群体中的风险获益比。03 ADC技术创新与新兴ADC靶点过去，ADC研发主要聚焦于靶点的选择、载荷和连接子的迭代以及偶联技术的优化。如今，这些技术日益成熟并催生出如德曲妥珠单抗、恩美曲妥珠单抗和维布妥昔单抗等年销售额数十亿美元的重磅ADC产品，ADC疗法的商业价值已被充分验证。当前，以双抗/多抗ADC、多载荷ADC等为代表的“高阶”创新形式正成为行业探索的新方向，并可能成为药企差异化竞争的关键所在。越来越多相关临床试验的成功，正为这一趋势写下生动注脚。百利天恒的BL-B01D1同时靶向EGFR和HER3，在经治的EGFR突变非小细胞肺癌患者中ORR达69%，外显子20插入突变患者ORR高达86%，中位无进展生存期（PFS）10.5个月。基石药业CS5007（EGFR/HER3）：临床前数据显示对双阳性肿瘤强效杀伤，稳定性优于传统ADC。优异的数据启发了大量药企布局双抗ADC赛道。科伦博泰Sac-TMT连接子：兼具pH依赖性和酶促裂解特性，优化旁观者效应并降低脱靶毒性。默克exatecan平台：采用新一代拓扑异构酶I抑制剂（TOPOi）载荷，开发中的CEACAM5靶向ADC（M9140）在结直肠癌I期试验ORR 31%，mPFS 6.9个月。各种连接子与毒素的创新赋予了ADC新的可能。在2025年的AACR中，也涌现了一批新颖ADC靶点，如CDH17、MLSN、PSMA以及CEACAM5等。01CDH17 ADCCDH17是钙粘蛋白超家族的成员，钙粘蛋白超家族是一组钙依赖性细胞粘附分子，对器官发育、组织完整性和癌症进展至关重要。▲ 图3 CDH17结构在正常组织中，CDH17高度局限于侧膜，隐藏在无法接近的肠道紧密连接处。相比之下，它在50%至90%的胃肠道癌症中过表达和重新分布，导致其暴露于癌细胞表面，因此变得更容易获得。这一独特功能使CDH17成为基于抗体的治疗的有前途的靶点。目前已布局CDH17的公司有：维立志博的LBL-054、华东医药的HDM2017、Tavotek Biotherapeutics的TAVO307、宜联生物的YL127、SOTIO Biotech的SOT109、博奥信生物的BSI-721、橙帆医药的VBC108、礼新医药的LM-350、先声药业的SCR-A008等。02MSLN ADCMSLN（Mesothelin，间皮素）是一种细胞表面分子，以成熟形式表达为通过糖基磷脂酰肌醇键固定在细胞膜上的40 kDa蛋白。MSLN的异常与很多疾病相关，在许多实体瘤中过表达，包括卵巢癌、胰腺癌、子宫内膜癌、肺癌和结直肠癌等。▲ 图4 MSLN相关信号通路自发现以来，MSLN一直是各种方式的抗肿瘤疗法开发的目标，有很多不同在研药物类型，包括抗体、CAR-T和多种ADC药物等。目前已布局MSLN的公司有：辉瑞与和铂医药合作开发的PF-08052666、荣昌生物的RC88等。03PSMA ADCPSMA（前列腺特异性膜抗原）是一种II型跨膜糖蛋白，包含跨膜结构域、细胞外结构域以及酶活性区域，PSMA具有N-乙酰基-α-氨基己糖苷酶（GluN）的酶活性，能够水解N-乙酰氨基己糖苷，这种酶活性在某些生理和病理过程中发挥作用。▲ 图5 PSMA的结构PSMA在绝大多数前列腺癌（PCa）细胞中高表达，因此是一个成熟的靶向前列腺癌的诊断和治疗领域的靶点。目前已布局PSMA的公司有：金赛药业开发的B7-H3 x PSMA双抗ADC GenSci143，Syndivia开发的SDV2102等。04CEACAM5 ADCCEACAM5（通常称为CEA）是癌胚抗原相关细胞黏附分子（CEACAM）家族的成员之一。▲ 图6 CEACAM家族成员结构CEACAM5在多种上皮肿瘤中高表达，包括结肠癌、胃癌、胰腺癌、卵巢癌和肺癌，靶向CEACAM5的治疗策略正在不断开发中，包括ADC药物、单域抗体药物偶联物（UdADC）、双特异性抗体以及CAR-T细胞疗法等目前已布局CEACAM5的公司有：百济神州开发的BG-C477，信达开发的新一代双载荷ADC IBI3020等。三优ADC药物研发系统解决方案针对ADC药物研发目前的4大痛点：▶ 1. 多次跨膜靶点的抗体开发困境，好分子一将难求▶ 2. ADC药物毒素元件研发面临安全性与疗效双重挑战▶ 3. 缺失参比品与Payload库▶ 4. 缺乏一体化研发服务三优生物皆可提供多种产品支持，并有专业的技术团队可提供完善的选型方案推荐，能够为客户带来“确定性”。三优生物建立的ADC偶联平台可以实现高通量和快速偶联。对于大多数偶联项目，可以实现一次性开发。下图显示了来自定期统计的平台偶联样品，其中8%在4天内完成，29%在7天内完成，63%在10天内完成。▲ 图7 平台交付周期（包括开发和偶联）更多三优ADC药物研发系统解决方案流程案例请见《三优ADC药物研发系统解决方案》Innovation Frontier｜Global ADC Drug Clinical Development in 2025: Key Targets and Technological InnovationsThe field of antibody-drug conjugates (ADCs) is undergoing unprecedented growth and volatility. As of 2025, over 200 ADC drugs have entered the clinical stage globally, targeting more than 50 different antigens. Notably, 10 core targets account for over 40% of the development pipeline. As of now, a total of 17 ADC drugs have been approved worldwide (see Table 1).Chinese pharmaceutical companies have made frequent breakthroughs in this area. Betta Pharmaceuticals’ EGFR/HER3 bispecific ADC achieved success in a pivotal Phase III trial, marking the first global breakthrough for a bispecific ADC. After licensing its Claudin18.2 ADC to Astellas for $1.5 billion, Syncell quickly advanced the asset into Phase III trials. Meanwhile, Henlius’ PD-L1 ADC leads globally, entering an international multicenter Phase II study ahead of competitors.▲ Table 1. Approved ADC Drugs Worldwide01 Global ADC Clinical Pipeline OverviewThe clinical development of ADCs has shown exponential growth. As of July 2025, approximately 230 ADC drugs are in clinical stages globally, spanning from Phase I to Phase III. Target selection shows a significant “target concentration effect,” with four major targets-HER2, TROP2, EGFR, and Claudin18.2-dominating the field and accounting for over 50% of clinical pipelines.▲ Figure 1. Popular ADC Targets GloballyScientific rationale underpins this distribution:HER2: A classic tumor driver gene, highly expressed in multiple solid tumors such as breast and gastric cancers. Its efficient internalization makes it ideal for ADCs. Three HER2 ADCs (T-DM1, DS-8201, RC48) have already been approved, reducing development risk.TROP2: Widely expressed in cancers with limited treatment options such as triple-negative breast cancer (TNBC), providing a breakthrough for unmet medical needs. The commercial success of Gilead’s Trodelvy validated this target’s market potential.EGFR: Overexpressed in several cancers, including non-small cell lung cancer (NSCLC) and head and neck cancers. The success of Betta Pharmaceuticals’ EGFR/HER3 bispecific ADC BL-B01D1 has sparked a surge in EGFR-targeting bispecific ADC pipelines.Claudin18.2: Highly tissue-specific (primarily in gastric mucosa) and expressed in 70%–80% of gastric cancer patients, making it the “Holy Grail” for targeted gastric cancer therapy. However, low-level expression in normal tissues poses potential safety risks.02 Clinical Progress and Technological Iteration of Popular Targets01HER2: Innovation in the Post-DS-8201 EraThe HER2 ADC field is undergoing a generational shift. Although three HER2 ADCs are already on the market, the target still holds substantial potential. The third-generation DS-8201 achieved global sales exceeding $4 billion in 2024 across five major cancers (breast, gastric, lung, etc.), setting a high benchmark in the ADC space.DS-8201’s success is attributed to its high drug-to-antibody ratio (DAR ~8) and cleavable linker technology, which contributed to breakthroughs in breast cancer treatment. However, the risk of interstitial lung disease (ILD) and resistance issues have prompted new development strategies.▲ Figure 2. Comparison of Domesticand International HER2 ADCsHowever, not all news is positive. In May 2025, Eisai terminated its up-to-$2 billion partnership with BioAtla on the HER2 ADC BB-1701 due to disappointing Phase I results-an objective response rate (ORR) of just 14.3%, compared to 21.4% ORR and 32.1% best response rate (BRR) from BioAtla’s own Study 206.02Claudin18.2: Learning from FailuresDevelopment of Claudin18.2-targeting ADCs has faced significant hurdles. Of the 12 Claudin18.2 ADCs in clinical development, 7 encountered safety issues in Phase II trials. The most recent failure was SYSA1801 (EO-3021) from CSPC Pharmaceutical.Nevertheless, some pipelines show promise. Innovent’s IBI343 reported outstanding Phase I results at ASCO 2025 for advanced pancreatic cancer: confirmed ORR of 22.7%, disease control rate (DCR) of 81.8%, median progression-free survival (PFS) of 5.4 months, and median overall survival (OS) of 9.1 months. Notably, no ≥ Grade 3 nausea or vomiting events occurred. Innovent launched a Phase III trial targeting pancreatic cancer in late June 2025.Syncell’s XNW27011 also demonstrated excellent safety. In the dose-escalation Phase I study, doses below 4.8 mg/kg showed no ≥ Grade 3 treatment-related adverse events, including no ILD or neurotoxicity. Its cleavable linker technology enhances drug release in the tumor microenvironment and showed efficacy even in low CLDN18.2 expressers.Other promising Claudin18.2 ADCs in clinical stages include SHR-A1904 (Hengrui), CMG-901 (Keymed Biosciences), and ATG022 (Antengene).03PD-L1: Rise of Immunomodulatory ADCsHenlius’ HLX43 pioneered the immunomodulatory ADC (iADC) concept. It leverages a dual anti-tumor mechanism: traditional ADC-mediated cytotoxicity and PD-L1 blockade-induced immune activation.Phase I data presented at ASCO 2025 showed efficacy across NSCLC patients with varying PD-L1 expression, including difficult-to-treat populations like EGFR-mutated and brain metastasis patients.Designed with a high DAR (~8), HLX43 pushes the payload boundary of ADCs, raising safety concerns. Its ongoing global Phase II trial will assess the benefit-risk balance in a broader population.03 ADC Technology Innovations and Emerging TargetsNow, advanced innovations-like bispecific/multispecific ADCs and multi-payload ADCs-are emerging as key differentiators. Successful trials are increasingly validating these next-gen strategies.BL-B01D1 (Betta Pharmaceuticals): Targets EGFR and HER3 simultaneously, achieving a 69% ORR in pretreated EGFR-mutant NSCLC patients and 86% in those with exon 20 insertions; median PFS of 10.5 months.CS5007 (CStone): Strong preclinical efficacy against EGFR/HER3 dual-positive tumors, with superior stability over traditional ADCs.Innovations in conjugation and payload chemistry include:Sac-TMT linker (Sichuan Kelun-Biotech): Combines pH sensitivity and enzymatic cleavage to optimize bystander effects and reduce off-target toxicity.Exatecan platform (Merck): A next-gen topoisomerase I inhibitor payload. M9140, a CEACAM5-targeting ADC, showed an ORR of 31% and median PFS of 6.9 months in Phase I colorectal cancer trials.The AACR 2025 conference spotlighted several novel ADC targets:01CDH17 ADCCDH17 is a cadherin superfamily member crucial for organ development, tissue integrity, and cancer progression.▲ Figure 3. CDH17 StructureIn normal tissues, CDH17 is restricted to the lateral membrane within intestinal tight junctions. In contrast, it is overexpressed and redistributed in 50%–90% of GI cancers, becoming exposed on the cell surface-making it highly accessible for antibody-based therapy.Companies with CDH17 ADC programs include: Leadsbiolabs’s LBL-054, Huadong Medicine’s HDM2017, Tavotek’s TAVO307, YL Biotech’s YL127, SOTIO Biotech’s SOT109, BioCeen’s BSI-721, Voronoi’s VBC108, Laekna’s LM-350, Simcere’s SCR-A008, among others.02MSLN ADCMesothelin (MSLN) is a GPI-anchored surface protein overexpressed in multiple solid tumors, including ovarian, pancreatic, endometrial, lung, and colorectal cancers.▲ Figure 4. MSLN-Associated Signaling PathwaysMSLN has long been a target for anti-tumor therapeutics, including monoclonal antibodies, CAR-Ts, and ADCs.Notable developers include: Pfizer and Harbour BioMed (PF-08052666), RemeGen (RC88).03PSMA ADCProstate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein with GluN enzymatic activity. It is highly expressed in most prostate cancer cells, making it an established target for prostate cancer diagnosis and treatment.▲ Figure 5. PSMA StructureCurrent developers include: GenSci’s GenSci143 (B7-H3 x PSMA bispecific ADC), Syndivia’s SDV2102, among others.04CEACAM5 ADCCEACAM5 (commonly known as CEA) is a member of the carcinoembryonic antigen-related cell adhesion molecule family.▲ Figure 6. CEACAM Family StructureHighly expressed in many epithelial cancers (e.g., colorectal, gastric, pancreatic, ovarian, lung), CEACAM5 is the target of multiple approaches including ADCs, UdADCs (single-domain antibody-drug conjugates), bispecific antibodies, and CAR-T cells.  Companies developing CEACAM5-targeting ADCs include: BeiGene (BG-C477), Innovent (dual-payload IBI3020).Sanyou ADC Drug Development SolutionsSanyou Bio offers comprehensive system solutions for ADC drug development, addressing four major challenges in the field:▶ 1. Difficulty in antibody discovery for multi-transmembrane targets—“one good molecule is hard to find.”▶ 2. Dual challenge of safety and efficacy in toxin development.▶ 3. Lack of reference standards and payload libraries.▶ 4. Need for integrated R&D services.Sanyou provides extensive product support and expert technical teams capable of delivering reliable target selection strategies, helping clients gain “development certainty.”Sanyou’s ADC conjugation platform supports high-throughput and rapid conjugation, with many projects achieving one-time development success. The chart below shows turnaround statistics: 8% of conjugates delivered within 4 days, 29% within 7 days, 63% within 10 days▲ Figure 7. Sanyou Platform Turnaround Time (Including Development and Conjugation)For more details, see “Sanyou’s System Solutions for ADC Drug Development.”推荐阅读三优十周年｜AI-STAL篇-千亿高等电点单域抗体库6类分子形式之环状多肽分子产生系统解决方案轻松玩转三优oneClick+线上9大云程序6类分子形式之mRNA分子产生系统解决方案三重好礼相送暨四种抗体制备解决方案全新上线三优生物单域抗体产生系统解决方案三优生物双抗参比品网站SY-BsAb正式上线三优ADC药物研发系统解决方案三优生物oneClick+平台再次上新三优磁阵列全人源小鼠抗体发现平台重磅发布三优超万亿全人单克隆抗体产生平台盘点三优磁阵列全人源小鼠抗体发现平台隆重上线共同轻链抗体产生之超万亿共轻库盘点三优生物73种全系列双抗参比品全新上线三优生物智能超万亿分子发现平台盘点及展望关于三优生物三优生物是一家以“让天下没有难做的创新生物药”为使命，以超万亿分子库和人工智能技术双驱的生物医药智能高新技术企业。公司以智能超万亿分子库为核心，打造了干湿结合、国际领先的创新生物药临床前智能化及一体化研发平台，通过“新药发现、临床前研究、智能化药物研发及前沿科学研究”等四个维度加速全球新药发现及靶标深度研究。公司总部位于中国上海，在美国、欧洲等地设有子公司，现有投产及布局的研发及GMP场地20000多平方米。公司为合作伙伴提供“差异化CRO、整合型CDO、协同型CPO、特色CRS”于一体的“创新生物药4C综合业务”。公司已建立全球营销网络，已与全球1200多家药企、生技公司等建立了良好的合作关系；已完成了1200多个新药发现及开发服务项目；已完成了50多个合作研发项目，其中9个合作项目已完成临床申报。公司已获得国家高新技术、上海市专精特新、上海市小巨人和上海“张江之星”企业认定。

作者：钟东英 薛超然美工：何国红 罗真真排版：马超01 引言单域抗体以其分子量小、组织穿透性强、结构稳定性高等独特优势，在生物医药领域展现出广阔的应用前景。三优生物基于对天然单域抗体结构的深度解析，融合自主知识产权的AI算法，结合高通量筛选与真核表达验证技术，成功构建千亿级高等电点单域抗体库。该平台通过精准调控等电点（8.0-9.0）及系统性排除PTM位点，显著提升抗体的稳定性与成药性，为全球创新药研发提供高效、精准的单域抗体发现解决方案。02 文库背景近年来，全球单域抗体领域迎来快速发展：2020年相关市场规模已突破50亿美元，预计到2025年将增长至120亿美元以上。长期来看，到2030年，这一细分市场有望突破300亿美元，成为抗体药物中增速最快的类别之一。中国单域抗体研发的活跃度更是显著高于全球，尤其在肿瘤和罕见病治疗领域展现出领先潜力。单域抗体因其分子结构精简、组织穿透性强以及稳定性高等独特优势，正成为生物医药创新的前沿方向。与传统抗体相比，其更易实现工程化改造，可针对复杂靶点（如GPCR、离子通道）设计高亲和力药物，同时生产成本更低，有望显著加速新型疗法开发并提升其在全球范围内的可及性。然而，传统单域抗体制备技术面临成药性不足的挑战，如低等电点导致的非特异性结合、翻译后修饰（PTM）位点引发的稳定性问题等，严重限制了抗体药物的开发效率。为突破这一瓶颈，三优生物凭借前瞻性的AI驱动技术布局，于2024年成功构建并验证了千亿级高等电点单域抗体库，并将于2025年进一步扩容升级，推出超万亿高等电点单域抗体库（Super Trillion-Optimized pI Single-Domain Library，ST-OPSD）。这一突破性进展标志着三优生物在单域抗体发现领域迈入了全新阶段，其超万亿级抗体库平台将极大加速针对难成药靶点的高稳定性单域抗体药物的开发进程。03 文库组成三优生物在万亿级人源化单域抗体库的基础上持续创新，建立了千亿级高等电点单域抗体库平台。该平台采用先进的人工智能算法，对纳米抗体进行全序列生成与优化，反向筛选出具有优异成药性的候选分子。通过精准调控，文库中纳米抗体的等电点严格控制在8.0-9.0，显著提高其在体内的稳定性，减少非特异性结合。同时，系统性排除影响成药性的翻译后修饰（PTM）位点，如糖基化位点、脱酰胺及异构化等，确保抗体分子的高稳定性和可开发性。目前总库容高达1.00千亿，2025年扩容完成后，库容可达超万亿，覆盖广泛的靶点结合多样性。扩充库容后的ST-OPSD具体组成如表1所示。▼ Table 1 Composition of ST-OPSD04 文库特性01抗体先导分子等电点高通过对千亿级高等点单域抗体库筛选测序，序列分析结果表明，等电点（pI）在8.0-9.0范围内的分子占比显著提高。能够改善溶解度、降低聚集倾向，并增强在体内的稳定性，从而显著提升候选药物的生物利用度和药代动力学特性。此外，该等电点范围内的分子通常表现出更低的非特异性结合，减少了潜在的脱靶效应，进一步提高了药物的安全性和有效性。▲ Fig. 1 Comparison of 8.0-9.0 pImolecule distribution02排除PTM位点通过对千亿级高等点单域抗体库筛选测序，序列分析结果表明，候选分子不含翻译后修饰（PTM）位点。无PTM位点意味着这些分子具有更高的结构稳定性、更低的免疫原性，从而显著提升了其成药性。此外，无PTM位点也降低了生产过程中出现异质性的风险，简化了纯化和质量控制流程。▼ Table 2 Post-Translational Modifications03人源化程度高三优构建的千亿级高等电点单域抗体库具有较高的人源化程度。通过130多个单域抗体分子的人源化项目经验积累，对单域抗体的骨架区（FR区）进行人源化改造，通过文库筛选，可以直接获得人源化程度高达98%的单域抗体，无需进行额外的人源化流程，大大缩短了项目周期。04全面成药性分析千亿级高等点单域抗体库筛选服务获得的分子构建全长后，对抗体的表达量及抗体的生化理化特性进行全面分析。如表所示，包括纯度及浓度测定、一级结构分析和亲和力及亲和动力学等多个维度。▼ Table 3 Developability of Antibodiesfrom ST-OPSD05先导分子数量多针对不同难度的靶点，该平台平均可获得35个序列独特、特异性强、成药性高的先导抗体，显著加速抗体药物的开发进程。该平台不仅适用于肿瘤、自身免疫性疾病等传统治疗领域，还可拓展至双特异性抗体、抗体偶联药物（ADC）、细胞治疗等前沿方向。▲ Fig. 2 The number of leadingmolecules from different projects05 代表案例01抗BCMA单域抗体的开发基本信息：BCMA（B细胞成熟抗原）是肿瘤坏死因子受体超家族（TNFR）的重要成员，在恶性浆细胞疾病和自身免疫性疾病治疗中具有关键作用。其主要配体：BAFF（B细胞激活因子）和APRIL（增殖诱导配体）。竞争格局：BCMA靶向疗法已在临床取得显著进展并获批上市，主要包括：CAR-T细胞疗法（如Abecma, Carvykti），通过基因改造T细胞直接杀伤肿瘤；抗体偶联药物（ADC）（如Blenrep），精准递送细胞毒药物至肿瘤；以及双特异性抗体（如Tecvayli），桥接T细胞和肿瘤细胞进行杀伤。药物MOA：作用机制均为特异性结合BCMA，从而介导肿瘤细胞的清除：CAR-T细胞直接裂解肿瘤，ADC释放毒性药物诱导细胞凋亡，双抗则激活T细胞对肿瘤进行杀伤。02BCMA抗体关键结果◆ 细胞水平的结合活性分析通过三优三优千亿级高等点单域抗体库筛选获得的单域抗体候选分子大多具有较好的细胞水平结合活性。如图3展示了采用FACS分析候选抗体与huBCMA-HEK293细胞的亲和力测定结果，其中全部候选抗体的亲和力水平优于对照抗体。▲ Fig. 3. Affinity testing of antibodies◆ 阻断活性分析采用ELISA方法检测候选抗体A001、A002、A003和A004是否阻断BAFF-NFC与huBCMA-ECD-His-Biotin蛋白的结合。结果如Fig. 4所示。候选抗体A001、A002、A003和A004阻断BAFF-NFC与huBCMA-ECD-His-Biotin蛋白的结合。▲ Fig. 4 Blocking testing of antibodies06 总结展望当前，全球抗体药物市场正迎来快速发展期，2023年全球抗体药物市场规模已突破2000亿美元，其中单域抗体因其可高效靶向传统抗体难以触及的特殊表位等独特的结构优势，正成为新一代治疗药物的研发热点。作为抗体药物开发的核心引擎，单域抗体文库的构建不仅直接决定了候选分子的多样性和质量，更是突破"不可成药"靶点、实现差异化创新的战略高地，已成为全球顶尖药企和生物技术公司竞相布局的关键赛道。三优生物依托在抗体工程领域多年的技术积淀，并基于成功建立的AI-STAL平台经验，已突破高等电点单域抗体库构建的各项技术壁垒，成功完成了千亿级高等电点单域抗体库的开发和验证。展望未来，三优生物将持续发挥其平台技术优势，在2025年完成万亿级高等电点单域抗体库的构建，排除PTM位点延长抗体半衰期、加速高难度靶点和高难度表位的单域抗体发现，以及持续优化深度学习算法，从头生成具有高成药潜力的单域抗体。通过这些创新技术突破，三优生物将显著提升单域抗体药物的开发效率，大幅缩短创新抗体药物的研发周期，为全球患者提供更加系统的解决方案。Sanyou 10th Anniversary: AI-STAL - 100 Billion Optimal pI Single-Domain Antibody Library01 IntroductionSingle-domain  antibodies (sdAbs) exhibit broad therapeutic potential in biomedicine  owing to their unique advantages of small molecular size, enhanced  tissue penetration, and superior structural stability. Based on  comprehensive structural analysis of natural sdAbs, Sanyou Biotech has  constructed a 100-billion-size optimal-pI sdAb library platform  integrating proprietary AI algorithms with high-throughput screening and  eukaryotic expression validation. This platform significantly enhances  antibody stability and druggability through precise pI modulation  (8.0–9.0) and systematic elimination of PTM sites, delivering an  efficient and precise sdAb discovery solution for global innovative drug  development.02 Library BackgroundThe  single-domain antibody (sdAb) field has experienced rapid global growth  in recent years, with the market value exceeding $5 billion in 2020 and  projected to surpass $12 billion by 2025. Long-term projections  indicate this segment may reach $30 billion by 2030, positioning sdAbs  among the fastest-growing antibody therapeutics. China's sdAb R&D  activity notably outpaces global trends, demonstrating leading potential  in oncology and rare disease therapeutics. Owing to their minimized  molecular architecture, enhanced tissue penetration, and superior  stability, sdAbs are emerging as a cutting-edge modality in  biomedicines. Compared to conventional antibodies, their engineerability  enables high-affinity drug design against complex targets (e.g., GPCRs,  ion channels), while lower production costs promise accelerated  therapeutic development and improved global accessibility.However,  traditional sdAb development faces critical drug developability  challenges, including nonspecific binding due to low pI and stability  issues caused by post-translational modification (PTM) sites, which  substantially constrain antibody drug development efficiency. To  overcome these limitations, Sanyou Biotech leveraged its pioneering  AI-driven platform to successfully construct and validate a  100-billion-member optimal-pI sdAb library in 2024. The platform will be  significantly expanded in 2025 with the launch of its ST-OPSD (Super  Trillion Optimal-pI Single-Domain Library), a multi-trillion high-pI  sdAb library. This breakthrough marks Sanyou's entry into a new era of  sdAb discovery, where its trillion-scale antibody platform will  dramatically accelerate development of highly stable sdAb therapeutics  targeting difficult-to-drug targets.03 Library CompositionBuilding  upon its trillion-scale humanized sdAb library, Sanyou Bio has  innovated to establish a 100-billion-member high-pI sdAb platform. This  system employs advanced AI algorithms for de novo nanobody sequence  generation and optimization, enabling reverse screening of candidates  with superior druggability. Through precise engineering, the platform  controls nanobody pI within 8.0–9.0, significantly enhancing in vivo stability  while reducing nonspecific binding. Concurrently, it systematically  eliminates druggability-compromising post-translational modification  (PTM) sites—including glycosylation sites, deamidation, and  isomerization hotspots—ensuring high molecular stability and  developability. The current library capacity reaches 100 billion  distinct antibody sequences, with planned expansion to multi-trillion  scale in 2025. This upgraded ST-OPSD library will provide unprecedented  target-binding diversity, with detailed composition metrics presented in  Table 1.▼ Table 1 Composition of ST-OPSD04 Library Characteristics01High Isoelectric Point (pI) of Lead MoleculesSequencing  analysis of the screened high-pI sdAb library revealed a significantly  higher proportion of molecules with a pI between 8.0 and 9.0. This pI  range improves solubility, reduces aggregation propensity, and enhances in vivo stability,  thus boosting the bioavailability and pharmacokinetic properties of  drug candidates. Moreover, molecules within this pI range typically  exhibit lower non-specific binding, reducing potential off-target  effects and further enhancing drug safety and efficacy.▲ Fig. 1 Comparison of 8.0-9.0 pImolecule distribution02Exclusion of PTM SitesSequencing analysis  of the screened optimal-pI sdAb library confirmed the absence of  post-translational modification (PTM) sites in candidate molecules.  PTM-free molecules exhibit enhanced structural stability and reduced  immunogenicity, significantly improving druggability. Additionally, the  absence of PTM sites mitigates heterogeneity risks during production and  streamlines purification and quality control processes.▼ Table 2 Post-Translational Modifications03High Humanization LevelSanyou  Bio’s high-pI sdAb library features advanced humanization. Leveraging  experience from >130 sdAb humanization projects, framework regions  (FRs) were engineered to achieve up to 98% humanization directly through  library screening. This eliminates additional humanization steps,  substantially shortening project timelines.04Comprehensive Druggability ProfilingFull-length antibodies  derived from the optimal-pI sdAb library undergo multi-dimensional  characterization, including: purity and concentration quantification,  primary structure analysis, affinity and binding kinetics assessment.▼ Table 3 Developability of Antibodiesfrom ST-OPSD05High Expression YieldThe  platform delivers an average of 35 unique, highly specific, druggable  lead antibodies per target across varying difficulties. This accelerates  antibody drug development for oncology, autoimmune diseases, bispecific  antibodies, ADCs, and cell therapies.▲ Fig. 2 The number of leadingmolecules from different projects05 Case Study01Anti-BCMA sdAb DevelopmentBackground: BCMA  (B-cell maturation antigen), a TNF receptor superfamily (TNFRSF)  member, is a validated target in plasma cell malignancies and autoimmune  disorders. Key ligands: BAFF (B-cell activating factor) and APRIL (a  proliferation-inducing ligand).Competitive Landscape: Approved  BCMA-targeted therapies include: CAR-T (e.g., Abecma®, Carvykti®):  Genetically modified T-cell-mediated tumor lysis; ADC (e.g., Blenrep®):  Tumor-specific cytotoxic payload delivery; Bispecific antibody (e.g.,  Tecvayli®): T-cell engagement for tumor killing.MOA: All  modalities specifically bind BCMA to eliminate tumor cells: CAR-T  induces direct cytolysis, ADC triggers apoptosis via toxin release, and  bispecific antibodies activate T-cell cytotoxicity.02Key Results for BCMA Antibodies◆ Cell-Based Binding AffinityMost  sdAb candidates from Sanyou Bio’s optimal-pI sdAb library demonstrated  superior cell-binding affinity. FACS analysis against huBCMA-HEK293  cells revealed all candidates outperformed the control antibody (Fig. 3).▲ Fig. 3. Affinity testing of antibodies◆ Blocking ActivityELISA confirmed candidates A001-A004 effectively blocked BAFF-NFC binding to huBCMA-ECD-His-Biotin (Fig. 4).。▲ Fig. 4 Blocking testing of antibodies06 Summary and OutlookThe  global antibody drug market is expanding rapidly, surpassing $200  billion in 2023. Single-domain antibodies (sdAbs) have emerged as  pivotal next-generation therapeutics due to their unique capacity to  target cryptic epitopes inaccessible to conventional antibodies.  Strategic Value of sdAb Libraries: As the core engine for antibody  discovery, high-quality sdAb libraries offer candidate molecular  diversity, drug developability and capability to address "undruggable"  targets. This positions sdAb library development as a competitive focus  for leading biopharma companies. Leveraging decades of antibody  engineering expertise and the AI-STAL platform, Sanyou Bio has overcome  technical barriers to establish a validated high-pI sdAb library.Sanyou  Bio will leverage its platform technologies to: construct a  trillion-scale high-pI sdAb library by 2025; extend antibody half-life  through PTM site exclusion; accelerate sdAb discovery against  challenging targets/cryptic epitopes; optimize deep learning algorithms  for de novo generation of highly druggable sdAbs. These innovations will  enhance sdAb drug development efficiency and shorten R&D cycles for  novel antibody therapeutics, delivering comprehensive solutions for  global patients.推荐阅读6类分子形式之环状多肽分子产生系统解决方案轻松玩转三优oneClick+线上9大云程序6类分子形式之mRNA分子产生系统解决方案三重好礼相送暨四种抗体制备解决方案全新上线三优生物单域抗体产生系统解决方案三优生物双抗参比品网站SY-BsAb正式上线三优ADC药物研发系统解决方案三优生物oneClick+平台再次上新三优磁阵列全人源小鼠抗体发现平台重磅发布三优超万亿全人单克隆抗体产生平台盘点三优磁阵列全人源小鼠抗体发现平台隆重上线共同轻链抗体产生之超万亿共轻库盘点三优生物73种全系列双抗参比品全新上线三优生物智能超万亿分子发现平台盘点及展望十年磨一剑之三优智能百万亿分子库发展历程关于三优生物三优生物是一家以“让天下没有难做的创新生物药”为使命，以超万亿分子库和人工智能技术双驱的生物医药智能高新技术企业。公司以智能超万亿分子库为核心，打造了干湿结合、国际领先的创新生物药临床前智能化及一体化研发平台，通过“新药发现、临床前研究、智能化药物研发及前沿科学研究”等四个维度加速全球新药发现及靶标深度研究。公司总部位于中国上海，在美国、欧洲等地设有子公司，现有投产及布局的研发及GMP场地20000多平方米。公司为合作伙伴提供“差异化CRO、整合型CDO、协同型CPO、特色CRS”于一体的“创新生物药4C综合业务”。公司已建立全球营销网络，已与全球1200多家药企、生技公司等建立了良好的合作关系；已完成了1200多个新药发现及开发服务项目；已完成了50多个合作研发项目，其中9个合作项目已完成临床申报。公司已获得国家高新技术、上海市专精特新、上海市小巨人和上海“张江之星”企业认定。