Tremelimumab

作者：于琦 薛超然美工：何国红 罗真真排版：马超01 引言抗体药物的传奇历程始于1975年单克隆抗体技术的诞生，这一里程碑彻底改变了疾病治疗的格局。随后的几十年里，嵌合、人源化及全人源抗体技术的不断突破，持续加速了这一领域的飞速发展。全球现已有超过170种抗体药物获批，广泛应用于肿瘤、自身免疫等重大疾病。抗体药物市场正经历爆发式增长，预计未来几年，抗体药物的市场份额将持续扩大，并有望在2030年突破数千亿美元，前景无限光明。在抗体药物蓬勃发展的浪潮中，三优生物致力于为客户提供从靶点发现到临床前候选药物（PCC）的一站式开发服务，仅需一个靶点，即可交付高质量的PCC分子，整个过程涵盖靶点调研、原材料制备、分子发现与优化、体内外药效评价以及成药性分析等环节。无论是传统的单克隆抗体、创新的双特异性抗体，还是前沿的抗体药物偶联物（ADC），三优生物均可提供定制化解决方案，助力加速创新生物药的研发进程。截至目前，三优生物已完成60余个PCC项目开发，其中10余个项目已进入临床阶段，最快推进至III期临床阶段。02 服务流程三优生物专注于抗体药物研发领域，提供涵盖靶点调研、原材料制备、分子产生、体外药效评价、分子优化、体内药效评价及成药性分析等关键环节的一站式服务。在研发过程中，首先会对靶点进行深入调研，明确其与疾病的相关性及研发价值，从而确定研发方向。随后将制备相关原材料，包括抗原蛋白、细胞株等，为后续研究奠定基础。基于超万亿创新分子库获得候选分子后，进行体外药效学评价，筛选出具有靶点活性的分子并进行特性优化，以进一步提高其生物活性和成药性。经优化后的分子将在动物模型中进行体内药效学验证，最终通过全面的成药性分析评估其安全性、药代动力学等关键特性。▲ Fig. 1 Target to PCC drug development flowchart01靶点调研在药物研发全流程中，靶点调研作为连接基础研究与临床转化的关键环节，具有核心战略意义。针对尚未满足的临床需求，开展创新抗体药物研发的首要步骤即是靶点调研。该环节会系统性地梳理目标靶点的生物学特征、在疾病发生发展中的分子机制，以及相关领域的研究进展与空白。唯有明确靶点的生物学特征、人群分布差异及与其他治疗手段的协同潜力，才能构建从机制创新到临床价值转化的完整逻辑链，让药物真正聚焦于“正确的靶点，正确的患者，正确的疗效”。三优生物在肿瘤、自身免疫性疾病、代谢性疾病、神经系统疾病、眼科疾病、心血管疾病、感染性疾病、衰老相关疾病以及宠物治疗等领域，均配备了经验丰富的高级科学家团队。针对各类靶点，公司已完成300余个靶点的系统性调研工作。目前，三优生物已有10余个项目通过授权转让进入临床阶段，这些成果充分体现了靶点调研的重要价值。▼ Table. 1 Reported IND project cases02原材料制备三优生物已构建了涵盖质粒、蛋白、mRNA、VLP及研究用细胞株等原材料的完整解决方案体系。该平台能够高效制备各类复杂蛋白，包括胞内蛋白、膜蛋白、胞外蛋白等不同细胞定位蛋白，以及GPCR靶点、离子通道靶点、细胞因子等特殊类型蛋白，充分满足客户对高难度蛋白制备的技术需求。三优生物的技术平台已达到行业领先水平，具备年产10万个蛋白和1000株研究用细胞株的制备能力。原材料制备效率卓越：mRNA包装仅需18天即可完成；足量且质检合格的蛋白可在2周内交付；高表达量、高稳定性的研究用细胞株仅需1个月即可获得。团队成员拥有丰富的项目经验，已成功完成500余个阶段性或整体性服务项目，为客户的抗体开发及药物筛选工作提供强有力的技术支持。▲ Fig. 2 Raw material preparation solution03分子产生三优生物建立了具有自主知识产权、各项性能指标全球领先的超万亿级创新分子库，可广泛应用于创新药物发现、诊断试剂开发、检测技术及科研用抗体定制等多个领域。分子库包含全人源抗体、单域抗体、动物免疫抗体和新型分子四大类，通过12种技术路径可产生全人源抗体、单域抗体、鼠源单抗、兔源单抗、双特异性抗体、多克隆抗体、靶向多肽及靶向小型蛋白等多种分子形式。结合一站式高通量自动化筛选平台，显著缩短了筛选周期，能够高效获得具有高亲和力、优异特异性和良好可开发性的候选分子，系统解决各类分子开发难题，有力推动药物研发进程。截止2025年3月份累计已完成900+项目的筛选，以合作开发或授权转让的模式协助客户完成10余个项目的IND申报，共递交国内外专利申请115件，获得专利授权28件。▲ Fig. 3 Diversified sources of molecules04体外药效评价体外药效筛选作为抗体功能评价的核心环节，可显著加速抗体药物的发现、筛选和优化进程。三优生物专注于创新抗体药物研发领域，构建了稳定、高效且可靠的体外药效筛选平台。该平台目前涵盖流式细胞分析、体外药效方法开发、体外药效样品检测及非特异性结合检测等模块，能够确保候选抗体以高效率、高通量和高标准完成体外药效筛选工作。平台建立了数十种多维度、立体化的体外药效评价体系，可满足抗原抗体结合、信号通路调控及细胞功能评估等多层次研究需求。平台目前拥有150余种经项目验证的靶点细胞株、20余种经项目验证的原代细胞、8大类51项子类检测方法，并配备92份标准化操作规程（SOP）支持。常规检测方法仅需1周即可完成，高难度检测方法可在4周内完成；常规方法开发周期为2周，高难度方法开发周期为8周。▲ Fig. 4 Solution for in vitropharmacological evaluation05分子优化三优生物凭借其完善的抗体工程改造技术平台，致力于为客户提供高效、专业的抗体优化服务。该平台涵盖了抗体优化的关键环节，包括人源化改造、亲和力成熟、成药性优化及半衰期延长。平台具有抗体各功能区域的精准改造能力，包括框架区（FR）、互补决定区（CDR）和恒定区（Fc）。通过对这些区域的精细操作，三优生物能够满足多样化的项目需求，并显著提升改造后抗体的性能，包括但不限于药效学与成药性显著提升、交叉反应性增强、靶点特异性改善、潜在修饰风险的消除。三优生物在效率方面处于行业领先地位，每轮抗体改造周期仅需6-8周即可高质量完成，显著加速了客户项目进入后续的功能筛选阶段。该平台由经验丰富的团队支撑，已成功完成500余例各类抗体分子的改造项目。其中，40余个设计抗体已进入临床申报阶段，10余个已进入临床试验阶段，充分验证了其技术平台的可靠性和成功率。▲ Fig. 5 Molecular optimization solutions06体内药效评价体内药效评价作为确定临床前候选分子的关键环节，可进一步验证候选分子在动物模型中的有效性和安全性。三优生物已建立高通量、高质量的候选分子体内药效评价平台，该平台涵盖体内药效方法开发系统、动物药效评价系统、药代动力学研究系统以及急性毒性检测系统。平台以国内外大小动物药效评价市场为核心，重点围绕肿瘤和自身免疫性疾病两大适应症，建立了完善的肿瘤CDx模型体系、自身免疫性疾病非肿瘤模型平台、细胞因子及血液标志物检测系统，且提供从小鼠到非人灵长类动物的完整药代动力学评价服务，全面满足临床前非GLP相关研究需求。目前平台已积累150余个经项目验证的CDx模型、数十种非肿瘤疾病模型、40余项标准操作规程（SOP），并成功支持10余个药效相关临床申报项目。▲ Fig. 6 Solution for in vivo drugefficacy evaluation07成药性分析三优生物经过多年的技术沉淀与升级，已建立起涵盖单抗、多抗和融合蛋白的多维表征分析平台。其中，抗体理化分析平台已开发出10种检测项目，具备多维表征、全面合规、高质高效的特点，可支持生物新药研发前期样品的质量控制。生化分析平台则通过优化各类生化检测方法，进一步丰富了检测内容。基于ELISA的生化分析技术具有周期短、重复性好、通量高、成本低等优势，可高效地从大量先导分子中筛选优质候选分子，显著提升“先导分子聚焦”效率。该技术已成功应用于数百个服务项目，覆盖早期药物研发、小试工艺开发等全研发阶段。同时，平台严格参照药典要求建立了完善的标准体系，凭借精准可靠的表征方法，为药物生产提供技术支持和工艺指导。▲ Fig.7 Solution for drug analysis03 服务特性01全流程覆盖三优生物靶点至PCC药物研发系统解决方案覆盖靶点调研、原材料制备、分子产生、体外药效评价、分子优化、体内药效评价及成药性分析等关键环节，实现研发流程的无缝整合。该模式有效规避了因技术标准差异、数据断层或沟通障碍导致的效率损失，确保从靶点发现到PCC研发的每个环节均能基于前期成果精准递进。通过全流程一体化设计，依托统一的质量控制体系和跨学科协作机制，可早期识别潜在风险（如抗体成药性不足或靶点选择性欠佳等），及时调整研发策略，从而显著缩短研发周期、降低重复投入，最终提高候选抗体的成药成功率，为创新药物研发提供高效可靠的技术支持。▲ Fig.8 Full process coverage02定制化适配三优生物靶点至PCC药物研发系统解决方案能够根据项目靶点特性及研发阶段需求，提供定制化的实验方案与技术路线。针对不同研发阶段和客户核心诉求，平台可动态调整实验方案，避免标准化研发模式导致的资源浪费与效率损失。这种高度灵活的模式既保证了研发策略与靶点生物学特性的精准匹配，又能聚焦项目核心目标，在提升候选抗体成药性的同时有效控制后期开发风险，为创新药物研发提供更加精准高效的解决方案。▲ Fig.9 Research and statistics on100+ targets of Sanyou Biotechnology03高效化推进三优靶点至PCC药物研发系统解决方案整合了多个技术平台与资深团队经验，能通过AI辅助设计和高通量实验平台加速先导分子的筛选效率，结合严格的质量控制体系确保数据可靠性，能在早期同步解决活性、选择性、成药性等关键问题，减少后期返工风险；此外，基于历史项目数据库建立的预测模型，可精准指导实验方向，大幅缩短从靶点到PCC的药物研发周期，降低研发风险，为客户提供从早期探索到候选分子确定的无缝衔接支持。▲ Fig.10 Project operation cycle04 案例展示01抗CTLA4单抗的开发基本信息：CTLA4（细胞毒性T淋巴细胞相关抗原4，CD152）属于免疫球蛋白超家族（IgSF），是一种跨膜蛋白，在细胞外区域含有IgV样结构域，与CD28具有高度同源性（约31%的氨基酸序列相似性）。两者都与抗原呈递细胞（APC）表面的B7分子（CD80/CD86）竞争性结合，但CTLA4具有更高的亲和力（约10-20倍），并通过抑制共刺激信号负调控T细胞活化。分布情况：CTLA4主要在活化的CD4+/CD8+T细胞和调节性T细胞（Treg）的表面表达，特别是在肿瘤微环境中，Treg高度表达CTLA4。竞争格局：根据Insight数据库的调查，全球有139种针对CTLA4的抗体药物正在开发中，其中5种已经上市，1种正在申请上市。首个获得美国食品药品监督管理局批准的CTLA4单克隆抗体（2011年），用于治疗黑色素瘤，2020年全球市场规模为17亿美元Tremelimumab：在癌症等适应症中进行III期临床试验。▲ Fig. 11 Mechanism of action of CTLA402抗CTLA4单抗的关键结果▶ 2.1. 细胞水平的结合活性分析通过三优生物分子产生平台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。Fig. 12A展示了采用FACS分析候选抗体与huCTLA-4 CHO细胞的结合活性，候选抗体与对照抗体相比，具有相当的结合活性。Fig. 12B展示了采用FACS分析候选抗体与cynoCTLA-4 CHO细胞的亲和力测定结果，候选抗体的与对照抗体相比，具有相当的结合活性。▲ Fig. 12 Binding affinity of antibody▶ 2.2. 细胞水平的阻断活性分析采用FACS方法检测候选抗体是否阻断配体CD80-ECD、CD86-ECD与huCTLA-4 CHO细胞的结合。Fig. 13A展示了候选抗体阻断CD80-ECD与huCTLA-4 CHO细胞的结合，阻断效果与对照抗体相当或优于对照抗体。Fig. 13B展示了候选抗体阻断CD86-ECD与huCTLA-4 CHO细胞的结合，阻断效果与对照抗体相当或优于对照抗体。▲ Fig. 13 Blocking activity of antibody ▶ 2.3. 人源化抗体细胞水平的结合活性分析针对NB25B-17和NB25gb-1通过三优生物分子优化平台进行人源化改造。对获得的单域抗体在细胞水平进行结合活性检测。Fig. 14A展示了采用FACS分析候选抗体与huCTLA-4 CHO细胞的亲和力测定结果。Fig. 14B展示了采用FACS分析候选抗体与cynoCTLA-4 CHO细胞的亲和力测定结果。结果表明，NB25B-17-9-H1-IgG1和NB25gb-1-11-H1-IgG1显示出比其他候选抗体更好的结合能力和交叉活性。▲ Fig. 14 Binding affinity of antibody▶ 2.4. 人源化抗体细胞水平的阻断活性分析采用FACS方法检测候选抗体是否阻断配体CD80-ECD、CD86-ECD与huCTLA-4 CHO细胞的结合。Fig. 15A展示了候选抗体阻断CD80-ECD与huCTLA-4 CHO细胞的结合。Fig. 15B展示了候选抗体阻断CD86-ECD与huCTLA-4 CHO细胞的结合。结果表明，NB25B-17-9-H1-IgG1、NB25gb-1-11-H1-IgG1和NB25gb-1-11-H2-IgG1对huCTLA-4 CHO的阻断活性优于对照抗体。▲ Fig. 15 Blocking activity of antibody▶ 2.5. 体内药效评价在HuCTLA4小鼠皮下接种MC38肿瘤细胞，当平均肿瘤体积达到约100 mm3时，将小鼠随机分为4个实验组，其中1组为对照组，3组为给药组，分别给3个不同的剂量。通过腹部给药给予抗体（每周2次，给药三周），在第32天结束给药。当肿瘤细胞进行Anti-CTLA4抗体给药时，发现肿瘤体积明显缩小。▲ Fig. 16 In vivo efficacy of antibody05 总结展望在从靶点到PCC的抗体药物研发全流程中，三优生物依托其超万亿级创新分子库和一体化研发平台优势，已成功完成60余个靶点的项目开发（其中10余个已推进至III期临床阶段）。经过十年深耕，三优生物构建了涵盖靶点调研至PCC交付的一站式、全流程服务体系，为客户提供全程研发支持。选择三优生物，即意味着选择高效、优质、高成功率的抗体药物研发解决方案，助力创新药物快速转化。展望未来，抗体药物的研发前景无疑是广阔而激动人心的。随着科学技术的不断进步，我们有理由相信，更多创新、高效的抗体药物将不断涌现，为全球患者带来新的希望和更优的治疗选择。三优生物期待与您携手，共同探索抗体药物的无限可能，将更多具有里程碑意义的创新疗法从实验室带到临床，最终惠及每一位需要的患者。Sanyou 10th Anniversary: Service Section Target to PCC Drug Development System Solution01 IntroductionThe legendary journey of antibody drugs began in 1975 with the advent of monoclonal antibody technology, a milestone that revolutionized disease treatment. Over the following decades, breakthroughs in chimeric, humanized, and fully human antibody technologies have continuously accelerated the rapid advancement of this field. Today, more than 170 antibody drugs have been approved worldwide, widely used for major diseases such as cancer and autoimmune disorders. The antibody drug market is experiencing explosive growth, with its share expected to expand further in the coming years. By 2030, it is projected to surpass hundreds of billions of dollars, showcasing a future of immense promise.In the thriving wave of antibody drug development, Sanyou Bio is dedicated to providing clients with one-stop services from target discovery to preclinical candidate (PCC) delivery. Starting with just a target, we deliver high-quality PCC molecules through a comprehensive process covering target research, raw material preparation, molecular discovery & optimization, in vitro/in vivo efficacy evaluation, and druggability analysis. From monoclonal antibodies, bispecific antibodies, to antibody-drug conjugates (ADCs), Sanyou offers customized solutions to accelerate innovative biopharmaceutical R&D. As of now, Sanyou Bio has completed the development of over 60 PCC projects, with more than 10 advancing to clinical stages, including one project in Phase III trials as the fastest progressing candidate.02 Service ProcessSanyou Bio specializes in the field of antibody drug R&D, offering one-stop services covering key stages including target investigation, raw material preparation, molecule generation, in vitro efficacy evaluation, molecule optimization, in vivo efficacy assessment, and druggability analysis. During the R&D process, in-depth target investigation is first conducted to clarify its disease relevance and research value, thereby defining the R&D direction. Subsequently, relevant raw materials—such as antigen proteins and cell lines—are prepared to establish the foundation for further studies. After obtaining candidate molecules based on a trillion-size innovative molecular library, in vitro pharmacological evaluation is conducted to screen for molecules with target activity and optimize their characteristics, in order to further improve their biological activity and drug efficacy. The optimized molecule will undergo in vivo pharmacological validation in animal models, and ultimately its safety, pharmacokinetics, and other key characteristics will be evaluated through comprehensive pharmacokinetic analysis.▲ Fig. 1 Target to PCC drug development flowchart01Target researchTarget identification and validation is a strategically pivotal step bridging basic research and clinical translation throughout the drug discovery pipeline. For addressing unmet clinical needs, target research constitutes the primary phase in innovative antibody drug development. This process systematically evaluates the biological characteristics of target molecules, their molecular mechanisms in disease pathogenesis, as well as current research advances and gaps in relevant fields. By understanding the biological characteristics of targets, distribution variations, and synergistic potential with other therapies, we can establish a complete plan from mechanistic innovation to clinical value translation, ensuring drugs truly focus on 'the right target, the right patient, the right efficacy'. Sanyou Bio has established experienced senior scientist teams across diverse therapeutic areas, including oncology, autoimmune diseases, metabolic disorders, neurological diseases, ophthalmic diseases, cardiovascular diseases, infectious diseases, aging-related diseases, and veterinary therapeutics. The company has completed systematic research on over 300 targets. To date, more than 10 Sanyou-developed programs have advanced to clinical stages via out-licensing, demonstrating the critical value of target profiling.▼ Table. 1 Reported IND project cases02Raw material preparationSanyou Bio has established a comprehensive solution system for raw materials, including plasmids, proteins, mRNA, VLPs, and research cell lines. This platform enables the efficient production of various complex proteins, such as intracellular proteins, membrane proteins, extracellular proteins, as well as specialized targets like GPCRs, ion channels, and cytokines, fully meeting customers' technical demands for challenging protein preparation. Sanyou Bio’s technology platform has achieved industry-leading standards, with an annual production capacity of 100,000 batches of proteins and 1,000 research cell lines. The platform demonstrates exceptional efficiency in raw material preparation: mRNA packaging can be completed in just 18 days; high-quality, QC-approved proteins can be delivered within 2 weeks; and high-expression, high-stability research cell lines are obtainable in just 1 month. The team brings extensive project experience, having successfully completed 500+ milestone or full-service projects, providing robust technical support for antibody development and drug screening.▲ Fig. 2 Raw material preparation solution03Antibody discoverySanyou has established a proprietary, ultra-trillion-scale innovative molecular library with globally leading performance metrics. This library is widely applicable to innovative drug discovery, diagnostic reagent development, detection technologies, and customized research antibodies. The molecular library comprises four major categories: fully human antibodies, single-domain antibodies, animal-derived immune antibodies, and novel molecules. Through 12 technological approaches, it can generate diverse molecular formats, including fully human antibodies, single-domain antibodies, murine monoclonal antibodies, rabbit monoclonal antibodies, bispecific antibodies, polyclonal antibodies, targeting peptides, and small targeting proteins. Integrated with a one-stop high-throughput automated screening platform, this approach significantly shortens the screening cycle and efficiently identifies candidate molecules with high affinity, excellent specificity, and favorable developability. It systematically addresses various molecular development challenges, strongly accelerating drug discovery progress. As of March 2025, the platform has completed screening for 900+ projects, assisted clients in submitting INDs for over 10 projects through co-development or licensing agreements, and filed 115 patent applications globally, with 28 patents granted.▲ Fig. 3 Diversified sources of molecules04In vitro efficacy evaluationIn vitro efficacy screening, as a core component of antibody functional evaluation, significantly accelerates the discovery, screening, and optimization of antibody drugs. Sanyou Bio specializes in innovative antibody drug R&D and has established a stable, efficient, and reliable in vitro efficacy screening platform. The platform currently encompasses modules including flow cytometry analysis, in vitro efficacy method development, sample testing, and non-specific binding detection, ensuring high-efficiency, high-throughput, and high-standard screening of candidate antibodies. The platform has established dozens of multidimensional in vitro efficacy evaluation systems capable of meeting diverse research needs, ranging from antigen-antibody binding and signaling pathway modulation to cellular function assessment. The platform currently offers over 150 project-validated target cell lines, more than 20 project-validated primary cell types, and 51 subcategories of detection methods across 8 major categories, supported by 92 standardized operating procedures (SOPs). Routine assays can be completed within 1 week, while complex assays require up to 4 weeks. Method development takes 2 weeks for standard protocols and 8 weeks for challenging ones.▲ Fig. 4 Solution for in vitropharmacological evaluation05Molecule optimizationSanyou Bio its advanced antibody engineering platform to deliver efficient and specialized antibody optimization services. The platform covers key optimization processes, including humanization, affinity maturation, developability optimization, and half-life extension. It enables precise modifications of functional antibody regions, such as the framework region (FR), complementarity-determining region (CDR), and constant region (Fc).Through refined engineering, Sanyou meets diverse project demands while significantly enhancing antibody performance, including but not limited to:Improved pharmacodynamics & developability、Enhanced cross-reactivity、Refined target specificity、Elimination of potential modification risks. With industry-leading efficiency, Sanyou completes each round of antibody optimization in just 6–8 weeks, accelerating clients' transition to functional screening. Backed by an expert team, the platform has successfully optimized 500+ antibody molecules, with 40+ designed antibodies in regulatory filing and 10+ in clinical trials, demonstrating its reliability and success rate.▲ Fig. 5 Molecular optimization solutions06In vivo efficacy evaluationIn vivo efficacy evaluation, as a critical step in identifying preclinical candidate molecules, further validates their effectiveness and safety in animal models. Sanyou Bio has established a high-throughput, high-quality in vivo efficacy evaluation platform for candidate molecules, encompassing: In vivo efficacy method development system, Animal efficacy evaluation system, Pharmacokinetics (PK) study system, Acute toxicity testing system. This platform focuses on the small and large animal efficacy evaluation market, with a core emphasis on oncology and autoimmune diseases. We have established a comprehensive tumor CDx model system, a non-oncology model platform for autoimmune diseases, as well as cytokine and blood biomarker detection systems. Additionally, we provide complete pharmacokinetic evaluation services from mice to non-human primates, fully meeting preclinical non-GLP research needs.To date, the platform has accumulated over 150 project-validated CDx models, dozens of non-oncology disease models, and more than 40 standard operating procedures (SOPs), successfully supporting over 10 efficacy-related clinical submission projects.▲ Fig. 6 Solution for in vivo drug efficacy evaluation07Developability assessmentAfter years of technological refinement and advancement, Sanyou has established a multidimensional characterization platform covering monoclonal antibodies, polyclonal antibodies, and fusion proteins. The Physicochemical Characterization Platform for antibodies has developed 10 assay items, featuring multidimensional analysis, full compliance, and high-quality efficiency, supporting quality control of early-stage samples in novel biologics development. The Biochemical Analysis Platform has further expanded its testing capabilities through optimized biochemical assay methodologies. ELISA-based biochemical analysis offers advantages including short cycles, high reproducibility, high throughput, and low cost, enabling efficient screening of high-quality candidates from lead molecules and significantly improving "lead molecule focusing" efficiency. This technology has been successfully applied in hundreds of service projects across all R&D stages, from early drug discovery to pilot process development. The platform has established a comprehensive standard system in strict compliance with pharmacopoeia requirements, providing reliable technical support and process guidance for drug manufacturing through accurate characterization methods.▲ Fig.7 Solution for drug analysis03 Service Features01Full process coverageSanyou Bio's Target-to-PCC Drug Discovery Comprehensive Solution covers key stages including target profiling, raw material preparation, molecule discovery, in vitro efficacy evaluation, lead optimization, in vivo efficacy assessment, and developability analysis, ensuring seamless integration across the R&D workflow. This model eliminates efficiency losses caused by inconsistent technical standards, data fragmentation, or communication barriers, enabling precise progression from target identification to PCC development based on prior achievements. Through integrated end-to-end design supported by a unified quality control system and interdisciplinary collaboration, potential risks (e.g., inadequate antibody developability or suboptimal target selectivity) can be identified early, enabling timely strategy adjustment. This approach significantly shortens development timelines, reduces redundant investments, and ultimately improves the success rate of candidate antibodies, providing efficient and reliable technical support for innovative drug development.▲ Fig.8 Full process coverage02Customized adaptationSanyou Bio's Target-to-PCC Drug Discovery System Solution offers customized experimental solutions and technical pathways tailored to target characteristics and project requirements at different R&D stages. This platform dynamically adjusts experimental designs based on developmental phases and client priorities, eliminating resource waste and efficiency loss inherent in standardized workflows. This highly flexible approach ensures precise alignment between research strategies and target biology while focusing on core objectives. It enhances antibody drugability while mitigating late-stage development risks, delivering a more accurate and efficient solution for innovative drug development.▲ Fig.9 Research and statistics on100+ targets of Sanyou Biotechnology03Efficient promotionSanyou Bio's Target-to-PCC Drug Discovery System Solution integrates multiple technology platforms and expert team experience. It accelerates lead molecule screening through AI-assisted design and high-throughput experimental platforms, while ensuring data reliability via stringent quality control systems. This approach enables synchronous resolution of key challenges (activity, selectivity, and druggability) in early stages, reducing late-stage rework risks. Additionally, predictive models built on historical project databases precisely guide experimental direction, significantly shortening the target-to-PCC timeline and mitigating development risks. The solution provides seamless support from early exploration to candidate compound identification.▲ Fig.10 Project operation cycle04 Case Presentation01Development of anti-CTLA4 monoclonal antibodyBasic information：CTLA4 (cytotoxic T-lymphocyte-associated antigen 4, CD152), a member of the immunoglobulin superfamily (IgSF), is a transmembrane protein containing an IgV-like domain in its extracellular region that shares high homology with CD28 (~31% amino acid sequence similarity). Both competitively bind to B7 molecules (CD80/CD86) on antigen-presenting cells (APCs), but CTLA4 exhibits higher affinity (approximately 10-20-fold) and negatively regulates T-cell activation by inhibiting co-stimulatory signals.Distribution condition：CTLA4 is mainly expressed on the surface of activated CD4+/CD8+T cells and regulatory T cells (Tregs), especially in the tumor microenvironment where Tregs highly express CTLA4.Competitive landscape：According to Insight Database, there are currently 139 CTLA4-targeting antibody drugs under development globally, with 5 already marketed and 1 under regulatory review. The first CTLA4 monoclonal antibody approved by the FDA (2011) for melanoma treatment reached a global market size of $1.7 billion in 2020. Tremelimumab is undergoing Phase III clinical trials for cancer and other indications.▲ Fig. 11 Mechanism of action of CTLA402Key results of anti-CTLA4 monoclonal antibody▶ 2.1. Cell level binding activity analysisMost single-domain antibody candidates generated via SanyouBio's molecular discovery platform exhibit favorable cell-binding activity. Fig. 12A demonstrates FACS analysis of candidate antibodies binding to huCTLA-4 CHO cells, showing comparable binding activity to the control antibody. Fig. 12B presents affinity measurement results via FACS analysis against cynoCTLA-4 CHO cells, where the candidate antibodies display similar binding activity relative to the control.▲ Fig. 12 Binding affinity of antibody▶ 2.2. Analysis of blocking activity at the cellular levelFACS was employed to assess whether the candidate antibody blocks the binding of ligands CD80-ECD and CD86-ECD to huCTLA-4 CHO cells. Fig. 13A demonstrates that the candidate antibody effectively blocks CD80-ECD binding to huCTLA-4 CHO cells, with efficacy comparable or superior to the control antibody. Fig. 13B shows that the candidate antibody similarly blocks CD86-ECD binding to huCTLA-4 CHO cells, with blocking efficiency equivalent to or better than the control antibody.▲ Fig. 13 Blocking activity of antibody ▶ 2.3. Cell level binding activity analysis of humanized antibodiesNB25B-17 and NB25gb-1 were humanized using the Trianni Mo™ antibody optimization platform. The binding activities of the obtained sdAbs were evaluated at cellular level. Fig. 14A presents the affinity measurement results of candidate antibodies binding to huCTLA-4 CHO cells by FACS analysis. Fig. 14B shows the affinity measurement results of candidate antibodies binding to cynoCTLA-4 CHO cells by FACS analysis. The results demonstrate that NB25B-17-9-H1-IgG1 and NB25gb-1-11-H1-IgG1 exhibit superior binding capability and cross-reactivity compared to other candidate antibodies.▲ Fig. 14 Binding affinity of antibody▶ 2.4. Analysis of blocking activity at the cellular level of humanized antibodiesFACS was employed to assess whether candidate antibodies block the binding of ligands CD80-ECD and CD86-ECD to huCTLA-4 CHO cells. Fig. 15A demonstrates the blockade of CD80-ECD binding to huCTLA-4 CHO cells by candidate antibodies, while Fig. 15B shows their inhibition of CD86-ECD binding. Results indicate that NB25B-17-9-H1-IgG1, NB25gb-1-11-H1-IgG1, and NB25gb-1-11-H2-IgG1 exhibit superior blocking activity against huCTLA-4 CHO cells compared to the control antibody.▲ Fig. 15 Blocking activity of antibody▶ 2.5. In vivo efficacy evaluationMC38 tumor cells were subcutaneously inoculated into HuCTLA4 mice. When the average tumor volume reached approximately 100 mm³, the mice were randomly divided into four experimental groups: one control group and three treatment groups receiving different antibody doses. The antibody was administered intraperitoneally (twice weekly for three weeks), with treatment concluding on day 32. Anti-CTLA4 antibody administration significantly reduced tumor volume.▲ Fig. 16 In vivo efficacy of antibody05 Summary and OutlookIn the antibody drug development process from target to PCC, Sanyou Bio leverages its ultra-trillion innovative molecule library and integrated R&D platform to successfully complete over 60 target projects (10+ advanced to III clinical stages). With a decade of expertise, Sanyou has established a one-stop, end-to-end service system covering target assessment to PCC delivery, providing comprehensive R&D support. Sanyou provides efficient, high-quality antibody drug solutions with superior success rates, accelerating innovative drug translation.Looking ahead, the future of antibody drug development is undoubtedly vast and exciting. With continuous advancements in science and technology, we are confident that more innovative and highly effective antibody drugs will emerge, offering new hope and better treatment options for patients worldwide. Sanyou Bio looks forward to collaborating with clients globally to explore the boundless potential of antibody therapeutics, translating more landmark innovations from the lab to the clinic, ultimately benefiting every patient in need.推荐阅读三优十周年｜靶点篇-六大恶性肿瘤靶点介绍创新前沿｜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。

WILMINGTON, Del.--(BUSINESS WIRE)--AstraZeneca’s supplemental Biologics License Application (sBLA) for IMFINZI® (durvalumab) has been accepted and granted Priority Review in the US for the treatment of patients with resectable, early-stage and locally advanced (Stages II, III, IVA) gastric and gastroesophageal junction (GEJ) cancers. The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions or enhancing patient compliance.1 The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision, is anticipated during the fourth quarter of 2025. IMFINZI was also recently granted Breakthrough Therapy Designation (BTD) by the FDA in this setting. BTD accelerates the development and regulatory review of potential new medicines intended to treat a serious condition and address a significant unmet medical need.2 Gastric (stomach) cancer is the fifth most common cancer worldwide and the fifth-highest leading cause of cancer mortality.3 In 2024, there were approximately 6,500 drug-treated patients in the US with early-stage and locally advanced gastric or GEJ cancer. 4 Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “This Priority Review reinforces the potential for a perioperative approach with IMFINZI to transform care for patients with early gastric and gastroesophageal junction cancers, who frequently face disease recurrence or progression even after curative-intent surgery and perioperative chemotherapy. This novel treatment is the only immunotherapy-based regimen to show a statistically significant reduction in the risk of progression, recurrence or death in this setting, and if approved, is poised to change the clinical paradigm." The sBLA is based on data from the MATTERHORN Phase III trial which was presented during the Plenary Session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in The New England Journal of Medicine. In the trial, patients were treated with neoadjuvant IMFINZI in combination with chemotherapy before surgery, followed by adjuvant IMFINZI in combination with chemotherapy, then IMFINZI monotherapy. In a planned interim analysis, patients treated with the IMFINZI-based perioperative regimen showed a 29% reduction in the risk of disease progression, recurrence or death versus chemotherapy alone (based on an event-free survival [EFS] hazard ratio [HR] of 0.71; 95% confidence interval [CI] 0.58-0.86; P<0.001). Estimated median EFS was not yet reached for the IMFINZI arm versus 32.8 months for the comparator arm. An estimated 78.2% of patients treated with the IMFINZI-based perioperative regimen were event-free at one year, compared to 74.0% in the comparator arm; the estimated 24-month EFS rate was 67.4% versus 58.5%, respectively, signaling a greater magnitude of benefit over time for the IMFINZI-based regimen. For the key secondary endpoint of overall survival (OS), a strong trend was observed in favor of the IMFINZI-based perioperative regimen (HR=0.78; 95% CI 0.62-0.97; P=0.025). The trial will continue to follow OS, which will be formally assessed at the final analysis. The safety profile for IMFINZI and FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) chemotherapy was consistent with the known profiles of each medicine, and the percentage of patients that completed surgery was similar compared to chemotherapy alone. Grade 3 or higher adverse events due to any cause were similar between the two arms. Regulatory applications are currently under review in the EU, Japan and several other countries based on the MATTERHORN results. IMPORTANT SAFETY INFORMATION There are no contraindications for IMFINZI® (durvalumab) or IMJUDO® (tremelimumab-actl). Severe and Fatal Immune-Mediated Adverse Reactions Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment or after discontinuation. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and before each dose. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue IMFINZI and IMJUDO depending on severity. See USPI Dosing and Administration for specific details. In general, if IMFINZI and IMJUDO requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Immune-Mediated Pneumonitis IMFINZI and IMJUDO can cause immune-mediated pneumonitis, which may be fatal. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients who did not receive recent prior radiation, the incidence of immune-mediated pneumonitis was 2.4% (34/1414), including fatal (<0.1%), and Grade 3-4 (0.4%) adverse reactions. In patients who received recent prior radiation, the incidence of pneumonitis (including radiation pneumonitis) in patients with unresectable Stage III NSCLC following definitive chemoradiation within 42 days prior to initiation of IMFINZI in PACIFIC was 18.3% (87/475) in patients receiving IMFINZI and 12.8% (30/234) in patients receiving placebo. Of the patients who received IMFINZI (475), 1.1% were fatal and 2.7% were Grade 3 adverse reactions. The incidence of pneumonitis (including radiation pneumonitis) in patients with LS-SCLC following chemoradiation within 42 days prior to initiation of IMFINZI in ADRIATIC was 14% (37/262) in patients receiving IMFINZI and 6% (16/265) in patients receiving placebo. Of the patients who received IMFINZI (262), 0.4% had a fatal adverse reaction and 2.7% had Grade 3 adverse reactions. The frequency and severity of immune-mediated pneumonitis in patients who did not receive definitive chemoradiation prior to IMFINZI were similar in patients who received IMFINZI as a single agent or with ES-SCLC or BTC when given in combination with chemotherapy. Immune‑mediated pneumonitis occurred in 1.3% (5/388) of patients receiving IMFINZI and IMJUDO, including fatal (0.3%) and Grade 3 (0.2%) adverse reactions. Immune-mediated pneumonitis occurred in 3.5% (21/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including fatal (0.5%), and Grade 3 (1%) adverse reactions. Immune-Mediated Colitis IMFINZI with IMJUDO and platinum-based chemotherapy can cause immune-mediated colitis, which may be fatal. IMFINZI and IMJUDO can cause immune-mediated colitis that is frequently associated with diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 2% (37/1889) of patients receiving IMFINZI, including Grade 4 (<0.1%) and Grade 3 (0.4%) adverse reactions. Immune‑mediated colitis or diarrhea occurred in 6% (23/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (3.6%) adverse reactions. Intestinal perforation has been observed in other studies of IMFINZI and IMJUDO. Immune-mediated colitis occurred in 6.5% (39/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy including fatal (0.2%) and Grade 3 (2.5%) adverse reactions. Intestinal perforation and large intestine perforation were reported in 0.1% of patients. Immune-Mediated Hepatitis IMFINZI and IMJUDO can cause immune-mediated hepatitis, which may be fatal. Immune-mediated hepatitis occurred in 2.8% (52/1889) of patients receiving IMFINZI, including fatal (0.2%), Grade 4 (0.3%) and Grade 3 (1.4%) adverse reactions. Immune‑mediated hepatitis occurred in 7.5% (29/388) of patients receiving IMFINZI and IMJUDO, including fatal (0.8%), Grade 4 (0.3%) and Grade 3 (4.1%) adverse reactions. Immune-mediated hepatitis occurred in 3.9% (23/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including fatal (0.3%), Grade 4 (0.5%), and Grade 3 (2%) adverse reactions. Immune-Mediated Endocrinopathies Adrenal Insufficiency : IMFINZI and IMJUDO can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. IMFINZI as a Single Agent Immune-mediated adrenal insufficiency occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. IMFINZI with IMJUDO Immune-mediated adrenal insufficiency occurred in 1.5% (6/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%) adverse reactions. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated adrenal insufficiency occurred in 2.2% (13/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.8%) adverse reactions. Hypophysitis : IMFINZI and IMJUDO can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate symptomatic treatment including hormone replacement as clinically indicated. IMFINZI as a Single Agent Grade 3 hypophysitis/hypopituitarism occurred in <0.1% (1/1889) of patients who received IMFINZI. IMFINZI with IMJUDO Immune-mediated hypophysitis/hypopituitarism occurred in 1% (4/388) of patients receiving IMFINZI and IMJUDO. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated hypophysitis occurred in 1.3% (8/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.5%) adverse reactions. Thyroid Disorders (Thyroiditis, Hyperthyroidism, and Hypothyroidism) : IMFINZI and IMJUDO can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement therapy for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. IMFINZI as a Single Agent Immune-mediated thyroiditis occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. Immune-mediated hyperthyroidism occurred in 2.1% (39/1889) of patients receiving IMFINZI. Immune-mediated hypothyroidism occurred in 8.3% (156/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. IMFINZI with IMJUDO Immune-mediated thyroiditis occurred in 1.5% (6/388) of patients receiving IMFINZI and IMJUDO. Immune-mediated hyperthyroidism occurred in 4.6% (18/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%) adverse reactions. Immune-mediated hypothyroidism occurred in 11% (42/388) of patients receiving IMFINZI and IMJUDO. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated thyroiditis occurred in 1.2% (7/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy. Immune-mediated hyperthyroidism occurred in 5% (30/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.2%) adverse reactions. Immune-mediated hypothyroidism occurred in 8.6% (51/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.5%) adverse reactions. IMFINZI with Carboplatin and Paclitaxel Immune-mediated hypothyroidism occurred in 14% (34/235) of patients receiving IMFINZI in combination with carboplatin and paclitaxel. Type 1 Diabetes Mellitus, which can present with diabetic ketoacidosis : Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. IMFINZI as a Single Agent Grade 3 immune-mediated Type 1 diabetes mellitus occurred in <0.1% (1/1889) of patients receiving IMFINZI. IMFINZI with IMJUDO Two patients (0.5%, 2/388) had events of hyperglycemia requiring insulin therapy that had not resolved at last follow-up. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated Type 1 diabetes mellitus occurred in 0.5% (3/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy including Grade 3 (0.3%) adverse reactions. Immune-Mediated Nephritis with Renal Dysfunction IMFINZI and IMJUDO can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.5% (10/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. Immune-mediated nephritis occurred in 1% (4/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.5%) adverse reactions. Immune-mediated nephritis occurred in 0.7% (4/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.2%) adverse reactions. Immune-Mediated Dermatology Reactions IMFINZI and IMJUDO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/L-1 and CTLA-4 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Immune-mediated rash or dermatitis occurred in 1.8% (34/1889) of patients receiving IMFINZI, including Grade 3 (0.4%) adverse reactions. Immune-mediated rash or dermatitis occurred in 4.9% (19/388) of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions. Immune-mediated rash or dermatitis occurred in 7.2% (43/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.3%) adverse reactions. Immune-Mediated Pancreatitis IMFINZI in combination with IMJUDO can cause immune-mediated pancreatitis. Immune-mediated pancreatitis occurred in 2.3% (9/388) of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions. Other Immune-Mediated Adverse Reactions The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% each in patients who received IMFINZI and IMJUDO or were reported with the use of other immune-checkpoint inhibitors. Cardiac/vascular : Myocarditis, pericarditis, vasculitis. Nervous system : Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy. Ocular : Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss. Gastrointestinal : Pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis. Musculoskeletal and connective tissue disorders : Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatic. Endocrine : Hypoparathyroidism. Other (hematologic/immune) : Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection, other transplant (including corneal graft) rejection. Infusion-Related Reactions IMFINZI and IMJUDO can cause severe or life-threatening infusion-related reactions. Monitor for signs and symptoms of infusion-related reactions. Interrupt, slow the rate of, or permanently discontinue IMFINZI and IMJUDO based on the severity. See USPI Dosing and Administration for specific details. For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses. Infusion-related reactions occurred in 2.2% (42/1889) of patients receiving IMFINZI, including Grade 3 (0.3%) adverse reactions. Infusion-related reactions occurred in 2.6% (10/388) of patients receiving IMFINZI and IMJUDO. Infusion-related reactions occurred in 2.9% (17/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.3%) adverse reactions. Complications of Allogeneic HSCT after IMFINZI Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/L-1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/L-1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/L-1 blocking antibody prior to or after an allogeneic HSCT. Embryo-Fetal Toxicity Based on their mechanism of action and data from animal studies, IMFINZI and IMJUDO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. In females of reproductive potential, verify pregnancy status prior to initiating IMFINZI and IMJUDO and advise them to use effective contraception during treatment with IMFINZI and IMJUDO and for 3 months after the last dose of IMFINZI and IMJUDO. Lactation There is no information regarding the presence of IMFINZI and IMJUDO in human milk; however, because of the potential for serious adverse reactions in breastfed infants from IMFINZI and IMJUDO, advise women not to breastfeed during treatment and for 3 months after the last dose. Adverse Reactions Unresectable Stage III NSCLC In patients with Stage III NSCLC in the PACIFIC study receiving IMFINZI (n=475), the most common adverse reactions (≥20%) were cough (40%), fatigue (34%), pneumonitis or radiation pneumonitis (34%), upper respiratory tract infections (26%), dyspnea (25%), and rash (23%). The most common Grade 3 or 4 adverse reactions (≥3%) were pneumonia (7%) and pneumonitis/radiation pneumonitis (3.4%). In patients with Stage III NSCLC in the PACIFIC study receiving IMFINZI (n=475), discontinuation due to adverse reactions occurred in 15% of patients in the IMFINZI arm. Serious adverse reactions occurred in 29% of patients receiving IMFINZI. The most frequent serious adverse reactions (≥2%) were pneumonitis or radiation pneumonitis (7%) and pneumonia (6%). Fatal pneumonitis or radiation pneumonitis and fatal pneumonia occurred in <2% of patients and were similar across arms. Resectable NSCLC In patients with resectable NSCLC in the AEGEAN study, the most common adverse reactions (occurring in ≥20% of patients) were anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash. In patients with resectable NSCLC in the neoadjuvant phase of the AEGEAN study receiving IMFINZI in combination with platinum-containing chemotherapy (n=401), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 6.7% of patients. Serious adverse reactions occurred in 21% of patients. The most frequent (≥1%) serious adverse reactions were pneumonia (2.7%), anemia (1.5%), myelosuppression (1.5%), vomiting (1.2%), neutropenia (1%), and acute kidney injury (1%). Fatal adverse reactions occurred in 2% of patients, including death due to COVID-19 pneumonia (0.5%), sepsis (0.5%), myocarditis (0.2%), decreased appetite (0.2%), hemoptysis (0.2%), and death not otherwise specified (0.2%). Of the 401 IMFINZI treated patients who received neoadjuvant treatment and 398 placebo-treated patients who received neoadjuvant treatment, 1.7% (n=7) and 1% (n=4), respectively, did not receive surgery due to adverse reactions. In patients with resectable NSCLC in the adjuvant phase of the AEGEAN study receiving IMFINZI as a single agent (n=265), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 8% of patients. Serious adverse reactions occurred in 13% of patients. The most frequent serious adverse reactions reported in >1% of patients were pneumonia (1.9%), pneumonitis (1.1%), and COVID-19 (1.1%). Four fatal adverse reactions occurred during the adjuvant phase of the study, including COVID-19 pneumonia, pneumonia aspiration, interstitial lung disease and aortic aneurysm. Metastatic NSCLC In patients with mNSCLC in the POSEIDON study receiving IMFINZI and IMJUDO plus platinum-based chemotherapy (n=330), the most common adverse reactions (occurring in ≥20% of patients) were nausea (42%), fatigue (36%), musculoskeletal pain (29%), decreased appetite (28%), rash (27%), and diarrhea (22%). In patients with mNSCLC in the POSEIDON study receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy (n=330), permanent discontinuation of IMFINZI or IMJUDO due to an adverse reaction occurred in 17% of patients. Serious adverse reactions occurred in 44% of patients, with the most frequent serious adverse reactions reported in at least 2% of patients being pneumonia (11%), anemia (5%), diarrhea (2.4%), thrombocytopenia (2.4%), pyrexia (2.4%), and febrile neutropenia (2.1%). Fatal adverse reactions occurred in a total of 4.2% of patients. Limited-stage Small Cell Lung Cancer In patients with limited-stage SCLC in the ADRIATIC study receiving IMFINZI (n=262), the most common adverse reactions occurring in ≥20% of patients receiving IMFINZI were pneumonitis or radiation pneumonitis (38%), and fatigue (21%). The most common Grade 3 or 4 adverse reactions (≥3%) were pneumonitis or radiation pneumonitis and pneumonia. In patients with limited-stage SCLC in the ADRIATIC study receiving IMFINZI (n=262), IMFINZI was permanently discontinued due to adverse reactions in 16% of the patients receiving IMFINZI. Serious adverse reactions occurred in 30% of patients receiving IMFINZI. The most frequent serious adverse reactions reported in ≥1% of patients receiving IMFINZI were pneumonitis or radiation pneumonitis (12%), and pneumonia (5%). Fatal adverse reactions occurred in 2.7% of patients who received IMFINZI including pneumonia (1.5%), cardiac failure, encephalopathy and pneumonitis (0.4% each). Extensive-stage Small Cell Lung Cancer In patients with extensive-stage SCLC in the CASPIAN study receiving IMFINZI plus chemotherapy (n=265), the most common adverse reactions (≥20%) were nausea (34%), fatigue/asthenia (32%), and alopecia (31%). The most common Grade 3 or 4 adverse reaction (≥3%) was fatigue/asthenia (3.4%). In patients with extensive-stage SCLC in the CASPIAN study receiving IMFINZI plus chemotherapy (n=265), IMFINZI was discontinued due to adverse reactions in 7% of the patients receiving IMFINZI plus chemotherapy. Serious adverse reactions occurred in 31% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least 1% of patients were febrile neutropenia (4.5%), pneumonia (2.3%), anemia (1.9%), pancytopenia (1.5%), pneumonitis (1.1%), and COPD (1.1%). Fatal adverse reactions occurred in 4.9% of patients receiving IMFINZI plus chemotherapy. Locally Advanced or Metastatic Biliary Tract Cancers In patients with locally advanced or metastatic BTC in the TOPAZ-1 study receiving IMFINZI (n=338), the most common adverse reactions (occurring in ≥20% of patients) were fatigue (42%), nausea (40%), constipation (32%), decreased appetite (26%), abdominal pain (24%), rash (23%), and pyrexia (20%). In patients with locally advanced or metastatic BTC in the TOPAZ-1 study receiving IMFINZI (n=338), discontinuation due to adverse reactions occurred in 6% of the patients receiving IMFINZI plus chemotherapy. Serious adverse reactions occurred in 47% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least 2% of patients were cholangitis (7%), pyrexia (3.8%), anemia (3.6%), sepsis (3.3%) and acute kidney injury (2.4%). Fatal adverse reactions occurred in 3.6% of patients receiving IMFINZI plus chemotherapy. These include ischemic or hemorrhagic stroke (4 patients), sepsis (2 patients), and upper gastrointestinal hemorrhage (2 patients). Unresectable Hepatocellular Carcinoma In patients with unresectable HCC in the HIMALAYA study receiving IMFINZI and IMJUDO (n=388), the most common adverse reactions (occurring in ≥20% of patients) were rash (32%), diarrhea (27%), fatigue (26%), pruritus (23%), musculoskeletal pain (22%), and abdominal pain (20%). In patients with unresectable HCC in the HIMALAYA study receiving IMFINZI and IMJUDO (n=388), serious adverse reactions occurred in 41% of patients. Serious adverse reactions in >1% of patients included hemorrhage (6%), diarrhea (4%), sepsis (2.1%), pneumonia (2.1%), rash (1.5%), vomiting (1.3%), acute kidney injury (1.3%), and anemia (1.3%). Fatal adverse reactions occurred in 8% of patients who received IMFINZI and IMJUDO, including death (1%), hemorrhage intracranial (0.5%), cardiac arrest (0.5%), pneumonitis (0.5%), hepatic failure (0.5%), and immune-mediated hepatitis (0.5%). Permanent discontinuation of treatment regimen due to an adverse reaction occurred in 14% of patients. Primary advanced or Recurrent dMMR Endometrial Cancer In patients with advanced or recurrent dMMR endometrial cancer in the DUO-E study receiving IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single-agent (n=44), the most common adverse reactions, including laboratory abnormalities (occurring in >20% of patients) were peripheral neuropathy (61%), musculoskeletal pain (59%), nausea (59%), alopecia (52%), fatigue (41%), abdominal pain (39%), constipation (39%), rash (39%), decreased magnesium (36%), increased ALT (32%), increased AST (30%), diarrhea (27%), vomiting (27%), cough (27%), decreased potassium (25%), dyspnea (25%), headache (23%), increased alkaline phosphatase (20%), and decreased appetite (18%). The most common Grade 3 or 4 adverse reactions (≥3%) were constipation (4.5%) and fatigue (4.5%). In patients with advanced or recurrent dMMR endometrial cancer in the DUO-E study receiving IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single-agent (n=44), permanent discontinuation of IMFINZI due to adverse reactions occurred in 11% of patients. Serious adverse reactions occurred in 30% of patients who received IMFINZI with carboplatin and paclitaxel; the most common serious adverse reactions (≥4%) were constipation (4.5%) and rash (4.5%). Muscle-Invasive Bladder Cancer (MIBC) In patients with muscle-invasive bladder cancer (MIBC), the most common adverse reactions, including laboratory abnormalities, in the overall study (occurring in ≥20% of patients) were decreased hemoglobin, decreased neutrophils, increased blood creatinine, decreased sodium, nausea, increased ALT, decreased calcium, decreased platelets, fatigue, increased potassium, decreased lymphocytes, increased AST, constipation, decreased magnesium, decreased appetite, increased alkaline phosphate, rash, pyrexia, diarrhea, vomiting and abdominal pain. In patients with MIBC in the neoadjuvant phase of the NIAGARA study receiving IMFINZI in combination with gemcitabine and cisplatin (n=530), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 9% of patients. Serious adverse reactions occurred in 24% of patients; the most frequent (≥1%) serious adverse reactions were pulmonary embolism (1.9%), febrile neutropenia (1.5%), acute kidney injury (1.3%), thrombocytopenia (1.3%), urinary tract infection (1.3%), and pneumonia (1.3%). Fatal adverse reactions occurred in 1.1% of patients including sepsis, myocardial infarction, and pulmonary embolism (0.2% each). One fatal adverse reaction of pneumonia was reported in 1 (0.2%) patient in the post-surgery phase before adjuvant treatment started. Of the 530 patients in the IMFINZI treatment arm and 526 patients in the chemotherapy treatment arm who received neoadjuvant treatment, 1 (0.2%) patient in each treatment arm did not receive surgery due to adverse reactions. The adverse reaction that led to cancellation of surgery in the IMFINZI treatment arm was interstitial lung disease. In patients with MIBC in the adjuvant phase of the NIAGARA study receiving IMFINZI as a single agent (n=383), permanent discontinuation of adjuvant IMFINZI due to an adverse reaction occurred in 5% of patients. Serious adverse reactions occurred in 26% of patients. The most frequent serious adverse reactions (occurring in ≥1% of patients) were urinary tract infection (7%), acute kidney injury (3.7%), hydronephrosis (2.1%), pyelonephritis (2.1%), urosepsis (1.8%) and sepsis (1.6%). Fatal adverse reactions occurred in 1.8% of patients, including COVID-19, severe acute respiratory syndrome, cardiopulmonary failure, gastrointestinal hemorrhage, and chronic hepatic failure (0.3% each). The safety and effectiveness of IMFINZI and IMJUDO have not been established in pediatric patients. Indications: IMFINZI, as a single agent, is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT). IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by IMFINZI continued as a single agent as adjuvant treatment after surgery, is indicated for the treatment of adult patients with resectable (tumors ≥4 cm and/or node positive) NSCLC and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements. IMFINZI, in combination with IMJUDO and platinum-based chemotherapy, is indicated for the treatment of adult patients with metastatic NSCLC with no sensitizing EGFR mutations or ALK genomic tumor aberrations. IMFINZI, as a single agent, is indicated for the treatment of adult patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT). IMFINZI, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC). IMFINZI, in combination with gemcitabine and cisplatin, is indicated for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC). IMFINZI in combination with IMJUDO is indicated for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC). IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) as determined by an FDA-approved test. IMFINZI in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by single-agent IMFINZI as adjuvant treatment following radical cystectomy, is indicated for the treatment of adult patients with muscle-invasive bladder cancer (MIBC). Please see additional Important Safety Information throughout and Full Prescribing Information including Medication Guide for IMFINZI and IMJUDO. You may report side effects related to AstraZeneca products. Notes Gastric and gastroesophageal junction cancers Gastric (stomach) cancer is the fifth most common cancer worldwide and the fifth-highest leading cause of cancer mortality.3 Nearly one million new patients were diagnosed with gastric cancer in 2022, with approximately 660,000 deaths reported globally.3 In many regions, its incidence has been increasing in patients younger than 50 years old, along with other gastrointestinal (GI) malignancies.5 In 2024, there were approximately 43,000 drug-treated patients in the US, European Union (EU), and Japan with early-stage and locally advanced gastric or GEJ cancer.4 Approximately 62,000 patients in these regions are expected to be newly diagnosed in this setting by 2030.6 GEJ cancer is a type of gastric cancer that arises from and spans the area where the esophagus connects to the stomach.7 Disease recurrence is common in patients with resectable gastric cancer despite undergoing surgery with curative intent and treatment with neoadjuvant/adjuvant chemotherapy. Approximately one in four patients with gastric cancer who undergo surgery develop recurrent disease within one year, and one in four patients do not survive beyond two years, reflecting a high unmet medical need.8-9 Additionally, the five-year survival rate remains poor, with less than half of patients alive at five years.10 MATTERHORN MATTERHORN is a randomized, double-blind, placebo-controlled, multi-center, global Phase III trial evaluating IMFINZI as perioperative treatment for patients with resectable Stage II-IVA gastric and GEJ cancers. Perioperative therapy includes treatment before and after surgery, also known as neoadjuvant/adjuvant therapy. In the trial, 948 patients were randomized to receive a 1500mg fixed dose of IMFINZI plus FLOT chemotherapy or placebo plus FLOT chemotherapy every four weeks for two cycles prior to surgery. This was followed by IMFINZI or placebo every four weeks for up to 12 cycles after surgery (including two cycles of IMFINZI or placebo plus FLOT chemotherapy and 10 additional cycles of IMFINZI or placebo monotherapy). In the MATTERHORN trial, the primary endpoint is EFS, defined as time from randomization until the date of one of the following events (whichever occurred first): RECIST (version 1.1, per blinded independent central review assessment) progression that precludes surgery or requires non-protocol therapy during the neoadjuvant period; RECIST progression/recurrence during the adjuvant period; non-RECIST progression that precludes surgery or requires non-protocol therapy during the neoadjuvant period or discovered during surgery; progression/recurrence confirmed by biopsy post-surgery; or death due to any cause. Key secondary endpoints include pathologic complete response rate, defined as the proportion of patients who have no detectable cancer cells in resected tumor tissue following neoadjuvant therapy, and OS. The trial enrolled participants in 176 centers in 20 countries, including in the US, Canada, Europe, South America and Asia. IMFINZI IMFINZI® (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumor's immune-evading tactics and releasing the inhibition of immune responses. In GI cancer, IMFINZI is approved in combination with chemotherapy in locally advanced or metastatic biliary tract cancer (BTC) and in combination with IMJUDO® (tremelimumab-actl) in unresectable hepatocellular carcinoma (HCC). IMFINZI is also approved as a monotherapy in unresectable HCC in Japan and the EU. In addition to its indications in GI cancers, IMFINZI is the global standard of care based on OS in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy (CRT). Additionally, IMFINZI is approved as a perioperative treatment in combination with neoadjuvant chemotherapy in resectable NSCLC, and in combination with a short course of IMJUDO and chemotherapy for the treatment of metastatic NSCLC. IMFINZI is also approved for limited-stage small cell lung cancer (SCLC) in patients whose disease has not progressed following concurrent platinum-based CRT; and in combination with chemotherapy for the treatment of extensive-stage SCLC. Perioperative IMFINZI in combination with neoadjuvant chemotherapy is approved in the US and other countries for patients with muscle-invasive bladder cancer based on results from the NIAGARA Phase III trial. Additionally, in May 2025, IMFINZI plus standard-of-care Bacillus Calmette-Guérin induction and maintenance therapy met the primary endpoint of disease-free survival for patients with high-risk non-muscle-invasive bladder cancer in the POTOMAC Phase III trial. IMFINZI in combination with chemotherapy followed by IMFINZI monotherapy is approved as a 1st-line treatment for primary advanced or recurrent endometrial cancer (mismatch repair deficient disease only in the US and EU). IMFINZI in combination with chemotherapy followed by olaparib and IMFINZI is approved for patients with mismatch repair proficient advanced or recurrent endometrial cancer in the EU and Japan. Since the first approval in May 2017, more than 414,000 patients have been treated with IMFINZI. As part of a broad development program, IMFINZI is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with NSCLC, bladder cancer, breast cancer, ovarian cancer and several GI cancers. AstraZeneca in GI cancers AstraZeneca has a broad development program for the treatment of GI cancers across several medicines and a variety of tumor types and stages of disease. In 2022, GI cancers collectively represented approximately 5 million new cancer cases leading to approximately 3.3 million deaths.11 Within this program, the Company is committed to improving outcomes in gastric, liver, biliary tract, esophageal, pancreatic, and colorectal cancers. In addition to its indications in BTC and HCC, IMFINZI is being assessed in combinations, including with IMJUDO, in liver, esophageal and gastric cancers in an extensive development program spanning early to late-stage disease across settings. Fam-trastuzumab deruxtecan-nxki, a HER2-directed antibody drug conjugate (ADC), is approved in the US and several other countries for HER2-positive advanced gastric cancer. Fam-trastuzumab deruxtecan-nxki is jointly developed and commercialized by AstraZeneca and Daiichi Sankyo. Olaparib, a first-in-class PARP inhibitor, is approved in the US and several other countries for the treatment of BRCA-mutated metastatic pancreatic cancer. Olaparib is developed and commercialized in collaboration with Merck & Co., Inc (MSD outside the US and Canada). The Company is also assessing rilvegostomig (AZD2936), a PD-1/TIGIT bispecific antibody, in combination with chemotherapy as an adjuvant therapy in BTC, in combination with bevacizumab with or without IMJUDO as a 1st-line treatment in patients with advanced HCC, and as a 1st-line treatment in patients with HER2-negative, locally advanced unresectable or metastatic gastric and GEJ cancers. Rilvegostomig is also being evaluated in combination with fam-trastuzumab deruxtecan-nxki in previously untreated, HER2-expressing, locally advanced or metastatic BTC. AstraZeneca is advancing multiple modalities that provide complementary mechanisms for targeting Claudin 18.2, a promising therapeutic target in gastric cancer. These include sonesitatug vedotin, a potential first-in-class ADC licensed from KYM Biosciences Inc., currently in Phase III development; AZD5863, a novel Claudin 18.2/CD3 T-cell engager bispecific antibody licensed from Harbor Biomed in Phase I development; and AZD6422, an armored autologous chimeric antigen receptor T-cell (CAR T) therapy, currently being evaluated in an investigator-initiated trial (IIT) in collaboration with AbelZeta in China. In early development, AstraZeneca is developing two Glypican 3 (GPC3) armored CAR Ts in HCC. AZD5851, currently in Phase I development, is being developed globally, and C-CAR031 / AZD7003 is being co-developed with AbelZeta in China where it is under evaluation in an IIT. AstraZeneca in immuno-oncology (IO) AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumor immune response and stimulate the body’s immune system to attack tumors. AstraZeneca strives to redefine cancer care and help transform outcomes for patients with IMFINZI as a monotherapy and in combination with IMJUDO as well as other novel immunotherapies and modalities. The Company is also investigating next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer, including cell therapy and T-cell engagers. AstraZeneca is pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. The Company is focused on exploring novel combination approaches to help prevent treatment resistance and drive longer immune responses. With an extensive clinical program, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure. AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience. AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. AstraZeneca AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit www.astrazeneca-us.com and follow the Company on social media @AstraZeneca. References FDA. Priority Review. Available at: https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review . Accessed July 2025 FDA. Frequently Asked Questions: Breakthrough Therapies. Available at: https://www.fda.gov/regulatory-information/food-and-drug-administration-safety-and-innovation-act-fdasia/frequently-asked-questions-breakthrough-therapies . Accessed July 2025. World Health Organization. International Agency for Research on Cancer. Stomach Fact Sheet. Available at: https://gco-iarc-who-int.libproxy1.nus.edu.sg/media/globocan/factsheets/cancers/7-stomach-fact-sheet.pdf . Accessed July 2025. AstraZeneca PLC. Investor Relations Epidemiology Spreadsheet. Available at: https://www.astrazeneca.com/investor-relations.html . Accessed July 2025. Li Y, et al. Global burden of young-onset gastric cancer: a systematic trend analysis of the global burden of disease study 2019. Gastric Cancer . 2024;27(4):684-700. Kantar Health, validated with SEER stage at diagnosis and Cabasag et al. and Kuzuu et al. 2021. National Cancer Institute. Gastroesophageal junction. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/gastroesophageal-junction . Accessed July 2025. Li Y, et al. Postoperative recurrence of gastric cancer depends on whether the chemotherapy cycle was more than 9 cycles. Medicine . 2022;101(5):e28620. Ilic M, Ilic I. Epidemiology of stomach cancer. World J Gastroenterol . 2022;28(12):1187-1203. Al-Batran SE, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomized, phase 2/3 trial. Lancet. 2019;393(10184):1948-1957. World Health Organization. World Cancer Fact Sheet. Available at https://gco-iarc-who-int.libproxy1.nus.edu.sg/media/globocan/factsheets/populations/900-world-fact-sheet.pdf . Accessed July 2025. US-103594 Last Updated 7/25