Bevacizumab

在2026年欧洲糖尿病研究协会（EASD）年会上，全球首创的胰高血糖素/胰高血糖素样肽-1（GCG/GLP-1）双受体激动剂玛仕度肽（Mazdutide）携三项重磅研究亮相，研究覆盖女性生殖代谢健康、脂肪组织产热机制和代谢相关脂肪性肝炎（MASH）及肝纤维化领域，全面展现了玛仕度肽双靶减重、燃脂护肝，具有“代谢-器官”多重获益潜力。 GLORY-2亚组分析 女性代谢生殖健康新突破 玛仕度肽改善肥胖育龄期女性月经周期规律性和胰岛素抵抗：GLORY-2研究亚组分析[1] Mazdutide improves menstrual cyclicity and insulin resistance in reproductive-aged women with obesity: a subgroup analysis from the GLORY-2 trial GLORY-2研究是由北京大学人民医院纪立农教授牵头开展的Ⅲ期临床研究，结果显示，与安慰剂相比，玛仕度肽9 mg能显著降低中国中重度成人肥胖患者的体重（-18.55% vs. -3.02%）。同时，玛仕度肽还为患者带来了多维度的代谢获益。[2]本研究进一步评估了玛仕度肽9 mg对GLORY-2研究中育龄期女性月经周期规律性和胰岛素抵抗的影响。 本亚组分析纳入GLORY-2研究中有月经日记和HOMA2评估的育龄期女性共284例，随机接受玛仕度肽9 mg或安慰剂治疗60周。研究进一步提取了月经稀发、月经紊乱和医生诊断的多囊卵巢综合征（PCOS）亚组。缺失数据采用末次观察结转法处理，组间变化比较采用Satterthwaite t检验；同时评估总体及三个亚组HOMA2-IR与HOMA2-β水平。 核心发现： 1. 月经规律性显著改善，早期起效且持续获益 玛仕度肽9 mg自第24周起即可改善月经规律性，且获益持续至第60周。 诊断PCOS亚组：第24周时，玛仕度肽组月经频次自基线8.71次/年增加1.39次/年，而安慰剂组自基线7.46次/年减少0.47次/年（P=0.0765）。 月经紊乱亚组：玛仕度肽组自基线8.06次/年增加1.67次/年，安慰剂组自基线8.74次/年增加0.19次/年（P=0.0037）。 月经稀发亚组：玛仕度肽组自基线4.81次/年增加3.32次/年（频次近基线2倍），安慰剂组从4.27次/年仅增加0.28次/年（P=0.0045）。 与此同时，所有玛仕度肽治疗亚组均观察到月经间期的一致性缩短，提示周期趋于正常化。 2. 胰岛素抵抗持续缓解，且未见平台期 第60周时，总体队列中玛仕度肽组HOMA2-IR较基线下降41.1%，呈持续下降趋势且未见平台期，提示胰岛素抵抗改善，同时各人群在胰岛素敏感性方面均观察到改善。胰岛素抵抗改善不仅有助于血糖控制，还可通过减轻脂毒性、慢性炎症和多器官代谢负担，降低糖尿病、心血管病、脂肪肝等胰岛素抵抗相关疾病风险。[3] 图1. 玛仕度肽9 mg对肥胖育龄期女性月经周期规律性和胰岛素抵抗的影响 本研究表明，在肥胖育龄期女性中，每周一次玛仕度肽9 mg改善了月经规律性、促进月经周期恢复正常并改善了胰岛素抵抗，HOMA2-IR的降低可持续至第60周。这些发现提示应早期关注肥胖女性胰岛素抵抗与月经紊乱，玛仕度肽为改善PCOS结局提供了早期干预的治疗策略。 玛仕度肽减重减脂效果优于司美格鲁肽：通过脂肪产热和TPH2介导的途径改善肥胖[4] Mazdutide ameliorates obesity through adipose thermogenesis and TPH2-mediated pathways 肥胖是与多种代谢并发症密切相关的全球性公共卫生问题。玛仕度肽通过协同激活能量消耗途径实现更优的减重和身体成分改善，广东省人民医院关海霞教授团队于EASD 2026发布研究，探讨玛仕度肽对减重，尤其是内脏脂肪减少及脂肪组织代谢调控的影响。 研究人员将C57BL/6J小鼠随机分为对照组（CD）、高脂饮食组（HFD）、司美格鲁肽组（阳性对照）和玛仕度肽组，每组5只。干预4周后记录体重变化，通过9.4T核磁共振成像（MRI）和双能X射线吸收法（DXA）评估体成分和脂肪含量，免疫组化检测脂肪组织产热标志物UCP1和炎症标志物F4/80，RNA测序分析附睾脂肪组织转录谱。 核心发现： 1. 减重减脂效果优于司美格鲁肽 与司美格鲁肽组相比，玛仕度肽组体重下降更为显著（-24.16% ± 9.14% vs. -43.71% ± 6.58%，P=0.003）。DXA和MRI分析显示，玛仕度肽治疗导致更显著的脂肪面积减少（5.98 vs. 6.97 cm²，P=0.05），且产热作用增强。 2. 产热增强、炎症减轻 免疫组化结果显示，玛仕度肽组UCP1阳性细胞显著增加，F4/80阳性巨噬细胞浸润减少，提示产热增强和炎症减轻。 3. TPH2完全逆转 RNA-seq分析显示，玛仕度肽可将高脂饮食诱导的TPH2异常上调完全恢复至正常水平，而司美格鲁肽仅实现部分逆转。这提示异常的TPH2上调可能是高脂饮食诱导的病理改变，而玛仕度肽使TPH2逆转有助于其改善能量代谢。 图2. 不同分组小鼠的身份成分和脂肪含量 本研究表明，玛仕度肽在减轻体重和内脏脂肪方面优于司美格鲁肽，这一优势与增强的脂肪组织产热作用及炎症减轻密切相关。TPH2可能是介导这种差异性疗效的关键分子，为理解双受体激动剂的独特代谢获益提供了新视角。 靶向肝细胞-肝星状细胞交互作用，玛仕度肽改善MASH及肝纤维化疗效优于司美格鲁肽[5] Targeting hepatocyte-hepatic stellate cell crosstalk with mazdutide (GCGR/GLP-1R dual agonist) ameliorates MASH and fibrosis MASH是一种涉及脂肪变性、炎症和纤维化的进行性肝病。此前玛仕度肽已在临床前模型中显示出缓解MASH和纤维化的作用，东南大学附属中大医院李玲教授、中国药科大学姜虎林教授团队在EASD 2026上发表的研究，进一步探讨了玛仕度肽对肝细胞的影响及其在调节肝细胞-肝星状细胞（HSC）交互作用中的角色。 C57BL/6J小鼠喂养AMLN饮食（高脂肪、果糖和胆固醇）32周后，随机接受溶媒、司美格鲁肽或玛仕度肽皮下注射，每两天一次，持续6周。通过免疫组化和生化检测评估炎症和肝纤维化，收集肝脏组织进行转录组和单细胞RNA测序分析。此外，利用棕榈酸和玛仕度肽处理的肝细胞，通过条件培养基和共培养实验研究其对HSC的影响。 核心发现： 1. 减重、降脂，均优于司美格鲁肽 玛仕度肽和司美格鲁肽均可有效降低体重、血清总胆固醇（TC）和甘油三酯（TG）水平。玛仕度肽减重幅度显著优于司美格鲁肽（45.11% vs. 18.82%，P<0.001），TC水平亦更低（2.136 mmol/L vs. 4.276 mmol/L，P<0.001）。 2. 组织学改善显著，抗纤维化疗效优于司美格鲁肽 肝脏组织学评估（H&E和油红O染色）显示，相比GLP-1单激动剂司美格鲁肽，玛仕度肽治疗组的小鼠肝组织形态更完整，能更显著减轻肝脏脂肪堆积、炎症，并降低胶原沉积和肝纤维化程度。[5,6] 图3. 不同组别小鼠肝脏的苏木精-伊红、Masson和天狼星红染色代表性图像 3. 多组学及细胞交互调控揭示分子机制 单细胞测序结果表明，玛仕度肽可通过肝细胞上的GCGR重新编程肝脏胆固醇代谢与稳态，并激活补体和凝血级联反应。体外共培养实验进一步证实，玛仕度肽可减少肝细胞脂质沉积和胆固醇含量，从而抑制肝细胞诱导的HSC活化并减少胶原分泌。此外，玛仕度肽还能调节脂质代谢和肠道微生物群。这些作用可能为MASH的治疗提供新的方法和靶点。[5,6] 研究表明，玛仕度肽通过调节肝细胞脂质代谢，间接抑制HSC活化，减少MASH小鼠的纤维化进程。这些发现为MASH和进行性肝纤维化的治疗提供了新的治疗途径。 小结 玛仕度肽作为中国首个获批的GCG/GLP-1双受体激动剂，在2026年EASD大会上以三项研究展现了从代谢重塑到器官保护的广阔治疗潜力。玛仕度肽可持续改善肥胖育龄期女性的月经规律性和胰岛素抵抗；通过增强脂肪组织产热和完全逆转TPH2异常上调，实现了优于司美格鲁肽的减重减脂效果；通过靶向肝细胞-HSC交互作用，玛仕度肽相比司美格鲁肽更有效减轻肝脏脂肪积累、改善MASH及肝纤维化。这些研究表明，玛仕度肽不仅能减重，还能减少内脏脂肪、改善代谢功能[7]，以其独特的双靶机制，为患者带来燃脂护肝及其他代谢性疾病的更优选择。 关于玛仕度肽（IBI362） 玛仕度肽（IBI362）是信达生物与礼来制药共同推进的一款胰高血糖素（GCG）/胰高血糖素样肽-1（GLP-1）双受体激动剂。作为一种哺乳动物胃泌酸调节素（OXM）类似物，玛仕度肽除了通过激动GLP-1受体促进胰岛素分泌、降低血糖和减轻体重外，还可通过激动GCGR增加能量消耗增强减重疗效，同时改善肝脏脂肪代谢。玛仕度肽已在多项临床研究中展现出优秀的减重和降糖疗效，以及降低腰围、血脂、血压、血尿酸、肝酶及肝脏脂肪含量，以及改善胰岛素敏感性，带来多重代谢获益。 信达生物当前共开展或完成了九项玛仕度肽的III期临床研究，包括： 在中国超重或肥胖参与者中开展的III期临床研究（GLORY-1）； 在中国中重度肥胖参与者中开展的III期临床研究（GLORY-2）； 在初治的中国2型糖尿病患者中开展的III期临床研究（DREAMS-1）； 在口服药物治疗血糖控制不佳的中国2型糖尿病参与者中开展的对比玛仕度肽和度拉糖肽的III期临床研究（DREAMS-2）； 在中国2型糖尿病合并肥胖的参与者中开展的对比玛仕度肽和司美格鲁肽的III期临床研究（DREAMS-3）; 在中国超重或肥胖合并代谢相关脂肪性肝病（MAFLD）参与者中开展的玛仕度肽与司美格鲁肽2.4mg对比的III期临床研究（GLORY-3）; 在中国阻塞性睡眠呼吸暂停（OSA）合并肥胖参与者中开展的III期临床研究（GLORY-OSA）； 在中国肥胖青少年参与者中开展的III期临床研究（GLORY-YOUNG）； 在中国高血压合并肥胖参与者中开展的III期临床研究（GLORY-H）。 其中，前五项III期临床研究均已达成终点，后四项III期临床研究还在进行中。 此外，玛仕度肽还有多项新临床研究进行中，其中包括：代谢相关脂肪性肝炎（MASH），射血分数保留心力衰竭（HFpEF），及更高剂量头对头替尔泊肽治疗中重度肥胖等临床研究。 *玛仕度肽已获NMPA批准两项适应症，第一项为在控制饮食和增加体力活动基础上对成人患者的长期体重控制，初始体重指数（BMI）为： BMI≥28 kg/m²（肥胖），或 BMI≥24 kg/m²（超重），并伴有至少一种体重相关的合并症（例如高血糖、高血压、血脂异常、脂肪肝、阻塞性睡眠呼吸暂停综合征等）。 第二项适应症为用于成人2型糖尿病患者的血糖控制： 单药治疗 单纯饮食控制和运动干预后血糖仍控制不佳的成人2型糖尿病患者； 联合治疗 在饮食控制和运动基础上，接受二甲双胍和/或磺脲类药物、接受二甲双胍和/或钠-葡萄糖共转运蛋白2抑制剂（SGLT2i）类药物治疗血糖仍控制不佳的成人2型糖尿病患者。 玛仕度肽凭借出色的研究数据多次获得学术及行业内的认可，研究结果陆续在世界顶级知名期刊《自然》主刊、《新英格兰医学杂志》、《美国医学会杂志》、《自然通讯》、Diabetes Care , eClinicalMedicine，《细胞》子刊 Med 发布。玛仕度肽是中国制药史上首款两项临床研究同期登陆《自然》主刊的药物，成为全球唯一同时登顶《自然》(Nature)主刊、《新英格兰医学杂志》(NEJM)和《美国医学会杂志》(JAMA)三大顶级刊物的GLP-1药物。玛仕度肽DREAMS-3临床研究结果显示，减重降糖及代谢综合疗效均优于司美格鲁肽。玛仕度肽已经进入中国临床多部减重及糖尿病专家共识，被视为硬科技。此前，玛仕度肽被知名医药领域网站FIERCE Pharma评入2025全球十大最受期待创新药榜单[8]，被《自然通讯》评选为临床转化医学领域最重要的50个研究之一并被列为主编精选研究[9]。 关于信达生物 “始于信，达于行”，开发出老百姓用得起的高质量生物药，是信达生物的使命和目标。信达生物成立于2011年，致力于研发、生产和销售肿瘤、自身免疫、代谢、眼科等重大疾病领域的创新药物，让我们的工作惠及更多的生命。公司已有20个产品获得批准上市，它们分别是信迪利单抗注射液（达伯舒®），贝伐珠单抗注射液（达攸同®），阿达木单抗注射液（苏立信®），利妥昔单抗注射液（达伯华®），佩米替尼片（达伯坦®），奥雷巴替尼片（耐立克®）， 雷莫西尤单抗注射液（希冉择®），塞普替尼胶囊（睿妥®），伊基奥仑赛注射液（福可苏®），托莱西单抗注射液（信必乐®），氟泽雷塞片（达伯特®），匹妥布替尼片(捷帕力®)，己二酸他雷替尼胶囊（达伯乐®），利厄替尼片（奥壹新®），替妥尤单抗N01注射液（信必敏®），玛仕度肽注射液（信尔美®），匹康奇拜单抗注射液（信美悦®），伊匹木单抗N01注射液（达伯欣®），阿贝西利片（唯择®）和盐酸奎扎替尼片（维复泰®）。目前，还有1个品种在NDA审评中，5条管线进入注册或关键性临床阶段，另有20条管线处于临床研究阶段。 公司已与礼来、罗氏、武田、辉瑞、赛诺菲、Incyte和MD Anderson 癌症中心等国际合作方达成30多项战略合作。信达生物在不断自研创新药物、谋求自身发展的同时，秉承经济建设以人民为中心的发展思想。多年来，始终心怀科学善念，坚守“以患者为中心”，心系患者并关注患者家庭，积极履行社会责任。公司陆续发起、参与了多项药品公益援助项目，让越来越多的患者能够得益于生命科学的进步，买得到、用得起高质量的生物药。截至目前，信达生物患者援助项目已惠及20余万普通患者，药物捐赠总价值40亿元人民币。信达生物希望和大家一起努力，提高中国生物制药产业的发展水平，以满足百姓用药可及性和人民对生命健康美好愿望的追求。 详情请访问公司网站：www.innoventbio.com或公司领英账号：Innovent Biologics。 声明： 1.本文仅为医学科学信息分享，不构成任何诊疗建议或用药指导，亦不涉及任何药品推荐。个体用药情况可能存在差异，请及时就医，处方药购买及使用需谨遵医嘱。 2.雷莫西尤单抗注射液（希冉择®），塞普替尼胶囊（睿妥®），匹妥布替尼片 （捷帕力®）和阿贝西利片（唯择®）由礼来公司研发。 参考文献： [1]L. Chen, et al. LBA 09 - Mazdutide improves menstrual cyclicity and insulin resistance in reproductive-aged women with obesity: a subgroup analysis from the GLORY-2 trial. EASD, September 29, 2026. [2]Gao L, et al. Treatment With 9-mg Mazdutide for Weight Reduction in Chinese Adults With Obesity: The GLORY-2 Randomized Clinical Trial. JAMA. 2026 Aug 4;336(5):377-388. [3]Li M, et al. Trends in insulin resistance: insights into mechanisms and therapeutic strategy. Signal Transduct Target Ther. 2022 Jul 6;7(1):216. [4]W. Feng, et al. 793 - Mazdutide ameliorates obesity through adipose thermogenesis and TPH2-mediated pathways. EASD, September 30, 2026. [5]W. Hui, et al. 181 - Targeting hepatocyte-hepatic stellate cell crosstalk with mazdutide (GCGR/GLP-1R dual agonist) ameliorates MASH and fibrosis. October 1, 2026. [6]Hui Wang, Ling Li. ePoster presented at: ADA 2025 Scientific Sessions; 1616-P.  [7]Ji L, et al. N Engl J Med. 2025 May 25. doi: 10.1056/NEJMoa2411528. [8]https://www.fiercepharma.com/marketing/top-10-most-anticipated-drug-launches-2025 [9]https://www.nature.com/ncomms/editorshighlights 前瞻性声明 本新闻稿所发布的信息中可能会包含某些前瞻性表述。这些表述本质上具有相当风险和不确定性。在使用“预期”、“相信”、“预测”、“期望”、“打算”及其他类似词语进行表述时，凡与本公司有关的，均属于前瞻性表述。 本公司并无义务不断地更新这些预测性陈述。这些前瞻性表述是基于本公司管理层在做出表述时对未来事务的现有看法、假设、期望、估计、预测和理解。这些表述并非对未来发展的保证，会受到风险、不确性及其他因素的影响，有些是超出本公司的控制范围，难以预计。因此，受我们的业务、竞争环境、政治、经济、法律和社会情况的未来变化及发展的影响，实际结果可能会与前瞻性表述所含资料有较大差别。 本公司、本公司董事及雇员代理概不承担 (a) 更正或更新本网站所载前瞻性表述的任何义务;及 (b) 若因任何前瞻性表述不能实现或变成不正确而引致的任何责任。

Collaboration Intends to Evaluate Ivonescimab in Combination with Datroway across Multiple Tumor Types Starting with a Phase III Study in First-Line Triple Negative Breast Cancer MIAMI--(BUSINESS WIRE)--Summit Therapeutics Inc. (Nasdaq: SMMT) today announced a clinical trial collaboration agreement with Daiichi Sankyo (TSE: 4568) and AstraZeneca (LSE/STO/NYSE: AZN) to evaluate ivonescimab, a novel, potential first-in-class investigational PD-1 / VEGF bispecific antibody, in combination with Datroway ® (datopotamab deruxtecan), a TROP2-directed antibody drug conjugate (ADC), across multiple solid tumor settings, intending to include breast and lung cancer. The companies intend to begin with a Phase III trial in first-line triple-negative breast cancer (TNBC). “We believe this collaboration with Daiichi Sankyo and AstraZeneca reflects increasing conviction in ivonescimab’s potential as a foundational next-generation immunotherapy and advances our ambition for ivonescimab to become the global PD-1 / VEGF partner of choice for novel combinations,” said Dr. Maky Zanganeh, President and Co-Chief Executive Officer of Summit Therapeutics. “Beginning with a Phase III study in first-line triple negative breast cancer, this collaboration represents an important expansion of Summit’s global development program into breast cancer and a path for additional solid tumor settings.” Under the terms of the agreement, each company will contribute their respective therapies for the planned combination trials which will be sponsored by AstraZeneca or Daiichi Sankyo. AstraZeneca, Daiichi Sankyo, and Summit will each contribute to trial costs, and each company will retain development and commercial rights to their respective medicines. “At Daiichi Sankyo, we are focused on maximizing the potential of our DXd antibody drug conjugate portfolio through innovative combinations and strategic collaborations that support the continued advancement of our pipeline,” said John Tsai, MD, Global Head, R&D, Daiichi Sankyo. “We are encouraged by the opportunity to explore ivonescimab in combination with Datroway to potentially deliver clinically meaningful benefit to patients.” “Central to our strategy to transform cancer outcomes is harnessing the power of immunotherapy and antibody drug conjugate combinations to drive deeper, more durable responses,” said Susan Galbraith, Executive Vice President, Oncology Hematology R&D, AstraZeneca. “We believe the combination of Datroway and ivonescimab has the potential to make a meaningful difference in multiple tumor types including lung and breast cancers.” Datroway is a specifically engineered TROP2-directed DXd ADC discovered by Daiichi Sankyo and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca. Designed using the proprietary DXd ADC Technology of Daiichi Sankyo, Datroway is one of seven DXd ADCs in the oncology pipeline of Daiichi Sankyo. About Ivonescimab Ivonescimab, known as SMT112 in Summit’s license territories, North America, South America, Europe, the Middle East, Africa, and Japan, and as AK112 outside of Summit’s license territories, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. By design, ivonescimab displays unique cooperative binding to each of its intended targets with multifold higher affinity to PD-1 when in the presence of VEGF. This design is intended to differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Summit believes ivonescimab’s specifically engineered tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the TME (Zhong, et al , iScience , 2025). This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design, together with a half-life of 6 to 7 days after the first dose (Zhong, et al , iScience , 2025) increasing to approximately 10 days at steady state dosing, is to improve upon previously established efficacy thresholds, side effects, and safety profiles associated with prior approved drugs to these targets. Ivonescimab was engineered by Akeso Inc. (HKEX Code: 9926.HK) and is currently utilized in multiple Phase III clinical trials. Over 5,000 patients have been treated with ivonescimab in clinical studies globally, and over 100,000 patients when considering those treated in a commercial setting in China, as noted by Akeso. There are currently 16 Phase III clinical studies that are either announced, ongoing, or have been completed studying ivonescimab, five of which are Summit-sponsored global studies, one of which is a multiregional study sponsored by a cooperative group, and 10 of which are being or have been conducted in China by Akeso. Summit began its clinical development of ivonescimab in NSCLC, commencing enrollment in 2023 in two multiregional Phase III clinical trials, HARMONi and HARMONi-3. In 2025, Summit began enrolling patients in HARMONi-7. Summit expanded its Phase III clinical development program into colorectal cancer (CRC) in the fourth quarter of 2025 by initiating enrollment in HARMONi-GI3. In 2026, Summit announced initiation of HARMONi-GU1, a Phase II/III study in urothelial carcinoma (bladder cancer) with global clinical trial site activations planned to begin by the fourth quarter of 2026. HARMONi is a Phase III clinical trial evaluating ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who were previously treated with a third-generation EGFR TKI (e.g., osimertinib). Detailed results of the study were provided in September 2025, and a Biologics License Application (BLA) was submitted to the United States Food and Drug Administration (FDA) for marketing authorization, which the FDA accepted for filing in January 2026; the goal Prescription Drug User Fee Act (PDUFA) date is November 14, 2026. HARMONi-3 is a Phase III clinical trial evaluating ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic, squamous or non-squamous NSCLC, irrespective of PD-L1 expression. The clinical trial is evaluating the two histologies as individual, separately powered cohorts with independent statistical powering. HARMONi-7 is a Phase III clinical trial evaluating ivonescimab monotherapy compared to pembrolizumab monotherapy in patients with first-line metastatic NSCLC whose tumors have high PD-L1 expression. HARMONi-GI3 is a Phase III clinical trial evaluating ivonescimab in combination with chemotherapy compared with bevacizumab plus chemotherapy in patients with first-line unresectable metastatic CRC. HARMONi-GU1 is a Phase II/III clinical trial evaluating ivonescimab plus the antibody drug conjugate (ADC) enfortumab vedotin (EV) compared to pembrolizumab plus EV as first-line therapy in patients with previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC). ILLUMINE is a Phase III study being conducted by GORTEC, a cooperative group dedicated to Head and Neck Oncology, in recurrent / metastatic head and neck squamous cell carcinoma (r/m HNSCC). ILLUMINE is a three-arm Phase III clinical trial designed to evaluate ivonescimab monotherapy, as well as ivonescimab in combination with ligufalimab, Akeso’s proprietary anti-CD47 monoclonal antibody, compared to monotherapy pembrolizumab in patients with PD-L1 positive r/m HNSCC. Five Phase III ivonescimab clinical trials have read out to date, all five with positive data. Four of these five studies are in NSCLC, and one is in biliary tract cancer (BTC). In addition to Summit’s positive HARMONi study, Akeso has had positive read-outs in three single-region (China), randomized Phase III clinical trials, HARMONi-A, HARMONi-2, and HARMONi-6, for ivonescimab in NSCLC, including a statistically significant overall survival benefit in all three studies from China. Akeso has also reported a statistically significant OS benefit in the single-region (China), randomized Phase III HARMONi-GI1 trial in advanced BTC. HARMONi-A was a Phase III clinical trial which evaluated ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with an EGFR TKI. HARMONi-2 is a Phase III clinical trial evaluating monotherapy ivonescimab against monotherapy pembrolizumab in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression. HARMONi-6 is a Phase III clinical trial evaluating ivonescimab in combination with platinum-based chemotherapy compared with tislelizumab, an anti-PD-1 antibody, in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous NSCLC, irrespective of PD-L1 expression. HARMONi-GI1 is a Phase III clinical trial evaluating ivonescimab in combination with chemotherapy compared with durvalumab plus chemotherapy as a first-line treatment for patients with advanced BTC. Akeso is actively conducting additional Phase III clinical studies in settings outside of NSCLC and biliary-tract cancer, including triple-negative breast cancer, head and neck squamous cell carcinoma, small cell lung cancer, colorectal cancer, and pancreatic cancer. Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. Ivonescimab was initially approved for marketing authorization in China in May 2024. About Summit Therapeutics Inc. Summit Therapeutics Inc. is a biopharmaceutical oncology company focused on the discovery, development, and commercialization of patient-, physician-, caregiver- and societal-friendly medicinal therapies intended to improve quality of life, increase potential duration of life, and resolve serious unmet medical needs. Summit was founded in 2003 and the company’s shares are listed on the Nasdaq Global Market (symbol "SMMT"). Summit is headquartered in Miami, Florida, with additional offices in Palo Alto, California, Princeton, New Jersey, Dublin, Ireland, and Oxford, UK. For more information, please visit and follow Summit on X @SMMT_TX . Summit Forward-Looking Statements Any statements in this press release about the Company’s future expectations, plans and prospects, including but not limited to, statements about the risk that the private placement does not close on the anticipated timeline or at all, including because required regulatory clearances are not obtained or other closing conditions are not satisfied, dilution to existing stockholders, and potential adverse effects on the market price of the Company's common stock, including from future sales by AstraZeneca, the Company's broad discretion over the use of proceeds, and the possibility that the proceeds will not be sufficient to fund operations as long as anticipated, AstraZeneca’s ownership and contractual rights, including Third Party acquisition participation, and registration rights, and potential conflicts of interest, the completion of the Private Placement does not depend on the parties entering into a definitive collaboration agreement, the Company's reliance on AstraZeneca for the supply of AstraZeneca’s products and other contributions to the clinical trials, the clinical and preclinical development of the Company’s product candidates, entry into and actions related to the Company’s partnership with Akeso Inc. and other collaborations, the intended use of the net proceeds from the private placements, the Company's anticipated spending and cash runway, the therapeutic potential of the Company’s product candidates, the potential commercialization of the Company’s product candidates, the timing of initiation, completion and availability of data from clinical trials, the potential submission of applications for marketing approvals, the expected timing of BLA submissions or FDA decisions, potential acquisitions, statements about the previously disclosed At-The-Market equity offering program (“ATM Program”), the expected proceeds and uses thereof, the Company’s estimates regarding stock-based compensation, and other statements containing the words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "would," and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including the Company’s ability to sell shares of our common stock under the ATM Program, the conditions affecting the capital markets, general economic, industry, or political conditions, including the effects of geopolitical developments, domestic and foreign trade policies, and monetary policies, the results of our evaluation of the underlying data in connection with the development and commercialization activities for ivonescimab, the outcome of discussions with regulatory authorities, including the Food and Drug Administration, the uncertainties inherent in the initiation of future clinical trials, availability and timing of data from ongoing and future clinical trials, the results of such trials, and their success, global public health crises, that may affect timing and status of our clinical trials and operations, whether preliminary results from a clinical trial will be predictive of the final results of that trial or whether results of early clinical trials or preclinical studies will be indicative of the results of later clinical trials, whether business development opportunities to expand the Company’s pipeline of drug candidates, including without limitation, through potential acquisitions of, and/or collaborations with, other entities occur, expectations for regulatory approvals, laws and regulations affecting government contracts and funding awards, availability of funding sufficient for the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements and other factors discussed in the "Risk Factors" and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” sections of filings that the Company makes with the Securities and Exchange Commission. Summit defines a “positive study” as a clinical study with one or more prespecified primary endpoints in which one of those endpoints achieves a statistically significant benefit according to the protocol or statistical analysis plan. Any change to our ongoing trials could cause delays, affect our future expenses, and add uncertainty to our commercialization efforts, as well as to affect the likelihood of the successful completion of clinical development of ivonescimab. Accordingly, readers should not place undue reliance on forward-looking statements or information. In addition, any forward-looking statements included in this press release represent the Company’s views only as of the date of this release and should not be relied upon as representing the Company’s views as of any subsequent date. The Company specifically disclaims any obligation to update any forward-looking statements included in this press release. Summit Therapeutics and the Summit Therapeutics logo are registered trademarks of Summit Therapeutics Inc. and/or its affiliates. Copyright © 2026, Summit Therapeutics Inc. All Rights Reserved. Contacts Summit Therapeutics’ Media & Investor Contacts: Nathan LiaBraaten Senior Director, Investor Relations Tracy Jones Director, Media & Public Relations investors@smmttx.com media@smmttx.com