Ifinatamab deruxtecan

为打造全球ADC/RDC未来产业高地，成都医学城拟于2024年4月18日-19日举办首届未来XDC新药大会！大会以“共创偶联药物产业未来”为主题，由同写意策划，安排一场主论坛和九场主题论坛，邀请“政、产、学、研、金、媒”各领域专家，通过“成果发布、主题演讲、热点对话、表彰颁奖、展览展示”五位一体的多元化的组织形式，迸发更多XDC产业新科技、新业态、新模式，构建XDC产业全新生态，触摸医药产业未来脉动。如果说2024年最火的肿瘤药是什么，当属ADC无疑。根据各大药企披露的财报，14款已上市ADC药物市场规模104亿美元，首次突破百亿美元。第一三共/阿斯利康的神药DS-8201（Enhertu）首次超过Kadcyla成为最畅销ADC药物。6款ADC销售额超过10亿美元跻身重磅炸弹。去年ADC市场规模为73亿美金，2023年市场规模增长40.5%！在医药市场表现不是很景气的当下，这个增幅和市场的规模堪称惊艳。Nature预测，2026年前十大ADC药物的规模将超过164亿美元。中国的ADC市场从2020年开始启动，预计2024年将达到74亿人民币。从市场规模上看，中国市场的体量并不算太大。ADC药物研发中，中国公司的起步虽然比较晚，但是进展迅速。自2021年8月开始，已经有23起ADC相关的交易。我们下面看一下国内外主要的ADC公司的策略和现状。1第一三共/阿斯利康/默沙东提到ADC，那么第一家要提到的公司就是日本的第一三共。第一三共目前应该是当之无愧的王者。第一三共2020年的治疗乳腺癌等癌症的新药Enhertu获批上市，在全球超过30个国家和地区成为处方药。在2023年销售额已经达到23.75亿美元，同比增长113%，超过了罗氏的Kadcyla，成为ADC领域的第一大药物，也被称为“神药”。为什么神呢?第一三共的Enhertu（又称DS8201）可精准灭杀表面有HER2蛋白的癌细胞。可以携带两倍于传统ADC抗癌药的药物，疗效较高。在临床试验中，使用Enhertu的乳腺癌患者的癌症无进展期中位数mPFS为28.8个月，是另一种ADC抗癌药Kadcyla（6.8个月）的4倍。Enhertu的另一个神奇之处在于，它不仅对HER2阳性的患者效果很好，对于HER2呈现弱阳性（HER2低表达），甚至只有微微阳性的患者同样有效。从市场的角度，一下子把市场从20%左右的乳腺癌患者，拓展到了70-80%甚至更大的乳腺癌人群。正是因为非常优异的临床数据，2019年，阿斯利康以69亿美元的总价拿下第一三共的HER2 ADC药物DS-8201。但第一三共不仅仅有DS8201，2023年10月19日，默沙东以220亿美元的总价打包拿下了第一三共的HER3-DXd、I-DXd、R-DXd三款ADC药物权益。算下来，一款ADC药物的平均售价在73亿美元左右。这是一个天价！拿目前处于临床试验阶段的药物HER3-DXd来说，该药物在肺癌领域也展现出强劲的实力。在名为HERTHENA-Lung01的临床试验中，对接受过EGFR-TKI和铂类药物化疗治疗的晚期EGFR突变NSCLC患者，使用5.6mg/kg HER3-DXd剂量组中，在中位研究持续时间为13.1个月时间里，患者的中位治疗持续时间为5.5个月，ORR为28.4%，PFS为5.5个月，OS为11.9个月。对于EGFR TKI治疗后出现耐药的患者而言，目前治疗手段相当有限，而HER3-DXd展示出的临床效果，无疑为这部分患者带来了一种新的治疗方案。默沙东看中的另一款B7-H3的ADC药物I-DXd，瞄准的则是小细胞肺癌（SCLC）患者。在肺癌中，小细胞肺癌占所有病例的15%，虽然这一规模不及非小细胞肺癌，但基于肺癌庞大的患者规模，这一适应症的患者群体也不在少数。更重要的是，一直以来小细胞肺癌患者都缺乏有效的治疗药物，预后很差。即便是接受化疗或PD-1/L1抑制剂治疗的小细胞肺癌患者，也会在半年至一年后内出现复发和耐药情况，因此小细胞肺癌对于新药开发需求十分迫切。小细胞肺癌领域，一直是医药研究的禁区，很少有药企在这个领域取得成功。这也是I-DXd的机会所在。在I/II期临床试验中，I-DXd治疗晚期转移性SCLC患者的ORR为52.4%，mPFS为5.6个月，mOS为12.2个月。这一结果，也初步显示出了I-DXd用于治疗SCLC的临床潜力。一般的PD-1/PD-L1的ORR也就在30%上下，超过50%的ORR是非常优秀的数据。在另一款针对卵巢癌的靶向CDH6的ADC药物R-DXd上，第一三共的进度同样全球领先。海外，除了第一三共，布局CDH6靶点的仅有诺华；国内，布局这一靶点的仅有昂阔生物和普众生物。第一三共无疑是ADC全球范围内的王者，其地位短期内尚无人可以撼动。2Seagen/辉瑞2023年3月，辉瑞以430亿美元收购了Seagen公司，以扩展其肿瘤学管线。Seagen是ADC开发方面的先驱公司，迄今为止FDA批准的12款ADC中，有4款使用该公司的ADC技术。Seagen公司拥有的4款获批药物中有三款为“first-in-class”ADC药物，包括靶向CD30的ADC产品Adcetris，靶向nectin-4的Padcev，以及获批治疗宫颈癌、靶向组织因子的Tivdak。此外，Seagen的研发管线中还包括15款处于1/2期临床试验阶段的在研疗法。其中，与荣昌生物联合开发的disitamab vedotin是一款靶向人表皮生长因子2（HER2）的抗体偶联药物，已经在中国获批治疗特定胃癌和尿路上皮癌患者。目前它与Keytruda联用，一线治疗尿路上皮癌患者的3期临床试验已经启动。Adcetris（维布妥昔单抗）在2023年销售额达到16.5亿美元，相比去年同期增长2%，在ADC里属于增长比较慢的。Adcetris是全球第一款获批上市的第二代ADC药物。Adcetris由Seagen公司研制，2009年武田与Seagen达成协议，获得Adcetris除美国和加拿大以外国家的商业化权益。2023年3月，辉瑞宣布以430亿美元收购Seagen。2021年，Adcetris被欧盟批准作为CD30表达的sALCL（复发或难治性系统性间变性大细胞淋巴瘤）一线治疗药物，成为全球第一个用于一线治疗的ADC。Adcetris已在全球获批多种适应症，包括霍奇金淋巴瘤、原发性皮肤间变性大细胞淋巴瘤、系统性间变性大细胞淋巴瘤、蕈样肉芽肿、血管免疫母细胞性T细胞淋巴瘤和外周T细胞淋巴瘤等。2020年5月，Adcetris（安适利）获中国国家药监局批准上市，治疗sALCL或CD30阳性霍奇金淋巴瘤（HL）成人患者。除了Adcetris之外，Seagen还有另一款ADC即Padcev。Padcev是首个获批的针对Nectin-4的ADC，由Seagen和Astellas共同开发。它最初在2019年12月获得FDA加速批准，并在2021年7月获得了完全FDA批准，用于治疗尿路上皮癌。除了单药治疗外，Padcev还在临床试验中与Keytruda联合研究。2023年10月，第三阶段EV-302试验报告了积极结果，该试验评估了Padcev与Keytruda联合治疗未经治疗的局部晚期或转移性尿路上皮癌（la/mUC）患者。与含铂化疗相比，EV-302研究达到了总生存期（OS）和无进展生存期（PFS）两个主要终点。联合治疗组的中位OS为31.5个月，而化疗组为16.1个月，表明与化疗组相比，联合治疗组患者的死亡风险降低了53%。联合治疗组的中位PFS为12.5个月，而化疗组为6.3个月，表示与化疗组相比，联合治疗组患者的癌症进展或死亡风险降低了55%。基于此，2023年12月15日，FDA批准Padcev与Keytruda联合用于治疗la/mUC的成人患者。这种联合治疗是首个获批的替代含铂化疗的方案，后者目前是la/mUC治疗的一线标准治疗方案。Padcev在2023年销售额超过了10亿美元，达到10.63亿美元，同比增长36%。3罗氏除了Seagen和第一三共之外，罗氏也是ADC的先驱公司。罗氏的Kadcyla（Adptrastuzumabemtansine，恩美曲妥珠单抗）由罗氏和ImmunoGen共同研发，于2013年2月22日被FDA批准用于HER2阳性转移性乳腺癌。2020年1月21日，该药成功在中国获批。它是我国首个上市的抗体药物偶联物（ADC），也是全球首款被批准用于实体瘤的ADC。2021年Kadcyla全球销售额为21.8亿美元，位居ADC类药物销售额首位。但是在2022年Kadcyla的销售额达到顶峰23.9亿美元后，在2023年销售额出现了微小下滑至23.6亿美元。一个重要的原因是DS8201也就是第一三共的Enhertu的强势崛起。从数据的角度来说，DS8201的确比EKadcyla要好很多。在2021年的头对头3期DESTINY-Breast03试验的高水平阳性结果表明：在HER2阳性转移性乳腺癌患者中，双方共同开发的HER2靶向ADC的Enhertu疗效优于罗氏HER2靶向ADC产品Kadcyla。但是罗氏也不是吃素的。除了Kadcyla之外，罗氏还有Polivy。2023年4月，罗氏宣布维泊妥珠单抗（Polivy）获FDA批准用于联合R-CHP方案（利妥昔单抗+环磷酰胺+多柔比星+泼尼松）治疗未经治疗的弥漫性大B细胞淋巴瘤（DLBCL）患者。与R-CHOP组相比，Polivy联合R-CHP组患者的PFS在统计学意义和临床意义上延长，可将患者的疾病进展、复发或死亡风险降低27%（HR=0.73；95%CI：0.57–0.95；p<0.02）。Polivy联合R-CHP组患者的2年PFS率为76.7%（95%CI：72.7–80.8），R-CHOP组这一比例为70.2%（95%CI：65.8-74.6）。2023年，Polivy销售额出现暴增，从2022年的2.2亿美元直接增长到12.0亿美元。2023年1月13日，罗氏制药中国宣布，旗下全球首个靶向CD79b的Polivy两项适应症获得中国国家药品监督管理局批准，分别为：联合利妥昔单抗、环磷酰胺、多柔比星和泼尼松用于治疗既往未经治疗的弥漫大B细胞淋巴瘤（DLBCL）成人患者；以及联合苯达莫司汀和利妥昔单抗用于治疗不适合接受造血干细胞移植的复发或难治弥漫大B细胞淋巴瘤成人患者。此外，罗氏与中国的宜联生物在2024年1月达成全球合作和许可协议，双方将合作开发靶向间质表皮转化因子（c-MET）的下一代抗体偶联药物候选产品YL211（c-MET ADC），用于治疗实体瘤。罗氏将向宜联生物支付首付款及近期里程碑付款5000万美元，另外还有近10亿美元的开发、注册和商业化潜在里程碑付款。根据协议条款，罗氏将获得宜联生物旗下靶向c-MET的下一代ADC项目YL211在全球范围内的开发、制造和商业化的独家权益。可见罗氏还将继续押注于ADC，未来虽然Kadcyla可能风头不在，但Polivy风头正劲，其他管线也有望开花结果。4吉利德2020年4月，吉利德的Trodelvy获得FDA加速批准，用于二线或以上治疗转移性三阴乳腺癌（mTNBC）成人患者，成为全球首个获批用于治疗三阴乳腺癌的ADC。2023年Trodelvy销售额突破10亿美元。从加速获批到跻身重磅，只用了三年，这个成绩仅次于“最佳ADC”Enhertu（DS8201）。TROP-2系人滋养细胞表面抗原2，一种跨膜糖蛋白，它在乳腺癌、胃癌、非小细胞肺癌、小细胞肺癌、结肠癌、胰腺癌等多种肿瘤组织中过表达，尤其是三阴乳腺癌，表达率高达90%以上。三阴乳腺癌（TNBC）是一类在癌组织免疫组织化学检查中雌激素受体（ER）、孕激素受体（PR）和人上皮生长因子受体2（HER-2）三项检查结果均为阴性的乳腺癌，约占所有乳腺癌病例的15%-20%。TNBC具有发病年龄早、肿瘤体积大、侵袭性强，易复发和生存率低的特点，被誉为“最凶险的乳腺癌”，而且现有可选的临床治疗手段有限。在ASCENT试验中，共纳入529例mTNBC患者，评估接受过至少两线既往治疗、其中至少1种针对晚期疾病的不可切除性或转移性三阴乳腺癌患者的疗效。研究显示，无论是否存在脑转移，Trodelvy可使死亡或疾病复发的风险降低57%，两组的中位无进展生存期（PFS）分别为4.8个月和1.7个月。研究还发现，Trodelvy使患者死亡风险降低49%，Trodelvy组、化疗组的中位总生存期（OS）分别为11.8个月和6.9个月。Trodelvy虽然表现突出，但是竞争对手也不少，第一三共的Dato-DXd即为其强大的竞争对手，此外，还有来自中国的科伦博泰借助OptiDC平台自主开发的靶向TROP-2的新型ADC，2022年5月，SKB264大中华区以外地区的权利被授予默沙东。5艾伯维2023年12月，艾伯维以总额达约101亿美元收购ImmunoGen，获得其“first-in-class”抗体偶联药物Elahere（mirvetuximab soravtansine）。ELAHER是美国FDA批准的首个用于铂耐药卵巢癌的ADC药 物，用于治疗叶酸受体α（FRα）阳性且既往接受过1-3线全身治疗方 案的铂耐药卵巢上皮性癌、输卵管癌或原发腹膜癌的成年患者。中国华东医药的子公司中美华东拥有该产品在大中华区（含中国大陆、香港、澳门和台湾地区）的独家临床开发及商业化权益。Elahere的2023年销售额达到3.5亿美元，对于获批一年的药物来说，这是一个非常不错的成绩。此外，ImmunoGen的新一代ADC管线亦补充艾伯维现有ADC平台与管线，其中包括目前处于1期临床阶段的IMGN-151和目前处于2期临床阶段的pivekimab sunirine。前者是用于治疗卵巢癌的新一代FRα靶向ADC，具潜力扩展到其他实体瘤适应症；后者则是一种针对母细胞性浆细胞样树突状细胞肿瘤（BPDCN）的CD123靶向ADC。6其他药企ADC现在是生物制药行业炙手可热的分子，前些年未能及时布局ADC的厂家现在也快马加鞭，开始了ADC领域的跑马圈地。最快的方式无疑是和Biotech合作。2024年1月，强生宣布斥资高达约20亿美元收购Ambrx Biopharma。Ambrx是一家临床阶段的生物医药公司，其利用扩展的遗传密码技术平台来发现和开发下一代ADC和其他疗法来调节免疫系统。其管线包括分别靶向前列腺特异性膜抗原（PSMA）与HER2的抗体偶联药物ARX517与ARX788。ARX517由人源化的抗PSMA单抗与Ambrx专有的强效微管抑制剂AS269连接而成。临床前研究显示，ARX517的癌细胞杀伤有效载荷AS269通过单抗释放到癌细胞中时具有很强的细胞毒性。ARX788则是一种靶向HER2的ADC产品，目前正在针对乳腺癌、胃癌/胃食管结合部（GEJ）癌和其他实体瘤临床试验中进行研究。前列腺癌是一个非常大的癌肿，是男性中第二常见的肿瘤，美国2020年大约有近20万人患前列腺癌，虽然死亡率不高，但仍然是一个无比巨大的市场。强生通过收购入局，进入PSMA市场值得期待。礼来收购了德国初创公司Emergence（后者的nectin-4靶向型ADC采用了Mablink Bioscience授权的连接子技术），随后礼来又收购了Mablink公司，以利用其ADC平台技术实现靶向有效载荷释放和提高药物抗体比。肿瘤巨头百时美施贵宝斥资收购了Tubulis公司的偶联技术，并支付了1亿美元的预付款购买Orum Therapeutics的1期临床抗体偶联蛋白质降解剂（antibody-protein degrader conjugate）项目。此外，百时美施贵宝还进一步通过与SystImmune的合作深化其在ADC领域的布局。GSK通过与豪森药业（Hansoh Pharma）的合作，获得了针对卵巢/子宫内膜肿瘤的ADC在中国以外国家和地区的开发权。阿斯利康和辉瑞也分别从LaNova Medicines和Nona Biosciences获取了ADC项目的许可，进一步彰显了医药行业对于ADC技术的持续关注。— 总结—  大药企主要关注大适应症和主要靶点，以First-in-Class为主要目标。其中第一三共和Seagen无疑是ADC领域的第一梯队。辉瑞是新冠的暴发户，那么其新冠所赚到的钱最主要的去处就是买了Seagen，可谓是All-in-ADC。Seagen被辉瑞以天价收购后，能否发挥出更强大的研发协同效力，尚需时日观察。第二梯队罗氏、吉利德也各自有其强项，其主打ADC药物也有望继续放量增长。更多优质内容，欢迎关注↓↓↓

BASKING RIDGE, N.J. & RAHWAY, N.J.--(BUSINESS WIRE)-- Daiichi Sankyo (TSE: 4568) and Merck & Co. (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that the first patient has been dosed in the REJOICE-Ovarian01 phase 2/3 trial evaluating the efficacy and safety of investigational raludotatug deruxtecan (R-DXd) in patients with platinum-resistant ovarian cancer. The phase 2 portion of the trial will be conducted to identify the dose of raludotatug deruxtecan to be used in the phase 3 part of the trial, which will evaluate raludotatug deruxtecan versus investigator’s choice of chemotherapy. Raludotatug deruxtecan is an investigational specifically engineered potential first-in-class CDH6 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed with Merck. Between 70% and 80% of patients diagnosed with advanced ovarian cancer will experience disease progression following standard treatment with platinum-based chemotherapy regimens.1 The median overall survival for advanced ovarian cancer following recurrence is approximately two years, with a five-year survival rate of less than 30%.2,3 Up to 85% of advanced ovarian tumors have overexpression of CDH6, which is associated with poor prognosis.4,5 The initiation of REJOICE-Ovarian01 is based on results from an ongoing phase 1 trial of raludotatug deruxtecan presented at the European Society for Medical Oncology Congress 2023 with a subgroup analysis presented at the Society for Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. “Raludotatug deruxtecan has shown promising activity in a phase 1 trial of patients with advanced ovarian cancer,” said Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo. “The REJOICE-Ovarian01 trial, which is our first trial initiation for raludotatug deruxtecan in collaboration with Merck, will evaluate the efficacy of this CDH6 directed DXd antibody drug conjugate versus investigator’s choice of chemotherapy in patients with platinum-resistant ovarian cancer.” “The prognosis for the majority of patients diagnosed with advanced ovarian cancer is bleak, with a low five-year survival rate, underscoring the critical need for the development of innovative and effective therapies,” said Marjorie Green, MD, Senior Vice President and Head of Late-Stage Oncology, Global Clinical Development, Merck Research Laboratories. “We look forward to working with our colleagues at Daiichi Sankyo to further evaluate the potential of raludotatug deruxtecan to provide a new treatment option for patients with platinum-resistant ovarian cancer.” About the REJOICE-Ovarian01 Trial REJOICE-Ovarian01 is a global, multicenter, randomized, open-label phase 2/3 trial evaluating the efficacy and safety of investigational raludotatug deruxtecan (R-DXd) in patients with platinum-resistant, high-grade ovarian cancer, including primary peritoneal or fallopian tube cancer, who received at least one and no more than three prior systemic lines of anticancer therapy, including prior treatment with mirvetuximab soravtansine for those with documented high-folate receptor alpha expression. The phase 2 part of REJOICE-Ovarian01 will assess the safety and tolerability of three doses of raludotatug deruxtecan (4.8 mg/kg, 5.6 mg/kg, or 6.4 mg/kg) to identify the recommended dose for the phase 3 part of the trial. The primary endpoint of the phase 2 part of the trial is objective response rate (ORR) as assessed by blinded independent central review (BICR). Secondary endpoints include ORR as assessed by investigator, duration of response (DoR), progression free survival (PFS) and disease control rate (DCR) – all assessed by both BICR and investigator – and overall survival (OS). The phase 3 part of REJOICE-Ovarian01 will assess the efficacy and safety of raludotatug deruxtecan at the selected dose compared to investigator’s choice of chemotherapy (paclitaxel, pegylated liposomal doxorubicin, gemcitabine, or topotecan). The dual primary endpoints of the phase 3 part of the trial are ORR and PFS as assessed by BICR. Secondary endpoints include PFS and ORR as assessed by investigator, DoR and DCR as assessed by both BICR and investigator, and OS. Pharmacokinetic and biomarker endpoints also will be assessed in both parts of the trial. The trial is expected to enroll approximately 650 patients across Asia, Europe, North America and South America. For more information, please visit ClinicalTrials.gov. About Ovarian Cancer More than 324,000 women were diagnosed with ovarian cancer worldwide in 2022.6,7 Between 70% and 80% of patients diagnosed with advanced ovarian cancer will experience disease progression following standard treatment with platinum-based chemotherapy regimens.1 The median overall survival for advanced ovarian cancer following recurrence is approximately two years, with a five-year survival rate of less than 30%.2,3 For patients that develop resistance to platinum-based chemotherapy, treatment options are limited.8 The introduction of targeted therapies has expanded treatment options and improved survival outcomes for some patients with ovarian cancer, but additional options are needed for patients with tumors that progress on available medicines.9 About CDH6 CDH6 (human cadherin-6) is a cadherin family protein overexpressed in several cancers, including ovarian tumors.4 An estimated 65% to 85% of patients with ovarian cancer have tumors that express CDH6, which is associated with poor prognosis.4,5 There is currently no CDH6 directed therapy approved for treatment of any cancer. About Raludotatug Deruxtecan Raludotatug deruxtecan (R-DXd) is an investigational, potential first-in-class CDH6 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, raludotatug deruxtecan is comprised of a humanized anti-CDH6 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. In addition to the REJOICE-Ovarian01 trial, raludotatug deruxtecan is being evaluated in a phase 1 trial in advanced ovarian cancer as part of a strategic collaboration with Sarah Cannon Research Institute (SCRI) with study operational oversight and delivery provided through SCRI’s early phase oncology clinical research organization, SCRI Development Innovations in Nashville, TN. About the Daiichi Sankyo and Merck Collaboration Daiichi Sankyo and Merck entered into a global collaboration in October 2023 to jointly develop and commercialize patritumab deruxtecan (HER3-DXd), ifinatamab deruxtecan (I-DXd) and raludotatug deruxtecan (R-DXd), except in Japan where Daiichi Sankyo will maintain exclusive rights. Daiichi Sankyo will be solely responsible for manufacturing and supply. About the DXd ADC Portfolio of Daiichi Sankyo The DXd ADC portfolio of Daiichi Sankyo currently consists of six ADCs in clinical development across multiple types of cancer. ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology to target and deliver a cytotoxic payload inside cancer cells that express a specific cell surface antigen, each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan and DS-3939 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established. About Daiichi Sankyo Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical needs. For more information, please visit . Merck’s Focus on Cancer Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit . About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn. Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2023 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site ( ). ______________________________________ References: 1 Pignata S, et al. Ann Oncol. 2017 Nov 1;28(suppl_8):viii51-viii56. 2 Shimokawa M, et al. J Cancer. 2018; 9(5):872. 3 Colombo N, et al. Int J Gynecol Cancer. 2017 Jul 1; 27(6). 4 Bartolome RA, et al. Mol Oncol. 2021 Jul; 15(7): 1849-18865. 5 Shintani D, et al. Gynecol Oncol. 2022;166(Suppl 1): S116. 6 Global Cancer Observatory. Population Fact Sheet. Updated 2022. Accessed March 2024. 7 SEER Cancer Stat Facts: Ovarian Cancer. Data from SEER 18 2011-2017. 8 Mor G, et al. Cancer biology & therapy. 2011;11(8), 708–713. 9 Kurnit K, et al. Obstetrics and Gynecology. 2021; 137(1): 108-121.