Lazertinib

▎追溯就在5月25日，本公众号报道HER3-DXD效果不佳，OS恐难达标。一语成谶，2025年5月29日，第一三共 和默沙东公布Patritumab deruxtecan （HER3-DXd）的生物制品许可申请(BLA)寻求在美国加速批准，该申请基于HERTHENA-Lung01第 2 期试验，用于治疗先前接受过两种或两种以上全身疗法治疗的局部晚期或转移性 EGFR 突变非小细胞肺癌 (NSCLC) 成年患者，现已自愿撤回。撤回生物制品许可申请 (BLA) 的决定基于验证性 HERTHENA-Lung02 3 期试验的顶线总生存期 (OS) 结果（该结果未达到统计学显著性），以及与美国食品药品监督管理局 (FDA) 的讨论。该决定与2024 年 6 月收到的完整回复函 (Complete Response Letter)无关，该函概述了对第三方生产设施的检查结果。Patritumab deruxtecan 是一种针对 HER3 的 DXd 抗体药物偶联物 (ADC)，由第一三共发现，并由第一三共和默沙东联合开发。HERTHENA-Lung02 第 3 阶段试验的结果（包括先前报告的具有统计学意义的无进展生存期 (PFS) 以及顶线 OS 结果）将于 2025 年 6 月 1 日星期日举行的 2025 年美国临床肿瘤学会 (#ASCO25) 年会上以口头报告 (#8506) 的形式进行报告。HERTHENA-Lung02 正在评估 patritumab deruxtecan 单药治疗对比双药化疗（铂类联合培美曲塞诱导化疗，随后进行培美曲塞维持化疗），用于治疗经第三代 EGFR 酪氨酸激酶抑制剂 (TKI) 治疗后病情进展的 EGFR 突变（外显子 19 缺失或 L858R 突变）晚期非小细胞肺癌 (NSCLC) 患者。根据研究者的评估，达到肿瘤缓解的患者将继续接受 patritumab deruxtecan 或化疗，直至病情进展。第一三共株式会社全球研发主管 Ken Takeshita 医学博士表示：“EGFR 突变的非小细胞肺癌已被证明在二线转移性治疗及后续治疗中难以治疗。虽然我们对 HERTHENA-Lung02 的总生存期结果感到失望，但我们正在进行进一步的生物标志物分析，以更好地识别可能受益于 patritumab deruxtecan 的患者，从而指导我们在肺癌领域的持续开发。我们对这款 HER3 靶向抗体药物偶联物的广泛开发项目充满信心，该项目目前已涵盖 15 种癌症的多项临床试验。”默沙东研究实验室高级副总裁、全球临床开发主管兼首席医疗官 Eliav Barr 医学博士表示：“肺癌是全球癌症相关死亡的主要原因之一，这些结果提醒我们，在二线及后续治疗中治疗这些 EGFR 突变型非小细胞肺癌患者是多么具有挑战性。我们衷心感谢患者、患者家属以及研究人员参与这项研究。”HERTHENA-Lung02 的安全性与之前肺癌临床试验中观察到的 patritumab deruxtecan 的安全性一致，没有发现新的安全信号。前文叙述：HER3 ADC在第一三共开发HER3-DXD后，行业内有不少跟进，在百利天恒EGFR/HER3 ADC被重金引进后，该双抗也成为开发重点。HER3这个靶点表达不高，几乎是研发界的共识，而ADC对于抗原表达有一定要求，又有这么多开发的，跟风式开发或引进，成为影响企业决策的主要因素。第一三共在2025年ASCO，公布HER3-DXD相关数据：Patritumab deruxtecan（HER3-DXd）用于第三代EGFR TKI治疗后耐药的EGFR突变型（EGFRm）晚期非小细胞肺癌（NSCLC）患者：HERTHENA-Lung02 III期研究背景：在接受第三代EGFR酪氨酸激酶抑制剂（TKI）治疗后出现疾病进展的EGFR突变型晚期NSCLC患者中，现有疗法疗效有限。HER3-DXd  是一种抗体药物偶联物（ADC），由靶向HER3的人源化单克隆抗体与拓扑异构酶I抑制剂通过稳定的四肽可切割连接子连接组成，在  HERTHENA-Lung01 研究中显示出有前景的疗效。方法：HERTHENA-Lung02（NCT05338970）为一项III期、随机、开放标签研究，比较HER3-DXd与以铂类为基础的化疗（PBC）在EGFR突变型（Ex19del或L858R）NSCLC患者中在第三代EGFR   TKI治疗失败后的疗效。主要终点为独立影像评估委员会（BICR）评估的无进展生存期（PFS），采用分层log-rank检验。关键次要终点为总生存期（OS）。结果：共586名患者被随机分配至HER3-DXd或PBC组（中位年龄64岁，女性占61%，亚洲人占60%）。截至2024年5月31日的PFS主要分析数据截止时间，中位随访时间为10.7个月（范围5.2-21.9个月），HER3-DXd组与PBC组的治疗持续时间分别为5.5个月（0.7-16.8）和4.6个月（0.7-16.5）。HER3-DXd在PFS方面相较PBC具有统计学上的显著改善（HR=0.77；95%  CI：0.63-0.94；P=0.011）。HER3-DXd组与PBC组的中位PFS分别为5.8个月（95%  CI：5.5-6.8）和5.4个月（95% CI：5.0-5.6）。HER3-DXd与PBC在不同时间点的PFS率如下：6个月：50% vs 38%；9个月：29% vs 19%；12个月：18% vs 5%。客观缓解率（ORR）为：HER3-DXd：35.2%（95% CI：29.7%-40.9%）；PBC：25.3%（95% CI：20.4%-30.6%）。中位缓解持续时间（DOR）分别为：HER3-DXd：5.7个月（95% CI：5.1-7.3）；PBC：5.4个月（95% CI：4.1-5.6）。OS数据仍不成熟。在基线伴有脑转移的患者中（由中枢神经系统BICR评估）：HER3-DXd组（n=105）中位颅内PFS为5.4个月（95% CI：4.0-5.9）PBC组（n=95）为4.2个月（95% CI：2.8-5.0）（HR=0.75；95% CI：0.53-1.06）安全性结果：HER3-DXd组所有患者（100%）和PBC组的99%均出现了治疗相关不良事件（TEAE）因TEAE导致停药的比例：HER3-DXd为11%（33例），PBC为10%（27例）最常见的不良事件包括：恶心：HER3-DXd 57.9%（168例），PBC 42.1%（118例）血小板减少：HER3-DXd 52.1%（151例），PBC 27.1%（76例）疲劳：HER3-DXd 50.3%（146例），PBC 42.1%（118例）3级及以上TEAE发生率：HER3-DXd：73%，PBC：57%。主要由于HER3-DXd中3级及以上血小板减少较多（30% vs 7.9%）每组各有1例3级以上出血事件与3级血小板减少相关。HER3-DXd组中有14例患者（5%）出现了被判定与药物相关的间质性肺病（ILD），包括：11例1/2级，1例3级，2例5级（致命）。以上数据展现出来的HER3-DXD有一定效果，但很难在一众ADC中有出彩，同时其OS本身可能也很难有统计学意义。PFS优势并不明显，HER3-DXd组与PBC组的中位PFS分别为5.8个月和5.4个月。做过ADC，大概都会对HER3的表达有一个大概的概念，这并不算是一个表达十分优异的靶点。但不得不承认ADC，在一定程度上是依赖于抗原的表达量的。众所周知，HER2阳性乳腺癌中的HER2是非常高的表达量，目前少有靶点可以与其匹敌，因此它在临床上就表现得非常亮眼。而目前HER3   DXD在OS上的获益还要等后期数据的披露。2024年9月17日，第一三共和默沙东公布HER3-DXD（ patritumab deruxtecan ）HERTHENA-Lung02 三期临床数据。Patritumab deruxtecan 在 EGFR 突变的非小细胞肺癌患者中表现出统计学上显著的无进展生存期改善，这些患者在接受 EGFR TKI 治疗后，尚未得到充分的治疗需求。HERTHENA-Lung02三期临床试验评估了Patritumab deruxtecan在接受过EGFR TKI治疗的局部晚期或转移性EGFR突变非小细胞肺癌（NSCLC）患者中的疗效。该试验达到了无进展生存期 (PFS) 的主要终点，与铂类加培美曲塞诱导化疗和培美曲塞维持化疗相比，有统计学上显著改善。总生存期 (OS) 数据尚不成熟，试验将继续进一步评估次要终点 OS。非小细胞肺癌约占全球所有肺癌的85%，其中高达70%的病例在晚期阶段确诊，全球14%至38%的非小细胞肺癌肿瘤发生EGFR激活突变。在接受EGFR突变转移性NSCLC的初次治疗后，许多患者经历疾病进展，当前可用的二线治疗非常有限。HERTHENA-Lung02试验中的安全性特征与之前在肺癌临床试验中观察到的Patritumab deruxtecan一致，未发现新的安全信号。大多数间质性肺疾病（ILD）事件为低级别（1级和2级）。观察到两例5级ILD事件。HERTHENA-Lung02是一项全球多中心、开放标签的3期试验，评估帕曲妥珠单抗德鲁昔单抗（每三周5.6     mg/kg）与四个周期的培美曲塞和铂类化疗在EGFR激活突变（外显子19缺失或L858R）的转移性或局部晚期NSCLC患者中的疗效和安全性。这些患者在接受第三代EGFR   TKI治疗（如奥希替尼、拉泽替尼等）失败后纳入研究。ADC具有较为明显的PFS获益，但OS是否获益逐步成为一个悬而未决的答案。如今对待ADC的看法也逐渐成熟，单纯的ORR，PFS，已经不足以证明ADC的对于OS的获益。或许未来还要进一步验证联合PD1抑制剂作为一线治疗是否能够超越PD1抑制剂联用化疗的效果，如果收益较小，可能还是会影响ADC的市场推广。目前，单药ADC仍然以末线治疗为主，走向前线治疗需要联用。如今第一三共和默沙东只公布了初步的PFS获益，OS获益还未成熟，使得HER3 DXD能否完全被接受认可还有一段路要走。不过凭借二期HERTHENA-Lung01研究数据，2023年12月22日，第一三共和默沙东共同宣布HER3-DXd（patritumab    deruxtecan）的生物制品许可申请（BLA）获FDA受理并予以优先审评，适应症为既往至少接受过两种系统治疗的EGFR突变型局部晚期或转移性非小细胞肺癌（NSCLC）。但很不幸，2024年7月，第一三共/默沙东的靶向HER3的抗体偶联药物（ADC）HER3-DXd（patritumab deruxtecan）的上市申请被FDA延期批准，其适应症为用于治疗既往至少接受过两种系统治疗的EGFR突变型局部晚期或转移性非小细胞肺癌（NSCLC）患者。据悉，被延期的原因主要是由于第三方制造设施检查相关的调查结果，其疗效和安全性数据并未存在问题。TROP2 DXD在非小细胞肺癌OS的失利，给ADC赛道蒙上一种不确定性。当然一定程度上还是靶点的因素，占据主要地位。2025年5月20日，辉瑞60.5亿美元引进三生制药PD-1/VEGF双抗，引爆行业，顺便提起一起陈年旧事，当年三生要剥离PD-1/TGFB双抗，PD-1/LAG-3双抗和PD-1/VEGF双抗几条管线出来，成立丹生生物，后来投资机构放弃这次投资机会，这笔交易因此就没有达成。如今成为很多人口中的笑谈。在当时的背景下，估值一亿美元，不投也是在情理之中，尤其PD-1/TGFB双抗这条管线，M7824都失败了，吸引力下降，PD-1/LAG-3双抗也没有很强的证据，包括PD-1/VEGF双抗在2022年也饱受争议，22年我写文章，夸AK112，评论区不少质疑我的，biotech不同于药企，药企有持续现金流，而biotech需要不断融资，试错机会并不多。而在这里面，康方起了非常重要的作用，其实该赛道都占了康方的光，也就是说，没有康方，几乎就没有现在PD1/VEGF双抗这些交易。但如果信达的363，再走出来，或者更优化的药物走出来，现在的交易，或许又是笑话，谁也不能保证。欢迎加入我的知识星球，可提供专业的免费咨询，同时可以获得Antibody Research生物药随谈回放视频。公众号已经建立读者实名讨论微信群，可以添加微信（zhuisu2210）后进群，添加时请主动注明姓名、企业、职位。

May 29, 2025 7:00 am ET BASKING RIDGE, N.J. & RAHWAY, N.J., May 29, 2025 – The Biologics License Application (BLA) seeking accelerated approval in the U.S. for Daiichi Sankyo (TSE: 4568) and Merck’s (NYSE: MRK), known as MSD outside of the United States and Canada, patritumab deruxtecan (HER3-DXd), based on the HERTHENA-Lung01 Phase 2 trial for the treatment of adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) previously treated with two or more systemic therapies, has been voluntarily withdrawn. The decision to withdraw the BLA is based on topline overall survival (OS) results from the confirmatory HERTHENA-Lung02 Phase 3 trial where OS did not meet statistical significance, as well as discussions with the U.S. Food and Drug Administration. The decision is unrelated to the Complete Response Letter that was received in June 2024 and outlined findings pertaining to an inspection of a third-party manufacturing facility. Patritumab deruxtecan is a specifically engineered HER3 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed by Daiichi Sankyo and Merck Results from the HERTHENA-Lung02 Phase 3 trial, including previously reported statistically significant progression-free survival (PFS) along with topline OS results, will be presented during an oral presentation (#8506) at the 2025 American Society of Clinical Oncology (#ASCO25) Annual Meeting on Sunday, June 1, 2025. HERTHENA-Lung02 is evaluating patritumab deruxtecan monotherapy versus doublet chemotherapy, consisting of platinum plus pemetrexed induction chemotherapy followed by pemetrexed maintenance chemotherapy, in patients with EGFR-mutated (exon 19 deletion or L858R mutated) advanced NSCLC after disease progression with a third generation EGFR tyrosine kinase inhibitor (TKI) treatment. Patients achieving tumor response will continue to receive patritumab deruxtecan or chemotherapy until disease progression, per investigator assessment. “EGFR-mutated non-small cell lung cancer has proven to be difficult-to-treat in the second-line metastatic setting and beyond,” said Ken Takeshita, MD, global head, R&D, Daiichi Sankyo. “While we are disappointed with the overall survival results of HERTHENA-Lung02, we are conducting further biomarker analyses to better identify patients that may benefit from patritumab deruxtecan to guide our continued development in lung cancer. We remain confident in the broad development program of this HER3 directed antibody drug conjugate, which currently includes multiple clinical trials across 15 types of cancer.” “Lung cancer is one of the leading causes of cancer-related deaths worldwide and these results are a reminder of how challenging it can be to treat these patients with EGFR-mutated non-small cell lung cancer in the second and later line settings,” said Eliav Barr, MD, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. “We would like to thank the patients, their families, and investigators for their participation in this study.” The safety profile seen in HERTHENA-Lung02 was consistent with that observed for patritumab deruxtecan in previous lung cancer clinical trials, with no new safety signals identified. About HERTHENA-Lung01 HERTHENA-Lung01 is a global, multicenter, open-label, two-arm Phase 2 trial evaluating the safety and efficacy of patritumab deruxtecan in patients with EGFR-mutated locally advanced or metastatic NSCLC following disease progression with an EGFR TKI and platinum-based chemotherapy. Patients were randomized 1:1 to receive 5.6 mg/kg (n=225) or an uptitration regimen (n=50). The uptitration arm was discontinued as the dose of 5.6 mg/kg of patritumab deruxtecan was selected following a risk-benefit analysis conducted from a separate Phase 1 trial assessing the doses in a similar patient population. The primary endpoint of HERTHENA-Lung01 was objective response rate (ORR) as assessed by blinded independent central review (BICR). Secondary endpoints included duration of response, PFS, disease control rate, and time to response – all assessed by both BICR and investigator assessment – as well as investigator-assessed ORR, OS, safety and tolerability. The ORR data and additional results for key secondary endpoints of HERTHENA-Lung01 were published in the Journal of Clinical Oncology in September 2023. HERTHENA-Lung01 enrolled 277 patients in Asia, Europe, North America and Oceania. For more information about the trial, visit ClinicalTrials.gov. About HERTHENA-Lung02 HERTHENA-Lung02 is a global, multicenter, open-label, Phase 3 trial evaluating the efficacy and safety of patritumab deruxtecan (5.6 mg/kg every three weeks) monotherapy versus four cycles of doublet chemotherapy) pemetrexed and platinum chemotherapy) in patients with metastatic or locally advanced NSCLC with an EGFR-activating mutation (exon 19 deletion or L858R) after failure of third-generation (e.g., osimertinib, lazertinib, aumolertinib, alflutinib) EGFR TKI therapy. Patients in the chemotherapy arm without disease progression after four cycles of pemetrexed and platinum chemotherapy are able to continue treatment with maintenance pemetrexed with no restriction on the number of cycles. The primary endpoint of HERTHENA-Lung02 is PFS as assessed by BICR. Secondary endpoints included OS, ORR, duration of response, clinical benefit rate, time to response, disease control rate, and safety. Patients enrolled in the study underwent brain imaging to allow for assessment of intracranial endpoints, including intracranial PFS as assessed by BICR. HERTHENA-Lung02 enrolled 586 patients in Asia, Europe, North America and Oceania. For more information about the trial, visit ClinicalTrials.gov. About EGFR-Mutated Non-Small Cell Lung Cancer Nearly 2.5 million lung cancer cases were diagnosed globally in 2022. Lung cancer is the most common cancer and the leading cause of cancer-related deaths worldwide.9 NSCLC accounts for about 87% of all lung cancers1. Approximately 10% to 15% of patients with NSCLC in the U.S. and Europe, and 30% to 40% of patients in Asia have an EGFR mutation.3,4 NSCLC is diagnosed at an advanced stage in up to 70% of patients.2 For patients with tumors that have an EGFR mutation, the established first-line treatment in the metastatic setting includes EGFR-directed therapy with or without platinum-based chemotherapy.While these therapies have improved outcomes, most patients eventually experience disease progression and receive subsequent therapies.5,6,7,8 About HER3 HER3 is a member of the HER family of receptor tyrosine kinases.11 It is estimated that about 83% of primary NSCLC tumors and 90% of advanced EGFR-mutated tumors express HER3 after prior EGFR TKI treatment.12 HER3 is associated with poor treatment outcomes, including shorter relapse-free survival and significantly reduced survival.13,14 There is currently no HER3 directed therapy approved for the treatment of any cancer. About Patritumab Deruxtecan Patritumab deruxtecan (HER3-DXd) is an investigational HER3 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, patritumab deruxtecan is composed of a fully human anti-HER3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. About the Patritumab Deruxtecan Clinical Development Program A comprehensive global clinical development program is underway evaluating the efficacy and safety of patritumab deruxtecan across cancers. Trials in combination with other anticancer treatments are also underway. 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. In August 2024, the global co-development and co-commercialization agreement was expanded to include gocatamig (MK-6070/DS3280), which the companies will jointly develop and commercialize worldwide, except in Japan where Merck will maintain exclusive rights. Merck will be solely responsible for manufacturing and supply for gocatamig. About the ADC Portfolio of Daiichi Sankyo The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo. The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where 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. The DXd ADC portfolio currently consists of ENHERTU®, a HER2 directed ADC, and DATROWAY®, a TROP2 directed ADC, which 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. The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform. Ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 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 www.daiichisankyo.com. Merck’s Focus on Cancer Every day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 25 novel mechanisms. With one of the largest clinical development programs across more than 30 tumor types, we strive to advance breakthrough science that will shape the future of oncology. By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care. Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit https://www-merck-com.libproxy1.nus.edu.sg/research/oncology. 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 www.merck.com 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, 2024 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov). ### Media Contacts: Merck Julie Cunningham (617) 519-6264 julie.cunningham@merck.com Michael McArdle (908) 447-9453 michael.mcardle@merck.com Daiichi Sankyo Global/US Media Jennifer Brennan (908) 900-3183 jennifer.brennan@daiichisankyo.com Japan Media: DS-PR@daiichisankyo.co.jp Investor Contacts: Merck Peter Dannenbaum (732) 594-1579 peter.dannenbaum@merck.com Steven Graziano (732) 594-1583 steven.graziano@merck.com Daiichi Sankyo DaiichiSankyoIR_jp@daiichisankyo.com References: