Exatecan mesilate

氨基观察-创新药组原创出品作者 | 蔡九18A久违的IPO火爆现象，重现江湖。4月10日，ADC明星药企映恩生物完成招股。据氨基君了解，结果堪称火爆，映恩生物完成超募，最终募资额超过2亿美元。这也意味着，映恩生物创造了2022年以来18A章节港股上市的多个“第一”：创近4年融资规模总额第一记录。投后估值较IPO前最后一轮融资估值增幅超3倍，是历史上估值step-up最大的18A。国际配售逾14倍，为2022年以来第一。基石投资者多达15名，且多为国际大长线和国内大公募。这样的结果，对于18A来说并不容易。自2021年行情转冷之后，港股市场融资难度加大，18A企业首当其冲。不仅成功上市数量大幅下滑，而且成功者要么流血上市，要么募资额极低，甚至基石投资者都是靠关系“东拼西凑”。然而，在4月8日关税影响下，尽管很多人认为映恩生物面临炼狱难度，但其依然备受机构认可，显得难能可贵。这或许也意味着，随着二级市场的持续回暖，优质创新药企港股IPO的机会已经来了。/ 01 /近4年18A章节唯一的现象级IPO对比过去4年18A企业IPO结果，映恩生物此次打新战绩堪称“现象级”表现。首先来看总规模方面。目前，根据投行信息，募资总额为2.1亿美元，折合人民币15.4亿元。这意味着，映恩生物刷新2022年以来18A融资额新纪录，而且远超均值。2021年年中，在诸多因素的影响下，国内创新药企二级市场走上下坡路，IPO也彻底进入冰封期，募资金额大滑坡。2022年至今成功上市的21家18A企业，募资中位数只有3.73亿元，甚至有多家企业低于2亿元，而超过10亿元的只有1家。2025年，IPO情绪并未回暖，率先登场的2家企业，募资额均未超过8亿元。由此，足以看到市场对于映恩生物的追逐。认购倍数，佐证了市场对于映恩生物的认可。基于公开信息来看，网上发行认购倍数100+，最终机构簿记超额认购逾14倍，同样是一个超现象级数字。从2022年以来的18A企业IPO来看，不管是网上发行认购倍数还是国际认购倍数均不高。其中，国际认购倍数均未超过2倍，中位数为1.26倍，甚至有企业出现不足1倍的情况。国际认购面向专业投资者，由此看到专业投资者对于这家新股的认可。另外还有两个维度，可以看到映恩生物IPO的备受瞩目。第一，映恩生物IPO投后估值为11亿美元，较IPO前最后一轮融资估值增幅达到307%（统计范围为募资规模超过5000万美元的IPO项目）。这并不容易，过去2年，18A主要是“流血上市”，也就是估值较一级市场有所折扣，部分企业甚至以低于C轮、B轮价格融资。而映恩生物高倍数的认购，却是建立在估值大幅上涨的情况下，进一步凸显了火爆程度。第二，吸引15家国际顶级长线基金及国内头部公募作为基石投资者参与。根据公开资料，包括明星药企、公募基金，具体为BioNTech SE、LAV Star、Lake Bleu Prime及Lake Bleu Innovation、TruMed、富国香港、富国基金、易方达基金管理、易方达香港、汇添富基金、盘京基金、MY Asian、EMHCP及WWHCP、及苏州苏创。这更不容易。基石投资者，在IPO前期推介阶段就需要签订认购协议，承诺以最终确定的IPO价格（无论高低）认购约定数量的股份，并接受6-12个月的锁定期限制。基石投资者愿意锁定资金并承担价格不确定性，作用是向市场传递了强有力的信心信号。但在行情较冷的时候，18A上市陷入“基石慌”，甚至部分企业是大股东关联方作为参与主体出现。而映恩生物，则截然相反。更重要的是，映恩生物的招股周期，刚好处于关税风波导致的港股的至暗时刻。这也更凸显了，映恩生物此次IPO的火爆。/ 02 /内因与外因共振映恩生物以远超预期的表现登场，得益于外因和内因。外因指的是，在多重有利因素下，医疗板块上演了一场史诗级的估值修复大戏，18A板块更是开启了狂飙模式，今年股价涨幅翻倍者不在少数。从逻辑上来看，二级市场的火热必然会传导至IPO，甚至是一级市场。这也是映恩生物此次IPO火爆值得市场关注的原因。这或许意味着，IPO真正的重启信号已经出现。当然，不是谁都能抓住这一红利，可能只有优质企业。映恩生物此次火爆更重要的原因，还是“内因”：其本身质地足够出色。映恩生物是国内ADC领域最具实力的药企之一。ADC企业看平台。平台越先进，ADC药物能携带的“子弹”越多，药效就越好，同时它能搭载的“毒素”种类也越广，毒副作用更低，研发出来的分子潜在战斗力也就越强。目前，映恩生物成功构建了DITAC（免疫毒素抗体偶联平台）、DIBAC（创新双特异性抗体偶联平台）、DIMAC（免疫调节抗体偶联平台）、DUPAC（有效载荷抗体偶联平台）四个新一代ADC技术平台。在全球范围内，映恩生物的四个新一代ADC技术平台不仅紧跟时代，甚至引领发展，兼顾稀缺性与高价值属性。例如，DITAC是基于拓扑异构酶抑制剂的ADC平台，不仅载荷符合国际主流研发趋势，而且该平台可以通过优化的毒素、连接子来拓宽治疗窗口，进而改善疗效和安全性。而DIBAC更是世界上为数不多的双特异性ADC平台之一，具有较高的准入门槛。DIBAC平台较传统的单特异性ADC不仅能够扩展靶向的肿瘤细胞，更具有靶点协同性以及相比于联合疗法的优势潜力。在彻底进入双打时代的ADC世界，DIBAC无疑能够创造更多价值。目前，公司已经建立了由13款自主研发的ADC候选药物组成的丰富管线。有技术的同时，映恩生物还讲究差异化策略。以DB-1303为例，众所周知，HER2 ADC赛道竞争激烈，而DB-1303进行了毒素升级。与DS-8201相比，其在Exatecan羟基乙酰基位置串入了环丁基。这一改进可以通过降低毒素活性的方式，带来安全性的提高。同时，其还在适应症方面下功夫，其首个适应证为子宫内膜癌，与已上市的同类药物错开，目前正处于全球单臂2期注册研究阶段，最早将于2025年向FDA申报加速批准。另一款靶向HER3的管线DB-1310，适应证为非小细胞肺癌，目前大部分同类药物研究集中在单药的二线治疗，但映恩生物的方向是与阿斯利康的奥希替尼联用，治疗EGFR TKI耐药的EGFR突变NSCLC患者。更重要的是，映恩生物的技术实力和差异化的管线得到了权威认证。首先，是监管机构的认可。映恩生物的三项临床阶段资产（包括核心产品DB-1303及DB-1311以及关键产品DB-1305）已获得FDA的快速通道认定。DB-1303已获得FDA及中国药监局针对特定适应症授予的突破性疗法认定。DB-1311还获得了FDA孤儿药认定。其次，是大药厂的认可。迄今为止，映恩生物已与BioNTech、百济神州、Adcendo、GSK、Avenzo、三生制药等国内外顶尖药企达成BD协议，交易总价值超60亿美元，其中截至2025年3月28日已收到约5亿美元。显而易见，映恩生物不仅能够创造高额合作，并且能够持续将合作潜在收益兑现。从技术平台到管线研发，映恩生物证明了其能够在火热的ADC赛道持续创造价值，但估值却不高。IPO前，其投后估值不到3亿美元，而国内上市的ADC药企，科伦博泰市值超过600亿港币，百利天恒更是近千亿人民币市值。考虑到实力并不逊色，因此巨大的市值差距，意味着映恩生物上市后会有不错的市场表现，也就不难理解为什么其受到追捧了。这也在告诉市场，IPO市场在回暖，但更重要的还是自身质地。/ 03 /见证更多中国创新药的DeepSeek时刻随着映恩生物打响18A企业IPO重启信号枪，未来我们势必能够在这一公开市场，看到更多中国创新药的DeepSeek时刻。原因不难理解。一方面，经过过去几年寒冬的洗礼，国内创新药企正在回归biotech的初心，聚焦核心管线研发，将自己的长处发挥到极致；另一方面，这些企业的发展，并没有受到寒冬的影响，相反可能已经度过打基础的阶段，进入成长加速期。正如映恩生物一样，其发展的核心目标，是希望完成“赶超”到“引领”的过程。所谓“赶超”，正如上文提到的那样，在HER-2等被验证过的靶点，通过技术的创新完成赶超，借此创收。然后通过“赶超”阶段创造的现金流反哺创新，投入更前沿领域管线的研发，从而成为引领者。也确实如映恩生物所想。目前，虽然还没有商业化产品，但映恩生物通过BD的方式有着非常不俗的“自我造血”能力，2023年、2024年，映恩生物的经营活动所得现金净额分别为8.16亿元、2.86亿元。这也使得，公司的管线布局，已经开始进入“引领”阶段：在双抗ADC以及自免ADC领域，映恩生物已经有成果。其中，映恩生物靶向B7-H3/PD-L1的双抗ADC DB-1419，是潜在的FIC，目前，其I期临床试验已经启动；在更少药企涉足的自免ADC领域，映恩生物也已经有成果，其DB-2304 ADC产品，靶向浆细胞样树突状细胞上的特异性靶点BDCA2，适应症为系统性红斑狼疮，首个人体试验正在澳大利亚进行中。这些成果，本身就为其后续创造更丰厚现金流提供基础，而随着此次IPO募资的完成，其也具备更深厚的实力，将会进一步推动开发技术平台的迭代，以持续突破ADC创新的边界。在领跑ADC开发的路上，映恩生物将会越走越快，上演飞轮效应：因为技术平台的良好基础，逐渐收获更多管线、合作伙伴，推动技术的升级迭代，继而带来更多高质量的合作伙伴、管线，继续形成正反馈，最终经营速度越转越快。当然，正如上文所说，映恩生物的表现，只是我国创新药产业表现的一个缩影。更多领域，均在上演“从模仿，到赶上，到逐渐超越”的过程。而随着他们有了资本市场的助力，也将加速发展，不仅持续上演中国创新药的高光时刻，也会相继成为市值巨无霸。PS：欢迎扫描下方二维码，添加氨基君微信号交流。

TOKYO, Japan & MUNICH, Germany I April 08, 2025 I DATROWAY ® (datopotamab deruxtecan) has been approved in the European Union (EU) for the treatment of adult patients with unresectable or metastatic hormone receptor (HR) positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received endocrine therapy and at least one line of chemotherapy in the advanced setting. DATROWAY is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN). The approval by the European Commission follows the positive opinion of the Committee for Medical Products for Human Use of the European Medicines Agency and is based on results from the TROPION-Breast01 phase 3 trial. In TROPION-Breast01, DATROWAY significantly reduced the risk of disease progression or death by 37% compared to investigator’s choice of chemotherapy (hazard ratio [HR]=0.63; 95% confidence interval [CI]: 0.52-0.76; p<0.0001) in patients with HR positive, HER2 negative metastatic breast cancer as assessed by blinded independent central review (BICR). Median progression free survival (PFS) was 6.9 months in patients treated with DATROWAY versus 4.9 months with chemotherapy. A confirmed objective response rate (ORR) of 36% was observed in the DATROWAY arm compared to an ORR of 23% observed in the chemotherapy arm. The median duration of response (DoR) was 6.7 months (95% CI: 5.6-9.8) in the DATROWAY arm compared to 5.7 months (95% CI: 4.9-6.8) in the chemotherapy arm. The final overall survival (OS) results of the trial did not achieve statistical significance (median OS of 18.6 months in the DATROWAY arm versus 18.3 months in the chemotherapy arm [HR 1.01; 95% CI: 0.83-1.22]) and may have been affected by subsequent ADC treatment. “With the majority of breast cancer cases historically considered HR positive, HER2 negative, additional treatment options are needed to improve outcomes for patients with metastatic disease that continues to progress following endocrine-based therapy and initial chemotherapy,” said Barbara Pistilli, MD, Head of the Breast Cancer Unit in the Medical Oncology Department of Gustave Roussy Cancer Center, Villejuif, France. “The approval of DATROWAY in the EU will provide these patients with a new treatment option that can help slow the progression of this disease.” “Treating metastatic HR positive, HER2 negative breast cancer presents challenges, particularly treatment resistance and disease progression that occur following endocrine-based therapy and initial chemotherapy,” said Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc. “DATROWAY represents the second antibody drug conjugate approved for breast cancer based on Daiichi Sankyo’s DXd technology and the third medicine to be approved in the EU from our oncology pipeline, underscoring our commitment to creating new medicines for patients with cancer.” “Though the HR positive breast cancer treatment landscape has evolved in the last several years, disease progression on front-line therapies remains a common and complex challenge for patients with metastatic disease,” said Dave Fredrickson, Executive Vice President, Oncology Hematology Business Unit, AstraZeneca. “With today’s approval of DATROWAY, patients in the EU with HR positive, HER2 negative breast cancer now have a new and needed alternative to conventional chemotherapy.” Grade 3 or higher adverse events from a pooled safety analysis of two clinical studies, including 443 patients who received DATROWAY (6 mg/kg) for a median duration of 6.2 months (range: 0.7-28.5), were stomatitis (7.9%), fatigue (4.3%), anemia (3.2%), AST increased (2.7%), vomiting (1.6%), ALT increased (1.6%), nausea (1.4%), urinary tract infection (1.4%), COVID-19 (1.1%), decreased appetite (1.1%), neutropenia (1.1%) and pneumonia (1.1%). Grade 5 adverse events occurred in 0.7% of patients due to interstitial lung disease/pneumonitis, dyspnea and sepsis. About TROPION-Breast01 TROPION-Breast01 is a global, randomized, multicenter, open-label phase 3 trial evaluating the efficacy and safety of intravenous DATROWAY (6 mg/kg) once per 21-day cycle versus investigator’s choice of single-agent chemotherapy (eribulin, capecitabine, vinorelbine or gemcitabine) in adult patients with unresectable or metastatic HR positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have progressed on and are not suitable for endocrine therapy per investigator assessment and have received at least one prior line of chemotherapy for unresectable or metastatic disease. Following disease progression or discontinuation of DATROWAY or chemotherapy, patients had the option to receive a subsequent treatment at the discretion of their physician. Crossover between trial arms was not permitted. The dual primary endpoints of TROPION-Breast01 are PFS as assessed by BICR and OS. Key secondary endpoints include ORR, DoR, investigator-assessed PFS, disease control rate, time to first subsequent therapy and safety. The PFS data and additional results for key secondary endpoints of TROPION-Breast01 were published in the Journal of Clinical Oncology and OS results were presented at a Virtual Plenary session hosted by the European Society for Medical Oncology in February 2025. TROPION-Breast01 enrolled 732 patients in Africa, Asia, Europe, North America and South America. For more information visit ClinicalTrials.gov . About Hormone Receptor Positive, HER2 Negative Breast Cancer Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide. 1 More than two million breast cancer cases were diagnosed in 2022 with more than 665,000 deaths globally. 1 In Europe, approximately 557,000 cases of breast cancer are diagnosed annually. 2 While survival rates are high for those diagnosed with early breast cancer, only about 30% of patients diagnosed with or who progress to metastatic disease are expected to live five years following diagnosis. 3 Approximately 70% of diagnosed cases are considered what has been historically called HR positive, HER2 negative breast cancer (measured as HER2 score of IHC 0, IHC 1+ or IHC 2+/ISH-). 3 Endocrine therapy is widely given consecutively in the early lines of treatment for metastatic HR positive breast cancer. 4 However, after initial treatment, further efficacy from endocrine therapy is often limited. 4 About DATROWAY DATROWAY (datopotamab deruxtecan) is a TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, DATROWAY is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. DATROWAY is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. DATROWAY is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic HR positive, HER2 negative breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease based on the results of the TROPION-Breast01 trial. About the DATROWAY Clinical Development Program A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of DATROWAY across multiple cancers, including non-small cell lung cancer, triple negative breast cancer and HR positive, HER2 negative breast cancer. The program includes eight phase 3 trials in lung cancer and five phase 3 trials in breast cancer evaluating DATROWAY as a monotherapy and in combination with other anticancer treatments in various settings. About the Daiichi Sankyo and AstraZeneca Collaboration Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU ® in March 2019 and DATROWAY in July 2020 , except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and DATROWAY. 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 & Co., Inc, Rahway, NJ, USA. 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 need. For more information, please visit www.daiichisankyo.com . SOURCE: Daiichi Sankyo