Datopotamab Deruxtecan

New study results presented at the European Lung Cancer Congress (ELCC) 2025, 26 to 29 March, demonstrate the role of AstraZeneca’s Tagrisso (osimertinib), as monotherapy and as the backbone for novel combinations, across stages and settings of epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC). Highlights include: LAURA Phase III trial of Tagrisso in unresectable, Stage III EGFRm NSCLC after chemoradiotherapy (CRT) (LBA4). SAVANNAH Phase II trial of Tagrisso plus Orpathys (savolitinib) in advanced EGFRm NSCLC with high levels of MET overexpression and/or amplification following disease progression on 1st-line Tagrisso (#2O). ORCHARD Phase II platform trial of Tagrisso plus Datroway (datopotamab deruxtecan) in advanced EGFRm NSCLC following disease progression on 1st-line Tagrisso (#1O). FLAURA2 Phase III trial of Tagrisso plus chemotherapy as 1st-line treatment for advanced EGFRm NSCLC (#53P). Myung-Ju Ahn, MD, PhD, Professor of Hemato-Oncology at the Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, said: “A critical goal in treating every patient with lung cancer is to not only extend a patient's life but also maintain quality of life while on treatment. The continued overall survival trend seen here at ELCC in the unresectable Stage III setting and the promising data for combinations that can address progression in the advanced setting, together reinforce osimertinib as an effective, safe and convenient treatment for patients with EGFR-mutated lung cancer across stages and lines of treatment.” Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “Having now treated more than one million patients around the world, Tagrisso has repeatedly transformed expectations for patients with EGFR-mutated lung cancer by not only extending survival but also showing it is possible to maintain quality of life during cancer treatment. The breadth of data at ELCC reinforce Tagrisso as the backbone therapy for patients with this disease and show that adding Orpathys or Datroway at the time of disease progression can help prolong patients’ responses to treatment.” Professor Virginia Harrison, EGFR Positive UK, said: “For people undergoing treatment for lung cancer, maintaining quality of life is so important, but it can be challenging. The development of simple and effective treatment regimens that minimise negative side effects can make a huge difference. We are excited to see this progress for patients with EGFR-mutated lung cancer, where there is still significant unmet need.” Tagrisso continued to demonstrate encouraging overall survival (OS) trend in unresectable, Stage III setting in LAURA trial Updated results from the LAURA Phase III trial showed an improved trend towards OS benefit with Tagrisso compared to placebo in patients with unresectable, Stage III EGFRm NSCLC (hazard ratio [HR] 0.67; 95% confidence interval [CI] 0.40, 1.14, maturity 31%). Median OS was 58.8 months (95% CI 54.1, not calculable [NC]) in patients treated with Tagrisso versus 54.1 months with placebo (95% CI 42.1, NC), despite 78% of patients on placebo receiving subsequent treatment with Tagrisso upon progression. The trial will continue to assess OS as a key secondary endpoint at the final analysis. Tagrisso previously demonstrated a statistically significant and highly clinically meaningful improvement in progression-free survival (PFS). These results were published in The New England Journal of Medicine and formed the basis for regulatory approvals around the world including in the US, EU and China. Safety results and discontinuation rates due to adverse events (AEs) were as expected and no new safety concerns were identified. Tagrisso plus Orpathys showed durable response rates in lung cancer patients with high levels of MET overexpression and/or amplification whose disease progressed on 1st-line Tagrisso in SAVANNAH trial Results from the SAVANNAH Phase II trial showed Tagrisso plus Orpathys (300mg twice-daily [BID]) demonstrated a clinically meaningful and durable objective response rate (ORR) in patients with EGFRmNSCLC with high levels of MET overexpression and/or amplification whose disease progressed on treatment with 1st-line Tagrisso. Among patients screened for enrollment in SAVANNAH, an estimated 62% had tumors with MET overexpression and/or amplification, and approximately 34% met the defined high MET level cut-off. Tagrisso plus Orpathys demonstrated a confirmed ORR of 56% (95% CI 45-67%), with a median duration of response (DoR) of 7.1 months (95% CI 5.6-9.6). Median PFS (mPFS) was 7.4 months (95% CI 5.5-7.6). Safety results and discontinuation rates due to AEs were consistent with the established profiles of each medicine and no new safety concerns were reported. In all patients treated with Tagrisso plus Orpathys (300mg BID), Grade 3 or higher AEs occurred in 57% of patients. Orpathys is an oral, potent and highly selective MET tyrosine kinase inhibitor (TKI) being jointly developed and commercialised by AstraZeneca and HUTCHMED. In 2023, Tagrisso plus Orpathys received Fast Track designation from the Food and Drug Administration (FDA) in this setting. Tagrisso plus Datroway showed encouraging response rates in patients whose disease progressed on 1st-line Tagrisso in ORCHARD trial First results from the Tagrisso plus Datroway module of the ORCHARD Phase II platform trial showed the combination demonstrated promising efficacy and manageable safety in patients with advanced EGFRm NSCLC whose disease progressed on treatment with Tagrisso. The module enrolled an all-comer population of patients with EGFRmNSCLC and evaluated two doses of Datroway (4 or 6mg/kg) which, in combination with Tagrisso, showed similar ORRs of 43% (80% CI 31-55%) and 36% (80% CI 25-49%), respectively. PFS and DoR results favoured the 6mg/kg dose with a mPFS of 11.7 months (95% CI 8.3, NC) and 64% of patients continuing to respond at 9 months versus a mPFS of 9.5 months (95% CI 7.2-9.8) and 15% of patients continuing to respond at 9 months on the 4mg/kg dose. The safety profile of Tagrisso plus Datroway was consistent with the known safety profiles of each medicine and no new safety concerns were identified at either dose level. Grade 3 or higher treatment-related AEs occurred in 34% and 56% of patients receiving the 4mg/kg or 6mg/kg doses, respectively. Datroway is a specifically engineered TROP2-directed antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo. The Companies are evaluating Datroway alone and with Tagrisso as treatment for patients with advanced or metastatic EGFRm NSCLC in the TROPION-Lung14 and TROPION-Lung15 Phase III trials. New results for Tagrisso plus chemotherapy in the 1st-line setting reinforce strong PFS benefit in FLAURA2 Phase III trial An exploratory post-hoc analysis of the FLAURA2 Phase III trial assessed PFS by length of exposure to pemetrexed maintenance treatment in patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) EGFRm NSCLC. Patients were treated with Tagrisso with the addition of chemotherapy (pemetrexed plus cisplatin) followed by maintenance treatment with Tagrisso and chemotherapy (pemetrexed) or Tagrisso alone. Results showed an mPFS of more than two years regardless of length of pemetrexed maintenance exposure, with a trend associating longer PFS with longer pemetrexed treatment. The safety profile of Tagrisso plus chemotherapy was consistent with the established profiles of the individual medicines. Grade 3 or higher chemotherapy-related AEs were reported in 16% of patients who received maintenance treatment for 3 to less than 9 months, and 10% for patients who received maintenance for 9 or more months. Chemotherapy discontinuation rates due to AEs were 18% and 10%, respectively. Tagrisso plus chemotherapy previously demonstrated a statistically significant and clinically meaningful improvement in PFS. These results were published in The New England Journal of Medicine and formed the basis for regulatory approvals around the world including in the US, EU, Japan and China. Previously presented OS data from the second interim analysis showed a favourable trend with the Tagrisso plus chemotherapy arm (HR 0.75; 95% CI 0.57-0.97, maturity 41%), with consistent results across all prespecified subgroups. The trial will continue to assess OS as a key secondary endpoint. Notes NSCLC Lung cancer is the leading cause of cancer death among men and women, accounting for about one-fifth of all cancer deaths.1 Lung cancer is broadly split into small cell lung cancer or NSCLC, the latter accounting for about 80% of cases.2 Approximately 10 to 15% of patients with NSCLC in the US and Europe and 30 to 40% of patients in Asia have an EGFR mutation.3-5 While EGFR-TKIs have significantly improved outcomes in the 1st-line setting, mechanisms of resistance and disease progression are extremely common, and a significant unmet need exists in later-line settings for effective and well-tolerated treatment options.6-9 LAURA LAURA is a randomised, double-blind, placebo-controlled, multi-centre, global Phase III trial in patients with unresectable, Stage III EGFRm NSCLC whose disease has not progressed following definitive platinum-based CRT. Patients were treated with Tagrisso 80mg once-daily (QD) oral tablets until disease progression, unacceptable toxicity or other discontinuation criteria were met. Upon progression, patients in the placebo arm were offered treatment with Tagrisso. The trial enrolled 216 patients in more than 145 centres across more than 15 countries, including in the US, Europe, South America and Asia. SAVANNAH SAVANNAH is an ongoing randomised, global Phase II trial studying the efficacy of Orpathys added to Tagrisso in patients with EGFRm, locally advanced or metastatic NSCLC with MET overexpression and/or amplification whose disease progressed following treatment with Tagrisso. Based on the original single-arm trial design, patients were treated with Orpathys 300 or 600mg QD or 300mg BID, in combination with oral Tagrisso 80mg QD. In 2022, a comparison of Orpathys 300mg BID and Tagrisso 80mg QD to Orpathys 300mg BID and placebo was added to the trial to evaluate contribution of components. The trial has enrolled 369 patients to date in more than 80 centres globally, including in the US, Canada, Europe, South America and Asia. The primary endpoint is ORR and key secondary endpoints include PFS and DoR. In August 2022, positive interim ORR results from the SAVANNAH trial were presented at the International Association for the Study of Lung Cancer 2022 World Conference on Lung Cancer (WCLC). The global SAFFRON Phase III trial will further assess the Tagrisso plus Orpathys combination versus platinum-based doublet chemotherapy in patients with EGFRm, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC following treatment with Tagrisso. Patients are being prospectively selected using the high MET level cut-off identified in SAVANNAH. ORCHARD ORCHARD (Osimertinib Resistance CoHorts, Addressing 1L Relapse Drivers) is an open-label, multi-centre Phase II platform trial evaluating numerous Tagrisso-based combinations as a treatment for patients with advanced EGFRm NSCLC whose disease has progressed on 1st-line Tagrisso. The trial has 10 modules examining the efficacy, safety and tolerability of these targeted and non-targeted combination options, including Tagrisso 80mg QD plus Datroway given intravenously at 4 or 6mg/kg on day one of every three-week cycle. The trial has enrolled 247 patients to date in more than 40 centres globally, including in the US, Europe and Asia. The primary endpoint is ORR. Key secondary endpoints include PFS and DoR. FLAURA2 FLAURA2 is a randomised, open-label, multi-centre, global Phase III trial in the 1st-line treatment of patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) EGFRm NSCLC. Patients were treated with Tagrisso 80mg QD oral tablets with the addition of chemotherapy (pemetrexed (500mg/m2) plus cisplatin (75mg/m2) or carboplatin (AUC5) every three weeks for four cycles, followed by Tagrisso with pemetrexed maintenance every three weeks. The trial enrolled 557 patients in more than 150 centres across more than 20 countries, including in the US, Europe, South America and Asia. The primary endpoint is PFS. The trial is ongoing and will continue to assess the secondary endpoint of OS. Tagrisso Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system metastases. Tagrisso (40mg and 80mg QD oral tablets) has been used to treat patients across its indications worldwide and AstraZeneca continues to explore Tagrisso as a treatment for patients across multiple stages of EGFRm NSCLC. There is an extensive body of evidence supporting the use of Tagrisso in EGFRm NSCLC. Tagrisso is the only targeted therapy to improve patient outcomes in early-stage disease in the NeoADAURA and ADAURA Phase III trials, locally advanced stages in the LAURA Phase III trial and late-stage disease in the FLAURA and FLAURA2 Phase III trials. As part of AstraZeneca’s ongoing commitment to treating patients as early as possible in lung cancer, Tagrisso is also being investigated in the early-stage adjuvant resectable setting in the ADAURA2 Phase III trial. Orpathys Orpathys (savolitinib) is an oral, potent, and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumours. MET is a tyrosine kinase receptor that has an essential role in normal cell development. Orpathys blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations), gene amplification or protein overexpression. MET overexpression and/or amplification can lead to tumour growth and the metastatic progression of cancer cells, and is a known mechanism of acquired resistance to EGFR TKIs. The prevalence of MET depends on the sample type, detection method and assay cut-off used. Orpathys is approved in China for the treatment of adult patients with locally advanced or metastatic NSCLC with MET exon 14 skipping alterations. It is currently under clinical development for multiple tumour types, including lung, kidney and gastric cancers as a single treatment and in combination with other medicines. Datroway Datroway (datopotamab deruxtecan-dlnk in the US; datopotamab deruxtecan in rest of world) 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 programmes in AstraZeneca’s ADC scientific platform. Datroway is comprised of a humanised 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 (6mg/kg) is approved in the US, Japan and Russia for the treatment of adult patients with unresectable or metastatic HR-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease based on the results from the TROPION-Breast01 Phase III trial. In the US, a Biologics License Application for Datroway is under Priority Review for the treatment of adult patients with locally advanced or metastatic EGFRm NSCLC who have received prior systemic therapies, including an EGFR-directed therapy. Datroway was also granted Breakthrough Therapy Designation by the FDA for this patient population. AstraZeneca in lung cancer AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most. The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including Tagrisso and Iressa (gefitinib); Imfinzi (durvalumab) and Imjudo (tremelimumab); Enhertu (trastuzumab deruxtecan) and Datroway in collaboration with Daiichi Sankyo; Orpathys in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action. AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment. 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 catalyse 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 (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation 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 astrazeneca.com and follow the Company on social media @AstraZeneca. Contacts For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here. References Oncology Corporate and financial

前沿π 前沿技术是创新药产业发展的跃迁支点。医药魔方Pro《前沿π》栏目邀请不同前沿技术赛道创新先锋企业共同探讨赛道成就、困局与未来之路。 栏目首期聚焦过去三年最火热的ADC赛道，邀请到启德医药创始人、董事长秦刚博士，评析ADC赛道2024年的发展，并分享其对ADC药物研发全球竞争、未来风向的最新洞察。 “ADC赛道的热度绝不会是昙花一现，我们正驶向XDC创新的星辰大海。” ——秦刚 回顾整个2024年，全球ADC赛道在市场规模增长、技术创新、临床开发和国际交易合作等方面都表现出了非常积极的态势：全球ADC药物市场规模持续增长，达到130亿美元，其中Enhertu的销售额增长至37.54美元，同比增长46%；临床开发持续开花结果，不断有新的ADC分子进入关键临床，并有多款ADC药物在国内外获批上市；国际合作上，ADC领域产生多起大额交易，多个跨国药企如强生、BMS、罗氏、诺华等通过合作授权、共同开发、并购等方式重金加注ADC赛道。 值得一提的是，中国已成为全球ADC研发以及交易的核心参与者，全年近6成的交易都有中国ADC药企或biotech参与。相较于2023年，尽管2024年的ADC交易有所回落，但在2025年初又产生了7项重大交易，这些交易的主体工作其实都发生在2024年。例如，信达生物授予罗氏IBI3009的全球开发、生产和商业化的独家权益，总交易金额约10.8亿美元；启德医药与美国纽交所上市药企Biohaven、韩国创新生物技术领先企业AimedBio达成重大商务合作，总体商务合作交易金额超过了130亿美元，创造了交易体量新纪录。 资料来源：根据公开信息公布的交易额；数据截至2025-01-31 启德医药在ADC药物研发方面究竟有何独到之处，以促成创纪录的新交易？对于火爆的ADC赛道来说，全球“玩家”当前的竞争主要是哪些层面的竞争？ADC领域蓬勃发展的火热态势还能够持续多久？全球瞩目的AI技术是否能够赋能ADC/XDC研发？近日，医药魔方Pro有幸邀请到启德医药创始人、董事长秦刚博士深入探讨了以上话题。 成立于2013年的启德医药在ADC赛道已经深耕了十余年，秦刚博士也因此一路见证了ADC赛道的飞跃，他表示：“ADC赛道的热度绝不会是昙花一现，我们正驶向XDC创新的星辰大海。” 秦刚，博士，启德医药创始人兼董事长，姑苏创新创业领军人才，负责包括国家重大新药创制专项在内的各级科技和人才类项目10余项，带领公司成功入选中国潜在独角兽企业、江苏省专精特新企业、苏州市独角兽培育企业。 2024突破不止 医药魔方Pro：2024年，以ADC为代表的XDC赛道取得了哪些里程碑？ 秦刚博士：从行业代表性事件来讲，2024年，以ADC为代表的XDC赛道取得了很多令人惊喜的成就，令人印象深刻的主要有： 首先，11月科伦博泰的TROP2 ADC新药芦康沙妥珠单抗获得NMPA批准上市，用于治疗既往至少接受过2种系统治疗晚期或转移性三阴乳腺癌（TNBC）成人患者，早于第一三共的DS-1062在日本获批上市。作为中国首个获得完全批准上市的国产ADC药物，它标志着中国在这一领域实现了自主创新的重要突破，中国药企在ADC领域正在由追跑者向领跑者转变。特别值得一提的是，针对TROP2 靶点的ADC药物虽然有Trodelvy获批在先，但科伦博泰转换赛道开发TROP2 ADC的时期正值ADC全行业的低谷期，他们也承担着极大的风险在全球范围内开展临床试验。如今芦康沙妥珠单抗开花结果也证明了其直面挑战的勇气与默默的长期坚守，这一点无疑是值得高度称赞的。 其次，核素偶联药物（RDC）在市场和临床等方面也取得了重要进展。诺华的Pluvicto 2024年收入达到近14亿美元，增长势头强劲；诺华的另一款产品Lutathera在治疗胃肠胰神经内分泌肿瘤（GEP-NET）的Ⅲ期临床研究（NETTER-2）中表现突出，将患者的无进展生存期（mPFS）从8.5个月显著增长至12.9个月。尽管 Pluvicto 的获批让 RDC在 XDC 领域迅速崭露头角，吸引了众多关注的目光。然而，我们必须清醒地认识到，目前的 RDC 技术依然有着相当大的改良与突破空间，亟待我们去深挖探索。与此同时，RDC的靶点多样性也处于相对匮乏的状态，急需进一步丰富拓展，以打破现有局限。据统计，全球临床在研核药中排名前十的靶点管线数量约占总数的42.5%，尤其是PSMA、SSTR和FAP三个靶点的临床在研管线都超过了30个。同时，新型靶向递送载体形式也亟待创新和临床开发，目前大多数RDC企业仍然沿用诺华早期的技术策略，选择靶向小分子和多肽作为靶向载体，而性能优异的靶向小分子和多肽资源有限，筛选难度大，这极大限制了RDC靶点选择的多样性。另外，RDC药物的临床疗效仍需改善，目前大多数RDC的血液循环半衰期较短，虽然这有助于提高安全性，但也影响了RDC药物在肿瘤部位的富集量和滞留时间，从而限制了其疗效。因此，RDC领域仍有很大改良空间。 最后，随着全球范围内ADC药物陆续获批上市，作为有高技术门槛的ADC CMC生产设施和产能提升将成为ADC药物可及性放量的关键。巨大的供给需求也推动着新的更大体量的生产设施的设立，例如2024年阿斯利康投入15亿美元在新加坡设立ADC生产基地，第一三共投入10亿欧元在德国设立ADC药物研发和生产基地，同时为了满足中国市场，第一三共宣布将在上海张江投资共约1.52亿美元用于筹建ADC新生产设施，用于DS-1062和Enhertu的生产等。可见，随着Enhertu 等重磅ADC药物的市场放量，全球ADC药物的产能和供应链将是全行业要共同面对的挑战。在此背景之下，让我们倍感鼓舞的是，启德医药自主开发的具有颠覆性创新的高效智能偶联生产系统iConjugation，在2024年7月实现了在抗体车间完成高度复杂的ADC药物大规模生产这一里程碑式跨越，极大地解决行业内面临的ADC产能问题。这一变革的深远意义，类同于卫星发射领域的SpaceX火箭回收技术，将给偶联药物产业带来深远变革，重塑未来XDC药物工业大生产模式。 医药魔方Pro：启德医药在2024年取得了哪些关键进展？ 秦刚博士：除了iConjugation带来的生产突破，2024年，启德医药在以下3个维度也取得了一些进展： 一是在管线开发方面，借助启德医药平台技术研发的靶向 HER2 的 ADC GQ1005 正步入关键临床阶段，具有BIC潜质，与 Enhertu 以及众多Fast Follow ADC 相比较，GQ1005 在疗效和安全性方面表现较为突出。GQ1005 的 II 期临床入组人群处于更后线，这与中国晚期肿瘤患者的实际治疗格局相契合。在这些入组患者中，有大量个体接受过其他 HER2 ADC 治疗，并且接近半数的患者接受过 TKI 治疗。即便在这样后线的受试者人群中，GQ1005 依然展现出了较为显著的有效性和安全性，体现了启德医药偶联技术平台的优势。目前，我们已将 GQ1005 的 I/II 期数据在WCLC、ESMO 等国际会议上进行了报告，其呈现出的药效与安全性，也受到了业内同行的广泛关注与探讨。 二是XDC药物临床价值巨大，市场前景广阔，有望超万亿，但因其结构复杂，开发成功率低，是全球公认的高壁垒、高挑战的创新药领域。传统主流的化学偶联技术依靠“设计”的低效模式，远远不能满足XDC药物开发和临床治疗需求。我们通过十余年砥砺前行、持续攻关，整合国际领先的偶联技术、智能智造技术以及信息化技术，启德医药成功打造了全球超高通量的生物偶联药物智能自动化发现系统—iDiscovery，其包含高通量制备iScreener与高通量筛选iEvaluator两套系统。iScreener是基于启德独有的酶促定点偶联技术和固定化酶技术，并整合自动化与智能化系统打造的XDC高通量制备利器。iEvaluator是基于源自真实患者的类器官模型，打造的智能自动化高通量药物筛选引擎。通过生态搭建与战略合作，启德类器官库已覆盖30多种适应症。在药物开发模式上，启德医药在全球首次实现XDC药物高通量快速制备与药物活性筛选，引领同领域研发模式从“by design”到“by screening”的重大变革。启德医药坚持以终为始，聚焦于临床未满足需求，利用iDiscovery平台的高通量制备和临床来源的模型药筛能力，可以在8个月内从成百上千的候选分中精准锁定PCC。可喜的是，在我们全面开放平台、搭建生态的合作理念下，基于iDiscovery的“by screening”模式已初步达成概念验证，将在今年AACR等会议上公开相关进展。 三是在商业合作上，在上述技术持续创新、生态搭建、赋能合作的战略下，过去一年，启德医药广泛与全球范围内的药企和Biotech公司探索各种维度的合作。我们欣喜地看到，越来越多的国际药企认可和肯定了启德医药的技术创新价值。2024年与2025年新旧交互之际，启德在苏州研发总部举行了重大商务合作签约仪式，与Biohaven以及AimedBio深化合作深度与广度，这不仅包括了FGFR3靶点同类首创ADC药物的开发授权，在中美顺利推进临床；也包括了21个靶点创新ADC药物的开发赋能，总体商务合作交易金额更是超过130亿美元，创造了中国药企的出海纪录。我们坚信，在这样深入且多维度的国际合作中，启德医药将携手全球合作伙伴，突破尚未攻克的治疗瓶颈，逐步共同填补患者未满足的临床治疗需求。 ADC“决胜三要素” 医药魔方Pro：过去一年，您对XDC开发有哪些新的思考？ 秦刚博士：XDC药物临床价值巨大，市场前景广阔，有望超万亿。尽管每年突破不断，但其中仍有不少尚待解决或进一步改进的问题值得探讨： 首先是常规ADC药物安全性和疗效方面的问题。ADC药物虽被视为靶向化疗，能减少对正常组织的毒性，但其复杂结构仍会导致多种毒性，如T-DM1可能引发肝毒性和血小板减少，Trodelvy可能导致中性粒细胞减少或腹泻。因此，降低副作用是关键，可通过动态监测、生物标志物筛选个体化治疗，或开发更安全的ADC分子，如升级抗体特异性、改进linker-payload选择性或采用新一代定点偶联技术。在疗效方面，肿瘤的异质性和适应性机制会导致耐药性，如Enhertu治疗HER2阳性乳腺癌时部分患者疗效下降。耐药性可能源于靶点抗原突变、下调或药物外排泵的表达提升。为克服耐药性，可优化抗体结构、探索药物联用策略，或开发基于新作用机制的ADC或双载荷ADC。这些都需要设计大量分子文库并进行有效筛选，而现有ADC制备和筛选平台在通量和临床转化性上存在局限，因此需要开发更先进的药物发现平台。 然后是需要进一步拓展XDC的靶点和适应症。目前全球范围内已有17款ADC药物获批上市，均是针对肿瘤适应症，而开发中的众多ADC药物也集中在一些热门的靶点。面临日益增加的同质化竞争，抗体偶联技术的灵活性和特异性则提供了将其应用于更多非肿瘤疾病领域的可能性，开创“万物皆可联”的新方向，并可以应用于包括自身免疫性疾病、代谢性疾病、神经系统疾病乃至感染性疾病等，展现出广阔的发展潜力。目前，业内正在探索将免疫激动剂、siRNA、PROTAC、激酶抑制剂、多肽药物、放射性核素等新的治疗性分子偶联到抗体上，制备形式多样的XDC药物，其差异化的作用机制，有希望突破传统ADC药物的局限性，拓展至更广泛的适应症上，提高治疗效果，并克服耐药性和提升安全性。 另外值得关注的方向还有XDC药物的全球化合作开发与布局。XDC药物的研发与推广已进入全球协同创新的新时代，构建开放式生态链成为推动其发展的关键，近些年中国在这一领域的地位已迅速提升。截至2024年底，中国企业在全球XDC研发管线中占比超过40%，已与国际企业在license-out、New-Co等形式下展开了多样化的合作。同时，许多中国企业在全球多中心进行高质量临床试验，充分利用了差异化的资源来验证药物疗效与安全性。而在全球范围内，各国研发机构在生物偶联技术、抗体工程和毒素开发方面各有优势，例如美国企业擅长毒素研发，欧洲在生物标志物识别领域领先，中国则在大规模生产和工艺优化中独具竞争力。通过资源整合，各方可以实现技术的快速迭代。此外，全球化合作可以充分利用各地临床资源，统一数据标准的多中心临床试验帮助优化适应症选择，国际数据共享与标准化监管将为快速评估药物的全球适用性铺平道路。可以预期未来XDC药物的开发将继续基于全球化的合作创新、协同发展，整合研发、生产和市场推广资源，打造贯穿全生命周期的XDC开放式生态圈，为全球患者带来更多、更好、更安全的变革性新型疗法。 医药魔方Pro：全球ADC玩家当前的竞争主要是哪些层面的竞争？ 秦刚博士：当然，合作与竞争是并行的。谈及XDC的竞争，以ADC为例，主要有以下三个层面： 一是靶点选择的竞争。目前，众多ADC药企正积极投身于各类靶点的快速开发与探索，无论是已被广泛验证的热门靶点，如HER2、TROP2、CLDN18.2、B7H3、EGFR，还是相对较少关注的靶点，如B7H4、CDH6等，都呈现出多元化且生机勃勃的研发态势。然而，这一趋势也预示着可供ADC选择的差异化靶点资源正日益稀缺。换言之，要想有效破解这一难题，企业必须深入到靶点研究的源头。但靶点创新需要企业在早期阶段投入大量资源，且面临较高的不确定性。加之现行专利制度的限制，企业难以实现对靶点的垄断。因此，从投入产出比来看，原创性靶点的开发将面临巨大挑战。不过，随着人工智能、基因组学、蛋白质组学和CRISPR等前沿技术的不断应用，未来这一局面有望得到显著改善。 二是临床资源的竞争。尤其在肿瘤领域，国内外都有着庞大的患者群体。不过，国外的临床资源获取情况，大多得依靠跨国药企，或者是和国外合作药企来协同开展。反观国内，虽说患者数量众多，但面临的困境也很明显，那就是高质量临床试验的专业人员相对短缺，同时，有着丰富经验以及先进设备的研究场所也不多见。当下，ADC 靶点的竞争局面日益呈现出同质化的态势。在这样的形势下，对于各家 ADC 企业来说，如何能够抢先一步，在众多竞争者里头，精准地筛选出足够多的符合要求的、带有特定肿瘤标志物的患者，并且顺利完成入组，这已经成了摆在各企业面前亟待攻克的现实问题，直接关乎到他们能否在激烈的市场竞争中崭露头角，脱颖而出。 三是可及性的竞争，ADC产能的提升更为迫切。随着 ADC市场规模的迅猛扩张，市场对于高品质、具备大批量稳定供应能力的 ADC 药物的需求呈现出急剧增长态势。然而，当下真正有能力满足如此庞大需求的高质量ADC 商业化生产平台却寥寥无几。正因如此，2024年阿斯利康与第一三共，以及国内的恒瑞、百济、信达等知名药企纷纷斥巨资，在国内外大规模地扩建 ADC 商业化工厂。展望未来，灵活高效地提升产能并确保产品高质量，将成为 ADC 赛道上各家企业发展的核心关键，是必须全力攻克的重要任务。启德自主开发的在抗体车间完成ADC药物大规模生产的高效智能偶联生产系统iConjugation，为这一挑战提供了一套差异化的解决方案。 ADC的红旗还能打多久？ 医药魔方Pro：能否谈谈ADC赛道下一个5年的风向和趋势以及突破点在哪？ 秦刚博士：总体来看，ADC赛道依然处于发展的黄金时期。最近一段时间，有同行提出了这样一个问题：考虑到整个行业的周期性变化，ADC领域蓬勃发展的火热态势还能够持续多久？我们认为这种顾虑实际上是杞人忧天。首先，对于以ADC为代表的传统抗体偶联药物来说，技术变革的态势已相对明朗。肿瘤治疗领域正在催生双靶点ADC、双载荷ADC以及全新靶点ADC药物，这将赋能整个赛道的持续发展。此外，以ADC药物为代表的XDC药物赛道正在从经典的抗体-连接子-毒素模式拓展到万物皆可联的全新局面。RDC、抗体小核酸偶联药（AOC）等新型偶联药物，将把生物偶联药物的适应症从肿瘤快速拓展至自身免疫性疾病、代谢性疾病、神经退行性疾病等治疗领域。 作为深耕ADC药物领域的老兵，我们想强调的一点心得体会是ADC并不仅仅代表着一种特定的治疗机制。与针对某一特定靶点范围进行药物开发的单向思维不同，ADC体现的是一种体系性的生物药物设计的底层逻辑。具体而言，它是一种跨学科的有机整合设计理念，将药物递送与药物作用机制进行了深度融合。因此，在可预见的未来，随着基础研究的持续推进以及新研发和大语言AI模型的不断赋能与闭环验证，XDC赛道不仅不会过时，反而会在其独特的整合思维框架下，逐渐展现出更大的临床价值。 医药魔方Pro：基于过去一年启德医药的技术平台的迭代发展，未来启德医药在技术平台开发和管线推动方面的战略和目标是怎样的？ 秦刚博士：在过去一年，启德医药的酶促定点偶联技术平台在临床和产业化方面得到了充分的验证和应用，也在技术迭代和应用拓展方面取得了重大进展。在临床验证方面，基于酶促定点偶联技术iLDC开发的GQ1005产品表现出优异的疗效和安全性，充分证明了启德医药的酶促定点偶联技术在ADC药物开发上的巨大应用潜力和优势。我们的酶促定点偶联技术适配于任何XDC药物的开发，已将这些技术推广到RDC和AOC领域，我们的新一代差异化RDC和AOC药物在成药性方面都具有良好的开发前景。同时，我们这套领先的技术体系也在全球进行赋能，开源开放搭建创新生态，目前海外授权金额已超过140亿美元，这也充分验证了我们平台的商业价值。 在我们自主创新搭建的技术平台中，智能自动化新药发现系统iDiscovery独树一帜，打通了XDC新药研发的两个关键步骤，即XDC药物高通量文库构建，以及基于病人来源的类器官疾病模型高通量筛选，形成了自动化、高通量XDC新药研发能力。这一颠覆性技术平台的正式上线，从根本上改变了XDC药物研发方式，从“by design”到“by screening”，显著提升了开发效率和临床转化成功率。另一个差异化优势是这个平台每天都在源源不断产生高度结构化、高品质的XDC新药研发数据。来源于真实世界的海量高品质研发数据，自然形成了与AI大语言模型的接口。因此，我们相信颠覆性创新平台iDiscovery将驱动XDC产业迈进AI时代，通过与不同合作伙伴的协同创新，开发出差异化创新的临床XDC产品。 未来已来，我们启德初心不改，秉承突破、厚德的理念，致力于差异化跨界创新，开源开放，搭建生态，开发更多更好的创新药物，让天下没有难治的疾病。 医药魔方Pro 洞察全球生物医药前沿趋势 赋能中国源头创新成果转化 媒体合作：15895423126 版权所有 © 2025 PHARMCUBE。保留所有权利。 欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。 免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。