Olaparib

Positive high-level results from a planned interim analysis of the DESTINY-Breast05 Phase III trial showed Enhertu (trastuzumab deruxtecan) demonstrated a highly statistically significant and clinically meaningful improvement in invasive disease-free survival (IDFS) versus trastuzumab emtansine (T-DM1) in patients with HER2-positive early breast cancer with residual invasive disease in the breast or axillary lymph nodes after neoadjuvant treatment and a high risk of disease recurrence. This is the second positive Phase III trial of Enhertu in the HER2-positive early breast cancer setting following positive results from the DESTINY-Breast11 Phase III neoadjuvant trial earlier this year. Overall survival (OS) was not mature at the time of this planned interim analysis and will be assessed at a subsequent analysis. Currently, approximately half of patients with HER2-positive early breast cancer have residual disease following neoadjuvant treatment, putting them at an increased risk of disease recurrence.1-7 Despite receiving additional treatment in the post-neoadjuvant setting with current standards of care, some patients still ultimately experience tumour progression to metastatic disease.8-10 New treatment options are needed in the early breast cancer setting to help reduce the likelihood of disease progression and improve long-term outcomes for more patients.10-11 Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “This landmark trial is the first to directly compare Enhertu and T-DM1 in early breast cancer, and the results clearly show that Enhertu delivers superior outcomes, indicating that it may be a better option for patients with high-risk HER2-positive disease in the post-neoadjuvant setting. These results from DESTINY-Breast05, coupled with DESTINY-Breast11, underscore our commitment to moving Enhertu into early-stage HER2-positive breast cancer where patients can achieve sustained long-term outcomes, increasing the opportunity for cure.” Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: “In patients with early breast cancer with residual disease following neoadjuvant treatment, it is critical to optimise treatment as this represents the last opportunity to prevent progression to metastatic disease. The results of DESTINY-Breast05 demonstrate that treatment with Enhertu following surgery increases the length of time patients are able to live free of invasive disease compared to the existing standard of care, potentially offering patients with HER2-positive early breast cancer a new treatment approach in this curative-intent setting." The safety profile of Enhertu observed in DESTINY-Breast05 was consistent with its known profile with no new safety concerns identified. Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo. Data from DESTINY-Breast05 (Abstract #LBA1) and DESTINY-Breast11 (Abstract #291O) will be presented during Presidential Symposium 1 on 18 October at the upcoming European Society for Medical Oncology (ESMO) Congress 2025. The DESTINY-Breast05 data will also be shared with global regulatory authorities. DESTINY-Breast05 was conducted in collaboration with the National Surgical Adjuvant Breast and Bowel Project Foundation (NSABP), the German Breast Group (GBG), Arbeitsgemeinschaft Gynäkologische Onkologie (AGO-B) and SOLTI Breast Cancer Research Group. Notes HER2-positive early breast cancer Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.12 More than two million breast cancer cases were diagnosed in 2022, with more than 665,000 deaths globally.12 HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast cancer.13 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.14 Approximately one in five cases of breast cancer are considered HER2-positive.15 Currently, approximately half of patients with HER2-positive early breast cancer have residual disease following neoadjuvant treatment, putting them at an increased risk of disease recurrence.1-7 Despite receiving additional treatment in the post-neoadjuvant setting, some patients still ultimately experience tumour progression to metastatic disease.8-10 Once patients are diagnosed with metastatic disease, the five-year survival rate drops from nearly 90 percent to approximately 30 percent.16 New treatment options are needed in the early breast cancer setting to help reduce the likelihood of disease progression in order to improve long-term outcomes for more patients.10-11 DESTINY-Breast05 DESTINY-Breast05 is a global, multicentre, randomised, open-label, Phase III trial evaluating the efficacy and safety of Enhertu (5.4 mg/kg) versus trastuzumab ematansine (T-DM1) in patients with HER2-positive primary breast cancer that are at high risk of recurrence and have residual invasive disease in breast or axillary lymph nodes following neoadjuvant therapy. High risk of recurrence was defined as presentation with inoperable cancer (prior to neoadjuvant therapy) or pathologically positive axillary lymph nodes following neoadjuvant therapy. The primary endpoint of DESTINY-Breast05 is investigator-assessed IDFS. IDFS is defined as the time from randomisation until first occurrence of invasive breast cancer recurrence, distant recurrence, or death from any cause. The key secondary endpoint is investigator-assessed disease-free survival. Other secondary endpoints include OS, distant recurrence-free interval, brain metastases-free interval and safety. DESTINY-Breast05 enrolled 1,635 patients in Asia, Europe, Oceania, North America and South America. For more information about the trial, visit ClinicalTrials.gov. Enhertu Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. Enhertu (5.4mg/kg) is approved in more than 85 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC 3+ or in-situ hybridisation [ISH]+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial. Enhertu (5.4mg/kg) is approved in more than 85 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial. Enhertu (5.4mg/kg) is approved in more than 45 countries/regions for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial. Enhertu (5.4mg/kg) is approved in more than 60 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumours have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Enhertu (6.4mg/kg) is approved in more than 70 countries/regions worldwide for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Continued approval in China for this indication may by contingent upon verification and description of clinical benefit in a confirmatory trial. Enhertu (5.4mg/kg) is approved in more than 10 countries/regions for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Enhertu development programme A comprehensive global clinical development programme is underway evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers. Trials in combination with other anti-cancer treatments, such as immunotherapy, also are underway. Daiichi Sankyo collaboration AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu in March 2019 and Datroway (datopotamab deruxtecan) 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. AstraZeneca in breast cancer Driven by a growing understanding of breast cancer biology, AstraZeneca is challenging, and redefining, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death. AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment. With Enhertu, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive, HER2-low and HER2-ultralow metastatic breast cancer, and are exploring its potential in earlier lines of treatment and in new breast cancer settings. In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and aims to reshape the HR-positive space with first-in-class AKT inhibitor, Truqap (capivasertib), the TROP2-directed ADC, Datroway (datopotamab deruxtecan), and next-generation oral SERD and potential new medicine camizestrant. PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in these settings. AstraZeneca is also exploring the potential of saruparib, a potent and selective inhibitor of PARP1, in combination with camizestrant in BRCA-mutated, HR-positive, HER2-negative advanced breast cancer. To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is collaborating with Daiichi Sankyo to evaluate the potential of Datroway alone and in combination with immunotherapy Imfinzi (durvalumab). 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 1. Gianni L, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13(1):25-32. 2. Schneeweiss A, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Annals of Oncol. 2013; 24:2278-2284. 3. Swain S, et al. Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study. Annals of Oncology. 2018; 29:646-653. 4. Hurvitz S, et al. Neoadjuvant Trastuzumab Emtansine and Pertuzumab in Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Three-Year Outcomes From the Phase III KRISTINE Study. J Clin Oncol. 2019; 37:2206-2216. 5. Huober J, et al. Atezolizumab With Neoadjuvant Anti–Human Epidermal Growth Factor Receptor 2 Therapy and Chemotherapy in Human Epidermal Growth Factor Receptor 2–Positive Early Breast Cancer: Primary Results of the Randomized Phase III IMpassion050 Trial. J Clin Oncol. 2022; 40:2946-2956. 6. Masuda N, et al. A randomized, 3-arm, neoadjuvant, phase 2 study comparing docetaxel + carboplatin + trastuzumab + pertuzumab (TCbHP), TCbHP followed by trastuzumab emtansine and pertuzumab (T-DM1+P), and T-DM1+P in HER2-positive primary breast cancer. Breast Cancer Res Treat. 2020; 180:135-146. 7. Gao H, et al. De-escalated neoadjuvant taxane plus trastuzumab and pertuzumab with or without carboplatin in HER2-positive early breast cancer (neoCARHP): A multicentre, open-label, randomised, phase 3 trial. Presented ASCO Annual Meeting 2025. 8. Von Minckwitz G, et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019;380(7):617-628 9. Geyer C, et al. Survival with Trastuzumab Emtansine in Residual HER2-Positive Breast Cancer. N Engl J Med. 2025; 392:249-57. 10. NCCN Clinical Practice Guidelines in Oncology. Breast Cancer. Version 4.2025. 11. Zaborowski AM, et al. Neoadjuvant systemic therapy for breast cancer. Br J Surg. 2023;110(7):765-772. 12. Bray F, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;10.3322/caac.21834. 13. Cheng X. A comprehensive review of HER2 in cancer biology and therapeutics. Genes. 2024;15(7):903. 14. Tarantino P, et al. ESMO expert consensus statements (ECS) on the definition, diagnosis, and management of HER2-low breast cancer. J An Onc. 2023;34(8):645-659. 15. Ahn S, et al. HER2 status in breast cancer: changes in guidelines and complicating factors for interpretation. J Pathol Transl Med. 2019;54(1):34-44. 16. National Cancer Institute. SEER Cancer Stat Facts: Female Breast Cancer Subtypes. Available at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html. Accessed September 2025 Matthew Bowden Company Secretary AstraZeneca PLC Oncology Corporate and financial

又一家生物科技公司向港股IPO发起冲刺。 9月26日，英派药业正式向港交所递交招股书，其财务数据随之浮出水面：2022年及2023年，公司年内亏损分别达到2.62亿元及2.59亿元。与此同时，其股东阵容中的两大巨头——腾讯与药明康德也格外引人注目。 这家持续亏损的公司，凭什么吸引产业与资本巨头的联手押注？其冲刺港股的底气又来自何方？聚焦合成致死，核心产品对标国际巨头 英派药业的核心故事，围绕“合成致死”这一前沿抗癌机制展开。 英派药业成立2009年，致力于研发具有自主知识产权的靶向抗癌药物，其研发管线核心是一款名为Senaparib（IMP4297）的PARP抑制剂。该药物已于2025年1月正式获批用于中国卵巢癌“全人群”一线维持治疗，并开始商业化，标志着公司迎来关键的“自我造血”转折点。后续研发管线还有ATR抑制剂、WEE1抑制剂、ATM抑制剂等。 PARP抑制剂赛道早已巨头云集，先驱者奥拉帕利（阿斯利康）在BRCA突变患者中疗效卓越；在卵巢癌全人群一线维持治疗这一领域，海外有尼拉帕利（再鼎医药/GSK）、鲁卡帕利（Clovis Oncology）等产品，国内也有氟唑帕利（恒瑞医药）等布局。 然而，英派药业的Senaparib凭借其优异的临床数据试图实现差异化竞争。根据发表于《自然医学》的III期注册临床研究数据，其核心优势体现在两方面： 卓越的疗效数据：在FLAMES研究中，塞纳帕利将疾病进展或死亡风险显著降低57%，风险比低至0.43。在所有获批用于卵巢癌「全人群」一线维持治疗的PARP1/2抑制剂中(非头对头研究)，展现出最大无进展生存期(PFS)获益，具体如下表所述。尤为突出的是，其在所有患者亚组中均展现出相似的PFS获益，包括通常更难治疗的BRCA野生型患者，这在此类药物中非常独特。 优异的安全性特征：与已上市的其他PARP抑制剂相比，塞纳帕利的非血液学不良事件发生率数值更低、程度更轻，且未观察到相关的高血压风险。这使得其因不良事件导致的停药率仅为4.4%，有助于提升患者治疗依从性。 塞纳帕利在与同类药物的非头对头比较中的优势地位（基于各药物关键III期试验数据） 塞纳帕利凭借其卓越的疗效和更佳的安全性，已在激烈的PARP抑制剂赛道中建立起强大的差异化优势，为其后续的商业化成功及更多适应症的拓展奠定了坚实基础。 财务数据摘要 据招股书，英派药业2023年、2024年营收分别为2.35亿、3355万；研发开支分别为2.15亿、1.95亿；期内亏损分别为1994万元、2.55亿元。 截至2025年6月30日，英派药业持有的现金及现金等价物为2.1亿元。 背后资本版图 英派药业并非“孤军奋战”，其背后的股东阵容包括LAVUSD（持股15.62%）、上海礼颐（13.91%）、德诚资本（10.06%）、腾讯持股（6.6^%）、华岭（5.34%）及无锡药明康德（1.2935%）等。其股东背景不仅为英派药业提供了资金保障，更带来了宝贵的产业资源和战略视野。 尽管前景可期，但英派药业面临的挑战依然严峻，其核心在于能否将技术优势转化为市场成功，从而实现扭亏为盈。PARP抑制剂市场已呈红海态势，除国际巨头外，国内亦有多家企业产品获批。作为后来者，塞纳帕利需凭借卓越疗效、差异化定位以及强大的商业化能力，方能在激烈竞争中抢占市场份额。 创新药的上市仅是企业发展的起点，后续包括适应症拓展、联合疗法开发等均需持续投入大量资金。在实现自我造血之前，公司仍将依赖融资以支撑运营与研发。此外，当前港股生物科技板块估值趋于理性，投资者更为关注企业的商业化潜力与盈利路径，英派药业也需向市场清晰证明其销售能力，才能获得持续资本支持。 “腾讯+药明康德”的组合，为其编织了一个从研发赋能到商业化的美好蓝图。 在资本与产业的双重加持下，英派药业能否突围成功，成为中国创新药企的又一典范？市场正拭目以待。 End 声明：本公众号所有发文章(包括原创及转载文章)系出于传递更多信息之目的，且注明来源和作者。本公众号欢迎分享朋友圈或大群，谢绝媒体或机构未经授权以任何形式转载至其他平台。 转载/商务/投稿 | 联系微信15618157102（sum_Gmi） 商务合作 稿件征集 点击了解详情 往期回顾 BD十年回顾：跨国药企的交易趋势与逻辑洞察 行业观察：裁员浪潮为什么还在席卷生物医药？