Docetaxel

2026年4月27日，来自埃默里大学等机构的研究人员在Nature Medicine上发表评论文章The arrival of digital twins and in silico trials in drug development，主要探讨了数字孪生（digital twins）和计算机模拟试验（in silico trials）如何从行业研发工具向监管级证据转变，并提出了确保这一转变安全、负责任的监管优先事项。 药物评价的监管格局正在发生转变。要使数字孪生和虚拟试验成为药物获批的可靠证据，这些数字工具需要监管机构和公共部门的参与，以确保其安全、负责任地应用。 数字孪生和虚拟试验（对个体患者及患者群体的计算机模拟）长期以来一直是行业用于优化临床试验设计和药物开发决策的工具。然而，这些技术正处于转折点，未来几年将从内部研发工具转变为支持药物获批的监管级证据。监管机构和公共部门的参与，对于确保这一转变安全、负责任地发生至关重要。 2025年4月，美国食品药品监督管理局（FDA）宣布立即计划逐步取消单克隆抗体及其他药物的动物试验要求——这一明确信号表明药物评价的监管格局正在转变。考虑到传统药物开发的有限成功率，这一举措不难理解。每款药物从I期到III期的完整临床试验周期平均耗资4.65亿美元，耗时约7年，然而仅有7.6%的候选药物能够成功上市。为应对这一挑战，数字孪生和虚拟试验作为旨在改善临床试验结果和药物开发效率的新兴技术，受到了广泛关注。 尽管数字孪生和虚拟试验历来被制药企业用于优化试验设计和降低开发决策风险，但FDA近期发布的允许更广泛使用真实世界证据支持监管批准的指南表明，这些技术可能很快就会被用于支持药物监管评价。 随着FDA接受越来越多的计算机模拟证据，迫切需要明确验证标准，以及计算证据相对于传统临床数据的合理权重。在此，我们提出FDA、欧洲药品管理局（EMA）等监管机构可以采取的协调步骤，以确保数字孪生和虚拟试验负责任地融入药物监管体系。 数字孪生：个体患者的计算模型 数字孪生是对个体患者（或其器官）的计算机模拟，旨在预测药物在给药前的疗效（图1）。这些模型整合了电子健康记录、实验室结果、基因组数据、影像和/或可穿戴设备的实时输入，结合分子药物相互作用、代谢通路和疾病进展的科学知识。随后，高级算法提取从分子相互作用到器官生理学等各变量之间的数学关系，实现针对特定患者的治疗疗效和不良事件预测。 图1：数字孪生及其开发流程 虚拟试验：从虚拟患者到虚拟人群 数字孪生聚焦于个体患者，而虚拟试验则将这些方法扩展至模拟整个人群（图2）。这些虚拟队列可以通过聚合多个数字孪生或生成保留人群统计特征的合成患者来创建。它们能够补充现有试验人群、减少对对照组的依赖，或探索在人类中不切实际或伦理上不可行的试验场景。例如，评估孕期胎儿药物暴露、在新生儿中开展存在不可接受风险的对照试验，或在患者数量不足的超罕见疾病中模拟药物疗效。 图2：虚拟试验 目前尚无仅基于虚拟试验数据获批的药物。然而，FDA已基于真实世界证据和外部对照组批准了多款药物，包括用于非小细胞肺癌的艾乐替尼、用于男性乳腺癌的帕博西尼，以及用于治疗胸苷激酶2缺乏症（一种影响线粒体修复的罕见致命疾病）的多西他赛-多柔比星——这表明非传统证据正逐步获得监管认可。这些先例显示出监管机构对通过模拟而非借用对照人群的计算方法持开放态度。EMA同样认可了模型引导药物开发的潜力，但全球范围内关于虚拟试验证据的正式指南仍处于初期阶段。 数字孪生与虚拟试验的新兴应用 数字孪生和虚拟试验有望生成个性化的治疗结局和不良事件预测、优化药物选择和给药方案，并加速实验室发现向人体试验的转化。与传统耗时漫长的临床试验不同，这些技术能够在数小时至数天内评估多种给药方案、入组标准和结局指标，使有前景的候选药物更早推进，无效或有害的化合物更早被淘汰。它们还可以通过虚拟患者补充人类参与者，减少临床试验所需的患者数量，提高罕见病和其他难招募人群试验的可行性。总体而言，这些能力能够提升患者安全性、提高临床试验成功率并降低开发成本。 这些潜在优势正推动其在越来越多场景中的探索应用。 患者风险评估。制药企业正在使用器官特异性数字孪生——尤其是心脏和肝脏模型——在首次人体试验前预测药物诱导的心律失常和肝损伤，从而指导化合物选择和剂量规划。 虚拟对照组与试验效率。在罕见病、肿瘤学等招募困难的领域，生物医学研究人员和制药企业正在探索用虚拟试验补充或部分替代传统对照组——这不仅能减少所需样本量，还能让更多患者接受有前景的在研疗法。 代表性不足和高风险人群建模。制药企业和学术研究人员正在开发计算模型，以支持在传统试验中常被排除的人群中开展药物开发，包括儿科患者、孕妇和具有罕见药物代谢表型的人群。例如，在儿科肿瘤学中，数字孪生可用于在儿童接受实验性治疗前预测化疗药物的疗效。 N-of-1和高度个性化试验设计。数字孪生还支持高度个体化的试验设计，即患者自身的虚拟对应体可作为对照。这些方法最适用于靶向和精准疗法，如针对患者特定分子改变的药物、基因和细胞疗法，以及患者群体小、生物学异质性高的超罕见疾病。 机制模型与统计模型 数字孪生和虚拟试验依赖两种基本的计算方法来预测药物疗效：机制建模和统计建模，二者各有优劣。机制模型编码已知的生物学、生理学和药理学过程，模拟干预如何在个体中产生效果。例如，心脏离子通道模拟通过机制建模药物与特定受体的相互作用，来预测心律失常风险。这类模型具有生物学可解释性，但需要大量先验知识和简化假设。 相比之下，统计和数据驱动模型直接从观测数据中推断关系。例如，基于电子健康记录训练的机器学习分类器，能够通过识别数千名患者中的模式来统计预测治疗反应。这类模型可以发现意想不到的关联，但通常以“黑箱”方式运行，给科学解释和透明度带来挑战。 除了计算方法的差异，构建数字孪生和虚拟试验所使用的数据类型和组合也各不相同——从电子健康记录和实验室数值，到整合的基因组学、蛋白质组学、影像学和实时生理监测数据。因此，数字孪生和虚拟试验应被理解为一类异质技术，而非单一的标准化方法，这凸显了在其迈向潜在监管应用的过程中，进行情境特异性评估的重要性。我们认为，数字孪生和虚拟试验的实施面临两大主要挑战。 技术与证据挑战：验证、准确性与数据质量 围绕数字孪生和虚拟试验的核心监管问题看似简单：多准确才算足够准确？与传统试验中已建立完善的统计阈值和预设效应量不同，基于模型的证据没有等效的基准。可接受的性能取决于监管情境和患者的风险承受能力。从监管角度来看，支持剂量选择的模型（此时仍有同步的人体试验数据验证疗效）与替代对照组或作为独立证据的模型，应接受不同程度的审查。从患者角度来看，那些面临严重或致命疾病的患者，可能愿意接受更高的证据不确定性，以换取更快获得有前景的疗法。 这种风险校准方法在FDA的医疗器械分类中已有监管先例。例如，FDA要求起搏器等III类植入式器械提供前瞻性试验数据，而对手动听诊器等低风险I类器械则允许简化审查。正如器械风险决定监管审查强度，计算模型的证据作用也应如此：计算证据的权重越大，所需的验证标准就越严格。 评估的复杂性还在于缺乏解决证据冲突的监管框架。设想这样一种场景：某制药企业的数字孪生平台预测某新型化合物的心脏安全性可接受，而另一个使用不同训练数据的独立平台则预测其存在显著的心律失常风险。在没有既定裁决框架的情况下，监管机构必须逐案处理每个冲突（且没有权衡相互竞争的计算主张的先例）——这种情况会导致监管审查不一致，并削弱对这些技术证据价值的信心。基于人工智能的数字孪生的有限可解释性带来了额外挑战，因为监管机构必须确定准确但不透明的模型是否可以作为可接受的证据来源。 伦理与监管挑战：知情同意、公平性与信任 除了技术性能，数字孪生和虚拟试验还引发了具有监管影响的重要伦理问题。当这些技术依赖真实患者数据时，知情同意要求尚未得到解决：FDA对“临床研究”的定义可能不适用于向虚拟而非人类受试者给药的情况（尽管最佳实践建议对已识别数据的使用寻求同意）。公平性问题也随之出现：基于资源充足系统的数据训练的模型，可能会编码人口统计学偏差，从而限制其泛化性——如果基于非代表性证据的批准导致上市后失败，这将带来监管和商业风险。此外，与加速批准路径一样，虚拟证据可能在批准时提供合理的获益预测，同时接受残留的不确定性（这些不确定性应在上市后研究中解决）。显然，需要明确标准来规定可接受的不确定性程度以及如何解决这些不确定性。透明的监管监督和关于数字证据作用的公开说明，对于赢得患者和处方医生的信任至关重要。 监管考量的优先事项 对于数字孪生和虚拟试验而言，从探索性建模转向潜在的证据使用，需要更清晰的标准、更强的监督以及开发者和监管机构之间的共同期望。为了负责任地应对这一转变，我们提出以下监管机构应考虑的优先事项（表1）。 情境特异性验证标准：证据阈值应与患者风险和模型的监管作用相匹配——作为独立批准证据的模型，应比仅补充同步试验数据的模型接受更严格的审查。 跨中心协调框架：数字孪生和虚拟试验横跨器械和药物评价领域，需要监管中心之间明确的管辖权指导。 解决证据冲突的协议：当计算预测与传统发现不一致时，监管机构需要既定的层级来权衡相互竞争的证据。 上市后要求：FDA应明确使用计算证据获批的药物是否需要以及何时需要确证性研究。 早期参与试点计划：监管机构与赞助商之间的自愿或激励性合作，将产生真实世界案例来为不断演变的标准提供信息——尤其是在传统试验招募有限的罕见病领域。 表1 数字孪生与虚拟试验治理的拟议监管优先事项 实现这些优先事项需要持续的资金和授权，以建设FDA的数字健康审查能力——包括专业技术人员、计算基础设施和培训项目，用于严格审查基于数字孪生和虚拟试验的药物申报。随着计算方法的成熟并证明能够补充传统方法，目前用于传统审查的资源可以转向这种能力建设。随着时间的推移，这项投资可以通过加快候选药物的评估速度、减少对大型资源密集型试验（如罕见患者群体的III期研究）的依赖，来减轻监管负担。 行业在确保数字孪生和虚拟试验负责任转型方面也发挥着关键作用。为了推进监管机构制定知情标准所需的证据基础，制药和生物技术公司应投资于竞争前联盟，开发共享的数字孪生和虚拟试验，同时减少重复工作和成本。关键路径研究所、综合体外致心律失常试验倡议和TransCelerate BioPharma等先例表明，这种合作可以产生监管级别的计算工具，同时减少赞助商之间的重复努力。要取得成功，行业需要将模型架构、训练数据来源和性能局限性的透明度作为标准做法，而非竞争例外。 国会行动同样重要，以确保数字孪生和虚拟试验的负责任转型。持续拨款支持FDA的数字健康审查能力（包括专业人员、计算基础设施和培训项目），将决定该机构能否跟上数字孪生和虚拟试验评估的步伐。明确的立法授权FDA开展评估虚拟证据的试点计划，也将为负责任地采用数字孪生和虚拟试验提供坚实的法律基础。 结论 数字孪生和虚拟试验在解决药物开发中长期存在的挑战方面具有巨大潜力。如果实施得当，这些技术可以重塑该领域的经济格局——使开发此前被认为商业上不可行的疾病疗法成为可能，减少患者接触无效药物的机会，并加速获得挽救生命的治疗。然而，要实现这一潜力，需要建立框架来解决FDA、EMA和其他全球监管机构面临的重要监管问题，这些机构的协调对于国际药物开发至关重要。归根结底，现在解决这些问题，将决定数字孪生和虚拟试验是能够负责任地加速药物开发，还是会超越旨在监管它们的监督体系。 参考资料： Eadie, A.L., Lynch, H.F., Scheinerman, N. et al. The arrival of digital twins and in silico trials in drug development. Nat Med (2026).  https://doi.org/10.1038/s41591-026-04344-3 --------- End --------- 感兴趣的读者，可以添加小邦微信加入读者实名讨论微信群。添加时请主动注明姓名-企业-职位/岗位或姓名-学校-职务/研究方向。

Primary results from the Phase II ARASEC trial show that NUBEQA ® (darolutamide) plus androgen deprivation therapy (ADT) showed a statistically significant improvement in progression-free survival (PFS) and overall survival (OS) in patients with metastatic castration-sensitive prostate cancer (mCSPC) compared to a matched ADT-alone arm from a historical control in the CHAARTED trial ARASEC is a multicenter, open-label trial in U.S. patients designed to be complementary to the pivotal Phase III ARANOTE trial Results are being presented today as a plenary session during the American Urological Association (AUA) Annual Meeting WHIPPANY, N.J.--(BUSINESS WIRE)--New data from the Phase II ARASEC trial show NUBEQA® (darolutamide) plus androgen deprivation therapy (ADT) resulted in a 71% reduction in the risk of progression or death per CHAARTED criteria compared to ADT alone (HR 0.29; 95% CI 0.20–0.40; P<0.001) in U.S. patients (N=320) with metastatic castration-sensitive prostate cancer (mCSPC). NUBEQA plus ADT was also associated with significant improvements in overall survival (OS) (HR 0.50; 95% CI 0.30–0.82; P=0.003), time to metastatic castration-resistant prostate cancer (mCRPC) (HR 0.26; 95% CI 0.18–0.38; P<0.001), and radiological progression-free survival (rPFS) (HR 0.30; 95% CI 0.19–0.48; P<0.001) vs a matched ADT alone arm from a historical control.1 Some notable limitations of the study include: open-label Phase II study design, the absence of randomization, and the use of historical external control. Primary results are being presented today as a plenary session during the American Urological Association (AUA) Annual Meeting. NUBEQA is indicated in the U.S. for the treatment of adult patients with mCSPC, both with and without docetaxel, and for the treatment of adult patients with non-metastatic castration-resistant prostate cancer (nmCRPC).2 In the ARASEC trial, no new safety signals were observed in the NUBEQA plus ADT arm, consistent with previous studies. Safety results were reported descriptively for the NUBEQA plus ADT arm only, as safety data were not routinely collected in the CHAARTED ADT-alone arm. In the NUBEQA plus ADT matched population, 58% of treatment-emergent adverse events (TEAEs) were grade 1/2 and 8% discontinued NUBEQA due to TEAEs. “Results from the Phase II ARASEC trial provide additional evidence regarding the efficacy and safety of darolutamide plus ADT in patients with mCSPC,” said Rana R. McKay, MD, Medical Oncologist and Professor of Medicine, Urology, and Radiation Medicine and Applied Sciences and Principal Investigator of the ARASEC trial. “The data further support NUBEQA’s ability to offer physicians and patients with prostate cancer a treatment option that is both effective and generally well tolerated.” Prostate cancer is the leading cancer diagnosis among men in the U.S.3 Around 313,780 men are diagnosed with prostate cancer each year and about 35,770 die from the disease in the U.S.3 By 2040, prostate cancer diagnoses are projected to increase to 2.9 million worldwide.4 For men with mCSPC, just over a third (~38%) will survive five years or more after diagnosis,5 and most progress to castration-resistant prostate cancer (CRPC), a condition with limited long-term survival.6,7 “The ARASEC trial was designed to further evaluate NUBEQA plus ADT in patients with metastatic castration-sensitive prostate cancer using a rigorous and innovative study approach,” said Yesmean Wahdan, Senior Vice President and Head of Medical Affairs, U.S. and North America Pharmaceuticals at Bayer. “Supported by our robust clinical development program, these results add to the growing body of evidence demonstrating the efficacy and tolerability of NUBEQA and reinforce our commitment to expanding treatment options for patients earlier in the disease.” About the ARASEC trial8 ARASEC (NCT05059236), is a U.S. prospective open-label, multicenter, Phase II study with an external control arm, complementary to the ARANOTE trial. The study compares NUBEQA plus ADT with a historical external ADT-alone control arm. Patients with mCSPC on conventional imaging and no prior systemic therapy were prospectively enrolled to receive NUBEQA 600 mg twice daily plus ADT. Patients were matched 1:1 to patients enrolled on the ADT-alone arm of the Phase III CHAARTED study using propensity scores based on baseline prognostic characteristics (age, ECOG performance status, CHAARTED-defined extent of disease, prior local therapy, Gleason score, baseline prostate-specific antigen [PSA]). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), time to metastatic castration-resistant prostate cancer (mCRPC), radiological PFS (rPFS; based on imaging frequency as clinically indicated), PSA <0.2 ng/mL response rates, and safety (reported descriptively for the darolutamide plus ADT arm only, as safety data were not routinely collected in the CHAARTED ADT-alone arm). Potential limitations of the study include: open-label Phase II study design, the absence of randomization, and the use of historical external control. Although propensity score matching was used, this method only adjusts for measured variables; unknown or unmeasured confounders may still remain. Use of a historical external control arm may introduce bias due to changes in standards of care over time, differences in endpoint definitions, and assessment methods. About NUBEQA® (darolutamide)2 NUBEQA® (darolutamide) is an androgen receptor inhibitor (ARi) with a distinct chemical structure that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription. NUBEQA was developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company. NUBEQA is an androgen receptor inhibitor indicated for the treatment of adult patients with: Non-metastatic castration-resistant prostate cancer (nmCRPC) Metastatic castration-sensitive prostate cancer (mCSPC) Metastatic castration-sensitive prostate cancer (mCSPC) in combination with docetaxel IMPORTANT SAFETY INFORMATION Warnings & Precautions Ischemic Heart Disease – Ischemic heart disease, including fatal cases, occurred in patients receiving NUBEQA. In a pooled analysis of ARAMIS and ARANOTE, ischemic heart disease occurred in 3.4% of patients receiving NUBEQA and 2.2% receiving placebo, including Grade 3-4 events in 1.4% and 0.3%, respectively. Ischemic events led to death in 0.4% of patients receiving NUBEQA and 0.4% receiving placebo. In ARASENS, ischemic heart disease occurred in 3.2% of patients receiving NUBEQA with docetaxel and 2% receiving placebo with docetaxel, including Grade 3-4 events in 1.3% and 1.1%, respectively. Ischemic events led to death in 0.3% of patients receiving NUBEQA with docetaxel and 0% receiving placebo with docetaxel. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue NUBEQA for Grade 3-4 ischemic heart disease. Seizure – Seizure occurred in patients receiving NUBEQA. In a pooled analysis of ARAMIS and ARANOTE, Grade 1-3 seizure occurred in 0.2% of patients receiving NUBEQA. Seizure occurred from 261 to 665 days after initiation of NUBEQA. In ARASENS, seizure occurred in 0.8% of patients receiving NUBEQA with docetaxel, including two Grade 3 events. Seizure occurred from 38 to 1754 days after initiation of NUBEQA. It is unknown whether anti-epileptic medications will prevent seizures with NUBEQA. Advise patients of the risk of developing a seizure while receiving NUBEQA and of engaging in any activity where sudden loss of consciousness could cause harm to themselves or others. Consider discontinuation of NUBEQA in patients who develop a seizure during treatment. Embryo-Fetal Toxicity – The safety and efficacy of NUBEQA have not been established in females. NUBEQA can cause fetal harm and loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception during treatment with NUBEQA and for 1 week after the last dose. Adverse Reactions In ARAMIS, serious adverse reactions occurred in 25% of patients receiving NUBEQA and in 20% of patients receiving placebo. Serious adverse reactions in ≥1% of patients who received NUBEQA included urinary retention, pneumonia, and hematuria. Fatal adverse reactions occurred in 3.9% of patients receiving NUBEQA and 3.2% of patients receiving placebo. Fatal adverse reactions that occurred in ≥2 patients who received NUBEQA included death (0.4%), cardiac failure (0.3%), cardiac arrest (0.2%), general physical health deterioration (0.2%), and pulmonary embolism (0.2%). The most common (>2% with a ≥2% increase compared to placebo) adverse reactions, including laboratory test abnormalities, were increased AST (23%), decreased neutrophil count (20%), fatigue (16%), increased bilirubin (16%), pain in extremity (6%), and rash (4%). Clinically relevant adverse reactions occurring in 2% or more of patients treated with NUBEQA included ischemic heart disease (4%) and heart failure (2.1%). In ARANOTE, serious adverse reactions occurred in 24% of patients receiving NUBEQA. Serious adverse reactions in ≥1% of patients who received NUBEQA included pneumonia (2%), urinary tract infection (1.8%), musculoskeletal pain (1.6%), hemorrhage (1.6%), arrhythmias (1.3%), and spinal cord compression (1.1%). Fatal adverse reactions occurred in 4.7% of patients receiving NUBEQA and those that occurred in ≥2 patients included sepsis (1.1%), craniocerebral injury (0.4%), and myocardial infarction (0.4%). The most common (≥10% with a ≥2% increase compared to placebo) adverse reaction is urinary tract infection (12%). The most common laboratory test abnormalities (≥15% with a ≥5% increase over placebo) are increased AST (32%), increased ALT (28%), increased bilirubin (17%), and decreased neutrophil count (16%). Clinically relevant adverse reactions in <10% of patients who received NUBEQA included arrhythmia (8.8%), pneumonia (3.6%), and myocardial infarction (0.7%). In ARASENS, serious adverse reactions occurred in 45% of patients receiving NUBEQA with docetaxel. Serious adverse reactions in ≥2% of patients who received NUBEQA with docetaxel included febrile neutropenia (6%), neutrophil count decreased (2.8%), musculoskeletal pain (2.6%) and pneumonia (2.6%). Fatal adverse reactions occurred in 4% of patients receiving NUBEQA with docetaxel. Fatal adverse reactions in ≥2 patients who received NUBEQA included COVID-19/COVID-19 pneumonia (0.8%), myocardial infarction (0.3%), and sudden death (0.3%). The most common (≥10% with a ≥2% increase over placebo with docetaxel) adverse reactions are constipation (23%), rash (20%), decreased appetite (19%), hemorrhage (18%), increased weight (18%), and hypertension (14%). The most common laboratory test abnormalities (≥30%) are anemia (72%), hyperglycemia (57%), decreased lymphocyte count (52%), decreased neutrophil count (49%), increased AST (40%), increased ALT (37%), and hypocalcemia (31%). Clinically relevant adverse reactions in <10% of patients who received NUBEQA with docetaxel included fractures (8%), ischemic heart disease (3.2%), seizures (0.6%), and drug-induced liver injury (0.3%). Drug Interactions Effect of Other Drugs on NUBEQA – Concomitant use of NUBEQA with a combined P-gp and strong or moderate CYP3A4 inducer decreases darolutamide exposure which may decrease NUBEQA activity. Avoid concomitant use of NUBEQA with combined P-gp and strong or moderate CYP3A4 inducers. Concomitant use of NUBEQA with a combined P-gp and strong CYP3A4 inhibitor increases darolutamide exposure which may increase the risk of NUBEQA adverse reactions. Monitor patients more frequently for NUBEQA adverse reactions and modify NUBEQA dosage as needed. Effects of NUBEQA on Other Drugs – NUBEQA is an inhibitor of BCRP transporter. Concomitant use of NUBEQA increases the AUC and Cmax of BCRP substrates, which may increase the risk of BCRP substrate-related toxicities. Avoid concomitant use with drugs that are BCRP substrates where possible. If used together, monitor patients more frequently for adverse reactions, and consider dose reduction of the BCRP substrate drug. NUBEQA is an inhibitor of OATP1B1 and OATP1B3 transporters. Concomitant use of NUBEQA may increase the plasma concentrations of OATP1B1 or OATP1B3 substrates. Monitor patients more frequently for adverse reactions of these drugs and consider dose reduction while patients are taking NUBEQA. Review the Prescribing Information of drugs that are BCRP, OATP1B1, and OATP1B3 substrates when used concomitantly with NUBEQA. For important risk and use information about NUBEQA, please see the accompanying full Prescribing Information. About Metastatic Castration-Sensitive Prostate Cancer Prostate cancer is the leading cancer diagnosis among men in the U.S.3 Around 313,780 men are diagnosed with prostate cancer each year and about 35,770 die from the disease in the U.S.3 At the time of diagnosis, most men have localized prostate cancer, meaning their cancer is confined to the prostate gland and can be treated with curative surgery or radiotherapy. mCSPC is an advanced form of prostate cancer, when the cancer has spread beyond the prostate to other organs but is still responding to hormone therapy that lowers testosterone, such as androgen deprivation therapy (ADT). Despite treatment, most men with mCSPC will eventually progress to castration-resistant prostate cancer, a condition with limited survival.6,7 About Oncology at Bayer Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer includes six marketed products and several other assets in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated. About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, “Health for all, Hunger for none,” the company’s products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2025, the Group employed around 88,000 people and had sales of 45.6 billion euros. R&D expenses amounted to 5.8 billion euros. For more information, go to www.bayer.com. © 2026 Bayer BAYER, the Bayer Cross and NUBEQA are registered trademarks of Bayer. Forward-Looking Statements This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments. References 1 McKay R, et al. Darolutamide plus androgen deprivation therapy (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC): ARASEC – US prospective, open-label phase 2 study with an external control arm. The Journal of Urology. May 14, 2026. https://doi.org/10.1097/01.JU.0001192572.07890.f8. Presented at AUA 2026. 2 NUBEQA® (darolutamide) [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; June 2025. 3 National Cancer Institute. Cancer Stat Facts: Common Cancer Sites. https://seer.cancer.gov/statfacts/html/common.html. Accessed January 2026. 4 James ND, et al. Lancet 2024; 403: 1683–722. 5 National Cancer Institute. Cancer Stat Facts: Prostate Cancer. https://seer.cancer.gov/statfacts/html/prost.html. Accessed January 2026. 6 Siegel DA, et al. MMWR Morb Mortal Wkly Rep 2020; 69:1473–1480. 7 Hahn A, et al. Am Soc Clin Oncol Educ Book. 2018; 23;38:363–371. 8 ClinicalTrials.gov NCT05059236. A Study to Learn How Well Darolutamide Administered Together With Androgen Deprivation Therapy (ADT) Works in Men With Metastatic Hormone-sensitive Prostate Cancer. Results Will be Compared With ADT Alone From a Previously Conducted Study. (ARASEC). https://clinicaltrials.gov/study/NCT05059236. Accessed January 2026.