An Open-Label, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of XL309 (ISM3091) as Single-Agent and Combination Therapy in Patients With Advanced Solid Tumors

This is a FIH, multicenter, open-label Phase I study to investigate the safety, tolerability, preliminary antitumor activity, as well as PK and pharmacodynamics of XL309 (previously ISM3091) administered alone or in combination with olaparib in subjects with advanced solid tumors.

开始日期2024-04-03

申办/合作机构

Exelixis, Inc.

100 项与 ISM-3091 相关的临床结果

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100 项与 ISM-3091 相关的转化医学

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100 项与 ISM-3091 相关的专利（医药）

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项与 ISM-3091 相关的新闻（医药）

2025-02-23

·肿瘤界

人工智能在抗肿瘤药物发现中的应用进展

点击蓝字关注我们引用本文：王超，丁晓，王亚洲，等．人工智能在抗肿瘤药物发现中的应用进展[J/CD]．肿瘤综合治疗电子杂志，2025，11（1）：36-43．通信作者：任峰 E-mail ：feng.ren@insilico.ai 【摘要】药物发现往往面临周期长、成本高、成功率低等问题，人工智能（artificial intelligence，AI）因算力、算法的不断更新迭代而飞速发展，为新药研发注入了强大动力。本文从靶点的发现与确证、蛋白质结构预测、先导化合物的发现与优化、分子性质预测以及加速临床试验等方面对AI在抗肿瘤药物发现中的应用进行简要介绍。随后，对AI参与的代表性抗肿瘤药物分子的临床进展进行了简要分析，以期为行业研究方向提供启发和参考。【关键词】人工智能；药物发现；抗肿瘤药物；临床进展人工智能（artificial intelligence，AI）的概念始于1956年达特茅斯会议，计算机科学家们提出建立具有完全人类智能的新型计算机，从而诞生了使用计算技术来模拟、延伸人类思维过程和智能行为的新技术科学[1]。至2010年后，深度神经网络在图像和语音识别等领域表现出色，AI技术已经在医疗影像、自然语言处理、医用材料等各个领域发挥着越来越重要的作用，已从理论转变为具有解决复杂问题能力的实际应用工具[2-6]。 2024年，瑞典皇家科学院将诺贝尔物理学奖授予科学家John J. Hopfield和Geoffrey E. Hinton，以表彰他们为推动利用人工神经网络进行机器学习作出的基础性发现和发明[7-8]。同时，诺贝尔化学奖颁给了科学家Demis Hassabis和John M. Jumper，表彰他们在计算蛋白质设计和蛋白质结构预测方面的贡献[9-11]。这2项科学研究的最高奖项更是将AI应用于生物医药的关注推向了新的高潮。在新药研发领域，众多跨国药企拥抱AI技术。全球疫苗市场中的四大巨头之一的赛诺菲提出“All in AI”战略，与Exscientia、Formation Bio、OpenAI、Insilico Medicine等AI公司建立合作，将数据、软件和经过调整的模型汇于一体，共同优化全周期的方案。阿斯利康利用Owkin庞大的数据网络，从数字化病理切片中优化胚系乳腺癌易感基因（germline breast cancer susceptibility gene，gBRCA）突变的预筛查，同时扩大与Immunai公司的合作，在癌症免疫疗法临床试验设计中使用AI驱动的免疫细胞图谱。诺华与药物研发平台Generate Biomedicine达成多靶点合作，以生成式AI发现和开发蛋白质疗法；最近又与分子胶AI公司Monte Rosa Therapeutics达成协议，推进靶向鸟嘌呤核苷酸交换因子1（vav guanine nucleotide exchange factor 1，VAV1）的分子胶蛋白降解剂的开发。礼来公司则与生物技术公司Genetic Leap达成合作协议，利用其AI平台寻找RNA靶向小分子药物。AI制药赛道的其他更多投融资和合作，表明AI对复杂制药领域的实际价值。本文旨在对AI在药物研发中的着力点进行简要介绍，同时通过简要分析AI参与的代表性抗肿瘤药物临床进展，以期为行业研究方向提供启发和参考。 1 人工智能在药物研发中的应用概述基于近年来算力、算法的不断发展，AI在制药领域发挥着越来越重要的作用[12-15]。AI应用主要包括了药物靶点发现与确证、蛋白结构预测及生成、先导化合物的发现与优化、分子性质预测以及加速临床试验等（图1）。 1.1 靶点发现与确证基于靶点的药物发现是药物研发的主流手段，药物靶点对整个新药研发项目起到决定性的作用[16]。系统生物学通过研究各个生物系统内部各成分间相互关系，建立整个系统的可理解模型，为有机体绘制完整图谱[17-19]。AI生物技术公司BERG开发的Interrogative Biology是一个基于AI的系统生物学平台，可生成数据驱动的无偏网络，用于识别靶点和疾病的生物标志物[20]。BenevolentAI推出的判断加强认知系统通过发现疾病、药物、试验数据等大量非结构化数据间的新联系，实现药物重定向（老药新用）[21]。Insilico Medicine的科学家基于信号通路激活分析提出了通路激活网络分解分析的方法，可以从大规模转录组学和蛋白质组学数据中提取生物学相关特征[22]。 1.2 蛋白结构预测及生成截至目前，针对蛋白结构预测的算法大致可分为同源建模、从头建模和基于机器学习建模3类[23]。基于深度学习的建模方法是一种数据驱动方法，其中AlphaFold[10]、RoseTTAFold[11]、ESMFold[24]和AminoBERT[25]等语言模型最具代表性。作为最先进的蛋白结构预测方法，AlphaFold2能以原子级精度预测蛋白质结构，并能大规模运行，这一重大突破展示了前所未有的应用场景[26]。进一步升级后的AlphaFold3则可更快、更高精度地预测核酸（DNA/RNA）和更小分子的3D结构，并揭示它们之间的相互作用以及预测结合模式，为活性配体的发现提供了更加广阔的前景[27]。除了结构预测之外，利用扩散模型对蛋白质进行生成也取得了重要进展。蛋白质设计先驱David Baker教授利用RFdiffusion能生成各种功能性蛋白质，包括在天然蛋白质中从未见过的拓扑结构[28]。Generate Biomedicines可利用扩散模型工具Chroma对蛋白质进行从头生成的工作，进一步拓展了蛋白质结构[29]。 1.3 先导化合物发现及优化基于深度学习的生成模型可从大量药物数据中学习化学分子结构与其生物和药理性质之间的非线性概率分布，然后根据所需性质，重新生成分子[30-33]。对于生成式建模，目前常用的是基于简化分子线性输入规范的字符串编码算法，代表性的研究包括基于分子图的生成对抗网络[34]、目标增强生成对抗网络[35]、对抗式自编码器[36]、高斯混合模型变分自编码器[37]及生成张量强化学习模型[38]等优化方法。 1.4 分子性质预测以机器学习、深度学习为代表的药物吸收、分配、代谢、排泄和毒性（absorption，distribution，metabolism，excretion，toxicity，ADMET）预测模型可从数据中学习化学结构与药代动力学性质的关联，避免不良未知空间的探索[39-40]。目前已有不少AI软件可用于ADMET性质的预测，例如，Simulation Plus公司的GastroPlus已经被多国药监部门广泛使用，可预测多个药代动力学参数以及药物经眼部、肺部等多个途径给药后的体内过程等。拜耳医药研究人员总结其ADMET计算工具时表示这些工具的成功主要取决于模型质量、与研究过程的模型相关性以及结果的可获取和解释性[41]。此外，药物晶型会对溶解度、溶出度、稳定性、疗效等产生影响，通过计算模拟进行晶型预测对保障药物研发的速度和质量具有重要意义[42]。晶态科技在与AbbVie公司合作的项目中将晶体堆积作用考虑进算法模型，可对具有相似骨架的同系列分子进行溶解度区分[43]。 1.5 加速临床试验众所周知，临床试验的高失败率导致药物研发的高成本和低效率，在药物研发后期于临床试验设计阶段的关键步骤中使用AI，有助于实现更精准的患者分层，提高招募效率，从而提高临床试验的成功率[44-45]。Insilico Medicine于2022年推出可预测临床试验的inClinico工具，其是一个基于Transformer模型的AI系统，预测临床试验Ⅱ～Ⅲ期的转化成功率[46]。inClinico整合了多种评分方法、多模态数据源（包括文本、组学、临床试验设计和小分子特性）以及生物学背景，并与最先进的深度学习模型相结合。在前瞻性验证中，inClinico在预测临床试验Ⅱ～Ⅲ期的转化成功率的准确率达到了79%。 2 人工智能参与的临床药物进展 AI在药物研发的整个流程中均已有不同程度的应用，目前已有不少AI参与研发的药物分子进入临床阶段（表1）[47-48]。接下来将对代表性药物分子的临床进展情况进行简要分析。早期AI参与的部分临床药物来自对传统药物分子的适应证拓展。例如，REC-2282是最早由俄亥俄州立大学研究开发的口服小分子HDAC抑制剂AR-42，早期临床试验显示，REC-2282在接受肿瘤切除术的成年患者前庭神经鞘瘤中抑制了异常的AKT、S6通路激活（NCT02282917）[49-50]。Recursion公司利用Recursion OS系统发现了REC-2282用于2型神经纤维瘤（neurofibromatosis type 2，NF2）的治疗潜力，并借助细胞和动物模型证明了这一发现。目前该分子正在开展针对进展性NF2脑膜瘤患者的Ⅱ/Ⅲ期临床试验（NCT05130866）。REC-4881是Recursion公司从武田制药公司引进的口服小分子MEK1/2变构抑制剂，Recursion公司利用Recursion OS平台发现特异性MEK1/2抑制剂在APC突变的多发性肠肿瘤小鼠模型中显示息肉和异常增生腺瘤的减少，目前REC-4881正在开展治疗家族性腺瘤息肉病（familial adenomatous polyposis，FAP）的临床Ⅰ/Ⅱ期研究（NCT05552755），于2022年7月获得欧盟委员会授予的用于潜在治疗FAP的孤儿药资格认证[51]。 AI参与设计的全新结构的药物分子逐渐进入临床研究。RLY-4008是Relay公司基于蛋白动力学设计的FGFR-2选择性抑制剂，在FGFR-2改变的胆管癌患者的临床试验中（NCT04526106），全部剂量统计下（n＝38）的客观缓解率（objective response rate，ORR）为57.9%，在推荐的Ⅱ期剂量70 mg/d的患者中（n＝17）ORR可达82.4%，明显优于获批的泛FGFR抑制剂。RLY-4008具有可控制的毒性特征，常见的3级治疗相关不良反应（n＝124）包括口腔炎（11%）、手足综合征（7%）、指甲毒性（3%）、疲劳（1%）以及视网膜色素上皮脱离（1%）[52-54]。NDI-101150为Nimbus公司通过基于结构的药物发现引擎研发的HPK1抑制剂，在临床前研究中显示了对同家族激酶＞ 300倍的高选择性[55]。在开展的临床Ⅰ/Ⅱ期试验中评估其作为单一疗法（50～200 mg剂量）或与帕博利珠单抗（200 mg）联合治疗晚期实体瘤（NCT05128487）。在已公布的临床数据中，16.7%（4/24）的患者临床获益，其中1例有肾细胞癌的患者获得了完全应答，3例患者维持了持续稳定的疾病超过6个月[56]。MRT-2359是Monte Rosa公司借助QuEEN平台设计研发的口服GSPT1分子胶降解剂，在体外试验和体内模型中均显示了良好的GSPT1降解以及抗肿瘤活性[57-58]。研究发现，MRT-2359在多种癌症细胞系中表现出显著的抗增殖活性，尤其在Myc驱动的细胞系中。在2023年公布的临床Ⅰ/Ⅱ期数据（NCT05546268）中显示，对21例给药患者中的15例进行疗效评估中，0.5～2.0 mg的给药区间均观察到外周血单核细胞和肿瘤组织活检GSPT1蛋白表达减少约60%。在6例生物标志物呈阳性的患者中，2例实现了部分缓解，1例达到了病情稳定。0.5 mg和1.0 mg剂量下仅观察到1级或2级治疗相关不良事件[59]。研究人员认为0.5 mg剂量下，给药21 d停药7 d的方案是潜在的推荐Ⅱ期剂量，目前正在进行0.75 mg剂量评估。 AI不仅在口服小分子药物的生成和优化中发挥了重要作用，也可应用于生物大分子的设计优化[60]。Aulos Bioscience公司通过机器学习发现特定突变位点，设计研发了特异性阻断IL-2与CD25结合的高度亲和性抗体AU-007，这是首款进入临床试验的AI大分子药物。AU-007于2022年进入临床研究，在2024年美国临床肿瘤学会年会上公布了积极的临床Ⅰ/Ⅱ期数据（NCT05267626）[61-62]。研究表明，在临床早期阶段即发现了AU-007具有显著的抗肿瘤活性，同时在部分患者中观察到肿瘤减少的持久性，表明形成了癌细胞的免疫记忆。与此同时，该药物显示了良好的耐受性（n＝53），除4例患者出现短暂性淋巴细胞减少（3级和4级）和1例患者出现3级贫血外，所有药物相关不良反应均为1级或2级，最常见的包括发热（18%）、疲劳（16%）、恶心（14%）、淋巴细胞减少（8%）和寒战（6%）。该治疗方法克服了由其他白细胞介素-2治疗引起的负反馈回路，并使免疫系统偏向激活，可能是潜在的最佳治疗方案，为AI辅助大分子药物设计打开了全新的窗口。临床阶段除了上述正在进行的分子，也有停止进展的案例。例如，EXS-21546是由Exscientia利用AI驱动平台和Evotec公司共同研发的腺苷A2A受体拮抗剂，在临床Ⅰ期的健康受试者的药代动力学（pharmacokinetics，PK）/药效学（pharmacodynamics，PD）及安全性研究中，EXS-21546在CD8阳性细胞中对环磷酸腺苷效应元件结合蛋白磷酸化表现出剂量依赖性抑制，PD特性可反映血浆暴露量，A2A受体信号转导的抑制作用在2次/d给药期间持续存在。同时，在单次给药剂量递增全部剂量以及多次给药剂量递增的150 mg 2次/d剂量下，未报告中枢神经系统不良反应（NCT04727138）。随后，在复发或难治性肾细胞癌和非小细胞肺癌患者中开展了与程序性死亡受体1抑制剂联用的Ⅰ/Ⅱ期临床研究。遗憾的是，2023年10月因疗效未达预期而终止了该临床研究（NCT05920408）[63-64]。目前，Exscientia管线中进展最快的药物是与GT Apeiron合作设计的CDK7抑制剂GTAEXS617，该药物正在进行临床Ⅰ/Ⅱ期测试，用于治疗晚期实体瘤，有望成为耐药性周期蛋白依赖性激酶（cyclin dependent kinases，CDK）4/6抑制剂有潜力的替代选择（NCT05985655）[65]。其他一些处于临床Ⅰ期阶段的药物分子，在临床前研究中显示了较好的抗肿瘤活性，目前尚无临床数据报道。XL309（ISM3091）是一款靶向USP1的潜在同类最佳小分子抑制剂，由Insilico Medicine自主研发的AI平台赋能开发，在BRCA突变的肿瘤模型中单药治疗或与靶向聚ADP核糖聚合酶抑制剂奥拉帕尼联合使用，均展示了强效的抗肿瘤活性[66]。Insilico Medicine授予Exelixis开发和商业化ISM3091及其他靶向USP1化合物的全球独家许可，于2023年第3季度获得8000万美元预付款，正在进行临床Ⅰ期研究（NCT05932862）。Schrödinger公司开发的MALT1蛋白酶抑制剂SGR-1505在体外酶活与细胞测试以及与B淋巴细胞瘤-2抑制剂维奈克拉的联用试验中均表现出优于临床分子JNJ-6633的活性，同时，对核因子-κB及相关信号通路的基因表达有更大的影响，目前正在针对B细胞恶性肿瘤患者进行临床Ⅰ期试验（NCT05544019）[67]。SGR-3515为Schrödinger公司研发的MYT1/WEE1（WEE家族蛋白激酶）共抑制剂，在临床前研究中对WEE1表现出强结合慢解离特性，同时特异性肿瘤组织分布，在A427和OVCAR3肿瘤模型中支持给药3 d停药11 d的间歇给药方案，减少潜在的骨髓抑制和消化道毒性。由于WEE1与MYT1的协同效应，SGR-3515显示出优于单独抑制WEE1或MYT1的抗肿瘤活性。目前，SGR-3515正在进行晚期实体瘤的Ⅰ期剂量递增研究（NCT06463340）[68]。PHI-101是Pharos iBio公司利用其基于大数据的AI平台Chemi-nverse研发的新一代FLT3小分子抑制剂。临床前研究表明，PHI-101有望克服多种耐药突变产生的耐药性，目前，在开展针对急性髓性白血病和高级别浆液性卵巢癌患者的临床Ⅰ期研究（NCT04842370/NCT04678102）[69-70]。ISN018_055是Insilico Medicine利用“端到端”药物开发平台Pharma.AI发现的Traf2和Nck相互作用激酶小分子抑制剂，AI深度赋能靶点发现、分子生成和临床方案设计全过程。2024年9月，Insilico Medicine公布了ISN018_055临床Ⅱa期积极结果，显示该药物具有良好的安全性和剂量依赖性的药效，是AI制药领域的里程碑[71-72]。 3 总结与展望新药的研发成本和周期不断提高，而成功率却不断下降，很多疾病仍得不到有效治疗，AI技术的发展无疑为这些困境带来突破口和强劲动力[73]。在传统药物分子设计存在挑战的领域，AI的参与将带来新的契机。例如，复杂靶点如G蛋白偶联受体和RNA等，其与配体的结合模式往往与常规蛋白有所不同；分子胶降解剂涉及蛋白-蛋白界面作用和探索全新口袋，三元复合物存在稳定性问题，给结合模式预测及分子生成带来较大难度[74-78]。传统中药作为我国千百年来实践经验的结晶，在治疗棘手疾病方面展现了巨大潜力，AI技术也已有所涉猎，例如，新的组合处方、药理机制、网络药理学、患者数据的相关性分析等[79-80]。大语言模型、扩散模型、多任务学习等新兴技术在这些具有挑战性的药物发现领域也具有广阔的前景[81-84]。高质量的数据是AI模型的基础，但制药领域的数据往往很有限，非常分散且格式多样，需要大量的清洗和整理工作[85]。另外面临负样本缺失的问题，缺少失败实验的相关数据，会导致机器学习模型中的协变量偏移，从而影响分类精度。随着AI技术的不断进步，需要保障数据隐私、算法透明度以及公平性等问题。通过实验室信息管理系统和电子实验记录本等方式，有望实现实验数据的有效管理和共享[86]。虽然AI技术可在不同阶段助力药物的发现与开发，但新药发现是个复杂且庞大的工程，整体而言仍需持谨慎乐观态度。一方面AI助力药物研发大多停留在早期发现阶段；另一方面进入临床的AI药物大部分仍在临床Ⅰ/Ⅱ期阶段，整体评价下药物安全性和PK/PD性质较良好，而在关键的Ⅱ期和Ⅲ期有效性验证中则表现不一，尚缺乏足够样本的有效性验证。除上述分析的抗肿瘤药物外，针对非肿瘤靶点的部分AI药物分子进展不如预期，例如，由Exscientia与住友制药共同开发的用于治疗强迫症的长效5-羟色胺1A受体激动剂DSP-1181，由于临床Ⅰ期研究未达到预期标准已停止开发。住友制药和大冢制药合作的精神分裂症药物ulotaront，以及BenevolentAI公司的特应性皮炎药物BEN-2293均由于药效未达预期终点而在临床中后期停止研究。近期2家诞生于AI制药初期的公司Recursion和Exscientia宣布合并，也启发了AI制药的商业模式[87]。随着高质量数据的不断累积、AI技术平台的不断优化以及AI制药公司商业模式的持续探索，未来会有更多临床真实数据帮助检验AI药物的安全性和有效性。相信未来AI药物将实现概念验证并获批上市，帮助解决未满足的临床需求，全面加速新药研发。参考文献向上滑动查看 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免疫疗法疫苗临床研究

2025-02-11

·Business Wire

Exelixis Announces Fourth Quarter and Fiscal Year 2024 Financial Results and Provides Corporate Update

ALAMEDA, Calif.--( BUSINESS WIRE )--Exelixis, Inc. (Nasdaq: EXEL) today reported financial results for the fourth quarter and fiscal year of 2024, provided an update on progress toward achieving key corporate objectives, and outlined its commercial, clinical and pipeline development milestones. “Exelixis delivered a strong fourth quarter of 2024, positioning us well to maximize success in 2025,” said Michael M. Morrissey, Ph.D., President and Chief Executive Officer, Exelixis. “Due to the continued outsized performance of the cabozantinib franchise, we generated net product revenues of $515 million and $1.81 billion in the fourth quarter and full year 2024, respectively. Our current 2025 guidance, which does not include any impact from a potential U.S. regulatory approval for CABOMETYX ® in advanced neuroendocrine tumors, points to solid growth for the cabozantinib franchise. We’re launch-ready for this important indication ahead of an April 3, 2025 PDUFA target action date for our U.S. regulatory filing.” Dr. Morrissey continued: “We expect zanzalintinib to take center stage in 2025 as our next franchise opportunity that could improve standards of care for patients with cancer. Our anticipated zanzalintinib pivotal data milestones include top-line results from STELLAR-303 in colorectal cancer and STELLAR-304 in non-clear cell renal cell carcinoma, and a decision to advance to the phase 3 portion of STELLAR-305 in head and neck cancer, all in the second half of the year pending event rates for each trial. We are also excited to deliver on our plan to initiate the STELLAR-311 trial of zanzalintinib in neuroendocrine tumors in the first half of 2025 and anticipate Merck to initiate two renal cell carcinoma studies evaluating zanzalintinib plus belzutifan this year. With so much in store for 2025, the entire Exelixis team has a singular focus on achieving our mission to help cancer patients recover stronger and live longer.” Fourth Quarter and Fiscal Year 2024 Financial Results Total revenues for the quarter and year ended December 31, 2024 were $566.8 million and $2,168.7 million, as compared to $479.7 million and $1,830.2 million for the comparable periods in 2023. Total revenues for the quarter and year ended December 31, 2024 included net product revenues of $515.2 million and $1,809.4 million, respectively, as compared to $429.3 million and $1,628.9 million for the comparable periods in 2023. The increases in net product revenues, for both periods, were primarily due to an increase in sales volume and an increase in average net selling price. Collaboration revenues, composed of license revenues and collaboration services revenues, were $51.5 million for the quarter ended December 31, 2024, as compared to $50.3 million for the comparable period in 2023. The increase in collaboration revenues was primarily related to royalty revenues for the sales of cabozantinib outside of the U.S. generated by Exelixis’ collaboration partners, Ipsen Pharma SAS and Takeda Pharmaceutical Company Limited, partially offset by a decrease in development cost reimbursements earned. Collaboration revenues were $359.3 million for the year ended December 31, 2024, as compared to $201.3 million for the comparable period in 2023. The increase was primarily related to the recognition of milestone-related revenues and higher royalty revenues for the sales of cabozantinib outside of the U.S. generated by Exelixis’ collaboration partners, partially offset by a decrease in development cost reimbursements earned. Research and development expenses for the quarter ended December 31, 2024 were $249.0 million, as compared to $244.7 million for the comparable period in 2023. The increase in research and development expenses for the quarter was primarily related to increases in license and other collaboration costs, personnel expenses and higher manufacturing costs to support Exelixis’ development candidates, partially offset by decreases in clinical trial costs, and consulting and outside services. Research and development expenses for the year ended December 31, 2024 were $910.4 million, as compared to $1,044.1 million for the comparable period in 2023. The decrease in research and development expenses for the year was primarily related to decreases in license and other collaboration costs, personnel expenses, consulting and outside services, and laboratory supplies, partially offset by higher manufacturing costs to support Exelixis’ development candidates and clinical trial costs. Selling, general and administrative expenses for the quarter ended December 31, 2024 were $134.3 million, as compared to $131.4 million for the comparable period in 2023. The increase in selling, general and administrative expenses for the quarter was primarily related to increases in personnel expenses and stock-based compensation expenses, partially offset by decreases in corporate giving and legal and advisory fees. Selling, general and administrative expenses for the year ended December 31, 2024 were $492.1 million, as compared to $542.7 million for the comparable period in 2023. The decrease in selling, general and administrative expenses for the year was primarily related to decreases in corporate giving, legal and advisory fees, technology costs, and stock-based compensation expenses, partially offset by an increase in personnel expenses. Provision for income taxes for the quarter and year ended December 31, 2024 was $44.9 million and $160.4 million, respectively, as compared to $17.5 million and $49.8 million for the comparable periods in 2023, primarily due to an increase in pre-tax income. GAAP net income for the quarter ended December 31, 2024 was $139.9 million, or $0.49 per share, basic and $0.48 per share, diluted, as compared to GAAP net income of $85.5 million, or $0.28 per share, basic and $0.27 per share, diluted, for the comparable period in 2023. GAAP net income for the year ended December 31, 2024 was $521.3 million, or $1.80 per share, basic and $1.76 per share diluted, as compared to GAAP net income of $207.8 million, or $0.65 per share, basic and diluted, for the comparable period in 2023. Non-GAAP net income for the quarter ended December 31, 2024 was $160.3 million, or $0.56 per share, basic and $0.55 per share, diluted, as compared to non-GAAP net income of $104.2 million, or $0.34 per share, basic and $0.33 per share diluted, for the comparable period in 2023. Non-GAAP net income for the year ended December 31, 2024 was $593.6 million, or $2.05 per share, basic and $2.00 per share, diluted, as compared to non-GAAP net income of $289.4 million or $0.91 per share, basic and $0.90 per share, diluted, for the comparable period in 2023. Non-GAAP Financial Measures To supplement Exelixis’ financial results presented in accordance with U.S. Generally Accepted Accounting Principles (GAAP), Exelixis presents non-GAAP net income (and the related per share measures), which excludes from GAAP net income (and the related per share measures) stock-based compensation expense, adjusted for the related income tax effect for all periods presented. Exelixis believes that the presentation of these non-GAAP financial measures provides useful supplementary information to, and facilitates additional analysis by, investors. In particular, Exelixis believes that these non-GAAP financial measures, when considered together with its financial information prepared in accordance with GAAP, can enhance investors’ and analysts’ ability to meaningfully compare Exelixis’ results from period to period, and to identify operating trends in Exelixis’ business. Exelixis has excluded stock-based compensation expense, adjusted for the related income tax effect, because it is a non-cash item that may vary significantly from period to period as a result of changes not directly or immediately related to the operational performance for the periods presented. Exelixis also regularly uses these non-GAAP financial measures internally to understand, manage and evaluate its business and to make operating decisions. These non-GAAP financial measures are in addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP. Exelixis encourages investors to carefully consider its results under GAAP, as well as its supplemental non-GAAP financial information and the reconciliation between these presentations, to more fully understand Exelixis’ business. Reconciliations between GAAP and non-GAAP results are presented in the tables of this release. 2025 Financial Guidance Exelixis is maintaining the previously provided financial guidance for fiscal year 2025. Net product and total revenues guidance do not currently reflect any revenues resulting from a potential U.S. regulatory approval and commercial launch of CABOMETYX ® (cabozantinib) for the treatment of patients with previously treated advanced neuroendocrine tumors (NET). The U.S. Food and Drug Administration (FDA) is currently reviewing Exelixis' supplemental New Drug Application (sNDA) for this proposed indication, with a Prescription Drug User Fee Act (PDUFA) target action date of April 3, 2025. Total revenues $2.15 billion - $2.25 billion Net product revenues $1.95 billion - $2.05 billion (1) Cost of goods sold 4% - 5% of net product revenues Research and development expenses $925 million - $975 million (2) Selling, general and administrative expenses $475 million - $525 million (3) Effective tax rate 21% - 23% ____________________ (1) Exelixis’ 2025 net product revenues guidance range includes the impact of a U.S. wholesale acquisition cost increase of 2.8% for CABOMETYX effective Jan. 1, 2025. (2) Includes $40.0 million of non-cash stock-based compensation expense. (3) Includes $60.0 million of non-cash stock-based compensation expense. Cabozantinib Highlights Cabozantinib Franchise Net Product Revenues and Royalties. Net product revenues generated by the cabozantinib franchise in the U.S. were $515.2 million during the fourth quarter of 2024, with net product revenues of $512.8 million from CABOMETYX and $2.4 million from COMETRIQ ® (cabozantinib). For the year ended December 31, 2024, net product revenues generated by the cabozantinib franchise in the U.S. were $1,809.4 million, with net product revenues of $1,798.2 million from CABOMETYX and $11.2 million from COMETRIQ. In 2024, global cabozantinib franchise net product revenues generated by Exelixis and its partners exceeded $2.5 billion. Based upon cabozantinib-related net product revenues generated by Exelixis’ collaboration partners during the quarter and year ended December 31, 2024, Exelixis earned $44.4 million and $166.9 million, respectively, in royalty revenues. Detailed Results from Subgroup Analysis of Phase 3 CABINET Pivotal Study Evaluating Cabozantinib in Advanced Gastrointestinal (GI) NET Presented at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI 2025). In January 2025, results from a subgroup analysis of the CABINET study of patients with extra-pancreatic neuroendocrine tumors (epNET) arising in the GI tract were featured in a poster session at ASCO GI 2025. The analysis showed cabozantinib was associated with an improvement in progression-free survival (PFS) compared with placebo in patients with advanced GI NET, which was a subgroup of the epNET cohort. Earlier in January, the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for Neuroendocrine and Adrenal Tumors were updated to include cabozantinib as category 1 for certain types of NET following specific treatments, and as a category 2A preferred regimen for several other forms of advanced NET, depending on site of origin and grade. Cabozantinib Data Presentations at the American Society of Clinical Oncology 2025 Genitourinary Cancers Symposium (ASCO GU). In February 2025, cabozantinib will be the subject of 16 presentations and poster sessions at this year’s ASCO GU, which is being held from February 13-15 in San Francisco. Notable presentations will include final follow-up results from the CheckMate -9ER trial (median follow-up of 67.6 months). Pipeline Highlights Encouraging Results from Phase 1b/2 STELLAR-001 Trial Evaluating Zanzalintinib Alone or in Combination with Atezolizumab ( Tecentriq ® ) in Metastatic Colorectal Cancer (CRC) Presented at ASCO GI 2025. In January 2025, results from an expansion cohort of the phase 1b/2 STELLAR-001 trial evaluating zanzalintinib alone or in combination with atezolizumab in patients with previously treated metastatic CRC were presented during a poster session at ASCO GI 2025. This cohort of the STELLAR-001 trial included 107 patients randomized 1:1 to receive single-agent zanzalintinib or zanzalintinib in combination with atezolizumab. Patients had unresectable, locally advanced or metastatic RAS wild-type CRC that is non-microsatellite instability-high or non-mismatch repair-deficient. Results from the presentation demonstrated that all efficacy parameters, including objective response rate, PFS and overall survival (OS) favored the combination of zanzalintinib plus atezolizumab versus zanzalintinib monotherapy in the overall population, as well as in a subgroup of patients without liver metastases. These data provide insights into the contribution of components for the zanzalintinib plus atezolizumab combination and support zanzalintinib’s ongoing pivotal development in metastatic CRC. Exelixis anticipates disclosing additional data from zanzalintinib’s phase 1b/2 studies in the first half of 2025. Initiation of Phase 1 Clinical Trial Evaluating XL495 in Patients with Advanced Solid Tumors. In November 2024, Exelixis announced the initiation of the dose-escalation stage of the first-in-human phase 1 clinical trial of XL495 in patients with advanced solid tumors. XL495 is a novel, potent, small molecule inhibitor of PKMYT1. The dose-escalation stage of this phase 1 study is designed to determine the maximum tolerated dose of XL495. The expansion cohorts are designed to further assess the tolerability and activity of XL495 both as monotherapy and in combination with select cytotoxic agents in tumor-specific indications. Exelixis plans to present data from the XL495 program, as well as XL309 (potentially best-in-class small molecule inhibitor of USP1) and XB010 (5T4-targeting antibody-drug conjugate), at a scientific meeting in 2025. Corporate Highlights Clinical Development Collaboration with Merck to Evaluate Zanzalintinib in Combination with KEYTRUDA ® (pembrolizumab) in Head and Neck Cancer and with WELIREG ® (belzutifan) in Renal Cell Carcinoma (RCC). In October 2024, Exelixis and Merck (known as MSD outside of the U.S. and Canada) announced a clinical development collaboration to evaluate zanzalintinib in combination with KEYTRUDA in head and neck squamous cell carcinoma (HNSCC), and zanzalintinib with WELIREG in RCC. Under the terms of the collaboration, Merck will supply KEYTRUDA, its anti-PD-1 therapy, for the ongoing, Exelixis-sponsored phase 3 STELLAR-305 pivotal trial in previously untreated PD-L1 positive recurrent or metastatic HNSCC. In addition, Merck will sponsor a phase 1/2 trial and two phase 3 pivotal trials evaluating zanzalintinib in combination with WELIREG, its oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, in RCC. Merck will fund one of these phase 3 studies, and Exelixis will co-fund the phase 1/2 trial and the other phase 3 study, as well as supply zanzalintinib and cabozantinib. Exelixis maintains all global commercial and marketing rights to zanzalintinib. Favorable Ruling in Second Cabozantinib Abbreviated New Drug Application (ANDA) Litigation Against MSN Pharmaceuticals, Inc. (MSN). In October 2024, the U.S. District Court for the District of Delaware (the District Court) ruled in Exelixis’ favor, rejecting MSN’s challenge to three Orange Book-listed patents related to cabozantinib (U.S. Patents No. 11,091,439 (crystalline salt forms), 11,091,440 (pharmaceutical composition) and 11,098,015 (methods of treatment)), which expire January 15, 2030. The District Court’s decision follows an earlier stipulation that MSN’s proposed generic cabozantinib product (ANDA No. 213878) infringes the ’439, ’440, and ’015 patents. The District Court also ruled that Exelixis’ U.S. Patent No. 11,298,349 (pharmaceutical composition) is not invalid and not infringed by MSN’s proposed ANDA product. To Exelixis’ knowledge, the FDA has not yet granted tentative approval of MSN’s proposed ANDA product. On October 23, 2024, the District Court entered final judgment reflecting the opinion. Based on the District Court’s final judgment should the FDA ultimately approve MSN’s ANDA, the effective date of any such approval and commercial launch in the U.S. of MSN’s proposed ANDA product shall not be a date earlier than January 15, 2030, subject to Exelixis’ potential additional regulatory exclusivity. On November 22, 2024, MSN noticed an appeal to the Court of Appeals for the Federal Circuit and Exelixis noticed a cross-appeal on November 26, 2024. In February 2025, Exelixis received notice that MSN submitted to the FDA a Paragraph IV certification regarding another Exelixis Orange Book patent: U.S. Patent No. 12,128,039 (low impurity), which expires in 2032. Exelixis is evaluating next steps and will continue to vigorously defend its cabozantinib intellectual property estate. Stock Repurchase Program. Under the ongoing 2024-25 $500 million stock repurchase program announced in August 2024, Exelixis has repurchased $205.6 million of the company’s common stock, at an average price of $33.62 per share as of the end of fiscal year 2024. This is the third stock repurchase program undertaken by Exelixis since March 2023. Stock repurchases under this program may be made from time to time through a variety of methods, which may include open market purchases, in block trades, accelerated stock repurchase transactions, exchange transactions, or any combination of such methods. The timing and amount of any stock repurchases under the stock repurchase program will be based on a variety of factors, including ongoing assessments of the capital needs of the business, alternative investment opportunities, the market price of Exelixis’ common stock and general market conditions. Announcement of Key Priorities and Anticipated Milestones for 2025. In January 2025, Exelixis announced its key priorities and anticipated milestones for 2025, including: the potential commercial launch of CABOMETYX for the treatment of patients with previously treated advanced NET following completion of the FDA’s review of Exelixis’ sNDA, which has a PDUFA action date of April 3, 2025; expansion of zanzalintinib’s pivotal development program with six ongoing or planned pivotal trials, including two pivotal RCC studies with Merck and additional studies to be announced in 2025, as well as initial clinical data readouts from the phase 1b/2 STELLAR-001 and STELLAR-002 clinical studies in the first half of the year and clinical updates from the pivotal STELLAR-303, -304 and -305 trials in the second half of 2025; accelerating the phase 1 development of XL309 as a potential therapy for tumors that have become refractory to PARP inhibitor (PARPi) therapy, as well as in combination with PARPi agents to deepen and prolong responses; continued progress of phase 1 clinical trials for XB010 and XL495; potentially filing three Investigational New Drug applications for the XB628 PD-L1-NKG2A bispecific antibody, XB064 ILT-2 monoclonal antibody and XB371 TF-topoisomerase I inhibitor antibody-drug conjugate. Exelixis presented the details of its key priorities and anticipated milestones at the 43 rd Annual J.P. Morgan Healthcare Conference. Basis of Presentation Exelixis has adopted a 52- or 53-week fiscal year that generally ends on the Friday closest to December 31. For convenience, references in this press release as of and for the fiscal periods ended January 3, 2025 and December 29, 2023, are indicated as being as of and for the periods ended December 31, 2024 and 2023, respectively . Conference Call and Webcast Exelixis management will discuss the company’s financial results for the fourth quarter and fiscal year 2024 and provide a general business update during a conference call beginning at 5:00 p.m. ET / 2:00 p.m. PT today, Tuesday, February 11, 2025. To access the conference call, please register using this link . Upon registration, a dial-in number and unique PIN will be provided to join the call. To access the live webcast link, log onto www.exelixis.com and proceed to the Event Calendar page under the Investors & News heading. A webcast replay of the conference call will also be archived on www.exelixis.com for one year. About Exelixis Exelixis is a globally ambitious oncology company innovating next-generation medicines and regimens at the forefront of cancer care. Powered by drug discovery and development excellence, we are rapidly evolving our product portfolio to target an expanding range of tumor types and indications with our clinically differentiated pipeline of small molecules, antibody-drug conjugates and other biotherapeutics. This comprehensive approach harnesses decades of robust investment in our science and partnerships to advance our investigational programs and extend the impact of our flagship commercial product, CABOMETYX ® (cabozantinib). Exelixis is driven by a bold scientific pursuit to create transformational treatments that give more patients hope for the future. For information about the company and its mission to help cancer patients recover stronger and live longer, visit www.exelixis.com , follow @ExelixisInc on X (Twitter), like Exelixis, Inc. on Facebook and follow Exelixis on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements, including, without limitation, statements related to: Exelixis’ ability to maximize success in 2025; Exelixis’ 2025 financial guidance, which does not include any impact from a potential U.S. regulatory approval for CABOMETYX in advanced neuroendocrine tumors, pointing to solid growth for the cabozantinib franchise; Exelixis’ launch readiness and the regulatory review process with respect to Exelixis’ sNDA for cabozantinib in previously treated advanced pNET and advanced epNET, including the Prescription Drug User Fee Act target action date assigned by the FDA; Exelixis’ expectation that zanzalintinib will take center stage in 2025 as Exelixis’ next franchise opportunity that could improve standards of care for patients with cancer; anticipated zanzalintinib pivotal data milestones with respect to the STELLAR-303, STELLAR-304, and STELLAR-305 trials and in the phase 1b/2 STELLAR-001 trial; Exelixis’ anticipated timing to initiate the STELLAR-311 trial of zanzalintinib in neuroendocrine tumors in the first half of 2025; Exelixis’ expectations with respect to its clinical development collaboration with Merck; Exelixis’ plans to present cabozantinib data at ASCO GU in February 2025; Exelixis’ plans to present data from the XL495 program, as well as XL309 and XB010, at a scientific meeting in 2025; Exelixis’ plans to vigorously defend its intellectual property estate; Exelixis’ key priorities and anticipated milestones for 2025; and Exelixis’ scientific pursuit to create transformational treatments that give more patients hope for the future. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis’ current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: the degree of market acceptance of CABOMETYX and other Exelixis products in the indications for which they are approved and in the territories where they are approved, and Exelixis’ and its partners’ ability to obtain or maintain coverage and reimbursement for these products; the effectiveness of CABOMETYX and other Exelixis products in comparison to competing products; the level of costs associated with Exelixis’ commercialization, research and development, in-licensing or acquisition of product candidates, and other activities; Exelixis’ ability to maintain and scale adequate sales, marketing, market access and product distribution capabilities for its products or to enter into and maintain agreements with third parties to do so; the availability of data at the referenced times; the potential failure of cabozantinib, zanzalintinib and other Exelixis product candidates, both alone and in combination with other therapies, to demonstrate safety and/or efficacy in clinical testing; uncertainties inherent in the drug discovery and product development process; Exelixis’ dependence on its relationships with its collaboration partners, including their pursuit of regulatory approvals for partnered compounds in new indications, their adherence to their obligations under relevant collaboration agreements and the level of their investment in the resources necessary to complete clinical trials or successfully commercialize partnered compounds in the territories where they are approved; complexities and the unpredictability of the regulatory review and approval processes in the U.S. and elsewhere; Exelixis’ continuing compliance with applicable legal and regulatory requirements; unexpected concerns that may arise as a result of the occurrence of adverse safety events or additional data analyses of clinical trials evaluating cabozantinib, zanzalintinib and other Exelixis product candidates; Exelixis’ dependence on third-party vendors for the development, manufacture and supply of its products and product candidates; Exelixis’ ability to protect its intellectual property rights; market competition, including the potential for competitors to obtain approval for generic versions of Exelixis’ marketed products; changes in economic and business conditions; and other factors detailed from time to time under the caption “Risk Factors” in Exelixis’ most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q, and in Exelixis’ other future filings with the Securities and Exchange Commission. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law. Exelixis, the Exelixis logo, CABOMETYX and COMETRIQ are registered trademarks of Exelixis, Inc. KEYTRUDA ® and WELIREG ® are registered trademarks of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, N.J., USA. TECENTRIQ (atezolizumab) is a registered trademark of Genentech, a member of the Roche Group. EXELIXIS, INC. CONDENSED CONSOLIDATED STATEMENTS OF INCOME (in thousands, except per share amounts) (unaudited) Three Months Ended December 31, Year Ended December 31, 2024 2023 2024 2023 Revenues: Net product revenues $ 515,232 $ 429,336 $ 1,809,395 $ 1,628,879 License revenues 49,343 45,229 349,244 178,635 Collaboration services revenues 2,180 5,087 10,062 22,694 Total revenues 566,755 479,652 2,168,701 1,830,208 Operating expenses: Cost of goods sold 19,965 21,753 76,216 72,547 Research and development 249,002 244,670 910,408 1,044,071 Selling, general and administrative 134,328 131,441 492,128 542,705 Impairment of long-lived assets — — 51,672 — Restructuring 254 — 33,660 — Total operating expenses 403,549 397,864 1,564,084 1,659,323 Income from operations 163,206 81,788 604,617 170,885 Interest income 21,295 21,388 77,156 86,543 Other income (expense), net 272 (137 ) (133 ) 93 Income before income taxes 184,773 103,039 681,640 257,521 Provision for income taxes 44,912 17,521 160,373 49,756 Net income $ 139,861 $ 85,518 $ 521,267 $ 207,765 Net income per share: Basic $ 0.49 $ 0.28 $ 1.80 $ 0.65 Diluted $ 0.48 $ 0.27 $ 1.76 $ 0.65 Weighted-average common shares outstanding: Basic 284,527 308,482 290,030 318,151 Diluted 293,546 313,023 296,132 321,464 EXELIXIS, INC. RECONCILIATION OF GAAP NET INCOME TO NON-GAAP NET INCOME (in thousands, except per share amounts) (unaudited) Three Months Ended December 31, Year Ended December 31, 2024 2023 2024 2023 GAAP net income $ 139,861 $ 85,518 $ 521,267 $ 207,765 Adjustments: Stock-based compensation - research and development expenses (1) 8,836 9,041 30,670 34,320 Stock-based compensation - selling, general and administrative expenses (1) 17,510 15,265 63,166 72,025 Income tax effect of the above adjustments (5,896 ) (5,629 ) (21,520 ) (24,691 ) Non-GAAP net income $ 160,311 $ 104,195 $ 593,583 $ 289,419 GAAP net income per share: Basic $ 0.49 $ 0.28 $ 1.80 $ 0.65 Diluted $ 0.48 $ 0.27 $ 1.76 $ 0.65 Non-GAAP net income per share: Basic $ 0.56 $ 0.34 $ 2.05 $ 0.91 Diluted $ 0.55 $ 0.33 $ 2.00 $ 0.90 Weighted-average common shares outstanding: Basic 284,527 308,482 290,030 318,151 Diluted 293,546 313,023 296,132 321,464 ____________________ (1) Non-cash stock-based compensation expense used for GAAP reporting in accordance with Accounting Standards Codification Topic 718, Compensation—Stock Compensation .

临床1期上市批准财报临床3期ASCO会议

2025-01-30

·生物制品圈

DeepSeek带你学AI | 药物研发的“马拉松”正被AI加速

传统药物研发耗时长（平均12年）、成本高（超28亿美元），且失败率高。生成式人工智能（Generative AI）通过加速分子设计、优化药效与安全性，正在改变这一局面。例如，AI模型能在21天内发现针对纤维化相关激酶的抑制剂，效率远超传统方法（图1）。图1 | 常见的生成式模型架构：(a) 循环神经网络（RNN）；(b) 变分自编码器（VAE）；(c) 生成对抗网络（GAN）；(d) 图神经网络（GNN）；(e) 标准化流模型。生成式AI的核心技术1. 分子生成模型变分自编码器（VAE）：通过压缩分子结构到潜在空间，再解码生成新分子。例如，ChemVAE能生成具有特定溶解度或活性的化合物。生成对抗网络（GAN）：生成器与判别器对抗训练，提升分子真实性。如ORGAN模型成功生成针对COVID-19蛋白酶抑制剂。图神经网络（GNN）：直接处理分子图结构，适用于蛋白质相互作用预测（图2d）。2. 优化技术强化学习（RL）：通过反馈机制优化分子属性。例如，DrugEx模型设计出针对腺苷A2A受体的高效拮抗剂。迁移学习（Transfer Learning）：利用预训练模型加速特定任务学习，如从通用分子库迁移到抗癌药物设计。图2 | (a) 扩散模型通过加噪与去噪生成分子；(b) Transformer模型通过自注意力机制生成SMILES序列；(c) 结合迁移学习与强化学习的分子设计流程。成功案例与临床进展案例1：COVID-19药物设计 Insilico Medicine利用GAN生成针对SARS-CoV-2主蛋白酶（Mpro）的候选分子，通过虚拟筛选获得40个潜在化合物（图3）。 Bung团队通过RNN模型优化QED和合成可行性，筛选出31个具有高结合力的候选药物。图3 | AMPTrans-1stm模型结合LSTM与Transformer生成新型抗菌肽，其多样性优于训练数据。案例2：JAK1激酶抑制剂 GraphGMVAE模型生成具有新颖骨架的分子，其中一种化合物在体外实验中显示出5.0 nM的高活性（图4），验证了AI设计的可行性。图4 | GraphGMVAE通过双消息传递网络（Dual-MPNN）实现骨架跃迁设计。挑战与解决方案1. 数据瓶颈问题：高质量生物活性数据稀缺，公共数据库（如ChEMBL）覆盖有限。对策：联邦学习（Federated Learning）实现跨机构数据协作，如MELLODDY项目联合10家药企共享加密数据。2. 模型可解释性问题：黑箱模型难以理解分子生成逻辑。对策：可解释AI（XAI）技术揭示关键分子特征，例如毒性基团识别。3. 合成可行性问题：AI生成分子可能难以合成。对策：集成合成路线预测工具（如RetroSyn），提前评估合成难度。未来展望跨学科合作：建立类似ImageNet的分子数据库，推动标准化评估。临床验证：目前已有15款AI设计药物进入临床试验（表5），如Exscientia的DSP-1181（治疗强迫症）和Insilico的ISM001-055（抗纤维化）。技术融合：结合量子计算与AI，探索更大化学空间。表5 | 部分AI设计药物临床阶段与靶点（示例：ISM3091为USP1抑制剂，用于癌症治疗）。结语：当AI在实验室里“做梦”，人类正在见证药物发现从“试错艺术”变为“预测科学”。这场变革不会取代科学家，而是赋予他们“超能力”。或许不久的将来，治愈癌症就像今天治疗感冒一样简单——而这背后，是一行行代码与试管碰撞出的火花。识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观，不代表本站立。

临床研究

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
晚期恶性实体瘤	临床1期	美国	Exelixis, Inc.	2023-09-12
实体瘤	临床申请批准	美国	InSilico Medicine, Inc.	2023-05-25
肿瘤	临床前	中国	英矽智能(香港)有限公司	2023-04-20