Ubamatamab

投资要点⚫TCE已在SCLC、mCRPC中读出成熟的临床数据，并显示出前线治疗的潜力。1）SCLC：塔拉妥单抗联合PD-L1抑制剂1线维持治疗ES-SCLC的DeLLphi-303临床中位OS达25.3个月，目前1线维持关键临床DeLLphi-312已开启，并将通过DeLLphi-306探索其在LS-SCLC中的应用前景。泽璟制药ZG006在3线及以上SCLC中，30mg剂量组ORR达63.3%，目前该分子已授权至艾伯维，有望与其SEZ6ADCABBV-706进一步探索联用前景；MSDGocatamig在2025ESMO更新的数据中，24mgQ2W剂量组cORR达46%，并布局与B7H3ADCI-Dxd的联用临床；2）mCRPC：Xaluritamig在I期临床针对经紫杉烷类治疗的既往中位治疗线数为4线的mCRPC患者中显示出明显疗效，在整体97名患者中mOS达到17.7月，在后线mCRPC中具备较强竞争力，安全性总体可控；JANX007因其突出的肝毒性问题，临床前景仍需后续大规模临床验证其是否具备突出的疗效优势；Pasritamig具备安全性优势，有望为其余疗法不耐受的患者提供选择。此外，B7H3ADCDB-1311在后线mCRPC中9个月rPFS率达58.0%，目前BioNTech已开启其mCRPC适应症的III期临床，参考目前SCLC的临床格局，我们认为B7H3ADC也有望与上述TCE探索联合用药的前景。⚫TCE在卵巢癌、消化系统肿瘤、肝细胞癌中已初步展现应用潜力，泛癌肿靶点有望实现突破。1）卵巢癌：首个MUC16TCEUbamatamab出现较大的安全性风险；维立志博的LBL-033在20例卵巢癌等恶性肿瘤中观察到了初步的肿瘤响应，有望实现TCE疗法在该适应症上的突破；2）消化系统肿瘤：CLDN18.2TCE已在胰腺癌与胃癌中读出了具备前景的临床数据，齐鲁制药QLS31905已推进至胰腺癌临床III期；3）肝细胞癌：GPC3TCE有望在肝细胞癌2线治疗中展现治疗潜力，SanofiGPC3/TCR纳米抗体初步读出数据，在18例基线甲胎蛋白≥20%的HCC患者中初步观察到肿瘤响应；4）泛癌肿靶点：EGFRTCE有望验证在NSCLC、mCRC、ESCC等EGFR阳性癌肿中的应用前景，时迈药业SMET12已在NSCLC中读出初步临床数据，后续包括JANX008、VIR-5525、CMDE005、VIB305在内的多款EGFR/CD3遮蔽肽TCE将陆续读出首次人体数据，有望突破TCE疗法的泛癌肿应用。⚫国内多条实体瘤TCE管线已读出具备竞争力的临床数据。持续关注当前实体瘤TCE管线已读出具备竞争力临床数据的标的：1）泽璟制药：ZG006数据具备较强竞争力，实现对艾伯维的出海授权，有望探索与其SEZ6ADCABBV-706的联用前景，ZGGS34已完成中美IND申报；2）百济神州：塔拉妥单抗上市申请已被纳入优先审评程序，BGB-B455有望引领CLDN6靶点的研发进度；3）中国生物制药：EpCAMTCEM701进度领先，有望成为中国首个恶性胸腹水标准治疗方案。$泽璟制药-U(SH688266)$$百济神州-U(SH688235)$$中国生物制药(01177)$一、TCE已在SCLC、mCRPC中读出成熟的临床数据，并显示出前线治疗的充分潜力（一）SCLC：DLL3TCE成为后线基石疗法，与PD-(L)1/ADC联用有望进一步扩展适用空间DLL3是神经内分泌肿瘤治疗的潜力靶点，肿瘤组织内表达特异性强。小细胞肺癌（（SCLC）是肺癌中侵袭性极强的异源性神经内分泌肿瘤，根据RudinCM（（2021）的研究显示，SCLC约占所有肺癌病例的13%-17%，SCLC患者预后较差，广泛期非小细胞肺癌（ES-SCLC）确诊后的中位生存期仅为6-12月。根据《中华肿瘤杂志》的统计数据显示，中国新发ES-SCLC患者约每年11万人；根据MountSinai统计数据显示，美国SCLC年新发患者约3-3.5万人。DLL3是一种Notch信号通路的抑制性配体，它通过阻止Notch受体在细胞表面的呈现来抑制Notch信号，从而促进肿瘤生长、增殖和转移，并抑制肿瘤微环境中的免疫反应。在神经内分泌肿瘤细胞表面异常高表达（尤其在小细胞肺癌中超80%），而在正常组织中表达极低。DLL3TCE填补SCLC后线治疗的空白。当前SCLC治疗一线治疗以免疫治疗联合铂类化疗为主，而标准二线疗法主要仍为化疗，例如拓扑替康、芦比替尼、紫杉醇等等，缺乏有效的靶向疗法，如今靶向DLL3的双特异性T细胞接合器、ADC、双/三抗等药物研发有望填补SCLC在靶向治疗上的空缺，为SCLC治疗开辟了全新路径。针对DLL3靶点的疗法主要包括多抗、ADC与细胞治疗。DLL3靶向疗法中多抗为代表的药物包括安进的CD3/DLL3双抗塔拉妥单抗，该疗法针对2线与3线的SCLC患者临床试验的疗效突出，已获批上市，并在2025WCLC中在1线化疗免疫联合治疗后联用PD-L1抑制剂维持治疗的DeLLphi-塔拉妥单抗外，泽璟制药ZG006目前已推进至III期临床阶段，BI/中国生物制药的obrixtamig、恒瑞医药的SHR-7787、第一三共/默沙东合作的Gocatamig已进入II期临床阶段。ADC疗法方面，再鼎医药的zocilurtatugpelitecan、恒瑞医药/IDEAYA的SHR-7787目前研发进度领先。塔拉妥单抗在1线维持治疗数据亮眼，泽璟制药ZG006临床数据具备较强竞争力，Gocatamig针对ES-SCLC脑转移患者具备差异化疗效。当前在研的DLL3TCE分子中，塔拉妥单抗联合PD-L1抑制剂1线维持治疗ES-SCLC的Ib期临床DeLLphi-303临床中mOS达25.3个月，与芦比替定IMforte临床中联合阿替利珠单抗1线ES-SCLC维持治疗13.2个月的mOS进行非头对头比较，具备显著的相对优势，当前联合PD-L1抑制剂1线维持治疗ES-SCLC的关键注册临床DeLLphi-312已启动。此外，塔拉妥单抗同时布局DeLLphi-306试验，该临床预计纳入400例完成以铂类为基础的同步放化疗，且无疾病进展局限期小细胞肺癌（LS-SCLC）患者，进一步拓展塔拉妥单抗在SCLC的适用范围。泽璟制药ZG006的临床数据展现了较强竞争力，在2025ESMOAsia中，最新ZG006-002数据显示10mgQ2W剂量组中，30例3线及以上的SCLC患者中mPFS达7.03m，相较塔拉妥单抗DELLphi–304临床2线治疗4.9m的mPFS仍具备相对优势，并展现了良好的安全性。MSD基于TriTAC平台的CD3/DLL3双抗Gocatamig当前披露的剂量递增临床结果中展现出了对脑转移患者的差异化疗效，2025ESMO更新的数据中，24mgQ2W剂量组cORR达46%，有望在后续剂量扩展试验与B7H3ADC联用临床中进一步验证其抗肿瘤活性与联用潜力。SCLCADC疗法靶点选择多样化，具备与TCE联用的临床前景。艾伯维的Rova-T是首个靶向DLL3的ADC药物，Rova-T在II期和III期临床试验中未达到预期的生存改善，且表现出独特的毒性特征，在2019年，艾伯维官宣终止Rova-T用于SCLC患者的研究和开发计划。再鼎医药的ZL-1310当前已读出初步数据，Ia期临床中，此前接受过至少一种含铂化疗方案治疗的广泛期小细胞肺癌患者中ORR达68%。相较各靶点ADC疗法，DLL3TCE在SCLC适应症具有更充分的临床数据验证，且3级及以上TRAE发生率低于ADC，更具备前线应用的潜力。此外，DLL3TCE疗法有与ADC联用的潜力，B7-H3ADCYL201当前已布局与塔拉妥单抗、PD-L1联用用于ES-SCLC的Ib期临床，ZG006在实现向艾伯维的License-out后，我们认为也具有与其SEZ6ADCABBV-706联用的潜力。（二）mCRPC：PSMA、STEAP1、KLK2等靶点均验证抗肿瘤潜力，TCE有望成为mCRCP的基石疗法PSMA：mCRPC经典靶点，临床适用场景有望推进至Pluvicto前线PSMA表达特异性强，已成为mCRPC诊疗的关键靶点。PSMA（（前列腺特异性膜抗原）是一种由750个氨基酸组成的II型跨膜糖蛋白，包含胞内区、跨膜区和胞外区三个结构域。在良性前列腺细胞中，PSMA主要分布于细胞质和腺体顶端面；恶性转化后，其定位转移至前列腺导管腔面，胞外区暴露并形成配体结合位点。前列腺腺癌中PSMA表达水平较良性组织升高100–1000倍，且随肿瘤去分化及转移性CRPC的进展进一步增加，因此PSMA成为诊疗一体化的理想靶点。PSMA胞外区含多个结合位点，可与放射性配体结合用于影像或放射性配体治疗（RLT）；同时，PSMA抑制剂通过叶酸结合位点或锌结合位点，抑制其酶功能并干预肿瘤生长，从而展现出在前列腺癌诊断与治疗中的重要价值。PSMA在前列腺之外，主要表达的器官为唾液腺，因此，唾液腺成为了PSMA靶向疗法主要的剂量限制器官，以JANX007Ia期数据为例，33%的患者（1%为3级及以上）出现口干的TRAE，这一靶点相关不良反应可能会成为相关疗法开发上值得注意的问题。Pluvicto突破mCRPC后线治疗，当前已在2线治疗中展现获益。在晚期mCRPC领域，传统治疗选择有限，一线主要依靠化疗（如多西他赛）或内分泌治疗（ARPI，如阿比特龙、恩杂鲁胺），而后线方案相对稀少，包括免疫检查点抑制剂（如帕博利珠单抗）或PARP抑制剂（如奥拉帕利），患者在1线及2线治疗失败后往往缺乏有效选择。近年来，PSMA靶向放射性配体治疗代表药物Pluvicto的出现，为mCRPC治疗开辟了新路径。Pluvicto通过衰变产生的β射线精准照射PSMA阳性肿瘤细胞，引发DNA损伤并实现肿瘤杀伤，实现了“精准+放疗+系统治疗”的三位一体模式。Pluvicto已在III期试验中验证出在2线mCRPC治疗中明确的生存获益，PSMAfore试验在1线ARPI进展且未接受过紫杉醇治疗的mCRPC患者中，相比更换ARPI的亚组，mPFS为11.6个月（HR=0.49），mOS约23.7个月，ORR50%，PSA反应率51%。除RLT外，PSMA靶向药物还包括ADC、TCE、双抗、CAR-T等，大部分适应症为后线mCRPC治疗。JANX007在5线mCRPC患者中展现出一定比例的肿瘤响应，前线患者中观察到初步疗效信号。根据JANX007在2025年12月1日更新的Ia期临床数据，在27例目标剂量为2mg以上患者中ORR达30%，在6/9mgQ2W剂量组的19名患者中，rPFS达8.9m；安全性方面，在经治的109名患者中，≥3级CRS出现在8%患者中，≥3级AST与ALT升高分别出现在23%与17%患者中，显示出一定的肝毒性。此外JANX007已初步在紫杉烷类化疗未经治的前线患者中观察到积极的PSA降低信号，有望在后续更新中读出具备竞争力的前线数据。除TCE外，PSMAADC疗法ARX517I/II期结果显示PSA≥50%下降率达52%，ARX517的剂量递增临床展现了良好的安全性，≥3级不良事件仅出现在9%的患者中。Pluvicto在针对3线mCRPC的VISION临床中，mPFS达8.7m，ORR为30%，PSMATCEJANX007在5线mCRPC患者中，最优剂量组mPFS与ORR数据与VISION临床数据相比具有一定的竞争力，但JANX007较强的肝毒性与CRS风险仍是该疗法后续开发的担忧点。STEAP1：Xaluritamig已推进至III期临床，CD28三抗TCE布局丰富STEAP1靶点在前列腺癌、膀胱癌等癌症中具有促进癌细胞增殖转移的作用。STEAP1（（SixTransmembraneEpithelialAntigenoftheProstate）表达在许多组织表面的细胞与细胞的连接处，尤其是在前列腺分泌上皮细胞的表达水平较高。STEAP1主要功能是调控细胞氧化还原平衡，并调节促炎性细胞因子相关通路，在前列腺癌、膀胱癌等癌症中，STEAP1显著高表达，能促进癌细胞的增殖和转移。在mCRPC中，STEAP1基因启动子的低甲基化和性激素（如DHT）的调控失衡共同导致了STEAP1蛋白的过度表达，高表达的STEAP1进而通过促进细胞增殖、抑制细胞凋亡、以及介导肿瘤细胞与基质细胞的通讯等方式，驱动mCRPC的进展。STEAP1与PSMA在mCRPC的表达上互补，相关疗法为mCRPC患者提供更丰富的靶点选择。PSMA表达在mCRPC患者中具有异质性，根据Bhatia（（2023）对华盛顿大学组织解剖样本库中332个样本的分析，通过实施H评分阈值为30的最小染色阈值，发现87.7%的可评估的mCRPC组织显示出H评分30以上的STEAP1染色，而H评分30以上的PSMA染色样本仅为60.5%，28.1%的mCRPC组织显示STEAP1染色但未出现PSMA染色，仅有0.9%的样本两靶点染色均未出现。这一研究预示着STEAP1靶向的mCRPC疗法相较PSMA靶向疗法可能具有更广泛的适用性，此外STEAP1xPSMA的双靶点疗法例如多禧生物与艾伯维的STEAP1xPSMAADC已推进至临床阶段，有望进一步消除mCRPC患者之间的异质性。Amgen推进至三期，布局多项前列腺癌适应症。相较PSMA靶点，STEAP1靶向疗法进入临床阶段的分子较少，Amgen的第二款实体瘤TCEXaluritamig已推进至III期临床，目前该疗法两项临床正在推进：（1）XALute：针对曾接受过化疗的mCRPC患者；（2）XALience研究：探索Xaluritamig与阿比特龙在未接受化疗的mCRPC患者疗效和安全性。除Amgen外，复宏汉霖布局全球首创CD3xCD28xSTEAP1三抗，当前尚处于临床前阶段。STEAP1靶点的其他疗法方面，多禧生物STEAP1xPSMA双靶点ADC已启动I期临床，其余疗法尚处于临床前阶段。KLK2：Pasritamig推进至III期，岸迈生物EM1031实现对外授权KLK2表达受雄激素调控，在前列腺癌进展中具有关键作用。KLK2（Humankallikrein2）是一种具有胰蛋白酶样活性的丝氨酸蛋白酶，主要在前列腺中表达，其在精浆中的浓度约为PSA的1%。KLK2作为激肽释放酶家族成员，在前列腺中与PSA协同发挥作用，能特异性切割proPSA的N端肽链，激活其功能，是PSA生物活性的关键调节因子。其基因表达受雄激素调控，启动子区域的雄激素反应元件（ARE）使其表达水平与雄激素受体（AR）活性密切相关，体现出典型的激素依赖性表达模式。KLK2还能促进血管生成和肿瘤微环境重塑，增强肿瘤侵袭性，尤其在前列腺癌进展中发挥重要作用。KLK2靶点的组织特异性较强，有望增强相关TCE疗法的安全性且避免靶点相关毒性。KLK2靶点的差异化优势在于极强的组织特异性，不同于PSMA在唾液腺等组织、STEAP1在乳腺（在正常乳腺中表达较高，乳腺癌中表达下调）等组织也有一定表达，KLK2仅在前列腺中表达，因此KLK2相关疗法有望规避例如PSMA靶向疗法出现的口干等不良反应。Pasritamig推进至临床III期，岸迈生物EM1031实现Newco出海。KLK2-TCE中Pasritamig全球进度领先，已于2025年9月启动适应症为mCRPC的III期临床。岸迈生物EM1031目前处于临床前研究阶段，2025年5月27日，岸迈生物与TCGLabsSoleil投资组合公司JuriBiosciences签署该分子的全球许可协议，岸迈生物有权收取高达2.1亿美元的资金，包括首付款，和开发、注册和商业化相关的里程碑付款。RLT疗法JNJ-69086420安全性风险较高，Pasritamig剂量递增阶段展现初步抗肿瘤活性。JNJ-69086420是首款靶向KLK2的放射性配体疗法，I期临床结果显示，JNJ-6420在75例患者中达到18%的ORR，PSA50反应率为44%，PSA90反应率为9%，该疗法安全性较差，≥3级TRAE发生率为61.3%，且导致4例患者死亡。CD3xKLK2TCEPasritamigI期临床试验剂量递增阶段数据显示，RP2D人群中位PFS为7.85个月，RP2D人群PSA50反应率为42.4%，总人群ORR为8.3%，Pasritamig安全性可控，≥3级TRAE发生率为45.4%，CRS发生率为24.7%,未发生3级以上CRS。强生目前已将Pasritamig推进至III期临床阶段，旨在评估该疗法联合最佳支持治疗（BSC）对比安慰剂联合BSC，在转移性去势抵抗性前列腺癌（mCRPC）患者中的疗效，预计纳入663例受试者。Xaluritamig有望成为mCRPC的基石疗法，ADC等其余疗法为后线患者提供丰富选择。Xaluritamig在I期临床针对经紫杉烷类治疗的既往中位治疗线数为4线的mCRPC患者中显示出明显疗效，在整体97名患者中mOS达到17.7月，展现了后线mCRPC的具备竞争力的疗效，安全性总体可控；JANX007因其突出的肝毒性问题，临床前景仍需后续大规模临床验证其是否具备突出的疗效优势；Pasritamig肿瘤应答比例一般，但其安全性具备优势，有望为其余疗法不耐受的患者提供选择。此外，B7H3ADCDB-1311在后线mCRPC中9个月rPFS率达58.0%，目前BioNTech已开启其mCRPC适应症的3期临床，参考目前SCLC的临床格局，我们认为PSMA、B7H3等ADC也有望与上述TCE探索联合用药的前景，目前强生的PSMAADCJNJ-95298177与其KLK2TCEPasritamig的前列腺癌联用Ib期临床已启动。二、TCE在卵巢癌、消化系统肿瘤、肝细胞癌中已初步展现应用潜力，泛癌肿靶点有望实现突破（一）卵巢癌：两款MUC16TCE读出初步临床数据MUC16是卵巢癌的特异性抗原，在肿瘤进展中扮演重要作用。MUC16是一种跨膜型粘蛋白，是膜结合型粘蛋白家族中的已知最大分子。它的结构主要包括高度糖基化的N端结构域、大量串联重复序列、跨膜区以及一个较短的胞质尾部。MUC16在超过80%的卵巢癌组织中高表达，而在正常卵巢组织中表达水平极低或不可检测。MUC16的跨膜结构及不同结构域能够协同介导多条信号通路，从而在肿瘤发生发展中发挥多方面功能，MUC16可通过激活PI3K/AKT信号通路等方式促进癌细胞黏附、生长和转移，从而推动肿瘤进展。多种药物类型均布局MUC16靶点。MUC16靶向药物的主要目标人群是复发性卵巢癌，特别是针对铂耐药卵巢癌（（PROC）。PROC的2线及后线标准治疗主要依赖非铂类单药化疗，如吉西他滨、紫杉醇、拓扑替康或联合靶向药物贝伐珠单抗、安罗替尼等，这些方案通常疗效有限，肿瘤应答率普遍较低。当前MUC16的在研管线主要包括Regeneron的两款TCEubamatamab（REGN4018）与REGN5668，此外两项CAR-T疗法目前均处于I期临床阶段。多项ADC疗法读出阳性数据，Ubamatamab在末线患者中出现一定安全性风险。当前PROC适应症中，FRαADCMirvetuximabsoravtansine（（Elahere）已在国内获批用于既往接受过1-3线系统性治疗的FRα阳性的铂类耐药的上皮性卵巢癌、输卵管癌或原发性腹膜癌成年患者，Trop2、HER2、CLDN6等靶点ADC也已在PROC患者中读出初步数据。实体瘤TCE方面，MUC16TCEUbamatamab，出现了较大的安全性风险，65.4%的患者发生≥3级的TEAE，并导致3例患者死亡。除Ubamatamab外，维立志博的LBL-033在20例卵巢癌等恶性肿瘤中观察到了初步的肿瘤响应，在20名可评估患者中5名达到疾病稳定，其中1名维持稳定超过9个月，临床前研究中，相较于ubamatamab类似物显示出了同等水平的细胞杀伤能力与显著更低的细胞因子释放水平，有望引领MUC16TCE的研发进度。（二）消化系统肿瘤：CLDN18.2TCE管线进入III期临床，MUC17靶点处于早期探索阶段CLDN18.2：国内企业TCE研发进度领先，有望满足后线胰腺癌、胃癌未满足的临床需求CLDN18.2在胃癌等肿瘤中参与肿瘤的侵袭与增殖。CLDN18.2是Claudin家族的成员之一，主要通过调控上皮细胞膜的选择性通透性维持组织屏障功能。在胃癌发生发展过程中，CLDN18.2的表达和定位发生显著异常：约20-30%的病例存在表达下调或缺失，并促进癌细胞的侵袭和增殖。正常情况下定位于紧密连接的CLDN18.2，在细胞极性丧失后暴露于细胞膜表面，成为可及的免疫和药物靶点；此外，CLDN18-ARHGAP融合基因（如CLDN18–ARHGAP26）在弥漫型和年轻患者胃癌中较常见，可推动恶性转化。这些异常不仅参与胃癌的发生发展，也凸显了CLDN18.2作为消化道肿瘤特异性治疗靶点的价值。多款国内企业CLDN18.2TCE进入临床阶段，齐鲁制药QLS31905进入III期临床阶段。胰腺癌预后较差，5年生存率仅为7.2%，存在巨大的未满足临床需求。目前，联合化疗仍是晚期胰腺癌患者的1线标准治疗方案，ORR约为20%，OS不足1年，目前全球尚未批准任何用于胰腺癌1线治疗的免疫疗法，目前晚期胰腺癌治疗仍以系统性化疗为基础。而在2线治疗中，临床选择同样十分有限，主要是1线方案以外的替换方案，化疗响应率仅为6-16%，中位生存期大约仅有3~6个月，存在巨大的未满足临床需求。CLDN18.2在胰腺癌患者中的表达率为50%~70%，有望成为胰腺癌靶向治疗的有效选择。齐鲁制药QLS31905采取将CD3scFv片段偶联至CLDN18.2全长抗体的设计方式，2025年9月8日，齐鲁制药宣布QLS31905用于1线治疗晚期胰腺癌的注册III期临床试验已完成首例受试者入组，旨在评估QLS31905联合白蛋白紫杉醇及吉西他滨化疗作为1线治疗在CLDN18.2阳性晚期胰腺癌患者中的疗效和安全性，成为全球首款进入III期临床试验靶向CLDN18.2的TCE疗法。此外，鲁南制药的LNF2007分别采取1个高亲和力的Fab臂与1个低亲和力的scFv片段靶向CLDN18.2与CD3，该分子目前处于I期临床阶段；阿斯利康/和铂医药的AZD5893（HBM7022）基于和铂医药HBICE®平台，其分子设计上采用2+1结构，采用高亲和力抗CLDN18.2和亲和力优化的抗CD3结构，在保证高杀伤性的同时，降低细胞因子风暴的风险，同时改造Fc端，有效延长半衰期，规避Fc交联和ADCC功能。已实现中美IND获批，全球多中心I期临床计划入组240位患者，预计2026年6月读出临床I期试验数据。后线GC/GEJ适应症中CLDN18.2靶向疗法以ADC为主，相关TCE疗法剂量递增阶段临床数据展现优于2线标准疗法的潜力。目前CLDN18.2TCE疗法中，读出后线GC/GEJ适应症较为成熟临床数据的疗法包括齐鲁制药QLS3190与信达生物IBI389，以2025CSCO指南中纳入的雷莫西尤单抗联合化疗与呋喹替尼联合化疗两类2线GC/GEJ标准疗法进行对比，QLS3190目前数据的ORR、mPFS与mOS与2线标准疗法相当，但考虑到目前的临床数据为剂量递增阶段的I期临床，且入组超过60%3线及以上患者，因此CLDN18.2TCE疗法有望在后续剂量扩展阶段与注册临床中在CLDN18.2阳性患者中展现相对目前2线GC/GEJ标准疗法的优效。后线PDAC适应症中CLDN18.2TCE有望成为Pan-RAS抑制剂的补充疗法。PDAC适应症中，RevolutionMedicines的Pan-RAS(ON)抑制剂Daraxonrasib的临床数据展现了极强的竞争力，其1期临床300mg剂量下在38例2线RAS突变PDAC患者中mPFS达8.1月，69例3线及以上PDAC患者160-300mg剂量下mPFS为4.4m。考虑到RAS突变是90%以上PDAC的驱动因素，因此Daraxonrasib等RAS抑制剂有望成为未来2线PDAC的标准疗法，并有望前移至1线治疗。目前，数据较为成熟的CLDN18.2TCE齐鲁制药QLS3190在CLDN18.2阳性后线PDAC患者中的mPFS为3.94个月，考虑到该数据为350~1200μg/kg剂量递增数据，该数据仍然展现了一定应用于后线PDAC的潜力，CLDN18.2TCE有望成为Pan-RAS抑制剂的后线补充疗法。MUC17：靶点探索处于初期阶段，国产TCE三抗引领靶点进度。MUC17在多种肠道肿瘤中具备作为肿瘤特异性抗原的潜力。MUC17是一种高分子量的跨膜型糖蛋白黏蛋白，主要在肠道上皮中表达，是肠道黏液的重要组成部分。其结构包含信号肽、大量串联重复序列、两个表皮生长因子样结构域、SEA结构域、跨膜区以及80个氨基酸的胞内尾部。MUC17的长N端胞外区高度糖基化，能够调节细胞黏附分子的相互作用，从而影响细胞间黏附，并在抵御细菌入侵、增强黏液屏障功能及减轻损伤黏膜处炎症中发挥重要作用。在结直肠癌中，MUC17的表达缺失与侵袭性和不良预后相关，同时MUC17在胰腺癌、胃癌及胃食管结合部癌中呈高表达，具有作为预后因子或治疗靶点的潜力。MUC17靶点探索仍处于初期，多款国内企业三抗TCE引领靶点进度。当前MUC17靶点尚未读出概念验证数据，当前共有3个中国企业研发的候选分子进入临床阶段。三生制药的SSS59（CD3xMuc17xCD28TCE）目前已披露I期临床的试验方案，I期临床将分为四个阶段：A1部分（每周给药的剂量递增和剂量扩展试验）、A2部分（每两周给药的剂量递增和剂量扩展试验）、A3部分（每三周给药的剂量递增和剂量扩展试验）、B部分（探究SSS59在Muc17阳性、标准治疗失败、不耐受标准治疗晚期胃癌或胃食管结合部腺癌患者的临床疗效）。华东医药HDM2012（Muc17ADC）与泽璟制药ZGGS34（CD3xMuc17xCD28）I期临床IND均已获得NMPA与美国FDA的批准，中国企业有望引领MUC17靶点的临床探索。（三）肝细胞癌：SanofiGPC3/TCR纳米抗体初步读出数据GPC3靶向疗法有望弥补肝癌2线治疗的空白。当前肝细胞癌（（HCC）治疗已进入“手术+系统治疗+局部治疗”多模式时代，肝癌1线治疗主要为靶向+免疫联合方案，而此前获批的2线药物（（如瑞戈非尼、卡博替尼和雷莫芦单抗等单药治疗），在1线已采用靶向加免疫治疗的前提下，无论单药使用还是联合免疫检查点抑制剂，有效率均较低，难以满足临床需求。GPC3（（脂酰肌醇醇蛋白糖糖3）是一种细胞膜锚定糖蛋白，在HCC中特异性高表达，GPC3参与HCC的进展，通过Wnt、Hippo/YAP等信号通路发挥促癌作用，该靶点是HCC诊断的临床生物标志物，也是肿瘤靶向疗法的有效靶标。当前针对GPC3靶点，已有多种药物形式进入临床研究阶段，包括TCE、ADC、肿瘤疫苗、CAR-T、靶向肽等，是当前肝细胞癌靶向疗法的重点领域。SanofiGPC3/TCR纳米抗体SAR444200在末线HCC中展现初步疗效。SAR444200为Sanofi开发的新型纳米抗体TCE，可同时结合TCRαβ和GPC3，使T细胞与GPC3+肿瘤细胞共结合。SAR444200I/II期临床中，入组33名既往治疗3-4线的晚期肿瘤患者（23名HCC），在18例基线甲胎蛋白（AFP）≥20%的HCC患者中，5名（27%）患者的AFP降低≥50%，10名（30.3%）患者报告疾病稳定（SD）。安全性方面，79%的受试者中出现CRS，其中在目标为70mg的两个剂量导入队列中共发生3例CRS被报告为DLT事件。（四）泛癌肿靶点：多款泛瘤种TCE疗法有望陆续迎来数据验证泛瘤种靶点主要包括HER2、EGFR、Trop2、EpCAM、B7H3、B7H4、CLDN6等，相关疗法的数据验证有望持续拓展TCE在实体瘤的应用空间。除EpCAM外，其余泛肿瘤靶点TCE主要处于早期研发阶段。EGFR与Trop2靶点方面，Janux的两款遮蔽肽TCE有望验证在泛肿瘤靶点的有效性与安全性，临床数据值得期待；在B7H3、B7H4、CLDN6等靶点方面，已有多款TCE分子进入临床阶段，国内公司管线例如和铂医药HBM7004、百济神州BGB-B455等有望引领相关靶点的研发进度。时迈药业SMET12EGFRTCE初步验证抗肿瘤活性，有望在食管癌、TNBC等适应症持续拓展。EGFR靶点方面，时迈药业SMET12在EGFR阳性的NSCLC患者开展了多队列I期临床，联合化疗及特瑞普利单抗的1线NSCLC、1线免疫治疗耐药患者、EGFRTKI耐药患者中，mPFS分别为8.3、4.2及7.2个月，DCR最高达100%，ORR分别为83.3%、22.2%和41.7%，安全性方面未出现3级及以上CRS与皮疹等EGFR靶点相关毒性。SMET121线队列数据相较特瑞普利单抗1线联合化疗CHOICE-01临床中的ORR66.7%具有潜在优势，与其8.4m的PFS处于同一水平。对于EGFRTKI耐药患者，其41.7%的ORR相较依沃西单抗联合化疗的HARMONi-A的50.6%略为逊色，7.2m的mPFS则与HARMONi-A中的7.1m处于同一水平。SMET12的初步数据展现了其在EGFR阳性实体瘤中的应用潜力，且具备良好的安全性，时迈药业预计将于2027年完成食管癌IIa期临床试验，并于2027年启动该适应症的III期临床试验，并计划于2026年下半年启动靶向三阴性乳腺癌的IIa期临床试验，有望持续拓展EGFR阳性泛癌肿的治疗前景。多款EGFR遮蔽肽TCE将持续读出首次人体实验数据，有望满足mCRC、HNSCC等EGFR扩增癌肿前线治疗的临床需求，并规避皮疹的靶点毒性。相较于EGFR双抗与ADC在EGFRTKI耐药肺癌中已有丰富的探索和布局，目前mCRC与HNSCC作为EGFR扩增的常见癌肿，尚有较大未被满足的临床需求。根据西妥昔单抗CRYSTAL研究结果，西妥昔单抗联合化疗在KRAS野生型患者中相较化疗mPFS从8.4个月提升至9.9个月（HR=0.696;p=0.0012），mOS仅从20.0个月提升至23.5个月（HR=0.796，p=0.0093），8.8%患者出现3级及以上皮疹；埃万妥单抗在OrigAMI-1研究中，1-2线RAS/BRAF野生型mCRC中，mPFS达9.2个月，OS达19.7个月，我们认为EGFR靶向疗法在mCRC中的总生存期仍有进一步延长的空间。HNSCC方面，目前在1线治疗中Petosemtamab（EGFRxLGR5）联合帕博利珠单抗在1线PD-L1阳性患者中mPFS达9.0个月，12个月OS率为79%，未出现3级及以上皮疹。当前多款EGFR遮蔽肽TCE已推进至临床阶段：（1）JANX008：2025年12月13日Janux宣布JANX008已完成1a期剂量递增阶段，后续将随试验进程更新数据；（2）VIR-5525：I期临床将入组NSCLC、CRC、HNSCC、cSCC等EGFR扩增癌肿，并将在后续探索与帕博利珠单抗的联用前景；（3）CMDE005：时迈药业的CMDE005的CD3结合与其未遮蔽形式相比减少10000倍，而竞争产品JANX008仅减少1000倍，该分子正在国内进行靶向EGFR阳性晚期实体瘤的I期临床试验，并于2025年4月获得FDA的IND批准，公司预计将于2027年完成该I/IIa期临床试验，并于2028年启动III期临床试验。（4）VIB305：信华药业遮蔽肽EGFRTCEVIB305于2025年12月26日启动I/II期临床试验。三、国内多条实体瘤TCE管线已读出具备竞争力的临床数据（一）泽璟制药：ZG006成功出海，ZGGS34已完成中美IND申报ZG006是全球首个三特异性抗体DLL3TCE，已进入关键性临床阶段。ZG006是GensunBiopharmaInc.通过其双/多特异性抗体研发平台开发的CD3及两个不同DLL3表位的三特异性抗体。ZG006被国家药品监督管理局药品审评中心纳入突破性治疗品种，并被美国FDA授予孤儿药资格认定。ZG006是全球第一个针对DLL3靶点的三特异性抗体，为全球同类首创分子形式。2025年9月16日，泽璟制药宣布收到CDE关于ZG006沟通交流申请附条件批准上市资格的反馈意见，基于注射用ZG006现阶段的安全性、有效性数据和拟定的目标人群，CDE同意注射用ZG006开展关键性临床试验，泽璟制药目前已完成首例受试者入组。ZG006临床数据亮眼，有望与艾伯维SEZ6ADC探索联用前景。2025ESMOAsia中，泽璟制药更新了ZG006-002最新的临床结果。截至2025年9月30日，共60例3线及以上SCLC患者按1:1随机接受ZG00610mgQ2W或30mgQ2W治疗，有效性方面，基于IRC评估的结果显示：10mgQ2W组（n=30）和30mgQ2W组（n=30）ORR分别为60.0%和66.7%，cORR分别为53.3%和56.7%，DCR两组均为73.3%；mPFS分别为7.03月和5.59月；6个月的DoR率分别为71.8%和69.5%，9个月的DoR率分别为61.6%和55.6%；6个月的OS率分别为83.2%和76.7%，12个月的OS率分别为69.1%和58.2%。安全性与耐受性良好。2025年12月30日，泽璟制药与艾伯维就ZG006的全球开发及商业化达成战略合作与许可选择权协议，艾伯维获得ZG006在大中华区（中国大陆、香港特别行政区、澳门特别行政区）以外地区独家开发与商业化权利，泽璟将获得1亿美元的首付款，及基于临床进展的近期里程碑付款和与许可选择相关的付款最高6000万美元，如艾伯维行使许可选择权，泽璟还有资格获得最高达10.75亿美元的里程碑付款，并就包含ZG006的产品在大中华区以外的净销售额收取从高个位数到中双位数的阶梯式特许权使用费。艾伯维目前在SCLC治疗领域的核心布局为SEZ6ADCABBV-706，I期临床中1.8mg/kg剂量组在3线ES-SCLC患者（n=16）中ORR达81%，4线以上患者（n=25）中ORR达40%，整体人群mPFS达6.8个月。当前ABBV-706已推进至II/III期1线ES-SCLC临床（NCT07155174），该临床旨在评估ABBV-706联合阿替利珠单抗对比标准治疗作ES-SCLC1线治疗的最佳剂量、安全性和疗效。我们认为，ZG006基于其突出的临床数据与合作方艾伯维在SCLC领域的协同布局，有望成为SCLC的基石疗法，并通过与免疫疗法与ADC的联用覆盖SCLC的全线治疗。ZG006良好的有效性安全性数据使其具备将应用场景通过与PD-(L)1抑制剂的联用推进至1线SCLC的潜力。2025年6月17日，ZG005（PD-1/TIGIT）与ZG006联合用于晚期SCLC或NEC的临床试验获NMPA批准。2025年11月5日，公司启动了ZG006联合PD-1/PD-L1免疫检查点抑制剂用于ES-SCLC一线维持治疗的Ib期研究，以评价ZG006联合PD-(L)1免疫检查点抑制剂治疗广泛期小细胞肺癌一线标准治疗后维持治疗的耐受性和安全性。ZGGS34中美临床获批，有望领跑MUC17靶点的临床探索。ZGGS34是泽璟制药子公司GensunBiopharmaInc.通过其双/多特异性抗体研发平台开发的三特异性抗体药物，ZGGS34分子的一端与肿瘤细胞表面MUC17相结合，抗CD3端和抗CD28端结合T细胞，相对于典型的T细胞结合器类分子，ZGGS34分子中引入了CD28激动抗体，CD28与抗原呈递细胞（APC）上的CD80/CD86结合后，降低TCR激活阈值，增强T细胞增殖、代谢及抗凋亡能力，从而使ZGGS34相对于典型的BiTE分子具有更强的激活T细胞能力，以及持续的T细胞肿瘤杀伤能力，增强抗肿瘤免疫作用。临床前研究结果显示，ZGGS34在多种肿瘤模型上具有显著的肿瘤抑制作用，可以导致肿瘤消退，在已完成的ZGGS34在非人灵长类动物中毒理研究显示其具有毒副作用可控等良好的安全性特征。2025年8月19日和9月17日，ZGGS34先后获得NMPA和FDA的IND审批，研发进度同靶点全球领先。（二）百济神州：塔拉妥单抗上市申请已被纳入优先审评程序，CLDN6TCE进入临床阶段与Amgen深度合作，塔拉妥中国以外权益转让获取大额现金流。2019年10月31日，百济神州与安进达成战略合作，安进将以约27亿美元现金收购百济神州20.5％的股份，安进将与百济神州合作推进安进20款前沿肿瘤产品管线在中国和全球市场的开发。除AMG510外，安进将向百济神州支付这些产品在中国市场以外的全球销售特许使用费，同时百济神州将获得这些产品在中国批准后七年的在中国的商业化权利（（包括AMG510）。此后，百济神州将保留对其中六款产品（不包括AMG510）在中国的权利，而其余产品的权利将归还安进。2025年8月25日，百济神州公告与RoyaltyPharma达成协议，向其出售塔拉妥单抗在中国以外的全球销售额收取特许权使用费的权利。塔拉妥单抗中国区临床已公布阳性结果，国内上市申请已被纳入优先审评程序。DeLLphi-307是一项糖焦中国SCLC人群的前瞻性、单臂、多中心II期临床研究，纳入既往接受过含铂化疗和至少一种其他治疗的ES-SCLC患者，研究共纳入31例患者，84%为男性；3线患者占比为71%，4线及以上患者占比29%。入组时伴有脑转移及肝转移的患者比例分别为35%及45%；所有患者既往均接受过PD-(L)1抑制剂治疗，截至2025年3月28日，接受治疗的患者确认ORR为39%，DCR为61%，中位PFS为2.9个月，中位OS尚未达到。塔拉妥单抗在中国3线及以上ES-SCLC展示出令人鼓舞的疗效及可控的安全性，支持塔拉妥单抗作为中国经治SCLC患者的新治疗选择，2025年7月16日，NMPA官网显示塔拉妥单抗上市申请已获受理，此前该药物已被纳入优先审评程序，拟用于既往接受过至少二线治疗（包括含铂化疗）失败的ES-SCLC成人患者的治疗。此外，Xaluritamig国内临床已于2023年底启动，有望在mCRPC国内人群中复现海外队列的亮眼数据。CLDN6TCE进入临床阶段，有望引领该靶点的研发进度。BGB-B455是一款靶向CLDN6和CD3的TCE分子，当前正在推进CLDN6阳性实体瘤患者的剂量扩增与剂量扩展I期临床试验。CLDN6的异常表达可参与乳腺癌、卵巢癌、宫颈癌、胃癌、肺癌等多种恶性肿瘤发生及发展过程，成为具有潜力的泛癌肿实体瘤治疗靶点。当前，CLDN6ADC已初步展现了该靶点的肿瘤治疗潜力，第一三共的CLDN6ADCDS-9606在I期临床试验的剂量递增阶段显示出对已知表达CLDN6的晚期实体瘤患者良好的临床活性和耐受性，该试验入组共53例中位接受过4线治疗的各类实体瘤患者，在剂量递增试验中未观察到剂量限制性毒性，且在≥0.072mg/kg剂量组中有4例患者达到确认的客观缓解。我们认为CLDN6是具有潜力的泛肿瘤治疗靶点，BGB-B455后续临床结果有望验证其在CLDN6阳性多癌肿的治疗潜力。（三）中国生物制药：M701有望成为中国首个恶性胸腹水标准治疗方案恶性胸腹水常见于中晚期癌症，M701有望成为中国首个恶性胸腹水标准治疗方案。恶性胸腹水是中晚期癌症患者的常见并发症，据公司统计数据显示，超10%的癌症患者在临床病程中会出现恶性胸腹水，中国每年预计有超过60万名新发恶性胸腹水。目前临床缺乏有效的标准治疗方案,仍以穿刺引流联合局部胸腹腔灌注药物为主,局部治疗药物选择有限，EpCAM/CD3双抗同时靶向肿瘤细胞表面的EpCAM和T细胞表面的CD3，从而将T细胞定向到肿瘤细胞,有效地杀伤肿瘤细胞。2024年10月8日，中国生物制药与友芝友签订合作协议，以3.1亿元作为首付款及研发里程碑费用，与最高7亿元的销售里程碑费用以及个位数至低双位数百分比之间的销售分成，获得EpCAM/CD3双抗M701中国大陆地区的权益。同类双抗卡妥索单抗退市后于欧盟重新上市，M701采取人源化设计，有望显示更优疗效。EpCAM/CD3双抗卡妥索单抗作为首款T细胞衔接双抗最初于2009年4月20日在欧盟获得上市许可，用于治疗标准疗法不可用或不再可行的EpCAM阳性成人癌症的恶性腹水，2017年6月2日，由于商业原因，该产品从欧盟退市。2025年2月14日，LindisBiotech与Pharmanovia重新推动该产品在欧盟获批。M701相较于卡妥索单抗进行了人源化改造,免疫原性显著降低,可以持续给药。同时，M701的非对称结构设计优化了CD3端抗体的亲和力,在保留药物效果的同时有效控制了药物的安全性风险。M701II期临床中疗效显著,所有三种类型的癌症患者(胃癌、结直肠癌、卵巢癌)均获益于M701，mPuFS和mOS均有不同程度的延长。除卡妥索单抗在国内由凌腾医药推进III期临床外，其余EpCAM/CD3双抗国内进度均处于临床前阶段，M701进度领先。当前M701恶性腹水单药治疗处于III期临床阶段，恶性胸水联合全身治疗处于II期临床阶段，中国生物制药预计该疗法有望2026年上市销售。通过与勃林格殷格翰达成合作，获得DLL3TCEBI764532的中国大陆权益。2024年4月28日，中国生物制药与勃林格殷格翰宣布签署战略合作协议，双方将依托各自优势和资源，共同在中国内地研发和商业化勃林格殷格翰的肿瘤药物管线，涉及的资产包含MDM2-p53拮抗剂Brigimadlin、选择性HER2抑制剂Zongertinib以及DLL3xCD3TCEBI764532。

New safety and pharmacokinetic data from Phase 3 C-POST trial provide insights on an every 6-week dosing regimen of adjuvant Libtayo® (cemiplimab) in high-risk cutaneous squamous cell carcinomaTARRYTOWN, N.Y., Oct. 15, 2025 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced new and updated data from its advancing oncology pipeline will be shared in seven abstracts at the European Society for Medical Oncology (ESMO) 2025 Meeting, taking place from October 17-21 in Berlin, Germany. Highlights include new Phase 3 C-POST data on an every 6-week dosing regimen for the PD-1 inhibitor Libtayo® (cemiplimab) as adjuvant treatment for cutaneous squamous cell carcinoma (CSCC) with a high risk of recurrence. “Our oncology presentations at ESMO represent important progress toward expanding options for people with difficult-to-treat cancers,” said Israel Lowy, M.D., Ph.D., Clinical Development Unit Head, Oncology, at Regeneron. “Notably, we look forward to sharing new data on a patient-centric every 6-week dosing option from our C-POST Phase 3 trial, which recently supported the FDA approval of Libtayo as the first immunotherapy for adjuvant treatment of adult patients with CSCC at high risk of recurrence after surgery and radiation.” The new safety and pharmacokinetic data from C-POST being presented at ESMO showcase a patient-centric approach to dosing. Patients received either adjuvant therapy with Libtayo or placebo intravenously, starting with 350 mg every 3 weeks for 12 weeks. The majority of patients were switched to every 6-week dosing after the initial 12 weeks, and the remaining patients continued with dosing every 3 weeks throughout the trial. Treatment continued until disease recurrence, unacceptable toxicity, or up to 48 weeks of treatment. Efficacy, pharmacokinetics and immunogenicity were similar across both regimens. The safety profile of Libtayo as adjuvant treatment of patients with CSCC at high risk of recurrence after surgery and radiation is consistent with the known safety profile for Libtayo monotherapy in advanced cancers. The full list of Regeneron presentations at ESMO includes: Abstract TitleAbstractPresenterSession Date/Time(CET)Libtayo skin cancerAnalysis of second primary cutaneous squamous cell carcinoma (CSCC) tumors (SPTs) reported during the C-POST trial, a randomized phase 3 study of adjuvant cemiplimab vs placebo for high-risk CSCCMini-oral presentation: 1603MODanny RischinSaturday, October 18,14:45-16:15Adjuvant cemiplimab for high-risk cutaneous squamous cell carcinoma: Evaluating dosing intervals in a phase 3 trialPoster presentation: 1660PDanny RischinMonday, October 20,12:00-12:45CemiplimAb-rwlc Survivorship and Epidemiology (CASE): A prospective, non-interventional study of the safety and effectiveness of cemiplimab in immunocompromised/immunosuppressed (IC/IS) patients with advanced cutaneous squamous cell carcinoma (CSCC) at 18 months’ follow-upPoster presentation: 1666PSoo J. ParkMonday, October 20,12:00-12:45Libtayo lung cancerAssociation between patient-reported outcomes (PROs) and overall survival (OS) in aNSCLC patients treated with first-line (1L) cemiplimab-based therapyPoster presentation: 1862PDavid R. GandaraSaturday, October 18,12:00-12:45UbamatamabRandomized Phase 2 study of ubamatamab ± cemiplimab in patients (pts) with platinum-resistant ovarian cancer (OC)Poster presentation: 1078PJung-Yun LeeSaturday, October 18,12:00-12:45REGN7075Mitigating infusion-related reactions (IRRs) with cetirizine and montelukast in patients (pts) receiving REGN7075, an EGFRxCD28 bispecific antibody (bsAb)Poster presentation: 1558PNeil H. SegalSunday, October 19,12:00-12:45Additional presentationsPredicting real-world overall survival in advanced melanoma using machine learningPoster presentation: 1632PFei WangMonday, October 20,12:00-12:45 The potential use of ubamatamab described above is investigational, and its safety and efficacy have not been evaluated by any regulatory authority. About Regeneron in Cancer We aspire to turn revolutionary discoveries into medicines that can transform the lives of those impacted by cancer. Our team around the world is driven to solve the needs and challenges of those affected by one of the most serious diseases of our time. Backed by our legacy of scientific innovation and a deep understanding of biology, genetics and the immune system, we’re pursuing potential therapies across more than 30 types of solid tumors and blood cancers. Our cancer strategy is powered by cutting-edge technologies and therapies that can be flexibly combined to investigate potentially transformative treatments for patients. Oncology assets in clinical development comprise nearly half of Regeneron’s pipeline, and include checkpoint inhibitors, bispecific antibodies and costimulatory bispecific antibodies. Our approved PD-1 inhibitor Libtayo serves as the backbone of many of our investigational combinations. To complement our extensive in-house capabilities, we collaborate with patients, healthcare providers, governments, biopharma companies and each other to further our shared goals. Together, we are united in the mission to serve as a beacon of transformation in cancer care. About Libtayo Libtayo is a fully human monoclonal antibody targeting the immune checkpoint receptor PD-1 on T cells and was invented using Regeneron's proprietary VelocImmune® technology. By binding to PD-1, Libtayo has been shown to block cancer cells from using the PD-1 pathway to suppress T-cell activation. Libtayo has been approved by regulatory authorities in more than 30 countries in one or more indications, including for certain adult patients with advanced basal cell carcinoma (BCC), CSCC that is advanced or at high risk of recurrence, advanced non-small cell lung cancer (NSCLC) and advanced cervical cancer. In the U.S., the generic name for Libtayo in its approved indications is cemiplimab-rwlc, with rwlc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. FDA. Outside of the U.S., the generic name of Libtayo in its approved indications is cemiplimab.   The extensive clinical program for Libtayo is focused on difficult-to-treat cancers. Libtayo is currently being investigated in trials as a monotherapy, as well as in combination with either conventional or novel therapeutic approaches for other solid tumors and blood cancers. These potential uses are investigational, and their safety and efficacy have not been evaluated by any regulatory authority. U.S. FDA-approved Indications Libtayo is a prescription medicine used to treat: Adults with a type of skin cancer called cutaneous squamous cell carcinoma (CSCC): that has spread or cannot be cured by surgery or radiation, orto help prevent CSCC from coming back if your CSCC is at high risk of coming back after it has been removed by surgery and radiation. Adults with a type of skin cancer called basal cell carcinoma (BCC) when your BCC cannot be removed by surgery (locally advanced BCC) or when it has spread (metastatic BCC) and have received treatment with a hedgehog pathway inhibitor (HHI), or cannot receive treatment with a HHI. Adults with a type of lung cancer called non-small cell lung cancer (NSCLC). LIBTAYO may be used in combination with chemotherapy that contains a platinum medicine as your first treatment when your lung cancer has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, or your lung cancer has spread to other areas of your body (metastatic lung cancer), and your tumor does not have an abnormal “EGFR,” “ALK,” or “ROS1” gene.LIBTAYO may be used alone as your first treatment when your lung cancer has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, or your lung cancer has spread to other areas of your body (metastatic lung cancer), and your tumor tests positive for high “PD-L1,” and your tumor does not have an abnormal “EGFR,” “ALK,” or “ROS1” gene. It is not known if Libtayo is safe and effective in children.  IMPORTANT SAFETY INFORMATION FOR U.S. PATIENTS  What is the most important information I should know about LIBTAYO?LIBTAYO is a medicine that may treat certain cancers by working with your immune system. LIBTAYO can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen anytime during treatment or even after your treatment has ended. Call or see your healthcare provider right away if you develop any new or worsening signs or symptoms, including: Lung problems: cough, shortness of breath, or chest painIntestinal problems: diarrhea (loose stools) or more frequent bowel movements than usual, stools that are black, tarry, sticky or have blood or mucus, or severe stomach-area (abdomen) pain or tendernessLiver problems: yellowing of your skin or the whites of your eyes, severe nausea or vomiting, pain on the right side of your stomach-area (abdomen), dark urine (tea colored), or bleeding or bruising more easily than normalHormone gland problems: headache that will not go away or unusual headaches, eye sensitivity to light, eye problems, rapid heartbeat, increased sweating, extreme tiredness, weight gain or weight loss, feeling more hungry or thirsty than usual, urinating more often than usual, hair loss, feeling cold, constipation, your voice gets deeper, dizziness or fainting, or changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulnessKidney problems: decrease in your amount of urine, blood in your urine, swelling of your ankles, or loss of appetiteSkin problems: rash, itching, skin blistering or peeling, painful sores or ulcers in mouth or nose, throat, or genital area, fever or flu-like symptoms, or swollen lymph nodesProblems can also happen in other organs and tissues. These are not all of the signs and symptoms of immune system problems that can happen with LIBTAYO. Call or see your healthcare provider right away for any new or worsening signs or symptoms, which may include: chest pain, irregular heartbeat, shortness of breath or swelling of ankles, confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs, double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight, persistent or severe muscle pain or weakness, muscle cramps, low red blood cells, or bruisingInfusion reactions that can sometimes be severe or life-threatening. Signs and symptoms of infusion reactions may include: nausea, vomiting, chills or shaking, itching or rash, flushing, shortness of breath or wheezing, dizziness, feel like passing out, fever, back or neck pain, or facial swellingRejection of a transplanted organ or tissue. Your healthcare provider should tell you what signs and symptoms you should report and monitor you, depending on the type of organ or tissue transplant that you have hadComplications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with LIBTAYO. Your healthcare provider will monitor you for these complications Getting medical treatment right away may help keep these problems from becoming more serious. Your healthcare provider will check you for these problems during your treatment with LIBTAYO. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may also need to delay or completely stop treatment with LIBTAYO if you have severe side effects. Before you receive LIBTAYO, tell your healthcare provider about all your medical conditions, including if you: have immune system problems such as Crohn’s disease, ulcerative colitis, or lupushave received an organ or tissue transplant, including corneal transplanthave received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)have received radiation treatment to your chest areahave a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndromeare pregnant or plan to become pregnant. LIBTAYO can harm your unborn baby Females who are able to become pregnant: Your healthcare provider will give you a pregnancy test before you start treatmentYou should use an effective method of birth control during your treatment and for at least 4 months after your last dose of LIBTAYO. Talk to your healthcare provider about birth control methods that you can use during this timeTell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with LIBTAYO are breastfeeding or plan to breastfeed. It is not known if LIBTAYO passes into your breast milk. Do not breastfeed during treatment and for at least 4 months after the last dose of LIBTAYO Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. The most common side effects of LIBTAYO when used alone to treat CSCC that has spread or cannot be cured by surgery or radiation, BCC or NSCLC include tiredness, muscle or bone pain, rash, diarrhea, and low levels of red blood cells (anemia). The most common side effects of LIBTAYO when used alone to help prevent CSCC from coming back include rash and itching. The most common side effects of LIBTAYO when used in combination with platinum-containing chemotherapy to treat NSCLC include hair loss, muscle or bone pain, nausea, tiredness, numbness, pain, tingling, or burning in your hands or feet, and decreased appetite. These are not all the possible side effects of LIBTAYO. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Regeneron Pharmaceuticals at 1-877-542-8296. Please see full Prescribing Information, including Medication Guide.  About Regeneron's VelocImmune Technology Regeneron's VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron's co-Founder, President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite® technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create a substantial proportion of all original, FDA-approved or authorized fully human monoclonal antibodies. This includes Dupixent® (dupilumab), Libtayo, Praluent® (alirocumab), Kevzara® (sarilumab), Evkeeza® (evinacumab-dgnb), Inmazeb® (atoltivimab, maftivimab and odesivimab-ebgn) and Veopoz® (pozelimab-bbfg). In addition, REGEN-COV® (casirivimab and imdevimab) had been authorized by the FDA during the COVID-19 pandemic until 2024. About Regeneron Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous approved treatments and product candidates in development, most of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, neurological diseases, hematologic conditions, infectious diseases, and rare diseases. Regeneron pushes the boundaries of scientific discovery and accelerates drug development using our proprietary technologies, such as VelociSuite®, which produces optimized fully human antibodies and new classes of bispecific antibodies. We are shaping the next frontier of medicine with data-powered insights from the Regeneron Genetics Center® and pioneering genetic medicine platforms, enabling us to identify innovative targets and complementary approaches to potentially treat or cure diseases. For more information, please visit www.Regeneron.com or follow Regeneron on LinkedIn, Instagram, Facebook or X. Forward-Looking Statements and Use of Digital Media This press release includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron Pharmaceuticals, Inc. (“Regeneron” or the “Company”), and actual events or results may differ materially from these forward-looking statements. Words such as “anticipate,” “expect,” “intend,” “plan,” “believe,” “seek,” “estimate,” variations of such words, and similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. These statements concern, and these risks and uncertainties include, among others, the nature, timing, and possible success and therapeutic applications of products marketed or otherwise commercialized by Regeneron and/or its collaborators or licensees (collectively, “Regeneron’s Products”) and product candidates being developed by Regeneron and/or its collaborators or licensees (collectively, “Regeneron’s Product Candidates”) and research and clinical programs now underway or planned, including without limitation Libtayo® (cemiplimab) as adjuvant treatment for cutaneous squamous cell carcinoma (“CSCC”) with a high risk of recurrence as well as the other programs discussed or referenced in this press release; uncertainty of the utilization, market acceptance, and commercial success of Regeneron’s Products (such as Libtayo as an adjuvant treatment for CSCC) and Regeneron’s Product Candidates and the impact of studies (whether conducted by Regeneron or others and whether mandated or voluntary), including the studies discussed or referenced in this press release, on any of the foregoing or any potential regulatory approval of Regeneron’s Products and Regeneron’s Product Candidates (such as those referenced above); the likelihood, timing, and scope of possible regulatory approval and commercial launch of Regeneron’s Product Candidates and new indications for Regeneron’s Products, such as the programs discussed or referenced in this press release; the ability of Regeneron’s collaborators, licensees, suppliers, or other third parties (as applicable) to perform manufacturing, filling, finishing, packaging, labeling, distribution, and other steps related to Regeneron’s Products and Regeneron’s Product Candidates; the ability of Regeneron to manage supply chains for multiple products and product candidates and risks associated with tariffs and other trade restrictions; safety issues resulting from the administration of Regeneron’s Products and Regeneron’s Product Candidates (such as those referenced above) in patients, including serious complications or side effects in connection with the use of Regeneron’s Products and Regeneron’s Product Candidates in clinical trials; determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron’s ability to continue to develop or commercialize Regeneron’s Products and Regeneron’s Product Candidates; ongoing regulatory obligations and oversight impacting Regeneron’s Products, research and clinical programs, and business, including those relating to patient privacy; the availability and extent of reimbursement or copay assistance for Regeneron’s Products from third-party payors and other third parties, including private payor healthcare and insurance programs, health maintenance organizations, pharmacy benefit management companies, and government programs such as Medicare and Medicaid; coverage and reimbursement determinations by such payors and other third parties and new policies and procedures adopted by such payors and other third parties; changes in laws, regulations, and policies affecting the healthcare industry; competing drugs and product candidates that may be superior to, or more cost effective than, Regeneron’s Products and Regeneron’s Product Candidates (including biosimilar versions of Regeneron’s Products); the extent to which the results from the research and development programs conducted by Regeneron and/or its collaborators or licensees may be replicated in other studies and/or lead to advancement of product candidates to clinical trials, therapeutic applications, or regulatory approval; unanticipated expenses; the costs of developing, producing, and selling products; the ability of Regeneron to meet any of its financial projections or guidance and changes to the assumptions underlying those projections or guidance; the potential for any license, collaboration, or supply agreement, including Regeneron’s agreements with Sanofi and Bayer (or their respective affiliated companies, as applicable), to be cancelled or terminated; the impact of public health outbreaks, epidemics, or pandemics on Regeneron's business; and risks associated with litigation and other proceedings and government investigations relating to the Company and/or its operations (including the pending civil proceedings initiated or joined by the U.S. Department of Justice and the U.S. Attorney's Office for the District of Massachusetts), risks associated with intellectual property of other parties and pending or future litigation relating thereto (including without limitation the patent litigation and other related proceedings relating to EYLEA® (aflibercept) Injection), the ultimate outcome of any such proceedings and investigations, and the impact any of the foregoing may have on Regeneron’s business, prospects, operating results, and financial condition. A more complete description of these and other material risks can be found in Regeneron’s filings with the U.S. Securities and Exchange Commission, including its Form 10-K for the year ended December 31, 2024 and its Form 10-Q for the quarterly period ended June 30, 2025. Any forward-looking statements are made based on management’s current beliefs and judgment, and the reader is cautioned not to rely on any forward-looking statements made by Regeneron. Regeneron does not undertake any obligation to update (publicly or otherwise) any forward-looking statement, including without limitation any financial projection or guidance, whether as a result of new information, future events, or otherwise. Regeneron uses its media and investor relations website and social media outlets to publish important information about the Company, including information that may be deemed material to investors. Financial and other information about Regeneron is routinely posted and is accessible on Regeneron's media and investor relations website (https://investor.regeneron.com) and its LinkedIn page (https://www.linkedin.com/company/regeneron-pharmaceuticals). Contacts:Media RelationsTaylor Ramsey SkottTel: +1 914-847-5459Taylor.Ramsey@Regeneron.comInvestor RelationsMark HudsonTel: +1 914-847-3482mark.hudson@regeneron.com