Elranatamab

随着MNC与国内Biotech的BD交易不断涌现，TCE疗法浮出水面，成为医药行业重点押注的赛道。 10月31日，艾伯维出手14.65亿美元，押注TCE，与EvolveImmune Therapeutics达成合作，利用其专有的TCE平台共同开发肿瘤药物。 10月29日，GSK宣布和恩沐生物达成协议，将以 3 亿美元的预付款收购恩沐生物处于临床阶段的靶向 CD19 和 CD20 的双重 T 细胞接合器 （TCE）CMG1A46。恩沐生物将有资格获得总计 5.5 亿美元CMG1A46开发和商业里程碑付款。 8月9日，默沙东通过13亿美元收购同润生物医药B细胞耗竭疗法在研TCE药物CN201：下一代CD19×CD3双抗。首付款到惊人的7亿美元，同润生物还有资格获得高达6亿美元的里程碑付款。 回看2024年国内药企的海外BD交易，多家Biotech的出海管线都直指TCE疗法，除了恩沐生物与同润生物外，嘉和生物、岸迈生物、康诺亚、药明生物等均实现了TCE疗法的BD授权，交易总金额已高达30亿美元。 现象级事件仍在出现，海外创新药企Candid Therapeutic在2024年9月中旬宣布完成3.7亿融资，创下2024年来生物医药行业最高募资金融的记录，旗下两款核心产品都是从中国药企刚成立的海外NewCo公司买来的，而且都是时下热门的自免疾病TCE双抗品种。 除了BD交易外，安进的TCE双抗药物Imdelltra在今年5月获得FDA批准上市，成为全球首款用于治疗实体瘤的TCE疗法。 从血液瘤到实体瘤，再扩展到自免疾病，TCE疗法或将成为医药行业众多玩家争夺的下一颗金苹果。 01 TCE双抗到底强在哪？ TCE（T cell Engager），即T细胞衔接器类药物，通过借助T细胞对肿瘤细胞的杀伤作用来实现癌症治疗，目前在血液瘤领域已经取得显著成效。 在血液瘤治疗中，TCE通过CD3与不同B细胞靶点（如CD19、CD20和BCMA）的结合，取得了显著的治疗效果。TCE双抗的一端通过CD3与T细胞结合，另一端（或两端）与TAA（肿瘤相关抗原）结合，帮助T细胞定位并激活其杀伤能力，从而达到对肿瘤细胞的杀伤目的。 TCE与CAR-T都是借助T细胞达到治疗疾病效果，并且从血液瘤到实体瘤再到自免疾病的扩张路径与CAR-T相似。基于TCE与CAR-T在作用机制方面的相似性，行业经常将两种疗法进行比较，看谁能在市场占得先机。那么与CAR-T相比，TCE到底差异化在哪里？ 首先在血液瘤领域，目前TCE及CAR-T均有多款产品上市，CAR-T的疗效更具优势，但已上市的CAR-T都是自体产品，成本高、生产周期长、价格昂贵。相比之下，TCE药物作为“现货”药物，更容易推广使用。 在实体瘤领域，随着安进的Tarlatamab（CD3/DLL3）于今年5月获得FDA批准上市治疗小细胞肺癌，TCE治疗实体瘤已经取得初步突破。尽管GPC3 CAR-T及Claudin 18.2 CAR-T在临床上已经看到一定的疗效，但离获批上市还有相当的距离。因此，预计在实体瘤治疗方面TCE会领先CAR-T一段时间。 在自免疾病领域，安全性方面CAR-T可能引起细胞因子风暴（CRS），而TCE药物通过调节剂量能更好地控制风险，例如Teclistamab在治疗中通过剂量爬坡，显示出良好的安全性，无神经毒性或骨髓抑制，仅有低级别CRS。 此外，自免疾病作为慢病，患者对于长期疗效、安全性、给药便宜性相较于肿瘤有更高的要求。CAR-T制备过程复杂，治疗过程亦包括单采、清淋等多个步骤，回输后患者还需住院观察。而TCE可以做成皮下给药，在给药、患者依从性方面都有着很大优势。 据行业资深人士介绍，TCE的机理跟ADC很相似，都具有三个结构域，一个结构域与T细胞受体的组分结合，一个结构域与肿瘤相关抗原结合，第三个结构域提供额外的功能，如延长半衰期。从机理上来看，与常规的IgG相比，TCE被认为比Fc介导的ADC更有效。此外，由于杀伤肿瘤细胞的过程是靠自身T细胞完成的，因此又比ADC的毒性更低。 正是基于诸多优势，TCE双抗尤其是靶向CD3+T细胞重定向双特异性抗体，成为近年来双抗的研究热点，也被称为接棒ADC的潜力药物。 02 血液瘤治疗成效显著，实体瘤研究迎新突破 通常来说，行业将TCE双抗的发展分为三个阶段，分别对应血液瘤、实体瘤、自免疾病这三个治疗领域。 在血液瘤领域，TCE双抗持续取得进展。据Mordor Inteligence数据，预计2024年全球血液瘤市场规模约670亿美元，2029年约980亿美元，年复合增长率7.8%。 目前全球共有10款TCE双抗获批上市，血液瘤占了7款，主要来自安进、罗氏、艾伯维，覆盖BCMA、GPRC5D、CD20和CD19等靶点，获批多发性骨髓瘤、弥漫大B细胞淋巴瘤等多个血液瘤适应症。其中中国获批2款产品，分别为安进/百济神州的贝林妥欧单抗和罗氏的格罗菲妥单抗。 已上市的10款TCE药物 此外，强生于2022年和2023年分别获批了TCE双抗药物，随着后续药物联用以及从末线到前线患者的全覆盖，强生对其两款Talquetamab和TeclistamabTCE双抗药物的预期销售额均接近50亿美元。 值得一提的是，TCE双抗的高性价比为末线多发性骨髓瘤（MM）患者提供了新的治疗选择。全球多发性骨髓瘤患者人数约45万人，当下常用药物包括蛋白酶体抑制剂，免疫调节剂以及抗CD38抗体等，但是复发和耐药性一直是难以解决的问题，也使得末线MM患者受益不佳。 细胞疗法和TCE双抗的出现，在R/R MM患者中展现出高缓解率，新版本NCCN指南建议接受过≥4线治疗的患者可以将CAR-T和TCE双抗作为优选疗法。 相较于CD38单抗，在末线MM患者中，Teclistamab和Elranatamab单药治疗RRMM展现出更高的客观缓解率（ORR：61-63% vs31%），且表现潜在翻倍的生存获益（mPFS：11.3 vs 3.7，mOS 18.3 vs 9.3）。虽然相较于CAR-T疗法，BCMA/CD3双抗的疗效略差（ORR:98% VS 61-63%），但是安全性更佳（CRS：95% vs 58%-72%），且治疗成本更低。TCE优秀的可及性给了这些患者另外一个选择。 在实体瘤领域，此前TCE双抗在实体瘤中相较于血液瘤的研究进展缓慢，这主要基于几大因素。一方面，早期针对实体瘤开发的靶点比如HER2、EGFR、TROP2以及MUC1等也在正常组织中表达，由于TCE双抗活性较高，导致T细胞在攻击目标时容易“误伤”。而提高剂量又会牺牲安全性，需要在疗效和安全性之间找到平衡点。 另一方面，肿瘤微环境的免疫抑制是一个重要因素，它限制了T细胞的活性和效果。不仅如此，T细胞浸润水平有限也限制了TCE双抗在实体瘤的治疗疗效。 随着对这些挑战的深入了解和新策略的开发，TCE双抗在实体瘤治疗中的潜力正在逐步被挖掘和实现。比如，新一代针对实体瘤的TCE双抗药物在设计上逐步打开思路。首先在靶点的选择上偏向于肿瘤特异性表达更强，如DLL3和PSMA等靶点。同时，优化抗原识别臂的效价和亲和力以提高对于肿瘤组织的选择性。最后，通过药物联用来突破免疫抑制。 今年5月，安进的塔拉妥单抗被FDA加速批准用于治疗三线小细胞肺癌，也成为首款治疗实体瘤的TCE药物，给TCE在实体瘤领域大放异彩探明了道路。此外，针对PSMA，STEAP-1等靶点的TCE双抗，也在不断释出针对前列腺癌的早期优异数据。未来，TCE药物在实体瘤领域的爆发拭目可待。 03 20余款自免产品在研，有望开辟下一个千亿市场 对于业内最近如此密集收购TCE双抗资产，有行业人士表示，这在一定程度上是由于MNC看到了TCE在自免疾病领域的应用，诸如系统性红斑狼疮、强直性脊柱炎以及银屑病等自免类疾病，相关治疗药物未来会越来越成为各大药企兵家必争之地。 众所周知，B细胞在多种自免疾病中扮演关键角色，深度清除B细胞能够治疗多种自免疾病。TCE双抗由于本身是在免疫细胞上做文章，自然能被开发成自身免疫调控的产品。也有观点认为，未来该赛道或将解绑肿瘤领域，成为下一个千亿市场的超级赛道。 事实上，在肿瘤深入探索的同时，部分药企也确实将目光瞄向自免市场。 目前全球共有20余款处于活跃状态的 TCE药物开展了自免相关的临床研究，靶点组合类型主要集中在 CD3×CD19、CD3×CD20、CD3×BCMA等。 全球在研的针对自免疾病的TCE双抗 在海外MNC中，罗氏的CD20/CD3双抗、安进BCMA/CD3双抗陆续开展了TCE双抗在自免适应症的临床试验，这也意味着，TCE双抗有可能打开自免这一广阔的市场空间。 此前默沙东斥资13亿美元收购同润生物的CD3xCD19双抗CN201，也是由于看中了CN201在自免领域突围的可能。正是在这一逻辑下，更多的MNC围猎国产分子，希望挖掘TCE多抗在自免市场的潜力。 目前国内在TCE自免应用领域，靶向CD3/BCMA的双抗中，除了达成交易的岸迈生物、康诺亚之外，智翔金泰、正大天晴、新时代药业、益科斯特也有同类产品进入临床研究阶段。 靶向CD3/CD19的双抗中，除同润生物外，益科斯特、亿一生物、绿竹生物、新时代药业的同类产品也已进入临床研究阶段。 靶向CD3/CD20的双抗中，爱思迈、康诺亚、亿腾嘉和、天广实、正大天晴、君实生物、神州细胞的同类产品也已进入临床研究阶段。 此外，信达生物的CD3/CLDN18.2双抗已进入II期临床阶段，研发进度在全球范围内都属领先。 04 国产TCE研发独辟蹊径，多种适应症中崭露头角 随着TCE平台的逐步成熟，国内企业也开始布局TCE平台。我们也发现，与国外主要以血液瘤到实体瘤再到自免疾病的研发路线相比，国内在TCE药物的研发布局方面则有所不同，很多企业甚至跳过了肿瘤领域，直接开始自免领域的研究。 对比之下，国外TCE研发初期主要集中在血液瘤领域，如多发性骨髓瘤和弥漫大B细胞淋巴瘤，并在部分血液瘤治疗中展现出显著的疗效，市场相对成熟。国内虽然也在积极推进TCE药物的研发，但由于市场相对较小，且大部分处于临床早期阶段，因此市场进展较为缓慢。 国内在初期更多关注的是实体瘤领域，但由于实体瘤的复杂性和安全性挑战，正在逐步加强自免领域的TCE药物研究。 在安全性方面，TCE药物的设计面临的挑战之一是如何平衡疗效和安全性，特别是在控制细胞因子风暴方面，国外公司在这方面的技术研究较为深入。国内公司在开发TCE药物时在积极探索降低CD3亲和力的设计，以提高药物的安全性。 总体来说，国内外在TCE研发上各有侧重和挑战，但随着技术的不断进步和临床数据的积累，TCE药物有望在更多癌症治疗中发挥重要作用。 目前国内来看，泽璟制药在实体瘤有所布局，其首款针对DLL3的三抗进度全球最优，潜力巨大。作为小细胞肺癌领域安进生物Tarlatamab（DLL3/CD3）国内对标品，并且相较于安进有着更高的活性，能更高的结合中低表达位点。 智翔金泰在血液瘤有所布局，核心产品GR1803的临床数据显示，其对于髓外病变患者展现出100% ORR，数据优异。 此外，信达生物在实体瘤及血液瘤均有布局；同润生物的CN201以及其他公司有望在自免适应症进行布局；岸迈生物拥有一款CD3/ROR1双抗；友芝友生物靶向CD3/EpCAM的双抗进展较快，已步入III期临床阶段等等。 未来随着国内企业在TCE上的研究日渐成熟，我们也看好后续各种类型的TCE类药物在多种适应症上迎来突破。 05 BD、融资、并购、NewCo……TCE多点开花 2024年，TCE双抗领域无疑成为了市场上的焦点，重磅交易、大额融资、并购还是NewCo模式……TCE都展现出了非凡的活力和热度，无论从哪个方面来看都可谓十分火爆。 2024年TCE交易情况（不完全统计） 在交易方面，据动脉网不完全统计，2024年共发生了将近20笔交易，总金额超85亿美元。在这些交易中，涉及国内项目金额最高的两笔交易分别为同润生物与默沙东达成的CD3/CD19双抗TCE交易（13亿美元），以及恩沐生物与GSK达成的CD3/CD19/CD20三抗TCE交易（8.5亿美元）。 在TCE领域，NewCo的资本运作模式也越来越受欢迎。比如今年9月岸迈生物的BCMA×CD3双抗EMB-06出海，便是以NewCo模式完成的，该笔交易中6000万美元的首付款有相当一部分将以股权形式支付。据了解，此次交易受让方Vignette Bio由Foresite capital孵化，启明创投也参与了其融资。今年9月，在该笔BD发生前，该公司被Candid Therapeutics收购。 值得一提的是，融资方面，也是在今年9月，此次交易之后，Candid Therapeutics获得了3.7亿美元A轮融资，用于治疗自身免疫疾病，也创下了今年欧美生命科学领域金额最大单轮融资记录。 收购方面，今年1月，默沙东宣布以每股23美元的价格，共计6.8亿美元收购了harpoon。通过这次收购，默沙东不仅获得了目前临床中具有前景的DLL3/CD3抗体，而且获得的Harpoon多个三特异抗体平台，包括下一代多特异抗体平台——在肿瘤微环境中特异性激活的ProTriTAC和TriTAC-XR三特异抗体平台，从而快速切入TCE赛道。 无论是从BD、融资、并购还是NewCo模式各方面来看，TCE赛道呈现出多点开花的局面，预示着该领域的蓬勃发展和未来潜力。 当然，对于一款药物来说，最核心的还是其临床竞争力。从这个方面来说，TCE不论是在血液瘤、实体瘤或是自免领域，都有着无穷的潜力和想象空间。 在多发性骨髓瘤领域，多款TCE双抗在全球与标准疗法进行头对头的一线和二线临床实验，希望在未来成为多发性骨髓瘤的新一代基石药物。在DLBCL领域，CD20/CD3双抗希望完成从三线走向二线、一线的跃迁。如果能够在临床上证明其获益，TCE双抗必然会与CAR-T、ADC等形成竞争。 目前，与CAR-T相比，TCE双抗虽然在疗效上较弱，但在安全性和便利性上有着更好的表现。面对火热的ADC，TCE双抗也有着显著的差异化，一方面对靶点表达量要求较低，但对肿瘤特异性要求更高，或可以与之形成错位竞争。 可以预见的是，TCE双抗在未来将继续引领行业热潮，催生更多具有里程碑意义的重磅交易。这不仅为医药企业带来了逆袭的机遇，而且有望在产品开发和市场布局上引发一场创新和颠覆的革命。 参考资料： TCE双抗，抗体药物的下一个爆发点，血液瘤+实体瘤+自免——辰小飞的log 双抗license out大爆发背后：两个风口与潜力新星——医药魔方Info TCE vs CAR-T：市场的反应——津津药道 TCE双抗还得更火——氨基观察 *封面图片来源：123rf 如果您认同文章中的观点、信息，或想进一步讨论，请与我们联系；也可加入动脉网行业社群，结交更多志同道合的好友。 近 期 推 荐 声明：动脉网所刊载内容之知识产权为动脉网及相关权利人专属所有或持有。未经许可，禁止进行转载、摘编、复制及建立镜像等任何使用。 动脉网，未来医疗服务平台

NEW YORK--( BUSINESS WIRE )--Pfizer Inc. (NYSE: PFE) will highlight the latest advancements from its growing hematology and breast cancer portfolios at the American Society of Hematology (ASH) Annual Meeting & Exposition (December 7-10) and the San Antonio Breast Cancer Symposium (SABCS, December 10-13). Data from more than 100 company-sponsored, investigator-sponsored, and collaborative research abstracts, including 13 oral presentations and four poster spotlights, will be shared across the company’s approved medicines and expanding portfolio of potential breakthroughs for patients with blood and breast cancers, as well as rare blood disorders. “ Our robust presence at ASH and SABCS reinforces Pfizer’s legacy of scientific innovation for people living with blood disorders and breast cancer,” said Chris Boshoff, Chief Oncology Officer and Executive Vice President, Pfizer. “ We are pleased to share the latest updates for some of our key approved medicines, including ADCETRIS, ELREXFIO, and IBRANCE, which continue to generate compelling data as foundations of care in their respective indications. We are also excited to present new results in hemophilia and from our expanding pipeline of innovative, next-generation therapy candidates for both blood and breast cancers, including new data on combination approaches across our core scientific modalities.” Key ASH Presentations Data from more than 75 company-sponsored, investigator-sponsored, and collaborative research abstracts will be presented at ASH, including updated analyses from the pivotal ECHELON-3 trial supporting the clinical benefit of ADCETRIS ® (brentuximab vedotin) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). New data for ELREXFIO ® (elranatamab-bcmm) in relapsed/refractory multiple myeloma (RRMM) will also be presented from the pivotal MagnetisMM-3 trial, as well as Phase 1 combination data from the MagnetisMM-20 trial. Pfizer will also present updates from its growing Hematology-Oncology pipeline, which includes next-generation CD30 antibody-drug conjugates and other novel and differentiated molecules, including the first presentation of combination data for SEA-CD70 in high-risk myelodysplastic syndromes. Additionally, Pfizer will present results across its portfolio of investigational and approved medicines in benign hematology. ADCETRIS: Additional analyses from the Phase 3 ECHELON-3 trial will be presented, highlighting the durability of complete responses and consistent benefit of ADCETRIS in combination with lenalidomide and rituximab in patients with relapsed/refractory DLBCL, including enrollment of elderly patients, those who are refractory to most recent treatment, and those who have received prior CAR-T therapy. These findings also underscore the overall survival (OS) advantage over lenalidomide and rituximab plus placebo in patients who have received at least two prior lines of therapy. In addition, updated two-year follow-up data from a Phase 2 study investigating the combination of ADCETRIS, nivolumab, doxorubicin, and dacarbazine in newly diagnosed early-stage classical Hodgkin lymphoma (cHL) will be presented highlighting promising efficacy and safety of this investigational novel combination. ELREXFIO: A post hoc analysis of the Phase 2 MagnetisMM-3 trial continues to show deep and durable responses after longer-term follow-up of nearly three years, and these responses were also maintained with a reduction to once-monthly dosing in RRMM. Data will also be shared from the ongoing Phase 1b MagnetisMM-20 trial that indicate encouraging clinical efficacy and predictable safety signals with ELREXFIO in combination with carfilzomib and dexamethasone after a median of two prior lines of therapy (range: one to three). SEA-CD70 (PF-08046040): Encouraging preliminary data from the ongoing Phase 1 study with PF-08046040, also known as SEA-CD70, a nonfucosylated monoclonal antibody targeting CD70 that is designed to enhance effector function, will be shared for the first time from the combination dose-optimization cohort with azacitidine in patients with higher-risk myelodysplastic syndromes (MDS). SEA-CD70 is being developed with the goal of being a best-in-class foundational medicine either alone or as combination treatment in myeloid malignancies. Key SABCS Presentations Data from 30 company-sponsored, investigator-sponsored, and collaborative research abstracts will be presented at SABCS, including nine real-world analyses affirming IBRANCE ® (palbociclib) as a first-line standard-of-care treatment for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). The company will also present new data from its expanding pipeline of innovative, next-generation therapy candidates that have the potential to address critical unmet patient needs across all subtypes and stages of breast cancer, including new and updated Phase 1 data for atirmociclib, vepdegestrant, and the novel KAT6 inhibitor, PF-07248144. IBRANCE : In P-VERIFY, the largest-ever real-world comparative overall survival analysis of first-line CDK4/6 inhibitors plus aromatase inhibitor (AI) therapy in HR+/HER2- MBC, numerically similar overall survival rates were observed across CDK4/6 inhibitor groups at 12, 24, and 30 months. Atirmociclib (PF-07220060): Updated data will be presented from a Phase 1/2a study of atirmociclib, a next-generation, highly selective CDK4 inhibitor, in combination with letrozole as a potential first-line treatment for patients with HR+/HER2- MBC. Atirmociclib is being developed as a potential future CDK inhibitor backbone therapy in HR+ MBC, and a Phase 3 study in the first-line setting is anticipated to start by early 2025. Vepdegestrant: For the first time, initial Phase 1b data will be shared from the Phase 1b/2 TACTIVE-U trial evaluating the combination of vepdegestrant, a potential first-in-class PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader, in combination with abemaciclib in patients with ER+/HER2- locally advanced or MBC. These data reinforce the potential of vepdegestrant as a new backbone endocrine therapy, and Pfizer and Arvinas anticipate topline Phase 3 data evaluating vepdegestrant as a monotherapy in the first quarter of 2025. KAT6 (PF-07248144) : Updated efficacy and safety data will be presented from a Phase 1 dose-expansion study of PF-07248144, a novel KAT6 inhibitor, in heavily pretreated ER+/HER2- MBC. These early data continue to provide strong clinical proof of concept for this novel target as a potential new treatment approach for ER+/HER2- MBC, and Pfizer anticipates initiating a Phase 3 study for PF-07248144 in the post-CDK4/6 inhibitor setting in mid-2025. Additional information on key Pfizer-sponsored abstracts at ASH and SABCS, including date and time of presentation, follow in the chart below. A complete list of Pfizer-sponsored accepted abstracts is available here: https://www.pfizer.com/ASH_and_SABCS_2024_Sponsored_Abstracts . Blood Cancers Updated Analysis of Brentuximab Vedotin, Nivolumab, Doxorubicin, and Dacarbazine for Nonbulky, Early-Stage Classical Hodgkin Lymphoma (Abstract #460) Abramson J Oral Presentation Sunday, December 8, 9:30-11:00 AM PST Presentation Time: 10:15 AM PST Efficacy of Elranatamab (ELRA) in Combination with Carfilzomib (CFZ) and Dexamethasone (DEX) in the Phase 1b MagnetisMM-20 Trial in Relapsed or Refractory Multiple Myeloma (RRMM) (Abstract #1024) Tomasson MH Oral Presentation Monday, December 9, 4:30-5:30 PM PST Presentation Time: 5:15 PM PST PF-08046040 (SEA-CD70), a Nonfucosylated CD70-Directed Antibody, in Combination with Azacitidine for Patients with Myelodysplastic Syndromes (MDS): A Phase 1 Dose-Finding and Dose Expansion Study (Abstract #1840) Poster Presentation Saturday, December 7, 5:30-7:30 PM PST Durability of Complete Responses in Patients from the ECHELON-3 Study (Abstract #3101) Yasenchak C Poster Presentation Sunday, December 8, 6:00-8:00 PM PST MagnetisMM-3: Long-Term Update and Efficacy and Safety of Less Frequent Dosing of Elranatamab in Patients with Relapsed or Refractory Multiple Myeloma (Abstract #4738) Prince M Poster Presentation Monday, December 9, 6:00-8:00 PM PST Outcomes in Older Patients with Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) from the ECHELON-3 Study (Abstract #4483) Bartlett N Poster Presentation Monday, December 9, 6:00-8:00 PM PST Outcomes by Refractory Status and Prior Therapies Received in Patients with Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) from the ECHELON-3 Study (Abstract #4489) Hahn U Poster Presentation Monday, December 9, 6:00-8:00 PM PST Hemophilia Efficacy and Safety of Giroctocogene Fitelparvovec in Adults with Moderately Severe to Severe Hemophilia Α: Primary Analysis Results from the Phase 3 AFFINE Gene Therapy Trial (Abstract #1053) Leavitt AD Oral Presentation Monday, December 9, 4:30-6:00 PM PST Presentation Time: 5:00 PM PST Descriptive Characterization of Bleeding Events in Participants with Severe Hemophilia Α or B without Inhibitors, Receiving Prophylactic Marstacimab Treatment (Abstract #716) Matino D Oral Presentation Monday, December 9, 10:30 AM-12:00 PM PST Presentation Time: 10:45 AM PST Sickle Cell Disease Qualitative Interview Study to Characterize the Treatment Experiences of Participants with Sickle Cell Disease and Assess Perceptions of Red Blood Cell Transfusions (Abstract #3691) Kosa K Poster Presentation Sunday, December 8, 6:00-8:00 PM PST Breast Cancer Comparative overall survival of CDK4/6is plus an aromatase inhibitor (AI) in HR+/HER2- MBC in the US real-world setting Rugo et al Poster Spotlight Presentation (PS2-03) Thursday, December 12, 7:00-8:30 AM CST PF-07248144, a first-in-class KAT6 inhibitor, in patients with HR+ HER2− metastatic breast cancer: Updated results from phase 1 dose expansion study Mukohara et al Poster Presentation (P4-10-28) Thursday, December 12, 5:30-7:00 PM CST Vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) Estrogen Receptor (ER) Degrader, Plus Abemaciclib in ER-Positive/Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Advanced or Metastatic Breast Cancer: TACTIVE-U Preliminary Phase 1b Results Hilton et al Poster Presentation ​(P4-12-03) Thursday, December 12, 5:30-7:00 PM CST The next-generation CDK4-selective inhibitor atirmociclib (PF-07220060) in combination with letrozole as first-line treatment in patients with HR+/HER2+ metastatic breast cancer Giordana et al Poster Presentation (P5-07-28) Friday, December 13, 12:30-2:00 PM CST About Pfizer Oncology At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and bispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives. About Pfizer Rare Disease There are over 10,000 known rare diseases that affect approximately 400 million people worldwide. 80% of these diseases have genetic origins and 50% affect children. Collectively, people living with a rare disease represent one of the largest underserved patient communities in the world, with less than 10% of known rare diseases having one or more approved treatments. At Pfizer, we believe that people living with a rare disease, along with the untold number of family members and caregivers who support them, deserve more. For more than 40 years, we have provided critical treatment options for patients with rare diseases including 11 Pfizer Rare Disease medicines that have received regulatory approval. Prescribing Information for Pfizer Medicines Please read full Prescribing Information , including BOXED WARNING, for ADCETRIS. Please read full Prescribing Information , including BOXED WARNING, for ELREXFIO. Please read full Prescribing Information for HYMPAVZI. Please see full Prescribing Information for IBRANCE ® (palbociclib) tablets and IBRANCE ® (palbociclib) capsules . About Pfizer: Breakthroughs That Change Patients’ Lives At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety, and value in the discovery, development, and manufacture of healthcare products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments, and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with healthcare providers, governments, and local communities to support and expand access to reliable, affordable healthcare around the world. For 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com . In addition, to learn more, please visit us on www.Pfizer.com and follow us on X at @Pfizer and @Pfizer_News , LinkedIn , YouTube , and like us on Facebook at www.facebook.com/Pfizer/ . Disclosure notice The information contained in this release is as of December 5, 2024. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments. This release contains forward-looking information about Pfizer’s hematology and breast cancer portfolio and pipeline, ADCETRIS (brentuximab vedotin), ELREXFIO (elranatamab-bcmm), SEA-CD70 (PF-08046040), IBRANCE (palbociclib), atirmociclib (PF-07220060), vepdegestrant, and the novel KAT6 inhibitor, PF-07248144 , including their potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, uncertainties regarding the commercial success of Pfizer’s breast cancer and hematology products and product candidates; the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when any applications may be filed with any regulatory authorities for any potential indications for brentuximab vedotin, elranatamab-bcmm, PF-08046040, palbociclib, PF-07220060, vepdegestrant, and PF-07248144, or any other product candidates; whether and when any applications that may be pending or filed for brentuximab vedotin, elranatamab-bcmm, PF-08046040 or any such other product candidates may be approved by regulatory authorities, which will depend on myriad factors, including making a determination as to whether the product’s benefits outweigh its known risks and determination of the product’s efficacy and, if approved, whether brentuximab vedotin, elranatamab-bcmm, PF-08046040, palbociclib, PF-07220060, vepdegestrant, and PF-07248144, or any such other product candidates will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of brentuximab vedotin, elranatamab-bcmm, PF-08046040, palbociclib, PF-07220060, vepdegestrant, and PF-07248144, or any such other product candidates; uncertainties regarding the impact of COVID-19 on our business, operations and financial results; and competitive developments. A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “ Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com .