Tolebrutinib

作者 | 辰公子来源 | 医界望远镜近几年创新药企可能会发现，他们面对的研发挑战和之前完全不一样了。随着近年来产业上下游服务的全面发展，新药研发的门槛迅速降低，爬上“巨人肩膀”开发Me-too药的难度直线下降。与此同时，“饱和式研发”的环境也让新晋Biotech们无所适从，“创新”的定义正在变得模糊，“创新”的评价标准也在新时代下重构。如何才能在激变的竞争格局里脱颖而出？最直接的办法是，专注源头创新，用First-in-class药物解决空白领域的临床需求，在以前没有标准疗法的疾病领域设立标准，从追赶者变成先行者，调动起投资人、临床医生和患者共同的期待。典型代表是迪哲医药。舒沃替尼填补了EGFR二十号外显子插入突变（ex20ins）非小细胞肺癌（NSCLC）近20年的治疗空白，在肺癌领域树立了新的治疗标杆；戈利昔替尼则直接成为全球首创（First-in-class）药物，打破外周T细胞淋巴瘤（PTCL）10年无新药上市的困境。今年ASCO大会上，迪哲管线内的潜力产品DZD8586更是崭露头角，切入了血液瘤最大的一块市场——B细胞非霍奇金淋巴瘤（B-NHL）。构建起多元血液瘤管线的迪哲医药，正在成为新时代Biotech的创新标杆。血液瘤——创新药的高地血液瘤是非常有利于创新药的疾病领域。根据《2022年全球癌症统计报告》，2022年全球新增近2000万癌症患者，其中新发血液瘤患者约130万，占比6.5%[1]左右。尽管看上去并不算多，但血液瘤大多生存期长于实体瘤，有很多复发/难治性患者，累积存量患者规模巨大。以我国为例，2021年国内血液瘤新增患者约24万，但非霍奇金淋巴瘤（NHL）患者存量规模已达到52万人。根据Frost & Sullivan预期，2030年全球与中国NHL将分别达到330/73万人。这也能解释，为什么看上去空间有限的血液瘤市场，不乏商业价值巨大的全球重磅炸弹药物。同时，血液瘤亚型众多的特点也注定，其始终存在着许多未被满足的临床需求亟待解决。如慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（CLL/SLL），作为B-NHL中最大的一类，尽管已经有了BTK抑制剂这样成熟且有效的治疗方案，但依然存在难以避免的耐药问题。复发/难治性患者的后线治疗并不理想。再比如外周T细胞淋巴瘤（PTCL），侵袭性强、预后差，5年OS率仅为30%左右[2]，是NHL中生存率最低的类型，治疗选择非常有限。PTCL的发病具有明显的地域差异，在我国，约占所有非霍奇金淋巴瘤（NHL）的25.6%，远高于西方国家的5%～10%[3]。大型MNC的研发动力因此非常弱，只能依赖本土创新药企填补治疗空白。而迪哲医药不仅为现有血液瘤领域临床需求提供了解决方案，更以源头创新的目标和极致巧妙的思路开辟了新天地。T细胞淋巴瘤潜在「最大单品」作为迪哲医药在血液瘤领域的首个First-in-class药物，戈利昔替尼展现出的研发逻辑是值得深入探讨的。JAK/STAT是自免领域的经典信号通路，是迪哲医药最早发现并验证了该通路治疗PTCL的潜力。但JAK抑制剂（JAKi）治疗PTCL仍存在一个巨大障碍，即药物选择性问题。JAK家族的4种蛋白（JAK1、JAK2、JAK3、TYK2）结构极其相似，分别负责激活下游的不同通路。其中主要负责PTCL发展的激酶是JAK1，需要足够高选择性的JAK1抑制剂，才能减少其他JAK激酶抑制导致的不良事件。既往聚焦在自免领域的药物多为泛JAKi，即便是该领域的高选择性JAK1i艾玛昔替尼片，对JAK1和JAK2的选择性差值也仅为9倍[4]，远远满足不了PTCL的治疗需求。戈利昔替尼针对JAK1的选择性高于JAK家族其它成员200-400倍[5]，可以在大幅提升PTCL治疗效果，并确保更好的安全性，这是迪哲医药强大研发实力体现。同时，由于JAK/STAT通路在免疫调节，抗炎等方面的作用，戈利昔替尼具有更立体的抗肿瘤机制，体现在临床数据上就是更长的生存获益。国际多中心关键注册临床JACKPOT8 Part B[6]研究中，戈利昔替尼治疗后的中位中生存期（mOS）达到24.3个月，是目前单药治疗复发/难治（r/r）PTCL最长的药物，突破2年治疗瓶颈。PTCL是异质性很强的疾病，可分成34种亚型[3]。在JACKPOT8 Part B研究中，戈利昔替尼对不同亚型的r/r PTCL均展现出了相较既往靶向治疗方案2倍的高客观缓解率（ORR）和完全缓解（CR）率，填补了既往治疗药物在多个亚型治疗上的空白。此外，迪哲还在持续深挖JAK1i的应用潜力，戈利昔替尼一项Ⅱ期前瞻性多中心临床研究JACKPOT26的最新2年随访数据，将首次亮相今年EHA大会，并在ICML以口头报告形式公布。研究结果表明，戈利昔替尼维持治疗经一线系统治疗后缓解的PTCL患者，具有良好的安全性和抗肿瘤疗效，且临床易管理。在入组首次完全缓解（CR1）患者的队列1中，24个月的无病生存期（DFS）率为74.2%，且在不同PTCL亚型中的疗效可比；在入组部分缓解（PR）患者的队列2中，完全缓解率（CRR）为50.0%，mDOR为23.9个月，mPFS为17.4个月，其中最长PFS达35.9个月，且患者仍在持续缓解中。在血液瘤领域，覆盖亚型的数量直接决定了血液瘤药物市场空间的上限。戈利昔替尼仅在r/r PTCL领域潜力，国内有望达到10亿元销售峰值；根据国海证券保守预测，进入全球市场后，其销售峰值有望突破20亿元大关。更值得期待的是，迪哲医药还在持续扩大戈利昔替尼的潜力，联合CHOP方案一线治疗PTCL、联合CHOP方案治疗初治单形性嗜上皮性肠道T细胞淋巴瘤（MEITL）、单药治疗复发/难治惰性T/NK细胞淋巴瘤、针对复发/难治T细胞大颗粒淋巴细胞白血病（r/r T-LGLL）以及针对r/r PTCL的真实世界研究等T细胞淋巴瘤领域的多项研究，在EHA大会都显示出了令人鼓舞的初步抗肿瘤活性和良好的安全性。而这些数据背后的含义是——戈利昔替尼或将成为全球T细胞淋巴瘤领域的最大单品。同时，迪哲医药另一款在研药物DZD8586也在悄然发力，以克服BTK抑制剂（BTKi）耐药作为核心机制，撬动着血液肿瘤最大的市场——B-NHL。撬动B-NHL的超级杠杆B-NHL是血液瘤里占比最大的类型，占比可以达到所有血液瘤的47%[7]，接近一半。B-NHL，顾名思义所有肿瘤细胞都都源于B细胞，所以能够高效针对恶性B细胞的BTK（布鲁顿酪氨酸蛋白激酶）抑制剂成为了“统治级赛道”，诞生了许多超级大单品。传奇抗肿瘤药伊布替尼的峰值销售额接近100亿美元，头对头击败伊布替尼的泽布替尼也成为了首个“国产十亿美元分子”。但BTKi耐药仍然是困扰临床的重要难题。目前研究发现，耐药机制主要有两种[8]。一种是BTK依赖性耐药，相对好处理，市场上非共价BTKi的开发主要就是为了解决C481X突变引起的耐药问题。另一种则是BTK非依赖性耐药，肿瘤细胞摆脱了主要通路对BTK的依赖，不吃馒头改吃杂粮饭了，即便BTK蛋白降解剂也未必能完全克服，目前没有好的解决办法。迪哲医药自主研发的DZD8586是全球首创（First-in-class）、可完全穿透血脑屏障的非共价LYN/BTK双靶点抑制剂。当BTK被阻断时，LYN可绕过 BTK直接激活下游分子，是BTK非依赖性耐药机制的代偿枢纽[9]。DZD8586可同时阻断 BCR 信号的 “上游启动”（LYN）和 “核心枢纽”（BTK）两个环节，不仅克服了BTK依赖性和非依赖性耐药，还能抑制BTK降解剂的耐药突变。DZD8586在今年的国际舞台上声音很大，接连入选ASCO、EHA和ICML国际顶尖学术大会，其中一项针对既往接受过共价或非共价BTKi和BTK降解剂治疗的CLL/SLL的Ⅰ/Ⅱ期临床研究的汇总分析，分获ASCO和ICML口头报告。结果显示， DZD8586治疗既往接受过重度治疗的CLL/SLL患者总体ORR高达84.2%，且安全性可控。在既往接受过BTK抑制剂、BTK降解剂或Bcl-2抑制剂治疗，以及携带经典BTK耐药突变（C481X），包括BTK激酶失活突变等其他BTK突变的患者中，均观察到肿瘤缓解，且安全可控，临床上未观察到药物相关出血、房颤或重大心脏风险。纵观血液肿瘤领域，“重磅炸弹”常有，而BTK不常有。在BTKi耐药后的治疗方案各有不同，新药研发的方向要么聚焦适应症寻求颠覆，要么开发新型BTKi与王者争锋。DZD8586则另辟蹊径，从耐药机制出发，在BTKi寻求更多血液瘤亚型覆盖的时候，绘出了“BTKi全覆盖”的图景，撬动了B-HNL的巨大杠杆，给予了市场充分的想象空间。结语迪哲医药能够不断输出潜在爆款单品，背后是简单而质朴的新药研发理念——做真正有价值的源头创新。但最简单的理念往往需要最高级别的靶点理解和最严苛的药物设计执行力去贯彻。戈利昔替尼展现了对临床需求 “庖丁解牛”式的挖掘能力，DZD8586则体现了从早期研发到临床转化的全链条技术的把控。这些“硬功夫”上的表现让迪哲医药成熟的简直不像一个Biotech，是其能够区别于其他Biotech的核心特征。更重要的是，迪哲医药的高光并非不可复制，这也是其给中国创新药产业带来的最大价值。迪哲医药，重新定义了新时代Biotech创新标杆。参考资料[1]Bray F, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263.[2]2025 中国肿瘤整合诊治指南（CACA）——淋巴瘤[3]戈利昔替尼治疗外周T细胞淋巴瘤临床应用指导原则（2024年版）[4]Singh R,et al. Emerging Role of Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis. Immunotargets Ther. 2020;9:255-272. Published 2020 Nov 10.[5]Su Q, ,et al. Discovery of (2R)-N-[3-[2-[(3-Methoxy-1-methyl-pyrazol-4-yl)amino]pyrimidin-4-yl]-1H-indol-7-yl]-2-(4-methylpiperazin-1-yl)propenamide (AZD4205) as a Potent and Selective Janus Kinase 1 Inhibitor. J Med Chem. 2020 May 14;63(9):4517-4527.[6]KIM W, CAI Q, SONG Y, et al. Golidocitinib in treating reactory or relapsed peripheral T-cell lymphoma: primary analysis of the multinational pivotal study results (JACKPOT8) [J]. Hematol Oncol, 2023, 41(S2): 79-80.[7]《血液瘤：创新技术层出，各亚型均有孵化“重磅炸 弹”药物潜力》-开源证券[8]Wang H, et al. The resistance mechanisms and treatment strategies of BTK inhibitors in B-cell lymphoma. Hematol Oncol. 2021 Dec;39(5):605-615.[9]Nguyen PH,et al. LYN Kinase in the Tumor Microenvironment Is Essential for the Progression of Chronic Lymphocytic Leukemia. Cancer Cell. 2016 Oct 10;30(4):610-622.版权/免责声明：本文内容仅用于医疗行业信息传播、知识分享，我们会对发表的内容进行溯源、求证，力求专业、可靠，但不对内容的准确性做出承诺；不提供任何医疗、商业、投资建议，欢迎个人转发至朋友圈分享。如需转载，请务必注明文章作者和来源，否则我们将保留追究法律责任的权利。对本文有异议或投诉、开白名单、商务合作请联系：editor.connect@dotnet-pr.com 👇🏻 点击关注，镜镜与你常相见 😉

SAN CARLOS, Calif.--(BUSINESS WIRE)--BeOne Medicines Ltd. (NASDAQ: ONC; HKEX: 06160; SSE: 688235), a global oncology company, will present new clinical data from three cornerstone hematology assets at the European Hematology Association (EHA) Congress. Four oral presentations highlight the promising clinical activity of BeOne’s next-generation BCL2 inhibitor sonrotoclax, BTK protein degrader BGB-16673, and the backbone of our hematology franchise, BTK inhibitor BRUKINSA (zanubrutinib), which has the broadest label globally of any approved BTK inhibitor. These data reinforce the company’s strategic vision to redefine the standard of care for B-cell malignancies. “The data presented at EHA 2025 underscore the strength of BeOne’s comprehensive hematology pipeline, built on the success of BRUKINSA, the only BTK inhibitor to demonstrate superior progression-free survival over ibrutinib in a Phase 3 trial,1” said Lai Wang, Ph.D. Global Head of R&D at BeOne. “With our potentially best-in-class BCL2 inhibitor, sonrotoclax, and first-in-class BTK degrader, BGB-16673, we are advancing innovative therapies aimed at addressing resistance mechanisms and improving outcomes for patients with B-cell malignancies.” The data presented at EHA 2025 support the ongoing advancement of sonrotoclax and BGB-16673 into Phase 3 studies and lay the groundwork for BeOne’s first regulatory submissions for these programs. The company’s integrated development approach—anchored in differentiated mechanisms and translational science—positions its programs to address key areas of unmet need in hematologic oncology. “While existing therapies have improved outcomes in CLL and related malignancies, many patients still relapse or develop resistance and continue to face limited options,” said Stephan Stilgenbauer, Professor of Medicine and Medical Director of the Comprehensive Cancer Center Ulm (CCCU), Head of the Early Clinical Trials Unit (ECTU), and Head of the Division of CLL Dept. of Internal Medicine III at Ulm University. “The updated data presented at EHA underscore the potential of novel approaches, including BTK degradation and BCL2-based combinations, to overcome known mechanisms of resistance and expand treatment options for patients.” Sonrotoclax + BRUKINSA Demonstrates Deep Responses in CLL and MCL BeOne’s data will highlight the emerging potential of its next-generation assets to address the unmet needs of patients with B-cell malignancies. Updated results from Phase 1 studies evaluating sonrotoclax in combination with BRUKINSA in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and with R/R mantle cell lymphoma (MCL) demonstrated consistent, deep responses and a manageable safety profile. Sonrotoclax is well-positioned to improve key aspects of the BCL2 inhibitor class and has demonstrated robust and durable antitumor activity and a tolerable safety profile across all dose levels. R/R CLL/SLL ( Oral Presentation S159 ): Overall response rate (ORR): 96%; complete response (CR): 52% across all dose levels Undetectable minimal residual disease (uMRD) was achieved in 82% of patients overall, with responses deepening over time No tumor lysis syndrome (TLS) or febrile neutropenia observed Overall response rate (ORR): 96%; complete response (CR): 52% across all dose levels Undetectable minimal residual disease (uMRD) was achieved in 82% of patients overall, with responses deepening over time No tumor lysis syndrome (TLS) or febrile neutropenia observed R/R MCL ( Oral Presentation S234 ): ORR: 79%; CR rate: 66%, with 84% of responders in ongoing response at data cutoff No TLS or atrial fibrillation/flutter reported; the most common grade ≥3 adverse event was neutropenia (19.6%) ORR: 79%; CR rate: 66%, with 84% of responders in ongoing response at data cutoff No TLS or atrial fibrillation/flutter reported; the most common grade ≥3 adverse event was neutropenia (19.6%) Robust Early Results in CLL and WM with Potentially First-in-Class BTK Degrader As the most clinically advanced BTK degrader, BGB-16673 continues to show potential in patients with various hematological malignancies. Updated data from the ongoing Phase 1 CaDAnCe-101 study of BGB-16673 in R/R CLL/SLL and R/R Waldenström macroglobulinemia (WM) showed substantial antitumor activity and a tolerable safety profile across heavily pretreated populations. R/R CLL/SLL ( Oral Presentation S158 ): ORR: 84.8% across all dose levels and 93.8% at the recommended phase 2 dose of 200mg Patients were heavily pretreated, with most previously treated with BTK and BCL2 inhibitors. The median number of prior therapies was four. Responses deepened over time Grade ≥3 adverse events included neutropenia (24%) and pneumonia (11%); no reported deaths were attributed to study drug ORR: 84.8% across all dose levels and 93.8% at the recommended phase 2 dose of 200mg Patients were heavily pretreated, with most previously treated with BTK and BCL2 inhibitors. The median number of prior therapies was four. Responses deepened over time Grade ≥3 adverse events included neutropenia (24%) and pneumonia (11%); no reported deaths were attributed to study drug R/R Waldenström Macroglobulinemia ( Oral Presentation S231 ): ORR: 84.4%; major response rate: 75.0%; very good partial response rate (VGPR): 31.3% Rapid onset of response (median: 1.0 month), with continued deepening over time Efficacy observed across genetic backgrounds and prior BTKi exposure Most common grade ≥3 TEAE was neutropenia/neutrophil count decreased (31%); no reported atrial fibrillation or febrile neutropenia. ORR: 84.4%; major response rate: 75.0%; very good partial response rate (VGPR): 31.3% Rapid onset of response (median: 1.0 month), with continued deepening over time Efficacy observed across genetic backgrounds and prior BTKi exposure Most common grade ≥3 TEAE was neutropenia/neutrophil count decreased (31%); no reported atrial fibrillation or febrile neutropenia. BRUKINSA Monotherapy Showed Sustained OS and PFS Benefit Data from Arm D of the SEQUOIA Phase 3 trial will also be presented at the meeting (Abstract PS1566), demonstrating that treatment with BRUKINSA plus venetoclax has the potential to drive progression-free survival and overall deep and durable responses across the frontline CLL patient spectrum, including patients with high-risk mutational status. SEQUOIA Arm D investigated BRUKINSA plus venetoclax in 114 patients with treatment-naïve (TN) CLL / SLL with or without del(17p) and/or TP53 high-risk mutations. At a median follow-up of 31.2 months, the combination induced a high 24-month progression-free survival (PFS) rate of 92% (95% CI, 85-96%) and an impressive overall response rate (ORR) of 97%. The 24-month overall survival (OS) rate was 96% (95% CI, 90%-98%). Notably, these benefits were observed regardless of del(17p)/TP53 mutational status. The safety profile of BRUKINSA was consistent with the results of prior studies with no new safety signals identified. Arm C of the SEQUOIA study investigated BRUKINSA monotherapy in patients with TN CLL / SLL and del(17p) mutations, representing the largest prospective cohort of CLL/SLL patients with del(17p), will be presented at EHA (Abstract: PS1565). At a median follow-up of over 5.5 years (65.8 months), most patients remained progression-free. Notably, at 60 months, 72.2% of patients who received BRUKINSA remained progression-free (95% CI, 62.4, 79.8). When adjusted for the impact of the COVID-19 pandemic, 73.0% of patients in the cohort remained progression-free (95% CI, 63.3, 80.6) at 60 months. The 60-month OS rate was 85.1% (95% CI, 76.9, 90.6) and 87.0% (95% CI, 79.0, 92.1) when adjusted for COVID-19. At the time of data cut-off, the ORR was 97.3%, and 62.2% of patients were still receiving treatment with BRUKINSA. The safety profile of BRUKINSA was consistent with the results of prior studies with no new safety signals identified. BeOne will host an investor R&D Day on June 26 at 8:30 am ET covering our deep and broad global innovation pipeline and platforms, as well as the Company's vision, differentiated capabilities, and value creation drivers. The live webcast can be accessed from the investors section of BeOne’s website at https://ir.beonemedicines.com/, https://hkexir.beonemedicines.com/, or https://sseir.beonemedicines.com/. An archived replay will be available to investors for 90 days following the event. About Sonrotoclax (BGB-11417) Sonrotoclax is designed to block the B-cell lymphoma 2 (BCL2) protein, which is one of several proteins that help cancer cells survive. It is part of a group of drugs called BH3 mimetics, which mimic natural cell death signals. Studies in the lab and during early drug development have shown that sonrotoclax is a potent and specific inhibitor of BCL2 with a short half-life and no accumulation. Sonrotoclax has shown promising clinical activity across a range of B-cell malignancies, and more than 1,900 patients have been enrolled to date across the global development program. The U.S. Food and Drug Administration (FDA) granted sonrotoclax Fast Track Designation for the treatment of adult patients with mantle cell lymphoma (MCL) and Waldenström macroglobulinemia (WM). About BGB-16673 BGB-16673 is an orally available Bruton’s tyrosine kinase (BTK) targeting protein degrader from BeOne’s chimeric degradation activation compound (CDAC) platform. BGB-16673 is designed to promote the degradation, or breakdown, of both wildtype and mutant forms of BTK, including those that commonly result in resistance to BTK inhibitors in patients who experience progressive disease. BGB-16673 is the most advanced BTK protein degrader in the clinic, with an extensive global clinical development program. The U.S. Food and Drug Administration (FDA) granted Fast Track Designation to BGB-16673 for the treatment of adult patients with relapsed or refractory (R/R) chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL), and adult patients with R/R mantle cell lymphoma (MCL). About BRUKINSA® (zanubrutinib) BRUKINSA is an orally available, small molecule inhibitor of Bruton’s tyrosine kinase (BTK) designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared with other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease-relevant tissues. BRUKINSA has the broadest label globally of any BTK inhibitor and is the only BTK inhibitor to provide the flexibility of once or twice daily dosing. Additionally, BRUKINSA is also the only BTK inhibitor to demonstrate PFS superiority to a first-generation BTK inhibitor in a Phase 3 study. The global BRUKINSA clinical development program includes about 7,100 patients enrolled in 30 countries and regions across more than 35 trials. BRUKINSA is approved for at least one indication in more than 75 markets, and more than 200,000 patients have been treated globally. Select Important Safety Information Serious adverse reactions, including fatal events, have occurred with BRUKINSA, including hemorrhage, infections, cytopenias, second primary malignancies, cardiac arrhythmias, and hepatotoxicity (including drug-induced liver injury). In the pooled safety population (N=1729), the most common adverse reactions (≥30%), including laboratory abnormalities, in patients who received BRUKINSA were neutrophil count decreased (51%), platelet count decreased (41%), upper respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain (31%). Please see full U.S. Prescribing Information including U.S. Patient Information. The information provided in this press release is intended for a global audience. Product indications vary by region. About BeOne BeOne Medicines is a global oncology company domiciled in Switzerland that is discovering and developing innovative treatments that are more affordable and accessible to cancer patients worldwide. With a portfolio spanning hematology and solid tumors, BeOne is expediting development of its diverse pipeline of novel therapeutics through its internal capabilities and collaborations. With a growing global team of more than 11,000 colleagues spanning six continents, the Company is committed to radically improving access to medicines for far more patients who need them. To learn more about BeOne, please visit www.beonemedicines.com and follow us on LinkedIn, X, Facebook and Instagram. Forward-Looking Statement This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding the strength of BeOne’s hematology pipeline; BeOne’s ability to advance innovative therapies and improve outcomes for patients with B-cell malignancies; the ability of BeOne’s assets to address unmet needs of patients with B-cell malignancies and areas of hematologic oncology; the ability of sonrotoclax to improve the BCL2 inhibitor class and the asset’s future capabilities; the future potential of BGB-16673 in patients with hematological malignancies; the ability for BTK degradation and BCL2-based combinations to expand treatment options for patients; and BeOne’s plans, commitments, aspirations, and goals under the heading “About BeOne.” Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeOne's ability to demonstrate the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing, and progress of clinical trials and marketing approval; BeOne's ability to achieve commercial success for its marketed medicines and drug candidates, if approved; BeOne's ability to obtain and maintain protection of intellectual property for its medicines and technology; BeOne's reliance on third parties to conduct drug development, manufacturing, commercialization, and other services; BeOne’s limited experience in obtaining regulatory approvals and commercializing pharmaceutical products and its ability to obtain additional funding for operations and to complete the development of its drug candidates and maintain profitability; and those risks more fully discussed in the section entitled “Risk Factors” in BeOne’s most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeOne's subsequent filings with the U.S. Securities and Exchange Commission. All information in this press release is as of the date of this press release, and BeOne undertakes no duty to update such information unless required by law. 1 Brown, Jennifer R et al. “Sustained benefit of zanubrutinib vs ibrutinib in patients with R/R CLL/SLL: final comparative analysis of ALPINE.” Blood vol. 144,26 (2024): 2706-2717. doi:10.1182/blood.2024024667