Sonrotoclax

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

产品出海已成为驱动本轮创新药行情反转的核心逻辑。典型案例如三生国健，就SSGJ-707与辉瑞达成授权后，短短半个月内股价即实现翻倍。亚盛医药自去年年中与武田就奥雷巴替尼达成授权合作以来，股价便开启强劲上涨通道。自2024年6月至今，其累计涨幅已达260%。这项被业界誉为“史诗级BD大单”的交易，不仅助推亚盛医药市值突破190亿，更带来了极为亮眼的财务表现——2024年公司营收同比激增342%，达到9.81亿元。在奥雷巴替尼的授权成功之后，亚盛医药的下一个重磅候选药物——新型Bcl-2抑制剂APG-2575，登场了。新引擎Bcl-2靶点的成药性挑战堪称肿瘤药物研发领域的“硬骨头”。其核心难点在于作用机制为蛋白-蛋白相互作用（PPI），靶点结合界面大且缺乏传统小分子药物可识别的“深口袋”结构，导致设计高亲和力抑制剂的难度极大。此外，Bcl-2蛋白定位于线粒体膜（细胞内最复杂的双膜结构），药物需先后跨越细胞膜和线粒体膜双层屏障才能发挥作用，进一步加剧了成药壁垒。自1972年靶点发现至今50余年，全球仅有艾伯维与罗氏联合开发的维奈克拉成功突围，成为首个也是唯一获批的Bcl-2抑制剂。亚盛医药自主研发的新型选择性Bcl-2抑制剂APG-2575（力胜克拉片）则开启了该领域的新征程。APG-2575新药上市申请（NDA）已于2024年11月获药品审评中心受理，并被推荐纳入优先审评程序，用于治疗难治或复发性慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（CLL/SLL）。APG-2575是首个在国内提交NDA的国产原研Bcl-2抑制剂，也有望成为继维奈克拉之后全球第二个上市的Bcl-2抑制剂。在2025年ASCO年会上，亚盛医药口头报告了APG-2575联合去甲基化药物阿扎胞苷（AZA）治疗初治或既往接受过维奈克拉治疗的髓系恶性肿瘤患者的1b/2期临床研究最新数据。数据显示，截至2025年4月，在28例既往维奈克拉耐药的复发/难治AML/混合表型急性白血病（MPAL）患者中，22例疗效可评估，总反应率（ORR）为31.8%（7/22），其中22.8%的患者达到完全缓解/完全缓解伴血细胞未完全恢复，4.6%的患者获部分缓解（PR），4.6%的患者获形态学无白血病状态（MLFS）。在6例疗效可评估的新诊断AML/MPAL患者中，ORR高达83.3%；在44例疗效可评估的R/R AML/MPAL患者中，ORR为43.2%。在骨髓增生异常综合征（MDS）及慢性粒单核细胞白血病（CMML）患者中，15例疗效可评估的ND患者ORR为80%，22例疗效可评估的R/R患者ORR为50%。安全性方面，APG-2575联合AZA治疗耐受性良好，安全性可控。值得关注的是，这是国际上首次报告一种Bcl-2抑制剂克服另一种Bcl-2抑制剂耐药的临床研究，表明APG-2575在髓系恶性肿瘤治疗领域具有显著的突破潜力。这不是APG-2575第一次显示出相对维奈克拉的差异化优势了。早在2024年美国血液学会年会上，亚盛医药就公布APG-2575单药或联合阿可替尼或利妥昔单抗治疗初治、复发/难治性或既往接受过维奈克拉治疗的CLL/SLL的临床数据。研究结果显示，在87例接受APG-2575联合阿可替尼治疗的患者中，ORR为96.6%；在既往接受过维奈克拉治疗的患者中，ORR为85.7%；而在既往接受过维奈克拉但未接受过BTK抑制剂治疗的患者中，ORR达到100%。这一结果表明，“APG-2575+BTK抑制剂”联用疗法相较于“Venetoclax+BTK抑制剂”具有潜在优势。凭借越来越多的循证医学证据，APG-2575展现出作为全球Best-in-class潜力品种应有的安全性和疗效。鉴于其优异的临床数据，APG-2575获2025版《CSCO淋巴瘤诊疗指南》推荐，用于单药治疗复发/难治性慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（CLL/SLL）患者。这是APG-2575首次纳入CSCO指南，也是唯一获得指南推荐的中国原研Bcl-2抑制剂，标志着亚盛医药在推动该创新品种惠及患者的道路上迈出了里程碑式的一步。在全球化布局方面，APG-2575正开展多项全球注册3期临床试验，包括获美国FDA许可的治疗经治慢性CLL/SLL患者的全球注册3期临床研究（GLORA）、治疗初治CLL/SLL患者的全球注册3期临床研究、一线治疗新诊断老年或体弱急性髓系白血病的全球注册3期临床研究，以及治疗新诊断中高危骨髓增生异常综合征患者的注册3期研究。此外，APG-2575已有5个适应症获得美国FDA授予的孤儿药资格认定，分别为华氏巨球蛋白血症、慢性淋巴细胞白血病、多发性骨髓瘤、急性髓系白血病和滤泡性淋巴瘤，彰显了其在国际肿瘤治疗领域的广泛潜力和认可。市场前景广阔维奈克拉2016年率先在美国上市，2020年12月落地中国市场。维奈克拉2023年全球销售额达22.88亿美元，2024年同比增长12.9%至25.83亿美元。艾伯维预测维奈克拉2026年峰值销售额将突破60亿美元。随着靶向细胞凋亡治疗领域的爆发，弗若斯特沙利文数据显示，全球该市场规模正以24%的复合年增长率高速扩张，预计2030年将突破220亿美元。在国产Bcl-2创新药赛道上，亚盛医药的APG-2575、百济神州的索托克拉片与诺诚健华的ICP-248是研发进度比较靠前的药物：APG-2575是国内首个提交上市申请的原研Bcl-2抑制剂，其临床数据展现出对维奈克拉耐药患者的突破潜力，且兼具剂量爬坡快、半衰期短、安全性更佳等差异化优势。图片来源：亚盛医药索托克拉片于2025年4月申报上市，此次申报的适应症为经治CLL/SLL成人患者；接受过抗CD20治疗和BTKi治疗的套细胞淋巴瘤（MCL）成人患者。ICP-248正在中国和全球开展一系列临床试验，包括联合奥布替尼一线治疗CLL/SLL的注册性3期临床试验，以及治疗AML的临床试验等。从研发进度看，亚盛医药凭借更早的NDA申报时间（早于百济神州的索托克拉片）和更靠前的审批状态，有望率先实现国产Bcl-2抑制剂零的突破，成为全球第二款上市药物。这一先发优势在当前只有维奈克拉获批且在售的市场格局下尤为关键——APG-2575不仅填补了国产同类药物的空白，更使其成为国际license-out的热门标的，未来在全球细胞凋亡治疗市场中具备显著商业想象空间。表1 全球Bcl-2抑制剂研发进度数据来源：药智数据向全球化进阶亚盛医药作为聚焦细胞凋亡通路的创新药企，已构建起覆盖肿瘤、代谢疾病等领域的多元化产品管线，核心布局包括Bcl-2、MDM2-p53等凋亡通路关键靶点抑制剂，以及针对激酶突变体的新一代靶向药物。2024年公司研发投入同比增长34%至9.47亿元，持续加码创新药研发。核心产品奥雷巴替尼（耐立克）是国内首个第三代BCR-ABL抑制剂，主要用于治疗伴有T315I突变的慢性髓细胞白血病（CML）慢性期（-CP）和加速期（-AP）患者，以及对第一代和第二代酪氨酸激酶抑制剂耐药或不耐受的CML-CP患者。自2021年11月上市后，相关适应症均纳入国家医保目录，2024年销售额同比增长52%至2.41亿元。在国际化进程中，耐立克已获美国FDA快速通道资格及孤儿药认证，其全球注册3期研究（POLARIS-2）正针对经治CML-CP患者展开，预计2026年申报美国上市，有望成为全球第二个上市的第三代BCR-ABL抑制剂。此外，耐立克联合治疗Ph+ALL及SDH缺陷型GIST的全球3期研究同步推进，早期数据显示其在TKI耐药患者中部分缓解率达25%，安全性与抗肿瘤活性兼具。东吴证券预测其海外峰值销售有望突破10亿美元。亚盛医药以凋亡通路为核心，形成多靶点、多适应症的研发梯队：Alrizomadlin为公司细胞凋亡管线重点品种，是首个在中国进入临床阶段的MDM2-p53抑制剂。2025年ASCO年会数据显示，其单药或联合PD-1抑制剂治疗晚期腺样囊性癌（ACC）等实体瘤时，单药组12例ACC患者ORR为16.7%，DCR达100%；联合治疗组6例胆道癌患者ORR为16.7%，DCR 100%，展现出可控安全性与初步疗效。APG-2449是小分子FAK/ALK/ROS1三联激酶抑制剂，2025年AACR大会数据显示，其联合一线/二线化疗在小细胞肺癌模型中可增强DNA损伤并诱导细胞凋亡，显示协同抗肿瘤效应。APG-5918是一款胚胎外胚层发育蛋白抑制剂，在2025年AACR大会上亚盛医药发布了关于该候选药物在前列腺癌临床前模型中的抗肿瘤活性及其与雄激素受体抑制剂恩扎卢胺的协同作用研究。截至目前，公司4个在研新药共获16项FDA和1项欧盟孤儿药资格认定，2项FDA快速通道资格以及2项FDA儿童罕见病资格认证。依托强大的知识产权布局，亚盛医药与武田、默沙东、阿斯利康等跨国药企，以及梅奥医学中心、丹娜法伯癌症研究院等顶尖学术机构建立全球合作。2025年1月24日，亚盛医药成功登陆美国纳斯达克主板，成为2025年全球生物医药第一股，亦是首家实现港股、美股双重主要上市的生物药企。本次IPO募资净额约1.325亿美元（约合人民币9.67亿元），为研发与商业化注入强劲动力，标志着其全球化战略进入新阶段。2024年亚盛医药实现收入9.81亿元，同比增幅达342%，主要得益于奥雷巴替尼的销售增长及技术授权收入。在创新药研发与商业化双轮驱动下，公司正以细胞凋亡通路为核心，加速向全球领先的生物制药企业迈进。结语展望未来，随着APG-2575等重磅品种的陆续上市、全球3期研究的持续推进，以及与跨国药企及顶尖学术机构的深度合作，亚盛医药有望在全球肿瘤治疗领域开拓更多“中国方案”。参考资料：1、各公司官网2、东吴证券3、药智数据声明：本内容仅用作医药行业信息传播，为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。责任编辑 | 史蒂文合作、投稿、转载开白 | 马老师 18323856316（同微信） 阅读原文，是受欢迎的文章哦