Lisaftoclax

Returning to the largest gathering for the international hematology community, over 10 clinical and preclinical studies on three key drugs in Ascentage Pharma’s (NASDAQ: AAPG; HKEX: 6855) pipeline (olverembatinib, lisaftoclax, and APG-5918) have been selected for presentations, including an Oral Report, at this year’s American Society of Hematology (ASH) Annual Meeting. This year, two studies of lisaftoclax (APG-2575) have been selected for presentations at the meeting, including an Oral Report featuring latest results from a registrational Phase II study of lisaftoclax monotherapy in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL); and a Poster Presentation featuring the latest data on lisaftoclax in combination with azacitidine (AZA) in patients with newly diagnosed or prior venetoclax–exposed myeloid malignancies. Entering the eighth consecutive year, multiple studies of olverembatinib (HQP1351) have been selected for presentations at the ASH Annual Meeting. They include poster presentations that will feature the first data readout from the global Phase III study (POLARIS-1) of olverembatinib in combination with low-intensity chemotherapy in patients with newly diagnosed (ND) Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), as well as data from multiple investigator-led studies. About Ascentage Pharma Ascentage Pharma Group International (NASDAQ: AAPG; HKEX: 6855) (“Ascentage Pharma” or the “Company”) is a global, commercial stage, integrated biopharmaceutical company engaged in the discovery, development and commercialization of novel, differentiated therapies to address unmet medical needs in cancer. The Company has built a rich pipeline of innovative drug products and candidates that includes inhibitors targeting key proteins in the apoptotic pathway, such as Bcl-2 and MDM2-p53, as well as next-generation kinase inhibitors. The lead asset, olverembatinib, is the first novel third-generation BCR-ABL1 inhibitor approved in China for the treatment of patients with CML in chronic phase (CML-CP) with T315I mutations, CML in accelerated phase (CML-AP) with T315I mutations, and CML-CP that is resistant or intolerant to first and second-generation TKIs. All indications are covered by the China National Reimbursement Drug List (NRDL). The Company is currently conducting an FDA-cleared, global registrational Phase III trial, or POLARIS-2, of olverembatinib for CML, as well as global registrational Phase III trials for patients with newly diagnosed Ph+ ALL and SDH-deficient GIST patients. The Company’s second approved product, lisaftoclax, is a novel Bcl-2 inhibitor for the treatment of various hematologic malignancies. Lisaftoclax is being commercialized in China following National Medical Products Administration (NMPA) approval for the treatment of adult patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have previously received at least one systemic therapy including Bruton’s tyrosine kinase (BTK) inhibitors. The Company is currently conducting four global registrational Phase III trials: the FDA-cleared GLORA study of lisaftoclax in combination with BTK inhibitors in patients with CLL/SLL previously treated with BTK inhibitors for more than 12 months with suboptimal response; the GLORA-2 study in patients with newly diagnosed CLL/SLL; the GLORA-3 study in newly diagnosed, elderly and unfit patients with acute myeloid leukemia ( AML); and the  GLORA-4 study in patients with newly diagnosed higher-risk myelodysplastic syndrome (HR MDS), a study that was simultaneously cleared by the US FDA, the EMA of the EU, and China CDE. Leveraging its robust R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships and other relationships with numerous leading biotechnology and pharmaceutical companies, such as Takeda, AstraZeneca, Merck, Pfizer, and Innovent, in addition to research and development relationships with leading research institutions, such as Dana-Farber Cancer Institute, Mayo Clinic, National Cancer Institute and the University of Michigan. For more information, visit https://ascentage.com/ Forward-Looking Statements This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements, other than statements of historical facts, contained in this press release may be forward-looking statements, including statements that express Ascentage Pharma’s opinions, expectations, beliefs, plans, objectives, assumptions or projections regarding future events or future results of operations or financial condition. These forward-looking statements are subject to a number of risks and uncertainties as discussed in Ascentage Pharma’s filings with the SEC, including those set forth in the sections titled “Risk factors” and “Special note regarding forward-looking statements and industry data” in its Registration Statement on Form F-1, as amended, filed with the SEC on January 21, 2025, and the Form 20-F filed with the SEC on April 16, 2025, the sections headed “Forward-looking Statements” and “Risk Factors” in the prospectus of the Company for its Hong Kong initial public offering dated October 16, 2019, and other filings with the SEC and/or The Stock Exchange of Hong Kong Limited we made or make from time to time that may cause actual results, levels of activity, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements. The forward-looking statements contained in this presentation do not constitute profit forecast by the Company’s management. As a result of these factors, you should not rely on these forward-looking statements as predictions of future events. The forward-looking statements contained in this press release are based on Ascentage Pharma’s current expectations and beliefs concerning future developments and their potential effects and speak only as of the date of such statements. Ascentage Pharma does not undertake any obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

编者按：白血病是威胁人类生命的常见恶性血液肿瘤。其中，慢性淋巴细胞白血病（CLL）是最常见的白血病类型之一。回望过去，CLL的治疗经历了从传统化疗到精准靶向的深刻变革。进入21世纪的过去25年间，美国FDA共批准了至少14款治疗CLL的新疗法，为患者不断扩展治疗边界。作为全球医药创新的赋能者，药明康德一直以来依托“一体化、端到端”的CRDMO赋能平台，助力全球合作伙伴，推进包括CLL在内的各类疾病的创新疗法开发，加速造福病患。 白血病是威胁人类健康的常见恶性血液肿瘤，其中，慢性淋巴细胞白血病（CLL）呈现出独特的临床特征。CLL是一种成熟B淋巴细胞的克隆性增殖肿瘤，典型表现为外周血淋巴细胞增多，患者多为中老年人。 目前，CLL唯一可根治的方式仍是异基因造血干细胞移植，但多数患者因年龄、体能状况或供者问题无法接受。因此，对于绝大多数患者而言，治疗目标是“带病生存”，尽可能长期维持良好的生活质量。 20世纪中叶之前，各类白血病几乎无有效疗法。从20世纪40到90年代，化疗的出现与发展将CLL缓解率提高到约50%，但化疗带来的细胞毒性始终限制着疗效与生活质量。 单克隆抗体疗法：开启靶向时代 进入21世纪，CLL治疗迎来重大变革，新型靶向疗法的出现不断重塑治疗格局。世纪之交，单克隆抗体的出现率先改变了CLL治疗只能依赖化疗的状态。其中最关键的突破之一来自靶点CD20。作为一种存在于绝大多数B细胞性淋巴瘤细胞表面的分化抗原，CD20在95%以上的相关肿瘤中表达，却不出现在造血干细胞、浆细胞及其他正常组织中，因此成为理想的靶向对象。 1997年，基因泰克与渤健共同推出首个CD20单抗——利妥昔单抗（rituximab，商品名 Rituxan）。这款药物迅速改变了CLL等多种癌症的治疗方式。2010年，FDA批准其新适应症，使其可联合化疗，用于初次治疗及既往治疗过的CD20+ CLL患者。 利妥昔单抗的成功也推动了CD20抗体的不断迭代。由Genmab与诺华联合开发的第二代药物奥法妥木单抗（ofatumumab，Arzerra）是一款全人源化抗体，结合位点与利妥昔单抗不同，适用于对其他疗法不再应答的患者。2009年，该药获FDA批准，用于对氟达拉滨和阿仑珠单抗耐药的CLL患者。 2013年，由GlycArt、基因泰克和渤健共同开发的第三代CD20单抗奥妥珠单抗（obinutuzumab，Gazyva）获批上市。奥妥珠单抗对CLL细胞的杀伤更直接、效力更强，且早期临床已显示其可迅速清除外周血中的B细胞。该药既可作为CLL的一线治疗方案，与化疗或靶向药物伊布替尼联合使用，也可单独用于复发或对其他疗法无效的患者。 除CD20靶点外，CLL治疗中还有针对 CD52 的单抗药物阿仑珠单抗（alemtuzumab，Lemtrada）。该药由拜耳与赛诺菲共同开发，并于2001年获FDA批准，用于治疗对烷化剂和氟达拉滨均已耐药的进展期CLL患者。 BTK抑制剂带来新变革 在近十多年的CLL治疗史中，BTK抑制剂的出现堪称一个关键转折，而伊布替尼（ibrutinib，Imbruvica）无疑是推动这一转折的重要力量。这款药物的问世背后，则是一段科学探索与产业接力交织的故事。 布鲁顿氏酪氨酸激酶（BTK）的发现要追溯到20世纪90年代。研究很快表明，BTK是B细胞受体信号通路中的核心节点，而在CLL癌细胞中，BTK水平则明显异常升高。至此，BTK成为B细胞恶性肿瘤中极具吸引力的靶点。 21世纪初，Celera Genomics公司在探索过程中得到了一款能够与BTK共价结合的小分子化合物。然而由于共价药物可能与人体正常蛋白发生非选择性、不可逆结合，引发严重毒性，研究者并未将其作为候选药物，仅仅把它当作筛选工具。随后，Pharmacyclics公司将这一小分子项目纳入旗下，并重新评估其潜力。 图片来源：123RF 2009年，Pharmacyclics推进了这款药物的1期临床试验。两年后，1b/2期试验积极结果公布后，强生旗下杨森制药（现强生创新制药）决定与Pharmacyclics携手，共同推进该药物的开发。 2013年11月，这款备受期待的小分子终于以“伊布替尼”之名获FDA加速批准，用于治疗套细胞淋巴瘤。此外，它在CLL治疗中也有优异表现，并在2014年2月获批用于既往接受过至少一种治疗的CLL患者。2015年公布的3年随访数据显示，近九成患者的肿瘤细胞明显减少甚至“几乎消失”，这意味着CLL患者第一次真正看到摆脱化疗的希望。 2015年，艾伯维收购了Pharmacyclics，并与强生继续推动伊布替尼的全球开发。2016年3月，FDA批准其第五项适应症，将其作为CLL一线单药治疗，这也是FDA首个无需化疗的CLL一线方案。推动此次获批的3期试验显示，伊布替尼一线治疗的总缓解率达82.4%，远高于化疗组的35.3%，无进展生存期显著延长，疾病进展或死亡风险降低了84%。 如今，伊布替尼已在全球超过100个国家和地区获批，累计惠及超过30万患者，是全球最具影响力的BTK抑制剂之一。另外，更多BTK靶向药物的不断丰富也让CLL及更广泛的B细胞恶性肿瘤患者迎来了治疗新时代。 更多新药不断登场 随着基础研究的持续推进，CLL治疗领域迎来了更多关键靶点的发现，也催生出一批具有里程碑意义的新药。与BTK相似，PI3K蛋白在多种B细胞恶性肿瘤中高度表达，而对PI3K的抑制不仅能影响B细胞受体信号通路，还会同时触及炎症调控、细胞信号传导以及血管生成等多个过程，从而干预肿瘤增殖所依赖的微环境。正是基于这样的科学认识，PI3K抑制剂逐渐成为CLL治疗探索中的核心方向之一。 由ICOS与吉利德共同开发的艾代拉利司（idelalisib，Zydelig）是最早的突破性成果。这款第一代口服PI3K-delta抑制剂于2014年获FDA批准用于复发或难治性CLL治疗。临床研究显示，它能够促使恶性细胞凋亡，抑制恶性B细胞及原发肿瘤细胞系的增殖，同时阻断多条关键信号通路，使肿瘤细胞的生存能力显著下降。 随后问世的度恩西布（duvelisib，商品名Copiktra）由Infinity Pharmaceuticals与Verastem共同研发，并于2018年获批用于至少经两种疗法治疗后的成人复发或难治性CLL患者。 在PI3K之外，BCL-2也是CLL治疗中不可忽视的关键靶点。BCL-2蛋白能够阻止细胞凋亡，而在多种癌症中过度表达，并与耐药形成密切相关。由艾伯维与罗氏旗下的基因泰克共同开发的维奈克拉（venetoclax，商品名Venclexta）便是这一靶点领域的代表性创新药物。作为选择性、口服的BCL-2抑制剂，它通过阻断BCL-2功能、恢复细胞正常的通讯系统，使癌细胞重新走向自我毁灭，从而达到抗肿瘤疗效。2016年至2019年间，维奈克拉陆续获得多项CLL相关适应症的批准。 今年，中国也迎来另一款BCL-2抑制剂——由亚盛医药研发的利沙托克拉，它同样获批用于CLL治疗，进一步丰富了可及疗法的选择。 图片来源：123RF 过去25年，美国FDA已经批准了至少14款治疗CLL的新疗法，构建起不断扩展的治疗版图。除了BTK、PI3K与BCL-2抑制剂，还包括2008年获批的化疗药物苯达莫司汀（bendamustine，商品名Treanda），以及2024年问世，靶向CD19的CAR-T细胞疗法 lisocabtagene maraleucel（liso-cel，商品名Breyanzi）。 在CLL领域的已获批上市的药物中，药明康德很高兴能为其中一些疗法提供赋能支持，助力合作伙伴的这些创新疗法来到全球患者身边。在25年发展历程中，药明康德始终致力于支持全球合作伙伴从药物研究发现（R）、开发（D）到商业化生产（M）各个阶段的需求，助力客户的突破性创新疗法加速研发进程。 在漫长而曲折的CLL抗争道路上，每一次机制的突破、每一款新药的诞生，都凝聚着学术、产业界工作者不断向未知发起挑战的勇气。正是这些跨越学科与机构界限的协作，让曾经束手无策的疾病逐渐变得可控，让众多CLL患者重新看见生的希望。药明康德也期待与业界同仁继续同行，助力全球合作伙伴让更多创新疗法来到患者身边。 参考资料： [1] Ponader, S., & Burger, J. 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Retrieved December 1, 2025, from https://www.biospace.com/article/releases/johnson-and-johnson-pharmacyclics-inc-breakthrough-drug-wins-fda-approval-/ [6] The drug that may make chemo a thing of the past. Retrieved December 1, 2025, from https://www.mdanderson.org/publications/conquest/spring-2014/the-drug-that-may-make-chemo-a-thing-of-the-past.html [7] New Drug Application (NDA): 205552. Retrieved December 1, 2025 from https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=205552 [8] AbbVie Completes Acquisition of Pharmacyclics.  Retrieved December 1, 2025 from https://investors.abbvie.com/news-releases/news-release-details/abbvie-completes-acquisition-pharmacyclics [9] Song, F., Tsahouridis, O., Stucchi, S. et al. A multi-kinase inhibitor screen identifies inhibitors preserving stem-cell-like chimeric antigen receptor T cells. Nat Immunol (2025). https://doi.org/10.1038/s41590-024-02042-1 [10] Ugur Uslu et al., CAR T cell combination therapies to treat cancer. Cancer Cell (2024). DOI:https://doi.org/10.1016/j.ccell.2024.07.002 欢迎转发到朋友圈，谢绝转载到其他平台。如有开设白名单需求，请在“学术经纬”公众号主页回复“转载”获取转载须知。其他合作需求，请联系wuxi_media@wuxiapptec.com。 免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 更多推荐 点个“在看”再走吧~