Alrizomadlin

Ascentage Pharma (NASDAQ: AAPG; HKEX: 6855) announced that it has released the latest data from a Phase Ib/II study of the investigational Bcl-2 inhibitor, lisaftoclax (APG-2575), in combination with hypomethylating agent azacitidine in patients with treatment-naïve (TN) or prior venetoclax-exposed myeloid malignancies, in an oral presentation at the 61st American Society of Clinical Oncology (ASCO) Annual Meeting.The ASCO Annual Meeting showcases the most cutting-edge research in clinical oncology and state-of-the-art advanced cancer therapies and is the world’s most influential and prominent scientific gathering of the clinical oncology community. As Ascentage Pharma returns to the ASCO Annual Meeting for the eighth consecutive year, two studies of lisaftoclax and MDM2-p53 inhibitor alrizomadlin (APG-115), key drug candidates in the company’s apoptosis-targeted pipeline, have been selected for presentations, including an oral presentation.Patricia Kropf, MD, Principal Investigator of the study from Novant Health Cancer Institute, was orally presenting clinical results at the ASCO meeting.The oral presentation gained wide attentionThis oral presentation reported results from a multi-country, multi-center Phase Ib/II study of lisaftoclax, which as of data cutoff in April 2025, enrolled a total of 103 patients, including patients with TN or relapsed/refractory (R/R) acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). Findings of this study once again underscored the promising antitumor activity and manageable tolerability of lisaftoclax in myeloid malignancies. Furthermore, for the first time, this study reported responses in venetoclax-refractory patients who received lisaftoclax, thus suggesting that lisaftoclax has favorable antitumor activity and is differentiated from other drugs in the same class.Lisaftoclax is a novel Bcl-2 inhibitor developed by Ascentage Pharma. In November 2024, the New Drug Application (NDA) for lisaftoclax for the treatment of R/R chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) was accepted and granted a Priority Review designation by the Center for Drug Evaluation (CDE) of China’s National Medical Product Administration (NMPA). With this submission, lisaftoclax has become the first China-developed Bcl-2 inhibitor to reach NDA submission in China, and the second Bcl-2 inhibitor with submitted NDAs anywhere in the world. At present, lisaftoclax is being evaluated in four global registrational Phase III studies in major indications such as CLL/SLL, AML, and MDS, including a US Food and Drug Administration (FDA)-cleared multi-country, registrational Phase III trial.Patricia Kropf, MDPrincipal Investigator of the study from Novant Health Cancer Institute“In this global, multicenter study, lisaftoclax in combination with azacitidine showed promising efficacy and a tolerable safety profile for patients with treatment-naïve or R/R AML and MDS.  This data supports the upcoming Phase III study using the combination therapy for this patient population. Interestingly, lisaftoclax showed the potential to overcome resistance to venetoclax in patients who failed prior treatment with venetoclax, suggesting that it might bring improved treatment outcome. We look forward to releasing more data from this study which will further validate lisaftoclax’s broad therapeutic potential.”Dr. Yifan ZhaiChief Medical Officer of Ascentage Pharma“In previous studies, lisaftoclax combined with azacitidine has already demonstrated significant activity in patients with various myeloid malignancies. In this oral presentation, we report the latest data from a multi-country, multicenter Phase Ib/II study that showed promising antitumor activity and good tolerability of the combination regimen in myeloid malignancies such as AML and MDS. In particular, lisaftoclax has shown therapeutic potential in venetoclax-refractory patients, making this study the first that reported a Bcl-2 inhibitor overcoming drug resistance to another Bcl-2 inhibitor, thus suggesting that lisaftoclax may bring about a breakthrough to the treatment of myeloid malignancies. For now, lisaftoclax is being evaluated in multi-country,  registrational Phase III studies in AML and MDS. We remain committed to our mission of addressing unmet clinical needs in China and around the world and plan to further accelerate our clinical programs to bring more novel therapeutics to patients as soon as possible.”Highlights of this abstract selected for presentation at ASCO 2025 are as follows:Phase 1b/2 Study of Lisaftoclax (APG-2575) Combined with Azacitidine (AZA) in Patients with Treatment-Naïve or Prior Venetoclax-Exposed Myeloid MalignanciesAbstract #: 6505Format: Oral PresentationSession Title: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and AllotransplantPrincipal Authors: Michael Francis Leahy, MBChB, Royal Perth Hospital, Australia; Shaun Fleming, MBBS(Hons), PhD, The Alfred Hospital & Australian Centre for Blood Diseases, Australia; Patricia Kropf, MD, Novant Health Cancer Institute, United States, et al.Highlights:Background:AML and MDS are hematologic malignancies with poor prognoses.Hypomethylating agents (HMAs) AZA and decitabine are approved for MDS and AML and have been shown to prolong survival in patients. However, additional treatment options that improve clinical outcomes, such as complete response (CR) and overall survival (OS), are needed.Lisaftoclax is an investigational, orally active, small-molecule Bcl-2 inhibitor that has shown enhanced treatment responses in AML and MDS when combined with AZA in preclinical1 and clinical2 studies.Efficacy results:As of the data cutoff in April 2025, 22 of 28 venetoclax-refractory patients with R/R AML/ Mixed Phenotype Acute Leukemia (MPAL) were efficacy-evaluable,  among whom, the overall response rate (ORR) was 31.8%, including 22.8%, 4.6%, and 4.6% achieving CR/CR with incomplete hematologicrecovery (CRi), partial response (PR), and the morphologic leukemia-free state (MLFS), respectively. All responsive patients had received multiple lines of therapy that included venetoclax, and most of them (71%, 5/7) harbored the TP53 mutation and had a complex chromosomal karyotype at baseline.In 6 efficacy-evaluable patients with newly diagnosed (ND) AML/ MPAL, the ORR was 83.3%, with CR/CRi and PR achieved by 33.3% and 50% of patients, respectively. In 44 efficacy-evaluable patients with R/R AML/MPAL, the ORR was 43.2%, with CR/CRi, PR, and MLFS achieved by 31.8%, 4.5%, and 6.8% of patients, respectively. In 15 efficacy-evaluable patients with ND MDS/chronic myelomonocytic leukemia (CMML), the ORR was 80%, with CR and marrow CR (mCR) achieved by 40% and 40% of patients, respectively. In 22 efficacy-evaluable patients with R/R MDS/CMML, the ORR was 50%, with CR, mCR, and PR achieved by 27.3%, 18.2%, and 4.5% of patients, respectively.Safety results: Lisaftoclax in combination with AZA was well tolerated, with a manageable profile. Common adverse events were mostly hematologic. Non-hematologic toxicity was uncommon. The majority of adverse events were manageable, reversible and tolerable.Conclusions: Lisaftoclax combined with AZA showed promising antitumor activity and favorable tolerability in patients with TN or R/R myeloid malignancies. Furthermore, lisaftoclax demonstrated the ability to overcome drug resistance to venetoclax, making this the first clinical study to report a Bcl-2 inhibitor overcoming venetoclax resistance.Reference: Zhai Y, Tang Q, Fang DD, et al. Lisaftoclax in Combination with Alrizomadlin Overcomes Venetoclax Resistance in Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia: Preclinical Studies. Clin Cancer Res. 2023;29:183-196. https://doi.org/10.1158/1078-0432.CCR-22-0978Wang H, Wei X, Jiang Q, et al. Safety and Efficacy of Lisaftoclax (APG-2575), a Novel BCL-2 Inhibitor (BCL-2i), in Relapsed or Refractory (R/R) or Treatment-Naïve (TN) Patients (Pts) with Acute Myeloid leukemia (AML), Myelodysplastic Syndrome (MDS), or Other Myeloid Neoplasms. Blood 2023;142(Suppl 1):2925. https://doi.org/10.1182/blood-2023-188489* Lisaftoclax (APG-2575) is an investigational compound and has not been approved by the US FDA.About Ascentage PharmaAscentage Pharma (NASDAQ: AAPG; HKEX: 6855) is a global biopharmaceutical company dedicated to addressing unmet medical needs in cancers. The company has built a rich pipeline of innovative drug candidates that includes inhibitors targeting key proteins in the apoptotic pathway, such as Bcl-2 and MDM2-p53 and next-generation kinase inhibitors.The lead asset, olverembatinib, is the first 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. It is 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 newly diagnosed Ph+ALL patients and SDH-deficient GIST patients.The second lead asset, lisaftoclax, is a novel Bcl-2 inhibitor for the treatment of various hematological malignancies. The NDA for the treatment of relapsed and/or refractory CLL and SLL was accepted with Priority Review designation by China’s National Medical Products Administration. The Company is currently conducting an FDA-cleared, global registrational Phase III trial, or GLORA, of lisaftoclax in combination with BTK inhibitors for patients with CLL/SLL previously treated with BTK inhibitors for more than 12 months with sub-optimal response, as well as global registrational Phase III trials for newly diagnosed CLL/SLL, AML and MDS patients.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/Cautionary Note Regarding Forward-Looking StatementsThis 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.

亚盛医药（纳斯达克代码：AAPG；香港联交所代码：6855）宣布，公司已在第61届美国临床肿瘤学会（ASCO）年会上，以壁报展示形式公布了MDM2-p53抑制剂alrizomadlin（APG-115）单药或联合PD-1抑制剂特瑞普利单抗治疗晚期腺样囊性癌（ACC）或其它实体瘤患者的II期临床研究最新进展。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，具有全球First-in-class潜力。一年一度的ASCO年会是全球肿瘤领域最重要的、最为权威的学术交流盛会，将展示当前国际最前沿的临床肿瘤学科研成果和肿瘤治疗技术。今年是亚盛医药连续第八年亮相ASCO年会，此次公司共有两项研究入选，包括细胞凋亡管线重点品种Bcl-2抑制剂lisaftoclax（APG-2575）和MDM2-p53抑制剂alrizomadlin，其中lisaftoclax获口头报告，alrizomadlin获壁报展示。此次展示的alrizomadlin治疗ACC等实体瘤患者的临床研究数据显示：alrizomadlin单药在晚期ACC或恶性外周神经鞘膜瘤（MPNST）患者中显示出潜在抗肿瘤活性；同时alrizomadlin联合特瑞普利单抗耐受性良好，在MPNST、胆道肿瘤（BTC）和脂肪肉瘤（LPS）中均显示出临床治疗潜力。郭晔教授该项临床研究的主要研究者上海东方医院肿瘤内科ACC作为一种罕见肿瘤，缺乏有效的治疗方案，临床常用的抗血管生成TKI治疗存在一定的局限性和安全性隐患。本次ASCO年会上我们团队公布的这项研究显示，alrizomadlin治疗ACC的客观缓解率（ORR）为16.7%，疾病控制率（DCR）为100%，提示靶向MDM2-p53通路治疗ACC具有潜在抗肿瘤活性，可能是ACC领域的新疗法。李宁教授该项临床研究的主要研究者中国医学科学院肿瘤医院MPNST、LPS等肉瘤患者可供选择的方案有效限。本研究中，alrizomadlin单药或联合PD-1治疗MPNST均显示出较好的抗肿瘤活性，特别是联合治疗，使2例MPNST患者获得了长期缓解（1例>60周，1例>96周）；alrizomadlin联合PD-1治疗LPS也显示出一定的疗效。这些结果提示alrizomadlin单药或联合治疗可能在肉瘤领域使更多患者获益。翟一帆博士亚盛医药首席医学官作为全球First-in-class潜力品种， alrizomadlin在此次ASCO年会上展示的数据表明其在ACC及多种实体瘤患者中具有良好的单药和联合治疗潜力，并再一次体现了该品种与现有免疫肿瘤药物之间的协同效应，有望为多种实体瘤患者带来新的治疗选择。未来，我们将继续秉持初心，坚守“解决中国乃至全球患者尚未满足的临床需求”这一使命，加快临床开发，早日惠及全球患者。在此次ASCO年会上展示的该临床研究核心要点如下：A Phase 2 Study of Novel MDM2 Inhibitor Alrizomadlin (APG-115) With or Without Toripalimab in Patients with Advanced Adenoid Cystic Carcinoma (ACC) or Other Solid Tumors一项评估新型MDM2抑制剂APG-115（Alrizomadlin）单药或联合特瑞普利单抗治疗晚期腺样囊性癌（ACC）或其它实体瘤患者（Pts）的II期临床研究摘要编号：6102展示形式：壁报展示分会场标题：头颈癌（Head and Neck Cancer）主要作者：上海东方医院肿瘤内科郭晔博士；中国医学科学院肿瘤医院李宁博士；中山大学肿瘤防治中心黑色素瘤与肉瘤内科张星博士；浙江省肿瘤医院方美玉博士；中国医学科学院肿瘤医院王书航博士等核心要点：    - Alrizomadlin是一款在研新型口服MDM2抑制剂，已在ACC中显示出可控的安全性和初步抗肿瘤活性。    - 截至2025年2月13日，研究共入组57例晚期ACC、恶性周围神经鞘瘤（MPNST）、晚期脂肪肉瘤（LPS）和胆管癌（BTC）等肿瘤的患者。Alrizomadlin单药在晚期ACC和MPNST患者中显示了抗肿瘤活性。Alrizomadlin联合特瑞普利单抗在MPNST、BTC和LPC患者中显示了良好的耐受性和抗肿瘤活性。    - 单药治疗组17例疗效可评估患者中，12例ACC患者的ORR为16.7%， DCR为100%；5例MPNST患者中，4例达到疾病稳定（SD），DCR为80%。24例安全可评估患者中，33.3%发生了≥3级与治疗相关的不良事件（TRAE）；研究中发生3例（12.5%）与治疗相关的SAE。1例受试者因TRAE终止治疗。    - 联合治疗组29例疗效可评估患者中，6例BTC患者的ORR为16.7%，DCR为100%；6例LPS患者的ORR为16.7%，DCR为66.7%； 2例MPNST患者达到经确认的PR且无进展生存期（PFS）显著延长（1例>60周，1例>96周）。150mg剂量组27例安全可评估患者中，12例（44.4%）患者发生了≥3级TRAE， 8例（29.6%）患者发生了与治疗相关的SAE，1例受试者因TRAE终止治疗。关于亚盛医药亚盛医药是一家综合性的全球生物医药企业，致力于研发创新药，以解决肿瘤等领域全球患者尚未满足的临床需求。2019年10月28日，公司在香港联交所主板挂牌上市，股票代码：6855.HK；2025年1月24日，公司在美国纳斯达克证券交易所挂牌上市，股票代码：AAPG。亚盛医药已建立丰富的创新药产品管线，包括抑制Bcl-2和 MDM2-p53 等细胞凋亡通路关键蛋白的抑制剂；新一代针对癌症治疗中出现的激酶突变体的抑制剂等。公司核心品种耐立克®是中国首个获批上市的第三代BCR-ABL抑制剂，且获批适应症均被成功纳入国家医保药品目录，目前，亚盛医药正在开展耐立克®一项获美国FDA许可的全球注册III期临床研究（POLARIS-2），用于治疗既往接受过治疗的慢性髓细胞白血病慢性期（CML-CP）成年患者。此外，耐立克®联合治疗新诊断费城染色体阳性急性淋巴细胞白血病（Ph+ ALL）患者和治疗琥珀酸脱氢酶（SDH）缺陷型胃肠道间质瘤（GIST）患者的全球注册III期研究正在开展中。公司另一重磅品种，新型Bcl-2选择性抑制剂APG-2575（Lisaftoclax）的新药上市申请（NDA）已获CDE受理，并被纳入优先审评。目前，亚盛医药正在开展APG-2575（Lisaftoclax）四项注册III期临床研究，分别为获美国FDA许可的治疗经治慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（CLL/SLL）患者的全球注册III期临床研究（GLORA）；治疗初治CLL/SLL患者的全球注册III期临床研究；一线治疗新诊断老年或体弱急性髓系白血病（AML）的全球注册III期临床研究；以及治疗新诊断中高危骨髓增生异常综合征（MDS）患者的注册III期研究。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。凭借强大的研发能力，亚盛医药已在全球范围内进行知识产权布局，并与武田、默沙东、阿斯利康、辉瑞、信达等领先的生物制药公司，以及梅奥医学中心（Mayo Clinic）、丹娜法伯癌症研究院（Dana-Farber Cancer Institute）、美国国家癌症研究所（NCI）和密西根大学等学术机构达成全球合作关系。亚盛医药已在原创新药研发与临床开发领域建立经验丰富的国际化人才团队，以及成熟的商业化生产与市场营销团队。亚盛医药将不断提高研发能力，加速推进公司产品管线的临床开发进度，真正践行"解决中国乃至全球患者尚未满足的临床需求"的使命，以造福更多患者。前瞻性声明本新闻稿包含根据美国《1995年私人证券诉讼改革法案》，以及经修订的《1933年证券法》第27A条和《1934年证券交易法》第21E条所界定的前瞻性陈述。除历史事实陈述外，本新闻稿中的所有内容均可能构成前瞻性陈述，包括亚盛医药对未来事件、经营成果或财务状况所发表的意见、预期、信念、计划、目标、假设或预测。这些前瞻性陈述受到诸多风险和不确定性的影响，具体内容已在亚盛医药向美国证券交易委员会（SEC）提交的文件中详细说明，包括2025年1月21日提交的经修订的F-1表格注册说明书和2025年4月16日提交的20-F表格中的"风险因素"和"关于前瞻性陈述及行业数据的特别说明"章节、2019年10月16日提交的首次发行上市招股书中的“前瞻性声明”、“风险因素”章节，以及我们不时向SEC或HKEX提交的其他文件。这些因素可能导致实际业绩、运营水平、经营成果或成就与前瞻性陈述中明示或暗示的信息存在重大差异。本前瞻性声明中的陈述不构成公司管理层的利润预测。因此，该等前瞻性陈述不应被视为对未来事件的预测。本新闻稿中的前瞻性陈述仅基于亚盛医药当前对未来发展及其潜在影响的预期和判断，且仅代表截至陈述发表之日的观点。无论出现新信息、未来事件或其他情况，亚盛医药均无义务更新或修订任何前瞻性陈述。