SUZHOU, China and ROCKVILLE, Md., June 4, 2024 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, announced today that it has released the latest results from a Phase Ib/II study of its Bcl-2 inhibitor lisaftoclax (APG-2575) in combination with azacitidine (AZA) in patients with treatment-naïve (TN) or relapsed/refractory (R/R) acute myeloid leukemia (AML), in a poster presentation at the 60th American Society of Clinical Oncology (ASCO) Annual Meeting taking place in Chicago, IL..

中国苏州和马里兰州罗克维尔，2024年6月4日，一家致力于开发癌症、慢性乙型肝炎（CHB）和年龄相关疾病新疗法的全球生物制药公司Ascentage Pharma（6855.HK）今天宣布，在第60届美国临床肿瘤学会（ASCOL）的海报展示中，它发布了Bcl-2抑制剂lisaftoclax（APG-2575）联合阿扎胞苷（AZA）治疗初治（TN）或复发/难治（R/R）急性髓细胞白血病（AML）患者的Ib/II期研究的最新结果。年会在伊利诺伊州芝加哥举行。。

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. Presenting clinical development progress at the ASCO Annual Meeting for the seventh consecutive year, Ascentage had four clinical studies of three of the company's proprietary drug candidates selected for presentations, including an oral report, at ASCO 2024..

ASCO年会展示了临床肿瘤学和最先进的先进癌症治疗方面最前沿的研究，是世界上临床肿瘤学界最具影响力和最突出的科学盛会。Ascentage连续第七年在ASCO年会上介绍临床开发进展，在ASCO 2024年会议上，Ascentage对该公司的三种专有候选药物进行了四项临床研究，包括一份口头报告。。

The data of lisaftoclax combined with AZA in elderly/unfit TN patients with AML who were intolerant of standard induction chemotherapies and patients with R/R AML showed excellent therapeutic potential and a favorable safety profile in terms of tumor lysis syndrome (TLS), low incidence of neutropenic fever, and low early mortality..

lisaftoclax联合AZA治疗不耐受标准诱导化疗的老年/不适TN AML患者和R/R AML患者的数据显示，在肿瘤溶解综合征（TLS）方面具有良好的治疗潜力和良好的安全性，中性粒细胞减少症发热发生率低，早期死亡率低。。

'As a proprietary novel Bcl-2 inhibitor, lisaftoclax has shown treatment responses comparable to the approved Bcl-2 inhibitor and a better safety profile,' said Prof. Jie Jin, a principal investigator of the study from the First Affiliated Hospital, Zhejiang University School of Medicine. 'The improved safety offered by lisaftoclax means lower treatment-related mortality, fewer dose adjustments, and earlier start of sequential chemotherapies that should contribute to patients' long-term survival.'.

浙江大学医学院第一附属医院首席研究员Jie Jin教授说：“作为一种专有的新型Bcl-2抑制剂，lisaftoclax的治疗反应与批准的Bcl-2抑制剂相当，安全性更好。”lisaftoclax提供的安全性提高意味着治疗相关死亡率降低，剂量调整减少，以及尽早开始序贯化疗，这应有助于患者的长期生存。

'The introduction of Bcl-2 inhibitors represents a major breakthrough for the treatment of AML. However, the hematologic safety issues associated with the approved Bcl-2 inhibitor have limited the clinical adoption and the long-term efficacy,' said Dr. Huafeng Wang, PhD, from the First Affiliated Hospital, Zhejiang University School of Medicine, and the presenter of the poster.

“Bcl-2抑制剂的引入代表了AML治疗的重大突破。然而，与批准的Bcl-2抑制剂相关的血液学安全性问题限制了临床采用和长期疗效，”浙江大学医学院附属第一医院的王华峰博士和海报的主持人说。

'As a novel drug, lisaftoclax was frequently presented and attracted broad interest. When combined with chemotherapies, lisaftoclax showed a rate of hematologic adverse events that was lower than that of the approved Bcl-2 inhibitor. More importantly, its hematologic adverse events were relatively mild and easy to manage.

“作为一种新药，lisaftoclax经常出现并引起广泛兴趣。当与化疗联合使用时，lisaftoclax的血液学不良事件发生率低于批准的Bcl-2抑制剂。更重要的是，其血液学不良事件相对轻微且易于管理。

Its hematologic toxicity-related serious adverse events such as neutropenic fever and 30-/60-day mortalities were very low. This suggests that lisaftoclax-associated hematologic toxicities are transient, less serious, easier to manage, and therefore would have less negative impact on sequential chemotherapies.

其血液毒性相关的严重不良事件，如中性粒细胞减少症和30/60天死亡率非常低。这表明lisaftoclax相关的血液学毒性是短暂的，不太严重，更容易管理，因此对顺序化疗的负面影响较小。

Overall, lisaftoclax has already shown a highly favorable clinical potential.'.

总体而言，lisaftoclax已经显示出非常有利的临床潜力。”。

'These efficacy and safety data of lisaftoclax combined with AZA in patients with AML are very encouraging because they reaffirmed the drug's global best-in-class potential as a hopeful new treatment option for patients with AML, a hematologic malignancy commonly associated with a poor prognosis,' said Dr.

“利沙托克联合AZA治疗AML患者的这些疗效和安全性数据非常令人鼓舞，因为他们重申了该药物的全球最佳潜力，作为AML患者的一种有希望的新治疗选择，AML是一种通常与预后不良相关的血液恶性肿瘤，”Dr。

Yifan Zhai, Chief Medical Officer of Ascentage Pharma. 'A global registrational Phase III study of lisaftoclax in AML is already underway. Remaining committed to the mission of addressing unmet clinical needs in China and around the world, we will accelerate the clinical development of lisaftoclax and bring this novel therapeutic to the broad population of patients with AML as soon as possible.'.

Ascentage Pharma首席医疗官翟一凡（音）一项针对反洗钱中lisaftoclax的全球注册III期研究已经在进行中。我们将继续致力于解决中国和世界各地未满足的临床需求，加快利沙夫托克的临床开发，并尽快将这种新型治疗方法带给广大AML患者。”。

Highlights of these data presented at ASCO 2024 are as follows:

在ASCO 2024上提供的这些数据的要点如下：

Safety and efficacy of lisaftoclax, a novel BCL-2 inhibitor, in combination with azacitidine in patients with treatment-naïve or relapsed or refractory acute myeloid leukemia

新型BCL-2抑制剂lisaftoclax联合阿扎胞苷治疗初治、复发或难治性急性髓细胞白血病的安全性和有效性

Abstract#: 6541

摘要#：6541

Session Title: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

课程名称：血液系统恶性肿瘤白血病，骨髓增生异常综合征和同种异体移植

Date and Time: June 3, 2024, Monday, 9:00 AM – 12:00 PM (Central Time)

Date and Time: June 3, 2024, Monday, 9:00 AM – 12:00 PM (Central Time)

First Author: Huafeng Wang, MD, PhD, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

第一作者：王华峰，医学博士，博士，浙江大学医学院第一附属医院，浙江杭州。

Highlights:

亮点：

Background and introduction: Early studies showed that lisaftoclax in combination with various agents can synergistically induce apoptosis in AML. This poster presents follow-up safety and efficacy data from a Phase Ib/II study of lisaftoclax combined with AZA in adults with AML.

背景与简介：早期研究表明，lisaftoclax联合各种药物可协同诱导AML细胞凋亡。这张海报展示了利沙托克联合AZA治疗成人AML的Ib/II期研究的随访安全性和有效性数据。

Patient enrollment and methods:

患者登记和方法：

This study enrolled elderly (≥75 years)/unfit TN patients with AML who were intolerant of standard induction chemotherapies and patients (≥18 years) with R/R AML. Lisaftoclax (400/600/800 mg) was administered orally once daily in 28-day cycles. In the first treatment cycle, a daily ramp up schedule was used to prevent TLS.

本研究纳入了不耐受标准诱导化疗的老年（≥75岁）/不适合TN的AML患者和R/R AML患者（≥18岁）。Lisaftoclax（400/600/800 mg）在28天的周期内每天口服一次。在第一个治疗周期中，使用每日递增时间表来预防TLS。

AZA was administered once daily on D1-D7 at 75 mg/m2..

AZA在D1-D7每天服用一次，剂量为75 mg/m2。。

As of January 25, 2024, 76 patients with AML were enrolled, including 37 patients with R/R AML and 39 elderly/unfit patients with TN AML who were intolerant of standard induction chemotherapies. The median (range) age was 66 (20-81) years.

截至2024年1月25日，共纳入76例AML患者，其中37例R/R AML患者和39例不耐受标准诱导化疗的老年/不适合TN AML患者。中位（范围）年龄为66（20-81）岁。

Efficacy results:

疗效结果：

In patients with R/R AML treated with lisaftoclax combined with AZA, the overall response rate ([ORR]=CR + CRi + morphologic leukemia-free state [MLFS] + PR) was 72.7%, and the composite complete remission rate (CRc = CR + CRi) was 45.5%. In the 600 mg cohort (n=30), the median duration of treatment was 3.8 months, the ORR was 76.7%, the CRc was 50.0%, the median time to CRc was 2.5 months, the median PFS was 10.2 months, and the median overall survival (OS) was 14.7 months..

利沙夫托克联合AZA治疗的R/R AML患者，总有效率（[ORR]=CR+CRi+形态无白血病状态[MLFS]+PR）为72.7%，综合完全缓解率（CRc=CR+CRi）为45.5%。在600 mg队列（n=30）中，中位治疗时间为3.8个月，ORR为76.7%，CRc为50.0%，CRc中位时间为2.5个月，中位PFS为10.2个月，中位总生存期（OS）为14.7个月。。

Among patients with TN AML treated with lisaftoclax combined with AZA, the ORR was 64.1%, and the CRc was 51.3%. In the 600 mg cohort (n=29), the median duration of treatment was 3.3 months, and the median time to CRc was 1.9 months. The median PFS and median OS were not reached.

利沙夫托克联合AZA治疗的TN AML患者中，ORR为64.1%，CRc为51.3%。在600 mg队列（n=29）中，中位治疗时间为3.3个月，中位CRc时间为1.9个月。未达到中位PFS和中位OS。

600 mg lisaftoclax combined with AZA was established as the recommended Phase II dose (RP2D)

600毫克lisaftoclax联合AZA被确定为推荐的II期剂量（RP2D）

Safety results: All patients treated with lisaftoclax combined with AZA reported treatment-emergent adverse events (TEAEs), with 89.5% experiencing grade 3/4 TEAEs and 43.4% experiencing serious adverse events (SAEs). Common Grade ≥ 3 TEAEs reported in ≥ 10% of patients included neutropenia (57.9%), thrombocytopenia (50.0%), anemia (27.6%), pneumonia (17.1%), and febrile neutropenia (10.5%).

安全性结果：所有接受lisaftoclax联合AZA治疗的患者均报告了治疗紧急不良事件（TEAE），其中89.5%经历了3/4级TEAE，43.4%经历了严重不良事件（SAE）。在≥10%的患者中报告的常见≥3级TEAE包括中性粒细胞减少症（57.9%），血小板减少症（50.0%），贫血（27.6%），肺炎（17.1%）和发热性中性粒细胞减少症（10.5%）。

No TLS was reported. The 30-day mortality rate was 1.3%..

没有报告TLS。30天死亡率为1.3%。。

Conclusions: These data support a promising role for the new Bcl-2 inhibitor lisaftoclax combined with AZA for the treatment of elderly/unfit TN patients with AML intolerant of standard induction chemotherapies and patients with R/R AML, especially given a potentially favorable safety profile in terms of TLS, the incidence of neutropenic fever, and low early mortality.

结论：这些数据支持新的Bcl-2抑制剂lisaftoclax联合AZA治疗不耐受标准诱导化疗的AML老年/不适合TN患者和R/R AML患者的有希望的作用，特别是考虑到潜在的有利安全性。TLS，中性粒细胞减少症发热的发生率和早期死亡率低。

A Phase III randomized, double-blind study is being conducted to determine whether lisaftoclax combined with AZA improves the survival of elderly/unfit TN patients with AML intolerant of standard induction chemotherapies..

正在进行一项III期随机双盲研究，以确定lisaftoclax联合AZA是否能改善不耐受标准诱导化疗的AML老年/不适合TN患者的生存率。。

*Lisaftoclax is an investigational drug that has not been approved in any country and region.

*Lisaftoclax是一种尚未在任何国家和地区获得批准的研究药物。

Appendix: The four clinical studies of Ascentage Pharma's three drug candidates, including lisaftoclax, presented at this year's ASCO Annual Meeting.

附录：Ascentage Pharma的三种候选药物（包括lisaftoclax）的四项临床研究在今年的ASCO年会上发表。

Drug Candidates

候选药物

Abstract Title

摘要标题

Abstract#

摘要#

Format

格式

Olverembatinib

奥列姆巴蒂尼

(HQP1351)

（HQP1351）

Updated efficacy results of olverembatinib (HQP1351) in patients with tyrosine kinase inhibitor (TKI)-resistant succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST) and paraganglioma.

olverembatinib（HQP1351）对酪氨酸激酶抑制剂（TKI）耐药琥珀酸脱氢酶（SDH）缺陷型胃肠道间质瘤（GIST）和副神经节瘤患者的最新疗效结果。

#11502

#11502

Oral

口头

Report

报告

Lisaftoclax

Lisaftoclax

（APG-2575）

（APG-2575）

Safety and efficacy of lisaftoclax, a novel BCL-2 inhibitor, in combination with azacitidine in patients with treatment-naïve or relapsed or refractory acute myeloid leukemia.

新型BCL-2抑制剂lisaftoclax联合阿扎胞苷治疗初治或复发或难治性急性髓细胞白血病患者的安全性和有效性。

#6541

#6541

Poster Presentation

海报展示

Updated efficacy and safety results of BCL-2 inhibitor lisaftoclax (APG-2575) alone or combined with ibrutinib or rituximab in patients (pts) with Waldenström macroglobulinemia (WM).

BCL-2抑制剂lisaftoclax（APG-2575）单独或联合依鲁替尼或利妥昔单抗治疗Waldenström巨球蛋白血症（WM）患者（pts）的最新疗效和安全性结果。

#7078

#7078

Poster Presentation

海报展示

APG-2449

APG-2449

Updated study results of novel FAK/ALK/ROS1 inhibitor APG-2449 in patients (pts) with non-small-cell lung cancer (NSCLC) resistant to second-generation ALK inhibitors.

新型FAK/ALK/ROS1抑制剂APG-2449在对第二代ALK抑制剂耐药的非小细胞肺癌（NSCLC）患者（pts）中的最新研究结果。

#3124

#3124

Poster Presentation

海报展示

About Ascentage Pharma

关于Ascentage Pharma

Ascentage Pharma (6855.HK) is a globally focused biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B, and age-related diseases. On October 28, 2019, Ascentage Pharma was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK..

Ascentage Pharma（6855。HK）是一家专注于全球的生物制药公司，致力于开发针对癌症，慢性乙型肝炎和与年龄有关的疾病的新型疗法。2019年10月28日，Ascentage Pharma在香港联合交易所主板上市，股票代码6855.HK。。

Ascentage Pharma focuses on developing therapeutics that inhibit protein-protein interactions to restore apoptosis, or programmed cell death. The company has built a pipeline of 9 clinical drug candidates, including novel, highly potent Bcl-2, and dual Bcl-2/Bcl-xL inhibitors, as well as candidates aimed at IAP and MDM2-p53 pathways, and next-generation tyrosine kinase inhibitors (TKIs).

Ascentage Pharma专注于开发抑制蛋白质-蛋白质相互作用以恢复细胞凋亡或程序性细胞死亡的疗法。该公司已经建立了9种临床候选药物的管道，包括新型高效Bcl-2和双重Bcl-2/Bcl-xL抑制剂，以及针对IAP和MDM2-p53途径的候选药物，以及下一代酪氨酸激酶抑制剂（TKIs）。

Ascentage Pharma is also the only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. The company is conducting more than 40 Phase I/II clinical trials, including 5 global registrational phase III studies, in the US, Australia, Europe, and China.

Ascentage Pharma也是世界上唯一一家针对所有三类已知的关键凋亡调节剂开展积极临床计划的公司。该公司正在美国、澳大利亚、欧洲和中国进行40多项I/II期临床试验，包括5项全球注册III期研究。

Ascentage Pharma has been designated for multiple Major National R&D Projects, including five Major New Drug Projects, one New Drug Incubator status, four Innovative Drug Programs, and one Major Project for the Prevention and Treatment of Infectious Diseases..

Ascentage Pharma已被指定参与多项重大国家研发项目，包括五个重大新药项目、一个新药孵化器项目、四个创新药物项目和一个传染病防治重大项目。。

Olverembatinib, the company's core drug candidate developed for the treatment of drug-resistant chronic myeloid leukemia (CML) and the company's first approved product in China, has been granted Priority Review Designations and Breakthrough Therapy Designations by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA).

Olverembatinib是该公司为治疗耐药慢性粒细胞白血病（CML）而开发的核心候选药物，也是该公司在中国的首个获批产品，已被中国国家医药产品管理局（NMPA）药物评估中心（CDE）授予优先审查指定和突破性治疗指定。

To date, the drug had been included into the China 2022 National Reimbursement Drug List (NRDL). Furthermore, olverembatinib has been granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA, and an Orphan Designation by the EMA of the EU. To date, Ascentage Pharma has obtained a total of 16 ODDs from the US FDA and 1 Orphan Designation from the EMA of the EU for 4 of the company's investigational drug candidates..

迄今为止，该药物已被纳入中国2022年国家报销药物清单（NRDL）。此外，olverembatinib已被美国FDA授予孤儿药名称（ODD）和快速通道名称（FTD），并被欧盟EMA授予孤儿名称。迄今为止，Ascentage Pharma已经从美国FDA获得了16个赔率，并从欧盟EMA获得了1个孤儿指定，用于该公司的4个研究候选药物。。

Leveraging its robust R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships with numerous renowned biotechnology and pharmaceutical companies and research institutes such as UNITY Biotechnology, MD Anderson Cancer Center, Mayo Clinic, Dana-Farber Cancer Institute, MSD, and AstraZeneca.

凭借强大的研发能力，Ascentage Pharma建立了全球知识产权组合，并与众多知名生物技术和制药公司以及研究机构建立了全球合作伙伴关系，如UNITY biotechnology、MD Anderson癌症中心、Mayo Clinic、Dana Farber癌症研究所、MSD和AstraZeneca。

The company has built a talented team with global experience in the discovery and development of innovative drugs and is setting up its world-class commercial manufacturing and Sales & Marketing teams. One pivotal aim of Ascentage Pharma is to continuously strengthen its R&D capabilities and accelerate its clinical development programs, in order to fulfil its mission of addressing unmet clinical needs in China and around the world for the benefit of more patients..

该公司建立了一支在创新药物的发现和开发方面具有全球经验的人才团队，并正在建立其世界一流的商业制造和销售与营销团队。Ascentage Pharma的一个关键目标是不断加强其研发能力，加速其临床开发计划，以实现其解决中国和世界各地未满足的临床需求的使命，造福更多患者。。

Forward-Looking Statements

前瞻性声明

The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, Ascentage Pharma undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events, or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events.

本文所作的前瞻性陈述仅与截至本文所作陈述之日的事件或信息有关。除法律要求外，Ascentage Pharma没有义务在声明发布之日后，由于新信息、未来事件或其他原因，或为了反映意外事件的发生，公开更新或修改任何前瞻性声明。

You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article.

您应该完整阅读本文，并了解我们未来的实际结果或表现可能与我们预期的有实质性差异。在本文中，我们或我们的任何董事或我们公司的意图的陈述或引用是在本文日期做出的。

Any of these intentions may alter in light of future development..

这些意图中的任何一个都可能根据未来的发展而改变。。

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SOURCE Ascentage Pharma

来源：Ascentage Pharma

Company Codes: HongKong:6855

公司代码：香港：6855