A Randomized, Double-blind, Placebo-controlled Phase I/II Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of APG-2575 in Patients With Mild-to-moderate Systemic Lupus Erythematosus.

To evaluate the safety, tolerability, pharmacokinetics and pharmacokinetics of multi-dose APG-2575 in mild-to-moderate systemic lupus erythematosus (SLE).

开始日期2024-08-09

申办/合作机构

Ascentage Pharma Group, Inc.

[+1]

NCT06401603 / Recruiting临床1期IIT

A Phase I Study of Decitabine, Lisaftoclax, and Olverembatinib in Patients With Advanced Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Myeloid Leukemia

To find the recommended doses of lisaftoclax and olverembatinib that can be given in combination with decitabine to participants with advanced CML and Ph+ AML.

开始日期2024-08-06

申办/合作机构

The University of Texas MD Anderson Cancer Center

[+1]

100 项与 Lisaftoclax 相关的临床结果

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100 项与 Lisaftoclax 相关的转化医学

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100 项与 Lisaftoclax 相关的专利（医药）

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项与 Lisaftoclax 相关的文献（医药）

2023-07-05·Clinical cancer research : an official journal of the American Association for Cancer Research

Novel BCL-2 Inhibitor Lisaftoclax in Relapsed or Refractory Chronic Lymphocytic Leukemia and Other Hematologic Malignancies: First-in-Human Open-Label Trial.

Article

作者: Ailawadhi, Sikander ; Davids, Matthew S ; Ahmad, Mohammad ; Glass, Laura ; Yang, Dajun ; Chen, Zi ; Huang, Bo ; Liang, Eric ; Men, Lichuang ; Wang, Hengbang ; Li, Mingyu ; He, Zhicong ; Mekala, Divya J ; Collins, Mary C ; Parrondo, Ricardo ; Zhai, Yifan ; Yannakou, Costas K ; Fu, Lei Tommy ; Lasica, Masa ; Chanan-Khan, Asher ; Paulus, Aneel

PURPOSE:

This global phase I trial investigated the safety, efficacy, pharmacokinetics, and pharmacodynamics of lisaftoclax (APG-2575), a novel, orally active, potent selective B-cell lymphoma 2 (BCL-2) inhibitor, in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (R/R CLL/SLL) and other hematologic malignancies (HMs).

PATIENTS AND METHODS:

Maximum tolerated dose (MTD) and recommended phase II dose were evaluated. Outcome measures were safety and tolerability (primary) and pharmacokinetic variables and antitumor effects (secondary). Pharmacodynamics in patient tumor cells were explored.

RESULTS:

Among 52 patients receiving lisaftoclax, MTD was not reached. Treatment-emergent adverse events (TEAEs) included diarrhea (48.1%), fatigue (34.6%), nausea (30.8%), anemia and thrombocytopenia (28.8% each), neutropenia (26.9%), constipation (25.0%), vomiting (23.1%), headache (21.2%), peripheral edema and hypokalemia (17.3% each), and arthralgia (15.4%). Grade ≥ 3 hematologic TEAEs included neutropenia (21.2%), thrombocytopenia (13.5%), and anemia (9.6%), none resulting in treatment discontinuation. Clinical pharmacokinetic and pharmacodynamic results demonstrated that lisaftoclax had a limited plasma residence and systemic exposure and elicited rapid clearance of malignant cells. With a median treatment of 15 (range, 6-43) cycles, 14 of 22 efficacy-evaluable patients with R/R CLL/SLL experienced partial responses, for an objective response rate of 63.6% and median time to response of 2 (range, 2-8) cycles.

CONCLUSIONS:

Lisaftoclax was well tolerated, with no evidence of tumor lysis syndrome. Dose-limiting toxicity was not reached at the highest dose level. Lisaftoclax has a unique pharmacokinetic profile compatible with a potentially more convenient daily (vs. weekly) dose ramp-up schedule and induced rapid clinical responses in patients with CLL/SLL, warranting continued clinical investigation.

2023-01-04·Clinical cancer research : an official journal of the American Association for Cancer Research

Lisaftoclax in Combination with Alrizomadlin Overcomes Venetoclax Resistance in Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia: Preclinical Studies

Article

作者: Zhang, Kaixiang ; Yang, Dajun ; Tang, Qiuqiong ; Xue, Sheng-Li ; Fang, Douglas D. ; Deng, Jing ; Yin, Yan ; Fu, Chengcheng ; Li, Na ; Wang, Qixin ; Zhai, Yifan ; Zhou, Feng

Abstract:

Purpose::

Despite approval of B-cell lymphoma (BCL)-2 inhibitor venetoclax for certain hematologic malignancies, its broader clinical benefit is curtailed by resistance. Our study aimed to determine if treatment with novel anticancer agents targeting BCL-2 and mouse double minute 2 (MDM2) could overcome venetoclax resistance in preclinical models.

Experimental Design::

Venetoclax-sensitive and venetoclax-resistant acute myeloid leukemia (AML) and acute lymphoblastic leukemia cells and xenograft models were used to evaluate antitumor effects and underlying mechanisms associated with combined BCL-2 inhibitor lisaftoclax (APG-2575) and MDM2 inhibitor alrizomadlin (APG-115).

Results::

The combination exhibited synergistic antiproliferative and apoptogenic activities in TP53 wild-type AML cell lines in vitro. This synergy was further exemplified by deep antitumor responses and prolonged survival in AML cell line–derived and patient-derived xenograft models. Interestingly, the combination treatment resensitized (to apoptosis) venetoclax-resistant cellular and mouse models established via chronic drug exposure or genetically engineered with clinically relevant BCL-2 gene mutations. Synergistic effects in reducing cellular viability and proliferation were also demonstrated in primary samples of patients with venetoclax-resistant AML treated with lisaftoclax and alrizomadlin ex vivo. Mechanistically, alrizomadlin likely primes cancer cells to BCL-2 inhibition-induced cellular apoptosis by downregulating expression of antiapoptotic proteins myeloid cell leukemia-1 and BCL–extra-large and upregulating pro-death BCL-2–associated X protein.

Conclusions::

Lisaftoclax in combination with alrizomadlin overcomes venetoclax resistance mediated by various mechanisms, including BCL-2 mutations. In addition, we posit further, putative molecular mechanisms. Our data rationalize clinical development of this treatment combination in patients with diseases that are insensitive or resistant to venetoclax.

2022-12-15·Clinical cancer research : an official journal of the American Association for Cancer Research

Lisaftoclax (APG-2575) Is a Novel BCL-2 Inhibitor with Robust Antitumor Activity in Preclinical Models of Hematologic Malignancy

Article

作者: Halder, Nabanita ; Ailawadhi, Sikander ; Ciccio, Gina ; Li, Caixia ; Miller, James ; Przybranowski, Sally ; Bai, Longchuan ; Wang, Guangfeng ; Wang, Hengbang ; Yang, Dajun ; Zhu, Saijie ; McEachern, Donna ; Manna, Alak ; Han, Bing ; Copland, John A. ; Fang, Douglas D. ; Deng, Jing ; Liu, Liu ; Stuckey, Jeanne A. ; Chen, Jianyong ; Dutta, Navnita ; Min, Ping ; Wu, Depei ; Yin, Yan ; Zhai, Yifan ; Wang, Shaomeng ; Ryan, Jeremy ; Wang, Mi ; Yang, Chao-Yie ; Chanan-Khan, Asher ; Letai, Anthony ; Paulus, Aneel

Abstract:

Purpose::

Development of B-cell lymphoma 2 (BCL-2)–specific inhibitors poses unique challenges in drug design because of BCL-2 homology domain 3 (BH3) shared homology between BCL-2 family members and the shallow surface of their protein–protein interactions. We report herein discovery and extensive preclinical investigation of lisaftoclax (APG-2575).

Experimental Design::

Computational modeling was used to design “lead” compounds. Biochemical binding, mitochondrial BH3 profiling, and cell-based viability or apoptosis assays were used to determine the selectivity and potency of BCL-2 inhibitor lisaftoclax. The antitumor effects of lisaftoclax were also evaluated in several xenograft models.

Results::

Lisaftoclax selectively binds BCL-2 (Ki < 0.1 nmol/L), disrupts BCL-2:BIM complexes, and compromises mitochondrial outer membrane potential, culminating in BAX/BAK-dependent, caspase-mediated apoptosis. Lisaftoclax exerted strong antitumor activity in hematologic cancer cell lines and tumor cells from patients with chronic lymphocytic leukemia, multiple myeloma, or Waldenström macroglobulinemia. After lisaftoclax treatment, prodeath proteins BCL-2‒like protein 11 (BIM) and Noxa increased, and BIM translocated from cytosol to mitochondria. Consistent with these apoptotic activities, lisaftoclax entered malignant cells rapidly, reached plateau in 2 hours, and significantly downregulated mitochondrial respiratory function and ATP production. Furthermore, lisaftoclax inhibited tumor growth in xenograft models, correlating with caspase activation, poly (ADP-ribose) polymerase 1 cleavage, and pharmacokinetics of the compound. Lisaftoclax combined with rituximab or bendamustine/rituximab enhanced antitumor activity in vivo.

Conclusions::

These findings demonstrate that lisaftoclax is a novel, orally bioavailable BH3 mimetic BCL-2–selective inhibitor with considerable potential for the treatment of certain hematologic malignancies.

204

项与 Lisaftoclax 相关的新闻（医药）

2024-09-19

·PRNewswire

Mantle Cell Lymphoma Clinical Trial Pipeline Insights Featuring 20+ Companies | DelveInsight

Mantle cell lymphoma is a rare and aggressive type of non-Hodgkin lymphoma originating from B-cells in the "mantle zone" of the lymph nodes. The development of novel targeted therapies and immunotherapies, such as Bruton's tyrosine kinase (BTK) inhibitors, is improving treatment outcomes and driving market growth for Mantle cell lymphoma. LAS VEGAS, Sept. 19, 2024 /PRNewswire/ -- DelveInsight's ' Mantle Cell Lymphoma Pipeline Insight 2024 ' report provides comprehensive global coverage of pipeline mantle cell lymphoma therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the mantle cell lymphoma pipeline domain. Key Takeaways from the Mantle Cell Lymphoma Pipeline Report DelveInsight's mantle cell lymphoma pipeline report depicts a robust space with 20+ active players working to develop 22+ pipeline therapies for mantle cell lymphoma treatment. Key mantle cell lymphoma companies such as AbbVie, Adicet Bio, InnoCare Pharma Inc., Guangzhou Lupeng Pharmaceutical Company LTD., BeiGene, Nurix, LegoChem Biosciences, Xynomic Pharmaceuticals, Merck & Co, Incyte Corporation, TG Therapeutics, Janssen/Pharmacyclics, Eternity Bioscience, Traws Pharm, Advenchen Laboratories, and others are evaluating new mantle cell lymphoma drugs to improve the treatment landscape. Promising mantle cell lymphoma pipeline therapies such as Venetoclax, ADI-001, Orelabrutinib, LP-168, BGB-11417, NX 2127, LCB 71, NX 5948, Abexinostat, Pembrolizumab, Parsaclisib, Umbralisib, Ibrutinib, Edralbrutinib, Narazaciclib, Lucitanib, and others are under different phases of mantle cell lymphoma clinical trials. In May 2024, AstraZeneca had announced positive interim results from the Phase III ECHO clinical trial, which evaluated Bruton's tyrosine kinase (BTK) inhibitor Calquence (acalabrutinib) in combination with standard chemoimmunotherapy for treating mantle cell lymphoma (MCL). In March 2024, BeiGene, Ltd. announced the presentation of emerging oncology pipeline data at the American Association for Cancer Research (AACR) Annual Meeting. Additional highlights include preclinical characterization data for an investigational BTK degrader, BGB-16673, currently in clinical development for B-cell malignancies, including mantle cell lymphoma In October 2023, Ascentage Pharma announced that it has entered into a clinical collaboration with AstraZeneca Investment. The two companies will jointly conduct a registrational Phase III study of the Bcl-2 inhibitor, APG-2575 (lisaftoclax), in combination with AstraZeneca's Bruton's tyrosine kinase (BTK) inhibitor, CALQUENCE® (acalabrutinib), in treatment-naive patients with first-line chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). In January 2023, the FDA granted an orphan drug designation to LP-284, a novel small-molecule, next-generation acylfulvene, for the treatment of mantle cell lymphoma (MCL), a rare and aggressive form of B-cell non-Hodgkin lymphoma (NHL), according to an announcement from Lantern Pharma. Request a sample and discover the recent advances in mantle cell lymphoma treatment drugs @ Mantle Cell Lymphoma Pipeline Report The mantle cell lymphoma pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage mantle cell lymphoma drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the mantle cell lymphoma clinical trial landscape. Mantle Cell Lymphoma Overview Mantle cell lymphoma (MCL) is a rare subtype of B-cell non-Hodgkin lymphomas (NHLs) characterized by the (11,14) translocation, leading to overexpression of the cyclin D1 (CCND1) gene. Its various morphological variants can make diagnosis challenging, though some cases are straightforward. Many individuals with MCL are asymptomatic in the early stages, but may later seek medical attention due to persistent, typically painless swelling of lymph nodes, especially in the neck and throat region (e.g., Waldeyer's ring). MCL is marked by a reciprocal chromosomal translocation t(11;14)(q13;q32), which places the cyclin D1 gene next to the immunoglobulin heavy chain gene, causing continuous cyclin D1 expression. This overexpression contributes to tumor cell proliferation through cell cycle dysregulation, chromosomal instability, and epigenetic changes. Rarely, MCL cases without this translocation may involve CCND2 or CCND3 translocations. Hypothetical molecular subtypes, based on the cell of origin, correlate with clinical phenotypes: classical or aggressive MCL arises from naive B cells lacking or having limited iGVH mutations and expressing SOX11, a neural transcription factor inhibiting terminal B cell differentiation. The indolent variant originates from antigen-experienced B cells with IGVH somatic hypermutations, typically SOX11-negative and genetically stable. Diagnosis of MCL involves detailed patient history, thorough clinical evaluation, and specialized tests, including biopsy of an affected lymph node or bone marrow. These tests confirm the NHL type and subtype, assess disease extent, and determine appropriate treatments. Treatment for MCL is multifaceted and tailored to each patient, often including chemotherapy, immunotherapy drugs like rituximab, targeted therapies such as ibrutinib, and stem cell transplants, particularly for aggressive disease or younger patients. Radiation therapy may target specific lymphoma areas. Participation in clinical trials can offer new treatment options. Treatment plans are developed collaboratively by healthcare professionals and patients, considering disease stage, overall health, and personal preferences. Regular monitoring and follow-up care are essential to track treatment response and manage side effects effectively. Find out more about mantle cell lymphoma treatment drugs @ Drugs for Mantle Cell Lymphoma Treatment A snapshot of the Mantle Cell Lymphoma Pipeline Drugs mentioned in the report: Learn more about the emerging mantle cell lymphoma pipeline therapies @ Mantle Cell Lymphoma Clinical Trials Mantle Cell Lymphoma Therapeutics Assessment The mantle cell lymphoma pipeline report proffers an integral view of the mantle cell lymphoma emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Mantle Cell Lymphoma Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Oral, Parenteral, Intravenous, Subcutaneous, Topical Therapeutics Assessment By Molecule Type: Recombinant fusion proteins, Small molecule, Monoclonal antibody, Peptide, Polymer, Gene therapy Therapeutics Assessment By Mechanism of Action: Apoptosis stimulants, Proto-oncogene protein c-bcl-2 inhibitors, Proteasome inhibitors, Immunologic cytotoxicity, T lymphocyte replacements, Agammaglobulinemia tyrosine kinase inhibitors Key Mantle Cell Lymphoma Companies: AbbVie, Adicet Bio, InnoCare Pharma Inc., Guangzhou Lupeng Pharmaceutical Company LTD., BeiGene, Nurix, LegoChem Biosciences, Xynomic Pharmaceuticals, Merck & Co, Incyte Corporation, TG Therapeutics, Janssen/Pharmacyclics, Eternity Bioscience, Traws Pharm, Advenchen Laboratories, and others Key Mantle Cell Lymphoma Pipeline Therapies: Venetoclax, ADI-001, Orelabrutinib, LP-168, BGB-11417, NX 2127, LCB 71, NX 5948, Abexinostat, Pembrolizumab, Parsaclisib, Umbralisib, Ibrutinib, Edralbrutinib, Narazaciclib, Lucitanib, and others Dive deep into rich insights for new drugs for mantle cell lymphoma treatment, visit @ Mantle Cell Lymphoma Drugs Table of Contents For further information on the mantle cell lymphoma pipeline therapeutics, reach out @ Mantle Cell Lymphoma Treatment Drugs Related Reports B-Cell Lymphoma Epidemiology B-Cell Lymphoma Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology as well as the B-cell lymphoma epidemiology trends. B-Cell Lymphoma Market B-Cell Lymphoma Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key B-cell lymphoma companies, including Vincerx Pharma, Ubix Therapeutics, Biomea Fusion Inc, Shanghai Hengrui Pharmaceutical, BeiGene, Hanmi Pharmaceutical, among others. Diffuse Large B-Cell Lymphoma Pipeline Diffuse Large B-Cell Lymphoma Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key DLBCL companies, including Genmab, Roche, Acerta Pharma, Autolus, Xynomic Pharmaceuticals, Genentech, Celgene, AbbVie, Mabion, among others. Diffuse Large B-Cell Lymphoma Market Diffuse Large B-Cell Lymphoma Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key B-cell lymphoma companies, including AbbVie, Genmab, Merck, Roche, Xencor and Janssen, Denovo Biopharma, Calithera Biosciences, IMV, Biogen, Autolus Therapeutics, Allogene Therapeutics, Novartis, Miltenyi Biomedicine, Regeneron Pharmaceuticals, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床3期免疫疗法孤儿药

2024-09-19

·药渡Daily

亚盛医药的成功上岸早在意料之中

亚盛医药的成功上岸早在意料之中。 2024年上半年，亚盛医药实现营业收入8.24亿元，同比增长477%；首次实现扭亏为盈，净利润达1.63亿元。抛开奥雷巴替尼出海带来的巨额收入不说，单就在国内的商业化成绩就已开始放量。2024年上半年，奥雷巴替尼的销售收入较2023年下半年及上半年分別增加120%及5%；进入国家医保定点医院数量较2023年底增加79%。7月又在澳门获批，适应症为治疗任何酪氨酸激酶抑制剂（TKI）耐药、并伴有T315I突变的慢性髓细胞白血病（CML）慢性期（-CP）和加速期（-AP）的成年患者，以及治疗对一代和二代TKI耐药及/或不耐受的CML-CP成年患者。奥雷巴替尼的最新进展还包括被纳入2024美国国家综合癌症网络（NCCN）慢性髓细胞白血病（CML）治疗指南、被纳入2024版《CSCO恶性血液病诊疗指南》，作为涉及慢性髓系白血病(CML)、费城染色体阳性急性淋巴细胞白血病（Ph+ ALL）领域的治疗的指南。临床研究也取得诸多进展，2024年5月，获国家药监局临床试验许可开展奥雷巴替尼针对系统性全身治疗失败的琥珀酸脱氢酶（SDH）缺陷型胃肠间质瘤（GIST）患者的注册III期临床研究POLARIS-3；2024年2月，获得美国FDA的许可开阵奥雷巴替尼针对过往接受过治疗的慢性髓细胞白血病慢性期（CML-CP，伴有及并无伴有T315I突变）患者的注册III期临床试验POLARIS-2。另外在EHA 2024、第60届ASCO年会、美国癌症研究协会（AACR）年会公布的最新临床数据都显示了奥雷巴替尼依旧强悍。奥雷巴替尼的商业化前景从来不是需要担忧的选项，但出海的预期却大大出人意料。 2024年6月，亚盛医药与武田订立独家选择权协议，授予武田制药独家选择权以就奥雷巴替尼订立独家许可协议。根据协议，武田拥有全球范围内（除中国、香港特别行政区、澳门特别行政区及台湾等地区以外）开发以及商业化奥雷巴替尼的独家权利。亚盛医药可收取1亿美元的选择权付款，并将有资格获得最高约12亿美元的选择权行使费和额外的潜在里程碑付款，以及年销售额两位数百分比的销售分成。此外，亚盛医药还向武田制药成功发行及配发合共2430.73万股股份，总额为7500万美元，武田由此成为亚盛医药的二股东。 MNC巨头的站台，无疑为亚盛医药巩固血液瘤龙头地位提供了有力支持，以至于其股价在三个月时间内就实现了翻倍。那么武田为何不惜下血本也要夺得奥雷巴替尼的海外权益？事实上，武田很早就拥有全球首款第三代BCR-ABL抑制剂，或许这个化学名对大部分中国人来说比较陌生，但如果换成“格列卫”，就耳熟能详了。电影《我不是药神》把治疗慢性粒细胞白血病（慢粒）的格列卫（一种BCR-ABL抑制剂）带入大众认知范围，伊马替尼为一代格列卫。伊马替尼疗效显著，但获得性耐药一直是慢粒白血病治疗的主要挑战。BCR-ABL激酶区突变是获得性耐药的重要机制之一，其中T315I突变是常见的耐药突变类型之一，在耐药慢粒白血病中的发生率为25%左右。因此二代达沙替尼、尼洛替尼和博舒替尼登场，但很快也耐药了，直到2012年12月，武田的三代格列卫普纳替尼在美国上市才缓解了耐药的局面。不过令人惋惜的是，一年以后，因“危及生命的血栓和血管重度狭窄”风险，美国FDA要求武田暂停这款药的销售和推广，普纳替尼也成了首个被要求撤市的小分子激酶抑制剂类抗肿瘤药。不过，由于临床需求太大，FDA最终没有让这款药物彻底退市，而是要求企业在说明书上以黑粗框警告风险。更让武田焦虑的是，2021年美国FDA批准诺华的阿思尼布用于慢性髓系白血病（Ph+CML-CP）的三线治疗，阿思尼布也是一款三代格列卫。阿思尼布在2023年销售额达4亿美元，入选2023年20大畅销新药，并且，今年6月1日，一项关于阿思尼布用于慢性髓系白血病一线治疗的三期临床达到主要终点，销售额可能还会再翻一番。武田的普纳替尼存在心脑血管不良事件等安全短板，而且专利在2026-2027年到期，选择和竞争对手亚盛医药合作，成了武田的最优选择。奥雷巴替尼目前已成为三代格列卫中事实上的Best-in-class，因其对普纳替尼、阿思尼布耐药或者无效的慢粒白血病患者有效。临床数据显示，奥雷巴替尼对比普纳替尼用于慢粒白血病慢性期的MMR率（主要分子学缓解率，是评估慢粒白血病患者治疗反应的重要指标）分别为53%和40%，对比用于慢粒白血病加速期的MMR率分别为40%和22%。从全球临床进展来看，奥雷巴替尼2024年2月获得FDA批准开展针对慢粒白血病慢性期的全球III期注册性临床，预计2026年完成注册临床并在美国申报上市，刚好与专利到期的普纳替尼实现无缝衔接。这是一个双赢的局面，武田获得续血的大秘宝，亚盛医药则成功获得巨额资金并将借此机会在美国申请高价发行股票上市。在现金流充裕之后，亚盛医药的脚步可能要更快了。根据半年报显示，截至上半年结束，亚盛医药的现金及银行结余为11亿元，7月，收到武田支付的独家选择权协议项下知识产权收入及选择权付款相关的1亿美元，后续很快还会有大额里程碑付款进账，如今的亚盛医药可谓兵强马壮，粮草充足。后续的研发进度可能将加快脚步。 Lisaftoclax（APG-2575）是一款由亚盛医药自主研发的、全球领先的Bcl-2选择性抑制剂，它通过阻断Bcl-2来恢复癌细胞的正常凋亡过程，已在中国、美国、澳洲及欧洲开展21项针对多种血液恶性肿瘤和实体瘤的Ib/II期临床研究，并获得了FDA授予的五项孤儿药资格认定。作为全球第二个进入全球注册临床试验的Bcl-2选择性抑制剂，Lisaftoclax相较于维奈克拉具备更优的有效性和安全性，展现出Best-in-class潜力。据临床验证，Lisaftoclax在治疗维奈克拉（唯一上市药物）无效的BTK耐药患者中显示出有效性，并且与BTKi联合使用时，对于TN CLL/SLL患者达到100%的ORR，对于r/r CLL/SLL患者也实现了98%的ORR。在安全性方面，Lisaftoclax中性粒细胞减少症和血小板减少症的发生率分别为30.3 %和13%，相较于维奈克拉显著降低（45%和21%），同时临床肿瘤溶解综合征的风险也较低。此外， Lisaftoclax与BTKi的联用中未观察到药物相互作用，且无剂量限制毒性，目前尚未达到最大耐受剂量。 2024年6月，在2024年欧洲血液学协会年会（EHA 2024）上，以壁报形式公布了Lisaftoclax联合新型治疗方案用于复发/难治性（R/R）多发性骨髓瘤（MM）或免疫球蛋白轻链（AL）淀粉样变性患者的最新数据。在A组（Lisaftoclax联合泊马度胺及地塞米松）中，ORR为70.4%，3级及以上治疗相关的中性粒细胞减少症发生率为14.3%。 2024年6月，在第60届美国临床肿瘤学会（ASCO）年会上以壁报展示形式公布了Lisaftoclax单药或联合治疗华氏巨球蛋白血症（WM）患者的全球多中心Ib/II期研究，以及Lisaftoclax联合阿扎胞苷（AZA）治疗新诊断AML或复发/难治性（R/R）急性髓性白血病（AML）患者的Ib/II期临床研究的最新成果。在39例新诊断为AML的老年/不耐受标准化疗的患者中，ORR及复合缓解率（CRc）分別为64.1%及51.3%。亚盛医药计划于2024年向国家药监局递交Lisaftoclax用于复发/难治性慢淋白血病/小淋巴细胞淋巴瘤的上市申请。除Lisaftoclax外，Pelcitoclax（APG-1252）、APG-2449（全球首个ALK/FAK/ROS1-TKI）、APG-5918（国内首个进入临床的EED抑制剂）都获得不错的进展。作为立志做BIC新药的企业，多年来亚盛医药十分执着且低调，以至于在某些时期非常不受投资者待见，股价长期被严重低估。但经过与武田合作一事，更进一步证明，坚持长期主义，坚持创新至上才是Biotech最好的出路。首度扭亏为盈值得纪念，今后很快将能摘B。在中国大地上，事实上还有很多这样坚持创新情怀的Biotech，正是这些药企在泥泞中的坚持，才让我们看到了中国创新药的未来。后续发展如何，药渡还将持续关注。

引进/卖出CSCO会议临床3期ASCO会议AACR会议

2024-08-27

·E药经理人

总收入创新高，头部创新药企2024上半年扭亏为盈

扭亏为盈一直是国内对未有盈利上市的Biotech的最大希冀。在资本寒冬下，一些Biotech已经走出亏损成功上岸，为中国创新药行业大大振奋了坚守与砥砺的信心。致力于在肿瘤等领域开发创新药物的领先的生物医药企业——亚盛医药（6855.HK）就成为了2024上半年最耀眼的港股创新药企之一。日前，亚盛医药公布2024年中期业绩。报告期内，公司在“全球创新”战略引导下，在对外合作、商业化、临床开发等方面均取得突破性进展。值得一提的是，2024年上半年公司总收入创新高，并首次实现盈利。 8月22日半年报发布后，亚盛医药已经连续两个交易日股价上涨，昨日涨幅近13%，成为港股医药板块领涨股。昨日收盘价32.4港元创下一年内新高，公司总市值突破百亿港元大关。报告期内，亚盛医药收入创新高，实现收入人民币8.24亿元，较去年同比增长477%，主要来源于产品销售收入和对外合作授权收入等。公司首次实现扭亏为盈，净利润达人民币1.63亿元。报告期内，公司首个上市品种奥雷巴替尼（商品名：耐立克）的商业化快速推进，实现销售收入人民币1.13亿元，较去年下半年环比增长120%，较去年上半年同比增长5%。公司与跨国制药企业武田就耐立克签署了一项独家选择权协议。一旦选择权被行使，武田将获得开发及商业化耐立克的全球权利许可，惟中国大陆、中国香港特别行政区、中国澳门特别行政区、中国台湾等地区除外。亚盛医药已收到选择权付款人民币7.2亿元和股权投资款项人民币5.4亿元。公司现金流持续获得改善，保持稳健充沛：截至2024年6月30日，货币资金余额为人民币11亿元；截至2024年7月初，货币资金余额为人民币18亿元。 01 开启重磅全球合作，达成中国小分子肿瘤药最大BD 亚盛医药一直积极寻求全球合作伙伴，在报告期内与跨国制药企业武田就耐立克达成独家选择权协议。该合作总交易额达人民币93.6亿元，包含7.2亿元的选择权付款，和共计86.4亿元的选择权行使费及额外的潜在里程碑付款。同时，公司还将获得基于年度销售额双位数的递增销售分成。截至目前，此项合作为国内小分子肿瘤药领域的最大的对外权益许可。此外，亚盛医药还获得武田的股权投资。该合作充分彰显了耐立克在全球的临床和商业化价值，也为其将来的全球商业化进程奠定了基石。目前，亚盛医药已收到武田人民币7.2亿元的选择权付款和人民币5.4亿元的股权投资款项。 02 耐立克商业化快速推进，造血能力不断增强随着公司原创1类新药耐立克的首个适应症于2023年1月获纳入医保；新适应症于2023年11月获批，耐立克正不断释放增长空间，亚盛医药的商业化造血能力也在逐步增强。报告期内，耐立克实现销售收入人民币1.13亿元，环比增长120%，同比增长5%。亚盛医药正快速推进上市品种的商业化。截至2024年6月30日，耐立克的全国准入医院和DTP药房共达到670家，其中准入医院数量较去年底增长达79%。继去年11月新适应症获批至今年6月30日，耐立克已获20个省83个城市114个项目的重特大疾病补充保险或惠民保报销，其中在河北省、海南省、内蒙古自治区、无锡、湖州、深圳、烟台等20个省级或者地市被纳入惠民保特殊药品目录，大大减轻患者就医负担，提高用药可及性。作为中国首个获批上市的第三代BCR-ABL抑制剂，耐立克的临床价值和潜力在报告期内不断得到国内外肿瘤领域的权威认可。2024年1月，该药物获纳入美国国家综合癌症网络（NCCN）慢性髓细胞白血病（CML）治疗指南；此外，耐立克于报告期内获2024 CSCO恶性血液病诊疗指南升级推荐，涉及CML、费城染色体阳性急性淋巴细胞白血病（Ph+ ALL）领域的治疗，并新增多项I级推荐。今年7月，耐立克在中国澳门获批上市，获批的适应症分别为治疗任何酪氨酸激酶抑制剂（TKI）耐药、并伴有T315I突变的CML慢性期（-CP）和加速期（-AP）的成年患者；以及治疗对一代和二代TKI耐药和/或不耐受的CML-CP成年患者。这是该药物继在中国内地获批上市后的又一重大里程碑。 03 全球创新成果斐然，8项注册临床全面推进在"全球创新"的战略引导下，亚盛医药于报告期内在临床开发方面取得多项里程碑进展，全球临床布局持续高速推进。截至目前，公司两大核心品种，耐立克及Bcl-2抑制剂APG-2575（Lisaftoclax）共斩获11项注册临床试验许可，其中3项已经完成，其他8项正全力推进。 2024年2月，耐立克获美国食品药品监督管理局（FDA）许可开展一项全球注册III期临床研究，用于治疗既往接受过治疗的CML-CP成年患者。这是耐立克获美国FDA许可的首个注册III期临床研究，也是亚盛医药全球血液肿瘤布局的重要一步。而在血液肿瘤之外，耐立克于今年6月获国家药品监督管理局（NMPA）药物审评中心（CDE）临床试验许可，开展其针对系统性全身治疗失败的琥珀酸脱氢酶（SDH）缺陷型胃肠间质瘤（GIST）患者的全球注册III期临床研究，这是公司在实体瘤领域临床开发的重大里程碑。此外，亚盛医药也在同步深耕Bcl-2选择性抑制剂APG-2575（Lisaftoclax）在血液肿瘤领域的临床布局。报告期内，APG-2575（Lisaftoclax）获CDE临床试验许可，开展一项该品种联合阿扎胞苷（AZA）一线治疗新诊断的中高危骨髓增生异常综合征（MDS）患者的注册III期临床研究，此为APG-2575（Lisaftoclax）获批开展的第四个注册III期临床研究。 04 耐立克商业化快速推进，造血能力不断增强作为始终聚焦全球创新的创新医药企业，亚盛医药打造了一条具有"First-in-class"与"Best-in-class"潜力的高价值产品管线，已在中国、美国、澳大利亚、欧洲及加拿大开展40多项临床试验。多管线品种在多领域的治疗潜力不断得到探索和验证，多项临床进展接连在各大国际学术会议上获得披露，进一步展现公司的产品研发优势与全球临床开发实力。报告期内，亚盛医药三个重点品种耐立克、APG-2575（Lisaftoclax）和APG-2449的四项临床进展入选2024美国临床肿瘤学会（ASCO）年会，这也是公司连续第七年在ASCO年会亮相。其中，耐立克治疗TKI耐药的SDH-缺陷型GIST患者的最新数据获口头报告。数据表明，耐立克在SDH-缺陷型GIST这一目前尚无标准治疗方案的疾病领域显示出良好的治疗前景，患者的临床获益率（CBR）达92.3%，中位无进展生存期（PFS）为 25.7个月。FAK/ALK/ROS1三联TKI APG-2449在非小细胞肺癌（NSCLC）患者中的最新数据也获ASCO年会展示，再次体现了该品种在NSCLC领域的治疗潜力。而在今年6月举办的2024年欧洲血液学协会年会（EHA 2024）上，亚盛医药展示了五项研究的最新进展，涉及耐立克、APG-2575（Lisaftoclax）和APG-5918三个重点品种，充分展现公司在血液肿瘤的竞争实力。耐立克有三项研究入选EHA 2024，其中一项在2023年美国血液学会（ASH）年会公布的数据基础上，更新了耐立克治疗CML和Ph+ ALL患者的中位1年随访数据。数据显示，耐立克在经过多个TKI治疗（包括对ponatinib或/和asciminib耐药），伴有或不伴有T315I突变的患者中，都表现出优异持续的临床疗效，且长期药物耐受性良好。 APG-2575（Lisaftoclax）在今年的ASCO年会和EHA年会上也有多项临床进展入选，均展现了该品种在多个血液肿瘤领域的治疗潜力。在本届ASCO年会上，亚盛医药展示了APG-2575（Lisaftoclax）联合AZA治疗初治（TN）或复发/难治性（R/R）急性髓性白血病（AML）患者的Ib/II期临床研究的最新积极数据、APG-2575（Lisaftoclax）单药或联合治疗华氏巨球蛋白血症（WM）患者的全球多中心Ib/II期研究最新积极数据。而在EHA 2024上，APG-2575（Lisaftoclax）治疗 R/R多发性骨髓瘤（MM）或免疫球蛋白轻链（AL）淀粉样变性患者的最新积极数据获展示。此外，耐立克、APG-115、APG-2449和APG-5918四个品种在今年美国癌症研究协会年会（2024AACR）上公布了三项临床前研究最新成果，为进一步临床探索提供了重要支持。 05 深化全球创新战略布局，迈向全新发展阶段为配合公司长期战略及发展，报告期内，亚盛医药已向美国证券交易委员会保密递交一份关于建议首次公开发售代表公司的普通股的美国存托股份的F-1表格登记草案。亚盛医药始终坚守"全球创新"战略，并坚持全球范围内的知识产权布局。截至2024年6月30日，公司在全球拥有520项授权专利，其中367项专利为海外授权。亚盛医药董事长、CEO杨大俊博士表示： “2024年上半年，亚盛医药在全球BD、产品商业化及全球临床开发方面均取得了多项里程碑式进展，充分展现了公司的全球创新实力、在血液肿瘤领域的竞争优势。报告期内，我们就耐立克与跨国制药企业武田达成高达逾人民币90亿元的全球合作，并将获得基于年度销售额双位数的递增销售分成。这是目前为止国内小分子肿瘤药的最大BD。此外，公司还获得武田5.4亿元人民币的股权投资。这一合作再次验证公司在行业的领先地位以及耐立克的全球实力，并有望在更多无药可医的领域释放临床价值。今年2月，耐立克获美国FDA许可，开展全球注册III期临床，也是该产品的全球化进程的重大里程碑。特别值得关注的是，公司在报告期内首次实现盈利。随着耐立克被纳入国家医保目录并获新适应症上市批准，公司商业化能力持续提升。同时，公司全球临床开发全面推进，管线重点品种的适应症获得不断拓展，进一步筑牢了公司在血液肿瘤领域的坚实竞争壁垒。未来我们将继续秉承以患者为中心、‘全球创新’的理念，进一步提升商业化能力，并加速在研品种在全球范围内的临床开发。我们期待能早日将多个全球创新药物推入国际市场，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，惠及全球患者，并为社会和股东创造更多价值。” 一审| 黄佳二审| 李芳晨三审| 李静芝

引进/卖出财报医药出海

100 项与 Lisaftoclax 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
急性髓性白血病	临床3期	中国	苏州亚盛药业有限公司	2024-06-11
急性髓性白血病	临床3期	中国	Ascentage Pharma Group, Inc.	2024-06-11
慢性淋巴细胞白血病	临床3期	俄罗斯	Ascentage Pharma Group, Inc.	2023-12-20
小淋巴细胞淋巴瘤	临床3期	俄罗斯	Ascentage Pharma Group, Inc.	2023-12-20
系统性红斑狼疮	临床2期	中国	Ascentage Pharma Group, Inc.	2024-08-09
系统性红斑狼疮	临床2期	中国	苏州亚盛药业有限公司	2024-08-09
复发性慢性淋巴细胞白血病	临床2期	中国	Ascentage Pharma Group, Inc.	2021-12-28
免疫球蛋白轻链淀粉样变性	临床2期	美国	Ascentage Pharma Group, Inc.	2021-12-23
ER阳性乳腺癌	临床2期	美国	苏州亚盛药业有限公司	2021-08-16
晚期恶性实体瘤	临床2期	美国	Ascentage Pharma Group, Inc.	2021-08-13

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


PRNewswire 人工标引	N/A	多发性骨髓瘤 \| 免疫球蛋白轻链淀粉样变性	44	APG-2575+泊马度胺+地塞米松 (MM)	繭簾襯構築鏇艱遞選願(顧壓夢製網餘鑰壓壓齋) = 蓋鑰積齋憲餘憲範齋鹽窪獵鹹範鏇壓餘廠襯鏇 (鏇構觸衊糧糧鏇觸餘繭 ) 更多	积极	2024-06-18
				APG-2575+达雷妥尤单抗+来那度胺+地塞米松 (MM)	鑰窪夢窪獵繭餘憲遞簾(繭構夢襯製淵網遞廠積) = 獵積鏇鏇積簾積衊糧衊鑰壓簾衊顧壓醖鏇獵遞 (窪壓衊蓋觸顧繭衊網糧 )
NCT04501120 (ASCO2024) 人工标引	临床1/2期	复发性急性髓细胞白血病 \| 难治性急性髓细胞白血病	72	Lisaftoclax+AZA (R/R AML)	鹹鏇觸壓膚夢膚糧獵鹽(餘鑰夢廠鬱繭構鏇憲鹽) = 積願壓鏇繭憲鬱膚醖廠壓壓鬱膚簾糧憲蓋蓋齋 (繭顧衊蓋糧獵觸夢鑰構, 28.1 ~ 63.6) 更多	积极	2024-05-24
				Lisaftoclax+AZA (Elderly/unfit AML)	鹹鏇觸壓膚夢膚糧獵鹽(餘鑰夢廠鬱繭構鏇憲鹽) = 齋鬱鹽鹽蓋糧襯夢積製壓壓鬱膚簾糧憲蓋蓋齋 (繭顧衊蓋糧獵觸夢鑰構, 34.8 ~ 67.6) 更多
NCT04260217 (APG2575WU101, ASCO2024) 人工标引	临床1/2期	巨球蛋白血症 MYD88 Gene Mutation Negative \| MYD88 \| CXCR4	46	Lisaftoclax	鏇廠遞夢簾積願襯餘衊(範憲觸簾淵艱憲衊範構) = 蓋繭鬱鑰蓋鬱鏇憲蓋餘顧鹹鑰範遞範艱網願構 (醖餘淵鑰廠醖積襯鏇選, 1 ~ 28) 更多	积极	2024-05-24
				Lisaftoclax + Ibrutinib	鏇廠遞夢簾積願襯餘衊(範憲觸簾淵艱憲衊範構) = 鏇顧鹽觸醖願艱襯製製顧鹹鑰範遞範艱網願構 (醖餘淵鑰廠醖積襯鏇選, 1 ~ 34) 更多
NCT04501120 (APG2575AC101, ASH2023) 人工标引	临床1/2期	髓系肿瘤 \| 急性髓性白血病 \| 骨髓增生异常综合征	115	Lisaftoclax monotherapy	餘遞願憲廠廠鏇鏇廠簾(糧顧糧顧網選遞艱簾窪) = 齋遞醖醖窪繭鏇觸遞築遞願鑰壓餘襯壓夢衊憲 (築顧鹽廠積簾觸醖願蓋 ) 更多	积极	2023-12-10
				Lisaftoclax+LD-HHT (R/R AML)	餘遞願憲廠廠鏇鏇廠簾(糧顧糧顧網選遞艱簾窪) = 築積願衊鬱窪艱遞壓壓遞願鑰壓餘襯壓夢衊憲 (築顧鹽廠積簾觸醖願蓋 ) 更多
NCT04942067 (APG-2575-MU101, ASH2023) 人工标引	临床1/2期	多发性骨髓瘤 \| 免疫球蛋白轻链淀粉样变性	30	Lisaftoclax + Pomalidomide + Dexamethasone (R/R MM)	壓蓋襯醖選壓膚蓋膚顧(鏇繭醖鹹膚願簾淵淵顧) = 衊憲醖鬱醖憲淵憲簾選餘鬱製窪顧鏇鹹窪繭鹹 (鏇淵壓壓鏇顧選憲網鬱 ) 更多	积极	2023-12-09
				Lisaftoclax + Daratumumab + Lenalidomide + Dexamethasone (R/R MM)	壓蓋襯醖選壓膚蓋膚顧(鏇繭醖鹹膚願簾淵淵顧) = 襯網築顧獵廠膚構艱齋餘鬱製窪顧鏇鹹窪繭鹹 (鏇淵壓壓鏇顧選憲網鬱 ) 更多
NCT04494503 \| NCT03913949 (APG-2575-CC101, ASH2023) 人工标引	临床1/2期	慢性淋巴细胞白血病	47	Lisaftoclax	蓋夢窪淵構壓餘簾選壓(鹽遞鏇網範願窪憲選簾) = 膚繭簾壓顧願膚蓋襯選鏇鏇製鹹構鹽齋廠鹽鹽 (齋憲築鏇廠夢獵衊築艱 ) 更多	积极	2023-12-09
NCT04260217 (ASCO2023) 人工标引	临床1/2期	巨球蛋白血症	46	Lisaftoclax (BTKi-resistant/intolerant pts + Arm A)	遞餘糧築艱繭製範艱築(遞簾蓋齋獵積艱鏇網壓) = At 1,200 mg, 1 DLT (grade 3 clinical TLS), due to pre-existing renal impairment, was reported. 顧壓襯製鑰鹽鏇簾鹹鬱 (選獵艱鬱鏇築齋築網製 ) 更多	积极	2023-05-26
				Ibrutinib+Lisaftoclax (treatment-naïve pts + Arm B)
NCT04215809 (ASH2022) 人工标引	临床2期	复发性慢性淋巴细胞白血病 \| 难治性小淋巴细胞淋巴瘤	141	Lisaftoclax	鏇窪夢願鹽構選艱製顧(範網繭鬱壓窪夢鏇窪夢) = Lisaftoclax 600 mg QD 壓膚網構網繭鬱齋鬱壓 (鹽築範顧獵獵繭鬱蓋製 ) 更多	积极	2022-11-15
				Acalabrutinib+Lisaftoclax
ASH2022 人工标引	临床2期	慢性淋巴细胞白血病 \| 小淋巴细胞淋巴瘤	141	Lisaftoclax	簾遞鏇鹹窪簾構憲衊襯(壓簾製獵醖鹽鏇襯範構) = 艱鹽窪積積鑰蓋壓糧顧鑰網願壓顧簾衊積憲觸 (獵鹹廠餘築積範艱夢衊 ) 更多	积极	2022-11-15
				Lisaftoclax+Rituximab	選醖繭窪夢製願網襯蓋(衊鏇遞襯選繭鏇鹹遞糧) = 糧壓範繭窪膚繭襯製蓋選糧觸鑰膚夢觸製範醖 (衊壓夢鑰鏇艱觸鹹願齋 ) 更多
NCT04494503 (ASCO2022) 人工标引	临床1/2期	复发性慢性淋巴细胞白血病 \| 难治性小淋巴细胞淋巴瘤	45	APG-2575	糧餘積餘構窪窪繭繭鹽(鏇廠遞鹹簾繭積糧齋觸) = 鏇繭艱鹽願製蓋製齋齋遞遞淵鬱壓衊夢淵蓋廠 (膚鹽窪糧鬱蓋構遞壓築 ) 更多	积极	2022-06-02