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更新于：2025-09-09

Venetoclax

维奈克拉

更新于：2025-09-09

概要

基本信息

药物类型

小分子化药

别名

VENCLYXTO、Venetoclax (JAN/USAN/INN)、维奈妥拉

+ [15]

靶点

Bcl-2

作用方式

抑制剂

作用机制

Bcl-2抑制剂(细胞凋亡调控因子Bcl-2抑制剂)

治疗领域

肿瘤免疫系统疾病血液及淋巴系统疾病+ [7]

在研适应症

复发性套细胞淋巴瘤难治性套细胞淋巴瘤难治性慢性淋巴细胞白血病+ [131]

非在研适应症

侵袭性非霍奇金淋巴瘤复发性B细胞淋巴瘤难治性B细胞淋巴瘤+ [22]

原研机构

在研机构

+ [31]

非在研机构

Janssen Research & Development LLCJanssen Scientific Affairs LLC

Janssen Pharmaceuticals, Inc.

权益机构

The University of Texas MD Anderson Cancer Center

Astex Pharmaceuticals, Inc.

Tolero Pharmaceuticals, Inc.

+ [4]

最高研发阶段批准上市

首次获批日期

美国 (2016-04-11),

慢性淋巴细胞白血病

最高研发阶段(中国)批准上市

特殊审评突破性疗法 (美国)、加速批准 (美国)、孤儿药 (美国)、孤儿药 (欧盟)、特殊审批 (中国)、孤儿药 (澳大利亚)、附条件批准 (中国)、孤儿药 (日本)

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结构/序列

分子式C45H50ClN7O7S

InChIKeyLQBVNQSMGBZMKD-UHFFFAOYSA-N

CAS号1257044-40-8

关联

767

项与维奈克拉相关的临床试验

NCT06802523

/ Recruiting临床1期IIT

A Phase I Study of Lintuzumab-Ac-225 in Combination With Venetoclax and ASTX-727 in Adults With Newly Diagnosed AML

This phase I trial tests the safety, side effects, and best dose of lintuzumab-Ac225 in combination with venetoclax and ASTX-727, and how well they work in treating patients with newly diagnosed acute myeloid leukemia (AML). Lintuzumab-Ac225 is a monoclonal antibody, called lintuzumab, linked to a radioactive agent called actinium Ac 225. Lintuzumab attaches to CD33 positive cancer cells in a targeted way and delivers actinium Ac 225 to kill them. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. ASTX-727 is a combination of two drugs, cedazuridine and decitabine. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Giving lintuzumab-Ac225 in combination with venetoclax and ASTX-727 may be safe and tolerable in treating patients with newly diagnosed AML and may improve the chance of going into remission and staying in remission for a longer period of time.

开始日期2026-04-21

申办/合作机构

National Cancer Institute

NCT06649812

/ Recruiting临床2期IIT

A Phase 2 Study of Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (ViPOR) in Relapsed or Refractory CD10-Negative Diffuse-Large B-Cell Lymphoma (DLBCL) and High-Grade B-Cell Lymphoma With MYC and BCL2 Rearrangements (HGBCL-DH-BCL2)

This phase II trial tests how well venetoclax, ibrutinib, prednisone, obinutuzumab, and Revlimid® (ViPOR) works in treating patients with CD10 negative diffuse large B-cell lymphoma (DLBCL) and high-grade lymphoma with MYC and BCL2 rearrangements that has come back after a period of improvement (relapsed) and/or that has not responded to previous treatment (refractory). Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Ibrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cell (a type of white blood cells) cancers at abnormal levels. This may help keep cancer cells from growing and spreading. Anti-inflammatory drugs, such as prednisone lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Obinutuzumab, a monoclonal antibody, binds to a protein called CD20, which is found on B cells and some types of leukemia and lymphoma cells. Obinutuzumab may block CD20 and help the immune system kill cancer cells. Revlimid, a type of anti-angiogenesis agent and a type of immunomodulating agent, may help the immune system kill abnormal blood cells or cancer cells. It may also prevent the growth of new blood vessels that cancers need to grow. ViPOR may be an effective treatment option for patients with relapsed and/or refractory CD10 negative DLBCL and high-grade B-cell lymphoma with MYC and BCL2 rearrangements.

开始日期2026-03-21

申办/合作机构

National Cancer Institute

NCT07153497

/ Not yet recruiting临床2期IIT

A Randomized Phase 2 Trial of Olutasidenib-Based Therapies in Patients With Newly Diagnosed IDH1-Mutant Myeloid Malignancies: A MyeloMATCH Substudy

This phase II MyeloMATCH treatment trial studies how well the addition of olutasidenib to usual treatment with cedazuridine-decitabine (ASTX727) with or without venetoclax works in treatment patients with higher-risk myelodysplastic syndrome (MDS) with a mutation in the IDH1 gene. Olutasidenib blocks the protein made by the mutated IDH1 gene. Blocking this protein may help keep cancer cells from growing. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Adding olutasidenib to the usual treatment (ASTX727 with or without venetoclax) may increase the likelihood of going into remission.

开始日期2026-02-26

申办/合作机构

National Cancer Institute

100 项与维奈克拉相关的临床结果

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100 项与维奈克拉相关的转化医学

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100 项与维奈克拉相关的专利（医药）

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5,001

项与维奈克拉相关的文献（医药）

2025-12-31·ANNALS OF MEDICINE

Significant prognostic improvement in elderly patients with acute myeloid leukemia treated with hypomethylating agents and venetoclax: outcomes from a retrospective real-world analysis

Article

作者: Wu, Yong ; Zheng, Jing ; Wu, Lanlan ; Chen, Yi ; Zhou, Jiayi ; Wu, Zhengjun ; Cai, Ruyu ; Wang, Zhengyang

OBJECTIVE:

This investigation aim to analyze the clinical features and therapeutic outcomes of elderly patients with acute myeloid leukemia (AML).

METHOD:

We conducted a retrospective analysis of the clinical and cytogenetic profiles of patients aged 60 years and older diagnosed with AML at the Fujian Medical University Union Hospital from 2016 to 2024.

RESULTS:

Our study cohort included 846 patients, with a median age of 67 years. The median duration of response (DOR) was 15.8 months, with 1-year, 3-year, and 5-year DOR rates of 55.3%, 23.4%, and 13.1%, respectively. The median overall survival (OS) was 21.8 months, with corresponding 1-year, 3-year, and 5-year OS rates of 58.7%, 41.2%, and 30.0%. Patients who received the azacitidine and venetoclax treatment protocol exhibited a complete remission (CR) rate of 57.1% and a minimal residual disease (MRD) - negative rate of 34.1%. These rates were comparable to the 59.2% CR rate and 39.4% MRD-negative rate observed in patients treated with intensive chemotherapy, and were superior to those with other low-intensity regimens. Compared to the treatment outcomes achieved at our center prior to 2016, when chemotherapy was the predominant treatment modality, which were characterized by a CR rate of 42.7%, a median OS of 9.2 months, and a mere 5-year OS rate of 13.5%, the remission rate and long-term survival of elderly patients with AML have been remarkable improved.

CONCLUSION:

The integration of hypomethylating agents and venetoclax into the treatment paradigm for elderly patients with AML has significantly enhanced survival rates.

2025-12-31·Hematology

Identification of t(X;1)(q28;q21) generating a novel GATAD2B::MTCP1 gene fusion in CMML and its persistence during progression to AML

Article

作者: Chen, Yu ; Zhu, Yi-yan ; Liu, Yi-zi ; Hou, Chun-xiao ; Zhang, Zhi-yu ; Chen, Su-ning ; Wang, Qian ; Zhang, Feng-hong

OBJECTIVE:

Hematological malignancies often involve chromosomal translocations and fusion genes that drive disease progression. While MTCP1 is well-known in T-cell prolymphocytic leukemia (T-PLL), its role in myeloid neoplasms is less understood. This report presents the first identification of the t(X;1)(q28;q21) translocation leading to the GATAD2B::MTCP1 fusion in acute myeloid leukemia (AML) transformed from chronic myelomonocytic leukemia (CMML).

METHODS:

The karyotypes were described according to the International System for Human Cytogenetic Nomenclature 2009. We performed targeted next-generation sequencing (NGS) on a panel of 172 genes commonly mutated in hematological malignancies (Supplemental Table 1), using an Illumina platform. RNA sequencing was conducted on total RNA extracted from bone marrow, also using the Illumina platform. The GATAD2B::MTCP1 fusion gene was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and Sanger sequencing, with specific primers for the fusion transcript (GATAD2B-F: CCTCTTTTTTTCGACGCC; MTCP1-R: ACTGAGCACAACACTTACGC).

RESULTS:

The GATAD2B::MTCP1 fusion results from a breakpoint on 1q21 within GATAD2B exon 1 and Xq28 within MTCP1 exon 2. The patient with the GATAD2B::MTCP1 fusion exhibited disease progression from CMML to AML. Despite achieving initial remission with venetoclax-based therapy and allo-HSCT, the patient relapsed and died.

CONCLUSIONS:

We propose that the GATAD2B::MTCP1 fusion upregulates MTCP1 expression rather than generating a fusion protein, thereby contributing to transformation and relapse in AML. Further investigations are needed to elucidate the precise role of this fusion event in myeloid malignancies.

2025-12-31·Hematology

First case report: near early T-cell precursor acute lymphoblastic leukemia with plasmacytoid dendritic cell proliferation effectively treated with Venetoclax plus HAG regimen

Article

作者: Feng, Yi ; Li, Dan ; Chen, Zhe ; Wang, Liping ; Luo, Hongqiang ; Liu, Fang ; Huang, Xin ; Han, Jiongping ; Feng, Weiying

BACKGROUND:

Near early T-cell precursor acute lymphoblastic leukemia represents a distinct subtype of T-cell acute lymphoblastic leukemia characterized by specific immunophenotypic and molecular biological characteristics. Currently, no standardized treatment protocol exists.

METHODS:

This study presents a case of near early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) characterized by plasmacytoid dendritic cell proliferation, which manifested clinically through pancytopenia and generalized multiple rashes.

RESULTS:

The patient underwent successful treatment with chemotherapy consisting of Venetoclax combined with HAG regimen administered for one cycle.

DISCUSSION:

This case report provides preliminary evidence suggesting that the combination of Venetoclax with HAG (homoharringtonine, cytarabine, and granulocyte colony-stimulating factor) regimen may constitute an effective and tolerable therapeutic approach for patients with near ETP-ALL. However, these initial observations necessitate further validation through comprehensive clinical studies with larger sample sizes to definitively establish the treatment's efficacy and safety profile.

1,609

项与维奈克拉相关的新闻（医药）

2025-09-09

·学术经纬

它掌控了癌细胞的生死！瞄准这种蛋白，多项研究有望从根源击杀肿瘤

编者按：细胞程序性死亡是个体生长发育、稳态维持与疾病调控的核心机制之一。BCL-2家族蛋白作为细胞生死决策的关键分子，通过精密调控凋亡与自噬，影响代谢、衰老乃至肿瘤发生。近年来，科学家以BCL-2家族蛋白为目标，从靶向抑制剂、PROTAC技术等多维度寻求更精准、安全的癌症治疗策略。长期以来，药明康德都在支持全球合作伙伴从药物研究（R）、开发（D）到商业化生产（M）各个阶段的需求，通过独特的一体化、端到端CRDMO模式，助力突破性疗法加速研发进程、早日惠及患者。本文系统梳理了BCL-2家族蛋白的功能机制与靶向治疗研究进展，并展望了未来方向。决定细胞命运的蛋白家族对个体来说，死亡意味着生命的终结。但在细胞世界里，死亡却是保持生命健康运转不可或缺的一环。多细胞生物的体内，每天都有大量细胞主动结束自己的生命，这个过程被称为细胞程序性死亡。这种主动诱导的死亡，包括细胞自噬与凋亡，对发育、稳态起到关键作用。例如，在胚胎发育时清除不需要的组织；清理受损或突变的细胞，避免无序生长；维持免疫系统的平衡，降低自身免疫风险。虽然这些过程各不相同，但它们有着共同的调控分子家族。BCL-2家族蛋白就是其中一类，它们会积极响应各类应激条件，并决定是否诱导凋亡。图片来源：123RF BCL-2家族根据功能和结构特征，可分为抗凋亡蛋白、促凋亡多结构域蛋白和BH3-only蛋白。其中，抗凋亡蛋白包括BCL-2、BCL-XL、MCL-1等，它们通过抑制线粒体外膜通透性，抑制细胞的凋亡；促凋亡多结构域蛋白（如BAX、BAK等）则可在激活后在线粒体外膜形成孔道，启动凋亡；而BH3-only蛋白作为细胞应激的感应器，可通过与抗凋亡蛋白结合或直接激活BAX/BAK，推动凋亡进程。 BCL-2的多重调节功能 BCL-2家族蛋白在多种生理过程中发挥着关键作用，其中之一是参与营养感知和代谢调节。当营养缺乏时，BCL-2蛋白被磷酸化，自噬水平的提升使得细胞开始将衰老或受损的细胞器分解为营养成分，为细胞供能。此外，BCL-2的表达和活性随年龄增长而下降，这会损害线粒体的功能，导致与年龄相关的病理特征加剧。 BCL-2家族蛋白还在癌症进展中扮演着重要角色。在多种癌症中，细胞为了逃避凋亡，常常通过遗传或表观遗传机制增强抗凋亡蛋白的表达或功能。通过大规模筛选，研究人员发现，BCL-2、BCL-XL和MCL-1在多种癌症中是维持癌细胞生存的关键基因。例如，慢性淋巴细胞白血病（CLL）对BCL-2高度依赖，而结直肠癌细胞则对BCL-XL表现出显著依赖性。基于这些发现，BCL-2家族蛋白成为极具潜力的癌症治疗靶点。图片来源：123RF 当下，一类癌症治疗策略是用小分子模拟BH3-only蛋白的结构。上文提到，BH3-only蛋白可与抗凋亡蛋白结合。而BH3结构域模拟物能够竞争性结合抗凋亡蛋白的疏水口袋，释放促凋亡蛋白来诱导癌细胞凋亡。科学家从本世纪初开始，一直在进行相关药物的研发。经过一系列结构改造以提高口服生物利用度、减轻毒副作用后，首个BCL2选择性抑制剂Venetoclax（ABT-199）诞生，它能模拟BH3的结构，与BCL-2蛋白结合，阻断BCL-2与促凋亡蛋白的相互作用。 2016年，FDA批准Venetocla用于治疗具有染色体17p缺失的复发/难治性CLL。随后，这款药物的适应症也在不断拓展。目前，Venetoclax联合CD20抗体用于CLL一线治疗，24个月无进展生存率高达88.2%；联合低甲基化药物Azacitidine治疗老年急性髓系白血病（AML）患者，中位生存期延长至14.7个月，显著优于传统化疗。靶向BCL-2，更多抗癌疗法在路上不过，在长期广泛使用中，Venetoclax的耐药问题也逐渐显现。耐药机制主要包括BCL-2基因突变（如G101V）、MCL-1或BCL-XL的代偿性上调，以及BAX/BAK的蛋白功能缺失。科学家们也在针对这些问题探索应对策略。比如，一项近期研究就针对MCL-1靶点获得了新突破。MCL-1的BH3结合沟槽较浅，难以与小分子结合，因此针对MCL-1的抑制剂设计难度更大。而该研究通过结构导向药物设计（SBDD）和大环化策略，成功开发出一系列高活性、高选择性的MCL-1抑制剂。其中最具代表性的化合物对MCL-1的抑制活性达到皮摩尔级别，并且具有良好的溶解性，适合静脉注射。这款化合物几乎不会与BCL-2、BCL-XL等蛋白结合，因此能避免血小板毒性等副作用。在多种血液肿瘤细胞系中，该化合物表现出强烈的促凋亡活性。在小鼠肿瘤模型中，单次静脉注射即可引起肿瘤显著缩小甚至完全消退，效果可持续数周。论文信息显示，药明康德为该研究提供了赋能。 PROTAC®技术助力未来疗法除了小分子抑制剂，科学家们还在持续探索其他的低毒副作用策略。其中，PROTAC®技术的发展为BCL-2靶向治疗提供了新思路。这类新型分子一端与靶蛋白结合，另一端与E3泛素连接酶结合，诱导泛素连接酶给靶蛋白打上泛素“标签”，标记它们被送入蛋白酶体降解。由Dialectic Pharmaceuticals 设计，具有PROTAC®作用机制的分子DT2216，一端携带了靶向BCL-2成分，另一端则可以介导VHL连接酶，诱导泛素化降解。在多种肿瘤模型中，DT2216单药即可克服抗肿瘤药物吉西他滨的耐药，且未引起骨髓或心脏毒性。目前，研究者正在开展1期临床试验，在复发/难治性血液及实体瘤患者中评估安全性和有效性。还有其他数种基于PROTAC®机制的分子同样处于研发阶段，例如SIAIS361034, PZ15227 和XZ739。它们针对的是BCL-XL蛋白，借助不同长度或化学性质的连接分子调整分子的稳定性，从而实现更强的降解效率。长期以来，药明康德都在支持全球合作伙伴从药物研究（R）、开发（D）到商业化生产（M）各个阶段的需求，通过独特的一体化、端到端CRDMO模式，助力突破性疗法加速研发进程、早日惠及患者。在PROTAC®技术领域，药明康德在该技术刚刚起步时，就前瞻性地布局了相关能力和技术，搭建了集发现、合成、分析纯化和测试等能力于一体的一体化赋能平台，助力全球合作伙伴高效推进药物从早期发现到临床试验阶段。伴随着新型靶向蛋白降解技术的持续涌现，药明康德紧跟科学前沿，迅速构建相关技术平台。依托一体化研发平台，药明康德可系统赋能PROTAC®从结构验证到分子机制解析、从DMPK评估到制剂优化全流程开发。公司构建了完善的研究体系，支持验证三元复合物形成及泛素-蛋白酶体通路介导的靶点降解，并搭建了专门应对溶解性、吸收性与代谢稳定性挑战的DMPK研究平台，同时提供多样化制剂方案，提升口服生物利用度。 BCL-2家族蛋白作为一类关键的调控节点，不仅能为细胞生死做出选择，也为癌症、神经退行性疾病等提供了新的干预思路。相信在未来，从基础机制到临床转化，更多针对BCL-2家族的研究将不断涌现，造福全球患者。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~

2025-09-09

·PRNewswire

iOnctura Expands Roginolisib Trials to the US, Advancing Multi-Indication Strategy in Oncology

US cancer centers begin enrolling patients into the global, randomized Phase II study of roginolisib in metastatic uveal melanoma Dana-Farber Cancer Institute launches new trial of roginolisib for Chronic Lymphocytic Leukemia, backed by Department of Defense grant GENEVA, AMSTERDAM and CAMBRIDGE, Mass., Sept. 9, 2025 /PRNewswire/ -- iOnctura, a clinical-stage precision oncology company focused on neglected and hard-to-treat cancers, today announces the expansion of its clinical trial program for lead candidate roginolisib into the United States. Several US trial sites are now enrolling patients in the OCULE-01 Phase II study in metastatic uveal melanoma, with an additional study, led by Dr Jennifer Brown, underway in chronic lymphocytic leukemia (CLL) at Dana-Farber Cancer Institute. Catherine Pickering, CEO and co-founder of iOnctura said, "We are proud to begin the next phase of iOnctura's global growth by making roginolisib available to US patients in our clinical studies. The enthusiastic response from US investigators, leading research centers, and patient communities highlights the significant opportunity to impact outcomes for individuals with limited treatment options." Roginolisib, an orally dosed small molecule allosteric modulator of PI3Kδ, is being investigated in multiple randomized Phase II studies in solid and hematological malignancies. The global Phase II randomized OCULE-01 study (NCT06717126) will assess whether roginolisib improves overall survival in patients with metastatic uveal melanoma who have progressed on prior therapy. Patients from both the US and Europe are now being treated in the study, which started in March 2025. Roginolisib is also being investigated in patients with non-small cell lung cancer (NSCLC) (NCT06879717) and myelofibrosis (NCT06887803). In these diseases, targeting the PI3Kδ pathway in combination with standard therapies has potential to reverse resistance[1],[2]. Seeing the promise of roginolisib as a combination therapy, the US Department of Defense (DoD) recently awarded a substantial grant to Dr. Jennifer Brown at Dana-Farber Cancer Institute in Boston, MA, to explore the potential of roginolisib in relapsed / refractory CLL in a Phase I / II study (NCT06644183). Dr. Jennifer R Brown, M.D. Ph.D., Director of the CLL Center of the Division of Hematologic Malignancies at Dana-Farber Cancer Institute and Principal Investigator on the study and grant said, "We are enthusiastic about the potential of roginolisib in enhancing treatment outcomes for CLL patients who have relapsed after prior Bruton's tyrosine kinase inhibitor therapy. We feel roginolisib offers a promising avenue to improve remission depth and duration in combination with venetoclax and rituximab, whilst minimizing treatment-related side effects." Recently published preclinical evidence by Sasi, Tarantelli et al. supports the synergistic potential of roginolisib and venetoclax in the treatment of CLL[3]. For more information contact: iOnctura Corporate Press Office: [email protected] About iOnctura iOnctura is a clinical-stage precision oncology company combating neglected and hard-to-treat cancers with a pipeline of first-in-class small molecules. The bold new treatments extend lives and improve healthspans, changing the outlook for patients and their families. Lead asset, roginolisib, is an allosteric modulator of PI3Kδ with a unique chemical structure and binding mode. Allosteric modulation is a new archetype for precise inhibition of PI3Kδ, promising clinical activity without the detrimental tolerability seen with previous generations of inhibitors. Roginolisib is being investigated in multiple randomized Phase II studies in solid and hematological malignancies. iOnctura is headquartered in Amsterdam, The Netherlands with subsidiaries located in Geneva, Switzerland and Cambridge, MA, USA. iOnctura is backed by specialist institutional investors including Syncona, M Ventures, Inkef Capital, EIC Fund, VI Partners, Schroders Capital and XGEN Venture. About roginolisib Roginolisib is an allosteric modulator of PI3Kδ with a unique chemical structure and binding mode. Allosteric modulation is a new archetype for precise inhibition of PI3Kδ, promising clinical activity without the detrimental tolerability seen with previous generations of inhibitors. The PI3K signaling pathway is one of the most commonly dysregulated pathways across multiple cancer types. The potential of roginolisib has been validated by positive clinical signals in Phase I in solid tumor and hematological malignancies, including a doubling of overall survival compared to historical controls in rare eye cancer, uveal melanoma. The company has carefully designed its clinical program to allow full development in uveal melanoma, while in parallel validating the program in larger market indications. The Phase II OCULE-01 study in uveal melanoma started in March 2025, the PULMO-01 study in NSCLC started in May 2025. Further studies in other malignancies, including myelofibrosis, are being initiated. [1] Exposito et al., Cancer Res (2023) 83 (15): 2513–2526 [2] Moyo et al., Clin Cancer Res (2023) 5; 29(13): 2375-2384 [3] Sasi, Tarantelli et al., Haematologica, published online June 2025 Logo - SOURCE iOnctura WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床2期临床1期

2025-09-05

·药时代

CD47的一次罕见成功！

融资的机会来了！~ 多家知名VC公司寻找优质投资标的，感兴趣的管线包括：（1）针对实体瘤的创新性TCE、（2）新靶点/新核素的创新性核药、（3）Abeta双靶点等CNS创新药、（4）新靶点/新MOA的自免创新药。请有相关产品的biotech公司立即联系药时代BD团队（BD@drugtimes.cn）！正文共：3204字 0图预计阅读时间：13分钟在沉寂许久后，CD47领域终于迎来了又一笔BD交易。 2025年8月28日，浙江昂利康制药股份有限公司（以下简称“昂利康”）发布公告，宣布其与亚飞(上海)生物医药科技有限公司（以下简称“亚飞生物”）、上海亲合力生物医药科技股份有限公司（以下简称“亲合力”）签署《战略合作协议之授权许可协议》，将获得靶向CD47的IMD-1005药物分子在中国（包括中华人民共和国大陆地区、香港特别行政区、澳门特别行政区以及中国台湾地区）的研发、生产、商业化独家权益。根据协议，昂利康将分阶段向亚飞生物、亲合力合计支付1.5亿元人民币首付款，以及向亲合力支付最高不超过6.2亿元人民币的研发、销售里程碑付款。此外，在协议约定的销售分成期间，昂利康需向亲合力支付12.8%的销售分成。近一两年，CD47研发领域整体并不乐观，失败案例数量远多于成功案例。昂利康的此次交易无疑为这一领域注入了新的活力。为什么说CD47是块难啃的硬骨头 2009年，斯坦福大学医学院Irving Weissman 教授团队在 Cell 上发表了一篇题为“CD47 Is an Adverse Prognostic Factor and Therapeutic Antibody Target on Human Acute Myeloid Leukemia Stem Cells“的论文。论文提到，经研究发现CD47在许多肿瘤细胞表面大量上调，通过使用抗CD47抗体，可以破坏CD47的“别吃我”信号，发出信号并释放巨噬细胞来吞噬肿瘤，在相关血液肿瘤中具有显著治疗作用。在这篇论文结果的助推下，CD47受到业内广泛关注，并被业界寄予"下一个PD-1"的期望。但十几年来，药企在CD47领域的探索并不顺利，或者宣布失败，或者半路退出。吉利德 2024年6月，吉利德在2024年欧洲血液学协会（EHA）会议上公布了其CD47单抗Magrolimab的III期 ENHANCE 研究新数据。数据显示，与安慰剂组相比，Magrolimab与化疗（阿扎胞苷+维奈克拉）的联用方案的完全缓解率更低，且死亡风险增加20.3%。也就是说，用了这款药，不仅病情得不到好转，还会增加死亡风险。 Magrolimab为吉利德49亿美元收购Forty Seven所得。2020年，通过这场价值不菲的收购，吉利德踌躇满志地入局CD47 ，跻身CD47领域头部玩家。但近4年的探索显示，CD47确实是个难啃的硬骨头。早在此项结果公布于众前，吉利德就已停止了这款CD47单抗的大部分临床试验的招募/研究（包括实体瘤和血液瘤）。 ENHANCE研究的停止意味着吉利德将全面放弃Magrolimab的开发。当时，吉利德表示，停止Magrolimab的研究是由于对该药物在实体瘤和血液肿瘤中所有可用的安全性和有效性数据进行了全面审查后的决定。艾伯维 2020年9月，天境生物同艾伯维就天境自主研发的CD47单抗——lemzoparlimab在全球开发和商业化开展合作。根据协议条款，艾伯维将向天境生物支付1.8亿美元的首付款、2000万美元的近期里程碑付款及最高17.4亿美元的里程碑付款。据悉，这是当时中国Biotech有史以来最大的跨国对外授权战略合作。但就在合作达成2年后（2022年中），艾伯维接连宣布终止了lemzoparlimab的两项临床试验：1）lemzoparlimab与口服或静脉注射地塞米松制剂联用或不联用，治疗成人多发性骨髓瘤（MM）的研究；2）lemzoparlimab+阿扎胞苷+venetoclax 联合治疗骨髓增生异常综合征（MDS）/AML的 I 期临床试验。在此基础上，2023年9月，艾伯维宣布终止了其与天境生物的这项合作，归还lemzoparlimab所有权益。 Arch Oncology和ALX Oncology Arch Oncology由Pamela Manning于2006年创立，是实打实的CD47领域的先驱玩家。凭借其CD47管线AO-176的积极研发进展，Arch Oncology成功于2016年、2019年及2021年分别筹集了 8600万美元、5000万美元及1.05亿美元，一时风头无两。但就在完成其C轮融资十几个月后，Arch Oncology突然宣布终止其在研CD47管线的所有研发工作，并解散了公司大部分员工。随后，Arch Oncology的CEO Laurence Blumberg 跳槽至ALX Oncology（以下简称为“ALX”）——另一家聚焦CD47领域的公司。ALX的核心管线为evorpacept（也称为 ALX148），也是一款CD47抑制剂。 ALX的CD47项目也毫无意外的不顺利。2023年8月，ALX宣布将终止evorpacept的ASPEN-02和ASPEN-05研究，这两项研究分别用于评估evorpacept与化疗药物联合治疗MDS和AML的有效性。目前evorpacept的研究仍在继续，研究结果有喜有悲。2024年7月，ALX报告了其ASPEN-06 II 期研究的顶线数据，结果显示，evorpacept联合疗法的ORR为 40.3%，对照组仅为 26.6%，有效改善了HER2阳性胃癌患者的肿瘤反应。但在今年早些时候，ALX也曾报告了evorpacept联合K药治疗转移性或不可切除的复发性头颈癌中的两项研究失败。辉瑞 2021年，辉瑞和Trillium Therapeutics（以下简称为“Trillium”）联合宣布，双方已达成协议，辉瑞将以约22.6亿美元的价格收购Trillium，获得其阻断CD47-SIRPα信号通路的两款在研疗法——TTI-622和TTI-621。目前，辉瑞的这两款CD47项目均已暂停。 2025年6月底，辉瑞宣布，因患者招募困难，将终止maplirpacept (TTI-622）与化疗药物（来那度胺）联合用于复发或难治性弥漫性大B细胞淋巴瘤患者的II期研究。但辉瑞特别强调，终止该研究是由于“招募受阻，并非安全或疗效翻车”。此前，辉瑞已将另一项CD47项目——TTI-621从管线列表中删除。 CD47 还需更多成功案例本次，昂利康的这笔交易的主要分子是IMD-1005。据昂利康信息，该分子由亲合力自研，是一款具有创新性的全球首创肿瘤微环境激活型遮罩型抗体药物，其抗体部分为CD47单抗。昂利康明确指出，IMD - 1005（昂利康将其重新命名为ALK - N002）作为全球创新的肿瘤微环境激活型IgG1亚型靶向CD47的遮罩型抗体药物，有望为肿瘤患者带来全新的免疫治疗方案，为肿瘤治疗领域注入新的活力。临床前研究结果显示，注射用IMD-1005在SHP77（人小细胞肺癌）及Raji（淋巴瘤）CDX肿瘤模型中，均能呈剂量依赖性抑制肿瘤生长，药效突出；在临床前动物安全性评价实验中，IMD-1005的安全性优秀。安全性问题是目前CD47领域的重点关注方向，此前很多项目都是折在了药物的安全性问题上。这与CD47表达机制有关。前文提到，CD47在许多肿瘤细胞表面大量上调。此前，正是因为这种机制层面上展现出的适应症拓展潜力，才吸引了不少药企和投资公司来此掘金。但需要注意的是，CD47不仅在肿瘤细胞表面表达，同时还在人体红细胞高度表达。当一款CD47抗体进入人体后，将优先和外周血中的红细胞和白细胞等正常细胞结合，未与正常细胞结合的 CD47抗体才能最终获得与肿瘤细胞结合的权力，起到肿瘤杀伤作用。因此，在研的 CD47管线一般剂量都不低。但这种高剂量会导致一个问题，即会有大量的CD47抗体与红细胞结合，并进一步导致红细胞被裂解/吞噬，最终导致溶血、贫血等不良反应发生。因此，如何绕开CD47的高剂量血液毒性是一众CD47管线在开发中重点考量的问题。昂利康此次交易的重点——IMD-1005主要是通过技术手段优化抗体结构，从而提升安全性。该CD47抗体对 CD47 靶点的结合活性因偶联了遮罩而大大降低，在血液中高度稳定，从而避免了CD47抗体活性所导致的血液毒性。目前CD47领域仍有大量类似IMD-1005的项目试图突破困境，改变该领域的研发现状。据智慧芽数据库信息显示，眼下全球仍有两百余条CD47管线在研，覆盖单抗、双抗、ADC、CAR-T等多个药物类型。其中，进入III期临床阶段的仅3家，分别为宜明昂科的timdarpacept、康方生物的ligufalimab及EpicentRx的nibrozetone。国内方面，宜明昂科现在正在推进两项相关III期临床，分别为：1）timdarpacept与替雷利珠单抗联用治疗PD(L)-1单抗难治性经典型霍奇金淋巴瘤；2）timdarpacept联合阿扎胞苷治疗慢性粒-单核细胞白血病。（信息来源于第一财经文章）康方生物针对ligufalimab的布局则涉及实体瘤及血液瘤两方面。其中，一项血液瘤临床研究是在美国开展的针对骨髓增生异常综合征的II期临床研究，一项实体瘤的临床研究是 CD47单抗联合 PD-1/VEGF双抗药物依沃西，对比K药一线治疗PD-L1表达阳性复发/转移性头颈部鳞状细胞癌的头对头III期临床试验。此外，在ASCO2025上，ImmuneOncia Therapeutics公布了其新一代CD47抗体IMC-002联合仑伐替尼治疗晚期肝细胞癌（HCC）患者的1b期临床试验中期结果。在这项剂量扩展阶段研究，IMC-002展现出良好的安全性特征，未报告中性粒细胞减少症或血小板减少症病例。13例患者中有2例（15%）出现轻度贫血，96%的不良事件为1-2级，且主要发生在首个治疗周期。目前，这些CD47产品均进展良好。这也说明一个问题，即：虽已有不少失败案例在前，但该领域仍有不少成功案例正在陆续披露。不过，仍需注意的是，在0个管线成功获批上市的前提下，CD47赛道的低成功率将导致投资者对该领域保持谨慎态度。一笔交易带给整个赛道的活力是有限的，无论交易还临床数据，CD47赛道仍在等待更多成功案例！接下来是一条会议宣传：目前，药时代与肝病新药联盟应行业需求，决定于2025年11月21-22日在上海举办“第四届肝病新药联盟年会暨减重新药论坛”活动（线下）。活动有幸邀请到了多位行业资深专家，将聚焦肝病及相关领域的最新科研成果、临床实践和未来发展方向，来自医院、药企、CRO、投资机构等单位的专家、学者们将齐聚一堂，从不同的角度分享他们的行业洞见和宝贵经验。欢迎感兴趣的读者持续关注，药时代公众号将持续更新会议最新动态。主办单位：肝病新药联盟、药时代协办单位：中国医药生物技术协会慢病管理分会、中国医师协会脂肪肝专家委员会、爱肝联盟。展位火热预定中！扫码立即咨询赞助形式包括但不仅限于演讲席位、会场展位、会刊彩页、晚宴赞助、会议用品宣传等。参考资料： 1.https://www.biospace.com/embattled-researchers-see-path-forward-for-anti-cd47-cancer-drugs 2.https://endpoints.news/scoop-roche-backed-startup-gives-up-on-cd47-as-ceo-most-employees-leave/ 3.https://endpoints.news/scoop-roche-backed-startup-gives-up-on-cd47-as-ceo-most-employees-leave/ 4.其他公开资料图片来源：即梦AI 刚刚！超10亿美元！恒瑞医药宣布Myosin抑制剂NewCo出海 2025-09-05 FDA推出新加速审评通道！直指超罕见遗传病 2025-09-04 这家Biotech融资2亿美元！曾与恒瑞达成合作... 2025-09-04 版权声明/免责声明本文为原创文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢! 药时代官方网站:www.drugtimes.cn 联系方式: 电话:13651980212 微信:27674131 邮箱:contact@drugtimes.cn 点击查看往期肝病新药联盟精彩活动！

引进/卖出临床3期并购

100 项与维奈克拉相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10679	维奈克拉	L01XX52	DB11581

研发状态

批准上市

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
复发性套细胞淋巴瘤	日本	AbbVie LLC	2025-03-27
难治性套细胞淋巴瘤	日本	AbbVie LLC	2025-03-27
难治性慢性淋巴细胞白血病	日本	AbbVie LLC	2019-09-20
复发性慢性淋巴细胞白血病	日本	AbbVie LLC	2019-09-20
小淋巴细胞淋巴瘤	美国	AbbVie, Inc.	2018-06-08
成人急性髓性白血病	欧盟	AbbVie Deutschland GmbH & Co. KG	2016-12-04
成人急性髓性白血病	冰岛	AbbVie Deutschland GmbH & Co. KG	2016-12-04
成人急性髓性白血病	列支敦士登	AbbVie Deutschland GmbH & Co. KG	2016-12-04
成人急性髓性白血病	挪威	AbbVie Deutschland GmbH & Co. KG	2016-12-04
急性髓性白血病	加拿大	AbbVie AS	2016-10-31
慢性淋巴细胞白血病	美国	AbbVie, Inc.	2016-04-11

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
肿瘤溶解综合征	临床3期	美国	AbbVie, Inc.	2024-08-05
肿瘤溶解综合征	临床3期	澳大利亚	AbbVie, Inc.	2024-08-05
肿瘤溶解综合征	临床3期	法国	AbbVie, Inc.	2024-08-05
肿瘤溶解综合征	临床3期	希腊	AbbVie, Inc.	2024-08-05
肿瘤溶解综合征	临床3期	塞尔维亚	AbbVie, Inc.	2024-08-05
肿瘤溶解综合征	临床3期	西班牙	AbbVie, Inc.	2024-08-05
肿瘤溶解综合征	临床3期	中国台湾	AbbVie, Inc.	2024-08-05
肿瘤溶解综合征	临床3期	英国	AbbVie, Inc.	2024-08-05
复发性急性髓细胞白血病	临床3期	美国	AbbVie, Inc.	2022-10-01
复发性急性髓细胞白血病	临床3期	美国	Genentech, Inc.	2022-10-01

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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


NCT05184842 (Phase II, CTgov)	临床2期	急性髓性白血病 \| 慢性粒单核细胞白血病 \| 骨髓增生异常综合征	-	Venetoclax+Decitabine	夢鹹憲鹽糧遞鏇蓋顧構 = 製夢獵廠鑰夢齋簾獵築蓋淵築鹽獵鹹窪餘壓襯 (衊鏇膚鏇網衊鹽壓鏇鬱, 齋鑰糧艱艱餘襯選鹽艱 ~ 艱夢顧願夢鑰選艱遞衊) 更多	-	2025-08-26
NCT04102020 (VIALE-M, CTgov)	临床3期	急性髓性白血病	112	Venetoclax+Azacitidine (Part 1: Venetoclax 400 mg + Azacitidine 20 mg/m^2)	網遞襯齋鬱餘構積窪齋 = 醖壓壓範窪廠憲簾窪壓憲醖繭膚繭遞鬱憲願願 (餘選構獵鏇淵艱壓膚鑰, 衊鑰繭繭蓋繭積選簾築 ~ 艱構餘鹹鏇夢範選範膚) 更多	-	2025-08-20
NCT04102020 (VIALE-M, CTgov)	临床3期	急性髓性白血病	112	Venetoclax+Azacitidine (Part 1: Venetoclax 400 mg + Azacitidine 36 mg/m^2)	網遞襯齋鬱餘構積窪齋 = 積選繭獵積鹽獵膚觸鏇憲醖繭膚繭遞鬱憲願願 (餘選構獵鏇淵艱壓膚鑰, 衊淵壓憲膚齋範獵醖獵 ~ 築觸築積憲齋廠憲蓋憲) 更多	-	2025-08-20
NCT03580928 (AMPLIFY \| AVO, CTgov)	临床2期	慢性淋巴细胞白血病	72	Acalabrutinib+Venetoclax+Obinutuzumab (Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With Non-high-risk CLL Disease)	築艱顧鏇鬱製襯艱願膚 = 廠鬱蓋鏇遞淵蓋簾鬱醖蓋顧顧窪製憲窪壓壓鏇 (襯願願簾蓋築鑰築願簾, 襯艱鹹願艱鑰夢構遞窪 ~ 糧觸壓醖衊願構廠網積) 更多	-	2025-08-12
NCT03580928 (AMPLIFY \| AVO, CTgov)	临床2期	慢性淋巴细胞白血病	72	Acalabrutinib+Venetoclax+Obinutuzumab (Acalabrutinib/Venetoclax/Obinutuzumab (AVO) With High-risk CLL Disease)	築艱顧鏇鬱製襯艱願膚 = 膚壓範夢範鏇窪襯壓淵蓋顧顧窪製憲窪壓壓鏇 (襯願願簾蓋築鑰築願簾, 襯顧夢選繭網繭壓廠壓 ~ 願製築衊壓淵選積淵夢) 更多	-	2025-08-12
NCT03013998 (Pubmed \| J Clin Oncol)	临床1期	难治性急性髓细胞白血病 NPM1m \| KMT2Ar	43	Azacitidine, Venetoclax, and Revumenib	觸遞製餘獵獵淵糧衊艱(構廠襯鑰廠獵鑰膚願糧) = present in 8 (19%) patients 顧鏇蓋淵簾構齋憲壓夢 (鬱齋窪壓選憲窪壓餘醖 ) 更多	积极	2025-08-10
NCT03872180 (CTgov)	临床2期	套细胞淋巴瘤	23	bendamustine+Venetoclax+Obinutuzumab	艱蓋鬱顧鬱選鏇衊蓋壓 = 觸醖鏇糧鬱鏇鏇窪繭窪鹹鹽獵繭淵範醖鹹觸獵 (餘遞願獵壓選鹽鑰鑰鬱, 網選築繭鹽鏇繭築簾鑰 ~ 憲繭廠鑰襯網鹽鹽築鑰) 更多	-	2025-08-06
NCT04797767 (Phase 1 trial of venetoclax with cladribine, cytarabine, G-CSF, and mitoxantrone for AML and high-grade myeloid neoplasm, Pubmed)	临床1期	髓系肿瘤 \| 急性髓性白血病	-	Venetoclax 400 mg	遞醖鬱夢膚鏇糧蓋鹽獵(獵醖鹽衊顧膚遞餘蓋醖) = 5% 壓鬱範鏇夢廠餘衊簾餘 (網壓廠鏇蓋窪網簾選醖 )	积极	2025-08-01
NCT02755597 (BELLINI, Pubmed \| Lancet Haematol)	临床3期	难治性多发性骨髓瘤	291	Venetoclax	膚蓋鏇衊簾網廠獵簾構(壓壓製顧築鹹餘淵範衊) = 30% of 193 vs 8% of 96 patients 遞壓範壓夢鏇衊齋繭鹽 (齋憲顧鏇鬱壓鹽繭蓋範 ) 更多	不佳	2025-08-01
NCT02755597 (BELLINI, Pubmed \| Lancet Haematol)	临床3期	难治性多发性骨髓瘤	291	Placebo		不佳	2025-08-01
NCT03112174 (SYMPATICO, CTgov)	临床3期	套细胞淋巴瘤	366	Ibrutinib+Venetoclax (Randomization Phase: Ibrutinb + Venetoclax)	廠選繭醖淵構糧遞鬱淵(糧選積遞鑰鑰壓夢醖顧) = 鑰觸觸襯觸鬱醖顧簾製範壓範憲網醖鑰選鏇繭 (艱醖鏇鑰鑰築積窪鑰醖, 膚廠網築蓋鹹築窪壓製 ~ 選淵蓋觸製鏇襯鹹醖壓) 更多	-	2025-07-22
NCT03112174 (SYMPATICO, CTgov)	临床3期	套细胞淋巴瘤	366	Placebo Oral tablet to match Venetoclax+Ibrutinib (Randomization Phase: Ibrutinib + Placebo)	廠選繭醖淵構糧遞鬱淵(糧選積遞鑰鑰壓夢醖顧) = 網繭積獵衊鹽鹽鬱膚鑰範壓範憲網醖鑰選鏇繭 (艱醖鏇鑰鑰築積窪鑰醖, 蓋衊衊觸蓋觸膚夢糧夢 ~ 觸衊鏇顧繭糧齋窪簾膚) 更多	-	2025-07-22
NCT02966756 (M14-728, NEWS) 人工标引	临床2期	慢性淋巴细胞白血病 Loss of Chromosome 17p	69	Venetoclax	憲壓製築範鹽艱夢簾鏇(願襯壓廠淵網憲憲壓鹹) = 願觸鏇醖壓獵憲壓廠選憲選憲顧範築鑰鑰蓋膚 (築鬱願鹽蓋憲積觸築築 ) 更多	积极	2025-07-20
NCT01889186 (M13-982, NEWS) 人工标引	临床2期	慢性淋巴细胞白血病 Loss of Chromosome 17p	153	维奈克拉	憲簾網膚蓋願醖鑰製積(鹹窪築餘顧觸憲遞鑰壓) = 夢廠積窪鏇壓衊製餘憲艱艱窪醖淵憲窪構壓築 (網選遞範網鑰憲顧簾齋, 22.8 ~ 37.1) 更多	积极	2025-07-20