A Randomized Phase II Trial of ASTX727 With Standard Duration Versus Shorter Duration of Venetoclax in Genomically Heterogenous AML Among Adults Aged 60 or Older and Less Fit for Intensive Therapy: A MyeloMATCH Substudy

This phase II MyeloMATCH treatment trial compares ASTX727 with standard duration versus shorter duration of venetoclax for the treatment of newly diagnosed acute myeloid leukemia (AML). ASTX727 is a combination of decitabine and cedazuridine. 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. 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. 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. Shorter duration venetoclax may be as effective as standard duration venetoclax when given with ASTX727 for the treatment of newly diagnosed AML.

开始日期2027-04-18

申办/合作机构

National Cancer Institute

NCT06917911

/ Recruiting临床2期IIT

Phase II Study of Cytarabine + Daunorubicin (7 + 3) + Gemtuzumab Ozogamicin vs. Cytarabine + Daunorubicin (7 + 3) + Venetoclax for the Treatment of Newly Diagnosed Core Binding Factor Acute Myeloid Leukemia (CBF-AML) in Younger Adults: A MyeloMATCH Substudy

This phase II MYELOMATCH treatment trial compares the effect of venetoclax to gemtuzumab ozogamicin, when given with cytarabine and daunorubicin ("7+3" regimen), for the treatment of patients with core binding factor acute myeloid leukemia (CBF-AML). 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. Gemtuzumab ozogamicin is a monoclonal antibody, called gemtuzumab, linked to an antitumor antibiotic drug, called ozogamicin. Gemtuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD33 receptors, and delivers ozogamicin to kill them. Chemotherapy drugs, such as cytarabine and daunorubicin work in different ways to stop the growth of cancer cells either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax with cytarabine and daunorubicin may have fewer side effects and be as effective or better than the combination with gemtuzumab ozogamicin in treating patients with core binding factor AML.

开始日期2027-02-02

申办/合作机构

National Cancer Institute

NCT07738887

/ Not yet recruiting临床2期IIT

Epcoritamab Plus Venetoclax Plus Ibrutinib in Patients With Chronic Lymphocytic Leukemia With TP53 Alterations

This is a phase 2, open-label, multicenter study evaluating the efficacy and safety of a fixed-duration combination of epcoritamab, venetoclax, and ibrutinib (EVI) in previously untreated patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have TP53 alterations.
Patients with TP53 abnormalities, including TP53 mutation and/or 17p deletion, have a poorer prognosis and are less likely to benefit from conventional chemoimmunotherapy. Targeted therapies such as ibrutinib and venetoclax have improved outcomes in this population, but many patients eventually experience disease progression. This study investigates whether adding epcoritamab, a CD3×CD20 bispecific antibody, to the combination of ibrutinib and venetoclax can improve the depth and durability of treatment responses while using a fixed-duration treatment approach.
Participants will receive sequential treatment with ibrutinib alone, followed by ibrutinib plus venetoclax, and then the triple combination of epcoritamab, venetoclax, and ibrutinib. The study will evaluate the effectiveness of this regimen, including the achievement of deep remission, as well as its safety and tolerability in this high-risk patient population.

开始日期2026-12-31

申办/合作机构

Le LYSARC

[+3]

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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5,475

项与维奈克拉相关的文献（医药）

2027-01-01·CLINICA CHIMICA ACTA

BCL-2 in leukemia: Enhancing clinical utility

Review

作者: Khan, Abida ; Khalid, Mohammad ; Bakht, Md Afroz ; Rehman, Zia Ur ; Singla, Neelam ; Ali, Md Imtiaz ; Kamal, Mohammad Azhar ; Imran, Mohd

B-cell lymphoma 2 (BCL-2) is an important anti-apoptotic protein in the mitochondrial cell death pathway and is biologically significant for leukemic cell survival, apoptosis resistance, drug resistance, and disease persistence. BCL-2 is clinically relevant in hematopathology and laboratory medicine, as it is a central regulator of apoptosis in several leukemia subtypes. This review evaluates BCL-2 primarily as a prognostic, treatment-stratifying, and venetoclax-related predictive biomarker in leukemia, while critically examining its more limited and context-dependent diagnostic contribution. We summarize existing data on the association of BCL-2 expression and functional dependency with leukemia biology, cytogenetic and molecular risk factors and survival. We also explore its use in distinguishing leukemic populations from non-malignant hematopoietic populations, primarily in conjunction with morphology, immunophenotyping, cytogenetics, molecular testing, and other markers of apoptosis. Laboratory considerations for clinical implementation are addressed, such as specimen selection, inter-platform variability, antibody and gating strategies, immunohistochemistry, flow cytometry, transcript-based assessment, functional apoptotic profiling, and preanalytical, analytical, and interpretative variability. We also discuss the clinical relevance of BCL-2 in venetoclax-based therapy, where dependence on BCL-2 may be more informative than expression. Overall, BCL-2 is better supported as prognostic and treatment-stratifying marker than a diagnostic marker in leukemia. To move BCL-2 assessment into routine laboratory practice, it will be necessary to establish harmonized thresholds for BCL-2 assays and to validate the analytical workflow and result in prospective studies. This review outlines the potential and current challenges of BCL-2 as an emerging biomarker in human leukemia within a laboratory medicine framework.

2026-12-01·Blood Research

The role of m6A RNA methyltransferase METTL3 in drug resistance mechanisms in acute myeloid leukemia

Review

作者: Prajapati, Suresh ; Patel, Mansi ; Gupta, Reeshu ; Jyotishi, Charmi

Abstract:

This review examines the role of METTL3, a core RNA methyltransferase, in therapeutic resistance in acute myeloid leukemia (AML) and discusses emerging strategies to address this challenge. METTL3 regulates N 6 -methyladenosine (m 6 A) modifications on transcripts involved in key cellular processes, including apoptosis (BCL2, MCL1), metabolism (PGC-1α, CSRP1), proliferation (MYC), autophagy (FOXO3), and bone marrow microenvironmental interactions (ITGA4, AKT1). These modifications enhance the stability and translation of resistance-associated genes, supporting leukemic cell survival under treatment pressure. Pharmacological targeting of METTL3 has shown efficacy in preclinical AML models. Inhibitors such as STM2457, METTL3-directed PROTACs, and rational drug combinations with agents including venetoclax, anthracyclines, and ATRA, have reversed resistance phenotypes and impaired leukemic cell fitness. Beyond canonical resistance mechanisms, METTL3 also regulates noncoding RNAs, autophagy, and metabolic–epigenetic crosstalk, including histone lactylation, linking epitranscriptomic regulation to broader resistance pathways. By integrating molecular, cellular, and microenvironmental evidence, this review underscores METTL3 as a central driver of drug resistance and a promising therapeutic target in relapsed or refractory AML. Unlike previous summaries, it highlights the convergence of METTL3-mediated m 6 A modifications with noncoding RNA regulation, autophagy, and niche adaptation, and critically evaluates emerging therapeutic approaches, including catalytic inhibitors, PROTACs, and natural compounds.

2026-12-01·Blood Research

Novel treatment strategies in acute myeloid leukemia

Review

作者: Simkhada, Shailesh ; Joshi, Utsav ; Dhakal, Prajwal

Acute myeloid leukemia (AML) is a molecularly diverse hematologic malignancy, with clinical outcomes driven by patient fitness, disease biology, and the depth of remission. Over the past decade, the increasing use of molecular studies has enabled genotype-directed therapy and accelerated the incorporation of targeted agents into both intensive and lower-intensity treatment regimens. FLT3 inhibitors are now well established across a wide disease spectrum, including frontline settings, relapsed/refractory disease, and post-allogeneic hematopoietic cell transplantation maintenance, with emerging evidence supporting measurable residual disease (MRD)-adapted maintenance approaches. IDH1/2 inhibitors offer therapy for specific molecular subsets, particularly in older or unfit patients, and are increasingly being evaluated in doublet and triplet combinations. Venetoclax-based regimens have become a cornerstone for older or unfit patients with AML and are being optimized through response-adapted dosing and careful partner selection to mitigate cytopenias while deepening remission. Menin inhibitors represent a major therapeutic advance for KMT2A-rearranged and NPM1-mutated AML and are rapidly moving into combination and earlier-line treatment strategies. In parallel, immune and cellular therapies, including antibody-drug conjugates, immune checkpoint modulation, bispecific engagers, and chimeric antigen receptor T-cell and chimeric antigen receptor natural killer constructs, are under investigation, although durable, practice-changing benefits outside select settings remain limited to date. This review synthesizes pivotal clinical data and translational principles informing emerging targeted, immune-based, and cellular strategies in AML, with an emphasis on remission depth, MRD-driven decision-making, and relapse prevention.

2,927

项与维奈克拉相关的新闻（医药）

2026-09-02

·氨基观察

消失的CD47们

氨基观察-创新药组原创出品作者 | 沙晓威还守在CD47牌桌上的玩家，越来越少了。 4个月前，又一名CD47玩家下线。辉瑞在2026年一季度业绩及最新管线中，一款CD47药物maplirpacept被从开发名单中剔除。至此，辉瑞花费23亿美元从Trillium收购而来的CD47全部出局。后续，赛道内或许还会有玩家陆续退出。翻看港股等上市药企最新半年报不难发现，部分曾经重点推介的CD47分子，如今在财报或者推介材料里的笔墨持续缩减。眼下，对于还在坚守的药企来说，CD47还值不值得做、又该怎么做下去，是必须思考的问题。 / 01 / “堡垒”相继倒下过去十年，CD47领域其实一直在迭代升级，但始终没有一款分子，能在临床上明确地证明自己。最引人瞩目的，是吉利德的magrolimab。 2020年，吉利德以约49亿美元收购FortySeven，将magrolimab收入囊中，该药是彼时全球进展最快的CD47单抗。且在治疗MDS和AML的早期试验中，联合阿扎胞苷曾展现出高达91%的总体反应率，被寄予厚望。在设计上，magrolimab采用IgG4型抗体，降低了与Fc受体的结合力，减少非特异性激活，并使用剂量递增的给药策略，希望解决CD47在正常红细胞上高表达所造成的贫血问题。但真正进入临床研究后发现，magrolimab的优化远远不够。ENHANCE-3研究显示：在既往未接受强化化疗、接受阿扎胞苷+维奈克拉治疗的AML患者中，加入magrolimab并没有改善总生存期，且增加了死亡风险。基于安全性风险及疗效不佳，吉利德提交了magrolimab的停药申请。这还是开始，2025年才是CD47的至暗时刻。海外最受关注的、CD47最后的“堡垒”们，接连倒下了。先是4月，ALX Oncology宣布其开发的CD47抑制剂Evorpacept，在与K药联用的两项Ⅱ期临床试验ASPEN-03和ASPEN-04中，均未达到主要终点目标。此前，该公司已终止了Evorpacept针对MDS和AML的临床试验。紧随其后的6月，辉瑞宣布收购而来的CD47靶向药物maplirpacept在治疗复发/难治性弥漫性大B细胞淋巴瘤的II期研究因患者招募困难终止，在此前另一款CD47产品ontorpacept也已从研发管线中消失。这些“堡垒”的倒下，让CD47的赛道一度深陷迷茫。 / 02 / “别吃我”不容易 CD47靶点的核心困境在于，毒性与疗效的平衡，难以达成。这也是这些重磅产品失败的共性原因。 CD47广泛表达于正常细胞，尤其是红细胞。阻断CD47-SIRPα信号，可以解除肿瘤细胞的“别吃我”保护，但也可能同时解除了对正常血细胞的保护。更麻烦的是，CD47抗体高亲和力容易被“中和”，引发“抗原沉默”，因此治疗需提高剂量。而高剂量，又带来贫血、溶血等严重的血液毒性。许多分子正是基于CD47这一困境，进行升级改造，但效果并不理想。例如，辉瑞的maplirpacept通过SIRPα-IgG4融合蛋白尝试减毒，但过度弱化结合力而使得疗效不足，进而采用高剂量给药。临床上，ontopacept和 maplirpacept的最大剂量分别为2 mg/kg和24 mg/kg。尽管临床结果中maplirpacept导致的≥3级不良事件比ontorpacept更少，但还是有30%的血小板减少事件出现。完全失活Fc的策略也不成立。ALX Oncology的evorpacept就是一个典型例子，其保留了高亲和力CD47结合结构，而采用失活Fc，目的就是降低与正常红细胞相关的Fc介导效应，从而改善传统CD47抗体的安全性。然而，更安全的设计并没有带来更好的疗效。Evorpacept联合K药治疗头颈鳞癌的研究，同样未达到主要终点。 Arch Oncology的AO-176也是针对IgG2 Fc段结合的CD47抗体，不激活ADCC，但具有直接杀伤作用，在非人灵长类动物的血液学参数影响甚微，未观察到短暂性贫血。然而，AO-176的I/II期临床试验中期数据显示，33%的患者出现血小板减少症（其中22%为3级短暂性血小板减少症），22%的患者出现贫血。显然，“别吃我”机制下，疗效与毒性之间的那条平衡线，始终是CD47药物迈不过的坎。而随着一批批优化后的分子失败，CD47的临床价值，也一次又一次受到质疑。 / 03 / 撤退OR前进在辉瑞这些选手相继倒下后，撤退还是继续前进，成了摆在所有坚守者面前的关键问题。眼下，仍有一批玩家在CD47上持续探索，也确实透出一些积极信号。 Evorpacept是联合疗法的典型代表。由于Fc段失活，Evorpacept几乎没有单药活性（ADCC、ADC、CDC等效应），无法触发巨噬细胞去吞噬肿瘤。因此必须采用联合疗法，依靠联用的其他单抗或ADC药物来提供“吃我”的活化信号，进一步发挥免疫效应。在随机II期ASPEN-06中，evorpacept联合曲妥珠单抗、雷莫芦单抗和紫杉醇治疗既往接受过抗HER2治疗的HER2阳性胃癌/胃食管结合部癌。 2025年更新数据显示，在确认HER2阳性的患者中，ORR达到48.9%，对照组为24.5%，mDOR为15.7个月对9.1个月。但FDA并没有给予高度评价，毕竟该适应症还有Enhertu这座大山横在面前。国内也有不少玩家在坚守。康方生物的AK117同样做了优化，将其定位为新一代CD47抗体，通过分子设计降低传统CD47抗体面临的红细胞凝集等问题。 2026年EHA公布的AK117-206是一项随机、双盲、安慰剂对照II期研究，60例初治且不适合强化化疗的AML患者接受AK117（或安慰剂）+阿扎胞苷+维奈克拉治疗。数据显示AK117组ORR为80.0%，对照组为66.7%。CRc为56.7%，安慰剂组为53.3%，CRc持续时间为10.4个月对6.5个月，优势明显。但其中细节仍值得玩味。首先安慰剂组CRc持续时间为6.5个月，但在AML标准治疗的临床数据中（VIALE-A），持续时间为14.7个月，当前对照组明显弱于以往。尽管这是基于患者基线情况引发的差异，但这一数据仍然让AK117的价值遭到质疑。安全性问题也不容忽略。该研究中两组治疗≥3级TEAE的发生率分别为96.7%和93.3%，均有43.3%的患者报告了≥3级贫血。这意味着，AK117没有显著加重贫血，却也未能消除CD47类药物固有的血液毒性负担。目前，康方生物正在开展AK117联合AK112的3项III期临床研究，是CD47赛道上目前进度最快的选手之一。在进度上能与它比肩的，还有宜明昂科的IMM01。该药为IgG1 Fc融合蛋白，通过在D1结构域引入突变、去除糖基化位点，降低与红细胞的结合亲和力。 IMM01联合阿扎胞苷治疗CMML的II期临床数据显示，ORR为72.7%（对照组为37.5%），CR率为27.3%，显著高于对照组8.3%。 2026年7月16日，宜明昂科宣布IMM01联合阿扎胞苷治疗初治CMML的III期临床已完成173例患者的全部入组工作，进度与AK117不相上下。这些坚守者的努力，或许能给CD47赛道带来一些新的希望。当然，也可能是又一次失望。 / 04 / 不要被“下一代PD-1”叙事掩盖未来，属于CD47的前途或许是光明的，但道路注定是曲折的。时至今日，CD47已经给我们带来了最大的教训——不要被“下一代PD-1”叙事掩盖。 PD-1成功之后，业内意识到，肿瘤免疫治疗并不只有进攻一种方式，“刹车”也是重要的手段。而研究发现与T细胞一样，巨噬细胞同样存在“刹车”。于是，CD47“别吃我”信号被包装成了新的肿瘤治疗免疫检查点。一时间，CD47被视作继PD-1之后最值得下注的免疫靶点之一。但事后来看，免疫系统还是太复杂了。首先，CD47不是一个简单的免疫“开关”。已有研究指出，CD47并不只是通过SIRPα传递“别吃我”信号，它广泛存在于人体细胞表面，并与SIRPα、整合素、VEGFR2、CD36、FAS等多个受体及信号通路发生相互作用。其次，多项研究汇总发现，CD47药物在人体诱导的肿瘤免疫抑制效果远不如在小鼠等动物模型中表现出的抗肿瘤活性。 2026年《Science》的一项最新研究，也揭示了CD47在血液瘤中的复杂性。研究团队利用人源AML细胞和人源巨噬细胞进行了全基因组CRISPR筛选，结果发现，CD47对小鼠巨噬细胞的吞噬抑制作用非常明显，但在人源巨噬细胞中，这种作用却非常有限。进一步研究发现，AML细胞表面的CD43及其O-糖基化、唾液酸化，是限制人源巨噬细胞吞噬的重要机制。这说明在人体系统里，控制巨噬细胞“别吃我”信号的，可能远远不只是CD47-SIRPα这一条通路。种种研究表明，CD47远比想象中复杂。而过去，面对它未知的那一面，产业理性恰恰被“下一代PD-1”的叙事所掩盖。这或许才是创新药研发最危险的时刻，不是一个靶点失败，而是产业对一个靶点过于乐观，乐观到忽略了它本就存在的风险。

2026-09-01

·GlobeNewswire-Health Care

NetraMark Strengthens Board of Directors with Appointment of Veteran Pharmaceutical Executive Dr. Keith Fournier

Pharmaceutical industry leader brings more than 20 years of global drug development, regulatory strategy and portfolio leadership experience across AbbVie, Merck KGaA, AstraZeneca and AbivaxTORONTO, Sept. 01, 2026 (GLOBE NEWSWIRE) -- NetraMark Holdings Inc. (the "Company" or "NetraMark") (TSX: AIAI) (OTCQB: AINMF) (Frankfurt: PF0), a clinical intelligence company transforming clinical trials with AI-powered precision analytics in the pharmaceutical industry, announced today the appointment of Dr. Keith M. Fournier, PhD, RAC, to its Board of Directors. Dr. Fournier is a highly experienced pharmaceutical executive with more than two decades of leadership across drug development, global regulatory strategy and cross-functional portfolio management. His career has spanned the development lifecycle from Investigational New Drug (IND) activities through global registration and lifecycle management, with senior positions at several of the world’s leading pharmaceutical organizations. Dr. Fournier currently serves as Senior Vice President, Head of Regulatory Affairs, at Abivax where he leads the company’s regulatory organization and strategy supporting advancement of its pipeline. Prior to Abivax, he served as Vice President, Global Regulatory Affairs at EMD Serono, the healthcare business of Merck KGaA, where he led approximately 75 regulatory leaders and project managers responsible for regulatory strategies across a broad global portfolio. Dr. Fournier also contributed to overall global regulatory organizational strategy as a member of the Regulatory, Quality and Safety leadership team. In addition, Dr. Fournier previously held a series of senior leadership positions at AbbVie. As an Asset Strategy Leader within AbbVie’s oncology organization, he led cross-functional strategy for VENCLEXTA® (venetoclax) programs across hematologic and solid tumors. He previously served as Senior Director and Therapeutic Area Lead for Global Regulatory Affairs in Immunology and as Global Regulatory Lead for HUMIRA®. Prior thereto, Dr. Fournier also spent five years at MedImmune, an AstraZeneca company, where he served as a Global Regulatory Lead across the respiratory, inflammation and autoimmune portfolio, including late-stage development programs in systemic lupus erythematosus, scleroderma and myositis. “Keith brings the type of pharmaceutical industry experience that we believe can add significant value to NetraMark as we continue expanding our relationships with drug developers,” said George Achilleos, CEO of NetraMark. “He has spent more than 20 years inside some of the world’s most sophisticated pharmaceutical organizations making decisions around regulatory strategy, clinical development and the advancement of important therapeutic assets. His understanding of how pharmaceutical companies evaluate clinical evidence, make development decisions and interact with regulators provides an extremely valuable perspective for our Board.” Achilleos continued, “As NetraMark works with pharmaceutical and biotechnology companies to seek to extract greater value from clinical trial data and inform subsequent clinical development strategies, we believe it is increasingly important that our Board combines expertise in artificial intelligence with executives who deeply understand how drugs actually move through the development and regulatory process. Keith significantly strengthens that capability.” Dr. Fournier commented, “Clinical development continues to face a fundamental challenge in understanding heterogeneous patient populations and identifying the factors that influence treatment response. NetraMark is approaching this problem with a differentiated technology designed specifically around the realities of clinical trial data. I am excited to join the Board and contribute my experience in drug development and regulatory strategy as the Company works to expand the application of NetraAI across the pharmaceutical industry.” Dr. Fournier earned his PhD in Pharmacology from the University of Pennsylvania School of Medicine and holds a Bachelor of Science in Biology and Bachelor of Arts in Economics, cum laude, from Duke University. He has also authored multiple peer-reviewed scientific publications. For more information on NetraMark and NetraAI, visit www.netramark.com. About NetraAI NetraAI is engineered to include focus mechanisms that separate small datasets into explainable and unexplainable subsets. Unexplainable subsets are collections of patients that can lead to suboptimal overfit models and inaccurate insights due to poor correlations with the variables involved. NetraAI uses explainable subsets to derive insights and hypotheses (including factors that influence treatment and placebo responses and adverse events), potentially increasing the likelihood of a clinical trial's success. Many other AI methods lack these focus mechanisms and assign every patient to a class, often leading to "overfitting," which drowns out critical information that could have been used to improve a trial's chance of success. About NetraMark NetraMark is focused on being a leader in the development of Generative Artificial Intelligence (Gen AI)/Machine Learning (ML) solutions that are targeted at the biotechnology and pharmaceutical industries. The Company's product offering uses a novel topology-based algorithm that has the ability to parse patient data sets into subsets of people that are strongly related according to several variables simultaneously. This allows NetraMark to use a variety of ML methods, depending on the character and size of the data, to transform the data into powerfully intelligent data that activates traditional AI/ML methods. The result is that NetraMark can work with much smaller datasets often prevalent in clinical trials, and accurately segment diseases into different types, as well as help to classify patients for sensitivity to drugs and/or efficacy of treatment. For further details on the Company please see the Company's publicly available documents filed on the System for Electronic Document Analysis and Retrieval+ (SEDAR+). Forward-Looking Statements This press release contains "forward-looking information" within the meaning of applicable Canadian securities legislation including statements regarding the potential impact and perspective that Dr. Fournier can bring to the Company's business and ability to engage with target markets, the Company’s anticipated business plans and strategies, and the potential for our technology to extract greater value from clinical trial data and inform subsequent clinical development strategies along with the potential expansion of the application of NetraAI across the pharmaceutical industry, which are based upon NetraMark’s current internal expectations, estimates, projections, assumptions and beliefs, and views of future events. Forward-looking information can be identified by the use of forward-looking terminology such as “expect”, “likely”, “may”, “will”, “should”, “intend”, “anticipate”, “potential”, “proposed”, “estimate” and other similar words, including negative and grammatical variations thereof, or statements that certain events or conditions “may”, “would” or “will” happen, or by discussions of strategy. Forward-looking information includes estimates, plans, expectations, opinions, forecasts, projections, targets, guidance, or other statements that are not statements of fact. The forward-looking statements are expectations only and are subject to known and unknown risks, uncertainties and other important factors that could cause actual results of the Company or industry results to differ materially from future results, performance or achievements. Any forward-looking information speaks only as of the date on which it is made, and, except as required by law, NetraMark does not undertake any obligation to update or revise any forward-looking information, whether as a result of new information, future events, or otherwise. New factors emerge from time to time, and it is not possible for NetraMark to predict all such factors. When considering these forward-looking statements, readers should keep in mind the risk factors and other cautionary statements as set out in the materials we file with applicable Canadian securities regulatory authorities on SEDAR+ at www.sedarplus.com including our Annual Information Form for the year ended September 30, 2025. These risk factors and other factors could cause actual events or results to differ materially from those described in any forward-looking information. The Toronto Stock Exchange does not accept responsibility for the adequacy or accuracy of this release. Contact Information: Swapan Kakumanu - CFO | swapan@netramark.com | 403-681-2549Adam Peeler – Investor Relations | adam.peeler@loderockadvisors.com | 416-427-1235 Media Contact:netramark@ampublicrelations.com

高管变更

2026-09-01

·BioPlus

下一代ADC拼什么？8类新载荷的机制与进展

作者：琉璃韵前言当TOP1抑制剂和微管抑制剂成为ADC开发的主流选择，下一轮差异化竞争正在从“更换靶点”进一步转向“更换药理机制”。新型载荷的核心价值，不只是提高细胞毒性，而是借助抗体的选择性递送，为过去受限于全身暴露、靶点相关毒性或耐药问题的小分子机制重新建立治疗窗口。因此，下一代载荷创新并不等同于寻找“毒性更强”的分子，而是筛选那些适合被ADC重新递送的药理机制。结合目前公开项目，新型载荷的探索已延伸至蛋白脂质化、PI3K/mTOR与RAS信号、DNA损伤应答、RNA剪接与翻译以及凋亡调控等多个方向。以下选取八类代表性机制进行梳理：八类新型载荷 01｜NMT抑制剂：从蛋白脂质化切入ADC N-肉豆蔻酰转移酶（NMT）催化蛋白N-肉豆蔻酰化。人体主要表达NMT1和NMT2，这一翻译后修饰参与多类蛋白的膜定位、稳定性与功能调控。抑制NMT可同时扰动肿瘤细胞依赖的多个蛋白网络，因此，NMT抑制剂（NMTi）为ADC提供了区别于TOP1抑制剂和微管抑制剂的新型作用机制。 Myricx Bio围绕NMTi载荷布局了多项ADC，包括HER2靶向的MYX2449、TROP2靶向的MYX2468和B7-H3靶向的MYX2470。公开资料显示，这些项目分别采用trastuzumab、sacituzumab和ifinatamab来源的抗体骨架。跨多个靶点的布局说明，Myricx并非只在验证单一候选药物，而是在验证NMTi载荷与不同抗体组合的适配性。在HER2阳性的NCI-N87胃癌和BT-474乳腺癌模型中，MYX2449显示出细胞杀伤活性；在体内模型中，MYX2449、MYX2468和MYX2470也分别在相应靶点相关模型中表现出肿瘤生长抑制。 MYX2449不仅可以杀伤HER2阳性的靶细胞，而且能够产生一定程度的旁观者效应，对邻近的HER2阴性细胞产生影响。NMTi作为payload可能有助于应对实体瘤中的抗原异质性。 2026年7月6日，Novartis宣布拟收购Myricx Bio。交易总价值最高15亿美元，包括11亿美元现金首付款及最高4亿美元潜在里程碑付款。Novartis在公告中明确将Myricx的两项领先ADC资产及NMTi载荷平台列为交易重点，反映出大型药企对新机制载荷及其平台化潜力的持续关注。映恩生物近期半年报首次明确，DUP10为一类新型NMT抑制剂。不过，DUP10目前仍处于全球IND申报准备阶段，具体结构、定量活性及毒理数据尚未公开。 02｜PI3K/mTOR抑制剂：以靶向递送重塑治疗窗 PI3K/AKT/mTOR通路广泛参与肿瘤细胞增殖、存活、代谢和蛋白合成，但该通路同样承担正常组织的生理功能，系统性抑制可能引发高血糖等机制相关毒性。将PI3K/mTOR抑制剂设计为ADC载荷，核心目的不是简单增强小分子效力，而是利用抗体介导的肿瘤选择性递送，改变其组织分布并降低非靶组织暴露。在公开的HCC-1954、HN5和BR156等CDX/PDX模型中，TROP2-PI3K/mTORi ADC显示出肿瘤生长抑制，部分模型观察到持续性肿瘤回缩。 03｜Gαq/11抑制剂：让ADC精准匹配肿瘤驱动通路 DYP688通过靶向PMEL17递送Gαq/11抑制剂SDZ475，用于探索GNAQ/GNA11突变黑色素瘤的精准治疗。ADC与PMEL17结合并内化后释放SDZ475，抑制异常激活的Gαq/11信号，并进一步影响PKC/MAPK、Rho/Rac、β-catenin和YAP等下游通路。与广谱细胞毒载荷相比，DYP688体现了“肿瘤抗原+驱动通路”的双重生物学匹配。 2026年发表的Ⅰ期研究显示，在66例可评估患者中， ORR为19.7%，47例患者（71.2%）出现不同程度的靶病灶缩小，mPFS为7.2个月；TRAE≥3级发生率为7.6%。 04｜pan-RAS抑制剂：重新设计适合ADC递送的小分子 RAS通路是肿瘤领域最重要的驱动机制之一。尽管近年来KRAS抑制剂取得快速进展，但系统性RAS抑制仍面临一个核心问题：如何在维持持续RAS通路抑制的同时，降低正常组织暴露。 Zymeworks的RASi-ADC开发首先解决的并不是“RAS是否值得抑制”，而是“什么样的RAS抑制剂适合成为ADC payload”。 Zymeworks针对ADC应用筛选了超过170个新型RASi分子，并从药效强度、疏水性及payload属性等维度进行优化。最终形成的RASi payload被设计用于高DAR偶联，并进一步拓展至PTK7、Ly6E和CLDN18.2等不同ADC靶点。在临床前实验中，RASi ADC显示出较低的正常组织payload暴露；与此同时，肿瘤内DUSP6等RAS通路药效学指标显示出持续抑制。因此，RASi ADC的核心价值并非简单提高RAS抑制剂的药效，而是通过抗体介导的递送，实现“更集中、更持续的肿瘤内RAS抑制” 。 05｜ATR抑制剂：从DNA损伤应答寻找TOP1之外的路径 ATR是DNA损伤应答和复制压力调控的关键激酶。存在DNA修复缺陷或高复制压力的肿瘤细胞，往往更依赖ATR维持复制叉稳定和细胞存活；抑制ATR可削弱复制压力应答，并可能诱导复制灾难。这为ATRi作为ADC载荷提供了明确的生物学基础。 DCx Biotherapeutics在AACR 2026公布了PD-L1-ATRi和TROP2-ATRi ADC的临床前研究。在携带TOP1 R364H等耐药相关改变的模型中，ATRi ADC仍保留体外活性，而Dato-DXd活性下降。表明ATRi载荷可能为TOP1抑制剂载荷不敏感或耐药场景提供差异化选择。 06｜RNA剪接抑制剂：从DNA和微管走向RNA加工 Akari Therapeutics开发的PH1代表另一类载荷思路：通过干扰剪接体（spliceosome）功能，引发广泛的异常RNA剪接，进而破坏关键蛋白的正常表达并产生细胞毒效应。该机制将ADC载荷的作用层级从微管和DNA进一步拓展至RNA加工。在公开的多药耐药（MDR）转运蛋白高表达模型中，PH1的体外活性未见明显下降，而MMAE的杀伤能力明显减弱。表明PH1可能在部分由药物外排泵介导的耐药背景中保留活性。 07｜MCL-1抑制剂：定向解除血液肿瘤的抗凋亡屏障 Servier开发的S227928是一款靶向CD74、偶联MCL-1抑制剂的ADC。MCL-1是BCL-2家族的重要抗凋亡蛋白，在AML等血液肿瘤中具有重要作用；MCL-1上调也与部分肿瘤对venetoclax耐药相关。 S227928与CD74结合并内化后，在细胞内释放MCL-1抑制剂S64315。解除MCL-1对BIM等促凋亡蛋白的抑制后，可促进BAX/BAK介导的线粒体凋亡。其开发逻辑是利用ADC提高MCL-1抑制剂在目标细胞中的相对暴露，以探索更可控的治疗窗，而不是将MCL-1抑制等同于传统广谱细胞毒机制。 08｜mRNA翻译抑制剂：切断肿瘤细胞的蛋白供应映恩生物开发的DUP5是一类新型mRNA翻译抑制载荷，DUP5选择性抑制真核翻译起始因子eIF4A，干扰帽依赖性（cap-dependent）蛋白翻译，从而下调多种致癌蛋白并诱导细胞周期阻滞与凋亡。 DUP5已被用于构建针对HER2、EGFR、GPC3和BCMA等多种靶点的ADC，相关ADC在多类实体瘤模型中显示抗肿瘤活性，并在部分对TOP1抑制剂载荷相对不敏感的模型中保留活性。其关键差异化假设，是通过抑制蛋白翻译绕开既有TOP1载荷的作用机制。 2026年8月27日，映恩生物与Genentech签订全球合作及许可协议，双方将基于映恩生物的DUPAC新型载荷平台，为Genentech选定的肿瘤靶点开发下一代ADC。映恩生物将获得4500万美元首付款，并有资格就全部合作项目获得合计超过10亿美元的开发、监管及商业化里程碑付款，以及获批产品净销售额的分层特许权使用费。需要强调的是，本次授权对象是DUPAC平台及合作产生的ADC，并非DUP5单一载荷；但DUP5与DUP9、DUP10同属DUPAC，DUP5的临床前数据构成该平台技术验证的重要组成部分。新型payload真正试图解决什么问题？新型载荷的竞争并非单一维度的“毒性升级”，而是在针对传统ADC与系统性小分子的不同瓶颈建立解决方案。小结 ADC正在从“抗体+经典细胞毒素”的组合，逐步演变为“靶向递送平台+机制型药物”的组合。TOP1抑制剂和微管抑制剂仍是当前最成熟的载荷类别，但NMT、PI3K/mTOR、Gαq/11、RAS、ATR、RNA剪接、MCL-1和mRNA翻译等机制的进入，正在持续拓宽ADC能够承载的药理空间。从研发角度看，真正值得关注的并不是新载荷数量本身，而是三个更具体的问题：载荷能否与抗体、连接子和DAR形成稳定可开发的整体；选择性递送能否在人体中实质性改变暴露—效应关系；新机制能否在既有载荷不敏感或耐药人群中提供可验证的临床获益。只有同时跨过这三道门槛，新型payload才可能从“机制新颖”走向“临床成立”。欢迎大家加入BioPlus Partners微信交流群。入群申请联系人：Lisa 邮箱：lisa.li@bp-bioplus.com 电话：18662346610（同微信）入群申请，请先添加Lisa微信，并分享名片入群画像：Biotech/药厂研发/BD、投资机构、临床医生等入群福利：不定时行业资料包分享参考资料 1. https://www.adcreview.com/wp-content/uploads/2023/10/ADC-world-Oct-2023-WADC-poster.pdf 2. 2026AACR poster 3. Carlino, M.S., Kapiteijn, E., Piperno-Neumann, S. et al. An anti-PMEL antibody−drug conjugate with a Gq/11 inhibitor payload in GNAQ/GNA11-mutant melanomas: a phase 1 trial. Nat Med (2026). 4. https://ir.zymeworks.com/static-files/f8d8a220-063a-4e40-a4a5-3ecc36145f58 5. 2026AACR poster 6. https://investor.akaritx.com/static-files/d0829da9-d8de-420a-9173-3ad62e1fdb86 7. 2024 ASH poster 8. 映恩生物管网资料

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,

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适应症	国家/地区	公司	日期
复发性套细胞淋巴瘤	日本	AbbVie GK	2025-03-27
难治性套细胞淋巴瘤	日本	AbbVie GK	2025-03-27
难治性慢性淋巴细胞白血病	日本	AbbVie GK	2019-09-20
复发性慢性淋巴细胞白血病	日本	AbbVie GK	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	Genentech, Inc.	2022-10-01
复发性急性髓细胞白血病	临床3期	美国	AbbVie, Inc.	2022-10-01

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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


NCT03054896 (CRC-043 \| phase 2, CTgov)	临床2期	里氏综合症	69	Etoposide+Cyclophosphamide+Pegfilgrastim+Prednisone+Venetoclax+Doxorubicin+Rituximab+Vincristine (VR-EPOCH (Cohort 1))	願鏇醖鹽鹽顧積願憲顧 = 鬱餘淵積顧艱鏇製顧構鑰艱蓋選網衊醖衊窪廠 (窪願網製夢顧鬱獵夢衊, 壓網蓋鹹網醖顧繭顧簾 ~ 製齋遞膚壓選鹽壓選顧) 更多	-	2026-07-10
				cyclophosphamide+prednisone+Venetoclax+doxorubicin+Vincristine Sulfate+rituximab (VR-CHOP (Cohort 2))	願鏇醖鹽鹽顧積願憲顧 = 簾製壓網蓋壓鹹淵積壓鑰艱蓋選網衊醖衊窪廠 (窪願網製夢顧鬱獵夢衊, 遞襯顧構窪構淵鏇廠壓 ~ 醖糧選製鏇壓膚構餘鹽) 更多
NCT04285567 (CRISTALLO, Pubmed \| Blood)	临床3期	慢性淋巴细胞白血病一线	166	Venetoclax-obinutuzumab (VenO)	積淵衊獵衊鏇簾積憲餘(選淵窪選觸淵鑰選範艱) = 鹽繭鬱觸艱構蓋鏇範廠製構襯製範窪糧襯願壓 (網遞製襯簾顧夢壓齋範 ) 更多	积极	2026-06-11
				Fludarabine, cyclophosphamide, and rituximab (FCR) or bendamustine-rituximab (BR)	積淵衊獵衊鏇簾積憲餘(選淵窪選觸淵鑰選範艱) = 淵顧衊選齋淵廠鹹窪遞製構襯製範窪糧襯願壓 (網遞製襯簾顧夢壓齋範 ) 更多
NCT03573024 (CTgov)	临床2期	急性髓性白血病	36	Venetoclax+Azacitidine	鹽鬱網鏇築繭廠鏇鬱製 = 廠範廠襯糧衊遞膚觸夢網鏇襯糧鏇獵艱構淵構 (遞遞網遞鹹艱鏇構獵鏇, 鏇鏇鏇簾簾鹽餘鑰憲齋 ~ 構鏇膚築顧衊簾構積觸) 更多	-	2026-06-11
NCT05025423 (CTgov)	临床2期	套细胞淋巴瘤 \| 难治性套细胞淋巴瘤	7	Venetoclax Oral Tablet [Venclexta]	網範遞築淵鏇餘襯顧簾 = 網構遞夢築願齋窪膚選構願壓獵選鏇夢選繭糧 (網衊願選構廠壓顧鑰獵, 簾衊獵膚憲鹹齋顧衊廠 ~ 壓艱繭製積願鏇範網範) 更多	-	2026-06-09
NCT04657081 (ASCERTAIN-V, Pubmed \| N Engl J Med)	临床1/2期	急性髓性白血病	189	Oral Decitabine-Cedazuridine + Oral Venetoclax	艱襯壓餘願鹹膚觸積選(鹹願鹹蓋蓋糧築鏇構蓋) = 淵窪鬱遞範淵鹽餘繭糧顧鑰構積積鹹範鹽選範 (夢蓋獵鏇簾壓蓋顧鹹鏇, 36 ~ 57) 更多	积极	2026-06-04
NCT05084027 (Pubmed \| Cancer)	临床2期	急性髓性白血病 \| 骨髓增生异常综合征	60	Venetoclax+Fludarabine+Melphalan	築簾鬱築齋鑰淵積糧獵(製鹹顧糧鏇遞醖積膚獵) = 獵廠餘觸餘壓網製範簾簾鏇餘窪簾蓋襯糧醖醖 (艱鑰繭襯鏇顧觸鏇積鹹, 64.8 ~ 86.8) 更多	积极	2026-06-01
ASCO2026	N/A	急性髓性白血病 \| 高危骨髓增生异常综合征	72	Cladribine (CLAD) + low-dose AraC (LDAC) + venetoclax (VEN)	壓壓鹽襯膚醖網憲夢顧(憲鏇鹹膚餘夢製築製餘) = 網齋蓋憲選蓋淵膚選顧鏇網壓壓鑰餘構窪蓋簾 (鬱範願鏇網壓醖願遞願 ) 更多	积极	2026-05-29
ASCO2026	N/A	急性髓性白血病	184	Venetoclax combined with HMA	構顧選廠淵顧簾膚餘艱(襯醖鏇築製範壓淵糧齋) = 壓淵壓願艱醖艱範窪膚蓋廠願鏇網願廠廠餘夢 (餘壓築廠鏇夢鹽選憲鏇 ) 更多	积极	2026-05-29
				Venetoclax combined with HMA	構顧選廠淵顧簾膚餘艱(襯醖鏇築製範壓淵糧齋) = 製遞鬱艱襯鑰繭網齋廠蓋廠願鏇網願廠廠餘夢 (餘壓築廠鏇夢鹽選憲鏇 ) 更多
ASCO2026	N/A	急性髓性白血病	55	Azacitidine	鬱積憲願齋夢鏇製觸淵(願襯範襯築夢淵鏇窪顧) = 網顧艱餘餘衊鹹襯膚餘觸夢鏇願獵窪網鹹廠淵 (鏇膚簾廠餘範築淵鬱鬱 ) 更多	积极	2026-05-29
				Combinations of HMAs±LDAC	夢觸網願構膚艱鑰鑰構(網構糧簾醖糧夢觸餘齋) = 積鏇齋齋願廠積積壓繭衊鏇鑰網醖壓願範蓋鏇 (壓簾壓觸齋淵衊積齋襯, 17 ~ 35) 更多
ASCO2026	N/A	急性髓性白血病诱导	154	3+7 regimen	膚襯鬱夢衊顧鹽淵製膚(鹽積積鹹範憲範網襯構) = 壓蓋遞願築壓顧艱遞網構壓夢構糧鏇蓋鹹鹽網 (餘遞齋鑰願繭餘膚鹹觸 ) 更多	积极	2026-05-29
				azacitidine + venetoclax (AZA + VEN)	膚襯鬱夢衊顧鹽淵製膚(鹽積積鹹範憲範網襯構) = 鏇鏇遞壓衊憲鬱壓窪顧構壓夢構糧鏇蓋鹹鹽網 (餘遞齋鑰願繭餘膚鹹觸 ) 更多