A Multicenter, Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of HMPL-523, a Syk Inhibitor, in Adult Subjects With Immune Thrombocytopenia

This is an open-label, multicenter study to evaluate the safety, tolerability, and efficacy of HMPL-523 in adult subjects with ITP.

开始日期2024-04-02

申办/合作机构

和黄医药（中国）有限公司

NCT05781906

/ Completed临床1期

Single-center, Open-label, Multi-dose Study to Investigate the Human Mass Balance in Healthy Adult Male Following Multiple Oral Doses of HMPL-523 Tablets Followed by a Single Oral Dose of 300 mg/150 µCi [14C]HMPL-523 Suspension

To evaluate the absorption, metabolism and excretion of HMPL-523 in healthy male Chinese subjects following multiple oral doses of HMPL-523 tablets followed by a single oral dose of [14C]HMPL-523 suspension

开始日期2023-02-08

申办/合作机构

和黄医药（中国）有限公司

NCT05720767

/ Completed临床1期

A Phase 1, Open-label, 2-Part, 2-Period Fixed-Sequence Crossover Study to Assess the Effect of Itraconazole, and the Effect of Rifampin on the Pharmacokinetics of HMPL-523 in Healthy Volunteers

A Phase 1, Open-label, 2-Part, 2-Period Fixed-Sequence Crossover Study to Assess the Effect of Itraconazole, a CYP3A and P-glycoprotein Inhibitor, and the Effect of Rifampin, a CYP Enzyme Inducer, on the Pharmacokinetics of HMPL-523 in Healthy Volunteers

开始日期2022-11-04

申办/合作机构

和黄医药（中国）有限公司

100 项与索乐匹尼布相关的临床结果

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100 项与索乐匹尼布相关的转化医学

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100 项与索乐匹尼布相关的专利（医药）

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项与索乐匹尼布相关的文献（医药）

2025-02-01·Lancet Haematology

Sovleplenib in patients with primary or secondary warm autoimmune haemolytic anaemia: results from phase 2 of a randomised, double-blind, placebo-controlled, phase 2/3 study

Article

作者: Zhou, Hu ; Li, Fei ; Luo, Xian ; Li, Yingmei ; Zhao, Xin ; Zhang, Zhihua ; Chen, Miao ; Li, Xin ; Han, Bing ; Guo, Xiaojun ; Yin, Hongyan ; Liu, Hong ; Su, Weiguo ; Wang, Xiaoqin ; He, Guangsheng ; Fan, Songhua ; Sun, Jing ; Zhang, Liansheng ; Zhang, Fengkui ; Hong, Mei ; Shi, Michael M ; Lei, Lei ; Li, Yang ; Gong, Tiejun

BACKGROUND:

Spleen tyrosine kinase inhibitors are potential treatment options for warm autoimmune haemolytic anaemia. This study aimed to assess the preliminary efficacy and safety of sovleplenib-an oral spleen tyrosine kinase inhibitor-in patients with warm autoimmune haemolytic anaemia in China. Here we report on the phase 2 results.

METHODS:

This randomised, double-blind, placebo-controlled, phase 2 part from the phase 2/3 study was conducted at 13 centres in China. Eligible patients, aged 18-75 years, with an Eastern Cooperative Oncology Group (ECOG) performance status of no more than 2, had primary or secondary warm autoimmune haemolytic anaemia (stable underlying disease not requiring drug intervention) with no response to previous glucocorticoid treatment, haemoglobin of less than 100 g/L with active haemolysis, and a positive direct antiglobulin test. The study comprised two periods; patients were randomly assigned (3:1) to receive sovleplenib or placebo at 300 mg orally once a day in the 8-week double-blind period. Upon completion, all patients entered an open-label treatment period for at least 16 weeks and received sovleplenib 300 mg once a day until 24 weeks after the last patient was randomly assigned. The primary endpoint for phase 2 of the trial was overall haemoglobin response rate (haemoglobin ≥100 g/L with an increase of ≥20 g/L from baseline at least once, and haemoglobin not affected by rescue therapy, such as red blood cell transfusions, intravenous immunoglobulin, and glucocorticoids) by week 24. Efficacy analyses in the 0-8 week double-blind period included all patients who were randomly assigned, analysed by intention-to-treat. Safety analysis in the double-blind period included patients in the intention-to-treat population who received at least one dose of the study medication. This phase 2/3 study is registered with ClinicalTrials.gov, NCT05535933, and the phase 3 part is ongoing.

FINDINGS:

Between Sept 26, 2022, and May 9, 2023, 34 patients were screened and 21 patients (four [19%] male and 17 [81%] female) were enrolled in the study and randomly assigned to receive either sovleplenib (n=16) or placebo (n=5). All 21 patients completed the 0-8-week double-blind treatment and entered the open-label treatment period. The overall haemoglobin response rate was 67% (14 of 21 patients) by week 24, and durable haemoglobin response rate was 48% (ten of 21 patients) by week 24. During the 0-8-week double-blind treatment, 13 (81%) of 16 patients in the sovleplenib group versus five (100%) of five patients taking placebo reported treatment-emergent adverse events (TEAEs), and four (25%) of 16 patients versus four (80%) of five patients reported grade 3 adverse events. Although all 21 patients had a TEAE during the 24-week treatment with sovleplenib, only seven (33%) patients had grade 3 events. The most common grade 3 TEAE was anaemia (four [19%] patients), which was not related to treatment. There were no grade 4 or 5 TEAEs.

INTERPRETATION:

Sovleplenib treatment achieved an encouraging overall haemoglobin response in Chinese patients with warm autoimmune haemolytic anaemia and was well tolerated. The phase 3 part of the study (ESLIM-02) is currently ongoing to further substantiate the efficacy and safety of sovleplenib in this setting.

FUNDING:

HUTCHMED.

2025-02-01·Lancet Haematology

Expanding treatment options for warm autoimmune haemolytic anaemia

Article

作者: Berentsen, Sigbjørn

A review.The treatment landscape for warm autoimmune haemolytic anemia (wAIHA) has gradually shifted from reliance on clin. experience to evidence-based strategies.In a significant contribution to this progress, Zhao et al.Conducted a randomized, placebo-controlled, double-blind phase 2 trial evaluating sovleplenib, an oral selective spleen tyrosine kinase (SYK) inhibitor, in adults with relapsed or refractory wAIHA.Among 21 patients, 67% achieved a Hb response by week 24, with a durable response in 48%.Compared to placebo, sovleplenib reduced transfusion needs and rescue therapy usage, and improved fatigue scores.The drug exhibited a distinct and manageable safety profile.These findings highlight sovleplenib as a promising third-line treatment option, particularly in light of limited efficacy and tolerability seen with other SYK inhibitors like fostamatinib.Further validation in larger phase 3 trials is warranted.Emerging therapies, including FcRn inhibitors, also hold potential, underscoring the evolving complexity of individualized wAIHA treatment.

2025-01-01·MEDIATORS OF INFLAMMATION

Efficacy and Safety of Syk and BTK Inhibitors in Immune Thrombocytopenia: A Comprehensive Review of Emerging Evidence

Review

作者: Fathabadi, Fatemeh ; Eghbali, Sara ; Behroozfar, Mohammad ; Heidari, Amirhossein ; Ghotbi, Negar ; Heidari, Nazila ; Mazid, Amirhossein Shahbazi

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by a reduced platelet count, resulting in bleeding risks and compromised quality of life. Advances in understanding ITP pathogenesis have revealed critical roles for spleen tyrosine kinase (Syk) and Bruton’s tyrosine kinase (BTK) in Fc receptor (FcR)‐mediated immune pathways, which are central to autoantibody production and platelet destruction. We sought to evaluate the efficacy and safety of Syk and BTK inhibitors in the management of ITP. PubMed/Medline, Scopus, and Web of Science databases were systematically searched up to July 28, 2024. Clinical studies with available full‐text in English were included. Fostamatinib, an FDA‐approved Syk inhibitor, has shown efficacy in enhancing platelet counts and reducing bleeding events in refractory ITP patients. Among the newer Syk inhibitors, sovleplenib demonstrated rapid and sustained platelet increases in clinical trials, with an 80% response rate at the 300 mg dosage and a favorable safety profile. Additionally, BTK inhibitors, including rilzabrutinib and orelabrutinib, have shown potential in clinical trials, offering increased platelet stability and favorable safety profiles in ITP cases. Syk and BTK inhibitors hold potential as targeted therapies for refractory ITP, with evidence supporting their ability to improve clinical outcomes and enhance patient quality of life. Continued research is warranted to optimize these therapies and confirm their long‐term efficacy and safety in diverse patient populations.

105

项与索乐匹尼布相关的新闻（医药）

2025-11-03

·蓝精灵壹号

和黄研发日PPT（61页）

如下是和黄药业于10月31日举办的研发日活动中文版材料。一、核心主旨：从成功商业化迈向下一代技术平台创新和黄医药通过此次会议展示了其作为一家综合性生物制药公司的进化：稳固的现有业务：拥有多款已成功商业化的产品（如呋喹替尼、索凡替尼、赛沃替尼），2025年上半年营收达1.628亿美元，并持续拓展新适应症。丰富的后期管线：拥有多个处于注册性临床阶段的产品，将在未来12-18个月内带来密集的催化剂。下一代技术平台：首次公开其创新的ATTC（抗体靶向偶联药物）平台，旨在解决当前ADC（抗体药物偶联物）疗法的局限性，并介绍了该平台的首个候选药物 HMPL-A251，标志着公司进入了新一轮的创新周期。二、创新平台：抗体靶向偶联药物（ATTC） ATTC是和黄医药提出的一个全新概念，旨在颠覆传统ADC的设计思路，以解决其核心痛点。1. ATTC vs. 传统ADC：根本性差异传统ADC使用细胞毒性药物（化疗药）作为弹头，通过抗体将其递送至癌细胞进行杀伤。而ATTC使用靶向治疗药物（小分子抑制剂）作为弹头，旨在更精准地干预癌细胞的生存信号通路。作用机制：传统ADC杀伤快速分裂的细胞；ATTC靶向癌症生长所需的特定蛋白质，与抗体产生协同效应。安全性：传统ADC常伴有严重的血液学、肝毒性等；ATTC的毒性与靶点相关，对正常组织影响更小，更适合长期用药。耐药性：传统ADC面临化疗耐药；ATTC有望克服对靶向药的耐药性。联合用药：传统ADC与化疗联合毒性叠加；ATTC更容易与标准化疗、免疫疗法等联合使用。生物标志物：传统ADC往往不明确；ATTC有明确的敏感人群（携带特定驱动基因突变的患者）。2. ATTC的设计目标与优势和黄医药设计ATTC旨在实现以下目标：精准靶向：针对特定的驱动突变。减毒增效：降低化疗毒性，与一线标准治疗联合。技术保障：高产量抗体生产、稳定的连接子技术。关键特性：通过抗体递送靶向药，降低血液循环中的游离药物浓度，从而减少脱靶毒性（如肝毒性），同时增强抗肿瘤疗效。三、首个ATTC候选药物：HMPL-A251 HMPL-A251是ATTC平台的第一个产物，是一款全球首创（First-in-Class）的药物，由抗HER2抗体与一种新型PI3K/PIKK抑制剂（代号609）偶联而成。1. 研发依据：解决HER2治疗中的核心难题背景：HER2是经过验证的靶点，但其下游的PI3K/AKT/mTOR（PAM）信号通路的激活是导致对抗HER2治疗（如曲妥珠单抗、DS-8201）产生耐药的主要原因之一。临床证据：数据显示，携带PAM通路突变（如PIK3CA突变）的HER2阳性患者，使用抗HER2药物的疗效（缓解率、无进展生存期）显著差于PAM野生型患者。未满足需求：虽然PAM抑制剂与HER2抗体联用有协同作用，但PAM抑制剂的全身性毒性（如口腔炎、高血糖等）限制了其临床应用剂量和疗效。ATTC策略有望将PAM抑制剂精准递送至肿瘤，解决这一难题。2. 有效载荷609：强效且独特的双重机制有效载荷HM5041609（609）是一种高效、高选择性的PI3K和PIKK激酶抑制剂。双重抑制：它不仅抑制经典的PAM通路（PI3Kα/β/γ/δ, mTOR），还能抑制PIKK家族（ATM, ATR, DNA-PK），这些激酶在DNA损伤修复中起关键作用。潜在“合成致死”：这种双重抑制机制有望导致DNA损伤积累，从而在癌细胞中诱发“合成致死”效应，增强抗肿瘤活性。3. 临床前数据：卓越的疗效与差异化优势临床前研究显示，HMPL-A251具有多重优势：高效内吞与肿瘤分布：能高效进入HER2阳性癌细胞，并在肿瘤组织中持续存在超过168小时，持续释放有效载荷。强效抑制信号通路：能强效阻断PAM和PIKK信号通路，诱导癌细胞凋亡和DNA损伤。克服耐药性：在对DS-8201（DXd）耐药的细胞模型中，HMPL-A251完全保持活性，而DS-8201的活性降低了超过500倍，展示了其克服耐药性的潜力。协同效应与旁观者杀伤：相比“裸抗体+游离609”的联合用药，HMPL-A251疗效更强，且耐受性更好（避免了游离609引起的血糖升高和体重下降）。并能杀伤HER2阴性细胞（旁观者效应），克服肿瘤异质性。广谱抗肿瘤活性：在HER2阳性（无论PAM突变与否）和HER2低表达且伴有PAM突变的多种癌种模型（乳腺癌、卵巢癌、子宫内膜癌、宫颈癌）中，HMPL-A251均显示出与DS-8201相当或更优的抗肿瘤活性。良好的药代动力学与安全性：在动物模型中表现出良好的药代动力学特征和连接子稳定性，预示其在人体内具有较好的安全性前景。4. 开发策略与市场潜力开发状态：美国IND已获批，中国IND正在审评中。I期临床试验计划于2025年第四季度启动。临床策略：采用“篮式试验”设计，同时探索在HER2阳性（伴或不伴PAM突变）和HER2低表达伴PAM突变的多种实体瘤（如乳腺癌、胃癌、结直肠癌等）中的疗效。市场潜力：PAM通路在众多癌种中突变率高（乳腺癌73%，结直肠癌69%等），与HER2/TROP2/EGFR等靶点共存率高，市场潜力巨大。HMPL-A251有潜力成为同类最佳疗法。四、后期研发管线最新进展和黄医药拥有一个极其丰富且多元化的后期临床管线，涵盖了多个接近商业化或已商业化的产品。1. 呋喹替尼（FRUZAQLA®）肾细胞癌（RCC）：FRUSICA-2研究结果在ESMO 2025上公布。呋喹替尼联合信迪利单抗 vs. 医生选择（阿昔替尼或依维莫司），在二线治疗中显示出压倒性优势：中位无进展生存期（PFS）：22.2个月 vs. 6.9个月（风险比HR=0.373, p<0.0001）。客观缓解率（ORR）：60.5% vs. 24.3%。基于该数据，中国的上市申请（NDA）已于2025年6月获受理，预计将获批。2. 赛沃替尼一款MET抑制剂，与阿斯利康合作。2025年6月在中国获批用于治疗MET ex14跳突NSCLC。拥有7项潜在的注册性研究，覆盖肺癌、肾癌、胃癌等多个适应症，是公司未来的核心增长驱动力之一。其中SAFFRON（全球III期）和SANOVO（中国III期）研究均已完成入组。3. 他泽司他一款EZH2抑制剂，与Ipsen合作。2025年3月在中国获批用于治疗三线滤泡性淋巴瘤（FL）。正在参与全球III期SYMPHONY-1研究，探索其联合疗法在更前线FL治疗中的应用。4. HMPL-453 一款FGFR抑制剂。用于治疗FGFR2融合/重排的胆管癌。注册性研究已于2025年2月完成入组，计划于2025年底提交中国NDA。5. 索乐匹尼布一款SYK抑制剂。用于治疗原发免疫性血小板减少症（ITP）。中国的NDA已于2024年获受理，因CMC问题需补充数据，计划于2026年上半年重新提交。在温抗体型自身免疫性溶血性贫血（wAIHA）的II期研究中表现出良好疗效，计划于2026年第二季度提交该适应症的NDA。五、总结与展望和黄医药正处于一个强劲的增长轨道上：财务健康：拥有13.6亿美元现金，市值约27亿美元，为未来发展和创新提供了坚实基础。短期催化剂密集：未来12个月，管线中的多个产品有望迎来新适应症获批、新药上市申请提交和关键数据读出。长期创新引擎：ATTC平台的推出标志着公司进入了新一轮的创新周期。HMPL-A251及其后续的ATTC产品（HMPL-A580, HMPL-A830）有潜力在未来解决癌症治疗中的重大未满足需求，为公司带来长期增长动力。

抗体药物偶联物免疫疗法

2025-11-03

·和黄医药官微

和黄医药举办最新研发进展投资者会议分享产品管线及业务进展

和黄医药举办最新研发进展投资者会议分享产品管线及业务进展 — 和黄医药介绍其创新ATTC平台，有望通过双重作用机制为癌症精准治疗带来变革 — — 首个候选药物HMPL-A251搭载选择性PI3K/PIKK抑制剂有效载荷，在临床前研究中展现出令人鼓舞的疗效与安全性 — — 全球及中国临床试验进展顺利，包括FRUSICA-2、SANOVO、索凡替尼的胰腺导管腺癌，以及HMPL-453的肝内胆管癌研究，推动和黄医药后期管线持续发展— 中国香港、上海和美国新泽西州: 2025年11月3日，星期一: 和黄医药 (中国)有限公司 (简称 "和黄医药" 或 "HUTCHMED") (纳斯达克/伦敦证交所: HCM; 香港交易所: 13) 于2025年10月31日举行的投资者会议中分享最新关键研发和业务进展。此次活动重点展示了和黄医药在推进创新癌症和免疫疾病治疗方面的最新进展，包括介绍其新一代抗体靶向偶联药物 ("ATTC") 平台，以及后期管线候选药物的最新进展。和黄医药研发负责人兼首席医学官石明博士表示："满足癌症和免疫疾病领域关键未被满足的医学需求是和黄医药的使命所在，驱动着我们持续致力推进创新疗法。ATTC平台有望重新定义癌症精准治疗，依托我们坚实的产品管线和合作策略，我们有信心能够为全球患者提供具有潜在变革性的癌症和免疫疾病治疗方案。" 突破性的ATTC平台及首个候选药物HMPL-A251 ATTC平台代表着癌症精准治疗领域一项潜在的突破性进展，通过将单克隆抗体与专利靶向小分子抑制剂有效载荷 (payload) 相连接，实现双重作用机制。不同于传统的基于细胞毒素的抗体偶联药物 ("ADC") ，ATTC通过结合靶向疗法，在临床前模型中展现出具有协同作用的抗肿瘤活性和持久缓解，相较于单独使用抗体或小分子抑制剂有着更好的疗效和安全性。靶向PAM通路的有效载荷克服癌症挑战: 第一波的ATTC候选药物主要采用靶向PI3K/AKT/mTOR ("PAM") 信号通路的有效载荷。PAM通路是一个关键的细胞内信号传导网络，参与细胞生长、存活和分裂。PAM通路改变在多种癌症中常与预后不良和对治疗的耐药性密切相关。然而，现有的PAM靶向药物面临着诸多局限，包括靶点毒性令使用剂量受限、反馈回路导致通路重新激活以及针对肿瘤的特异性递送不足。ATTC策略则是通过向目标的肿瘤组织直接靶向递送PAM抑制剂来尝试解决上述的挑战，从而在最大化治疗获益的同时尽可能降低全身性的药物暴露。和黄医药ATTC平台首个候选药物HMPL-A251: HMPL-A251是一种PAM-HER2 ATTC，由高选择性、强效的PI3K/PIKK抑制剂作为有效载荷和人源化抗HER2 IgG1抗体通过可裂解的连接子 (linker) 偶联而成。其临床前数据近期已于2025年AACR-NCI-EORTC分子靶向和癌症治疗国际会议上公布。在体外实验中，其PI3K/PIKK抑制剂有效载荷在多种肿瘤细胞系中展现出高选择性和强效的抗肿瘤活性。HMPL-A251在体外模型中表现出HER2依赖的抗肿瘤活性，在HER2阳性的肿瘤细胞中，无论其PAM改变情况如何，均对其生长展现出强效的抑制作用；而在HER2低表达幷伴有PAM改变的细胞系中，HMPL-A251的活性则略有降低。值得注意的是，当与HER2阳性细胞共同培养时，HMPL-A251还对HER2无表达细胞展现出强效的旁观者效应。在体内实验中，HMPL-A251相较于单独使用抗体或有效载荷亦有着更好的抗肿瘤疗效和耐受性。与德曲妥珠单抗 (T-DXd，一种目前常见的靶向HER2的ADC) 相比，HMPL-A251在大多数试验模型中以等效剂量实现了更佳或相若的疗效。此外，由于游离有效载荷的血浆暴露量远低于HMPL-A251剂量，因此有效载荷相关的毒性预计较低。基于这些在无论PAM改变情况如何的HER2阳性和HER2低表达模型中取得的令人鼓舞的临床前数据，和黄医药计划采取以数据为导向的策略，从2025年底开始推动HMPL-A251进入临床开发。初期研究将评估该候选药物在伴有不同HER2及PAM改变状态的多个瘤种中的表现。灵活的有效载荷和抗体设计解锁多样化机制: 除了靶向HER2的抗体外，和黄医药亦计划广泛探索更多不同的抗体选择，选取与有效载荷的信号通路具有协同效应的抗体，利用抗体作为递送载体充分发挥联合优势。有效载荷的选择亦相当多元化，可针对多种不同的信号通路，使ATTC能够灵活应对耐药性并改善治疗效果。此外，ATTC还显示出潜力，与基于化疗的一线标准疗法联合用药，或是作为可长期用药的去化疗的辅助治疗选择，丰富其作为联合疗法在前线治疗中应用的可能性。多个ATTC分子的成功研发有望在未来带来合作和授权机会。潜在合作伙伴的初步反馈非常积极。后期项目快速推进除ATTC平台以外，此次活动中还分享了一些后期项目的最新进展：呋喹替尼FRUSICA-2研究: 呋喹替尼联合信迪利单抗用于二线治疗肾细胞癌的III期研究数据于2025年ESMO大会上公布。该联合疗法实现了22.2个月的无进展生存期 (PFS)，而目前的标准治疗阿昔替尼或依维莫司则为6.9个月 (风险比[HR]：0.37; p<0.0001)。客观缓解率提高了一倍以上，达到60.5%，而对照组则为24.3%；中位缓解持续时间为23.7个月，对照组则为11.3个月。赛沃替尼注册研究: 用于一线治疗伴有MET过表达的EGFR突变非小细胞肺癌患者的SANOVO中国III期研究已完成患者招募。用于二线治疗伴有MET扩增或过表达的EGFR突变非小细胞肺癌患者的SAFFRON全球III期研究入组进展顺利，预计将于2025年年底完成患者招募。索凡替尼用于胰腺癌: 索凡替尼联合恒瑞的卡瑞利珠单抗 (一种PD-1抗体)、白蛋白紫杉醇和吉西他滨用于一线治疗转移性胰腺导管腺癌的II/III期研究进展顺利。II期部分的结果将于即将举行的科学会议上公布。索乐匹尼布用于免疫性血小板减少症和温抗体型自身免疫性溶血性贫血症: 如2025年中期报告所述，我们正在准备用于二线治疗免疫性血小板减少症的新药上市申请，计划于2026年第二季度重新提交。用于二线治疗温抗体型自身免疫性溶血性贫血症的ESLIM-02研究已完成入组，预计于2026年年初读出顶线数据。 HMPL-453在中国: 用于治疗晚期肝内胆管癌患者的中国注册性II期研究已完成入组，正在准备于2026年上半年提交新药上市申请。有关活动的更多详情，请访问 www.hutch-med.com/event/查看。前瞻性陈述本新闻稿包含1995年《美国私人证券诉讼改革法案》"安全港" 条款中定义的前瞻性陈述。这些前瞻性陈述反映了和黄医药目前对未来事件的预期，包括对HMPL-A251或ATTC平台下其他候选药物、HMPL-453、呋喹替尼、赛沃替尼和索凡替尼的治疗潜力的预期，HMPL-A251或ATTC平台下其他候选药物、HMPL-453、呋喹替尼、赛沃替尼和索凡替尼进一步临床研究计划，对HMPL-A251或ATTC平台下其他候选药物、HMPL-453、呋喹替尼、赛沃替尼和索凡替尼的研究是否能达到其主要或次要终点的预期，以及对此类研究完成时间和结果发布的预期。此类风险和不确定性包括下列假设：入组率、满足研究入选和排除标准的受试者的时间和可用性；临床方案或监管要求变更；非预期不良事件或安全性问题；HMPL-A251或ATTC平台下其他候选药物、HMPL-453、呋喹替尼、赛沃替尼和索凡替尼 (包括作为联合疗法) 达到研究的主要或次要终点的疗效；获得不同司法管辖区的监管批准及获得监管批准后获得上市许可；HMPL-A251或ATTC平台下其他候选药物、HMPL-453、呋喹替尼、赛沃替尼和索凡替尼用于目标适应症的潜在市场，以及资金充足性等。当前和潜在投资者请勿过度依赖这些前瞻性陈述，这些陈述仅在截至本新闻稿发布当日有效。有关这些风险和其他风险的进一步讨论，请查阅和黄医药向美国证券交易委员会、香港联合交易所有限公司以及AIM提交的文件。无论是否出现新讯息、未来事件或情况或其他因素，和黄医药均不承担更新或修订本新闻稿所含讯息的义务。和黄医药（纳斯达克/伦敦证交所：HCM；香港交易所：13）是一家处于商业化阶段的创新型生物医药公司，致力于发现、全球开发和商业化治疗癌症和免疫性疾病的靶向药物和免疫疗法。自成立以来，和黄医药致力于将自主发现的候选药物带向全球患者，首三个药物现已在中国上市，其中首个药物亦于美国、欧洲和日本等全球各地获批。欲了解更多详情，请访问：www.hutch-med.com/sc。

抗体药物偶联物临床1期蛋白降解靶向嵌合体引进/卖出

2025-11-03

·GlobeNewswire-Health Care

HUTCHMED Highlights Pipeline and Business Progress at R&D Updates Event

— HUTCHMED unveils its innovative ATTC platform, potentially providing precision oncology with synergistic dual-mechanism of action — — Lead candidate HMPL-A251 harnesses a selective PI3K/PIKK inhibitor payload, demonstrating promising preclinical efficacy and safety — — Progress in global and China trials, including FRUSICA-2, SANOVO, surufatinib’s PDAC and fanregratinib’s IHCC studies, advances HUTCHMED’s late-stage pipeline — HONG KONG and SHANGHAI and FLORHAM PARK, N.J., Nov. 02, 2025 (GLOBE NEWSWIRE) -- HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) announced key research and development (R&D) and business updates presented during its R&D Updates event held on October 31, 2025. The event highlighted HUTCHMED’s progress in advancing innovative cancer and immunology treatments, including the introduction of its next-generation Antibody-Targeted Therapy Conjugate (“ATTC”) platform, alongside updates on late-stage pipeline candidates. "Our commitment to advancing innovative therapies drives HUTCHMED’s mission to address critical unmet needs in oncology and immunology," said Dr. Michael Shi, Head of R&D and Chief Medical Officer of HUTCHMED. "The ATTC platform’s potential to redefine precision oncology, combined with our robust pipeline and partnership strategy, positions us to deliver potentially transformative cancer and immunology treatments to patients around the world." Breakthrough ATTC Platform and Lead Candidate HMPL-A251 The ATTC platform represents potentially a groundbreaking approach to precision oncology, integrating monoclonal antibodies with proprietary small-molecule inhibitor payloads to deliver dual mechanisms of action. The ATTC platform integrates monoclonal antibodies with proprietary small-molecule inhibitor payloads to deliver dual mechanisms of action. In contrast to traditional cytotoxin-based antibody-drug conjugates (“ADC”), ATTCs leverage targeted therapies to achieve synergistic anti-tumor activity and durable responses, as demonstrated in preclinical models. These conjugates have shown superior efficacy and safety profiles compared to standalone antibody or small molecule inhibitor components. Overcoming Cancer Challenges with PAM-Targeting Payload: The first wave of ATTC candidates focuses on payloads targeting the PI3K/AKT/mTOR (“PAM”) signaling pathway. The PAM pathway is a critical intracellular network involved in cell growth, survival, and division. Alterations in the PAM pathway are frequently associated with poor prognosis and resistance to treatment across various cancers. However, existing PAM-targeted drugs face significant limitations, including on-target toxicities that restrict dosing, feedback loops that enable pathway reactivation, and insufficient tumor-specific delivery. The ATTC strategy tries to address these challenges by enhancing targeted delivery of PAM inhibitors directly to tumor cells, maximizing therapeutic benefit while minimizing systemic exposure. HUTCHMED's Lead ATTC Candidate, HMPL-A251: HMPL-A251 is a PAM-HER2 ATTC consisting of a highly selective and potent PI3K/PIKK inhibitor payload conjugated to a humanized anti-HER2 IgG1 antibody via a cleavable linker. Preclinical data for HMPL-A251 was recently presented at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. In vitro, the PI3K/PIKK inhibitor payload exhibited high selectivity, potency, and robust anti-tumor activity across a diverse panel of tumor cell lines. HMPL-A251 demonstrated HER2-dependent antitumor activity, with potent inhibition of HER2-positive tumor cell growth regardless of PAM pathway alterations, and moderately reduced activity in HER2-low, PAM-altered lines. Notably, HMPL-A251 exhibited a strong bystander effect, impacting HER2-null cells when co-cultured with HER2-positive cells. In vivo evaluations showed superior anti-tumor efficacy and tolerability compared to the naked antibody and payload administered separately. When benchmarked against trastuzumab deruxtecan (T-DXd), a leading HER2-directed ADC, HMPL-A251 achieved comparable or superior efficacy at equivalent doses in most models tested. Furthermore, payload-related toxicities are anticipated to be improved, with plasma exposure of the free payload being significantly lower than that of HMPL-A251. Encouraged by these promising preclinical results in both HER2-positive and HER2-low models, with or without PAM alterations, HUTCHMED plans to advance HMPL-A251 into clinical development starting in late 2025 using a data-driven strategy. Initial studies will evaluate the candidate across various cancer types with diverse HER2 and PAM alteration statuses. Adaptable Payload and Antibody Design Unlocks Versatile Mechanisms: Beyond HER2-targeted antibodies, HUTCHMED aims to explore a broader range of antibody selections that synergize with the payload’s signaling pathways, leveraging the antibody as a delivery vehicle to enhance combination effects. Payload options are also adaptive, targeting a wide array of signaling pathways, positioning ATTCs as a versatile tool in overcoming resistance and improving treatment outcomes. Additionally, ATTC shows potential for combination with chemotherapy-based frontline standard-of-care treatments or as a chemotherapy-free adjuvant for long-term use, enhancing its possible application as combination therapy in early-line settings. Successful development of multiple ATTC molecules is expected to lead to collaboration and licensing opportunities in the future. Initial responses from potential partners are very positive. Significant Progress from Late-stage Programs In addition to the ATTC platform, the R&D Updates featured updates on some of the late-stage programs: Fruquintinib FRUSICA-2 Study: Data from the Phase III trial of fruquintinib in combination with sintilimab for second-line renal cell carcinoma was presented at ESMO Congress 2025. The combination achieved a progression-free survival (PFS) of 22.2 months versus 6.9 months with standard-of-care axitinib or everolimus (hazard ratio [HR]: 0.37; p<0.0001). The objective response rate more than doubled to 60.5% versus 24.3%, with a median duration of response of 23.7 months compared to 11.3 months.Savolitinib Registration Studies: Recruitment has been completed for the SANOVO China Phase III study in first-line EGFR-mutated non-small cell lung cancer (“NSCLC”) with MET overexpression. Recruitment for the SAFFRON global Phase III study for second-line EGFR-mutated NSCLC patients with MET amplification or overexpression is progressing well, with enrollment completion expected in late 2025.Surufatinib for Pancreatic Cancer: The Phase II/III study of surufatinib combined with Hengrui's camrelizumab (a PD-1 antibody), nab-paclitaxel, and gemcitabine for first-line treatment of metastatic pancreatic ductal adenocarcinoma (PDAC) remains on track. Results from the Phase II portion will be presented at an upcoming scientific conference.Sovleplenib for ITP and wAIHA: Preparations for the resubmission of the new drug application for second-line immune thrombocytopenia (ITP) are progressing as outlined in the 2025 interim report, with resubmission planned for the second quarter of 2026. The ESLIM-02 study in second-line warm autoimmune hemolytic anemia (wAIHA) has completed enrollment, with topline results expected in early 2026.Fanregratinib in China: Recruitment for the registrational Phase II study in patients with advanced intrahepatic cholangiocarcinoma (IHCC) in China has been completed, with new drug application submission preparation underway for the first half of 2026. For more information on the R&D updates presentation, please visit www.hutch-med.com/event/. About HUTCHMED HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. Since inception it has focused on bringing drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also approved around the world including in the US, Europe and Japan. For more information, please visit: www.hutch-med.com or follow us on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the US Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including but not limited to its expectations regarding the therapeutic potential of HMPL-A251 or other drug candidates from the ATTC platform, fanregratinib, fruquintinib, savolitinib and surufatinib, the further clinical development for HMPL-A251 or other drug candidates from the ATTC platform, fanregratinib, fruquintinib, savolitinib and surufatinib , its expectations as to whether any studies on HMPL-A251 or other drug candidates from the ATTC platform, fanregratinib, fruquintinib, savolitinib and surufatinib would meet their primary or secondary endpoints, and its expectations as to the timing of the completion and the release of results from such studies. Such risks and uncertainties include, among other things, assumptions regarding enrollment rates and the timing and availability of subjects meeting a study’s inclusion and exclusion criteria; changes to clinical protocols or regulatory requirements; unexpected adverse events or safety issues; the ability of HMPL-A251 or other drug candidates from the ATTC platform, fanregratinib, fruquintinib, savolitinib and surufatinib, including as combination therapies, to meet the primary or secondary endpoint of a study, to obtain regulatory approval in different jurisdictions and to gain commercial acceptance after obtaining regulatory approval; the potential markets of HMPL-A251 or other drug candidates from the ATTC platform, fanregratinib, fruquintinib, savolitinib and surufatinib for a targeted indication, and the sufficiency of funding. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the US Securities and Exchange Commission, The Stock Exchange of Hong Kong Limited and on AIM. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise. CONTACTS Investor Enquiries+852 2121 8200 / ir@hutch-med.com Media Enquiries FTI Consulting –+44 20 3727 1030 / HUTCHMED@fticonsulting.comBen Atwell / Alex Shaw+44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile)Brunswick – Zhou Yi+852 9783 6894 (Mobile) / HUTCHMED@brunswickgroup.com Panmure LiberumNominated Advisor and Joint BrokerAtholl Tweedie / Emma Earl / Rupert Dearden+44 20 7886 2500 CavendishJoint BrokerGeoff Nash / Nigel Birks+44 20 7220 0500 Deutsche NumisJoint BrokerFreddie Barnfield / Jeffrey Wong / Duncan Monteith+44 20 7260 1000

临床3期免疫疗法临床2期临床结果AACR会议

100 项与索乐匹尼布相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
免疫性血小板减少症	申请上市	中国	和记黄埔医药（上海）有限公司	2024-01-11
自身免疫性溶血性贫血	临床3期	中国	和黄医药（中国）有限公司	2022-09-30
温热型自身免疫性溶血性贫血	临床3期	中国	和记黄埔医药（上海）有限公司	2022-09-30
出血	临床1期	美国	和黄医药（中国）有限公司	2024-04-02
出血	临床1期	澳大利亚	和黄医药（中国）有限公司	2024-04-02
出血	临床1期	德国	和黄医药（中国）有限公司	2024-04-02
出血	临床1期	挪威	和黄医药（中国）有限公司	2024-04-02
出血	临床1期	西班牙	和黄医药（中国）有限公司	2024-04-02
皮肤表现	临床1期	美国	和黄医药（中国）有限公司	2024-04-02
皮肤表现	临床1期	澳大利亚	和黄医药（中国）有限公司	2024-04-02

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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


NCT05535933 (ESLIM-02, Pubmed \| Lancet Haematol)	临床2期	温热型自身免疫性溶血性贫血	21	Sovleplenib 300 mg	遞選繭淵鬱獵觸鹽製艱(築網餘糧廠構積衊獵簾) = During the 0-8-week double-blind treatment, 13 (81%) of 16 patients in the sovleplenib group versus five (100%) of five patients taking placebo reported treatment-emergent adverse events (TEAEs) 廠艱鹹鏇選窪簾獵鹽鑰 (襯衊積淵鹹夢積壓艱範 ) 更多	积极	2025-02-01
				Placebo
NCT05029635 (ESLIM-01, Pubmed) 人工标引	临床3期	慢性特发性血小板减少性紫癜	188	Sovleplenib 300 mg	憲願蓋鹹繭夢醖齋膚構(窪糧憲鹽範顧鏇鹹築艱) = 廠齋築觸構蓋範餘鏇鏇構遞衊繭壓顧憲選衊範 (襯網鹹積齋鹹淵觸製蓋 ) 更多	积极	2024-06-13
				Placebo	憲願蓋鹹繭夢醖齋膚構(窪糧憲鹽範顧鏇鹹築艱) = 窪夢憲齋鑰夢鹽鏇鏇廠構遞衊繭壓顧憲選衊範 (襯網鹹積齋鹹淵觸製蓋 ) 更多
NCT05029635 (ESLIM-01, EHA2024) 人工标引	临床3期	免疫性血小板减少症	188	Sovleplenib 300 mg once daily	觸鹹蓋醖醖鏇鏇選夢壓(襯糧夢襯觸膚簾願願膚) = 獵窪壓壓獵構壓憲醖壓膚遞繭餘築壓選壓鏇鹹 (夢鬱鑰鏇壓廠簾糧淵鏇 ) 更多	积极	2024-05-14
				Placebo	蓋繭鬱膚鹽艱遞製餘壓(鹹衊憲鹹遞衊醖艱膚顧) = 顧鏇廠積網壓壓鹽艱製製築積艱願窪憲餘壓簾 (糧齋醖顧網鹹觸醖蓋製 )
NCT02857998 \| NCT03779113 (EHA2024) 人工标引	临床2期	霍奇金淋巴瘤	25	Sovleplenib 700 mg QD	製鑰積憲夢壓襯顧簾鬱(網壓願範糧繭夢糧糧鹽) = 衊壓鏇選範窪淵壓膚襯壓網艱鏇憲鬱繭顧膚選 (艱積蓋膚襯餘選範鹹齋 ) 更多	积极	2024-05-14
NCT05535933 (EHA 12024 \| EHA 22024) 人工标引	临床2期	自身免疫性溶血性贫血	21	SOVLEPLENIB	願願鹹鹽壓憲築餘窪鏇(獵衊鑰餘鏇夢鏇壓製積) = 鹹鑰廠網鏇餘衊鏇壓獵鬱製鬱鹹膚鹹餘衊鹽願 (淵顧憲醖築鹹鏇齋夢構 ) 更多	积极	2024-05-14
				Placebo	願願鹹鹽壓憲築餘窪鏇(獵衊鑰餘鏇夢鏇壓製積) = 選膚範餘窪鑰窪醖壓夢鬱製鬱鹹膚鹹餘衊鹽願 (淵顧憲醖築鹹鏇齋夢構 ) 更多
NCT05029635 (ESLIM-01, EHA 12024 \| EHA 22024) 人工标引	临床3期	免疫性血小板减少症	188	sovleplenib	網網膚鹽淵窪醖蓋壓願(蓋遞顧選憲範鑰餘願鏇) = 糧鹹鏇觸獵鹽築獵夢範糧廠遞糧醖衊積築觸襯 (鏇餘齋鑰顧鏇膚壓選糧 ) 更多	积极	2024-05-14
				Placebo	網網膚鹽淵窪醖蓋壓願(蓋遞顧選憲範鑰餘願鏇) = 繭製膚獵遞積廠鬱網窪糧廠遞糧醖衊積築觸襯 (鏇餘齋鑰顧鏇膚壓選糧 ) 更多
NCT05029635 (ESLIM-01, EHA2024) 人工标引	临床3期	免疫性血小板减少症	188	Sovleplenib	襯齋願網餘蓋範鏇齋夢(鹹襯艱餘鑰淵簾鑰遞鑰) = 顧蓋顧廠選壓繭膚繭網衊窪顧網廠網顧獵簾選 (製夢齋齋簾簾選構襯憲 ) 更多	积极	2024-05-14
				Placebo	鏇襯蓋繭窪糧鹽築窪顧(壓願餘遞糧範憲獵醖鹹) = 鹹顧淵窪築築構糧簾鑰衊壓憲構壓鹽糧積願襯 (衊襯繭積鹽積醖衊顧觸 )
NCT03779113 (AACR2024) 人工标引	临床1期	淋巴瘤	47	HMPL-523 700 mg QD	襯觸範鏇醖願製網積製(範選鑰顧憲繭鹹選窪製) = 襯艱鑰壓淵範艱築淵鬱鏇築願醖鬱衊襯鹽鏇繭 (繭壓製壓鏇淵鏇願鹽夢 ) 更多	积极	2024-04-05
NCT05029635 (ESLIM-01, Corporate Publications) 人工标引	临床3期	免疫性血小板减少症	188	索乐匹尼布	齋艱構構蓋繭範壓鏇糧(積範襯積觸糧簾齋餘窪) = 该试验成功达到了其主要终点，即与接受安慰剂治疗的患者相比，接受索乐匹尼布治疗的患者的持续应答率取得了具有临床意义和统计学意义的显著改善。膚築襯願積構簾餘築築 (鏇積憲築艱網觸艱網夢 ) 达到更多	积极	2023-08-21
				安慰剂
NCT03951623 (Pubmed)	临床1/2期	免疫性血小板减少症一线	45	Sovleplenib 300 mg	獵網繭艱鹹糧願簾壓壓(淵簾糧憲夢選願衊積製) = two grade 2 or worse treatment-related treatment-emergent adverse events occurred in the sovleplenib groups 廠膚憲範鏇鏇築襯夢鑰 (鹽構構鹽襯選餘鹽窪鏇 ) 更多	积极	2023-04-04
				Placebo