Rituximab

— Sovleplenib demonstrated rapid and durable hemoglobin response with favorable safety profile — —The ESLIM-02 study underscores sovleplenib’s potential to address critical unmet needs in a treatment landscape currently devoid of approved targeted therapies — HONG KONG and SHANGHAI and FLORHAM PARK, N.J., June 12, 2026 (GLOBE NEWSWIRE) -- HUTCHMED (China) Limited (“ HUTCHMED ”) (Nasdaq/AIM:HCM; HKEX:13) today announces results from the Phase III part of the ESLIM-02 study of sovleplenib in patients with warm antibody autoimmune hemolytic anemia (“wAIHA”) in China were presented on Thursday, June 11, 2026 during the European Hematology Association (“EHA”) Congress in Stockholm, Sweden. Supported by data from the ESLIM-02 study, a New Drug Application (“NDA”) for sovleplenib for the treatment of adult patients with wAIHA who have had an insufficient response to at least one previous glucocorticoid treatment has been accepted for review and granted priority review by the China National Medical Products Administration (“NMPA”) in April 2026. The NMPA granted Breakthrough Therapy Designation to sovleplenib for the treatment of wAIHA in March 2026. The ESLIM-02 presentation was selected for the official EHA Press Program. Professor Bing Han of Peking Union Medical College Hospital , and co-leading Principal Investigator of the ESLIM-02 study, said: “The wAIHA treatment paradigm has remained stagnant for decades, with patients often trapped in a cycle of high-dose steroids and frequent relapses. The ESLIM-02 data are transformative as they demonstrate that targeting the Syk pathway can achieve both rapid and durable control of hemolysis. We are particularly encouraged by the robust data across all patient subgroups, regardless of their prior treatments. Sovleplenib’s ability to significantly reduce the need for rescue therapies and blood transfusions represents a major step forward in restoring the quality of life for these patients.” ESLIM-02 is a randomized, double blind, placebo-controlled China Phase II/III study in adult patients with primary or secondary wAIHA who had relapsed or were refractory to at least one prior line of standard treatment ( NCT05535933 ). Results from the Phase II part of the study were published in The Lancet Haematology in January 2025. In Phase III part of the study, 90 patients were randomized 1:1 to receive either sovleplenib (n=44) or placebo (n=46) at a dose of 300 mg once daily for 24 weeks. The study met its primary endpoint, with sovleplenib demonstrating a significantly higher durable response rate during weeks 5–24 compared to placebo (66% vs 15%, p<0.0001). During the 24-week double-blind treatment period, sovleplenib demonstrated superior efficacy across several key metrics; specifically, the overall response rate—defined as hemoglobin (Hb) ≥100 g/L with an increase of ≥20 g/L from baseline without rescue therapy—was significantly increased (70% vs 22%, p<0.0001). The use of protocol-defined rescue therapy was significantly reduced with sovleplenib (16% vs 54%, p=0.0001), fewer patients received red blood cell transfusion (11% vs 43%) and higher patients with tapering or discontinuation of glucocorticoids or other baseline concomitant anti-wAIHA therapies (50% vs 15%, p=0.003​). Median time to response was 3.1 weeks for sovleplenib versus 6.3 weeks for placebo, while the median cumulative duration of response among overall responders was 16.1 versus 6.1 weeks, respectively. Additionally, an improvement in hemolytic markers was observed with sovleplenib compared with placebo, showing an alleviation of active hemolysis. These efficacy findings remained consistent across all sensitivity analyses, and all subgroup analyses further supported the primary endpoint results. Notably, in patients who had received prior rituximab therapy, the durable response rate continued to favor sovleplenib over placebo (69% vs 16%, p=0.0022). Sovleplenib demonstrated a favorable safety profile. Grade ≥3 treatment-emergent adverse events (“TEAE”) were reported in 43% patients in the sovleplenib arm and 59% patients in the placebo arm. The most common Grade ≥3 TEAEs, occurring in at least 10% of patients, were warm autoimmune hemolytic anemia (18% vs 43%) and upper respiratory tract infection (2% vs 11%). There were no TEAE-related deaths or treatment discontinuations reported in the sovleplenib group. Details of the presentation are as follows: Title: A randomized, double-blind, placebo-controlled Phase 3 study of ESLIM-02 for efficacy and safety of sovleplenib (HMPL-523) in patients with warm autoimmune hemolytic anemia in China Lead Author: Bing Han, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China Session: Oral Session (Targeted therapies in rare red cell and metabolic disorders) Presentation ID: S301 Date & Time: Thursday, 11 June 2026, 17:00 CEST Location: A13 Hall About Sovleplenib and wAIHA Sovleplenib is a novel, investigational, selective small molecule inhibitor for oral administration targeting Syk. Syk is a major component in B-cell receptor and Fc receptor signaling and is an established target for the treatment of multiple subtypes of B-cell lymphomas and autoimmune disorders. The accelerated clearance of antibody-coated RBCs by immunoglobulin Fc-gamma receptor (FcγR) bearing macrophages is thought to be the pathogenic mechanism in wAIHA. 1 Activated Syk mediates downstream signaling of the activated Fc receptors in phagocytic cells, resulting in phagocytosis of RBCs. 2 In addition, activation of Syk through the B-cell receptor mediates activation and differentiation of B-lymphocytes into antibody secreting plasma cells. 3 Inhibition of Syk may have potential effects in the treatment of wAIHA through inhibition of phagocytosis and reduction of antibody production. In addition to wAIHA, sovleplenib is also being studied in immune thrombocytopenia (“ITP”). Positive results from ESLIM-01 (NCT05029635), a Phase III trial in China of sovleplenib in patients with primary ITP, have been published in The Lancet Haematology . The NMPA accepted for review the resubmitted NDA filing for the treatment of ITP and granted it priority review in February 2026. According to IQVIA, China has 430,000 existing patients with 41,000 new ITP patients each year. About half of ITP patients fail to have satisfactory results from currently approved treatments such as TPO (thrombopoietin) / TPO-RAs (thrombopoietin receptor agonists). HUTCHMED currently retains all rights to sovleplenib worldwide. 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: 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 sovleplenib, the further clinical development for sovleplenib, its expectations as to whether any studies on sovleplenib 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 sovleplenib, 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 sovleplenib 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. Medical Information This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development. CONTACTS Investor Enquiries +852 2121 8200 / ir@hutch-med.com Media Enquiries FTI Consulting – +44 20 3727 1030 / HUTCHMED@fticonsulting.com Ben Atwell / Tim Stamper +44 7771 913 902 (Mobile) / +44 7779 436 698 (Mobile) Brunswick – Zhou Yi +852 9783 6894 (Mobile) / HUTCHMED@brunswickgroup.com Panmure Liberum Nominated Advisor and Joint Broker Atholl Tweedie / Emma Earl / Rupert Dearden +44 20 7886 2500 Cavendish Joint Broker Geoff Nash / Nigel Birks +44 20 7220 0500 Deutsche Numis Joint Broker Duncan Monteith / Ramin Naji +44 20 7545 8000 ______________________ REFERENCES 1 Barros MM, Blajchman MA, Bordin JO. Warm autoimmune hemolytic anemia: recent progress in understanding the immunobiology and the treatment. Transfus Med Rev. 2010; 24(3):195‐210. doi: 10.1016/j.tmrv.2010.03.002. 2 Barcellini W, Fattizzo B, Zaninoni A. Current and emerging treatment options for autoimmune hemolytic anemia. Expert Rev Clin Immunol. 2018; 14(10):857‐872. doi: 10.1080/1744666x.2018.1521722. 3 Davidzohn N, Biram A, Stoler‐Barak L, Grenov A, Dassa B, Shulman Z. SYK degradation restrains plasma cell formation and promotes zonal transitions in germinal centers. J Exp Med. 2020; 217(3):e20191043. doi: 10.1084/jem.20191043.

边缘区淋巴瘤（MZL）是一种异质性惰性B细胞恶性肿瘤，包括脾（SMZL）、淋巴结（NMZL）和结外（EMZL）亚型。由于其发病率低且表现多样，前瞻性随机数据有限。大多数NMZL的治疗方案参照滤泡性淋巴瘤，而局限性EMZL常采用局部治疗或针对幽门螺杆菌相关胃病的抗生素治疗。IELSG-19试验仍是MZL中唯一一项针对组织学亚型的系统性一线治疗III期研究，该研究表明利妥昔单抗联合苯丁酸氮芥相较于任一单药可延长无进展生存期（PFS），但未显示总生存期（OS）获益。基于在惰性淋巴瘤中苯达莫司汀-利妥昔单抗（BR）方案相较于环磷酰胺为基础的联合方案显示更优PFS的试验证据，BR已在美国很大程度上取代了其他化学免疫治疗方案。小样本研究报告各MZL亚型的5年PFS率为80-87%，然而尚无研究证实其相较于利妥昔单抗单药治疗具有OS或生活质量优势，而后者可以较低毒性实现持久缓解。鉴于苯达莫司汀的长期免疫抑制作用和复发性MZL的惰性特性，BR方案相较于利妥昔单抗单用的生存影响比较亟需阐明。     我们使用两个大型真实世界数据集评估了PFS和OS：美国国家癌症数据库（NCDB），这是美国外科医师学会癌症委员会和美国癌症学会的联合项目，以及一个多机构的MZL真实世界数据（MZL-RWD）回顾性队列，并应用因果推断方法以最小化治疗选择偏倚。     NCDB 2022文件筛选了2013年至2018年间诊断为MZL的成人（≥18岁）。这一时期涵盖了利妥昔单抗特异性编码的引入以及至少5年的随访。NCDB变量包括人口统计学特征、分期、B症状以及初始治疗，初始治疗分为免疫治疗（主要是利妥昔单抗）或细胞毒化疗，但无具体药物级别的详细信息（在线补充表S1）。我们排除了在报告机构未经治疗、缺乏组织学确认、未接受免疫治疗或诊断至治疗间隔缺失的患者。MZL-RWD数据集包含了2010年至2020年间在美国十个中心接受治疗的878例患者，具有详细的临床病理、实验室、治疗和生存数据，其中541例接受了一线利妥昔单抗或BR治疗。缺失值通过均值替代法填补。所有数据均经过去标识化处理，分析获得机构审查委员会批准；两个数据集之间无关联。分析按照先前描述的框架分别针对NCDB和MZL-RWD进行。采用逻辑回归模型生成倾向评分，纳入治疗选择模型中的所有变量以及年龄（NCDB数据中使用限制性立方样条）与MZL亚型之间的交互作用。在NCDB数据中，患者在倾向评分标准差的10%卡钳范围内进行匹配（1:1匹配），而在MZL-RWD中采用逆概率治疗加权法（IPTW，经1:1匹配验证）。协变量平衡定义为标准化均值差（SDM）<0.1。     结局指标为OS（NCDB）以及PFS加OS（MZL-RWD），采用含稳健标准误的Cox模型进行分析。结果以风险比（HR）及其95%置信区间（95% CI）报告。双重稳健模型和按治疗医院分层分析确认了结果的稳定性。敏感性分析针对潜在的未测量混杂因素进行：（i）剔除极端倾向评分（≤25%）的患者；（ii）模拟一个未测量的混杂因素（HR=2.0），并设定不同的患病率差异。     在NCDB数据集（N=8,110）中，58%的患者接受了单纯免疫治疗，42%接受了化学免疫治疗。中位随访时间为3.9年。5年OS率为75.8%（95% CI: 74.6-76.9），EMZL最高（79.3%），NMZL（73.0%）和SMZL（74.0%）较低（图1A, B）。接受化学免疫治疗者更年轻，男性更多见，且更可能为NMZL、晚期或伴有B症状（在线补充表S2）。2013至2018年间，治疗比例保持稳定（约60%接受单纯免疫治疗）（图1C）。不同机构间的差异显著（P<10⁻⁵），但与学术型或社区型机构状态无关（图1D）。胃、肺、皮肤、唾液腺或眼部起源的EMZL最常采用利妥昔单抗单药治疗，而中枢神经系统EMZL患者最常接受化学免疫治疗（图1E）。在接受化疗的患者中，68%采用单药方案，30%采用多药联合方案，这与既往报道的BR方案占主导的情况一致。 图1. 2013-2018年美国国家癌症数据库中边缘区淋巴瘤患者的治疗与结局(A) 按边缘区淋巴瘤（MZL）组织学类型分层的患者总生存期。(B) 各MZL组织学亚型中使用化学免疫治疗或单纯免疫治疗的情况（显示每种组织学类型中接受免疫治疗的患者百分比）。(C) 每个日历年度中化学免疫治疗与免疫治疗的使用情况（显示接受免疫治疗的患者百分比）。(D) 各报告医院中化学免疫治疗（vs. 免疫治疗）相对使用情况的差异；圆圈大小对应各医院报告的MZL病例数；机构按接受联合化学免疫治疗的患者比例升序排列，仅纳入报告至少6例MZL的机构。(E) 特定原发解剖部位的结外MZL患者接受化学免疫治疗或单纯免疫治疗的人数。OS：总生存期；y：年；SMZL：脾MZL；NMZL：淋巴结MZL；EMZL：结外MZL；GI tract：胃肠道；Conn. tissue：结缔组织；GU tract：泌尿生殖道；CNS/neuro：中枢神经系统/神经。     倾向评分匹配产生了2534对匹配，协变量平衡极佳（平均SDM，0.018）（图2A-C）。两组间的OS无差异（HR=1.07；95% CI: 0.94-1.21；P=0.30）（图2D）。免疫治疗组的5年OS率为76.6%（95% CI: 74.4-78.6），化学免疫治疗组为76.2%（95% CI: 74.1-78.2）。在医院分层模型（HR=1.10）和双重稳健模型（HR=1.08）中结果一致。亚组分析显示，按年龄或倾向评分四分位数未见异质性，且存在显著残余未测量混杂的可能性较低，但在SMZL中，化学免疫治疗的使用与较差的OS相关（图2E, F）。组织学特异性模型证实，EMZL（HR=1.06；95% CI: 0.85-1.31）或NMZL（HR=1.08；95% CI: 0.91-1.28）的OS无差异，而SMZL中显示的不良预后（HR=1.42；95% CI: 1.04-1.96）似乎对中等程度的模拟混杂较为敏感。剔除倾向评分分布的尾部并未实质性地改变结果（数据未显示）。 图2. 美国国家癌症数据库数据集分析(A) 用于一对一倾向评分（PS）匹配的变量；最终PS模型包含所有列出的变量，年龄和距诊断时间使用限制性立方样条建模，并包含年龄与边缘区淋巴瘤（MZL）亚型间的交互项。(B) 匹配前后PS的分布。(C) PS模型中纳入的主要混杂因素的绝对标准化均值差（SDM）；保险类别和收入中位数未列出但已充分平衡（最大SDM=0.021）。(D) 匹配队列中比较接受单纯免疫治疗与联合化学免疫治疗患者的总生存期（OS）；显示了5年OS率。(E) 根据PS五分位数、年龄五分位数或MZL组织学类型评估OS结局异质性的亚组分析。(F) 敏感性分析，调查在额外调整一个假定未观察到的混杂因素（与HR 2.0相关）并改变其在两组研究中的患病率时，模型风险比（HR）和统计学显著性（以阴影表示）的变化。NMZL：淋巴结MZL；SMZL：脾MZL；EMZL：结外MZL；HR：风险比；95% CI：95%置信区间。     从MZL-RWD队列中，我们筛选了355例接受利妥昔单抗和186例接受BR方案的患者（总计N=541）（图3A）。总体而言，在MZL-RWD研究中，化学免疫治疗包括BR方案（75%）和基于环磷酰胺的方案（25%）。中位随访时间为4.6年。中位PFS为5.8年（95% CI: 4.7-7.1）；5年OS率为86.5%（95% CI: 82.7-89.6）。未经调整的分析显示BR组的PFS和OS更长，但该组患者更年轻，且分期和乳酸脱氢酶浓度更高（在线补充表S3）。利妥昔单抗在SMZL（74%）和EMZL（69%）中占主导。组织学转化在利妥昔单抗组发生率为2.8%，BR组为4.3%。     IPTW模型平衡了所有已测量的协变量（平均SDM，0.022）（图3A, B）。BR方案的PFS显著更优（HR=0.57；95% CI: 0.40-0.81；P=0.0018），其5年PFS率为66.3%，而利妥昔单抗组为48.7%（图3C）。医院分层分析和双重稳健分析中结果仍稳健。未观察到按亚型的异质性（图3D），且模拟混杂需达到≥30%的不平衡才能否定显著性（图3E）。OS无差异（HR=0.86；95% CI: 0.46-1.64；P=0.65）（图3F）；5年OS率在BR组为86.2%，利妥昔单抗组为87.2%。按年龄、亚型或倾向性五分位数进行的亚组分析结果一致（数据未显示）。SMZL患者表现出OS较差的非显著性趋势（HR=1.50；95% CI: 0.51-4.44）。验证性1:1匹配（N=314）产生了相似的结果——BR方案PFS更优（HR=0.50；95% CI: 0.34-0.73）但OS无差异（HR=0.82；95% CI: 0.40-1.68）。结果对替代的缺失数据处理策略不敏感（数据未显示）。 图3. 边缘区淋巴瘤真实世界数据集分析(A) 用于逆概率治疗加权倾向评分（PS）模型的变量；最终PS模型包含所有列出的变量，以及年龄与边缘区淋巴瘤（MZL）亚型间的交互项。(B) PS模型中纳入的主要混杂因素的绝对标准化均值差。(C) 调整后队列中比较接受利妥昔单抗或苯达莫司汀联合利妥昔单抗（BR）治疗患者的无进展生存期（PFS）；显示了5年PFS估计值。(D) 根据PS五分位数、年龄五分位数或MZL组织学类型评估PFS结局异质性的亚组分析。(E) 敏感性分析，调查在额外调整一个假定未观察到的混杂因素（与HR 2.0相关）并改变其在两组研究中的患病率时，模型风险比（HR）和统计学显著性（以阴影表示）的变化。(F) 调整后队列中比较接受利妥昔单抗或BR治疗患者的总生存期（OS）；显示了5年OS估计值。IPTW：逆概率治疗加权；LDH：乳酸脱氢酶；NMZL：淋巴结MZL；SMZL：脾MZL；EMZL：结外MZL；HR：风险比；95% CI：95%置信区间。     在两项互补的真实世界数据集中，一线化学免疫治疗与利妥昔单抗单药治疗在MZL中产生了可比的OS，尽管BR方案在5年内将PFS提高了约15%。这些结果与IELSG-19试验数据相似，后者发现利妥昔单抗联合苯丁酸氮芥相较于利妥昔单抗单药治疗延长了PFS，但无OS获益。在MZL患者中，复发往往是惰性且无症状的，PFS可能无法转化为有意义的生存或生活质量改善。由于复发后生存期长且有效的再治疗方案可用，证明OS改善本身就极其困难。我们的发现强化了这样一个理念：BR方案的毒性特征——持续性血细胞减少、免疫抑制及潜在的继发性髓系恶性肿瘤风险——应与PFS延长进行权衡。既往研究中，感染并发症发生率高达13%，包括4%的带状疱疹，这促使了预防性用药的建议。在老年患者中，以及可能在SMZL患者中，这些风险更高，因为BR方案在EMZL（GELTAMO试验中7年PFS为93%）患者中的疗效优于SMZL（BRISMA/IELSG36试验中5年PFS为83%）患者，且BR在后者中引发了显著的感染毒性。利妥昔单抗维持治疗或再治疗可延长PFS，从而可能减少前期化疗的需求。     NCDB（全国范围覆盖，临床细节有限）与MZL-RWD（临床资料丰富，多中心）之间的一致性支持了外部真实性。在SMZL中观察到的化学免疫治疗的OS劣势应谨慎解读，因为这一现象未在MZL-RWD中重现，且可能反映了未测量的混杂因素。本研究中观察到的BR方案的PFS获益与II期试验估计值相似（本研究5年PFS为66%，试验中约为80%），提示真实世界结果可能因纳入更为年长、经选择较少的群体而略逊于临床试验基准。     本研究的局限性包括缺乏毒性、生活质量数据和死亡原因，以及与MZL预后评分相比，变量覆盖不完整。此外，无法考虑患者的治疗偏好、EMZL的抗生素治疗使用情况，或特定的潜在合并症和虚弱状态。中心病理复核是临床试验方法的关键组成部分，但它在常规临床实践中并不开展，因此预计存在一定程度的组织学错误分类。NCDB缺乏具体治疗细节，尽管治疗比例反映了当代美国以BR方案为主、苯丁酸氮芥使用极为罕见的临床实践。我们未分析利妥昔单抗维持治疗或苯达莫司汀的不同剂量，因为这些治疗后因素会引入 immortal-time偏倚。来自治疗选择过程可能不同的国家的国际视角将具有额外价值。     总之，在两个独立、方法学稳健的真实世界队列中，BR方案作为MZL的一线治疗与利妥昔单抗单药治疗相比，实现了更长的PFS，但无OS优势。鉴于相似的生存情况和化疗带来的更大毒性，治疗选择应纳入患者对生活质量、治疗风险承受能力及负担偏好的考量。利妥昔单抗单药治疗仍是一项合理的一线标准治疗方案，并为未来联合靶向药物或生物制剂的方案提供了平台。 参考文献：Olszewski AJ, Ollila TA, Chihara D, et al. Comparative effectiveness of immunotherapy alone or with chemotherapy as first-line treatment for marginal zone lymphoma. Haematologica. 2026;111(5):1840-1846. doi:10.3324/haematol.2025.288946 免责声明：本公众号私信自动回复功能由AI生成，AI基于公众号文献集进行训练，仅为互动参考，不代表本公众号运营方的正式观点与态度。如涉及专业问题，请以专业人士及官方信息为准。 版权声明：本文供医学专业人士参考，未经著作人许可，不可出版发行。同时，欢迎个人转发分享，其他任何媒体、网站如需转载或引用本网页版权所有内容，须获得授权。 编辑：LCN 审核：CSY