复星医药子公司复宏汉霖7项创新成果将于2026 AACR公布，展现Hanjugator™ ADC与TCE平台FIC/BIC潜力
2026年4月17日，复星医药子公司复宏汉霖（2696.HK）宣布，将于美国当地时间4月17日至22日在圣地亚哥举行的美国癌症研究协会年会（AACR 2026）上，集中公布7款创新管线的最新临床前数据。此次展示的创新成果依托公司前沿的Hanjugator™ 抗体偶联药物（ADC）平台及多特异性T细胞衔接器（TCE）平台，全面覆盖PD-L1、B7-H3、STEAP1、EGFR、cMET、HER2、ADAM9、ALPP/ALPPL2等极具开发潜力的前沿靶点。研究数据显示，其中多款候选分子在临床前头对头比较中展现出同类最优（best-in-class, BIC）或同类首创（first-in-class, FIC）的治疗潜力。
（一） TCE平台：引入CD28共刺激信号，重塑实体瘤“免疫沙漠”
实体瘤治疗中，肿瘤微环境（TME）内T细胞浸润不足及免疫抑制状态是制约TCE疗效的关键瓶颈。为突破这一障碍并优化TCE在实体瘤中的治疗窗口，复宏汉霖开发了引入CD28共刺激信号的多特异性TCE平台。该平台通过同时提供CD3激活信号（第一信号）与CD28共刺激信号（第二信号），显著增强了T细胞在抑制性肿瘤微环境中的持久杀伤能力。此外，借助靶点依赖性激活、亲和力调控及CD3/CD28顺式结合等多重协同机制，该平台在提升抗肿瘤疗效的同时，有效控制了系统性毒性风险。目前，基于该平台已孵化了超过5款早期创新分子，其中HLX3901（DLL3xDLL3xCD3xCD28四特异性抗体）和HLX3902（STEAP1×CD3×CD28 三特异性抗体）作为该领域的代表产品，分别聚焦小细胞肺癌和前列腺癌等实体瘤的治疗，已加速推进至IND/IND受理阶段。
HLX3902（STEAP1×CD3×CD28 三抗TCE）
作为该领域布局的核心资产之一，三特异性抗体HLX3902能够精准靶向前列腺癌中高度表达的STEAP1， 并同时衔接CD3与CD28。临床前研究显示，HLX3902具有靶点依赖性的T细胞激活与细胞毒性，在1:5-1:10的低靶比条件下尤为显著。相较双特异性 TCE 及其联合方案，该分子显著增强 T 细胞功能、增殖及记忆 T 细胞扩增，并表现出更持久的体外细胞毒性。此外，在体内模型中，单次0.01 mg/kg剂量的HLX3902抗肿瘤活性优于AMG509（STEAP1 x CD3 双抗TCE），且作用更持久，同时促进 T 细胞浸润与激活，并通过 CD28 共刺激维持瘤内 CD8⁺ T 细胞的持续效应功能。在食蟹猴每周静脉注射45 μg/kg剂量下，HLX3902耐受性良好。目前，该分子的新药临床试验（IND）申请已获得中国国家药品监督管理局审评中心（CDE）受理。
摘要标题：一款新型CD3×CD28×STEAP1三特异性T细胞衔接器在前列腺癌中展现强效、持久的抗肿瘤应答
A novel anti-CD3×CD28×STEAP1 tri-specific T-cell engager with enhanced and durable antitumor responses in prostate cancer
分会场：Redefining Targeted Therapy: Bispecific T-Cell Engagers and Antibody-Drug Conjugates 2
展示形式：壁报
摘要编号：5397
展示时间：美国当地时间4月21日 9:00 AM-12:00 PM
展示地点：第48区，展板#10
此外，基于该平台开发的另一款潜力TCE分子HLX3901为靶向DLL3双表位、CD3和CD28的四特异性抗体，其IND申请已于2026年3月获得国家药品监督管理局（NMPA）批准。HLX3901结合了公司AI驱动的智能药物设计与TCE平台技术，通过精巧的分子设计，该产品兼具持久的特异性T细胞激活、攻克低T细胞浸润肿瘤及显著降低细胞因子释放综合征（CRS）等多重优势，旨在克服第一代TCE在实体瘤治疗中的主要障碍。临床前研究显示，HLX3901在低效靶比条件下展现出更优的细胞毒性效应。在人类泛T细胞重构模型中，HLX3901比同类产品（如Tarlatamab）表现出更强且更持久的抗肿瘤活性。同时，在食蟹猴的初步毒性研究中，HLX3901耐受性良好，显示出较宽的治疗窗口。该产品的临床前数据于全球抗体工程顶级会议2025 Antibody Engineering & Therapeutics上首次发布。
（二） Hanjugator™ ADC平台：可调节毒性载荷，拓展治疗窗口
在抗体偶联药物（ADC）的设计中，高毒性载荷虽然能有效杀伤肿瘤细胞，但也严重限制了临床给药剂量，使其难以达到最佳抗体水平，导致治疗窗口狭窄。为突破这一技术瓶颈，复宏汉霖自主开发了新一代ADC技术平台Hanjugator™——一个可定制、模块化的喜树碱类连接子-载荷平台。该平台的核心优势在于采用高亲水性喜树碱连接子-载荷设计，可根据靶点特异性选择最适载荷强度（可选毒素活性范围低至DXd活性的的三分之一，高至与 exatecan相当），从而在拓宽治疗窗口的同时，确保抗体功能充分发挥，在“抗体介导的信号阻断/内化功能”与“小分子毒素的强效杀伤功能” 之间找到最优平衡，实现 1+1 > 2 的治疗效果。
此外，该平台产生的ADC旁观者杀伤效应比基于deruxtecan的ADC强10倍以上，有望有效克服肿瘤异质性问题。差异化的载荷设计亦有助于规避常见毒素耐药，为下一代ADC药物的开发提供了差异化的解决方案。目前，Hanjugator™平台已孵化了超过12款早期创新分子，包括HLX48（EGFR/c-MET双抗ADC）、HLX49（HER2双表位ADC）、HLX403（CDH17 ADC）、HLX402（ADAM9 ADC）、HLX85（ALPP/ALPPL2 ADC）、HLX41（LIV-1 ADC）等。
HLX48（EGFR/c-MET双抗ADC）
作为Hanjugator™ ADC平台的代表性成果，HLX48由靶向EGFR与c-MET的双抗与喜树碱类DNA拓扑异构酶I抑制剂类毒素偶联而成。鉴于EGFR/cMET双抗ADC往往需要较高的临床剂量以实现最佳受体占有率，该分子采用了高亲水性基团连接策略与中等效力的载荷设计，抗体药物比（Drug-to-Antibody Ratio, DAR）约为4，旨在实现强大抗肿瘤活性与可管理毒性的最佳平衡。临床前药理学研究证明，HLX48在多种肿瘤模型中展现出显著的抗肿瘤活性，单次3 mg/kg剂量即可诱导显著肿瘤消退，在HT29结直肠癌模型中其疗效优于同类产品AZD9592。同时，HLX48在食蟹猴中60 mg/kg（每三周一次）剂量下耐受性良好，验证了其中等毒性载荷设计策略的可行性。
摘要标题：Hanjugator喜树碱平台：高效低毒设计最大化抗体潜能，孵化潜在同类最优的EGFR/cMET双抗ADC
Hanjugator camptothecin platform: effective, low-toxicity design maximizing antibody functionality and enabling a potential best-in-class EGFR/cMet bispecific ADC
分会场：Tumor Microenvironment, Multispecifics, and Immunomodulation
展示形式：壁报
摘要编号：5856
展示时间：美国当地时间4月21日 2:00 PM-5:00 PM
展示地点：第17区，展板#25
HLX49（HER2双表位ADC）
HLX49是一款基于曲妥珠单抗（汉曲优®）与dulpatatug*（新表位HER2单抗）开发的HER2双表位ADC候选分子，可同时结合HER2的不同结构域。该产品采用高效、低毒的载荷设计，允许更高剂量给药和更优的受体覆盖，从而增强肿瘤细胞杀伤效果。在BT-474和NCI-N87细胞系中，HLX49的内化效率优于KN026（HER2靶向的双特异性抗体）及德曲妥珠单抗（HER2 ADC）。在多个细胞系中，该双表位ADC显示出优于德曲妥珠单抗的抗肿瘤疗效。在涵盖HER2阳性（IHC 3+、IHC 2+/FISH+）、HER2低表达（IHC 2+/FISH- 或 IHC 1+）以及HER2超低表达（IHC <1+）的多种异种移植模型中，单次6 mg/kg剂量即可诱导显著的肿瘤消退，且在与德曲妥珠单抗的头对头比较中表现更优。初步毒理学研究显示，食蟹猴接受60 mg/kg剂量的HLX49三次给药后耐受性良好。
摘要标题：一款潜在同类最优的新型HER2双表位ADC，通过高效低毒设计最大化抗体功能
A best-in-class HER2xHER2 novel biparatopic antibody-drug conjugate with an efficacious, low-toxicity design that maximizes antibody functionality
分会场：Antibody Technologies and Platforms 2
展示形式：壁报
摘要编号：4395
展示时间：美国当地时间4月21日 9:00 AM-12:00 PM
展示地点：第11区，展板#3
HLX402（ADAM9 ADC）
ADAM9（解整合素金属蛋白酶9）在胰腺癌、肺癌、胃癌等多种实体瘤中过表达，但既往同类针对该靶点的候选药物曾因药物相关眼毒性而终止临床开发。HLX402采用新型喜树碱连接子-载荷，旨在避免此类眼毒性并具有更宽的治疗窗。临床前研究显示，HLX402的抗体对人和食蟹猴的ADAM9具有纳摩尔级亲和力。此外，抗体在多个肿瘤细胞系（MKN-45、MiaPaCa-2 和 Calu-3）中表现出时间依赖的高效内化（4小时>50%），并展现出强大的细胞毒性和旁观者杀伤效应。在Calu-3（非鳞状非小细胞肺癌）CDX模型中，单次3 mg/kg剂量下实现了109.3%的肿瘤生长抑制率（TGI），显著优于基准ADC的91.1%；在DLD-1（结直肠癌）CDX模型中，同剂量下HLX402的TGI达90.2%，而基准ADC仅为39.2%。在大鼠中，HLX402表现出优异的血浆稳定性和良好的药代动力学特征，游离毒素释放极少且具有类似抗体的半衰期。
摘要标题：靶向ADAM9的喜树碱ADC临床前数据亮眼，具备同类最优潜力
Preclinical characterization of a potential best-in-class camptothecin-based antibody-drug conjugate targeting ADAM metallopeptidase domain 9
分会场：Antibody Technologies and Platforms 2
展示形式：壁报
摘要编号：4418
展示时间：美国当地时间4月21日 9:00 AM-12:00 PM
展示地点：第11区，展板#26
HLX85（ALPP/ALPPL2 ADC）
ALPP（胎盘型碱性磷酸酶）和ALPPL2（胎盘样碱性磷酸酶2）因在卵巢癌（60%）、子宫内膜癌（50%）、胰腺癌（30%）和胃癌（15%）等多种实体瘤中表达而在正常组织中表达极低，成为颇具潜力的开发靶点。HLX85是潜在同类首个靶向ALPP/ALPPL2的新型抗体偶联药物（ADC），通过可被蛋白酶切割的连接子将专利喜树碱类载荷与高亲和力单克隆抗体偶联而成。临床前研究显示，HLX85在体外HEP2（ALPP/ALPPL2高表达）和NCI-H1651（ALPP/ALPPL2中表达）的细胞中表现出靶点介导的细胞毒性。其旁观者杀伤效应是deruxtecan类ADC的10倍以上。在体内，单次1 mg/kg剂量的HLX85即在Capan-1 CDX模型中诱导了显著的肿瘤消退；而在对含MMAE载荷的ADC耐药的胃腺癌PDX模型中，单次8 mg/kg剂量的HLX85实现了深度肿瘤缓解。在非人灵长类动物中，HLX85展现出线性药代动力学和优异的耐受性，最高非严重毒性剂量（HNSTD） ≥40 mg/kg。
摘要标题：潜在同类首个靶向ALPP/ALPPL2的喜树碱ADC展现强效抗肿瘤活性和卓越耐受性
Development of a first-in-class camptothecin-based antibody-drug conjugate targeting ALPP/ALPPL2 with potent antitumor activity and excellent tolerability
分会场：Antibody Technologies and Platforms 2
展示形式：壁报
摘要编号：4419
展示时间：美国当地时间4月21日 9:00 AM-12:00 PM
展示地点：第11区，展板#27
（三） 更多在研创新分子
HLX43（PD-L1 ADC）
在深耕前沿技术平台的同时，复宏汉霖亦在持续探索具备突破性作用机制的创新分子。HLX43是一款具有潜在同类最优（best-in-class）特征的广谱抗肿瘤PD-L1 ADC，兼具免疫检查点阻断与载荷介导细胞毒性的作用机制。该分子由经工程化改造的人源化抗PD-L1 IgG1抗体HLX20，通过蛋白酶可裂解的三肽连接子与高效喜树碱衍生型拓扑异构酶I抑制剂C24偶联而成，DAR约为8。
HLX43的作用机制整合了免疫检查点抑制、靶向细胞毒作用以及肿瘤微环境（tumor microenvironment, TME）调节等多重机制。作为抗PD-L1分子，HLX43能够有效阻断PD-1/PD-L1免疫检查点通路，从而恢复T细胞活性。在混合淋巴细胞反应（MLR）实验中，可观察到细胞因子IL-2和IFN-γ分泌水平显著增加。HLX43的直接细胞毒作用主要来源于其拓扑异构酶I抑制剂载荷诱导的DNA损伤，从而抑制DNA修复并诱导肿瘤细胞凋亡。此外，HLX43还能够诱导免疫原性细胞死亡（immunogenic cell death, ICD），进一步增强抗肿瘤免疫反应。在肿瘤微环境中，HLX43的连接子可被基质金属蛋白酶（matrix metalloproteinases, MMPs）及半胱氨酸蛋白酶等蛋白酶裂解，从而释放细胞毒载荷，该过程并不完全依赖于PD-L1靶点结合。在细胞外释放的载荷能够在肿瘤组织中扩散，通过“旁观者效应”（bystander effect）杀伤邻近的PD-L1阴性肿瘤细胞。因此，即使在PD-L1表达高度异质的患者来源异种移植（PDX）模型中，HLX43仍能展现出良好的抗肿瘤疗效。除直接杀伤肿瘤细胞外，HLX43还可重塑肿瘤微环境。动物模型体内研究显示，该药物能够显著增加CD8⁺细胞毒性T细胞在肿瘤组织中的浸润，降低调节性T细胞（Tregs）的比例，并增强CD8⁺T细胞的效应功能，从而进一步强化抗肿瘤免疫反应。
摘要标题：临床前研究揭示蛋白酶介导的载荷释放及肿瘤免疫/免疫调节效应在HLX43的抗肿瘤活性中发挥重要作用
Preclinical studies reveal that protease-mediated payload release and immuno-oncology/immunomodulatory effects contribute to the antitumor activity of HLX43
分会场：Mechanisms of Anticancer Drug Action
展示形式：壁报
摘要编号：5704
展示时间：美国当地时间4月21日 2:00 PM-5:00 PM
展示地点：第12区，展板#20
HLX316（B7-H3×唾液酸酶融合蛋白）
HLX316是一款潜在同类首创（first-in-class）的B7-H3靶向人源唾液酸酶融合蛋白，由复宏汉霖与Palleon Pharmaceuticals合作开发。HLX316针对癌症中的一个关键免疫逃逸机制，即肿瘤细胞表面异常升高的唾液酸化修饰可与免疫细胞上的Siglec受体结合，从而抑制先天性和适应性免疫反应。HLX316通过B7-H3靶点介导在肿瘤组织中富集，发挥强效去唾液酸化作用，从而解除由唾液酸-Siglec轴介导的糖免疫检查点抑制，恢复肿瘤微环境中的免疫细胞功能，增强先天性和适应性免疫介导的抗肿瘤反应。
临床前研究显示，在B7-H3阳性且高度唾液酸化的肿瘤细胞系中，HLX316的去唾液酸化活性较非靶向唾液酸酶提高超过1,000倍。体内研究进一步表明，HLX316在肿瘤组织中的去唾液酸化作用更加持久，并在疾病模型中显著延长药效持续时间。同时，HLX316还能够增强抗体依赖的细胞介导细胞毒作用（ADCC）和抗体依赖的细胞吞噬作用（ADCP），从而强化抗体介导的免疫效应对肿瘤细胞的清除。在多个小鼠肿瘤模型中，HLX316均表现出显著的单药抗肿瘤活性；在A375人源化小鼠模型中，其疗效优于B7-H3抗体、非靶向唾液酸酶以及抗PD-1抗体。非人灵长类动物GLP一个月重复给药毒性研究结果显示，HLX316耐受性良好，未观察到明显毒性反应，其NOAEL（未观察到有害作用水平）为150 mg/kg。
摘要标题：E-688/HLX316：一款潜在“同类首创”的、靶向B7-H3的唾液酸酶，用于增强先天性和适应性抗肿瘤免疫/一款靶向B7-H3的人唾液酸酶融合蛋白，可协同增强先天及适应性抗肿瘤免疫反应
E-688/HLX316: A first-in-class B7-H3 targeted sialidase for boosting innate and adaptive anti-tumor immunity/Human sialidase-armed anti-B7-H3 antibody that enhances innate and adaptive antitumor immune responses
分会场1：New Drugs on the Horizon: Part 2
展示形式1：口头报告
摘要编号：ND05
展示时间：美国当地时间4月19日 3:05 PM - 3:20 PM
展示地点：Ballroom 20 CD - Upper Level - Convention Center
分会场2：Overcoming Microenvironmental and Delivery Barriers in Cancer Therapy
展示形式2：壁报
摘要编号：7158
展示时间：美国当地时间4月22日 9:00 AM-12:00 PM
展示地点：第15区，展板#15
关于复宏汉霖
复宏汉霖（2696.HK）是一家国际化创新生物制药企业，致力于为全球患者提供高品质、可负担的生物药，产品覆盖肿瘤、自身免疫疾病、眼科疾病等领域。自2010年成立以来，公司已构建涵盖全球研发、临床、注册、生产及商业化的全产业链平台，拥有全球员工近4,000人，并在中国、美国和日本等多地设有运营及分支机构。依托生物类似药形成的稳健现金流反哺创新研发，复宏汉霖正稳步迈入“全球化2.0”阶段，持续打造可复制、可持续的全球增长模式。截至2026年初，公司共有10款产品在全球60多个国家和地区获批上市，其中7款已在中国获批。在欧美主流生物药市场，复宏汉霖亦取得多项里程碑式突破，已有4款产品获得美国FDA批准、4款产品获得欧盟EC批准，充分体现了公司在研发体系、质量管理及生产能力方面已全面对标国际最高标准。
在创新驱动方面，复宏汉霖依托上海、美国等多地协同布局的研发体系，构建了多元化、平台化的创新技术矩阵，覆盖免疫检查点抑制剂、免疫细胞衔接器（包括多特异性TCE）、抗体偶联药物（ADC）以及AI驱动的早期研发平台等前沿方向。目前，公司拥有50余项处于早期阶段的创新资产，其中约70%具备同类最佳（Best-in-Class）潜力，并在全球同步推进30余项临床研究。核心产品H药 汉斯状®（斯鲁利单抗，欧洲商品名：Hetronifly®）作为全球首个获批一线治疗小细胞肺癌的抗PD-1单抗，正加速全球布局，已在全球40余个市场获批上市；同时，多款潜力创新资产，包括PD-L1 ADC HLX43及新表位HER2单抗HLX22正全面推进全球关键性临床研究。依托通过中、欧、美三地GMP认证的生产体系，复宏汉霖已建成总产能达84,000升的生物药生产平台，形成覆盖全球六大洲的稳定供应网络。未来，复宏汉霖将始终坚持以患者为中心，聚焦未满足的临床需求，持续推动创新成果向临床价值与患者可及转化，在全球生物医药创新生态中创造长期而稳健的价值。
AACR 2026 Preview: Henlius to Present Seven Innovative Programs, Hanjugator™ ADC and TCE Platforms Advance Multiple FIC/BIC Candidates
On April 17, 2026, Shanghai Henlius Biotech, Inc. (2696.HK) announced that it will present the latest prelinical data from seven innovative pipeline programs at the American Association for Cancer Research (AACR) Annual Meeting 2026, to be held from April 17 to 22 in San Diego, USA.
The innovations to be presented are enabled by the company’s advanced proprietary technology platforms, including the Hanjugator™ antibody–drug conjugate (ADC) platform and the multispecific T-cell engager (TCE) platform, covering a broad range of high-potential cutting-edge targets with strong development potential, including PD-L1, B7-H3, STEAP1, EGFR, c-MET, HER2, ADAM9, ALPP, and ALPPL2. Preclinical data indicate that several of these molecules have demonstrated first-in-class or best-in-class potential in head-to-head comparisons.
(I) TCE Platform: Incorporation of CD28 Co-stimulation to Remodel Immunologically “Cold” Solid Tumors
In the treatment of solid tumors, insufficient T-cell infiltration and an immunosuppressive tumor microenvironment (TME) represent key bottlenecks limiting the efficacy of TCE therapies. To address this challenge and optimize the therapeutic window of TCEs in solid tumors, Henlius has developed a multispecific TCE platform incorporating CD28 co-stimulatory signaling. By simultaneously delivering CD3 activation (signal 1) and CD28 co-stimulation (signal 2), the platform significantly enhances sustained T-cell–mediated cytotoxic activity. In addition, through multiple synergistic mechanisms—including target-dependent activation, affinity tuning, and cis-binding of CD3/CD28—the platform improves antitumor efficacy while effectively controlling systemic toxicity risk. More than five early-stage innovative molecules have been generated from this platform. Among them, HLX3901 (DLL3×DLL3×CD3×CD28 tetraspecific antibody) and HLX3902 (STEAP1×CD3×CD28 trispecific antibody) represent key assets in this field, focusing on the treatment of solid tumors such as small cell lung cancer and prostate cancer, and have been advanced to the IND or IND-accepted stage.
HLX3902 (STEAP1×CD3×CD28 trispecific TCE)
HLX3902 is a trispecific antibody that precisely targets STEAP1, which is highly expressed in prostate cancer, as well as CD3 and CD28, and represents one of the company’s core assets in this field. Preclinical studies show that HLX3902 induces target-dependent T-cell activation and cytotoxicity, with particularly pronounced activity under low effector-to-target (E:T) ratios (1:5–1:10). Compared with bispecific TCEs and their combination approaches, this molecule significantly enhances T-cell function, proliferation, and memory T-cell expansion, and demonstrates more durable in vitro cytotoxicity. In addition, in in vivo models, HLX3902 demonstrated superior and more durable antitumor activity compared with Amgen’s AMG509(STEAP1×CD3 bispecific TCE) at a single dose of 0.01 mg/kg. This activity is accompanied by increased T-cell infiltration and activation, as well as sustained intratumoral CD8⁺ T-cell effector function mediated by CD28 co-stimulation. In cynomolgus monkeys, HLX3902 showed good tolerability at weekly intravenous dosing of 45 μg/kg. The IND application for this molecule has been accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China
·Title: A novel anti-CD3×CD28×STEAP1 tri-specific T-cell engager with enhanced and durable antitumor responses in prostate cancer
·Session Title: Redefining Targeted Therapy: Bispecific T-Cell Engagers and Antibody-Drug Conjugates 2
·Format: Poster Session
·Abstract Number: 5397
·Date and Time: April 21, 2026, 9:00 AM-12:00 PM
·Location: Poster Section 48, Board #10
In addition, HLX3901, another promising TCE molecule derived from this platform, is a tetraspecific antibody targeting DLL3 dual epitopes, CD3, and CD28, and its IND application was approved by the National Medical Products Administration (NMPA) in March 2026. HLX3901 integrates AI-driven drug design with the TCE platform. Through its optimized molecular design, the molecule enables sustained and specific T-cell activation, enables activity in tumors with low T-cell infiltration, and significantly reduces the risk of cytokine release syndrome (CRS), aiming to address key limitations of first-generation TCEs in solid tumors. Preclinical studies show that HLX3901 demonstrates superior cytotoxicity under low E:T ratio conditions. In human pan-T cell reconstitution models, HLX3901 exhibits stronger and more durable antitumor activity compared with benchmark molecules such as tarlatamab. In addition, preliminary toxicology studies in cynomolgus monkeys indicate that HLX3901 is well tolerated and shows a wider therapeutic window. Preclinical data for this molecule were first presented at the 2025 Antibody Engineering & Therapeutics conference.
(II) Hanjugator™ ADC Platform: Tunable Payload Design to Expand the Therapeutic Window
In the design of antibody–drug conjugates (ADCs), highly potent payloads can effectively eliminate tumor cells but may also significantly limit clinically achievable dosing, making it difficult to reach optimal antibody exposure and resulting in a narrow therapeutic window. To address this challenge, Henlius has developed a next-generation ADC technology platform, Hanjugator™, a customizable and modular camptothecin-based linker–payload platform. A key advantage of this platform lies in its highly hydrophilic camptothecin linker–payload design, which enables selection of optimal payload potency based on target characteristics, with cytotoxic activity ranging from approximately one-third that of DXd to levels comparable to exatecan. This approach broadens the therapeutic window while preserving antibody functionality, achieving an optimal balance between antibody-mediated signaling blockade/internalization and potent small-molecule cytotoxicity, thereby delivering synergistic therapeutic effects.
In addition, ADCs generated from this platform exhibit a bystander killing effect more than ten-fold greater than that of deruxtecan-based ADCs, which may help overcome tumor heterogeneity. The differentiated payload design may also help circumvent common resistance mechanisms associated with conventional toxins, providing a differentiated approach for next-generation ADC development. To date, the Hanjugator™ platform has generated more than 12 early-stage innovative assets, including HLX48 (EGFR/c-MET bispecific ADC), HLX49 (HER2 biparatopic ADC), HLX403 (CDH17 ADC), HLX402 (ADAM9 ADC), HLX85 (ALPP/ALPPL2 ADC), and HLX41 (LIV-1 ADC).
HLX48 (EGFR/c-MET bispecific ADC)
HLX48 is a novel ADC candidate independently developed by Henlius based on the Hanjugator™ platform, comprising an EGFR/c-MET bispecific antibody conjugated to a camptothecin-derived topoisomerase I inhibitor payload. Given that dual-targeting EGFR/c-MET ADCs often require relatively high clinical doses to achieve optimal receptor occupancy, HLX48 adopts a highly hydrophilic linker strategy combined with a moderate-potency payload design, with a drug-to-antibody ratio (DAR) of approximately 4, aiming to achieve an optimal balance between potent antitumor activity and manageable toxicity. Preclinical pharmacology studies demonstrate that HLX48 exhibits significant antitumor activity across multiple tumor models, with a single dose of 3 mg/kg inducing marked tumor regression. In the HT29 colorectal cancer model, its efficacy surpassed that of AstraZeneca’s AZD9592. In addition, HLX48 showed good tolerability in cynomolgus monkeys at 60 mg/kg (every three weeks), supporting the feasibility of its moderate-potency payload design.
·Title: Hanjugator camptothecin platform: effective, low-toxicity design maximizing antibody functionality and enabling a potential best-in-class EGFR/cMet bispecific ADC
·Session Title: Tumor Microenvironment, Multispecifics, and Immunomodulation
·Format: Poster Session
·Abstract Number: 5856
·Date and Time: April 21, 2026, 2:00 PM-5:00 PM
·Location: Poster Section 17, Board #25
HLX49 (HER2 biparatopic ADC)
HLX49 is a HER2 biparatopic ADC candidate engineered to target two distinct epitopes within domain IV, derived from Henlius’s proprietary rastuzumab (Hanquyou®) and dulpatatug*(a novel anti-HER2 antibody), thereby enabling biparatopic engagement. This molecule adopts an efficient, low-toxicity payload design, enabling higher dosing and improved receptor coverage, thereby enhancing tumor cell killing. In BT-474 and NCI-N87 cell lines, HLX49 demonstrated superior internalization efficiency compared with KN026 (a HER2-targeting bispecific antibody from Alphamab Oncology) and trastuzumab deruxtecan (a HER2 ADC). Across multiple cell lines, this biparatopic ADC showed improved antitumor activity relative to trastuzumab deruxtecan. In various xenograft models, a single dose of 6 mg/kg induced significant tumor regression. In head-to-head comparisons with trastuzumab deruxtecan, HLX49 demonstrated superior efficacy across a range of models, including HER2-positive (IHC 3+, IHC 2+/FISH+), HER2-low (IHC 2+/FISH− or IHC 1+), and HER2 ultra-low (IHC <1+) tumors. Preliminary toxicology studies showed that HLX49 was well tolerated in cynomolgus monkeys following three doses at 60 mg/kg.
·Title: A best-in-class HER2xHER2 biparatopic antibody-drug conjugate with an efficacious, low-toxicity design that maximizes antibody functionality
·Session Title: Antibody Technologies and Platforms 2
·Format: Poster Session
·Abstract Number: 4395
·Date and Time: April 21, 2026, 9:00 AM-12:00 PM
·Location: Poster Section 11, Board #3
HLX402 (ADAM9 ADC)
ADAM9 (a disintegrin and metalloproteinase domain-containing protein 9) is overexpressed in multiple solid tumors, including pancreatic, lung, and gastric cancers; however, prior clinical development efforts on the target have been discontinued due to drug-related ocular toxicity. HLX402 incorporates a novel camptothecin-based linker–payload design, aiming to mitigate such ocular toxicity while providing a wider therapeutic window. Preclinical studies demonstrate that the antibody component of HLX402 exhibits nanomolar affinity to ADAM9 in both humans and cynomolgus monkeys. The antibody shows efficient, time-dependent internalization (>50% at 4 hours) across multiple tumor cell lines (MKN-45, MiaPaCa-2, and Calu-3), along with potent cytotoxicity and a strong bystander killing effect. In the Calu-3 (non-squamous NSCLC) CDX model, a single dose of 3 mg/kg achieved a tumor growth inhibition (TGI) of 109.3%, significantly outperforming a benchmark ADC (91.1%). In the DLD-1 (colorectal cancer) CDX model, HLX402 achieved a TGI of 90.2% at the same dose, compared with 39.2% for the benchmark ADC. In rats, HLX402 demonstrated excellent plasma stability and favorable pharmacokinetics, with minimal release of free payload and an antibody-like half-life.
•Title: Preclinical characterization of a potential best-in-class camptothecin-based antibody-drug conjugate targeting ADAM metallopeptidase domain 9
•Session Title: Antibody Technologies and Platforms 2
•Format: Poster Session
•Abstract Number: 4418
•Date and Time: April 21, 2026, 9:00 AM-12:00 PM ET
•Location: Poster Section 11, Board#26
HLX85 (ALPP/ALPPL2 ADC)
ALPP (placental alkaline phosphatase) and ALPPL2 (placental-like alkaline phosphatase 2) are promising targets due to their expression in multiple solid tumors and minimal expression in normal tissues, including ovarian cancer (60%), endometrial cancer (50%), pancreatic cancer (30%), and gastric cancer (15%). HLX85 is a potential first-in-class ADC targeting ALPP/ALPPL2, consisting of a high-affinity monoclonal antibody conjugated via a protease-cleavable linker to a proprietary camptothecin-based payload. Preclinical studies demonstrate that HLX85 exhibits target-mediated cytotoxicity in vitro in HEP2 (high ALPP/ALPPL2 expression) and NCI-H1651 (moderate expression) cell lines. Its bystander killing effect is more than ten-fold greater than that of deruxtecan-based ADCs. In vivo, a single dose of 1 mg/kg induced significant tumor regression in the Capan-1 CDX model. In a gastric adenocarcinoma PDX model resistant to MMAE-based ADCs, a single dose of 8 mg/kg achieved deep tumor remission. In non-human primates, HLX85 demonstrated linear pharmacokinetics and excellent tolerability, with a highest non-severely toxic dose (HNSTD) ≥40 mg/kg.
•Title: Development of a first-in-class camptothecin-based antibody-drug conjugate targeting ALPP/ALPPL2 with potent antitumor activity and excellent tolerability
•Session Title: Antibody Technologies and Platforms 2
•Format: Poster Session
•Abstract Number: 4419
•Date and Time: April 21, 2026, 9:00 AM-12:00 PM
•Location: Poster Section 11, Board#27
(III) Additional Innovative Pipeline Candidates
HLX43 (PD-L1 ADC)
In parallel with advancing its technology platforms, Henlius continues to discover innovative molecules featuring breakthrough mechanisms of action. HLX43 is a potential best-in-class pan-tumor PD-L1–targeted antibody-drug conjugate (ADC), combining immune checkpoint blockade with payload-mediated cytotoxicity. The molecule comprises an engineered humanized anti-PD-L1 IgG1 antibody (HLX20) conjugated via a protease-cleavable tripeptide linker to a potent camptothecin-derived topoisomerase I inhibitor (C24), with a drug-to-antibody ratio (DAR) of approximately 8. Preclinical studies show that HLX43 retains the binding affinity and internalization properties of HLX20, while demonstrating favorable stability and potent antitumor activity.
Its mechanism of action integrates immune checkpoint inhibition, targeted cytotoxicity, and tumor microenvironment (TME) modulation. As an anti-PD-L1 agent, HLX43 effectively blocks the PD-1/PD-L1 axis, restoring T-cell activity, as evidenced by increased IL-2 and IFN-γ secretion in mixed lymphocyte reaction (MLR) assays. Its direct cytotoxicity is driven by DNA damage induced by the topoisomerase I inhibitor payload, leading to inhibition of DNA repair and induction of tumor cell apoptosis. In addition, HLX43 induces immunogenic cell death (ICD), further enhancing antitumor immune responses. Within the TME, the linker can be cleaved by proteases such as matrix metalloproteinases (MMPs) and cysteine proteases, enabling payload release that is not strictly dependent on PD-L1 binding. The released payload diffuses within tumor tissue and exerts a bystander effect, killing adjacent PD-L1-negative tumor cells. Therefore, HLX43 demonstrates robust antitumor activity even in PDX models with highly heterogeneous PD-L1 expression. Beyond direct tumor cell killing, HLX43 also remodels the TME, significantly increasing infiltration of cytotoxic CD8⁺ T cells, reducing regulatory T cells (Tregs), and enhancing CD8⁺ T-cell effector function.
•Title: Preclinical studies reveal that protease-mediated payload release and immuno-oncology/immunomodulatory effects contribute to the antitumor activity of HLX43
•Session Title: Mechanisms of Anticancer Drug Action
•Format: Poster Session
•Abstract Number: 5704
•Date and Time: April 21, 2026, 2:00 PM-5:00 PM
•Location: Poster Section 12, Board #20
HLX316 (B7-H3 × Sialidase Fusion Protein)
B7-H3 is an immune checkpoint-related protein highly expressed across multiple solid tumors—including lung, breast, colorectal, pancreatic, prostate, and ovarian cancers—and is associated with tumor progression and poor prognosis, while exhibiting low expression in normal tissues. HLX316 is a potential first-in-class B7-H3-targeted human sialidase fusion protein, co-developed by Henlius and Palleon Pharmaceuticals. It addresses a key immune evasion mechanism in cancer, whereby hypersialylation on tumor cell surfaces engages Siglec receptors on immune cells, suppressing both innate and adaptive immune responses.
HLX316 selectively accumulates in tumor tissue via B7-H3 targeting and exerts potent desialylation activity, thereby reversing glyco-immune checkpoint suppression mediated by the sialic acid–Siglec axis, restoring immune cell function in the TME, and enhancing both innate and adaptive antitumor immunity.
Preclinical studies show that in B7-H3-positive, highly sialylated tumor cell lines, HLX316 demonstrates over 1,000-fold higher desialylation activity compared with non-targeted sialidases. In vivo, HLX316 exhibits more durable desialylation activity in tumors and significantly prolongs pharmacodynamic effects. Additionally, HLX316 enhances antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), thereby strengthening antibody-mediated immune clearance of tumor cells. Across multiple mouse tumor models, HLX316 demonstrated significant monotherapy antitumor activity. In the A375 humanized mouse model, its efficacy exceeded that of B7-H3 antibodies, non-targeted sialidase, and anti-PD-1 antibodies. GLP repeat-dose toxicology studies in non-human primates showed that HLX316 was well tolerated, with no significant toxicity observed, and a no observed adverse effect level (NOAEL) of 150 mg/kg.
·Title: E-688/HLX316: A first-in-class B7-H3 targeted sialidase for boosting innate and adaptive anti-tumor immunity / Human sialidase-armed anti-B7-H3 antibody that enhances innate and adaptive antitumor immune responses
·Session 1: New Drugs on the Horizon: Part 2
·Format: Oral Session
·Abstract Number: ND05
·Date and Time: April 19, 3:05 PM–3:20 PM
·Location: Ballroom 20 CD - Upper Level - Convention Center
·Session 2: Overcoming Microenvironmental and Delivery Barriers in Cancer Therapy
·Format: Poster Session
·Abstract Number: 7158
·Date and Time: April 22, 9:00 AM–12:00 PM
·Location: Section 15, Poster #15
About Henlius
Shanghai Henlius Biotech, Inc. (2696.HK) is a global, innovation-driven biopharmaceutical company committed to delivering high-quality, affordable biologic therapies to patients worldwide. The Company focuses on major disease areas including oncology, autoimmune diseases, and ophthalmic diseases. Founded in 2010, Henlius has established an integrated, end-to-end biopharmaceutical platform encompassing global R&D, clinical operations, regulatory affairs, manufacturing, and commercialisation. The Company employs nearly 4,000 people globally and operates across multiple regions, including China, the United States, and Japan. Leveraging the stable cash flow generated from its biosimilar portfolio to support innovation, Henlius is steadily advancing into its “Globalisation 2.0” phase, building a scalable and sustainable global growth model. As of early 2026, Henlius has achieved regulatory approvals for 10 products across over 60 countries and regions worldwide, including seven approvals in China. The Company has also reached multiple milestones in major biopharmaceutical markets, with four products approved by the U.S. Food and Drug Administration (FDA) and four products approved by the European Commission (EC), reflecting its globally aligned R&D capabilities, quality systems, and manufacturing standards.
Driven by innovation, Henlius has built a diversified, platform-based technology ecosystem through coordinated R&D efforts across Shanghai, the United States, and other regions. Its innovation platforms span immune checkpoint inhibitors, immune cell engager technologies (including multispecific T cell engagers), antibody-drug conjugates (ADCs), and AI-enabled early discovery platforms. The Company currently has more than 50 early-stage innovative assets, approximately 70% of which are expected to be best-in-class, with over 30 clinical trials ongoing globally. Henlius’ core product, serplulimab (trade name: Hetronifly® in Europe), is the world’s first anti–PD-1 mAb approved for first-line treatment of small cell lung cancer and has been approved in more than 40 markets worldwide with an accelerated globalisation process. In parallel, multiple high-potential innovative assets—including the PD-L1 ADC HLX43 and the novel epitope anti-HER2 mAb HLX22—are advancing through global pivotal clinical development. Supported by a biologics manufacturing network with a total capacity of 84,000L and GMP certifications from regulatory authorities in China, Europe, and the United States, Henlius has established a stable global supply system serving six continents. Guided by a patient-centred mission, Henlius remains focused on addressing unmet medical needs and translating scientific innovation into meaningful clinical value and patient access, contributing sustainably to the global biopharmaceutical ecosystem.
To learn more about Henlius, visit https://www.henlius.com/en/ and connect with us on LinkedIn at https://www.linkedin.com/company/henlius/.
*注：药品通用名处于pINN状态
*Note: This INN is currently under review (pINN status)
