复星医药子公司复宏汉霖TCE平台数据首秀2026 AACR，潜在同类最优分子产出能力持续获验证
上海，2026年4月22日 —— 复星医药子公司复宏汉霖（2696.HK）今日宣布，公司在2026年美国癌症研究协会（AACR）年会上以壁报形式首次公布了其在研新型CD3×CD28×STEAP1靶向三特异性T细胞衔接器（T Cell Engager, TCE）HLX3902的临床前研究数据。公司正持续推进该平台在更多“免疫荒漠”型实体瘤中的拓展应用，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）作为该领域的代表性资产，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批准/受理阶段。值得一提的是，基于该平台开发的另一款分子HLX3901（DLL3xDLL3xCD3xCD28四特异性TCE）亦在临床前研究中展现出同类最优的治疗潜力，印证了该平台在实体瘤治疗领域的高效产出和可拓展性。
自建多特异性TCE平台：引入CD28共刺激信号，重塑实体瘤“免疫沙漠”
——优效，更宽的治疗窗口
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。为突破这一挑战并优化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），从而实现T细胞的定向募集与有效激活，并增强其活化、增殖水平，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。
复宏汉霖对该TCE平台的机制设计进行了系统性优化：CD3激活采用靶点依赖性机制，在无肿瘤靶抗原存在时，不触发CD3激活信号，从而降低脱靶激活风险；CD28共刺激信号采用条件性激活设计，仅在CD3信号被触发后发生，并与CD3协同激活调控T细胞。此外，通过将CD3和CD28的结合区域置于TCE分子的同侧，促进其与同一T细胞上的CD3和CD28进行顺式结合（cis-结合），以减少非特意性的T细胞激活和互相攻击，进而有效控制了系统性毒性风险，实现了更宽的治疗窗口。
AACR展示：HLX3902（CD3×CD28×STEAP1 三抗TCE）在前列腺癌中实现强效持久抗肿瘤应答
STEAP1在前列腺癌中呈高表达，是理想的肿瘤特异性靶点。HLX3902是一款靶向STEAP1、CD3和CD28的三特异性TCE，在精准靶向前列腺癌中高表达STEAP1的同时，实现T细胞CD3与CD28的共激活，具备同类最优的治疗潜力，目前其IND申请已获中国国家药品监督管理局药品审评中心（CDE）受理。
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体外研究表明，HLX3902可诱导靶点依赖性的T细胞活化及细胞毒性
图1：HLX3902的靶点依赖性T细胞活化和细胞毒性数据
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与仅靶向CD3的双特异性T细胞衔接器相比，HLX3902在低效应细胞/靶细胞比（E/T ratio）条件下（1:5-1:10）显示出更强的细胞毒活性。
图2：HLX3902与双特异性TCE在低效靶比下的细胞毒性对比
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在重复抗原刺激模型中，含有CD28共刺激信号的三特异性抗体HLX3902较CD3双特异性抗体表现出更持久的细胞毒性。该效应伴随更持续的T细胞活化、增殖，以及记忆T细胞扩增效应【包括中央记忆性T细胞（TCM）和效应记忆性T细胞（TEM）】。
图3：与双特异性T细胞衔接器相比，HLX3902增强的T细胞功能及持久的体外细胞毒作用
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体内抗肿瘤活性：在C4-2/hPBMX异种移植模型中，HLX3902表现出较双特异性TCE更强的抗肿瘤活性。组织学分析提示，增强的疗效与肿瘤微环境中T细胞浸润增加、T细胞活化增强及T细胞持久性提高相关。
图4：HLX3902在C4-2/hPBMX异种移植模型中的抗肿瘤活性
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体内抗肿瘤活性：在阿比特龙耐药的患者来源异种移植（PDX）/hPBMX模型中，HLX3902在0.05 nmol/kg（0.01 mg/kg）剂量下表现出显著优于AMG509的抗肿瘤疗效，该剂量为AMG509目标临床剂量范围内。
图5：HLX3902在阿比特龙耐药PDX/hPBMX模型中的疗效
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安全性结果：在食蟹猴中开展的一项初步药代动力学及毒性研究中，HLX3902耐受性良好，安全性可控，支持其进一步临床开发。
AET 2025首次发布： AI驱动设计的新一代实体瘤TCE HLX3901（DLL3xDLL3xCD3xCD28四抗TCE）
HLX3901是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。
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HLX3901采用DLL3双表位设计，可同时结合DLL3两个不同表位以增强结合能力，增强靶向药效。
图1： HLX3901分子设计与人工智能驱动的表位优化
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在表位发现阶段，复宏汉霖基于AI预测分析筛选DLL3潜在抗体结合区域，确定Repeat 3及Repeat 4为主要表位区域，并据此设计靶向EGF-like 3及EGF-like 4的双表位抗体。体外实验结果显示，该双表位设计在不同效靶比条件下均表现出更优的细胞毒活性。
图2：双表位设计（EGF-like 3/EGF-like 4）增强DLL3表达肿瘤细胞靶向性
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此外，HLX3901采用了Fc段沉默设计，在延长体内半衰期的同时，降低Fc介导的非特异性免疫效应，有助于提升安全性特征。
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体外研究中：HLX3901在低/靶比条件下表现出优于对照分子（Tarlatamab）的细胞毒性效应。同时，HLX3901能够上调抗凋亡标志物Bcl-xL，并扩增记忆性CD8⁺ T细胞亚群，提示其具有促进T细胞存活及记忆形成的潜力。
图3：HLX3901与Tarlatamab在低效靶比下的细胞毒性对比数据
图4：HLX3901诱导Bcl-xL上调及记忆CD8⁺ T细胞扩增
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体内抗肿瘤活性：在人类泛T细胞重构的SHP77细胞系来源异种移植（CDX）模型中，HLX3901在剂量依赖性条件下表现出显著的肿瘤抑制作用。与已上市的DLL3×CD3双特异性TCE Tarlatamab相比，HLX3901表现出更强且更持久的抗肿瘤活性。
图5：HLX3901可增强T细胞在肿瘤微环境（TME）中的浸润，并展现出较Tarlatamab更强的抗肿瘤活性
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安全性结果：与Tarlatamab相比，HLX3901在人类外周血单个核细胞（hPBMC）中诱导的非特异性CD4⁺及CD8⁺ T细胞活化显著减弱。在肿瘤细胞（SHP77）与hPBMC共培养条件下，HLX3901组的IL-2、IFN-γ、TNF-α及IL-6释放水平均低于Tarlatamab组，提示其具有更低的CRS风险。在食蟹猴的初步毒性研究中，HLX3901耐受性良好，未观察到不良反应剂量（NOAEL）为10 mg/kg，显示出较宽的治疗窗口。
图6：HLX3901未观察到非特异性T细胞激活，且较Tarlatamab细胞因子释放水平更低
基于HLX3901的作用机制，其具备与复宏汉霖自研免疫肿瘤管线联合应用的战略潜力。例如，与抗PD-1单抗斯鲁利单抗（H药汉斯状®）联用，一方面可连接T细胞并诱导其产生针对小细胞肺癌的靶向杀伤，另一方面可解除由PD-L1/PD-1抑制信号通路介导的T细胞耗竭，从而实现协同增效的抗肿瘤疗效。
目前，复宏汉霖已全面建立起涵盖多特异性TCE、抗体偶联药物（ADC）及人工智能驱动早期研发平台等多元创新技术平台。未来，复宏汉霖将继续聚焦未满足的临床需求，依托平台化研发能力，加速创新成果向临床价值的转化，为全球患者提供更多高质量、可负担的治疗选择。
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。
Henlius Showcases HLX3902 Preclinical Data at AACR 2026, Highlighting Its CD28-Enabled Multispecific TCE Platform
Shanghai, China, April 22, 2026 — Shanghai Henlius Biotech, Inc. (2696.HK) today announced the first presentation of preclinical data for its novel CD3×CD28×STEAP1 trispecific T cell engager (TCE), HLX3902, at the 2026 Annual Meeting of the American Association for Cancer Research (AACR) in a poster session. Henlius continues to expand its proprietary TCE platform into multiple “immune desert” solid tumors. To date, the platform has generated more than five early-stage innovative assets.
Among them, HLX3901 (DLL3×DLL3×CD3×CD28 tetraspecific antibody) and HLX3902 (STEAP1×CD3×CD28 trispecific antibody) represent key pipeline candidates targeting solid tumors including small cell lung cancer (SCLC) and prostate cancer, respectively, and have advanced to the IND approval/acceptance stage. Notably, HLX3901 has demonstrated potential best-in-class therapeutic profile in preclinical studies, further validating the platform’s productivity and scalability in solid tumor drug discovery.
Proprietary Multispecific TCE Platform Incorporating CD28 Co-stimulation to Remodel “Immune Desert” Solid Tumors— Enhanced efficacy with an expanded therapeutic window
Limited T cell infiltration and an immunosuppressive tumor microenvironment (TME) remain major barriers to the efficacy of TCE therapies in solid tumors. To address these challenges, Henlius has developed a multispecific TCE platform incorporating CD28 co-stimulatory signaling. By delivering both signal 1 (CD3-mediated activation) and signal 2 (CD28 co-stimulation), the platform enables targeted T cell recruitment and robust activation, enhancing T cell proliferation, persistence, and cytotoxic activity within suppressive TMEs.
The platform incorporates multiple engineering strategies to optimize safety and efficacy, including target-dependent CD3 activation to minimize off-target T cell activation, conditional CD28 co-stimulation that is triggered only upon CD3 engagement, and a cis-binding design of the CD3 and CD28 domains to reduce nonspecific T cell activation and fratricide. Together, these features contribute to an expanded therapeutic window and an improved safety profile.
AACR 2026: HLX3902 Demonstrates Potent and Durable Antitumor Responses in Prostate Cancer
STEAP1 is highly expressed in prostate cancer and represents an attractive tumor-specific target. HLX3902, a CD3×CD28×STEAP1 trispecific TCE, enables dual T cell activation while selectively targeting STEAP1-expressing tumor cells. Its IND application has been accepted by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA).
Key preclinical findings:
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In vitro, HLX3902 induced target-dependent T cell activation and cytotoxicity
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Compared with CD3-only bispecific TCEs, HLX3902 demonstrated enhanced cytotoxicity at low E:T ratios (1:5–1:10)
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In repeated antigen stimulation models, HLX3902 demonstrated more sustained cytotoxic activity, along with enhanced T cell activation, proliferation, and expansion, and an increased proportion of memory T cell populations, including both central memory (TCM) and effector memory (TEM) T cells.
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In vivo, HLX3902 demonstrated superior antitumor activity compared with bispecific TCEs in C4-2/hPBMC xenograft models, with enhanced efficacy associated with increased T cell infiltration within the tumor microenvironment, as well as improved T cell activation and persistence.
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In abiraterone-resistant PDX/hPBMC models, HLX3902 also showed superior antitumor efficacy versus AMG509 at 0.05 nmol/kg (0.01 mg/kg), a dose within AMG509’s reported clinical target range.
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In a preliminary pharmacokinetic and toxicology study in cynomolgus monkeys, HLX3902 was well tolerated with a manageable safety profile, supporting its further clinical development.
AET 2025: HLX3901 – AI-Designed Next-Generation TCE for Solid Tumors
AET 2025 marked the first disclosure of HLX3901, a DLL3×DLL3×CD3×CD28 tetraspecific TCE and a key asset derived from Henlius’ proprietary platform. The IND application for HLX3901 was approved by the NMPA in March 2026. By integrating AI-driven epitope discovery with multispecific TCE engineering, HLX3901 is designed to achieve durable and highly specific T cell activation, overcome the challenge of low T cell infiltration in solid tumors, and reduce the risk of cytokine release syndrome (CRS).
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HLX3901 employs a dual-epitope targeting strategy against DLL3, enabling simultaneous binding to two distinct epitopes to enhance binding avidity and improve target engagement and pharmacological activity.
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During epitope discovery, Henlius used AI-based prediction to identify DLL3 antibody-binding regions, selecting Repeat 3 and Repeat 4 as the primary epitope sites. Based on this, a dual-epitope antibody targeting EGF-like 3 and EGF-like 4 was designed. In vitro studies showed that this design achieved improved cytotoxic activity across different effector-to-target ratios.
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HLX3901 incorporates an Fc-silenced design that extends systemic half-life while reducing Fc-mediated nonspecific immune activation.
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In preclinical studies, HLX3901 demonstrated superior cytotoxicity compared with Tarlatamab, particularly at low effector-to-target ratios, along with upregulation of Bcl-xL and expansion of memory CD8⁺ T cell populations in vitro.
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In vivo, it showed dose-dependent tumor growth inhibition in SHP77 CDX models, with stronger and more durable antitumor efficacy than Tarlatamab, accompanied by enhanced T cell infiltration within the tumor microenvironment.
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From a safety perspective, HLX3901 exhibited reduced non-specific CD4⁺ and CD8⁺ T cell activation and lower cytokine release (including IL-2, IFN-γ, TNF-α, and IL-6) compared with Tarlatamab. In cynomolgus monkeys, it was well tolerated with a no-observed-adverse-effect level (NOAEL) of 10 mg/kg, suggesting a wider therapeutic window.
Beyond monotherapy potential, HLX3901 also shows promise for combination strategies within Henlius’ immuno-oncology(IO) portfolio. In combination with the anti–PD-1 antibody serplulimab (trade name: Hetronifly® in Europe), it may enhance tumor-directed T cell killing while relieving PD-1/PD-L1-mediated T cell exhaustion, thereby potentially achieving synergistic antitumor activity.
Looking forward, Henlius has established a diversified innovation ecosystem spanning multispecific TCEs, antibody-drug conjugates (ADCs), and AI-enabled early discovery platforms. The company remains committed to addressing unmet clinical needs and accelerating the translation of innovative assets into clinical value, with the goal of delivering high-quality and accessible therapies to patients worldwide.
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 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/.
