创新加速度 | 下一代TCE破局难治实体瘤，复宏汉霖四抗HLX3901完成I期研究首例患者给药

• HLX3901完成临床首例受试者给药，标志公司自主多特异性TCE平台进入临床验证阶段

• DLL3×CD3×CD28多重机制协同激活T细胞，有望突破SCLC等难治实体瘤免疫治疗瓶颈

• 创新平台驱动管线加速推进，多款前沿资产持续迈入临床阶段

2026年4月30日，上海 —— 复宏汉霖（2696.HK）宣布，基于自主研发的创新型T细胞衔接器（T-cell engager, TCE）平台开发的首个创新分子HLX3901（DLL3×DLL3×CD3×CD28四特异性抗体）在晚期小细胞肺癌（SCLC）或神经内分泌癌患者中开展的I期临床研究（HLX3901-FIH101）已完成首例患者给药。这一进展标志着公司多特异性TCE平台成功实现从技术构建向临床验证的关键跨越。

Delta样配体3（Delta-like ligand 3）是一种抑制性Notch配体^1-2，在约80%的SCLC及多种神经内分泌肿瘤中高表达^3-5，而在正常组织中表达水平极低^6-7，使其成为当前SCLC治疗的理想靶点。目前，已有靶向DLL3及CD3的TCE双特异性抗体获批上市⁸，并展现出良好的治疗前景⁹。然而，肿瘤微环境（TME）中的T细胞浸润不足和免疫抑制状态仍然是限制TCE疗效的关键瓶颈^10-11。在缺乏共刺激信号（第二信号）的情况下，单纯的CD3激活信号（第一信号）极易导致T细胞失能¹²，难以实现持久且深入的抗肿瘤疗效。CD28是表达于T细胞表面的关键共刺激分子，其通过与抗原呈递细胞（APC）表面的配体CD80（B7-1）和CD86（B7-2）结合，能够提供T细胞活化的第二信号，对T细胞的完全活化极为关键^13-14。

针对上述挑战，复宏汉霖自研的新一代T细胞衔接器HLX3901通过四特异性分子设计，同时靶向DLL3双表位、CD3及CD28，从而构建“第一信号+共刺激信号”的协同激活机制，通过同步作用于T细胞表面的CD3与CD28，实现对T细胞的双重激活，从而增强T细胞对DLL3阳性肿瘤细胞的靶向杀伤能力，提升抗肿瘤疗效。另一方面，这种双信号协同机制极大地优化了治疗窗口，不仅能够促进T细胞活化、增殖及存活，还能延长抗肿瘤免疫应答的持续时间，使其在低T细胞浸润的环境中依然展现出优异的抗肿瘤活性。

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的抗肿瘤活性较同类分子（如塔拉妥单抗）更强且更持久。此外，在食蟹猴的初步毒性研究中，HLX3901表现出良好的耐受性，并显示出较宽的治疗窗口，为其临床开发提供了坚实的科学依据与数据支持。

作为复宏汉霖在免疫细胞衔接器领域的重要布局，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。该分子的快速推进，印证了复宏汉霖在多特异性抗体领域的系统性研发能力。依托上述技术积累，公司正持续探索下一代TCE在实体瘤中的应用潜力。目前，公司已搭建起包括PD(L)1为核心的免疫检查点抑制剂平台、免疫细胞衔接器平台（如多特异性TCE平台）、Hanjugator™ ADC以及AI驱动的一站式早期研发平台HAI Club在内的多维创新平台矩阵，为具备全球竞争力创新管线的持续产出与高质量推进提供支撑。

深耕未满足的临床需求，公司加速扩充由高潜力分子组成的早期管线储备，多款产品于近期取得里程碑进展，HLX701（新型SIRPα-Fc融合蛋白）凭借潜在更优的安全性，已启动在国内的II期临床研究；HLX37（创新抗PD-L1/VEGF双特异性抗体）针对晚期/转移性实体瘤的I期临床已完成首例患者给药；HLX97（新型KAT6A/B口服小分子抑制剂）获得中国临床试验许可；HLX3902（STEAP1xCD3xCD28三特异性TCE）、HLX49（HER2双表位ADC）、HLX48（EGFRxcMET双抗ADC）、HLX105（一款抗体融合蛋白）在内的多个前沿分子也将加速迈向临床，为公司创新管线不断注入新鲜血液。

未来，复宏汉霖将继续坚持“以患者为中心”的研发理念，依托平台化、系统化的创新体系，加速推进具有全球竞争力的差异化创新管线布局，为全球患者提供更可及、更有效的创新治疗选择。

关于HLX3901-FIH101

本研究是一项评估HLX3901在晚期小细胞肺癌或神经内分泌癌患者中的安全性、耐受性、药代动力学特征以及初步疗效的开放性、首次人体1期临床研究。研究分为两个阶段开展：1a期剂量递增及回填阶段以及1b期剂量扩展阶段。1a期共设置0.1mg至30mg的7个剂量水平，每4周为一个治疗周期，其中0.1mg剂量组采用加速滴定设计，其余6个剂量组采用“3+3”设计，剂量递增期间，在安全性得到验证后，部分剂量组允许受试者回填。1b期暂定10mg、20mg和30mg三个剂量组进行扩展研究，其给药策略与1a期对应剂量组相同。本研究的主要目的为评估HLX3901在晚期小细胞肺癌或神经内分泌癌患者中的安全性和耐受性，确定其最大耐受剂量（MTD）和2期推荐剂量（RP2D），并对其抗肿瘤疗效进行初步评价。主要终点为剂量限制性毒性（DLT）事件的发生率、HLX3901的MTD和RP2D，以及研究者评估的客观缓解率（ORR）。

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余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、5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’ Next-Generation Tetra-Specific TCE HLX3901 Doses First Patient in Phase 1 Study, Advancing Multi-Specific Platform into Clinical Validation

First patient dosed with HLX3901, marking clinical validation of Henlius’ proprietary multi-specific TCE platform
DLL3×CD3×CD28 synergistic mechanism designed to overcome immunotherapy resistance in hard-to-treat tumors such as SCLC
Innovation-driven pipelines continue to advance, with multiple next-generation assets entering clinical stages

Shanghai, China – April 30, 2026 – Shanghai Henlius Biotech, Inc. (2696.HK) today announced that the first patient has been dosed in a phase 1 clinical study (HLX3901-FIH101) of HLX3901, a next-generation tetra-specific antibody (DLL3×DLL3×CD3×CD28) developed based on the company’s proprietary T-cell engager (TCE) platform, in patients with advanced small cell lung cancer (SCLC) or neuroendocrine carcinoma. This milestone marks the initial clinical validation of Henlius’ multi-specific TCE platform.

Delta-like ligand 3 (DLL3) is an inhibitory Notch ligand^1-2 highly expressed in approximately 80% of SCLC and various neuroendocrine carcinomas,^3-5 while showing minimal expression in normal tissues,^6-7 making it an ideal therapeutic target. To date, bispecific TCEs targeting DLL3 and CD3 have been approved⁸ and demonstrated promising clinical activity.⁹ However, insufficient T-cell infiltration and the immunosuppressive state within the tumor microenvironment (TME) remain critical bottlenecks limiting the efficacy of TCEs.^10-11

Importantly, in the absence of co-stimulatory signaling (signal 2), CD3-mediated activation alone (signal 1) may lead to T-cell anergy,¹² thereby restricting the durability of anti-tumor responses. CD28, a critical co-stimulatory receptor expressed on T cells, provides the essential second signal for full T-cell activation through interaction with its ligands CD80 (B7-1) and CD86 (B7-2) on antigen-presenting cells (APCs) .^13-14

HLX3901 is designed to address these challenges through a tetra-specific architecture targeting dual epitopes of DLL3, CD3, and CD28, enabling a “dual-signal” mechanism that integrates T-cell activation (signal 1) with co-stimulation (signal 2). By simultaneously engaging CD3 and CD28 on the T-cell surface, HLX3901 enhances T-cell activation, proliferation, and survival, thereby strengthening targeted cytotoxicity against DLL3-positive tumor cells. This synergistic activation is expected to improve the therapeutic window and sustain anti-tumor immune responses, even in tumors with low T-cell infiltration.

Preclinical studies indicate that HLX3901 exhibits enhanced cytotoxic effects at low effector-to-target ratios. In human pan-T cell reconstitution models, HLX3901 demonstrated stronger and more durable anti-tumor activity compared to reference molecules such as tarlatamab. Furthermore, preliminary toxicity studies in cynomolgus monkeys showed that HLX3901 was well-tolerated with a broad therapeutic window, supporting its further clinical development.

Developed through the synergistic integration of AI‑driven molecular design and the company’s TCE platform, HLX3901 exemplifies a next‑generation TCE engineered to overcome key limitations of earlier constructs in solid tumors—achieving sustained and specific T‑cell activation, improved efficacy in the tumor microenvironment (TME) with low TIL density, and a reduced risk of cytokine release syndrome (CRS). The rapid advancement of HLX3901 highlights Henlius’ systematic R&D capabilities in multi-specific antibody engineering.

Building on these capabilities, Henlius has established a diversified innovation platform ecosystem, including PD(L)1-based immune checkpoint inhibitor platform, immune cell engager platforms (such as multi-specific TCEs), the proprietary Hanjugator™ ADC platform, and the AI-powered, all-in-one early-stage R&D platform HAI Club. Together, these platforms support the continuous generation and efficient advancement of a globally competitive innovation pipeline.

Focusing on areas of high unmet medical need, Henlius continues to expand its early-stage pipeline with high-potential assets. Several programs have recently achieved key milestones. Among them, HLX701 (a novel SIRPα-Fc fusion protein) has initiated a phase 2 clinical trial in China, leveraging its potentially improved safety profile. HLX37 (an innovative anti-PD-L1/VEGF bispecific antibody) has received IND approval for advanced/metastatic solid tumors and finished dosing its first patient. HLX97 (a novel oral small molecule KAT6A/B inhibitor) has recently received IND approval from the CDE. Additional next-generation candidates, including HLX3902 (STEAP1×CD3×CD28 tri-specific antibody TCE), HLX49 (HER2 dual-epitope ADC), HLX48 (cMET × EGFR bispecific antibody ADC), and HLX105 (a fusion protein), are expected to rapidly advance into clinical development.

Looking ahead, Henlius will continue to adhere to its "patient-centric" R&D philosophy. Leveraging its integrated, platform‑based innovation engine, the company is committed to accelerating the development of a differentiated, globally competitive innovative pipeline, striving to provide more accessible and effective treatment options for patients worldwide.

About HLX3901-FIH101

This is an open-label, first-in-human phase 1 clinical study to evaluate the safety, tolerability, pharmacokinetic profiles, and preliminary efficacy of HLX3901 in patients with advanced small cell lung cancer or neuroendocrine carcinoma. The study consists of two stages: phase 1a dose-escalation and backfill stage and phase 1b dose-expansion stage. Phase 1a includes seven dose levels ranging from 0.1 mg to 30 mg, with a 4‑week treatment cycle. The 0.1 mg dose level employs an accelerated titration design, while the remaining six dose levels use a standard “3+3” dose-escalation design; During dose escalation, backfilling of subjects into certain dose cohorts is permitted once safety has been verified. Phase 1b is planned to include three dose-expansion cohorts at 10 mg, 20 mg, and 30 mg, with dosing strategies consistent with those used in the corresponding phase 1a dose levels. The primary objectives of this study are to evaluate the safety and tolerability of HLX3901 in patients with advanced small cell lung cancer or neuroendocrine carcinoma, to determine its maximum tolerated dose (“MTD”) and recommended phase 2 dose (“RP2D”), and to preliminarily evaluate its antitumor efficacy. The primary endpoints include the incidence of dose-limiting toxicities (DLTs), the MTD and RP2D of HLX3901, and the investigator-assessed objective response rate (ORR).

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 five 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/index.html and connect with us on LinkedIn at https://www.linkedin.com/company/henlius/.

参考文献

References

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2. Ladi E, et al. The divergent DSL ligand Dll3 does not activate Notch signaling but cell autonomously attenuates signaling induced by other DSL ligands. J Cell Biol. 2005;170(6):983-992.

3. Owen DH, et al. DLL3: an emerging target in small cell lung cancer. J Hematol Oncol. 2019;12(1):61.

4. Tanaka K, et al. Prevalence of Delta-like protein 3 expression in patients with small cell lung cancer. Lung Cancer. 2018;115:116–120.

5. Yao J, et al. DLL3 as an Emerging Target for the Treatment of Neuroendocrine Neoplasms. Oncologist. 2022 Nov 3;27(11):940-951.

6. Rudin CM, et al. Emerging therapies targeting the delta-like ligand 3 (DLL3) in small cell lung cancer. J Hematol Oncol. 2023;16(1):66.

7. Lobenhofer E, et al. P1.12-18 Nonclinical Safety Assessment of AMG 757, a DLL3 Bispecific T Cell Engager, in the Cynomolgus Monkey. Journal of Thoracic Oncology. 2019;14(10):S541.

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9. Ahn MJ, et al. Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer. N Engl J Med. 2023;389(22):2063-2075.

10. Hegde PS, Chen DS. Top 10 Challenges in Cancer Immunotherapy. Immunity.2020;52(1):17-35.

11. Belmontes B, et al. Immunotherapy combinations overcome resistance to bispecific T cell engager treatment in T cell-cold solid tumors. Sci Transl Med. 2021;13(608): eabd1524.

12. Schwartz RH. T cell anergy. Annu Rev Immunol. 2003;21:305-334.

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14. Bhatia S, et al. Different cell surface oligomeric states of B7-1 and B7-2: implications for signaling. Proc Natl Acad Sci U S A. 2005;102(43):15569-15574.

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投资者：IR@Henlius.com