2025年12月1日，复宏汉霖（2696.HK）宣布，公司自研的HLX37（重组人源化抗PD-L1与VEGF双特异性抗体）用于晚期/转移性实体瘤治疗的I期临床研究获中国国家药品监督管理局（NMPA）批准。

PD-L1（Programmed Cell Death Ligand-1），又称作 B7H1 和 CD274，是肿瘤免疫逃逸的关键分子，通过与 T 细胞表面的 PD-1 受体结合，抑制 T 细胞活化与增殖，从而削弱机体对肿瘤的免疫监视能力^[1]。研究表明，PD-L1 在多种实体瘤中高表达，如非小细胞肺 癌、胃癌、卵巢癌等，且其表达水平与免疫治疗疗效相关^[2,3]。PD-1/L1 抑制剂已在临床中广泛应用，但单药治疗响应率有限，部分患者因适应性耐药或 T 细胞耗竭而复发^[4]。VEGFA（vascular endothelial growth factor A）又称作 VEGF，是肿瘤血管生成的核心调控因子，可促进异常血管生成，为肿瘤提供氧气和营养支持，同时形成免疫抑制性微环境^[5]。VEGF 是 VEGF 蛋白家族（包括VEGFA、VEGFB、VEGFC、VEGFD 和胎盘生长因子 PIGF）的一员，可与受体 VEGFR1和 VEGFR2 结合^[6]。VEGF 驱动的肿瘤血管发育不全会导致缺氧和酸性微环境，促进 PD-L1 表达，同时招募免疫抑制细胞（如调节性 T 细胞），加剧 T 细胞耗竭，削弱抗 PD-1/L1 治疗的疗效。PD-L1介导的T 细胞抑制也能释放促血管生成因子（如 IL-8、VEGF 自身），形成“免疫-血管生成”恶性循环^[7]。因此，靶向PD-L1 和VEGF 能够在治疗肿瘤上发挥良好的协同作用。

HLX37 是复宏汉霖自研的重组人源化抗PD-L1 与 VEGF 双特异性抗体。其作用机制结合了两种治疗路径：1）阻断PD-1 /PD-L1结合：通过阻断肿瘤细胞表面的PD-L1蛋白与免疫细胞（如T细胞）上的PD-1受体结合，解除肿瘤免疫抑制，恢复T 细胞对肿瘤的杀伤能力；2）阻断血管生成通路：靶向VEGF，减少肿瘤血管生成，从而限制肿瘤的血液供应生长和转移。这种双靶点设计有望产生协同抗肿瘤效应，并可能降低耐药性风险，通过特异性结合肿瘤细胞PD-L1实现肿瘤内部具有抗VEGF功能的HLX37 双抗分子的富集，实现大于抗PD-L1 单抗和抗VEGF 单抗的联合疗效。临床前研究表明，HLX37具有优异的抗肿瘤活性且安全性可控，同时能增强肿瘤富集效应，其在多类肿瘤中具有广泛的应用潜力。该研究结果在2025年美国癌症研究协会（AACR）年会上首次发布^[8]。

未来，复宏汉霖将继续秉持“以患者为中心”的初心和理念，深耕实体瘤这一重要疾病领域，通过不断挖掘患者未满足的临床需求，持续夯实更多创新分子的差异化布局，为更多肿瘤患者带来高质量、可负担的新型治疗方案。

【参考文献】

[1] Parvez A, Choudhary F, et al. PD-1 and PD-L1: architects of immune symphony and immunotherapy breakthroughs in cancer treatment. Front Immunol. 2023; 14:1296341.

[2] Yu, H., Boyle, T. A., et al. (2016). PD-L1 Expression in Lung Cancer. Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer, 11(7), 964–975.

[3] Cozac-Szőke, A. R., Cozac, D. A., et al. (2025). Immune Cell Interactions and Immune Checkpoints in the Tumor Microenvironment of Gastric Cancer. International journal of molecular sciences, 26(3), 1156.

[4] Sun, J. Y., Zhang, D., et al. (2020). Resistance to PD1/PD-L1 blockade cancer immunotherapy: mechanisms, predictive factors, and future perspectives. Biomarker research, 8, 35.

[5] Pérez-Gutiérrez, L., & Ferrara, N. (2023). Biology and therapeutic targeting of vascular endothelial growth factor A. Nature reviews. Molecular cell biology, 24(11), 816–834.

[6] Khan, K. A., & Kerbel, R. S. (2018). Improving immunotherapy outcomes with anti-angiogenic treatments and vice versa. Nature reviews. Clinical oncology, 15(5), 310–324.

[7] Hack, S. P., Zhu, A. X., & Wang, Y. (2020). Augmenting Anticancer Immunity Through Combined Targeting of Angiogenic and PD-1/PD-L1 Pathways: Challenges and Opportunities. Frontiers in immunology, 11, 598877

[8] Song G, Chen Y-S, et al. Abstract 7303: A novel anti-PD-L1/VEGF bispecific antibody (HLX37) with immune checkpoint inhibition, anti-angiogenic, and antineoplastic activities. Cancer Res 15 April 2025; 85 (8_Supplement_1): 7303. AACR Annual Meeting 2025.

guidelines): gastric cancer (Version 3.2025).

关于复宏汉霖

复宏汉霖（2696.HK）是一家国际化的创新生物制药公司，致力于为全球患者提供可负担的高品质生物药，产品覆盖肿瘤、自身免疫疾病、眼科疾病等领域，已在全球获批上市10款产品，3个上市申请分别获中国药监局和欧盟EMA受理。自2010年成立以来，复宏汉霖已建成一体化生物制药平台，高效及创新的自主核心能力贯穿研发、生产及商业运营全产业链。公司已建立完善高效的全球创新中心，按照国际药品生产质量管理规范（GMP）标准进行生产和质量管控，不断夯实一体化综合生产平台，其中，公司商业化生产基地已相继获得中国、欧盟和美国GMP认证。

复宏汉霖前瞻性布局了一个多元化、高质量的产品管线，涵盖约50个分子，并全面推进基于自有抗PD-1单抗H药 汉斯状的肿瘤免疫联合疗法。截至目前，公司已获批上市产品包括全球首个获批一线治疗小细胞肺癌的抗PD-1单抗汉斯状（斯鲁利单抗，欧洲商品名：Hetronifly）、自主研发的中美欧三地获批单抗生物类似药汉曲优（曲妥珠单抗，美国商品名：HERCESSI，欧洲商品名：Zercepac）、国内首个生物类似药汉利康（利妥昔单抗）、地舒单抗生物类似药Bildyos和Bilprevda，以及帕妥珠单抗POHERDY。公司亦同步就19个产品在全球范围内开展30多项临床试验，对外授权全面覆盖欧美主流生物药市场和众多新兴市场。

Henlius Receives the NMPA IND Approval for Its Innovative PD-L1/VEGF Bispecific Antibody HLX37

Shanghai, China, December 1, 2025—Shanghai Henlius Biotech, Inc. (2696.HK) today announced that the investigational new drug (IND) application for a Phase 1 clinical trial of HLX37, a recombinant humanized anti-PD-L1 and anti-VEGF bispecific antibody, has been approved by the China National Medical Products Administration (NMPA), for the treatment of advanced/metastatic solid tumors.

Programmed cell death-ligand 1 (PD-L1), also known as B7-H1 or CD274, is a key molecule in tumor immune evasion. It inhibits T-cell activation and proliferation by binding to the PD-1 receptor on T cells, thereby suppressing the body's immune surveillance of tumors ^[1]. Research indicates that programmed death-ligand 1 (PD-L1) is highly expressed in various solid tumors, including non-small cell lung cancer, gastric cancer, and ovarian cancer, and its expression level correlates with the efficacy of immunotherapy ^[2,3]. Although PD-1/PD-L1 inhibitors are widely used in clinical practice, two significant limitations remain: 1) a modest objective response rate to single-agent therapy, and 2) disease progression in many patients attributable to adaptive resistance and T-cell exhaustion ^[4]. Vascular endothelial growth factor A (VEGFA), commonly referred to as VEGF, is a central regulator of tumor angiogenesis. It promotes the formation of abnormal blood vessels that supply oxygen and nutrients to the tumor, simultaneously fostering an immunosuppressive microenvironment ^[5]. VEGF, a key member of the VEGF family (encompassing VEGFA, VEGFB, VEGFC, VEGFD, and PlGF), exerts its biological effects primarily by binding and activating its cognate receptors VEGFR1 and VEGFR2^[6]. In the tumor context, VEGF-induced aberrant angiogenesis results in hypoxic and acidic conditions that promote PD-L1 upregulation and recruit immunosuppressive cell populations, including regulatory T cells. This process intensifies T-cell exhaustion and compromises the effectiveness of anti-PD-1/L1 immunotherapy. Furthermore, immunosuppression mediated by PD-L1 can trigger the secretion of pro-angiogenic factors like IL-8 and VEGF, establishing a detrimental feed-forward loop between angiogenesis and immune evasion ^[7]. Consequently, co-targeting PD-L1 and VEGF represents a therapeutic strategy with significant synergistic potential.

HLX37 is a recombinant humanized anti-PD-L1 and anti-VEGF bispecific antibody developed by Henlius. Its mechanism of action integrates two therapeutic pathways: (1) Blocking PD-1/PD-L1 interaction: by inhibiting the binding of PD-L1 on tumor cells to the PD-1 receptor on immune cells (e.g., T cells), it reverses tumor-induced immunosuppression and restores T cell-mediated antitumor activity; (2) Anti-angiogenic pathway: by neutralizing VEGF, it suppresses tumor angiogenesis, thereby cutting off the blood supply essential for tumor growth and metastasis. This dual-targeting design is expected to generate a synergistic antitumor effect and may reduce the risk of drug resistance. Specifically, through its specific binding to PD-L1 on tumor cells, HLX37 achieves enhanced enrichment of the bispecific antibody within the tumor microenvironment, leading to superior efficacy compared to the combination of anti-PD-L1 and anti-VEGF monoclonal antibodies. Preclinical studies demonstrated that HLX37 has strong antitumor activity and favorable safety profile, with enhanced tumor enrichment, indicating its broad therapeutic potential across multiple tumor types. These findings were first presented at the 2025 American Association for Cancer Research (AACR) Annual Meeting ^[8].

By strategically prioritizing solid tumor domain as a core therapeutic area, Henlius continues to uphold its patient-centric mission, accelerating differentiated innovation to address unmet medical needs and delivering high-quality, affordable therapies to tumor patients worldwide.

About Henlius

Henlius (2696.HK) is a global biopharmaceutical company with the vision to offer high-quality, affordable and innovative biologic medicines for patients worldwide with a focus on oncology, autoimmune diseases and ophthalmic diseases. To date, 10 products have been approved for marketing across multiple countries and regions, and 3 marketing applications have been accepted for review in China and the EU, respectively. Since its inception in 2010, Henlius has built an integrated biopharmaceutical platform with core capabilities of high-efficiency and innovation embedded throughout the whole product life cycle including R&D, manufacturing and commercialization. It has established global innovation centre and Shanghai-based commercial manufacturing facilities certificated by China, the EU and U.S. GMP.

Henlius has pro-actively built a diversified and high-quality product pipeline covering about 50 molecules and has continued to explore immuno-oncology combination therapies with proprietary HANSIZHUANG (anti-PD-1 mAb) as the backbone. To date, the company's launched products include HANSIZHUANG (serplulimab, trade name: Hetronifly in Europe), the world’s first anti-PD-1 mAb for the first-line treatment of SCLC, HANQUYOU (trastuzumab, trade name: HERCESSI in the U.S., Zercepac in Europe), a China-developed mAb biosimilar approved in China, Europe and U.S., HANLIKANG (rituximab), the first China-developed biosimilar, denosumab Bildyos and Bilprevda, and pertuzumab Poherdy. What’s more, Henlius has conducted over 30 clinical studies for 19 products, expanding its presence in major markets as well as emerging markets.

To learn more about Henlius, visit and connect with us on LinkedIn at ·收藏 ·点赞 ·在看

(复宏汉霖)