创新加速度 | 复宏汉霖创新PD-L1xVEGF双抗加速推进I期临床

2025年12月29日，复宏汉霖（2696.HK）宣布，公司自主研发的创新型重组人源化抗PD-L1与VEGF双特异性抗体HLX37在晚期/转移性实体瘤受试者中开展的首次人体临床试验（HLX37-FIH101）已于中国完成受试者给药。

HLX37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。研究表明，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，HLX37能够实现大于抗PD-L1 单抗和抗VEGF 单抗的联合疗效。临床前研究表明，该候选分子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，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^[1]。

HLX37由抗VEGF 抗体与抗PD-L1的VHH片段融合而成, 该VHH序列筛选自复宏汉霖的合成VHH库。复宏汉霖已构建起“从源头发现到规模化生产”的一体化抗体技术平台，成为驱动差异化抗体药物研发的核心引擎。平台聚焦功能阻断性抗体开发，打造了强大的天然/合成人源化/免疫羊驼VHH多样化抗体库，可针对不同靶点灵活筛选出高亲和力、高特异性的纳米抗体（VHH）及scFv，为多特异性抗体等创新分子的开发奠定基础。同时，基于长期行业积淀，公司已系统性建立多特异性抗体（双抗/三抗/四抗）与抗体融合蛋白的发现、构型设计与功能表征数据库，显著提升了复杂抗体分子的开发效率与成功率。依托于该平台，公司已累计实现了10款产品的获批上市，并持续推进19款临床阶段资产（涵盖创新单抗/ADC/融合蛋白/生物类似药）的高效开发，在研临床项目超过30项，通过全链条的开发能力与获验证的规模化CMC体系，加速推动潜力候选分子转化为高质量的临床与商业化产品。

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] 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.

关于HLX37-FIH101

HLX37-FIH101是一项评估HLX37在晚期/转移性实体瘤受试者中安全性、耐受性、药代动力学（PK）特征及初步疗效的开放性、首次人体I期临床试验，共分为Ia期剂量递增（含单药及联合治疗）和Ib期剂量扩展两个阶段。Ia期单药治疗针对晚期实体瘤受试者，设置1.0 mg/kg至45.0 mg/kg共6个剂量水平，每三周给药一次；联合治疗将在晚期非小细胞肺癌受试者中探索不同剂量HLX37联合培美曲塞或白蛋白紫杉醇/紫杉醇及卡铂的方案；Ib期的给药方案及拟扩展瘤种将根据Ia期研究结果决定。本研究的主要终点旨在评估剂量限制性毒性（DLT）发生率，以确定单药及联合治疗的最大耐受剂量（MTD）和II期推荐剂量（RP2D）；次要终点包括不良事件等安全性指标、PK参数、免疫原性，以及客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）等疗效指标，同时探索潜在预测性生物标志物。

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，5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 Doses First Patient in Phase 1 Trial of Novel PD-1xVEGF Bispecific Antibody HLX37 for Solid Tumors

Shanghai, China, December 29, 2025—Shanghai Henlius Biotech, Inc. (2696.HK) today announced that the first patient has been dosed in a first in human phase 1 clinical trial for HLX37(HLX37-FIH101), an innovative recombinant humanized anti-PD-L1 and anti-VEGF bispecific antibody independently developed by the company. This milestone marks the initiation of clinical development for HLX37 in patients with advanced/metastatic solid tumors in China.

The mechanism of action of HLX37 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 anti-tumor activity; (2) Anti-angiogenic pathway: by neutralizing VEGF, it suppresses tumor angiogenesis, thereby cutting off the blood supply essential for tumor growth and metastasis. By specifically 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 indicate that HLX37 has strong anti-tumor 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^[1].

HLX37 is a bispecific antibody combining an anti-VEGF mAb with an anti-PD-L1 VHH domain, derived from Henlius’s synthetic humanized llama VHH library. The company has established an integrated antibody discovery-to-manufacturing platform that serves as the core engine for differentiated antibody-based therapeutics. The platform focuses on the development of function-blocking antibodies and features a robust, diversified VHH libraries encompassing natural, synthetic humanized, and immunized llama VHHs. It enables efficient selection of high-affinity and highly specific VHHs and scFvs against diverse targets, providing a solid foundation for the design of next-generation multispecific antibodies. Furthermore, leveraging deep industry expertise, Henlius has systematically developed a comprehensive discovery and characterization database for multispecific antibodies—including bispecific, trispecific, and tetraspecific formats—as well as antibody fusion proteins. This database supports rational design and functional profiling, enhancing the probability of success development of complex antibody therapeutics. Built upon this platform, the company has advanced 10 products to marketing approval while fostering a pipeline of 19 clinical-stage assets with over 30 clinical studies ongoing, covering mAbs, ADCs, fusion proteins, and biosimilars. Leveraging its end-to-end capabilities and a validated, scalable CMC system, the company accelerates the translation of high-potential candidates into high-quality clinical and commercial products.

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 HLX37-FIH101

HLX37-FIH101 is an open-label, first-in-human Phase I clinical trial evaluating the safety, tolerability, pharmacokinetic (PK) profiles, and preliminary efficacy of HLX37 in subjects with advanced/metastatic solid tumors. The study consists of two phases: Phase Ia dose escalation (comprising monotherapy and combination therapy) and Phase Ib dose expansion. The Phase Ia monotherapy arm is conducted in subjects with advanced solid tumors, evaluating 6 dose levels ranging from 1.0 mg/kg to 45.0 mg/kg (administered Q3W); the combination therapy arm will explore different doses of HLX37 in combination with pemetrexed or albumin-bound paclitaxel/paclitaxel and carboplatin in subjects with advanced non-small cell lung cancer (NSCLC). The dosing regimen and tumor types for Phase Ib will be determined based on the results of Phase Ia. The primary endpoints aim to evaluate the incidence of dose-limiting toxicity (DLT) to determine the maximum tolerated dose (MTD) and the recommended Phase II dose (RP2D) for both monotherapy and combination therapy. Secondary endpoints include safety indicators such as adverse events, PK parameters, and immunogenicity, as well as efficacy indicators including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), alongside the exploration of potential predictive biomarkers.

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

联系方式

媒体：PR@Henlius.com

投资者：IR@Henlius.com