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。

　　[1]Song G,Chen Y-S,et al.Abstract7303:A novel anti-PD-L1/VEGF bispecific antibody(HLX37)with immune checkpoint inhibition,anti-angiogenic,and antineoplastic activities.Cancer Res15April2025;85(8_Supplement_1):7303.AACR Annual Meeting2025.

　　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1.0mg/kg至45.0mg/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。

　　 Henlius Doses First Patient in Phase1Trial of Novel PD-1xVEGF Bispecific Antibody HLX37for Solid Tumors Shanghai,China,December29,2025—Shanghai Henlius Biotech,Inc.(2696.HK)today announced that the first patient has been dosed in a first in human phase1clinical trial for HLX37(HLX37-FIH101),an innovative recombinant humanized anti-PD-L1and anti-VEGF bispecific antibody independently developed by the company.This milestone marks the initiation of clinical development for HLX37in patients with advanced/metastatic solid tumors in China.

　　 The mechanism of action of HLX37integrates two therapeutic pathways:(1)Blocking PD-1/PD-L1interaction:by inhibiting the binding of PD-L1on tumor cells to the PD-1receptor 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-L1on tumor cells,HLX37achieves enhanced enrichment of the bispecific antibody within the tumor microenvironment,leading to superior efficacy compared to the combination of anti-PD-L1and anti-VEGF monoclonal antibodies.Preclinical studies indicate that HLX37has 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 the2025American Association for Cancer Research(AACR)Annual Meeting[1].

　　 HLX37is a bispecific antibody combining an anti-VEGF mAb with an anti-PD-L1VHH 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 advanced10products to marketing approval while fostering a pipeline of19clinical-stage assets with over30clinical 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-FIH101is an open-label,first-in-human Phase I clinical trial evaluating the safety,tolerability,pharmacokinetic(PK)profiles,and preliminary efficacy of HLX37in 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,evaluating6dose levels ranging from1.0mg/kg to45.0mg/kg(administered Q3W);the combination therapy arm will explore different doses of HLX37in 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.