复宏汉霖 PD-L1 ADC HLX43联合H药 汉斯状®的Ib/II临床研究完成首例受试者给药

近年来，以抗PD-1/L1抗体为代表的免疫检查点抑制剂（ICI）促进了肿瘤免疫治疗的高速发展，成为肿瘤患者各线治疗的主要手段之一。然而，部分患者对该疗法无响应，或者出现耐药^[1]。对于免疫治疗耐药或经免疫治疗等标准治疗失败后的患者人群，尚缺少有效的后线治疗方案，亟待探索更前沿的新型治疗方案，进一步提高患者的临床获益。ADC作为当下肿瘤治疗中疗效最突出的新型疗法，已在乳腺癌、肺癌、食管癌、胃癌等多项实体瘤中展现出初步的治疗潜力，成为重要的探索方向^[2]。而PD-L1在非小细胞肺癌、结直肠癌、三阴性乳腺癌、鳞状细胞癌等多种癌种中均有表达，且在正常组织中的表达有限，使其成为开发ADC药物的潜力靶点，为肿瘤治疗带来新的途径^[3]。

HLX43兼具抗体分子的高度靶向性和细胞毒素的强大杀伤力，可通过与肿瘤细胞表面PD-L1 抗原特异性结合，经内吞后释放小分子毒素，从而发挥抗肿瘤作用。其采用的毒素DNA拓扑异构酶I（Topoisomerase I）抑制剂在血液中的半衰期更短，安全性更好，同时其更强的膜穿透性和细胞膜亲和力便于产品发挥旁观者效应^[4]，独特的作用机制使得HLX43较同类ADC产品具有更大的治疗窗口，增强ADC在实体肿瘤中的治疗效果。临床前研究及I期临床研究提示，HLX43在抗PD-1/PD-L1单抗耐药的非小细胞肺癌等多个瘤种中显示出显著疗效，且耐受性良好，临床前研究数据于2023欧洲肿瘤内科学会（ESMO）大会以壁报形式进行展示。基于此，公司于近期启动了HLX43在食管鳞癌等潜在实体瘤适应症中的II期临床试验，以进一步评HLX43的疗效和安全性。在加速拓展抗体偶联药物（ADC）产品布局的同时，复宏汉霖亦积极探索ADC与免疫治疗药物的联用方案，前瞻性布局IO+ADC治疗领域，以期实现协同增效的抗肿瘤疗效，进一步提高患者的临床获益，解决未满足的临床需求。

未来，复宏汉霖将持续立足于未满足的临床需求，充分发挥公司在抗体药物和抗体偶联药物领域的一体化平台优势，加速推动更多前沿治疗方案的研究和开发，为全球患者带来更多高质量、可负担的创新治疗方案。

First Subject Dosed for a Phase 1b/2 Clinical Trial of Henlius' PD-L1-Targeting ADC HLX43 in Combination with Novel Anti-PD-1 mAb Serplulimab

Shanghai, China, April 9, 2025 — Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first subject has been dosed for a phase 1b/2 clinical trial of HLX43 for Injection, the novel Programmed Death-Ligand 1 (PD-L1)-targeting antibody-drug conjugate (ADC) that developed by the company based on the collaboration with MediLink Therapeutics, in combination with the Henlius' independently developed innovative anti-PD-1 monoclonal antibody (mAb) HANSIZHUANG (serplulimab injection), for the treatment of patients with advanced/metastatic solid tumours in Chinese mainland.  Recently, the company has also completed the first subject dosing for a phase 2 clinical trial of HLX43 for monotherapy or combination therapy to treat patients with advanced/metastatic solid tumours. At present, no PD-L1 targeting ADC has been approved for marketing globally, and only SGN-PDL1V from Pfizer is about to initiate a phase 3 clinical trial. HLX43 is the world's second and China's first PD-L1-targeting ADC to progress to clinical research.

Immune checkpoint inhibitors represented by PD-1/PD-L1 monoclonal antibodies have emerged in recent years and revolutionised all lines of treatment for tumour patients. However, there are still many patients with positive PD-L1 expression who do not respond to or develop resistance to PD-1/PD-L1-targeted therapy ^[1]. To date, there has been no subsequent-line treatment for patients who are resistant to PD-1/L1 immunotherapy or failed to benefit from the standard treatments including immunotherapy, indicating a significant unmet medical need to further improve the clinical benefits for these patients. As a novel targeting therapy with the most prominent anti-tumour efficacy, ADCs have shown preliminary therapeutic potential in the treatment of multiple advanced solid tumours, such as breast cancer (BC), lung cancer (LC), esophageal cancer (EC) and gastric cancer (GC), making it a promising therapeutic in solid tumours ^[2]. PD-L1 is expressed in patients across a broad spectrum of tumour types including non-small cell lung cancer (NSCLC), colorectal cancer (CRC), triple negative breast cancer (TNBC), squamous cell carcinoma and displays limited expression on normal tissues, highlighting the potential of PD-L1 as a target for ADCs, which may bring new options for cancer treatment ^[3].

Combining the selectivity of targeted monoclonal antibodies with the highly potent cytotoxic agent, HLX43 could exert anti-tumour effects through specific binding to the PD-L1 expressed on the surface of tumour cells and release cytotoxic payloads after internalisation by the cancer cells. The cytotoxic payload of HLX43 is a novel DNA topoisomerase-I inhibitor which are known for their potent anti-tumor activity, shorter half-life in the bloodstream, and improved safety profile ^[4]. This next generation design allows HLX43 to possess a higher therapeutic index and potency for treatment of solid tumours. Several non-clinical studies and the phase 1 clinical trial have shown that, HLX43 has good anti-tumour effects and a favorable tolerability profile in non-small cell lung cancer (NSCLC), and other tumour types that were PD-1/L1 mAb-resistant. The results of the pre-clinical studies were published as poster presentation at the 2023 European Society of Medical Oncology (ESMO) Congress. Based on these compelling results, Henlius has initiated phase 2 clinical trials of HLX43 in potential solid tumour indications including ESCC 安定other solid tumours to further evaluate the efficacy and safety of HLX43. While accelerating the development of ADCs and diversified drug conjugates, Henlius is also actively exploring combination therapies involving ADCs with immunotherapy to encourage progress in the next wave innovation of “IO+ADC”, further providing more effective treatment options to fulfill the unmet clinical needs.

Moving forward, Henlius remains committed to addressing unmet medical needs by leveraging its antibody drug R&D platform, actively driving the development of innovative therapies to deliver high-quality and affordable treatment options to patients worldwide.

媒体：PR@Henlius.com

投资者：IR@Henlius.com