美国首例入组完成，复宏汉霖PD-L1 ADC HLX43 全球II期临床全速推进

• 全球开发提速：HLX43针对NSCLC的国际多中心II期临床在中美日澳等地启动，加速产品全球开发进程

• NSCLC全人群覆盖：HLX43在鳞状/非鳞状、有无EGFR突变、有无脑/肝转移、PD-L1阳性/阴性的NSCLC患者中都展现疗效，且安全性良好

• “高效低毒”持续验证：HLX43扩大样本数据即将亮相2025 WCLC，持续验证“高效低毒”特质，提示其一线治疗潜力

First Subject Dosed in the US for a Phase 2 International Clinical Trial of Henlius’ PD-L1 ADC HLX43 for NSCLC

• Global Development Accelerated:  Phase 2 Multi-Regional Clinical Trials for HLX43 in NSCLC Launched Across China, the U.S., Australia and Japan

• Broad Efficacy in NSCLC: HLX43 demonstrates broad efficacy in NSCLC patients, regardless of histology (squamous or non-squamous), EGFR mutation status, presence of brain/liver metastases, or PD-L1 expression, with a favorable safety profile

• Sustained Validation of "High Efficacy with Low Toxicity"：Updated data on HLX43 to be released at 2025 WCLC indicates its potential as first line setting in NSCLC

Shanghai, China, August 22, 2025 — Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first subject has been dosed in the US for HLX43-NSCLC201, a phase 2 international muticenter clinical trial of HLX43, its innovative programmed death-ligand 1 (PD-L1) targeting antibody-drug conjugate (ADC), for the treatment of patients with advanced non-small cell lung cancer (NSCLC). Henlius is vigorously advancing the global development of HLX43, with an international multi-region phase 2 clinical trial initiated in China, the US, Australia, and Japan. At present, no PD-L1 targeting ADC has been approved for marketing globally. 

Lung cancer is the most common cancer worldwide in terms of incidence and mortality. According to GLOBOCAN 2022, there were over 2.48 million new cases of lung cancer globally in 2022, accounting for 12.4% of all new cancer cases^[1]. The majority of lung cancer patients are diagnosed at advanced stages^[2], indicating a significant unmet clinical need. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer (approximately 85%). By histology, NSCLC can be classified into squamous cell carcinoma (approximately 30%), adenocarcinoma (approximately 50%) and other subtypes including large cell carcinoma. EGFR wild-type cases account for 70%-85% of all NSCLC patients, including nearly all squamous cell carcinoma cases and 50-55% of adenocarcinoma cases^[3]. Currently, the treatment landscape of EGFR wild-type NSCLC remains limited by a scarcity of highly effective options, particularly in second-line and later (2L+) therapy, where docetaxel-based chemotherapy continues to serve as the standard of care despite its suboptimal efficacy^[4,5].

HLX43 is a broad-spectrum anti-tumor ADC candidate targeting PD-L1, composed of a fully humanized anti-PD-L1 IgG1 antibody, a novel tripeptide linker and topoisomerase inhibitor payload. The drug-to-antibody ratio (DAR) is around 8. Its mechanisms of action integrate targeted cytotoxic delivery and immune checkpoint activation through PD-L1/PD-1 blockade. Upon bonding to tumor cells with PD-L1 expression, the cytotoxic payload of HLX43 will be delivered into tumor cells via dual mechanisms. HLX43 will undergo receptor-mediated endocytosis, releasing the cytotoxic payload intracellularly via linker cleavage, and the payload further diffuses into neighboring tumor cells via bystander effect, thereby blocking DNA replication and triggering tumor cell apoptosis. Meanwhile, the anti-PD-L1 antibody of HLX43 activates immune modulation and blocks immune checkpoints, driving synergistic anti-tumor efficacy. The results from the phase 1 clinical trial of HLX43 has been first released at the 2025 ASCO Annual Meeting, demonstrating manageable safety profile and encouraging efficacy in various solid tumors especially in patients with NSCLC, including squamous and non-squamous NSCLC patients (sqNSCLC and nsqNSCLC), patients with or without EGFR mutation, patients with or without brain/liver metastasis, and PD-L1 positive or negative patients.

According to the updated abstract released for 2025 WCLC, HLX43 consistently demonstrates a high response rate in the expanded patient cohorts with advanced solid tumors, particularly in pretreated NSCLC patients who failed checkpoint inhibitor therapy. HLX43 exhibits superior efficacy in specific subgroups, with an objective response rate (ORR) of 47.4% in EGFR wild-type non-squamous NSCLC, while maintaining a favorable safety profile. Notably, HLX43 demonstrates robust efficacy regardless of PD-L1 expression, indicating its biomarker-independent antitumor potential.

The company is currently accelerating the clinical development of HLX43 and actively exploring its therapeutic potential in various solid tumors, including NSCLC, thymic squamous cell carcinoma (TSCC),  gastric or gastroesophageal junction adenocarcinoma, hepatocellular carcinoma (HCC), esophageal squamous cell carcinoma (ESCC), head and neck squamous cell carcinoma (HNSCC), cervical cancer (CC) and nasopharyngeal cancer (NPC).  Both monotherapy and combination therapies of HLX43 are ongoing simultaneously to further exploit the synergistic effects of ADC-mediated cytotoxicity and other agents . HLX43 may benefit more patients with advanced or metastatic solid tumors by providing a novel treatment option for those who are unresponsive or have developed resistance to PD-1/PD-L1-targeted therapies, as well as the patients who have failed prior chemotherapy or TKI therapies.

By strategically prioritizing lung cancer 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.