• Breakthrough Potential in Thymic Carcinoma (TC):

HLX43, the first PD-L1 ADC demonstrating promising efficacy in thymic carcinoma (TC), is positioned to address the critical gap as ADC therapies for this rare, highly aggressive malignancy

• Potential Best-in-Class Pan-Tumor ADC:

HLX43 exhibits "high efficacy and low toxicity" across solid tumors including NSCLC and thymic squamous cell carcinoma (TSCC), highlighting its broad-spectrum therapeutic potential

• Leading Global Development of PD-L1 ADC:

HLX43 is the first PD-L1 ADC advancing to Phase 2 trials globally. The company is accelerating multicenter studies of HLX43 in China, the U.S., Japan, and Australia to expedite global launch to benefit broader patient populations

Recently, Shanghai Henlius Biotech, Inc. (2696.HK) announced that HLX43 for Injection, the company‘s innovative programmed death-ligand 1 (PD-L1) targeting antibody-drug conjugate (ADC) has been approved by the United States Food and Drug Administration (FDA) to initiate a phase 1 clinical trial incorporating thymic carcinoma (TC) cohort to  benefit a broader range of tumor patients globally. Previously, HLX43 has already been approved to conduct phase 2 MRCT in patients with advanced non-small cell lung cancer (NSCLC) in China, U.S., Japan and Australia. To date, no PD-L1 targeting ADC has been approved for marketing globally. HLX43 is the first PD-L1 ADC progressed to phase 2 clinical trial development globally.

Thymic Carcinoma (TC) is a rare malignant neoplasm originating from thymic epithelial cells, accounting for approximately 14%-22% of all thymic epithelial tumors (TETs) ^[1]. TC demonstrates aggressive behavior characterized by local invasion, intrathoracic lymph node metastasis, and distant dissemination, correlating with poor prognosis^[2]. Histopathologically, thymic squamous cell carcinoma (TSCC) constitutes the predominant subtype (∼70%), followed by lymphoepithelial carcinoma and undifferentiated carcinoma^[3]. Epidemiological studies indicate a median age at diagnosis of 50-60 years^[1], with a stable global annual incidence of 0.15 per 100,000 person-years; however, increasing diagnostic rates have been observed in recent years^[2]. For localized early-stage patients, surgical resection remains the primary therapeutic approach, while advanced or recurrent/metastatic cases require first-line platinum-based combination chemotherapy followed by second-line systemic therapies (including chemotherapy, targeted therapies, and immunotherapy). Critical therapeutic limitations persist, including lack of actionable driver mutations, complex drug resistance mechanisms, significant treatment-related toxicities, and suboptimal efficacy, underscoring the urgent unmet medical need for safer and more effective novel treatment strategies^[4-8]. 

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 binding 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. Notably, encouraging preliminary efficacy was observed in thymic squamous cell carcinoma (TSCC) patients, 75% patients with TSCC achieved partial response (ORR=75%, 3/4). Updated phase 1 clinical data will be presented in the poster tour session by Jie wang from Cancer Hospital Chinese Academy of Medical Sciences, the leading PI（principal investigator) of this study at the upcoming 2025 World Conference on Lung Cancer (WCLC) .

The company is currently accelerating the clinical development of HLX43 and actively exploring its therapeutic potential in various solid tumors, including NSCLC, TSCC, hepatocellular carcinoma (HCC), esophageal squamous cell carcinoma (ESCC), head and neck squamous cell carcinoma (HNSCC), cervical cancer (CC) and nasopharyngeal cancer (NPC). Both monotherapy studies and a phase 1b/2 trial combining HLX43 with serplulimab (Henlius' proprietary anti-PD-1 monoclonal antibody) are ongoing simultaneously to further exploit the synergistic effects of ADC-mediated cytotoxicity and immunotherapy-induced immune activation. 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.

Looking forward, Henlius will accelerate the global development of HLX43, continuously strengthening the differentiated layout of more innovative molecules to bring high-quality, affordable innovative treatment options to tumor patients worldwide.

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