· FDA's grant of ODD for HLX43 in Thymic Epithelial Tumors (TETs) marks another milestone in its global development, qualifying it for certain incentives in R&D, registration, and commercialization in the U.S.

· Thymic Carcinoma (TC) is a relatively rare yet highly aggressive subtype of TETs with a poor prognosis. Current later-line treatments show limited efficacy, indicating a significant unmet medical need for this disease

· As the world's first PD-L1 ADC developed for TETs, HLX43 has demonstrated promising preliminary efficacy in the later-line treatment of patients with TC. It is positioned to address the unmet clinical need for ADC therapies in this rare and highly aggressive malignancy

Shanghai, China, October 20, 2025 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) for HLX43, the company's innovative programmed death-ligand 1 (PD-L1) targeting antibody-drug conjugate (ADC), for the treatment of thymic epithelial tumors (TETs).

Dr. Marina Garassino, MD, Professor of Medicine at the University of Chicago and leading principal investigator of the HLX43 Thymic Study in the U.S., said: “Thymic epithelial tumors remain a challenging and understudied disease area, especially for patients with advanced thymic carcinoma who currently have very limited treatment options. The encouraging preliminary efficacy observed with HLX43 brings new hope to patients with advanced thymic epithelial tumors. I’m pleased to see this innovative PD-L1 ADC receiving Orphan Drug Designation from the U.S. FDA, a milestone that further validates its potential to address a significant unmet medical need.”

According to the U.S. FDA, the drug or biological product receives an ODD will be eligible for certain development incentives, including but not limited to: 1) tax credits for clinical trial costs; 2) waiver of BLA user fees for new drugs; and 3) seven years of market exclusivity without being affected by patent, aiming to accelerate the development process so that patients can benefit from the products as soon as possible. HLX43 is the world's first PD-L1-targeting ADC developed for TETs. Its phase 1 clinical data released at 2025 ASCO has demonstrated "high efficacy with low toxicity" in solid tumors such as thymic carcinoma (TC),with an ORR of 75% in TC patients. Regarding this indication, the company is accelerating multicenter studies of HLX43 in China, the U.S., Japan, and Australia to expedite its global launch to benefit broader patient populations. Receiving an ODD for HLX43 signifies international recognition of its breakthrough therapeutic potential to treat patients with TETs and marks another milestone in its global development, positioned to address the unmet medical need for ADC treatments in this rare and aggressive malignancy.

Thymic epithelial tumors (TETs) are a group of relatively rare tumors originating from thymic epithelial cells and represent the most common primary tumors of the anterior mediastinum. The World Health Organization (WHO) classifies them into various subtypes, primarily including thymomas, thymic carcinomas, and thymic neuroendocrine tumors ^-1. Among these, thymic carcinoma (TC) accounts for approximately 14% to 22% of all TETs ^[3]. It is characterized by high aggressiveness, including local infiltration, intrathoracic lymph node involvement, and distant metastases, and is associated with a relatively poor prognosis ^[4]. Histopathologically, thymic squamous cell carcinoma (TSCC) constitutes the predominant subtype (∼70%), followed by lymphoepithelial carcinoma and undifferentiated carcinoma ^[5]. Epidemiological studies indicate a median age at diagnosis of 50-60 years ^[3], with a stable global annual incidence of 0.15 per 100,000 person-years; however, increasing diagnostic rates have been observed in recent years ^[4]. 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. 

HLX43 is a broad-spectrum anti-tumor ADC candidate targeting PD-L1, which exhibits dual mechanisms integrating immune checkpoint blockade and payload-mediated cytotoxicity. Preclinical data have shown that, HLX43 has good anti-tumor effects and a favorable tolerability profile in NSCLC, cervical cancer (CC), esophageal squamous cell carcinoma (ESCC), and other tumor types that were PD-1/L1 mAb-resistant. 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 updated data released at the 2025 WCLC, HLX43 continues to demonstrate superior efficacy in an expanded cohort of NSCLC patients, and highlights its therapeutic potential in specific subgroups such as EGFR wild-type NSCLC patients. Confirmed objective response rate (cORR) was 46.7% for patients with an EGFR wild-type non-squamous NSCLC. Among these patients, cORR was 60.0% for those receiving HLX43 at 2.5 mg/kg, along with a favorable safety profile. Notably, HLX43 exhibits robust efficacy in PD-L1 negative (TPS <1%) patients, with an ORR of 38.1% and DCR of 85.7%, indicating its differentiated therapeutic potential to cover a broader patient population regardless of PD-L1 expression.

Currently, Henlius is advancing the clinical development of HLX43 at full speed, with over 400 patients enrolled globally and patient recruitment progressing smoothly in multiple countries including China, the U.S., Japan and Australia. Additionally, the company is actively exploring HLX43's therapeutic potential across 10 clinical studies in various solid tumors, including NSCLC, TC, cervical cancer (CC), hepatocellular carcinoma (HCC), esophageal squamous cell carcinoma (ESCC), head and neck squamous cell carcinoma (HNSCC), nasopharyngeal cancer (NPC), colorectal cancer (CRC), and gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Both monotherapy and combination therapies of HLX43 are ongoing simultaneously to further exploit the synergistic effects of ADC-mediated cytotoxicity and other agents.

As HLX43's efficacy validated in later-line treatment of NSCLC, Henlius will further promote the front-line regimens for HLX43, accelerating the delivery of this novel treatment option to more patients with advanced or metastatic solid tumors.

【Reference】

[1] Detterbeck F C, Parsons A M. Thymic tumors: A review of current diagnosis, classification, and treatment[M]. 2008.

[2]国际胸腺恶性肿瘤协作组织(ITMIG)关于胸腺瘤和胸腺癌的WHO组织学分类的共识

[3] Luis Cabezón-Gutiérrez, et al. Update on thymic epithelial tumors: a narrative review. Mediastinum 2024;8:33.

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[5] World Health Organization. WHO Classification of Tumors Online, Thoracic Tumors, Tumors of the Thymus, 5th ed.; World Heath Organization: Geneva, Switzerland 2021. Available online: https://tumorclassification.iarc. who.int/chapters/35.

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