Henlius' PD-L1 ADC HLX43 Receives FDA Orphan Drug Designation for Thymic Epithelial Tumors

Key Insights

• Henlius' investigational antibody-drug conjugate HLX43, targeting PD-L1, has been granted Orphan Drug Designation by the U.S. FDA for treating thymic epithelial tumors.
• The drug combines a novel DNA topoisomerase I inhibitor with Henlius' self-developed PD-L1-targeting antibody and is currently in Phase I clinical trials across China, the United States, and Japan.
• HLX43 represents a first-in-class approach, as no antibody-drug conjugates targeting PD-L1 have been approved for marketing globally.

Henlius Biotech has achieved a significant regulatory milestone with its investigational antibody-drug conjugate HLX43 receiving Orphan Drug Designation from the U.S. FDA for the treatment of thymic epithelial tumors (TETs). The designation, announced by parent company Fosun Pharma in October, highlights the potential of this novel PD-L1-targeting therapy in addressing rare cancer indications.

Novel ADC Technology Platform

HLX43 represents an innovative approach to cancer treatment, combining Henlius' proprietary PD-L1-targeting antibody with a novel DNA topoisomerase I inhibitor. The company developed this antibody-drug conjugate through conjugation of a small-molecule toxin-peptide linker licensed from a third party with its self-developed antibody platform. This design is intended for treating advanced and metastatic solid tumors.

The therapeutic approach is particularly noteworthy as no antibody-drug conjugates targeting PD-L1 have received marketing approval globally, positioning HLX43 as a potential first-in-class treatment option.

Clinical Development Progress

HLX43 is currently advancing through Phase I clinical trials in China, with the thymic carcinoma cohort being part of an international multicenter study that has received approval for Phase I trials in both the United States and Japan. This global development strategy demonstrates Henlius' commitment to advancing the therapy across multiple regulatory jurisdictions simultaneously.

Combination Therapy Approach

In addition to the monotherapy development, Henlius has received approval from China's National Medical Products Administration (NMPA) to conduct clinical trials combining HLX43 with HLX07, a recombinant anti-EGFR humanized monoclonal antibody injection. This combination therapy targets advanced and metastatic solid tumors, with Henlius planning to initiate a Phase Ib/II clinical trial in mainland China.

HLX07, classified as a Therapeutic Biological Product Class 1, is an innovative biologic independently developed by Henlius that targets the EGFR receptor for treating advanced solid tumors. The dual-targeting approach combining PD-L1 and EGFR pathways represents a strategic effort to enhance therapeutic efficacy in difficult-to-treat cancer populations.

Regulatory Significance

The FDA's Orphan Drug Designation provides several advantages for HLX43's development in thymic epithelial tumors, including potential market exclusivity, tax credits for clinical trial costs, and expedited regulatory review processes. This designation is particularly valuable given the rarity of thymic epithelial tumors and the limited treatment options currently available for patients with this condition.

The regulatory approvals in multiple jurisdictions underscore the scientific merit of Henlius' ADC platform and its potential to address significant unmet medical needs in oncology. As the company continues to advance both monotherapy and combination approaches, HLX43 could represent a meaningful advancement in PD-L1-targeted cancer therapy.