May 13, 2026 – Shanghai Henlius Biotech, Inc. (2696.HK) announced that its independently developed c-Met/EGFR bispecific antibody–drug conjugate (ADC), HLX48 for injection, has received approval from the Human Research Ethics Committee (HREC) in Australia and been acknowledged by the Therapeutic Goods Administration (TGA). The study is intended to evaluate HLX48 in patients with advanced or metastatic solid tumors, with a first-in-human (FIH) Phase I clinical trial planned in Australia. As the first bispecific ADC developed by Henlius, the clinical approval of HLX48 reflects the company’s platform-based R&D system and pipeline advancement capabilities. It also may provide a new treatment option for patients with solid tumors such as non-small cell lung cancer (NSCLC) and colorectal cancer with EGFR/c-Met pathway abnormalities, including those with acquired resistance.

EGFR (epidermal growth factor receptor, ErbB1/HER1) and MET (hepatocyte growth factor receptor, HGFR), encoded by the MET proto-oncogene, are receptor tyrosine kinases that are widely expressed or aberrantly activated across mltiple tumor types. Studies have shown that co-activation of EGFR and MET signaling pathways is an important driver of tumor resistance and recurrence, and MET amplification has been identified as a major mechanism of acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) .¹ Therefore, simultaneous targeting of EGFR and MET is considered a key strategy to overcome resistance and improve treatment outcomes. Although EGFR/c-Met bispecific antibodies have demonstrated clinical efficacy and have been approved in NSCLC,² monotherapy still faces limitations such as modest response rates and disease progression. Accordingly, bispecific ADCs, which combine targeted binding with cytotoxic payload delivery, represent an important therapeutic approach with significant unmet clinical need.³

HLX48 is a novel ADC candidate developed by Henlius based on its proprietary Hanjugator™ ADC platform. It consists of an c-Met/EGFR bispecific antibody conjugated to a camptothecin- based DNA topoisomerase I inhibitor payload. The molecule features a highly hydrophilic linker-payload strategy and a moderate-potency payload design, with a drug-to-antibody ratio (DAR) of approximately 4, aiming to achieve an optimal balance between robust anti-tumor activity and manageable toxicity, thereby maximizing the clinical dose and fully leveraging the signal-blocking and immunomodulatory functions of the bispecific antibody. Preclinical pharmacological studies have demonstrated that HLX48 exhibits significant anti-tumor activity in multiple tumor models. Its conjugate exhibits bystander killing over 10-fold stronger compared with deruxtecan. In preliminary toxicology studies, HLX48 showed good tolerability in cynomolgus monkeys at 60 mg/kg administered once every three weeks (Q3W) for three doses.

HLX48 simultaneously binds with high affinity to EGFR and c-Met on the tumor cell surface, blocking their interaction with respective ligands (e.g., epidermal growth factor [EGF] and hepatocyte growth factor [HGF]), thereby synergistically inhibiting both key tumor growth and survival signaling pathways at the source, and is expected to overcome EGFR-targeted therapy resistance caused by MET amplification. Furthermore, through a specific affinity-differentiated design, HLX48 exhibits higher affinity for c-Met than for EGFR, enabling preferential targeting of c-Met, which is often aberrantly overexpressed in tumors, while reducing target-related toxicity caused by widespread EGFR expression in normal tissues, potentially broadening its therapeutic window. Upon target binding, HLX48 is rapidly internalized into tumor cells, where it releases the cytotoxic payload, directly inducing irreversible DNA damage and triggering tumor cell apoptosis. Additionally, thanks to the optimized linker-payload design, the released toxin from HLX48 possesses potent bystander killing effects, allowing it to diffuse to adjacent tumor cells with low or no antigen expression, thereby overcoming tumor heterogeneity to some extent and enhancing overall anti-tumor activity.

Hanjugator^™ is Henlius’ next-generation proprietary ADC technology platform. It employs a highly hydrophilic camptothecin-based linker–payload system that can flexibly tune payload potency across different targets. The platform preserves antibody biological functions while synergistically enhancing anti-tumor activity and expanding the therapeutic window. It also supports multiple cytotoxic mechanisms, and differentiated payload design may help overcome common drug resistance, providing a differentiated solution for next-generation ADC development.

Looking ahead, Henlius remains committed to a patient-centered R&D philosophy and will continue to leverage its integrated innovation platforms to accelerate the delivery of high-quality, affordable innovative therapies to patients worldwide.