HLX43 is a novel ADC candidate that targeting programmed death-ligand 1 (PD-L1). As one of the first ADC candidates of Henlius to enter into clinical development, HLX43 is designed to address the issues of unresponsiveness or resistance to PD-1/L1 immunotherapies. With Henlius’ diversified portfolio and cornerstone product HANSIZHUANG, the company will further explore the potential of ADCs combining immunotherapies to provide more effective treatment options to fulfill the unmet clinical needs.
Combining the selectivity of targeted mAb with the highly potent cytotoxic agent, HLX43 has exhibited good anti-tumour effects and a favorable safety profile in preclinical studies, pharmacokinetic studies and safety evaluation. HLX43 has shown potent tumour suppression in several CDX and PDX models that were PD-1/L1 mAb resistant. What’s more, the results of the preclinical studies of HLX43 and HLX42 (an EGFR-targeting ADC) were published as poster presentations at the 2023 European Society of Medical Oncology (ESMO) Congress.
Looking forward, Henlius will further take efforts to promote the layout of our innovative portfolio by focusing on antibody and novel conjugating technologies, bringing more high-quality and affordable therapeutics for patients worldwide.
HLX43 is a novel PD-L1-targeting ADC candidate, comprised of a high-affinity fully human IgG1 mAb targeting PD-L1 conjugated with a novel cytotoxic payload through cleavable linkers, with the drug-to-antibody ratio is about 8. The cytotoxic payload of HLX43 is a novel DNA topoisomerase-I inhibitor which can cause double-strand breaks (DSBs) of DNA, block the replication machinery, thus trigger cancer cell apoptosis. When injected intravenously into the body, HLX43 linker-payload will be cleaved and released in tumour microenvironment (TME) with strong bystander killing effects. This unique mechanism of TME activation and payload release allows HLX43 to possess a higher therapeutic index and potency for treatment of solid tumours.