Henlius Receives the NMPA IND Approval for Its PD-L1-Targeting ADC HLX43 in Combination with Novel Anti-PD-1 mAb Serplulimab
Shanghai, China, January 6, 2025 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the investigational new drug (IND) application for a phase 1b/2 clinical trial of HLX43 for Injection, the antibody-drug conjugate (ADC) product that developed by the company based on the collaboration with MediLink Therapeutics, in combination with the company's independently developed innovative anti-PD-1 monoclonal antibody (mAb) HANSIZHUANG (serplulimab), has been approved by the China National Medical Products Administration (NMPA), for the treatment of advanced/metastatic solid tumours. In December 2024, a phase 1b/2 clinical trial of HLX43 has been approved by the NMPA for monotherapy or combination therapy to treat patients with advanced/metastatic solid tumours. At present, no PD-L1 targeting ADC has been approved for marketing globally.
Immune checkpoint inhibitors represented by PD-1/PD-L1 monoclonal antibodies have emerged in recent years and revolutionised all lines of immuno-oncology (IO) therapies for tumour patients. However, there are still many patients do not respond to or develop resistance to PD-1/PD-L1-targeted therapies[1]. Therefore, immunotherapy in combination with other treatments is expected to be a promising therapeutic strategy for patients who develop drug resistance or with “cold” tumours. Meanwhile, the emergence of varied new modalities has provided new options for immunotherapies to combined with. From which, ADC is a novel targeting therapy with the most prominent anti-tumour efficacy, while the utility of ADC as a monotherapy is also limited by issues such as drug resistance. Therefore, the combination of ADCs and immunotherapies may exert synergistic anti-tumour activities that ultimately leading to potent efficacy and durable responses of the IO therapeutics, and potentially reversing the emergence of resistance, further providing more effective treatment options to fulfill the unmet clinical needs[2].
HANSIZHUANG (serplulimab), Henlius’ first self-developed innovative Anti-PD-1 mAb, is the world’s first anti-PD-1 mAb for first-line treatment of extensive-stage small cell lung cancer (ES-SCLC). It has been approved in China and several Southeast Asian countries, benefiting over 90,000 patients. Focusing on lung and gastrointestinal cancer, the synergy of HANSIZHUANG with in-house products of the company and innovative therapies are being actively promoted. Up to date, HANSIZHUANG has been approved by the NMPA for the treatment of 5 indications, such as squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC), esophageal squamous cell carcinoma (ESCC) and non-squamous non-small cell lung cancer (nsNSCLC). Furthermore，the marketing applications of the first-line treatment for ES-SCLC is under review by the European Medicines Agency (EMA), which is expected to be approved in 2025. Meanwhile, the company has initiated more than 10 clinical trials on immuno-oncology combination therapies in a wide variety of indications with more than 4,600 subjects enrolled in China, the U.S., Turkey, Poland, Georgia and other countries and regions.
HLX43 is one of the first ADC candidates of Henlius to enter into clinical development. In November 2023, the company has dosed the first subject for a phase 1 clinical trial of HLX43, making it the first PD-L1-targeting ADC in China to enter a clinical trial. Combining the selectivity of targeted monoclonal antibodies with the highly potent cytotoxic agent, HLX43 could exert anti-tumour effects through specific binding to the PD-L1 expressed on the surface of tumour cells and release cytotoxic payloads after internalisation by the cancer cells. Up to date, HLX43 has exhibited good anti-tumour effects and a favorable safety profile in nonclinical pharmacology, pharmacokinetic studies and safety evaluation. The results of the studies were published as poster presentation at the 2023 European Society of Medical Oncology (ESMO) Congress. Leveraging the company’s competitive edge of an integrated antibody drug R&D platform, Henlius is accelerating the development of ADCs and diversified drug conjugates, and actively exploring combination therapies involving ADCs and immunotherapies to encourage progress in the next wave innovation of “IO+ADC”.
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.
【Reference】
[1] Attili I, et al. Strategies to overcome resistance to immune checkpoint blockade in lung cancer[J]. Lung cancer: Journal of the International Association for the Study of Lung Cancer, 2021(154-):154.
[2] Eleonora.Nicolò, et al. "Combining antibody-drug conjugates with immunotherapy in solid tumors: current landscape and future perspectives." Cancer treatment reviews 106(2022):102395.
