Shanghai, China, April 28th, 2022 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the investigational new drug application (IND) for a phase 1 clinical trial of HANSIZHUANG (serplulimab), an innovative anti-PD-1 monoclonal antibody (mAb) independently developed by the Company, in combination with HLX26, an innovative anti-LAG-3 mAb, for the treatment of advanced/metastatic solid tumours or lymphomas has been approved by the National Medical Products Administration (NMPA). To date, there is no anti-PD-1 mAb and anti-LAG-3 mAb combination therapy approved in China. The combination therapy of dual immune checkpoint inhibitors is expected to bring new treatment for patients with solid tumours and lymphomas in China.
Synergistic effects in anti-tumour shown on HLX26 combined with HANSIZHUANG
LAG-3 (lymphocyte-activation gene 3) is an immune checkpoint receptor and a new generation of immunotherapy target after PD-1/L1 and CTLA-4. LAG-3 is mainly expressed on human immune cells, including activated T cells and part of NK cells, and negatively regulates T cells' proliferation, activation, and homeostasis[1-2]. Clinical studies have shown that LAG-3 inhibitors are effective against lung cancer, breast cancer, melanoma, head and neck cancer, hematological malignancy and so on.
HLX26 is a human mAb targeting LAG-3 extracellular domains, which developed independently by Henlius. The first subject has been dosed with HLX26 for the phase 1 clinical trial in patients with advanced/metastatic solid tumours or lymphomas. HLX26 can block the LAG-3-mediated signaling pathway to restore the killing function of T-cell. Pre-clinical studies have proven that HLX26 has the anti-tumour effect and favorable tolerability and safety. Particularly in in vitro and animal studies shown that HLX26 in combination with serplulimab have a significant synergistic effect in anti-tumour. These results lay the foundation for further clinical studies on combination usage. Thus, the FDA has approved the anti-PD-1 mAb combined with anti-LAG-3 mAb for the first-line treatment of metastatic melanoma, indicating a promising prospect in tumour therapy.
Immuno-oncology combination therapies are conducted with HANSIZHUANG
HANSIZHUANG (serplulimab) is the first innovative mAb developed by Henlius. It has been approved by the NMPA for the treatment of microsatellite instability-high (MSI-H) solid tumours. Henlius actively promotes HANSIZHUANG in conjunction with in-house products of the company such as tumour-specific target, angiogenesis target, immunotherapeutic target, etc. and chemotherapy drugs to conduct immune combination therapies in a wide variety of indications, such as lung cancer, hepatocellular carcinoma, esophageal carcinoma, head and neck squamous cell carcinoma and gastric cancer, etc. The IND for a phase 2 clinical trial of HANSIZHUANG in combination with HANBEITAI (bevacizumab biosimilar) and HLX07 for the first-line treatment of unresectable or metastatic hepatocellular carcinoma has been approved by the NMPA. In the first-line treatment of lung cancer, HANSIZHUANG in combination with HLX07 for the first-line treatment of EGFR high expression squamous non-small cell lung cancer (sqNSCLC). In addition, the NDAs of the treatment for sqNSCLC and extensive-stage small cell lung cancer (ES-SCLC) have been accepted by the NMPA. Henlius also plans to file MAA on ES-SCLC in the EU in 2022. Up to date, no PD-1 has been approved globally for first-line treatment of SCLC, and HANSIZHUANG would potentially be the world’s first PD-1 inhibitor for the first-line treatment of SCLC.
Underpinned by the patient-centric strategy, Henlius has achieved an overall layout of the immune checkpoint products of PD-1/L1, CTLA-4, LAG-3, etc., proactively exploring immuno-oncology combination therapy. The company has been developing a forward-looking presence in bispecific antibodies and the antibody-drug conjugates (ADC), committing to bringing affordable and high-quality innovative biologics to patients around the world.
About HANSIZHUANG
HANSIZHUANG (recombinant humanized anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first innovative monoclonal antibody developed by Henlius. Up to date, 1 indication is approved for marketing in China, 2 NDAs have been accepted by the NMPA, and 9 clinical trials are ongoing across the world.
HANSIZHUANG was approved by the NMPA for the treatment of MSI-H solid tumors in March 2022 and actively promotes its synergy with in-house products of the company and innovative therapies. It has successively obtained clinical trial licenses in China, the United States, the European Union and other countries and regions to initiate 9 clinical trials on immuno-oncology combination therapies worldwide in a wide variety of indications, such as lung cancer, esophageal carcinoma, head and neck squamous cell carcinoma and gastric cancer, etc., and covering the full range of first-line treatments of lung cancers. As of now, the company has enrolled more than 2,800 subjects in China, Turkey, Poland, Georgia and other countries and regions, and the proportion of Caucasian is over 30% in two MRCTs, making HANSIZHUANG an anti-PD-1 mAb with one of the largest global clinical data pools. The NDAs of the treatment for squamous non-small cell lung cancer (sqNSCLC) and the first-line treatment of extensive small-cell lung cancer (ES-SCLC) have been accepted by the NMPA, and the FDA granted orphan drug designation to HANSIZHUANG for treatment of small cell lung cancer (SCLC). The MAA of ES-SCLC is expected to be filed in the EU in 2022, which makes HANSIZHUANG potentially the world’s first anti-PD-1 mAb for the first-line treatment of SCLC.
References
[1] Ruffo E, Wu R C, Bruno T C, et al. Lymphocyte-activation gene 3 (LAG3): the next immune checkpoint receptor[C] //Seminars in immunology. Academic Press, 2019, 42: 101305.
[2] Solinas C, Migliori E, De Silva P, et al. LAG3: the biological processes that motivate targeting this immune checkpoint molecule in human cancer[J]. Cancers, 2019, 11(8): 1213.