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Henlius Novel Anti-GARP and Anti-PD-1 Dual mAb Therapy Received Clinical Trial Approval in Australia



Shanghai, China, Aug 26th, 2022 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the phase 1 clinical trial for the company’s self-developed HLX60, a novel anti-GARP monoclonal antibody (mAb), in combination with HANSIZHUANG (serplulimab), an innovative anti-PD-1 mAb independently developed by the company for the treatment of advanced or metastatic solid tumours has been approved by the relevant Human Research Ethics Committee (HREC), and Clinical Trial Notification (CTN) has been acknowledged by the Therapeutic Goods Administration (TGA), Australia. At present, no anti-GARP antibody has been approved for marketing globally.

Immune checkpoint inhibitor (ICI) therapies have offered a novel way to attack tumour cells in recent years. Current research on immune checkpoint inhibitors is mainly focused on anti-CTLA-4 (cytotoxic T lymphocyte associated antigen-4) antibody, anti-PD-1 (programmed cell death protein 1) antibody, and anti-PD-L1 (programmed cell death-ligand 1) antibody. PD-1/PD-L1 plays a vital role in immune suppression and have been approved for treating melanoma, non-small cell lung cancer, hepatocellular carcinoma, classical Hodgkin lymphoma, etc. However, only 30-40% of patients benefit from the treatment of immune checkpoint inhibitors and their tumours still recur or progress. Some cancer species still lack response to ICIs [1-2]. Therefore, there is an urgent need to develop new therapies to meet the huge medical needs.

Transforming growth factor-β (TGF-β) is a pleiotropic cytokine expressed by the majority of cells and found in many tissues. There are three TGF-β receptor ligands: TGF-β1, TGF-β2, and TGF-β3, with TGF-β1 playing critical roles in a variety of biological processes including cell proliferation, development, apoptosis, fibrosis, angiogenesis, wound healing, cancer, and many others [3–5]. The glycoprotein-A repetitions predominant (GARP) is highly expressed on the surface of activated Tregs and platelets and acts as a docking receptor by binding to latent transforming growth factor-β1 (LTGF-β1) [6]. It concentrates LTGF-β1 on the cell surface and releases active TGF-β1 in the tumour microenvironment (TME), thus inhibiting anti-tumour immune response and inducing tumour cell growth, proliferation and invasion [7-8].

HLX60 is a self-developed novel anti-GARP mAb that binds to GARP and specifically blocks the release of GARP mediated TGF-β1, thus relieving the immunosuppression caused by TGF-β1, reversing the immunosuppressive TME, and improving anti-tumour immune response. Furthermore, by inducing antibody dependent cell-mediated cytotoxicity (ADCC) effect, HLX60 can deplete GARP positive tumour cells as well as immunosuppressive cells such as Tregs. Several pre-clinical studies have shown that combining HLX60 and HANSIZHUANG has a synergistic effect in inhibiting tumour growth and has good tolerance and safety. These findings suggested that the combination therapy of HLX60 and HANSIZHUANG is superior to either HANSIZHUANG or HLX60 monotherapy.

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. Meanwhile, 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, esophageal carcinoma, head and neck squamous cell carcinoma and gastric cancer, etc., committing to bringing affordable and high-quality innovative biologics to patients around the world.

About Serplulimab

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, 3 NDAs have been accepted by the NMPA, and 11 clinical trials are ongoing across the world.

HANSIZHUANG was approved by the NMPA for the treatment of MSI-H solid tumours 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 11 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 3,100 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 first-line treatment for squamous non-small cell lung cancer (sqNSCLC), extensive small-cell lung cancer (ES-SCLC), and esophageal squamous cell carcinoma (ESCC) have been accepted by the NMPA, which makes HANSIZHUANG potentially the world’s first anti-PD-1 mAb for the first-line treatment of SCLC. Furthermore, HANSIZHUANG was recommended by the 2022 CSCO Guidelines for Diagnosis and Treatment of Small Cell Lung Cancer (SCLC) for the treatment of ES-SCLC and was also granted orphan drug designation by the FDA for treatment of SCLC.


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