Shanghai, China, Oct 17th, 2022 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the investigational new drug (IND) application for clinical trial of HLX60 (recombinant anti-GARP humanised monoclonal antibody injection), independently developed by the company, was approved by the National Medical Products Administration (NMPA) for the treatment of solid tumours and lymphomas. HLX60 is the first IND approved anti-GARP monoclonal antibody (mAb) in China and is expected to be the first-in-class anti-GARP mAb.
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) [1]. 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 [2–4]. 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 [5-6].
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 HLX60 has anti-tumour effects and has a good safety profile. Plus, HLX60 in combination with HANSIZHUANG (serplulimab), an innovative anti-PD-1 mAb independently developed by Henlius, demonstrating a synergistic effect in inhibiting tumour growth. It is worth mentioning that it only takes Henlius about 16 months to move HLX60 from molecular determination to clinical stage with a robust cross-functional coorperation. Recently, the phase 1 clinical trial application of HLX60 in combination with HANSIZHUANG for the treatment of advanced or metastatic solid tumours has been approved in Australia.
Underpinned by the patient-centric strategy, Henlius has built an innovative product pipeline with many emerging targets, including PD-1/L1, LAG-3, GARP, TIGIT, BRAF etc. Regarding antibody technology as a core, Henlius will continue conducting clinical studies for more innovative products in bispecific antibodies and the antibody-drug conjugates (ADC) and exploring combination therapies with improved efficacy to provide patients with quality and affordable biologics.
Reference
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