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First Subject Dosed in China on Phase 1/2 Trial of Henlius' Anti-PD-L1×TIGIT Bispecific Antibody

2022-07-06


Shanghai, China, July 6th, 2022-Shanghai Henlius Biotech, Inc. (2696.HK) today announced that the first subject has been dosed in a phase 1/2 clinical trial of HLX301, a recombinant anti-PD-L1 and anti-TIGIT bispecific antibody (BsAb), for the treatment of locally advanced or metastatic solid tumours or lymphomas in China. At present, no BsAb targeting PD-1/PD-L1 and TIGIT has been approved for marketing globally. HLX301 is expected to be a first-in-class anti-PD-L1×TIGIT BsAb.


T-cell immunoglobulin and ITIM domains (TIGIT) is an inhibitory receptor, mainly expressed on natural killer (NK) cells and activated CD8+ T cells, CD4+ T cells, and T regulatory cells. TIGIT binds to the ligand CD155 (poliovirus receptor, PVR), mainly expressed on antigen-presenting cells (APC) or the surface of tumour cells, to down-regulate T cell and NK cell functions[1-2]. As an inhibitory receptor, TIGIT can inhibit innate and adaptive responses in various mechanisms of action and act as a “brake” like PD-1/PD-L1 does to stop T cells from attacking tumours[3].


HLX301 is an innovative anti-PD-L1 and anti-TIGIT bispecific antibody, composed of an anti-PD-L1 IgG1 subtype monoclonal antibody coupled with an anti-TIGIT variable domain of heavy-chain antibody. Its TIGIT binding domain is derived from VHH fragments with high affinity and high specificity to TIGIT, selected from the company’s synthetic humanized llama VHH library. HLX301 can simultaneously block both PD-1/PD-L1 and TIGIT/PVR pathways, inhibit tumour growth. It is expected to treat a variety of advanced cancers, including non-small cell lung cancer, head and neck squamous cell carcinoma, esophageal squamous cell carcinoma, etc. Pre-clinical studies reported that HLX301 is superior to blocking either pathway alone or anti-PD-L1 + anti-TIGIT combinational therapy, and can restore TCR signaling, stating a good tolerance and safety, thus paving the way for further clinical development. In February 2022, the first subjct has been dosed HLX301 in a phase 1 clinical study for the treatment of locally advanced or metastatic solid tumors in Australia. In March 2022, the application of a phase 1 clinical trial of HLX301 for the treatment of advanced tumours has been approved by the National Medical Products Administration.


Underpinned by the patient-centric strategy, Henlius has built an innovative product pipeline with many emerging targets, including PD-1/L1, LAG-3, TIGIT, BRAF, etc. and has been developing a forward-looking presence in bispecific antibodies, the antibody-drug conjugates (ADC) and fusion protein based on our own core antibody technologies. Looking forward, Henlius will continue its momentum for innovation, bringing more high-quality and affordable therapies to patients worldwide.


About HLX301 Phase 1/2 Trial


This open-label, multicentre, phase 1/2 study aims to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumour efficacy of HLX301 in patients with locally advanced/metastatic solid tumour or lymphoma. The study consists of three parts: phase 1a dose escalation, phase 1b dose expansion, and phase 2 clinical expansion. Eligible patients will receive intravenous infusion of HLX301 as a single agent every two weeks. Phase 1a uses the Bayesian optimal interval (BOIN) design to investigate safety, and determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of HLX301. Phase 1b will further evaluate the pharmacokinetic and pharmacodynamic characteristics as well as the preliminary efficacy, to determine the recommended phase 2 dose (RP2D). The primary objective of the phase 2 study is to evaluate the antitumour activity of HLX301 in patients with locally advanced/metastatic solid tumour or lymphoma. The primary endpoints are objective response rate (ORR), disease control rate (DCR), and duration of response (DOR) assessed by investigators. Secondary objectives are to evaluate the safety of HLX301 and to investigate the association between PD-L1 expression levels and the antitumour activity of HLX301 in these patients.


Reference

[1] Chauvin JM, Zarour HM. TIGIT in cancer immunotherapy. J Immunother Cancer. 2020;8(2).

[2] Sanchez-Correa B, Valhondo I, Hassouneh F, et al. DNAM-1 and the TIGIT/PVRIG/TACTILE Axis: Novel Immune Checkpoints for Natural Killer Cell-Based Cancer Immunotherapy. Cancers (Basel). 2019;11(6):877.

[3] Yue C, Gao S, Li S, Xing Z, Qian H, Hu Y, Wang W and Hua C (2022) TIGIT as a Promising Therapeutic Target in Autoimmune Diseases. Front. Immunol. 13:911919.