Shanghai, China, Mar 15th, 2023 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the phase 1 clinical trial for the company’s self-developed HLX51, a novel humanized agonistic anti-OX40 monoclonal antibody (mAb) for the treatment of patients with advanced/metastatic solid tumours and lymphomas has been approved by the National Medical Products Administration (NMPA). At present, there is no anti-OX40 mAb has been approved for marketing globally.
Immune checkpoints are playing a crucial part in immunotherapy, which has emerged in recent years as a novel approach to combating tumour cells with distinct advantages and enormous promise [1]. In general, immune checkpoints fall into two categories: immunosuppressive checkpoints such as PD-11/PD-L1 and CTLA-4, and stimulatory immune checkpoints such as OX40 (Tumour necrosis factor receptor superfamily member 4) [2]. OX40, also known as CD134 and TNFRSF4, is mainly expressed on activated T cells. When OX40 is combined with its ligand OX40L, it induces co-stimulatory signals, which prevent activation induced cell death and consequently promote the survival of effector T cells, resulting in the generation of memory T cells [3-4]. Unlike immune checkpoint inhibitors, which "removes the brakes" on the tumour immune response by releasing inhibitory signals that activate T cells, immune checkpoint agonists that target stimulatory immune checkpoints can enhance T cells by "stepping on the gas pedal", becoming a popular target for next-generation immunotherapy [5].
HLX51 is an agonistic anti-OX40 humanized mAb independently developed by Henlius. By competitively binding OX40 with OX40L, HLX51 can replace OX40L to activate OX40 without reducing the downstream signal of OX40, thereby promoting the proliferation of immune cells, and promoting the killing ability of T cells. it can also inhibit the differentiation and activity of regulatory T cells (Treg), relieve the immunosuppression mediated by Treg and in the tumour microenvironment and further enhance the function of effector T cells. Preclinical studies have shown that HLX51 can inhibit tumour growth and has good tolerance and safety.
Underpinned by the patient-centric strategy, Henlius has achieved an overall layout of the immune checkpoints of PD-1/L1, CTLA-4, LAG-3, TIGIT, etc., proactively exploring immuno-oncology combination therapy. Future exploration of HLX51 is also anticipated to involve combinations with various in-house antitumor medicines. Looking forward, Henlius will continue conducting clinical studies for more innovative products in bispecific antibodies and the antibody-drug conjugates (ADC) and exploring combination therapies with enhanced efficacy to provide patients with quality and affordable biologics.
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