SHANGHAI, China I June 26, 2023 I Shanghai Henlius Biotech, Inc. (2696.HK) announced that the investigational new drug application (IND) of its ipilimumab biosimilar HLX13, an recombinant anti-CTLA-4 fully human monoclonal antibody(mAb) injection, has been approved by the National Medical Products Administration (NMPA), for the treatment of hepatocellular carcinoma(HCC).

HLX13 is a biosimilar of ipilimumab independently developed by Henlius in accordance with Chinese Biosimilar Guidelines. HLX13 can block T-cell inhibitory signals induced by the CTLA-4 pathway, increasing the number of reactive T-effector cells which mobilize to mount a direct T-cell immune attack against tumour cells. CTLA-4 blockade can also reduce T-regulatory cell function, which may contribute to an anti-tumour immune response. HLX13 may selectively deplete T-regulatory cells at the tumour site, leading to an increase in the intratumoral T-effector/ T-regulatory cell ratio which drives tumour cell death. Strictly following the principles of comparability, stepwise development, consistency and similarity assessment, Henlius has conducted a series of head-to-head pre-clinical studies to compare the chemical manufacture and control (CMC), pharmacology, pharmacokinetics and toxicokinetics profiles, immunogenicity and toxicity profile of HLX13 and originator ipilimumab. Results from these studies showed that there is a high similarity or no significant difference between HLX13 and originator ipilimumab.

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 addition to PD-1/L1 and LAG-3, CTLA-4 is also an inhibitory immune checkpoint which expressed on regulatory T cells and activated T cells and has a higher affinity to B7 molecules compared with CD28, thus can competitively bind to B7 molecule to inhibit the proliferation and activation of T cells[2]. Meanwhile, the potential of the combination therapy of anti-CTLA-4 mAb and anti-PD-1/L1 mAb is becoming more and more attractive. Based on their mechanisms of action (MoA), there is probably a synergistic effect between these two immune checkpoint inhibitors, which is expected to bring additional clinical benefit to patients[3].

Henlius has established a diversified product pipeline and an overall layout of the immune checkpoints of PD-1/L1, CTLA-4, LAG-3, TIGIT, etc., proactively exploring immuno-oncology combination therapy. With HANSIZHUANG, which was launched in March 2022, as a backbone product, Henlius continues to explore the combination therapies between HANSIZHUANG and self-developed products, covering a wide variety of indications including lung cancer, esophageal squamous cell carcinoma, head and neck squamous cell carcinoma and gastric cancer. Underpinned by the patient-centric strategy, Henlius will continue to broaden its innovative layout in immuno-oncology combination therapy, and commit to bringing affordable and high-quality innovative biologics to patients around the world.

[1] Robert C. A decade of immune-checkpoint inhibitors in cancer therapy[J].Nature Communications,2020,11(1). 

[2] Wolchok J D , Saenger Y .The Mechanism of Anti‐CTLA‐4 Activity and the Negative Regulation of T‐Cell Activation[J].The Oncologist,2008,13 Suppl 4(Supplement 4):2-9.

[3] Victor T S, Rech A J, Maity A,et al.Radiation and Dual Checkpoint Blockade Activates Non-Redundant Immune Mechanisms in Cancer[J].Nature, 2015, 520(7547).

SOURCE: Henlius Biotech