Shanghai, China, Jan 4th, 2022 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the application for an investigational new drug (IND) of HLX35 (recombinant humanised anti-EGFR and anti-4-1BB bispecific antibody injection) for the treatment of advanced malignant solid tumors independently developed by the company was approved by the National Medical Products Administration (NMPA). The company is proposing to commence the Phase 1 clinical trial in Chinese Mainland (excluding Hong kong, Macau and taiwan region) in the near future. At present, no bispecific antibody targeting EGFR and 4-1BB has been approved for marketing globally. HLX35 is expected to be a first-in-class anti-4-1BB×EGFR bispecific antibody.
Based on EGFR and 4-1BB, two key targets in the anti-tumour process, Henlius explored new therapeutic methods to further meet the clinical needs of patients. Being a member of the tumour necrosis factor receptor superfamily, 4-1BB, also known as CD137, is expressed on the surface of activated T cells, NK cells, NKT cells, mast cells and so on. It provides co-stimulatory signals and activates cytotoxic effects of CD8+ T cells and facilitates the development memory T cells. In addition, 4-1BB signaling can activate NK cells and dendritic cells which further supports cytotoxic T cell activation. These features make 4-1BB a popular target for enhanced cancer immunotherapy. Most 4-1BB monoclonal antibodies (mAbs) and bispecific antibodies are currently in the early clinical or preclinical stage, with indications for advanced solid tumours, melanoma and non-Hodgkin's lymphoma. Early clinical studies showed that 4-1BB antibodies had acceptable safety, tolerability, and certain antitumor efficacy. EGFR belongs to the receptor tyrosine kinases family and plays an important role in maintaining normal cell functions such as cell proliferation, differentiation and migration. Mutation or overexpression of EGFR is considered to be closely associated with the occurrence of various solid tumours including non-small cell lung cancer, colorectal cancer, head and neck cancer, breast cancer, cervical cancer, bladder cancer, thyroid cancer, and gastric cancer. Anti-EGFR mAb is currently approved for EGFR-positive tumours in combination chemotherapy or radiotherapy, or monotherapy for non-small cell lung cancer, colorectal cancer, and squamous cell carcinoma, etc.
HLX35 is an innovative anti-EGFR and anti-4-1BB bispecific antibody independently developed by Henlius. According to the results of pre-clinical studies, HLX35 showed a superior tumour-suppressive effect than mono or combo therapy of anti-4-1BB and anti-EGFR mAb. Bispecific antibody drugs effectively combine the advantages of both targets. HLX35 binds to the EGFR molecules on the tumour surface, suppresses the EGFR activation and downstream signaling pathways phosphorylation to kill tumour cells. Also, HLX35 binds to the 4-1BB molecules on the surface of immune cells (T and NK cells), with EGFR cross-linking to gather more immune cells around the tumor and stimulate the activity of immune cells in the microenvironment, to synergistically kill the tumour cells and improve the efficacy. In November 2020, the company has granted Binacea pharma Inc., in respect of HLX35, a license for it to research, develop, manufacture and commercialise the HLX35 globally except for China (including Hong Kong, Macau and Taiwan region).
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. The company has also built an innovative product pipeline with many emerging targets, including c-MET, TROP2, TIGIT, BRAF, etc. and has been developing a forward-looking presence in bispecific antibodies and the antibody-drug conjugates (ADC). Looking forward, Henlius will continue its momentum for innovation, further strengthening the in-licensing and collaboration on external innovative assets, and bringing more high-quality and affordable therapies to patients worldwide.
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