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First Subject Dosed of the Phase 1 Clinical Trial on Henlius Novel Anti-EGFR×4-1BB Bispecific Antibody HLX35 for the Treatment of Advanced or Metastatic Solid Tumours

2022-06-07



Shanghai, China, June 6th, 2022 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first subject was dosed of Phase 1 clinical trial of HLX35, an recombinant humanised anti-EGFR and anti-4-1BB bispecific antibody injection independently developed by the company, for the treatment of advanced or metastatic solid tumours. 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-EGFRx4-1BB 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. 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[1]. Being a member of the tumour necrosis factor receptor superfamily, 4-1BB is expressed on the surface of activated T cells, NK cells, NKT cells and so on[2]. 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[3]. These features make 4-1BB a popular target for enhanced cancer immunotherapy. The potential indications of anti-4-1BB monoclonal antibodies (mAbs) and bispecific antibodies are advanced solid tumours, melanoma, non-Hodgkin's lymphoma and so on.


HLX35 is an innovative anti-EGFR and anti-4-1BB bispecific antibody independently developed by Henlius. It is expected to be used for the treatment of advanced malignant solid tumours. According to the results of pre-clinical studies, HLX35 showed a superior tumour-suppressive effect than mono or combo therapy of anti-EGFR and anti-4-1BB 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 tumour 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). At present, the phase 1 Clinical Trial Notification of HLX35 has been acknowledged by the Therapeutic Goods Administration 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, TIGIT, BRAF, etc., and has been pushing its early R&D research capabilities further while also upgrading the technology platform. The company is currently taking effort to explore different forms of antibody conjugates based on our own core antibody technologies and by using of novel conjugating technologies. Looking forward, Henlius is actively accelerating its evolution to an innovative Biopharma and improving efficiency through innovations. It will preserve its momentum for innovation by further strengthening the in-licensing and collaboration on external innovative assets and bringing more high-quality and affordable therapies to patients worldwide.


About NCT05360381

This multicentre, open-label phase 1 study aims to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of HLX35 in patients with advanced or metastatic solid tumours. The study has two parts: phase 1a is a dose-escalation study following “3+3” design; phase 1b is a dose-expansion study. Eligible patients will receive intravenous infusion of HLX35 every two weeks. The primary endpoints include the safety profile, dose limiting toxicity (DLT), maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of HLX35. The secondary endpoints include the pharmacokinetic parameters, pharmacodynamic parameters, immunogenicity, objective response rate (ORR), disease control rate (DCR) and duration of response (DOR) of HLX35.



References

[1] Guo, G., Gong, K., Wohlfeld, B., Hatanpaa, K. J., Zhao, D., and Habib, A. A. (2015). Ligand-independent EGFR signaling. Cancer Res.75, 3436–3441.

[2] Croft M. The role of TNF superfamily members in T-cell function and diseases[J]. Nature Reviews Immunology, 2009, 9(4): 271-285.

[3] Hashimoto K. CD137 as an Attractive T Cell Co-Stimulatory Target in the TNFRSF for Immuno-Oncology Drug Development[J]. Cancers, 2021, 13(10): 2288.