Release Date: 23-Jan-2025
FS118 is a promising tetravalent bispecific antibody developed by F-star Therapeutics, a subsidiary of InvoX Pharma, designed to target two key immune checkpoints: lymphocyte-activation gene 3 (LAG-3) and programmed cell death ligand 1 (PD-L1). These two targets play significant roles in immune evasion by tumors, making them prime candidates for cancer immunotherapy. FS118’s dual action aims to enhance the body’s immune response by inhibiting both LAG-3 and PD-L1, which are often involved in suppressing T-cell activity and promoting tumor survival. This strategy has the potential to overcome the immune suppression that limits the effectiveness of current immune checkpoint inhibitors (CPIs).
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One of the critical advantages of FS118 over traditional treatments is its ability to engage both checkpoint pathways simultaneously, which has shown greater preclinical activity compared to monoclonal antibody combinations. The dual targeting of LAG-3 and PD-L1 could offer a more effective strategy for overcoming immune resistance, particularly in patients who have failed CPI treatments. In preclinical models, FS118 has demonstrated the ability to downregulate LAG-3 on tumor-infiltrating lymphocytes (TILs), a critical aspect of modulating the immune response within tumors. Additionally, FS118 has been shown to increase soluble LAG-3 (sLAG-3) in the serum, a mechanism that is believed to play a pivotal role in overcoming resistance to anti-PD-1 therapies.
The design of FS118 as a tetravalent bispecific antibody is central to its mechanism of action. This structure enables it to induce a novel shedding of LAG-3, a process that has been linked to improved immune response and enhanced anti-tumor activity. This novel mechanism of action is crucial for addressing the growing need for more effective cancer treatments, especially for patients who do not respond well to existing therapies.
Currently, FS118 is undergoing Phase 2 clinical trials targeting several cancers, including diffuse large B-cell lymphoma, head and neck cancer, and non-small cell lung cancer. These trials aim to evaluate the therapeutic potential of FS118 in both CPI-resistant and CPI-naive patients, with the goal of improving clinical outcomes across a range of solid and hematological malignancies.