F-star Therapeutics Ltd., a clinical-stage biopharmaceutical company focused on transforming the lives of patients with cancer through the development of innovative tetravalent bispecific (mAb2TM) antibodies, today announces the publication of preclinical data on the potent anti-tumor activity of FS120, a first-in-class dual-agonist tetravalent bispecific antibody targeting CD137 and OX40, in leading peer-reviewed journal Cancer Immunology Research.
Preclinical data from the article show that FS120 delays tumor growth by improving the activation and proliferation of peripheral T cells. These data also reinforce the superiority of dual agonist targeting over alternative TNFR-targeting agonists and support the clinical development of FS120 to treat patients with cancer.
FS120 is a first-in-class dual agonist bispecific antibody that has the potential to address ‘cold’ tumors and overcome cancer resistance by simultaneously targeting CD137 (4-1BB) and OX40 (CD134, TNFRSF4), two receptors which are part of the Tumor Necrosis Factor Receptor family (TNFRSF) of receptors and broadly expressed on activated T-cells and NK cells. Most (TNFRSF) -targeting antibodies require cross-linking via Fcγ receptors (FcγRs), which can limit their clinical activity and lead to undesirable toxicity effects. Preclinical data from this study show that FS120 can activate both CD4+and CD8+ T-cells in an FcγR-independent mechanism, therefore promoting focused immune stimulation. FS120 is currently a clinical stage program, with the investigational new drug application being accepted by the Food and Drug Administration (FDA) earlier this year.
In this study, FS120 showed greater anti-tumor activity than a combination of CD137 and OX40 agonists, which was associated with activation and proliferation of CD4+ and CD8+ T-cells independently of FcγR interaction. Furthermore, FS120 induced lower levels of liver T-cell infiltration when compared to a crosslink-independent CD137 agonist monoclonal antibody.
A link to the full study can be found here.
Neil Brewis, CSO of F-star, said: “Driven by the open IND filed earlier this year, these data are a great validation of F-star’s tetravalent bispecific technology and a further endorsement for the clinical development of FS120. FS120 exhibits disruptive activity in cold tumors and has been shown to successfully induce T-cell activation in an FcγR-independent manner, which can potentially display broader clinical activity, likely to be used in a combination drug therapy, compared to already existing compounds. This is an exciting time for us as we continue to develop our pipeline and progress our research towards improving treatment outcomes for patients with difficult-to-treat cancers.”
About F-star Therapeutics Ltd
F-star is a leading clinical-stage biopharmaceutical company delivering tetravalent bispecific antibodies for a paradigm-shift in cancer therapy. By developing medicines that seek to block tumorimmune evasion, the Company’s goal is to offer patients greater and more durable benefits thancurrent immuno-oncology treatments. Through its proprietary tetravalent, bispecific antibody(mAb2TM) format, F-star is generating first- and best-in-class drug candidates with monoclonal antibody-like manufacturability. Building on the combined expertise of its world-class management team and scientific leadership, F-star is poised to deliver the next breakthrough immunotherapies for patients with cancer. For more information visit www.f-star.com.
Article sourced from: http://www.f-star.com/media/93055/fs120-data-publication-final-csc.pdf
Published on: 09.04.2020
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