On November 8, 2019 F-star Therapeutics ("F-star"), a clinical-stage biopharmaceutical company focused on transforming the lives of patients with cancer through the development of innovative tetravalent bispecific (mAb2) antibodies, reported that new preclinical data on FS120, a mAb² product candidate targeting OX40 and CD137, will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2019 Annual Meeting in National Harbor, Maryland, United States, being held from 06 – 10 November 2019 (Press release, f-star, NOV 8, 2019, View Source [SID1234550823]).

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FS120 is a potentially best-in-class dual agonist that has the potential to overcome cancer resistance by simultaneously engaging OX40 (CD134, TNFRSF4) and CD137 (4-1BB), two receptors found on the surface of tumor-infiltrating lymphocytes. Targeting this class of receptors using bispecific tetravalent binding mobilizes multiple arms of the immune system, which research shows is essential for eliminating tumors. F-star’s preclinical data demonstrated that FS120’s crosslink-dependent approach has the potential to provide therapeutic benefit, for example in combination with checkpoint antagonists, and reverse T cell exhaustion in immunosuppressive tumor environments.

Neil Brewis, CSO of F-star said "Recent clinical trials involving agonist molecules have reported that a meaningful anti-cancer response is often associated with liver toxicity, in line with preclinical observations. F-star’s OX40/CD137 mAb² antibody is showing preclinical evidence that an effective tumor-killing response can be decoupled from liver inflammation. We look forward to progressing FS120 into the clinic as we aim to potentially improve treatment outcomes for patients with difficult-to-treat cancers."

Some CD137 agonist antibodies have been shown to induce adverse effects either in clinical or in preclinical studies as they constitutively activate T cells and thus release cytotoxic immunity outside of the tumor. In contrast, FS120 is designed to mitigate off-target toxicity through conditional, crosslink-dependent activation upon binding to both OX40 and CD137, which are predominantly present on T cells in the tumor microenvironment.

F-star expects to submit an IND application for FS120 during the fourth quarter of 2019.

Details of the poster are below:

Crosslink-independent CD137 agonism is associated with liver inflammation

Abstract poster number: P775
Poster hall location: Prince George AB
Poster hall hours: 07:00 to 20:00 on Friday 08 November 2019
Poster presentation hours: 12:30 to 14:00 and 18:30 to 20:00 on Friday 08 November 2019