F-star Therapeutics, Inc. announced new clinical data from its potentially best-in-class clinical asset FS222, a CD137/PD-L1 targeting tetravalent bispecific antibody, at the European Society of Medical Oncology Immuno-Oncology (ESMO-IO) Annual Congress which is being held from December 7 - 9, 2022, in Geneva. FS222 targets critical tumoral immune-suppressing pathways via PD-L1 checkpoint blockade and has exhibited important costimulatory effects through potent clustering and activation of CD137, which in turn, synergistically promotes T cell activation and enhanced cytotoxic T cell responses. In preclinical models, engagement of PD-L1 and CD137 by FS222 induced T cell proliferation and cytokine production that was associated with significant tumor regression compared to the combination of CD137 and PD-L1 targeting monospecific antibodies.

Phase 1 Interim Efficacy and Safety Results on FS222 as of the Cut-Off Date of July 20, 2022: 33 patients had been treated to date with FS222 at dose levels of: 300 µg (n=1), 1 mg (n=1), 3 mg (n=1), 10 mg (n=1), 30 mg (n=5), 0.75 mg/kg (n=15), and 1 mg/kg (n=9); Median time on study was 58 days (range 19-359 days) with 11 patients ongoing; One non-squamous NSCLC, PD-L1 naïve patient experienced a complete response (CR) at 8 weeks, at a dose of 1mg/kg. The CR has remained persistent for 40.9 weeks as of 20th July 2022. 6 patients had disease stabilization (SD), 16 had progressive disease (RECIST 1.1), 2 were discontinued before week 8, and 8 were awaiting their week 8 evaluation.

FS222 showed a manageable safety profile with most adverse events (AEs) Grade 1-2. One patient experienced a DLT of Grade 3 febrile neutropenia. No patients discontinued FS222 due to an AE. Maximum tolerated dose was not reached, and dose escalation is ongoing.

The pharmacological activity was demonstrated by increased peripheral soluble target receptors and proliferating CD4+ and CD8+ T cells. Details of the poster presentation are as follows: Abstract Title: “First-in-human study to evaluate the safety and activity of FS222, a tetravalent bispecific antibody targeting PD-L1 and CD137, in patients with advanced solid tumors”; Abstract Number: 173P; Presenter: Dr. Guillermo De Velasco, Hospital Universitario 12 de Octubre, Madrid, Spain; Session Date: December 8, 2022; Dr. Neil Brewis, F-star's Chief Scientific Officer will have an oral presentation on Multi-specific Antibody-like Platforms on December 8 at 16:50 CET in Room C.