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Unique Structure and Tetravalency of FS118 Is Required to Modulate LAG-3 Cell Surface Expression
CAMBRIDGE, United Kingdom and CAMBRIDGE, Mass., April 08, 2022 (GLOBE NEWSWIRE) -- F-star Therapeutics, Inc. (NASDAQ: FSTX), a clinical-stage biopharmaceutical company dedicated to developing next generation immunotherapies to transform the lives of patients with cancer, today announced that preclinical, mechanistic data on FS118, a bispecific antibody targeting LAG-3 and PD-L1, will be presented in a poster session at the American Association for Cancer Research (AACR) Annual Meeting, taking place April 8-13, 2022, in New Orleans, Louisiana.
FS118 is a dual checkpoint inhibitor developed to overcome tumor evasion mechanisms promoted by two highly immunosuppressive pathways, LAG-3 and PD-L1. In addition to simultaneously blocking both inhibitory pathways, FS118 demonstrated a highly differentiated, novel mechanism of action in preclinical models and in the clinic that translated into prolonged disease control in patients with cancer. The data presented in the poster reveals that the tetravalent and unique structure of FS118 plays a critical role in driving LAG-3 shedding and cell surface reduction by TILs, enabling FS118 to overcome compensatory upregulation of LAG-3 induced by PD-(L)1 blockade.
“We continue to be very encouraged by this additional mechanistic data on FS118, demonstrating the superiority of tetravalent binding in evoking the LAG-3 shedding mechanism,” said Neil Brewis, Ph.D., Chief Scientific Officer of F-star Therapeutics. “These results further validate our bispecific approach and give us greater confidence in the efficiency and effectiveness of tetravalent binding. We look forward to generating additional data and leveraging the potential of FS118 to overcome immunotherapy resistance.”
The presentation demonstrates that bivalent LAG-3 binding by FS118 was required for maximal LAG-3 shedding and a reduction in cell surface LAG-3 expression by TILs in mouse models. By contrast, a reduction in LAG-3 cell surface expression by TILs was not observed with a LAG-3/PD-1 bispecific. These data demonstrate the importance of tetravalent binding by FS118 which may be crucial to overcoming compensatory upregulation of LAG-3 induced by blockade of PD-L1 in patients with cancer.
The abstracts are currently available on the AACR meeting website. The poster will be available online at https://investors.f-star.com/events-and-presentations following the presentation.
Poster Presentation Details
Abstract Number: 2254
Poster: 2874 The tetravalent structure of FS118, a bispecific antibody targeting LAG-3 and PD-L1, is required for its novel mechanism of LAG-3 shedding
Date/Time: Tuesday, April 12 2022, 9:00 AM to 12:30
Session: Therapeutic Antibodies 1, Poster Section 37
About F-star Therapeutics, Inc.
F-star Therapeutics, Inc. is a clinical-stage biopharmaceutical company dedicated to developing next generation immunotherapies to transform the lives of patients with cancer. F-star is pioneering the use of tetravalent (2+2) bispecific antibodies to create a paradigm shift in cancer therapy. The Company has four second-generation immuno-oncology therapeutics in the clinic, each directed against some of the most promising IO targets in drug development, including LAG-3 and CD137. F-star’s proprietary antibody discovery platform is protected by an extensive intellectual property estate. F-star has over 500 granted patents and pending patent applications relating to its platform technology and product pipeline. The Company has attracted multiple partnerships with biopharma targeting significant unmet needs across several disease areas, including oncology, immunology, and CNS.
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