Th193 - Application of HiFiBiO Drug Intelligence Science (DIS®) Translational Platform to Guide the Clinical Development of HFB200604, a Phase I BTLA Agonist Monoclonal Antibody

Abstract Text: BTLA (B and T lymphocyte attenuator) is a co-inhibitory immune checkpoint expressed on B, T and dendritic cells. In contrast to blockade of individual cytokines, BTLA agonism has the potential to restore tolerance by impacting multiple pathogenic cell types and inflammatory cytokines. To date, BTLA agonistic antibodies have failed to demonstrate the expected outcomes in patients with lupus and atopic dermatitis. Different factors might account for this, including inadequate antibody pharmacological profile and/or the selection of appropriate indications. Combining single cell technology and AI/ML algorithms, we applied our unique Drug Intelligence Science (DIS®) platform to discover and develop a best-in-class antibody, HFB200604, and to identify appropriate indications to address these challenges.
HFB200604 is a differentiated BTLA agonist with optimized Fc-mediated agonism that significantly suppresses B cell proliferation, production of IFNγ, TNFα, and IL-17, and T cell activation and proliferation, both in vitro and in vivo. HFB200604 clinical evaluation is guided by DIS® single immune cell profiling of autoimmune diseases and focused on indications with reduced HVEM expression and BTLA signaling, where deregulated BTLA function can be restored through BTLA agonism. Based on the enrichment of a BTLA activation signature, we have prioritized autoimmune diseases where B and T cells exhibit lower levels of pathway activation.
In conclusion, DIS® interrogation of patient datasets supports HFB200604 as a promising therapy to treat autoimmune diseases where BTLA suppressive functions are not fully engaged.