W118 - HFB202501, a Novel Anti-PD-1 Antibody with Enhanced Effector Functions for Precision Depletion of Pathogenic T Cells in Autoimmune Diseases

Abstract Text: Precision depletion of pathogenic immune cells is an attractive therapeutic strategy with the potential to reset the immune response and restore tolerance while retaining aspects of protective immunity. The immune checkpoint PD-1 has drawn interest as a therapeutic target in autoimmune and inflammatory diseases where it marks multiple pathogenic T cell subtypes. These include T peripheral and follicular helper (Tph and Tfh) cells, critical for the maturation and development of autoreactive B cells, which express very high levels of PD-1, and activated effector cells which contribute to inflammation and tissue damage and express lower levels of PD-1. Antibodies that agonize PD-1-expressing T cells and deplete PD-1(high) T cells have recently demonstrated clinical proof-of-concept in rheumatoid arthritis.

We present here HFB202501, an anti-PD-1 agonist antibody engineered for enhanced depletion of PD-1+ cells. HFB202501 shows more potent and deeper depletion of PD-1+ T cells in vitro compared to clinical-stage benchmark antibodies. HFB202501 is able to deplete multiple PD-1+ cell populations from human tonsils in vitro and is highly efficacious in a mouse model of lupus. Deep depletion of PD-1+ cells has the potential for broad application in autoantibody-mediated autoimmune diseases and other indications where activated PD-1+ effector cells play a pathogenic role. HFB202501 is progressing towards preclinical development with a biomarker strategy for identifying patients with expanded PD-1+ cells populations.