Tu113 - A Novel Biparatopic KLRG1 Antibody Selectively Depletes Effector Memory CD8+ T Cells for Autoimmune Disease Treatment

Abstract Text: Cytotoxic CD8+ T cells contribute to multiple inflammatory and autoimmune diseases through tissue damage and destruction. KLRG1 (Killer cell Lectin-like Receptor G1) marks highly cytotoxic effector memory (TEM) and effector memory CD45RA+ (TEMRA) CD8+ T cell subsets that are expanded in the inflamed tissues or peripheral blood of autoimmune disease patients. Selective depletion of KLRG1+ CD8+ T cells is an attractive therapeutic approach that could offer lasting clinical benefits in selected autoimmune disease patients without global immune suppression.
Using our proprietary single cell microfluidic platform, we identified a series of anti-human KLRG1 antibodies with high binding affinity and functional activity. Selected binding domains were used to design a biparatopic antibody, HFB04373, with single-digit nanomolar affinity to human and cynomolgus KLRG1 and capable of inducing more potent ADCC and ADCP of KLRG1+ cells than a mono-specific benchmark in vitro. HFB04373 selectively depleted CD8+ TEM and TEMRA subsets from PBMCs collected from healthy donors and autoimmune patients, sparing other T cells. HFB04373 also demonstrated potent and sustained dose-dependent depletion of KLRG1+ KG1 cells in vivo.
HiFiBiO’s Drug Intelligent Science (DIS®) single-cell immune profiling platform provides insights into the abundance and activity of immune cell subsets in particular disease contexts, allowing precise targeting of pathogenic cell populations that drive autoimmunity in individual patients. Based on its potent pharmacological activity and favorable developability profile, HFB04373 is currently being developed as a novel immunotherapy for cytotoxic T cell-mediated autoimmune diseases coupled with a DIS®-enabled patient biomarker strategy.