W173 - Rosnilimab, a Novel PD-1 Agonist Monoclonal Antibody, Demonstrated Modulation of Peripheral T Cell Activity and Reduction of Circulating PD-1high Expressing CD4 and CD8 T Cells in a Phase 1 Healthy Volunteer Clinical Trial

Genetic studies have demonstrated that PD-1 pathway mutations increase human susceptibility to multiple autoimmune diseases and insufficient PD-1 signaling can lead to dysregulated T cell responses.  Rosnilimab is a PD-1 agonist antibody designed to modulate activated T cells for the treatment of inflammatory diseases. 

Rosnilimab’s pharmacodynamic activity resulted in rapid and sustained reduction in the quantity and functional activity of PD-1+ T cells, which are known to be pathogenic drivers of inflammatory diseases.  Conventional T (Tcon) cells expressing PD-1 were reduced, on average through Day 30 in single ascending dose cohorts where full receptor occupancy was sustained following rosnilimab treatment, by approximately 50%, including in both CD4+ and CD8+ subsets, in a dose-dependent manner and in correlation with receptor occupancy.  This reduction was maximized on high PD-1 expressing Tcon cells, with approximately 90% reduction relative to baseline.  Rosnilimab did not modulate total T cells, total Tcon cells, or total regulatory T (Treg) cells, resulting in a favorable shift in the ratio of PD-1+ Tcon cells to total Treg cells post-treatment.  No effect was observed on any of the aforementioned cell types in placebo-dosed subjects.  In addition, an antigen-specific functional T cell assay measuring ex vivo interferon-gamma released in response to antigen challenge, was inhibited to a maximum of approximately 90% relative to baseline within 30 days following single rosnilimab dose, while placebo administration had no effect.  Based upon these data, we believe rosnilimab’s in vivo mechanism has the potential to treat T-cell driven human inflammatory diseases.