Rosnilimab — Overview
Rosnilimab is a novel PD-1 checkpoint agonist antibody that reduces overactive T cell inflammation
It has two distinct mechanisms of action, depletion and agonism, prevalent both in inflamed tissue and the periphery, targeting PD-1+ T cells broadly impacting multiple drivers of disease pathogenesis
Rosnilimab optimizes PD-1+ T cell inhibitory signaling by enabling tight immune synapse formation
1. Adapted from Suzuki et al., Sci. Immunol. 8, eadd4947 (2023).
Rosnilimab restores immune balance bringing T cell composition to a less activated state
PD-1 expression on both CD4 and CD8 T cells correlates with activation state
Rosnilimab targets only a small proportion of T cells
In healthy volunteers:
- Deplete PD-1high T cells: ~5-8% of total T cells
- Agonize remaining PD-1int T cells: ~15% of total T cells
Data illustrative, based on Phase 1 data from healthy volunteer study. Data on file with Anaptys.
1. Healthy donor T cells + NK cells (1:5 ratio) + antibody in in-vitro ADCC assay, representative data from N=5 donors.
2. Healthy donor purified DCs + autologous total T cells stimulated with anti-CD3, cultured for 3 days for assessment of T cell proliferation
Two-way ANOVA. Tukey’s multiple comparison test. ****P<0.0001, ***p<0.001, **p<0.01, *p<0.05.
Potent and sustained reduction in peripheral PD-1+ T cells for >30 days across P1 HV and P2a AA1 studies
Consistent PD-1+ T cell effect2
- >90% reduction of PD-1high T cells
- >50% reduction of PD-1+ T cells
Overall T cell composition in less activated state
- Positive bias to Treg ratio
AA patients are in a low systemic inflammatory state
- Represented by no significant increase in peripheral PD-1+ T cells relative to healthy controls
1. AA=Alopecia Areata; 2. Results shown from 400mg subcutaneous dose (single dose in healthy and monthly dose in AA).
PD-1+ T cells are prevalent in inflamed tissue and periphery in RA and UC
- ~1.5x in RA
- ~2x in UC