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
“A shared feature of agonist mAbs is recognition of the membrane-proximal extracellular region…” and “…activity depends on Fc receptor–supported crosslinking” -Suzuki, et al. 2023
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.
Comparative data of rosnilimab demonstrates consistently higher reduction of peripheral PD-1high and PD-1+ T cells
1. AA=Alopecia Areata; 2. Rosnilimab clinical results shown from 400mg subcutaneous dose (single dose in healthy and monthly dose in AA); 3. Anti-CD3+ anti-CD28 stimulation of RA patient PBMCs for assessment of depletion and agonism MOA, representative data from N=8 donors. Two-way ANOVA, Tukey’s multiple comparison test. ****P<0.0001, ***p<0.001, **p<0.01, *p<0.05. 4. Benschop, R. ACR 2023, Eli Lilly peresolimab Phase 2a data.
PD-1+ T cells are prevalent in inflamed tissue and periphery in RA and UC
In systemic inflammatory diseases, a multiple fold increase of PD-1+ T cells is observed in periphery compared to healthy controls1
- ~1.5x in RA
- ~2x in UC
Adapted from Nguyen et al, Human Pathology (2022) 126, 19e27; Guo et al, PLoS One 2018; 13(2). Roosenboom et al, Scand J of Gastro. 2021; 56(6):671-679. 1. Murray-Brown et al, RMC Open, 2022. Shi et al. (2023), PeerJ, DOI 10.7717/peerj.15481.
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