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.

Rosnilimab demonstrates potent depletion and agonism at clinically relevant concentrations

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

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): e0192704. Shi et al. (2023), PeerJ, DOI 10.7717/peerj.15481. 1. Murray-Brown et al, RMC Open, 2022, Shi et al. (2023), PeerJ, DOI 10.7717/peerj.15481.

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