PD-1+ T cell activation broadly impacts multiple clinically validated drivers of UC pathogenesis

Adapted from Gastroenterology & Hepatology Volume 18, Issue 8 August 2022.

Reduction of elevated PD-1^high Tph cells in both UC colon and periphery correlates with remission

Reduction of plasma cell generation & autoantibody levels, including anti-microbial IgG antibodies contributing to colonic inflammation and barrier disruption

PD-1^high Tph cells defined by CD3+CD4+CD45RA-PD-1+TIGIT+ICOS+CXCR5-). Long et al, Immunology Letters 233 (2021) 2-10., Rao et al, Nature, 2017. *** p<0.001

Prophylactic or therapeutic dosing of PD-1 agonists induce and maintain remission in murine models

Rosnilimab and HM226 bind to the membrane proximal “epitope 7” of PD-1 that contributes to maximal PD-1 agonism. Rosnilimab formatted to mIgG2a to mediate effector function in mice. Suzuki et al., Sci. Immunol. 8, eadd4947 (2023).

Rosnilimab’s potent depletion and agonism reduces T cell proliferation and inflammatory cytokines that disrupt barrier function

Anti-CD3+ anti-CD28 stimulation of UC patient PBMCs for assessment of depletion and agonism MOA, representative data from N=6 donors.

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