Mo1093 ALPN-101, A FIRST-IN-CLASS DUAL ICOS/CD28 ANTAGONIST, DEMONSTRATES EFFICACY IN PATIENT-DERIVED PBMC IN VITRO AND IN AN IN VIVO T CELL TRANSFER MODEL OF CHRONIC INFLAMMATORY BOWEL DISEASE (IBD)

First‐in‐human study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of ALPN‐101, a dual CD28/ICOS antagonist, in healthy adult subjects

“…It is a Fc dimer of an ICOSL vIgD domain, derived by directed evolution to bind both CD28 and ICOS, fused to an effector function negative IgG1 Fc, with a predicted molecular weight of 80.8 kilodaltons. Nonclinical studies of ALPN-101 demonstrate potent inhibition of disease activity, in association with suppressed pathogenic T and/or B cell responses where appropriate, in mouse models of GVHD (28), inflammatory arthritis (29), sialoadenitis (Sjögren's syndrome), SLE (30), inflammatory bowel disease (31), and uveitis (32). Furthermore, in preclinical studies in mice or with cells from patients with various inflammatory diseases, ALPN-101 exhibited immunomodulatory activity superior to that achievable by combining biologic inhibitors of the CD28 and ICOS pathways, suggesting a unique, possibly synergistic, advantage of ALPN-101 over currently available therapeutic reagents (29,30).…”

In vivo human keyhole limpet hemocyanin challenge in early phase drug development: A systematic review

“…Qualitatively similar effects of acazicolcept seen in a mouse model of collagen induced arthritis, with reduced anti‐collagen antibodies, paw inflammation, and serum cytokine concentrations, 85 and in studies of mice challenged with KLH and SRBC, with reduced antibody titers, germinal center formation, and T follicular helper cells 86 …”