(Anaveon) ANV600, a cis-signaling αPD-1/IL-2Rβ/γ agonist, expands both CD4 + and CD8 + tumor specific T cells by acting in the tumor microenvironment and draining lymph nodes

Abstract

Background

ANV600 combines a unique non-blocking PD-1 targeting approach with an IL-2Rβ/γ selective agonistic principle

The cytokine bearing arm (blue) of the bispecific antibody is composed of IL-2 fused to an anti-IL-2 antibody, which sterically prevents IL-2Rα from binding to the fusion protein. It therefore selectively signals through IL-2Rβ/γ. The targeting arm (green) consists of a high affinity αPD-1 antibody to selectively deliver ANV600 to tumor antigen experienced PD-1+ T cells. The anti-PD-1 arm binds to a unique epitope on PD-1 that enables combination of ANV600 with PD-1 checkpoint inhibitors.

ANV600 anchoring to PD-1 increases IL-2Rsignaling potency on PD-1+ cells

Potency measurements of STAT5 phosphorylationin PD-1+Jurkat T cells demonstrate a strong PD-1 targeting effect of ANV600. Compared to a non targeted IL-2Rβ/γ agonist control molecule, ANV600 has an 88-fold increased IL-2R signaling potency on PD-1 expressing cells.