OncoMed Pharmaceuticals Inc. presented preclinical data during the American Association for Cancer Research (AACR) Annual Meeting related to two of its therapeutic candidates, anti-TIGIT (OMP-313M32), currently in the Phase 1a portion of a Phase 1a/b study, and GITRL-Fc trimer (OMP-336B11), currently in a Phase 1a study. In addition, preclinical data was presented exploring the ability of OncoMed’s Wnt antagonist vantictumab (anti-FZD, OMP-18R5) to potentiate immune responses to checkpoint agents. A series of preclinical studies (Abstract 70, Abstract 2726, Abstract 3826) from OncoMed highlighted the ability of GITRL-Fc, a novel linkerless ligand trimer that binds to the co-stimulatory receptor GITR (glucocorticoid-induced TNF receptor family-related protein), to function as a robust GITR agonist by both stimulating T-cell and NK responses and reducing the abundance of Tregs in tumors. The studies also investigated the impact of aging on anti-tumor immune response, an important and often underappreciated parameter impacting the efficacy of immuno-oncology strategies. Another preclinical study (Abstract 1733) examined the synergistic impact of OncoMed’s Wnt pathway antagonist vantictumab on the ability of checkpoint agents to promote an effective anti-tumor immune response. These data add to a growing recognition of the importance of the Wnt pathway in shaping immune function. Abstract 5627 -Anti-TIGIT biomarker study: Inhibition of TIGIT induces loss of Tregs from tumors and requires effector function for tumor growth inhibition Using a surrogate anti-TIGIT antibody, potent single-agent dose-dependent anti-tumor efficacy was demonstrated on large established CT26 WT tumors. Anti-TIGIT efficacy was shown to require effector function for tumor growth inhibition and biomarker analysis demonstrated reduction of Treg frequency and activation of T-cells and NK cells as part of the mechanism of action of anti-TIGIT. CD226, a co-receptor for TIGIT’s ligands PVR and PVRL2, was significantly upregulated in T-cells, Tregs and NK cells, reflecting a feedback loop activated by the inhibition of TIGIT activity. Anti-TIGIT gene signatures in tumors and in blood were identified from multiple syngeneic models and may be potential biomarkers for measuring anti-TIGIT activity. Additionally in a human tissue study, TIGIT expression on Tregs was found to be considerably higher than on CD8+ T-cells in multiplexed IHC panels across a panel of multiple solid tumors types.