Prostaglandin E2 (PGE2) is produced by both the tumor and stroma, and is a potent immunosuppressive factor in the tumor microenvironment (TME). Prostaglandin signaling promotes the differentiation of and skewing towards immunosuppressive cell populations (e.g., myeloid-derived suppressor cells, regulatory T cells, and M2 macrophages) in concert with the decrease in the differentiation, maturation, activation and proliferation of inflammatory cell populations (e.g. dendritic cells, NK cells, and CD8 positive T-cells).

Prostaglandins are Immune Suppressive

Four E-prostanoid receptors (EP1, EP2, EP3, and EP4 respectively) are the primary mediators of prostaglandin signaling in the TME. Data generated by Tempest in addition to studies in the published literature indicate that selectively blocking signaling through EP2 and EP4, and not EP1 and EP3, is the most effective strategy to abrogate prostaglandin driven immunosuppression. Tempest, in collaboration with Inception Sciences, is developing novel highly selective and potent EP2-EP4 dual antagonists, that block the immune suppressive impact of prostaglandin signaling and promote effective anti-tumor immunity.

Antagonizing both EP2 and EP4 is the Optimal Approach to Overcome Immune Suppression.

Tempest is advancing a novel EP2-EP4 dual antagonist, which has a unique profile and higher potency compared to other single EP4 antagonists in clinical development. The molecule is now advancing into IND enabling studies and is anticipated to be in the clinic in late 2019 / early 2020.