The Tempest team leverages both established knowledge and novel scientific insights in selecting targets and the methods to modulate them, in all cases to address unmet medical need or to improve standard of care for cancer patients with differentiated oncology drug candidates. Tempest takes an open-minded, scientifically-driven approach in the selection of new programs, without the constraint of a specific platform or pathway bias.
Peroxisome proliferator-activated receptor alpha (PPARα) is a transcription factor that regulates fatty acid oxidation (FAO) and inflammation and is highly expressed by many cancers, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) to a significant degree. Tempest is advancing TPST-1120 as a first-in-class antagonist tartgeting PPARα.
Dual EP2/EP4 Antagnosim
EP2 and EP4 are two receptors in the prostaglandin (PGE2) signaling pathway promoting both tumor-growth and immune suppression, and are expressed together by many cancers, including colorectal and endometrial cancers. Tempest is advancing TPST-1495 as a first-in-class dual antagonist of EP2 and EP4.
The exonuclease TREX-1 is the sentinel of cytosolic dsDNA and dampens the activation of cGAS/STING to avoid immune recognition. Inhibition of TREX-1 results in enhanced activation of STING and Interferon (IFN) β, leading to induction of tumor-specific immunity. Tempest is currently moving the program through lead optimization.