Science
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.
PPARα Antagonism
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. TPST-1120 has completed monotherapy dose escalation, and is progressing through a Phase 1/1b study in combination with nivolumab (NCT03829436) and a randomized Phase 1b/2 study in combination with atezolizumab (TECENTRIQ®) and bevacizumab (Avastin®) in frontline patients with advanced hepatocellular carcinoma (HCC) pursuant to a collaboration with F. Hoffmann-La Roche Ltd.
Dual EP2/EP4 Antagonsim
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. TPST-1495 is progressing through Phase 1/1b monotherapy and combination studies.
TREX-1 Inhibitor
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.