Tempest is advancing TPST-1120, a first-in-class antagonist against peroxisome proliferator-activated receptor alpha (PPARα). PPARα is a transcription factor that regulates fatty acid oxidation (FAO) and inflammation.

PPARα is a Central Regulator of Fatty Acid Oxidation

Tempest and our research partners have demonstrated that blocking PPARα with TPST-1120 promotes a more inflamed tumor microenvironment (TME) through decreased FAO. Mediated by the inhibition of FAO, TPST-1120 shifts the metabolic balance of immune cells towards glycolysis and favors the bioenergetic needs of effector immune cell populations, including M1 tumor associated macrophages (TAMs) and effector T Cells (Teff).  Treatment with TPST-1120 does not support the bioenergetic needs of immunosuppressive cell populations including M2 macrophages, myeloid suppressor cells and regulatory T cells, all of which utilize FAO.

Inhibition of FAO Promotes Inflamed Cell Phenotypes

TPST-1120 has shown efficacy in multiple syngeneic tumor models both as a single agent and in combination with anti-cancer therapies. This molecule is now being advanced through IND-enabling studies, and we anticipate that TPST-1120 will enter first-in-human trials in 2019.