TPST‐1120 elicits its potent anti‐tumor effects through direct binding of the PPAR alpha transcription factor, inhibiting the expression of its regulated genes that are critical for fatty acid oxidation. Several malignancies such as hepatocellular carcinoma and renal cell cancer are reliant on fatty acid oxidation. In addition, suppressive immune cells in the tumor microenvironment such as a particular subset of macrophages, regulatory T cells and myeloid‐derived suppressor cells all favor fatty acid oxidation. The utilization of fatty oxidation by tumor cells and suppressive immune cells underlines the tumor‐intrinsic and tumor‐extrinsic anti‐tumor properties of TPST‐1120.
“Immuno‐metabolism is a rapidly evolving field, and it is increasingly recognized that regulating particular metabolic checkpoints that are essential to promote bio‐energetic pathways necessary for sustaining tumor growth are important new targets in oncology. Our poster provides the rationale for advancing TPST‐1120 into patients with advanced cancers and also provides insights into the clinical development of this first‐in‐human molecule,” said Tom Dubensky, Ph.D., president and CEO of Tempest.