Peloton Therapeutics, Inc. presented preclinical data on its lead investigational candidate, PT2385, at the American Association for Cancer Research Annual Meeting in New Orleans, LA. PT2385 is the first clinical stage antagonist of hypoxia inducible factor-2a (HIF-2a), a transcription factor implicated in the development and progression of renal and other cancers. In addition to its direct role in transcription regulation of growth-promoting genes in renal tumors, HIF-2a has been proposed to affect the tumor microenvironment.

In a poster titled “PT2385, a Novel HIF-2a Antagonist, Combines with Checkpoint Inhibitor Antibodies to Inhibit Tumor Growth in Preclinical Models by Modulating Myeloid Cells and Enhancing T Cell Infiltration," the combination of PT2385 with antibodies to immune checkpoint control molecules (PD-1, PD-L1, and CTLA4) yielded additive or synergistic efficacy in preclinical tumor models. The combination of PT2385 and immune checkpoint inhibitors is planned for evaluation in clinical trials. 'PT2385 has now been shown to affect the tumor microenvironment, even for tumors that do not express HIF-2a.

This potentially broadens the applicability of PT2385 to a larger variety of tumor types, including melanoma and lung cancers, which have been shown to have a strong immunological component.