The proposed non-clinical studies will investigate pharmacodynamic biomarkers for ST316, a first-in-class β-catenin antagonist, and evaluate the impact of ST316 on the tumor microenvironment (TME) in patient-derived cancer models. 

"This award provides further validation of our novel approach with ST316 to impact the Wnt/β-catenin signaling pathway, a known oncogenic driver of many cancers and a key regulator of the tumor microenvironment," said Jim Rotolo, Ph.D., SVP, Translational Pharmacology and Head of Research of Sapience Therapeutics. "ST316 has tremendous therapeutic promise, with a robust preclinical data package that includes a favorable safety profile and significant anti-tumor activity.  We look forward to building upon these data with this grant award and evaluating ST316 in patients in our upcoming Phase 1-2 clinical study."

ST316 is a first-in-class peptide antagonist of the interaction between β-catenin and its co-activator BCL9, a complex that drives oncogenesis in multiple cancers where aberrant Wnt/β-catenin pathway signaling is observed. In March 2023, Sapience announced that it received clearance from the U.S. Food and Drug Administration (FDA) to proceed with a Phase 1-2 clinical trial of ST316 for the treatment of solid tumors.  In addition, at the American Association for Cancer Research (AACR) Annual Meeting 2023, Sapience presented late-breaking data on ST316 highlighting its immunotherapeutic potential. 

The award will utilize patient-derived xenograft (PDX) models to investigate pharmacodynamic (PD) biomarkers and evaluate the impact of ST316 on the TME, namely macrophage polarization, tumor infiltrating lymphocyte (TIL) expression in tumors and the impact in combination with a PD-1 inhibitor.  This grant was supported by the National Cancer Institute of the National Institutes of Health under Award Number 2R44CA265503-02A1.  The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.