Sapience Therapeutics, Inc. has announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for ST316, allowing the company to proceed with a Phase 1-2 clinical trial in patients with solid tumors. Patient dosing is anticipated to begin in the first half of 2023.
ST316 is a first-in-class β-catenin antagonist designed to inhibit the Wnt signaling pathway, a key driver in over 50% of solid tumors. The Wnt pathway's role in oncogenesis and immune suppression makes it a compelling therapeutic target, though traditional Wnt-blockade strategies have been challenging due to side effects. ST316 aims to selectively target oncogenic activity while preserving normal β-catenin function.
Targeting Wnt-Driven Tumors with ST316
ST316 functions by suppressing the transcription of Wnt target genes involved in oncogenic proliferation, migration, invasion, and metastasis, as well as genes regulating immunosuppression within the tumor microenvironment. This targeted approach is intended to provide a more selective and tolerable treatment option for Wnt-driven cancers.
"FDA clearance of the ST316 IND is an exciting achievement for Sapience, representing the second therapeutic candidate we discovered to advance into clinical development," said Dr. Barry Kappel, CEO and President of Sapience.
Clinical Trial Design and Target Patient Population
The Phase 1 portion of the study will be a dose-escalation trial in patients with tumors likely to harbor abnormalities in the Wnt/β-catenin signaling pathway. The Phase 2 dose-expansion phase will focus on four specific tumor types: cholangiocarcinoma, colorectal cancer, triple-negative breast cancer, and ovarian cancer.
Dr. Abi Vainstein-Haras, Sapience’s Chief Medical Officer, stated, "As the first peptide antagonist of β-catenin to enter the clinic, we are thrilled to progress ST316 to a Phase 1-2 study in the first half of 2023... With preclinical studies demonstrating a favorable safety profile and significant anti-tumor activity, we look forward to bringing ST316’s first-in-class approach to targeting Wnt-driven tumors to the cancer community."
Mechanism of Action
ST316 is designed to disrupt the interaction between β-catenin and its co-activator BCL9, a complex that drives oncogene expression in cancers with aberrant Wnt/β-catenin pathway signaling. This interaction has been historically difficult to target with small molecules or antibodies. ST316 contains a cell penetration moiety for intracellular access and a domain that binds to the first armadillo repeat domain of β-catenin, a site utilized by BCL9.
