Sapience Therapeutics Begins Phase 2 Trial of ST316 in Colorectal Cancer

Sapience Therapeutics, Inc., a biotechnology firm specializing in peptide therapeutics to combat cancer, has initiated the Phase 2 dose expansion study of its pioneering β-catenin antagonist, ST316, by enrolling its first patient. The Phase 1 dose escalation segment was completed in July 2024.

ST316 targets the Wnt/β-catenin signaling pathway, which is highly active in several cancers, including colorectal cancer (CRC). By inhibiting this pathway selectively in tumor cells, ST316 aims to provide anti-cancer benefits without the associated toxicity. The Wnt/β-catenin pathway plays a crucial role in over 80% of colorectal cancers, the initial focus of the Phase 2 expansion study. In the United States alone, over 1 million individuals are living with CRC, and an additional 150,000 are expected to be diagnosed this year.

Dr. Abi Vainstein-Haras, Chief Medical Officer at Sapience, highlighted the encouraging outcomes from the Phase 1 study, emphasizing ST316's potential as a treatment for Wnt pathway-driven cancers, including CRC. Dr. Vainstein-Haras remarked on ST316's promising safety and tolerability profile, complemented by robust pre-clinical data, indicating the company's commitment to exploring ST316's potential in various therapeutic combinations and treatment phases.

Dr. Barry Kappel, Sapience's founder and Chief Executive Officer, underscored the urgency of developing new treatments for CRC patients who do not respond to existing therapies. Given CRC's status as the second leading cause of cancer-related deaths in the U.S. and its rising incidence among younger populations, Dr. Kappel stressed the importance of expanding treatment options.

The ST316-101 study is an open-label, first-in-human Phase 1-2 trial designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and initial efficacy of ST316. The Phase 1 segment tested different doses of ST316 in patients with advanced solid tumors characterized by Wnt/β-catenin pathway abnormalities, including CRC. Having completed Phase 1 enrollment in July 2024, the Phase 2 expansion now involves testing ST316 in CRC patients in conjunction with standard treatments and across various treatment lines. This phase is being conducted at multiple sites across the U.S.

ST316 functions as a first-in-class peptide antagonist, disrupting the interaction between β-catenin and its co-activator BCL9. This interaction is crucial for the oncogene expression driven by abnormal Wnt/β-catenin signaling in several cancers. By preventing the nuclear localization of β-catenin, ST316 inhibits the formation of the Wnt enhanceosome protein complex, thereby selectively suppressing the transcription of oncogenic Wnt target genes that facilitate tumor cell proliferation, migration, invasion, and metastasis. Furthermore, ST316 promotes a pro-immune tumor microenvironment and has shown potential synergism with checkpoint inhibitors in preclinical models. Its specific targeting and modulation of the Wnt/β-catenin pathway offer a promising approach to treating Wnt/β-catenin-driven cancers without the toxicities seen with previous Wnt pathway inhibitors.

Sapience Therapeutics is a clinical-stage biotechnology company focused on developing peptide therapeutics that address oncogenic and immune dysregulation driving cancer. With its in-house discovery capabilities, Sapience has created a pipeline of therapeutic candidates known as SPEARs™ (Stabilized Peptides Engineered Against Regulation), designed to disrupt intracellular protein-protein interactions. The company is advancing two main clinical programs through Phase 2: ST316, an antagonist of β-catenin, and ST101, an antagonist of C/EBPβ.