Sapience Therapeutics Presents ST316 Phase 1 Dose Escalation Data at the 2025 American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium

TARRYTOWN, N.Y., Jan. 27, 2025 /PRNewswire/ -- Sapience Therapeutics, Inc., a clinical-stage biotechnology company focused on the discovery and development of peptide therapeutics to address oncogenic and immune dysregulation that drive cancer, today announced that it presented Phase 1 safety and biomarker data on ST316, a novel peptide antagonist of β-catenin, during a poster session at the 2025 American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium.  

ST316 is a first-in-class antagonist of β-catenin and its co-activator, BCL9, that is designed to selectively shut down the Wnt/β-catenin signaling pathway. The Phase 1 Dose Escalation study enrolled patients with advanced solid tumors likely to harbor abnormalities in the Wnt/β-catenin pathway to assess the safety, pharmacokinetics (PK), biomarker and preliminary activity of ST316, and to recommend a Phase 2 dose.

"With signals of anti-tumor activity, strong pharmacodynamic data, and a clean safety profile, we are pleased that the ST316 Phase 1 Dose Escalation study demonstrated clinical proof-of-concept as a single agent, in a patient population in which single agent response is limited," commented Dr. Abi Vainstein-Haras, Sapience's Chief Medical Officer. "ST316's tolerability as a single agent, together with the biomarker data from its Phase 1 study, are encouraging for its continued development in our ongoing Phase 2 Dose Expansion study, which is evaluating ST316 across multiple combinations and lines of treatment in colorectal cancer (CRC)." 

Summary of Phase 1 Dose Escalation Results:

• ST316 disrupts the interaction of β-catenin with BCL9 to result in Wnt/β-catenin pathway inhibition.
• ST316 was shown to be safe and well tolerated at all doses tested.
• The prolonged stable disease noted with single agent ST316 is consistent with early signals of anti-tumor activity.
• ST316 demonstrates tumor uptake and target engagement, as shown by a shift in the localization of β-catenin from nucleus to cytoplasm/membrane following treatment in 4 of 7 patients assessed.
• ST316 significantly reduced the expression of immunosuppressive polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in all Phase I patients that displayed elevated baseline levels (n=7).
• Based on the safety and pharmacodynamic effects that are consistent with the mechanism of action, ST316 is now being tested in combination with chemotherapy in advanced colorectal cancer patients across different lines of treatment.

Poster Presentation:

Title: "Safety and biomarker assessment of ST316, a novel peptide antagonist of ß-catenin, in patients with advanced solid tumors"
Session: Poster Session C: Cancers of the Colon, Rectum and Anus
Date/Time: Saturday, January 25, 2025, 7:00 am to 7:55 am PST
Abstract Number: 286
Presenting Author: Anthony El-Khoueiry, MD

More information can be found on the ASCO GI website.

About ST316
ST316 is a first-in-class antagonist of the interaction between β-catenin and its co-activator, BCL9, a complex responsible for driving oncogene expression and immune exclusion in multiple cancers where aberrant Wnt/β-catenin pathway signaling is observed. ST316 exposure in cancer cells prevents BCL9-driven nuclear localization of β-catenin and inhibits formation of the Wnt enhanceosome protein complex. Disruption of this interaction selectively suppresses the transcription of oncogenic Wnt target genes that regulate proliferation, migration, invasion and the metastatic potential of tumor cells, as well as genes that regulate the immunosuppression of the tumor microenvironment. ST316 creates a pro-immune tumor microenvironment and in preclinical models has shown to be synergistic with checkpoint inhibition. Due to its selectivity and downstream modulation of the Wnt/β-catenin pathway, ST316 presents an opportunity to safely and effectively target Wnt/β-catenin driven pathologies without the toxicities previously seen with other Wnt pathway agents. 

ST316-101 (NCT05848739) is a first-in-human, open-label, Phase 1-2 Dose Escalation and Expansion study designed to determine the safety, tolerability, PK, PD and early efficacy of ST316. The Phase 1 Dose Escalation portion of the study tested various dose levels of ST316 in patients with select advanced solid tumors that are known to harbor abnormalities of the Wnt/β-catenin signaling pathway, including CRC.  ST316 is currently being tested in the Phase 2 portion of the study in CRC patients in combination with relevant standards of care and in multiple lines of treatment. The U.S. FDA has granted Orphan Drug Designation to ST316 for the treatment of familial adenomatous polyposis (FAP). 

About Sapience Therapeutics
Sapience Therapeutics, Inc. is a privately held, clinical-stage biotechnology company focused on discovering and developing peptide therapeutics to address oncogenic and immune dysregulation that drive cancer.  With in-house discovery capabilities, Sapience has built a pipeline of therapeutic candidates called SPEARs™ (Stabilized Peptides Engineered Against Regulation) that disrupt intracellular protein-protein interactions, enabling targeting of transcription factors which have traditionally been considered undruggable. Sapience can also direct cargo to cell surface targets with their new class of molecule called SPARCs™ (Stabilized Peptides Against Receptors on Cancer), enabling delivery of payloads such as α-particles to cancer cells. Sapience is advancing its lead programs, lucicebtide (formerly known as ST101), a first-in-class antagonist of C/EBPβ, and ST316, a first-in-class antagonist of β-catenin, through Phase 2 clinical trials. 

For more information on Sapience Therapeutics, please visit https://sapiencetherapeutics.com/ and engage with us on LinkedIn.

Media and Investor Contact:
Amy Conrad
Juniper Point
(858) 366-3243
[email protected]

SOURCE Sapience Therapeutics, Inc.