Sapience Therapeutics Announces First Patient Dosed in Phase 1-2 Clinical Study of its First-in-Class β-catenin Antagonist, ST316, in Advanced Solid Tumors

TARRYTOWN, N.Y., June 13, 2023 /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, announced today that the first patient has commenced treatment in its Phase 1-2 study evaluating the Company's first-in-class antagonist of β-catenin, ST316. Though a principal driver of many cancers, β-catenin has evaded drug discovery efforts for more than 30 years. ST316 is designed to selectively target oncogenic activation of the Wnt/β-catenin signaling pathway, without impacting its activity in normal cells.

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 will test 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. With its first patient dosed on June 5, 2023, the Company expects to complete the Phase 1 portion of the study in the second half of 2024. Following completion of the study's Phase 1 portion, the recommended dose will advance to the Phase 2 portion of the study, in which ST316 will be tested in four advanced solid tumor types that are known to harbor abnormalities of the Wnt/β-catenin signaling pathway. Sapience is conducting the Phase 1 study across several sites in the United States.

"Dosing our first patient with ST316 is a significant accomplishment for our team, which has remained undaunted by the challenge of drugging one of the most challenging cancer targets, the Wnt/β-catenin pathway," said Dr. Abi Vainstein-Haras, Sapience's Chief Medical Officer. "We are thrilled to advance our second molecule from the bench to the clinic. Given the relevance of Wnt/β-catenin in the development of multiple cancers, we are excited about ST316's potential to make a meaningful difference for the many patients suffering from cancers driven by abnormalities in this pathway."

In March 2023, Sapience announced that it received IND 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. At the American Association for Cancer Research (AACR) Annual Meeting 2023, Sapience presented late-breaking data on ST316 highlighting its immunotherapeutic potential. In May 2023, Sapience was awarded a $2 million SBIR grant from the National Cancer Institute (NCI) of the National Institutes of Health (NIH) to support non-clinical studies for ST316.

About the Wnt/β-catenin Pathway
β-catenin is a critical member of the canonical Wnt signaling pathway, a well-known pathway that is critically involved in embryonic development and adult tissue homeostasis. Wnt pathway hyperactivity is known to play a role in greater than 50% of solid tumors, in which it is a driver of oncogenesis and immune suppression. Because of the importance of the Wnt pathway in normal functioning adult cells, development of β-catenin-targeted therapies that block the Wnt pathway has been hampered by toxicity and off-target effects. There are currently no approved drugs that target the Wnt/β-catenin pathway. 

About ST316
ST316 is a first-in-class peptide antagonist of the interaction between β-catenin and its co-activator, BCL9, a complex that drives oncogene expression 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 cancers without the toxicities previously seen with other Wnt pathway agents.

The Phase 1 dose-escalation portion of the Phase 1-2 study has begun enrolling and dosing patients with select advanced solid tumors that are known to harbor abnormalities of the Wnt/β-catenin signaling pathway. The Phase 2 dose-expansion portion will utilize the recommended ST316 dose to assess its safety and early efficacy in four specific tumor types that are known to harbor abnormalities of the Wnt/β-catenin signaling pathway.

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. Sapience's in-house discovery platform, PADS™ Peptide Antagonist Discovery System), enables the rational design of novel peptides with optimized properties for clinical development. Leveraging PADS™, 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 is advancing its lead programs, ST316, a first-in-class antagonist of β-catenin, and ST101, a first-in-class antagonist of C/EBPβ, through Phase 1-2 clinical trials. 

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

Cautionary Note on Forward-Looking Statements

This press release contains forward-looking statements. Any statements herein other than statements of historical fact could be deemed to be forward-looking statements. These forward-looking statements may include, among other things, statements regarding future events that involve significant risks and uncertainties (including with respect to Sapience's preclinical and clinical development programs). These forward-looking statements are based on management's current expectations, and actual results and future events may differ materially as a result of certain factors, including, without limitation, our ability to obtain additional funds, and meet applicable regulatory standards and receive required regulatory approvals. Forward-looking statements speak only as of the date of this press release. Sapience does not undertake any obligation to update any forward-looking statements as a result of new information, future events, changed assumptions or otherwise, except as required by law.

Contacts
Sapience Therapeutics, Inc.:
Barry Kappel, Ph.D., M.B.A.
President and Chief Executive Officer
[email protected]

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

SOURCE Sapience Therapeutics, Inc.