BCL9

TARRYTOWN, N.Y., Oct. 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, today announced the presentation of two posters at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, taking place October 11-15, 2023, in Boston, MA. Poster Presentation Details: Title: "Clinical and Biological Activity of ST101, a Peptide Antagonist of C/EBPβ, in Recurrent Glioblastoma (rGBM) Patients. Results From the rGBM Cohort of a Multi-Cohort Phase 2 Study" Poster Number: B038 Session Title: Poster Session B Date/Time: Friday, October 13, 2023, 12:30 pm-4:00 pm Session location: Level 2, Exhibit Hall D ST101 is a first-in-class antagonist of C/EBPβ that has demonstrated clinical proof-of-concept in advanced solid tumors. ST101 is currently being evaluated in the Phase 2 portion of an ongoing Phase 1-2 clinical study in patients with advanced unresectable and metastatic solid tumors (NCT04478279). The poster summarized clinical data from ST101's recurrent Glioblastoma (rGBM) Phase 2 expansion cohort of 30 patients. The GBM cohort showed ≥ 1 response in the first 15 patients, triggering the criteria to expand to a total of 33 patients enrolled; 30 were evaluable for efficacy in this cohort. Key Conclusions: ST101 demonstrates the ability to pass through the blood-brain-barrier and engage C/EBPβ. Single agent ST101 demonstrated clinical activity and tissue treatment effect. This data snapshot also demonstrated that patients receiving ST101 monotherapy exhibited encouraging response and survival outcomes. Results from the ST101-101 study warrant further assessment of ST101 as part of a combination treatment approach for patients with rGBM. Title: "Anti-tumor and Immunostimulatory Properties of ST316, a Peptide Antagonist of β-Catenin for Treatment of Cancers with Aberrant Wnt Pathway Activity" Poster Number: B149 Session Title: Poster Session B Date/Time: Friday, October 13, 2023, 12:30 pm-4:00 pm Session location: Level 2, Exhibit Hall D ST316, a first-in-class antagonist of β-catenin, is designed to selectively target oncogenic activation of the Wnt/β-catenin signaling pathway without impacting its activity in normal cells. ST316 is currently being evaluated in the Phase 1 portion of a Phase 1-2 study, ST316-101 (NCT05848739), which is a limited solid tumor basket study for tumors likely to harbor abnormalities in the Wnt pathway, such as colorectal cancers. The poster summarized preclinical data demonstrating the anti-tumor and immunostimulatory properties of ST316 in multiple cancer models. Key Conclusions: ST316 effectively inhibits the transcriptional activity of oncogenic β-catenin, resulting in reduction of Wnt target genes involved in carcinogenesis, cell division, cell migration and immunoinhibitory processes. ST316 treatment results in reduced cell viability and tumor growth inhibition, marked by the reduced expression of Wnt target genes within tumor tissue. ST316 induces polarization of hPBMC-derived M2 macrophages toward the M1 phenotype and enhances CD8+ T cell activation in mixed cultures of macrophages and T cells. Furthermore, subpharmacologic ST316 augments the efficacy of anti-PD-1 antibody in an orthotopic 4T1 TNBC tumor model. These findings underscore ST316's potential as a therapeutic agent for targeting cancers characterized by aberrantly activated Wnt signaling pathways, showcasing its antitumor and immunostimulatory effects. More information can be found on the AACR-NCI-EORTC website. About ST101 ST101, a first-in-class antagonist of C/EBPβ, is currently being evaluated in the Phase 2 portion of an ongoing Phase 1-2 clinical study in patients with advanced unresectable and metastatic solid tumors (NCT04478279). ST101-101 is an open-label, Phase 1-2 dose-finding study designed to determine the safety, tolerability, PK, PD, and proof-of-concept efficacy of ST101 in patients with advanced solid tumors. The study consists of two phases: Phase 1 dose escalation/regimen exploration and Phase 2 dose expansion. In the ongoing Phase 2 dose expansion part of the study, ST101 has demonstrated clinical proof-of-concept with a mRANO-confirmed partial response in a patient with recurrent GBM and evidence of long-lasting stable disease in several additional patients. ST101 has been granted Fast Track designation for recurrent GBM and advanced cutaneous melanoma in patients who have disease progression on or after anti-PD-1/anti-PD-L1 therapy, as well as orphan designations from the FDA for Stage IIb-IV melanoma, glioma and AML, and from the European Commission for the treatment of glioma. 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. 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 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. 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 dose expansion portion of the study. 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 enables the rational design of novel peptides with optimized properties for clinical development. Leveraging our 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 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 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.

TARRYTOWN, NY, USA I June 13, 2023 I 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 . SOURCE: Sapience Therapeutics

TARRYTOWN, NY, USA I May 4, 2023 I 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 it was awarded a $2 million, two-year Small Business Innovation Research (SBIR) grant from the National Cancer Institute (NCI) of the National Institutes of Health (NIH). 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. About ST316 ST316, a first-in-class β-catenin antagonist, is in Phase 1 clinical development following the clearance of its Investigational New Drug (IND) application by the U.S. Food and Drug Administration in March 2023.  β-catenin is a critical member of the canonical Wnt signaling pathway, a well-known development stage pathway that has been considered an "undruggable" cancer target, as small molecules have proven ineffective or toxic.  Disruption of the interaction between BCL9 and β-catenin with ST316 reduces oncogenic Wnt-signaling, suppressing transcription of Wnt target genes resulting in tumor cell death and a pro-inflammatory tumor microenvironment, without disruption of homeostatic Wnt function. In the second quarter of 2023, the Phase 1 dose-escalation portion of the Phase 1-2 study will begin enrolling patients with selected advanced solid tumors likely to harbor abnormalities of the Wnt/β-catenin signaling pathway. The Phase 2 dose-expansion portion aims to continue to assess the safety of ST316 as well as proof of concept in four specific tumor types 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. Its pipeline of SPEARs™ (Stabilized Peptides Engineered Against Regulation) disrupt intracellular protein-protein interactions, enabling targeting of transcription factors which have traditionally been considered undruggable. Sapience's lead program, ST101, is a first-in-class antagonist of C/EBPβ that has demonstrated clinical proof-of-concept in advanced solid tumors.  Sapience has received IND clearance to proceed with its second program, ST316, a first-in-class antagonist of β-catenin.  For more information on Sapience Therapeutics, please visit www.sapiencetherapeutics.com and engage with us on LinkedIn . SOURCE: Sapience Therapeutics