ST316 / Sapience Therap - LARVOL DELTA

Reprogramming of MDSCs by ST316, a clinical peptide antagonist of b-Catenin/BCL9, enhances anti-tumor immuno- and chemotherapy (AACR 2025) - P1 | "In combination studies, ST316 significantly enhances the anti-tumor efficacy of anti-PD-1 immunotherapy and standard-of-care chemotherapies for advanced CRC such as FOLFIRI...Our results reveal a novel role for Wnt/β-catenin signaling in MDSC biology and demonstrate that ST316 can suppress the increase of therapy-driven MDSCs in vivo. These data suggest that therapeutically targeting the BCL9/β-catenin interaction may be an effective strategy to enhance both chemotherapy and immunotherapy in Wnt-driven tumors that respond poorly to monotherapy."

Clinical • IO biomarker • Colorectal Cancer • Oncology • Solid Tumor • BCL9 • BCL9L

An ex vivo organoid study to identify biomarkers of sensitivity to ST316, a clinical-stage β-catenin antagonist peptide (AACR 2025) - "Given the importance of MAPK signaling in cancer, we evaluated dual inhibition of β-catenin and BRAF by combining ST316 with the BRAF inhibitor encorafenib in BRAF-mutant organoids. Given the poor prognosis and limited treatment options for BRAFV600E-mutant CRC, ST316 offers a promising new therapeutic approach for this difficult-to-treat cancer. Our findings support rational combinations of ST316 with clinically relevant MAPK inhibitors."

Preclinical • Colorectal Cancer • Oncology • Solid Tumor • BCL9 • CTNNB1 • NF1 • NRAS • TP53

Safety and biomarker assessment of ST316, a novel peptide antagonist of ß-catenin, in patients with advanced solid tumors. (ASCO-GI 2025) - P1 | "Monotherapy ST316 was well-tolerated with dose-proportional PK and substantial tumor uptake. Pharmacodynamic analyses demonstrate mechanistic evidence of antagonism of ß-catenin signaling, including redistribution of ß-catenin subcellular localization and significant depletion of the ß-catenin-driven immunosuppressive PMN-MDSC population. Based on these data, ST316 advanced into P2 in CRC pts in combination with SoC in 2nd and 3rd line."

Biomarker • Clinical • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BCL9

Sapience Therapeutics Presents ST316 Phase 1 Dose Escalation Data at the 2025 American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium (PRNewswire) - P1/2 | N=130 | NCT05848739 | Sponsor: Sapience Therapeutics | "Summary of Phase 1 Dose Escalation Results:...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."

P1 data • Trial status • Colorectal Cancer

ST316, a peptide antagonist of β-Catenin, depletes immunosuppressive myeloid cell populations and enhances anti-cancer immune responses in in vivo tumor models and in patients (SITC 2024) - P1 | "Samples were processed and analyzed for PMN-MDSC expression (CD3-CD19-CD14-HLADRlowCD11b+CD15+) by flow cytometry. ST316 significantly reduced PM"

IO biomarker • Preclinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BCL9 • CD14 • CD163 • CD19 • CD8 • CD80 • CTNNB1 • IFNG • IL4 • PD-L1

ST316 Poster Presentation Details (PRNewswire) - P1/2 | N=130 | NCT05848739 | "ST316 disrupts β-catenin-driven immune-exclusion, promoting a shift to an immune-active TIME via depletion of immunosuppressive MDSCs and TAMs, resulting in enhanced cytotoxic T cell activity; In the clinic, ST316 depletes highly immunosuppressive PMN-MDSCs in Phase I patients; In human PBMCs, ST316 induces a dose-dependent decrease in immunosuppressive M2 macrophages and a concomitant increase in M1 proinflammatory macrophages, resulting in increased T cell activation; In murine tumor models, ST316 inhibition of tumor growth is accompanied by a reduction in MDSC population and repolarization of TAMs to an M1-like phenotype."

P1 data • Preclinical • Oncology • Solid Tumor

Sapience Therapeutics Announces Multiple Presentations at the Society for Immunotherapy of Cancer's (SITC) 39th Annual Meeting (PRNewswire) - "Sapience Therapeutics, Inc...announced multiple presentations at the Society for Immunotherapy of Cancer's (SITC) 39th Annual Meeting, being held November 6-10, 2024, in Houston, TX....Sapience to present data on its two lead programs, including an oral presentation on the ST101 window of opportunity study and a poster on ST316, a peptide antagonist of ß-Catenin."

Clinical data • Preclinical • Glioblastoma • Solid Tumor

Sapience Therapeutics Enrolls First Patient in Phase 2 Study of ST316, a First-in-Class β-catenin Antagonist, in Colorectal Cancer (PRNewswire) - "Sapience Therapeutics...announced today that the first patient has been enrolled in its Phase 2 dose expansion study evaluating ST316, the Company's first-in-class antagonist of β-catenin. Enrollment of the study's Phase 1 monotherapy dose escalation portion was completed in July 2024....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..."

Trial status • Colorectal Cancer

ST316, a clinical peptide antagonist of beta-catenin, induces anti-tumor immune responses by multiple mechanisms of action (AACR 2024) - P1 | "Second, ST316 induced CD155/PVR upregulation and T-cell activation in the presence of anti-TIGIT antibody. Collectively these results suggest a novel immune-modulatory role for ST316 in the TIME and provide rational for combination therapy with checkpoint inhibitors."

Clinical • IO biomarker • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BCL9 • CD163 • CD209 • CD8 • CD80 • CTNNB1 • IFNG • IL4 • PVR • TIGIT

Sapience Therapeutics Presents Three Posters at the American Association for Cancer Research (AACR) Annual Meeting 2024 (PRNewswire) - "Abstract Number: 5332:...ST316 increases the ratio of proinflammatory M1 macrophages to immunosuppressive M2 macrophages, decreases PD-L1 expression on M2 macrophages and decreases PD1 expression on CD8+ T cells. ST316 promotes cell surface expression of CD155/PVR to activate T cells in the presence of anti-TIGIT antibody. In nonclinical in vivo studies, ST316 in combination with anti-PD-1 treatment displays significant anti-tumor activity with accompanied reduction in M2 macrophages."

Preclinical • Oncology

Sapience Therapeutics to Present Multiple Posters at the American Association for Cancer Research (AACR) Annual Meeting 2024 (PRNewswire) - "Sapience Therapeutics...announced three poster presentations at the 2024 American Association for Cancer Research (AACR)....Sapience will present non-clinical immunotherapy results at AACR from both of its clinical programs, ST316, a first-in-class antagonist of β-catenin, and ST101, a first-in-class antagonist of C/EBPβ. Sapience will also present first disclosure of pre-clinical data describing its first-in-class AP-1 complex antagonist targeting the interaction of cJun with Fra1."

Preclinical • Triple Negative Breast Cancer

Sapience Therapeutics Presents ST101 Clinical Data and ST316 Preclinical Data at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (GlobeNewswire) - "Sapience Therapeutics...announced the presentation of two posters at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics....The poster summarized preclinical data demonstrating the anti-tumor and immunostimulatory properties of ST316 in multiple cancer models....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."

Preclinical • Oncology • Triple Negative Breast Cancer

Anti-tumor and immunostimulatory properties of ST316, a peptide antagonist of beta-catenin for treatment of cancers with aberrant Wnt pathway activity. (AACR-NCI-EORTC 2023) - No abstract available

Oncology • CTNNB1

A Phase 1-2 of ST316 With Selected Advanced Unresectable and Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=156 | Recruiting | Sponsor: Sapience Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Breast Cancer • Cholangiocarcinoma • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Sarcoma • Solid Tumor • Synovial Sarcoma • Triple Negative Breast Cancer • BRCA • MSI • PD-L1

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 (PRNewswire) - "Sapience Therapeutics, Inc...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....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."

Trial status • Breast Cancer • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Sarcoma • Skin Cancer • Solid Tumor • Synovial Sarcoma

A Phase 1-2 of ST316 With Selected Advanced Unresectable and Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=156 | Not yet recruiting | Sponsor: Sapience Therapeutics

New P1 trial • Breast Cancer • Cholangiocarcinoma • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Sarcoma • Solid Tumor • Synovial Sarcoma • Triple Negative Breast Cancer • BRCA • MSI • PD-L1

Sapience Therapeutics Awarded $2 Million Grant to Evaluate the Therapeutic Potential of ST316, a First-in-Class β-catenin Antagonist (PRNewswire) - "Sapience Therapeutics, Inc...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...and evaluate the impact of ST316 on the tumor microenvironment (TME) in patient-derived cancer models....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."

Financing • Preclinical • Oncology

Immunotherapeutic potential of ST316, a peptide antagonist of β-catenin (AACR 2023) - "Anti-tumor activity was accompanied by an increase the M1/M2 ratio. Overall, these results support the immuno-therapeutic potential of ST316 and extend the application range of ST316 to include Wnt-driven cancers with poor clinical response to immune checkpoint blockade and other immunotherapeutic agents."

IO biomarker • Late-breaking abstract • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BCL9 • CD163 • CD80 • CD86 • CTNNB1 • IFNG

Sapience Therapeutics to Present Late-Breaking Data on ST101 and ST316 at the American Association for Cancer Research (AACR) Annual Meeting 2023 (PRNewswire) - "Sapience Therapeutics...announced today the presentation of two late-breaking research posters during the American Association for Cancer Research (AACR) Annual Meeting 2023....ST316 Abstract Highlights:...Nonclinical data indicate that ST316 exposure to human peripheral blood mononuclear cells shifts M2 macrophages to the M1 phenotype and increases CD8 T-cell activation in macrophage/T-cell mixed cultures. ST316 enhances the anti-tumor activity of anti-PD-1 checkpoint inhibition in a preclinical triple-negative breast cancer model."

Late-breaking abstract • Preclinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Sapience Therapeutics Announces Late-Breaking Research Poster Presentations on ST101 and ST316 at the American Association for Cancer Research (AACR) Annual Meeting 2023 (PRNewswire) - "Sapience Therapeutics, Inc...announced today that it will present two late-breaking research posters during the American Association for Cancer Research (AACR) Annual Meeting 2023, taking place April 14-19, 2023, in Orlando, Florida."

Clinical data • Late-breaking abstract • Oncology

Sapience Therapeutics Receives IND Clearance from FDA to Proceed with Phase 1-2 Study of ST316 in Patients with Solid Tumors (PRNewswire) - "Sapience Therapeutics...announced today that the U.S. Food and Drug Administration (FDA) cleared the Company to proceed with its Phase 1-2 clinical trial of ST316 for the treatment of solid tumors. Sapience expects to begin patient dosing in the Phase 1 dose escalation portion of the study in the first half of 2023 to evaluate the safety, clinical activity, pharmacokinetics and pharmacodynamics of ST316....The Phase 2 dose-expansion portion of the study will enroll patients in four specific tumor types known to harbor abnormalities of the Wnt/β-catenin signaling pathway, including cholangiocarcinoma, colorectal, triple negative breast and ovarian cancers."

IND • New P1/2 trial • Biliary Cancer • Biliary Tract Cancer • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Sapience Therapeutics Announces $41 Million Series B Financing to Advance Pipeline of Peptide Therapeutics Targeting Protein-Protein Interactions (PRNewswire) - "Sapience Therapeutics...announced today the completion of a $41 million Series B financing. The financing was led by new investor NexPoint and included participation from existing investors Bristol Myers Squibb, Eshelman Ventures and Kingdon Capital....The proceeds will support the advancement of its lead program, ST101, which is currently in Phase 2 for patients with advanced solid tumors, and progress its second program, ST316, from IND-enabling studies to the commencement of a Phase 1 study."

Financing • Oncology • Solid Tumor

β-catenin antagonist peptide, ST316, attenuates Wnt-dependent oncogenic activity (AACR 2022) - "ST316 (5 mg/kg) administered three times weekly by subcutaneous injection resulted in 99.6% tumor growth inhibition vs. vehicle controls (p<0.05), while a negative control peptide had no significant impact on tumor growth. These data demonstrate the potential of ST316 as a potent therapeutic candidate for Wnt/β-catenin-dependent cancers."

Late-breaking abstract • Breast Cancer • Chronic Lymphocytic Leukemia • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor • APC • BCL9 • CDK4 • CTNNB1

Sapience Therapeutics Presents Late-Breaking Data at AACR 2022 Demonstrating the Potential of Targeting Intracellular Interactions to Drug Well-Validated Cancer Pathways (PRNewswire) - "Following administration of ST101 in TNBC mice, significant tumor growth inhibition was observed, and the exposures required to achieve IC50 and IC90 predicts that 1 mg/kg in humans will exceed the exposure associated with the IC90 in mice....Sapience scientists presented preclinical data on ST316 demonstrating target engagement with β-catenin, in vitro activity demonstrating disruption of β-catenin nuclear localization, changes in target gene expression in HCT116 cells and significant anti-tumor activity in vivo."

Preclinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Sapience Therapeutics Announces Multiple Poster Presentations at the American Association for Cancer Research (AACR) Annual Meeting 2022 (Sapience Press Release) - "Sapience Therapeutics...announced today that two abstracts have been accepted for presentation during the late-breaking research sessions at the American Association for Cancer Research (AACR) Annual Meeting taking place April 8-13, 2022 in New Orleans, LA."

Preclinical • Breast Cancer • Oncology