ST316 / Sapience Therap - LARVOL DELTA

A Safety Study of ST316 in Participants With Familial Adenomatous Polyposis (FAP). (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: Sapience Therapeutics

New P1 trial • Genetic Disorders

ST316-101: A Phase 1-2 of ST316 With Selected Advanced Unresectable and Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=130 | Active, not recruiting | Sponsor: Sapience Therapeutics | Recruiting ➔ Active, not recruiting | Trial completion date: May 2027 ➔ Dec 2027 | Trial primary completion date: May 2026 ➔ Dec 2026

Enrollment closed • Trial completion date • Trial primary completion date • Breast Cancer • Colon Cancer • Colorectal Cancer • Hepatocellular Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Safety and efficacy of ST316, a first in class ß-catenin antagonist, in metastatic colorectal cancer (mCRC). (ASCO 2026) - P1 | "ST316 monotherapy was generally well tolerated, safe, and resulted in significant on-target suppression of tumor Wnt/ß-catenin transcriptional signatures. In 2L metastatic CRC, ST316 combined with FOLFIRI/bevacizumab reached a confirmed ORR of 46.7% and disease control rate of 93.4%, which compare favorably with 2L FOLFIRI/bevacizumab historical ORR of 11% (Iwamoto et al, EAGLE), supporting a clinically meaningful combination effect. Liver enzyme elevations were reversible and asymptomatic."

Clinical • Metastases • Colorectal Cancer • Neutropenia • Oncology • Solid Tumor • BCL9

Antagonism of β-Catenin/BCL9 interaction suppresses polymorphonuclear myeloid-derived suppressor cell generation and maintenance (AACR 2026) - P1 | "In addition, ST316 reduced expression of several myeloid markers associated with neutrophil differentiation, including CD101, CD300a, and Siglec-F, suggesting that these markers reflect β-catenin/BCL9 controlled dynamics of MDSCs generation. Overall, our results identify a new role for β-catenin/BCL9 signaling in MDSC generation and maintenance, and identify suppression of MDSCs as a consequence of ST316 exposure in nonclinical and clinical tumor settings."

Clinical • Myeloid-derived suppressor cells • Colorectal Cancer • Oncology • Solid Tumor • BCL9

ST316, a first in class β-catenin antagonist, demonstrates safety and efficacy in metastatic colorectal cancer (mCRC) (AACR 2026) - "In Ph2, 15 2L CRC pts (median age 53, range 22-62), 100% MSS, 73% RAS mut, were treated with ST316 + FOLFIRI/bevacizumab and evaluable for response...Liver enzyme elevations were reversible and asymptomatic. Together, the data support further evaluation of ST316 in combination with SOC in early-stage CRC."

Clinical • Metastases • Colorectal Cancer • Oncology • Solid Tumor • BCL9 • CTNNB1 • TGFB1

In the ST316 Phase 1 monotherapy dose escalation study, trial objectives were achieved… (PRNewswire) - "Potent on-target pharmacodynamic effects, including significant and consistent knock down of Wnt-related signatures in tumor cells but not in adjacent normal cell types, recapitulation of a β-catenin/BCL9 genetic knock-out signature, reduced expression of Wnt target genes, and loss of cancer stem cell features. Dose-proportional pharmacokinetics that achieve predicted efficacious exposures. A well-tolerated safety profile, with no dose-limiting toxicities (DLTs) or related serious adverse events (SAEs) observed."

dMMR • MSI-H • P1 data • Colorectal Cancer • Microsatellite Instability

Sapience Therapeutics Presents First Clinical Results from Phase 2 Study of ST316, First-in-Class β-catenin Antagonist, in Second-Line Colorectal Cancer at the American Association for Cancer Research (AACR) Annual Meeting 2026 (PRNewswire) - "As of an April 13, 2026 cutoff date: The confirmed objective response rate (ORR) per RECIST 1.1 was 47%, with 7 of 15 patients having a confirmed Partial Response (PR). This ORR compares favorably to historical studies evaluating the combination of anti-VEGF and chemotherapy in 2L CRC (ORR range: 5 - 23%). The disease control rate (DCR) was 93%, with 14 patients classified as having Stable Disease (SD) or PR. Responses were seen in RAS-mutated and RAS-wild type patients, patients with liver metastases, and patients treated with prior bevacizumab."

dMMR • MSI-H • P2 data • Colorectal Cancer • Microsatellite Instability

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

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

Sapience Therapeutics to Present Multiple Posters at the American Association for Cancer Research (AACR) Annual Meeting 2026 (PRNewswire) - "Sapience will present clinical and non-clinical results from ST316, a first-in-class antagonist of β-catenin, as well as results from its preclinical Fra1 antagonist peptide (FraAP) program, a first-in-class antagonist of the activator protein 1 (AP-1) complex."

Preclinical • Colorectal Cancer • Squamous Cell Carcinoma of Head and Neck

Antagonism of Beta-catenin/Bcl9 impairs generation of immune-suppressive MDSCs and promotes enhanced immune responses. (SITC 2025) - P1 | "These observations are consistent with ST316 anti-tumor activity as monotherapy and in combination with standard-of-care agents in CRC. Overall, these data help dissect the role of Wnt/b-catenin in PMN-MDSC development and further support antagonism of b-catenin/BCL9 with ST316 as a novel therapeutic approach for CRC.Ethics Approval All aspects of animal care were in accordance with the Guide for Care and Use of Laboratory Animals and all experiments were approved by the Institutional IACUC at New York Medical College (NYMC)."

Colorectal Cancer • Oncology • Solid Tumor • BCL9 • BCL9L • CTNNB1 • GZMB • IFNG

Clinical-stage Wnt/β-catenin antagonist peptide ST316, suppresses colorectal cancer tumor growth by promoting BCL9 degradation (AACR-NCI-EORTC 2025) - "Combination studies in the HCT116 xenograft model utilizing sub-pharmacologic ST316 with Lonsurf (20mg/kg 1x/week) or Folfiri (5 mg/kg 5-FU and 10 mg/kg irinotecan QD) indicated significantly enhanced tumor growth inhibition in the combination setting compared to either single agent, highlighting the potential of ST316 for integration into standard of care regimens. Our nonclinical data demonstrating ST316 mediated disruption of the β-catenin- BCL9 complex, subsequent BCL9 degradation and potent antitumor efficacy in CRC models support its continued development as a promising therapeutic strategy for CRC with enhanced effectiveness when combined with standard-of-care treatments."

Clinical • Colorectal Cancer • Oncology • Solid Tumor • BCL9 • BCL9L • CTNNB1

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

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