On March 26, 2025 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, reported four poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025, taking place April 25-30, 2025, in Chicago, Illinois (Press release, Sapience Therapeutics, MAR 26, 2025, View Source [SID1234651492]). Sapience will present non-clinical results from both of its clinical programs, lucicebtide (formerly known as ST101), a first-in-class antagonist of C/EBPβ, and ST316, a first-in-class antagonist of β-catenin and its co-activator, BCL9, 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.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"We are thrilled to be presenting a compendium of non-clinical data supportive of our clinical and preclinical SPEARs programs, including lucicebtide, ST316, and our FraAP program, at the upcoming AACR (Free AACR Whitepaper) Annual Meeting," said Jim Rotolo, Ph.D., Sapience’s Chief Scientific Officer. "Results from our lucicebtide and ST316 studies further elucidate their respective mechanisms of action and highlight their potential for combination strategies. Additionally, preclinical data demonstrate the potential of our FraAP program to induce anti-cancer activity by targeting the AP-1 complex, particularly in head and neck squamous cell carcinoma."
Poster Presentation Details and Abstract Highlights:
Title: "The clinical C/EBPβ antagonist peptide lucicebtide synergizes with molecularly targeted therapies in GBM"
Session Title: Targeted Therapies and Combinations 1
Location: Poster Section 34
Abstract Number: 839
Date and Time: Sunday, April 27, 2025, 2:00 pm – 5:00 pm CDT
Abstract Summary:
In non-clinical studies, the mechanism of lucicebtide, which has previously demonstrated antitumor activity via direct cell death and immune activation within the tumor microenvironment, enabled a synthetic lethal effect with molecularly targeted therapeutics, such as EGFR inhibitors, that are typically not effective when used as monotherapies for the treatment of glioblastoma (GBM). Transcriptional analysis utilizing GBM genetics and signatures of C/EBPβ activity were performed to identify potential target populations likely to benefit from lucicebtide combinations.
Title: "FraAP, a peptide antagonist against the activator protein 1 transcription factor complex, demonstrates cancer cell cytotoxicity and reduced invasion in vitro and tumor regression in vivo in HNSCC models"
Session Title: Gene Regulation and Transcription Factors 2
Location: Poster Section 10
Abstract Number: 1415
Date and Time: Monday, April 28, 2025, 9:00 am – 12:00 pm CDT
Abstract Summary:
FraAP selectively binds to and inhibits key oncogenic drivers of the AP-1 transcription factor complex, resulting in the suppression of AP-1 driven pathways required for cancer cell cycle progression, proliferation, and invasion and promotes apoptosis in preclinical studies. Further, in a head and neck squamous cell carcinoma (HNSCC) xenograft model, administration of FraAP results in significant tumor growth inhibition, further demonstrating the anti-cancer potential of targeting the AP-1 complex.
Title: "An ex vivo organoid study to identify biomarkers of sensitivity to ST316, a clinical-stage β-catenin antagonist peptide"
Session Title: Biomarkers and Molecular Targets for Prevention
Location: Poster Section 43
Abstract Number: 2361
Date and Time: Monday, April 28, 2025, 9:00 am – 12:00 pm CDT
Abstract Summary:
Analysis of 60 patient-derived tumor organoids revealed that tumors with TP53 WT and mutations in the MAPK pathway significantly correlate with sensitivity to ST316, a β-catenin antagonist peptide. Further, in non-clinical models, combining ST316 with encorafenib, a BRAF inhibitor, showed synergistic effects in BRAFV600E-mutant colorectal cancer (CRC) organoids, demonstrating a promising combination approach in this poor prognosis and underserved patient population. Across studies, findings support rational combinations of ST316 with clinically relevant MAPK inhibitors.
Title: "Reprogramming of MDSCs by ST316, a clinical peptide antagonist of β-Catenin/BCL9, enhances anti-tumor immuno- and chemotherapy"
Session Title: Modifiers of Tumor Microenvironment
Location: Poster Section 30
Abstract Number: 3275
Date and Time: Monday, April 28, 2025, 2:00 pm – 5:00 pm CDT
Abstract Summary:
Results reveal a novel role for Wnt/β-catenin signaling in myeloid-derived suppressor cell (MDSC) biology, a key mediator of immune-suppression, whereby antagonism of β-catenin with ST316 leads to suppression of MDSC expansion. 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. While anti-PD-1 and FOLFIRI alone each resulted in expansion of immunosuppressive MDSCs, combination with ST316 prevented this expansion. These data suggest that therapeutically targeting the β-catenin/BCL9 interaction may be an effective strategy to enhance both chemotherapy and immunotherapy in Wnt-driven tumors that respond poorly to monotherapy.
More information can be found on the AACR (Free AACR Whitepaper) Annual Meeting 2025 website.
About Lucicebtide (formerly known as ST101)
Lucicebtide, a first-in-class antagonist of C/EBPβ, has completed the main portion of a Phase 2 dose expansion study in recurrent GBM (rGBM) (NCT04478279). An ongoing window-of-opportunity sub-study is evaluating lucicebtide in combination with radiation and temozolomide in patients with newly diagnosed GBM (ndGBM) and as a monotherapy in patients with rGBM, with patients receiving ST101 before and after surgical resection in both cohorts. ST101 has been granted Fast Track designation for rGBM from the U.S. Food and Drug Administration (U.S. FDA) and orphan designations for glioma from the U.S. FDA and the European Commission.
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 formation of the 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 colorectal cancer (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. Food and Drug Administration (U.S. FDA) has granted Orphan Drug Designation to ST316 for the treatment of familial adenomatous polyposis (FAP).