Lucicebtide

TARRYTOWN, N.Y., Jan. 27, 2025 /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 that it presented Phase 1 safety and biomarker data on ST316, a novel peptide antagonist of β-catenin, during a poster session at the 2025 American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium. ST316 is a first-in-class antagonist of β-catenin and its co-activator, BCL9, that is designed to selectively shut down the Wnt/β-catenin signaling pathway. The Phase 1 Dose Escalation study enrolled patients with advanced solid tumors likely to harbor abnormalities in the Wnt/β-catenin pathway to assess the safety, pharmacokinetics (PK), biomarker and preliminary activity of ST316, and to recommend a Phase 2 dose. "With signals of anti-tumor activity, strong pharmacodynamic data, and a clean safety profile, we are pleased that the ST316 Phase 1 Dose Escalation study demonstrated clinical proof-of-concept as a single agent, in a patient population in which single agent response is limited," commented Dr. Abi Vainstein-Haras, Sapience's Chief Medical Officer. "ST316's tolerability as a single agent, together with the biomarker data from its Phase 1 study, are encouraging for its continued development in our ongoing Phase 2 Dose Expansion study, which is evaluating ST316 across multiple combinations and lines of treatment in colorectal cancer (CRC)." Summary of Phase 1 Dose Escalation Results: ST316 disrupts the interaction of β-catenin with BCL9 to result in Wnt/β-catenin pathway inhibition. 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. Poster Presentation: Title: "Safety and biomarker assessment of ST316, a novel peptide antagonist of ß-catenin, in patients with advanced solid tumors" Session: Poster Session C: Cancers of the Colon, Rectum and Anus Date/Time: Saturday, January 25, 2025, 7:00 am to 7:55 am PST Abstract Number: 286 Presenting Author: Anthony El-Khoueiry, MD More information can be found on the ASCO GI website. 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 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 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 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. FDA has granted Orphan Drug Designation to ST316 for the treatment of familial adenomatous polyposis (FAP). 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. With in-house 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 can also direct cargo to cell surface targets with their new class of molecule called SPARCs™ (Stabilized Peptides Against Receptors on Cancer), enabling delivery of payloads such as α-particles to cancer cells. Sapience is advancing its lead programs, lucicebtide (formerly known as ST101), a first-in-class antagonist of C/EBPβ, and ST316, a first-in-class antagonist of β-catenin, through Phase 2 clinical trials. For more information on Sapience Therapeutics, please visit and engage with us on LinkedIn. Media and Investor Contact: Amy Conrad Juniper Point (858) 366-3243 [email protected] SOURCE Sapience Therapeutics, Inc. 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-ST101 Phase 2 data demonstrates activation of the tumor immune microenvironment in glioblastoma (GBM)- -ST316 Phase 1 data demonstrates antagonism of β-catenin-driven immune exclusion- TARRYTOWN, N.Y., Nov. 9, 2024 /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 clinical and non-clinical results on its lead programs, ST101 and ST316, at the Society for Immunotherapy of Cancer's (SITC) 39th Annual Meeting, being held November 6-10, 2024, in Houston, TX. ST101 is a first-in-class antagonist of C/EBPβ, currently being evaluated in patients with recurrent and newly diagnosed GBM in the Phase 2 portion of a Phase 1-2 clinical study (NCT04478279). 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 in multiple cancers where aberrant Wnt/β-catenin pathway signaling is observed and immune-exclusion in the tumor microenvironment. ST316 is being evaluated in colorectal cancer patients in the Phase 2 portion of a Phase 1-2 study (NCT05848739). Dr. Jim Rotolo, Sapience's SVP, Research and Translational Sciences, commented, "I am thrilled to have presented new clinical and biomarker data on ST101, which provides further evidence that C/EBPβ is a multi-faceted target for the treatment of newly diagnosed and recurrent GBM. The inclusion of our presentation in SITC's press briefing earlier this week, as one of 8 abstracts of the more than 1,500 received, highlights the novelty and importance of the data we are observing in our clinical study. Through our Phase 2 and Window-of-Opportunity studies, ST101 has demonstrated impressive disease control as well as modulation of the tumor immune microenvironment (TIME) from immunosuppressive to immune-active. This TIME shift is highly compelling given the immunosuppressive environment that is known to limit the efficacy of immune-oncology (I/O) agents in the treatment of GBM." Dr. Rotolo continued, "We also presented initial clinical pharmacodynamic data from our ST316 Phase 1 study, demonstrating that ST316 dramatically depletes immunosuppressive cells from peripheral blood of patients. In non-clinical studies, we were pleased to see that treatment with ST316 and PD-1 checkpoint inhibitors had positive effects on tumor outcomes and immune activation. These results at SITC, coupled with the data we have from the Phase 1 study, provide further validation that ST316 has the potential to improve existing I/O approaches." ST101 Oral Presentation Highlights Include: Title: "ST101, an inhibitor of the transcription factor C/EBPβ, promotes an immune-active tumor microenvironment in a window of opportunity (WoO) study of patients with glioblastoma (GBM)" Abstract #: 991 Session Title: Biotech Breakthroughs – Solid Tumor IO at the Tipping Point Date/Time: Friday, November 8, 2024, 1:45 pm – 3:20 pm CST Session Location: George R. Brown Convention Center, Level 3 – Grand Ballroom B Presenting Author: Jim Rotolo, Ph.D., SVP, Research & Translational Sciences, Sapience Therapeutics C/EBPβ activity within tumors promotes GBM growth, chemo-resistance, EMT, and invasion. C/EBPβ activity in immune cells promotes an immuno-suppressive environment. ST101, a C/EBPβ antagonist, has demonstrated safety and proof-of-concept activity in a Phase 2 clinical study, showing that treatment with ST101 leads to impaired tumor growth and increased immune activity. ST101 Window-of-Opportunity study in Newly Diagnosed GBM cohort (n=9, with 8 evaluable): 87.5% post-surgery disease control rate (DCR), with one complete response (CR) and six stable diseases (SD) as of the data cutoff date 8/9 patients are alive as of the data cutoff date (11-76 weeks) 7/9 patients remain on study with median treatment duration of 9.5 months, with 3 patients remaining on the study for greater than 17 months ST101 Window-of-Opportunity study in Recurrent GBM cohort (n=9): 4/9 (44%) patients had disease control, with 2 PRs and 2 SDs Window-of-Opportunity biomarker results demonstrate: ST101 uptake past the blood-brain barrier (BBB) and into the tumor Disruption of target C/EBPβ Shift in TIME from immunosuppressive to immune-active These data support the combination of ST101 with checkpoint inhibitors as a potential treatment for patients with GBM. ST101 Poster: Title: "ST101, an inhibitor of the transcription factor C/EBPß, promotes an immune-active tumor microenvironment in a window of opportunity (WoO) study of patients with glioblastoma (GBM)" Abstract #: 991 Session: Poster Hall Date/Time: Friday, November 8, 2024: 9:00 am – 7:00 pm CST Session Location: George R. Brown Convention Center, Level 1 – Exhibit Halls AB ST316 Poster Presentation Details: Title: "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" Abstract #: 1451 Session: Poster Hall Date/Time: Friday, November 8, 2024, 9:00 am – 7:00 pm CST Session Location: George R. Brown Convention Center, Level 1 – Exhibit Halls AB Presenting Author: Claudio Scuoppo, Ph.D., Principal Scientist, Sapience Therapeutics 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. In murine tumor models, anti-tumor activity of anti-PD-1 treatment is significantly enhanced by combination with ST316, an event accompanied by a reduction of M2-TAMs. These data provide support for the advancement ST316 through the current Phase 2 study and in combination with existing immune-oncology approaches to improve responses. About ST101 ST101, 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 ST101 as a monotherapy in patients with rGBM and in combination with radiation and temozolomide in patients with newly diagnosed GBM (ndGBM), 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. FDA and orphan designations for glioma from the U.S. FDA and the European Commission. About ST316 ST316 is a first-in-class peptide antagonist of the interaction between β-catenin and its co-activator, BCL9, a complex responsible for driving oncogene expression in multiple cancers where aberrant Wnt/β-catenin pathway signaling is observed. ST316 is being evaluated in the Phase 2 portion of a Phase 1-2 dose-escalation and expansion study (NCT05848739). The Phase 1 portion completed enrollment in July 2024. In the Phase 2 dose expansion, ST316 is being tested in colorectal cancer patients in combination with relevant standards of care and in multiple lines of treatment. Sapience is conducting the Phase 2 study across several sites in the United States. 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. With in-house 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, and can direct cargo to cell surface targets with their new class of molecule called SPARCs™ (Stabilized Peptides Against Receptors on Cancer), enabling delivery of payloads such as α-particles to cancer cells. 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 2 clinical trials. For more information on Sapience Therapeutics, please visit and engage with us on LinkedIn. Media and Investor Contact: Amy Conrad Juniper Point (858) 366-3243 [email protected] SOURCE Sapience Therapeutics, Inc. 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