lucicebtide (ST101) / Sapience Therap - LARVOL DELTA

Sapience Therapeutics Provides Data Update from Phase 2 Trial of Lucicebtide in Patients with Glioblastoma at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting (PRNewswire) - P1/2 | N=125 | NCT04478279 | Sponsor: Sapience Therapeutics | "Lucicebtide was well-tolerated as a monotherapy and in combination with standard-of-care (SOC) agents; Lucicebtide combination with SOC Window-of-Opportunity study in newly diagnosed GBM cohort (n=9), data cut May 6, 2025: 5/9 patients yet to experience disease progression (10-24+ months). 6/9 patients are alive as of the data cutoff date (10-26+ months); Lucicebtide Window-of-Opportunity study in recurrent GBM cohort (n=9), data cut May 6, 2025: 4/9 patients had disease control, with two partial responses. 3/9 patients remain alive as of data cutoff; Data support lucicebtide and C/EBPβ antagonism as a differentiated and promising therapeutic approach for patients with GBM."

P2 data • Glioblastoma

Use of lucicebtide (ST101) in glioblastoma patients by antagonism of C/EBPβ-dependent mesenchymal cell transition and immunosuppressive M2 macrophage polarization. (ASCO 2025) - P1/2 | "Lucicebtide is well-tolerated as monotherapy and in combination with SoC. Improvements in PFS and OS in GBM patients following lucicebtide exposure demonstrated penetration across the BBB and target engagement, resulting in on-target pharmacodynamic activity including a dramatic reduction in mesenchymal gene signature in tumor cells and a remodeling towards a more permissive immune TME. These data provide the mechanistic rationale for continued clinical evaluation of lucicebtide as a novel approach for patients with GBM."

Clinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CD8

Sapience Therapeutics Announces Oral Presentation at the Upcoming 2025 American Society of Clinical Oncology (ASCO) Annual Meeting Featuring Lucicebtide Phase 2 Results (PRNewswire) - "Sapience Therapeutics, Inc...announced that data from its Phase 2 clinical trial of lucicebtide (formerly known as ST101), a first-in-class antagonist of C/EBPβ, in patients with glioblastoma will be featured during an oral presentation at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 30-June 3, 2025, in Chicago and online."

P2 data • Glioblastoma

The clinical C/EBPβ antagonist peptide lucicebtide synergizes with molecularly targeted therapies in GBM (AACR 2025) - P1/2 | "These studies demonstrate the potential of lucicebtide to enhance the activity of molecularly targeted therapeutics such as EGFRi that are typically not effective when used as monotherapies in GBM. Biomarker analysis utilizing GBM genetics and signatures of C/EBPβ activity was performed to identify potential target populations likely to benefit from ST101 combinations."

Clinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CDK4 • MDM4 • PDGFRA

Sapience Therapeutics to Present Multiple Posters at the American Association for Cancer Research (AACR) Annual Meeting 2025 (PRNewswire) - "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."

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

The C/EBPβ antagonist peptide lucicebtide (ST101) induces macrophage polarization toward a pro-inflammatory phenotype and enhances anti-tumor immune responses. (PubMed, Front Immunol) - "Lucicebtide synergizes with anti-PD-1 therapy and overcomes resistance to checkpoint inhibition in anti-PD-1-refractory tumors, but in vivo responses are impaired by systemic macrophage depletion, indicating that macrophage reprogramming is integral to lucicebtide activity. These results identify lucicebtide as a novel immunomodulator that reprograms immunosuppressive macrophage populations to enhance anti-tumor activity and suggests its utility for combination strategies in cancers with poor response to ICIs."

Journal • Breast Cancer • Colorectal Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

ST101-101: A Phase 1-2 Study of ST101 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=125 | Active, not recruiting | Sponsor: Sapience Therapeutics | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial primary completion date • Brain Cancer • Breast Cancer • Castration-Resistant Prostate Cancer • CNS Tumor • Genito-urinary Cancer • Glioblastoma • Hormone Receptor Positive Breast Cancer • Melanoma • Oncology • Prostate Cancer • Solid Tumor • BRAF

ST101 Oral Presentation Highlights Include (PRNewswire) - P1/2 | N=125 | NCT04478279 | Sponsor: 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."

P2 data • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

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) (SITC 2024) - P1/2 | "Consistent with a defined role for C/EBPß in maintenance of the immunosuppressive M2 program in macrophages, ST101 drives an increase in the M1/M2 ratio of TAMs in resected rGBM and ndGBM tumors. Collectively, these results demonstrate an anti-tumor/pro-inflammatory role for ST101 on TAMs and CD8+ T cells and support clinical evaluation of ST101 in combination with checkpoint inhibition."

Biomarker • Clinical • Tumor microenvironment • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CD163 • CD68 • CD8

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

ST101-101: A Phase 1-2 Study of ST101 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=125 | Active, not recruiting | Sponsor: Sapience Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Brain Cancer • Breast Cancer • CNS Tumor • Genito-urinary Cancer • Glioblastoma • Hormone Receptor Positive Breast Cancer • Melanoma • Oncology • Prostate Cancer • Solid Tumor • BRAF

Efficacy and biomarker analysis of phase 2 (P2) and window-of-opportunity (WoO) cohorts of patients with recurrent glioblastoma (rGBM) treated with ST101, an inhibitor of the transcription factor C/EBPβ. (ASCO 2024) - P1/2 | "Monotherapy ST101 in pts with rGBM has an excellent safety profile and results in comparable outcomes to current 2 nd line treatments. ST101 crosses the BBB, engages its target, and potentially induces treatment-related necrosis. These encouraging clinical activity, safety, and tissue findings, as well as preclinical data showing additive activity in combination with lomustine, support advancing ST101 to a randomized, placebo-controlled study comparing ST101 + lomustine vs."

Biomarker • Clinical • P2 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Sapience Therapeutics Presents Positive Clinical and Biomarker Data from ST101 Phase 2 Study in GBM at ASCO 2024 in Oral Presentation (PRNewswire) - P1/2 | N=162 | NCT04478279 | Sponsor: Sapience Therapeutics | "Outcome data presented from multiple cohorts of GBM patients (n=42). Main study: monotherapy in recurrent GBM, n=30; 2 patients with PRs, on study treatment for 55 weeks and 59+ weeks; 7 patients with SD with on study treatment for a range of 13-79 weeks; 53% OS and 40% OS at 9 and 12 months, respectively. Window-of-Opportunity Study: ST101 monotherapy in recurrent GBM, n=6; 2 PRs (1 unconfirmed), 1 ongoing; 2 SD, 1 ongoing; Median OS ~12 months; 3/6 patients alive (41-62 wks)....Biomarker data presented from Window-of-Opportunity study cohorts: ST101 crosses the BBB and penetrates tumor tissue as shown by IHC; Target (C/EBPβ) engagement and degradation shown by IHC; Modulation of the tumor immune microenvironment to promote anti-tumor activity."

Biomarker • P2 data • Glioblastoma

Sapience Therapeutics to Showcase Clinical and Biomarker Data from ST101 Phase 2 Study in GBM at ASCO 2024 (PRNewswire) - "Sapience Therapeutics...announced that clinical and biomarker data from its ST101 Phase 2 study in GBM will be delivered during an oral presentation on June 1, 2024 at the upcoming 2024 American Society of Clinical Oncology (ASCO) Annual Meeting....Outcome data to be presented from multiple cohorts of GBM patients - Main study: monotherapy in recurrent GBM; Window-of-Opportunity Study: mono/combination-therapy in GBM. Biomarker data to be presented from Window-of-Opportunity study cohorts: ST101 crosses the BBB and penetrates tumor tissue as shown by IHC; Target (C/EBPβ) engagement and degradation shown by IHC."

Biomarker • P2 data • Glioblastoma

Sapience Therapeutics Announces Oral Presentation at the Upcoming 2024 ASCO Annual Meeting Featuring ST101 Phase 2 Results in GBM (PRNewswire) - "Sapience Therapeutics, Inc...announced that data from its Phase 2 study of ST101 will be presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 31-June 4, 2024, in Chicago, IL and online. 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 an ongoing Phase 1-2 clinical study (NCT04478279)."

P2 data • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

ST101, a clinical CEBPβ antagonist peptide, promotes an immune-active tumor microenvironment by multiple cellular mechanisms (AACR 2024) - P1/2 | "Overall, these results provide novel evidence for the contribution of C/EBPβ to the expression of multiple IS cancer-associated cell types and support the use of ST101 to antagonize C/EBPβ and promote an immune-active TME. Further, these data provide rational for evaluating the clinical impact of ST101 in combinations with immune checkpoint inhibitors."

Biomarker • Clinical • IO biomarker • Tumor microenvironment • Brain Cancer • Breast Cancer • CNS Tumor • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • CD80 • FOXP3 • IFNG • SIGLEC5

Sapience Therapeutics Presents Three Posters at the American Association for Cancer Research (AACR) Annual Meeting 2024 (PRNewswire) - "Abstract Number: 2909:...In animal models, ST101 enhances the activity of anti-PD-1 treatment by increasing the M1/M2 ratio in the TAM population. Gene expression analysis of clinical biopsies indicates that ST101 modulates the tumor immune microenvironment by suppressing genes required for M2 macrophage polarization, resulting in an enhanced CD8/Treg ratio. ST101 represents a novel approach to enhance anti-tumor immune activity and these data suggest its utility for combination strategies in cancers with poor response to immune checkpoint inhibition."

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

ST101-101: A Phase 1-2 Study of ST101 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=162 | Recruiting | Sponsor: Sapience Therapeutics

Metastases • Trial completion date • Trial primary completion date • Brain Cancer • Breast Cancer • CNS Tumor • Genito-urinary Cancer • Glioblastoma • Hormone Receptor Positive Breast Cancer • Melanoma • Oncology • Prostate Cancer • Solid Tumor • BRAF

Sapience Therapeutics Presents New ST101 Phase 2 Clinical Data in GBM at the 2023 Society for Neuro-Oncology (SNO) Annual Meeting (PRNewswire) - P2 | N=162 | NCT04478279 | Sponsor: Sapience Therapeutics | "Sapience Therapeutics, Inc...today announced the presentation of new Phase 2 clinical data for ST101 at the 2023 Society for Neuro-Oncology (SNO) Annual Meeting 2023...As of November 7, 2023, 12 patients received 2-4 doses of ST101 before surgery and were evaluable (6 with ndGBM and 6 with rGBM)...Key Results as of November 7, 2023...83% Disease Control Rate (DCR), including 1 Complete Response (CR) and 4 patients with Stable Disease (SD), in 6 patients treated with neoadjuvant and adjuvant ST101 as part of their standard of care treatment...67% DCR, including 2 Partial Responses (PRs) and 2 SD, in 6 patients treated with neoadjuvant and adjuvant ST101 monotherapy....'I look forward to continuing to evaluate ST101 in the ongoing Phase 2 study and delivering hope to my GBM patients and their families."

P2 data • Trial status • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

Neoadjuvant treatment with ST101, C/EBPβ antagonist, triggers necrosis as a pathological response in newly diagnosed GBM patients. Tissue-based analysis from a surgical window of opportunity trial. (SNO 2023) - P1/2 | "After surgery, patients will continue ST101 QW + standard chemoradiation with temozolomide. ndGBM treated with neoadjuvant ST101 monotherapy shows extensive treatment effects on the tumors that have never been treated with chemoradiation. Stability of enhancing lesions after ST101 monotherapy may not reflect the extent of treatment effect as revealed by treatment-related necrosis in the resected tissue. Analyses of the pharmacodynamics effects of ST101 on GBM cells and tumor microenvironment will be completed and presented."

Clinical • Oncology

Sapience Therapeutics Announces Poster Presentation with New Clinical Data for ST101 in GBM at the 2023 Society for Neuro-Oncology (SNO) Annual Meeting (PRNewswire) - "Sapience Therapeutics, Inc...announced that data from the Phase 2 portion of its Phase 1-2 study of ST101 will be presented at the 2023 Society for Neuro-Oncology (SNO) Annual Meeting, taking place November 15-19, 2023, in Vancouver, Canada."

P2 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

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) - P1/2 | N=162 | NCT04478279 | Sponsor: Sapience Therapeutics | "Sapience Therapeutics...announced the presentation of two posters at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics....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....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."

P2 data • Glioblastoma

Sapience Therapeutics Announces Presentation of ST101 Clinical Data at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (PRNewswire) - "Sapience Therapeutics, Inc...announced that an abstract on ST101 has been accepted for a poster presentation at the upcoming AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, taking place October 11-15, 2023 in Boston, MA....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 to be presented will summarize clinical data from ST101's recurrent Glioblastoma (rGBM) Phase 2 expansion cohort of 30 patients."

P2 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

ST101, a peptide antagonist of novel I/O target CEBPβ,reprograms MDSCs and promotes an immunoactive tumor microenvironment (AACR 2023) - P1/2 | "The result is a decrease in intratumoral regulatory T cell (Treg) vs. TIL ratio, indicating a shift towards a more immunoactive TME. Overall, these results support a novel, macrophage-driven mechanism of action for ST101 as anticancer agent and suggest the exploration of ST101 in immune-oncology therapeutic strategies."

Biomarker • IO biomarker • Late-breaking abstract • Tumor microenvironment • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD163 • CD80 • CD86 • FOXP3 • IFNG • IL4 • MRC1 • SIGLEC5