lucicebtide (ST101) / Sapience Therap - LARVOL DELTA

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

The transcription factor C/EBPβ promotes hyperglycemia-elicited glycolysis and liver cancer progression. (PubMed, Nat Commun) - "Remarkably, hyperglycemia-accelerated hepatocellular glycometabolism and hepatocellular carcinoma progression in male mice are greatly prevented by hepatocyte-specific C/EBPβ deletion or Lucicebtide (ST101) treatment, a clinical phase-II C/EBPβ inhibitory peptide. Moreover, human C/EBPβ isoform LAP1 mimics the effect of hyperglycemia to boost hepatocellular glycometabolism and accelerate hepatocellular carcinoma progression. Thus, C/EBPβ is a critical regulator and potential therapeutic target for glucose-fueled cancer progression."

Journal • Diabetes • Hepatocellular Cancer • Liver Cancer • Metabolic Disorders • Oncology • Solid Tumor • ATF4 • HRAS • LDHA • SLC2A1

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

CEBPB COUPLES B-CELL RECEPTOR SIGNALING TO CLL CELL PROLIFERATION AND SURVIVAL (EHA 2026) - P1/2 | "CEBPB can be inhibited by antagonist peptide lucicebtide in therapeutically-relevant concentrations. Supported by the Ministry of Health of the Czech Republic (NU22-03-00117, NW24-03-00369), Czech Science Foundation (25- 15368X), MH CZ-DRO (FNBr,65269705), MUNI/A/1733/2025."

IO biomarker • Brain Cancer • Chronic Lymphocytic Leukemia • Glioblastoma • Hematological Malignancies • Leukemia • Solid Tumor • BCL2 • CD40LG • CD5 • CEBPB • CXCR4 • IL21 • IL4 • IL6 • MYC

Lucicebtide (ST101) plus chemoradiation in newly diagnosed GBM patients: Efficacy, pharmacodynamics, and safety from phase 2 window-of-opportunity study. (ASCO 2026) - P1/2 | "Lucicebtide is well-tolerated as monotherapy and in combination with SoC. Improvements in PFS and OS have been seen in GBM patients following lucicebtide exposure. Analysis of tumor resections demonstrate penetration across the BBB and target engagement, and on-target pharmacodynamic activity, including a dramatic reduction in mesenchymal gene signature in tumor cells and a remodeling towards a more permissive immune TME."

Clinical • P2 data • PK/PD data • Brain Cancer • Glioblastoma • Solid Tumor • CD8

Patients with ndGBM treated with lucicebtide in combination with SOC achieved PFS and OS outcomes that exceed those reported in the published literature (PRNewswire) - “Projected mPFS of 28.4 months meaningfully exceeds the 4.0 to 6.9-month historic benchmark range 4,5 mOS not yet reached; 6 of 9 patients remain alive beyond 22.3 months (per the cutoff date), exceeding the 14.6 to 17.0-month historic benchmark range.”

P2 data • Glioblastoma

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

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

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 completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Dec 2026

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

C/EBPβ Inhibition by Lucicebtide in a Window-of-Opportunity Surgical Trial for Glioblastoma Suppresses the Mesenchymal Phenotype and Promotes an Immunostimulatory Tumor Microenvironment (SNO 2025) - "Lucicebtide (ST101) is a first-in-class peptide antagonist of C/EBPβ that has demonstrated anti-tumor activity and TAM reprogramming in preclinical models, making it a promising therapeutic candidate in GBM...This unique clinical trial demonstrates that Lucicebtide effectively engages its target in human GBM, leading to suppression of the mesenchymal GBM state and a reprogramming of the TME. These findings support further clinical development of Lucicebtide as a novel therapeutic approach for GBM."

Biomarker • Tumor microenvironment • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CD8

C/EBPβ Inhibition by Lucicebtide in a Window-of-Opportunity Surgical Trial for Glioblastoma Suppresses the Mesenchymal Phenotype and Promotes an Immunostimulatory Tumor Microenvironment (WFNOS 2025) - "Lucicebtide (ST101) is a first-in-class peptide antagonist of C/EBPβ that has demonstrated anti-tumor activity and TAM reprogramming in preclinical models, making it a promising therapeutic candidate in GBM...This unique clinical trial demonstrates that Lucicebtide effectively engages its target in human GBM, leading to suppression of the mesenchymal GBM state and a reprogramming of the TME. These findings support further clinical development of Lucicebtide as a novel therapeutic approach for GBM."

Biomarker • Tumor microenvironment • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Solid Tumor • CD8

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 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

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

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

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

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

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