# Efficacy and PK/PD of a C/EBP beta antagonist in orthotopic breast cancer

> **NIH NIH R44** · SAPIENCE THERAPEUTICS, INC. · 2022 · $631,607

## Abstract

ABSTRACT
Breast cancer (BC) remains an immense clinical challenge, particularly for late stage and metastatic disease.
Prognosis for late-stage and metastatic disease is grim, with 5-year survival for Stage 4 metastatic disease at
22%, with a median survival of 3 years, resulting in approximately 40,000 deaths annually. As evident by these
clinical outcomes, late stage and metastatic BC remains a high unmet medical need. Sapience’s ST101 provides
a new opportunity to treat advanced or metastatic HER2-negative BC. The target of ST101 is C/EBPβ, which is
a novel protein target active in cancer cells. C/EBPβ was previously considered an ‘undruggable’ target due to
its (1) location inside of the nucleus of a cell and (2) activity dependent on protein-protein interactions, and not
enzymatic activity. ST101 is a peptide antagonist of C/EBPβ interactions in tumor cells, resulting in transcriptional
inhibition of survival factors, thereby triggering synthetic lethality and tumor apoptosis. Based on promising pre-
clinical results, ST101 has moved into the clinical phase; it is currently in an open-label, two-part, phase 1/2
dose-finding study in patients with advanced, unresectable and metastatic solid tumors who have failed first- and
second-line therapies. To further support the development of ST101 and improve its chances of clinical success,
Sapience proposes to identify predictive and pharmacodynamic (PD) biomarkers for ST101 activity and
demonstrate their utility in non-clinical patient-derived breast cancer (PDBC) models. Specific Aim #1 will identify
predictive biomarkers of ST101 activity by screening a panel of PDBC models in 3-dimensional culture in vitro,
and will identify genetic and/or C/EBPβ translational or post-translational modifications that correlate with ST101
sensitivity (or resistance). In Specific Aim #2, the identified biomarkers will be interrogated in in vivo patient-
derived xenograft (PDX) mouse models, to assess whether they indeed predict ST101 success or failure. Finally,
Specific Aim #3 proposes to identify PD biomarker(s) via differential gene expression (DGE) in tissue specimens
used during Specific Aims #1 and #2, before and after ST101 exposure. In a clinical setting, these discoveries
will be utilized for patient selection and tracking responses during treatment as an accompanying
diagnostic/prognostic screen for ST101. The biomarkers would also be used to optimize dose or regimen.

## Key facts

- **NIH application ID:** 10384382
- **Project number:** 2R44CA250786-02
- **Recipient organization:** SAPIENCE THERAPEUTICS, INC.
- **Principal Investigator:** Jim Rotolo
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $631,607
- **Award type:** 2
- **Project period:** 2020-08-05 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10384382

## Citation

> US National Institutes of Health, RePORTER application 10384382, Efficacy and PK/PD of a C/EBP beta antagonist in orthotopic breast cancer (2R44CA250786-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10384382. Licensed CC0.

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