Efficacy and PK/PD of a c/EBP beta antagonist in orthotopic breast cancer
Ended Project Grant Awarded Last action
- Award ID
- R44CA250786
- Recipient
-
Sapience Therapeutics, Inc. UEI ERRLJEYAUMC8
- Awarding agency
-
National Cancer Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $2,066,693
Award facts
- Assistance listing
- 93.395 Cancer Treatment Research
- Completion date
- Place of performance
- New York, USA
Award details come from USAspending.gov.
Description
- 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/ebpss, which is a novel protein target active in cancer cells. C/ebpss 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/ebpss 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/ebpss 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.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Amendment | $803,479 | |
| Amendment | $631,607 | |
| Original award | $631,607 |
Quick answers
Who received award R44CA250786?
R44CA250786 was awarded to Sapience Therapeutics, Inc. by National Cancer Institute (National Institutes of Health) on August 5, 2020.
How much is award R44CA250786 worth?
$2,066,693 has been obligated on R44CA250786.
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