Non-small cell lung cancer (NSCLC) is the most common lung cancer. Half of NSCLC shows WNT activation, marking poor survival. StemSynergy Therapeutics Inc (SSTI) has identified a family of WNT inhibitors based on a novel chemical scaffold, with our lead molecule (SST-215) demonstrating efficacy against WNT-driven colorectal cancer. In Phase I SBIR studies, many NSCLC cell lines were also exquisitely sensitive to SSTI compounds. Remarkably, SST-215 showed efficacy against both therapy-resistant cell lines derived from lung metastases, in KRAS mutant lung cancer lines, and in a patient-derived NSCLC xenograft model--a high bar for efficacy. Despite this promise, SST-215 is metabolized and accumulates to low levels in lung and brain (sites of NSCLC metastases). We propose to test derivatives of our lead molecule scaffold, many of which are already synthesized, to identify compounds with bioavailability and distribution characteristics optimized for the lung cancer, including the common sites of metastases. Potent compounds will be further stratified by absorption, distribution, metabolism, excretion and toxicity (ADMET) characteristics. Efficacy will be assessed in a spectrum of lung cancer mouse models, with a goal of advancing a lead molecule into clinical development for the treatment of metastatic lung cancer.

Public Health Relevance

Lung cancer is the most common type of cancer and accounts for more deaths than the next four most common tumor types combined. Deregulated Wnt signaling occurs in >50% of lung cancer patients and there are no drugs available to inhibit the pathway. StemSynergy Therapeutics has developed a bioavailable and effective inhibitor of the pathway.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44CA171489-03
Application #
8928059
Study Section
Special Emphasis Panel (ZRG1-OTC-T (10))
Program Officer
Weber, Patricia A
Project Start
2012-09-20
Project End
2016-08-31
Budget Start
2015-09-01
Budget End
2016-08-31
Support Year
3
Fiscal Year
2015
Total Cost
$907,344
Indirect Cost
Name
Stemsynergy Therapeutics, Inc.
Department
Type
DUNS #
826941754
City
Miami
State
FL
Country
United States
Zip Code
33136