Development of a WNT Inhibitor for Advanced Stage Lung Cancer

DESCRIPTION provided by applicant 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 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 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 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 andgt 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