ABSTRACT Burns represent one of the most traumatic and debilitating injuries affecting over 2 million people in the United States. Reparative processes occurring after acute burn injury ultimately result in fibrosis (scarring). In experimental systems, WNT pathway activation promotes scarring, while inhibition leads to regeneration. We have identified pyrvinium (SST-024), an FDA approved anthelminthic drug, as a potent inhibitor of WNT signaling. Our preliminary studies in mouse wound models indicate that topical delivery of SST-024 promotes regenerative wound healing, increased tensile strength, and reduced fibrosis after cutaneous injury. The goal of this Phase I proposal is a concerted effort between StemSynergy Therapeutics, Inc. (SSTI) and Vanderbilt University to evaluate a novel class of small molecule CK1? agonists that promote regenerative healing/reduced scarring of burn injuries with improved efficacy compared to SST- 024. Preliminary topical formulation and efficacy studies involving SSTI?s lead CK1? agonists will be assessed in two well-established animal models of regenerative healing. Successful completion of these studies will allow us to evaluate and prioritize our CK1? agonists for more comprehensive formulation and efficacy studies in a Phase II application.