Repurposing of Pyrvinium Pamoate for Familial Adenomatous Polyposis (FAP)

ABSTRACT Individuals with the rareinherited disorder Familial Adenomatous PolyposisFAPdevelop thousands of precancerous polyps at an early age and ultimately develop colorectal cancerCRCThe current standard of care for FAP is colectomyHoweverunavoidable side effects of colectomy are debilitatingFurthermorecolectomy does not prevent subsequent development of extra colonic intestinal tumorsthe main cause of death post colectomyThere are currently no drugs FDA approved for the treatment or chemoprevention of FAP patientsWe have demonstrated that pyrvinium can be repurposed as a potent inhibitor of WNT signaling and is efficacious in an animal model of FAPOral dosing of pyrvinium pamoate produces negligible systemic exposure and limits the exposure to the gut which reduces the likelihood of toxicitySubmitting these data to the FDAwe were awarded an Orphan Drug Designation to market pyrvinium exclusively for FAP patientsTo clarify the steps required to take pyrvinium back into the clinic as a repurposed agent for FAP patientsusing abregulatory mechanismwe recently had a pre IND meeting with the FDAThis Phase I II Fast Track application is driven by the FDA s recommendations for a successful Investigational New DrugINDapplication for pyrvinium in the treatment of FAPThe repurposing of pyrvinium for FAP patientsif successfulwould representA major improvement in therapy and in the quality of lifeandThe successful bench to bedside application of a rationally selected targeted therapy NARRATIVE Familial Adenomatous Polyposis is an aggressive disease caused by a genetic mutation in the WNT signaling pathway with no effective treatment optionsPatients are typically in their teenage years when they develop hundreds of polyps in their colon and subsequently require the removal of their colonWe propose to develop a WNT inhibitorpyrviniumunder the orphan drug program to treat this disease