THERAPYX, INC. — Department of Health and Human Services SBIR Phase I: 300

Description

Project Summary Abstract Familial adenomatous polyposisFAPis an autosomal dominant genetic disease that leads to the development of hundreds to thousands of adenomas in the rectum and the colonCurrent medical management involves endoscopic monitoringresection of advanced polyps and ultimately colectomy in the second decade of lifeThe risk of developing colorectal cancer isand chemoprevention has not been successfulWe have demonstrated that oral administration of our proprietary sustained release particulate formulation of InterleukinILNanoCapsuppressesaintestinal polyposis in the APCminmouse modelbintestinal colon carcinogenesis in the APCminmouseBacteroides fragilis compound modeland csporadic adenocarcinoma in the CDX P NLS Cre APCloxP genetic colon cancer modelThese findingswhich were published in Cancer Research and Oncoimmunology provide the requisite milestones and the underpinning rationale for this Fasttrack applicationIn Phase I segmentAimwe will establish final proof of principle for in vivo therapeutic efficacy of our recently developed scaled up commercial batch ILNanoCap in the APCminBacteroides fragilis murine FAP modelIn Phase II segmentAimwe will optimize the treatment protocoldetermine longterm efficacy in earlypreventiveand establishedtreatmentdisease settings using the new regimendelineate the effect of long term treatment on gut systemic immune activityidentify serum response markersand obtain preliminary PK PD data in the above modelIn Aimwe will produce multiple large batches of bulk human ILNanoCapdemonstrate lot to lot consistency and determine long term stability prior to use in standard GLP rat toxicology studiesAimThe pre clinical data from Aimswill constitute the basis of the written questions and the briefing package that will be submitted to the FDA for a type C pre pre IND meetingAimSuccessful completion of these studies will inform and incentivize future SBIR Phase IIb supported non human primate toxicology and an open IND in preparation for clinical trials NARRATIVE PUBLIC HEALH RELEVANCE Familial Adenomatous PolyposisFAPis an incurable autosomal dominant genetic disease afflicting someAmericansHundreds to thousands of adenomas develop in the rectum and colonforcing colectomy usually in the second decade of lifeto avoid colorectal cancerThis Fast track proposal seeks to further the development of an oral formulation of the key regulatory cytokine interleukinILNanoCapas a novel therapy for FAP that can safelysustainably and conveniently deliver this potent immune signal directly to the gut