Project Grant R43HL167432

DEVELOPMENT OF BIO 300 AS A NOVEL TREATMENT FOR IDIOPATHIC PULMONARY FIBROSIS - PROJECT SUMMARY IDIOPATHIC PULMONARY FIBROSIS (IPF) IS A SERIOUS LUNG DISEASE CHARACTERIZED BY PROGRESSIVE SCARRING OF THE TISSUE IN THE LUNGS. IPF IS ASSOCIATED WITH A PARTICULARLY POOR PROGNOSIS WITH MOST PATIENTS SUCCUMBING TO THE DISEASE WITHIN 3-5 YEARS FROM THE TIME OF DIAGNOSIS. TWO ANTIFIBROTIC THERAPIES, NINTEDANIB AND PIRFENIDONE, HAVE BEEN APPROVED IN RECENT YEARS FOR THE TREATMENT FOR IPF BASED ON THEIR ABILITY TO SLOW THE RATE OF DECLINE IN LUNG FUNCTION IN PATIENTS, HOWEVER, NEITHER TREATMENT HAVE BEEN SHOWN TO LEAD TO MEANINGFUL IMPROVEMENTS IN PATIENT QUALITY OF LIFE, AND BOTH HAVE ISSUES WITH PATIENT TOLERABILITY. HUMANETICS IS DEVELOPING BIO 300, A NANOSUSPENSION OF SYNTHETIC GENISTEIN, AS A THERAPY TO MITIGATE PULMONARY FIBROSIS RESULTING FROM EXPOSURE OF THE LUNGS TO IONIZING RADIATION. GENISTEIN HAS BEEN SHOWN TO EXHIBIT ANTIFIBROTIC ACTIVITY IN A VARIETY OF IN VITRO AND IN VIVO MODEL SYSTEMS THROUGH ITS INHIBITION OF PROINFLAMMATORY AND PROFIBROTIC GENE EXPRESSION INDUCED BY ACTIVATION OF THE CANONICAL NF-B AND TGF-SS SIGNALING PATHWAYS. BASED ON THESE FINDINGS, WE HYPOTHESIZE THAT BIO 300 MAY HAVE SIGNIFICANT THERAPEUTIC POTENTIAL AS A THERAPY FOR IPF PATIENTS. IMPORTANTLY, BIO 300 HAS DEMONSTRATED AN EXCEPTIONAL CLINICAL SAFETY PROFILE IN CLINICAL STUDIES IN BOTH HEALTHY VOLUNTEERS AND LUNG CANCER PATIENTS UNDERGOING RADIOTHERAPY, WHICH WILL STREAMLINE ITS PATH TOWARD FUTURE CLINICAL EVALUATION AS AN IPF TREATMENT. THE GOAL OF THIS PHASE 1 SBIR PROJECT IS TO EVALUATE THE UTILITY OF BIO 300 AS A TREATMENT FOR IPF BY MEASURING ITS ABILITY TO MITIGATE PULMONARY FIBROSIS IN THE BLEOMYCIN LUNG INJURY MOUSE MODEL - THE PREFERRED MODEL FOR EVALUATING CANDIDATE IPF THERAPEUTICS. SPECIFIC AIM 1 IS A BIO 300 DOSE RANGING STUDY TO DETERMINE THE THERAPEUTIC EFFICACY OF BIO 300 TO REDUCE PULMONARY FIBROSIS AND EXPRESSION OF DISEASE-RELATED BIOMARKERS IN THE BLEOMYCIN LUNG INJURY MOUSE MODEL. SPECIFIC AIM 2 WILL ASSESS THE IMPACT OF COMBINING BIO 300 WITH EACH OF THE CURRENTLY APPROVED IPF DRUGS TO DETERMINE IF COMBINATION THERAPY PROVIDES AN ADDITIONAL TREATMENT BENEFIT. SPECIFIC AIM 3 WILL BE TO REQUEST AND CONDUCT A TYPE C MEETING WITH THE FDA TO DISCUSS THE NONCLINICAL DATA OBTAINED FROM THE STUDIES COMPLETED UNDER THE FIRST TWO SPECIFIC AIMS, AND SOLICIT GUIDANCE ON FUTURE DEVELOPMENT ACTIVITIES AIMED AT ADVANCING BIO 300 TOWARD CLINICAL EVALUATION AS AN IPF TREATMENT.