PROJECT SUMMARY/ABSTRACT Heart Failure with preserved Ejection Fraction (HFpEF) is one of the major drivers of healthcare costs in the western world and arguably the largest unmet need in cardiology. Currently, there are no FDA approved drugs to treat the vast majority of patients with HFpEF. Recently, the Phase II PIROUETTE trial showed that the immunomodulatory drug pirfenidone, marketed for the treatment of a rare lung disease, has marked beneficial effects in patients with HFpEF. Unfortunately, pirfenidone is a suboptimal drug. In fact, because of its poor pharmacokinetics, patients need to take 2 large pills three times a day and they often develop mild to moderate side effects that lead to dose reduction or discontinuation of treatment (38% of treated patients had to discontinue pirfenidone in the PIROUETTE trial). Moreover, from a commercial point of view, pirfenidone has no intellectual property protection and therefore pharmaceutical companies have no incentive to develop it for further applications. i-Cordis has PEGylated pirfenidone to obtain “Pegydone”, a new molecular entity with better exposure, less toxicity and superior therapeutic effects than pirfenidone. i-Cordis has completed proof of concept studies in rodent models. In this SBIR Phase II grant i-Cordis requests support to complete critical pre-clinical studies to de-risk its drug development effort in the eyes of potential investors. Following completion of the Phase II grant, the company plans to raise dilutive funding to complete IND filing, and progress through clinical trials, FDA approval and commercialization of Pegydone as a prescription drug for the treatment of HFpEF.