Development of a novel immunomodulatory pyridone for the treatment of acute heart damage

Project summary abstract In the USpeople per year develop heart failure from acute heart damagemostly from heart attacksApproximatelyof them die withinyears of the heart failure diagnosisCurrentlythere are no therapies to prevent the development of heart failure after acute heart damageA growing body of evidence points at Pirfenidonea pyridone currently approved for the treatment of a rare disease through an unknown mechanism of actionas a powerful cardioprotective drugPirfenidone is a poorly tolerated drug because of its unfavorable pharmacokineticsInnovative research recently conducted at Washington University in St Louis discovered that Pirfenidone protects the heart through an immunomodulatory effect on B lymphocytesPinpointing the cellular target of Pirfenidonethis research created the opportunity to optimize PirfenidoneWe expect that PEGylation of Pirfenidone with small PEG chainsandltDaltonswill produce a cardioprotective pyridone with favorable pharmacological propertiesPEGylation has been shown to be an effective method to improve the pharmacokinetic profile of small moleculesWe have shown that PEGylated Pirfenidone maintains its immunomodulatory effect on B cells in vitro and has prolonged half life after IV administration in vivoWe have secured IP on PEGylated PirfenidoneIn this Phase I applicationwe seek support to optimize the pharmacokinetics of PEGylated Pirfenidone through highly targeted medicinal chemistry modifications and in vivo measurements in miceand to test the cardioprotective effects of PEGylated Pirfenidone in clinically relevant in vivo murine models of acute heart injuryIn Phase II we will refine the properties of the lead PEGylated compoundcharacterize its cardioprotective effects in large animal modelsand perform initial toxicology studies in preparation of Investigational New Drug INDapplicationIf successfulthis project will produce a first in class immunomodulatory small molecule for the treatment of acute heart damage and for the prevention of injury induced heart failureBased on available pre clinical data on Pirfenidone and on available clinical data on damage induce heartfailurejust in the US such drug would be expected to save andgtlives and andgt$bn in projected cost of care every year Project narrativepublic health statement In the USpeople per year develop heart failure from acute heart damage andof them end up dying withinyears from the heart failure diagnosisCurrently there are no therapies to prevent the development of heart failure after acute heart damageIn this Phase I SBIRi Cordis seeks support to develop a first in class immunomodulatory small molecule to severe the connection between acute heart damage and heart failure