Development Plan

EpiGen is currently investigating the use of histone deacetylase (HDAC) inhibitors for reducing myocardial infarct size following acute MI.  EpiGen plans to leverage the current regulatory approval of existing HDAC inhibitors and utilize the FDA 505(b)(2) regulatory pathway, which has the potential for minimizing the need to do additional preclinical and clinical studies.  EpiGen anticipates the need for formulation development to make existing HDAC inhibitors suitable for use in cardiac patients and plans to conduct clinical trials in MI patients.

Competitive Landscape

Currently, HDAC inhibitor development has been focused on oncology. There are no HDAC inhibitors currently in development for ischemia-reperfusion injury.  Furthermore, no pharmaceutical intervention to date has consistently shown to improve outcomes in patients following reperfusion injury in STEMI [Kloner Circ Res. 2013].

Intellectual Property

EpiGen has the option from the University of Pennsylvania to license their HDAC inhibitor reperfusion therapy patents and anticipates fully licensing the patents in the near term.

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Unmet Medical Need & Rationale

Myocardial infarction (MI) remains a common and serious disease worldwide. Although rapid intervention to re-establish myocardial perfusion limits infarct size and improves patient survival, restoration of blood flow and reversal of ischemia is often followed by cellular and functional changes that lead to further tissue damage known as reperfusion injury. This longer term consequence remains an unmet medical need. There currently exists no recognized effective pharmaceutical intervention for protecting the cardiomyocyte from reperfusion injury in acute MI [Hausenloy Cardiovasc Res 2013].  Thus, new therapies aimed at new cellular targets are still in demand [Kloner Circ Res 2013].

The emerging science of epigenetics (which relates to the control of gene products by factors other than an individual's DNA sequence) is unveiling how epigenetic changes can switch genes on or off and determine which and to what extent proteins are transcribed in cells, tissues, and organs.  Within cells, there are three systems that can interact with each other to modulate genes: DNA methylation, histone modifications, and RNA-associated silencing [Simmons Nat Edu 2008].  Histones are ubiquitous. Alterations in the enzymes mediating histone acetylation affect gene expression, and have been demonstrated to be involved in ischemia within the brain [Formisano Proc Natl Acad Sci USA 2007] and most recently in myocardial ischemia [Granger FASEB 2008].