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TECHNOLOGY OVERVIEW

VentriNova is revolutionizing cardiac regenerative medicine by reversing cardiac damage pharmacologically. With no cure available and unlike current exogenous repair approaches (stem cells, skeletal myoblasts), VentriNova’s pioneering approach of cyclin A2 modulation stimulates endogenous growth of new myocytes (heart muscle cells). Therapeutic regeneration of myocytes has been significantly demonstrated in small animals and in a large animal model of porcine myocardial infarction.

VN-100, Gene Therapy

The Company’s lead product, is viral vector-based gene therapy that induces cardiomyocyte division in adult heart tissue by delivery of the cyclin A2 gene – the principal gene regulating cell cycle activity. VN-100 has been tested extensively in small and large animal models and has been shown to significantly improve ejection fraction along with clear evidence of cellular regeneration via cardiomyocyte mitotic division.

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Figure 1: Analysis of cardiac function by MRI demonstrates significant enhancement of cardiac function in porcine hearts injected with cyclin A2 (denoted by blue) compared with porcine hearts injected with null adenovirus (denoted by red) after myocardial infarction was induced.

VentriNova is now poised to request investigational new drug approval from the FDA, and seeks to complete toxicity testing and verify the proof-of concept data obtained in large animals with GLP-compliant delivery systems over the next 18 months. VentriNova is pursuing parallel paths of testing the delivery of forms of cyclin A2 in large animals and the identification of a biologic/small molecule to activate the endogenous cyclin A2 gene in order to achieve the same effect.

The Science

Dr. Chaudhry’s seminal publication (Journal of Biological Chemistry, August 2004) demonstrated for the first time that mitosis in postnatal cardiomyocytes in the mouse heart could be achieved by continuously expressing cyclin A2, a gene that is normally silenced in mammalian hearts after birth. When these mouse hearts were subjected to myocardial infarction, new myocytes grew in the infarcted areas and restored cardiac function in a dramatic way when compared to control mice.

These results have been published in Circulation Research and made the cover of the June 22, 2007 issue. Furthermore, when delivered exogenously via viral vector to genetically naive rat hearts after myocardial infarction, cyclin A2 conferred significant enhancement of cardiac function with cellular regeneration of cardiomyocytes. These results were published in Circulation in 2006. These studies have been confirmed using viral delivery of cyclin A2 in the porcine model of myocardial infarction, and a manuscript describing these results is in submission.

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Figure 2: Porcine cardiac tissues that received cyclin A2 exhibit significantly enhanced mitotic index within cardiomyocytes, p=0.003. Green staining denotes alpha-actinin, a structural component of cardiomyocytes, red staining denotes phosphohistone H3, a crucial marker of mitosis, and blue denotes DNA (nuclei).