Resverlogix Corp.

Neurodegenerative Diseases

Epidemiological and mechanistic evidence indicate a link between CVD and neurodegenerative diseases such as dementia and Alzheimer’s disease (“AD”). A growing body of evidence now supports a strong and possibly causal relationship between the two. Both diseases are most prevalent in aged individuals and they share many of the same risk factors including, but not limited to, smoking, hypertension, altered glucose metabolism, obesity, genetic susceptibility (i.e., ApoE allele status), inflammation, and abnormal blood lipids. Multiple studies have now demonstrated that factors affecting CVD such as moderate-to-high mid-life cholesterol values, diabetes, obesity, and smoking approximately double the risk of AD. There are also links to cognition demonstrating an association between risk of cognitive decline (and dementia) with a history of stroke, myocardial infarction, peripheral artery disease, and carotid plaques. Other findings demonstrate similar relationships between AD and coronary artery disease, myocardial infarction, cardiac arrest, carotid atherosclerosis, and hypercholesterolemia.

Based on its epigenetic mechanism, apabetalone (RVX-208) has been shown to affect expression of numerous targets important for both CVD and AD such as ApoA-I/HDL, inflammatory mediators, components of the complement cascade and others. Moreover, apabetalone has been shown to repress pro-inflammatory, pro-atherosclerotic and pro-thrombotic pathways that can contribute to CVD and AD risk.

To further evaluate the potential of BET inhibition in neurodegenerative disease, such as AD, a variety of studies are underway to investigate the role of epigenetic modification in this disease and specifically the role of apabetalone mediated modulation of neuroinflammation and innate immunity. With leading experts on the neurodegenerative clinical and scientific advisory board providing input and guidance, a Phase 2 clinical study in this therapeutic area is planned.