Epigenetics

While most people are familiar with the inheritance of genes via DNA from one generation to the next, the activity of these genes is actually determined by epigenetics, which literally means “on top of” genetics. DNA is considered the hardware of the human body, while epigenetics can be referred to as the software. DNA contains the code that tells our cells what to do, and this coded message is the same in every cell and does not change with time. However, our cells do not behave in the exact same way across time, particularly when disease is involved. Epigenetic changes to the DNA allow the message in the genes to be turned up or down like a dimmer switch, telling the cells which products to make more, or less of. During this process the DNA is not altered. The epigenetic control over the genetic message in the DNA underlies many diseases, and for this reason, epigenetics has become an exciting forefront for the discovery of new medicines.

Apabetalone – A New Drug

Apabetalone has the world lead in a new class of drugs which will be able to treat a multitude of diseases due to its unique epigenetic mechanism. One drug that targets multiple disease causing factors. Traditional therapeutics target a single factor and single outcome. What differentiates apabetalone from other drugs is that it has a positive effect on multiple biological processes that cause disease - leading a new paradigm shift in the treatment of diseases. Rather than targeting each of these disease states individually with a multitude of drugs, apabetalone affects key factors that underlie multiple disease states.

Unique Mechanism of Action

Apabetalone is a selective inhibitor of the Bromodomain and Extraterminal Domain (BET) proteins. BET proteins are key players in 'epigenetics' and have a hand in controlling the activity of cells. For example, when you are sick, BET proteins may act on DNA to “turn up” genes that tell the cell to make proteins such as those that cause inflammation. Apabetalone inhibits the BET proteins, which limits the production of these proteins.


 

How can Apabetalone have an impact on so many diseases?

The answer lies in looking at how we develop illnesses. Inappropriate inflammation, via your body’s immune response underlies many diseases. Since apabetalone targets inflammation, it is able to reduce the inflamed state and return the body to a healthier state. To put it simply, apabetalone helps your cells stay healthy by regulating the level of certain proteins that cause diseases.

Proof in the Data

A key feature of apabetalone is that it affects multiple processes which contribute to the onset and worsening of disease. This is consistent with observed reductions in Major Adverse Cardiac Events (MACE) that we have seen in our clinical trials. Essentially, patients who have taken apabetalone have had less heart attacks, strokes and cardio-related deaths. Our data has also shown that proteins associated with and those that drive kidney disease are “turned down” after a single dose of apabetalone.

Apabetalone is a bromodomain extra-terminal (BET) protein inhibitor which can regulate the expression of genes and restore the function of pathways underlying the pathogenesis of cardiovascular disease

 

A Bright Future

As apabetalone is a twice daily tablet, it will be an affordable and easy to administer treatment for all patients. Most importantly, apabetalone has proven exceptionally safe. Due to its unique epigenetic mechanism, we are discovering more ways that apabetalone can benefit patients among a broader range of diseases, including neurodegenerative diseases, peripheral artery disease and Orphan diseases. Apabetalone is currently in a Phase 3 clinical trial BETonMACE and will be fully enrolled within the first half of 2018.

More information is pulished in the European Biopharmaceutical Review Journal article titled: "New Direction."