The University of Sydney - CVD

Project title: Small molecule inhibitors of the P2X7 receptor as a safe and effective way of tackling the inflammatory contribution to atherosclerosis

One Australian suffers a heart attack every nine minutes. Up to 27 per cent of those that present with heart attack do not have traditional risk factors including hypertension, cholesterol, and diabetes. Coronary artery disease is not all "solved", and new drugs are needed. Our solution involves the development of a safe and effective treatment targeting the inflammatory driver of atherosclerosis.

Cardiovascular disease remains the leading killer of adults globally. Whilst inflammation is known to play a key role in the progression of atherosclerotic plaque and rupture causing a heart attack, pharmacotherapeutic attempts to target this have been limited. Our multi-disciplinary team, with expertise spanning from medicinal chemistry to preclinical models of disease and clinical translation, have developed a new class of "anti-inflammatory" compounds that shows promise for a broad range of common cardiovascular disease states.

Our small molecules targeting the P2X7 receptor have been developed with the strategic advantage over downstream anti-inflammatory approaches, eliminating the risk of side effects such as sepsis. Activation of P2X7R leads to release of Il-1b and Il-18 which are strongly implicated in atherosclerosis and heart attack. There are no known off-target effects of P2X7R blockade. In the two years of our project, we will perform med-chem molecule optimisation, in vitro studies including in monocytes from heart attack patients, PK/PD and toxicity studies, and preclinical studies of our novel series of compounds targeting P2X7R.

Targeting the inflammatory driver of atherosclerosis complements existing therapies addressing the established risk factors., offering a novel and safe therapy to prevent heart attacks by directly treating the inflammatory-driven components of heart failure.

TTRA Project Round:  Two

State:  New South Wales

Project Partners:

• ProKardia
• Northern Sydney Local Health District
• NSW Health
• Bayer

Funding:

• TTRA: $750,000
• Industry Contribution: $100,000 cash, $786,588 in-kind

Duration:  September 2022 – October 2024

Website: www.sydney.edu.au  |  LinkedIn: University of Sydney

Twitter: @Sydney_Uni