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THE COMPANY

Background

  • Prokardia founders Prof Gemma Figtree - Head of the Australian Cardiovascular Alliance and global leader in vascular biology and Prof Michael Kassiou - Academic Director, USyd Drug Discovery Initiative.

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  • Chronic low-grade inflammation contributes to the development of cardiovascular disease and the P2X7 receptor mediates inflammation and cellular death.

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  • Activation of P2X7R increases IL-1β and IL-18 which have been implicated in the development of many cardiovascular conditions including pulmonary hypertension and atherosclerosis.

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  • PKT100 known mechanism of action in two papers and uses a patent licensed from the University of Sydney. 

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  • Promising in pulmonary artery hypertension - protecting against right ventricular remodelling, and improving survival - in a manner that is synergistic to current clinical treatments and addresses the most important prognostic aspect of this highly fatal disease.

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  • Further research has resulted in superior PKT200 analogs.

Unmet Medical Need

  • Cardiovascular disease remains the leading global cause of death with broad health, social and economic impact. Biomarkers of inflammation have been shown to be associated with clinical cardiovascular risk.

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  • The importance of unravelling new markers for CAD is highlighted by our recent data showing that, in 2015, approximately 27% of patients presenting to the Royal North Shore Hospital in Sydney with identified plaque rupture and life-threatening ST-elevation myocardial infarction (STEMI) had none of the Standard Modifiable Risk Factors (SMuRFs: a term coined by our clinician EMCR Dr Vernon).

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  • This proportion has risen steadily from 14% over 10 years. We have confirmed that the increase in the proportion of SMuRFless STEMI patients is a national phenomenon in the CONCORDANCE cohort (3081 STEMI patients)17 and we have led a global effort to understand mechanisms, outcomes, and management of this patient group.

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  • Working with the SWEDEHEART registry (62,048 STEMI patients), we reported in The Lancet in 2021 the unexpected and concerning finding that early mortality (<30 days) is approximately 50% higher in patients with no SMuRFs and worst in females, for whom absolute mortality reaches nearly 18% at 30-days

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  • New therapeutics are urgently required that target the exaggerated host inflammatory process independently of cholesterol and high blood pressure.

P2X7R - A New Target for Management of CV Disease

  • Accumulating evidence demonstrates that the purinergic P2X7 receptor plays a prominent role in chronic inflammatory conditions, including cardiovascular disease.

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  • The CANTOS study demonstrated the clinical benefits of blocking the inflammatory cytokine interleukin -1b, but the use of a monoclonal antibody to do this was associated with increased risk of sepsis.  Inhibiting P2X7R only blocks sterile inflammation such as that in CVD - not sepsis.

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  • Activation of P2X7R increases IL-1β and IL-18 which have been implicated in the development of many cardiovascular conditions including pulmonary hypertension and atherosclerosis.

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  • P2X7 receptor mediated endothelial dysfunction and inflammation direct atherosclerotic plaque formation and rupture.

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  • In ischemic injury in the heart, P2X7 receptor activation promotes cardiomyocyte death and enhances inflammation leading to cardiovascular dysfunction.

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  • P2X7 receptor inhibitors may provide a new avenue for treatment of cardiovascular disease.

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