Clinicians

ViCardia and GP531

ViCardia is entering Phase 2 with GP531, a potent, long-lasting, infusion therapy that treats mitochondrial dysfunction that leads to chronic heart failure and ultimately to acute decompensated heart failure.

Considerable Research Confirms How GP531 Works

Milestones Achieved - a lot of work has already been done.
Completed to Date 1H 2021
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Acadesine

1st Generation ARA R&D

An AMPK activator for treatment of ischemic reperfusion injury (IRI). Extensively researched in over 9,000 patients.

GP531

Pre-Clinical Drug Development

Completed series of PK/PD studies and a number of animal studies over an eight year period.

GP531 Phase 1

Clinical Trials

Three separate Phase 1 trials completed in 84 healthy volunteers – excellent safety and tolerability profile.

GP531 Pilot Phase 2

Clinical Trials

Phase 2 PILOT clinical trial completed in 18 patients with ischemic HF with strong clinical results supporting further research.
Results
Research efforts and our patent portfolio provide exceptionally strong support for further investment to pursue FDA approval.

GP531
Mechanism of Action

GP531 acts as an Adenosine Mono-Phosphate Kinase (AMPK) activator that stimulates glucose & fatty acid uptake, enhances the energy (ATP) output of the Mitochondria and increases mechanical function of the heart.

The Importance of What We Do

Adequate amounts of ATP must be generated to support the heart’s contractile demands and maintain viability for the other main organs. Abnormalities in cardiac metabolism, such as a lack of ATP-ADP metabolism, causes mechanical failure of the heart.

Dysfunctional mitochondria produce less cellular energy (ATP) and produce increased unhealthy levels of reactive oxygen species (ROS), both of which lead to oxidative stress and ultimately to Heart Failure.

Role of Endogenous Adenosine

Endogenous Adenosine is released in myocytes undergoing net-ATP catabolism and provides a natural defense against myocardial injury.
  • At the cellular level, endogenous adenosine protects the cell from multiple pathways of cellular stress & injury, including inflammation and oxidative stress, apoptosis and necrosis.
  • At the molecular level, endogenous adenosine acts as a “retaliatory metabolite” that turns off ATP catabolism and depletion - and as such - acts as a key regulator of cellular energetics.
Endogenous ADO levels are elevated in HF patients.
  • Reflecting ongoing net –ATP catabolism-depletion.
  • But not to levels sufficient to provide cardioprotection or to alter cellular energetics to improve global cardiac function.

Mechanism of Action

Change to: Acadesine is converted to AICA ribotide (ZMP) by adenosine kinase, which also converts adenosine to adenosine monophosphate (AMP). Acadesine selectively increases endogenous adenosine levels during episodes of cellular stress in which the breakdown of ATP exceeds ATP synthesis.

GP531, an analogue of Acadesine, directly activates of AMPK and indirectly augments endogenous adenosine, reducing cardiac injury.

Mitochondrial Biogenesis

Mitochondrial biogenesis impairment is an early event in the development of heart failure, and reversal of this process is cardioprotective.
Mitochondria are dynamic organelles, continuously undergoing biogenesis through fission, fusion, and autophagy. In addition to effects on metabolism, AMPK also regulates mitochondrial biogenesis, autophagy, cell polarity, cell growth and proliferation. Severe energetic stress is harmful to mitochondria and, over time, all mitochondria become damaged and need to be replaced.
The metabolic changes observed in the mitochondria are considered a critical landmark in the development of HF. Therefore, mitochondrial pathophysiology provides an important therapeutic target for reviving the contractile function of the myocardium, reversing events leading up to HF. Currently no approved therapy specifically targets mitochondrial biogenesis in Heart Failure.
Treating the Underlying Cause of Heart Failure
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