ViCardia - Model GP531 - Potent, Long-Lasting, Infusion Therapy

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.

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.

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 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.