The primary indication of AKIi-5 is the prevention of Acute Kidney Injury (AKI), also known as Acute Renal Failure (ARF) initially in high-risk patients undergoing major cardiovascular surgery. AKI is a serious disease that develops rapidly (within hours to days) post-surgery with a mortality rate of 65%. There are no effective therapies for AKI.
AKIi-5 is an siRNA drug candidate that acts to temporarily inhibit the expression of human p53. Its development is based on the proprietary concept of temporary and reversible inhibition of p53 for therapeutic purposes, first described by Quark scientists in 1999 in Science magazine and covered by an allowed US patent and several patent applications. p53 is a transcription factor that is activated by stresses such as DNA damage and hypoxia, leading to the activation of cellular pathways that induce either cell cycle arrest, cell senescence, or apoptosis in damaged cells. In acute settings such as in AKI, the temporary inhibition of p53 at the time of injury delays the induction of cell death, thereby allowing natural repair mechanisms to restore normal DNA and cellular integrity. In cells with unrecoverable damage AKIi-5 accumulates rapidly and predominantly in kidneys, specifically in proximal tubules, following intravenous administration. Experiments using the rat renal ischemia/reperfusion model have shown that p53-targeted siRNA inhibits the development of AKI following a single intravenous injection. Subsequent pharmacokinetic, distribution, and toxicity studies in rats and monkeys showed that AKIi-5 has a favorable safety profile and has a relatively short residence time in the kidney.
** QUARK is conducting A Dose Escalation Trial of the Safety and Pharmacokinetics of a Single Intravenous Injection of I5NP (AKIi5) in Patients Undergoing Major Cardiovascular Surgery. This study is currently recruiting participants: clinicaltrials.gov