Commences Phase I Clinical Trial of Proprietary siRNA Molecule in Acute Renal Failure.
Fremont, California, November 19, 2007 – Quark Pharmaceuticals, Inc., a development-stage pharmaceutical company focused on discovering and developing novel RNA interference-based therapeutics, announced today that it has commenced systemic dosing in humans of its proprietary product candidate, AKIi-5, a siRNA compound discovered and developed by Quark for the treatment of Acute Renal Failure (ARF), also called Acute Kidney Injury (AKI). Based on publicly available information, Quark believes that this is the first human clinical trial involving the systemic delivery of siRNA.
The Phase I clinical trial is a multi-center, double-blind, placebo controlled, dose-escalation trial assessing the safety and pharmacokinetics of AKIi-5 administered intravenously as a single dose to patients undergoing major cardiac surgery. Patients will be enrolled in the trial in a number of centers in the United States, Europe and Israel. Quark expects to complete the trial in early 2008. Depending on the results of this trial, Quark expects to initiate a dose-ranging Phase II clinical trial measuring AKIi-5 clinical activity.
Daniel Zurr, Chief Executive Officer, commented, “The initiation of human dosing in our Phase I trial in ARF signifies a very important step in Quark’s clinical program and marks an important milestone in the RNAi industry. For Quark, the trial serves to further validate the strength of our pipeline and our overall expertise in the RNAi arena. With AKIi-5 now in the clinic, RTP801i-14, which we licensed to Pfizer, in a Phase I/IIa clinical trial for the treatment of wet age-related macular degeneration, AHLi-11 in IND-enabling studies and additional RNAi-based candidate drugs in pre-clinical testing, we believe Quark has one of the most robust RNAi product portfolios in the industry.
“For the RNAi industry, the trial may be even more noteworthy as it represents the first documented systemic dosing of siRNA in humans. While the science of RNAi has been well-established, a key step in the acceptance of the technology as a promising therapeutic is the ability to deliver RNAi-based compounds systemically. We look forward to leading this important advance for the industry and, at the same time, continuing the development of this and other siRNA products in our pipeline.”
Quark was granted an IND by the Food and Drug Administration (FDA) for AKIi-5 for the prevention of Acute Renal Failure in high-risk patients undergoing major cardiovascular surgery. AKIi-5 is a synthetic, chemically modified siRNA molecule discovered and patented by Quark that has an AtuRNAi technology-based structure licensed from Silence Therapeutics. Quark has also licensed certain intellectual property from Alnylam.
Quark has conducted pre-clinical studies of AKIi-5 for the prevention of acute renal failure in rats and monkeys. Rats treated with a single bolus injection of AKIi-5 were significantly protected from ischemia/reperfusion-induced acute kidney injury. In the rat studies, AKIi-5 effectively prevented the development of acute renal failure. Quark’s pharmacokinetic, distribution, and toxicity studies in rats and monkeys indicate that AKIi-5 appears to have a favorable safety profile and has a relatively short residence time in the kidney.
AKIi-5 is a synthetic, chemically modified siRNA molecule designed to temporarily inhibit the expression of p53, a gene which plays a significant role in ARF by inducing tubular cell death (apoptosis) in response to injury. AKIi-5 is based on Quark’s proprietary, patented concept of temporary and reversible inhibition, for therapeutic purposes, of the expression of the transcription factor human p53, which is associated with DNA repair and apoptosis. The concept was first published by Quark with the University of Illinois in a breakthrough paper in Science magazine (Science. 1999 Sep 10;285). Using RNA interference technology to temporarily inhibit p53 in acute settings such as acute kidney injury, apoptosis is delayed thereby allowing natural repair mechanisms to restore normal DNA and cellular integrity.
About Acute Renal Failure (ARF) / Acute Kidney Injury (AKI)
ARF is a syndrome characterized by a rapid decline of kidney function leading to death in a high percentage of cases. Major cardiac surgery is one of the many causes of ARF. During cardiac bypass surgery, lack of oxygen caused by reduced local blood flow to the kidneys, followed by rapid reintroduction of oxygen, or reperfusion, to the kidneys upon removal of the patient from cardiopulmonary bypass, initiates a chain of events that can lead to ARF. Currently, there are no approved drug therapies that effectively prevent or treat ARF.
About Quark Pharmaceuticals, Inc.
Quark Pharmaceuticals, Inc. is a development-stage pharmaceutical company focused on discovering and developing novel therapeutics based on its proprietary gene discovery science and technology, with an initial focus on drug candidates that work through the natural mechanism in the cell known as RNA interference, or RNAi, for the treatment of diseases associated with oxidative stress. Quark believes that its proprietary target gene discovery platform, BiFARTM, combined with its ability to design and successfully deliver synthetic molecules of the new class of RNAi therapeutics known as small-interfering RNA, or siRNA, to specific organs in the body, enables the Company to rapidly develop drug candidates. Quark has two internally discovered and developed clinical stage lead product candidates: RTP801i-14 in phase I/IIa clinical trial for the treatment of wet age-related macular degeneration, and AKIi-5 in phase I for the prevention of acute renal failure both of which have an AtuRNAi technology-based structure licensed from Silence Therapeutics, as well as a license from Alnylam. The Company has licensed RTP801i-14 to Pfizer on an exclusive worldwide basis. Quark has, in addition, a product candidate portfolio of RNAi therapeutics based on novel targets and therapeutic concepts discovered using BiFAR™ and designed for the treatment of oxidative stress associated diseases of the inner ear, lungs and additional organs of the body.
Quark is headquartered in Fremont, California and operates research and development facilities in Boulder, Colorado and Ness-Ziona, Israel. Additional information is available at www.quarkpharma.com