Quark Pharmaceuticals Inc. Announces Nature Medicine Publication for Role of RTP801 in Pulmonary Injury and Emphysema
To study the role of RTP801 in pulmonary injury and emphysema, Quark Pharmaceuticals collaborated closely with three of the top research groups exploring cigarette smoke induced lung injury, led by Drs. Rubin Tuder, at Johns Hopkins University School of Medicine, and University of Colorado; Syam Biswal, at the Johns Hopkins School of Public Health; and Steven Shapiro, at Harvard University and University of Pittsburgh..
"Oxidative stress triggered by cigarette smoke initiates lung inflammation and cell death and contributes to tissue injury," said Professor Rubin Tuder, Program Director in Translational Lung Research of the Division of Pulmonary and Critical Care Medicine at the University of Colorado at Denver School of Medicine, one of the senior authors of this publication. "RTP801, a stress-response protein induced by cigarette smoke, amplifies these damaging effects. Its activation is necessary for induction of inflammation and death of lung cells in response to cigarette smoke since inflammatory response to cigarette smoke was inhibited in the lungs of mice that did not express RTP801 (knockout mice). Moreover, artificial overexpression of RTP801 in the lungs appeared sufficient to initiate the cascade of the pathological events."
Researchers found increased levels of RTP801 mRNA and protein in the lungs of humans suffering from emphysema and in the lungs of mice exposed to cigarette smoke. Unlike normal mice, mice that could not express RTP801 (knockout mice) did not develop emphysema following six months of intensive exposure to cigarette smoke.
"Our in vivo studies support the notion that RTP801 may represent a major trigger of molecular sensing and mediation of cigarette smoke-induced lung injury," said Professor Steven Shapiro, Chairman of the Department of Medicine of the University of Pittsburgh. "These results support further investigation of RTP801 as a target for inhibition to treat pulmonary injury and emphysema."
Elena Feinstein of Quark Pharmaceuticals, sharing senior authorship of this paper with Prof. Tuder, said, "The findings published in the prestigious Nature Medicine broaden the therapeutic potential of targeting RTP801. Our siRNA molecule inhibiting RTP801 is currently in clinical trials being conducted by Pfizer for age-related macular degeneration and diabetic macular edema. New data in pulmonary injury and emphysema provide a support for additional clinical applications of this drug, such as treatment of acute and chronic lung injury."
RTP801 is Quark's proprietary target discovered using its BiFAR target discovery platform. BiFAR identifies clinically relevant critical genes and proteins that reverse the disease phenotype when inhibited. The Company owns a family of patents covering the RTP801 gene, its RNA and protein product sequences, specific antibodies, and gene inhibition across different pathologies.
An siRNA therapeutic candidate targeting RTP801 (PF-04523655) was licensed to Pfizer in 2006 and is currently in two Phase II clinical trial for treatment of AMD and DME being conducted by Pfizer in collaboration with Quark.
About Quark Pharmaceuticals, Inc.
Quark Pharmaceuticals, Inc is a leader in the discovery and development of novel RNAi therapeutics. Quark has a fully integrated drug development platform that spans therapeutic target identification to drug development. The Company's technology platform includes novel disease targets and siRNA structures and chemistry, providing Quark with freedom to operate in the siRNA intellectual property arena. Quark's approach to delivery allows targeting of tissues and organs including the eye, kidney, ear, lung, spinal cord and brain.
In addition to PF-04523655, Quark's development pipeline features QPI-1002, the first systemically administered siRNA drug in human clinical trials. QPI-1002 is being evaluated for the prevention of acute kidney injury (AKI) following major cardiovascular surgery and the prophylaxis of delayed graft function after kidney transplantation. Enrollment was successfully completed recently in Phase I studies in these indications. For the structure of these products, Quark has obtained licenses from Silence Therapeutics and from Alnylam Pharmaceuticals.
In the first quarter of 2010, Quark initiated a Phase 1/2 study of a new synthetic siRNA, QPI-1007, as a neuroprotective agent for eye diseases. QPI-1007 utilizes a proprietary structure developed in collaboration with BioSpring GmbH, that Quark believes provides freedom to operate in the siRNA intellectual property arena. The structure and modifications utilized in QPI-1007 preserve RNAi activity while ameliorating potential off-target and immunostimulatory effects of siRNAs. In addition, Quark has a broad pipeline of siRNA drug candidates that have arisen from Quark's research activities. The Company is committed to developing novel siRNA structures and expects to utilize these improvements to develop additional RNAi drug candidates based on the Company's productive R&D engine.
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
Quark Pharmaceuticals, Inc.
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