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Arrowhead Presents Data On DPC System At TIDES 2012

Arrowhead Research Corporation (NASDAQ:ARWR) today announced that Darren Wakefield, Ph.D., one of its Senior Scientists at its Madison, WI research and development facility presented data at the TIDES: Oligonucleotide and Peptide Research, Technology and Product Development Conference in Las Vegas, NV. Dr. Wakefield’s poster presentation titled, “Liver-targeted and reversibly masked-polycation co-delivery improves cholesterol-conjugated siRNA efficacy,” describes the ability of Arrowhead’s PBAVE polymer to dramatically decrease the effective dose needed. PBAVE is one of the polymers included in Arrowhead’s proprietary Dynamic Polyconjugate (DPC) siRNA delivery platform.

“Linkage to cholesterol is one strategy that has been used by other siRNA therapeutic developers to prolong circulation time and to facilitate uptake into hepatocytes via the LDL receptor,” said Dr. Wakefield. “However, three daily injections of 50 mg/kg of cholesterol-conjugated apoB siRNA were previously required to achieve 50% gene silencing. Over the past few years, no real improvements have been reported to optimize the delivery of cholesterol or other lipophilic siRNA conjugates in vivo. Using our delivery technology, we are able to achieve similar gene silencing with a dramatically lower dose. This demonstration is one example of the potential of our DPC platform to broaden the utility and safety of siRNA therapeutics.”

Arrowhead’s chemists employed a new delivery approach to achieve similar gene silencing after a single injection of 0.2 mg/kg of cholesterol-conjugated siRNA, a 750-fold improvement in effective dose. This enhanced efficacy is attained by the co-delivery of an asiologlycoprotein receptor (ASGPr)-targeted and reversibly-masked cationic polymer, PBAVE. The injection of cholesterol-conjugated siRNA and modified-polymer can be temporally separated up to four hours without significant effects on gene silencing, suggesting that delivery does not depend on the association of targeted PBAVE and the cholesterol-conjugated siRNA in the blood. Genetic knockout of the ASGPr eliminates effective delivery of the cholesterol-conjugated siRNA, indicating that delivery depends on proper targeting of the PBAVE polymer.

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