Arrowhead Presents Data Showing 99% Target Knockdown in Monkeys Without Toxicity Using Subcutaneous Formulation of Dynamic Polyconjugate siRNA Delivery System

Press Release

October 29, 2012

Arrowhead Presents Data Showing 99% Target Knockdown in Monkeys Without Toxicity Using Subcutaneous Formulation of Dynamic Polyconjugate siRNA Delivery System

PASADENA, Calif. — October 29, 2012 — Arrowhead Research Corporation (NASDAQ: ARWR), a targeted therapeutics company, announced that David Lewis, Ph.D., Vice President Biology and Site Head of its Madison, WI research and development facility will present data today at the Annual Meeting of the Oligonucleotide Therapeutics Society in Boston. The oral presentation titled, “Dynamic PolyConjugate (DPC) technology for Targeted Delivery of siRNA,” describes advancement of a new subcutaneous formulation of the company’s DPC delivery system. Data from new studies in mice and non-human primates show high levels of target gene knockdown at very low doses with no toxicity. Dr. Lewis will also present data on the drug candidate ARC-520 against chronic hepatitis B virus (HBV) infection.

“The subcutaneous DPCs have shown striking levels of target gene knockdown, which we are pleased to have the opportunity to discuss at the OTS meeting,” said Bruce D. Given, M.D., COO and Head of R&D for Arrowhead. “Subcutaneous delivery is preferable for some indications but the high doses of siRNA required to achieve meaningful knockdown have been prohibitive. We believe the unprecedented efficiency of this DPC formulation opens up many opportunities for Arrowhead and could represent a leap forward for the RNAi therapeutics field.”

Dr. Lewis’ presentation illustrates the efficacy of DPCs formulated for subcutaneous administration using Arrowhead’s latest proprietary polymer masking technology. Using DPCs to deliver siRNA, high-level target gene knockdown is observed at low siRNA doses without toxicity in rodents and non-human primates. Arrowhead studies have shown knockdown of 99% in monkeys after a single injection of 1 mg/kg, >90% at 0.5 mg/kg, and 80% in mice at 0.05 mg/kg. PK and biodistribution studies indicate that the new masking technology is highly stable, allowing for maximal bioavailability and long circulation times. Arrowhead is developing this formulation for use in multiple therapeutic areas including oncology.

Dr. Lewis will also present data on Arrowhead’s clinical candidate, ARC-520, for the treatment of chronic hepatitis B. According to the World Health Organization, some 360 million people, or 5% of the world’s population, suffer from chronic hepatitis B and are at significant risk for development of liver cirrhosis and hepatocellular carcinoma. Existing drugs for the treatment of chronic hepatitis B seldom produce a functional cure and can cause significant side-effects.

In mouse models of HBV infection, a single injection of ARC-520 containing NAG-polymer and chol-siRNAs targeting conserved regions of the HBV transcripts resulted in multi-log reductions in circulating viral antigens and HBV DNA, and dramatically reduced HBV RNA and DNA replicative intermediates in the liver. The duration of effect is unprecedented, with HBsAg reduced >99% for one month following a single injection. These results suggest that ARC-520 holds great promise as a new therapeutic modality for patients chronically infected with HBV.

Vince Anzalone

Arrowhead Research

Lauren Glaser

The Trout Group, LLC