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Calando Pharmaceuticals Publishes the First Non-Human Primate Study,on Targeted, Systemic Delivery of siRNA in National Academy of,Sciences Journal

PASADENA, Calif.--(BUSINESS WIRE)--Mar 20, 2007 - Calando Pharmaceuticals, a leading siRNA therapeutics company and a majority-owned subsidiary of Arrowhead Research Corporation (NASDAQ: ARWR) announced the publication in the Proceedings of the National Academy of Sciences (PNAS), the scientific journal of the NAS, of the first non-human primate study to use multiple, systemic dosing with Calando's lead siRNA therapeutic candidate that is a nanoparticle containing non-chemically modified siRNA and a transferrin protein targeting agent.

The paper, entitled "Administration in non-human primates of escalating intravenous doses of targeted nanoparticles containing ribonucleotide reductase subunit M2 siRNA," was published online in the Early Edition of the PNAS. This paper details the results of a pilot safety study of Calando's lead siRNA-containing nanoparticle formulation (CALAA-01) in monkeys. In this dose-escalation experiment, systemically-administered nanoparticles were well-tolerated at doses significantly above those that had been previously shown to be efficacious with a similar formulation in murine cancer models. Overall, this study shows that multiple, systemic doses of CALAA-01 can safely be administered to non-human primates, and is the first example of multiple systemic dosing of siRNA in monkeys.

The formulation investigated contains Calando's proprietary delivery technology with a non-chemically modified siRNA duplex targeting the M2 subunit of ribonucleotide reductase, a well-established cancer target. This duplex, developed by Calando, demonstrates potent anti-proliferative activity across multiple types of cancer in vitro and in vivo. The objective of this escalating-dose pilot study was to assess numerous safety-related parameters for this formulation in non-human primates since it is known that proper evaluation of complement activation is best performed in this type of animal prior to
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