The results, published in the October issue of Cancer Research, demonstrate that Calando Pharmaceuticals’ proprietary delivery technology can deliver short interfering RNA (“siRNA”) to targeted cancer cells and inhibit tumor growth in mice by silencing the target gene. In addition to serving as a potentially powerful new tool in the fight against a wide range of cancers, Calando’s delivery system might also be used to treat a number of other diseases.

“Although the discovery of the siRNA mechanism has been heralded as a major breakthrough, using siRNA therapeutics to attack diseases and conditions that can only be treated systemically in an effective way has been problematic,” said R. Bruce Stewart, President of Arrowhead. “Many diseases, including many forms of cancer, are caused by genes gone haywire throughout the body, not just in one discreet location. The ability to shut down problem genes selectively with siRNA throughout the body could provide a means to treat a variety of human diseases. These results demonstrate Calando’s potential to unleash RNAi as a powerful new class of therapeutics.”

As described in Cancer Research, Caltech and Children’s Hospital Los Angeles investigators using Calando’s delivery technology performed experiments on a mouse model of Ewing’s sarcoma, a deadly form of metastatic cancer. One group of mice received a targeted formulation of siRNA and Calando’s proprietary delivery technology and other control groups received either no treatment, or various combinations of correct and incorrect siRNA sequences, with and without Calando’s proprietary delivery technology and tumor targeting ligands. The data show that only the targeted formulation of the correct siRNA sequence and Calando’s delivery technology provided any anti-tumor efficacy. Additionally, the data demonstrate that Calando’s technology does not result in physiological abnormalities or produce an immune response.

“The results from the Caltech-CHLA collaboration conclusively show sequence-specific anti-tumor effects and the molecular targeting to and within tumor cells by the delivered siRNAs,” said Dr. Mark Davis, professor of Chemical Engineering at Caltech and founder of Calando. “This study shows that the polymer system can deliver siRNA therapeutics by a route of administration and at a dose amenable to use in humans.”

Insert Therapeutics, Inc., another majority-owned subsidiary of Arrowhead Research, is expecting to begin human clinical trials early next year with a conjugate of Cyclosert, a sister polymeric drug delivery technology developed in the labs of Dr. Davis at Caltech, with the small molecule anti-cancer compound camptothecin.

“In light of these results and our experience working with these nanomaterials at Insert, we expect a quick path to human clinical trials for Calando,” Mr. Stewart said.