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Home > Press > Intradigm Study Shows Ability of siRNAs Systemically Delivered With TargeTran(TM) System to Suppress Tumor-Induced Angiogenesis in Mice

Abstract:
Intradigm Corporation, a leading developer of targeted, systemic RNA interference (RNAi) therapeutics, today announced study results that demonstrated the company's TargeTran(TM) delivery system is capable of delivering vascular endothelial growth factor (VEGF) targeted small interfering RNAs (siRNAs) that suppress tumor-induced angiogenesis by silencing target gene expression in mice. The study findings support the preclinical development of ICS-283 a nanoparticle-based compound comprised of siRNAs that target both VEGF and its main receptor. Complete study findings were presented by Intradigm scientists today at the 2007 AACR- NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics.

Intradigm Study Shows Ability of siRNAs Systemically Delivered With TargeTran(TM) System to Suppress Tumor-Induced Angiogenesis in Mice

PALO ALTO, CA | Posted on October 24th, 2007

This preclinical study was designed to examine the anti-angiogenic efficacy, in multiple cancer types, of VEGF-targeted siRNAs administered systemically with Intradigm's proprietary RNAi Nanoplex(TM) delivery technology using the TargeTran(TM) delivery system. At the study's outset, tumor cells (both human colorectal and renal cell carcinoma) were implanted into a group of mice. At both two and five days post tumor cell introduction, a portion of the mice were given intravenous (IV) administration of several siRNAs targeting VEGF ligand, VEGFR1, VEGFR2, or various combinations of the three. The remaining mice received either a negative control siRNA treatment or a positive control treatment using VEGF antibody Bevacizumab. At eight days, tumor-induced angiogenesis as well as target gene knockdown were analyzed. The results showed highly significant anti-angiogenic effect that is RNAi-mediated in all active siRNA treatment groups targeting different VEGF-pathways genes.

"These study results are very encouraging as they demonstrate the ability of our RNAi Nanoplex(TM) technology to systemically deliver siRNA therapeutics directly to tumor vasculature and tumor cells," said Mohammad Azab, M.D., president and chief executive officer of Intradigm. "The targeting of the VEGF pathway with RNAi represents a novel approach for anti-angiogenesis-based therapeutics, and with the tumor selectivity offered by our TargeTran(TM) system, we believe we are developing an innovative therapeutic candidate that may possess efficacy and/or safety advantages over existing or other anti-angiogenic agents in development."

ICS-283 is currently in preclinical development for a variety of cancer indications and the company expects to initiate clinical development of this candidate in 2008. The findings presented today support data from several other in vivo models, including xenograft models of different cancers, which have confirmed an RNAi-mediated anti-angiogenic effect following systemic administration similar to VEGF antibody. VEGF, as an established target in the treatment of cancer, provides a clear clinical development path to validate the success of Intradigm's systemic delivery of siRNA in man.

ABOUT INTRADIGM'S siRNA DELIVERY TECHNOLOGY

To address the issue of effective and targeted delivery of RNAi therapeutics, Intradigm has developed its proprietary RNAi Nanoplex(TM) technology, a powerful combination of advanced delivery systems. The RNAi Nanoplex(TM) technology is a multi-component delivery vector that carries active siRNA molecules in its core and in its targeted form (TargeTran(TM)) carries a ligand attached to its surface for specific tissue targeting. This platform is unique in its ability to offer tissue specific targeting of siRNA and intracellular delivery against the intracellular machinery of the target tissue. In addition, Intradigm also developed the PolyTran(TM) delivery system, a novel biodegradable polycation polymer that also shows great promise as an RNAi delivery system. Intradigm believes that this Nanoplex(TM) platform is one of the most versatile siRNA systemic delivery technologies currently in development.

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About Intradigm Corporation
Intradigm is a private biotechnology company dedicated to the development of targeted, systemic RNA interference (RNAi) therapeutics for the treatment of serious diseases with an initial focus on oncology.

At present, Intradigm is working to build a high-value internal pipeline of RNAi oncology therapeutics, and is actively advancing its lead drug candidate, ICS-283, for a variety of cancer indications. The company is also establishing collaborative relationships with pharmaceutical and biotechnology companies through which Intradigm's advanced RNAi delivery technology may be applied to a broad range of therapeutic targets.

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3350 W Bayshore Rd, Suite 100;
Palo Alto, CA 94303
Phone: (650) 855 9696
Fax: (650) 855 9699

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