| Posted: October 24, 2007 |
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Intradigm Study Shows Ability of siRNAs Systemically Delivered With TargeTran System to Suppress Tumor-Induced Angiogenesis in Mice
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(Nanowerk News) Intradigm Corporation, a
leading developer of targeted, systemic RNA interference (RNAi)
therapeutics, today announced study results that demonstrated the company's
TargeTran™ 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.
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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™ delivery
technology using the TargeTran™ 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.
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"These study results are very encouraging as they demonstrate the
ability of our RNAi Nanoplex™ 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™ 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."
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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.
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To address the issue of effective and targeted delivery of RNAi
therapeutics, Intradigm has developed its proprietary RNAi Nanoplex™
technology, a powerful combination of advanced delivery systems. The RNAi
Nanoplex™ technology is a multi-component delivery vector that carries
active siRNA molecules in its core and in its targeted form (TargeTran™)
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™
delivery system, a novel biodegradable polycation polymer that also shows
great promise as an RNAi delivery system. Intradigm believes that this
Nanoplex™ platform is one of the most versatile siRNA systemic delivery
technologies currently in development.
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ABOUT INTRADIGM
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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.
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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. For more
information on Intradigm, please visit http://www.intradigm.com.
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