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Intradigm Drops Lead Cancer Rx Candidate


Intradigm has shelved its lead cancer therapeutic ICS-283, which had been projected to enter phase I testing this year, in order to focus on developing RNAi drugs against undisclosed targets that are currently undruggable by other technologies.

At the same time, the company has closed a $2.9 million final tranche of its $21.4 million Series B round of financing, which will help it rebuild its pipeline and continue developing its proprietary delivery technology.

Intradigm has also made its second major change in leadership since it was founded in 2001, appointing Phil Haworth to be its new CEO. Haworth, formerly Intradigm's vice president of business development, replaces Mohammad Azab, who remains on Intradigm's board.

ICS-283 is an siRNA targeting vascular endothelial growth factor that is delivered using Intradigm's so-called nanoplex technology, which consists of an RNAi payload surrounded by a polyethylene glycol coat and decorated with targeting ligands.

As early as 2004, Intradigm officials had been saying the drug was on the cusp of entering human testing. After a series of delays and a sweeping corporate reorganization in 2006, the company pushed that clinical timeline back to sometime in 2009.

According to Haworth, however, Intradigm eventually deemed RNAi drugs targeting VEGF as not commercially promising enough to warrant further development.

VEGF was "a rational target at the time" ICS-283 was originally developed, he says. "We have now rethought how to use [RNAi] technology on what we consider to be previously undruggable targets." He did not provide specifics about these targets, but notes that the company plans to keep its in-house focus on oncology.

With a well-validated role in a variety of diseases including certain cancers and ocular disorders, VEGF has been a popular target for many RNAi drug candidates.

Doug Macron

RNAi Notes

Quark Pharmaceuticals says it has dosed the first patient in its trial of an siRNA-based drug to prevent delayed graft function in people undergoing kidney transplants. The drug is designed to temporarily inhibit p53 expression.

Abbott has acquired Ibis Biosciences from Isis Pharmaceutical for $215 million plus earn-out payments. Ibis sells the Ibis T5000 Biosensor System, which is currently used for research purposes, but Abbott says it will seek clearance for clinical diagnostics applications.

Alnylam Pharmaceuticals submitted an investigational new drug application for its systemic liver cancer drug candidate. The drug contains two siRNAs, one targeting kinesin spindle protein and the other targeting vascular endothelial growth factor.

$15 million

Amount the Massachusetts Life Sciences Center awarded to support collaborations to develop RNAi delivery technologies.

Funded Grants

$75,606/FY 2008
A genome-wide RNAi screen for Neuronal Cell Fate Mutants
Grantee: Oliver Hobert, Columbia University
Began: Sep. 15, 2008; Ends Aug. 31, 2010
With this grant money, Hobert plans to use a genome-wide RNAi approach to find which genes control the ASE sensory neurons in C. elegans. In addition to finding those genes, he also hopes to identify the genes involved in the left/right asymmetric developmental program.
He and his lab have already done RNAi analysis of chromosome 1 and want to ramp it up to cover all six chromosomes.

$270,000/FY 2008
A Genome-Wide RNAi Vulnerability Map for Myeloma
Grantee: Alexander Keith Stewart, Mayo Clinic Arizona
Began: Sep. 15, 2008; Ends Jul. 31, 2012
Stewart will be applying functional genomics strategies to identify and validate genes involved in multiple myeloma. He and his lab will be extending their studies to a high-throughput synthetic lethal RNAi screen of 17,000 genes. After validating their findings, they will use pharmacogenomics and classical molecular biology techniques to determine whether their findings are clinically relevant.

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