Small wonders

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PALO ALTO, Calif.—Intradigm Corp., announced at the Bio-Europe Spring 2008 conference in Madrid, Spain,  that it has licensed key intellectual property (IP) covering certain efficacy-enhancing structural elements of small interfering RNA (siRNA) from the University of Massachusetts Medical School. The licensed IP includes parameters for the structural modifications for next generation siRNAs including the "Zamore Design Rules" that significantly improve the potency and efficacy of RNAi therapeutics. This licensed technology allows Intradigm to incorporate novel siRNA sequences into the company's proprietary RNAi delivery systems to create potent and effective siRNA therapeutics.
PALO ALTO, Calif.—Development-stage RNAi therapeutics company Intradigm Corp. formally announced late last month that it selected its novel cancer agent ICS-283 as its lead RNAi product candidate and in conjunction, announced it had selected the Boulder, Colo.-based Nucleic Acid Solutions Division of Agilent Technologies to manufacture the siRNA component of this potential therapeutic.

"There are several players that we [examined] who could have provided this service to us," says Mohammad Azab, president and CEO of Intradigm. "Agilent has invested a lot of time, thought and money into the process and we understand that they have been working on a process that will greatly reduce the cost of production of our siRNA. As a small company wanting to make a relatively expensive product, that was very important."

In fact, the latest developments for Intradigm come as the company has, since late last year, moved its base of operations from Maryland to California, raised $16 million in a Series A financing round and built out its management team all with an eye toward development of its RNAi candidates.
"The timing worked out well for us to attract management," notes Azab. "It was around the time that Abgenix was acquired by Amgen, so we were able to attract some Abgenix people who were looking to move on."

This included Stephen Chamow, as senior VP of chemistry, manufacturing and control; Mike Riley, VP of corporate development; and Xiao-Dong Yang, VP of research and preclinical development and a key player at Abgenix in the development of Vectibix (panitumumab), currently in Phase III trials.

The task now for Intradigm is to advance ICS-283 quickly through early trials. The anticancer agent targets the Vascular Endothelial Growth Factor (VEGF) pathway for multiple indiciations. It's a crowded field, to be sure, with heavyweights Genentech (Avastin), Pfizer (Sutent) and Bayer/Onyx (Nexavar) and others in late clinical trials that target either kinases or receptors in the VEGF pathway.

But that was exactly the reason Intradigm focused its early efforts on VEGF. "It's well-known and clinically validated and that should allow us a fast track for ICS-283 compared to the time it would take us if opted to use a target that is not validated," Azab notes. "There is a lot of risk management in drug development and what we are trying to do with our lead candidate is manage that risk effectively."

But this is not just a me-too therapeutic. Where ICS-283 has a potential advantage is in Intradigm's nanoparticle RNAi delivery technology that allows it to package different siRNA molecules targeting different genes, all enclosed by a binding ligand. The result, according to company information, is ligand-mediated active targeting and receptor-mediated intracellular delivery of the RNAi payload that can target RNAi therapeutics to specific tissues with systemic administration.

Azab feels the potential advantage for Intradigm is two-fold. First, ICS-283 will target both the VEGF ligand and receptor, where currently marketed products focus on one or the other. Second, its nanoparticle technology allows for systemic as opposed to local RNAi administration, one of the biggest hurdles in the development of RNAi therepeuctics.

"By taking this combination approach to VEGF, we see the potential for real advantages over others in this area," Azab notes.

Meanwhile, its selection of Agilent was both money- and technology-minded.

That's not a real surprise to James Powell, general manager of the nucleic acid solutions division. In operation since 2002 when it was founded by Powell, and under a number of owners since then, the Boulder operation has become a well-known GMP facility for the production of oligonucleotides.

"What we have is a flexible, multi-product set of assets," says Powell. "We can make three APIs in parallel at any one time, but it is also the service offering that helps us stand apart."

What also attracted Intradigm was the potential to dramatically reduce its siRNA production costs. In May, Agilent presented information at the TIDES conference in Las Vegas showing a significant improvement in RNA synthesis.

"This new chemistry should allow us to make far better and cheaper RNA-based drugs," says Powell. "We are in the process in the next few months of getting it up and running here. We were doing quite well without it, but we believe this should really boost our business."

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