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RXi Deal with Philips to Explore Ultrasound-Guided Drugs; Rx Strategy Due This Week

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By Doug Macron

RXi Pharmaceuticals last week announced that it had formed a collaboration with technology giant and imaging specialist Royal Philips Electronics to explore the use of ultrasound-guided RNAi therapeutics.

The deal marks the latest move by RXi to expand its access to new delivery approaches, coming about two months after the RNAi shop said that it would be working with TransDerm on new technologies for skin disorders.

It also may offer some clues as to the therapeutic course RXi is setting for itself, which the company said it will disclose at the Jefferies 2010 Global Life Sciences conference later this week.

Under the terms of the deal, the companies will test RXi's self-delivering rxRNA molecules, which are designed to reach target tissues and organs without a delivery vehicle, in conjunction with Philips' ultrasound platform.

According to RXi President and CEO Noah Beerman, the sd-rxRNAs have been shown in preclinical studies to effectively enter target cells when delivered directly, with delivery to the skin, eye, and central nervous system appearing especially promising.

For example, earlier this year, RXi's Vice President of Pharmaceuticals Development Pamela Pavco presented data showing that the company's sd-rxRNAs could knock down a target gene in skin cells when delivered via intradermal injection.

But in terms of systemic delivery, the company still faces challenges in getting the molecules out of the bloodstream to tissues of interest.

"That's where the ultrasound-mediated delivery might be an important solution," Dmitry Samarsky, RXi's vice president of technology development, told Gene Silencing News this week.

Aside from its use in medical imaging, ultrasound has the potential for improving drug delivery based on its ability to create pressure, Oliver Steinbach, senior director and head of biomolecular engineering at Philips Research, said.

Specifically, Philips has developed a contrast agent it calls microbubbles, which are "gas-filled lipid shells the size of a few micrometers" that collect within the ultrasound field. But at higher frequencies, the bubbles burst, creating an effect dubbed extravasation, which creates large openings in the endothelium of blood vessels, permitting drugs in circulation to "leak" through into the surrounding tissue when they ordinarily would be too large to do so.

"It's kind of like we're localizing systemic delivery using their ultrasound-mediated technology," Beerman noted.

Samarsky added that another benefit of the ultrasound approach is the potential to minimize the risk of side effects "because you're not only opening the organ for uptake by the molecules, but you are defining the organ where you want delivery to occur."

Once out of the vasculature, the ultrasound waves trigger an effect called sonoporation, which works similarly to electroporation, and "transiently makes cell membranes more permeable to take up large molecules," which could enhance the uptake of RXi's sd-rxRNAs, Steinbach told Gene Silencing News.

Philips has already conducted proof-of-concept work on the ultrasound-delivery approach, primarily with small molecules and plasmid-based reporters, he noted. However, "we have not done extensive experiments ourselves with small interfering RNAs.

"That's why we were looking for a competent and leading partner" and are collaborating with RXi, he added.

Steinbach described the deal with RXi as a "joint research agreement … [focused around] an initial feasibility study where both parties bring … contributions to the lab bench."

RXi is contributing the sd-rxRNA molecules and related expertise, while Philips is providing the ultrasound technology and will conduct the majority of the studies. These studies, which it will run in its labs in the Netherlands, will include both in vitro and in vivo experiments.

Steinbach said that he expects that the deal could result in a larger alliance with RXi and, because it is non-exclusive, it could also lay the groundwork for Philips to work with other companies interested in RNAi drug delivery.

Philips is also permitted to publish certain of the data resulting from the deal, he said, adding that data from the effort is expected to be available in less than a year.

Beerman noted that the collaboration could also extend beyond that timeframe depending on the outcome.

In a statement announcing their deal, RXi and Philips cited the potential for RNAi therapeutics in cardiovascular disease and cancer, but Beerman told Gene Silencing News that the ultrasound-based delivery approach could also prove useful in a broad variety of indications.

He declined to elaborate, but noted that he will provide specific details about RXi's therapeutic strategy later this week at the Jeffries event in New York.

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