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Dendritic Nanotech Becomes RNAi Reagent Provider Through Marketing Deal With EMD

Starpharma this week announced that its subsidiary Dendritic Nanotechnologies has granted EMD Biosciences the exclusive, worldwide rights to sell its PrioFect transfection reagents for in vitro applications.
Under the terms of the deal, DNT will supply the reagents to EMD for sale to the DNA and siRNA transfection research markets. In exchange, DNT will receive royalties and milestone payments, and will retain the rights to the technology for in vivo applications.
In fact, a DNT official said the company is “aggressively recruiting” RNAi firms that may pursue this technology for in vivo applications.
Additional terms of the license arrangement were not disclosed. Officials from EMD, which is a unit of Germany’s Merck, did not return requests for comment.
“The license and supply agreement with EMD Biosciences … is significant because it will lead to the first commercial application” of the reagents, Jackie Fairley, Starpharma CEO, said in a statement.
According to DNT, the reagents are based on the company’s so-called Priostar dendrimers, which are branched polymer nanostructures formed into spheres through a set of “repeating chemical synthesis procedures that build up from the molecular level to the nanoscale region.”
“The beauty of the architecture is that we get very precise size control and also have control over the number of surface groups,” Robert Berry, president of DNT, told RNAi News this week. “So if you start with four in the core, by the time we amplify it, we’re at 12 surface groups. … If we amplify it again, we add another layer, and so forth.”
This amplification process allows for precise size control, an important feature for siRNA delivery and one that Berry said differentiates the Priostar technology from those used in siRNA transfection reagents.
“We’re seeing quite a differentiation between the size [of delivery agents] and the cell types as to the transfection efficiency,” he said.
“For example, biodistribution and excretion studies have shown that small dendrimer-based agents synthesized with surface-conjugated chelates are primarily excreted during the first pass through the kidney,” while larger agents are excreted more slowly and take up in the reticuloendothelial system, DNT states on its website.
“You have to have nanometer-size control” to optimize delivery, Berry added. “And we’re not aware of another technology that’s as specific” in doing so as Priostar.
Another key aspect of the technology is the ability to bind targeting agents, such as antibodies or ligands, to the surface of the dendrimers, Lori Reyna, senior scientist and manager of life sciences at DNT, added.
This feature, however, may prove the most beneficial for in vivo applications, an area to which DNT has now shifted its attention having signed the deal with EMD.
Berry noted that DNT’s small size — it currently employs 16 people — was one of the main reasons why it sought a partner to sell the Priostar technology in the research market, but added that the firm’s desire to play in the biopharmaceutical market also played a part.
“Quite frankly, for us to invest in setting up a sales and distribution channel and do all the marketing … is a very tough role when you’re already [competing against] established players in the field,” he said. At the same time, “while the research market is interesting … we really think that our focus at DNT should remain on the in vivo aspects of transfection.”

“While the research market is interesting … we really think that our focus at DNT should remain on the in vivo aspects of transfection.” in vivo

In line with this, DNT is currently looking to license the Priostar technology to groups that would use it in RNAi-based therapeutic applications.

“We’ve had a fairly significant relationship with a very large pharmaceutical company … and we have significant interest from other companies,” including pure-play RNAi drug shops, Berry said. Right now, “we’re aggressively recruiting established partners in [the RNAi] area that want to take this technology in vivo.”
How a potential deal might look remains unclear, he said, adding that “if you … get your choice of how you’d want to [structure a deal], obviously you’d like to license [the technology] off by indication.”
However, “the companies we’ve worked with thus far with have come to us with some rather specific targets in mind,” he said, stressing that talks with potential licensees are still preliminary.
“The Priostar [technology] wasn’t announced … until May of last year,” Berry added. “Since then, because it’s been all new development, we’ve gone through this regimen of proving the transfection and licensing it off. We’re just beginning now to turn our attention to the in vivo world.”
As such, data on the use of Priostar dendrimers in vivo is limited.
Under a collaboration with the National Cancer Institute, DNT’s dendrimers of different sizes have been tested successfully for their ability to deliver MRI-contrasting atoms to different parts of a mouse when administered via intravenous injection (see figure).

Images by H. Kobayashi and M.W. Brechbiel, NIH. Provided by DNT.
DNT noted that this was strictly a proof-of-concept experiment “conducted in the absence of genetic material.” However, the company added that it expects that “potentially analogous results may be achieved with PrioFect complex with siRNA.”
Berry also said that the NCI is exploring the use of the dendrimer technology as a chemotherapeutic delivery agent and that DNT is conducting some additional preclinical work in the siRNA field in-house.
But “it’s very early on,” he said.

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