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Targeted Genetics Takes Over Huntington’s Program Developed by Sirna and U of Iowa

Targeted Genetics said last week that it will take over from Merck subsidiary Sirna Therapeutics a program to develop treatments for Huntington’s disease based on adeno-associated virus delivery of RNAi that was originally established under an agreement between Sirna and the University of Iowa.
Under the arrangement, which will give TG its first in-house RNAi-based drug candidate, UI has directly transferred from Sirna to TG a license covering intellectual property related to AAV-expressed RNAi. TG will use the license together with related IP from Merck to continue pre-clinically developing the drug with UI, a company official said this week.
As reported last week by BTW sister publication RNAi News, Sirna had penned a collaboration in 2005 to combine its siRNA expertise with TG’s AAV vector-based delivery systems. The deal was to build on an existing collaboration Sirna had forged with UI researcher Beverly Davidson one year earlier.
When research coming out of the Sirna-UI collaboration showed that AAV-based delivery of RNAi showed promise as a treatment for HD, “TG began working with Sirna to develop a product in that area,” Susan Robinson, vice president of business development for TG, told BTW this week. “That then triangulated with the UI agreement.”
At that point, Robinson said, TG had no official relationship with UI save for an unofficial alliance made through Sirna. In addition, she said, TG’s original agreement with Sirna mandated that if either party in the future decided not to advance the program, the other party would be provided with the means to do so on its own.
“Not ever knowing what the specifics are when you are negotiating a deal, we put in place a structure that said that as long as there was data, somebody was going to move this forward, and one party would make available to the party taking it forward the IP necessary to do so,” Robinson said. “There was IP in all these different areas that would need to be put into one place to move the product.”
Such a scenario did in fact happen soon after Merck acquired Sirna in 2006, and Merck decided that the RNAi-based HD therapeutic program was not in its plans.
As a result, TG and Sirna/Merck decided that TG would be best suited to move the program forward, at which point it became apparent that “we were going to need and want access to the University of Iowa IP,” Robinson said. “That was in full discussion with UI, and I think based on TG’s expertise and the relationship we had with UI made perfect sense to UI as well.”
As part of the arrangement, TG created an “amended and restated collaboration” with Sirna whereby TG “would get rights to technology held by Sirna if it was necessary to develop and commercialize a product.”
“We don’t know exactly what that might be, or if there ever will be [one] … but Merck would provide us with freedom to operate if there is anything in its portfolio that is necessary for us to develop and commercialize,” Robinson said.
Targeted Genetics will also pay Sirna an undisclosed royalty on sales of any products that may arise from the program.

“Merck did purchase Sirna … and whenever these things happen you want to determine where your project falls on the new corporate hierarchy.”

According to Zev Sunleaf, licensing manager for the University of Iowa Research Foundation, the university was comfortable with transferring the IP to TG because it had previously worked closely with the company, including through sponsored research agreements and the licensing of UI technologies to TG in other unspecified and unrelated areas.
Merck purchased Sirna, “and whenever these things happen you want to determine where your project falls on the new corporate hierarchy,” Sunleaf said. “They were very supportive, but I think that they saw it as possibly not their highest priority, and they approached us … about having TG continue with the research and take over the license.
“Based on the standard diligence requirements we would ask of any licensee, we were fine with that,” Sunleaf said. “We think TG is a good partner. We have had a long-standing relationship with them on other projects, and so we view them as having all the necessary capabilities, and the background — not only technically, but in other related IP — to move this forward.”
Sunleaf said the agreement should not be confused with a sublicense agreement — “we no longer have a direct relationship with Merck on any of this IP” — but instead is a direct transfer of the original licensing agreement with Sirna to TG.
“There were specific milestones, both diligence and financial, in the original license, and they just carry over,” he said. “Everything that was due before is still due as far as requirements to develop and any financial outcomes based on that development. If there is something due at year five, or a payment that is due when a product is approved for marketing – those things would be the same as before, but it would just be a different licensee paying those fees.”
Both TG and UI declined to provide specific diligence or financial details of the agreement.
“We’re eventually hoping to treat at minimum some people with HD, and hopefully to develop an even wider array of therapies in which AAV-related RNAi can help,” Sunleaf said.
According to RNAi News, TG said that the HD therapeutic program is expected to reach clinical testing in late 2009. “Huntington’s is a brain disease, [and] it’s not going to be easy to either deliver oligonucleotides across the blood-brain [barrier] or do repeated injections,” Barrie Carter, TG’s CSO, told RNAi News. Therefore, an expressed RNAi approach like the one using TG’s AAV vectors seems promising, because the vectors “persist for extraordinary lengths of time, particularly in non-dividing cells like neurons,” Carter said.
The program also received a boost this week in the form of a paper published by Davidson’s lab and TG scientists in the Proceedings of the National Academy of Sciences that suggested an artificial miRNA scaffold approach could be used to reduce neurotoxicity that was observed in mouse models treated with short-hairpin RNAs targeting Huntington’s-related mRNAs.
According to TG’s Robinson, the unique expertise provided by Davidson’s lab, as demonstrated in this paper, makes UI an invaluable partner in the HD therapeutic program moving forward.
“It’s safe to say we have an ongoing relationship with Beverly Davidson,” Robinson said, although she declined to provide specific details of an ongoing sponsored research program, stating only that such an arrangement would be made separately from the IP license transference agreement.
“What we have really valued is her experience with animal models – both behavioral models and biological models,” Robinson added. “It’s also the relevance of her being able to place the work that we’re doing in the context of the other research she has done in the past. A lot of it is the pre-clinical development — the basic biology, research, and animal model expertise that she has that will form a fundamental part of the program.”
UI’s Sunleaf added that “we have a longstanding collaborative research program with [TG], and I would expect that to continue.”

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