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Silence, AstraZeneca Ink siRNA Rx-Discovery Deal; Initial Focus on Respiratory Diseases

Silence Therapeutics last week announced that it has signed an siRNA-based drug-discovery deal with AstraZeneca that could be worth up to ₤200 million ($404 million) in milestones to the RNAi therapeutics firm.
The deal marks the second collaboration between an RNAi drugs firm and a big pharma in as many weeks. Earlier this week, Alnylam Pharmaceuticals announced an alliance with Roche that could be worth up to $1 billion (see related story, this issue).
“We are delighted to partner with Silence Therapeutics in developing their siRNA technology and build on our investments made in biopharmaceutical and vaccine areas,” Jan Lundberg, executive vice president of discovery research at AstraZeneca, said in a statement. The technology “will enable AstraZeneca to target disease mechanisms intractable to small molecules and other approaches.”
Under the terms of the three-year deal, Silence will grant AstraZeneca a license to use its proprietary siRNA technology to develop RNAi drugs against five undisclosed targets, three of which will be associated with respiratory diseases.
In exchange, AstraZeneca will pay Silence an upfront cash fee of ₤2.5 million. In addition, AstraZeneca has agreed to make a ₤5 million equity investment in Silence, which translates to an almost three percent stake in the company.
Iain Ross, chairman of Silence, noted this week in an e-mail to RNAi News this week that AstraZeneca also has the option to select up to two of the five targets in therapeutic fields outside of respiratory disease in exchange for additional payments to Silence.
The companies will collaborate on early-stage siRNA identification and optimization work, while clinical development and commercialization efforts will be handled entirely by AstraZeneca.
Ross said that the partners also expect to work together to develop delivery methods for siRNAs created through the deal, but that this kind of collaboration “will be the subject of a further agreement” that has yet to be finalized.
Additional terms of the arrangement were not disclosed.
Officials from AstraZeneca declined to comment further on the deal.
Target by Target
To Silence, the AstraZeneca deal “provides further validation of the potential application” of its AtuRNAi molecules, Ross said in a statement last week. “In addition, [the] agreement highlights our ability to execute collaboration deals in line with our stated corporate strategy” of signing target-specific technology licensing deals.
Silence’s AtuRNAi technology involves roughly 19-mer duplexes that lack 3' overhangs and have been chemically stabilized with alternating 2'-O-methyl sugar modifications on both strands. Earlier this year, researchers from Silence published data showing that these blunt-ended molecules, when administered with the company’s lipid-based delivery technology, can trigger an RNAi response in mice.

“Our strategy is to carve up the landscape by licensing a limited number of specific targets as opposed to licensing out our technology platform across therapeutic areas.”

Silence, at the time known as SR Pharma, acquired the technology when it bought Atugen in July 2005 (see RNAi News, 7/29/2005).
While developing its own drug candidates based on the technology, Silence has also sought to profit from the technology by out-licensing it to other companies on a target-by-target basis.
“Our strategy is to carve up the landscape by licensing a limited number of specific targets as opposed to licensing out our technology platform across therapeutic areas,” Ross wrote in his e-mail this week. “The interest [from potential partners] is tremendous and our target-by-target strategy is working well.”
Indeed, Silence has already licensed two siRNA agents based on its AtuRNAi technology to Quark Pharmaceuticals. The first, RTP-801i, recently entered phase I development for age-related macular degeneration after Quark licensed it to Pfizer in a deal that resulted in milestone payments of up to $95 million to Silence (see RNAi News, 9/29/2006).
The second, AKIi-5, which is also licensed to Quark, recently entered phase I testing as a treatment for acute renal failure.
Now, through its deal with AstraZeneca, Silence is poised to see as many as five additional RNAi therapeutic candidates based on its technology enter human testing. Furthermore, Ross noted that Silence anticipates inking “at least one more big pharma deal” this year, in addition to “extending existing agreements.”
Silence’s target-by-target licensing approach has also allowed it to keep certain disease targets proprietary.
Ross pointed out in his e-mail that targets already selected by AstraZeneca under the companies’ licensing deal do not overlap with those being pursued by Silence and its partners, and that “we have already blocked a number of targets.”
Additionally, future target selection will be overseen by an “independent expert” for possible infringement, he added.

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