Jumping into the RNA fray

Deal with Silence Therapeutics gives AstraZeneca a good foot forward in siRNA research

Jeffrey Bouley
LONDON—Joining the ranks of other industry heavy-hitterslike Roche and Merck, AstraZeneca has made the jump to invest heavily in RNAitechnology for drug design—as opposed to the more long-standing uses for thetechnology, such as gene screening and target identification and validation. InAstraZeneca's case, it has done so by penning a deal with London- andBerlin-based Silence Therapeutics plc. Roche took a similar tack in a licensingand research site purchase deal with Alnylam (see story page 1), while Mercktook the route of buying a company outright in the RNAi field—SirnaTherapeutics.

Under the three-year research and development collaborationwith Silence announced in July, AstraZeneca is looking to discover and developproprietary siRNA molecules against up to five specific targets in therespiratory disease area, keeping open the possibility that it might laterextend the collaboration into other disease areas of interest. For the work,Silence Therapeutics will receive initial access fees, clinical development andcommercial milestone payments of up to approximately $400 million, plusroyalties on product sales. The initial access fees include SilenceTherapeutics providing AstraZeneca with a license to its proprietary siRNAtechnology for a fee of approximately $15 million, of which around $10 millionis an equity investment in Silence that would give AstraZeneca just under 3 percentof the total voting rights in the company.

Silence Therapeutics and AstraZeneca will jointlycollaborate in the early phase of identification and optimization of novelsiRNA molecules. AstraZeneca will retain full responsibility for the clinicaldevelopment and commercialization.

AstraZeneca has no other deals at this time involving siRNAtechnologies, notes Dr. Frances A. Sutcliffe, communications director forAstraZeneca's global R&D division. Some industry watchers have couched thisRNAi deal as the latest move in the company's efforts—following the recent dealto buy U.S.biotech firm MedImmune for more than $15 billion—to build up its developmentpipeline, particularly in biotechnology, with an eye toward dealing withindustry pressures such as competition from generics.

Sutcliffe does acknowledge that both deals are part of acore externalization strategy to access new technology and innovative science,but didn't draw any specific parallels between the deals or their potentialimpact on responding to stressors like generic competition.

"The [MedImmune] acquisition creates a new fully functioningbiologics and vaccines business within AstraZeneca and enhances our R&Dscience base through which we will deliver a stronger product pipeline,"Sutcliffe says. "The acquisition delivers our biologics strategy faster thananticipated and offers a complementary fit with our existing therapeutic areastrengths in oncology, infection and inflammation."

As for the more recent silence deal, Sutcliffe says: "AstraZenecaidentified gene silencing by siRNA as a promising technology for intracellulartargeting, which is expected to open up new product concepts."

Among those concepts is identifying and creatingtherapeutics that are not currently feasible using either small molecules orconventional monoclonals, notes Jan M. Lundberg, AstraZeneca's executive vicepresident, discovery research. "We are delighted to partner with SilenceTherapeutics in developing their siRNA technology and build on our investmentsmade in biopharmaceutical and vaccine areas," he adds.

Silence Therapeutics, for its part, says it is excited todelve into this collaboration with AstraZeneca, which Silence Chairman IainRoss notes "has a significant franchise in the respiratory area."

 "We look forward to working with AstraZenecato develop new RNAi therapeutics for the treatment of respiratory diseases,"Ross says, "whilst concurrently continuing to create further significantshareholder value via the development of our proprietary oncology pipeline."
 

Jeffrey Bouley

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