Sirna Therapeutics, as part of its respiratory disease collaboration with GlaxoSmithKline, said last week that it will develop RNAi compounds against asthma and respiratory syncytial virus, and would later begin working on chronic obstructive pulmonary disease and allergic rhinitis.
"Sirna has demonstrated the ability to develop chemically modified and optimized siRNA compounds and then deliver those compounds effectively into the lung with our nanoparticle formulations," Barry Polisky, Sirna's CSO, said in a statement. "Further, we have demonstrated that our proprietary approach to targeting the conserved region of a viral genome has resulted in significant viral knockdown in a non-human primate model.
"With these encouraging results and together with the combined efforts of Sirna and GSK scientific teams, we expect to expedite the development of novel RNAi-based therapies -- those efforts initially focused on asthma and RSV," Polisky said.
But Sirna and GlaxoSmithKline's foray into RSV therapeutics could potentially trigger an IP dispute with key rival Alnylam, which has been developing its own RNAi-based RSV drug.
Terms of Glaxo and Sirna's alliance, which was announced in early April, call for Sirna to deliver optimized and formulated siRNAs against respiratory targets specified by GlaxoSmithKline, which will assume all development and commercialization responsibilities for the compounds (see RNAi News, 4/6/2006). In exchange, Sirna received $12 million upfront, half in cash and half in the form of an equity investment, and stands to be paid milestones and royalties.
"Sirna has demonstrated the ability to develop chemically modified and optimized siRNA compounds and then deliver those compounds effectively into the lung with our nanoparticle formulations."
The selection of asthma as an initial focus for the companies' partnership comes as no surprise, given GlaxoSmithKline's long-standing interest in the lucrative market. The company's top-selling Advair asthma treatment, for example, pulled in roughly $1.5 billion in the first quarter this year alone.
Sirna has long maintained an interest in asthma, as well. Late last year, the company presented in vivo data showing that a 1 mg/kg dose of a modified siRNA targeting IL-4R alpha -- one of the targets the company has identified as important in the disease -- achieved a 70-percent reduction in lung inflammation and an 80-percent inhibition in airway constriction.
Sirna President and CEO Howard Robin had also previously said that his company was gearing up to move an asthma drug candidate into the clinic as early as 2007 (see RNAi News, 11/11/2005).
Though not as high-profile, the RSV market also holds significant money-making potential: MedImmune's Synagis, currently the best-selling preventative for the condition, generated $463 million in worldwide sales in the first quarter. Alnylam Pharmaceuticals, Sirna's biggest rival, is convinced there is a market for a therapeutic to complement MedImmune's vaccine and is developing an RNAi-based RSV drug, which is in phase I trials.
There is currently no RSV therapeutic on the market.
IP Battle Shaping Up?
It was not immediately clear whether Sirna and GlaxoSmithKline are developing a treatment or prophylactic in their RSV program. Regardless, the companies' foray into the RNAi-for-RSV arena leaves the door open for a potential conflict with Alnylam down the road -- especially in light of the strong statements both Alnylam and Sirna have made in the past regarding the strength of their intellectual property estates.
Both companies have touted their patent portfolios as the best in the business, with Alnylam focusing on IP covering the fundamentals of RNAi as Sirna takes a more target-specific approach.
Indeed, Alnylam has snapped up the rights to many patents and patent applications covering the basics of RNAi, including the Tuschl-2 family, which covers the use of siRNAs, between 19 and 25 nucleotides long, to mediate RNAi, as well as the use of overhangs on the 3' ends of dsRNAs to mediate target RNA cleavage. A patent within this family recently received a notice of allowance from the US Patent and Trademark Office (see RNAi News, 1/19/2006).
But Sirna has not neglected fundamental RNAi IP to ensure its ability to develop RNAi drugs; The company holds the co-exclusive rights with Alylam to the Tuschl-1 patent family, which covers the use of 21 to 23 nucleotide-long siRNAs, sans the 3' overhangs, to induce RNAi in mammalian cells.
Sirna has also been aggressive in filing patent applications on the use of short-interfering nucleic acids against specific targets, and earlier this year the company was issued the first of these (see RNAi News, 4/6/2006). The awarded patent, No. 7,022,828, claims the use of nucleic acid molecules against IKK-gamma.
"The 250 patent [applications] we filed ... were instances where we ... synthesized hundreds of siRNAs, tested them in vivo or in vitro, and ultimately demonstrated which ones worked the best [in order to] file fully enabling IP.
According to Sirna, it has filed a similar patent application on the use of siRNAs against RSV, which it expects to be awarded based on the issuance of the IKK-gamma patent.
Sirna's Robin noted last week during a conference call to discuss the company's first-quarter financial results that he considers the IKK-gamma patent a "proxy" for the roughly 250 other target-specific patent applications the company has filed -- including the one related to RSV. Additionally, he said he is confident of the strength of those patent applications given the work that was conducted to support them.
"When we filed on those 250 patents, they were not paper filings," he said during the call. "The 250 patent [applications] we filed ... were instances where we ... synthesized hundreds of siRNAs, tested them in vivo or in vitro, and ultimately demonstrated which ones worked the best [in order to] file fully enabling IP. [The granted patent] is an excellent proxy and, in essence, every one of those 250 target patents was filed in a very similar fashion to the one that was recently issued on IKK-Gamma."
Officials from Sirna and Alnylam were not available for comment. Gwenan Evans, director of science communications for GlaxoSmithKline, told RNAi News in an e-mail that her company is not commenting on Sirna's announcement.
-- Doug Macron ([email protected])