By Doug Macron
While recently announced plans by three key big pharmas to alter their therapeutic RNAi efforts raised red flags for many industry watchers, many alliances for the gene-silencing technology remain ongoing.
Among these is a deal between Dicerna Pharmaceuticals and Japan's Kyowa Hakko Kirin, announced this week, that expands their drug-development partnership to include work in immunologic and inflammatory diseases.
The companies originally began working together in January to develop a drug against a specific cancer target based on Dicerna's Dicer-substrate RNAi technology (GSN 1/7/2010).
As part of the deal, Dicerna received a $4 million upfront payment from Kyowa and stands to pocket up to $120 million in research funding and milestones in exchange for the exclusive rights to the undisclosed target.
Under the expanded deal, Dicerna said it will receive a cash payment if Kyowa Hakko Kirin exercises an option to bring another target into the collaboration. Additional terms of the deal were not disclosed.
“This new agreement is a vote of confidence in Dicerna" and its Dicer-substrate molecules, Dicerna CEO Douglas Fambrough said in a statement.
But it is also an indication that the pharmaceutical industry hasn't turned its back on RNAi, despite a number of high-profile changes in strategy regarding the technology.
In a particularly big blow to the sector, last month Roche announced that it was shutting down its in-house RNAi research and development activities as part of a sweeping restructuring that included eliminating 4,800 jobs (GSN 11/18/2010).
The Swiss biopharmaceutical giant called the move a reaction to "increased price pressures and a more challenging market environment." However, many interpreted it as a reflection of drug makers' overall disillusionment in RNAi as a therapeutic modality.
Such sentiments were in no small part influenced by Novartis' decision in September not to exercise an option to take broad, non-exclusive access to one-time partner Alnylam Pharmaceuticals' RNAi-related technology and intellectual property (GSN 9/30/2010).
The transaction would have triggered a $100 million payment to Alnylam and would have been a kind of continuation of the companies' now-concluded five-year partnership to optimize siRNAs against targets that Novartis would own and take through the clinic.
Notably, Novartis did select the maximum number of targets allowable under that deal — 31 — which it will work on internally going forward.
Also raising questions about big pharma's dedication to RNAi was the decision by Pfizer to step back from previous plans to file an investigational new drug application on an in-house siRNA candidate in 2011 (GSN 10/28/2010).
As first reported by Gene Silencing News in October, Pfizer had decided that the IND coming out of its Research Technology Center next year will be for an "an in-house nucleic acid drug" rather than one necessarily based on RNAi, according to RTC CSO Art Krieg.
But despite these developments, there continues to be much collaboration between the pharmaceutical and RNAi industries.
In addition to the newly expanded deal with Kyowa, Dicerna earlier this year signed a deal to work with France's Ipsen on RNAi drugs in the fields of oncology and endocrinology.
Meanwhile, Alnylam announced last month that it received a funding commitment from the CHDI Foundation to advance an siRNA-based treatment for Huntington's disease through its ongoing neurodegenerative disorder alliance with Medtronic (GSN 11/4/2010).
Alnylam also continues to work with Takeda Pharmaceutical to discover, and potentially develop and commercialize, siRNA drugs in oncology and metabolic disease. At the same time, the RNAi firm has signed on Kyowa and Cubist Pharmaceuticals as partners for its respiratory syncytial virus program.
And as for Pfizer, despite changes to its internal pipeline it remains a key player for Tacere Therapeutics, having acquired its preclinical expressed RNAi treatment for hepatitis C, TT-033, in 2008. In addition, Pfizer holds the rights to Quark's phase II age-related macular degeneration drug RTP-801.
Quark also has found big pharma support in Japan's Nitto Denko, which is working with the Israeli company to develop siRNA-based drugs for fibrotic diseases. And this summer, Novartis exclusively optioned Quark's phase II p53 inhibitor QPI-1002, which is being developed as a prophylactic against acute kidney injury in patients undergoing cardiac surgery, and to prevent delayed graft function associated with kidney transplantation.
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