By Doug Macron
When Lundbeck announced its plan to work with the University of Massachusetts Medical School to develop an shRNA-based Huntington's disease treatment and Debiopharm said it was picking up Marina Biotech's bladder cancer program, they became the latest in a line of biopharmaceutical players to dip their toes in the RNAi waters (related stories, this issue, here & here).
Companies like Novartis, Merck, and, until recently, Roche (GSN 11/18/2010), having struck some of the earliest, broadest, and priciest deals in the space, have dominated the RNAi-drug headlines for years.
For instance, Novartis began working with Alnylam Pharmaceuticals in 2005 as part of a now-completed deal to develop siRNAs against up to 31 disease targets (GSN 9/9/2005). One year later, in what remains one of the biggest deals in the space, Merck paid $1.1 billion to buy Sirna Therapeutics (GSN 11/2/2006).
But over the past year, a handful of other companies have formed more modest collaborations to see whether they can take advantage of RNAi as a therapeutic modality.
Among these is Japanese drug giant Kyowa Hakko Kirin, which in early 2010 announced a deal with Dicerna Pharmaceuticals to develop an RNAi-based treatment for cancer, extending its work with the gene-silencing technology after it acquired the Asian rights to Alnylam's respiratory syncytial virus drug ALN-RSV01 (GSN 1/7/2010 & 6/19/2008).
Under the terms of the partnership, Dicerna received $4 million upfront from Kyowa and stands to receive up to $120 million in research funding and milestones in exchange for the exclusive rights to an undisclosed cancer target.
The companies said they will begin by selecting and optimizing one of Dicerna's Dicer-substrate molecules — essentially 27-nucleotide long RNA duplexes capable of triggering an RNAi effect — against the target, a process expected to take a couple of years. Once that work is done, Kyowa will take over development of the molecule, although Dicerna has the option to co-promote the drug in the US should it reach the market.
The deal also allows Kyowa to add around 12 additional targets, each of which would be worth as much as $120 million to Dicerna.
Dicerna's technology also caught the attention of French biotech Ipsen. Last year, the companies agreed to co-discover RNAi therapies for cancer and endocrinology disorders (GSN 4/1/2010).
The alliance combines the Dicer-substrates with Ipsen's peptide-based targeting vectors, which the firms said will allow cell-specific, intracellular delivery of the RNAi molecules.
Although they are focused on drug discovery, Dicerna and Ipsen said that "may collaborate further to move the programs discovered under this partnership into development and eventual commercialization."
Another Japanese drug developer looking to RNAi is Nitto Denko, which last summer began working with Quark Pharmaceuticals to develop therapeutic siRNAs for fibrotic diseases (GSN 7/15/2010).
Few details of that alliance were disclosed, but the partners said they would join Quark's siRNA expertise with Nitto's drug-delivery technologies and that they expect to file an investigational new drug application in 2012.
Still on the Field
While Roche made a splash late last year when it announced it was pulling the plug on its in-house RNAi drug activities, other big biopharmas working in the field have largely stayed on track.
Much was made of Novartis' decision not to exercise a non-exclusive option to Alnylam's technology when the companies' alliance reached the end of its term, but Novartis did select the maximum number of targets with which it could work using the RNAi firm's know-how, giving it plenty of opportunities to move an RNAi drug forward (GSN 9/30/2010).
Novartis also holds options to an inflammatory bowel disease drug candidate under development by Marina Biotech, and an option to Quark's p53-targeting agent QPI-1002. The candidate is being developed as a prophylactic against acute kidney injury in patients undergoing cardiac surgery, and as a way to help prevent delayed graft function associated with kidney transplantation.
Meanwhile, Alnylam continues to work with Takeda Pharmaceutical on siRNA-based drugs for cancer and metabolic disease. Although partner Cubist Pharmaceuticals recently decided to stop work on a follow-on to ALN-RSV01 for pediatric patients, it still has the opt-in rights to the first-generation version.
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