AstraZeneca (AZ) and Roche have became the latest big pharma firms to invest in RNA interference (RNAi), having penned separate licensing deals with two of the industry's leading specialists in the field.
Roche has today announced it has committed "over a billion dollars" to a deal with Alnylam Pharma. This includes $331m (€243m) to license Alnylam's RNAi technology and also buy its research site in Germany, which will become Roche's 'Center of Excellence' for RNAi.
Meanwhile, AZ has agreed to pay Silence Therapeutics up to £200m (€295m) to develop RNAi drugs based on small interfering RNA (siRNA) technology for up to five disease targets nominated by AZ. The two companies stated that although these are "primarily" respiratory diseases, the deal could be extended to cover other therapeutic areas.
The two firms are just the latest in a string of pharma heavyweights that have invested heavily in RNAi technology for drug design - as opposed to its other main uses, such as gene screening and target identification and validation. Of those investors, only Merck & Co. has bought a whole company, rather than doing licensing deals. It bought Sirna Therapeutics for $1.1bn (€850m), and one company insider told DrugResearcher.com, the move has "re-invigorated" the company.
In addition to the upfront payment, Roche has also set aside over $700m - the exact amount is undisclosed - for a joint research programme with Alnylam against one or more disease targets in oncology, respiratory diseases, metabolic diseases and certain liver diseases.
Roche's head of global pharma research, Lee Babiss, said the deal provides it "with new capabilities to target complex diseases within our focus areas."
Similarly, AZ entered its collaboration with Silence to build on investments in biopharma and vaccines. Jan Lundberg, head of discovery research at AZ, explained that it will enable the company to "target disease mechanisms intractable to small molecules and other approaches."
Silence Therapeutics, which changed its name from SR Pharma in April, will receive a much smaller initial fee of £7.5m and the rest of the £200m will be in the form of undisclosed milestone payments. Should the three-year collaboration bear fruit, it will also receive royalties on product sales.
"This transaction provides further validation of the potential application of Silence Therapeutics' proprietary AtuRNAi molecules and our leading position in the fast developing field of RNAi therapeutics," said Iain Ross, chairman of Silence Therapeutics.
That technology comes from Silence's acquisition of Atugen back in 2005. Ross explained that its technology may prove to be superior to other siRNAs for several reasons. It is chemically modified to be blunt-ended and stabilised against nuclease degradation. This could lead to a longer half-life, lower doses and less frequent administration. Also, AtuRNAi molecules are based only on naturally occurring RNA and so there are no toxic metabolites.
Should this latest deal between AZ and Silence Therapeutics be extended beyond respiratory diseases, it may be worth noting that Silence Therapeutics is a self-confessed cancer specialist and, of all of the drugs in the smaller company's pipeline, only its anticancer programmes remain unlicensed.
That is because this is actually the second time Silence has benefited from big pharma interest in its research. Another of its drugs was licensed - from Atugen - to Quark Biotech, which subsequently licensed it to Pfizer.
RTP-801i, which blocks the REDD-1 gene, is in development for three separate indications. The only programme to have reached the clinic so far is for wet Age-related Macular Degeneration (AMD) where aberrant blood vessels beneath the retina leak blood and fluid into the eye, causing vision loss. The other two indications that Pfizer and Quark are pursuing are diabetic retinopathy and chronic obstructive pulmonary disease.
It is also the second time Alnylam has attracted big pharma attention: Novartis has a stake in the company that was founded by the leading scientists who pioneered the discovery of RNAi. Alnylam currently has one product in clinical development - ALN-RSV01 - in Phase I trials for Respiratory Syncytial Virus.
It is unusual, but becoming less so, for big pharma to throw large sums of money at such early stage technology: there are currently only five siRNA drugs in clinical trials. Until more clinical data is released, the companies involved will be holding their collective breath to see how worthwhile their investment has been.
"If RNAi can be shown to be delivered systemically, we will see a new drug class," concluded Ross.