After a series of big pharma pullbacks Servier’s substantial deal with Miragen this week is encouraging news for companies striving to unlock the therapeutic potential of RNA. Struck over three candidates and involving $45m in financing over the next three years, the Colorado company has retained US and Japanese rights to the compounds – a well structured piece of deal making that should greatly benefit both partners, if all goes well in the clinic.
Miragen is working with microRNA - short, single-stranded RNA molecules that control the expression of entire sets of genes and pathways – a potential master switch for gene expression. The company believes drugs can be developed to target these molecules without hitting the delivery problems that have stymied much progress in the RNA field. Although its candidates have yet to make it into the clinic encouraging advances elsewhere likely persuaded Servier to have a punt on a field of research that desperately needs success stories (Vantage Point -Clinical progress required to reignite RNAi field, May 20, 2011).
Single molecular entities that dictate the expression of fundamental regulatory pathways, microRNAs are thought to represent potential drug targets for controlling many biologic and disease processes. Unlike messenger RNA they do not encode proteins, but function by preventing the translation of mRNA into proteins or triggering its breakdown.
Rather than a simple on/off switch, they fine tune cellular function, particularly during stress situations.
Founded in 2007 and having only raised $18m so far and employing 20 people, Miragen has made much progress in its short life. It has identified multiple microRNA targets with potential therapeutic application and has three pre-clinical candidates approaching the clinic, with others following behind.
Miragen licensed Santaris Pharma’s Locked Nucleic Acid platform to generate drugs to hit these targets. This technology can generate very small oligonucleotides with high affinity, which can inhibit RNA targets without the need for complex delivery vehicles.
Santaris has been enjoying success recently with the most advanced microRNA targeting compound in development, miravirsen, in hepatitis C. Phase IIa data will be presented next month's at the liver conference AASLD, establishing proof-of-concept for a drug that inhibits miR-122, a liver specific microRNA that the hepatitis C virus requires for replication.
GlaxoSmithKline has an option over the candidate under a broad ranging deal struck in 2007 – choosing to take this up would give companies in this field another reason to cheer.
The deal incorporates Miragen’s two lead programmes – miR-208 and miR-15/195 – and one as yet unidentified cardiovascular disease target.
The former is implicated in the pathogenesis and progression of heart failure; inhibition of the target may improve cardiac function and survival rates during heart failure, the company believes. Meanwhile inhibition of miR-15 may stimulate cardiomyogenesis – the process whereby new heart muscle cells are formed – resulting in less heart tissue death and an improvement in cardiac function after heart attack.
Servier has a strong cardiovascular franchise and although not one of the industry’s most prolific deal makers should make a committed partner. Negotiating to retain US and Japanese rights meanwhile is a canny move, which will allow Miragen to seek further non-dilutive fundraising in the future, pending clinical progress.
As well as the upfront, research support and near-term milestone payments over three years which makes up the $45m, clinical and commercial milestones take the deal value up to $1bn. Considering the stage of development and the novelty of this technology, that figure is a long way from being achieved.
But the $45m is tangible, and will provide essential funding for a technology is struggling to find friends.