Regulus Therapeutics and French pharma giant Sanofi-Aventis announced today that they would co-develop MicroRNA Therapeutics with an initial focus on fibrosis (PR by S-A, PR by Regulus, PR by Alnylam and ISIS). The deal demonstrates the need for innovative approaches for the treatment of diseases for which the pharmaceutical industry has long failed to develop meaningful therapies. The deal, valued at potentially over $750M, includes a $25M upfront, relatively realistic $50-60M in mid-term option fees and equity investments and major R&D support by Sanofi-Aventis, and provides Regulus with a nice cash cushion going forward. The ~$50M in realized partnership funding to date from GSK and Sanofi-Aventis should also make shareholders of both RNAi Therapeutics company Alnylam and antisense company ISIS Pharmaceuticals happy which are still the majority owners of Regulus.
Today’s announcement comes less than a month after Regulus Therapeutics secured exclusive access from the University of Wuerzburg to intellectual property related to fundamental work on the role of microRNA-21 in cardiac fibrosis. This should also be the lead program in the collaboration and justify Sanofi-Aventis transferring $25M of hard cash. Beyond the heart, fibrosis, a form of tissue scarring, is also widely observed in other organs such as the lung, kidney, and liver, and new treatment options are desperately sought after. Witness the fate of a drug for idiopathic pulmonary fibrosis (IPF) developed by Intermune of which the data appeared to be somewhat borderline, but which an FDA advisory panel recommended for approval earlier this year essentially because of the very significant unmet medical need (it was subsequently rejected by the FDA).
In addition to miR-21, other microRNAs have also been found to play a role in fibrosis, and both microRNA antisense and microRNA replacement approaches are conceivable. Given that these microRNAs often occur in various tissues, targeted delivery approaches may be preferable. On the other hand, should less specific delivery prove to be well tolerated, it is possible that the same drugs may be of use in other indications such as cancer for which some of these microRNAs, especially miR-21, have also been found to play a role.
The previous deals with GSK involved up to 4 microRNA targets in inflammation and targeting miR-122 for the treatment of Hepatitis C viral infection. Danish competitor Santaris also has an agreement with GSK covering up to 4 antiviral MicroRNA Therapeutics programs. Given that there are significantly less microRNAs than there are genes and microRNA biology is still relatively young, these deals seem to balance the concern of unwittingly giving away too much to Big Pharma with allowing enough flexibility for data-driven drug development.
In addition to proving to be a very good investment for Alnylam and ISIS, being part of Regulus also allows these companies to establish new relationships with major pharmaceutical companies. It is probably not a coincidence that the initial GSK-Regulus partnership was followed by the ISIS-GSK rare and infectious disease deal earlier this year. Of note, Sanofi-Aventis, under the new leadership of CEO Chris Viehbacher, recently entered into a relationship with California company Traversa for the development of protein-based RNAi delivery.Overall, it is very encouraging to see that a number of companies in Big Pharma do understand the need to invest in potentially transformative new technologies to address major unmet medical needs. I hope that this summer will provide more such proof points.