In June 2010, Regulus and Sanofi entered into the largest-to-date strategic alliance on microRNA therapeutics valued at potentially over $750 million. The agreement includes a $25 million upfront fee, a $10 million equity investment, and annual research support for three years with the option to extend for two additional years. The alliance will initially focus on the therapeutic area of fibrosis. Regulus and Sanofi will collaborate on up to four microRNA targets, including Regulus’ lead fibrosis program targeting microRNA-21. Regulus is eligible to receive preclinical milestones, as well as development and sales milestones for collaboration targets. In addition, Regulus is also eligible to receive royalties on microRNA therapeutic products commercialized by Sanofi. Sanofi will support 100% of the development and commercialization costs associated with identified therapeutic targets. Regulus has granted Sanofi an option to enter into a technology alliance worth $50 million that could provide Sanofi with access to Regulus’ microRNA platform and a limited number of product licenses. Should the technology alliance option be exercised, Regulus will have certain predetermined opt-in rights to participate in the development and commercialization of future Sanofi clinical microRNA programs. Regulus will also be eligible to receive milestone payments and royalties on microRNA therapeutic products developed and commercialized under the technology alliance option.

In April 2008, Regulus and GlaxoSmithKline announced the first-ever microRNA-focused strategic alliance to discover, develop and commercialize novel microRNA-targeted therapeutics to treat inflammatory diseases. Potentially valued at nearly $600 million, the alliance provides GSK with an option to exclusively license drug candidates directed at four different microRNA targets with relevance to inflammatory diseases. Under the agreement, Regulus is responsible for the discovery and development of microRNA antagonists through completion of clinical proof-of-concept, and GSK has the option to license each drug developed by Regulus for the relevant microRNA target for further development and commercialization on a worldwide basis.

In February 2010, Regulus and GSK announced a new collaboration to develop and commercialize microRNA therapeutics targeting microRNA-122 (miR-122) for the treatment of hepatitis C (HCV) infection. miR-122 is a liver-expressed microRNA that has been shown to be a critical endogenous ‘host factor’ for HCV replication, and anti-miRs targeting miR-122 have been shown to block HCV infection. Regulus exclusively controls patent rights covering miR-122 antagonists and their uses as HCV therapeutic agents. As part of the agreement with GSK, miR-122 becomes one of the four microRNA alliance targets and Regulus will receive additional upfront and early-stage milestone payments with the potential to earn more than $150 million in miR-122-related combined payments throughout the development process.