GlaxoSmithKline (GSK) and Regulus Therapeutics LLC (Regulus) have entered into a worldwide strategic alliance to discover, develop and market novel microRNA-targeted therapeutics to treat inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. Regulus is a joint venture between Alnylam Pharmaceuticals, Inc. and Isis Pharmaceuticals, Inc.

The alliance leverages Regulus' unique expertise and intellectual property position in the discovery and development of microRNA-targeted therapeutics and provides GSK with an option to license product candidates directed at four different microRNA targets with relevance in inflammatory disease. Regulus will be responsible for the discovery and development of the microRNA antagonists through completion of clinical proof of concept, unless GSK chooses to exercise its option earlier. After exercise of the option, GSK will have an exclusive license to drugs developed under each programme by Regulus for the relevant microRNA target for further development and commercialisation on a worldwide basis. Regulus will have the right to further develop and commercialise any microRNA therapeutics which GSK chooses not to develop or commercialise.

Regulus will receive $20 million in upfront payments from GSK, including a $15 million option fee and a $5 million note (guaranteed by Isis and Alnylam) that will convert into Regulus common stock in the future under certain specified circumstances. Regulus could also be eligible to receive up to $144.5 million in development, regulatory and sales milestone payments for each of the four microRNA-targeted therapeutics discovered and developed as part of the alliance. In addition to the potential of nearly $600 million Regulus could receive in option, license and milestone payments, Regulus would also receive tiered royalties up to double digits on worldwide sales of products resulting from the alliance.

"We are focused on finding innovative medicines through both internal efforts and by 'virtualising' a portion of the inflammatory diseases pipeline. We are very excited to be working with Regulus and exploring the therapeutic opportunities in inflammation offered by targeting microRNAs, an exciting new area of biology," said Jose Carlos Gutierrez-Ramos, Ph.D., senior vice president and head, immuno-inflammation centre of excellence for drug discovery, GSK. "When associated with an aberrant inflammatory response, microRNAs represent disease targets whose therapeutic modulation could revolutionize the way we treat immune diseases and provide benefits not readily achievable with today's medicines."

microRNAs are a recently discovered class of genetically encoded small RNAs, approximately 20 nucleotides in length, and are believed to regulate the expression of a large number of human genes. microRNA therapeutics represent a new approach for the treatment of a wide range of human diseases. The inappropriate absence or presence of specific microRNAs in various cells has been shown to be associated with specific human diseases including cancer, viral infection, and metabolic disorders. Targeting microRNAs with novel therapeutic agents could result in high-impact and broadly acting treatments for human diseases.

"GSK is an outstanding partner for Regulus, and we look forward to expanding our efforts in inflammation where a new class of therapeutics could offer novel options to treat disease," said Kleanthis G. Xanthopoulos, Ph.D., president and chief executive officer, Regulus. "microRNA therapeutics represent an exciting new frontier for pharmaceutical research, opening many opportunities including those present in inflammation and immune diseases. As a leading microRNA therapeutics company, Regulus has the expertise and access to proprietary antisense technologies, which provide the tools and potential to quickly move therapeutic programs toward the clinic. Through its relationship with Alnylam and Isis, Regulus also has a vast patent estate in microRNAs."