Strategic Alliances

Our unparalleled intellectual property (IP) position, success in creating a robust product platform, and advances in delivery are widely recognized by leading, innovative pharmaceutical and biotechnology companies. This recognition is reflected by the major strategic alliances that we have formed. These innovative alliances are true win-win partnerships that drive our business forward while enabling our partners to develop and commercialize RNAi therapeutics worldwide. They are a keystone element of our strategy to build a leading biopharmaceutical company that creates important therapeutics and , in turn, value for our stockholders.

sanofi–aventis: In June 2010, Regulus entered into a global, strategic alliance with sanofi–aventis to discover, develop, and commercialize microRNA therapeutics. The alliance will initially focus on the therapeutic area of fibrosis. Regulus a nd sanofi–aventis will collaborate on up to four microRNA targets, including Regulus' lead fibrosis program targeting microRNA-21. Sanofi–aventis will provide annual research support for three years with the option to extend two additional years. Regulus is eligible to receive royalties on microRNA therapeutic products commercialized by sanofi aventis. Sanofi-aventis will support 100 percent of the costs of clinical development and commercialization of each program. In addition, sanofi–aventis also receives an option for a broader technology alliance that provides Regulus certain rights to participate in development and commercialization of resulting products. Alnylam and Isis are each eligible to receive 7.5 percent of all potential milestone payments, in addition to royalties on product sales.
Cubist Pharmaceuticals, Inc.: In January 2009, Alnylam and Cubist formed a strategic collaboration to develop and commercialize Alnylam's ALN-RSV program. The RSV-specific RNAi therapeutic program includes ALN-RSV01 as well as several other potent and specific second-generation RNAi-based RSV inhibitors in pre-clinical studies. The collaboration is structured as a 50/50 co-development and profit share arrangement in North America, and a milestone- and royalty-bearing license arrangement in the rest of the world outside of Asia, where ALN-RSV is partnered with Kyowa Hakko Kirin. After achieving certain development milestones, Alnylam could convert the North American co-development and profit share to a royalty-bearing license with development and sales milestones. Cubist will have sole rights for commercialization of the ALN-RSV program worldwide outside of Asia, subject to the cost and profit sharing in North America.
Kyowa Hakko Kogyo Co., Ltd.: In June 2008, Alnylam and Kyowa Hakko formed an exclusive alliance to develop and commercialize ALN-RSV01, a RNAi therapeutic in clinical development for the treatment of respiratory syncytial virus (RSV) infection, in Japan and other major markets in Asia. The partnership also includes additional RSV-specific RNAi therapeutic compounds that comprise the ALN-RSV program. In the rest of the world outside of Asia, ALN-RSV is partnered with Cubist Pharmaceuticals as a milestone- and royalty-bearing license arrangement, and a 50-50 co-development and profit share arrangement in North America.
Takeda Pharmaceutical Company Limited: In May 2008, Alnylam and Takeda formed a strategic platform alliance that provides Takeda with broad, worldwide, non-exclusive access to and enablement with Alnylam's RNAi therapeutics platform technology and intellectual property in the fields of oncology and metabolic disease, with the right to expand the number of therapeutic fields in the future. The agreement also includes the transfer of platform technology from Alnylam to Takeda, a collaboration and cross-license of delivery technologies between the two companies, and a drug discovery collaboration on certain RNAi therapeutic targets. In addition, Alnylam retains the right to opt-in as late as the beginning of Phase III to co-develop and co-commercialize four Takeda RNAi therapeutic programs in the U.S. market on a 50-50 basis. This landmark alliance is the first major RNAi therapeutics partnership between a Japanese pharmaceutical company and a U.S. biotechnology company and represents a new frontier in the advancement of RNAi therapeutics to patients on a global basis.
GlaxoSmithKline plc: In April 2008, GSK and Regulus Therapeutics formed the first ever microRNA-focused strategic alliance to discover, develop and market novel microRNA-targeted therapeutics to treat inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease. The alliance provides GSK with options for exclusive worldwide licenses to develop and commercializes candidates directed at four different microRNA targets. Regulus is responsible for the discovery and development of these microRNA antagonists through completion of clinical proof of concept.
F. Hoffmann-La Roche Ltd: In July 2007, Roche and Alnylam entered into a strategic platform alliance in which Roche obtained a non-exclusive license to Alnylam's IP and technology platform for the development and commercialization RNAi in four therapeutic areas: oncology, respiratory diseases, metabolic diseases and certain liver diseases with the right to expand the number of therapeutic fields in the future. Alnylam and Roche also will collaborate on RNAi drug discovery for one or more disease targets in these therapeutic areas. In addition, Roche acquired Alnylam's European research site located in Kulmbach, Germany. This site has become Roche's Center of Excellence for RNAi therapeutic research.
Medtronic, Inc.: In July 2007, Alnylam and Medtronic advanced their collaboration initiated in February 2005, following positive pre-clinical data generated under the initial joint technology development phase of the program. This collaboration focuses on developing a drug-device combination for the treatment of Huntington's disease. The product is expected to consist of an RNAi therapeutic targeting the Huntington's disease gene that will be delivered by Medtronic's implantable infusion pump. In addition, the companies may jointly decide to collaborate on the development of similar drug-device combinations using Alnylam's RNAi therapeutics platform and Medtronic's implantable infusion pump for the treatment of other neurodegenerative diseases, such as Parkinson's disease.

The agreement was also revised as a 50/50 co-development and profit share in the U.S. Medtronic will commercialize the therapy consisting of the RNAi therapeutic compound and an advanced delivery device. In the U.S., Alnylam has the opportunity to invest in clinical development of this therapy through product launch. In Europe, Medtronic is solely responsible for development and commercialization.
Biogen Idec: In September 2006, Alnylam and Biogen Idec, Inc. formed a collaboration to develop RNAi therapeutics for the treatment of progressive multifocal leukoencephalopathy (PML). PML is caused by infection of the central nervous system with a virus called "JC virus" and can occur in certain immune-suppressed patients, including those receiving immunomodulatory therapies. Alnylam and Biogen Idec will initially conduct investigative research into the potential of using RNAi technology to develop therapeutics to treat PML. Under terms of the collaboration, Biogen Idec, Inc. funds all research and development activities.
Novartis AG: In September 2005, Alnylam and Novartis Institute for BioMedical Research (NIBR), the research institute of Novartis AG, formed a landmark RNAi therapeutics alliance. The alliance will discover, develop, and commercialize RNAi therapeutics for a defined number of gene targets exclusively selected by Novartis. In addition, Novartis has an option to obtain a non-exclusive platform license in exchange for an additional upfront payment on pre-defined terms. In July 2008, Novartis elected to extend the research term of the partnership for at least one additional year through October 2009.

In February 2006, Alnylam and Novartis formed a second collaboration to jointly advance RNAi therapeutics for pandemic flu.
Isis Pharmaceuticals, Inc.: In March 2004, Alnylam entered into a broad, strategic collaboration and license agreement with Isis, a leading developer of single-stranded antisense oligonucleotide drugs. The agreement enhances Alnylam's intellectual property position with respect to RNAi-based therapeutics and its ability to develop and commercialize RNAi therapeutics. Isis granted Alnylam licenses to its current and future patents and patent applications relating to oligonucleotide chemistry and to RNA-targeting mechanisms for the research, development and commercialization of RNAi therapeutics.