Building on our progress in translating the science of RNAi into a robust product engine and strong intellectual property position, Alnylam has established important alliances with leading pharmaceutical and medical technology companies to drive further development of it's product pipeline capabilities. These alliances have brought Alnylam about >$500M in funding that provides adequate cash to build our pipeline of proprietary and collaborative products.

Regulus Therapeutics LLC is a biopharmaceutical company formed to discover, develop and commercialize miRNA therapeutics. In September 2007, the company was created as a joint venture between Alnylam Pharmaceuticals, a leader in RNAi therapeutics, and Isis Pharmaceuticals, a leader in antisense technologies and therapeutics. Isis and Alnylam scientists and collaborators were the first to discover miRNA antagonist strategies that work in vivo in animal studies (Krutzfeldt et al. (2005) Nature 438, 685-689; Esau et al. (2006) Cell Metab., 3, 87-98). Isis and Alnylam have also created and consolidated key IP believed by the companies to be required for development and commercialization of miRNA therapeutics. The company, founded in 2007, maintains facilities in Carlsbad, California. For more information, visit www.regulusrx.com.

In July 2007, Alnylam and Medtronic advanced the collaboration initiated in February 2005, following positive pre-clinical data generated under the initial joint technology development phase of the program. The companies will focus 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 has also been revised as a 50/50 relationship in the United States. Medtronic will commercialize the therapy consisting of the identified RNAi compound and advanced delivery devices. In the United States, 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.

In September 2005, Alnylam and Novartis Institute for BioMedical Research (NIBR), the research institute of Novartis AG, formed a landmark alliance focused on the discovery of innovative therapeutics based on RNAi. The alliance will discover, develop and commercialize RNAi therapeutics across multiple therapeutic areas. The partnership, valued at >$700M, brings together the leader in RNAi with one of the largest and most successful innovation-based pharmaceutical company.

In February 2006, Alnylam and Novartis formed a second collaboration to jointly advance RNAi therapeutics for pandemic flu

In September 2006, Alnylam and Biogen Idec announced a collaboration to develop RNAi therapeutics for the potential 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 will fund all research and development activities.

In July 2007, Roche and Alnylam entered into a major alliance in which Roche obtains a non-exclusive license to Alnylam's technology platform for developing RNAi therapeutics. The alliance will initially cover four therapeutic areas: oncology, respiratory diseases, metabolic diseases and certain liver diseases. Alnylam and Roche also will collaborate on RNAi drug discovery for one or more disease targets in these therapeutic areas. In addition, Roche will acquire Alnylam's European research site located in Kulmbach, Germany, subject to regulatory approval. This site will become Roche's Center of Excellence for RNAi therapeutics discovery.