Update on Regulus and sanofi-aventis collaboration

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY):

“We and Isis congratulate Regulus on forming this important new alliance with sanofi-aventis. Regulus stands as the leader in the emerging field of microRNA therapeutics, and this new partnership reflects the high level of interest across the pharmaceutical industry for innovative medicines based on this new biology”

• New Partnership Validates Alnylam and Isis Strategy for Shareholder Value Creation
• Regulus, Alnylam and Isis to Host Conference Call Webcast to Discuss Regulus-Sanofi-aventis Collaboration on June 22, 2010 at 8:30 a.m. ET (5:30 a.m. PT)

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY) and Isis Pharmaceuticals, Inc. (Nasdaq: ISIS) announced today that, as a result of the newly formed alliance Regulus has established with sanofi-aventis, each company will receive a payment of $1.8 million from Regulus. This represents 7.5% of the $25 million upfront payment from sanofi-aventis to Regulus. In addition, Alnylam and Isis are each eligible to receive a similar percentage of potential future success-based milestone payments from the alliance.

"We and Isis congratulate Regulus on forming this important new alliance with sanofi-aventis. Regulus stands as the leader in the emerging field of microRNA therapeutics, and this new partnership reflects the high level of interest across the pharmaceutical industry for innovative medicines based on this new biology," said John Maraganore, Ph.D., Chief Executive Officer of Alnylam and Chairman of the Board of Regulus. "Regulus is also representative of Alnylam's strategy to actively pursue new business opportunities across the broader dimensions of RNA biology and technology. In the case of the new partnership between Regulus and sanofi-aventis, the agreement will enable substantial funding for the advancement of microRNA therapeutics, while Alnylam maintains its significant ownership level to the benefit of our shareholders."

"In Regulus, Isis and Alnylam have created a focused company that leverages the collective expertise and intellectual property of both companies in the exciting field of microRNA therapeutics. We believe that this approach provides Regulus with a clear and unmatched advantage in developing microRNA therapeutics, including the ability to form industry-leading partnerships that access capabilities and funding. Certainly, the newly formed relationship between Regulus and sanofi-aventis exemplifies the high pharmaceutical interest in microRNAs and Regulus' leadership within that field," said Stanley T. Crooke, M.D., Ph.D., Isis Pharmaceuticals Chairman and CEO and member of the Board of Directors of Regulus. "Not only have we created the leading microRNA company, but we are also able to share early in its successes and reap the benefits of our innovation. We believe that this type of deal brings significant value to our shareholders and further validates the strategy behind the unique business model that we have developed at Isis."

Regulus entered into a global, strategic alliance with sanofi-aventis to discover, develop, and commercialize microRNA therapeutics. The alliance represents the largest microRNA partnership formed to date, valued at potentially over $750 million, and includes a $25 million upfront fee, a $10 million future equity investment subject to mutual agreement on company valuation, and annual research support for three years with the option to extend two additional years. In addition, Regulus is eligible to receive royalties on microRNA therapeutic products commercialized by sanofi-aventis. Sanofi-aventis will support 100% of the costs of clinical development and commercialization of each program. The alliance will initially focus on the therapeutic area of fibrosis. Regulus and sanofi-aventis will collaborate on up to four microRNA targets, including Regulus' lead fibrosis program targeting microRNA-21. 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. If exercised, this three-year option is worth up to an additional $50 million to Regulus. Alnylam and Isis are each eligible to receive 7.5% of all potential milestone payments, in addition to royalties on product sales.

Alnylam Pharmaceuticals and Isis Pharmaceuticals formed Regulus in 2007, with each company currently owning approximately 50% of the preferred stock.