InterfeRx^™ & Reagent Licenses

In addition to forming strategic alliances with major pharmaceutical and top-tier biotechnology companies, Alnylam is committed to enabling the broader biomedical industry with access to its IP by offering target-specific therapeutic licenses in areas outside Alnylam's strategic focus through the company's InterfeRx^™ program. Alnylam also offers non-therapeutic license agreements to life science reagent and service providers.

Driven by the strength of our leading IP estate, we believe that 50% of all clinical-stage RNAi therapeutics, and more than 75% of sales of RNAi products in the research reagent market are currently covered under our IP.

Alnylam's InterfeRx Licenses

Sylentis, S.A.

In November 2011, Alnylam granted Sylentis a non-exclusive option for a new target-specific InterfeRx license. This license would enable the discovery, development, and commercialization of a synthetic siRNA directed towards an undisclosed target for the treatment of glaucoma. The program is currently in a Phase I/II clinical trial. Upon exercise of this option, Alnylam would receive upfront and milestone payments, as well as royalties on sales of products covered by the licensing agreement.

Tekmira Pharmaceuticals Corp.

In March 2006, Alnylam and Tekmira entered into a license and research collaboration under which the two companies agreed to pursue the potential of liposomal formulations for the delivery of RNAi therapeutics.

In January 2007, Alnylam took a worldwide exclusive license to Tekmira's liposomal delivery formulation technology for the discovery, development, and commercialization of RNAi therapeutics, and the companies expanded their technology research and manufacturing alliance on lipid-based delivery technology. In addition, Tekmira received three InterfeRx^™ license options.

In June 2008, as part of the completed Tekmira-Protiva merger, Alnylam completed a new agreement expanding our access to key technology and intellectual property for the delivery of RNAi therapeutics with liposomal delivery technologies. Alnylam has exclusive license to Tekmira's rights to the Semple (U.S. Patent No. 6,858,225) and Wheeler (U.S. Patent Nos. 5,976,567 and 6,815,432) patents, which we believe are required for cationic liposomal delivery. As part of the merger, we also amended our existing agreement to include additional InterfeRx licenses for a total of seven license grants for targets subject to Alnylam review and third-party obligations. Further, Alnylam obtained the right to opt-in for 50/50 co-development and co-commercialization of Tekmira's RNAi cancer program targeting the gene polo-like kinase 1, or PLK1.

Calando Pharmaceuticals, Inc.

In August 2006, Alnylam granted Calando an InterfeRx license to discover, develop, and commercialize an RNAi therapeutic utilizing a synthetic siRNA, together exclusively with Calando's proprietary delivery technology, that is directed towards RRM2, a cancer target.

In July 2008, Alnylam granted Calando a second InterfeRx license for the HIF-2a cancer gene target. In this new license grant, Alnylam also obtained a right of first negotiation to license the Calando program for development and commercialization of this cancer program in the U.S. market.

Quark Pharmaceuticals, Inc.

In September 2006, Alnylam granted Quark InterfeRx licenses to discover, develop, and commercialize RNAi therapeutics targeting the p53 and RTP801 genes for certain diseases. Quark has filed investigational new drug (IND) applications for RNAi therapeutics for both targets, in the case of p53 for the treatment of renal failure, and in the case of RTP801 for the treatment of ocular diseases, specifically macular degeneration. Quark has formed a partnership with its RTP801 program with Pfizer for the RTP801 program, currently in Phase II clinical studies.

Benitec, Ltd.

In April 2005, Alnylam and Benitec formed a licensing agreement covering fundamental IP in the field of RNAi. Under the agreement, Alnylam will provide Benitec and its licensees an option to non-exclusively license Alnylam-controlled IP in the field of expressed RNAi for a specific number of targets. Expressed RNAi relates to targeted gene silencing that is mediated by short "hairpin" RNAs ("shRNAs") generated from DNA constructs introduced into cells. Benitec also provides Alnylam rights to non-exclusively license Benitec IP.

GeneCare Research Institute Co., Ltd.

In January 2005, Alnylam granted GeneCare, a Japanese biotechnology firm, an InterfeRx license through the InterfeRx^™ licensing program to discover, develop, and commercialize RNAi therapeutics directed against two DNA helicase genes associated with cancer. In addition, Alnylam retains the right to negotiate co-development and co-promotion arrangements for such products in the U.S. market.

Alnylam's Reagent Licenses

Alnylam also offers non-therapeutic license agreements to life science reagent and service providers, and has agreements with a variety of companies and institutions, including: