Isis Pharmaceuticals, based in Carlsbad, Calif., and Alnylam Pharmaceuticals, based in Cambridge, Mass., have formed a new agreement, extending their existing strategic partnership—formed originally in 2004—to lead the development and commercialization of RNA therapeutics.

The new agreement includes a cross-license of intellectual property (IP) on four disease targets, providing each company with exclusive RNA therapeutic license rights for two programs. The agreement also includes a non-exclusive technology IP cross-license, providing each company rights to certain of each other's technology advances for RNA therapeutics through April 2019.

Stanley T. Crooke, M.D., Ph.D., CEO of Isis Pharmaceuticals, said, "Since we began our collaborative efforts in 2004, Alnylam has been a great partner and has made excellent progress in its RNAi therapeutic programs. This expansion of our license agreement will enable both companies to enhance drug development efforts in particular disease areas while also sharing IP access. We look forward to continuing to innovate in the field of RNA-targeted therapeutics and advance our maturing pipeline of drugs to patients who are in need."

John Maraganore, Ph.D., CEO of Alnylam, said, "This extended agreement adds a new feature, enabling further advancement of specific therapeutic programs on an exclusive basis, while allowing for the continued sharing of IP on technology. Based on the benefit that we believe innovative RNA therapeutics may bring to patients across a broad range of diseases, we look forward to continued success for both companies."

Alnylam and Isis are forming an IP cross-license with reciprocal economic terms on four therapeutic targets, where each company obtains exclusive license rights to two therapeutic programs. Alnylam is granting Isis an exclusive, royalty-bearing license to its chemistry, RNA-targeting mechanism and target-specific IP for oligonucleotide therapeutics against two targets: Factor XI and apolipoprotein (a)—or Apo(a). Isis currently is developing an investigational antisense drug toward Factor XI for the prevention of thrombosis. ISIS-FXIRx currently is in phase II clinical development.

Isis also currently is developing an investigational antisense drug targeting Apo(a) to treat cardiovascular disease. ISIS-APO(a)Rx currently is in a phase II clinical trial. In exchange, Isis is granting Alnylam an exclusive, royalty-bearing license to its chemistry, RNA-targeting mechanism and target-specific IP for oligonucleotide therapeutics against two targets: antithrombin (AT) and aminolevulinic acid synthase-1 (ALAS-1).

Alnylam currently is developing an investigational RNAi therapeutic targeting AT for the treatment of hemophilia and rare bleeding disorders. ALN-AT3 is currently in a phase I clinical trial enrolling hemophilia subjects. Alnylam also is currently developing an investigational RNAi therapeutic targeting ALAS-1 for the treatment of hepatic porphyrias, including acute intermittent porphyria (AIP); Alnylam has just filed a clinical trial application (CTA) to begin a phase I clinical trial with ALN-AS1.

The new agreement also includes an extended technology IP cross-license. Specifically, Alnylam is granting Isis a royalty-bearing, non-exclusive license to new platform technology arising from May 2014 through April 2019 for single-stranded antisense therapeutics. In turn, Isis is granting Alnylam a royalty-bearing, non-exclusive license to new platform technology arising from May 2014 through April 2019 for double-stranded RNAi therapeutics. This IP cross-license includes chemistry, motif and mechanism patents, but excludes patent claims on formulations, manufacturing, and specific targets.

Under the 2004 agreement, Isis licensed to Alnylam its patent estate related to antisense mechanisms and oligonucleotide chemistry for double stranded RNAi drugs in exchange for a technology access fee, participation in fees for Alnylam's partnering programs and future milestone and royalty payments from Alnylam for programs that incorporate Isis' IP. In turn, Alnylam non-exclusively licensed to Isis Alnylam's patent estate relating to antisense motifs and mechanisms and oligonucleotide chemistry to research, develop and commercialize single-stranded antisense therapeutics, ssRNAi therapeutics and to research double-stranded RNAi compounds. Isis also received a license to develop and commercialize double-stranded RNAi drugs targeting a limited number of therapeutic targets on a non-exclusive basis. Such licenses for RNAi therapeutics were granted by Alnylam in exchange for option fees, and future milestone and royalty payments from Isis for RNAi programs that incorporate certain Alnylam IP.