Isis Pharmaceuticals and Alnylam Pharmaceuticals, leaders in RNA-targeted therapeutics, announced they have formed a new agreement, extending their existing strategic partnership formed originally in 2004 to lead the development and commercialisation of RNA therapeutics. This new agreement includes a cross-licence of intellectual property (IP) on four disease targets, providing each company with exclusive RNA therapeutic licence rights for two programmes. 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.

“Isis and Alnylam lead the RNA-targeted therapeutics space and are innovators in understanding the science and developing the technologies to support RNA-targeted drug discovery. At Isis, we have dedicated ourselves to advancing the core understanding of RNA-based drugs, continually evolving and optimising our technology and creating an extensive IP position. We believe that providing access to our IP supports our business strategy of generating revenue from our partners while focussing our efforts on our internal programmes and promising pipeline of maturing products,” said Stanley T. Crooke, MD, chief executive officer of Isis Pharmaceuticals. “Since we began our collaborative efforts in 2004, Alnylam has been a great partner and has made excellent progress in its RNAi therapeutic programmes. This expansion of our licence 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.”

“We and Isis have each benefited enormously from our long-standing collaborative efforts over the last decade. We believe that our collaboration has enabled both companies to succeed as leaders in the development and commercialisation of RNA therapeutics,” said John Maraganore, chief executive officer of Alnylam. “This extended agreement adds a new feature, enabling further advancement of specific therapeutic programmes 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.”

Per the terms of the new agreement, Alnylam and Isis are forming an IP cross-license with reciprocal economic terms on four therapeutic targets, where each company obtains exclusive licence rights to two therapeutic programmes. Alnylam is granting Isis an exclusive, royalty-bearing licence 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 is currently developing an investigational antisense drug toward Factor XI for the prevention of thrombosis. ISIS-FXIRx is currently in phase 2 clinical development. Isis is also currently developing an investigational antisense drug targeting Apo(a) to treat cardiovascular disease. ISIS-APO(a)Rx is currently in a phase 2 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 is currently developing an investigational RNAi therapeutic targeting AT for the treatment of haemophilia and rare bleeding disorders. ALN-AT3 is currently in a phase 1 clinical trial enrolling hemophilia subjects. Alnylam is also 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 1 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 licence to new platform technology arising from May 2014 through April 2019 for double-stranded RNAi therapeutics. This IP cross-licence 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 programmes and future milestone and royalty payments from Alnylam for programmes 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 commercialise single-stranded antisense therapeutics, ssRNAi therapeutics and to research double-stranded RNAi compounds. Isis also received a license to develop and commercialise double-stranded RNAi drugs targeting a limited number of therapeutic targets on a non-exclusive basis. Such licences for RNAi therapeutics were granted by Alnylam in exchange for option fees, and future milestone and royalty payments from Isis for RNAi programmes that incorporate certain Alnylam IP.