Strategic Alliances

Our partnering strategy has allowed us to build a development pipeline of 38 drugs, to create a broad base of potential license fees, milestone payments, royalties, profit sharing and earn out payments and to control our drug development expenses. In this way, we remain a focused and efficient research and development organization that can continue to discover new drugs and expand our and our partners’ pipelines. In 2014, we began the next phase of our business strategy by forming Akcea Therapeutics, Inc., to develop and commercialize the drugs from our lipid franchise.

Through the efficiency of our drug discovery platform we can develop drugs to almost any gene target. We concentrate on developing antisense drugs in our core therapeutic areas with an emphasis on cardiovascular, metabolic, severe and rare diseases, including neurological disorders, and cancer. Our partnering strategy provides us the flexibility to license each of our drugs at what we believe is the optimal time to maximize the near- and long-term value of our drugs. Using this strategy, we can expand our and our partners’ pipelines with antisense drugs that we design to address significant medical needs while remaining small and focused. Just as we have advanced and matured our technology and pipeline, we have evolved our partnering strategy in order to maximize the value of each of our assets. We employ a multifaceted partnering strategy by which we partner certain research programs or drugs early, other drugs after we have completed proof-of-concept, and still other drugs after we have advanced them into later stages of development.

We also form preferred partner transactions for certain therapeutic programs for which a partner brings expertise that we do not have in house and that could provide us with an increased likelihood of successfully bringing the program to market. Typically these collaborations are focused on drugs in therapeutic areas of high risk, like severe neurological diseases, or in areas in which Phase 2 results would likely not provide a significant increase in value, like cancer. For these programs, we partner early, occasionally prior to clinical development. In this way, we have a vested partner, such as with AstraZeneca, Biogen, GSK, Janssen Pharmaceuticals and Roche, early in the development of a drug. Typically, these preferred partner transactions allow us to develop select drugs that could have significant commercial potential with a knowledgeable and committed partner with the financial resources to fund later-stage clinical studies and expertise to complement our own development efforts. As in our other partnerships, we benefit financially from upfront payments, milestone payments, licensing fees and royalties.

We form traditional partnering alliances that enable us to discover and conduct early development for drugs in our pipeline that we feel could address large patient populations or multiple indications. For these drugs, late-stage development is often costly and requires complex Phase 3 development programs. In this strategy, we are responsible for clinical development to proof-of-concept, at which time we outlicense our drugs to partners, such as when we licensed ISIS-FXIRx to Bayer HealthCare to develop and commercialize for the prevention of thrombosis.  This transaction maximizes value of the ISIS-FXIRx program and provides us with significant potential to participate in commercial success of ISIS-FXIRx.

And finally, we have evolved our business strategy to retain greater control over the development of our drugs and retain a larger portion of the commercial revenue.  For example, in late 2014, we established a wholly owned subsidiary, Akcea Therapeutics, Inc., to develop and commercialize the drugs from our lipid franchise. Akcea is focused on developing volanesorsen (ISIS-APOCIIIRx), ISIS-APO(a)Rx and ISIS-ANGPTL3Rx, plus more potent follow on drugs for these programs. We hired a senior business leader with commercialization expertise in severe and rare and cardiovascular diseases to lead Akcea and to maximize the value of our lipid franchise assets. Moving our lipid assets into a company that we own and control keeps our core focus at Isis on innovation and allows us to maintain control over and retain more value from our lipid drugs.

We also work with a consortium of companies that can exploit our drugs and technologies outside our primary areas of focus. We call these companies satellite companies. We benefit from the disease-specific expertise of our satellite company drug development partners, who are advancing drugs in our pipeline in areas that are outside of our core focus. Through this strategy we can expand the therapeutic range of antisense drugs into diseases that need new and innovative treatment options. We also benefit from our ownership in these satellite companies.  For example, Regulus is a satellite company partner that we co-founded to discover and develop antisense drugs targeting microRNAs. In 2014, we sold a portion of our shares in Regulus for more than $20 million of cash, and we remain a significant shareholder in the company.

In addition to our satellite company drug development partners, we form satellite company partnerships focused on developing and advancing certain RNA-targeting therapeutic technologies. These partnerships take advantage of our dominant RNA-targeting intellectual property estate, and leverage our investments in our core technologies. These collaborations typically involve a cross-license between us and our partner and allow us to participate in newly emerging approaches to RNA-targeting therapeutics and augment our active programs in these areas.

The broad applicability of our drug discovery technology and the clinical successes of the drugs in our pipeline continue to create new partnering opportunities. Since January 2012, we have initiated seven new partnerships that involve antisense drugs for the treatment of various disorders, including neurological diseases, autoimmune disorders of the GI tract and cancer. We formed a broad alliance with Janssen to discover and develop antisense drugs to treat autoimmune disorders in the GI tract, four strategic alliances with Biogen Idec to discover and develop antisense drugs to treat neurologic diseases, a strategic alliance with AstraZeneca to discover and develop antisense drugs to treat cancer and a strategic alliance with Roche to discover and develop antisense drugs to treat Huntington’s disease. Additionally, we and our partner, GSK, are developing five drugs, including ISIS-TTRRx, which is in Phase 3 development.  In 2015, we also licensed ISIS-FXIRx to Bayer HealthCare, a leader in developing and commercializing antithrombotics, to develop and commercialize ISIS-FXIRx for the prevention of thrombosis.  We have the potential to earn significant revenue from these partnerships and our other partnered programs. Since 2007 we have received more than $1.4 billion in cash from upfront and licensing fees, equity purchase payments, milestone payments and research and development funding from our partnerships. We have the potential to earn over $8.5 billion in future milestone payments and licensing fees from all of our partnerships. We also have the potential to share in the future commercial success of our inventions and drugs resulting from our partnerships through earn out, profit sharing, or royalty arrangements.

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