PART I
Item1. Business
Overview
We are the leading company in RNA-targeted drug discovery and development, exploiting a proven novel
drug discovery platformwe created to generate a broad pipeline of first-in-class or best-in-class antisense drugs.
The efficiency and broad applicability of our drug discovery platform allows us to discover and develop
antisense drugs to treat a wide range of diseases with an emphasis on cardiovascular, metabolic, severe and rare
diseases, including neurological disorders, and cancer. The efficiency of our drug discovery technology allows us
to employ a unique business strategy designed to maximize the value of our drugs and technology while
maintaining an effective cost structure that limits our cash needs. Our business strategy is supported by our
platform technology, our robust pipeline of drugs and our multifaceted partnering strategy, which have enabled us
to focus on doing what we do best – to discover and develop novel antisense drugs.
We have created a mature and broad pipeline of 38 drugs in development that represents the potential for
significant commercial opportunities in many therapeutic areas. We have a number of drugs in later-stage
development that we believe represent significant near-term commercial opportunities. ISIS-APOCIII
Rx
is a drug
we designed to treat patients with severely high triglyceride levels, including patients with a severe and rare
genetic condition called familial chylomicronemia syndrome, or FCS and patients with partial lipodystrophy,
another severe and rare genetic condition. We have completed a broad Phase 2 program in which patients treated
with ISIS-APOCIII
Rx
experienced significantly reduced triglyceride and apolipoprotein C-III, or apoC-III, levels
when evaluated as a single agent and in combination with fibrates. We initiated a Phase 3 study in patients with
FCS in the third quarter of 2014, with data expected in 2016/2017, that is designed to support a regulatory filing
for marketing approval for ISIS-APOCIII
Rx
. In addition to ISIS-APOCIII
Rx
, we are also evaluating ISIS-TTR
Rx
and ISIS-SMN
Rx
in Phase 3 studies. We designed these drugs to treat patients with severe and rare diseases, such
as transthyretin amyloidosis, or TTR, and spinal muscular atrophy, or SMA, who have very limited therapeutic
options. The significant unmet medical need and the severity of these diseases could warrant a rapid path to
market. We believe all three of these drugs have the potential to reach the market in the next several years. We
also have numerous drugs in our pipeline advancing in mid-stage clinical development that could represent
significant near and mid-term licensing opportunities. Through February 2015, we and our partners reported
clinical data from 20 studies, of which 17 were positive.
Our novel lipid-lowering product, KYNAMRO (mipomersen sodium) injection, is on the market in the
United States for patients with homozygous familial hypercholesterolemia, or HoFH. Patients with HoFH are at
high cardiovascular risk and cannot reduce their low-density lipoprotein cholesterol, or LDL-C, sufficiently with
currently available lipid-lowering therapies. In January 2013, the U.S. Food and DrugAdministration, or FDA,
approved the marketing application for KYNAMRO for patients with HoFH. Genzyme, a Sanofi Company, has
also obtained marketing approval in other countries, includingMexico, Argentina, South Korea and Peru, and is
pursuing marketing approval in multiple additional markets. Genzyme is evaluating KYNAMRO in a late-stage
clinical study, FOCUS FH, in patients with severe heterozygous familial hypercholesterolemia, or HeFH, and
they plan to report data from this study in 2015.
The efficiency and broad utility of our drug discovery technology supports the continued growth of our
pipeline of antisense drugs. To maximize the value of our drugs and technologies, we have a multifaceted
partnering strategy. 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. In this way, we can expand
our and our partners’ pipelines with antisense drugs that we design to address significant medical needs while
remaining small and focused. Most recently, we established a wholly owned subsidiary, Akcea Therapeutics, Inc.,
to develop and commercialize the drugs from our lipid franchise. Akcea will focus on the development and
commercialization of ISIS-APOCIII
Rx
, ISIS-APO(a)
Rx
and ISIS-ANGPTL3
Rx
, as well as more potent follow on
drugs for these programs. To leadAkcea, we hired a senior business leader with commercialization expertise in
severe and rare and cardiovascular diseases to maximize the value of our lipid franchise assets. Moving our lipid
drugs into a company that we own and control ensures that our core focus at Isis remains on innovation while
allowing us to maintain control over and retain more value from our lipid drugs.
Another component of our partnering strategy is to form traditional partnering alliances that enable us to
discover and conduct early development of new drugs, outlicense our drugs to partners, such as when we
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