building a broad proprietary portfolio of drugs applicable to many disease targets and creating opportunities to
generate substantial revenue. We also continue to improve our scientific understanding of our drugs, including
how our drugs impact the biological processes of the diseases we target.
With our expertise in discovering and characterizing novel antisense inhibitors, our scientists can optimize
the properties of our antisense drugs for use with particular targets. Our scientists have made significant advances
in chemistries, which we call our second-generation antisense drugs. Second-generation antisense drugs have
increased potency, stability, oral bioavailability and an improved side effect profile. Our scientists have further
improved upon our second-generation chemistry with our generation 2.5 chemistry; an advancement that further
increases the potency of our drugs and could make oral administration commercially feasible. We currently have
four generation 2.5 drugs in development, ISIS-AR-2.5
Rx
, ISIS-DMPK-2.5
Rx
, ISIS-RHO-2.5
Rx
and
ISIS-STAT3-2.5
Rx
, and we expect that some of our future drugs will also incorporate our generation 2.5
chemistry. In addition to improving the chemical foundation of our drugs, we have also created ligand-conjugated
antisense, or LICA, technology, which we designed to enhance the delivery of our drugs to particular tissues. We
believe that our LICA technology could further enhance the potency of our drugs. For example, our LICA
technology directed toward liver targets produced a ten-fold increase in potency in preclinical studies in both our
second-generation and our generation 2.5 drugs. We currently have eight second generation-LICAdrugs in our
pipeline, ISIS-AGT-L
Rx
, ISIS-ANGPTL3-L
Rx
, ISIS-APO(a)-L
Rx
, ISIS-APOCIII-L
Rx
, ISIS-GHR-L
Rx
,
ISIS-GSK4-L
Rx
, ISIS-GSK6-L
Rx
, and ISIS-TMPRSS6-L
Rx
, all of which we designed to inhibit targets in the
liver. We expect we can also enhance some of our future drugs, including our generation 2.5 drugs, with our
LICA technology.
Our scientists have utilized our chemistry advancements to expand the therapeutic and commercial
opportunities of our pipeline. These advancements, along with the manufacturing and analytical processes that are
the same for all of our drugs, shorten our timeline from initial concept to the first human dose when compared to
small molecule drugs.
The following table lists our commercialized products and each of our and our partners’ drug development
projects, their targets, disease indications and the development status of each. Typically, we identify our drugs by
the target, such as ISIS-APOCIII
Rx
or ISIS-SMN
Rx
. Unless indicated otherwise, the majority of the drugs in our
pipeline are second generation antisense drugs. For our generation 2.5 drugs, we differentiate these drugs by
adding a 2.5 notation at the end of the drug name. For our LICAdrugs, we differentiate by adding an L at the
end of the drug name. We also plan to add generation 2.5 drugs that incorporate our LICA technology. We will
identify these drugs by the addition of both the 2.5 and L into the drug name. For some of our partnered drugs,
we refer to a drug by the partner’s own compound number, such as ATL1103 or RG-101. As the drugs in our
pipeline advance in clinical development, we will adopt nonproprietary names given to each drug from the
United States Adopted Names Council. For example, mipomersen is a nonproprietary name that we obtained for
ISIS 301012 in 2007. Once we or our partners establish a brand name, like KYNAMRO for mipomersen, we
will adopt the brand name.
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