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As an innovator inRNA-targetingdrugdiscovery anddevelopment, we design and execute our patent strategy toprovide us
with extensive protection for our drugs andour technology. Withour ongoing research anddevelopment, we continue to add toour
substantial patent estate. Our patents not onlyprotect our key assets—our technology and our drugs—they also form the basis for
lucrative licensing andpartnering arrangements. Todate,we have generated $410million fromour intellectual property sale and
licensingprogram that helps support our internal drugdiscovery anddevelopment programs.
Below is a list of some of our key accomplishments for 2013 and early2014.
DrugDevelopmentHighlights
We andGenzymewere successful inbringingKYNAMRO to themarket in theUnitedStates,Mexico, SouthKorea and
Argentina for patientswithhomozygous FH. These patients are at high cardiovascular risk andmaynot be able to reduce
their LDL-C sufficientlywith currently available lipid-lowering therapies.
We received a $25millionmilestone payment fromGenzyme related to themarketing approval ofKYNAMROby
theFDA.
Genzyme notes trends toward increases in qualifiedphysicians, prescriptions andpatients ondrug, withoptimism
that these trendswill continue in 2014. Genzyme is supporting the commercial success ofKYNAMROby:
Qualifyinghundreds of treatingphysicians under theKYNAMRORiskEvaluationMitigationStrategy, or
REMS, program to prescribeKYNAMRO.
Completing aPhase 1KYNAMRO study in Japan to support ongoingdiscussionswith Japan regulatory
authorities regarding the next steps indevelopment.
ExpandingKYNAMRO commercialmarkets byobtainingmarketing approval forKYNAMRO in the
UnitedStates,Mexico, Argentina andSouthKorea andpursuing regulatory approvals inother countries.
Genzyme has stated that it has the infrastructure in place to successfully bringKYNAMRO to patients in
these newmarkets.
We reported five sets of positive Phase 2data demonstrating that ISIS-APOCIII
Rx
can effectively lower triglyceride levels in
patientswithhigh to extremelyhigh triglyceride levels and canwork as effectively as a single agent or in combinationwith
fibrates. In addition, we reported that treatedpatientswith type 2diabetes experienced improvements inglucose controlwith
trends toward enhanced insulin sensitivity.
We publisheddata in the journal CirculationResearchdemonstrating that antisense inhibition ofApoC-III produced
significant reductions ofApoC-III and triglycerides inhumans andother animal species.
We receivedEuropeanOrphanDrugDesignation for ISIS-APOCIII
Rx
for the treatment of patientswith familial
chylomicronemia syndrome.
We reportedpositive clinical data in children and infantswithSMAdemonstrating that ISIS-SMN
Rx
iswell toleratedwith
increases inmuscle function scores observed in the type 2/3 children.
We presented interim results frombothmultiple-dosePhase 2 studies in infants and childrenwithSMA
demonstrating that ISIS-SMN
Rx
continues tobewell tolerated at all doses. In the infant study, all four infants from
the 6mg cohort have been in the study for over sixmonths and all have received three doses of ISIS-SMN
Rx
, and
one infant has received a fourth dose of ISIS-SMN
Rx
. In the childhoodonset study, we reporteddose- and time-
dependent increases inmuscle function scores in children treatedwithmultiple-doses of ISIS-SMN
Rx
. In children
treatedwith9mg of ISIS-SMN
Rx
, we reported an average increase inmuscle function score of 3.7points.
We reported results from an assay thatmeasures SMN protein levels in the cerebral spinal fluid. We observeddose-
dependent increases inSMNprotein levels in children treatedwith ISIS-SMN
Rx
fromboth the single- andmultiple-
dose studies.
Dr. KathySwoboda presented followupdata from a single-dose open-label Phase 1 studyof ISIS-SMN
Rx
in
childrenwithSMA at the International Congress of theWorldMuscleSociety. In this study, data suggest that
children from the twohighest doses continued to show increases inmuscle function scores up to14months after a
single injectionof ISIS-SMN
Rx
.
Dr. ClaudiaChiriboga reportedPhase 1data on ISIS-SMN
Rx
at theAmericanAcademy ofNeurology. In this open-
label study conducted in a small population, ISIS-SMN
Rx
waswell tolerated in childrenwithSMA and increases in
muscle function scoreswere observed in a number of these children.
We received a positive opiniononEuropeanOrphanDrugDesignation in theEU for ISIS-TTR
Rx
for the treatment of patients
withTTR amyloidosis.
We andour partners reportedpositive data from six drugs includingmultiple results fromPhase 2 studies of ISIS-SMN
Rx
and
ISIS-APOCIII
Rx
, andwe added five drugs toour pipeline.
We andour partners initiated clinical studies on tendrugs.
