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CorporateHighlights
We formed a broad strategic alliancewithBiogen Idec to discover anddevelop antisense drugs to treat neurological
disorders, which combinesBiogen Idec’s expertise inneurologywithour leadership in antisense technology.
We received a $100millionupfront payment fromBiogen Idec.
We are eligible to receive substantialmilestone payments, license fees and royalty payments for all treatments
developed through this collaboration.
We formed a new alliancewithRoche todiscover anddevelop antisense drugs to treatHuntington’s disease.
We received a $30millionupfront payment and are eligible to receive up to $362million in a license fee and
milestone payments.
In addition, we are eligible to receive up to $136.5million inmilestone payments for each additional drug
successfully developed plus up to $50million in commercialmilestones if a drug usingRoche’s proprietary brain
shuttle technology is successfully commercialized.
We are also eligible to receive tiered royalties on sales of drugs arising from the alliance.
We received$6million fromAstraZeneca related to the continuation of the research collaborationbetweenAstraZeneca and
us todiscover anddevelopnovel antisense drugs to treat cancer.
In2014 todate, we have earnedmore than$16million inpayments fromour partners as our andour partners’ drugs in
development continue tomature.
We successfully completed a public offering of common stock raising$173.3million in net proceeds. We are using the
proceeds from this offering to support thePhase 3development of ISIS-APOCIII
Rx
, retain other drugs longer indevelopment
and advance the rest of our pipeline.
We addedMr. BreauxCastleman and JosephLoscalzo,M.D., Ph.D. toourBoardofDirectors.
Our founder, CEO and chairmanof the boardof directors, StanleyT. Crooke, Ph.D.,M.D., was awarded the 2013Director of
theYearAward for Companies inTransitionby theCorporateDirectors Forum and the 2013DistinguishedScientistAward
by theSanDiego sectionof theAmericanChemical Society.
DrugDiscoveryandDevelopment
Introduction toDrugDiscovery
Proteins are essentialworkingmolecules in a cell. Almost all human diseases result from inappropriate proteinproductionor
improper protein activity. Scientists use traditional drugdiscoverymethods todesigndrugs to interactwith the proteins in the body
that are supportingor causing a disease.Antisense drugs are different from traditional smallmolecule drugs because antisense drugs
interrupt the productionof disease-causingproteins by targetingRNAs. RNAs are naturallyoccurringmolecules in the body that
provide the information the cell needs toproduce proteins.Whenour antisense drugs bind to the specificRNAs of a particular gene,
theywill ultimately inhibit or alter the expressionof the protein encoded in the target gene.
OurDevelopment Projects
We are the leader in the discovery anddevelopment of an exciting class of RNA-targeted drugs called antisense drugs.With
our proprietarydrugdiscoveryplatformwe can rapidly identifydrugs, providing awealth of potential targets to treat a broad range of
diseases.We focus our efforts in therapeutic areaswhere our drugswillworkbest, efficiently screeningmany targets inparallel and
carefully selecting the best drugs.Whenwe combine this efficiencywithour rational approach to selectingdisease targets, we can
build a large anddiverse portfolioof drugs designed to treat a varietyof health conditions, with an emphasis on cardiovascular,
metabolic, severe and rare diseases, includingneurological disorders, and cancer. We andour partners are developing antisense drugs
for systemic, intrathecal and local delivery.We expect to continue to addnew drugs toour pipeline, creatingopportunities for future
licensing transactions andbuilding a broadproprietaryportfolioof drugs applicable tomanydisease targets.We also continue to
improve our scientific understandingof our drugs, includinghowour drugs impact the biological processes of the diseaseswe target.
Withour expertise in discovering and characterizing novel antisense inhibitors, our scientists canoptimize the properties of
our antisense drugs for usewith particular targets. Our scientists havemade significant advances in chemistries, whichwe call our
second-generation antisense drugs. Second-generation antisense drugs have increasedpotency, stability, oral bioavailability and an
improved side effect profile. Our scientists have further improveduponour second-generation chemistrywithour generation2.5
chemistry, an advancement that we believewill further increase the potencyof our drugs andmake oral administration commercially
feasible.We currentlyhave three generation2.5drugs indevelopment, ISIS-STAT3
Rx
, ISIS-AR
Rx
and ISIS-FVII
Rx
, andwe expect that
some of our future drugswill also incorporate our generation2.5 chemistry.
