2
Our flagship product, KYNAMRO (mipomersen sodium) injection, is on themarket in theUnitedStates for patientswith
homozygous familial hypercholesterolemia, orHoFH. PatientswithHoFH are at high cardiovascular risk and cannot reduce their
low-density lipoprotein cholesterol, or LDL-C, sufficientlywith currently available lipid-lowering therapies. In January2013, the
U.S. Food andDrugAdministration, or FDA, approved themarketing application forKYNAMRO for patientswithHoFH.
Genzyme, a Sanofi Company, has alsoobtainedmarketing approval inother countries, includingMexico, Argentina andSouthKorea,
and is pursuingmarketing approval inmultiple additionalmarkets. Genzyme has substantial expertise in successfullymarketing drugs
in theUnitedStates and internationally for severe and rare diseases and is leveraging this expertise to reachpatientswithHoFH, who
are indesperate needof new treatment options. Genzyme is concentratingmarketing and sales efforts on lipid specialists, and
physicianswho referHoFH patients to these specialists, to reach patientswithHoFH in theUnitedStates andother countries.
We have created amature andbroadpipeline that goeswell beyondKYNAMRO.We have a pipeline of 31drugs in
development that represents the potential for significant commercial opportunities inmany therapeutic areas. We believe five drugs in
our pipeline couldbe in registration formarketing approval or on themarket by2018. One of these drugs, ISIS-APOCIII
Rx
, is a
triglyceride-loweringdrugwe designed to treat patientswith severelyhigh triglyceride levels, includingpatientswith a severe and rare
genetic condition called familial chylomicronemia syndrome, or FCS. We have completed a broadPhase 2programdemonstrating
that ISIS-APOCIII
Rx
significantly reduced triglyceride and apolipoproteinC-III, or apoC-III, levels inpatientswhen evaluated as a
single agent and in combinationwith fibrates. We plan to initiate aPhase 3program in 2014 to support a potential 2016 regulatory
filing formarketing approval for ISIS-APOCIII
Rx
. In addition to ISIS-APOCIII
Rx
, we have several drugs in late-stage development
thatwe believe represent significant near-term commercial opportunities, such as ISIS-TTR
Rx
and ISIS-SMN
Rx
. We designed these
drugs to treat patientswith severe and rarediseases, such as transthyretin amyloidosis, or TTR, and spinalmuscular atrophy, or SMA,
andwhohave very limited therapeutic options. Because of the significant unmetmedical need and the severity of these diseases, new
therapeutic approaches couldwarrant an acceleratedpath tomarket. ISIS-TTR
Rx
is already inPhase 3development, andwe plan to
initiate a Phase 3program for ISIS-SMN
Rx
midyear in2014. We believe that bothof these drugs have the potential to reach the
market in the next several years. We alsohave numerous drugs inour pipeline advancing inPhase 2 clinical development. Eachof
these drugs, including ISIS-GCCR
Rx
, ISIS-GCGR
Rx
, ISIS-FXI
Rx
and ISIS-PTP1B
Rx
, could represent significant near andmid-term
licensingopportunitieswith the potential for Phase 2datawithin the next nine to15months.
Tomaximize the value of our drugs and technologies, we have amultifaceted partnering strategy. Our partnering strategy
provides us the flexibility to license eachof our drugs at anoptimal time tomaximize the near- and long-termvalue for eachdrug. In
thisway, we can expandour andour partners’ pipelineswith antisense drugs thatwe design to address significantmedical needswhile
remaining small and focused. We form traditional partnering alliances that enable us todiscover and conduct earlydevelopment of
newdrugs, outlicense our drugs topartners, such asGenzyme, andbuild a base of license fees,milestone payments, profit share and
royalty income. We also formpreferredpartner transactions that provide uswith a vestedpartner, such asAstraZeneca, Biogen Idec,
GlaxoSmithKline, orGSK, andRoche, early in the development of a drug. Typically, the drugswe partner early indevelopment are
in therapeutic areas of high risk, like severe neurological diseases, or in areaswherePhase 2 resultswould likelynot provide a
significant increase invalue, like cancer. These preferredpartner transactions allowus todevelop select drugs that could have
significant commercial potentialwith a knowledgeable and committed partnerwith the financial resources to fund later-stage clinical
studies and expertise to complement our owndevelopment efforts. We benefit from this strategybecause it allows us to expand and
broadenour drugdiscovery efforts tonewdisease targets. For example, throughour broad strategic partnershipwithBiogen Idec, we
are capitalizing onBiogen Idec’s extensive resources and expertise inneurological diseases to create a franchise of novel treatments
for neurological disorders. Similar to our other partnerships, withour preferredpartner transactionswe benefit financially from
upfront payments,milestone payments, licensing fees and royalties.
We alsoworkwith a consortiumof smaller companies that can exploit our drugs and technology. We call these smaller
companies our satellite companies. We benefit from the disease-specific expertise of our satellite companypartners, who are
advancingdrugs inour pipeline in areas that are outside of our core focus.We alsomaintain our broad ribonucleic acid, or RNA,
technology leadership through collaborationswith satellite companies. All of these different types of relationships are part of our
partnership strategy, which allowus tomaximize the value of our assets,minimize the development risks of a broadpipeline of novel
newdrugs, andprovide uswith significant reliable near-term revenue.
The broad applicability of our drugdiscovery technology and the clinical successes of the drugs in our pipeline continue to
create newpartneringopportunities. Since January2012, we have initiated sixnew partnerships that involve antisense drugs for the
treatment of neurological diseases or cancer, including four strategic allianceswithBiogen Idec todiscover anddevelop antisense
drugs for the treatment of neurologic diseases, a strategic alliancewithAstraZeneca todiscover anddevelop antisense drugs to treat
cancer and a strategic alliancewithRoche todiscover anddevelop antisense drugs to treatHuntington’s disease. We have received
more than$230million inupfront payments andhave the potential to earnnearly$6billion in futuremilestone payments and
licensing fees from these partnerships. In addition, we have the potential to earnnearly$3billion in futuremilestone payments and
licensing fees fromour other partneredprograms.We alsohave the potential to share in the future commercial success of our
inventions anddrugs resulting fromour partnerships through earnout, profit sharing, or royalty arrangements. Since 2007, our
partnerships have generated an aggregate ofmore than$1.1billion inpayments fromupfront and licensing fees, equitypurchase
payments, milestone payments and research anddevelopment funding.
