18
Inpreclinical studies, ISIS-AR
Rx
demonstrated antitumor activity in animalmodels of prostate cancer, including amodel
resistant to enzalutamide, a smallmolecule antagonist oftenused in patientswith castration-resistant prostate cancer. AstraZeneca
plans to initiate aPhase 1/2 study for ISIS-AR
Rx
inpatientswithAR-related cancers in 2014.
OtherDrugs inDevelopment
The broad applicabilityof our antisense technology allows us to create promising drugs, such as the ocular and antiviral
drugs under our preferredpartner collaborationwithGSK, in a varietyof disease areas. We have successfullydevelopednovel drugs
designed to treatmanydifferent diseases. In therapeutic areas that are outside of our core areas of development, we have licensedour
drugs tohighly focused satellite companies that have the specific expertise and resources to continue developing the drugs. Together
withour partnerswe continue to advance drugs in clinical development that are outside of our core therapeutic areas.
Plazomicin
—Plazomicin, formerlyACHN-490, is a next-generation aminoglycoside drug thatAchaogen, Inc. is developing
for the treatment ofmulti-drug resistant gram-negative bacterial infections. Aminoglycosides are a groupof antibiotics that inhibit
bacterial protein synthesis and that clinicians use to treat serious bacterial infections. Achaogendiscoveredplazomicin basedon
technology licensed fromus.
Plazomicin has displayedbroad-spectrum activity in animals againstmulti-drug resistant gram-negative bacteria that cause
systemic infections, includingE. coli, and againstmethicillin-resistant staphylococcus aureus, orMRSA. Inpreclinical studies,
plazomicin demonstrated an acceptable safetyprofile and the potential for once-dailydosing. Achaogenhas completed a Phase 1
studyof plazomicin in healthyvolunteers and aPhase 2 study. In thePhase 2 study, Achaogen evaluatedplazomicin compared to
levofloxacin for the treatment of complicated urinary tract infections and acute kidney infections in adults. In this study, patients
treatedwithplazomicin tolerated the drugwell andpatients demonstrated favorable activity of plazomicin as compared to
levofloxacin.
In 2014, Achaogenplans to initiate a Phase 3 study evaluatingplazomicin inpatientswith seriousmulti-drug resistant, or
MDR, gram-negative bacterial infections. Achaogen announced that it had reached agreement with theFDA to conduct the study
under aSPA. Achaogen reported that thePhase 3 study is designed as a superiority study to evaluate the efficacy and safety of
plazomicin comparedwith colistin inpatientswithbloodstream infections andnosocomial pneumonia causedby a class ofMDR
bacteria known as carbapenem-resistant enterobacteriaceae.
EXC001
—EXC001 is an antisense drug that targets connective tissue growth factor, orCTGF, a growth factor that is over-
expressed indamaged skin or tissue following a traumatic event.We co-discoveredEXC 001withExcaliardPharmaceuticals, Inc.
and exclusively licensed it toExcaliard for the local treatment of fibrotic diseases, including scarring. Fibrosis represents a significant
and expanding area of unmetmedical needwhere antisense drugs couldoffer a unique advantage as anti-fibrotic agents. In
November 2011, Pfizer Inc. acquiredExcaliard. Pfizer continues to evaluateEXC001 in aPhase 2programdesigned to provide
information, including the optimizationof the dose, for the designof thePhase 3program for EXC001.
iCo-007
—
iCo-007 is an antisense drugwe designed to reduce c-Raf kinase. In preclinical studies, clinicians associated
antisense inhibition of c-Raf kinasewith a reduction in the formation and leakage of newbloodvessels in the eye, suggesting
inhibiting c-Raf kinase canhelp patientswithdiabeticmacular edema and diabetic retinopathy. Diabetic retinopathy is one of the
leading causes of blindness inpeople in theUnitedStates, and a highpercentage of type 1diabetics have evidence of retinopathyby
age 20. Additionally, up to21percent of peoplewith type 2diabetes have retinopathy at the time of the first diagnosis of diabetes, and
most will eventually develop some degree of retinopathy over time.We discovered iCo-007 and licensed it to iCoTherapeutics Inc.,
or iCo, for the treatment of various eye diseases that occur as complications of diabetes.
InMay2010, investigators evaluating iCo-007 inpatientswithdiffuse diabeticmacular edema presentedpositive results
from thePhase 1 study showing that subjects tolerated iCo-007well. In this study, a number of individuals exhibited a decrease of
centralmacular edema compared tobaseline using an analyticalmethod called optical coherence tomography. iCo is currently
evaluating iCo-007 in aPhase 2 study inpatientswithdiabeticmacular edema andplans to report data in2014.
ATL1102
—
ATL1102 is an antisense drug thatATL is developing for the treatment ofmultiple sclerosis, orMS. ATL1102
inhibitsCD49d, a subunit ofVeryLateAntigen-4, orVLA-4. Studies in animalmodels have demonstrated that inhibitingVLA-4
positively affects a number of inflammatorydiseases, includingMS. We licensedATL1102 toATL inDecember 2001 and in
February2008, ATL licensedATL1102 toTeva. In2008,ATL andTeva reportedPhase 2a results ofATL1102 showing significantly
reduceddisease activity in patientswith relapsing remittingMS. In2010, Teva terminated its agreement withATL and returned
ATL1102back toATL. ATL is currentlyundertaking a chronic toxicology study inprimates to support a potential Phase 2b trial of
ATL1102 inpatientswithMS.
