10
Table 1: Comparisonof the effects onkey lipids for patients treatedwith300mg/weekof ISIS-APOCIII
Rx
SingleAgent in
DiabeticswithHighTG
SingleAgent in
VeryHighTG
InAddition toFibrates
inVeryHighTG
SingleAgent in
FCS
BaselineMeanmg/dL (range)
ApoC-III
14 (9-20)
23 (14-33)
18 (12-30)
25 (19-35)
Triglycerides 259 (187-356)
559 (291-952)
394 (224-932)
1844 (1406-2083)
HDL-C
43 (35-55)
34 (22-52)
34 (14-53)
13 (8-16)
Non-HDL-C 178 (128-300)
175 (76-312)
185 (118-243)
262 (214-327)
Mean%Change fromBaseline (StandardDeviation)
ApoC-III
-88% (6.0)
-80% (9.3)
-70% (12.5)
-81% (9.8)
Triglycerides -72% (8.3)
-71% (14.1)
-64% (8.9)
-69% (15.6)
HDL-C
+40% (19.8)
+46% (24.0)
+52% (23.7)
+78% (74.6)
Non-HDL-C -28% (16.4)
-11% (38.3)
-19% (28.8)
-58% (14.3)
Consistent across the Phase 2program, ISIS-APOCIII
Rx
demonstrated a good safetyprofile andwaswell tolerated. Themost
common adverse eventwas injection site reactions, whichwere predominantlymild and typically resolved rapidly. Therewere no flu-
like symptoms, no treatment-related elevations in liver enzymes greater than three times the upper limit of normal, no abnormalities in
renal function andno clinicallymeaningful changes inother laboratoryvalues.
In 2014, we plan to initiate aPhase 3 program that will include evaluating ISIS-APOCIII
Rx
in patientswithFCS and in
patientswith severelyhigh triglyceride levels of greater than880mg/dL.
ATL1103
—ATL1103 is an antisense drug that targets the growthhormone receptor, orGHr, a receptor that, when inhibited,
reduces the level of circulating insulin-like growth factor-1, or IGF-1, produced in the liver. IGF-1 is a hormone that contributes to
various diseases, including acromegaly, an abnormal growth disorder of organs, face, hands and feet. IGF-1 also contributes to
diabetic retinopathy, a common disease of the eye and a leading cause of blindness, diabetic nephropathyof the kidney and certain
forms of cancer. In preclinical studies, ATL1103demonstrated significant reductions in IGF-1 levels in the blood and inhibitionof
neovascularization, or newbloodvessels, in the eye in amouse retinopathymodel.
AntisenseTherapeutics Limited, orATL, is developingATL1103 andhas completed a Phase 1 study inhealthyvolunteers
demonstrating thatATL1103was safe andwell tolerated. ATL is evaluatingATL1103 in aPhase 2 study inpatientswith
acromegaly. ATL reported interim results from this study showing that patients treatedwith the highest dose, 200mg twiceweekly
for 3months, experienced an average of 30percent reduction in serum insulin-like growth factor-I, or sIGF-I, the primary activity
endpoint for the study. ATLplans to report the complete analysis from this study in2014.
ISIS-GCCR
Rx
— ISIS-GCCR
Rx
is an antisense drug that targets the glucocorticoid receptor, orGCCR. Glucocorticoid
hormones affect a varietyof processes throughout the body, and excessive levels of glucocorticoidhormones canhave a detrimental
effect onmanyof the tissues andorgans in the body. Cushing’s Syndrome is anorphandisease causedbyprolonged exposure tohigh
levels of glucocorticoids. If untreated, patientswithCushing’s Syndrome candevelophypertension, diabetes and impaired immune
functions andhave an increased riskof earlydeath. Although there are approved treatments for Cushing’s Syndrome, current
medicines are associatedwith significant side effects, such as hypertension and diabetes, and there remains a highunmetmedical need
for new therapies for these patients.We have alreadydemonstrated that subjects tolerated ISIS-GCCR
Rx
well in aPhase 1 study in
healthyvolunteers, andwe observed reductions ofGCCR specifically in the liver and fat tissues, consistentwithour preclinical
observations. Formore information on ISIS-GCCR
Rx
and type 2 diabetes, please refer to the ISIS-GCCR
Rx
sectionunder the
subheading “MetabolicDisease Franchise”.
We are currently evaluating ISIS-GCCR
Rx
in aPhase 2 study inpatientswith type 2diabetes andplan to initiate a clinical
study to evaluate ISIS-GCCR
Rx
in patientswithCushing’s Syndrome in2014.
