Slide 1: ISIS 301012 Phase 2 Results and Program Overview
November 13, 2006 ISIS 301012 Phase 2 Results and Program Overview
Slide 2: Today's Program
Today’s Program Opening Remarks Stanley T. Crooke, MD, PhD Chairman and Chief Executive Officer, Isis Pharmaceuticals, Inc. ISIS 301012 Clinical Results and Review Mark K. Wedel, MD, JD Senior Vice President and Chief Medical Officer, Isis Pharmaceuticals, Inc. Clinician’s Perspective John J. P. Kas
Slide 3: Isis Pharmaceuticals Summary of Key Assets
Isis Pharmaceuticals Summary of Key Assets Three Near Term Product Opportunities ISIS 301012 u ISIS 113715 u Alicaforsen Deep Portfolio of Second-Generation Antisense Product Opportunities Cardiovascular u Metabolic u Inflammation u Ocular u Cancer Ibis Biosciences Biosensor Products and Technology
Slide 4: Drug Development Pipeline: Isis Internal
Drug Development Pipeline Isis Internal Isis Asthma IL-4R ISIS 369645 (A) Isis PTP-1B Diabetes ISIS 113715 (SC) Alicaforsen (E) ICAM-1 Ulcerative Colitis Isis (ISIS 2302) Isis* High Cholesterol ApoB-100 ISIS 301012 (SC) Isis CRP ISIS 353512 (SC) Cardiovascular / Inflammation A = Aerosol E = Enema SC
Slide 5: Drug Development Pipeline: Partners
Drug Development Pipeline Partners ATL1102 (SC) VLA-4 MS ATL C-Raf kinase Ocular Diseases iCo iCo 007 (I) I = Intravitreal IT = Intrathecal IV = Intravenous SC = Subcutaneous T = Topical OncoGenex OGX-011 (IV) Clusterin Cancer LY2181308 (IV) Survivin Cancer Lilly LY2275796 (IV) eIF-4E Cancer Lilly O
Slide 6: Antisense: A Novel Approach to Drug Discovery
Antisense: A Novel Approach to Drug Discovery Through Inhibition of Translation of a Specific Targeted Protein Antisense Strand Sense-Antisense Duplex RNase H DNA mRNA Nucleus Cytoplasm Cell Membrane 2 nd Generation Antisense Drugs ~20X more potent 1X/week to 1X/quarter dosing Better tolerated Lower
Slide 7: Human ApoB-100 is an Ideal Target for a 2nd Generation Antisense Drug
Human ApoB-100 is an Ideal Target for a 2 nd Generation Antisense Drug Expressed in the liver Essential for the synthesis and transport of VLDL and LDL-C Plays a crucial role in lipid management Biologically validated, but undruggable target for small molecules An apoB-100 inhibitor should have a un
Slide 8: Summary of Preclinical Properties
ISIS 301012 Summary of Preclinical Properties Potent dose-dependent reduction of liver mRNA and protein levels, and serum apoB-100 in normal and hyperlipidemic animals 50 to 90% reduction of apoB mRNA in all species evaluated Attractive safety profile in mice and other species Antisense inhibition o
Slide 9: Clinical Development Strategy
ISIS 301012 Clinical Development Strategy We intend for ISIS 301012 to be: The drug of choice for patients at risk who are unable to achieve target levels when added to statins & ezetimibe initially in patients with Familial Hypercholesterolemia (FH) ultimately in patients with polygenic hypercholes
Slide 10: ISIS 301012 Clinical Results and Review
Mark Wedel, MD, JD ISIS 301012 Clinical Results and Review
Slide 11: Clinical Program Overview
ISIS 301012 Clinical Program Overview Phase 1 Healthy volunteers Drug-drug interaction Phase 2 Hypercholesterolemic subjects Monotherapy Co-administration with statins High-risk populations Homozygous familial hypercholesterolemia (HoFH) Heterozygous familial hypercholesterolemia (HeFH)
Slide 12: Phase 1 Design
ISIS 301012 – Phase 1 Design Normal Volunteers with Mild Hypercholesterolemia Single Dosing SQ 4 Weeks - weekly fasting cholesterol Wk 1 IV Fasting Lipid Panel Wk 2 SQ Wk 3 SQ Wk 4 SQ Multi Dosing Fasting Lipid Panel
Slide 13: Phase 1 Dose-Dependent Prolonged Reduction in Serum ApoB & LDL-C
ISIS 301012 – Phase 1 Dose-Dependent Prolonged Reduction in Serum ApoB & LDL-C* % Change at Day 39** % Change at Day 39** ApoB LDL-C ** 14 days post dosing (n=2) (n=7) (n=8) (n=8) (n=8) (n=2) (n=7) (n=8) (n=8) (n=8) * Kastelein JJP, et.al. Circulation 2006;114:1729-35.
Slide 14: Phase 1 Reductions in Serum ApoB, LDL-C and TG
ISIS 301012 – Phase 1 Reductions in Serum ApoB, LDL-C and TG (dose: 350 mg/wk, 1 month) 60% ApoB 46% Triglycerides 54% LDL-C Median Reductions ApoB LDL-C Triglycerides N = 6 treated N = 12 placebo
Slide 15: Phase 1 Drug-Drug Interaction Study
ISIS 301012 – Drug-Drug Interaction Study Study Design Simvastatin: 40 mg ISIS 301012: 200 mg IV 1 4 6 8 11 Day: Ezetimibe: 10 mg ISIS 301012: 200 mg IV 1 8 10 12 15 Day:
Slide 16: Phase 1 Drug-Drug Interaction Study: Lack of PK Interaction
ISIS 301012 – Drug-Drug Interaction Study Lack of PK Interaction with Oral Lipid Lowering Drugs ISIS 301012 alone ISIS 301012 with simvastatin n= 10 0.001 0.010.11101000510152025Time (hr)0.0011000.010.11100510152025Time (hr) WITH and WITHOUT EZETIMIBE ISIS 301012 alone ISIS 301012 with ezetimibe n=
Slide 17: Pharmacokinetics Summary
ISIS 301012 Pharmacokinetics Summary Elimination half-life: 31 days at 200 mg/week dose No clinically significant PK or metabolism interactions seen with simvastatin or ezetimibe supporting further work in combination
Slide 18: Monotherapy Study Design
ISIS 301012 Monotherapy Study Design Randomized, placebo-controlled, double-blind, dose-escalation trial with 10 subjects per cohort (1:4) Study population: hypercholesterolemic subjects with LDL-C > 130 mg/dL on diet alone Dosing cohorts: 50 mg/wk 100 mg/wk 200 mg/wk midpoint safety data review 300
Slide 19: Monotherapy Patient Demographics & Baseline Lipid Values
ISIS 301012 Monotherapy Patient Demographics & Baseline Lipid Values 139 (109-160) 130 (93-150) 129 (100-185) 156 (106-184) 135 (110-154) ApoB 178 (119-232) 173 (135-210) 154 (132-266) 172 (132-218) 163 (127-181) LDL-C 8 8 8 8 8 n 55 48 40 50 53 age 8/0 7/1 7/1 7/1 6/2 M/F 248 (194-298) 252 (208-279
Slide 20: Monotherapy Dose-Dependent ApoB & LDL-C Reduction
ISIS 301012 Monotherapy Dose-Dependent ApoB & LDL-C Reduction % Change at Day 99* % Change at Day 99* ApoB LDL-C * 14 days post dosing (n=7) (n=8) (n=8) (n=7) (n=8) (n=7) (n=8) (n=8) (n=7) (n=8)
Slide 21: Monotherapy Dose-Dependent Total-C & Non-HDL-C Reduction
ISIS 301012 Monotherapy Dose-Dependent Total-C & Non-HDL-C Reduction % Change at Day 99* % Change at Day 99* Total Cholesterol non-HDL-C * 14 days post dosing (n=7) (n=8) (n=8) (n=7) (n=8) (n=7) (n=8) (n=8) (n=7) (n=8)
Slide 22: Monotherapy Dose-Dependent TG & VLDL-C Reduction
ISIS 301012 Monotherapy Dose-Dependent TG & VLDL-C Reduction % Change at Day 99* % Change at Day 99* Triglyceride VLDL-C * 14 days post dosing (n=7) (n=8) (n=8) (n=7) (n=8) (n=7) (n=8) (n=8) (n=7) (n=8)
Slide 23: Monotherapy Median % Change from Baseline, Day 99
ISIS 301012 Monotherapy Median % Change from Baseline, Day 99 46 % P=0.0003 34 % P=0.0002 15 % P=0.09 12 % P=0.33 6 % TC 15 %* P=0.009 1 % P=0.72 5 % P=0.40 9 % P=0.28 2 % HDL-C 54 % P=0.006 46 % P=0.02 44 % P=0.0002 42 % P=0.0002 47% P=0.0002 200 mg/wk 52 % P=0.04 43 % P=0.04 54 % P=0.0003 62 % P=0
Slide 24: Monotherapy ApoB/ApoA1 and TC/HDL Ratios
ISIS 301012 Monotherapy ApoB/ApoA1 and TC/HDL Ratios % D Day 99 Baseline apoB/apoA1 -51 % P=0.0003 46 % P=0.0002 -26 % P=0.002 -22 % P=0.007 11 % 1.1 (1.0-1.7) 1.0 (0.7-1.3) 0.8 (0.7-1.3) 1.1 (0.6-1.4) 1.0 (0.8-1.1) 0.6 (0.4-0.9) 0.5 (0.3-0.9) 0.6 (0.5-1.1) 0.8 (0.4-1.1) 1.0 (0.9-1.2) 200 mg/wk 300
Slide 25: Monotherapy PK/PD Model Predicts Trough Concentrations and Response
ISIS 301012 Monotherapy PK/PD Model Predicts Trough Concentrations and Pharmacologic Response 100 mg weekly dose 0 20 40 60 80 100 0 20 40 60 80 100 120 -80 -60 -40 -20 0 20 Predicted Plasma Trough ISIS 301012 Conc. Observed Plasma Trough ISIS 301012 Conc. Predicted Apo B (%Change) Observed Apo B (%
Slide 26: Monotherapy Safety Observations
ISIS 301012 Monotherapy Safety Observations Serious Adverse Events: one ‘unrelated’ SAE (encephalitis) Adverse Events (> 10%): painless, transient erythema at site of injection Laboratory Findings: one subject with confirmed ALT > 3x ULN elevation, which resolved pending 4 2 2 4 Nasopharyngitis pend
Slide 27: Added to Statins Study Design
ISIS 301012 added to Statins Study Design Randomized, placebo-controlled, double-blind, dose-escalation trial with 10 subjects per cohort (1:4) Study population: hypercholesterolemic subjects with LDL-C > 100 mg/dL on stable dose of < 40 mg simvastatin or atorvastatin for > 3 months Dosing cohorts:
Slide 28: Added to Statins Patient Demographics & Baseline Lipid Values
ISIS 301012 added to Statins Patient Demographics & Baseline Lipid Values 133 (122-159) 112 (78-141) 106 (69-147) 95 (86-116) 114 (84-137) ApoB 168 (143-216) 131 (107-162) 134 (84-189) 107 (95-154) 137 (110-175) LDL-C 8 8 8 8 9 n 57 58 59 59 62 age 4/4 6/2 4/4 6/2 6/3 M/F 257 (199-293) 212 (170-265)
Slide 29: Added to Statins Dose-Dependent ApoB & LDL-C Reduction
ISIS 301012 added to Statins Dose-Dependent ApoB & LDL-C Reduction % Change at Day 59* % Change at Day 59* ApoB LDL-C * 30 days post dosing (n=8) (n=7) (n=8) (n=6) (n=7) (n=8) (n=7) (n=8) (n=6) (n=7)
Slide 30: Added to Statins Dose-Dependent Total-C & Non-HDL-C Reduction
ISIS 301012 added to Statins Dose-Dependent Total-C & Non-HDL-C Reduction % Change at Day 59* % Change at Day 59* Total Cholesterol Non-HDL-C * 30 days post dosing (n=8) (n=7) (n=8) (n=6) (n=7) (n=8) (n=7) (n=8) (n=6) (n=7)
Slide 31: Added to Statins Dose-Dependent TG & VLDL-C Reduction
ISIS 301012 added to Statins Dose-Dependent TG & VLDL-C Reduction % Change at Day 59* % Change at Day 59* Triglyceride VLDL-C (n=8) (n=7) (n=8) (n=6) (n=7) (n=8) (n=7) (n=8) (n=6) (n=7) * 30 days post dosing
Slide 32: Added to Statins Median % Change from Baseline, Day 59
ISIS 301012 added to Statins Median % Change from Baseline, Day 59 42 % P=0.0006 -20 % P=0.03 -15 % P=0.02 5 % P=0.61 -3 % TC 5 % P=0.24 2 % P=0.04 4% P=0.05 1 % P=0.09 12 % HDL-C 28 % P=0.46 20 % P=0.90 26 % P=0.07 30 % P=0.002 - -24 % P=0.05 200 mg/wk 63 % P=0.19 41 % P=0.15 51 % P=.0003 51 % P=0.
Slide 33: Added to Statins ApoB/ApoA1 and TC/HDL Ratios
ISIS 301012 added to Statins ApoB/ApoA1 and TC/HDL Ratios % D Day 59 Baseline apoB/apoA1 -55 % P=0.0003 30 % P=0.02 -15 % P=0.10 0 % P=0.78 -1 % 0.8 (0.6-1.0) 0.6 (0.4-1.0) 0.7 (0.5-1.1) 0.6 (0.5-0.7) 0.7 (0.4-0.9) 0.4 (0.2-0.7) 0.4 (0.2-0.9) 0.6 (0.4-0.7) 0.6 (0.5-0.7) 0.7 (0.5-20.7) 200 mg/wk 300
Slide 34: Added to Statins Safety Observations
ISIS 301012 added to Statins Safety Observations Serious Adverse Events: none Adverse Events: painless, transient erythema at site of injection Laboratory Findings: one subject with confirmed ALT > 3x ULN 2 0 3 1 1 Nasopharyngitis 1 4 2 2 4 Headache 7 5 8 6 0 Injection site erythema 300 mg/wk 200 mg
Slide 35: Phase 2 Conclusions
ISIS 301012 Phase 2 Conclusions ISIS 301012 results in a potent, dose-dependent, linear reduction in atherogenic lipids and lipoproteins in hypercholesterolemic subjects demonstrates prolonged effects consistent with a greater than 30 day elimination half-life is comparable in effect when used as mo
Slide 36: Clinical Development Strategy
ISIS 301012 Clinical Development Strategy We intend for ISIS 301012 to be: The drug of choice for patients at risk who are unable to achieve target levels when added to statins & ezetimibe initially in patients with Familial Hypercholesterolemia (FH) ultimately in patients with polygenic hypercholes
Slide 37: Development Path: Near and Longer Term Opportunities
ISIS 301012 Development Path Near and Longer Term Opportunities Parallel approach Clinical studies in severe populations Homozygous familial hypercholesterolemia (HoFH) Heterozygous familial hypercholesterolemia (HeFH) Parallel clinical studies addressing the large cholesterol market Polygenic hyper
Slide 38: Market Opportunity: HoFH and HeFH
ISIS 301012 – Market Opportunity HoFH and HeFH: Unmet Need, Accelerated Path to Market Homozygous Familial Hypercholesterolemia (HoFH) Most severe and therapy-resistant form of high cholesterol (LDL levels > 500mg/dL) HoFH patients do not achieve target levels of LDL with existing treatments Prevale
Slide 39: Market Opportunity: In Combination with Statins and Statin-Intolerant Patients
ISIS 301012 – Market Opportunity In Combination with Statins and in Statin-Intolerant Patients As an Add-On to Statins: a more $3 billion U.S. market >16 million High-Risk patients (CHD or equivalent) are not meeting target LDL-C >5 million Moderately High-Risk U.S. patients in category ( > 2 risk f
Slide 40: Anticipated Initial Product Efficacy and Safety Profile
ISIS 301012 Anticipated Initial Product Efficacy and Safety Profile Product Efficacy Profile Achieves statin-like reductions in cholesterol via a non-statin mechanism Enables more patients to safely achieve target lipid levels when combined with statins and ezetimibe May be dosed at convenient inter
Slide 41: Next Steps
ISIS 301012 Next Steps Polygenic Hypercholesterolemia Monotherapy Report results of 400 mg/week dose for three months Combination with Statins Report results of 400 mg/week dose for 5 weeks Report results 200 and 300 mg/week doses for three months Define induction and maintenance doses in longer ter
Slide 42: Cardiovascular Advisory Board
ISIS 301012 Cardiovascular Advisory Board John Kastelein, MD, PhD, Amsterdam Thomas Michel, MD, PhD, Boston Steve Nissen, MD, Cleveland Dan Rader, MD, Philadelphia Paul Ridker, MD, Boston Evan Stein, MD, PhD, Cincinnati Erik Stroes, MD, PhD, Amsterdam Steve Young, MD, Los Angeles Willis Maddrey, MD,
Slide 43: Clinician's Perspective
Clinician’s Perspective John J.P. Kastelein, MD, PhD Chairman, Department of Vascular Medicine Academic Medical Center Amsterdam, The Netherlands
Slide 44: LDL-C Concentrations and CHD Risk
LDL-C Concentrations and CHD Risk Linear relationships exist between LDL-C and CHD outcomes in primary prevention, secondary prevention and diabetes secondary prevention populations * Relationship between LDL-cholesterol & CHD risk (Heart 90:336, 2004)
Slide 45: Effects of LDL-C Reduction on CHD Outcomes
Effects of LDL-C Reduction on CHD Outcomes Every 2 mg/dL reduction in LDL-C results in 1% reduction in CHD event rate Benefits of LDL-C lowering have been demonstrated in higher risk patients including diabetics as well as patients with relatively low LDL-C levels Reduction in LDL-C level (mg/dL) Pr
Slide 46: Lower LDL-C is Better When It Comes to Preventing Cardiovascular Disease
Lower LDL-C is Better When It Comes to Preventing Cardiovascular Disease NIH Post CABG: 4.5 year treatment of lovastatin 2.5 mg vs 80 mg ® significant difference in coronary stenosis and CAD events ASAP: 2-year treatment of FH patients with atorvastatin 80 mg vs simvastatin 40 mg ® significant diffe
Slide 47: TNT - Changes in LDL-C by Treatment Group
TNT- Changes in LDL-C by Treatment Group Final Screen 0 3 12 24 36 48 60 P <0.001 Baseline 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 Mean LDL-C (mmol/L) Mean LDL-C level = 101 mg/dL (2.6 mmol/L) Mean LDL-C level = 77 mg/dL (2.0 mmol/L) 0 20 40 60 80 100 120 160 Study visit (months) Mean LDL-C (mg/dL) Atorva
Slide 48: TNT - Primary Efficacy Outcome Measure
TNT - Primary Efficacy Outcome Measure: Time to First Major Cardiovascular Event* HR = 0.78 (95% CI 0.69, 0.89) P=0.0002 *CHD death, nonfatal non-procedure-related MI, resuscitated cardiac arrest, fatal or nonfatal stroke 0 0.05 0.10 0.15 Atorvastatin 10 mg Atorvastatin 80 mg Proportion of patients
Slide 49: ASTEROID Trial: Principal Findings
ASTEROID Trial: Principal Findings LDL levels were reduced from 130.4 mg/dL at baseline to a mean of 60.8 mg/dL at 2 year follow-up (p<0.001), with 75% of patients achieving an LDL <70 mg/dL HDL levels were increased from 43.1 mg/dL at baseline to a mean of 49.0 mg/dL at follow-up (p<0.001) LDL/HDL
Slide 50: ASTEROID Trial: Primary Endpoint
ASTEROID Trial: Primary Endpoint Regression in percent atheroma volume was observed in 63.6% of patients, whereas progression was observed in 34.6% Regression vs. progression change in % atheroma volume (%) % patients 63.6 34.6 0 8 16 24 32 40 48 56 64 Regression Progression
Slide 51: Evolution of Lipid Management Guidelines
Evolution of Lipid Management Guidelines: The National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) ATP I (1988) ATP II (1993) ATP III (2001) Diet, low-dose non-statin monotherapy High-dose statin, combination therapy Moderate to high-dose statin therapy Increasing aggressiveness
Slide 52: ATP III: Greatest Increase in Individuals Requiring Drug Therapy
ATP III: Greatest Increase in Individuals Requiring Drug Therapy in Category of CHD or CHD-Risk Equivalent Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497. 0 5 10 15 20 25 CHD or equivalent 2+ risk factors < 2 risk factors Millions A
Slide 53: Most Patients Fail to Achieve Even ATPII LDL-C Goals
Most Patients Fail to Achieve Even ATPII LDL-C Goals with Lipid-Lowering Therapy < 160 mg/dL < 130 mg/dL < 100 mg/dL Pearson TA et al. Arch Intern Med. 2000;160:459-467 Jacobson TA et al. Arch Intern Med. 2000;160:1361-1369 Sloan KL et al. Am J Cardiol. 2001;88:1143-1146; Sueta CA et al. Am J Cardio
Slide 54: Unmet Medical Need
Unmet Medical Need A drug or combination lipid-lowering therapy with the following profile: LDL-C reductions > those achieved with statins lipid-lowering effects additive to those of statins lowers all major atherogenic lipoproteins and TGs beneficially impacts key risk ratios (e.g., apo B/apo AI) l
Slide 55: Produces Apo B and LDL-C Reductions Greater Than Most Potent Statins
ISIS 301012 Produces Apo B and LDL-C Reductions Greater Than Those Achieved With the Most Potent Statins 38 - 41 33 - 35 42 - 43 33 - 40 52 - 61 24 - 47 % apo B reduction 40 mg qd 20 mg qd 20 mg qd 10 mg qd 300 mg qw 200 mg qw Dose 50 - 52 43 - 50 47 - 48 42 - 46 51 - 62 30 - 42 % LDL-C reduction CS
Slide 56: Produces LDL-C, VLDL-C, and TG Reductions Additive to Statins
ISIS 301012 Produces LDL-C, VLDL-C, and TG Reductions That Are Additive to Those of Statins These additive effects are at least 2-fold greater than those reported for any other marketed statin add-on therapies % Change from Baseline LDL-C VLDL-C TG Results are shown for the 300-mg dose cohorts -70 -
Slide 57: Lowers all Major Atherogenic Lipoprotein Classes and Triglycerides
ISIS 301012 Lowers all Major Atherogenic Lipoprotein Classes and Triglycerides non-HDL-C Triglyceride VLDL-C LDL-C
Slide 58: Preferentially Reduces Small Dense LDL
ISIS 301012 Preferentially Reduces Small Dense LDL Phase 1: 200 mg & 400 mg cohorts combined 558 836 345 309 0 100 200 300 400 500 600 700 800 900 Large LDL-P Small LDL-P* LDL Subclass (nmole/L) Particle No. Baseline Day 39 p = 0.005
Slide 59: Beneficially Impacts Key Risk Ratios: ApoB/ApoA1 and TC/HDL
ISIS 301012 Beneficially Impacts Key Risk Ratios: ApoB/ApoA1 and TC/HDL Ratios % D Day 99 Baseline apoB/apoA1 -51 % P=0.0003 46 % P=0.0002 -26 % P=0.002 -22 % P=0.007 11 % 1.1 (1.0-1.7) 1.0 (0.7-1.3) 0.8 (0.7-1.3) 1.1 (0.6-1.4) 1.0 (0.8-1.1) 0.6 (0.4-0.9) 0.5 (0.3-0.9) 0.6 (0.5-1.1) 0.8 (0.4-1.1) 1.
Slide 60: Produces a Linear Dose Response
ISIS 301012 produces a linear dose response (dose doubling = doubling of response) Results show % change at day 99 in phase 2 monotherapy study Apo B (n=7) (n=8) (n=8) (n=7) (n=8) (n=7) (n=8) (n=8) (n=7) (n=8) LDL-C
Slide 61: Has Limited Potential for Drug-Drug Interactions
ISIS 301012 Has Limited Potential for Drug-Drug Interactions ISIS 301012 alone ISIS 301012 with simvastatin n= 10 0.001 0.010.11101000510152025Time (hr)0.0011000.010.11100510152025Time (hr) WITH and WITHOUT EZETIMIBE ISIS 301012 alone ISIS 301012 with ezetimibe n= 10 WITH and WITHOUT SIMVASTATIN Mea
Slide 62: Summary: ISIS 301012 Profile Satisfies Key Unmet Medical Needs
Summary: ISIS 301012 Exhibits a Compelling Profile That Satisfies Key Unmet Medical Needs Prolonged reductions of key lipid parameters including apoB, LDL-C, TG, VLDL-C and non-HDL-C Reductions in these parameters meet or exceed and are additive to those achieved with statins Beneficial impact on ke
Slide 63: Clinical Utility and Target Patient Populations for ISIS 301012
Clinical Utility and Target Patient Populations for ISIS 301012 How Would I Use ISIS 301012 in Practice? Patients not meeting LDL-C goal on maximally tolerated therapy FH patients High-risk patients (e.g., CHD-equivalent) patients with low LDL-C targets Statin hyporesponders Patients intolerant of s
Slide 64: Concluding Remarks
Stanley T. Crooke, MD, PhD Concluding Remarks
Slide 65: 2006: What a Great Year - ISIS 301012
2006: What a Great Year ISIS 301012 Studies in patients with polygenic high cholesterol Report single agent Phase 2 data Demonstrate safety and activity as a single agent after 3 months of treatment (2Q06) Define dose and schedule for longer term studies (2Q06) Report data from higher dose in patien
Slide 66: 2006: What a Great Year - ISIS 113715 and New Diabetes Drugs
2006: What a Great Year ISIS 113715 and New Diabetes Drugs ISIS 113715 Report single agent Phase 2 data in Type 2 diabetes patients Report results on safety and activity after 6 weeks treatment Report initial results demonstrating safety and activity after 12 weeks treatment Initiate mechanistic stu
Slide 67: 2006: What a Great Year - Partner Pipeline
2006: What a Great Year Partner Pipeline Partner Development Pipelines OncoGenex: OGX-011 (Targeting Clusterin, for treatment of cancer) Advance 5 Phase 2 trials (3 in prostate, 1 in NSCLC, 1 in breast) Report Phase 1 data on NSCLC OncoGenex: OGX-427(Targeting Heat Shock Protein 27 in cancer) Initia
Slide 68: 2006: What a Great Year - Ibis
2006: What a Great Year Ibis Continue growth in revenue Orders for first assay kits received Assay service business established and contract for 10,000 samples received Deliver additional Ibis T5000 Biosensor Systems NHRC (Naval Health Research Center) system delivered CDC (Centers for Disease Contr
Slide 69: Forward-looking statements
This presentation includes forward-looking statements regarding Isis Pharmaceuticals’ business, the financial outlook for Isis’ Ibis Biosciences division, and the commercial potential of the Company’s technologies and products in development. Any statement describing Isis’ goals, expectations, finan