Slide 1: CP-690,550 Update
CP-690,550 Update EULAR June 12, 2009 1
Slide 2: Forward-Looking Statements and Non-GAAP Financial Information
Forward-Looking Statements and Non-GAAP Financial Information f Our discussions during this presentation will include forward-looking statements. Actual results could differ materially from those projected in the forward-looking statements. The factors that could cause actual results to differ are d
Slide 3: CP-690,550 Update
CP-690,550 Update Bernhardt Zeiher, M.D. Inflammation Disease Area Lead Copenhagen, June 2009 3
Slide 4: CP-690,550 Update
CP-690,550 Update f Compound overview and mechanism of action f Overview of Phase 2 RA Program f New presentations at EULAR ` 12 week interim analysis of 6-month monotherapy study (Study 1035) ` 12-week Japanese study on background MTX (Study 1039) ` Update on Open Label Extension study (Study 1024)
Slide 5: CP-690,550 Update
CP-690,550 Update f Compound overview and mechanism of action f Overview of Phase 2 RA Program f New presentations at EULAR ` 12 week interim analysis of 6-month monotherapy study (Study 1035) ` 12-week Japanese study on background MTX (Study 1039) ` Update on Open Label Extension study (Study 1024)
Slide 6: CP-690,550 – A Potentially Exciting New Development in the Treatment of RA
CP-690,550 – A Potentially Exciting New Development in the Treatment of RA f If successful, CP-690,550 could be the first new oral DMARD to be marketed in more than 10 years f CP-690,550 is the first Janus Kinase inhibitor, a novel immune pathway mechanism that has the potential to treat patients wi
Slide 7: Pharmacology of CP-690,550
Pharmacology of CP-690,550 f CP-690,550 is an orally available, highly selective inhibitor of the Janus kinase (JAK) family of enzymes f Pharmacokinetics are dose proportional (“well behaved”), t½: 2 to 5 hours f Primarily eliminated by urinary excretion; 30% unchanged f Substrate for CYP3A4/5 (with
Slide 8: CP 690,550 is a Selective Inhibitor of Janus Kinases
CP 690,550 is a Selective Inhibitor of Janus Kinases Cytokines Signaling Through JAK1/3 IL-2, IL-4, IL-7, IL-9, IL-15, IL-21 Cytokines Signaling Through Other JAK1 Combinations IL-6, IFNγ, IFNα/β, IL-22, IL-34 8
Slide 9: CP-690,550 is Being Evaluated in a Number of Inflammatory and Immunologic Diseases
CP-690,550 is Being Evaluated in a Number of Inflammatory and Immunologic Diseases Rheumatoid Crohn’s Ulcerative Indications Psoriasis Transplant Dry Eye Arthritis Disease Colitis Disease Burden Phase III IIb IIb IIa IIa IIa 9
Slide 10: CP-690,550 Update
CP-690,550 Update f Compound overview and mechanism of action f Overview of Phase 2 RA Program f New presentations at EULAR ` 12 week interim analysis of 6-month monotherapy study (Study 1035) ` 12-week Japanese study on background MTX (Study 1039) ` Update on Open Label Extension study (Study 1024)
Slide 11: CP-690,550 Phase 2 RA Program
CP-690,550 Phase 2 RA Program f Extensive Phase 2 Program ` 6-week monotherapy POC study (Study 1019) ` 24-week Phase 2b study on background MTX (Study 1025) ` 24-week Phase 2b Monotherapy Study (Study 1035) ` 12-week Phase 2b Japanese study on background MTX (Study 1039) ` Patients enrolled in Stud
Slide 12: CP-690,550 RA Program
CP-690,550 RA Program 2006 2007 2008 2009 2010 1019 1025 (MTX) Phase III RA Program RA POC 1035 (Monotherapy) 1029 (F/U off Drug) Open Label Extension Studies (1024) P2 1039 (Japan MTX) ACR 2006 P2 1040 (Japan Monotherapy) ACR 2008 EULAR 2009 12
Slide 13: CP-690,550 Update
CP-690,550 Update f Compound overview and mechanism of action f Overview of Phase 2 RA Program f New presentations at EULAR ` 12 week interim analysis of 6-month monotherapy study (Study 1035) ` 12-week Japanese study on background MTX (Study 1039) ` Update on Open Label Extension study (Study 1024)
Slide 14: Definition of ACR Response
Definition of ACR Response ACR-20/50/70 Criteria Achieved When All of the Following Are True: f 20/50/70% improvement from baseline in the tender joint count f 20/50/70% improvement from baseline in the swollen joint count f 20/50/70% improvement from baseline in at least 3 of the 5 variables: 1 Pat
Slide 15: 1035: 6-Month Monotherapy, in Inadequate Responders to DMARDs
Study 1035: 6-Month Monotherapy, in Inadequate Responders to DMARDs Adalimumab 40 mg QOW + Placebo CP-690,550 CP-690,550 5 mg BID 15 mg BID injection Placebo injection ++CP-690,550 CP-690,550 10 mg BID 5 mg BID Placebo 3 mg BID 1 mg BID Placebo Week 0 2 4 6 8 10 12 16 20 24 Primary Efficacy: ACR 20
Slide 16: Study 1035: Patient Disposition (Week 0-12)
Study 1035: Patient Disposition (Week 0-12) D / C For Adverse D/C Events That Treatment Group for May Be D / C for Adverse Treatment- Treatment- Lack of D/C Events related Efficacy N N(%) N(%) N(%) N(%) CP-690,550 1 mg BID 54 10 (18.5) 2 (3.7) 1 (1.9) 3 (5.6) 3 mg BID 51 4 (7.8) 2 (3.9) 0 1 (2.0) 5
Slide 17: Week 12 ACR Responder Rates, % (SE)
Study 1035: Week 12 ACR Response Rate (nonresponder imputation) Week 12 ACR Responder Rates, % (SE) 90 *** *** 80 70 *** 60 *** * *** 50 BOCF ** 40 30 * ** ** 20 * 10 0 ACR20 ACR50 ACR70 CP 1 mg BID CP 3 mg BID CP 5 mg BID CP 10 mg BID CP 15 mg BID ADA PBO Difference from placebo *p<0.05; **p<0.001;
Slide 18: Time Course of ACR20 Response
Study 1035: Time Course of ACR20 Response 100 80 *** *** ACR20 Response *** *** *** % (SE) BOCF *** *** *** *** 60 *** *** *** ** *** *** * * * 40 ** * 20 0 0 2 4 6 8 10 12 Weeks CP 1 mg BID CP 3 mg BID CP 5 mg BID CP 10 mg BID CP 15 mg BID ADA PBO Difference from placebo *p<0.05; **p<0.01; ***p<0.0
Slide 19: Change in HAQ-DI Score at Week 12
Study 1035: Change in HAQ-DI Score at Week 12 CP 1 mg CP 3 mg CP 5 mg CP 10 mg CP 15 mg BID BID BID BID BID ADA PBO Mean Change from Baseline in HAQ-DI Score 0.0 -0.1 -0.2 -0.3 -0.4 -0.5 -0.6 * -0.7 *** -0.8 -0.9 *** -1.0 Difference from placebo *p<0.05; **p<0.001; ***p<0.0001 19 ADA, adalimumab; CP
Slide 20: Study 1035: Most Common Treatment-Emergent AEs
Study 1035: Most Common Treatment-Emergent AEs (≥5% (≥5% in in Any Any Treatment Treatment Group, Group, Baseline Baseline to to Week Week 12) 12) CP-690,550 (mg BID) MedDRA Preferred ADA PBO Term, n (%) 1 3 5 10 15 n 54 51 49 61 57 53 59 Urinary tract infection 2 (3.7) 1 (2.0) 5 (10.2) 2 (3.3) 4 (7
Slide 21: Study 1035: Serious AEs (Baseline-Week 12)
Study 1035: Serious AEs (Baseline-Week 12) Dose Serious Adverse Event 1 mg BID None 3 mg BID Anemia/Gastric Ulcer 5 mg BID None 10 mg BID None 15 mg BID Gastritis, Pneumonia Pneumococcal Adalimumab Renal cell carcinoma, Total knee replacement Placebo Panic Attack 21 Based upon week 12 interim analys
Slide 22: Absolute Neutrophil Count at Week 12
Study 1035: Absolute Neutrophil Count at Week 12 7.0 6.0 Neutrophils (103 / mm3) * 5.0 ** ** *** 4.0 3.0 Lower Limit 2.0 of Normal (LLN) 1.0 0.0 CP 1 mg CP 3 mg CP 5 mg CP 10 mg CP 15 mg ADA PBO BID BID BID BID BID No Cases of Severe Neutropenia or Discontinuations Due to Neutropenia Difference from
Slide 23: Change in Hemoglobin at Week 12
Study 1035: Change in Hemoglobin at Week 12 Mean Change from Baseline in Hemoglobin 0.3 * 0.2 0.1 0.0 (g / dL) -0.1 -0.2 -0.3 -0.4 -0.5 CP 1 mg CP 3 mg CP 5 mg CP 10 mg CP 15 mg ADA PBO BID BID BID BID BID No Significant Decrease in Hemoglobin Difference from placebo *p<0.05; **p<0.001; ***p<0.0001
Slide 24: Change in HDL and LDL Cholesterol at Week 12
Study 1035: Change in HDL and LDL Cholesterol at Week 12 HDL LDL Mean Change from Baseline HDL Choleterol Mean Change from Baseline LDL Choleterol 14.0 35.0 *** 12.0 *** *** 30.0 *** 10.0 ** 25.0 ** 8.0 ** 20.0 ** 6.0 * 15.0 (mg/dL) (mg/dL 4.0 10.0 2.0 5.0 0.0 0.0 -2.0 -5.0 -4.0 -10.0 CP CP CP CP CP
Slide 25: Study 1035: Summary of Interim Analysis
Study 1035: Summary of Interim Analysis f CP-690,550 dosed 3 – 15 mg BID was superior to placebo in ACR20 and ACR50 response rates at week 12 ` Responses were rapid with separation from placebo in ACR20 response at the earliest time point of 2 weeks f CP-690,550 dosed 5 – 15 mg BID was superior to p
Slide 26: CP-690,550 Update
CP-690,550 Update f Compound overview and mechanism of action f Overview of Phase 2 RA Program f New presentations at EULAR ` 12 week interim analysis of 6-month monotherapy study (Study 1035) ` 12-week Japanese study on background MTX (Study 1039) ` Update on Open Label Extension study (Study 1024)
Slide 27: 1039: A 12-Week Phase 2 Japanese Study on Background Methotrexate
Study 1039: A 12-Week Phase 2 Japanese Study on Background Methotrexate CP-690,550 10 mg BID 5 mg BID Methotrexate 3 mg BID 1 mg BID Placebo Week 0 1 2 4 8 12 Primary Efficacy: ACR 20 Responder Rate f Patients must have received MTX for at least 4 months consecutively, and must have received doses o
Slide 28: Study 1039: Patient Disposition
Study 1039: Patient Disposition D/C AE Related Dose Treated D/C AE† to CP† LOE† 1 mg BID (n=28) 28 2 (7.1) 0 0 0 3 mg BID (n=28) 27 4 (14.3) 2 (7.4) 1 (3.7) 1 (3.7) 5 mg BID (n=28) 27 4 (14.3) 4 (14.8) 3 (11.1) 0 10 mg BID (n=28) 26 5 (17.9) 4 (15.4) 4 (15.4) 0 Placebo (n=28) 28 5 (17.9) 2 (7.1) 2 (
Slide 29: 1039: Week 12 ACR Response Rates
Study 1039: Week 12 ACR Response Rates ACR Week 12 Responder Rates % 100 *** *** *** *** 80 *** *** (SE) LOCF 60 ** ** ** 40 20 0 ACR20 ACR50 ACR70 1 mg BID 3 mg BID 5 mg BID 10 mg BID Placebo Compared to placebo; **p≤0.01; ***p≤0.001 29 LOCF, last observation carried forward; SE, standard error
Slide 30: 1039: Time Course of ACR20 Response
Study 1039: Time Course of ACR20 Response 100 *** *** *** ACR20 Response Rate 80 *** *** *** *** % (SE) LOCF *** *** *** 60 *** *** *** *** 40 *** ** ** * ** 20 0 2 4 6 8 10 12 Week 1 mg BID 3 mg BID 5 mg BID 10 mg BID Placebo 30 Compared to placebo *p≤0.05; **p≤0.01; ***p≤0.001
Slide 31: 1039: Change in HAQ-DI Score at Week 12
Study 1039: Change in HAQ-DI Score at Week 12 1 mg BID 3 mg BID 5 mg BID 10 mg BID Placebo 0.0 Mean (SE) Change from Baseline -0.1 -0.2 -0.3 -0.4 ** *** -0.5 -0.6 *** *** -0.7 31 Compared to placebo *p≤0.05; **p≤0.01; ***p≤0.001
Slide 32: Study 1039: Adverse Events Occurring in at Least 3 Patients in Any Arm
Study 1039: Adverse Events Occurring in at Least 3 Patients in Any Arm, n (%) 10 mg 1 mg BID 3 mg BID 5 mg BID BID Placebo MedDRA N=28 N=27 N=27 N=26 N=28 Gastrointestinal disorders 4 (14.3) 0 5 (18.5) 3 (11.5) 2 (7.1) Stomach discomfort 0 0 3 (11.1) 0 0 Infections and infestations 3 (10.7) 8 (29.6)
Slide 33: Study 1039: Incidence of Transaminase Elevations
Study 1039: Incidence of Transaminase Elevations ALT, n (%) AST, n (%) Dose (n) Abnormal >1x >2x >3x Abnormal >1x >2x >3x Baseline ULN ULN ULN Baseline ULN ULN ULN 1 mg BID (28) 1 (4) 4 (15) 1 (4) 0 0 4 (14) 0 0 3 mg BID (27) 2 (8) 3 (12) 1 (4) 0 0 2 (7) 1 (4) 0 5 mg BID (27) 2 (8) 6 (24) 2 (8) 2 (8
Slide 34: Study 1039: Adverse Events That Led to Discontinuation From Treatment
Study 1039: Adverse Events That Led to Discontinuation From Treatment Dose Adverse Event 1 mg BID – f Osteoarthritis 3 mg BID f ALT and AST increased f Femur fracture 5 mg BID f White blood cell count decreased f ALT and AST increased (2 patients) f Cardiac failure and pneumonia f Dyspnoea 10 mg BID
Slide 35: 1039: Absolute Neutrophil Count
Study 1039: Absolute Neutrophil Count 7.0 Mean (SE) Neutrophils (10 3 / mm 3) 6.0 5.0 * 4.0 3.0 Lower Limit 2.0 of Normal (LLN) 1.0 0.0 1 mg BID 3 mg BID 5 mg BID 10 mg BID Placebo 35 Compared to placebo *p≤0.05
Slide 36: 1039: Change in Hemoglobin
Study 1039: Change in Hemoglobin 0.5 Mean (SE) Change From Baseline g / dL 0.4 0.3 0.2 0.1 0.0 1 mg BID 3 mg BID 5 mg BID 10 mg BID Placebo No Significant Change in Hemoglobin 36
Slide 37: 1039: Change in HDL and LDL Cholesterol
Study 1039: Change in HDL and LDL Cholesterol HDL LDL Mean (SE) Change from Baseline mg/dL Mean (SE) Change from Baseline mg/dL 15.0 25.0 *** *** *** *** *** 10.0 20.0 ** 5.0 ** 15.0 10.0 0.0 5.0 -5.0 0.0 -10.0 1 mg 3 mg 5 mg 10 mg Placebo 1 mg 3 mg 5 mg 10 mg Placebo BID BID BID BID BID BID BID BID
Slide 38: Study 1039: Conclusions
Study 1039: Conclusions f All CP-690,550 doses were efficacious vs. placebo ` ACR20 response rates: all doses statistically significantly superior to placebo at Week 12 ` ACR50 response rates: all doses except 1 mg BID significantly superior to placebo at Week 12 ` ACR70 response rates: 5 mg BID and
Slide 39: Study 1039: Conclusions (continued)
Study 1039: Conclusions (continued) f CP-690,550 was generally well-tolerated ` No serious infections or opportunistic infections ` No significant decreases in hemoglobin ` Dose-related decreases in mean absolute neutrophil counts ` Dose-dependent increases in LDL and HDL cholesterol ` ALT/AST incre
Slide 40: CP-690,550 Update
CP-690,550 Update f Compound overview and mechanism of action f Overview of Phase 2 RA Program f New presentations at EULAR ` 12 week interim analysis of 6-month monotherapy study (Study 1035) ` 12-week Japanese study on background MTX (Study 1039) ` Update on Open Label Extension study (Study 1024)
Slide 41: Study 1024 Design
Study 1024 Design Study 1025 24 weeks, background MTX Study 1035 Study 1024 (5 mg BID CP-690,550) 24 weeks, monotherapy Open-label, long-term, multicenter safety study Study 1035 24 weeks, monotherapy * * * * * * * * * Screening 0 1 2 3 6 9 12 15 18 21 Days -28 to 0 Months * Study assessments f Roll
Slide 42: Study 1024: Interim Analysis
Study 1024: Interim Analysis f Data from 655 patients, enrolled as of Dec 01, 2008 f At data cut-off, the number of patients completing treatment through 6 and 12 months was: ` 446 patients: 6 months ` 125 patients: 12 months f Median duration of treatment was: ` 161.0 days (range 1-658 days) f Base
Slide 43: Study 1024: Summary of Safety Data at Interim Analysis
Study 1024: Summary of Safety Data at Interim Analysis f Most AEs mild to moderate in severity ` 10 Severe AEs: » Acne, acute renal failure, diarrhea, disseminated tuberculosis*, diverticulitis*, herpes zoster*, pneumonia*, staphylococcal infection*, upper abdominal pain, urinary tract infection* f
Slide 44: Study 1024: Laboratory Data at Interim Analysis
Study 1024: Laboratory Data at Interim Analysis All Patients Baseline Month 6 Month 12 (Mean ± SD) (n=635-646) (n=301-316) (n=56-59) Neutrophil count, 103/mm3 5.72 ± 2.38 4.89 ± 1.95 4.64 ± 2.27 Hemoglobin, g/dL 13.05 ± 1.41 13.14 ± 1.27 12.96 ± 1.42 LDL, mg/dL 112.04 ± 34.46 129.54 ± 38.55 131.00 ±
Slide 45: Study 1024: Conclusions from Interim Analysis
Study 1024: Conclusions from Interim Analysis f CP-690,550 was generally well-tolerated and had a similar safety profile compared to that observed in the randomized index studies 45
Slide 46: CP-690,550 Update
CP-690,550 Update f Compound overview and mechanism of action f Overview of Phase 2 RA Program f New presentations at EULAR ` 12 week interim analysis of 6-month monotherapy study (Study 1035) ` 12-week Japanese study on background MTX (Study 1039) ` Update on Open Label Extension study (Study 1024)
Slide 47: CP-690,550 RA Phase 2 Program Conclusions
CP-690,550 RA Phase 2 Program Conclusions f 4/4 studies achieved statistical significance on the primary endpoint (ACR20 Response) f Extensive Phase 2 RA Program enrolled >1,000 patients and explored a CP-690,550 dose range of 1 to 30 mg BID f CP-690,550 dosed ≥ 3 mg BID was generally efficacious, c
Slide 48: CP-690,550 RA Phase 2 Program Conclusions
CP-690,550 RA Phase 2 Program Conclusions f Safety profile will continue to be monitored and further characterized throughout Phase 3 including: ` Decreases in absolute neutrophil counts and hemoglobin ` Increases in total, LDL and HDL cholesterol ` Increases in transaminases ` Infections » Current
Slide 49: Phase 3 Clinical Studies Enrolling
Phase 3 Clinical Studies Enrolling Patient Number of CP- CP-690,550 Control / Study # Objectives Duration Population Subjects Dosage Active Comp Signs & Inadequate Symptoms 5 mg BID A3921044 response to 750 24 months Placebo Structure 10 mg BID bkgd MTX Physical Fxn Signs & 5 mg BID A3921045 Monothe
Slide 50: CP-690,550 – A Potentially Exciting New Development in the Treatment of RA
CP-690,550 – A Potentially Exciting New Development in the Treatment of RA fCP-690,550 is the first Janus Kinase inhibitor, a novel immune pathway mechanism that has the potential to treat patients with RA as well as a number of other autoimmune diseases fIf successful, CP-690,550 could be the first
Slide 51: Thank You Questions?
Thank You Questions? 51
Slide 52: CP-690,550 Update
CP-690,550 Update EULAR 2009 52