Pfizer, Inc. · NYSE:PFE
Pfizer — American College of Rheumatology (ACR) Annual Meeting 2008 Analyst & Investor Briefing
76 slides from Pfizer's conference presentation, Oct 28, 2008
Slide 1: Analyst & Investor Briefing
Analyst & Investor Briefing American College of Rheumatology October 28, 2008
Slide 2: Forward-Looking Statements and Non-GAAP Financial Information
Forward-Looking Statements and Non-GAAP Financial Information • Discussions at this meeting 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 discussed in P
Slide 3: Ken Verburg, Ph.D., Development Head for Pain Therapeutics
Ken Verburg, Ph.D. Development Head for Pain Therapeutics October 28, 2008
Slide 4: Chronic Pain Population Continues to Expand While Unmet Needs Continue to Increase
Chronic Pain Population Continues to Expand While Unmet Needs Continue to Increase Prevalence of Chronic Pain • Steady growth in patients in Major Global Markets (2011) chronic pain reflects aging 160MM population 40 ~250 million patients • Physicians express displeasure 35 with the current therapie
Slide 5: Few Existing Therapeutic Classes
Few Existing Therapeutic Classes >50% of Patients Report These Therapies to Be Suboptimal in Relieving Their Pain* • Acute Pain/ • Neuropathic Pain Musculoskeletal Pain – Anti-depressants – Acetaminophen – Anti-epileptics – NSAIDs – Topical capsaicin – Opiates – Local anesthetics – Local anesthetics
Slide 6: Going Beyond Traditional Analgesic Drugs
Going Beyond Traditional Analgesic Drugs • Transduction • Modulation • Conduction • Sensitization • Transmission • Processing/perception Neuron Microglia Astrocyte Sensitization/ Transduction Conduction Transmission Inhibition TRPV1, TRPV2, TRPV3, NGF, TrkA, TRPV1, NaV1.8, NaV1.7, CaV2.2, mGluR, TRP
Slide 7: Pain Portfolio: Oct '08
Pain Portfolio: Oct ’08 Progress to Innovative Medicines NeP Pain Arthritis Pain Fibromyalgia Broad Pain PF- PF-3557156 PDE7i Sev Chr Pain Acute Pain PF- PF-4191834 PF- PF-4480682 5-LO inhibitor PDE5i + α2δ 4 Compounds PF- PF-3864086 PH- PH-797804 Lyrica & Unique P38 kinase i TRPV1 antag post- post-
Slide 8: Tanezumab: Overview
Tanezumab: Overview • Nerve growth factor (NGF) Heavy – Key pain mediator in pain Chain • Humanized, IgG2 monoclonal antibody – High specificity and affinity for NGF – Fc mutation limits Ab-dependent cell mediated toxicity & complement activation NGF • Efficacy in multiple preclinical models of pain
Slide 9: Neurotrophic Factors (Neurotrophins)
Neurotrophic Factors (Neurotrophins) • A substance that controls neuronal maturation & survival during development of functional contacts (neuronal circuits) But practically, • Neurotrophic factors have effects on adult neurons – Upregulate sensitivity, transmitter synthesis/release – Protect from m
Slide 10: Neurotrophins and Their Receptors on Sensory Neurons
Neurotrophins and Their Receptors on Sensory Neurons BDNF NGF NT4/5 NT3 trkA trkB trkC Nociceptors/ Slowly adapting Proprioceptors/ thermoreceptors Mechanoreceptors large cutaneous Pain/temperature Proprioception, Light touch sensitivity vibration
Slide 11: NGF: Pain Signaling
NGF: Pain Signaling • NGF sensitizes TRPV1 ion channels – Noxious heat/acidity (capsaicin receptor) – NGF causes phosphorylation of TRPV1 which leads to increased transport to cell surface and increased channel activity • NGF activates mast cells • NGF triggers changes in gene expression – Increases
Slide 12: Anti-NGF Treatment Does Not Affect Acute Pain Sensation or Neuron Survival in Animals
Anti-NGF Treatment Does Not Affect Acute Pain Sensation or Neuron Survival in Animals Heat Pain 12 Latency (sec.) 8 4 0 Mechanical Pain 6 50% Threshold 4 • 26-week study in adult cynomolgous 2 monkeys with 0, 1, 10 & 30 mg/kg/week – No target organ toxicities 0 – Extensive evaluation of nervous syst
Slide 13: Clinical Program Overview
Clinical Program Overview • Exposure – >675 patients treated with at least 1 dose – ~250 patients → 6 months treatment – ~60 patients → 12 months treatment • Osteoarthritis – Phase 2 program complete – Encouraging open-label data ≤1 yr with 50 µg/kg IV q 8 wks • Phase 2 studies – Chronic low back pa
Slide 14: Dose-Ranging Knee OA Study 1008: Study Design
Dose-Ranging Knee OA Study 1008: Study Design placebo (n=75) tanezumab 10 µg/kg (n=75) tanezumab 25 µg/kg (n=75) Screening tanezumab 50 µg/kg (n=75) tanezumab 100 µg/kg (n=75) tanezumab 200 µg/kg (n=75) Study Day -30 -3 1 14 28 42 56 70 84 112 136 182 Visits Randomization Baseline Pain 2nd Dose 1st
Slide 15: WOMAC Pain Scale (VAS 0-100 mm)
WOMAC Pain Scale (VAS 0-100 mm) placebo (n=73) tanezumab 50 µg/kg (n=72) tanezumab 10 µg/kg (n=74) tanezumab 100 µg/kg (n=74) tanezumab 25 µg/kg (n=75) tanezumab 200 µg/kg (n=72) -5 -15 Mean change (se) * -25 ** *** *** *** *** *** *** * *** -35 *** *** *** *** *** *** -45 *** *** *** *** *** *** **
Slide 16: WOMAC Function Scale (VAS 0-100 mm)
WOMAC Function Scale (VAS 0-100 mm) placebo (n=73) tanezumab 50 µg/kg (n=72) tanezumab 10 µg/kg (n=74) tanezumab 100 µg/kg (n=74) tanezumab 25 µg/kg (n=75) tanezumab 200 µg/kg (n=72) -5 -15 Mean change (se) * -25 ** *** *** *** *** *** ** *** * -35 *** *** *** *** *** *** *** *** -45 *** *** *** ***
Slide 17: Pain Responder Rates at Week 16
Pain Responder Rates at Week 12 placebo (n=73) tanezumab 10 µg/kg (n=74) 100 tanezumab 25 µg/kg (n=75) 90 *** *** tanezumab 50 µg/kg (n=72) 80 tanezumab 100 µg/kg (n=74) *** *** tanezumab 200 µg/kg (n=72) *** * *** Percent of Patients 70 * 60 ** ** 50 40 *** 30 *** ** 20 * * 10 0 30% Responders 50%
Slide 18: Pain Responder Rates With an NSAID in Phase 3 OA Trials at Week 12
Pain Responder Rates With an NSAID in Phase 3 OA Trials at Week 12 100 placebo (n=660) 90 Dose 1 (n=671) 80 Dose 2 (n=641) Percent of Patients 70 Dose 3 (n=646) 60 50 * * * 40 * * 30 * 20 10 0 30% Responders 50% Responders 90% Responders p≤0.05 *Active treatment group vs. placebo: p≤
Slide 19: Summary of Safety
Summary of Safety placebo (n=74) tanezumab 10 µg/kg (n=74) 90 tanezumab 25 µg/kg (n=74) tanezumab 50 µg/kg (n=74) 80 78 tanezumab 100 µg/kg (n=74) Incidence (% of Patients) 69 tanezumab 200 µg/kg (n=74) 70 66 69 60 60 55 50 40 30 20 11 10 8 5 4 1 1 3 3 3 0 0 0 0 Adverse Events Withdrawals due to Ser
Slide 20: Summary of Safety
Summary of Safety • Most frequent adverse events across tanezumab groups: – Headache (8.9%) 90 – URTI (7.3%) – Paresthesia (6.8%) 80 78 – Hypoesthesia (5.7%) Incidence (% of Patients) 70 69 69 – Arthralgia (5.7%) 66 60 • Infusion site reactions (pain or burning) 60 55 were rare (0.5% each) 50 • Inci
Slide 21: Summary of Safety
Summary of Safety • Only arthralgia and worsening diabetes led to withdrawal in more 90 than one patient 80 78 • Arthralgia – 2 patients (100, 200 ug/kg doses) Incidence (% of Patients) 70 69 69 66 • Diabetes – 3 patients (10, 50 and 60 200 ug/kg) 60 55 • One patient discontinued the 50 study due to
Slide 22: Summary of Safety
Summary of Safety 90 • Only 7 patients in total experienced serious adverse 80 78 events (all considered unrelated to study medication) Incidence (% of Patients) 70 69 69 66 • Chest pain (pbo) 60 60 cellulitis, appendicitis (10µg/kg) 55 breast cancer, bacterial arthritis 50 (50µg/kg) syncope, lumbar
Slide 23: Adverse Events Related to Abnormal Peripheral Sensation
Adverse Events Related to Abnormal Peripheral Sensation • Allodynia – Clothing/touch evoke pain sensation • Dysesthesia: – Sensitivity to touch and clothing – Sunburn/hot sensation • Paresthesia – Tingling, pricking, or pins & needles sensation • Hyperesthesia (Hypoesthesia) – High (low) sensitivity
Slide 24: Adverse Events Related to Abnormal Peripheral Sensation
Adverse Events Related to Abnormal Peripheral Sensation (µg/kg) tanezumab (µ placebo 10 25 50 100 200 Combined n (%) N=74 N=74 N=74 N=74 N=74 N=74 N=370 Any AE 2 (2.7) 4 (5.4) 4 (5.4) 4 (5.4) 13 (17.6) 12 (16.2) 37 (10.0) Allodynia 0 0 0 0 1 (1.4) 1 (1.4) 2 (0.5) Dysesthesia 0 0 0 0 1 (1.4) 1 (1.4)
Slide 25: Tanezumab: Summary
Tanezumab: Summary • Therapeutic potential in a number of pain conditions • Fixed low doses administered 6 times per year • Encouraging safety profile to date • Dose-related transient abnormal cutaneous sensations have been observed – not treatment limiting • Long-term effects on sensory and autonom
Slide 26: Management of Fibromyalgia with Esreboxetine
Management of Fibromyalgia with Esreboxetine
Slide 27: Fibromyalgia: Clinical Characteristics
Fibromyalgia: Clinical Characteristics • A syndrome characterized by: – Widespread soft tissue and muscular pain – Decreased pain threshold (tenderpoints) Fibromyalgia Tender Points – Fatigue: 81% – “usually or always too tired”1 – Disturbed sleep: 75% consider their sleep nonrestorative1 – Anxiety
Slide 28: Esreboxetine: Unmet Patient Needs
Esreboxetine: Unmet Patient Needs % of Fibromyalgia Patients with Symptoms* 97% 91% 90% 67% 36% Pain Fatigue Poor Depressive Difficulty Sleep Symptoms Concentrating Key Value Drivers Widespread Difficulty Fatigue Poor Sleep Function Depression Pain Concentrating Lyrica 9 Unmet 9 Unmet duloxetine 9 N
Slide 29: Esreboxetine
Esreboxetine • Selective norepinephrine reuptake inhibitor (NRI) O H • More selective isomer of Edronax O (racemic reboxetine) – Approved for depression in over O 40 countries outside the US H NH MeSO3H • Different pharmacologic approach than Lyrica Esreboxetine • Once daily administration [S,S] - r
Slide 30: Putative Site and Mechanism of Action: Enhancing Norepinephrine Transmission
Putative Site and Mechanism of Action: Enhancing Norepinephrine (NE) Transmission at Spinal Cord Dorsal Horn Cortex Esreboxetine Increases Descending Brainstem NE Inhibition for Pain Relief Dorsal Root nociceptor Ganglia Spinal cord Specific knock- knock-out of NE transporter reuptake mechanism enha
Slide 31: Phase 2 Study Design: Study 1034
Phase 2 Study Design: Study 1034 Eligible Patients Had ACR Defined Fibromyalgia; Score 8 mg qd ≥40 mm on 100 mm Pain Visual Analog Scale and Mean Score ≥4 on a 0-10 Numerical Pain Rating Scale One- One-step dose reduction 6 mg qd esreboxetine (n=134) One- One-step dose reduction 4 mg qd One- One-ste
Slide 32: Efficacy in Fibromyalgia
Efficacy in Fibromyalgia placebo (n=133) esreboxetine (n=134) Pain Reduction Improvement in Function 0 0 Mean Change In NRS Score Mean Change in FIQ Score -0.5 -5 -1.0 -10 -8.1 -1.0 -1.5 -15 -1.6 -2.0 -20 -15.6 * * Scale 0 (no pain) to 10 (worst pain) Scale 0 (none) to 100 (max impairment) Baseline
Slide 33: Efficacy in Fibromyalgia
Efficacy in Fibromyalgia placebo (n=133) esreboxetine (n=134) Improvement in Fatigue Patient Global Impression 0 60 * Mean Change in MAF Score 42.6 50 -2 Percent of Patients 40 -4 30 23.4 -2.8 * 17.1 20 -6 10 3.8 -8 -6.4 0 * Very Much/ Very Much Scale 0 (none) to 50 (maximum) Much Improved Improved
Slide 34: Time Course of Pain Relief
Time Course of Pain Relief 0.0 placebo (n=133) esreboxetine (n=134) -0.4 Mean Change from Baseline Score -0.8 * -1.2 * * * * -1.6 * -2.0 1 2 3 4 5 6 7 8 Study week * p<0.05 vs. placebo Mean (SD) Baseline Score; placebo = 6.8 (1.4); esreboxetine = 6.8 6.8 (1.4)
Slide 35: Responder Rates: Reductions in Pain
Responder Rates: Reductions in Pain placebo (n=133) esreboxetine (n=134) 40 * 37.6 35 30 (% of patients) Responders 25 22.6 20 ** 18.1 15 10 8.3 5 0 30% Response Rate 50% Response Rate (Clinically Important) (Substantial Improvement) *p=0.004; **p=0.01 vs. placebo
Slide 36: Summary of Safety
Summary of Safety placebo (n=133) 100 esreboxetine (n=134) Incidence (% of Patients) 80 72 60 57 40 20 8.2 3.0 0.7 0.7 0 Adverse Withdrawals Serious Adverse Events due to Events Adverse Events
Slide 37: Incidence of Adverse Events (≥5%)
Incidence of Adverse Events (≥5%) placebo (n=133) esreboxetine (n=134) n (%) n (%) Constipation 7 (5.3) 26 (19.4) Insomnia 5 (3.8) 24 (17.9) Dry mouth 3 (2.3) 22 (16.4) Headache 5 (3.8) 19 (14.2) Nausea 4 (3.0) 12 (9.0) URTI 7 (5.3) 6 (4.5) Dizziness 2 (1.5) 9 (6.7) Nasopharyngitis 6 (4.5) 5 (3.7) F
Slide 38: Effects on Blood Pressure and Heart Rate
Effects on Blood Pressure and Heart Rate placebo (n=133) esreboxetine (n=134) Baseline At 8 weeks Baseline At 8 weeks Parameter Mean (SD) Mean (SD) Mean (SD) Mean (SD) Systolic BP (mmHg) 123.6 (13.7) 123.8 (14.1) 120.6 (14.4) 120.9 (14.5) Diastolic BP (mmHg) 77.0 (8.5) 76.7 (9.1) 76.3 (8.4) 77.7 (8.
Slide 39: Esreboxetine: Summary
Esreboxetine: Summary • Therapeutic potential in fibromyalgia – Pain, function, fatigue and cognition – Potential for study with Lyrica – Differentiation from mixed reuptake inhibitors – Benefit: risk optimized in phenotypic subgroups • Encouraging safety profile to date – Differentiation from mixed
Slide 40: CP-690,550 Update
CP-690,550 Update Ethan Weiner, M.D. Development Head for Inflammation Therapeutics October 28, 2008
Slide 41: CP-690,550 Update
CP-690,550 Update • Significant Unmet Need • Mechanism of Action • Review of Program and Previous RA Data • New Presentations at ACR – 12 week dose response data (study 1025) – Open Label Extension (study 1024) – MTX DDI Study (study 1013) • Summary
Slide 42: CP-690,550 Update
CP-690,550 Update • Significant Unmet Need • Mechanism of Action • Review of Program and Previous RA Data • New Presentations at ACR – 12 week dose response data (study 1025) – Open Label Extension (study 1024) – MTX DDI Study (study 1013) • Summary
Slide 43: Unmet Need in RA Market
Unmet Need in RA Market • Limitations of current products • Needs of physicians and patients • A significant need exists for new oral treatments beyond the treatments of the last three decades
Slide 44: CP-690,550 – A Exciting Potential New Development in the Treatment of RA
CP-690,550 – A Exciting Potential New Development in the Treatment of RA • If successful, CP-690,550 could be the first new oral DMARD to be marketed in more than 10 years • CP-690,550 is the first Janus Kinase inhibitor, a novel immune pathway mechanism that has the potential to treat patients affl
Slide 45: CP-690,550 Update
CP-690,550 Update • Significant Unmet Need • Mechanism of Action • Review of Program and Previous RA Data • New Presentations at ACR – 12 week dose response data – Open Label Extension – MTX DDI Study • Summary
Slide 46: Cytokine Signaling of JAK
Cytokine Signaling of JAK Common γ chain shared by receptors for: IL- IL-2R, IL- IL-4R, IL- IL-7R, IL- IL-9R, IL- IL-15R, IL- IL-21R IL- 2 NK Cell Cytokine Effector IL- 4 T Cell IL- 21 X X Expansion IL- 2 Expansion IL- 15 CP-690,550 T JAK 1 JAK 3 blocks this Cell point in the P P signaling Monocyte
Slide 47: CP-690,550 Update
CP-690,550 Update • Significant Unmet Need • Mechanism of Action • Review of Program and Previous RA Data • New Presentations at ACR – 12 week dose response data (study 1025) – Open Label Extension (study 1024) – MTX DDI Study (study 1013) • Summary
Slide 48: Study 1019: Design
Study 1019: Design 1o anal- ysis Weeks 0 1 2 3 4 5 6 7 8 9 10 11 12 5 mg BID (N=64) Screening Days -28 to 0 15 mg BID (N=61) 30 mg BID (N=61) Informed Consent Placebo (N=68) Follow-Up Double-Blind Off Drug • Subjects with active RA who had failed either methotrexate ≥ 15 mg/wk or a TNF- inhibitor, b
Slide 49: The ACR 20/50/70
The ACR 20/50/70 ACR-20/50/70 Criteria Achieved When All of the Following Are True: • 20/50/70% improvement from baseline in the tender joint count • 20/50/70% improvement from baseline in the swollen joint count • 20/50/70% improvement from baseline in at least 3 of the 5 variables: 1 Patient Globa
Slide 50: Study 1019: Week 6 ACR Response Rates
Study 1019: Week 6 ACR Response Rates 81% Placebo 77% 5 mg 70% 15 mg 30 mg 54% 51% 33% 29% 28% 22% 13% 6% 3% ACR 20 ACR 50 ACR 70
Slide 51: 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
Slide 52: CP-690,550 Update
CP-690,550 Update • Significant Unmet Need • Mechanism of Action • Review of Program and Previous RA Data • New Presentations at ACR – 12 week dose response data (study 1025) – Open Label Extension (study 1024) – MTX DDI Study (study 1013) • Summary
Slide 53: A3921025 Study Design
A3921025 Study Design Interim Analysis Week 0 2 4 6 8 10 12 14 16 18 20 22 24 20 mg QD (N=80) 15 mg BID (N=75) 10 mg BID (N=75) Methotrexate 5 mg BID (N=71) 3 mg BID (N=68) 1 mg BID (N=71) Placebo (N=69) Efficacy (Primary) Durability (Secondary) Safety Signals • Subjects with RA and inadequate respo
Slide 54: Study 1025: Week 12 ACR Response Rates
Study 1025: Week 12 ACR Response Rates 70% Placebo ACR Week 12 Responder Rates, LOCF (%) * * 1 mg BID * * * 60% 3 mg BID 5 mg BID 50% ** 10 mg BID 15 mg BID 40% * * 20 mg QD 30% * * * 20% * 10% 0% ACR20 ACR50 ACR70 * p≤0.05 ** p≤0.0001
Slide 55: Study 1025: ACR Response Rates Over Time
Study 1025: ACR 20 Response Rates Over Time 100 Placebo 1 mg BID 90 3 mg BID 5 mg BID 80 10 mg BID 15 mg BID 70 20 mg QD Response Rate P<=0.05 60 (nominal significance vs. Placebo) 50 40 30 20 10 0 0 2 4 6 8 10 12 Week
Slide 56: Study 1025: Week 12 Efficacy Summary
Study 1025: Week 12 Efficacy Summary • All doses except 1 mg bid showed a significantly better response than placebo, confirming efficacy from earlier 1019 study • Efficacy generally improved with higher doses with maximal effects generally observed at 15 mg bid • Onset of efficacy was as early as 2
Slide 57: Study 1025: Serious Infections
Study 1025: Serious Infections CP-690,550 MTX Weekly Event Dose Dose Age Pneumonia 3 mg BID 15 mg 40 Urinary tract 3 mg BID 15 mg 52 infection Pneumonia 5 mg BID 15 mg 56 Respiratory 10 mg BID 20 mg 68 tract infection Pneumonia 20 mg QD 17.5 mg 53 Serious infection was defined as one requiring hospi
Slide 58: Study 1025: Mean Changes from Baseline in HGB and ANC at Week 12
Study 1025: Mean Changes from Baseline in HGB and ANC at Week 12 HGB Change ANC Change Dose g/dl Dose k/µl 1 mg BID 0.02 1 mg BID -0.80 3 mg BID 0.11* 3 mg BID -0.50 5 mg BID 0.14* 5 mg BID -0.82 10 mg BID -0.42 10 mg BID -0.83 15 mg BID -0.40 15 mg BID -1.18* 20 mg QD -0.12 20 mg QD -0.32 placebo -
Slide 59: Study 1025: Severe Anemia and Neutropenia
Study 1025: Severe Anemia and Neutropenia Incidence Through Week 12 of • 3 subjects had ANC’s Subjects with Anemia That Is less than 1000 k/µl Severe or Life Threatening Anemia Rates – 15 mg bid Above – 15 mg bid Dose N n Observed Placebo placebo 67 2 3.0% – 1 mg bid 1 mg BID 69 3 4.4% 1.4% • No pot
Slide 60: Study 1025: Incidence of Transaminase Elevations
Study 1025: Incidence of Transaminase Elevations (Subjects with Normal BL) AST > 3 X ULN ALT > 3 X ULN 1 mg BID 0 0 3 mg BID 0 0 5 mg BID 0 0 10 mg BID 1 (1%) 1 (1%) 15 mg BID 2 (3%) 4 (5%) 20 mg QD 2 (3%) 1 (1%) placebo 0 1 (2%) No subject met “Hy’ Hy’s rule” rule”: ALT > 3 X ULN and Bilirubin > 2
Slide 61: Study 1025: Mean Changes from Baseline in HDL and LDL at Week 12
Study 1025: Mean Changes from Baseline in HDL and LDL at Week 12 HDL Change LDL Change Dose mg/dl Dose mg/dl 1 mg BID 2.22* 1 mg BID 6.31** 3 mg BID 3.63** 3 mg BID 8.14** 5 mg BID 6.11** 5 mg BID 12.97** 10 mg BID 2.71* 10 mg BID 16.17** 15 mg BID 4.74** 15 mg BID 15.23** 20 mg QD 5.78** 20 mg QD 9
Slide 62: Study 1025: Safety Summary (Week 12)
Study 1025: Safety Summary (Week 12) • Serious infections were few and not dose responsive • Dose related changes in hemoglobin and neutrophils were seen. Incidences of OMERACT severe or life-threatening anemia and neutropenia were low. No subject was withdrawn for protocol specified hemoglobin or n
Slide 63: Study 1025: Overall Conclusions
Study 1025: Overall Conclusions • An efficacy and safety profile justifying progression to Phase III was observed • The data presented, plus the 24 week data from this study, plus data anticipated from study 1035 will provide a robust database to inform Phase III dosing
Slide 64: CP-690,550 Update
CP-690,550 Update • Significant Unmet Need • Value Proposition and Mechanism • Review of Program and Previous RA Data • New Presentations at ACR – 12 week dose response data (study 1025) – Open Label Extension (study 1024) – MTX DDI Study (study 1013) • Summary
Slide 65: Study A3921024: Open-label, Long-term, Multicenter Study
Study A3921024: Open-label, Long-term, Multicenter Study Months 0 3 6 9 12 Study A3921025 24 weeks, background MTX Screening Days -28 to 0 CP-690,550 5 mg BID Study A3921019 6 Weeks, Monotherapy • Patients could continue their stable background RA therapy, including approved DMARDs and glucocorticoi
Slide 66: Study 1024: Interim Analysis
Study 1024: Interim Analysis • An interim analysis was conducted of all safety data for all 129 patients enrolled as of 22-Feb-2008 • Comparisons in laboratory data and DAS were made at 1 and 6 months – 40 patients had completed 6 months in study as of 22-Feb-2008
Slide 67: Study 1024: Adverse Events in 129 Subjects
Study 1024: Adverse Events* in 129 Subjects • Total AEs = 160 – Mild = 93 – Moderate = 64 – Severe = 3 (myocardial infarction, RA, acne) • Infections = 32 – Mild = 13 – Moderate = 19 – Severe = 0 – No serious AE’s related to infection by data cut * At time of Feb 22, 2008 data cut
Slide 68: Study 1024: Laboratory Values at 6 Months
Study 1024: Laboratory Values at 6 Months CP-690,550 5 mg BID 1025 1019 All Serum creatinine, mg/dL 0.92 ± 0.23 0.86 ± 0.20 0.88 ± 0.21 Neutrophil count, 103/mm3 5.27 ± 1.56 5.01 ± 1.81 5.09 ± 1.73 Hemoglobin, g/dL 12.31 ± 0.91 13.70 ± 1.30 13.28 ± 1.35 LDL, mg/dL 117.02 ± 34.36 145.45 ± 34.90 136.9
Slide 69: Study 1024: DAS28-3 (CRP)
Study 1024: DAS28-3 (CRP) Study 1025 Study 1019 All Patients 6.0 5.0 Mean (SD) DAS28-3 Score 4.0 3.0 2.0 1.0 0.0 N=68 N=32 N=100 N=12 N=27 N=39 Month 1 Month 6
Slide 70: Study 1024: DAS28-4 (ESR)
Study 1024: DAS28-4 (ESR) Study 1025 Study 1019 All Patients 7.0 6.0 Mean (SD) DAS28-4 Score 5.0 4.0 3.0 2.0 1.0 0.0 N=69 N=6 N=75 N=12 N=20 N=32 Month 1 Month 6
Slide 71: Study 1024: Conclusions
Study 1024: Conclusions • CP-690,550 5 mg BID was well tolerated and efficacious in patients with moderate to severe active RA over a median of 109.0 days • DAS 28 was similar in all patients at 6 months, regardless of prior study experience • Mean laboratory values remained within normal limits at
Slide 72: CP-690,550 Update
CP-690,550 Update • Significant Unmet Need • Value Proposition and Mechanism • Review of Program and Previous RA Data • New Presentations at ACR – 12 week dose response data (study 1025) – Open Label Extension (study 1024) – MTX DDI Study (study 1013) • Summary
Slide 73: Study 1013: MTX DDI Study Summary
Study 1013: MTX DDI Study Summary • Study Objectives: – To estimate the effects of MTX on the pharmacokinetics (PK) of CP-690,550 when administered to subjects with RA – To estimate the effects of multiple doses of CP-690,550 (30 mg Q 12 h) on the PK of MTX – To evaluate the short-term safety and to
Slide 74: 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) 1024 (Open Label Extension) P2 1039 (Japan MTX) ACR 2006 P2 1040 (Japan Monotherapy) ACR 2008
Slide 75: Conclusion
Conclusion • Current products for RA have significant limitations • CP-690,550 may offer benefits of both a small molecule and a biologic • Data to date for CP-690,550 has demonstrated a promising profile • Robust clinical program underway / Plans for Phase III trial progressing
Slide 76: Q&A
Q&A