Incyte Corporation · NASDAQ:INCY
Incyte — ASCO 2008 Investor Meeting
26 slides from Incyte's conference presentation, Jun 2, 2008
Slide 1: Review of Phase I/II Study of INCB18424 in Patients with Myelofibrosis
Review of Phase I/II Study of INCB18424 in Patients with Myelofibrosis June 2, 2008
Slide 2: Safe Harbor Statement
Safe Harbor Statement Except for the historical information set forth herein, the matters set forth in this presentation, including without limitation statements regarding our plans and expectations with respect to advancing our JAK inhibitor drug candidates through clinical trials and the potential
Slide 3: Agenda
Agenda Welcome / Introductions Pam Murphy, Vice President, Corporate Communications/IR Richard Levy, M.D. , Senior Vice President, Development Presentation Srdan Verstovsek, M.D., Ph.D. Associate Professor Leukemia Department, Myeloproliferative Disorders Program Leader, University of Texas M.D. And
Slide 4: A phase I/II study of INCB018424 in primary and post-PV/ET myelofibrosis
A phase I/II study of INCB018424, an oral, selective JAK inhibitor, in patients with primary myelofibrosis (PMF) and post polycythemia vera/essential thrombocythemia myelofibrosis (Post-PV/ET MF) Srdan Verstovsek, MD, PhD,1 Hagop Kantarjian, MD,1 Animesh Pardanani, MD, PhD,2 Deborah Thomas, MD,1 Jor
Slide 5: Disclosure
Disclosure Author Disclosure Srdan Verstovsek Advisor - Incyte Corporation Hagop Kantarjian Advisor - Incyte Corporation Animesh Pardanani Advisor – Incyte Corporation Deborah Thomas None Jorge Cortes None Ruben Mesa Advisor – Incyte Corporation William Hogan None John Redman Employee – Incyte Corpo
Slide 6: INCB018424 Background
INCB018424 Background • INCB018424 is a potent and selective inhibitor of JAK1 and JAK2 – >80-fold selectivity against JAK3 and non-JAK family kinases – Preclinical toxicology findings restricted to myelosuppression and reduced lymphoid organ cellularity at high doses • Phase I dose escalation study
Slide 7: Study INCB 18424-251: Current Enrollment Status
Study INCB 18424-251: Current Enrollment Status 93 patients enrolled as of May 31, 2008 INCB 18424-251 INCB 18424-251 BID Dosing Once Daily Dosing 25 mg QD 50 mg QD 100 mg QD 200 mg QD 10 mg BID 25 mg BID 50 mg BID N=6 N=22 N=6 N=3 N=12 N=27 N=5 Maintenance Expansion Switch N=5 N=7 Current presentat
Slide 8: Patient Baseline Characteristics
Patient Baseline Characteristics Parameter 25 mg BID 10 mg BID N 27 12 Median Age (range) 64 63 (40-80) (50-77) Male/Female 19/8 5/7 PMF 12 (44.5%) 6 (50.0%) Post-PVMF 10 (37.0%) 4 (33.3%) Post-ETMF 5 (18.5%) 2 (16.7%) Median Time on Drug 190 days 85 days % With JAK2 Mutation 89% 100% Baseline Splee
Slide 9: INCB18424 Results in Rapid and Profound Reduction in Spleen Size
INCB18424 Results in Rapid and Profound Reduction in Spleen Size 22.5 25 mg BID 24 Patients with Palpable Spleen or Liver 20.0 10 mg BID 12 Patients with Palpable Spleen or Liver 17.5 N=11 Spleen Size, cm 15.0 N=8 12.5 10.0 7.5 N=19 5.0 N=17 N=9 N=2 2.5 0.0 0 28 56 84 112 140 168 196 224 252 Days on
Slide 10: Responder Analysis - Spleen or Liver Size
Responder Analysis - Spleen or Liver Size % Reduction in Spleen or Liver 100 0-25% Proportion of Subjects >25-49% 75 50% or More 50 25 0 25 mg BID 10 mg BID N=24 N=12 1 0
Slide 11: Effect of Dose Reductions on Maintenance of Spleen Size Reduction
Effect of Dose Reductions on Maintenance of Spleen Size Reduction 25 20 N=6 Spleen size, cm 15 10 N=6 N=6 N=3 5 0 Baseline On 25 mg BID 1 Mo Post 3 Mo Post Mean + SEM for N=6 Changing dose to 25 mg QD 1 1
Slide 12: Improvement in Constitutional Symptoms
Improvement in Constitutional Symptoms - 1 25 mg BID 10 mg BID 7 N=14 N=11 Fatigue MFSAF Score (Maximum = 10) 6 Night Sweats N=10 N=8 Pruritis N=7 N=8 5 4 3 2 1 0 o o B Mo o B Mo o B Mo B Mo o e e e e e e M in in in in in in M M M M 1 el el el el el el 1 3 1 3 3 1 1 1 as as as as as as B B Includes
Slide 13: Improvement in Constitutional Symptoms
Improvement in Constitutional Symptoms - 2 25 mg BID 10 mg BID Ability to move around Ability to bend N=13 N=11 7 N=13 N=6 6 MFSAFScore(Maximum=10) 5 4 3 2 1 0 o o o o o o e e e e M M M M M M in in in in el el el el 1 3 1 3 1 1 as as as as B B B B Includes only patients with assessment for all time
Slide 14: Improvement in Body Weight
Improvement in Body Weight 5 Change in total body weight, Kg (mean ± SEM) 4 N=18 25 mg BID N=22 3 2 1 N=24 N=6 N=2 10 mg BID } Weight Gain N=11 } 0 14 28 42 56 70 84 Loss of ascites time -1 and/or organomegaly -2 NOTE: Data is censored after a dose change or dose interruption 14
Slide 15: Improvement of ECOG Performance Status
Improvement of ECOG Performance Status of Patients on INCB018424 Therapy (25 mg BID) 100 N=27 N=26 N=23 N=22 ECOG Status Proportion of Patients 0 75 1 2 3 50 4 25 0 0 28 56 84 Days on Study Note: Subjects with ECOG scores of 3 or 4 were not eligible to enroll 15
Slide 16: Effect of INCB018424 Treatment on the Percentage of V617F JAK2
Effect of INCB018424 Treatment on the Percentage of V617F JAK2 Ratio of V617F to WT JAK2 assessed by quantitative genotypic analysis Peripheral Blood V617F Bone Marrow V617F V617F (% of baseline) V617F (% of baseline) 100 N=21 100 P=0.001 90 90 N=19 P=0.013 N=7 N=6 N=18 P=0.054 N=2 P=0.005 80 P=0.02
Slide 17: Inflammatory Cytokines are Elevated in MF Patients
Inflammatory Cytokines are Elevated in MF Patients fold change (Log2) Patient: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 • Levels of inflammatory cytokines and markers are increased in MF patients • Plasma from MF patients compared to plasma from healthy volunteers using unbiased proteom
Slide 18: INCB018424 Treatment Reduces Inflammatory Cytokines
INCB018424 Treatment (25 mg BID X 28 Days) Reduces Inflammatory Cytokines fold change (Log2) Patient: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 • Baseline patient samples were compared to Day 28 plasma samples using unbiased proteomics approach • INCB018424 modulated cytokine levels in a
Slide 19: INCB018424 Treatment Modulates Growth Factors
INCB018424 Treatment (25 mg BID X 28 Days) Modulates Growth Factors Patient: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 fold change (Log2) • Baseline patient samples were compared to Day 28 plasma samples using unbiased proteomics approach • 18424 treatment resulted in – Increased EPO – D
Slide 20: Other Aspects of Myelofibrosis
INCB018424 Treatment (25 mg BID): Other Aspects of Myelofibrosis • Bone Marrow – No significant changes in fibrosis score or cellularity – No significant change in blasts • Peripheral Blood – No significant change in LDH – No significant change in CD34+ cells 20
Slide 21: INCB018424: Clinical Adverse Events
INCB018424: Clinical Adverse Events INCB18424 is well tolerated Adverse events (all causalities) occurring in more than one patient (all AEs mild to moderate in severity) MedDRA Term 25 mg BID 10 mg BID N 27 12 Diarrhea 2 0 Edema 2 0 Dyspnea 2 0 Rash 2 0 Urinary tract infection 2 1 21
Slide 22: INCB01842: Hematologic Abnormalities
INCB01842: Hematologic Abnormalities 25 mg BID 10 mg BID Parameter N=27 N=12 CTCAE Grade Hgb* ANC Platelets Hgb* ANC Platelets N=13 N=4 3 2 1 6 0 0 0 4 0 0 2 1 0 0 9 patients had grade 3 or 4 hematological abnormalities *Includes only subjects who were transfusion independent at entry 22
Slide 23: Current Status of BID Cohorts: Dose Modifications and Discontinuations
Current Status of BID Cohorts: Dose Modifications and Discontinuations Study INCB 18424-251 25 mg BID 10 mg BID N=27 N=12 On Study Discontinue On study N=23 N=4 N=12 Remain on 25 mg BID Myelosuppression Remain on 10 mg BID N=16 N=2 N=8 Dose Reduction Disease Progression/other Dose increase N=7 N=2 N
Slide 24: Spleen Size Reduction with Once Daily Doses: Preliminary Data
Spleen Size Reduction with Once Daily Doses: Preliminary Data 27.5 25 mg QD, N=6 25.0 50 mg QD, N=7 22.5 100 mg QD, N=3 20.0 Spleen Size, cm 17.5 N=6 15.0 N=5 12.5 N=7 N=3 10.0 7.5 N=3 N=3 5.0 2.5 0.0 0 10 20 30 40 50 Days on Study 24
Slide 25: Summary
Summary INCB018424: • Is well tolerated at clinically active doses – Reversible thrombocytopenia is the dose limiting toxicity • Manageable with dose reduction (or if necessary, dose interruption) in most patients • Is associated with marked and durable improvement in spleen size • Is associated wit
Slide 26: INCB018424-251: Ongoing Cohorts
INCB018424-251: Ongoing Cohorts • Assessment of QD regimens • Individual dose titrations between 10 mg BID and 25 mg BID • Exploration of functional and symptomatic end points of clinical efficacy 26