Previous Clinical Experience The RESPONSE Trial CINC424B2301 Previous Clinical Experience Victor Sandor, MD VP Global Oncology Drug Development Incyte Corporation 1

Outline INC424 clinical experience in healthy volunteers Key findings from: Single and multiple ascending dose studies Drug interaction studies Pharmacokinetics in patients with renal or hepatic insufficiency INC424 clinical experience in MPNs Polycythemia vera Essential thrombocythemia Myelofibrosis 2

Clinical Evaluation of INC424 in Phase I 3

INC424 Phase I Clinical Summary Study # Study Description # of Subjects 131 Single ascending dose in HVs 30 132 10-day multiple ascending dose in HVs 71 133 One-way interaction with ketoconazole and erythromycin in HVs 31 134 Single Dose mass balance and metabolite profile in HVs 6 135 One-way interaction with rifampin in HVs 12 136 Two-way interaction with methotrexate in RA patients 18 137 PK evaluation of 25 mg in subjects with hepatic dysfunction 32 138 Definitive QT study in HVs 50 139 Relative bioavailability of INC424 SR formulation in HVs 9 142 PK evaluation of 25 mg in subjects with renal impairment 40 4

INC424 Phase I Key Findings Safety and tolerability Well tolerated: most common AEs were headache, dizziness and nausea occurred with similar frequency in PBO and INC424 groups Moderate to severe neutropenia noted in 3/9 subjects at 50 mg BID (highest dose evaluated in HVs): defined MTD as 25 mg BID Pharmacokinetics and pharmacodynamics Rapid absorption, PK linear with respect to dose, T1/2 = 3 hr No accumulation of drug or metabolites with repeat administration No significant effect of food (can be taken without regard to meals) Dose-dependent inhibition of STAT3 phosphorylation in blood Effects of renal Impairment Subjects requiring dialysis showed prolonged PD activity; no significant effects observed in mild, moderate or severe impairment Subjects with severe kidney disease (eGFR < 30) or on dialysis will be excluded from Phase III 5

INC424 Phase I Key Findings (cont’d) Effects of hepatic dysfunction AUCs were 88%, 29% and 66% higher in subjects with mild, moderate or severe hepatic dysfunction (vs. normal), respectively Subjects with known hepatocellular disease or evidence of encephalopathy will be excluded from Phase III Drug-drug interactions Ketoconazole (potent CYP inhibitor) increased AUC 2x Decrease INC424 dose with concomitant potent CYP inhibitors Erythromycin (moderate CYP inhibitor) no significant impact on PK No INC424 dose adjustment necessary Rifampin (potent CYP inducer) decreased Cmax and AUC by 52% and 71%, respectively Potent inducers (rifampin, St. John’s Wort) excluded from Phase III Moderate inducers (e.g. rifabutin, phenytoin) will not require dose modification, but additional PK sampling will be required during use 6

Clinical Evaluation of INC424 in Phase II: Advanced PV 7

Phase II Study in Advanced PV and ET Part 1 Evaluation of 10 mg BID, 25 mg BID and 50 mg QD regimens in patients with advanced PV and ET for 8 weeks (6-8/group) Part 2 Expansion at 10 mg BID in PV and 25 mg BID in ET with allowance for individualized dose titration Polycythemia Vera (N=34) Open-label, single arm study of INC424 N = 73 patients 34 patients with PV 39 patients with ET Eligibility criteria HU refractory or intolerant PV: HCT>45% or q3mo phlebotomy requirement ET: Platelet count > 650K 10 mg BID* (n=7) 25 mg BID* (n=8) 50 mg QD (n=7) 10 mg BID (n=12) Part 1 Part 2 Essential Thrombocythemia (N=39) 10 mg BID (n=8) 25 mg BID (n=8) 50 mg QD (n=8) 25 mg BID (n=15) Part 1 Part 2 Individualized dose titration was allowed subsequent to Week 8 8

PV Patient Characteristics Characteristic (median) PV (n = 34) Age, years 58 Female 50% Months from Diagnosis 115 Refractory to HU 74% Hct % 46.7 Phlebotomy in last 6 months 76% Platelets x109/L 527 WBC x109/L 13.2 Splenomegaly Size, cm (range) 9 (1-21) No. Prior Therapies 1 (1-3) JAK2V617F positive 100% JAK2V617F allele burden 72%

PV Patient Disposition 28 of 34 (82%) continue on study with a median follow-up 15 months (range 8-21 mos) 6 patients (18%) have discontinued treatment 2 due to AEs, 1 lack of response, 2 withdrew consent, 1 for disease progression Majority of patients on study are being treated at doses of 5 mg BID (25%) or 10 mg BID (39%) Median duration on 5 mg BID is 11 months Median duration on 10 mg BID is 6 months

Treatment-related AEs* Overall Safety in PV INC424 (N=34) Treatment-related AEs* All Grades Grade 3 Anemia 25 (73.5%) 0 (0%) Thrombocytopenia 10 (29.4) 2 (5.9) Leukopenia 5 (14.7) 0 (0.0) Weight increased Diarrhea 3 ( 8.8) Hyperuricemia Insomnia Palpitations *Occurring in at least 3 subjects; at least ‘possibly’ related No treatment-related Grade 4 AEs have occurred on study Hematologic AEs are generally reversible and managed with dose reduction or temporary interruption 11

Serious Adverse Events in PV Five subjects have reported 8 treatment-emergent serious adverse events (SAEs) Pneumonia and, one year later, congestive heart failure (both unrelated): subject continued on study Pneumonia (unrelated): subject continued on study Renal tumor (possibly related): subject discontinued Gastric bleeding (unlikely related): subject continued on study Atrial flutter (possibly related); thrombocytopenia and anemia (unrelated) 6 weeks post-treatment: subject discontinued

Hematocrit Control Hematocrit Control Response Rate Through Week 32 94% of patients have achieved hematocrit normalization in the absence of phlebotomy after 32 weeks of treatment This is an ITT analysis.

Threshold for response Reduction in Palpated Spleen Length Reduction in Palpated Spleen Length Through Week 36 8 5 4 4 3 Threshold for response by palpation Mean ± SE The mean reduction in palpated spleen length after 36 weeks of treatment for patients with ≥ 5 cm spleen length at baseline is 74% 69% of patients achieved ≥ 50% reduction in spleen length after 36 weeks

Response Durability and Hematologic Remission Phlebotomy independence and spleen response have been maintained in 100% of responding patients at their last follow-up visit (median duration > 1 year) Complete Hematologic Remission 32% of patients with leukocytosis and/or thrombocytosis at baseline achieved complete hematologic remission (normal hematocrit, white count and platelet count) after 32 weeks of treatment

Mean Symptom Severity Scores Symptomatic Improvement Mean Symptom Severity Scores Through Week 36 Rapid improvements in patient reported symptom scores observed following INC424 treatment Responses have been durable in the majority of responding patients through the last follow-up visit on study Pruritus Bone pain Night sweats 4 8 12 24 36

Starting Dose Selection in PV Three regimens, 10 mg BID, 25 mg BID, and 50 mg QD, were evaluated in Phase 2 10 mg BID has achieved an optimal balance of efficacy and safety All regimens equally effective at reducing palpable spleen length, however 10 mg BID and 25 mg BID were most effective in achieving HCT control without phlebotomy and normalizing platelets and WBCs 10 mg BID exhibited an attractive hematologic safety profile, with 2 of 19 subjects exhibiting ≥ Grade 2 toxicity, and both managed with dose modification/interruption 10 mg BID (n=19) 25 mg BID (n=8) 50 mg QD (n=7) Anemia 2 (Gr. 2) Leukopenia 1 (Gr. 2) 2* (Gr. 2) Thrombocytopenia 1 (Gr. 3) 1* (Gr. 2) *Same subject

Starting Dose Selection in PV Subsequent to Week 8 of treatment, when individualized dose titrations are allowed, the majority of subjects are being maintained on doses of 5, 10, or 15 mg BID 10 mg BID will be the initial starting dose of INC424 in the Phase 3 RESPONSE study 10 mg QD if receiving a concomitant CYP inhibitor Treatment Duration 5 mg BID 10 mg BID 15 mg BID >15 mg BID 3 months 35% 32% 3% 30% 9 months 18% 15% 15 months 14% 38% 17%

Clinical Evaluation of INC424 in Phase II: Advanced ET 19

ET Patient Characteristics Characteristic (median) ET (n = 39) Age, years 51 Female 64% Months from Diagnosis 88 Refractory to HU 87% Hct % 41.0 Platelets x109/L 849 (mean 1009) WBC x109/L 8.2 Splenomegaly Size, cm (range) 10% 5 (3-7) No. Prior Therapies 1 (1-3) JAK2V617F positive 65% JAK2V617F allele burden 16%

ET Patient Disposition 29 of 39 (74%) continue on study with a median follow-up 15 months (range 4-21 mos) 10 patients (26%) have discontinued treatment 4 due to AEs, 4 lack of response, 2 withdrew consent Majority of patients on study are being treated at 10 BID or 25 BID (each 23%) with 60% at < 15 mg BID Median duration on 10 mg BID is 12 months Median duration on 25 mg BID is 18 months

Treatment-related AEs* Overall Safety in ET INC424 (N=39) Treatment-related AEs* All Grades Grade 3 Anemia 29 (74.4%) 0 (0%) Weight increased 9 (23.1) Herpes zoster 2 (5.1) 0 (0.0) Hyperuricemia Leukopenia Pain in extremity Palpitations *Occurring in at least 2 subjects; at least ‘possibly’ related No treatment-related Grade 4 AEs have occurred on study Hematologic AEs are generally reversible and managed with dose reduction or temporary interruption 22

Serious Adverse Events in ET Six subjects have reported 6 treatment-emergent SAEs Gastric bleeding (unrelated): subject continued on study Bronchitis (unrelated): subject continued on study Diarrhea (unrelated): subject continued on study Renal failure (possibly related): subject discontinued Cholecystitis (unlikely related): subject continued on study Headache (unlikely related): subject continued on study

Platelet Count Reduction in ET 46% achieved normal platelet counts; 82% achieved < 600,000 or a > 50% reduction 16 of 18 subjects with baseline platelet counts > 900,000 have achieved greater than a 50% reduction

Clinical Evaluation of INC424 in Phase II: Myelofibrosis 25

Phase I / II Study Design in MF Established 25 mg BID and 100 mg QD as maximum tolerated doses Phase 2 Expansion of 25 mg cohort Individualized dose optimization based on safety and efficacy N=153 patients Myeloproliferative neoplasm Primary myelofibrosis (MF) Post-essential thrombocythemia MF Post-polycythemia vera MF Eligibility criteria Relapsed / refractory disease or severe side effects from therapy Newly diagnosed patients with intermediate- or high-risk disease (Lille system) or symptomatic splenomegaly / hepatomegaly ECOG 0-2 Neutrophils >1500 cells/μL Platelets >100,000 cells/μL INCB018424 (twice daily dosing) (n=116) 10 mg BID* (n=29) 15 mg BID* (n=35) 25 mg BID (n=47) 50 mg BID (n=5) *Dose increases allowed (monthly, 5-mg increments) up to 25 mg daily, if no response and no toxicity (individualized dose adjustment). INCB018424 (once daily dosing) (n=37) 25 mg QD (n=6) 50 mg QD (n=22) 100 mg QD (n=6) 200 mg QD (n=3) Dose reductions/interruptions were allowed for patients who developed grade 3/4 toxicities. If toxicity did not resolve within 2 cycles, therapy was discontinued. Verstovsek S, et al. N Engl J Med. 2010;363:1117-1127. 26

75% of randomized patients remain on study after 2+ years of follow-up Non-hematologic Toxicities in MF 75% of randomized patients remain on study after 2+ years of follow-up Related Adverse Events* All Grades, % Grade 3 or 4, % Diarrhea 5.9 Fatigue 4.3 1.3 Headache 3.3 Peripheral edema 2.6 Pain in extremities Urinary tract infection Dizziness Dyspnea *AEs thought to be at least possibly related to study medication occurring in >2% of the study population. 27

Hematologic Toxicities in MF 35% had dose escalation to 20 or 25 mg 60% had dose reduction / interruption Twice Daily Dosing 10 mg BID (n=29) 15 mg BID (n=35) 25 mg BID (n=47) Thrombocytopenia, n (%) Grade 3 Grade 4 3 (10%) 1 (3%) 11 (23%) 3 (6%) New-onset anemia* n / N (%) 3 / 19 (16%) 2 / 24 (8%) 8 / 30 (27%) *Among patients who were transfusion-independent at baseline. 28

At Least Possibly Related Serious Adverse Events Serious Adverse Events All Causality No. of Patients (%) At Least Possibly Related All SAEs 59 (39) 12 (7.8) Common SAEs Pneumonia 10 (6.5) 1 (0.7) Fever 6 (3.9) 2 (1.3) Anemia 4 (2.6) 3 (2.0) Acute Myeloid Leukemia Asthenia Systemic Inflammatory Response Syndrome Anxiety Constitutional symptoms Insomnia Use of gradual dose tapering or short-term courses of corticosteroids have been used in MF patients requiring treatment discontinuation 29

Rapid reduction in spleen size, durable beyond 1 year of therapy Reduction in Palpated Spleen Lengths and MRI-Based Volumetric Assessment Rapid reduction in spleen size, durable beyond 1 year of therapy Parallel reduction in spleen size as detected by physical exam (length) and MRI (volume) 30

Percent of Patients Exhibiting a ≥ 50% Improvement in Symptom Score Symptomatic Improvement in MF Percent of Patients Exhibiting a ≥ 50% Improvement in Symptom Score Symptoms scores were assessed using a modified version of the patient-reported Myelofibrosis Symptom Assessment Form (MFSAF) 31

Phase III Program in MF Progressing US Registration Study: COMFORT-I Agreement with FDA on SPA Design: Blinded, randomized 1:1 INCB018424 vs. placebo Endpoints Primary: A statistically significant proportion of patients achieving at least 35% reduction in spleen volume at 24 weeks as compared to placebo Secondary: Durability of maintenance of a ≥ 35% reduction in spleen volume & a statistically significant proportion of patients achieving a ≥ 50% reduction in symptom score as compared to placebo EU Registration Study: COMFORT- II Received scientific advice from EMA Design: Unblinded, randomized 2:1 INCB018424 vs. best available Endpoints Primary: A statistically significant proportion of patients achieving at least 35% reduction in spleen volume at 48 weeks as compared to best available Secondary: Durability of maintenance of a ≥ 35% reduction in spleen volume Fully enrolled; 309 patients NDA filing expected 1H/2011 Fully enrolled; 219 patients MAA filing expected mid-2011

INC424 Clinical Summary The primary clinical risks with treatment are sequelae of decreased hematopoietic proliferation secondary to the inhibition of growth factor pathways by JAK2 inhibition Anemia, thrombocytopenia and less frequently neutropenia have been observed in MPN patients and are generally managed by dose modification and/or dose interruption INC424 has achieved marked and durable benefits in patients with myeloproliferative neoplasms Spleen size, symptomatic burden, weight and exercise capacity in MF Platelet count and symptomatic burden in advanced ET Splenomegaly, phlebotomy dependence, leukocytosis, thrombocytosis, and symptomatic burden in advanced PV