This document summarizes a Phase 2 clinical trial exploring the safety, tolerability, and efficacy of escalating doses of INCB039110, an oral JAK1 inhibitor, in subjects with chronic plaque psoriasis over 28 days. The trial found that INCB039110 produced statistically significant improvements in psoriasis severity compared to placebo based on measures like the static Physician's Global Assessment and PASI 50 response. Treatment was generally well tolerated with no evidence of myelosuppression. Decreases in platelets and increases in LDL and HDL were observed but remained within normal limits. The results demonstrate the potential for JAK1 inhibition as an effective oral treatment for psoriasis.

1. 1
INCB018424
Topical JAK1/JAK2 Inhibitor:
A Double-Blind, Placebo-Controlled Study
Exploring the Safety, Tolerability, and Efficacy
of a 28-Day Course of Escalating Doses of an
Oral JAK 1 Inhibitor (INCB039110) in Subjects
with Stable, Chronic Plaque Psoriasis
R. Bissonnette, A. Menter, R. Fidelus-Gort, S. Jackson,
H. Zhang, R. Flores, R. Newton, P. Scherle,
S. Yeleswaram, X. Chen, M. Luchi
European Academy of Dermatology and Venereology
Istanbul, Turkey
October 3, 2013

2. 2
Disclosures
 R. Bissonnette
– Received grants or honoraria serving as a consultant or investigator for:
Abbvie, Amgen, Astellas, Celgene, Eli Lilly, Galderma, GSK-Stiefel,
Incyte, Merck, Isotecknica, Janssen, LEO Pharma, Novartis, Pfizer
 A. Menter
– Received grants or honoraria serving as a consultant, investigator,
advisory board member, or speaker for: Abbott, Allergan, Amgen,
Celgene, Eli Lilly, Galderma, Janssen, LEO Pharma, Novartis, Novo
Nordisk, Pfizer, Stiefel, Syntrix Biosystems, Wyeth
 S. Jackson, H. Zhang, R. Flores, R. Newton, P. Scherle,
S. Yeleswaram, X. Chen, M. Luchi
– Employee and stock/stock options: Incyte Corporation
 R. Fidelus-Gort
– Former employee: Incyte Corporation

3. 3
INCB039110 Is a Potent and Selective Inhibitor of JAK1
 Janus kinase (JAK) inhibition has demonstrated therapeutic activity in
oncology/hematology and chronic inflammatory diseases
 JAK1-selective inhibition offers the possibility of achieving anti-inflammatory
effects while avoiding the potential deleterious side effects arising from
JAK2 (i.e. myelosuppression) and JAK3 (i.e. immunosuppression) inhibition
 INCB039110 is a potent and selective inhibitor of JAK1, with >20 and
>200-fold selectivity over JAK2 and JAK3, respectively
 INCB039110 is efficacious in the rat
adjuvant-induced arthritis model at
exposures that do not effect EPO-
induced stimulation of reticulocytes
 INCB039110 is being studied in
multiple PoC Phase 2 trials —
psoriasis, rheumatoid arthritis and
myelofibrosis — to define its clinical
efficacy and safety profile
%Inhibition

4. 4
 28-day, double-blind, placebo-controlled dose escalation study
– 4 staggered groups of 12 subjects each (9 active and 3 placebo)
 Primary endpoint: Mean percent change from baseline in sPGA at Day 28
 Key secondary endpoints:
– Percentage of patients achieving sPGA 0 or 1 (clear or minimal)
– Percentage of patients achieving PASI 50
INCB39110-250: Phase 2 Study Design
Dec
Study
Period
Study Day
Screen
-28 to -1
28-Day Treatment Period Follow-up
42+ 56
100 mg QD
Placebo QD
200 mg QD
Placebo QD
200 mg BID
Placebo BID
600 mg QD
Placebo QD
*Randomization on Day 1 +Telephone Contact
Jun OctAug Nov

5. 5
INCB39110-250: Phase 2 Study Population
Inclusion Criteria
 History of chronic plaque psoriasis for ≥ 6 months at screening
 Body surface area (BSA) of plaque psoriasis ≥ 5%
 Psoriasis Area and Severity Index (PASI) score of ≥ 5
 Static Physician’s Global Assessment (sPGA) score of ≥ 3
 Prior inadequate response to topical therapies for the treatment of psoriasis
Exclusion Criteria
 Previous systemic therapy within 4 weeks before randomization (including
psoralens, UV A light therapy, cyclosporine, methotrexate, steroids,
retinoids, MMF, AZA, vitamin D3)
 Phototherapy (including UV B or tanning beds) within 4 weeks prior to
randomization
 History of neutropenia, thrombocytopenia, anemia or evidence of bone
marrow function impairment (ANC < 2 x 109/L, platelet count < 125 x 109/L)

6. 6
INCB39110-250: Demographics and Baseline
Disease Characteristics
Placebo
(N=12)
INCB039110
100 mg QD
(N=9)
200 mg QD
(N=9)
200 mg BID
(N=9)
600 mg QD
(N=11)
Mean age, y 49 48 47 53 46
Gender, n 8 Male 6 Male 8 Male 5 Male 5 Male
Race, n 12 White 9 White 9 White 9 White 11 White
Median BMI,
kg/m2
27.1 27.5 28.4 29.1 26.6
Median sPGA
score
3.0 3.0 3.0 3.0 3.0
Median PASI
score
8.9 9.6 8.6 9.8 12.4
Median BSA of
psoriasis, %
7.6 7.8 6.8 8.5 9.9
Median DLQI
score
5.0 4.0 7.0 12.0 7.0

7. 7
INCB39110-250:
Patient Disposition (mITT Population)
 The majority of patients completed the study
Variable, n (%)
Placebo
(N=12)
INCB039110
Total
(N=50)
100 mg QD
(N=9)
200 mg QD
(N=9)
200 mg BID
(N=9)
600 mg QD
(N=11)
Patients
completed study
12
(100.0)
9
(100.0)
8
(88.9)
8
(88.9)
11
(100.0)
48
(96.0)
Patients
withdrawn
0 0 1
(11.1)
1
(11.1)
0 2
(4.0)
Primary reason
for withdrawala:
Consent
withdrawn
0 0 0 1
(11.1)
0 1
(2.6)
Noncompliance
with study drug
0 0 1
(11.1)
0 0 1
(2.6)
a No patients were withdrawn from the study because of a TEAE, protocol deviation, lack of efficacy, death, or were lost to follow-up

8. 8
INCB39110-250:
Summary of Efficacy Endpoints at Day 28
 Evidence of efficacy as assessed by sPGA observed at all doses
compared to placebo
 Efficacy also observed for percent of patients who achieved clear or
almost clear sPGA and for PASI 50 as compared to placebo
Placebo
(N=12)
INCB039110
100 mg QD
(N=9)
200 mg QD
(N=9)
200 mg BID
(N=9)
600 mg QD
(N=11)
Mean %
change sPGA
–12.5% –22.2% –29.4% –35.2% –42.4%*
% sPGA clear
or minimal
0% 11.1% 22.2% 33.3% 45.5%*
% PASI 50 8.3% 22.2% 66.7%* 44.4% 81.8%*
*P <0.05 vs placebo.

9. 9
INCB39110-250: Mean Percent Change in sPGA
at Day 28
*P <0.05 vs placebo
INCB039110

10. 10
INCB39110-250: Percentage of Patients with
sPGA of 0 or 1 at Day 28
-0.7
*P <0.05 vs placebo
INCB039110

11. 11
INCB39110-250: Percentage of Patients
Achieving PASI 50 at Day 28
-0.7
*P <0.05 vs placebo
INCB039110

12. 12
INCB39110-250: Response Rates for Patients with
BSA ≥ 10% versus Patients with BSA < 10% at Day 28
Parameter
BSA ≥ 10% (n=15) BSA < 10% (n=35)
Placebo
(n=1)
INCB039110
600 mg QD
(n=5)
All other
INCB039110
doses
(n=9)
Placebo
(n=11)
INCB039110
600 mg QD
(n=6)
All other
INCB039110
doses
(n=18)
Mean % change
of sPGA
0% –40.0% –33.3% –13.6% –44.4% –26.8%
Proportion of
patients who
achieve PASI 50
0% 100% 44.4% 9.1% 66.7% 44.4%
 Skin involvement as measured by BSA does not appear to influence
efficacy of INCB039110

13. 13
INCB39110-250:
Treatment-Emergent Adverse Events
Overall Summary of Treatment-Emergent Adverse Events
Treatment-Emergent Adverse Events in ≥ 2 Patients in Total of Active Groups
Variable, n (%)
Placebo
(N=12)
INCB039110
Total
INCB039110
(N=38)
100 mg QD
(N=9)
200 mg QD
(N=9)
200 mg BID
(N=9)
600 mg QD
(N=11)
Death 0 0 0 0 0 0
SAE 0 0 0 0 0 0
TEAE 4 (33.3) 3 (33.3) 5 (55.6) 6 (66.7) 5 (45.5) 19 (50.0)
TEAE ≥ Grade 3 0 0 0 0 0 0
Treatment-related TEAE 2 (16.7) 0 2 (22.2) 1 (11.1) 1 (9.1) 4 (10.5)
Withdrawal or discontinuation
from the study because of a
TEAE
0 0 0 0 0 0
MedDRA Preferred Term, n (%)
Placebo
(N=12)
INCB039110
Total
INCB039110
(N=38)
100 mg QD
(N=9)
200 mg QD
(N=9)
200 mg BID
(N=9)
600 mg QD
(N=11)
Patients with any TEAE 4 (33.3) 3 (33.3) 5 (55.6) 6 (66.7) 5 (45.5) 19 (50.0)
Nasopharyngitis 1 (8.3) 1 (11.1) 2 (22.2) 1 (11.1) 3 (27.3) 7 (18.4)
AST increased 0 0 2 (22.2) 0 0 2 (5.3)
Headache 0 1 (11.1) 0 0 1 (9.1) 2 (5.3)
Hypertriglyceridemia 0 0 1 (11.1) 0 1 (9.1) 2 (5.3)

14. 14
INCB39110-250:
Hematologic Parameters at Day 28
Placebo
INCB039110
100 mg
QD
200 mg
QD
200 mg
BID
600 mg
QD
Hemoglobin,
g/dL
14.60
(0.02)
13.38
(–0.30)
14.99
(0.13)
15.04
(0.09)
14.15
(–0.31)
Lymphocytes,
x109/L
1.686
(0.096)
1.809
(–0.030)
1.861
(0.054)
2.089
(0.356)
2.155
(0.256)
Neutrophils,
x109/L
4.631
(–0.120)
4.007
(–0.846)
4.910
(0.128)
4.716
(0.069)
4.759
(–0.498)
Platelets,
x109/L
251.4
(14.2)
218.0
(–12.7)
207.3
(–19.5)
190.1
(–32.6)
207.6
(–51.9)
Mean Value at Day 28 (absolute change from baseline)

15. 15
INCB39110-250: Lipid Parameters at Day 28
Placebo
INCB039110
100 mg
QD
200 mg
QD
200 mg
BID
600 mg
QD
Total Cholesterol,
mmol/L
5.665
(0.313)
4.672
(0.253)
5.957
(0.779)
5.409
(0.637)
6.205
(1.099)
HDL, mmol/L
1.618
(0.003)
1.169
(–0.017)
1.476
(0.113)
1.531
(0.286)
1.697
(0.281)
LDL, mmol/L
3.272
(0.249)
2.616
(0.115)
3.637
(0.393)
2.943
(0.229)
3.576
(0.698)
HDL/LDL Ratio
0.530
(–0.118)
0.466
(–0.036)
0.423
(–0.008)
0.604
(0.098)
0.554
(0.008)
Mean Value at Day 28 (absolute change from baseline)

16. 16
Conclusions
 INCB039110, a potent and selective inhibitor of JAK1, has
demonstrated proof-of-concept in chronic plaque psoriasis
 Treatment with INCB039110 demonstrated efficacy in sPGA and
PASI 50 over 4 weeks of therapy
 INCB039110 treatment was generally well tolerated, with no
evidence of myelosuppression
– Decreases in platelet counts occurred and generally remained
within normal limits, reflecting a positive impact on this acute
phase reactant
– Increases in LDL and HDL were also noted, with no dose
associated change in HDL/LDL ratio
 These results demonstrate the potential for JAK1 inhibition as an
effective oral approach to the treatment of psoriasis

17. 17
INCB39110-250 Investigators
R. Bissonnette, MD / INNOVADERM Research Inc., Montreal, QC, Canada
M. Bourcier, MD / Durondel C.P. Inc/Dermatology Clinic, Moncton, NB, Canada
S. Kempers, MD / Minnesota Clinical Study Center, Fridley, MN, United States
Y. Poulin, MD / Centre de Recherche Dermatologique du Québec Métropolitain, Québec, QC, Canada
R. Sofen, MD / Dermatology Research Associates, Los Angeles, CA, United States
D. Stewart, DO / Michigan Center Skin Care Research, Clinton Township, MI, United States
D. Stough, MD / Burke Pharmaceutical Research, Hot Springs, AR, United States
J. Tan, MD / Windsor Clinical Research, Windsor, ON, Canada
J. Tu, MD / Skin Search of Rochester, Inc., Rochester, NY, United States