Celgene I&I Overview Celgene I&I Overview Scott Smith Senior VP , Global Head of I&I
Celgene I&I OverviewCelgene I&I Overview
Scott Smith Senior VP, Global Head of I&I,
Forward Looking Statements and Adjusted Financial Information
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In addition to financial information prepared in accordance with U.S. GAAP, this presentation alsocontains adjusted financial measures that we believe provide investors and management withsupplemental information relating to operating performance and trends that facilitate comparisonsbetween periods and with respect to projected information. These adjusted financial measures arenon-GAAP and should be considered in addition to but not as a substitute for the informationnon GAAP and should be considered in addition to, but not as a substitute for, the informationprepared in accordance with U.S. GAAP. We typically exclude certain GAAP items thatmanagement does not believe affect our basic operations and that do not meet the GAAP definitionof unusual or non-recurring items. Other companies may define these measures in different ways.Further information relevant to the interpretation of adjusted financial measures, and reconciliations
f th dj t d fi i l t th t bl GAAP b f d
2
of these adjusted financial measures to the most comparable GAAP measures, may be found onour website at www.Celgene.com in the “Investor Relations” section.
Agenda
• Welcome / Introduction Scott Smith
• PALACE Program Efficacy Chris Edwards MD
• PALACE Program Safety, Behçet’s Artie Kavanaugh MD
• Q&A
• Apremilast Positioning Mark Krestonp g
• Launch Readiness Terrie Curran
• Conclusion Scott SmithConclusion Scott Smith
• Q&A
3
Building I&I Through Executing Successful Business Strategy
Target Target significant markets with high unmet1 Target Markets
Target significant markets with high unmet medical need1
Clinical Development
Conduct leading edge clinical development programs2
Launch Capabilities Build world class global launch capabilities3
Accelerate Portfolio
Accelerate I&I portfolio by developing pipeline through internal and external opportunities
4
4
Strong Execution with Multiple Positive Phase III Studies
20102010 20112011 20122012 20132013Q1Q1 Q2Q2 Q3Q3 Q4Q4 Q1Q1 Q2Q2 Q3Q3 Q4Q4 Q1Q1 Q2Q2 Q3Q3 Q4Q4 Q1Q1 Q2Q2 Q3Q3 Q4Q4
PALACE 1 PALACE 1 (n=504)(n=504)PALACE 1 PALACE 1 (n=504)(n=504)
PALACE 2PALACE 2 (n=488)(n=488)PALACE 2PALACE 2 (n=488)(n=488)
PALACE 3 PALACE 3 (n=505)(n=505)PALACE 3 PALACE 3 (n=505)(n=505)
PALACE 2 PALACE 2 (n=488)(n=488)PALACE 2 PALACE 2 (n=488)(n=488)
ESTEEM 1 (n=844)ESTEEM 1 (n=844)ESTEEM 1 (n=844)ESTEEM 1 (n=844)
PALACE 4 PALACE 4 (n=529)(n=529)PALACE 4 PALACE 4 (n=529)(n=529)
Behçet'sBehçet's--001 (n=111001 (n=111))Behçet'sBehçet's--001 (n=111001 (n=111))
ESTEEM 2 (n=413)ESTEEM 2 (n=413)ESTEEM 2 (n=413)ESTEEM 2 (n=413)
Approximately 3,500 patients in registration program
5
Significant Phase III Data Enhancing Profile
• PALACE Program (1-3) – PALACE 2 52-week Results (Oral)PALACE 2 52 week Results (Oral)– PALACE 3 52-week Update– Pooled Safety– Pooled Enthesitis/Dactylitis (Oral)– Pooled Laboratory Datay– Pooled HAQ-DI– Pooled TJC and SJC
• PALACE 4 DMARD Naïve 52-weekresults (Late Breaking)
• BCT -001 (Oral Plenary)
• CC-220 ( 2 Posters and Oral)– Moving to Phase II in 2014
6
Apremilast, an Oral Phosphodiesterase p , p4 Inhibitor, in Patients With Psoriatic
Arthritis and Current Skin Involvement: Results of a Phase 3, Randomized,
Controlled Trial (PALACE 3)Christopher J. Edwards, MD, FRCP
University Hospital SouthamptonSouthampton, UK
Charles Birbara1; Francisco J. Blanco2; Jeffrey Crowley3; ChiaChi Hu4; Randall M. Stevens4; Christopher J. Edwards5
1University of Massachusetts Medical School, Worcester, MA; 2INIBIC-Hospital Universitario A C ñ G li i S i 3B k fi ld D t l B k fi ld CA 4C l C tiCoruña, Galicia, Spain; 3Bakersfield Dermatology, Bakersfield, CA; 4Celgene Corporation,
Warren, NJ; 5University Hospital Southampton, Southampton, UK
Presented at: the 2013 ACR/ARHP Annual Meeting; October 26 -30, 2013; San Diego, CA. Abstract 311
7
PsA: Clinical Presentation
Back involvement
S
DIP involvement
Skin Involv
In the majority of patients, cutaneous lesions precede the
onset of joint pain
Nail psoriasis
vement
Peripheral involvement
E th th
Dactylitis
Enthesopathy
DIP: Distal interphalangeal
8
Summary of the ApremilastPALACE Programg
Study PALACE 1 PALACE 2 PALACE 3 PALACE 4 Patient Moderate to Moderate to Moderate to DMARD naïvePatient population (Active PsA)*
Moderate to severe psoriatic
arthritis
Moderate to severe psoriatic
arthritis
Moderate to severe psoriatic
arthritis withskin lesions
DMARD naïve moderate to
severe psoriatic arthritis
Prior treatments
Stratified by previous
DMARD and
Stratified by previous
DMARD and
Stratified by previous
DMARD and
None
biologic use/failure
biologic use/failure
biologic use/failure
Concurrent use with
Allowed Allowed Allowed No use with DMARDs Patients randomized
504 484 505 527randomized
9*Most patients had moderate to severe PsA
PALACE: Study Design
Baseline Week 4 Week 16 Week 24 Week 52 5 Years
Active Treatment Phase/Long-term Safety PhasePlacebo-Controlled
Phase
Apremilast 30 mg BID O
e§
Week –4 Apremilast 30 mg BIDApremilast 30 mg BID
*SCREEN Placebo
AN
DO
MIZ
E*1:
1:1
Es
cape
rand
omiz
e‡
RA
Early
Re-
r
Apremilast 20 mg BID Apremilast 20 mg BID Apremilast 20 mg BID
Stratify by DMARD use
(PALACE 1‒3)
Primary End Point: ACR20 at Week 16
and BSA ≥3% (PALACE 3)
*All doses were titrated over the first week of treatment.§Placebo patients whose swollen and tender joint counts had not improved by at least 20% at week 16 were required to be re-randomized to apremilast20 mg or 30 mg BID. ‡At week 24, all remaining placebo patients were re-randomized to apremilast 20 mg BID or 30 mg BID.DMARD=disease-modifying antirheumatic drug; BSA=body surface area; ACR20=20% improvement in modified American College of Rheumatology response criteria.
10
PALACE 3: ACR20/50/70 Responses Over 52-Weeks
Patients Receiving Apremilast From BaselineData as Observed
ACR20
Apremilast 20 mg BIDApremilast 30 mg BID
evin
g an
ns
e (%
)Pa
tient
s A
chie
AC
R R
espo
n
ACR50
10%
16 24 40 52
ACR70
Weeks
16 24 40 52
Edwards et al, ACR 2013. Abstract 311
11
PALACE 3: 52-Week Key Secondary Endpoints: SJC/TJC and DAS-28 (CRP)
M di % Ch i SJC/TJC
p ( )
% A hi i R i i
Patients Receiving Apremilast From BaselineData as Observed
Median % Change in SJC/TJC Over 52 Weeks
50
% Achieving Remission
20
30
40
ts A
chie
ving
(CR
P) <
2.6
(%)
30%
-70%
-79%
0
10
20
Patie
ntD
AS-
28 (
SJC and TJC
Apremilast 20 mg BID, n 162 146 127 122
Apremilast 30 mg BID, n 154 147 131 127
DAS-28 <2.6
Apremilast 20 mg BID, n/m 30/158 40/143 40/126 34/121
Apremilast 30 mg BID, n/m 31/154 33/145 39/131 38/127
16 24 40 52
Weeks
0
Edwards et al, ACR 2013. Abstract 311
12
Apremilast 20 mg BID Apremilast 30 mg BID
PALACE 3: 52-Week Key Secondary Endpoints: Skin Response and Disabilityp p y
M Ch i HAQ DIPASI 50 d PASI 75 R
Patients Receiving Apremilast From BaselineData as Observed
Mean Change in HAQ-DI
)
PASI-50
PASI-50 and PASI-75 Response
55%
an C
hang
e m
Bas
elin
e
ents
Ach
ievi
ngI R
espo
nse
(%)
PASI-7539%
Mea
Fro
Patie
PASI
-0.35%
HAQ-DIApremilast 20 mg BID, n 161 146 126 122Apremilast 30 mg BID, n 153 147 132 127
16 24 40 52
Weeks
016 24 52
Weeks
0
PASI-50Apremilast 20 mg BID, n/m 31/84 33/75 31/63Apremilast 30 mg BID, n/m 37/78 36/74 35/64
PASI 75PASI-75Apremilast 20 mg BID, n/m 19/84 21/75 18/63Apremilast 30 mg BID, n/m 19/78 23/74 25/64
Edwards et al, ACR 2013 . Abstract 311
13
Apremilast 20 mg BID Apremilast 30 mg BID
Psoriatic Arthritis: Clinical Presentation of Enthesitis and Dactylitisy
Enthesopathy Dactylitis
ACR Slide Collection on the Rheumatic Diseases. 3rd ed. 1994.
14
PALACE 1-3: Change in Enthesitis and Dactylitis Over 52-WeeksyPatients Receiving Apremilast From Baseline
Data as ObservedE th iti D t liti
ES
Weeks0 16 24 52
Enthesitis Dactylitis
0 16 24 52Weeks
ange
in M
ASE Apremilast 20 mg BID
Apremilast 30 mg BID
ent C
hang
e s
Cou
nt
Med
ian
% C
ha
Med
ian
Perc
ein
Dac
tylit
i
Apremilast 20 mg BID, n 291 264 215 197 188 157
‒100%‒66.7%
15
MASES=Maastricht Ankylosing Spondylitis Entheses Score.Note: A decrease in MASES or dactylitis count indicates symptom improvement.
Apremilast 30 mg BID, n 298 288 254 202 196 170
PALACE 1, 2 and 3Gladman et al ACR 2013 Abstract 311
PALACE 1-3: Primary Endpoint: ACR20 Responses at Week 16p
Per-Protocol Population, NRI
‡
pons
e (%
)
‡§
*
‡
*§
ving
AC
R R
esp *
atie
nts
Ach
iev
P
PALACE 1 PALACE 2 PALACE 3
168 163 161 154 159 151 164 163 159n=
16
*P<0.05, §P<0.005, ‡P≤0.0001 vs. placeboACR20=20% improvement in modified American College of Rheumatology response criteria; NRI=non-responder imputation.
Placebo Apremilast 20 mg BID Apremilast 30 mg BID
PALACE 1‒3: ACR20 Over 52-Weeks
80
ACR20 at Week 52Data as Observed
60
70
80PALACE 1 PALACE 2 PALACE 3
)
63%
40
50
60
s A
chie
ving
es
pons
e (%
)
55%53%
20
30
40
Patie
nts
AC
R20
Re
0
10
20
0
17
Weeks16 24 40 52
PALACE 1, 2 and 3Apremilast 30 mg BID arm
Apremilast in the Treatment of DMARD N ï P i i A h i iDMARD-Naïve Psoriatic Arthritis
Patients: Results of a Phase 3 RandomizedRandomized,
Controlled Trial (PALACE 4)Alvin F WellsAlvin F. Wells
Rheumatology and Immunotherapy CenterFranklin, WI
Alvin F. Wells1; Christopher J. Edwards2; Adewale O. Adebajo3; Alan J. Kivitz4; Paul Bird5; Kamal Shah6; ChiaChi Hu6; Randall M. Stevens6; Jacob A. Aelion7
Late Breaking Abstracts
18
Tuesday, October 29, 2013 2:30-4:00 PMSan Diego Convention Center: 6 A
Presentation Number: L4
PALACE 4: ACR20, ACR50, and ACR70 Scores at Week 52
Week 52 Data in Patients Originally Randomized to ApremilastData as observed
Apremilast 20 mg BID Apremilast 30 mg BID
n 131 138n 131 138
ACR20 (% responders) 53 59
ACR50 (% responders) 27 32ACR50 (% responders) 27 32
ACR70 (% responders) 14 18
• The primary end point was ACR20 at Week 16– Placebo: 16.9%– Apremilast 20 mg BID: 29.2% (P=0.0076 vs. placebo)– Apremilast 30 mg BID: 32.3% (P=0.0011 vs. placebo)
19 PALACE 4Wells et al, ACR 2013 Late Breaking Abstract # L4
PALACE: Summary
• In 4 Phase 3 trials, apremilast demonstrated clinically meaningful activity in the treatment of PsA includingmeaningful activity in the treatment of PsA, including signs and symptoms and physical functionality over 52-weeks
• Across various manifestations of PsA– Swollen / Tender Joints, Enthesitis, Dactylitis, Psoriasis
• Across the spectrum of patient populations – DMARD Naïve to Biologic Failure
A t bl f t fil d ll ll• Acceptable safety profile and was generally well tolerated
20
Considerations of Psoriatic Arthritis Therapy Selection
Arthur Kavanaugh, MDUniversity of California San DiegoUniversity of California, San Diego
21
Considerations of Psoriatic Arthritis Therapy Selectionpy
• Clinical Efficacy• Co-morbidity• Complicationsp• Convenience
Cost• Cost
22
PALACE 1‒3: ACR20 Over 52-Weeks
80
ACR20 at Week 52Data as Observed
60
70
80PALACE 1 PALACE 2 PALACE 3
)
63%
40
50
s A
chie
ving
es
pons
e (%
)
55%53%
20
30
Patie
nts
AC
R20
Re
0
10
23
Weeks
16 24 40 52
PALACE 1, 2 and 3Apremilast 30 mg BID arm
Comorbidities in PsA Patients
Psoriasis patients• Psychosocial burden• Reactive depression
Ocular inflammation(iritis/uveitis/episcleritis)
• Higher suicidal ideation• Alcoholism
IBD
Metabolic Syndrome• Hyperlipidemia• Hypertension PALACE 1, 2, & 3 Patient Population • Insulin resistant • Diabetes • Obesity Higher risk of cardiovascular
disease
• BMI >30 ~45% of pts• Hypertension ~40%• Hypercholesterolemia ~15%• Hyperlipidemia ~9%• Type 2 diabetes ~7.5%disease
24
PALACE 1-3: Pooled Safety: Overall Safety Profiley
Placebo-Controlled Phase(Weeks 0 to 24)*
Apremilast-Exposure Period(Weeks 0 to ≥52)§
Patients
Placebo(n=495)
APR 20 mg BID(n=720)
APR 30 mg BID(n=721)
n (%)EAIR/100
Patient-Years n (%)EAIR/100
Patient-Years n (%)EAIR/100
Patient-Years
1 AE 235 (47 5) 200 7 524 (72 8) 163 5 534 (74 1) 174 0≥1 AE 235 (47.5) 200.7 524 (72.8) 163.5 534 (74.1) 174.0
≥1 SAE 19 (3.8) 11.5 49 (6.8) 6.5 52 (7.2) 7.0
≥1 severe AE 19 (3.8) 11.5 48 (6.7) 6.5 60 (8.3) 8.2
AE leading to drug withdrawal
21 (4.2) 12.5 54 (7.5) 7.1 60 (8.3) 7.9
Death 0 (0.0) 0.0 1‡ (0.1) 0.1 0 (0.0) 0.0
*Includes all data through week 16 for patients initially assigned to placebo who escaped and all data through week 24 for all other patients
25
Includes all data through week 16 for patients initially assigned to placebo who escaped, and all data through week 24 for all other patients. §Includes all patients who received ≥1 dose of apremilast, regardless of when they were randomized.‡Multiorgan failure not suspected by the investigator to be treatment-related.
EAIR=exposure-adjusted incidence rate.Mease et al, ACR 2013 Abstract # 310
PALACE 1, 2 and 3
PALACE 1-3: Most Common Adverse Events
Placebo-Controlled Phase(Weeks 0 to 24)*
Apremilast-Exposure Period(Weeks 0 to ≥52)§
Patients
Placebo(n=495)
APR 20 mg BID(n=720)
APR 30 mg BID(n=721)
n (%)EAIR/100
Patient-Years n (%)EAIR/100
Patient-Years n (%)EAIR/100
Patient-Years
14 (2 8) 8 5 88 (12 2) 12 8 118 (16 4) 17 7Diarrhea 14 (2.8) 8.5 88 (12.2) 12.8 118 (16.4) 17.7
Nausea 23 (4.6) 14.0 71 (9.9) 9.9 111 (15.4) 16.2
Headache 23 (4.6) 14.1 65 (9.0) 9.1 80 (11.1) 11.3
URTI 15 (3.0) 9.1 82 (11.4) 11.6 67 (9.3) 9.3
Nasopharyngitis 13 (2.6) 7.8 57 (7.9) 7.9 50 (6.9) 6.8
*Includes all data through week 16 for patients initially assigned to placebo who escaped and all data through week 24 for all other patientsIncludes all data through week 16 for patients initially assigned to placebo who escaped, and all data through week 24 for all other patients. §Includes all patients who received ≥1 dose of apremilast, regardless of when they were randomized.‡Multiorgan failure not suspected by the investigator to be treatment-related.
26
EAIR=exposure-adjusted incidence rate.Mease et al, ACR 2013 Abstract # 310
PALACE 1-3: Diarrhea
18%
20%
N=1441 Patients in Apremilast-Exposure Period(Weeks 0 to ≥52)Severe
Mild/Moderate
6 pts
12%
14%
16%
18%
14.3%
6%
8%
10%
12%
200 pts 37 pts 22 pts0%
2%
4%
6%
1.5%2.6%
p p 22 pts0%Diarrhea Any Grade Used OTC Anti-Diarrheals Discontinuations due to
Diarrrhea– Occurred most often in the first 2 weeks of exposure to apremilast and resolved by week 4
(fi t t d i it) R d d i id ft th fi t th f d i
*
27
(first study visit). Reduced incidence seen after the first month of dosing– >80% patients that reported diarrhea, did not use OTC Anti-Diarrheal Medications – Most cases were self-limited and did not recur despite continued treatment with apremilast
*1 serious adverse event in patient with C. Difficile
PALACE 1-3: MACE, Malignancy, and Infection Rates
PlaceboPatient-Years=168.2
EAIR/100 Patient-
APR 20 mg BIDPatient-Years=766.4
EAIR/100 Patient-
APR 30 mg BIDPatient-Years=769.0
EAIR/100 Patient-
Apremilast TotalPatient-Years=1,535.4
EAIR/100 Patient-Years Years Years Years
MACE 0.0 0.3 0.1 0.2Potential MACE 0.6 0.5 0.5 0.5
Malignancy events
Hematologic 0.0 0.1 0.0 0.1Skin (excluding melanoma) 1.2 0.4 0.5 0.5
Solid (including melanoma) 0.6 0.3 0.1 0.2
Infection events
Non-opportunistic serious 0 6 0 4 0 5 0 5Non opportunistic serious infection 0.6 0.4 0.5 0.5
Systemic opportunistic infection 0.6 0.0 0.0 0.0
EAIR per 100 patient ears is 100 times the n mber (n) of patients reporting the e ent di ided b patient ears ( p to the first e ent start date for patients reporting
28
EAIR per 100 patient-years is 100 times the number (n) of patients reporting the event divided by patient-years (up to the first event start date for patients reporting the event). EAIR per 100 patient-years for major adverse cardiac events (MACE), serious infection, including systemic opportunistic infection, and malignancies were comparable to placebo.
PALACE 1, 2 and 3
EAIR=exposure-adjusted incidence rate.Mease et al, ACR 2013 Abstract # 310
PALACE 1-3: Select Marked Abnormalities in Clinical Chemistry Laboratory Parameters
Placebo-Controlled Phase
(Weeks 0 to 24)*
Apremilast-Exposure Period(Weeks 0 to ≥24)§
Apremilast-Exposure Period(Weeks 0 to ≥52)§
Marked Abnormalities‡
( )
Placebo(n=495)
Apremilast Apremilast
20 mg BID(n=720)
30 mg BID(n=721)
20 mg BID(n=720)
30 mg BID(n=721)
ALT >3X ULN 1/492 (0 2) 5/710 (0 7) 9/709 (1 3) 8/713 (1 1) 9/713 (1 3)ALT >3X ULN 1/492 (0.2) 5/710 (0.7) 9/709 (1.3) 8/713 (1.1) 9/713 (1.3)
Creatinine >1.7X ULN 1/492 (0.2) 1/710 (0.1) 1/709 (0.1) 1/713 (0.1) 1/713 (0.1)
Leukocytes <1.5 X 109/L 0/489 (0.0) 0/700 (0.0) 0/706 (0.0) 0/712 (0.0) 0/713 (0.0)
Neutrophils <1 X 109/L 2/488 (0.4) 1/698 (0.1) 1/705 (0.1) 4/712 (0.6) 4/713 (0.6)
Platelets <75 X 109/L 0/487 (0.0) 0/700 (0.0) 0/705 (0.0) 1/712 (0.1) 0/713 (0.0)
Hemoglobin, male <10.5 g/dL female <8 5 g/dL 1/489 (0.2) 3/700 (0.4) 3/706 (0.4) 5/712 (0.7) 6/713 (0.8)g/dL, female <8.5 g/dL ( ) ( ) ( ) ( ) ( )
• Marked abnormalities were infrequent and transient, resolving without intervention or discontinuation, and did not recur despite continuation of study drug
29
*Includes all data through week 16 for patients initially assigned to placebo who escaped, and all data through week 24 for all other patients. §Includes all patients who received ≥1 dose of apremilast, regardless of when they were randomized.‡Represents the number of patients with ≥1 occurrence of the abnormality at any time point/number of patients with ≥1 post-baseline value.Mease et al, ACR 2013 Abstract # 348
PALACE 1, 2 and 3
Apremilast for the Treatment of Behçet’s Syndrome: A Phase IIBehçet s Syndrome: A Phase II
Randomized, Placebo-Controlled, Double-Blind StudyDouble Blind Study
Gulen Hatemi1; Melike Melikoglu1; Recep Tunc2; Cengiz Korkmaz3; Banu Turgut Ozturk2; Cem Mat1; Peter A. Merkel4; Kenneth T. Calamia5;
Ziqi Liu6; Lilia Pineda6; Randall M. Stevens6; Hasan Yazici1; Yusuf Yazici7
1Istanbul University Cerrahpasa Medical School, Istanbul, Turkey; 2Selçuk University, Konya, Turkey; 3Eskişehir Osmangazi University, Eskişehir, Turkey; 4Boston University School of Medicine, Boston,
MA, USA; 5Mayo Clinic College of Medicine, Jacksonville, FL, USA; 6Celgene Corporation, Warren, NJ, USA; 7New York University School of Medicine New York NY USA
30
Hatemi et al, ACR 2013 Abstract # 761
USA; New York University School of Medicine, New York, NY, USA.
Primary End Point: Mean Number of Oral Ulcers at Week 12
3.5
Intent-to-Treat Population, LOCF (N=111)
2.1 (2.58)2.5
3.0
3.5
Ora
l Ulc
ers Placebo crossover to
apremilastApremilast discontinuation
0.5 (1.03)*1.0
1.5
2.0
n N
umbe
r of
wk0 wk2 wk4 wk6 wk8 wk10 wk12 wk14 wk16 wk18 wk20 wk22 wk24 wk26 wk28Placebo 2.9 1.7 1.9 1.9 1.6 1.4 2.1 0.4 0.4 0.6 0.5 0.3 0.4 1.3 1.6
0.0
0.5
Mea
n
30 mg BID 2.7 0.3 0.7 0.5 0.5 0.7 0.5 0.6 0.6 0.6 0.7 0.2 0.6 1.9 1.7
• 71% Complete Response, 89% Partial Response
31
*P<0.0001 vs. placebo.
Hatemi et al, ACR 2013 Abstract # 761
Q & AQ & A
32
I&I Global MarketingMark Kreston
VP I&I Gl b l M k tiVP, I&I Global Marketing
The Multinational Assessment of Psoriasisand Psoriatic Arthritis (MAPP) Survey
Conducted in 2012 by Celgene and overseen by an academic steeringcommittee of dermatology and rheumatology experts from around the world
3,426 PATIENTS WERE SURVEYED FROM 139,948 SCREENED HOUSEHOLDS IN7 COUNTRIES IN NORTH AMERICA AND EUROPE
34
Symptoms Contributing to Disease Severity
Psoriasis Patients (%) PsA Patients (%)Psoriasis Patients (%)
Bleeding, 3%
PsA Patients (%)
Lack of Sleep
Bleeding, 1%
Other, 9%
Itching, 38%Pain/Swelling of Joints, 5%
Lack of Sleep, 3%
gOther, 13%
Itching, 18%
Location/Size,
Lack of Sleep, 7%
, %
Location/SizeScales 11%
Flaking, 10%
, ,10%
Scales,5%Pain/Swelling of
Joints, 45%
Location/Size, 17%
Scales, 11%
Flaking, 5%
35
Lebwohl M, et al. Poster presented at the 22nd annual meeting of the European Academy of Dermatology and Venereology, 2013.
Medical Care and Treatment of PsA and Psoriasis
No Rx Topical only Oral +/- topical Oral + biologic Biologic +/- topical
2
8 55
14
80
100
8
55 52
31
19
40
60
Patie
nts
(%)
59% of PsA
32 3728
20
40P
patients are on No Rx or Topicals only
0 Moderate Psoriasisn=393
Severe Psoriasisn=166
PsA patientsn=712
Body Surface Area
36
Lebwohl M, et al. Poster presented at the 22nd annual meeting of the European Academy of Dermatology and Venereology, 2013.
Body Surface AreaData does not include use of phototherapy as monotherapy for psoriasis.
Patients Report an Overwhelming Desirefor Improved Therapies
54%of psoriasispatients and
57%of psoriasispatients and85%p
52%of psoriatic
arthritispatients said
biologic
p
45%of psoriatic
arthritispatients
discontinued
85%of Patients
Reported a Needfor Betterbiologic
therapy wasburdensome
discontinuedtheir biologic
therapyTherapies
37
Desired Attributes in PsA and PsO therapy
Efficacy SafetyStrong and durable
efficacy acrossmultiple disease
A unique safetyprofile with no known apparent risk ofmultiple disease
manifestationsapparent risk of malignancy or serious infection, and no exacerbation of comorbidities
Ease of UseA convenient treatment regimen
with oral dosing and lack of screening / lab monitoring
requirements
38
Apremilast Profile Has High Preference for Both Rheumatologists and Patients
Question: For your next 100 active Psoriatic Arthritis patients, to what percentage would you prescribe each option?
Question: If your physician provided you with the opportunity to SWITCH or ADD any one of the following products, which one, if any, would you choose?
36% 35%33%
30%
26%
n = 100 n = 31
16%
11% 10%
3%
11%
Stay with current therapy
Apremilast Methotrexate Humira Enbrel
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Source: Research conducted between March 25th and April 15th 2013
Apremilast Enbrel Humira Methotrexate
Rheumatologists Plan To Use Apremilast Before Biologics
Question: Of your next 100 patients on Apremilast, what percent of patients would you distribute to each of the following points in the therapy sequence?
~66% of patients would be pre-biologic
12% 54% 34%12% 54% 34%
0% 50% 100%
Before 1st DMARD DMARD Experienced After ≥ 1 biologic
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Before 1st DMARD DMARD Experienced After ≥ 1 biologic
Source: National Analysts, n=150 U.S. rheumatologists, Review of Apremilast PALACE 1-3 24 week Target Product Profile Q3 2013
PsA Launch ReadinessTerrie Curran
S CVP – US Commercial
Building a Global BrandApremilast PsA Strategic Imperatives
Increase rheumatologists’ appreciation of the unique characteristicsof PsA and the major unmet market need11
Build a strong brand that will transform the way physicians treat psoriatic disease22
Generate awareness of apremilast among patients anddrive brand requests33 q
Ensure access and successful trial and adoption44
Establish Celgene I&I as acommitted and trusted new partner55
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committed and trusted new partner
Launch Leadership Team Actively Managing Critical Launch Activities
Ensuring Accurate Demand Forecasting/ Securing Favorable Hiring and EffectivelyDemand Forecasting/ Readiness for Early
Launch
Securing Favorable Market Access On-Boarding the
Salesforce
• Pressure testing multiple scenarios and developing mitigation plans
• Identifying potential
• Both Regional Medical Liaisons and market access team expanded and in field
• Key Leadership in place:
– RSDs and DSMs
• Field Force recruitment Identifying potential actions that can be implemented at risk to expedite supply availability
• Conducting research with payer and Specialty Pharmacy for input in to the US Market Access strategy
on track:
– Recruiting Rheumatology Sales Force
strategy
• Initial discussions with payers
– On-board Jan 2014
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“Aggressive Customizers” and “High Biologic Users”Are Priority Segments
% of Rheums % of TRx Summary
C Hi h t TR l“Aggressive Customizers” 32% 50% • Highest TRx volume • Earlier adopters• Use broad range of drugs• Ready to embrace new optionsReady to embrace new options
“High Biologic Users ” 23% 25% • Efficacy-focused MDs who readily use biologics
• Least concerned re risks associated w/ biologicsassociated w/ biologics
“Low Volume/Conservative”
18% 3% • Desire to defer biologics• Slow Adopters
“C ti S iti t t d f t / i k“CautiousCost Conscious”
27% 22% • Sensitive to cost and safety/risk profile of products
• Slow adopters
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*% of TRx = Segment share of sum of DMARD Market TRx and Biologic Market TRx.
Patient Support Programs Are Critical Drivers of Pharmaceutical Adoption and Patient Adherence
Program Type
Brand
Starter Kits Sampling CouponsCustomer Cost
Savings –Annual OOP
Patient Assistance
Brand
• Rebates• Trial Offer $60 YES
• Trial Offer$• Rebates
• Loyalty Card$60 YES
• Support card • Trial Offer• Rebates $0 YESRebates• Brand Loyalty
Card
$0 YES
• Cost Support• Co-pay $60 YES
Reduction Card
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Sources: Campbell Alliance Analysis, September 2013; Brand and manufacturer websites, accessed September 2013.Notes: OOP=out-of-pocket; Trial Offer= represents a temporary free or discounted offer, to encourage patients to purchase products; Copay Reduction/Savings Card is a card provided to a patient that sets a maximum co-payment for a specific transaction or time period.
Building Towards a World Class Launch
• Secured US commercial organization: sales management, marketing, operations, market access & training
• Secured additional payer and contracting capability WorldSecured additional payer and contracting capability. payer profiling has commenced
• RML structure expanded
• Accelerating all key US branding activities
Class LaunchQ1.14
Accelerating all key US branding activities
• Building premium patient and physician support offering to simplify and expedite access
• Finalizing pricing and payer contracting strategyFinalizing pricing and payer contracting strategy
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SummaryScott Smith
S G f &Senior VP, Global Head of I&I
PALACE 1-4: ACR 20 Response Through Week 52 Observed Data 30 mg BID
80Primary End-Point
50
60
70a y d o t
63%59%55%53%
30
40
50 53%
10
20
0week 0 week 16 week 24 week 40 week 52
PALACE 1 PALACE 2 PALACE 3 PALACE4
48
ACR 20 Results at 1 Year
ACR20 at ~1 year
80Data as Observed
55 53
6359
6460
67
60
70
CR
20
48
30
40
50
s ac
hiev
ing
AC
10
20
30
% o
f pat
ient
s
0APR 30mg
OralPALACE 1
APR 30mgOral
PALACE 2
APR 30 mgOral
PALACE 3
APR 30 mgOral
PALACE 4
Enbrel25mg SC
Stelara90mg SC
PSUMMIT2
Stelara90mg SC
PSUMMIT1
Simponi 50mg SC
*
Data from individual studies
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Source: Mease et al J Rheumatol 2006; Ritchlin ACR 2013; McInnes Lancet 2013; Kavanaugh et al Arthritis Rheum 2012.
Data from individual studies
Phase III Safety Profile Differentiated
Apremilast* DMARDs Biologics
Serious infection
TB and opportunistic infection
Increased frequency of ymalignancies
Requirements for monitoring
Organ toxicity
Pregnancy Category C/B
GI tolerability
Competitive Advantage Competitive Disadvantage
50
p g p g
*Based on Phase III 52 week data vs. MTX and biologic PIs
Apremilast POSTURE Trial in Ankylosing Spondylitis
• Fully enrolled months ahead of scheduleschedule
• More than 2 million patients in the US and EU
• No oral disease-modifying treatment options
• Top Line data expected H1:14• Top-Line data expected H1:14
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I&I Pipeline Projects Continue To Advance
Preclinical Phase I Phase II Phase III Regulatory Filing& Approval
APREMILASTPsoriatic Arthritis
Psoriasis
Ankylosing Spondylitis
Behçet’s Disease
Crohn’s Disease
Ulcerative Colitis
Atopic Dermatitis
SOTATERCEPT (ACE-011)SOTATERCEPT (ACE-011)Renal Anemia / Bone
POMALIDOMIDESystemic Sclerosis (POC)
CC 292CC-292SLE/B-Cell mediated diseases (POC)
CC-220Systemic Sclerosis / SLE / Sarcoidosis
CC 90001CC-90001IPF / Liver Fibrosis
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I&I Pipeline Projects Continue To Advance
Preclinical Phase I Phase II Phase III Regulatory Filing& Approval
APREMILASTPsoriatic Arthritis
Psoriasis
Ankylosing Spondylitis
Behçet’s Disease
PsO NDA and combined PsA/PsO MAA
Crohn’s Disease
Ulcerative Colitis
Atopic Dermatitis
SOTATERCEPT (ACE-011)
PsA/PsO MAA on track Q4:13
SOTATERCEPT (ACE-011)Renal Anemia / Bone
POMALIDOMIDESystemic Sclerosis (POC)
CC 292CC-292SLE/B-Cell mediated diseases (POC)
CC-220Systemic Sclerosis / SLE / Sarcoidosis
CC 90001CC-90001IPF / Liver Fibrosis
53
I&I Has Transformational Potential for Patients and for Celgene
Apremilast
• 52 week data for apremilast supports i ifi t t it lti l
Potential to createa new cornerstone
significant opportunity across multiple segments of the market
• Submissions progressing on schedule
for treatment ofpsoriatic diseaseas well as other
serious immunologic
• Preparations for Q1:14 Launch ongoing
• Commercial build-out on track, hiring talented, experienced leadership in Sales, g
diseases, p p ,
Marketing and Medical Affairs
• ACR is a significant meeting in advance of the US PsA launch
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