Psoriasis pharmascape cv

Pharmascape
Psoriasis therapy: today & tomorrow
All information herein is publically available
This document is meant only to illustrate Oliver Vit’s professional competences
and does not reflect Actelion Pharmaceuticals Ltd s corporate views
Ltd’s

Psoriasis; approved biologics

Etanercept, Enbrel®

Adalimumab, Humira ®

Infliximab, Remicade ®

Ustekinumab, Stelara ®

2 Life Cycle Management
Competitive intelligence analysis

Psoriasis therapies; EU market protection estimates

1st
Indication Use in
Parent Market Parent psoriasis Market
patent authorisation patent patent SPC exclusivity
Compound Parent patent # filing (estimated) expiry expiry (estimated) (estimated)

Enbrel EB 0418014 10-Sep-90 03-Feb-00 10-Sep-10 31-Jan-15 03-Feb-10

Remicade EP 0610201 18-Mar-92 13-Aug-99 18-Mar-12 12-Aug-14 13-Aug-09

Humira EP 0929578 10-Feb-97 08-Sep-03 10-Feb-17 16-Apr-18 08-Sep-13

Stelara
S EP 1309692 07-Aug-01
0 01 16-Jan-09
16 09 07-Aug-21
0 21 15-Jan-24
1 24 16-Jan-19
16 19

Briakinumab EP 1175446* 24-Mar-00 (Apr-11) 24-Mar-20 (24-Mar-25) (Apr-21)
* may not be granted


Psoriasis therapies; US market protection estimates

1st
Use in Indication Use in
Parent Use in psoriasis Market Parent psoriasis PT
patent psoriasis patent authorisation patent patent extension
Compound Parent patent # filing patent # filing (estimated) expiry expiry (estimated)

Enbrel Re.36,755 10-May-90 US 5,605,690 08-Feb-95 02-Nov-98 07-Mar-12 25-Feb-14 23-Oct-12

Remicade US 6284471 04-Feb-94 24-Aug-98 04-Sep-18 none

Humira US 6090382 09-Feb-96 31-Dec-02 09-Feb-16 31-Dec-16

Stelara
St l US 6902734 01-Aug-01
01 A 01 (Oct-09)
(O t 09) 24-Jul-22
24 J l 22 (Oct-23)
(O t 23)

Briakinumab US 6914128 24-Mar-00 (Apr-11) 24-Mar-20 (Aug-23)


Licensed indications
Rheumatoid Crohn‘s Juvenile Psoriatic Ulcerative Ankylosing
Psoriasis
Arthritis
A th iti disease Arthritis Arthritis Colitis Spondylitis
S d liti

 
Enbrel®  (≥2 yrs US;
yrs,  
(≥8 yrs, EU)
(etanercept) ≥4 yrs, EU)


Remicade®  ( yrs
(≥6 y    
(infliximab) EU& US)


Humira®   (≥4 yrs, US;   
(adalimumab) ≥13 yrs, EU)

Stelara®

(EU & CA
only)
onl )
(ustekinumab)

Dosing regimens for adults US & EU

Rheumatoid Psoriatic Ankylosing Plaque
Arthritis* Arthritis Spondylitis Psoriasis
25 mg twice weekly
Enbrel® or
25 mg twice weekly 50 mg weekly
(etanercept)
or or
subcutaneous 50 mg weekly 50 mg twice weekly for 12 weeks
injections followed by 50 mg weekly
y g y
(max 24 weeks in EU)

Annual cost
€13,400 €19,326*
per patient $20,190 $24,848**
(ex-factory price)
Annual global sales
$3.6 bio
(2008)
* Average of FR & DE prices & based on 1 yr continuous use
** Wholesale Acquisition Cost (WAC)


Rheumatoid Psoriatic Ankylosing Crohn‘s Ulcerative Plaque
Arthritis* Arthritis Spondylitis Disease Colitis Psoriasis
3 mg/kg induction
3 mg/kg weeks 2 & 6
g g
Remicade® 5 mg/kg induction
3 mg/kg every 8
(infliximab) weeks 5 mg/kg weeks 2 & 6
Incomplete 5 mg/kg every 8 weeks
intravenous infusion responders up to
7.5mg/kg
7 5mg/kg

Annual cost per patient €17,400 €21,573*
(ex-factory price) $19,510 $21,166**

Annual global sales
$3.7 bio
(2008)
* Average of FR & DE prices & based on 1 yr continuous use


Psoriatic Ankylosing Crohn‘s Plaque
Rheumatoid Arthritis Arthritis Spondylitis Disease Psoriasis
Humira®
80 mg induction
g
(adalimumab)
( ) 80 mg induction
i d ti
40 mg every other week 40 mg at week 3
40 mg every
subcutaneous (12 week maximum exposure for Pso.Ar. & A.S.) 40 mg every other week
other week
injections
Annual cost
€14,200 €3,300 €14,700 €15,898*
per patient $18,886 $18,886 $20,339 $18,886**
(ex-factory price)
Annual global sales
$4.5 bio
(2008)
* Average of FR & DE p
g prices & based on 1 y continuous use
yr


Prescribing paradigm

• Enbrel® i li
E b l® is licensed f chronic th
d for h i therapy i th US & ≤ 24 weeks i th EU
in the k in the
• Remicade® is licensed for chronic therapy in both the US & EU
• Humira® is licensed for chronic therapy in both the US & EU
• Stelara® is licensed for chronic therapy in the EU

• Treatment of psoriasis may vary from the label & is dependent upon
– visible efficacy
– long term side effects; both perceived & real
–d t
doctor-patient relationship
ti t l ti hi

• Awareness of malignancies & serious opportunistic infections is on the rise


Enbrel® (etanercept)
• Dimeric fusion protein which binds TNFα and lowers the concentration of free TNFα
left in circulation
• Dosing regimens vary geographically with a 24 week maximum treatment period in
the EU and no cap in the US; yearly treatment with 50 mg weekly subcutaneous
injections is on the rise
• 34% of 25 mg twice weekly patients reached PASI 75 @ week 12 with continued
improvement to 44% @ week 24 in Study-2
• SAEs: malignancies (breast and lung carcinomas, lymphomas, non-melanoma skin
cancers), demyelinating disorders, fatal haematological reactions, fatal bacterial,
viral & fungal opportunistic infections including TB and hepatitis B reactivation
• 7% of patients tested positive for anti-etanercept antibodies after 1 year
• Contraindicated with Anakinra®, abatacept, sulfasalazine, cyclophosphoamides,
congestive heart failure, alcoholic hepatitis, Wegener‘s granulomatosis and live
vaccines
• No signals from developmental toxicity study in rats & rabbits; long term
observational pregnancy registry in place
• No head-to-head comparative trials
• Abandoned indications: idiopathic pulmonary fibrosis asthma uveitis cachexia
fibrosis, asthma, uveitis, cachexia,
myelodysplastic syndrome, congestive heart failure, Wegener‘s granulomatosis

Enbrel® – Development overview
1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
RA PsA AS Pso
MA MA MA MA

Rheumatoid Arthritis
Study I / II / III
3 Phase III registration trials

Psoriatic Arthritis
NCT00317499
single Phase III registration

Ankylosing spondylitis

Psoriasis
Study I / II


Enbrel® – Psoriasis development
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Study-1
20021632

Study-2
20021639

NCT00121615
OL ext

NCT00111449
50 mg twice weekly

NCT00333034
50 mg once weekly

NCT00110981
UVB combination Tx

MAA MA Launch


Remicade® (infliximab)
• Chimeric monoclonal antibody targeting TNFα delivered by i.v. infusion 5 mg/kg at
weeks 0, 2 & 6 followed by maintainance infusions every 8 weeks
• 80% of patients in EXPRESS I acheived PASI 75 with 5 mg/kg by week 10
sustained at 82% PASI 75 @ week 24, p<0.001;
• EXPRESS II demonstrates better efficacy of chronic over cyclical therapy
• SAEs include malignancies, serious infections (bacterial, viral, fungal) &
cardiovascular events
• Most common AEs: arthralgia, nasopharyngitis, URT infections, cough, injection site
reactions, headache
• Black box warning: serious & fatal fungal, viral & bacterial infections inclusive of TB,
and hepatosplenic T-cell lymphomas
• ~20% of patients develop infliximab antibodies and efficacy wanes over time
• Contraindicated with mild-to-severe heart failure and live vaccines
• No developmental toxicity results available; administration to pregnant women
limited by medical need
• Early development strategy was to use pivotal Phase IIb trial data in conjunction with
single Phase III trial experience with multiple label extensions per indication
• Abandoned indications: congestive heart failure asthma, COPD, sarcoidosis,
failure, asthma COPD sarcoidosis
multiple myeloma

Remicade® – Development overview
1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
Crohn‘s RA AS PsA UC Pso
MA MA MA MA MA MA

Crohn‘s disease
ACCENT I
i l Ph i t ti

ATTRACT

NCT00207701

Psoriatic Arthritis
NCT00051623

Ulcerative Colitis
UCI NCT00096655 & UC II NCT00036439
2 Phase III trials

Psoriasis
EXPRESS I NCT00106834
14 Life Cycle Management EXPRESS II NCT00106847
Competitive intelligence analysis 2 Phase III trials

Remicade® – Psoriasis development
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
SPIRIT
Phase IIb

EXPRESS I

EXPRESS II
NCT00687401
Standard Tx & biologic Tx failures

NCT00251641
MTX head-to-head
NCT00358670
OL ext
NCT00527072
Etanercept Tx failures

NCT00833053 dose optimization
p

NCT00686595
Etanercept switch

Long term observation, registry &
cross-indication surveillance
MAA MA Launch


Humira® (adalimumab)
• Fully humanized TNFα inhibitor
• Dosing regimen of subcutaneous injection of 40 mg every other week
• 71% of patients acheive PASI 75 by week 12 in Study Ps-I
• 28% of patients lose adequate response by week 52 as defined by a 50%
p q p y y
reduction from baseline improvement witnessed at week 33
• SAEs include malignancies, cardiovascular events & serious infections
• Most common AEs: infections, injection site reactions, headache, & rash
j
• Black box warning: TB, invasive fungal infections & other occassionally fatal
opportunistic infections
• Contraindicated with Anakinra® and live vaccines
• No signals from perinatal toxicity study in cynomolgus monkey; long term
observational pregnancy registry in place
• Development abandoned in asthma


Humira® – Development overview
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
RA PsA AS CD Pso JIA UC
MA MA MA MA MA MA MA

Studies I / II / III / IV / V
Psoriatic Arthritis Study
PsA-I, NCT00646386
NCT00646178
NCT00085644
single Phase III registration trial
Crohn‘s Disease
CD-II, NCT00105300
CD-III, NCT00077779

Psoriasis
Ps-I, NCT00237887

Juvenile Idiopathic Arthritis
NCT00237887

Ulcerative Colitis
17 Life Cycle Management NCT00408629 & NCT00385736
Competitive intelligence analysis 2 Phase III registration trials

Humira® – Psoriasis development
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012

NCT00646191
NCT00645905
NCT00645892
OL extention

Study Ps-II

Study Ps-I
Ps I
NCT00566722
OL in suboptimal response patients
CHAMPION
MTX & placebo controlled

NCT00195676
Phase III catch-all OL extention

NCT00735787
Hands & Feet

ESPRIT, NCT00799877
10 year post marketing safety study

MAA MA Launch


Ustekinumab

• Fully humanized anti IL-12/23 antibody delivered by subcutaneous injection via
anti-IL
induction at weeks 0 & 4 followed by quarterly maintainance regimen
• 67% of patients in both PHOENIX trials acheived PASI 75 with 45 mg, the lower
dose, by week 12, p<0.0001; maximum effect 75% PASI 75 @ week 20 with 45 mg
y g
• SAEs include malignancies, serious infections (bacterial, viral, fungal) &
cardiovascular events
• Most common AEs: arthralgia, nasopharyngitis, URT infections, cough, injection site
reactions, headache
• Marketed as Stelara® in EU, US & CA for psoriasis
• Additional indications
– Psoriatic arthritis
– Crohn‘s disease
– previously abandoned MS
• Ustekinumab specific antibodies noted i 5% of patients
U ki b ifi ib di d in % f i

Ustekinumab – Development overview
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

NCT00267956
Psoriatic arthritis
x

NCT00771667
Crohn‘s disease
(pivotal IIb/III)

Crohn‘s disease
(confirmatory III)

PHOENIX I
Psoriasis
P i i

PHOENIX II
Psoriasis

MAA MA Launch MAA MA Launch


Ustekinumab – Psoriasis development
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

NCT00320216 x

PHOENIX I

PHOENIX II

PHOENIX 5yr OL

NCT00454584
Enbrel® controlled
x
NCT00723528 JP

NCT00747344 KR TW

MAA MA Launch


Efficacy & median time to relapse
Half life Elimination PASI 75 Median time to relapse
(t1/2) (5 x t1/2) (50%≤PASI 50)

Enbrel 0.6 weeks 3 weeks 34% @ week 12 12 weeks1
(etanercept)

Remicade ~ 1.5 weeks ~ 7.5 weeks 80% @ week 10 >20 weeks2
(infliximab)

Humira ~ 2 weeks ~ 10 weeks 71% @ week 12 ~ 24 weeks3
(adalimumab)

Stelara ~ 3 weeks ~ 15 weeks 67% @ week 12 ~ 24 weeks4
(ustekinumab)
1 http://www.wyeth.com/news/archive?nav=display&navTo=/wyeth_html/home/news/pressreleases/2004/1145887154280.html

22 Life Cycle Management 2 SPIRIT trial, http://www.mims.co.uk/news/891873/Remicade-approved-use-psoriasis/
3 Study Ps-I, Extrapolated from graph
Competitive intelligence analysis 4 Phoenix I, trial Etrapolated from graph

Psoriasis therapy: competitive environment

IL-12/IL-23 inhibitor TNFα inhibitor
CNTO 1959

ART621

Briakinumab

Phase I Phase II Phase III Launched

BMS-582949

CP-690.550
R348

JAK inhibitor
p38 kinase
inhibitor


Compounds in clinical development for psoriasis

Briakinumab, ABT874

ART621

BMS-582949

CP-690.550

R348

CNTO 1959


Briakinumab
• Fully humanized anti-IL-12/23 antibody
anti IL 12/23
• Monthly subcutaneous injection with 200 mg induction at weeks 0 & 4 followed by
100 mg monthly maintainance regimen; t½ ~ 8- 10 days
• Positive results from 180 patient Phase IIb trial
• 90% reach PASI 75 by week 12, p<0.001 and 3 months following cessation 85%
maintain at least PASI 50 with one 200 mg injection/week for 4 weeks
• Patients were allowed to relapse in a 12 week blinded withdrawal period; 69%
regain PASI 75 within 12 weeks following retreatment
• Well tolerated; no SAEs, most common AEs: injection site reactions,
nasopharyngitis, URT infections
• Comparator trials versus Enbrel® and MTX (ongoing)
• Phase III results expected 04Q09; filing in 2010
– previously abandoned MS & RA programs


Briakinumab – Psoriasis development
2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

NCT00292396

NCT00570986

NCT00691964
Enbrel® head-to-head
placebo controlled

NCT00710580
Enbrel® head-to-head
placebo controlled

NCT00679731
MTX controlled

NCT00626002
OL catch-all ext.

NCT00870948
Bioavailability for CMC process

MAA MA Launch


ART621

• Subcutaneous anti-TNFα monoclonal antibody; i
S b t ti TNF l l tib d incorporates d
t domain i
antibodies (dAb) which being smaller improves manufacturing yield, lowers
immunogenicity and improves tissue penetration
• PoC
– factorial-design, randomised, double-blind, placebo-controlled, dose
optimisation, pharmacokinetics, safety, efficacy study
– multiple dose administration of ART621.
lti l d d i i t ti f ART621
– 1 site in NZ
– results from Mar09; well tolerated and exhibiting a safety profile
consistent with anti-TNF activity
i t t ith ti TNF ti it
• IND filed in Rheumatoid Arthritis


BMS-582949

• Oral
O l once daily p38 mitogen-activated protein (MAP) kinase inhibitor
d il 38 it ti t d t i ki i hibit
promising to halt the inflammatory cytokine cascade
• 99 patient 12 week PoC in psoriasis completed in Apr09
• previously abandoned Eczema/dermatitis
• other p38MAP kinases abandoned due to toxicity
– Johnson & Johnson, talmapimod
p
– Vertex, VX-745


CP-690550
• Selective oral JAK-3 inhibitor (IL-2,4,7,9,15,21 receptors only) which limits the
effects to T and NK cell development and B-cell function
B cell
• Preclinical models show efficacy
– arthritis
– asthma
– transplant
• Additional indications: Crohn‘s disease, Rheumatoid Arthritis, psoriasis,
renal t
l transplant
l t
• NK cell levels reduced with no reduction in CD4+ or CD8+ levels

Results from
58 patient PoC


CP-690550
• Phase II trials
– Dose dependent increase in HDL & LDL levels
– Increased ALT & AST levels > 3 x ULN
– 3 sudden cardiac deaths
• 1 in 12 week study
• 2 in long term follow-up 6-12 months
– 9 serious infections in 9 patients
• Bacterial
• Viral
• Fungal


R348

• Oral d l JAK-3 Syk inhibitor
O l dual JAK 3 & S k i hibit
• EIM Jan08; combi SAD/MAD
• Preclinical models show efficacy
– arthritic symptoms, bone destruction & swelling
– psoriasis
– transplant
p
• Planned clinical programs
– psoriasis
– Rheumatiod Arthritis
– renal transplant
– Graft vs host disease


CNTO 1959

• Fully humanized anti-IL-12/23 antibody
F ll h i d ti IL 12/23 tib d
• EIM June 2009
– Phase I placebo-controlled trial
– 3 US sites
– 71 healthy volunteers & psoriasis patients
– evaluating the PK p
g profile and antibody development with both i.v.
y p
infusion and subcutaneous formulations
– 11 month estimated duration


Back-ups


• US label
– RA
• reducing signs and symptoms, inducing major clinical response,
inhibiting the progression of structural damage, and improving physical
function in patients with moderately to severely active rheumatoid
arthritis. ENBREL can be initiated in combination with MTX or used
alone
– Polyarticular juvenile idiopathic arthritis
• reducing signs and symptoms of moderately to severely active
polyarticular juvenile idiopathic arthritis in patients ≥ 2 yrs
• reducing signs and symptoms, inhibiting the progression of structural
damage of active arthritis and improving physical function in patients
arthritis,
with psoriatic arthritis. ENBREL can be used in combination with MTX
for those patients who do not respond adequately to MTX alone

34 Competitive intelligence analysis

• US label, continued
– Ankylosing spondylitis
• reducing signs and symptoms in patients with active ankylosing
spondylitis
– Plaque psoriasis
• treatment of patients ≥ 18 yrs with chronic moderate to severe plaque
psoriasis who are candidates for systemic therapy or phototherapy


• EU label
– RA
• in combination with MTX for the treatment of moderate to severe active
rheumatoid arthritis in adults when the response to disease-modifiying
antirheumatic drugs including MTX (
g g (unless contraindicated) has been
)
inadequate
• can be given as monotherapy in case of intolerance to MTX or when
continued treatment with MTX is inappropriate
• treatment of severe, active and progressive rheumatoid arthritis in
adults not previously t t d with MTX
d lt t i l treated ith
• alone or in combination with MTX, Enbrel reduces the rate of
progression of joint damage as measured by X-ray and to improve
physical function
• treatment of active polyarticular juvenile idiopathic arthritis in children
and adolescents ≥ 4 yrs who have had an inadequate response to, or
who have proved intolerant of, MTX. Enbrel has not been studied in
children < 4yrs


• EU label, continued
,
• treatment of active and progressive psoriatic arthritis in adults when the
response to previous disease-modifying antirheumatic drug therapy has
been inadequate. Enbrel has been shown to improve physical function
in patients with psoriatic arthritis and to reduce the rate of progression
arthritis,
of peripheral joint damage as measured by X-ray in patients with
polyarticular symmetrical subtypes of the disease
• treatment of adults with moderate to severe plaque psoriasis who failed
to
t respond t or who h
d to, h have a contraindication t or are i t l
t i di ti to, intolerant t
t to
other systemic therapy including cyclosporine, MTX and PUVA
– Paediatric plaque psoriasis
• treatment of chronic severe plaque psoriasis in children and
adolescents ≥ 8 years who are inadequately controlled by, or are
y q y y,
intolerant to, other systemic therapies or phototherapies
• treatment of adults with severe active ankylosing spondylitis who have
has an inadequate response to conventional therapy


• US label
– Rheumatoid arthritis
• REMICADE, in combination with MTX, is indicated for reducing signs
and symptoms, inhibiting the progression of structural damage, and
improving physical function in patients with moderate to severely active
rheumatoid arthritis
h t id th iti
• REMICADE is indicated for reducing signs and symptoms and inducing
and maintaining clinical remission in adult and pediatric patients with
moderately se erel acti e
moderatel to severely active Crohn‘s disease who ha e had an
ho have
inadequate response to conventional therapy
• REMICADE is indicated for reducing the number of draining
enterocutaneous and rectovaginal fistulas and maintaining fistula
closure in adult patients with fistulizing Crohn‘s disease
Crohn s
• REMICADE is indicated for reducing signs and symptoms in patients
with active ankylosing spondylitis


• US label, continued
– Ulcerative colitis
• REMICADE is indicated for reducing signs and symptoms, inducing and
maintaining clinical remission and mucosal healing, and eliminating
corticosteroid use in patients with moderately to severely active
ulcerative colitis who have had an inadequate response to conventional
q p
therapy
• REMICADE is indicated for reducing signs and symptoms of active
arthritis, inhibiting the progression of structural damage, and improving
physical function in patients with psoriatic arthritis
• REMICADE is indicated for the treatment of adult patients with chronic
severe (i.e., extensive and/or disabling) plaque psoriasis who are
candidates for systemic therapy and when other systemic therapies are
medically less appropriate REMICADE should only be administered to
appropriate.
patients who will be closely monitored and have regular follow-up visits
with a physician


• EU label
Remicade, in combination with MTX, is indicated for:
the reduction of signs and symptoms, as well as improving physical function in:
– patients with active disease when the response to disease-modifying anti-
rheumatic drugs (DMARDs), including MTX has been inadequate
(DMARDs)
– patients with severe, active and progressive disease not previously treated
with MTX or other DMARDs
In these patient populations, a reduction in the rate of the progression of joint
damage, as measured by X-ray, has been demonstrated
– Ulcerative colitis
Remicade is indicated for:
– treatment of moderately to severely active ulcerative colitis in patients who
have had an inadequate response to conventional therapy including
corticosteroids and 6-MP or AZA, or who are intolerant to or have medical
6 MP
contraindications for such therapies
– treatment of severe, active ankylosing spondylitis, in adult patients who have
responded inadeq atel to con entional therap
inadequately conventional therapy


– Adult Crohn‘s disease
– treatment of severe, active Crohn‘s disease, in patients who have not
responded despite a full and adequate course of therapy with a corticosteroid
and/or immunosuppressant; or who are intolerant to or have medical
contraindications for such therapies
– treatment of fistulising, active Crohn‘s disease, in patients who have not
responded despite a full and adequate course of therapy with conventional
treatment (including antibiotics, drainage and immunosuppressive therapy)
– Paediatric Crohn‘s disease
Crohn s
– treatment of severe, active Crohn‘s disease, in paediatric patients aged 6 to
17 years, who have not responded to conventional therapy including a
corticosteroid and an immunomodulator and primary nutrition therapy; or who
are intolerant to or have contraindications for such therapy Remicade has
therapy.
been studied only in combination with conventional immunosuppressive
therapy


– Psoriasis
– treatment of moderate to severe plaque psoriasis in adults who failed to
respond to, or who have a contraindication to, or are intolerant to other
systemic therapy including cyclosporine, MTX and PUVA
cyclosporine
– treatment of active and progressive psoriatic arthritis in adults when the
response to previous DMARD therapy has been inadequate
Remicade should be administered
– in combination with MTX
– or alone in patients who show intolerance to MTX or for whom MTX is
contraindicated
Remicade has been shown to improve physical function in patients with psoriatic
arthritis, and to reduce the rate of progression of peripheral joint damage as
measured by X-ray in patients with polyarticular symmetrical subtypes of the
disease


H i ® ( d li b)
• US label
• reducing signs and symptoms, including major clinical response, inhibiting
the
th progression of structural damage, and i
i f t t ld d improving physical f
i h i l function i
ti in
adult patients with moderate to severely active disease
– Juvenile idiopathic arthritis
• reducing signs and symptoms of moderately to severely active polyarticular
juvenile idiopathic arthritis in patients ≥ 4yrs
• reducing signs and symptoms of active arthritis, inhibiting the progression of
structural damage, and improving physical function
• reducing signs and symptoms in patients with active disease
• reducing signs and symptoms and inducing and maintaining clinical
remission in adult patients with moderately to severely active Crohn‘s
disease who have had an inadequate response to conventional therapy therapy.
Reducing signs and symptoms and inducing clinical remission in these
patients if they have lost response to or are intolerant to infliximab
• the treatment of adult patients with moderate to severe chronic plaque
psoriasis who are candidates f systemic th
i i h did t for t i therapy or phototherapy, and
h t th d
when other systemic therapies are medically less appropriate

H i ® ( d li b)
• EU label
• Humira in combination with MTX is indicated for:
– the treatment of moderate to severe active rheumatoid arthritis in adult
patients when the response to disease-modifying anti-rheumatic drugs
including MTX has been inadequate
– the treatment of severe, active and progressive rheumatoid arthritis in
adults not previously t t d with MTX
d lt t i l treated ith
• Humira can be given as monotherapy in case of intolerance to MTX or
when continued treatment with MTX is inappropriate
• Humira has been shown to reduce the rate of progression of joint damage
as measured by X-ray and to improve p y
y y p physical function, when g
given in
combination with MTX
bi ti ith
• Humira in combination with MTX is indicated for the treatment of active
polyarticular juvenile idiopathic arthritis, in adolescents aged 13 to 17 years
who have had an inadequate response to one or more disease-modifying
disease modifying
ant-rheumatic drugs (DMARDs). Humira can be given as monotherapy in
case of intolerance to MTX or when continued treatment with MTX is
inappropriate
• treatment of adults with severe active ankylosing spondylitis who have had
an inadequate response to conventional therapy

Crohn s
• treatment of severe, active Crohn‘s disease, in patients who have not
responded despite a full and adequate course of therapy with a
corticosteroid and/or an immunosuppressant; or who are intolerant to or
have medical contraindications for such therapies. For induction
p
treatment, Humira should be given in combination with corticosteroids.
Humira can be given as monotherapy in case of intolerance to
corticosteroids or when continued treatment with corticosteroids is
inappropriate
– Psoriasis
• treatment of moderate to severe chronic plaque psoriasis in adult patients
who failed to respond to or who have a contraindication to, or are intolerant
to other systemic therapy including cyclosporine, MTX or PUVA
• Humira is indicated for the treatment of active and progressive psoriatic
arthritis in adults when the response to previous disease-modifying anti-
rheumatic drug therapy has been inadequate. Humira has been shown to
reduce the rate of progression of peripheral joint damage as measured by
X ray
X-ray in patients with polyarticular symmetrical subtypes of the disease
and to improve physical function

Enbrel® – Clinical trials overview
• Study-1, 20021632
– 25 mg vs placebo (1:1)
– °
1° endpoints
• Proportion of patients achieving PASI 75 @ week 12
– 2° endpoints
• Proportion of patients achieving PASI 50 & 90 @ week 24
• Proportion of patients with PGA score of cleared or minimal @ week 24
• QoL; DLQI
– 112 moderate-to-severe patients
– 24 week trial

• Study-2,
St d 2 20021639
– 25 mg, 25 mg twice weekly, 50 mg twice weekly vs placebo (1:1:1:1)
– 1° endpoints
– 2° endpoints
• QoL; DLQI
– 24 week trial
– 5 months recruitment
– 47 sites
– US only


Enbrel® – Study-1; study design
2003 ARCH DERMATOL

Double blind core study

scr x 2 4 8 12 16 20 24 weeks

Etanercept 25 mg

Placebo

PASI
PGA

DLQI


Enbrel® – Study-1; patient flow
2003 ARCH DERMATOL


Enbrel® – Study-1; baseline characteristics
2003 ARCH DERMATOL


Enbrel® – Study-1; study results
2003 ARCH DERMATOL


2003 ARCH DERMATOL


2003 ARCH DERMATOL

• Efficacy endpoints
– 1° endpoints
 30% of patients achieving PASI 75 @ week 12
– 2° endpoints
 77% patients achieving PASI 50 @ week 24
 53% patients with PGA score of cleared or minimal @ week 24
p
 improvement in DLQI from baseline

met x not met ~trend


Enbrel® – Study-1; safety & tolerability
2003 ARCH DERMATOL

No treatment associated SAE was reported
Most common AEs – URT infections, headache & injection site reactions


Enbrel® – Study-2; study design
2003 NEJM

Double blind core study Follow-up period

scr x 2 4 8 12 16 20 24 weeks

Etanercept 25 mg
(once weekly)

Etanercept 25 mg
(twice weekly)

Etanercept 50 mg
(twice weekly)

Placebo

PASI
PGA

x blood & urine analysis
y x

DLQI

x = entanercept antibody assay


Enbrel® – Study-2; baseline characteristics
2003 NEJM


2003 NEJM


2003 NEJM

– 1° endpoints
 14% of 25 mg weekly patients achieving PASI 75 @ week 12
 34% of 25 mg twice weekly patients achieving PASI 75 @ week 12
– 2° endpoints
 25% of 25 mg weekly patients achieving PASI 75 @ week 24
% f S
 improvement in both PGA & DLQI scores at week 12 from baseline


Enbrel® – Study-2; safety & tolerability
2003 NEJM


Remicade®


Remicade® – Clinical trials overview
• SPIRIT (NCT00230529), Study III
– 2 doses vs placebo (2:2:1)
– 1° endpoints
• Proportion of p
p patients achieving ≥PASI 75 @ week 10
g
– 2° endpoints
• Anitbodies to infliximab
• QoL: DLQI
– 249 patients
– 26 week trial

• EXPRESS I (NCT00106834), Study I
– 1 dose vs placebo (4:1)
– 1° endpoints
d i
– 2° endpoints
• Proportion of patients with PGA score of cleared or minimal @ week 10, 24 & 50
• Proportion of patients @ week 10, 24, & 50 acheiving:
– PASI 50
– PASI 90
– % improvement in PASI from baseline
p
– % improvement in NAPSI
– 66 week trial
– 32 sites
– 8 countries, (AT, BE, CA, CH, DE, DK, FR, UK, US)

• EXPRESS II (NCT00106847), Study II
– 1° endpoints
• Proportion of patients achieving ≥PASI 75 @ week 10
– 2° endpoints
• Efficacy of 4 maintenance regimens
• QoL: DLQI, SF-36 & Economic Questionnaire
– 66 week trial
– 63 sites
– 4 countries, (AT, CA, FR, IT, US)


Remicade® –SPIRIT; study design
2005 New Medicines Profile


scr x 2 6 10 26 weeks

Infliximab 3 mg/kg

Infliximab 5 mg/kg
g g

Placebo
PASI
PGA

DLQI


Remicade® –SPIRIT; patient flow
2004 Gottlieb J Am Acad Dermatol


Remicade® –SPIRIT; baseline characteristics


Remicade® –SPIRIT; study results
2005 New Medicines Profile

Infliximab Infliximab Placebo
3 mg/kg 5 mg/kg

PASI 75 @ week 10
(p<0.001) 72% 88% 6%

DLQI
Median ∆ from baseline* -8 -10 0
(p<0.001)
* median baseline values 11,12,14 respectively


Remicade® –SPIRIT; safety & tolerability


Remicade® – EXPRESS I; study design
2005 Lancet, Infliximab induction and maintenance therapy


scr x 2 6 10 14 22 24 26 30 38 46 50 66 weeks

Infliximab 5 mg/kg x x x x x x x x x x x

Placebo x x x x x x
PASI
PGA

NAPSI

[Infliximab
serum]

Infliximab antibodies

Anti-nuclear & anti-double
stranded DNA antibodies

71 Competitive intelligence analysis x 5 mg/kg adminsitration

Remicade® – EXPRESS I; patient flow


Remicade® – EXPRESS I; baseline characteristics


Remicade® – EXPRESS I; study results

Effi d i t
– 1° endpoints
 80% of patients achieving PASI 75 @ week 10
– 2° endpoints
2
 83%, 74%, 53% patients with PGA score of cleared or minimal @ week 10, 24 & 50
̶ Proportion of patients @ week 10, 24, & 50 acheiving:
 91% 90% 69% PASI 50
91%, 90%,
 57%, 58%, 45% PASI 90
 86%, 84%, 64% improvement in PASI from baseline
 26%, 56%, 56% improvement in NAPSI

met trend


Remicade® – EXPRESS I; pre-infusion concentrations


Remicade® – EXPRESS I; safety & tolerability


Remicade® – EXPRESS I; antibody development


Remicade® – EXPRESS II; study design
2005 FDA website, Clinical Study Report

Double blind core study Follow-up
period
scr x 2 6 10 14 16 18 22 30 38 46 50 66 weeks

x x x x
Infliximab 3 mg/kg x x x x

x x x x
Infliximab 5 mg/kg x x x x x x x x x x

Placebo x x x

PASI
PGA

Infliximab antibodies

Anti-nuclear anti double
Anti nuclear & anti-double stranded DNA antibodies

80 Competitive intelligence analysis x 3 or 5 mg/kg group adminsitration
x placebo re-rand. group adminsitration

Remicade® – EXPRESS II; study results

Infliximab Infliximab Placebo
3 mg/kg 5 mg/kg

≥ PASI 75 @ week 10
(p<0.001)
(p<0 001) 71% 76% 2%

PASI 90 @ week 10
(p 0 00 )
(p<0.001) 37% 45% 0.5%
0 5%

PGA score of excellent
or cleared @ week 10 70% 76% 1%

DLQI
Median ∆ from baseline
baseline* -9
9 -9
9 0
(p<0.001)
81 Competitive intelligence analysis * median baseline value 12

Remicade® – EXPRESS II; study results

≥PASI 75 @ week 50
S
(p<0.001)
Continuous
Infliximab 44%
3 mg/kg
Intermittant
Infliximab 24%
3 mg/kg

Continuous
Infliximab 55%
5 mg/kg
Intermittant
Infliximab 38%
5 mg/kg

Remicade® – EXPRESS II; safety & tolerability

• Therapy associated adverse event profile
– Serious infections
• tuberculosis (2)
• undisclosed (9)
– Cardiovascular events
• congestive heart failure (1)
– Malignancies
• basal cell carcinomas (9)
• squamous cell carcinomas (1)
• adenocarcinoma (1)
• breast cancer (1)
– Lupus erythematosus (4)
– Increased liver enzymes @ week 50
• 4.9% patients had markedly abnormal ALT values
p y
• 3.1% patients had markedly abnormal AST values
– Increased antibodies @ week 50
• 55% of anti-Infliximab antibody-positive patients presented with titers ≤ 1:40;
however 5 mg/kg was associated with lower titers than 3 mg/kg
• 65% patients were newly positive for ANA antibodies
• 26.8% patients were newly positive for anti-dsDNA antibodies

Humira® – Clinical trials overview
• Phase II, Study Ps-II (NCT00645814)
– 40 mg weekly or eow vs placebo (1:1:1)
– 1° endpoints
• Proportion of patients achieving ≥PASI 75 @ weeks 12 & 24
PASI
• Proportion of patients with an improved PGA score at weeks 12 & 24
– 2° endpoints
• Proportion of patients achieving PASI 50 @ weeks 12 & 60
• Proportion of patients achieving PASI 90 @ weeks 12 & 60
• Proportion of patients with an improved PGA score @ weeks 12 & 60
– 147 patients
– 60 week trial
– 18 sites
– 2 countries, (CA, US)

• Phase III, Study Ps-I (NCT00237887)
– 40 mg eow vs placebo (2:1 Period A & 1:1 Period C)
– 1° endpoints
• Proportion of patients losing adequate response after week 33 & on or before week 52
– 1212 patients
– 52 week trial
– 81 sites

• Phase III, CHAMPION (NCT00235820)
– 40 mg eow vs methotrexate vs placebo (2:2:1)
– 1° endpoints
– 2° endpoints
• Proportion of patients with an improved PGA score @ week 16
– 271 patients
– 16 week trial
– 28 sites
– CA, Europe


Humira® – Study Ps-II; study design
2006 Gordon, J Am Acad Dermatology

2 4 8 16 20 22 28 32 36 44 52

PASI
S
PGA

Humira® – St d Ps-II; patient flow
H i ® Study P II ti t fl


Humira® – Study Ps-II; baseline characteristics


Humira® – Study Ps-II; study results

– 1° endpoints
 53% of eow patients achieving ≥PASI 75 @ weeks 12 & 24
 80% of weekly patients achieving ≥PASI 75 @ weeks 12 & 24
– 2° endpoints
̶ Proportion of eow patients @ week 12, & 60 acheiving:
 76%, 64% PASI 50
 24%, 33% PASI 90
% % S
 49%, 44% improvement from baseline to PGA clear or almost clear
̶ Proportion of weekly patients @ week 12, & 60 acheiving:
 88%, 66% PASI 50
 48%, 48% PASI 90
 76%, 52% improvement from baseline to PGA clear or almost clear

trend


Humira® – Study Ps-II; safety & tolerability


Humira® – Study Ps-II; safety & tolerability

– Serious infections (1)
• palpitations
• coronary artery disease
– Malignancies (5)
• malignant melanoma (2)
li l
• squamous cell carcinoma (1)
• breast carcinoma (1)
• gastric adenocarcinoma (1)
– Cerebrovascular accidents (2)
• undisclosed; 1 death
– Tuberculosis
• recent-onset latent TB (1)
– Others
• migraines
• bronchitis
• osteoarthritis
• kidney stones

– 2 patients discontinued due to liver enzyme increases between 3 - 3.5 ≥ ULN

No cases of lymphoma, demyelinating syndrome, or lupuslike syndrome were reported


Humira® – Study Ps-I; study design
2008 Menter, J Am Acad Dermatology

4 8 12 24 36 40 44 48
PASI
PGA


Humira® – Study Ps-I; patient flow

Placebo
Adalimumab 40 mg

7% progress 71% progress

85% progress 85% progress

6% ≤ PASI 50
@ week 54

39% ≤ PASI 50
@ week 54

Humira® – Study Ps-I; baseline characteristics


Humira® – Study Ps-I; study results



39% @ wk 54

28% @ wk 52
6% @ wk 54
5% @ wk 52


Humira® – Study Ps-I; safety & tolerability



• tuberculosis (1)
• oral candidiasis (1)
• undisclosed (10)
( )
• congestive heart failure (1)
• basal cell carcinoma (3)
• squamous cell carcinoma (3)
• atypical endophytic epidermoid proliferation (1)
• undisclosed (2)
– Increased liver enzymes @ week 52
• 2.8% patients had ≥ 2.5 ULN ALT values
– Increased antibodies @ week 52
• 8.8% of patients tested positive for anti-adalimumab antibodies

No cases of lymphoma demyelinating syndrome lupuslike syndrome or rebound were reported
lymphoma, syndrome, syndrome,


Humira® – CHAMPION; study design
2007 Saurat, British Journal of Dermatology

PASI/PGA week 0 1 2 4 8 12 16


Humira® – CHAMPION; baseline characteristics


Humira® – CHAMPION; study results

– 1° endpoints
d i t
 80% of 40 mg eow patients achieving PASI 75 @ week 16
 36% of MTX patients achieving PASI 75 @ week 16
 19% of placebo patients achieving PASI 75 @ week 16
– 2° endpoints
̶ Proportion of 40 mg eow patients @ week 16 acheiving:
 88% PASI 50
 51% PASI 90
 17% PASI 100
̶ Proportion of MTX patients @ week 16 acheiving:
 62% PASI 50
 14% PASI 90
 7% PASI 100
̶ Proportion of placebo patients @ week 16 acheiving:
 9% PASI 50
 11% PASI 90
 2% PASI 100
̶ Proportion of patients @ week 16 acheiving a clear or minimal PGA score:
 73% 40 mg eow
 30% MTX
 11% placebo
NB: unusually high placebo rate attributed to (1) european population (2) folate suppliment (3) MTX naïve inclusion criteria


– nonserious infections (51)
– nasopharyngitis (30)
– headache (14)
– pancreatitis (1)
– enlargement of ovarian cyst (1)

– 2% of patients showed liver enzyme increases

No serious adverse events nor any cases of TB, lymphoma, demyelinating
syndrome, or lupuslike syndrome or associated deaths were reported


Ustekinumab


Ustekinumab – Clinical trials overview
• PHOENIX I (NCT00267969)
– 1° endpoints
– 2° endpoints
• ∆ dermatology QoL @ week 12
• Time to loss of PASI 75 response following randomized withdrawal
– 76 week trial
– 48 sites
– 3 countries (US, CA, BE)

• PHOENIX II (NCT00307437)
– 1° endpoints
– 2° endpoints
• Proportion of p
p patients with PGA score of cleared or minimal @ week 12
• ∆ dermatology QoL @ week 12
• # of visits with PASI 75 response between weeks 40 and 52 in the intensified groups compared to maintained dosing
– 70 sites
– 7 countries, (AT, CA, CH, DE, FR, UK, US)


Ustekinumab – PHOENIX I; study design
2008 Lancet, Efficacy and safety of ustekinumab


Ustekinumab – PHOENIX I; patient flow


Ustekinumab of ustekinumab
2008 Lancet, Efficacy and safety
– PHOENIX I; baseline characteristics


– PHOENIX I; endpoints & results

– 1° endpoints
67% of patients achieving PASI 75 @ week 12 with 45 mg
f ti t hi i k ith
85%
– 2° endpoints
Sustained improved PGA score of cleared or minimal @ week 12
Sustained improved ∆ dermatology QoL @ week 12
Median time to loss of PASI 75 response following randomized withdrawal
was 15 weeks


– PHOENIX I; results


– PHOENIX I; safety & tolerability
– Serious infections
• viral syndrome (1)
• foot ulcer of diabetic patient (1)
• osteomyelitis (1)
• gastroenteritis (1)
• appendicitis (1)
• myocardial infarction (2)
• stroke (1)
– Malignancies
• prostate cancer (1)
• thyroid cancer (1)
• colon cancer (1)
• lentigo maligna (1)
• transitional cell carcinoma (1)


– PHOENIX I; safety & tolerability


Ustekinumab – PHOENIX II; study design


Ustekinumab – PHOENIX II; patient flow


Ustekinumab – PHOENIX II; baseline characteristics


– PHOENIX II; endpoints & results

– 1° endpoints
– 2° endpoints
Sustained improved PGA score of cleared or minimal @ week 12
Sustained improved ∆ dermatology QoL @ week 12
90 mg every 8 weeks was the only group to show an advantage with
intensified dosing

• Further analysis
• 75% of patients acheiving PASI 75 @ week 20 with 45 mg
• 84% of patients acheiving PASI 75 @ week 20 with 90 mg
• only 5-7% of all patients with less than PASI 50 @ week 28

 t x not met ~trend
met t t t d


– PHOENIX II; results


– PHOENIX II; safety & tolerability
– Cardiovascular events (5, including 1 death)
• angina
• non-ischaemic sudden cardiac death with underlying dilated
non ischaemic
cardiomyopathy (90 mg)
• transient palpitations
• ventricular extrasystoles
• hypertension
• Cutaneous (6)
• basal cell carcinoma
• squamous cell carcinoma

No dose proportional observations in the rates of adverse reactions


– PHOENIX II; safety & tolerability


Briakinumab


Briakinumab – Clinical trials overview
• Phase IIb NCT00292396
– 5 doses vs placebo (1:1:1:1:1:1)
– 1° endpoints
– 180 patients
– 48 week trial

• Phase III NCT00570986
– 1° endpoints
• Proportion of p
p patients with PGA score of cleared or minimal @ week 12
• Proportion of patients maintaining PGA score of cleared or minimal @ week 52
– 2° endpoints
• ∆ DLQI score between baseline & week 12
• ∆ NAPSI score between baseline & week 12
p
– 52 week trial
– 122 sites


Briakinumab – Clinical trials overview
– 1 dose vs Enbrel® vs placebo (1:1:1)
– 1° endpoints
– 2° endpoints
– 347 patients
– 12 week trial
– 33 sites
– US only

– 1 dose vs Enbrel® vs placebo (1:1:1)
– 1° endpoints
– 2° endpoints
– 350 patients
– 12 week trial
– 41 sites
– US only

– 1 dose vs MTX (1:1)
– 1° endpoints
P i f i hi i k 2
– 2° endpoints
• ∆ DLQI from baseline @ week 24
• ∆ DLQI from baseline @ week 52
– 317 patients
– 52 week trial
– 44 sites
– 14 countries (AT, BE, CA, CH, DE, DK, ES, FI, FR, GR, IT, NL, SE, UK)


Competitors in development
• Rejected for lack of efficacy or an unsuitable safety & tolerability profile


Golimumab

• Never assessed in plaque psoriasis
• Marketed as Simponi® for Rheumatoid Arthritis, Psoriatic Arthritis &
Ankolysing Spondylitis in the US & CA
• Clinical trials in Ulcerative Colitis ongoing
• previously abandoned Uveitis, Crohn‘s Disease, chronic asthma


Cimzia® (Certolizumab pegol)
• PEGylated Fc free anti-TNFα antagonist delivered by subcutaneous
Fc-free anti TNFα
injection; t½ ~ 2 weeks
• PoC
– 200 or 400 mg vs placebo every 2 weeks for 12 weeks
– 176 patients (1:1:1)
– 75% and 83% acheived PASI 75 respectively at week 12, p<0.001
– placebo like tolerability
• Registered in the US & CA for Crohn‘s Disease and Rheumatoid Arthritis
• EMEA rejected the MAA for Crohn‘s Disease citing low & potentially waning
efficacy and safety concerns of long-term immunosuppression;
opportunistic infections and malignancy
t i ti i f ti d li
• Phase III program in psoriasis terminated; UCB product pipeline lists
Crohn‘s Disease and Rheumatoid Arthritis in the EU only
• previously abandoned A k l i S
i l b d d Ankylosing Spondylitis, P i ti A th iti
d liti Psoriatic Arthritis

Cimzia® (Certolizumab pegol)
• US label
• CIMZIA is a tumor necrosis factor (TNF) blocker indicated for:
– Reducing signs and symptoms of Crohn‘s disease and maintaining
clinical response in adult patients with moderately to severely active
disease who have had an inadequate response to conventional
therapy
in combination with methotrexate (MTX), for the treatment of moderate to
severe active rheumatoid arthritis (RA) in adult patients when the
response to disease-modifying antirheumatic drugs (DMARDs)
disease modifying (DMARDs),
including MTX, has been inadequate. In these patients, Cimzia(R) can
be given as monotherapy in case of intolerance to MTX or when
continued treatment with MTX is inappropriate. Cimzia(R) has been
shown to reduce the rate of progression of joint damage as measured
by X-ray and to improve physical function, when given in combination
X ray
with MTX.


Apremilast
• Oral twice daily phosphodiesterase IV inhibitor promising to halt the
inflammatory cytokine cascade
• POC
– 260 patients, 20 mg BID vs placebo
– 24.4% reach PASI 75 at week 12 (p=0.023)
– 57% reach PASI 50 at week 12 (p<0.001)
– Placebo-like tolerability profile
• no SAE
SAEs
• most common AEs nausea, nasopharyngitis, headache and diarrhea
• Phase IIb
– 348 patients,10, 20, 30 mg BID vs placebo
patients 10 20
– exploring the % of patients reaching PASI 75 at week 16
– 10 sites, US only
– 6 month treatment period; study duration Sep08 – Sep09

Apremilast
• additional indications
– Psoriatic Arthritis; phase II
– Bechet‘s Syndrome; phase II
• IIS
– Discoid cutaneous lupus erythematosus
– Uveitis
– Chronic prostatitis & chronic pelvic syndrome
– Chronic cutaneous sarcoidosis
– Vulvodynia
– P i nodularis
Prurigo d l i
• previously abandoned asthma


Voclosporin

• Twice day
T i a d oral C l i
l Calcineurin i hibit promises superior efficacy th
i inhibitor; i i ffi than
cyclosporin-A with less toxicity
• Phase III psoriasis program completed in CA & EU Oct06; no registration
– renal transplant
– Uveitis


Bimosiamose

• Subcutaneous i j ti of cell adhesion molecule (CAM) inhibitor which
S b t injection f ll dh i l l i hibit hi h
prevents the signaling leukocyte tethering to the vascular endothelial cells
• PoC ongoing
• No listing of the compound in Pfizer‘s pipeline


SCH 527123

• Once daily oral CXCR2/IL 8β G protein coupled receptor inhibitor
CXCR2/IL-8β G-protein
• Psoriasis development halted with Phase II; results available in Oct07,
however Product Pipeline Apr 09 mentions only COPD


INCB-18424

• Selective JAK 2 inhibitor
JAK-2
• JAK-1/2 inhibitors have shown perinatal and embryonic lethality
• Topical cream for psoriasis
– 2 x PoCs; 28 day, 28 patient, twice daily application
• improved lesion score; thickness, erythema and scaling
• supported increased body surface area (BSA) 2-7%
• well tolerated
• Systemic exposure assessed in Rheumatoid Arthritis, Myelofibrosis,
Polycythaemia vera, & Thrombocythaemia


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