Download IR meeting for interim financial results ended September 30, 2006

R&D strategy
Director & Corporate Officer
Development Headquarters
Ken-ichi Yanagisawa
November 7, 2006
0
Development Pipeline Status
1
1
Development status of new products - NDA filed
Product
(Generic name)
Remicade
(Infliximab)
Maintate
(Bisoprolol)
Anti-TNFα monoclonal
antibody (Behcet’s disease)
Selective β1 antagonist
(Chronic heart failure)
In-house
Origin: Centocor
In-house
Origin: E.Merck
Modiodal
(Modafinil)
Psychoneurotic agent
(Narcolepsy)
Alfresa Pharma
Talion
(Bepotastine)
Anti-allergic agent
(Orally disintegrating tablet)
Category (Indications)
Development
In-house
2
In most advanced stage, we have 4 products NDA filed.
Remicade for behcet’s disease, Modiodal for narcolepsy, and Talion for orally disintegrating
tablet
are expected to obtain approval within the current fiscal year.
2
Development status of new products – Phase III
Product
(Generic name)
Gastrom
(Ecabet)
Remicade
(Infliximab)
Remicade
(Infliximab)
Remicade
(Infliximab)
Remicade
(Infliximab)
Category (Indications)
Stage
Japan EU/US
Gastrointestinal mucus
protecting agent
(Ulcerative colitis)
Anti-TNFα monoclonal
antibody
(Crohn’s disease, maintenance)
Anti-TNFα monoclonal
antibody
(RA, dose escalation)
Anti-TNFα monoclonal
antibody
(Ulcerative Colitis)
Anti-TNFα monoclonal
antibody
(Psoriasis)
III
II (US)
III
III
III
III
Development
JP:In-house
US: Tanabe
AAI LLC
In-house
Origin:
Centocor
In-house
Origin:
Centocor
In-house
Origin:
Centocor
In-house
Origin:
Centocor
Blue: Stage changed since FY2005
3
Blue letter expresses having changed since FY2005.
In Phase III clinical trial stage,
Remicade/ crohn’s disease, maintenance therapy, phase III clinical trial
was completed and being under preparation for NDA filing.
Remicade/ RA for dose escalation, phase III is in progress aiming
NDA filing in the next year.
Remicade/ ulcerative colitis and psoriasis, phase III has started.
Remicade/ ankylosing spondyltis, being prepared phase III and waiting for starting
3
Development status of new products– Phase III
Product
(Generic name)
TA-8317
APTA-2217
（Roflumilast)
Category (Indications)
Stage
Japan EU/US
Narcotic analgesic
(breakthrough cancer pain)
PDEIV inhibitor (asthma)
II/III
PDEIV inhibitor (COPD）
II/III
III
Development
In-house
Origin: Cephalon
Co-development
with Altana
Pharma
Blue: Stage changed since FY2005
4
TA-8317, narcotic analgesic for breakthrough cancer pain,
phase II ended and phase III has started.
APTA-2217, phase II/III is ongoing for both asthma and COPD.
4
Development status of new products– Phase II
Product
Category (Indications)
(Generic name)
TA-6666
TA-5538
TA-1790
(Avanafil)
TA-2005
(Carmoterol)
T-0047
DPP-IV inhibitor
(type II diabetes)
NK-1 receptor antagonist
(overactive bladder)
PDEV inhibitor
(erectile dysfunction)
Long-acting β2 agonist
(asthma, COPD)
Cell adhesion inhibitor
(MS, IBD etc.)
Stage
Japan EU/US
I
Development
II (US)
In-house
II (EU)
In-house
II (US)
Licensed to Vivus
II (EU)
Licensed to Chiesi
II
Licensed to GSK
(EU/US)*
Blue: Stage changed since FY2005
* Clinical Hold by the FDA
5
In Phase II clinical trial stage,
TA-6666, DPPIV inhibitor for diabetes, is in phase II in the US, and phase I has started in Japan.
TA-5538, NK-1 antagonist for overactive bladder has entered phase II in EU.
T-0047 has been precautionary taken a clinical hold by the FDA because of Tysabri which is an
MS biologic agent.
Since Tysabri has resumed on the market, GSK is communicating with the authorities about T0047 resuming as well, expecting a conclusion within this year.
5
Development status of new products– Phase I
Product
Category (Indications)
Stage
Japan
EU/US
Development
T-0128
DNA topoisomerase I
inhibitor (cancer)
I (EU)
Licensed to
Menarini
TA-1702
BK channel opener
(overactive bladder)
I (US)
Licensed to
GSK
TA-5493
p38 mapkinase inhibitor
(RA, Psoriasis)
I (EU) In-house
Blue: Stage changed since FY2005
6
We have a new compound started phase I.
The compound, TA-5493, a p38 mapkinase inhibitor, we began phase I in EU
for the targeting indication of RA and Psoriasis, by ourselves, in-house development.
6
Priority Disease Areas
1.
2.
3.
Cardiovascular and Metabolism
Urology
Immunology and Inflammation
7
In Tanabe’s Medium-Term Management plan announced in May, we focused our R&D on three
disease areas.
Cardiovascular and Metabolism
Urology
Immunology and Inflammation
I explain the development status of each area.
7
Priority Therapeutic Area (CV, Metabolism)
Diabetes
In-house New Chemical Entities
-
TA-6666 (DPPIV inhibitor)
Phase II is ongoing in the US
Phase I start in Japan
-
Other NCEs (Pre-clinical)
8
In this priority area, CV and Metabolism,
we facilitate producing in-house new chemical entities especially in Diabetes.
TA-6666, DPPIV inhibitor is in phase II in the US and phase I started in Japan.
Furthermore two development candidates with other different mechanism are
now preparing for entering clinical phase.
We accelerate much more prioritizing diabetes area with these compounds.
8
Priority Therapeutic Area (Urology)
Overactive Bladder
In-house New Chemical Entities
-
TA-5538
・NK-1 receptor antagonist
・Phase II start in EU
TA-1702
・BK channel opener)
・Phase I is ongoing in the US (GSK)
-
9
In urology area, In-house two NCEs with different mechanism of action are being developed
targeting overactive bladder.
TA-5538, NK-1 receptor antagonist, phase II started in EU.
TA-1702, BK channel opener is under phase I in the US by GSK.
These two compounds have different mechanisms of action from M3 antagonists
which are popularly prescribed on current market.
The compounds are expected to be unique compounds in efficacy and safety.
9
Priority Therapeutic Area (Immunology, Inflammation)
Rheumatoid Arthritis
Maximizing Remicade, In-Licensing product
and In-house New chemical entity.
-
Remicade i.v. : Dose-escalation clinical trial
CNTO 148 s.c. : In-License
Methotrexate TANABE: Launch
TA-5493 p.o. : Phase I start
Others
- Remicade: Clinical trials for other indications
10
In Immunology and Inflammation area, we focus on maximizing Remicade targeting RA
and also focus on in-licensing and in-house development.
In RA, Remicade dose-escalation study is cunducted in phase III.
We have licensed-in CNTO148, anti-hTNFα monoclonal antibody as a s.c. injection.
Newly marketed methotrexate by Tanabe is expected to produce synergistic effect
on Remicade marketing promotion.
Additionally orally active RA agent, TA-5493, in-house NCE, phase I has started in EU.
As shown above Tanabe is working for full-line strategy in RA area.
Furthermore, Remicade’s clinical trials for other indications are ongoing.
10
CNTO 148 (Golimumab)
-
Licensed-in from Centocor in Aug. 2006
-
Humanized anti-TNFα monoclonal antibody
9 Development Status
••Co-development
Co-developmentwith
withJANSSEN
JANSSENPharmaceutical
PharmaceuticalK.K.
K.K.
••Phase
PhaseII
••Rheumatoid
Rheumatoidarthritis
arthritis
••Every
Every4weeks
4weeks s.c.
s.c.
11
CNTO148 (Golimumab), anti-hTNFα monoclonal antibody, was licensed-in
from Centocor in Aug 2006.
In Japan, Janssen pharmaceutical is implementing phase I trial and clinical trials
from phase II are scheduled to be conducted jointly by Tanabe and Janssen pharmaceuticals.
The products, targeting RA and other related diseases, is scheduled to be administered
every 4 weeks by s.c. injection.
We expect CNTO148 has a better characteristics in terms of compliance for the patient.
11
TA-5493: Phase I start in EU
9 Strength
・・Strong
Strong&
&selective
selectivep38
p38mapkinase
mapkinaseinhibitor
inhibitor
・・Suppress
Suppressthe
thecytokine
cytokineproduction
production
in
invitro:
vitro:TNFα,
TNFα,IL-1β,
IL-1β,IL-6
IL-6and
andIL-8
IL-8
in
invivo
vivo(oral
(oralefficacy):
efficacy):TNF
TNFα
α
・・Express
Expressanti-inflammatory
anti-inflammatoryeffects
effects））
9 Development Status
・・Expected
Expectedindication:
indication:Rheumatoid
Rheumatoidarthritis,
arthritis,Psoriasis
Psoriasis
・・Phase
I
Phase I
No
Nosignificant
significantadverse
adverseevent
eventwas
wasobserved
observed
Dose
dependant
inhibition
for
TNFα,
Dose dependant inhibition for TNFα,IL-6,
IL-6,IL-8
IL-8(ex-vivo)
(ex-vivo)
12
TA-5493, started phase I in EU, is a p38 mapkinase inhibitor.
Some compounds of this class are reported their efficacy for RA.
TA-5493 selectively inhibits p38α mapkinase and suppresses the cytokine production
(TNFα, IL-1β, IL-6, IL-8) in vitro. In animal models, inhibitory effects on TNFαproduction
are exhibited.
In addition, p38α is known to relate differentiation of osteoclasts responsible for born resorption.
The compound exhibit inhibitory effects on both differentiation of ostelclasts and born resorption.
Accordingly, TA-5493, in combination with TNFα inhibition is expected to have born resorption
inhibition.
through ostelclast system and is expected to prevent joint destruction more prominently than
methotrexate.
No significant adverse event was observed in non-clinical safety studies and phase I.
Expected indications are RA, and Psoriasis.
12
Remicade (Behcet’s disease) : NDA filed
Phase II and Long-term study
N=13
N=12
Long-term
study
Phase II
Retrospective
period
Additional study
Observation
period
Additional clinical study
Retrospective
period
Evaluation
period
0 2 6
10W
5mg/kg、10mg/kg
Evaluation
period
Observation
period
0 2 6W
0 2 6 14 22 30 38 46W
5mg/kg 、10mg/kg
5mg/kg
単位期間（14週間）あたりの眼発作回数の推移
25.00
20.00
15.00
10.00
5.00
0.00
Pre
Post
13
Regarding behcet’s disease, we filed NDA in 2003 after phase II and long-term studies.
Left figure shows the number of optical events per 14 wks period in phase II and long-term
studies.
During the period when Remicade is not administered, optical events occur,
but number of events decreases by Remicade administration.
In long-term study, yearlong efficacy and safety are confirmed.
Right figure shows the result of the additional clinical study.
The result shows the same effectiveness as the previous phase II study.
We have submitted those data to authority and expect an approval within FY2006.
13
Remicade (Crohn’s disease, maintenance): Phase III completed
- Well controlled with every 8 weeks for one year
Well maintenance result with every 4 weeks for
patients who respond and then lose their response
with every 8 weeks.
- As good as ACCENT 1 study (EU/US pivotal study)
NDA is scheduled to be filed by the end of 2006
14
Remicade for Crohn’s disease, maintenance therapy, phase III trial has been completed,
and is now under preparing for NDA filing by the end of this year .
The results suggested that the symptoms were well controlled with every 8 weeks injection for
one year.
Well maintenance result was also observed for patients with every 4 weeks injection whose
responses were partially insufficient with every 8 weeks injection.
Those satisfactory results are consistent with that of EU/US pivotal study (ACCENT1).
NDA is scheduled to be filed by the end of this year.
14
Remicade (Ulcerative Colitis) : Phase III
„
„
„
„
„
Moderately to severely active Ulcerative Colitis
Efficacy evaluation: Mayo score
Placebo-controlled double-blind design
Patient population:
Have failed to successfully taper, tolerate or
respond to existence therapy
Endpoint:
Efficacy (clinical response), safety and
pharmacokinetics
15
Remicade for ulcerative colitis, phase III study has been started in July.
Patients with active ulcerative colitis, who have failed to response,
have failed to successfully taper or have medical complications
to other existing medications are included.
Efficacy will be assessed by Mayo score, clinical index.
The double-blinded, parallel-group comparative clinical study will be conducted
to show the superiority of Remicade comparing with placebo.
15
EU/US study results (Ulcerative colitis)
Mucosal healing （%）
Clinical response (%)
Clinical remission (%)
ACT(Active Ulcerative Colitis Trials)1，ACT2（n=364 each）
Clinical response: Decrease from baseline in the total Mayo score of at
least 3 points
and at least 30%, with an accompanying decrease in the subscore for rectal
bleeding
Of at least 1 point or an absolute subscore for rectal bleeding of 0 or1.
Clinical remission: Total Mayo score of 2 points or lower, with no
individual subscore
Exceeding 1 point.
Mucosal healing: Absolute subscore for endoscopy of 0 or 1
Mayo score at 8 weeks
N Engl J Med 2005; 353: 2462-76
16
EU/US study results（Ulcerative colitis)
CENTCOR completed two pivotal phase III studies (ACT1, ACT2) including
patients with active ulcerative colitis having failed to successfully taper,
tolerate or respond to existing therapy such as steroid and azathioprine.
Three dosage groups (placebo, 5, 10mg/kg) were compared.
As a primary endpoint, Mayo score (clinical response) at 8 wks was evaluated.
Figure shows the positive data for clinical response of Mayo score,
clinical remission and muscosal healing.
Using these data, Remicade was approved for ulcerative colitis in EU in Feb 2006
and in the US in Sep 2005.
We will file an NDA by bridging these data in Japan.
Mayo score (0-12) consists of 4 subscores (0-3 each) such as frequency of
fecal evacuation, rectal bleeding, endoscope observation, physician’s general evaluation.
16
Remicade (Psoriasis): Phase III
„
„
„
„
„
„
Psoriasis
Primary Endpoint: PASI score
Aim: Confirm the superiority of TA-650 to placebo
Placebo-controlled double-blind design
Patient population:
Who are candidates for systemic therapy or phototherapy
and have a psoriasis area, and have certain number of total
body surface area involved.
Endpoint:
Efficacy (clinical response), safety and pharmacokinetics
17
Remicade for psoriasis, phase III started in October.
The study includes psoriasis patients who are candidates for systemic therapy
or phototherapy.
As a primary endpoint, PASI score is evaluated to confirm the superiority of
Remicade by placebo controlled, double-blinded, parallel-group comparative clinical study.
17
EU/US study result (Psoriasis)
Phase III：Randomized placebo-controlled
75% improvement in PASI at 10 weeks
100
80*
80
60
40
20
3
0
Placebo
n=77
PASI(Psoriasis area and severity index)
Lancet 2005: 366:1367-74
infliximab
5 mg/kg
n=301
*p<0.001 vs. placebo
18
CENTCOR completed two pivotal phase III studies (EXPRESS, EXPRESS II)
including patients who were candidates for phototherapy or systemic therapy.
Remicade exhibited high effectiveness in PASI score in 75% improvement.
Using these data, indication for psoriasis vulgaris was approved in EU in Sep 2005
and in the US in Sep 2006.
In Japan we will file an NDA by bridging these data.
18
PLCM strategy for Remicade
Ankylosing spondylitis preparing
Psoriasis Ph3
Ulcerative colitis Ph3
Rheumatoid arthritis/dose escalation
Ph3
Crohn’s disease/maintenance therapy Ph3
Behcet’s disease Rheumatoid arthritis
sNDA
Launched
Getting approval in series to 2010
Crohn’s disease /induction therapy Launched
2006
2007 2008
2009 2010
19
Tanabe is strictly focusing PLCM (Product Life Cycle Management) strategy of Remicade.
In addition to Crohn’s disease (induction of remission) and rheumatoid arthritis both approved,
indications for Behcet’s disease as third indication, Crohn’s disease (maintenance)
and RA for dose escalation are well progressing.
Further, phase III studies for ulcerative colitis and psoriasis, have started
and phase III study for ankylosing spondlitis will begin soon.
We will obtain the approval for all above indications one by one from 2006 to 2010
and maximize the potential of Remicade.
19
Forward-Looking Statements
¾The statements contained in this presentation is
forward-looking statements based on a number of
assumptions and belief in light of the information
currently available to management and is subject to
risks and uncertainties.
¾Actual results or performance may differ materially
from those anticipated in these statements depending
on a number of factors.
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