Presentation Material

Mitsubishi Tanabe Pharma Corporation
Progress and Future of
Development Pipeline
Deutsche Securities Inc.
Japan Pharmaceutical Conference 2010
September 29, 2010
Hotel Seiyo Ginza/Tokyo
Masayuki Mitsuka, Ph.D.
Board Director,
Executive Officer
Head of Global Product Strategy
Corporate Strategy in R&D
■ Clearly product distinction in Japan/the U.S. and Europe
Specialty and primary in Japan
Specialty in the U.S. and Europe
■ Good balance between self-development products and
licensing-in/out products
Create the robust pipeline using alliances
■ Reviw of our priority fields
Current priority fields: metabolism and circulation
(especially diabetes and cerebral infarction)
⇒ Reviewing of the priority fields in looking back on the
Medium-Term Management Plan 08-10
Page.1
Reviewing the 08-10 Medium-Term Period
(Domestic)
Phase
Self-Development Products (Domestic)
Remicade
RA: dose escalation
Ph1
Ph2
Ph3
NDA
filed
Approved
Psoriasis
Ankylosing spondylitis
Ulcerative colitis
Crohn's disease: dose escalation
MP-424
Chronic hepatitis C
FTY720
Multiple sclerosis
MP-513
Type 2 diabetes mellitus
TA-7284
Diabetes mellitus
Co-Marketing Product (Domestic)
Escitalopram
Depression
Filed by Mochida
Co-marketing with
Mochida
Page.2
Reviewing the 08-10 Medium-Term Period
(Overseas)
Phase
Self-Development Products (US,EU)
MCI-196
Hyperphosphatemia
MP-146
Chronic kidney disease
Ph1
Ph2
Ph3
NDA
filed
Approved
Licensing-Out Products (US, EU)
FTY720
Multiple sclerosis
TA-7284
Diabetes mellitus
(US)
Licensed to
Novartis Pharma
Licensed to Johnson &
Johnson
Page.3
Immunology & Inflammation
Remicade
MP-424 (Chronic hepatitis C）
FTY720 (Multiple sclerosis）
Page.4
Remicade
Infliximab
(Anti-TNFα monoclonal antibody)
Project
Contents
Mechanism
Remicade
(Infliximab)
Stage
Profile
Anti-TNFα monoclonal antibody
Domestic
z
z
RA: dose escalation
Approved in July
2009
Psoriasis
Approved in Jan.
2010
Ankylosing spondylitis
Approved in Apr.
2010
Ulcerative colitis
Approved in June
2010
Crohn s disease: dose
escalation
Ph3
Fast-acting and strong effect
Effective for 2 months by a single dose
Page.5
Remicade: Sales Growth & LCM
（JPY Billion)
・Ankylosing spondylitis
・Ulcerative Colitis
(Additional)
600
60
500
50
・Dose escalation for RA
・Psoriasis (Additional)
400
40
Crohn s disease maintenance
(Additional)
Behcet s disease
(Additional)
300
30
200
20
10
100
Completion of PMS for RA
Crohn s
disease
(Initial
indication)
RA
(Additional)
0
FY2002
FY2003
FY2005 2006年度
FY2006
FY2007
FY2008
FY2009
FY2004 2005年度
FY2010
2002年度
2003年度
2004年度
2007年度
2008年度
2009年度
2010年度
Page.6
Remicade: Market Potential (Domestic)
Indications
Number of Patients
Other Major Biologics
Launch: Enbrel
Humira
Actemura
Orencia
Under development: Golimumab
Cimzia
RA
700,000
（MTX 200,000）
Anlylosing
spondylitis
2,000
Psoriasis
82,000
Launch: Humira
Under development: Ustekinumab
27,000
Under development: Humira
Cimzia
97,000
Under development: Golimumab
Humira
Crohn’s disease
Ulcerative colitis
Under development: Humira
Page.7
Remicade:
Comparison with Other Biologics
Anti-TNFα antibody
Anti-IL-6
receptor
antibody
CTLA4-Ig
Product name
Remicade
Enbrel
Humira
Golimumab
Cimzia
Actemra
Orencia
RA approval
2003
2005
2008
Under
development
Under
development
2008
2010
Company
MTPC
Takeda
/Pfizer
Abbott
/Eisai
Janssen
/MTPC
UCB
/Otsuka
Chugai
BMS
Indications
RA, CD
BD, Ps
AS, UC
RA
JIA
RA, Ps
（CD, AS
UC, JIA）
（RA, UC）
（RA、CD）
Administration
method
IV
SC
SC
SC
SC
IV
IV
Administration
interval
Every 8
weeks
Once or
twiceweekly
Every 2
weeks
Every 4
weeks
Every 4
weeks
Every 4
weeks
Every 4
weeks
RA
CD
BD
Ps
Rheumatoid Arthritis
Crohn s disease
Behcet s disease
Psoriasis
AS Ankylosing Spondylitis
UC Ulcerative Colitis
JIA Juvenile Idiopathic Arthritis
Castleman,
RA
RA, JIA
（ ）Under development
IV : Intravenous Injection
SC :Subcutaneous Injection
Page.8
Remicade: New indications
Results of clinical trials in Japan
PASI 75 response
at Week 10
Remicade
ASAS 20 response
（Week 24, 48）
97.0% 96.9%
Placebo
Mayo score at
Week 8
68.6%
54.8%
35.6%
0.0%
n=19
n=35
n=33
(24w)
n=32
（48w）
n=104
n=104
Psoriasis
Anlylosing spondylitis
Ulcerative colitis
Approved in Jan. 2010
Approved in Apr. 2010
Approved in June 2010
Page.9
MP-424 (Telaprevir)
/VX-950
Project
Contents
Licensed from Vertex Pharmaceuticals
Mechanism
Inhibition of HCV NS3-4A serine protease
MP-424
(Telaprevir)
Stage
Chronic
Hepatitis C
Domestic
Ph3
Overseas
US, EU：
（Vertex）
Ph3
（Tibotec）
MTPC
territory
Features
15 Asian countries including Japan and China
z
z
High efficacy compared with existing therapy
Oral drug
Page.10
Current Treatment for HCV in Japan
Estimated number of patients
■ Asymptomatic HCV carriers: 1.5 - 2 million
■ Patients who visit doctors: 400,000 - 500,000 patients/year
■ Patients on IFN:
30,000 - 50,000 patients/year
Treatment Options
■ Current standard of therapy （antiviral therapy）
Peginterferon + Ribavirin (48 weeks)
Price for one course of therapy: approx. JPY 2.1 million
■ New treatment with MP-424
MP-424 + Peginterferon + Ribavirin (24 weeks)
Treatment period of MP-424: 12 weeks
Page.11
MP-424: Clinical Results -1 <Naive Patients>
SVR Rate for Telaprevir in Treatment-Naive Patients
PR:PEG-IFN and RBV
T：MP-424
（31/75）
（48/79）
（53/79）
（38/82）
（49/82）
（56/81）
（7/10）
T12/PR12
N Engl J Med 360:1827, April 30, 2009 （PROVE1）, N Engl J Med 360:1839, April 30, 2009 （PROVE2）
Annual report2010, grant-in-aid from the Ministry of Health, Labor and Welfare, Japan. (Toranomon)
Page.12
Clinical Results -2 <Experienced Patients>
SVR Rate in Treatment
-Experienced Patients;
Prior Null Responders
SVR Rate in Treatment
-Experienced Patients ;
Prior Relapsers
PR:PEG-IFN and RBV
T：MP-424
PR:PEG-IFN and RBV
T：MP-424
（8/41）
（29/42）
PROVE3
（31/41）
（24/25）
（3/3）
Study107
N Engl J Med 362:1292, April 8, 2010 （PROVE3）, Berg T, EASL2010 （Study 107）
（15/27）
（4/24）
Study107
Berg T, EASL2010 （Study 107）
Page.13
Development Products for HCV
■Protease inhibitor
Telaprevir (Vertex/Tibotec/Mitsubishi Tanabe)
The most advanced protease inhibitor
Ph3 in US and EU, three times daily
Expected NDA for FDA in 2010
Boceprevir (Merck)
The second most advanced protease inhibitor
Ph3 in US and EU、 three times daily
Expected NDA for FDA in 2010
TMC435 (Medivir/Tibotec/Janssen)
Strong protease inhibitor, once-daily, Ph2 in US ,EU, Japan
■Polymerase inhibitor, others
RG7128 (Pharmasset/Roche)
One of the most advanced polymerase inhibitor, twice-daily
Ph2 in US and EU
BMS-790052(BMS)
Strong NS5A inhibitor, Ph2 in US and EU
Page.14
FTY720 （Fingolimod hydrochloride）
Project
Contents
Mechanism
FTY720
（Fingolimod
hydrochloride）
Modulation of sphingosine 1-phosphate (S1P) receptor
Domestic
（Co-development with
Novartis Pharma K.K.）
Stage
Profile
Multiple
sclerosis
(MS)
Overseas
（Licensed to Novartis
Pharma）
Ph2
US：
Approved in Sep.
2010
EU：
Filed in Dec. 2009
・More effective than interferon
・World’s first oral MS drug
Page.15
World Distribution of the MS Patients
‹Multiple Sclerosis (MS)
Multiple sclerosis (MS) is caused by demyelination in central nervous system. MS
presents acute attacks of diverse neurological dysfunction followed by remission
of functions.
‹Number of Patients
2,500,000
U.S.A.
400,000
Russia
250,000
Canada
50,000
U.K.
85,000
France
80,000
Germany
122,000
Italy
54,000
Spain
40,000
Japan
10,000
(MSIF2010 All right reserved)
MSIF: Multiple Sclerosis International Federation
Page.16
FTY720
・Status
Overseas : Licensed to Novartis Pharma
Approved in US and Russia in September 2010
Filed in US and EU in December 2009
by Novartis Pharma
Domestic : Co-development with Novartis Pharma K.K.
Expected to be filed in 2010
Mechanism : Facilitation of lymphocyte homing
・Competitive product
Cladribine
Approved in Russia in July 2010
in Australia in September 2010
Filed in US in July 2010 (Result is expected in 4Q.)
Mechanism : Cytotoxic effect against lymphocyte
Page.17
FTY720（Placebo-controlled study）
Dose: 0.5 or 1.25 mg, once a day
ARR*1
0.40
54% down
60% down
ARR*1
0.4
0.3
0.2
0.18
0.16
FTY720
0.5mg
FTY720
1.25mg
0.1
0
Placebo
*1 : Annualized relapse rate
N Engl J Med 2010;362:387-401.
Page.18
FTY720（Comparative trial with IFN）
【Poster presentaion at AAN in Apr. 2010】
TRANSFORMS extension study
ARR
MS activities
0.31
ARR*1
0.3
−29%
0.22
0.2
0.1
0
IFN 1y
IFN 1y → FTY720 0.5mg 1y
*1 : Annualized relapse rate
Cumlative number*2
2.1
2
−67%
1
0.7
0
IFN 1y
IFN 1y → FTY720 0.5mg 1y
*2 : Cumlative number of new/newly enlarged T2 lesions
Page.19
Diabetes
TA-7284
MP-513
Page.20
Page.20
Major Development Project (Diabetes)
Project
Contents
Mechanism
TA-7284
(Canagliflozin)
Stage
Profile
Mechanism
MP-513
(Teneligliptin)
Stage
Profile
Inhibition of SGLT2
Domestic
Ph2
Overseas
（Johnson & Johnson*）
Ph3
Low risk of hypoglycemia, body weight
reduction
Inhibition of DPP4
Domestic
Ph3
Overseas
Ph2
Superior inhibitory activity, long-acting
effect and renal excretion & hepatic
metabolism
*Ortho-McNeil-Janssen Pharmaceutical
Page.21
Canagliflozin (JNJ-28431754/TA-7284)
Overseas Ph2b Study： HbA1c
SGLT2 Inhibition for Type 2 DM: MET + Canagliflozin Dose-Ranging Study
Mean Baseline HbA1c
0
(%)
7.71
8.01
7.81
-0.79
-0.76
*
*
7.57
7.70
7.71
7.62
-0.2
-0.22
HbA1c
Change From
Baseline
(%)
-0.4
-0.6
-0.8
-1
-1.2
-0.70
*
-0.74
-0.92
*
PBO
50 mg
QD
100 mg
QD
CANA
200 mg
QD
300 mg
QD
-0.95
*
300 mg
BID
*
SITA
100 mg
QD
*P<0.001 vs placebo calculated using LS means.
"Canagliflozin is being developed by Johnson & Johnson Pharmaceutical Research and Development, LLC in collaboration with Mitsubishi
Tanabe Pharma Corporation."
Source: Presentation slides at ADA on June 26, 2010 by Dr. Julio Rosenstock (partially modified)
Page.22
Canagliflozin (JNJ-28431754/TA-7284)
Overseas Ph2b Study： Body Weight
SGLT2 Inhibition for Type 2 DM: MET + Canagliflozin Dose-Ranging Study
Mean Baseline Weight
0
(kg)
85.5
87.5
87.7
87.7
87.8
86.3
-0.6
-1
Body Weight
Change From
Baseline
(%)
87.0
-1.1
-2
-2.3
*
-3
-2.6
*
-2.7
*
-3.4
-4
*
PBO
50 mg
QD
100 mg
QD
CANA
200 mg
QD
300 mg
QD
-3.4
*
300 mg
BID
SITA
100 mg
QD
*P<0.01 vs placebo calculated using LS means.
"Canagliflozin is being developed by Johnson & Johnson Pharmaceutical Research and Development, LLC in collaboration with Mitsubishi
Tanabe Pharma Corporation."
Source: Presentation slides at ADA on June 26, 2010 by Dr. Julio Rosenstock (partially modified)
Page.23
MP-513 (teneligliptin)
Japanese Ph2a Study： HbA1c
Placebo (N=43)
teneligliptin 2.5 mg (N=47)
teneligliptin 10 mg (N=39)
teneligliptin 40 mg (N=45)
LS mean change from baseline
in HbA1c (%)
0.6
0.4
0.36
* p<0.0001 vs placebo
0.2
0
-0.2
-0.4
-0.30
*
-0.6
-0.64
-0.8
*
-1
-0.75
*
Change from baseline in HbA1c at Week 12
＊The data are expressed as LS
mean values±S.E.
Source: Presentation slides at Japan Diabetes Society in May, 2010 by Dr. Takashi Kadowaki (partially modified)
Page.24
Competition: SGLT2 Inhibitors
Company Name
Product Name/Generic Name
Development Stage (Overseas)
Bristol-Myers Squibb/AstraZeneca
Dapagliflozin (BMS512148)
US/EU： Ph3
Johnson & Johnson
Canagliflozin （JNJ-28431754/TA-7284）
US/EU： Ph3
Boehringer Ingelheim
BI-10773
US/EU： Ph3
Roche
RG7201 (CSG452)
US/EU： Ph2b
Astellas
ASP-1941
US/EU： Ph2b
Lexicon
LX4211
US/EU： Ph2a
Pfizer
PF-04971729
US/EU： Ph2a
ISIS
ISIS 388626
EU： Ph1
Company Name
Product Name/Generic Name
Development Stage (Japan)
Astellas
ASP-1941
Ph3
Chugai
CSG452 (RG7201)
Ph2/3
Mitsubishi Tanabe
Canagliflozin (TA-7284/JNJ-28431754)
Ph2b
Bristol-Myers Squib/AstraZeneca
Dapagliflozin (BMS512148)
Ph2b
Taisho
TS-071
P2
Boehringer Ingelheim
BI-10773
Ph2
Source: Companies Website/Investor Relations
Page.25
Competition：DPP4 Inhibitors
Company Name
Product Name/Generic Name
Development Stage (Overseas)
Merck
Januvia® (sitagliptin)
US/EU： Launched
Novartis
Galvus® (vildagliptin)
EU： Launched, US：Not Approved
Bristol-Myers Squibb/AstraZeneca
Onglyza® (saxagliptin)
US/EU： Launched
Takeda
Alogliptin (SYR-322)
US/EU： Ph3
Boehringer Ingelheim
Linagliptin (BI-1356/Ondero®)
US/EU： Ph3
Mitsubishi Tanabe
Teneligliptin (MP-513)
EU： Ph2, US： Ph1
Dainippon Sumitomo
DSP-7238
EU： Ph1
Company Name
Product Name/Generic Name
Development Stage (Japan)
Banyu
Januvia® (sitagliptin)
Ono
Glactiv® (sitagliptin)
Novartis
Equa® (vildagliptin)
Launched (April, 2010）
Takeda
Nesina® (alogliptin)
Launched (June, 2010)
Mitsubishi Tanabe
Teneligliptin (MP-513)
Ph3
Boehringer Ingelheim
Linagliptin (BI 1356)
Ph3
Sanwa Kagaku
Anagliptin (SK-0403)
Ph3
Otsuka
Saxagliptin (OPC262)
Ph2/3
Source: Companies Website/Investor Relations
Launched （December, 2009）
Page.26
Others
Escitalopram (Depression）
TA-1790 （ED）
Page.27
Page.27
Escitalopram
（Selective Serotonin Reuptake Inhibitors SSRI)
Project
Contents
Mechanism Selective Serotonin Reuptake Inhibitors （SSRI）
Stage
Depressants
Escitalopram
z
z
Features
z
z
Japan
（Mochida）
Filed by Mochida
※Co-marketing with Mochida＊
＊Co-promotion with
Yoshitomiyakuhin at psychiatric
institution
Highest selective SSRI
High efficacy and tolerability
Low drug interaction
W/W Sales 3,845M $**
**Uto Brain 2009/07
Page.28
Sales of Anti-Depressant Drugs
Market of anti-depressant drugs in Japan
Current NIH price basis
1,200
120
About 100 billion yen
Sales売上高（億円）
(JPY Billion)
1,000
100
800
80
600
60
40
400
200
20
0
2001
2002
2003
2004
2005
2006
2007
2008
2009
Source: © 2009 IMS Japan Jan. 2001-Dec. 2009 JPM
All rights reserved
Page.29
Efficacy and Tolerability of Escitalopram
Escitalopram
1.2
Good
●
Bupropion
● ● Citalopram
1.1
(OR) Tolerability
● Sertraline
1.0
● Fluoxetine
Mirtazapine
Venlafaxine
●
●
● Paroxetine
0.9
Duloxetine
0.8
0.8
0.9
●
● Fluvoxamine
1.0
1.1
Efficacy (OR)
1.2
1.3
1.4
Good
Meta-analysis demonstrated that escitalopram possesses high efficacy and tolerability.
Source: Lancet(2009)
Page.30
TA-1790 (Avanafil）
Project
Contents
Mechanism
TA-1790
(Avanafil)
Stage
Features
Inhibition of PDE5
Erectile
Dysfunction
US
(VIVUS）
Ph３
Korea
（Choongwae）
Ph３
High potency, good safety, rapid onset
Page.31
TA-1790 (Avanafil) Clinical Data
Co-primary SEP 3: Percent of successful sexual attempts
(SEP:Sexual Encounter Profile)
Mean Successful Attempts
60%
50%
Baseline
End of Treatment
40%
30%
20%
10%
0%
placebo
Avanafil 50mg
Avanafil 100mg
Avanafil 200mg
*p<0.001 active vs. placebo change from baseline
Resource: Press release by VIVUS on Nov. 18, 2009
Page.32
Others (Filed and Approved) ①
New Molecular Entities
Phase
Development code
(Generic name)
Category
Indications
CNTO148 Anti-TNFα
monoclonal
antibody
RA
Narcotic
analgestic
Breakthrough cancer
pain: oral transmucosal
Vaccine
Prophylaxis of pertussis
diphteria, tetanus, an
poliomyelitis
（Golimumab）
TA-8317/Acref
（Fentanyl citrate）
BK-4SP
Ph1
Ph2
Ph3
NDA
Filed
Approved
Filed in June 2010
(filed by Janssen Pharma,
co-development Janssen Pharma)
Filed in Aug. 2008
Co-development
(BIKEN*）
* The research Foundation for Microbial of Osaka University
Page.33
Others (Filed and Approved) ②
Additional Indications
Development code
(Generic name)
Phase
Category
Indications
Polymyositis,
Dermatomyositis
Venoglobulin IH
(Polyethlene glycoltreated human normal
immunoglobulin)
Human
immunoglobulin G
Hypo and
gammagloblinemia:
additional dose
Ph1
Ph2
Ph3
NDA
Filed
Approved
Filed in May 2003
Approved in May 2010
Systemic sclerosis
Myasthenia gravis
Modiodal
(Modafinil)
Pazucross
(Pazufloxacin mesilate)
Psychoneurotic
Obstructive sleep apnea
agent
New quinolone
antibacterial
agent
Severe or intractable
case: additional
dose,septis,
pneumococcus
Filed in May 2010
Approved in July 2010
Page.34
Cautionary Statement
The statements contained in this presentation is based on a number
of assumptions and belief in light of the information currently available
to management of the company and is subject to significant
risks and uncertainties. Actual financial results may differ materially from
these forecasts depending on a number of important factors.
Page.35