Takeda R&D Strategy Tadataka Yamada, M.D. Chief Medical & Scientific Officer Deborah Dunsire, M.D. President and CEO, Millennium: The Takeda Oncology Company
Nikko Hotel, San Francisco January 8, 2013
Takeda R&D Value
Takeda is a pppyharmaceutical company committed to the discovery and development of innovative solutions addressing unmet medical needs of patient s th rough R&D inves tmen t
1 | R&D Meeting | January 8, 2013 Takeda R&D Mission
Meet the future promise of Takeda as a ldithhleader in the pharmaceu tiltical industry by providing solutions to patien ts with unme t medi ca l nee ds
Transform the R&D organization to be an engine of growth that is an industry leader in R&D productivity
2 | R&D Meeting | January 8, 2013
Takeda R&D Principles
URGENCY INNOVATION
Focus on Patients
PARTNERSHIP MEASUREMENT
3 R&D Meeting | January 8, 2013 Takeda R&D Principles
URGENCY
4 | R&D Meeting | January 8, 2013
Takeda R&D Principles INNOVATION
New Frontier Science
Novel New TAK-875 TAK-375SL Novel Molecular TAK-438 AD-4833/TOMM40 Life Cycle Entity MLN0002 Lupron 6M Depot Management
Drug Discovery Unit CMC Center
5 | R&D Meeting | January 8, 2013 Takeda R&D Principles MEASUREMENT
POC&C CtConcept
Value Creation
POC&C: Proof of Concept & Competitiveness
6 | R&D Meeting | January 8, 2013
Takeda R&D Principles
Why POC&C?
Valid surrogate of value - 50% success to market
More proximate measure of value creation
Focus measurement on peak year sales
Better tool to predict future corporate performance
Set targgpets for therapeutic area units
7 | R&D Meeting | January 8, 2013 Takeda R&D Principles PARTNERSHIP
In-license
Takeda Affymax, Lundbeck, Discovery California Millenni um NdNycomed Orexigen, Novartis, (formerly Syrrx) Seattle Genetics, etc.
• BRINTELLIX* • Advinus • NESINA • MLN0002 • DAXAS • REVESTIVE • Lurasidone • Envoy • SYR-472 • MLN9708 • REVESTIVE • ADCETRIS • LigoCyte • MLN8237 •Veltuzumab •OMONTYS • ATL-962 • Intracellular • MLN0264 • Namilumab •RIENSO • AMG 386 Therapies • Alvesco • CONTRAVE • AMG 706 • Omnaris • LOTRIGA • TAK-816 • TAK-361S • ITI-214
*Proposed brand name of Lu AA21004
8 | R&D Meeting | January 8, 2013
6 Therapeutic Areas
Pipeline Assets in Phase 2 or Beyond
Metabolic / CV Oncology CNS
• BLOPRESS • CONTRAVE • VELCADE • MLN9708 • BRINTELLIX* • TAK-375SL • EDARBI • ATL-962 • LUPRON • MLN8237 • Lurasidone • SOVRIMA • AZILVA • TAK-875 • ADCETRIS • TAK-700 • NESINA • SYR-472 • AMG 706 • TAK-428 • AMG 386
Respiratory & General Medicine Vaccine Inflammatory
• DAXAS • TAKEPRON • MLN0002 • TAK-816 • Veltuzumab • DEXILANT • TAK-438 • TAK-361S • REVESTIVE • TAK-385 • Norovirus • OMONTYS vaccine • RIENSO • AMITIZA
*Proposed brand name of Lu AA21004
9 | R&D Meeting | January 8, 2013 R&D Budget in FY2012-2014 (average)
Cardiovascular & Metabolic Oncology 31% 27%
4% 12% Vaccine 12% Respiratory & Immunology 14%
General Medicine Central Nervous System
10 | R&D Meeting | January 8, 2013
NESINA / SYR-322 (alogliptin) First DPP-4 inhibitor with prospective CV outcome data
Cardiovascular Respiratory & Central Nervous System General Medicine Vaccine Oncology & Metabolic Inflammatory
Program Status First DPP-4 inhibitor to have prospective CV outcome data in a high CV risk population (EXAMINE trial) Treatment as monotherapy and in fixed-dose combination with pioglitazone or metformin PDUFA dates of alogliptin and alogliptin/pioglitazone FDC in late January 2013
Mechanism of Action Key Data – Phase 3
0 Incretin (GLP‐1 or GIP) ‐0.1 deactivated ‐0.2 ‐0.3 baseline
26 ‐0.4 m
o k ‐0.5 fr ***
W ‐0.6 ***
at *** *** ‐0.7 *** *** ***
change *** ‐0.8 *** c
1 ‐0.9 *** A momo SU Met TZD Ins therapy add‐on add‐on add‐on add‐on Placbo ‐0.02 0 ‐0.1 ‐0.19 ‐0.13 Active site DPP‐4 enzyme Alo 12.5mg ‐0.56 ‐0.38 ‐0.61 ‐0.66 ‐0.63
*** P<0.001 vs. placebo Alo 25mg ‐0.59 ‐0.52 ‐0.59 ‐0.8 ‐0.71
11 | R&D Meeting | January 8, 2013 Contrave® First obesity agent with prospective CV outcome data
Cardiovascular Respiratory & Central Nervous System General Medicine Vaccine Oncology & Metabolic Inflammatory
Program Status Fixed-dose, sustained-release combination of naltrexone-HCl and bupropion-HCl CV outcome “LIGHT STUDY” underway to meet FDA requirement. The first obesity agent to be supported by prospective cardiovascular outcome data Due to fast enrollment into LIGHT STUDY, accrual of events needed for interim analysis could occur as early as second quarter of calendar 2013. Partnership with Orexigen Therapeutics, Inc.
Mechanism of Action Key Data – Phase 3 m BL o change fr change % % LS Mean
***p<0.001 vs placebo; completers at endpoint
12 | R&D Meeting | January 8, 2013
TAK-875 First-in-class GPR40 agonist for type 2 diabetes
Cardiovascular Respiratory & Central Nervous System General Medicine Vaccine Oncology & Metabolic Inflammatory
Program Status
Once-daily insulin-secretagogue with clear differentiation from competitors: In Phase 2 trials, all doses had a markedly lower incidence of hypoglycemia compared to glimepiride (TAK-875 2.0%, glimepiride16.1%) Phase 3 studies (including CV outcome study) ongoing in the US, EU & Japan Head to head and concomitant trials with DPP4 inhibitor ongoing Projected launch in FY2015
Mechanism of Action Key Data – Phase 2
K+/ATP Channel ) 0 Glucose GLUT2 % -020.2 GK X -0.4 Mitochondria K+ Insulin Granule TAK-875 ↑ ATP ↓ Exocytosis -0.6 Insulin -0.8 in HbA1c ( in HbA1c
G Granules e qPLC -1 *# DAG PKC * IP3 -1.2 GPR40 * * Free Fatty Acid Chang -1.4 * * Ca2+ ↑ 2+ Endoplasmic Ca Channel* p<0.05 vs placebo RtiReticu lum -CllCell # p<0.05 vs Glimepiride
13 | R&D Meeting | January 8, 2013 DAXAS® (roflumilast) The first oral drug in new class of treatment for COPD
Cardiovascular Respiratory & Central Nervous System General Medicine Vaccine Oncology & Metabolic Inflammatory
Program Status
Once daily oral selective phosphodiesterase 4 (PDE4) enzyme inhibitor for COPD Approved in the EU for maintenance treatment of severe COPD and currently filed or approved in several emerging markets. Out-licensed to Forest in the US. Clinical POM study ongoing for new combination with alogliptin for type 2 diabetes.
Mechanism of Action Key Data - preclinical Combination of PDE4 inhibitors and DPP4 inhibitors increases Intestine DPP4‐i – Pancreas active plasma GLP-1 levels (db/db mice) DPP4 Vehicle GLP‐1 ↑ PDE4 inhibitor (10 mg/kg) Januvia (100 mg/kg) GLP‐1R PDE4 inhibitor + Januvia ↑ Mean+SE (n=10) Insulin + + ↑ cAMP + GLP‐1 PDE4 – cAMP PDE4i PDE4 – AMP PDE4i Beta cells AMP Intestinal L cells
14 | R&D Meeting | January 8, 2013
BRINTELLIX* / Lu AA21004 (vortioxetine) Novel multimodal antidepressant for major depressive disorder
Cardiovascular Respiratory & Central Nervous System General Medicine Vaccine Oncology & Metabolic Inflammatory
Program Status The US NDA includes data from 6 global Phase 3 trials (including a study in elderly patients) that demonstrated significant efficacy in dose range of 5 to 20mg/day Potential for favorable short and long term safety and tolerability and improvement of cognitive dysfunction of depression Lower incidence of treatment emergent sexual dysfunction No impact on sleep and weight neutrality Absence of discontinuation symptoms US NDA filed byy, Takeda in October 2012, & Japan NDA filing expected in mid-FY2013 Key Data – Phase 3 Partnership with H. Lundbeck A/S 0.7 rsus
e 060.6 Acute Major Depression in Elderly Patients V
0.5 Vortioxetine Size
0.4 * ** Duloxetine * 0.33 0.32 * 0.27 * Effect
lacebo 0.3 0.25 0.24 d P *p<0.05; **p<0.01 versus placebo. 0.2 DSST: Digit Symbol Substitution Test 0.07 RAVLT: Rey Auditory Verbal Learning Test 0.1 6E‐16 Standardize ‐0.1 DSST RAVLT Acquisition RAVLT Delayed *Proposed brand name of Lu AA21004 Recall
15 | R&D Meeting | January 8, 2013 Lurasidone Atypical antipsychotic for schizophrenia & bipolar depression
Cardiovascular Respiratory & Central Nervous System General Medicine Vaccine Oncology & Metabolic Inflammatory
Program Status Demonstrated robust schizophrenia maintenance efficacy in a 52 week study against Seroquel XR (QXR: atypical antipsychotic) 27% improved reduction in relapse compared to Seroquel XR 57% imppppqroved reduction in the risk of hospitalization compared to Seroquel XR Lack of significant effects on metabolic parameters including body weight Met primary and key secondary Key Data - Phase 3 endpoints in two phase 3 trials in bipolar I depression 52 week double-blind extended study EU MAA filed by Takeda in September 2012 for schizophrenia Partnership with F
DiiDainippon Sum itomo Pharma avorable
16 | R&D Meeting | January 8, 2013
MLN0002 (vedolizumab) A precision-based strike on inflammatory bowel disease
Cardiovascular Respiratory & Central Nervous System General Medicine Vaccine Oncology & Metabolic Inflammatory
Program Status A novel class of gut-selective monoclonal antibody targets α4β7 integrin on leukocytes involved in ulcerative colitis (UC) and Crohn’s disease (CD): Phase III UC study GEMINI I met primary endpoints of response (induction) and remission (maintenance) Phase III CD study GEMINI II met primary endpoints of remission (both induction and maintenance) MLN0002 has demonstrated efficacy in patients who are TNF naïve and those with prior anti-TNF failure in both UC and CD Key Data – Phase 2 UC CD
17 | R&D Meeting | January 8, 2013 TAK-438 (vonoprazan) Longgpper, faster, better acid suppression
Cardiovascular Respiratory & Central Nervous System General Medicine Vaccine Oncology & Metabolic Inflammatory
Program Status First-in-class potassium competitive acid blocker (PCAB) More rapid onset of action as compared with a PPI (lansoprazole) High accumulation in parietal cells – potent/prolonged acid suppression No food effect, a limitation of PPIs No interaction with CYP2C19 Phase III ongoing in Japan
Mechanism of Action Key Data – Phase 1
Intragastric pH from MRD Study (comparison with lansoprazole)
18 | R&D Meeting | January 8, 2013
Acquisition of LigoCyte Gains First-in-Class Norovirus Vaccine Candidate & Virus-Like Particle Platform
Cardiovascular Respiratory & Central Nervous System General Medicine Vaccine Oncology & Metabolic Inflammatory
A major step forward in the expansion of Takeda’s global Vaccine Business Unit *Virus-Like Particles (VLPs) mimic the external protein structure of a virus without including the genetic material (DNA or RNA). Enhances Takeda’s R&D capacity with The human immune system responds as if en counte rin g a liv e vir us, all owin g i t to buil d the acquisition of VLP* technology immune defenses
Expands Takeda ’ s development pipeline with first-in-class norovirus
vaccine (P-I/II) and pre-clinical assets LigoCyte’s norovirus VLP for RS virus, influenza and rotavirus Credit: LigoCyte Pharmaceuti ca ls, Inc.
19 | R&D Meeting | January 8, 2013 Oncology R&D Strategy
Cardiovascular Respiratory & Central Nervous System General Medicine Vaccine Oncology & Metabolic Inflammatory Continue building a sustainable pipeline to transform outcomes for patients
RESEARCH Focus on discovering first-in-class molecules or best-in-class combinations Small molecules approach Biotherapeutics approach Attack cellular infrastructure networks critical to cancer cell growth, survival irrespective of Induce cancer cell death through targeted oncogenic driver / mutation patterns delivery of potent toxin payloads to cancer cell Areas of focus selective surface proteins • Protein quality control • Cancer metabolism Areas of focus: antibody drug conjugates • Signal transduction
DEVELOPMENT
Focus on optimizing patient benefit and product potential Patient benefit Product potential
Novel combination exploration Biomarkers to aid decision making Quick to POC&C Patient enrichment / selection Differentiation strategies Companion diagnostics Global development
20 | R&D Meeting | January 8, 2013
Translational medicine will help us optimize R&D investment Cardiovascular Respiratory & Central Nervous System General Medicine Vaccine Oncology & Metabolic Inflammatory
BUILDING REDUCING an infrastructure to risk by identifying capture and interpret markers of response genomic data with our drugs Translational Medicine
DEVELOPING SPEEDING new standards of care time to market by by pursuing matching our drugs to experimental patients most likely to combinations respond
21 | R&D Meeting | January 8, 2013 Innovation Drives Approach
Cardiovascular Respiratory & Central Nervous System General Medicine Vaccine Oncology & Metabolic Inflammatory
To achieve our aspirations we must evolve our processes • Implementation of(CS/f companion diagnostics (ex. ADCETRIS/ Ventana) • Push regulatory agencies for novel endpoints (ex. MLN9708 in AL) • Patient selection based on understood biomarkers (ex. VELCADE DLBCL)
22 | R&D Meeting | January 8, 2013
The Leader in Proteasome Inhibition
May 2003: VELCADE approved December 2006: June 2008: for patients with MM VELCADE VELCADE January 2010: who have received at approved for approved in VISTA 3-year least 2 prior therapies patients with front line MM overall survival November 2011: June 2012: and have demonstrated MCL who have in combination (OS) VISTA 5-year OS Phase 3 study for progression on the last received at least with MP advantage advantage added MLN9708 in R/R therapy (SUMMIT trial) 1 prior therapy (VISTA trial) added to label to label MM begins
PROTEASOME INHIBITION
March 2005: Sept 2007: November 2009: January 2012: October 2012: 2015: VELCADE Trial for patients MLN9708, first Approval for Phase 3 study Launch of approved for in front line MM oral proteasome subcutaneous for MLN9708 in MLN9708 patient s with MM (VISTA t ri al) in hibitor en ters adiittidministration R/R amy lo idos is who have received stopped early; clinical trials of VELCADE begins at least 1 prior patients allowed therapy (APEX to cross over to trial) VELCADE
23 | R&D Meeting | January 8, 2013 VELCADE Robust clinical development program delivers LCM
Cardiovascular Respiratory & Central Nervous System General Medicine Vaccine Oncology & Metabolic Inflammatory
Subcutaneous Administration
5-year Overall $2,008 $2,000 Survival Update
$1,750 3-year Overall Survival Update $1,626
$1,500 Frontline MM illion $1,407 Approval m
$1,250 MM $1,151 with CKF t Sales $ $1,000 Five-year overall survival e MCL bfitdbtbenefit and subcutaneous Approval $794 $750 administration added to label WW N 2nd Line in FY2011 Approval $562 $500 Phase III trial in front-line $370 mantle cell lymphoma $250 ongoing
2005 2006 2007 2008 2009 2010 2011
24 | R&D Meeting | January 8, 2013
VELCADE Leading Therapy Across All Lines of MM Treatment
Cardiovascular Respiratory & Central Nervous System General Medicine Vaccine Oncology & Metabolic Inflammatory
Key Data
+27% U.S. Growth (FY12 YoY)
VELCADE leadership built 70% on practice -changing clinical experience: 60% 6 pivotal clinical studies* 50%
9+ years of clinical experience Share 40% Nearly 400,000 patients treated 30% #1 VELCADE is the only agent to deliver #1 a sustained overall survival advantage Patient 20% M
in MM M #1 10% VELCADE is the only therapy approved in rela psed mantle cell 0% lymphoma (MCL after 1 prior therapy) 1st Line 2nd Line 3rd + Line
Source: MPI market Research *SUMMIT, APEX, VISTA, MMY3021, PINNACLE , VELCADE+DOXIL
25 | R&D Meeting | January 8, 2013 VELCADE Subcutaneous administration in all indications
Cardiovascular Respiratory & Central Nervous System General Medicine Vaccine Oncology & Metabolic Inflammatory
Key Data
SC VELCADE demonstrated efficacy consistent with IV for the primary endpoint, with a difference in incidence of PN (Grade 3/4: 6% with SC vs. 16% with IV) 66% of physicians using SC VELCADE in all VELCADE patients 78% of VELCADE patients are receiving SC VELCADE
90% 80% 78% 70% 60% 50% SC 40% IV 30% 20% 22% 10% 0% Jan'12 Feb'12 Mar'12 Apr'12 May'12 Jun'12 July'12 August'12 Sept'12 Source: MPI market Research
26 | R&D Meeting | January 8, 2013
MLN9708 (ixazomib citrate) Innovation Drives our Continued Leadership in Proteasome Inhibition
Cardiovascular Respiratory & Central Nervous System General Medicine Vaccine Oncology & Metabolic Inflammatory
Program Status
Designing the Optimal Proteasome Inhibitor Potential to be a market-transforming Efficacious best-in-class product Tolerable Global rights Combinable Front-line MM data at ASH show Convenient
MLN9708: aspiration to develop the optimal proteasome inhibitor First oral proteasome inhibitor in randomized phase 3 trials Developing the all-oral regimen in both R/R MM and front line MM Single oral weekly dose 10 on-going clinical trials including two Phase III trials (RR MM and RR AL) and registration supportive trials 5 more trials in start-up including Ph 3 ND MM (+Rd)
27 | R&D Meeting | January 8, 2013 MLN9708 (ixazomib citrate) Innovation Drives our Continued Leadership in Proteasome Inhibition
Cardiovascular Respiratory & Central Nervous System General Medicine Vaccine Oncology & Metabolic Inflammatory
Key Data – Phase 2 Phase 2 data presented at ASH 2012: Of 3 response-evaluable patients who Preliminary responses with MLN9708, lenalidomide have completed 12 cycles, 2 achieved and dexamethasone CR and 1 VGPR 100 ORR 95% ORR 94% ORR 90% 90 Minimal Residual Disease samples 19 collected from patients achieving CR (N=9) 80 32 23 MRD-evaluable samples 8/9 (89%) 70 ≥VGPR MRD-negative samples 7/8 (88%) 49% ≥VGPR ≥VGPR 60 30 58% (κ:λ light chain ratio 0.3–3) 58% 50 26 35
40
30% CR 45 20 37 32 VGPR 10 PR
0 After 4 cycles After 8 cycles Overall (n=47) (n=19) (n=52)
28 | R&D Meeting | January 8, 2013
ADCETRIS (brentuximab vedotin) Building the foundation of care for CD30+ malignancies
Cardiovascular Respiratory & Central Nervous System General Medicine Vaccine Oncology & Metabolic Inflammatory
Mechanism of Action Program Status First-in-class CD30-directed antibody- Partnered with Seattle Genetics drug conjugate for relapsed/refractory HL EMA approved MAA submission in and sALCL October 2012, activities underway for Un ique, hig hly eff ec tive targe te d therapy ROW sub mi ss ions with clear patient selection opportunities. FDA approved BLA submission from Seattle Commercially, ADCETRIS is a “game- Genetics in August 2011 changer.” Physicians have been deeply Lifecycle Activities unsatisfied with existing therapy options. AETHERA Phase 3 study fully enrolled ADCETRIS binds to CD30 and is 3 Phase 3’s underway: FL CD30+ MTCL; internalized, resulting in MMAE release. CD30+ CTCL; FL HL Enrollment completed ahead of schedule in MMAE disrupts the microtubulin network, the Ph1/2 r/r HL and sALCL study in Japan inducing cell cycle arrest and apoptosis. Diagnostic development underway for CD30+ MTCL and CD30+ CTCL
29 | R&D Meeting | January 8, 2013 ADCETRIS (brentuximab vedotin) First-in-class CD30 antibody-drug conjugate
Cardiovascular Respiratory & Central Nervous System General Medicine Vaccine Oncology & Metabolic Inflammatory
Complete remission Key Data – Phase 2 e) n 94% of HL patients achieved tumor reduction Data from pivotal Phase 2 studies in relapsed/ refractory Hodgkin lymphoma (HL) and relapsed/refractory systemic anaplastic large ge from Baseli
Lymphoma cell ly(ymphoma (sALCL)g) show high overall n n n response rates and complete response rates. or Size (% Cha R/R Hodgki ORR CR m Tu R/R HL* 76% 35% † Complete remission R/R sALCL 86% 57% ne) i
97% of ALCL patients achieved tumor reduction * Relapsed/Refractory Hodgkin lymphoma † Systemic anaplastic large cell lymphoma ALCL nge from Basel s s a R/R or Size or Size (% Ch m Tu
.
30 | R&D Meeting | January 8, 2013
ADCETRIS (brentuximab vedotin) First-in-class CD30 antibody-druggjg conjugate
Cardiovascular Respiratory & Central Nervous System General Medicine Vaccine Oncology & Metabolic Inflammatory Long Term Vision: The Foundation of Care For Patients With CD30+ Disease
Investigation of “Sustain and Grow the Brand” other lymphomas Other CD30+ malignancies Front-line Hodgkin
lymphoma tial
“Consolidate the n Post-ASCT relapse prevention in high- Brand” st risk HL (AETHERA) HL 1 line/relapse prevention and CTCL Pote Front-line Mature T-cell lymphoma
“Establish the arket
Brand” M R/R Hodgkin’s Lymphoma and R/R sALCL
31 | R&D Meeting | January 8, 2013 TAK-700 (orteronel) Continuing to build our prostate cancer leadership
Cardiovascular Respiratory & Central Nervous System General Medicine Vaccine Oncology & Metabolic Inflammatory
Mechanism of Action Program Status Selective, non-steroidal, small-molecule Updated Phase 2 data reported at ASCO 2012 1 inhibitor of 17,20-lyase , a key enzyme in the Two Phase 3 trials in metastatic castration- androgen synthesis pathway2 resistant prostate cancer (mCRPC) began in Orteronel inhibits 17,20-lyyyase activity and 20104 steroid production in the human NCI-H295R C21004: global Phase 3 in chemotherapy naïve adrenocortical carcinoma cell line3 mCRPC patients, co-primary endpoints of PFS and OS . Enrollment completed in June 2012 C21005: global Phase 3 in docetaxel relapsed mCRPC patients, primary endpoint of OS. Enrollment completed in November 2012 Following PMDA discussions, bridging study to enable Japan participation in global Phase 3 trials initiated in September 2012 Initiated RTOG steroid-free dosing study (July 2012) Successf ul FDA adand EMA int eacoseractions regarding non-metastatic CRPC plan ROW submission strategy in development
1. Yamaoka M, et al. AACR 2010 (oral presentation) 2. Mostaghel EA, et al. Best Pract Res Clin Endocrinol Metab 2008;22:243–58 3. Yamaoka M, et al. EORTC-NCI-AACR 2010 (Abstract #163) 4. ClinicalTrials.gov. Available at: www.clinicaltrials.gov
32 | R&D Meeting | January 8, 2013
TAK-700 (orteronel) Selective, non-steroid dependent 17,20 lyase inhibitor
Cardiovascular Respiratory & Central Nervous System General Medicine Vaccine Oncology & Metabolic Inflammatory Steroid Hormone Synthesis Pathway orteronel
ACTH gonadotropin
Cholesterol
17-hydroxylase 17,20-lyase Androgens
Pregnenolone 17-OH-pregnenolone DHEA Estrogens
Progesterone 17-OH-progesterone Androstenedione Estrone
Corticosterone Cortisol Testosterone Estradiol
ACTH = adrenocorticotropic hormone Aldosterone DHEA = dehydroepiandrostenedione
1. Kaku TetalT, et al. Bioor gMed Chem 2011;19:6383–6399 1. Yamaoka M , et al . AACR 2010 (oral presentation ) 2. Yamaoka M, et al. J Steroid Biochem Mol Biol. 2012 Jan 12;129(3-5):115-128 2. Mostaghel EA, et al. Best Pract Res Clin Endocrinol Metab 2008;22:243–58 3. Dreicer R, et al. ASCO-GU 2010, San Francisco, CA, USA (Abstract 1030) 3. Yamaoka M, et al. EORTC-NCI-AACR 2010 (Abstract #163) 4. Agus DB, et al. ASCO 2011 (Abstract #4531)
33 | R&D Meeting | January 8, 2013 MLN8237 (alisertib) First-in-class oral Aurora A inhibitor with potential in solid tumor and hematological malignancies Cardiovascular Respiratory & Central Nervous System General Medicine Vaccine Oncology & Metabolic Inflammatory
Mechanism of Action Program Status Global Phase 3 program initiated in relapsed/refractory PTCL Single-agent clinical activity observed in aggressive lymp homas (ORR= 32%) Phase 1/2 combination with rituximab + vincristine ongoing in relapsed/refractory DLBCL and TFL (Transformed Follicular Lymphoma) Early single-agent clinical activity observed in solid tumor malignancies Aurora A inhibition results in mitotic defects (n=5) and/or delay in mitotic progression Randomized Phase 2 combination High incidence of abnormal w/weekly paclitaxel in ovarian cancer mitotic spindles often with ongoing: 38% ORR (RECIST and/or unseparated centrosomes Ca125) in Phase I escalation Chromosome alignment defects in metaphase, lagging chromosomes in anaphase and chtibidihromatin bridges in tltelop hase
34 | R&D Meeting | January 8, 2013
AMG706 (motesanib) for Japan Oral, small molecule inhibitor with potential in Asian non-small cell lung cancer patients Cardiovascular Respiratory & Central Nervous System General Medicine Vaccine Oncology & Metabolic Inflammatory Mechanism of Action Program Status >2700 patients have been enrolled in ~20 clinical trials since 1993 MONET-1 Phase 3 trial in NSCLC failed to meet ppyprimary endpoint of im pgproving overall survival leaving no path forward in U.S. and E.U. Sub-group analysis identified possible path forward in Japan and Asia Received feedback from PMDA that overall survival endpoint is “recommended” to support filing in NSCLC setting Efficacy and safety in other indications (e. g. BC, CRC) was not confirmed. Oral, small molecule inhibitor of VEG-F, PDGFR MONET-A (Asia) Phase 3 trial to confirm Asian and C-Kit sub-population efficacy in 1st line non- squamous NSCLC FPI July 12, 2012 AMG706 In-Licensing Revised agreement with Amgen executed on June 29, 2012
35 | R&D Meeting | January 8, 2013 Top 10 Companies by Pipeline Size 2012
Position 2012 No. of R&D products No. of originated Company (2011) 2012 (2011) products 1 (2) GlaxoSmithKline 257 (269) 147
2 (1) Pfizer 225 (284) 152 3 (3) Merck & Co 223 (236) 150 4(4)4 (4) NtiNovartis 218 (200) 151 5 (5) Hoffmann-La Roche 198 (183) 147 6 (()6) Sanofi 178 (()182) 91 7 (12) Takeda 149 (103) 80 8 (9) Bristol-Myers Squibb 146 (149) 113 9 (8) AstraZeneca 144 (167) 85 10 (7) Johnson & Johnson 142 (171) 85
Citeline: Pharma R&D Annual Review 2012
36 | R&D Meeting | January 8, 2013
Top 10 Companies by Ph-3 Ratio in total Clinical Pipeline (Nov 2012)
Company % of Ph-3 1 Takeda 31%
2 Merck & Co 28% 3 Bayer 28% 4 Boehringer Ingelheim 22% 5 NtiNovartis 20% 6 Sanofi 20% 7 Eli Lilly 19% 8 Glaxo SmithKline 19% 9 Johnson & Johnson 15% 10 Bristol-Meyers Squibb 15% Industrial average 19.9%
EvaluatePharma® (as of November 2012)
37 | R&D Meeting | January 8, 2013 Ensuring Steady Pipeline Approval
FY12 FY13 FY14 FY15-FY16
Lotriga (TAK-085) ATL-962 SYR-472 Lu AA21004 TAK-875 MLN0002
TAK-536/CCB2 TAK-438 MLN9708 TAK-385 JP SGN-35 TAK-700 TAK-816
SYR-322 Lu AA21004 TAK-700 TAK-875 SYR-322/MET3 MLN0002 MLN9708 US SYR-322/PIO4 MLN8237
ADCETRIS (SGN-35) SYR-322 Lurasidone TAK-491/CLD5 TAK-875 Revestive (teduglutide) SYR-322/MET3 Peginesatide MLN0002 MLN9708 EU Rienso (ferumoxytol) SYR-322/PIO4 TAK-390MR TAK-700
In emerging markets, compounds including SYR-322, TAK-491, SGN-35, MEPACT, TAK-375, TAK-390MR, DAXAS will be launched consecutively. EM1 Already-approved drugs in red 1 Emerging Market , 2 Calcium Channel Blocker , 3 Metformin, 4 Pioglitazone (ACTOS), 5 Chlorthalidone Note: Some in-licensed pipelines (including Amgen products) are not publicly disclosed based upon the In-house In-license disclosure policies of the originator companies.
38 | R&D Meeting | January 8, 2013
Takeda R&D Value
Takeda is a pppyharmaceutical company committed to the discovery and development of innovative solutions addressing unmet medical needs of patient s th rough R&D inves tmen t
39 | R&D Meeting | January 8, 2013 40 | R&D Meeting | January 8, 2013
Forward-Looking Statements
This presentation contains forward-looking statements regarding the Company's plans, outlook, strategies, and results for the future. All forward -looking statements are based on judgments derived from the information available to the Company at this time. Forward looking statements can sometimes be identified by the use of forward- looking words such as "may," "believe," "will," "expect," "project," "estimate," "should," "anticipate," "plan," "continue," "seek," "pro forma," "potential," "target, " "forecast," or "intend" or other similar words or expressions of the negative thereof. Certain risks and uncertainties could cause the Company's actual results to differ materially from any forward looking statements contained in this presentation. These risks and uncertainties include, but are not limited to, (1) the economic circumstances surrounding the Company's business, including general economic conditions in the US and worldwide; (2) competitive pressures; (3) applicable laws and regulations; (4) the success or failure of product development programs; (5) decisions of regulatory authorities and the timing thereof; (6) changes in exchange rates; (7) claims or concerns regarding the safety or efficacy of marketed products or product candidates; and (8) integration activities with acquired companies. We assume no obligation to update or revise any forward-looking statements or other information contained in this presentation, whether as a result of new information, future events, or otherwise.
2013/2/5