LONG-TERM VALUE FOR
PATIENTS, SOCIETY ANDINVESTORS15SCIENCE
DRIVENCOMPANY
WITH A
FOCUSEDMIND
BRINGING
INNOVATIONTO PATIENTSPositioned for Sustainable Revenue Growth
Potential Wave 2 pipeline not included
WAVE 1PIPELINE*1

Vyvanse
VelcadeAzilvaWAVE 1PIPELINE

Hemophilia
14
GLOBAL
BRANDS

2018

PRO-FORMAREVENUE

14
GLOBAL
BRANDS

Others2024

Entyvio
Others2029

Note: The above chart represents conceptual changes in revenue through 2024 and 2029 demonstrating growth over time offsetting loss of exclusivities and achieving a single digit growth as compared to 2018 pro forma revenue
which represents the sum of Takeda revenue for FY2018 plus Shire revenue for the same period (not including the Legacy Shire oncology business, which was sold in August 2018), converted to JPY at the rate of $1 = 111 JPY, andconverted from US GAAP to IFRS. Actual future net sales achieved by our commercialized products and pipelines will be different, perhaps materially so, as there is a range of possible outcomes from clinical development, driven by anumber of variables, including safety, efficacy and product labelling. In addition, if a product is approved, the effect of commercial factors including the patient population, the competitive environment, pricing and reimbursement isalso uncertain. Sales estimate in Wave 1 Pipeline is non-risk adjusted.

17

R&D DAY AGENDA – NEW YORK, NOVEMBER 14, 2019
TIME

AGENDA

12:30 – 12:35

Welcome and Opening Remarks
Sheelagh Cawley-Knopf, Head R&D Global Portfolio Strategy

12:35 – 12:45

Takeda: A Global Values-Based, R&D-Driven Biopharmaceutical Leader
Christophe Weber, President & CEO Takeda

12:45 – 13:20

Translating Science into Highly Innovative, Life-changing Medicines
Andy Plump, President R&D

13:20 – 13:45

Oncology and Cell Therapies with Spotlight on CAR-NK
Chris Arendt, Head Oncology Drug Discovery Unit

13:45 – 14:05

Spotlight on Oncology Opportunities• TAK-788 : Rachael Brake, Global Program Lead
• Pevonedistat : Phil Rowlands, Head Oncology Therapeutic Area Unit

14:05 – 14:20

Break

14:20 – 14:45

Rare Diseases & Gene Therapy
Dan Curran, Head Rare Disease Therapeutic Area Unit

14:45 – 15:00

Spotlight on Orexin2R agonists
Deborah Hartman, Global Program Lead

15:00 – 15:20

Therapeutic Area Focus in GI with Spotlight on Celiac Disease
Asit Parikh, Head GI Therapeutic Area Unit

15:20 – 16:00

Panel Q&A Session

16:00

Drinks reception

19

TRANSLATING SCIENCE INTO HIGHLY INNOVATIVE
LIFE-CHANGING MEDICINES
Andy Plump MD, PhD
President R&D
Takeda Pharmaceutical Company Limited
New York, NY
November 14, 2019

WHAT YOU WILL HEAR TODAY

1

Our portfolio
and pipeline will
drive growth andoffset key patent
expirations

2

We are investing in
novel mechanisms
and capabilities fora sustainable
future3

We have cultivatedan environment of
empowerment,
accountability andagility21

WE ARE POSITIONED TO DELIVER NEAR-TERM & SUSTAINED GROWTHWAVE 11TARGET
APPROVAL

FY20

FY21
TAK-7883

ONCOLOGYRARE
DISEASES

FY23
TAK-007

CLINICAL-STAGE NMEs

2L NSCLC

Hematologic
malignancies

TAK-9243

TAK-788

TAK-620

TAK-611

HR-MDS

CMV infect. intransplant

Immunology
Hematology
Metabolic

FY22

TAK-609

Hunter CNS (IT)TAK-924
AML

TAK-607

cTTP

DEE

Multiple cancers

TAK-0794

TAK-754

MG, ITPCELL THERAPYAND IMMUNEENGAGERS

TAK-981

R/R MMHemA

TARGETED
NEXT-GENINNATECHECKPOINTIMMUNE
MODULATION MODULATORS

TAK-755
iTTP, SCDGENE
THERAPY

Hunter CNS

Orexin2R-ag(TAK-925/994)
Narcolepsy T1

TAK-341
Parkinson’s
DiseaseTAK-418

NEUROSCIENCE

TAK-252

Solid tumors

TAK-531

TAK-755
TAK-935

TAK-164

GI malignancies

TAK-573

Complications ofprematurity

PLATFORMS

FY25 AND BEYOND

FY24

1L NSCLC

MLD (IT)WAVE 22

Kabuki Syndrome

Orexin2R-ag
Sleep Disorders

TAK-653
TRD

TAK-041
CIAS NSGENE
THERAPY

TAK-831CIAS NSOTHER
PLATFORMS

RNA Modulation
Antibody Transport
VehicleWVE-120101 WVE-120102

GASTROENTEROLOGY

TAK-721
EoE

Huntington’s
Disease

Huntington’s
DiseaseKuma062

TAK-101

Celiac Disease

TAK-954POGD

VACCINES

TAK-003

Dengue Vaccine

TAK-214
Norovirus
VaccineCeliac Disease

TAK-906

Gastroparesis

TAK-426

Zika Vaccine

TAK-018

Crohn’s Disease(post-op and ileitis)

TAK-951

TAK-671

Acute
Pancreatitis

GENE
THERAPY

MICROBIOME

CELL
THERAPY

Nausea &vomiting

TAK-021

EV71 vaccine

1. Projected timing of approvals depending on data read-outs; some of these Wave 1 target approval dates assume accelerated approval
2. Some Wave 2 assets could be accelerated into Wave 1 if they have breakthrough data
3. Projected approval date assumes filing on Phase 2 data
4. TAK-079 to be developed in Rare Diseases indications myasthenia gravis (MG) and immune thrombocytopenic purpura (ITP) (FPI projected in each indication in 2H FY19)

Orphan potential in at least one indication
Estimated dates as of November 14, 201922

2019: A WATERSHED YEAR FOR TAKEDAINTEGRATION OF SHIRE• 18 assets added to the clinical pipeline*

EXPANSION OF OUR GLOBAL BRANDS• Creation of a Rare Diseases Therapeutic Area

• VARSITY study demonstrated head-to-headsuperiority of Entyvio vs Humira and publishedin New England Journal of Medicine• Access to world-class Gene Therapy
capabilities• TAKHZYRO indication expansions in bradykinin
mediated angioedema• Expecting >15 approvals in China over the next
5 years* Including approved products with ongoing R&D investment

UNPRECEDENTED NMEs
• 17 NMEs in Phase 2 and Phase 3• Potentially curative novel mechanisms (e.g.
TAK-101, Orexin2R-ag, CAR-NK)• Momentum in Cell Therapies, including newpartnership with MD Anderson

23

PATIENT-DRIVEN AND SCIENCE-FIRST IN 3 CORE AREAS

INNOVATIVE BIOPHARMAONCOLOGY

RARE DISEASESNEUROSCIENCEGASTROENTEROLOGYPLASMA DERIVED THERAPIESVACCINES BUSINESS UNIT

Complementing ourrare disease focus

DifferentiatedDengue vaccine

24

WE ARE DOING MORE FOR OUR PATIENTS~40

8POTENTIAL BIC/FIC NMEs IN
PIVOTAL STUDIES1

DIVERSIFIEDMODALITIESIN RESEARCH~70%

NEW MOLECULAR
ENTITY CLINICAL
STAGE ASSETS~50%

1. BIC/FIC Best-In-Class/First-In-Class (incl. relugolix). Three NMEs in pivotal studies in 2018
2. 31 Orphan Drug Designations in at least one indication for assets in Phase 1 through LCM in 2019 versus 15 in 2018

PIPELINE WITH
ORPHAN DRUG
DESIGNATION2~4,500R&D EMPLOYEESGLOBALLY

200+

ACTIVE PARTNERSHIPS

25

WE ARE TAKING COURAGEOUS RISKS TO MAKE A CRITICAL DIFFERENCE“There is a considerable needfor improved treatments forindividuals with NT1, which is
caused by the loss of orexinproducing neurons in the brain”
Dr. Makoto Honda, Sleep
Disorders Project Leader,Tokyo Metropolitan
Institute of Medical Science

Cell Tx
Gene Tx
Biologics
Peptides~70%

Oligonucleotide
Microbiome
Small Molecule

Data presented at World Sleep conference

NOVEL TARGETMECHANISMS WITH
HUMAN VALIDATIONMODALITY
DIVERSIFICATION

5
20
19

Accelerated programs
NME stage-ups since FY18
Indications terminated or
externalized since FY18

FAST GO / NO-GO
DECISION MAKING26

WE ARE CULTIVATING THE BEST SCIENCE THROUGH
DIFFERENTIATED PARTNERSHIPS…
Select partnerships*

Access to Innovation

RESEARCH
COLLABORATIONS

IN-LICENSE~ 110

Risk-Sharing~ 50

Expanding Capacity
JOINT
DEVELOPMENTNEWCOFORMATION

~ 20

~ 20

Total Value in Public & Private Equity>$1B* Externalizations and venture investments are not included27

WE ARE NURTURING INNOVATION WHEREVER IT OCCURSTAKEDADEVELOPS &COMMERCIALIZESTAKEDA/PARTNERSHARE DEVELOPMENT& COMMERCIALIZATION

Representative examples only

CHARACTERISTICS

TAKEDAGREATER VALIDATION
AND / OR LOWER
DEVELOPMENT COST

TAK-925, TAK-994 Narcolepsy

TAK-573 Multiple Myeloma

TAK-951 Vomiting Syndromes

CD19 1XX (CAR-T)

TAK-924 Myelodysplastic Syndrome

Kuma-062 Celiac

Psychiatry Assets

Alzheimer Disease

UNCERTAIN SCIENCE
AND / OR HIGH
DEVELOPMENT COST

PARTNER-SOURCED

28

TO DRIVE HIGHER RETURN ON OUR $4.5B ANNUAL R&D INVESTMENTPRIORITIZED R&D PORTFOLIOFLEXIBLE R&D FUNDING MODELBALANCED SPENDTARGETED POPULATIONSPARTNERSHIP MODEL

Minimize internal spend andinfrastructure

Smaller trials, lower costs, potential
longer exclusivity

Success driven milestone
payments

29

A RESEARCH ENGINE FUELING A SUSTAINABLE PIPELINEPOTENTIAL NME PIVOTAL STUDY STARTS BY YEAR

IMPROVED PRODUCTIVITY

Projected
Replenishment
ResearchEngineClinicalPipeline
11
8

6
4

4
2

FY

2019

2020

2021

2022

2023

2024

• Research momentum building
with a projected ~18 portfolio
entries in FY19
• Productivity likely to increase withexpansion of cell and genetherapy capabilities• Leveraging partnerships to accessthe best clinical or preclinicalinnovation

Note: Projections assume successful data readouts

30

PIPELINE INVESTMENTS SUPPORTING NEAR-TERM GROWTHWAVE 1INNOVATIVE EXPANSIONSNEW MOLECULAR ENTITIES

31

WE ARE DRIVING EXPANSION OF OUR GLOBAL BRANDSSELECT GLOBAL GROWTH BRANDS
TAU

ONC

Therapies

Target (FY)2020

Alunbrig

1L Non Small Cell Lung Cancer

NinlaroND MM Maintenance (non-SCT and post-SCT)

Entyvio

Bradykinin Mediated Angioedema

2024

Prophylactic Treatment of von Willebrand Disease

2021

Rare

GI

New Indications / Geographic Expansions*

2020 / 2022

2019 / 2020

Alofisel

Ulcerative Colitis, Crohn’s Disease (subcutaneous formulation)

Takhzyro

Graft versus Host Disease (prophylaxis)

2022

Complex Perianal Fistulas

2021

SELECT REGIONAL EXPANSIONSRegionTherapies

China

ND MM: newly diagnosed multiple myeloma
SCT: stem cell transplant* VONVENDI is emerging as a global brandEstimated dates as of November 14, 2019

RegionTherapiesJapan

relugolix, cabozantinib,
niraparib
32

WAVE 1 NEW MOLECULAR ENTITIES HAVE POTENTIAL
TO DELIVER >$10B AGGREGATE PEAK SALES…
TARGET APPROVAL1

FY20

FY21
TAK-7882

FY22

FY23

FY24

TAK-007

TAK-924

2L NSCLC

Hematologic
malignancies

TAK-9242

TAK-788

TAK-620

TAK-611

TAK-609

TAK-755AML

ONCOLOGY
HR-MDSRARE
DISEASES

CMV infect. intransplant

Immunology
Hematology
MetabolicHunter CNS (IT)VACCINES

MLD (IT)

TAK-607

Complications ofprematuritycTTP

TAK-935

NEUROSCIENCEGASTROENTEROLOGY

1L NSCLC

DEE

TAK-721
EoE

Orexin2R-ag(TAK-925/994)
Narcolepsy T1

14 potential NME
launches which
represent
best-in-classorfirst-in-classtherapies
to advance patient
standard of care

TAK-003

Dengue Vaccine

Peak sale estimate of >$10B is non-risk adjusted
1. Projected timing of approvals depending on data read-outs; some of these Wave 1 target approval dates assume accelerated approval
2. Projected approval date assumes filing on Phase 2 data

Orphan potential in at least one indication
Estimated dates as of November 14, 201933

…AND ARE EXPECTED TO DELIVER LIFE-CHANGING MEDICINES
POTENTIAL FIRST-IN-CLASS OR BEST-IN-CLASS NMEs

ADDRESSABLE
POPULATION(IN US)2

ADDRESSABLE
POPULATION(WW)2,3

PRODUCTMECHANISM

INDICATIONTARGET
APPROVAL DATE(FY)1TAK-788

EGFR inhibitor (exon 20)

NSCLC – 2L / 1L

20214 / 2023

~2k

~20 - 30k

pevonedistat (TAK-924)

NAE inhibitor

HR-MDS / AML

20214 / 2024

~7k / ~12k

15 - 20k / 20 - 25k

TAK-007

CD19 CAR-NK

Hematologic malignancies

2023

~9k

~15 - 25k

TAK-609

ERT / I2S replacement

Hunter CNS (IT)

2021

~250

~1 - 1.5k

maribavir (TAK-620)

UL97 kinase inh

CMV infect. in transpl.

2021~7 - 15k~25 - 45k

TAK-607

IGF-1/ IGFBP3

Complications of prematurity

20245

~25k

~80 - 90k

TAK-611

ERT / arylsulfatase A

MLD (IT)

2023

~350

~1 - 2k

TAK-755

ERT/ ADAMTS-13

cTTP / iTTP

2023 / 2025

~500 / ~2k

2 - 6k / 5 - 18k

Orexin programs

Orexin 2R agonist

Narcolepsy Type 1

2024

70 - 140k

300k - 1.2M

TAK-935

CH24H inhibitor

Developmental and Epileptic
Encephalopathies (DEE)

2023

~50k

~70 - 90k

GASTROENTEROLOGY

TAK-721

Oral anti-inflammatory

Eosinophilic Esophagitis

2020

~150k

Under evaluation

VACCINES

TAK-003

VaccineDengue

2021

~32M

~1.8B

ONCOLOGYRARE
DISEASES
Immunology
Hematology
Metabolic

NEUROSCIENCE

1. Projected timing of approvals depending on data read-outs; some of these target approval dates assume accelerated approval
2. Estimated number of patients projected to be eligible for treatment in markets where the product is anticipated to becommercialized, subject to regulatory approval
3. For TAK-788, TAK-924, TAK-007, TAK-607 and TAK-620 the addressable population represent annual incidence

4. Projected approval date assumes filing on Phase 2 data
34
5. Currently in a non-pivotal Ph 2; interim stage gates may advance program into pivotal trial fortarget approval by 2024
Currently in pivotal study or potential for registration enabling Ph-2 study (note: table excludes relugolix)

IN SUMMARY: ROBUST NEAR-TERM GROWTH
TAK-609

Hunter CNS (IT)

Potential NME Approval

TAK-003

Dengue vaccine

Potential Global Brand Extension

sc UC/CD, US, EU, JP2

maribavir
TAK-620

CMV transplant

Potential Regional Brand Extension

NINLARONDMM nSCT, US,EU

pevonedistat
HR-MDS
TAK-924

ALUNBRIG

1L NSCLC, US, EU
2L NSCLC, JP

TAK-788

2L NSCLC3GATTEX

SBS, JP

TAKHZYRO

HAE, JPGATTEX

SBS, CN

TAK-755

cTTP 5

TAKHZYRO

HAE, CNALUNBRIG

1L NSCLC, CN
2L NSCLC, CN

NINLARONDMM SCT, US,EU

TAK-007

Hematologic
malignancies

VIPRIV

Gaucher Disease,CN

ALUNBRIG

H2H alectinib, EU
Post-2Gen, US, EU

ALUNBRIG

H2H alectinib, US

TAK-611MLD (IT)

Eosinophilic
Esophagitis1

TAK-721

UC/CD, CN

ENTYVIOREGIONAL

ENTYVIO

sc UC, US
CD, JPFIRAZYRHAE CNNINLARO

NDMM, US, EU, JP
NDMM nSCT, JP

ENTYVIO

GvHD, EU

TAK-935DEE4GATTEX

Pediatric, US

REPLAGAL

Fabry Disease, CN

ALOFISEL

CPF, JPVONVENDI

Peds, US, EU, JP

TAK-788

1L NSCLC4,5

TAK-607

Complications ofprematurity

NINLARONDMM SCT, JP

niraparib

Ovarian 1L, 2L, JP
Ov Salvage 1L, JP

cabozantinib 1L RCC, JP

ICLUSIG

1L Ph+ ALL, US

ALOFISEL

CPF, USCCF

Orexin 2R ag

Narcolepsy T1

ADCETRIS

FL PTCL, JP

VONVENDI

VWD, JPvonoprazan

OD ARD, JP

ADYNOVATEHemA, CNVONVENDI

Prophy, JP

pevonedistat
AML5
TAK-924cabozantinib 2L RCC, JP

ADCETRIS

FL PTCL, EU

relugolix

Prostate, JPrelugolix

Prostate, CN

ICLUSIG

1L Ph+ ALL, EU, JP

TAKHZYRO

BMA, USVONVENDI

Prophy, US, EU

OBIZURCHAWI, EU

OBIZURCHAWI, US

NINLARONDMM nSCT, CN

vonoprazan

Acid Reflux Dis.
JP, CN

FY19

cabozantinib HCC, JP

FY20

1. China approval in 2023
2. US approval for sc CD, EU approval for sc UC & CD, Japan approval for sc CD
3. Includes approval in China
4. China approval in 2024
5. New indication for currently unapproved asset

FY21

FY22

FY23

FY24

Potential approvals by fiscal year as of November 14, 2019
The target dates are estimates based on current data and subject to change

35

SUSTAINED GROWTH BEYOND FY25

WAVE 2NOVEL MECHANISMS

NEXT-GENERATION PLATFORMS

36

DRIVEN BY A CLINICAL PIPELINE OF NOVEL MECHANISMS…
FY25 AND BEYONDTARGET APPROVAL1
TAK-164

ONCOLOGY

Immunology
RARE
Hematology
DISEASES Metabolic

GI malignancies

TAK-573

TAK-252

Solid tumors

TAK-981

R/R MM

Multiple cancers

TAK-0792

TAK-754

TAK-755

TAK-341

Orexin2R-ag

TAK-041

TAK-418

TAK-653

TAK-831

MG, ITP

HemA

iTTP, SCD

TAK-531

Hunter CNS

Parkinson’s
DiseaseNEUROSCIENCE

Kabuki Syndrome

Sleep Disorders

TRD

CIAS NSCIAS NS

WVE-120101 WVE-120102
Huntington’s
DiseaseGASTROENTEROLOGY

Kuma062

TAK-101

Celiac Disease

Celiac Disease

TAK-954

TAK-906

POGD

VACCINES

Huntington’s
DiseaseTAK-214
Norovirus
VaccineGastroparesis

TAK-426

Zika Vaccine

TAK-018

Crohn’s Disease(post-op and ileitis)

TAK-671

Acute
Pancreatitis

Rich earlyclinicalpipeline ofpotentiallytransformativeand curative
NMEs

TAK-951
Nausea &vomiting

TAK-021

EV71 Vaccine

1. Some Wave 2 assets could be accelerated into Wave 1 if they have breakthrough data
2. TAK-079 to be developed in Rare Diseases indications myasthenia gravis (MG) and immune thrombocytopenic purpura (ITP) (FPI
projected for 2H FY19)

Orphan potential in at least one indication
Estimated dates as of November 14, 201937

…AND WITH OUR NEXT-GENERATION PLATFORMS
FY25 AND BEYONDTARGET APPROVALCELL THERAPIES ANDIMMUNE ENGAGERS

Attenukine
Teva
STING
CuraDev, Takeda
SUMOylation
TakedaCAR-T
GammaDelta
MSKCC, NoileCAR-T
ImmuneGammaDelta Tx
T-CiRA, Takeda Conditional T cell
CAR-NK
engagers
MD Anderson
Maverick

ONCOLOGYRARE
DISEASESTARGETED INNATE IMMUNE
MODULATION

Immunology
Hematology
Metabolic

NEXT-GEN CHECKPOINT
MODULATORS

Agonist-redirected checkpoints
Shattuck
Humabodies
Crescendo

Harnessing thepotential of cell andgene therapies andother diverse
modalities

GENE THERAPY

Hemophilia
Lysosomal Storage Diseases

GENE THERAPYNEUROSCIENCE

Neurodegenerative Diseases
StrideBio

GASTROENTEROLOGY

GENE THERAPYOTHER PLATFORMS

RNA Modulation
Wave, Skyhawk
Antibody Transport Vehicle
Denali

Liver
Ambys

Some Wave 2 assets could be accelerated into Wave 1 if they have breakthrough data

MICROBIOME

FIN-524
FInch
Microbial Consortia
NuBiyota

CELL THERAPY
Ambys

Estimated dates as of November 14, 201938

INVESTING IN CAPABILITIES TO POSITION US FOR SUCCESS• 5 clinical programs by end of FY20

Cell Therapy

Gene Therapy

Data Sciences• Disruptive platforms, including off-theshelf cell-therapies• World-class gene therapy
manufacturing• Accessing innovation throughpartnerships (e.g. Stridebio, Ambys)• Accelerate clinical development withreal world data (e.g. TAK-788)• Use machine learning to identify raredisease patients39

COMMITTED TO OUR PEOPLE

40

LIVING OUR VALUES THROUGHOUT THE INTEGRATION PROCESS

December 2018
Leadership Team and Proposed R&D
Operating Model Announced
April 2019
Prioritization of Combined
Pipeline and Portfolio
August 2019
R&D Employees Informedof Employment Status** Where legally cleared

41

STRONG LEADERSHIP EXECUTING ON OUR VISIONASIT PARIKH
Head, Gastroenterology
Therapeutic Area Unit

PHIL ROWLANDS
Head, Oncology
Therapeutic Area UnitDAN CURRAN
Head, Rare Diseases
Therapeutic Area UnitEMILIANGELO RATTIHead, Neuroscience
Therapeutic Area Unit

SARAH SHEIKH
Head, Neuroscience
Therapeutic Area Unit*

New hire*Sarah Sheik to succeed Emiliangelo Ratti

upon his retirement beginning November 25†includes Regulatory, Global Patient Safety

Evaluation, Development Operations, andClinical Supply Chain

STEVE HITCHCOCK
Head, Research

NENAD GRMUSA
Head, Center for
External Innovation

GEORGIA KERESTY
R&D Chief Operating Officer

ANNE HEATHERINGTON
Head, Data Sciences Institute

WOLFRAM NOTHAFT
Chief Medical Officer

STEFAN WILDTHead, Pharmaceutical Sciences
and Translational Engine, Cell
Therapies

JEREMY CHADWICK
Head, Global Development
Office†WOLFGANG HACKEL
Head, Global R&D Finance

ERIKA MARDER
Head, Global R&D Human
Resources

COLLEEN BEAUREGARD
Head, Global R&D
Communications

TOSHIO FUJIMOTO
General Manager, Shonan
Health Innovation Park (iPark)

42

OUR COMMITMENT TO OUR PEOPLE IS BEING RECOGNIZED43

WE ARE POSITIONED TO DELIVER NEAR-TERM & SUSTAINED GROWTHWAVE 11TARGET
APPROVAL

FY20

FY21
TAK-7883

ONCOLOGYRARE
DISEASES

FY23
TAK-007

CLINICAL-STAGE NMEs

2L NSCLC

Hematologic
malignancies

TAK-9243

TAK-788

TAK-620

TAK-611

HR-MDS

CMV infect. intransplant

Immunology
Hematology
Metabolic

FY22

TAK-609

Hunter CNS (IT)TAK-924
AML

TAK-607

cTTP

DEE

Multiple cancers

TAK-0794

TAK-754

MG, ITPCELL THERAPYAND IMMUNEENGAGERS

TAK-981

R/R MMHemA

TARGETED
NEXT-GENINNATECHECKPOINTIMMUNE
MODULATION MODULATORS

TAK-755
iTTP, SCDGENE
THERAPY

Hunter CNS

Orexin2R-ag(TAK-925/994)
Narcolepsy T1

TAK-341
Parkinson’s
DiseaseTAK-418

NEUROSCIENCE

TAK-252

Solid tumors

TAK-531

TAK-755
TAK-935

TAK-164

GI malignancies

TAK-573

Complications ofprematurity

PLATFORMS

FY25 AND BEYOND

FY24

1L NSCLC

MLD (IT)WAVE 22

Kabuki Syndrome

Orexin2R-ag
Sleep Disorders

TAK-653
TRD

TAK-041
CIAS NSGENE
THERAPY

TAK-831CIAS NSOTHER
PLATFORMS

RNA Modulation
Antibody Transport
VehicleWVE-120101 WVE-120102

GASTROENTEROLOGY

TAK-721
EoE

Huntington’s
Disease

Huntington’s
DiseaseKuma062

TAK-101

Celiac Disease

TAK-954POGD

VACCINES

TAK-003

Dengue Vaccine

TAK-214
Norovirus
VaccineCeliac Disease

TAK-906

Gastroparesis

TAK-426

Zika Vaccine

TAK-018

Crohn’s Disease(post-op and ileitis)

TAK-951

TAK-671

Acute
Pancreatitis

GENE
THERAPY

MICROBIOME

CELL
THERAPY

Nausea &vomiting

TAK-021

EV71 vaccine

1. Projected timing of approvals depending on data read-outs; some of these Wave 1 target approval dates assume accelerated approval
2. Some Wave 2 assets could be accelerated into Wave 1 if they have breakthrough data
3. Projected approval date assumes filing on Phase 2 data
4. TAK-079 to be developed in Rare Diseases indications myasthenia gravis (MG) and immune thrombocytopenic purpura (ITP) (FPI projected in each indication in 2H FY19)

Orphan potential in at least one indication
Estimated dates as of November 14, 201944

R&D DAY AGENDA – NEW YORK, NOVEMBER 14, 2019
TIME

AGENDA

12:30 – 12:35

Welcome and Opening Remarks
Sheelagh Cawley-Knopf, Head R&D Global Portfolio Strategy

12:35 – 12:45

Takeda: A Global Values-Based, R&D-Driven Biopharmaceutical Leader
Christophe Weber, President & CEO Takeda

12:45 – 13:20

Translating Science into Highly Innovative, Life-changing Medicines
Andy Plump, President R&D

13:20 – 13:45

Oncology and Cell Therapies with Spotlight on CAR-NK
Chris Arendt, Head Oncology Drug Discovery Unit

13:45 – 14:05

Spotlight on Oncology Opportunities• TAK-788 : Rachael Brake, Global Program Lead
• Pevonedistat : Phil Rowlands, Head Oncology Therapeutic Area Unit

14:05 – 14:20

Break

14:20 – 14:45

Rare Diseases & Gene Therapy
Dan Curran, Head Rare Disease Therapeutic Area Unit

14:45 – 15:00

Spotlight on Orexin2R agonists
Deborah Hartman, Global Program Lead

15:00 – 15:20

Therapeutic Area Focus in GI with Spotlight on Celiac Disease
Asit Parikh, Head GI Therapeutic Area Unit

15:20 – 16:00

Panel Q&A Session

16:00

Drinks reception

45

TAKEDA ONCOLOGY: INNOVATIVE CELL THERAPIES& NEW FRONTIERS IN IMMUNO-ONCOLOGY
Chris Arendt, PhD

Head of Oncology Drug Discovery Unit
Takeda Pharmaceutical Company Limited
New York, NY
November 14, 2019

A CURATIVE-INTENT IMMUNO-ONCOLOGY PIPELINE IS TAKING SHAPEWAVE 1

WAVE 2

NMEs that complement our global brands

Leading platforms in immuno-oncology and cell therapies

Hematologic
Malignancies

TAK-924

Immuno-Oncology

Hematologic
Malignancies

FY21 target approval

TAK-007

FY23 target approval

Lung Cancer &Solid Tumors

Lung Cancer &Solid Tumors

TAK-788

FY21 target approval

47

PARTNERSHIPS DRIVE OUR DIFFERENTIATED EARLY CLINICAL PIPELINE

UniquePartnership
Model

DifferentiatedPortfolio• Innovative, disruptive platforms• Harness innate immunity• Agility in ‘open lab’ model• Eye towards solid tumors

48

THE FIRST BREAKTHROUGHS IN CANCER IMMUNOTHERAPYTARGET T CELLSFIRST-GEN CAR-Ts

T CELL CHECKPOINT INHIBITORS
PD-1

T cellT cellCAR

CTLA-4

Cancer cell death49
Adapted from Chen & Mellman, Immunity 2013

OUR FOCUS IS ON NOVEL MECHANISMS IN THE
CANCER-IMMUNITY CYCLE
2Novel-scaffold immune
checkpoint platforms

3

1

Innate immunomodulation

Next-gen cell therapy &immune engager platforms

Cancer cell death

50
Adapted from Chen & Mellman, Immunity 2013

EMERGING STRENGTH IN TARGETED INNATE IMMUNE
1
MODULATIONHIGH UNMET
NEED

OUR
DIFFERENTIATED
APPROACH

Patients refractory/ unresponsive to current
immunotherapies

Systemic therapies leveraging innate immunity toenhance response breadth, depth & durability

Cancer cell death

PLATFORM

PARTNERMECHANISM-OF-ACTION PROGRAMSSTING agonism• Innate-to-adaptive priming

SUMOylation• Innate immune enhancer

AttenukineTM
ADCC = Antibody-dependent cellular cytotoxicity• Targeted attenuated IFN-α

PRE-CLINICAL

PH 1

TAK-676 (STING agonist)
Targeted STING agonist
TAK-981TAK-981 (ADCC combo)
TAK-573 (CD38-AttenukineTM)
Next-gen AttenukineTM= first-in-class51

ATTENUKINETM PLATFORM ELICITS BOTH DIRECT
1
TUMOR KILL AND IMMUNE ACTIVATIONTARGETED ATTENUATED TYPE I IFN PAYLOAD

TAK-573 POM IN ONGOING PHASE 1 R/R MM STUDY

TAK-573

Activation of CD8+ T cells in bone marrow

Human IgG4 Fc

Includes CD8+ T cell
migration / activation

Attenuated IFNα2bBaseline

Cycle 1 Day 16

Cycle 2 Day 2

7.3%

18.4%

28.8%

CD8+ T cells

Immunomodulation in
preclinical models

Binds CD38

Activation Marker (CD69+)

NEXT-GENATTENUKINETM

Binds innate
immunetargetAttenuated IFNα2b

FPI = first patient in

R/R MM = Relapsed / refractory multiple myeloma

POM = proof-of-mechanism

EXPECTEDMILESTONES (FY)2019
Ph1 FPI in solid
tumors

2020
Ph1b MM (incl.
combinations)521 NOVEL SCAFFOLD NEXT-GENERATION CHECKPOINT MODULATORSHIGH UNMETNEEDCurrent checkpoint modulators fail to improveoverall survival in majority of patientsOUR
DIFFERENTIATED
APPROACH

New classes of checkpoint inhibitors designed
to increase breadth and depth of responses

Cancer cell death

PLATFORM

PARTNERMECHANISM-OF-ACTION

Humabody Vh• Unique pharmacology

Agonist-redirected
checkpoints• Co-inhibition & costimulation

Vh = Variable heavy domain

PROGRAMS

PRE-CLINICAL

PH 1Concept 1
Concept 2
TAK-252 / SL-279352 (PD1-Fc-OX40L)
TAK-254 / SL-115154 (CSF1R-Fc-CD40L)= first-in-class53

BRINGING 5 NOVEL CELL THERAPY PLATFORMS
1
TO THE CLINIC BY THE END OF FY20
HIGH UNMET
NEED

OUR
DIFFERENTIATED
APPROACH

Current CAR-T therapies have significant
challenges & fail to address solid tumors

Leverage novel cell platforms & engineering toaddress shortcomings in liquid & solid tumors

Cancer cell death

INNATE IMMUNE PLATFORMS• Multiple mechanisms of tumor killing• ‘Off-the-shelf’• Utility in solid tumors

Innate tumor sensors & effectors
NK &
γδT
cells

Engineered CAR
Fc-mediated killing54

NK = Natural killer

A NETWORK OF TOP INNOVATORS IS
1FUELING TAKEDA’S CELL THERAPY ENGINECUTTING-EDGE ENGINEERING & CELL PLATFORMS
ArmoredCAR-TsNext-gen
CARs

IPSC
CAR-TsCAR-NK
platform

ShinyaYamanaka

AdrianHaydayKoji
TamadaMichelSadelain

Shin
KanekoKanekoKaty
Rezvani

Dec 2015

May 2017

Sept 2017

2019

2018

2017

γδT cellplatform

2016

IPSC
expertise

July 2018

Takeda Cell Therapy
Translational Engine
IPSC = Induced pluripotent stem cell

NK = Natural killer

Dr. Sadelain is a co-inventor on patents relative to next-gen CARs, intellectual property that MSK has licensed to Takeda. As aresult of these licensing arrangements, Dr. Sadelain and MSK have financial interests related to these research efforts.

April 2019

Nov 2019

First Development-Stage
Partnership
55

TAKEDA IS EMBARKING ON A TRANSFORMATIVE CAR-NK
1
PARTNERSHIP THAT COULD ENTER PIVOTAL TRIALS IN 2021
IL-15

NK CAR
Platform

Activating
NK receptor

Multiple mechanismsof tumor killing
Potentiation of innate& adaptive immunity

CAR19

56

1 FOUR NOVEL, OFF-THE-SHELF CAR-NK THERAPIES IN DEVELOPMENT
PATIENT VALUE PROPOSITION

PLATFORM VALUE INFLECTIONS

Rapid and deep responses with a short-time-to-treatment,
safe, off-the-shelf CAR-NK available in outpatient &community settings
Initial opportunity in G7 countries (CD19)*
3L+ DLBCL~8,0003L+ CLL~5,0003L+ iNHL~6,000Potential to move into earlier lines of therapy

PLATFORM

Ongoing maturation of clinical data: Efficacious dose,
2H 2020 durability, partial vs. full allo, cryopreserved product
Manufacturing process complete

2021

Pivotal trials in r/r DLBCL / CLL / Indolent NHL

2023

BLA filing

PROGRAMSPRECLINICAL

PH 1

TAK-007 (CD19 CAR-NK)

CAR-NK(allo cord blood)

MECHANISM-OF-ACTIONPARTNERFY•
Dr. Katy Rezvani

Non-autologous NK cell therapy

BCMA CAR-NK
Platform expansion= first-in-class

CLL = Chronic lymphocytic leukemia DLBCL = Diffuse large B-cell lymphoma iNHL = Indolent non-Hodgkin’s lymphoma*Estimated number of patients projected to be initially eligible for treatment in G7 markets, subject to regulatory approval57

1 DRAMATIC COMPLETE RESPONSE IN FIRST PATIENT TREATEDKINETICS OF CAR-NK VERSUS ENDOGENOUS T AND B
CELLS IN PERIPHERAL BLOOD
CAR-NK cells% positive cells

47-YEAR OLD MALE WITH RELAPSED TRANSFORMEDDOUBLE-HIT (C-MYC / BCL-2) DLBCL

X1000/ml of blood

Days post-CAR-NK infusion

Baseline scan
Data from Dr. Katy Rezvani, MD Anderson Cancer CenterDay 30 post CAR19-NK

T cells
B cells
Days post-CAR-NK infusion
58

1 IMPRESSIVE RESPONSES IN OTHER HEAVILY PRETREATED PATIENTS
61-YEAR OLD MALE CLL/RICHTER’S TRANSFORMATION(5 PRIOR LINES OF THERAPY)

60-YEAR OLD FEMALE WITH CLL / ACCELERATED CLL(5 PRIOR LINES OF THERAPY)CAR-NK

Baseline scanDay 30 post CAR19-NK
CR in Richter’s; SD in CLL

CLL = Chronic lymphocytic leukemia CR = Complete response SD = Stable disease
Data from Dr. Katy Rezvani, MD Anderson Cancer Center

Baseline scanDay 30 post CAR19-NK
59

CAR-NK CELLS PERSIST IN PATIENTS AND DO NOT TRIGGER1CYTOKINE RELEASE SYNDROME (CRS)
CAR-NK CELLS PERSIST UP TO 4 MONTHS POST INFUSION

IL-6 LEVLS POST CAR-NK INFUSION DO NOT INDICATE CRS

IL-6 (pg/ml)

Vector transgene copy per µg of genomic DNA

Median IL-6 level in grade 2-5 CRS post-CAR-T treatment*

Time from infusion (days)
CRS = Cytokine Release Syndrome*Turtle et al. 2017
Data from Dr. Katy Rezvani, MD Anderson Cancer Center

Time from infusion (days)
60

1 CAR-NK EFFICACY & TOXICITY TREATING MULTPLE DIAGNOSES
Lines ofTreatment

HLA Match

CRS /Neurotox

Complete
Response

3

Partial match

None



DLBCL - Refractory

7

Partial match

None

PD

CLL

4

Partial match

None



4

Partial match

None

PD

5

Partial match

None

5

Partial match

None

Diagnosis
DLBCL - Relapsed transformed double-hit
Dose
Level 1CLL
Dose
Level 2

CLL/Richter’s transformation
CLL/Accelerated CLL
CLL
DLBCL - Refractory

Dose
Level 3DLBCL - Relapsed transformed double-hit
Follicular lymphoma - Relapsed
Follicular lymphoma - Relapsed

Data from Dr. Katy Rezvani, MD Anderson Cancer Center

Incl. ASCT

Incl. ibrutinib & venetoclax
Incl. ibrutinib
Incl. ibrutinib
Incl. ibrutinib & venetoclax*Richter’s

CLL = Chronic lymphocytic leukemia

4Partial match

None

11

Partial match

None

4

Partial match

None

4

Mismatch

None

PD*Complete response for Richter’s

4Mismatch

None



61

Incl. ibrutinib
Incl. ASCT
Incl. ASCT
Incl. ASCTCRS = Cytokine release syndrome
DLBCL = Diffuse large B-cell lymphoma
ASCT = Autologous stem cell transplant
HLA = Human leukocyte antigen
PD = Progressive disease

FAST-TO-CLINIC CELL THERAPY ENGINE WILL MAXIMIZE
1LEARNINGS ON MULTIPLE ‘DISRUPTIVE’ PLATFORMS
5 CLINICAL-STAGE PROGRAMS EXPECTED BY END OF FY20

TAK-007

Off-the-shelf
CAR-NK productTAK-102
CD19 1XX-CAR-T

Hematology

FY21+:FY20

FY19

GDX012

Cytokine +chemokine
armed CAR-T

Other celltherapycandidates

Next-gen CART
signaling domain
Gamma-delta
T cells

Solid tumors

GCC CAR-T

Colorectal
Cancer62

A RICH AND POTENTIALLY TRANSFORMATIVE EARLY CLINICAL
1
ONCOLOGY PIPELINEPLATFORM

PARTNER(S)MECHANISM-OF-ACTION

PROGRAMSPRECLINICAL PH1

TAK-676 (STING agonist)

STING agonism• Innate-to-adaptive priming

SUMOylation• Innate immune enhancer

AttenukineTM• Targeted attenuated IFN-α

Agonist-redirected
checkpoints• Co-inhibition & co-stimulation

Shiga-like toxin A• Novel cytotoxic payload

TAK-169 (CD38-SLTA)

IGN toxin• Solid tumor-targeted ADC

TAK-164 (GCC-ADC)

Conditional T
cell engagers• Novel solid tumor platform

MVC-101 (EGFR COBRATM)

Cell therapy
platforms• Off-the-shelf cell therapies

UNDISCLOSEDTARGETS

Targeted STING agonist
TAK-981TAK-981 (ADCC combo)
TAK-573 (CD38-AttenukineTM)
TAK-252 / SL-279353
TAK-254 / SL-115154

TAK-007 (CD19 CAR-NK)
5 cell therapies expected in clinic by end of FY20
= first-in-class

Hematology

Solid tumors

63

NME MILESTONES ACHIEVED IN FY19 AND LOOKING AHEAD TO
OTHER POTENTIAL MILESTONES1 THROUGH FY20
PIVOTAL STUDY STARTS, APPROVALS

 TAK-611
 TAK-755

MLD
Ph 2 start2

 PEVONEDISTAT
TAK-924

AML
Ph 3 startTAK-721

EoE
ApprovalcTTP
Ph 3 startTAK-788

1L NSCLC
Ph 3 startmHTT ASO

Huntington’s Disease
Pivotal start

2H FY 2019

1H FY 2019
Narcolepsy
POC TAK-925
 TAK-721

EoE
Ph 3 data (induction)

 TAK-101

Celiac Disease
POC PEVONEDISTAT
TAK-924
 TAK-007

1H FY 2020

2H FY 2020

HR-MDSPh 2 Overall Survival

TAK-788

2L NSCLC
Ph 2 Pivotal

TAK-620

R/R CMV SOT & HSCT
Ph 3 data

Hem. Malignancies
POC

TAK-573

R/R MM, Solid Tumor
POC

TAK-755

iTTP
POC

TAK-609

Hunter (IT)Ph 3 data 2yr extension

TAK-935DEE
POC

mHTT ASO

Huntington’s Disease
POC

TAK-906

Gastroparesis
POC

TAK-721

EoE
Ph 3 data (maintenance)

TAK-951

Nausea & Vomiting
POC

Oncology
Rare Disease
Neuroscience
Gastroenterology
 Denotes milestones that have been achieved.

KEY DATA READOUTS

1. Potential key milestone dates as of November 14, 2019. The dates included herein are estimates based on current data and are subject to change
2. Potentially registration enabling

64

SUMMARY1

Total transformationof preclinical & earlyclinical pipeline2

Differentiatedopportunities in IO
leveraging innate
immunity & celltherapies

3

Multiple near-term
catalysts informing
momentum towards
solid tumors

65

R&D DAY AGENDA – NEW YORK, NOVEMBER 14, 2019
TIME

AGENDA

12:30 – 12:35

Welcome and Opening Remarks
Sheelagh Cawley-Knopf, Head R&D Global Portfolio Strategy

12:35 – 12:45

Takeda: A Global Values-Based, R&D-Driven Biopharmaceutical Leader
Christophe Weber, President & CEO Takeda

12:45 – 13:20

Translating Science into Highly Innovative, Life-changing Medicines
Andy Plump, President R&D

13:20 – 13:45

Oncology and Cell Therapies with Spotlight on CAR-NK
Chris Arendt, Head Oncology Drug Discovery Unit

13:45 – 14:05

Spotlight on Oncology Opportunities• TAK-788 : Rachael Brake, Global Program Lead
• Pevonedistat : Phil Rowlands, Head Oncology Therapeutic Area Unit

14:05 – 14:20

Break

14:20 – 14:45

Rare Diseases & Gene Therapy
Dan Curran, Head Rare Disease Therapeutic Area Unit

14:45 – 15:00

Spotlight on Orexin2R agonists
Deborah Hartman, Global Program Lead

15:00 – 15:20

Therapeutic Area Focus in GI with Spotlight on Celiac Disease
Asit Parikh, Head GI Therapeutic Area Unit

15:20 – 16:00

Panel Q&A Session

16:00

Drinks reception66TAK-788: PURSUING A FAST-TO-PATIENT STRATEGYFOR NSCLC PATIENTS WITH EGFR EXON 20 INSERTIONSRachael L Brake, PhD

Global Program Leader, Oncology
Takeda Pharmaceutical Company Limited
New York, NY
November 14, 2019

THE SIZE OF THE LUNG CANCER CHALLENGE IS VAST

228,0001

Survival of Lung cancer is amongst
the lowest of all cancers

New Lung cancer
cases / year

143,0001

Lung cancer deaths/ yr
More than breast, colon,
and prostate cancer
combined
1. American Cancer Society; Cancer facts and figures 2019
2. Office for National Statistics UK (www.ons.gov.uk)

MaleFemalesurvival

survival

10%

13%

5 yr survival estimates among adults diagnosed withlung cancer between 2007-20112
68EXON 20 INSERTIONS ARE A RARE SUBSET OF EGFR MUTANT NSCLC
Non-Sq NSCLC
200,000 pts/yr1

EGFR Exon 20 insertions
2,000 pts/yr2
EGFR Sensitizing Mutations 19.4%

No Mutations 1.2%

EGFR exon18 4%
EGFR exon19 45%

UMD 12.0%

EGFR exon21 41%
Other Drivers 2.9%
PTEN loss 0.7%
CDKN2A loss 1.9%
BRAF nonV600E 1.3%

Insertion variants

EGFR 28%

1.

V769_D770insASV

2.

D770_N771insSVD (≈19%)

EGFR T790M 5.5%

3.

H773_V774insH(≈8%)

EGFR exon20 2.1%

4.

A763_Y764insFQEA(≈7%)

EGFR WT Amp 1.0%

5.

H773_v774insPH(≈5%)

ALK fusion 3.8%

6.

H773_V774insNPH(≈4%)

ROS1 fusion 2.6%

7.

N771_P772insN

(≈3%)

8.

H773_V774insAH

(≈3%)

9.

Other

(≈31%)

NF1 loss 1.9%

KRAS 25.3%
KRAS 25.3%

RET fusion 1.7%
BRAF V600E 2.1%
MET splice 3.0%
FGFR ½ ½ 0.7%
NRAS 1.2%
PIK3CA 2.0%
MAP2K1 0.7%

ERBB2 Mut 2.3%(≈20%)MET Amp 1.4%
ERBB2 Amp 1.4%
BRCA ½ loss 1.3%
TSC ½ loss 0.7%

Sources: Leduc C et al., Ann Oncol 2017; Jorge S et al. Braz J Med Biol Res 2014; Kobayashi Y & Mitsudomi
T. Cancer Sci 2016; Arcila M et al. Mol Cancer Ther 2013; Oxnard G et al. J Thorac Oncol 2013

1.
2.

Estimated US annual incidence of non-squamous NSCLC
Represents annual incidence of the US addressable patient population

69

PATIENTS WITH EGFR EXON 20 INSERTIONS HAVE NO EFFECTIVE THERAPY
POOR RESPONSE TO EXISTING TKIs 1

POOR RESPONSE TO ANTI PD-1/PDL-1 THERAPY 2

EGFR exon 20 insertions do not demonstratesignificant PFS benefit with 1st and 2nd gen EGFR TKIs

EGFR exon 20 ins patients demonstrate limited
benefit to anti PD-1 directed therapy
100%
80%

80
60

Hazard ratio= 12.3 (p<0.0001)

40
20
0

10

20
30
Time (months)

Group

1.
2.

Best change in target lesions (%)

Progression-free survival (%)

100

40

50

Classic EGFR EGFR exon 20

60%
40%
20%
0%
-20%
-40%
-60%

Median PFS (months)

Group

Individual patient responses

Median PFS (months)

PDL-1 expression ≥1%

EGFR exon 20 ins (n=9)

2.0

EGFR exon 20 ins (n=20)

2.7 (1.7-3.8)

40%Classical EGFR mut (n=129)

12.0Classical EGFR mut (n=22)

1.8 (1.2-2.4)

25%

Robichaux et al., WCLC 2016.
Adapted from Negrao et al., WCLC 2019

70

OVERCOMING THE DRUG DEVELOPMENT CHALLENGE
IN EXON 20 INSERTIONS
L858R EGFR mutation
Wild type EGFREGFR exon 20 NPG insertion
Wild type EGFRClassical EGFR
mutation
L858R

TAK-788

TAK-788

EGFR exon 20 insertion
EGFR D770 ins NPG

EGFR exon 20 insertion mutations
have a similar structure and similar affinity for
ATP to wild type EGFR
Source. TAK-788 bound to EGFR kinase domain containing D770 ins NPG, crystal structure (data on file)

Classical EGFR mutations
Significantly alter both structure and affinity
for ATP compared to wild type EGFR

71

TAK-788 PROOF OF CONCEPT DATA IN EGFR EXON 20 INSERTIONS• Confirmed ORR: 12/28 patients: 43% (24.5-62.8%)

Median PFS: 7.3 months (4.4 mo - NR)

SAFETY SUMMARY IN PATIENTS TREATED WITH TAK-788

ANTITUMOR ACTIVITY IN EGFR EXON 20 INS AT 160 MG DAILYBest change in target lesions (%)

•

N (%)

80
60
40
20
0
-20
-40
-60
-80
-100

All Patients
160 mg qd (n=72)

Treatment-related AE

Individual patient responses

Prior TKI:

N

N

N

N

Y

N

N

N

N

N

N

N

Y

N

N

N

N

N

N

N

N

N

Y

Y

N

Prior IO:

N

Y

Y

N

Y

N

N

N

N

Y

Y

N

Y

Y

N

Y

Y

Y

N

N

Y

N

Y

Y

Y

Any grade68 (94)

Grade ≥3

29 (40)

Dose reduction due to AE

18 (25)

Dose interruption due to AE

36 (50)Discontinuation due to treatmentrelated AE

10 (14)

TAK-788 has not been approved for the use or indications under investigation in the clinical trials (and there is no guarantee it will be approved for such use or indication). Claims of safety and effectiveness can only bemade after regulatory review of the data and approval of the labeled claims.
Adapted from Riley et al. ASCO. 201972

ENCOURAGING EFFICACY AND SAFETY HAS BEEN OBSERVED
WITH TAK-788
Select signs of efficacy
TAK-788 1
n=28

Poziotinib 2
n=50

Afatinib 3
n=23

Osimertinib 4
n=15

ITT confirmed ORR (%)

43%

NR

8.7%

0%

Evaluable confirmed ORR (%)

NR

43%

NR

NR

ITT median PFS (months)

7.3

5.5

2.7

3.5

Clinical feature

Select treatment related adverse events attributable to wild type EGFR inhibition
TAK-788 1
n=72

Poziotinib 2
n=63

Afatinib 5
n=229

Osimertinib 6
n=279

Diarrhea ≥ Gr3

18%

17.5%

14%

1%

Rash ≥ Gr3

1%

35%

16%

1%

Paronychia ≥ Gr3

0%

9.5%

11%

0%

52%

2.9%

Grade ≥ 3 Adverse event

Total dose reduction rates
AE related dose reductions (%)

25%

60%

Direct cross-trial comparison can not be made between TAK-788 and other treatments due to different studies with different designs
ITT = Intention to treat, ORR = Overall response rate, PFS = progression free survival, NR = Not reported.
Sources: 1. Riley et al. ASCO. 2019; 2. Haymach et al. WCLC 2018; 3. Yang et al., Lancet. 2016.; 4. Kim et al., ESMO 2019; 5. Yang et al., Lancet. 2012; 6. Mok et at., NEJM 201773

STRONGER DIARRHEA MANAGEMENT SHOULD = ENHANCED EFFICACY

June 2016
FIRST IN HUMAN
Diarrhea
management verylate - medicate
when at Grade 2

Average time on TAK-788
7.9 months
Diarrhea
Grade 3
Grade 2
Grade 1
No diarrhea

Time onTreatment (Mo)
4.6
9.8
12.7
12.1

Feb 2019 new trial

Comprehensive
diarrhea management
guidelines
implemented earlier

WE HAVE MODIFIED OUR APPROACH TO GI ADVERSE EVENT MANAGEMENT WITH THE AIM TO IMPROVE EFFICACY

Source. TAK-788 Clinical trial database (data on file)742021: EXPECTED FIRST APPROVAL IN EGFR EXON 20 INSERTIONS•••· Single arm Phase 2 trial· Refractory EGFR Exon 20 insertion patients· Supporting data generation· Real world evidence (RWE) data collection

Previously treated, ≤2 systemic anticancer chemotherapy
Locally advanced or metastatic
NSCLC harboring EGFR exon 20 insertion

RWE will be used to assess the benefit of conventional
standard of care (SOC) agents in patients with
EGFR Exon 20 insertions
EMR claims databases and Medical Chart Review

TAK-788 at 160 mg qd
1.
2.
3.
4.

Overall Response Rate
Duration of Response
Median Progression Free Survival
Overall survival· ACTIVELY ENROLLING US, EU, AND ASIA
· POTENTIAL APPROVAL MID 2021

Source. https://clinicaltrials.gov/ct2/show/NCT02716116, https://www.exclaimstudy.com/

Chemo +/- VEGFR
1.
2.
3.
4.
5.

Immunotherapy

Other

Overall Response Rate
Time to treatment failure
Median progression free survival
Duration of Response
Overall survival· US (FLAT IRON HEALTH) · JP (SCRUM-JAPAN)· EU AND CHINA CHART REVIEW

75

NEW ACTIVATION: A TRIAL FOR NEWLY DIAGNOSED PATIENTS· Randomized, controlled, Phase 3 trial· Treatment-naïve EGFR exon 20 insertion patients••

Advanced or metastatic
Treatment-naïve patients diagnosed with NSCLC harboring
EGFR exon 20 insertion mutations

-2

R
1:1

TAK-788 at 160 mg qd

2 year enrollment
Anticipated approval 2023

1.
2.
3.
4.

Platinum doublet

Median Progression Free Survival
Overall Response Rate
Duration of Response
Overall survival

Electronic patient reported outcomes

Source. https://clinicaltrials.gov/ct2/show/NCT04129502· ACTIVELY ENROLLING· US, EU, LATIN AMERICA AND ASIA-PACIFIC

76

SUMMARY

1

NSCLC patients with
EGFR Exon 20 insertions
are underserved withthe current available
therapies2

TAK-788 is the first
purposely designed
inhibitor and clinicalproof-of-concept has
demonstrated efficacy

3

The EXCLAIM trial inrefractory patients
could lead to the first
approval of TAK-788
by 202177