etokyorddayallslidesfina TAKEDA R&D INVESTOR DAY 2019 Tokyo, Japan

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TAKEDA R&D INVESTOR DAY 2019 Tokyo, Japan November 21, 2019

R&D DAY AGENDA - TOKYO, NOVEMBER 21, 2019 TIME AGENDA Welcome and Introduction of Presenters 11:00 - 11:05 Ayako Iwamuro, Investor Relations, Global Finance Realizing the Potential of Plasma derived Therapies 11:05 - 11:45 Julie Kim, President, Plasma Derived Therapies Business Unit A New Dedicated Focus on Innovative, Sustainable Solutions for Plasma Derived Therapies 11:45 - 12:15 Christopher Morabito, M.D., Head of R&D, Plasma Derived Therapies 12:15 - 12:45 Q&A session 12:45 - 13:25 Lunch Break Welcome back and Introduction of Presenters 13:25 - 13:35 Ayako Iwamuro, Investor Relations, Global Finance Takeda: A Global Values Based, R&D Driven Biopharmaceutical Leader 13:35 - 13:45 Christophe Weber, President & CEO Takeda Translating Science into Highly Innovative, Life changing Medicines 13:45 - 14:15 Andy Plump, President R&D Oncology and Cell Therapies with Spotlight on CAR NK 14:15 - 14:40 Chris Arendt, Head Oncology Drug Discovery Unit Spotlight on Oncology Opportunities 14:40 - 15:00 TAK 788: Rachel Brake, Global Program Lead Pevonedistat: Phil Rowlands, Head Oncology Therapeutic Area Unit 15:00 - 15:20 Break Rare Diseases & Gene Therapy 15:20 - 15:45 Dan Curran, Head Rare Disease Therapeutic Area Unit Spotlight on Orexin2R agonists 15:45 - 16:00 Deborah Hartman, Global Program Lead Therapeutic Area Focus in GI with Spotlight on Celiac Disease 16:00 - 16:20 Asit Parikh, Head GI Therapeutic Area Unit 16:20 - 17:00 Panel Q&A Session 1 17:00 Drinks reception

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For more information on these and other factors which may affect Takeda's results, performance, achievements, or financial position, see "Item 3. Key Information-D. Risk Factors" in Takeda's most recent Annual Report on Form 20 F and Takeda's other reports filed with the U.S. Securities and Exchange Commission, available on Takeda's website at: https://www.takeda.com/investors/reports/sec filings/ or at www.sec.gov. Future results, performance, achievements or financial position of Takeda could differ materially from those expressed in or implied by the forward looking statements. Persons receiving this presentation should not rely unduly on any forward looking statements. Takeda undertakes no obligation to update any of the forward looking statements contained in this presentation or any other forward looking statements it may make, except as required by law or stock exchange rule. Past performance is not an indicator of future results and the results of Takeda in this presentation may not be indicative of, and are not an estimate, forecast or projection of Takeda's future results. Medical information This presentation contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development. Financial information Takeda's financial statements are prepared in accordance with International Financial Reporting Standards ("IFRS"). The revenue of Shire plc ("Shire"), which were presently, presented in accordance with accounting principles generally accepted in the United States ("U.S. GAAP"), have been conformed to IFRS, without material difference. The Shire acquisition closed on January 8, 2019, and our consolidated results for the fiscal year ended March 31, 2019 include Shire's results from January 8, 2019 to March 31, 2019. References to "Legacy Takeda" businesses are to our businesses held prior to our acquisition of Shire. References to "Legacy Shire" businesses are to those businesses acquired through the Shire acquisition. This presentation includes certain pro forma information giving effect to the Shire acquisition as if it had occurred on April 1, 2018. This pro forma information has not been prepared in accordance with Article 11 of Regulation S X. This pro forma information is presented for illustrative purposes and is based on certain assumptions and judgments based on information available to us as of the date hereof, which may not necessarily have been applicable if the Shire acquisition had actually happened as of April 1, 2018. Moreover, this pro forma information gives effect to certain transactions and other events which are not directly attributable to the Shire acquisition and/or which happened subsequently to the Shire acquisition, such as divestitures and the effects of the purchase price allocation for the Shire acquisition, and therefore may not accurately reflect the effect on our financial condition and results of operations if the Shire acquisition had actually been completed on April 1, 2018. Therefore, undue reliance should not be placed on the pro forma information included herein. 2 2

ZURICH TOKYO Takeda Global HQ GREATER BOSTON SINGAPORE AREA Global Hub 5

GREATER TOKYO BOSTON Takeda AREA Global HQ Global Hub 3 36 RESEARCH MANUFACTURING SITES SITES 6

GREATER TOKYO BOSTON Takeda AREA Global HQ Global Hub COUNTRIES 27 7

TRANSLATING SCIENCE INTO HIGHLY INNOVATIVE LIFE CHANGING MEDICINES Andy Plump MD, PhD President R&D Takeda Pharmaceutical Company Limited Tokyo November 21, 2019

WHAT YOU WILL HEAR TODAY 132 Our portfolio We are investing in We have cultivated and pipeline will novel mechanisms an environment of drive growth and and capabilities for empowerment, offset key patent a sustainable accountability and expirations future agility 21

WE ARE POSITIONED TO DELIVER NEAR TERM & SUSTAINED GROWTH WAVE 11 WAVE 22 TARGET CLINICAL STAGE NMEs PLATFORMS APPROVAL FY20 FY21 FY22 FY23 FY24 FY25 AND BEYOND TAK 7883 TAK 007 TAK 924 TAK 164 TAK 252 2L NSCLC Hematologic AML GI malignancies Solid tumors TARGETED malignancies CELL THERAPY INNATE NEXT GEN ONCOLOGY AND IMMUNE IMMUNE CHECKPOINT TAK 9243 TAK 788 TAK 573 TAK 981 ENGAGERS MODULATION MODULATORS HR MDS 1L NSCLC R/R MM Multiple cancers TAK 620 TAK 611 TAK 607 TAK 0794 TAK 754 TAK 755 CMV infect. in MLD (IT) Complications of MG, ITP HemA iTTP, SCD Immunology transplant prematurity GENE RARE Hematology THERAPY DISEASES Metabolic TAK 609 TAK 755 TAK 531 Hunter CNS (IT) cTTP Hunter CNS TAK 935 Orexin2R ag TAK 341 Orexin2R ag TAK 041 DEE (TAK 925/994) Parkinson's Sleep Disorders CIAS NS OTHER Narcolepsy T1 Disease GENE PLATFORMS RNA Modulation THERAPY Antibody Transport TAK 418 TAK 653 TAK 831 Vehicle NEUROSCIENCE Kabuki Syndrome TRD CIAS NS WVE 120101 WVE 120102 Huntington's Huntington's Disease Disease TAK 721 Kuma062 TAK 101 TAK 018 TAK 671 EoE Celiac Disease Celiac Disease Crohn's Disease Acute (post op and ileitis) Pancreatitis GENE CELL GASTRO MICROBIOME ENTEROLOGY TAK 951 THERAPY THERAPY TAK 954 TAK 906 Nausea & POGD Gastroparesis vomiting TAK 003 TAK 214 TAK 426 TAK 021 VACCINES Norovirus Dengue Vaccine Vaccine Zika Vaccine EV71 vaccine 1. Projected timing of approvals depending on data read outs; some of these Wave 1 target approval dates assume accelerated approval Orphan potential in at least one indication 2. Some Wave 2 assets could be accelerated into Wave 1 if they have breakthrough data 22 Estimated dates as of November 14, 2019 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)

2019: A WATERSHED YEAR FOR TAKEDA INTEGRATION OF SHIRE EXPANSION OF OUR GLOBAL BRANDS UNPRECEDENTED NMEs 18 assets added to the clinical pipeline* VARSITY study demonstrated head to head 17 NMEs in Phase 2 and Phase 3 superiority of Entyvio vs adalimumab and Creation of a Rare Diseases Therapeutic Area published in New England Journal of Medicine Potentially curative novel mechanisms (e.g. TAK 101, Orexin2R ag, CAR NK) Access to world class Gene Therapy TAKHZYRO indication expansions in bradykinin capabilities mediated angioedema Momentum in Cell Therapies, including new partnership with MD Anderson Expecting >15 approvals in China over the next 5 years 23 * Including approved products with ongoing R&D investment

PATIENT DRIVEN AND SCIENCE FIRST IN 3 CORE AREAS INNOVATIVE BIOPHARMA ONCOLOGY RARE DISEASES NEUROSCIENCE GASTROENTEROLOGY PLASMA DERIVED THERAPIES VACCINES BUSINESS UNIT Complementing our Differentiated rare disease focus Dengue vaccine 24

WE ARE DOING MORE FOR OUR PATIENTS 8 ~40 ~4,500 POTENTIAL BIC/FIC NMEs IN NEW MOLECULAR R&D EMPLOYEES PIVOTAL STUDIES1 ENTITY CLINICAL GLOBALLY STAGE ASSETS PIPELINE WITH DIVERSIFIED ~70% ~50% ORPHAN DRUG MODALITIES 2 200+ DESIGNATION IN RESEARCH ACTIVE PARTNERSHIPS 1. BIC/FIC Best In Class/First In Class (incl. relugolix). Three NMEs in pivotal studies in 2018 25 2. 31 Orphan Drug Designations in at least one indication for assets in Phase 1 through LCM in 2019 versus 15 in 2018

WE ARE TAKING COURAGEOUS RISKS TO MAKE A CRITICAL DIFFERENCE "There is a considerable need for improved treatments for Accelerated programs Cell Tx 5 individuals with NT1, which is Gene Tx caused by the loss of orexin Biologics producing neurons in the brain" NME stage ups since FY18 Peptides ~70% 20 Dr. Makoto Honda, Sleep Oligonucleotide Disorders Project Leader, Tokyo Metropolitan Microbiome Indications terminated or Institute of Medical Science Small Molecule 19 externalized since FY18 Data presented at World Sleep conference NOVEL TARGET MODALITY FAST GO / NO GO MECHANISMS WITH DIVERSIFICATION DECISION MAKING HUMAN VALIDATION 26

WE ARE CULTIVATING THE BEST SCIENCE THROUGH DIFFERENTIATED PARTNERSHIPS Select partnerships* Access to Innovation RESEARCH IN LICENSE Risk Sharing COLLABORATIONS ~ 110 ~ 50 Expanding Capacity JOINT NEWCO DEVELOPMENT FORMATION ~ 20 ~ 20 Total Value in Public & Private Equity >$1B * Externalizations and venture investments are not included 27

WE ARE NURTURING INNOVATION WHEREVER IT OCCURS CHARACTERISTICS TAKEDA PARTNER SOURCED TAKEDA GREATER VALIDATION TAK 925, TAK 994 Narcolepsy TAK 573 Multiple Myeloma DEVELOPS & AND / OR LOWER COMMERCIALIZES DEVELOPMENT COST TAK 951 Vomiting Syndromes CD19 1XX (CAR T) TAK 924 Myelodysplastic Syndrome Kuma 062 Celiac TAKEDA/PARTNER UNCERTAIN SCIENCE Psychiatry Assets Alzheimer Disease SHARE DEVELOPMENT AND / OR HIGH & COMMERCIALIZATION DEVELOPMENT COST 28 Representative examples only

TO DRIVE HIGHER RETURN ON OUR $4.5B ANNUAL R&D INVESTMENT PRIORITIZED R&D PORTFOLIO FLEXIBLE R&D FUNDING MODEL BALANCED SPEND TARGETED POPULATIONS PARTNERSHIP MODEL Minimize internal spend and Smaller trials, lower costs, potential Success driven milestone infrastructure longer exclusivity payments 29

A RESEARCH ENGINE FUELING A SUSTAINABLE PIPELINE POTENTIAL NME PIVOTAL STUDY STARTS BY YEAR IMPROVED PRODUCTIVITY Research momentum building with a projected ~18 portfolio Projected Clinical ReplenishmentResearch entries in FY19 Pipeline Engine Productivity likely to increase with 11 expansion of cell and gene 8 therapy capabilities 6 4 4 Leveraging partnerships to access 2 the best clinical or preclinical FY 2019 20202021 2022 2023 2024 innovation Note: Projections assume successful data readouts 30

PIPELINE INVESTMENTS SUPPORTING NEAR TERM GROWTH WAVE 1 INNOVATIVE EXPANSIONS NEW MOLECULAR ENTITIES

WE ARE DRIVING EXPANSION OF OUR GLOBAL BRANDS SELECT GLOBAL GROWTH BRANDS TAU Therapies New Indications / Geographic Expansions Target (FY) Alunbrig 1L Non Small Cell Lung Cancer 2020 ONC Ninlaro ND MM Maintenance (non SCT and post SCT) 2020 / 2022 Entyvio Bradykinin Mediated Angioedema 2024 Rare * Prophylactic Treatment of von Willebrand Disease 2021 Alofisel Ulcerative Colitis, Crohn's Disease (subcutaneous formulation) 2019 / 2020 Takhzyro Graft versus Host Disease (prophylaxis) 2022 GI Complex Perianal Fistulas 2021 SELECT REGIONAL EXPANSIONS Region Therapies Region Therapies relugolix, cabozantinib, China Japan niraparib 32 ND MM: newly diagnosed multiple myeloma * VONVENDI is emerging as a global brand SCT: stem cell transplant Estimated dates as of November 14, 2019

WAVE 1 NEW MOLECULAR ENTITIES HAVE POTENTIAL TO DELIVER >$10B AGGREGATE PEAK SALES TARGET APPROVAL1 FY20 FY21 FY22 FY23 FY24 2 TAK 007 TAK 788 Hematologic TAK 924 2L NSCLC malignancies AML ONCOLOGY TAK 9242 TAK 788 HR MDS 1L NSCLC 14 potential NME launches which TAK 620 TAK 611 TAK 607 CMV infect. in Complications of MLD (IT) prematurity Immunology transplant represent RARE Hematology DISEASES Metabolic TAK 609 TAK 755 best in class Hunter CNS (IT) cTTP or TAK 935 Orexin2R ag first in class NEUROSCIENCE DEE (TAK 925/994) Narcolepsy T1 therapies GASTRO TAK 721 to advance patient ENTEROLOGY EoE standard of care TAK 003 VACCINES Dengue Vaccine Peak sale estimate of >$10B is non risk adjusted Orphan potential in at least one indication 33 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 Estimated dates as of November 14, 2019

AND ARE EXPECTED TO DELIVER LIFE CHANGING MEDICINES POTENTIAL FIRST IN CLASS OR BEST IN CLASS NMEs TARGET ADDRESSABLE ADDRESSABLE PRODUCT MECHANISM INDICATION APPROVAL DATE POPULATION POPULATION (FY)1 (IN US)2 (WW)2,3 TAK 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 ONCOLOGY TAK 007 CD19 CAR NK Hematologic malignancies 2023 ~9k ~15 25k TAK 609 ERT / I2S replacement Hunter CNS (IT) 2021 ~250 ~1 1.5k RARE maribavir (TAK 620) UL97 kinase inh CMV infect. in transpl. 2021 ~7 15k ~25 45k DISEASES TAK 607 IGF 1/ IGFBP3 Complications of prematurity 20245 ~25k ~80 90k Immunology Hematology TAK 611 ERT / arylsulfatase A MLD (IT) 2023 ~350 ~1 2k Metabolic 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 NEUROSCIENCE TAK 935 CH24H inhibitor Developmental and Epileptic 2023 ~50k ~70 90k Encephalopathies (DEE) GASTRO ENTEROLOGY TAK 721 Oral anti inflammatory Eosinophilic Esophagitis 2020 ~150k Under evaluation VACCINES TAK 003 Vaccine Dengue 2021 ~32M ~1.8B 1. Projected timing of approvals depending on data read outs; some of these target approval dates assume accelerated approval 4. Projected approval date assumes filing on Phase 2 data 2. Estimated number of patients projected to be eligible for treatment in markets where the product is anticipated to be 5. Currently in a non pivotal Ph 2; interim stage gates may advance program into pivotal trial for 34 commercialized, subject to regulatory approval target approval by 2024 3. For TAK 788, TAK 924, TAK 007, TAK 607 and TAK 620 the addressable population represent annual incidence 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 Eosinophilic TAK 721 TAK 003 Dengue vaccine Esophagitis1 Potential Global Brand Extension UC/CD, CN maribavir ENTYVIO CMV transplant sc UC/CD, US, EU, JP2 TAK 620 Potential Regional Brand Extension NDMM nSCT, US, pevonedistat NINLARO HR MDS EU TAK 924 1L NSCLC, US, EU ALUNBRIG TAK 788 2L NSCLC3 2L NSCLC, JP GATTEX SBS, JP TAKHZYRO HAE, JP GATTEX SBS, CN TAK 755 cTTP5 1L NSCLC, CN NDMM SCT, US, Hematologic TAKHZYRO HAE, CN ALUNBRIG NINLARO TAK 007 2L NSCLC, CN EU malignancies Gaucher Disease, H2H alectinib, EU VIPRIV ALUNBRIG ALUNBRIG H2H alectinib, US TAK 611 MLD (IT) CN Post 2Gen, US, EU sc UC, US NDMM, US, EU, JP ENTYVIO FIRAZYR HAE CN NINLARO ENTYVIO GvHD, EU TAK 935 DEE4 CD, JP NDMM nSCT, JP Complications of GATTEX Pediatric, US REPLAGAL Fabry Disease, CN ALOFISEL CPF, JP VONVENDI Peds, US, EU, JP TAK 788 1L NSCLC4,5 TAK 607 prematurity Ovarian 1L, 2L, JP CPF, US NINLARO NDMM SCT, JP niraparib cabozantinib 1L RCC, JP ICLUSIG 1L Ph+ ALL, US ALOFISEL Orexin 2R ag Narcolepsy T1 Ov Salvage 1L, JP CCF pevonedistat ADCETRIS FL PTCL, JP VONVENDI VWD, JP vonoprazan OD ARD, JP ADYNOVATE HemA, CN VONVENDI Prophy, JP AML5 TAK 924 cabozantinib 2L RCC, JP ADCETRIS FL PTCL, EU relugolix Prostate, JP relugolix Prostate, CN ICLUSIG 1L Ph+ ALL, EU, JP TAKHZYRO BMA, US REGIONAL Acid Reflux Dis. vonoprazan cabozantinib HCC, JP VONVENDI Prophy, US, EU OBIZUR CHAWI, EU OBIZUR CHAWI, US NINLARO NDMM nSCT, CN JP, CN FY19 FY20 FY21 FY22 FY23 FY24 1. China approval in 2023 Potential approvals by fiscal year as of November 14, 2019 2. US approval for sc CD, EU approval for sc UC & CD, Japan approval for sc CD The target dates are estimates based on current data and subject to change 3. Includes approval in China 4. China approval in 2024 35 5. New indication for currently unapproved asset

SUSTAINED GROWTH BEYOND FY25 WAVE 2 NOVEL MECHANISMS NEXT GENERATION PLATFORMS

DRIVEN BY A CLINICAL PIPELINE OF NOVEL MECHANISMS TARGET APPROVAL1 FY25 AND BEYOND TAK 164 TAK 252 GI malignancies Solid tumors ONCOLOGY TAK 573 TAK 981 R/R MM Multiple cancers TAK 0792 TAK 754 TAK 755 MG, ITP HemA iTTP, SCD RARE Immunology Rich early Hematology DISEASES Metabolic TAK 531 Hunter CNS clinical TAK 341 pipeline of Parkinson's Orexin2R ag TAK 041 Disease Sleep Disorders CIAS NS potentially NEUROSCIENCE TAK 418 TAK 653 TAK 831 Kabuki Syndrome TRD CIAS NS transformative WVE 120101 WVE 120102 Huntington's Huntington's Disease Disease and curative Kuma062 TAK 101 TAK 018 TAK 671 Crohn's Disease Acute NMEs GASTRO Celiac Disease Celiac Disease (post op and ileitis) Pancreatitis ENTEROLOGY TAK 951 TAK 954 TAK 906 Nausea & POGD Gastroparesis vomiting TAK 214 TAK 426 TAK 021 VACCINES Norovirus Vaccine Zika Vaccine EV71 Vaccine 1. Some Wave 2 assets could be accelerated into Wave 1 if they have breakthrough data Orphan potential in at least one indication 2. TAK 079 to be developed in Rare Diseases indications myasthenia gravis (MG) and immune thrombocytopenic purpura (ITP) (FPI projected for 2H FY19) Estimated dates as of November 14, 2019 37

AND WITH OUR NEXT GENERATION PLATFORMS TARGET APPROVAL FY25 AND BEYOND CELL THERAPIES AND TARGETED INNATE IMMUNE NEXT GEN CHECKPOINT IMMUNE ENGAGERS MODULATION MODULATORS Attenukine Agonist redirected checkpoints CAR T GammaDelta Teva MSKCC, Noile CAR T Shattuck ONCOLOGY Immune GammaDelta Tx STING Humabodies CuraDev, Takeda T CiRA, Takeda Conditional T cell Crescendo CAR NK engagers SUMOylation MD Anderson Maverick Takeda RARE Immunology GENE THERAPY Hematology Harnessing the DISEASES Metabolic Hemophilia Lysosomal Storage Diseases potential of cell and gene therapies and OTHER PLATFORMS GENE THERAPY RNA Modulation other diverse NEUROSCIENCE Neurodegenerative Diseases Wave, Skyhawk StrideBio Antibody Transport Vehicle Denali modalities MICROBIOME GASTRO GENE THERAPY FIN 524 CELL THERAPY FInch Liver Ambys ENTEROLOGY Ambys Microbial Consortia NuBiyota Some Wave 2 assets could be accelerated into Wave 1 if they have breakthrough data Estimated dates as of November 14, 2019 38

INVESTING IN CAPABILITIES TO POSITION US FOR SUCCESS 5 clinical programs by end of FY20 Cell Therapy Disruptive platforms, including off the shelf cell therapies World class gene therapy manufacturing Gene Therapy Accessing innovation through partnerships (e.g. Stridebio, Ambys) Accelerate clinical development with real world data (e.g. TAK 788) Data Sciences Use machine learning to identify rare disease patients 39

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 Informed of Employment Status* 41 * Where legally cleared

STRONG LEADERSHIP EXECUTING ON OUR VISION ASIT PARIKH PHIL ROWLANDS DAN CURRAN EMILIANGELO RATTI SARAH SHEIKH New hire Head, Gastroenterology Head, Oncology Head, Rare Diseases Head, Neuroscience Head, Neuroscience Therapeutic Area Unit Therapeutic Area Unit Therapeutic Area Unit Therapeutic Area Unit Therapeutic Area Unit* *Sarah Sheik to succeed Emiliangelo Ratti upon his retirement beginning November 25 includes Regulatory, Global Patient Safety Evaluation, Development Operations, and Clinical Supply Chain STEVE HITCHCOCK NENAD GRMUSA GEORGIA KERESTY ANNE HEATHERINGTON WOLFRAM NOTHAFT Head, Research Head, Center for R&D Chief Operating Officer Head, Data Sciences Institute Chief Medical Officer External Innovation STEFAN WILDT JEREMY CHADWICK WOLFGANG HACKEL ERIKA MARDER COLLEEN BEAUREGARD TOSHIO FUJIMOTO Head, Pharmaceutical Sciences Head, Global Development Head, Global R&D Finance Head, Global R&D Human Head, Global R&D General Manager, Shonan and Translational Engine, Cell Office Resources Communications Health Innovation Park (iPark) Therapies 42

OUR COMMITMENT TO OUR PEOPLE IS BEING RECOGNIZED 43

WE ARE POSITIONED TO DELIVER NEAR TERM & SUSTAINED GROWTH WAVE 11 WAVE 22 TARGET CLINICAL STAGE NMEs PLATFORMS APPROVAL FY20 FY21 FY22 FY23 FY24 FY25 AND BEYOND TAK 7883 TAK 007 TAK 924 TAK 164 TAK 252 2L NSCLC Hematologic AML GI malignancies Solid tumors TARGETED malignancies CELL THERAPY INNATE NEXT GEN ONCOLOGY AND IMMUNE IMMUNE CHECKPOINT TAK 9243 TAK 788 TAK 573 TAK 981 ENGAGERS MODULATION MODULATORS HR MDS 1L NSCLC R/R MM Multiple cancers TAK 620 TAK 611 TAK 607 TAK 0794 TAK 754 TAK 755 CMV infect. in MLD (IT) Complications of MG, ITP HemA iTTP, SCD Immunology transplant prematurity GENE RARE Hematology THERAPY DISEASES Metabolic TAK 609 TAK 755 TAK 531 Hunter CNS (IT) cTTP Hunter CNS TAK 935 Orexin2R ag TAK 341 Orexin2R ag TAK 041 DEE (TAK 925/994) Parkinson's Sleep Disorders CIAS NS OTHER Narcolepsy T1 Disease GENE PLATFORMS RNA Modulation THERAPY Antibody Transport TAK 418 TAK 653 TAK 831 Vehicle NEUROSCIENCE Kabuki Syndrome TRD CIAS NS WVE 120101 WVE 120102 Huntington's Huntington's Disease Disease TAK 721 Kuma062 TAK 101 TAK 018 TAK 671 EoE Celiac Disease Celiac Disease Crohn's Disease Acute (post op and ileitis) Pancreatitis GENE CELL GASTRO MICROBIOME ENTEROLOGY TAK 951 THERAPY THERAPY TAK 954 TAK 906 Nausea & POGD Gastroparesis vomiting TAK 003 TAK 214 TAK 426 TAK 021 VACCINES Norovirus Dengue Vaccine Vaccine Zika Vaccine EV71 vaccine 1. Projected timing of approvals depending on data read outs; some of these Wave 1 target approval dates assume accelerated approval Orphan potential in at least one indication 2. Some Wave 2 assets could be accelerated into Wave 1 if they have breakthrough data 44 Estimated dates as of November 14, 2019 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)

TAKEDA ONCOLOGY: INNOVATIVE CELL THERAPIES & NEW FRONTIERS IN IMMUNO ONCOLOGY Chris Arendt, PhD Head of Oncology Drug Discovery Unit Takeda Pharmaceutical Company Limited Tokyo November 21, 2019

A CURATIVE INTENT IMMUNO ONCOLOGY PIPELINE IS TAKING SHAPE WAVE 1 WAVE 2 NMEs that complement our global brands Leading platforms in immuno oncology and cell therapies Hematologic Hematologic Immuno Oncology Malignancies TAK 924 Malignancies FY21 target approval TAK 007 FY23 target approval Lung Cancer & Lung Cancer & Solid Tumors Solid Tumors TAK 788 FY21 target approval 47

PARTNERSHIPS DRIVE OUR DIFFERENTIATED EARLY CLINICAL PIPELINE Unique Differentiated Partnership Portfolio Model Innovative, disruptive platforms Harness innate immunity Agility in open lab' model Eye towards solid tumors 48

THE FIRST BREAKTHROUGHS IN CANCER IMMUNOTHERAPY TARGET T CELLS T CELL CHECKPOINT INHIBITORS FIRST GEN CAR Ts PD 1 T cell CAR T cell CTLA 4 Cancer cell death 49 Adapted from Chen & Mellman, Immunity 2013

OUR FOCUS IS ON NOVEL MECHANISMS IN THE CANCER IMMUNITY CYCLE 2 Novel scaffold immune checkpoint platforms Next gen cell therapy & 3 immune engager platforms 1 Innate immuno modulation Cancer cell death 50 Adapted from Chen & Mellman, Immunity 2013

EMERGING STRENGTH IN TARGETED INNATE IMMUNE 1 MODULATION HIGH UNMET Patients refractory/ unresponsive to current NEED immunotherapies OUR Systemic therapies leveraging innate immunity to DIFFERENTIATED enhance response breadth, depth & durability APPROACH Cancer cell death PLATFORM PARTNER MECHANISM OF ACTION PROGRAMS PRE CLINICAL PH 1 TAK 676 (STING agonist) STING agonism Innate to adaptive priming Targeted STING agonist TAK 981 Innate immune enhancer SUMOylation TAK 981 (ADCC combo) TAK 573 (CD38 AttenukineTM) AttenukineTM Targeted attenuated IFN Next gen AttenukineTM 51 ADCC = Antibody dependent cellular cytotoxicity = first in class

ATTENUKINETM PLATFORM ELICITS BOTH DIRECT 1 TUMOR KILL AND IMMUNE ACTIVATION TARGETED 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 Binds CD38 Immunomodulation in Baseline preclinical models Cycle 1 Day 16 Cycle 2 Day 2 7.3% 18.4% 28.8% Human IgG4 Fc Includes CD8+ T cell migration / activation CD8+ T cells Attenuated IFN 2b Activation Marker (CD69+) NEXT GEN Binds innate TM immune ATTENUKINE target EXPECTED 2019 2020 MILESTONES (FY) Ph1 FPI in solid Ph1b MM (incl. tumors combinations) Attenuated IFN 2b FPI = first patient in R/R MM = Relapsed / refractory multiple myeloma POM = proof of mechanism 52

2 NOVEL SCAFFOLD NEXT GENERATION CHECKPOINT MODULATORS HIGH UNMET Current checkpoint modulators fail to improve NEED overall survival in majority of patients OUR New classes of checkpoint inhibitors designed DIFFERENTIATED to increase breadth and depth of responses APPROACH Cancer cell death PLATFORM PARTNER MECHANISM OF ACTION PROGRAMS PRE CLINICAL PH 1 Concept 1 Humabody Vh Unique pharmacology Concept 2 Agonist redirected Co inhibition & co TAK 252 / SL 279352 (PD1 Fc OX40L) checkpoints stimulation TAK 254 / SL 115154 (CSF1R Fc CD40L) = first in class 53 Vh = Variable heavy domain

BRINGING 5 NOVEL CELL THERAPY PLATFORMS 3 TO THE CLINIC BY THE END OF FY20 HIGH UNMET Current CAR T therapies have significant NEED challenges & fail to address solid tumors OUR Leverage novel cell platforms & engineering to DIFFERENTIATED address shortcomings in liquid & solid tumors APPROACH Cancer cell death INNATE IMMUNE PLATFORMS Innate tumor sensors & effectors Multiple mechanisms of tumor killing NK & Engineered CAR Off the shelf' T cells Utility in solid tumors Fc mediated killing 54 NK = Natural killer

A NETWORK OF TOP INNOVATORS IS 3 FUELING TAKEDA'S CELL THERAPY ENGINE CUTTING EDGE ENGINEERING & CELL PLATFORMS IPSC T cell Armored Next gen IPSC CAR NK expertise platform CAR Ts CARs CAR Ts platform Shinya Adrian Koji Michel Shin Katy Yamanaka Hayday Tamada Sadelain Kaneko Rezvani 2019 2016 2017 2018 Dec 2015 May 2017 Sept 2017 July 2018 April 2019 Nov 2019 Takeda Cell Therapy First Development Stage Translational Engine Partnership IPSC = Induced pluripotent stem cell NK = Natural killer 55 Dr. Sadelain is a co inventor on patents relative to next gen CARs, intellectual property that MSK has licensed to Takeda. As a result of these licensing arrangements, Dr. Sadelain and MSK have financial interests related to these research efforts.

TAKEDA IS EMBARKING ON A TRANSFORMATIVE CAR NK 3 PARTNERSHIP THAT COULD ENTER PIVOTAL TRIALS IN 2021 IL 15 Activating NK CAR NK receptor Platform Multiple mechanisms of tumor killing Potentiation of innate & adaptive immunity CAR19 56

3 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, FY safe, off the shelf CAR NK available in outpatient & Ongoing maturation of clinical data: Efficacious dose, community settings 2H 2020 durability, partial vs. full allo, cryopreserved product Initial opportunity in G7 countries (CD19)* Manufacturing process complete 3L+ DLBCL ~8,000 Pivotal trials in r/r DLBCL / CLL / Indolent NHL 3L+ CLL ~5,000 2021 3L+ iNHL ~6,000 Potential to move into earlier lines of therapy 2023 BLA filing PLATFORM PARTNER MECHANISM OF ACTION PROGRAMS PRECLINICAL PH 1 TAK 007 (CD19 CAR NK) CAR NK Non autologous NK cell therapy BCMA CAR NK (allo cord blood) Dr. Katy Rezvani Platform expansion = first in class CLL = Chronic lymphocytic leukemia DLBCL = Diffuse large B cell lymphoma iNHL = Indolent non Hodgkin's lymphoma 57 *Estimated number of patients projected to be initially eligible for treatment in G7 markets, subject to regulatory approval

3 DRAMATIC COMPLETE RESPONSE IN FIRST PATIENT TREATED 47 YEAR OLD MALE WITH RELAPSED TRANSFORMED KINETICS OF CAR NK VERSUS ENDOGENOUS T AND B DOUBLE HIT (C MYC / BCL 2) DLBCL CELLS IN PERIPHERAL BLOOD CAR NK cells % positive cells Days post CAR NK infusion T cells X1000/ml of blood B cells Baseline scan Day 30 post CAR19 NK Days post CAR NK infusion 58 Data from Dr. Katy Rezvani, MD Anderson Cancer Center

3 IMPRESSIVE RESPONSES IN OTHER HEAVILY PRETREATED PATIENTS 61 YEAR OLD MALE CLL/RICHTER'S TRANSFORMATION 60 YEAR OLD FEMALE WITH CLL / ACCELERATED CLL (5 PRIOR LINES OF THERAPY) (5 PRIOR LINES OF THERAPY) CAR NK Baseline scan Day 30 post CAR19 NK Baseline scan Day 30 post CAR19 NK CR in Richter's; SD in CLL 59 CLL = Chronic lymphocytic leukemia CR = Complete response SD = Stable disease Data from Dr. Katy Rezvani, MD Anderson Cancer Center

CAR NK CELLS PERSIST IN PATIENTS AND DO NOT TRIGGER 3 CYTOKINE RELEASE SYNDROME (CRS) CAR NK CELLS PERSIST UP TO 4 MONTHS POST INFUSION IL 6 LEVLS POST CAR NK INFUSION DO NOT INDICATE CRS Median IL 6 level in grade 2 5 CRS post CAR T treatment* g of genomic DNA IL 6 (pg/ml) Vector transgene copy per Time from infusion (days) Time from infusion (days) CRS = Cytokine Release Syndrome 60 *Turtle et al. 2017 Data from Dr. Katy Rezvani, MD Anderson Cancer Center

3 CAR NK EFFICACY & TOXICITY TREATING MULTPLE DIAGNOSES Lines of CRS / Complete Diagnosis HLA Match Treatment Neurotox Response DLBCL Relapsed transformed double hit 3 Partial match None Incl. ASCT Dose DLBCL Refractory 7 Partial match None PD Level 1 CLL 4 Partial match None Incl. ibrutinib & venetoclax CLL 4 Partial match None PD Incl. ibrutinib CLL/Richter's transformation 5 Partial match None * Dose Incl. ibrutinib Richter's Level 2 CLL/Accelerated CLL 5 Partial match None Incl. ibrutinib & venetoclax CLL = Chronic lymphocytic leukemia CLL 4 Partial match None Incl. ibrutinib CRS = Cytokine release syndrome DLBCL = Diffuse large B cell lymphoma DLBCL Refractory 11 Partial match None Incl. ASCT ASCT = Autologous stem cell transplant DLBCL Relapsed transformed double hit 4 Partial match None HLA = Human leukocyte antigen Incl. ASCT Dose PD = Progressive disease Level 3 Follicular lymphoma Relapsed 4 Mismatch None PD *Complete response for Richter's Incl. ASCT Follicular lymphoma Relapsed 4 Mismatch None 61 Data from Dr. Katy Rezvani, MD Anderson Cancer Center

FAST TO CLINIC CELL THERAPY ENGINE WILL MAXIMIZE 3 LEARNINGS ON MULTIPLE DISRUPTIVE' PLATFORMS 5 CLINICAL STAGE PROGRAMS EXPECTED BY END OF FY20 FY19 FY20 FY21+: Other cell Cytokine + therapy TAK 007 Off the shelf TAK 102 chemokine CAR NK product candidates armed CAR T CD19 1XX CAR T Next gen CART signaling domain Hematology GDX012 Gamma delta T cells Solid tumors GCC CAR T Colorectal Cancer 62

A RICH AND POTENTIALLY TRANSFORMATIVE EARLY CLINICAL 3 ONCOLOGY PIPELINE PLATFORM PARTNER(S) MECHANISM OF ACTION PROGRAMS PRECLINICAL PH1 TAK 676 (STING agonist) STING agonism Innate to adaptive priming UNDISCLOSED Targeted STING agonist TARGETS TAK 981 SUMOylation Innate immune enhancer TAK 981 (ADCC combo) AttenukineTM Targeted attenuated IFN TAK 573 (CD38 AttenukineTM) Agonist redirected TAK 252 / SL 279353 Co inhibition & co stimulation checkpoints TAK 254 / SL 115154 Shiga like toxin A Novel cytotoxic payload TAK 169 (CD38 SLTA) IGN toxin Solid tumor targeted ADC TAK 164 (GCC ADC) Conditional T Novel solid tumor platform MVC 101 (EGFR COBRATM) cell engagers Cell therapy TAK 007 (CD19 CAR NK) Off the shelf cell therapies platforms 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 MLD PEVONEDISTAT AML EoE TAK 611 TAK 721 Ph 2 start2 TAK 924 Ph 3 start Approval cTTP 1L NSCLC Huntington's Disease TAK 755 TAK 788 mHTT ASO Ph 3 start Ph 3 start Pivotal start 1H FY 2019 2H FY 2019 1H FY 2020 2H FY 2020 Narcolepsy PEVONEDISTAT HR MDS 2L NSCLC R/R CMV SOT & HSCT TAK 925 TAK 788 TAK 620 POC TAK 924 Ph 2 Overall Survival Ph 2 Pivotal Ph 3 data EoE Hem. Malignancies R/R MM, Solid Tumor iTTP TAK 721 TAK 007 TAK 573 TAK 755 Ph 3 data (induction) POC POC POC Celiac Disease Hunter (IT) DEE TAK 101 TAK 609 TAK 935 POC Ph 3 data 2yr extension POC Huntington's Disease Gastroparesis mHTT ASO TAK 906 POC POC EoE Nausea & Vomiting TAK 721 TAK 951 Ph 3 data (maintenance) POC Oncology Rare Disease Neuroscience Gastroenterology Denotes milestones that have been achieved. KEY DATA READOUTS 64 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

SUMMARY 132 Total transformation Differentiated Multiple near term of preclinical & early opportunities in IO catalysts informing clinical pipeline leveraging innate momentum towards immunity & cell solid tumors therapies 65

TAK 788: PURSUING A FAST TO PATIENT STRATEGY FOR NSCLC PATIENTS WITH EGFR EXON 20 INSERTIONS Rachael L Brake, PhD Global Program Leader, Oncology Takeda Pharmaceutical Company Limited Tokyo November 21, 2019

THE SIZE OF THE LUNG CANCER CHALLENGE IS VAST Survival of Lung cancer is amongst 228,0001 the lowest of all cancers New Lung cancer cases / year Male Female 1 10% 13% 143,000 survival survival Lung cancer deaths/ yr More than breast, colon, and prostate cancer combined 5 yr survival estimates among adults diagnosed with lung cancer between 2007 20112 1. American Cancer Society; Cancer facts and figures 2019 68 2. Office for National Statistics UK (www.ons.gov.uk)

EXON 20 INSERTIONS ARE A RARE SUBSET OF EGFR MUTANT NSCLC Non Sq NSCLC EGFR Exon 20 insertions 1 200,000 pts/yr 2,000 pts/yr2 EGFR Sensitizing Mutations 19.4% No Mutations 1.2% EGFR exon18 4% UMD 12.0% EGFR exon19 45% EGFR exon21 41% Other Drivers 2.9% Insertion variants PTEN loss 0.7% CDKN2A loss 1.9% BRAF nonV600E 1.3% EGFR 28% 1. V769_D770insASV ( 20%) NF1 loss 1.9% 2. D770_N771insSVD ( 19%) EGFR T790M 5.5% 3. H773_V774insH ( 8%) EGFR exon20 2.1% 4. A763_Y764insFQEA ( 7%) KRAS 25.3% EGFR WT Amp 1.0% 5. H773_v774insPH ( 5%) ALK fusion 3.8% 6. H773_V774insNPH ( 4%) KRAS 25.3% ROS1 fusion 2.6% 7. N771_P772insN ( 3%) RET fusion 1.7% 8. H773_V774insAH ( 3%) BRAF V600E 2.1% MET splice 3.0% 9. Other ( 31%) FGFR ½ ½ 0.7% MET Amp 1.4% NRAS 1.2% ERBB2 Amp 1.4% PIK3CA 2.0% BRCA ½ loss 1.3% MAP2K1 0.7% TSC ½ loss 0.7% ERBB2 Mut 2.3% Sources: Leduc C et al., Ann Oncol 2017; Jorge S et al. Braz J Med Biol Res 2014; Kobayashi Y & Mitsudomi 1. Estimated US annual incidence of non squamous NSCLC 69 T. Cancer Sci 2016; Arcila M et al. Mol Cancer Ther 2013; Oxnard G et al. J Thorac Oncol 2013 2. Represents annual incidence of the US addressable patient population

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 demonstrate EGFR exon 20 ins patients demonstrate limited significant PFS benefit with 1st and 2nd gen EGFR TKIs benefit to anti PD 1 directed therapy 100 100% Classic EGFR EGFR exon 20 80% 80 60% 60 Hazard ratio 40% = 12.3 (p<0.0001) 40 20% 0% Progression free survival (%) 20 20% Best change in target lesions (%) 0 10 20 30 40 50 40% Time (months) 60% Individual patient responses Group Median PFS (months) Group 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) 12.0 Classical EGFR mut (n=22) 1.8 (1.2 2.4) 25% 1. Robichaux et al., WCLC 2016. 70 2. Adapted from Negrao et al., WCLC 2019

OVERCOMING THE DRUG DEVELOPMENT CHALLENGE IN EXON 20 INSERTIONS EGFR exon 20 NPG insertion L858R EGFR mutation Wild type EGFR Wild type EGFR Classical EGFR mutation L858R TAK 788 TAK 788 EGFR exon 20 insertion EGFR D770 ins NPG EGFR exon 20 insertion mutations Classical EGFR mutations have a similar structure and similar affinity for Significantly alter both structure and affinity ATP to wild type EGFR for ATP compared to wild type EGFR 71 Source. TAK 788 bound to EGFR kinase domain containing D770 ins NPG, crystal structure (data on file)

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) ANTITUMOR ACTIVITY IN EGFR EXON 20 INS AT 160 MG DAILY SAFETY SUMMARY IN PATIENTS TREATED WITH TAK 788 All Patients 80 N (%) 160 mg qd (n=72) 60 40 Treatment related AE 20 0 Any grade 68 (94) 20 Grade 3 29 (40) 40 60 Dose reduction due to AE 18 (25) Best change in target lesions (%) 80 Dose interruption due to AE 36 (50) 100 Discontinuation due to treatment Individual patient responses 10 (14) related AE Prior TKI: NNNNYNNNNNNNYNNNNNNNNNY YN Prior IO: NYYNYNNNNYYNYYNYYYNNYNYYY 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 be made after regulatory review of the data and approval of the labeled claims. 72 Adapted from Riley et al. ASCO. 2019

ENCOURAGING EFFICACY AND SAFETY HAS BEEN OBSERVED WITH TAK 788 Select signs of efficacy TAK 788 1 Poziotinib 2 Afatinib 3 Osimertinib 4 Clinical feature n=28 n=50 n=23 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 Select treatment related adverse events attributable to wild type EGFR inhibition TAK 788 1 Poziotinib 2 Afatinib 5 Osimertinib 6 Grade 3 Adverse event n=72 n=63 n=229 n=279 Diarrhea Gr3 18% 17.5% 14% 1% Rash Gr3 1% 35% 16% 1% Paronychia Gr3 0% 9.5% 11% 0% Total dose reduction rates AE related dose reductions (%) 25% 60% 52% 2.9% 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. 73 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 2017

STRONGER DIARRHEA MANAGEMENT SHOULD = ENHANCED EFFICACY Average time on TAK 788 June 2016 7.9 months Feb 2019 new trial FIRST IN HUMAN Time on Diarrhea Diarrhea Treatment (Mo) management very Comprehensive Grade 3 4.6 late medicate diarrhea management when at Grade 2 Grade 2 9.8 Grade 1 12.7 guidelines No diarrhea 12.1 implemented earlier WE HAVE MODIFIED OUR APPROACH TO GI ADVERSE EVENT MANAGEMENT WITH THE AIM TO IMPROVE EFFICACY 74 Source. TAK 788 Clinical trial database (data on file)

2021: EXPECTED FIRST APPROVAL IN EGFR EXON 20 INSERTIONS Single arm Phase 2 trial Supporting data generation Refractory EGFR Exon 20 insertion patients Real world evidence (RWE) data collection Previously treated, 2 systemic anticancer chemotherapy RWE will be used to assess the benefit of conventional Locally advanced or metastatic standard of care (SOC) agents in patients with NSCLC harboring EGFR exon 20 insertion EGFR Exon 20 insertions EMR claims databases and Medical Chart Review TAK 788 at 160 mg qd Chemo +/ VEGFR Immunotherapy Other 1. Overall Response Rate 1. Overall Response Rate 2. Time to treatment failure 2. Duration of Response 3. Median progression free survival 3. Median Progression Free Survival 4. Duration of Response 4. Overall survival 5. Overall survival ACTIVELY ENROLLING US, EU, AND ASIA US (FLAT IRON HEALTH) JP (SCRUM JAPAN) POTENTIAL APPROVAL MID 2021 EU AND CHINA CHART REVIEW 75 Source. https://clinicaltrials.gov/ct2/show/NCT02716116, https://www.exclaimstudy.com/

NEW ACTIVATION: A TRIAL FOR NEWLY DIAGNOSED PATIENTS Randomized, controlled, Phase 3 trial Treatment na ve EGFR exon 20 insertion patients Advanced or metastatic Treatment na ve patients diagnosed with NSCLC harboring EGFR exon 20 insertion mutations R 2 1:1 TAK 788 at 160 mg qd Platinum doublet 2 year enrollment 1. Median Progression Free Survival Anticipated approval 2023 2. Overall Response Rate 3. Duration of Response 4. Overall survival Electronic patient reported outcomes ACTIVELY ENROLLING US, EU, LATIN AMERICA AND ASIA PACIFIC 76 Source. https://clinicaltrials.gov/ct2/show/NCT04129502

SUMMARY 132 NSCLC patients with TAK 788 is the first The EXCLAIM trial in EGFR Exon 20 insertions purposely designed refractory patients are underserved with inhibitor and clinical could lead to the first the current available proof of concept has approval of TAK 788 therapies demonstrated efficacy by 2021 77

PEVONEDISTAT (TAK 924): A POTENTIAL NEW TREATMENT FOR HR MDS AND AML Phil Rowlands, PhD Head Oncology Therapeutic Area Unit Takeda Pharmaceutical Company Limited Tokyo November 21, 2019

BUILDING ON THE TAKEDA ONCOLOGY FOUNDATION IN HEMATOLOGIC MALIGNANCIES Next Generation Cell therapies Type I IFN I/O Novel checkpoints GROWING MDS/AML LEADERSHIP Phase 3 POSITION IN pevonedistat HEMATOLOGIC MALIGNANCIES Lymphoma Chronic Myeloid Leukemia Improving Patient Outcomes in Multiple Myeloma 79

HIGH RISK MYELODYSPLASTIC SYNDROME (HR MDS) AND ACUTE MYELOID LEUKEMIA (AML) HAVE LIMITED TREATMENT OPTIONS CONTINUUM OF HR MDS AND AML CLINICAL TREATMENT BM failure cytopenias Clinical treatment goals: Blasts Fatigue (anemia) Alleviate cytopenias 20% 30% Infection (neutropenia) Improve patient quality of life Bleeding (thrombocytopenia) Improve survival HR MDS AML Low Blast AML Fit Younger Unfit Older Fewer co morbidities Unfit for intensive chemotherapy HR MDS and AML are both rare bone marrow Patients Better performance status Patients and/or stem cell transplant related cancers that share foundational biology, clinical features, and genetic Intensive Chemotherapy Chemotherapy mutations* azacitidine decitabine Low dose ara c Incidence highest in elderly (>70 years old) Targeted therapies (AML only) BCL2 Overall survival several months to a few years, IDH1/2 depending on risk category Stem Cell Transplant FLT3 (Only curative treatment) 10% HR MDS, ~45% AML 80 * 30% of HR MDS patients progress to AML

CURRENT STANDARD OF CARE IS INADEQUATE FOR HR MDS PATIENTS MDS SURVIVAL BY PROGNOSTIC RISK No new treatments have been approved for MDS in over a decade Transplant ineligible patients treated with first line therapy: Median OS = 15mo; 2yr OS rate 35% Survival (probability) Economic burden is substantial hospitalizations are common among patients and many are transfusion dependent Time (months) Schanz et al., J Clin Oncol. 2012, 30:820 829 Median survival ~6 months to 5 years 81

PEVONEDISTAT: A UNIQUE FIRST IN CLASS NAE INHIBITOR Pevonedistat is a small molecule inhibitor of NAE (NEDD 8 activating enzyme), a protein involved in the ubiquitin proteasome system NAE acts upstream of the proteasome and catalyzes the first step in the neddylation pathway Amir T. Fathi Blood 2018;131:1391 1392 82

ENCOURAGING RESPONSES IN AML PATIENTS TREATED WITH PEOVNEDISTAT + AZACITIDINE 60% ORR with a trend towards improved survival in secondary AML Response rates not influenced by AML genetic risk or leukemia burden Initial data drove interest to move to registration Ronan T Swords et al. Blood 2016;128:98 83

A PHASE 2 STUDY IN HR MDS TO CONFIRM THE RISK / BENEFIT PROFILE OBSERVED IN AML Phase 2, Randomized, Open label, Global, Multicenter Study Comparing Pevonedistat Plus Azacitidine vs. Azacitidine in Patients with Higher Risk MDS, CMML, or Low Blast AML Mature OS data will be n = 117 available in November Pevonedistat + Azacitidine Pevo: 20 mg/m2 on Days 1, 3, 5 2 Aza: 75 mg/m on Days 1 5 ,8, 9 Data will be presented in 1:1 Repeat every 28 days upcoming congress Randomization Azacitidine Aza: 75 mg/m2 on Days 1 5, 8, 9 Potential approval in FY21* Primary endpoint: Secondary endpoints: . OS . EFS . ORR 84 * Projected approval date assumes filing on Phase 2 data

THE PHASE 3 PANTHER STUDY WAS INITIATED AT RISK TO ACCELERATE DEVELOPMENT Phase 3, Randomized controlled trial of Pevonedistat Plus Azacitidine Versus Single Agent Azacitidine as First Line Treatment for Patients with Higher risk MDS/CMML, or Low blast AML n = 450 Completed global enrollment Pevonedistat + Azacitidine Pevo: 20 mg/m2 on Days 1, 3, 5 10 months earlier than Aza: 75 mg/m2 Days 1 5 ,8, 9 originally projected* 1:1 Repeat every 28 days Randomization Azacitidine Indicative of demand for new Aza: 75 mg/m2 Days 1 5, 8, 9 innovative therapies Primary endpoint: Secondary endpoints: . EFS . OS * Closed to global enrollment; Open for extended enrollment in China 85

EXPANDING PATIENT CENTRIC DEVELOPMENT OF PEVONEDISTAT Continuum of disease HR MDS NEW STUDIES IN UNFIT AML Ph2 (P2001) Ph3 (P3001) Ph3 PEVOLAM Potential Utilizing partnership approval in FY21* pevo + aza vs. aza (PETHEMA) for Currently enrolling patients efficient development Ph2 (P2002) Combo Unique MOA and pevo + venetoclax + aza vs. biologic hypothesis to venetoclax + aza support combination Study will open in 2020 86 * Projected approval date assumes filing on Phase 2 data

SUMMARY 132 Unmet need in High Pevonedistat is a The Ph2 HR MDS trial risk MDS and AML selective first in class has reached the remain high with few inhibitor with updated OS endpoint treatment options potential to be first data readout and the new therapy in over PANTHER Ph3 trial a decade for HR MDS has completed global enrollment 87

RARE DISEASES & GENE THERAPY Dan Curran, MD Head Rare Diseases Therapeutic Area Unit Takeda Pharmaceutical Company Limited Tokyo November 21, 2019

RARE DISEASES: AN OPPORTUNITY TO TRANSFORM TREATMENT HIGH UNMET NEED SCIENTIFIC AND REGULATORY ADVANCES Diseases are genetic Distinct rare diseases1 7,000 80% in origin Recombinant 350 Transformative engineering & delivery Patients worldwide million therapies of proteins and nucleic acids 2 Orphan drug approvals Diseases have no FDA approved ~90% benefited from 95% treatment 100%3 expedited review 1. Rare diseases defined by prevalence in line with regulatory agencies (US: <7 in 10,000, EU: < 5 in 10,000 and JPN: <4 in 10,000), Global Genes, NIH National Human Genome Research Institute; 2. Comprises four pathways in US: Accelerated approval, breakthrough therapy designation, fast track designation, priority review designation; 3. Three pathways in JPN: Priority review, Sakigake designation and conditional approval, CIRS R&D Briefing 70, New drug 90 approvals in six major authorities 2009 2018

RARE DISEASE MARKET IS EXPECTED TO DOUBLE IN SIZE GLOBAL ORPHAN DRUG1 SALES EXCLUDING ONCOLOGY2, USD BN % share of global, branded Rx sales 7% 11% 17% Orphan drugs expected to make 124 up ~17% of global branded Rx sales by 2024 12% Growth driven by advances in new CAGR modalities and new indications 62 9% Orphan cell and gene therapies 37 CAGR estimated at ~$20 bn by 2024, up from ~$2bn in 2018 2012 2018 2024 91 1. Orphan drugs generally used as synonym for rare disease due to lack of uniform definition, including also non rare, but neglected diseases lacking therapy (e.g., tropical infectious diseases); 2. EvaluatePharma (03 June 2019)

TAKEDA IS THE LEADER IN RARE DISEASES PATIENT IMPACT SCIENCE & INNOVATION CAPABILITIES AND SCALE Foundation of >30 year history Multiple opportunities for Engagement with key of leadership in rare diseases transformational therapies stakeholders within the across therapeutic areas ecosystem e.g. patient groups, Leading portfolio of rare regulators disease therapies: 11 out of 14 Emerging, cutting edge global brands spanning platforms to drive high impact Pioneering regulatory pathways Hematology, Metabolic, GI and pipeline Global footprint Immunology Investments in technologies to accelerate diagnosis 92

OUR STRATEGY IS TO TRANSFORM AND CURE RARE DISEASES As the global leader in Rare Diseases, we aspire to provide transformative and curative treatments to our patients Transformative Curative Programs with transformative Emerging early pipeline of AAV potential in devastating gene therapies to redefine disorders with limited or no treatment paradigm in treatment options today monogenic rare diseases 93

WE ARE POSITIONED TO DELIVER NEAR TERM & SUSTAINED GROWTH WAVE 11 WAVE 22 TARGET CLINICAL STAGE NMEs PLATFORMS APPROVAL FY20 FY21 FY22 FY23 FY24 FY25 AND BEYOND TAK 620 TAK 607 TAK 7883 TAK 007 TAK 924 TAK 164 CMV infect. in TAK 252 2L NSCLC Hematologic AML GI malignancies Solid tumors Complications of TARGETED malignancies transplant CELL THERAPY prematurityINNATE 5 NEXT GEN ONCOLOGY AND IMMUNE IMMUNE CHECKPOINT TAK 9243 TAK 788 TAK 573 TAK 981 ENGAGERS MODULATION MODULATORS HR MDS 1L NSCLC R/R MM Multiple cancers TAK 620 TAK 607 4 CMV infect. in TAK 611 Complications of TAK 079 TAK 754 TAK 755 MLD (IT) 5 MG, ITP HemA iTTP, SCD Immunology transplant prematurity GENE RARE Hematology THERAPYTAK 755 DISEASES Metabolic TAK 609 TAK 755 TAK 531 cTTP Hunter CNS (IT) cTTP Hunter CNS TAK 935 Orexin2R ag TAK 341 Orexin2R ag TAK 041 DEE (TAK 925/994) Parkinson's Sleep Disorders CIAS NS OTHER Narcolepsy T1 Disease GENE PLATFORMS RNA Modulation THERAPY Antibody Transport NEUROSCIENCE TAK 418 TAK 653 TAK 831 Orexin2R agVehicle Kabuki Syndrome TRD CIAS NS (TAK 925/994) WVE 120101 WVE 120102 Narcolepsy T1 Huntington's Huntington's Disease Disease TAK 721 Kuma062 TAK 101 TAK 018 TAK 671 EoE Celiac Disease Celiac Disease Crohn's Disease Acute (post op and ileitis) Pancreatitis GENE CELL GASTRO TAK 721 MICROBIOME ENTEROLOGY EoE TAK 951 THERAPY THERAPY TAK 954 TAK 906 Nausea & POGD Gastroparesis vomiting TAK 003 TAK 214 TAK 426 TAK 021 VACCINES Norovirus Dengue Vaccine Vaccine Zika Vaccine 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 Orphan potential in at least one indication 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 94 Estimated dates as of November 14, 2019 myasthenia gravis (MG) and immune thrombocytopenic purpura (ITP) (FPI projected in each indication in 2H FY19); 5. Currently in a non pivotal Phase 2 study; planning underway to include interim stage gates that can advance the program into a pivotal trial

POTENTIAL APPROVALS OF TRANSFORMATIVE THERAPIES WAVE 11 Phase 3 Phase 3 Phase 3 Phase 2 Phase 2Phase 1/2 Phase 2b TAK 721 TAK 620 TAK 755 TAK 611 TAK 935 Orexin TAK 607 Eosinophilic Cytomegalovirus Congenital Metachromatic Developmental Narcolepsy Type 1 Complications of Esophagitis (CMV) infection Thrombotic Leukodystrophy and Epileptic (NT1) Prematurity2 (EoE) in transplant Thrombocytopenic (MLD) Encephalopathies Purpura (cTTP) (DEE) TARGET APPROVAL POSSIBLE WAVE 1 FY 2020 FY 2021 FY 2023 FY 2023 FY 2023 FY 2024 APPROVAL2 ADDRESSABLE POPULATION IN US/WW3,4 ~150k/Under ~7 15k/ ~500/ ~350/ ~50k/ 70 140k/ ~25k/ evaluation ~25 45k 2 6k ~1 2k ~70 90k 300k - 1.2M ~80 90k 1. Projected timing of approvals depending on data read outs; some Wave 1 target approval dates assume accelerated approval 2. Currently in a non pivotal Phase 2 study; planning underway to include interim stage gates that can advance the program into a pivotal trial 95 3. Estimated number of patients projected to be eligible for treatment, in markets where the product is anticipated to be commercialized, subject to regulatory approval 4. For TAK 620 and TAK 607, the addressable population represents annual incidence

SELECTED TRANSFORMATIVE PROGRAMS Potential first treatment of CMV infection in transplant patients in over 10 years. TAK 620 Inhibitor of protein kinase UL97. Potential best in class therapy for Thrombotic Thrombocytopenic Purpura (TTP). TAK 755 Recombinant ADAMTS13. Potential first pharmacologic therapy in >20 years to prevent complications of TAK 607 prematurity. Recombinant IGF 1 growth factor. 96

TAK 620: POTENTIAL BEST IN CLASS TREATMENT FOR POST TRANSPLANT CMV INFECTION BURDEN OF CMV INFECTION IN TRANSPLANT RECIPIENTS TAK 620: NOVEL MOA TARGETING PROTEIN KINASE UL97 CMV infection is the most common 1 post transplant viral infection1 2 Affects >25% of transplants 4 5 CMV infection can be fatal2,3 Higher rates of graft failure: 2.3X and mortality: 2.6X 3 Current therapies have significant toxicities 4,5,6,7 TAK 620 and resistance Existing therapies 3 Replication 3 Replication Incidence of neutropenia >20% and renal 4 Maturation and encapsidation toxicity >50% 5 Egress of viral capsids 97 1. Minerva Med. 2009 Dec; 100(6): 479 501; 2. Blood. 2016 May 19;127(20):2427 38; 3. Infect Chemother. 2013 Sep; 45(3): 260-271; 4. Antimicrob Agents Chemother. 2014 Jan; 58(1): 128-135; 5. Transplantation. 2016 Oct;100(10):e74 80;. 6. Clin Microbiol Infect. 2015 Dec;21(12):1121.e9 15; 7. Clin Transplant 2009: 23: 295-304

TAK 620 ADDRESSES UNMET NEED IN BOTH FIRST LINE AND RESISTANT / REFRACTORY SETTING CMV Failure First Line: Newly Resistant/ Transplant treatment Viremia First Line diagnosed CMV Refractory (R/R) CMV TAK 620: Ph 3 Study 303 ~100K ~30K ~5K Solid organ transplant (SOT) patients1,2: TAK 620: Ph 3 Study 302 Hematopoietic Stem Cell Transplants ~90K ~15K ~5K (HSCT) patients1,2: CMV 10K NON CMV 5K 98 1. Solid organ and allogeneic HSCT transplants in global major markets: US, Europe, Canada, Japan, China , Australia and Korea 2. UNOS Data 2018; CIBMR2017IRODaT Registry 2017, EBMT activity survey 2019 , Shire CMV Epi Study, Feb. 2018

TAK 620 DEMONSTRATED SIMILAR EFFICACY AND BETTER SAFETY VERSUS SOC IN A PHASE 2 STUDY IN FIRST LINE PATIENTS DEMONSTRATED SIMILAR ANTI VIRAL ACTIVITY TO NEUTROPENIA WAS TREATED WITH GROWTH FACTORS MORE VALGANCICLOVIR (VGV) ACROSS ALL DOSES1 OFTEN IN THE VGV ARM (15%) VS. TAK 620 ARM (7%)2 TAK 620: TAK 620: Dose 400, 800 or 1200 mg BID2 VGV Dose 400, 800 or 1200 mg BID VGV (N=40) (N=40) All Doses (N=119) All Doses (N=119) Confirmed Neutropenia that undetectable occurred or worsened plasma CMV DNA 79% 67% during treatment 5% 18% within 6 weeks through week 12 1. Confirmed undetectable CMV DNA in plasma was defined as two consecutive CMV DNA polymerase chain reaction assay values measure during treatment that were below the level of quantitation (i.e., <200 copies per millimeter according to the central laboratory) separated by at least 5 days. For the primary analyses of confirmed undetectable CMV DNA within 3 weeks and 6 weeks, data were missing for 3 patients: 1 each in the 400 mg TAK 620 group, the 1200 mg TAK 620 group and the valganciclovir group 99 2. N Engl J Med 2019; 381:1136 47. Overall risk ratio (95% CI) relative to the Valganciclovir reference was 1.20 (0.95 1.51)

TAK 620: GRANTED BREAKTHROUGH DESIGNATION IN RESISTANT OR REFRACTORY CMV INFECTION Efficacy in seriously ill R/R CMV in SOT and HSCT recipients with 1 multiple risk factors predictive of poor outcomes TAK 620 Dose: 400 mg, 800 mg, 1200 mg BID1 Primary efficacy endpoint All doses (Total N = 120) Historical outcomes: High (~50%) failure Patients with confirmed undetectable rates / relapse rates3,4,5 80 plasma CMV DNA within 6 weeks in (66.7%) ITT2 population Superior renal safety profile did not result in treatment Renal impairment is the primary reason 2 discontinuations for discontinuation with SOC (Foscarnet, Cidovir); nephrotoxicity is > 50%6 1. Clin Infect Dis. 2019 Apr 8;68(8):1255 1264; 2. ITT Intent to treat; 3. Antimicrob Agents Chemother, 58, 128 35; 4. Mehta et al, 2016 American Transplant Congress, Meeting abstract C279; 5. J Heart Lung Transplant. 2019 Sep 10; 100 6. Transplantation. 2016 Oct; 100(10): e74-e80

TAK 620: TWO ONGOING PIVOTAL STUDIES; EXPECT FIRST APPROVAL IN RESISTANT OR REFRACTORY CMV IN 2021 TAK 620 PHASE 3 STUDY 303 TAK 620 PHASE 3 STUDY 302 Resistant/Refractory CMV Patients with SOT or HSCT HSCT Recipients With First CMV Infection 2:1 Randomization 1:1 Randomization TAK 620 400mg BID Investigator's choice TAK 620 400mg BID 900mg BID VGV (N=234) (N=117) (N=275) (N=275) Primary Endpoint: Viremia @ 8 wks of Rx Primary Endpoint: Viremia @ 8 wks of Rx EXPECTED EXPECTED 2020 2021 2022 2021 2022 MILESTONES (FY) MILESTONES (FY) 2H 2020: 2021: 2022: 1H 2021: US Approval Ph 3 Readout US Approval EU Approval Ph 3 Readout EU Approval 101

CONGENITAL AND IMMUNE TTP HAVE SUBSTANTIAL MORTALITY AND MORBIDITY BURDEN DUE TO INADEQUATE SOC CONGENITAL TTP (cTTP) Sub therapeutic dose with plasma infusions Patients still experience ischemic injury of brain, kidneys and heart Poor long term outcomes IMMUNE TTP (iTTP) ~30% relapse rate with plasma exchange (PEX) New market entrant reduces relapse rate, but has ADDRESSABLE POPULATION significant limitations3,4 (WW)1,2 - Enhanced risk of bleeding: cTTP 2,000 - 6,000 Gingival bleeding 18% vs. 1% placebo iTTP 5,000 - 18,000 Epistaxis 32% vs. 3% placebo 103 1. Global major markets: US, Europe, Canada, JPN, and Global Emerging Markets; 2. Haematologica September 2010 95: 1444 1447; 3. N Engl J Med 2019;380:335 46.; 4. N Engl J Med 2016; 374:511 522

TAK 755 DIRECTLY ADDRESSES UNDERLYING CAUSE OF TTP TAK 755 REPLACES ADAMTS13, DEFICIENCY OF WHICH LEADS TO TTP Platelet Von Willebrand Factor (VWF) Normal ADAMTS13: clotting Cleaves VWF multimers that mediate cascade platelet aggregation and clotting Blood vessel ADAMTS13 deficiency: TTP Formation of microthrombi due to accumulation of large VWF multimers 104

TAK 755: POTENTIAL TRANSFORMATIVE THERAPY FOR TTP TAK 755 PHASE I, OPEN LABEL, DOSE TAK 755 PK PROFILE AND PD EFFECT ON ESCALATION STUDY IN cTTP1 VWF CLEAVAGE AT 40 IU/KG 100% Mean FRETS ADAMTS13 Activity 100% 176 kDa VWF Cleavage Product Administered as a single dose 90% 90% 80% 80% (%) TTP diagnosis requires in 15 cTTP patients 2 70% confirmation of 70% 60% ADAMTS13 activity <10% 60% TAK 755 was well tolerated 50% 50% 40% 40% No anti ADAMTS13 30% 30% antibodies detected ADAMTS13 Activity 20% 20% 10% 10% VWF Cleavage Product (%) 0% 0% 0 24 48 72 96 120 144 168 192 216 240 264 288 Time (hours) 105 1. Blood 2017; vol. 130, number 19, 2055 63; 2. Measured using FRETS (fluorescence resonance energy transfer)

TAK 755: ONGOING PHASE 3 CONGENITAL TTP STUDY TAK 755 PHASE 3 PROPHYLAXIS STUDY cTTP patients (N = 26 - 42) 1:1 Randomization All patients roll over to a 6 month TAK 755 extension TAK 755 40 IU/kg SOC Every other week1 Phase 3 study has a cohort of acute cTTP Tx duration: 6 months patients who receive TAK755. Patients are eligible to enter the prophylaxis study upon TAK 755 40 IU/kg SOC completion of acute treatment Every other week Tx duration: 6 months Primary Endpoint: Incidence of acute TTP episodes EXPECTED 2019 2021 2023 2025 MILESTONES (FY) 1H: Ph 3 initiated 2H: Ph 3 ReadoutUS Approval EU Approval2 106 1. A single dose modification to 1x/week may be mandated based on clinical outcomes; 2. Plan to seek deferral of pediatric data requirement in EU for initial filing, which would enable possible approval in EU in 2023

TAK 755 IMMUNE TTP PHASE 2 STUDY DESIGN Primary or relapse acute iTTP episode (N=30) PEX Day 1 1:1:1 Randomization Placebo TAK 755 Low dose TAK 755 High dose + + + SOC SOC SOC Remission Phase Placebo or TAK 755 Primary endpoints: PK/PD EXPECTED 2020 2021 2023 2025 MILESTONES (FY) 2H: Ph 2 Readout 2H: Ph 3 Start 2H: Ph3 Readout US/EU Approval 107

EXTREMELY PREMATURE INFANTS EXPERIENCE CONSIDERABLE MORBIDITY ~80,000 90,000 0 Therapies Extremely preterm for prevention of babies (<28 wks complications of gestational age) born prematurity WW2,3 ~40% have lung ~$200,000 1 Morbidity (%) by birth year, US data complications hospitalization 100% in addition to 4 Bronchopulmonary dysplasia (BPD) costs per infant 80% Severe intraventricular hemorrhage (IVH) morbidities in brain, 60% eye that adversely impact 40% development and learning 20% 0% 1992 1996 2000 2004 2008 2012 109 1. Stoll B, JAMA, 2015;314(10): 1039-1051; 2. CDC; 3. UN data and published sources; 4. Mowitz M et al. Co occurrence and Burden of Complications of Prematurity Among Extremely Preterm Infants in the US AAP 2017 Poster 76

TAK 607 REPLENISHES IGF 1, A FETAL GROWTH FACTOR THAT IS DECREASED IN PRETERM INFANTS TAK 607: IGF 1 / IGFBP 31 COMPLEX IGF 1 LEVELS ARE LOW IN PRETERM INFANTS2 IGF 1 is an important fetal growth factor supplied by the mother that is involved in the IGF 1 in normal in utero fetus development of multiple organs IGF 1 in preterm infants Mean predicted value Upper prediction interval (95th) IGF 1 is low or absent in premature infants th born before 28 weeks2 Lower prediction interval (5 ) TAK 607 demonstrated beneficial effects in lung development and brain vasculature in preclinical models3,4 110 1. Recombinant insulin like growth factor 1 (rIGF 1), IGFBP 3 IGF binding protein 3; 2. Hellstrom et al., Acta P diatrica 2016 105, pp. 576-586; 3. Seedorf G et al. EAPS. Geneva 2016 (manuscript in preparation) 4. Ley D et al. jENS 2019

TAK 607: PHASE 2 STUDY INFORMED DOSE AND ENDPOINT SELECTION ROP 2008 01: RANDOMIZED, CONTROLLED PHASE 2 STUDY OF TAK 607 TAK 607 IMPACTED BPD AND IVH2 Pre term infants with a gestational age (GA) <28 weeks (N = 120) 100 Standard of care IGF 1/IGFBP 3 Assessed outcomes in ITT and "evaluable" sets (40% patients 80 1 ) who achieved target exposure of IGF 1 levels) 2 60 55% Primary endpoint: ROP not met 40 Pre specified secondary endpoints: Bronchopulmonary 29% Dysplasia (BPD) was reduced and Intra Ventricular (evaluable set 23% Number of infants % 20 Hemorrhage (IVH) showed a positive trend 8% Granted FDA fast track designation 0 BPD (Moderate IVH (Grade 3 4) and Severe) 1. Evaluable set: 70% IGF 1 measurements within targeted intrauterine range (28 109 g/L) AND 70% intended duration of treatment 111 2. Ley D, J Pediatrics, 2018 ROP - retinopathy of prematurity

TAK 607: FOOTPRINTS STUDY DESIGNED TO DEMONSTRATE REDUCTION IN THE COMPLICATIONS OF PREMATURITY Open label, 1:1:1 Randomization Treatment Post Treatment (N = 200/arm) (2 7 wks based on GA) Follow up period TAK 607 250 g/kg/24 h Rx: Day 1 Rx End: 29 wk + Primary endpoint: continuous IV 6 d PMA 12 months corrected age Premature infants: TAK 607 400 g/kg/24 h continuous IV <28 weeks GA Outpatient: Respiratory Standard Neonatal Care morbidity assessments/week Primary endpoint: Duration of supplemental oxygen use through 1 year corrected age1 EXPECTED 2019 2023 MILESTONES (FY) 1H: Ph 2b initiated 1H: Ph 2b Readout 112 1. Supplemental oxygen use defined by one of the following: a) Any fraction of inspired oxygen (FiO2) >21%, b) Non invasive respiratory support delivered via a nasal interface (e.g., continuous positive airway pressure [CPAP], nasal cannula, etc.), c) Invasive respiratory support (mechanical ventilation) via an endotracheal tube or tracheostomy

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