wave1presentation

WAVE 1 PIPELINE MARKET OPPORTUNITY CALL December 8, 2020 (ET) / December 9, 2020 (JST) Takeda Pharmaceutical Company Limited

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These forward-looking statements are based on assumptions about many important factors, including the following, which could cause actual results to differ materially from those expressed or implied by the forward-looking statements: the economic circumstances surrounding Takeda’s global business, including general economic conditions in Japan and the United States; competitive pressures and developments; changes to applicable laws and regulations; the success of or failure of product development programs; decisions of regulatory authorities and the timing thereof; fluctuations in interest and currency exchange rates; claims or concerns regarding the safety or efficacy of marketed products or product candidates; the impact of health crises, like the novel coronavirus pandemic, on Takeda and its customers and suppliers, including foreign governments in countries in which Takeda operates, or on other facets of its business; the timing and impact of post-merger integration efforts with acquired companies; the ability to divest assets that are not core to Takeda’s operations and the timing of any such divestment(s); and other factors identified 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. Takeda does not undertake 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 or statements of Takeda in this presentation may not be indicative of, and are not an estimate, forecast, guarantee or projection of Takeda’s future results. Certain Non-IFRS Financial Measures This presentation and materials distributed in connection with this presentation include certain financial measures not presented in accordance with International Financial Reporting Standards (“IFRS”), such as Underlying Revenue, Core Operating Profit, Underlying Core Operating Profit, Core Net Profit, Underlying Core EPS, Net Debt, EBITDA, Adjusted EBITDA and Free Cash Flow. Takeda’s management evaluates results and makes operating and investment decisions using both IFRS and non-IFRS measures included in this presentation. These non-IFRS measures exclude certain income, cost and cash flow items which are included in, or are calculated differently from, the most closely comparable measures presented in accordance with IFRS. By including these non-IFRS measures, management intends to provide investors with additional information to further analyze Takeda’s performance, core results and underlying trends. Takeda’s non-IFRS measures are not prepared in accordance with IFRS and such non-IFRS measures should be considered a supplement to, and not a substitute for, measures prepared in accordance with IFRS (which we sometimes refer to as “reported” measures). Investors are encouraged to review the reconciliation of non-IFRS financial measures to their most directly comparable IFRS measures, which are on slides 158 and 159. 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”). 1 | IMPORTANT NOTICE

AGENDA TIME (EST) TIME (JST) AGENDA 17:00 – 17:10 07:00 – 07:10 Takeda: A Global Values-Based, R&D-Driven Biopharmaceutical Leader Christophe Weber, President & CEO 17:10 – 17:25 07:10 – 07:25 Following Through On Our Commitment To Deliver Innovative Medicines To Patients: Spotlight On Select Wave 1 Programs Andy Plump, President, R&D 17:25 – 17:35 07:25 – 07:35 Entyvio Case Study: Building A Gold Standard Therapy Along The Patient Journey Ramona Sequeira, President, USBU & Global Portfolio Commercialization 17:35 – 18:05 07:35 – 08:05 TAK-721 Deep Dive: Potential To Be First FDA-Approved Agent With Indication For Eosinophilic Esophagitis Mike Nedham, Global Program Leader for TAK-721, Global Product & Launch Strategy 18:05 – 18:35 08:05 – 08:35 TAK-003 Deep Dive: Live-Attenuated Tetravalent Vaccine For Prevention Of Dengue Disease Rajeev Venkayya, President, Global Vaccine Business Unit 18:35 – 19:15 08:35 – 09:15 Panel Q&A Session Appendix 1: Wave 1 Pipelines One-Pager Summaries Appendix 2: Epidemiology Data Appendix 3: Clinical Trial Summary 2 |

A VALUES-BASED AND R&D-DRIVEN BIOPHARMACEUTICAL LEADER 4 | Better health for people, brighter future for the worldPURPOSE Discover and deliver life-transforming treatments, guided by our commitment to patients, our people and the planet VISION IMPERATIVES PATIENT • Responsibly translate science into highly innovative, life-changing medicines and vaccines • Accelerate access to improve lives worldwide PEOPLE • Create an exceptional people experience PLANET • Protect our planet UNLEASH THE POWER OF DATA AND DIGITAL • We strive to transform Takeda into the most trusted, data-driven, outcomes-based biopharmaceutical company VALUES We are guided by our values of Takeda-ism which incorporate Integrity, Fairness, Honesty, and Perseverance, with Integrity at the core. They are brought to life through actions based on Patient-Trust-Reputation- Business, in that order

TRANSFORMATION TO TOP 10 GLOBAL R&D-DRIVEN BIOPHARMA COMPANY 2014 Today Next 10 Years Strategic Evolution We Are One Takeda Accelerating Growth & Patient Impact GLOBALIZATION R&D TRANSFORMATION VALUES BASED, R&D-DRIVEN GLOBAL BIOPHARMA COMPANY 5 KEY BUSINESS AREAS AND 14 GLOBAL BRANDS 12 NEW MOLECULAR ENTITIES IN WAVE 1 PIPELINE TRANSFORM SCIENCE INTO LIFE-CHANGING MEDICINES WAVE 1 AND WAVE 2 PIPELINE GROWTH OPPORTUNITIES FY2014 TOP 20 GLOBALLY REPORTED REVENUE JPY 1,778BN UNDERLYING CORE PROFIT1 MARGIN 17% FY2020 TOP 10 GLOBALLY REPORTED REVENUE FORECAST JPY 3,200BN UNDERLYING CORE PROFIT1 MARGIN LOW 30%s LONG TERM GLOBAL PATIENT IMPACT ACCELERATING GROWTH REVENUE GOAL JPY 5TN2 BY FY2030 1. Underlying Core Operating Profit. Please refer to slide 157 for its definition and slides 158 and 159 for reconciliation. 2. Includes incremental revenues on a non-PTS (probability of technical success) basis (i.e., figures represent best case scenarios, including technical success that Takeda does not currently consider probable to occur and should not be seen as a forecast or target figure). Further, 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 a number of variables, including safety, efficacy and product labelling. Does not include any potential impacts imposed by the Most Favored Nation Model interim final rule issued by the U.S. Centers for Medicare & Medicaid Services (CMS) on November 20, 2020, which are currently being assessed. In addition, if a product is approved, the effect of commercial factors including the patient population, the competitive environment, pricing and reimbursement is also uncertain. As shown in slide 8, Takeda’s base case (i.e., its estimate of revenue based on technical milestones it believes it is probable to achieve) is achieving low single digit Compound Annual Growth Rate (CAGR) as compared to FY2019 baseline. FY2019 currency assumption rate is applied for FY2030 revenues. 5 |

14 GLOBAL BRANDS HAVE POTENTIAL TO DELIVER SIGNIFICANT GROWTH WITH INCREMENTAL REVENUE OPPORTUNITY OF >$8B BY FY2024 1. Includes Albumin Glass, Flexbumin and Kenketsu Albumin. 2. USD included for reference calculated at JPY/USD of 107 yen. 3. New peak revenue estimates for these products are based on combination of base case scenario projection adjusted for development and regulatory risk and best case scenarios without such adjustments. Note: Absolute values are presented on an IFRS (reported) basis; Year-on-year changes are underlying growth. Does not include any potential impacts imposed by the Most Favored Nation Model interim final rule issued by the U.S. Centers for Medicare & Medicaid Services (CMS) on November 20, 2020, which are currently being assessed. FY2019 REVENUE PREVIOUS PEAK REVENUE NEW PEAK REVENUE ESTIMATE3(MM USD)2 versus PY (underlying) 3,189 +32.9% $4.0 – 5.0BN $5.5 – 6.5BN 568 +21.7% N/A $0.7 – 0.8BN 3 N/A N/A $0.5 – 0.8BN 627 +318% N/A $1.8 – 2.2BN 712 +28.5% $1.5 – 2.0BN $1.5 – 2.0BN 66 +43.1% $1BN $0.8 – 1.0BN LONG-TERM OUTLOOK IMMUNOGLOBULIN 2,744 +7.2% “High single digit CAGR” for the next decade ALBUMIN/FLEXBUMIN1 617 +20.3% “Mid single digit CAGR” for the next decade 14 Global Brands Total 10,152 +21.7% 6 |

PRODUCT INDICATION FULL MARKET OPPORTUNITY2 TAKEDA’S PEAK REVENUE POTENTIAL3 Orexin programs4 Narcolepsy type 1 (NT1) Narcolepsy type 2 (NT2) Idiopathic hypersomnia $3,000 – 4,000MN (NT1) $1,000 – 2,000MN (NT2 + IH) soticlestat (TAK-935) Lennox-Gastaut syndrome, Dravet syndrome and other indications Not disclosed Eohilia5 (TAK-721) Eosinophilic Esophagitis $300 – 500MN TAK-9996 Alpha-1 Antitrypsin-Associated Liver Disease Not included TAK-003 Prevention of dengue $700 – 1,600MN CoVIg-19 Treatment ofCOVID-19 PRODUCT INDICATION FULL MARKET OPPORTUNITY2 TAKEDA’S PEAK REVENUE POTENTIAL3 mobocertinib (TAK-788) Exon 20 non-small cell lung cancer 1L Exon 20 non-small cell lung cancer 2L $300 – 600MN pevonedistat (TAK-924) Higher risk-Myelodysplastic syndromes Unfit Acute myeloid leukemia $400 – 800MN TAK-007 3L+ Diffuse Large B-Cell Lymphoma 3L+ Chronic Lymphocytic Leukemia 3L+ Follicular Lymphoma $700 – 1,500MN TAK-609 Hunter CNS (intrathecal)1 <$100MN maribavir (TAK-620) CMV infection in transplant patients (R/R & 1L) $700 – 800MN TAK-611 Metachromatic leukodystrophy (intrathecal) $300 – 450MN TAK-755 cTTP / iTTP, Sickle cell disease $1,000 – 1,500MN ONCOLOGY RARE GENETIC & HEMATOLOGY GASTROENTEROLOGY (GI) NEUROSCIENCE VACCINES PDT WAVE 1 PIPELINE ASSETS HAVE SIGNIFICANT MARKET POTENTIAL Not disclosed Up to $0.5BN $0.5BN to $1.0BN $1.0BN to $3.0BN More than $3.0BN 1. MPSII market in total (somatic + CNS) 2. Market potential indicates Takeda’s best estimate about addressable market size, based on available data and estimates. 3. Non-PTS (probability of technical success) adjusted figures represent best case scenarios, including technical success that Takeda does not currently consider probable to occur and should not be seen as a forecast or target figure. 4. Other rare indications than NT1, NT2 and IH are not included in the calculation. 5. Eohilia is the proposed brand name for TAK-721. TAK-721 is an investigational treatment and has not been approved for use by the U.S. Food and Drug Administration or other regulatory authorities. 6. TAK-999 has the potential to accelerate into Wave 1. Note: Does not include any potential impacts imposed by the Most Favored Nation Model interim final rule issued by the U.S. Centers for Medicare & Medicaid Services (CMS) on November 20, 2020, which are currently being assessed. 7 |

PTS ADJUSTED4 FY2019-FY2030 Revenue CAGR: Low single digit 4,000 6,000 5,000 0 1,000 2,000 3,000 FY2024 14 Global Brands 14 Global Brands Hemophilia Wave 2 PTS adjusted3,4 Vyvanse/Velcade/Azilva All Others FY2019 Actual Wave 2 non-PTS adjusted1,3 Wave 1 non-PTS adjusted1 Wave 1 PTS adjusted4 14 Global Brands FY2030 +$8BN by 14 Global Brands ~($4.5BN) POSITIONED FOR ORGANIC & SUSTAINABLE REVENUE GROWTH; GOAL TO REACH JPY 5TN ($47BN) REVENUE BY FY20301 1. Shows incremental revenues on a non-PTS (probability of technical success) basis; i.e. figures represent best case scenarios, including technical success that Takeda does not currently consider probable to occur and should not be seen as a forecast or target figure. 2. The assumption in this chart is for biosimilar entry for ENTYVIO in Europe in May 2024 and U.S. in May 2026, based on expiry of data exclusivity periods in each region. There are also patents for ENTYVIO that expire in 2032, and therefore the exact timing of biosimilar entry is uncertain at this time. 3. Only a select subset of eight Wave 2 programs (TAK-906, TAK-954, TAK-951, TAK-062, TAK-101, TAK-573, TAK-676, and TAK-981) are included for this analysis which are either in Phase 2 clinical development or have “Accelerate” designation with broad early investment. If all Wave 2 assets were included, the potential revenue contribution would be higher. 4. PTS (Probability of Technical Success) adjusted figures represent Takeda’s base case, i.e. its estimate of revenue based on technical milestones it believes it is probable to achieve. The above chart represents conceptual changes in revenue through FY2024 and FY2030 demonstrating growth over time offsetting loss of exclusivities and achieving single digit Compound Annual Growth Rate as compared to FY2019 baseline. 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 a number of variables, including safety, efficacy and product labelling. Does not include any potential impacts imposed by the Most Favored Nation Model interim final rule issued by the U.S. Centers for Medicare & Medicaid Services (CMS) on November 20, 2020, which are currently being assessed. In addition, if a product is approved, the effect of commercial factors including the patient population, the competitive environment, pricing and reimbursement is also uncertain. FY2019 currency assumption rate is applied for FY2024 and FY2030 revenues. Assuming Entyvio biosimilar entry in Europe (May 2024) and the U.S. (May 2026) at the earliest2 JPY BN 8 | GOAL JPY 5TN ($47BN) by FY2030 FY2019-FY2030 Revenue CAGR: Mid single digit

TODAY’S SPEAKERS CHRISTOPHE WEBER President & CEO ANDY PLUMP President, Research & Development RAJEEV VENKAYYA President, Global Vaccine Business Unit Available for Q&A COSTA SAROUKOS Chief Financial Officer TERESA BITETTI President, Global Oncology Business Unit RAMONA SEQUEIRA President, USBU & Global Portfolio Commercialization MICHAEL NEDHAM Global Program Leader for TAK-721, Global Product & Launch Strategy 9 |

Following Through On Our Commitment to Deliver Innovative Medicines To Patients Spotlight on Select Wave 1 Programs Andy Plump President, R&D

PLASMA-DERIVED THERAPIES VACCINES CELL THERAPY GENE THERAPY DATA SCIENCES ONCOLOGY GASTROENTEROLOGY (GI)NEUROSCIENCE RARE GENETIC & HEMATOLOGY R&D FOCUS INNOVATIVE BIOPHARMA INNOVATIVE PIPELINE • 12 Wave 1 NMEs 5 programs with BTD, 3 with FTD and 1 with Sakigake designation • ~30 Wave 2 NMEs A GLOBAL VALUES-BASED BIOPHARMACEUTICAL COMPANY WITH A PATIENT-DRIVEN AND SCIENCE-FIRST R&D ENGINE ROBUST PARTNERSHIP MODEL • Takeda’s Labs are designed to access innovation wherever it originates • Investments in novel mechanisms and capabilities for a sustainable future NME: New Molecular Entity; BTD: Breakthrough Therapy Designation; FTD: Fast Track Designation.12 |

Total Upfront Investment ~$1B IN FY19/20 Access to Innovation Risk-Sharing Expanding Capacity IN-LICENSE RESEARCH COLLABORATIONS NEWCO FORMATION JOINT DEVELOPMENT ~ 150 ~ 50 ~ 20 ~ 25 WE ARE ACCESSING INNOVATION BY INTEGRATING TAKEDA’S WORLD CLASS LABORATORY WITH A NETWORK OF PARTNERS Non-Viral Gene Therapies RNA Splicing Small Molecules Targeting Neurologic Disease TAK-007 & CAR-NK Platform Psychiatry Partnership TAK-999, RNAi therapy TAK-605 and Oncolytic Virus Platform Fibrotic, Rare Liver Diseases Select new partnerships from FY19 and FY20 13 |

MOMENTUM IN OUR DYNAMIC PIPELINE BASED ON EMERGING DATA 1. Projected approval dates depend on data read-outs; some Wave 1 target approval dates assume accelerated approval 2. Potential for data driven acceleration of some Wave 2 programs into Wave 1 3. Approval date assumes filing on Phase 2 data 4. Approval expected Q4 FY20 or early Q1 FY21 For glossary of disease abbreviations please refer to appendix. TARGET APPROVAL FY27 AND BEYONDFY20 FY21 FY22 FY23 FY24 FY25/26 WAVE 11 WAVE 22 CLINICAL-STAGE NMEs ONCOLOGY RARE GENETIC & HEMATOLOGY GASTRO- ENTEROLOGY NEUROSCIENCE VACCINES PDT TAK-981 Multiple cancers Orexin2R-ag Sleep Disorders TAK-573 R/R MM TAK-755 iTTP, SCD mezagitamab MG, ITP TAK-062 Celiac Disease TAK-906 Gastroparesis mobocertinib 2L NSCLC with EGFR exon 20 insertion mutation3 pevonedistat HR-MDS TAK-007 CD19+ hematologic malignancies pevonedistat Unfit AML TAK-609 Hunter CNS (IT) maribavir R/R CMV infect. in transplant TAK-611 MLD (IT) TAK-755 cTTP soticlestat DEE Orexin2R-ag (TAK-925/994) Narcolepsy T1 TAK-7214 EoE TAK-003 Dengue Vaccine TAK-426 Zika Vaccine mobocertinib 1L NSCLC with EGFR exon 20 insertion mutation CoVIg-19 COVID-19 H-IG (Formerly TAK-888) TAK-252 Solid tumors TAK-169 R/R MM TAK-341 Parkinson’s Disease WVE-120102 Huntington’s Disease WVE-120101 Huntington’s Disease sibofimloc Crohn’s Disease (post-op and ileitis) TAK-671 Acute Pancreatitis TAK-954 POGD TAK-607 Complications of prematurity TAK-605 Multiple cancers mobocertinib HER2 mutant NSCLC TAK-676 Solid tumors TAK-039 Hepatic encephalopathy TAK-101 Celiac Disease TAK-653 TRD TAK-041 Anhedonia in MDD TAK-831 CIAS NS maribavir 1L CMV infect. in HSCT TAK-214 Norovirus Vaccine TAK-102 Multiple cancers TAK-940 CD19+ hematologic malignancies TAK-9995 AAT Liver Disease Orphan potential in at least one indication Part 1: Wave 1 investor eventBreakthrough or Fast Track China Breakthrough designation• • •• • • • • • TAK-951 Nausea & vomiting 5. Pending deal close All timelines are approximate estimates of December 8, 2020.14 |

DEVELOPMENT STAGE PROGRAM INDICATION NEXT MILESTONE EXPECTED TIMING Regulatory Milestones TAK-721 Eosinophilic esophagitis Approval Q4FY201 TAK-003 Prevention of dengue fever Submission Q4FY20 TAK-609 Hunter syndrome CNS Submission Q4FY20 mobocertinib NSCLC exon 20 insertion mutation (2L) Submission Q4FY20 Pivotal Data Readout maribavir Cytomegalovirus infection in transplant Phase 3 readout Q3FY20 CoVIg-19 Treatment of COVID-19 Phase 3 readout Q4FY20 pevonedistat Higher-risk myelodysplastic syndromes Phase 3 readout Q4FY20 TAK-755 Congenital thrombotic thrombocytopenic purpura Phase 3 readout H1FY22 TAK-611 Metachromatic leukodystrophy Phase 22 readout H2FY22 Pivotal Study Starts soticlestat Developmental and epileptic encephalopathies Phase 3 start Q1FY21 TAK-007 CD19+ hematologic malignancies Phase 22 start H1FY21 TAK-994 Narcolepsy Phase 3 start H2FY21 1. Approval expected Q4 FY20 or early Q1 FY21 2. Potential pivotal study ALL WAVE 1 MEDICINES HAVE NEAR-TERM PIVOTAL MILESTONES 15 |

TODAY IS THE FIRST IN A SERIES OF INVESTOR EVENTS TO CONNECT CLINICAL DATA TO THE MARKET POTENTIAL OF OUR WAVE 1 PIPELINE 1. Date to be confirmed TODAY’S EVENT APRIL 6, 20211 Regulatory filing for Dengue vaccine in endemic region US NDA submission for eosinophilic esophagitis PART 1 WAVE 1 MARKET OPPORTUNITY INVESTOR EVENT PART 2 WAVE 1 MARKET OPPORTUNITY INVESTOR EVENT TAK-721 TAK-003 US NDA submission for 2L R/R post transplantation CMV infection 18.8 36.1 36.7 0 10 20 30 40 50 TAK-925 5 mg (n=6) TAK-925 11. 2 mg (n=4) TAK-925 44. 8 mg (n=4) *** *** *** *** P value <0.001 Pl ac eb o- ad ju st ed o bs er ve d va lu e (m in ut es , 9 5% C I) MAINTENANCE OF WAKEFULNESS TEST maribavirOrexin agonists TAK-994 (oral) and TAK-925 (IV) orexin agonists for narcolepsy Type 1 and other sleep disorders Oncology Update Wave 1 Pipeline Development Status Commercial Potential Supplemental Data 16 |

Entyvio Case Study: Building A Gold Standard Therapy Along The Patient Journey Ramona Sequeira President, USBU & Global Portfolio Commercialization

19 | ENTYVIO: THE GOLD STANDARD THERAPY FOR IBD illustrative FY2019 Actual SUBCUTANEOUS LAUNCH1 Peak revenue estimate4 Leadership in IBD $5.5-6.5BN $3.2BN3 1. Per approval by country Regulatory Authority 2. Based on head-to-head trial that compared clinical remission rates for Entyvio and adalimumab in adults with moderately to severely active UC 3. USD included for reference calculated at JPY/USD of 107 yen. 4. PTS (Probability of Technical Success) adjusted figures represent Takeda’s base case, i.e. its estimate of revenue based on technical milestones it believes it is probable to achieve. Note: Does not include any potential impacts imposed by the Most Favored Nation Model interim final rule issued by the U.S. Centers for Medicare & Medicaid Services (CMS) on November 20, 2020, which are currently being assessed. NEEDLE-FREE DEVICE LAUNCH GEOGRAPHIC EXPANSION CLINICAL2 DIFFERENTIATION REAL WORLD EVIDENCE

20 | GLOBAL MULTI-PRONGED GROWTH STRATEGY TO MAXIMIZE POTENTIAL OF ENTYVIO 1. Per approval by country Regulatory Authority 2. Based on head-to-head trial that compared clinical remission rates for Entyvio and adalimumab in adults with moderately to severely active UC SUBCUTANEOUS (SC) LAUNCH1 GEOGRAPHIC EXPANSION E.G. CHINA CLINICAL DIFFERENTIATION REAL WORLD EVIDENCE NEEDLE-FREE DEVICE LAUNCH (LAUNCH IN 2023) • Takeda is investing in development of the China IBD market • Capture potential opportunities with approximately 67K Entyvio patients peak in China • FY2030 target: 36% peak share CD and 49% UC in China • Meet the needs of IBD patients • SC or IV options offer flexibility to find optimal route of administration (RoA) • VISIBLE Trial • VARSITY2 • GvHD • Pouchitis • Pediatric Ph3 program • Long-term Safety (PASS) • Explorer (CD natural history) • Verdict (UC T2T) • Victory • Evolve • Versify • The only, Entyvio exclusive and first- to-market IBD product with jet- injector (needle- free) technology, in partnership with PORTAL instruments

Source: Sands et al. Vedolizumab versus Adalimumab for Moderate-to-Severe Ulcerative Colitis. N Engl J Med 2019; 381:1215-1226 Lukin D, et al; on behalf of VICTORY Collaboration. Comparative safety and effectiveness of vedolizumab to tumour necrosis factor antagonist therapy for ulcerative colitis. Clin Gastroenterol Hepatol. 2020; S1542-3565(20)31388-4. IBD: Inflammatory Bowel Disease; UC: ulcerative colitis; CD: Crohn’s Disease ROBUST RESEARCH PORTFOLIO TO HELP INFORM CLINICAL PRACTICE COMPETITIVE POSITIONING REAL WORLD EVIDENCE VARSITY: 1st Head-to-Head study in IBD (UC) • Vedolizumab was superior to adalimumab on the primary endpoint of clinical remission at week 52 VICTORY: Largest real-world registry with over 1,000 Vedolizumab-treated patients with UC or CD • Higher rates of remission in UC with vedolizumab versus TNF- antagonist therapy in routine practice Clinical Remission (Primary endpoint) Comparative effectiveness of VDZ to TNF- antagonist therapy (IPW ATE match set) Vedolizumab IV 300mg Q8W Adalimumab SC 40mg Q2W 22.5 31.3 ∆ = 8.8% (95% CI: 2.5%, 15.0%) p=0.006 21 |

22 | Bringing our pipeline to life GLOBAL CAPABILITIES to deliver LIFE TRANSFORMING TREATMENTS LAUNCH EXCELLENCE Patient Journey & Diagnosis Data, Insights & Analytics Patient Services Value Based Partnerships Digital Evidence Generation

AGENDA 23 | TIME (EST) TIME (JST) AGENDA 17:00 – 17:10 07:00 – 07:10 Takeda: A Global Values-Based, R&D-Driven Biopharmaceutical Leader Christophe Weber, President & CEO 17:10 – 17:25 07:10 – 07:25 Following Through On Our Commitment To Deliver Innovative Medicines To Patients: Spotlight On Select Wave 1 Programs Andy Plump, President, R&D 17:25 – 17:35 07:25 – 07:35 Entyvio Case Study: Building A Gold Standard Therapy Along The Patient Journey Ramona Sequeira, President, USBU & Global Portfolio Commercialization 17:35 – 18:05 07:35 – 08:05 TAK-721 Deep Dive: Potential To Be First FDA-Approved Agent With Indication For Eosinophilic Esophagitis Mike Nedham, Global Program Leader for TAK-721, Global Product & Launch Strategy 18:05 – 18:35 08:05 – 08:35 TAK-003 Deep Dive: Live-Attenuated Tetravalent Vaccine For Prevention Of Dengue Disease Rajeev Venkayya, President, Global Vaccine Business Unit 18:35 – 19:15 08:35 – 09:15 Panel Q&A Session Appendix 1: Wave 1 Pipelines One-Pager Summaries Appendix 2: Epidemiology Data Appendix 3: Clinical Trial Summary

TAK-721 Deep Dive: Potential To Be First FDA-Approved Agent With Indication For Eosinophilic Esophagitis Michael Nedham TAK-721 Global Program Lead, Global Product & Launch Strategy

KEY TAKEAWAYS FOR TAK-721 IN EOE (EOSINOPHILIC ESOPHAGITIS) 1 32 TAK-721 is an investigational treatment and has not been approved for use by the U.S. Food and Drug Administration or other regulatory authorities. Neither Breakthrough Therapy Designation nor Orphan Drug Designation guarantee approval or commercial availability. Unmet need in EoE is high, leadership needed TAK-721 is specifically designed to tackle EoE Takeda is strongly positioned to launch TAK-721 • Chronic inflammatory disease which impacts QoL and can lead to long term fibrosis. • Incidence and prevalence growing and no FDA approved treatments • As an established leader with proven capabilities launching GI products • US launch expected in H1 FY2021 • Has breakthrough therapy designation and completed registration studies • NDA submitted and if approved will be the 1st FDA approved agent 25 |

Over time, untreated chronic inflammation can progress to fibrotic disease, narrowing of the esophagus, and associated food impactions. Diagnosed through biopsy confirming high eosinophil count (>15/hpf) in the esophagus. EoE is a rare, chronic, inflammatory, immune-mediated disease of the esophagus, often resulting in dysphagia (difficulty swallowing) in adults and children. WHAT IS EOE (EOSINOPHILIC ESOPHAGITIS)? 26 |

WHAT IS IT LIKE FOR PATIENTS LIVING WITH EOE? Physical PAIN Staying NOURISHED Social ISOLATION 27 | “I sometimes go for days or weeks without an impaction, but I always feel like I’m living on the edge of another choking incident. I wish I could go back to not having to constantly think about food.” Source: “Illuminating the Emotions & Needs of the EoE Patient,” ethnographic market research, 2018

PATIENT JOURNEY INVOLVES MULTIPLE SPECIALTIES AND LONG DIAGNOSIS TIMES 28 | PRE-EOE DIAGNOSIS (6 MONTHS) EOE DIAGNOSIS PROCEDURE 1ST EOE DIAGNOSIS TREATMENT INITIATION PERSISTENCE • 72% of patients are diagnosed with endoscopy • 25% have had an endoscopy prior but may not have had a biopsy Rxs: • 50% are untreated • 34% are on PPI Comorbidities: • 30% of patients have allergy disease • 45% have GERD and/or dysphagia • 62% of patients are diagnosed by gastroenterologists • 8% of patients are diagnosed by allergist • 77% of patients are treated within 18 months • 63% of treated patients are initiated by gastroenterologists PPI: Proton Pump Inhibitor, GERD: Gastroesophageal Reflux Disease. Source: 2019 EoE Patient Flow Analysis, IQVIA Pharmetrics Plus data, Jan 2013 - Dec 2018. • On average, patients are on therapy for a total of 6.5 months within the 12 months from treatment initiation

EOE IS STILL RELATIVELY NEW AND RARE, BUT PREVALENCE IS GROWING 29 | Approximately 1 in 2000 people in the US live with EoE1-5 Emerging evidence suggests environmental factors such as microbes, early-life events affecting the microbiome, and other factors may be contributing to the rise in prevalence of EoE1,10-14 EoE can affect all ages, but predominantly adults under 50 and adolescents, and twice as common in men.4,6-9 11. Furuta GT, Katzka DA. N Engl J Med. 2015;373(17):1640-1648. 12. Harris JK, Fang R, Wagner BD, et al. PLoS One. 2015;10(5):e0128346. 13. Carr S, Chan ES, Watson W. Allergy Asthma Clin Immunol. 2018;14(Suppl 2):58. 14. Alexander ES, Martin LJ, Collins MH, et al. J Allergy Clin Immunol. 2014;134(5):1084-1092. 6. Muir AB, Brown-Whitehorn T, Godwin B, et al. Clin Exp Gastroenterol. 2019;12:391-399. 7. Lucendo AJ, Molina-Infante J, Arias Á, et al. United European Gastroenterol J. 2017;5(3):335-358. 8. Shaheen NJ, Mukkada V, Eichinger CS, et al. Dis Esophagus. 2018;31(8):1-14. 9. Mansoor E, Cooper GS. Dig Dis Sci. 2016;61(10):2928-2934. 10. Dellon ES, Hirano I. Gastroenterology. 2018;154(2):319-332.e3. 1. O’Shea KM, Aceves SS, Dellon ES, et al. Gastroenterology. 2018;154(2):333-345. 2. Dellon ES, Jensen ET, Martin CF, et al. Clin Gastroenterol Hepatol. 2014;12(4):589-596. 3. Dellon ES. Gastroenterol Clin North Am. 2013;42(1):133-153 4. Dellon ES. Gastroenterol Clin North Am. 2014;43(2):201-218. 5. Spergel JM, Book WM, Mays E, et al. J Pediatr Gastroenterol Nutr. 2011;52(3):300-306.

ACADEMIC INTEREST AND RESEARCH ACTIVITIES RAMPING UP First international consensus recommendations on EoE Initial series characterizing EoE in adults AGA/AAAAI joint taskforce guidelines Case reports of EoE in adults Topical steroid therapy prescribed in children ICD-9 classification for EoE FDA drug development guidance for EoE 1970 1990 2010 1980 2000 2020 30 | AGA: American Gastroenterological Association, AAAAI: American Academy of Allergy, Asthma & Immunology, ICD-9: International Classification of Diseases 9th Revision. “[Patients] will tell you “I am eating fine” but that they stopped eating meat because they have this fear that they are going to get another food impaction…. so it’s not really that their disease got better, their symptoms got better because they are avoiding food…” Dr Ikuo Hirano, Professor of Medicine at Northwestern University Feinberg School of Medicine

CURRENT U.S. TREATMENT APPROACHES ARE LIMITED 31 | Patient Adaptive Behaviors Active Diet Management Esophageal Dilation Off-Label Treatments Homemade “slurry” Swallowing inhaled steroids Compounding pharmacy PPIs PPI: Proton Pump Inhibitor.

SUMMARIZING THE OPPORTUNITY IN EOE • Increasing prevalence and incidence of EoE • Limited access to high quality treatment options • Challenge in consistency in managing disease, but high interest and excitement from HCPs • Low overall patient awareness and education with long diagnosis times • Need for leadership in EoE 32 |

TAK-721 is a synthetic second-generation, non- halogenated corticosteroid having potent topical anti-inflammatory and glucocorticoid activity TAK-721 has a wide range of inhibitory activities against multiple cell types Topically active, oral viscous suspension of budesonide, formulated specifically to target inflammation in the esophagus TAK-721 IS A POTENTIAL SOLUTION TO THE UNMET NEED IN EOE 33 | Davis BP. Clin Rev Allergy Immunol. 2018;55(1):19-42

34 | Orphan Drug Designation in EoE (2006) Breakthrough Therapy Designation in EoE (2016) NDA submitted on EoE (2020) Comprehensive development program of EoE specific Ph2 & Ph3 studies, aligned with FDA, and largest completed studies specific to EoE To develop and validate with FDA a Patient Reported Outcome tool specific to EoE – Dysphagia Symptom Questionnaire (DSQ) Ph3 program covering histology, symptoms & endoscopy, as well as adolescents and adults in one program PIONEERING CLINICAL DEVELOPMENT PROGRAM OF FIRSTS FOR EOE, PARTNERING WITH FDA

1.0% 53.1% 0 10 20 30 40 50 60 Pr op or ti on o f p at ie nt s ( % ) Placebo (n = 105) 2 mg BID (n = 213) p < 0.001 39.1% 52.6% 0 10 20 30 40 50 60 Pr op or ti on o f p at ie nt s ( % ) Placebo (n = 105) 2 mg BID (n = 213) p = 0.024 Results presented at presidential plenary at ACG, Texas, Oct 2019 35 | 1. DSQ score: Dysphagia Symptom Questionnaire patient reported outcome score eos/hpf: peak eosinophils per high-powered field from endoscopic biopsies ACG: American College of Gastroenterology ORBIT 1 STUDY: CO-PRIMARY ENDPOINTS MET FOR HISTOLOGY & SYMPTOMS Histologic Response at 12 Weeks (peak ≤ 6 eosinophils/hpf on biopsy) Declare statistical significance if p < 0.05 Symptom Response at 12 Weeks (≥ 30% reduction in DSQ score1) Declare statistical significance if p < 0.05

-7.6 -55.2 -80 -60 -40 -20 0 LS m ea n (S EM ) c ha ng e Placebo (n = 92) 2 mg BID (n = 201) p < 0.001 -9.1 -13.0 -15 -10 -5 0 LS m ea n (S EM ) c ha ng e Placebo (n = 89) 2 mg BID (n=197) p = 0.015 KEY SECONDARY EFFICACY ENDPOINT MET 36 | LS: least squares, SEM: standard error of the mean Change in overall peak eosinophil counts from baseline to week 12 of therapy Change in DSQ score from baseline to week 12 of therapy P value required = 0.05

ENDOSCOPIC APPEARANCE (EREFS) ENDPOINT MET AT 12 WEEKS Individual patient example from ORBIT 1 study 37 | Change to total EREFS score from baseline to week 12 of therapy -2.2 -4.0 -5 -4 -3 -2 -1 0 LS m ea n (S EM ) c ha ng e Placebo (n = 93) 2 mg BID (n = 202) p < 0.001

TAK-721 was well tolerated Treatment-emergent adverse events (TEAEs) were similar for TAK-721 (61.0%) and placebo (61.0%) groups after 12 weeks Most TEAEs reported were mild or moderate in severity SAFETY RESULTS CONSISTENT WITH KNOWN SAFETY PROFILE OF BUDESONIDE 38 |

A LEADERSHIP PATH TO 1ST POTENTIAL U.S. APPROVAL NEXT YEAR Orphan Drug Designation granted (2006) Breakthrough Therapy Designation granted (2016) ORBIT 1 Ph3 study (completed 2019) ORBIT 2 Ph3 study (completed 2020) NDA submission (FY2020 Q3) Ph2 studies (Completed 2015) 1st FDA product (if approved) 1 2 3 4 5 6 39 | NDA: New Drug Application.

TAK-721 1st FDA product (if approved) 40 | 1st line Therapy Later Line TherapyBiologic Treatments Currently in trials TAK-721 POTENTIAL LAUNCH AS 1ST FDA APPROVED PRODUCT IN EOE TO SET STANDARD AS 1ST LINE THERAPY

WE AIM TO ACHIEVE BROAD ACCESS FOR PATIENTS TO AN APPROVED TREATMENT Broad Patient Access 41 | Strong value proposition for payers Many patients currently pay full out-of-pocket for off-label treatments Objective to make TAK-721 accessible to as many patients as possible Services and solutions to enable access to TAK-721

U.S. BUSINESS UNIT WELL PREPARED FOR LAUNCHING TAK-721 BRAND 42 |

U.S. BUSINESS UNIT WELL PREPARED FOR LAUNCHING TAK-721 BRAND 43 | HCP PATIENT Field Force • Medical, Thought Leader Liaisons and Sales personnel already hired and established to support EoE launch Disease State Education • New Digital approach to bolster EoE awareness with the launch of SeeEoE.com KOL Engagement and Congress Presence • First disease state awareness effort launched at ACG, as well as commercial and medical advisory boards completed. Patient Awareness • Launch of a patient centric disease state awareness campaign through digital channels Product Access • Ensuring the right support with patient services and market access plans in place Launch formulation • Development of new formulation for launch Partnership with patient advocacy • To understand educational and support gaps to improve diagnosis and standard of care ACG: American College of Gastroenterology

44 | Leadership in Inflammatory Bowel Disease (IBD) Leadership in Short Bowel Syndrome (SBS) Leadership in Motility & Acid Related Disorders Leadership in EOE TOGETHER. BEYOND.

REINFORCING LEADERSHIP IN GI WITH POTENTIAL FIRST FDA APPROVED THERAPY IN EOE 45 | 1 32 Unmet need in EoE is high, leadership needed Eohilia is specifically designed to tackle EoE Takeda is strongly positioned to launch Eohilia TAK-721 is an investigational treatment and has not been approved for use by the U.S. Food and Drug Administration or other regulatory authorities. Neither Breakthrough Therapy Designation nor Orphan Drug Designation guarantee approval or commercial availability.

TAK-003 Deep Dive: Live-Attenuated Tetravalent Vaccine For Prevention Of Dengue Disease Rajeev Venkayya President, Global Vaccine Business Unit

48 | 1. World Health Organization (WHO). Top ten threats to global health in 2019. https://www.who.int/news- room/spotlight/ten-threats-to-global-health- in-2019 2. WHO. Dengue and Severe Dengue. https://www.who.int/news-room/fact-sheets/detail/dengue-a nd-severe- dengue DENGUE IS A TOP TEN THREAT TO GLOBAL HEALTH World Health Organization, 20191 >100 Endemic countries, primarily in Asia and Latin America2 390 M Estimated infections each year2 A leading cause of hospitalization and death in children and adults in endemic regions2 >3.9 BILLION people around the globe are at risk of dengue2

49 | 1. WHO. https://www.who.int/images/default-source/departments/ntd-libra ry/dengue/infographics-and- illustrations/dengue-infographic.png?sfvrsn=ae8ce604_8 2. WHO. Promoting dengue vector surveillance and control https://www.who.int/activities/promoting-dengue- vector-surveillance-and-control 3. Mol Biol Evol. 2010 Apr; 27(4): 811–818. Epidemic Dynamics Revealed in Dengue Evolution: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877535/ FASTEST-SPREADING MOSQUITO-BORNE VIRAL DISEASE1 Four strains of the dengue virus (DENV) 1-4 spread by the Aedes aegypti and Aedes albopictus mosquitos2 All four strains of dengue may be circulating at any time, and it is not always known which strain is present3 The second infection with a different strain could lead to more severe disease4 Unlike other mosquito-borne diseases, such as malaria, a targeted treatment for dengue does not exist5,6 4. J R Soc Interface. 2013 Sep 6; Interactions between serotypes of dengue highlight epidemiological impact of cross- immunity. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730691 5. WHO. Malaria. https://www.who.int/news-room/fact-sheets/detail/malaria 6. WHO. Dengue and Severe Dengue. https://www.who.int/news-room/fact-sheets/detail/dengue-a nd-severe-dengue

50 | GEOGRAPHICAL RANGE OF DENGUE IS EXPANDING More than 90% of dengue cases occur in Middle Income Countries* (MICs)2,3,4 • Brazil: 2 million cases, 20195 • Philippines, ~400,000 cases, 20196 Dengue is found mostly in urban and semi-urban areas in tropical and sub-tropical climates. Globalization, urbanization and climate change are contributing to rise in disease1 More than 6 billion people could be at risk for dengue by 2080 due to population growth in endemic areas1 *MICs are defined as those with a GNI per capita between $1,036 and $12,5353 It includes countries classified as Low Middle Income and High Middle Income. Limited data on dengue burden in low income countries Burden of dengue is placing additional strain on countries dealing with COVID-197 1. 5.Messina, J.P., Brady, O.J., Golding, N. et al. The current and future global distribution and population at risk of dengue. Nat Microbiol 4, 1508–1515 (2019). https://doi.org/10.1038/s41564-019-0476-8 2. Cases: Supplement to Stanaway JD, Shepard DS, Undurraga EA, et al. The global burden of dengue: an analysis from the Global Burden of Disease Study 2013. Lancet Infect Dis 2016; published online Feb 10. http://dx.doi.org/10.1016/S1473- 3099(16)00026-8. Accessed Jan 14, 2019. 3. Income Classification: World Bank: List of Economies (June 2018). https://datahelpdesk.worldbank.org/knowledgebase/articles/906519-world-bank-country-and-lending-groups 4. 2018 World Development Indicators. World Bank. https://databank.worldbank.org/data/reports.aspx?source=2&series=NY.GDP.MKTP.CD&country=#. 5. WHO. https://www.who.int/news/item/21-11-2019-who-region-of-the-americas-records-highest-number-of-dengue-cases-in- history-cases-spike-in-other-regions 6. WHO. https://www.who.int/docs/default-source/wpro---documents/emergency/surveillance/dengue/dengue- 20201105.pdf?sfvrsn=fc80101d_42 7. Harapan H, Ryan M, Yohan B, et al. Covid-19 and dengue: Double punches for dengue-endemic countries in Asia [published online ahead of print, 2020 Sep 18]. Rev Med Virol. 2020;e2161. doi:10.1002/rmv.2161

51 | 1. PLOS. Neglected Tropical Disease. Societal impact of dengue outbreaks: Stakeholder perceptions and related implications. A qualitative study in Brazil, 2015 2. WHO scales up response to worldwide surge in dengue https://www.who.int/news- room/feature-stories/detail/who-scales-up-response-to-worldwide-surge- in- dengue It was scary. Both public and private service centres were overflowing. The urgent care centres in private hospitals were also over capacity.1 • Areas may see more than 400%+ increase of cases in one month1 • Thousands of patients may be admitted to hospitals in just a few days2 • Makeshift treatment wards, and ordinary wards are converted to dengue wards1 • Average cost range $36-$2,000 per person hospitalized in endemic countries3 • Families may spend 15-23% of monthly household income for hospitalizations, or more, depending on socioeconomic factors4,5 Hospitals and clinics struggle with increased cases Medical costs of dengue can be great. Households bear a substantial burden of this cost 3. Shepard, et al. Lancet Infect Dis 2016;16:935–41 4. Tozan Y, Ratanawong P, Sewe MO, Wilder-Smith A, Kittayapong P. Household costs of hospitalized dengue illness in semi-rural Thailand. PLoS Negl Trop Dis. 2017;11(9):e0005961 5. Sri Lanka Journal of Child Health, 2014; 43(4): 205-207 . Economic cost of hospitalized non-fatal paediatric dengue at the Lady Ridgeway Hospital for Children in Sri Lanka OUTBREAKS CAN OVERWHELM HOSPITALS AND FAMILIES

52 | THE ECONOMIC IMPACT OF DENGUE IS BROAD1–4 Health care expenditures Direct medical and non-medical costs Care-related productivity Indirect costs: time off work & school for patients and their caregivers Vector control, surveillance and communication costs Dengue outbreak control costs Additional expenses for communication, surveillance, vector control, health care personnel, etc. Economy and social Trade and tourism, foreign direct investment Country productivity Long-term fatigue impacts educational level, labor supply and productivity Behavior Investment for children and young adults, economic condition within family and community (consumption of goods) HOUSEHOLD MACROECONOMIC IMPACTGOVERNMENT 1. Drummond, et al. Vaccine 2007;25:5945–57 2. Deogaonkar, et al. BMC Public Health 2012;12:878 3. Bärnighausen, et al. Semin Immunol 2013;25:104–13 4. Bloom, 4th International Conference on Tropical Medicine 2014

Larger and more diverse cohorts • Urban and rural dwellers • Children, adolescents, adults • Men and women LARGE ELIGIBLE POPULATION FOR DENGUE VACCINATION Vaccine Eligible Population In Endemic Countries For A Dengue Vaccine Far Exceeds Any Recently Launched Vaccine1 % of Overall Population that is Vaccine Eligible (Brazil)2 RECENTLY LAUNCHED VACCINES HPV Pneumococcal 15% 7% Rotavirus Varicella 1% 1% 85% ~180 million eligible for Dengue vaccine DENGUE 53 | 1. Brazil data shown as proxy for endemic countries2. Recommended population/country population

4 9 14 19 24 29 34 39 44 49 54 59 64Age $1500 $600 $300 $60 Pe r ca pi ta A ve ra ge M on th ly In co m e (U SD ) Po pu la ti on p er ce nt ag e (% ) 3% 59% 26% 10% 2% Mexico example PLAN TO MAXIMIZE ACCESS IN ENDEMIC COUNTRIES Statistical data from: Pew Research Center analysis of data from the World Bank PovcalNet database (Center for Global Development version available on the Harvard Dataverse Network) and the Luxembourg Income Study database. 2011 The diagrams shown are tentative for illustrative purposes only. Real program scope may differ.54 |

4 9 14 19 24 29 34 39 44 49 54 59 64Age $1500 $600 $300 $60 Expanded National Immunization Programs • Government Financing • Procurement modalities Pe r ca pi ta A ve ra ge M on th ly In co m e (U SD ) Po pu la ti on p er ce nt ag e (% ) 3% 59% 26% 10% 2% Mexico example PLAN TO MAXIMIZE ACCESS IN ENDEMIC COUNTRIES Statistical data from: Pew Research Center analysis of data from the World Bank PovcalNet database (Center for Global Development version available on the Harvard Dataverse Network) and the Luxembourg Income Study database. 2011 The diagrams shown are tentative for illustrative purposes only. Real program scope may differ.56 |

4 9 14 19 24 29 34 39 44 49 54 59 64Age $1500 $600 $300 $60 Private Sector Activation • Individual Financing options Pe r ca pi ta A ve ra ge M on th ly In co m e (U SD ) Po pu la ti on p er ce nt ag e (% ) 3% 59% 26% 10% 2% Mexico example PLAN TO MAXIMIZE ACCESS IN ENDEMIC COUNTRIES Expanded National Immunization Programs • Government Financing • Procurement modalities Statistical data from: Pew Research Center analysis of data from the World Bank PovcalNet database (Center for Global Development version available on the Harvard Dataverse Network) and the Luxembourg Income Study database. 2011 The diagrams shown are tentative for illustrative purposes only. Real program scope may differ.57 |

4 9 14 19 24 29 34 39 44 49 54 59 64Age $1500 $600 $300 $60 Private Sector Activation • Individual Financing options Access to Medicines • Patient Assistance Programs • Vulnerable populations Pe r ca pi ta A ve ra ge M on th ly In co m e (U SD ) Po pu la ti on p er ce nt ag e (% ) 3% 59% 26% 10% 2% Mexico example PLAN TO MAXIMIZE ACCESS IN ENDEMIC COUNTRIES Expanded National Immunization Programs • Government Financing • Procurement modalities Statistical data from: Pew Research Center analysis of data from the World Bank PovcalNet database (Center for Global Development version available on the Harvard Dataverse Network) and the Luxembourg Income Study database. 2011 The diagrams shown are tentative for illustrative purposes only. Real program scope may differ.58 |

UTILITY FOR TRAVEL AND NON-ENDEMIC MARKETS Map is illustrative of trips traveled from the US, Canada and Europe, and does not detail specific numbers or timeframes More than 90 million arrivals* from the US, Canada and Europe to dengue endemic countries in 20183 Dengue is a leading cause of fever among travelers returning from Latin America, the Caribbean, and Southeast Asia1,2 surpassing malaria *non-resident visitors 59 | 1. Halstead S, Wilder-Smith A. Severe dengue in travelers: pathogenesis, risk and clinical management. J Travel Med. 2019;26(7). 2. CDC. Yellow Book. https://wwwnc.cdc.gov/travel/yellowbook/2020/travel-related-infectious-diseases/dengue 3. World Tourism Organization Yearbook of Tourism Statistics, Data 2014 – 2018, 2020 Edition https://tillvaxtverket.se/download/18.5d4267f7170c014f2fcbbaa/1583832450663/Yearbook_2020_ed.pdf

Based on a live-attenuated dengue serotype 2 virus, which provides the genetic “backbone” for four dengue serotypes represented in the vaccine Designed to stimulate multiple arms of the immune system TAK-003 is being developed by Takeda to protect children and adults against all four virus serotypes, regardless of previous dengue exposure TAK-003 HAS THE POTENTIAL TO HELP ADDRESS THE MASSIVE GLOBAL BURDEN OF DENGUE 60 |

Part 3Part 2 PIVOTAL PHASE 3 TRIAL DESIGN DEN-301: 20,099 children (aged 4–16 years) were randomized 2:1 to receive either TAK-003 or placebo in endemic countries in Latin America and Asia; subjects were balanced across geographies1 Primary endpoint: Overall vaccine efficacy Secondary efficacy endpoints: Efficacy by serotype, baseline serostatus, severity 3 Years Part 1 6 Months 3 Months 1 Month 1 Year Long term efficacy and safety Ongoing safety analysis End of 2020 36-month data available 61 | 1. ClinicalTrials.gov Identifier: NCT02747927

TAK-003 EFFICACIOUS AGAINST DENGUE ILLNESS WITH A STRONG SAFETY PROFILE 80.2% (73.3 to 85.3; p<0.001) overall vaccine efficacy (VE) * across serotypes and serostatus1 90.4% (82.6 to 94.7; p<0.001) VE against hospitalized dengue across serotypes and serostatus2 TAK-003 was generally well tolerated, with a strong safety profile to date1,2 BROAD PROTECTION 80% EFFICACY AGAINST DENGUE ILLNESS 90% EFFICACY AGAINST HOSPITALIZATION VE was similar in baseline seropositive and seronegative individuals: 76.1% (68.5 to 81.9) VE and 66.2% (49.1 to 77.5) VE, respectively2 VARIED RESULTS BY SEROTYPE2 DEN-301 met the majority of secondary endpoints at 18 months2DEN-301 met the primary endpoint at 12 months1 DENV1: 69.8% VE (54.8 to 79.9) DENV2: 95.1% VE (89.9 to 97.6) DENV3: 48.9% VE (27.2 to 64.1) DENV4: Insufficient cases to determine VE Seronegative at baseline: seronegative to all four dengue serotypes Seropositive at baseline: reciprocal neutralizing antibody titer ≥10 for one or more dengue serotypes VE: Vaccine Efficacy.(95% CI) 62 | 1. Biswal S, et al. Efficacy of a tetravalent dengue vaccine in healthy children and adolescents. N Engl J Med. 20192. Biswal S, et al. Efficacy of a tetravalent dengue vaccine in health children aged 4-16 years: a randomized, placebo-controlled, phase 3 trial. Lancet. 2020. doi:10.1016/S0140-6736(20)30414-1

Overall VE 89.2% (82.4, 93.3) Baseline Sero- 87.0% (70.1, 94.3) Baseline Sero+ 90.0% (81.9, 94.5) HOSPITALIZATIONS REDUCED BY APPROXIMATELY 90% Through 24 Months1 63 | Seronegative at baseline: seronegative to all four dengue serotypes; Seropositive at baseline: reciprocal neutralizing antibody titer >= 10 for one or more dengue serotypes. VCD: virologically confirmed dengue VE: Vaccine Efficacy (95% CI) 1. Takeda data on file. Presented at the American Society of Tropical Medicine and Hygiene Annual Meeting, November 17, 2020 Time since first doe in months Pa rt ic ip an ts w it h ho sp it al iz ed V CD (% ) TAK-003, Seropositive TAK-003, Seronegative Placebo, Seropositive Placebo, Seronegative 0.0 0.5 1.0 1.5 2.0 0 3 6 9 12 15 18 21 24 27

Overall VE 72.7% (67.1 to 77.3) Baseline Sero- 67.0% (53.6, 76.5) Baseline Sero+ 74.8% (68.6, 79.8) DENGUE ILLNESS REDUCED BY MORE THAN 70% Through 24 Months1 64 | Seronegative at baseline: seronegative to all four dengue serotypes; Seropositive at baseline: reciprocal neutralizing antibody titer >= 10 for one or more dengue serotypes. VCD: virologically confirmed dengue VE: Vaccine Efficacy (95% CI) 1. Takeda data on file. Presented at the American Society of Tropical Medicine and Hygiene Annual Meeting, November 17, 2020 TAK-003, Seropositive TAK-003, Seronegative Placebo, Seropositive Placebo, Seronegative Pa rt ic ip an ts w it h V CD ( % ) Time since first doe in months 0 3 6 9 12 15 18 21 24 27 0 1 2 3 4 5 6

EFFICACY VARIED BY SEROTYPE WITH GREATEST REDUCTIONS IN DENGUE ILLNESS OBSERVED FOR THE MOST PREVALENT SEROTYPE, DENV-2* Through 24 Months1 69.0% 90.8% 51.4% 50.4% 0 10 20 30 40 50 60 70 80 90 100 DENV-1 DENV-2 DENV-3 DENV-4‡ VE a ga in st V CD % (57.1, 77.5) (85.6, 94.1) (34.0, 64.2) (-19.3, 79.3) VE against dengue illness up to 24 Months, by serotype† 65 | First dose to Year 2 post-second dose in the safety set * DENV-1 and DENV-2 have been seen most commonly in the study while DENV-4 least commonly. †Data includes baseline seropositives and seronegatives ‡The total number of DENV-4 cases was low Seronegative at baseline: seronegative to all four dengue serotypes; Seropositive at baseline: reciprocal neutralizing antibody titer >= 10 for one or more dengue serotypes. VCD: virologically confirmed dengue VE: Vaccine Efficacy (95% CI) 1. Takeda data on file. Presented at the American Society of Tropical Medicine and Hygiene Annual Meeting, November 17, 2020 **

SAFETY AND TOLERABILITY OF TAK-003 Through 24 Months No evidence of disease enhancement in seronegative individuals1,2,3 Slight increase in dengue fever* in the DENV-3 seronegative population at 18 months. Stabilized at 24 months1,3 Strong safety profile up to 24 months after second dose of TAK-0031 *The finding was not statistically significant, a lack of efficacy. 66 | 1. Takeda data on file. Presented at the American Society of Tropical Medicine and Hygiene Annual Meeting, November 17, 2020 2. Biswal S, et al. Efficacy of a tetravalent dengue vaccine in healthy children and adolescents. N Engl J Med. 2019 3. Biswal S, et al. Efficacy of a tetravalent dengue vaccine in health children aged 4-16 years: a randomized, placebo-controlled, phase 3 trial. Lancet. 2020. doi:10.1016/S0140-6736(20)30414-1

STRONG EFFICACY AND SAFETY PROFILE TWO YEARS AFTER VACCINATION Continued efficacy against dengue, with some waning efficacy seen between year 1 and year 2; evaluating potential for a booster1 Robust reduction of hospitalized dengue1 Similar efficacy regardless of previous dengue exposure1 The observed level of efficacy continued to vary by serotype1 Well-tolerated in trial participants1 Strong safety profile up to 24 months after second dose of TAK- 0031 67 | 1. Takeda data on file. Presented at the American Society of Tropical Medicine and Hygiene Annual Meeting, November 17, 2020

EXPECTED MILESTONES Launch in EU Approval in EU Regulatory filing in US First approvals in 1st Wave endemic countries and US FY21FY20 FY22 FY23 FY24 FY25 FY26 2nd Wave countries: first approvals and launches 3rd Wave countries: approvals and launches (TBD) DEN-301 36-month data readout • 1st Wave: Indonesia, Malaysia, Thailand, Colombia, Brazil, Mexico, Singapore, Sri Lanka, Argentina, United States, Multiple EU Countries • 2nd Wave:, Canada, Israel, Ecuador, Guatemala, Paraguay, Peru, Costa Rica, El Salvador, Panama, Nicaragua, D. Republic, Philippines, Hong Kong, Australia, Vietnam • 3rd Wave: Cuba, Honduras, Venezuela, China, India Regulatory filings: 1st Wave endemic countries, EU Launch in 1st Wave endemic countries Launch in US 68 |

1 32 Takeda building up capacity to fulfill 50+ million doses per year, meeting urgent need for a new dengue vaccine Estimate the dengue vaccine market could reach USD 1.5-2 billion annually by 20291 First regulatory filings in endemic countries (Article 58), Europe and US expected in 2021 SUMMARY 69 | 1. VacZine Analytics’ Global Dengue report

TIME (EST) TIME (JST) AGENDA 17:00 – 17:10 07:00 – 07:10 Takeda: A Global Values-Based, R&D-Driven Biopharmaceutical Leader Christophe Weber, President & CEO 17:10 – 17:25 07:10 – 07:25 Following Through On Our Commitment To Deliver Innovative Medicines To Patients: Spotlight On Select Wave 1 Programs Andy Plump, President, R&D 17:25 – 17:35 07:25 – 07:35 Entyvio Case Study: Building A Gold Standard Therapy Along The Patient Journey Ramona Sequeira, President, USBU & Global Portfolio Commercialization 17:35 – 18:05 07:35 – 08:05 TAK-721 Deep Dive: Potential To Be First FDA-Approved Agent With Indication For Eosinophilic Esophagitis Mike Nedham, Global Program Leader for TAK-721, Global Product & Launch Strategy 18:05 – 18:35 08:05 – 08:35 TAK-003 Deep Dive: Live-Attenuated Tetravalent Vaccine For Prevention Of Dengue Disease Rajeev Venkayya, President, Global Vaccine Business Unit 18:35 – 19:15 08:35 – 09:15 Panel Q&A Session Appendix 1: Wave 1 Pipelines One-Pager Summaries Appendix 2: Epidemiology Data Appendix 3: Clinical Trial Summary 70 | AGENDA

TODAY’S SPEAKERS 71 | CHRISTOPHE WEBER President & CEO ANDY PLUMP President, Research & Development RAJEEV VENKAYYA President, Global Vaccine Business Unit Available for Q&A COSTA SAROUKOS Chief Financial Officer TERESA BITETTI President, Global Oncology Business Unit RAMONA SEQUEIRA President, USBU & Global Portfolio Commercialization MICHAEL NEDHAM Global Program Leader for TAK-721, Global Product & Launch Strategy

Appendix 1 Wave 1 Pipelines One-Pager Summaries

MECHANISM EGFR TKI specifically designed for Exon20 insertions PATIENT JOURNEY/ UNMET NEED Patients with EGFR Exon20 insertion mutations have no approved targeted therapy • Approved EGFR TKIs are not designed to treat Exon20 insertions • Current treatment approaches including chemotherapy, approved EGFR inhibitors at recommended dose, and immunotherapy all deliver <6 months PFS across all lines of therapy • Greatest unmet need for the exon 20 insertion population is a targeted therapy that improves survival with an acceptable side effect profile KEY DATA Phase 1/2 study of mobocertinib in 2L+ NSCLC with Exon20 insertions showed promising efficacy with a 43% confirmed response rate in the intent-to-treat population with a DOR of 13.9 months and a 7.3 months PFS MARKET OPPORTUNITY Globally, 1-2% of non-small cell lung cancer cases have an EGFR Exon20 insertion mutations (~4K patients in U.S., 20-30K WW) DEVELOPMENT STATUS & EXPECTED MILESTONES • Ph1/2 EXCLAIM study (single-arm) in relapsed/refractory patients could support first filings in FY20 • Ph-3 EXCLAIM-2 study (vs. chemo) in first-line now recruiting • Partnerships for companion diagnostic for EGFR exon 20 insertions with Thermo Fisher in the US/JP/EU, Foundation Medicine in the US & Amoy Diagnostics in China MOBOCERTINIB (TAK-788) Potential New Standard Of Care For NSCLC Patients With EGFR Exon20 Insertion Mutations -2 BTD (China) BTD FTD 2L+ NSCLC Exon20 Approval (US) 1L NSCLC Exon20 Approval (US/EU) 2L+ NSCLC Exon20 Approval (CN) 2L+ NSCLC Exon20 Ph2 data readout (H1) 1L NSCLC exon 20 Ph3 data readout FY22 FY23 FY24FY20 FY21 Approved EGFR TKIs do not demonstrate significant PFS benefit in EGFR exon20 insertions ORR: Overall response rate PFS: Progression free survival WW: World Wide annual incidence Robichaux, J.P., Elamin, Y.Y., Tan, Z. et al. Mechanisms and clinical activity of an EGFR and HER2 exon 20–selective kinase inhibitor in non–small cell lung cancer. Nat Med 24, 638–646 (2018). https://doi.org/10.1038/s41591-018-0007-9 73 | ODD

MECHANISM NEDD8-activating enzyme (NAE) inhibitor PATIENT JOURNEY/ UNMET NEED Patients with HR-MDS have a poor prognosis, diminished QoL, higher chance of transformation to AML and limited treatment options • Outcomes are poor and, even with current treatment options, mortality rates remain high. Median survival for HR-MDS is 12-15 months, and 10 - 15 months for AML • Economic burden of supportive care is substantial: Hospitalizations are common and many patients are transfusion dependent KEY DATA HR-MDS: combination of pevonedistat and azacitidine demonstrated benefit across several clinically meaningful endpoints, including OS, EFS, CR and transfusion independence, with a safety profile similar to azacitidine alone. • Adding pevonedistat to azacitidine doubled CR (51.7% vs. 26.7%), and demonstrated potential to improve OS and EFS Unfit AML: promising clinical activity in elderly AML in a Phase 1b study • ORR 60% with a trend towards improved survival in secondary AML MARKET OPPORTUNITY 1L HR-MDS: ~7K patients in U.S., 15-20K in G7 (~80% transplant ineligible) 1L AML: ~19K patients in U.S., 35-40K in G7 (~50% transplant ineligible) DEVELOPMENT STATUS & EXPECTED MILESTONES • US FDA granted BTD in July 2020 • Clinical development efforts in emerging markets including China have been integrated into overall program strategy • Combination study with pevonedistat, venetoclax and azacitidine actively enrolling • External collaborations have also been broadly but strategically leveraged to develop additional pevonedistat combinations in other AML/MDS populations PEVONEDISTAT (TAK-924) Potential To Be First Novel Therapy In HR-MDS In Over A Decade ODD BTD P2001: Phase 2 proof of concept In HR-MDS FY22 1L HR-MDS Approval (US/EU/JP) FY23 Unfit AML Ph3 data FY24FY20 FY21 1L Unfit AML Approval HR-MDS Ph3 data n=67, HR 0.539, p=0.045 EFS: Event free survival, defined as death or transformation to AML 74 |

TAK-007 Potential Transformative “Off-the-shelf” Cell Therapy For Multiple Cancers MECHANISM CD19 CAR-NK cell therapy PATIENT JOURNEY/ UNMET NEED Significant need for an efficacious, off-the-shelf cell therapy with an improved toxicity profile • Patients with CD19 positive B-cell malignancies who cannot receive CAR-T have a median overall survival of <10 months • Current CAR T-cell therapies require a multi-week manufacturing process, use is restricted to specialized transplant centers, and they are associated with toxicity including cytokine release syndrome or neurotoxicity KEY DATA Encouraging Phase 1/2 data in CD19+ B-cell malignancies, with efficacy comparable to CAR-T therapies • 73% of patients responded to therapy (8/11) and 64% of patients had a complete response (7/11) • No occurrence of cytokine release syndrome, neurotoxicity, or graft-versus host disease Opportunity to broaden access due to lower total cost of care and easier logistics • “Off the shelf” therapy enables treatment of patients without delay, and can be administered outpatient, which can reduce logistic burden and decrease health resource utilization and costs MARKET OPPORTUNITY 3L+ DLBCL, CLL, iNHL: ~9K patients in U.S., 15-25K in G7 Potential to advance to 2L therapy and to expand CAR-NK platform to other malignancies DEVELOPMENT STATUS & EXPECTED MILESTONES • Potential to advance to 2L therapy and to expand CAR-NK platform to other malignancies BASELINE SCAN DAY 30 POST CAR19-NK Data from Dr. Katy Rezvani, MD Anderson Cancer Center PH1/2 DATA: 47-YEAR OLD MALE WITH RELAPSED TRANSFORMED DOUBLE-HIT (C- MYC/BCL-2) DLBCL Validation of the cryopreservation process 3L+ DLBCL, CLL, iNHL Pivotal study start 3L+ DLBCL, CLL, iNHL Approval FY22 FY23 FY24FY20 FY21 ODD 75 |

MARIBAVIR (TAK-620) Potential 1st Approved Treatment In Over 10 Years For Patients With Post-transplant CMV Infection MECHANISM Maribavir is an oral benzimidazole riboside with activity against cytomegalovirus, that blocks nuclear egress of viral capsids through the inhibition of protein kinase UL971-7 PATIENT JOURNEY/ UNMET NEED Existing therapies are unapproved for treatment of post-transplant CMV infection; clinical utility is significantly limited by severe toxicities requiring hospitalization and resistance development • Existing SOC are 1st L valganciclovir, ganciclovir; 2nd L foscarnet, cidofovir- all are unapproved for post-transplant CMV treatment, and all have severe toxicities (myelosuppression and nephrotoxicity) • A CMV prophylaxis therapy was approved in US (2017), EU (2018), Japan (2018). Label limited to CMV prophylaxis only, in high-risk HSCT patients (so not for Solid Organ transplant). KEY DATA • In a Phase 2 trial in pre-emptive treatment (1L) post-transplant CMV patients, TAK-620 demonstrated similar efficacy with lower incidence of myelosuppression versus standard of care (valganciclovir.) • In a Phase 2 trial in refractory/resistant (R/R) post-transplant CMV patients, maribavir ≥400 mg twice daily was active; no new safety signals were identified. MARKET OPPORTUNITY • >46k patients experience CMV infection (14k in the USA) • >20k patients w/ treatment-limiting toxicity or recurrent CMV (6k in the USA) • >10k patients fail 1st line SOC, so refractory/resistant to SOC DEVELOPMENT STATUS & EXPECTED MILESTONES • 303 Study: Multicenter, Randomized, Active-controlled, Open-label maribavir vs. investigator-assigned treatment in HSCT and SOT patients with CMV infections, disease resistant or refractory to prior therapy • 302 Study: Multicentre, Randomized, Double-blind, Non-Inferiority study of maribavir vs. valganciclovir as a pre-emptive therapy of 1st episode CMV infection in treatment naïve HSCT recipients PHASE 2 DATA IN 2L R/R CMV PUBLISHED IN CLINICAL INFECTIOUS DISEASES6 BTD R/R Ph3 Data Readout (H2) R/R Approval (US) 1L Ph3 Data Readout 1L Approval (EU) 1L Approval (US) FY22 FY23 FY24FY20 FY21 R/R Approval (EU) Efficacy endpoint: Clearance of CMV DNA within 6 weeks Large improvement over historical outcomes (~50%)8-11 No treatment discontinuation due to nephrotoxicity and myelosuppression Overall: 67% efficacy Favorable safety profile PHASE 2 DATA IN 1L CMV PUBLISHED IN NEJM10 Efficacy endpoint: Clearance of CMV DNA within 6 weeks Maribavir Valganciclovir Clearance of CMV 79% 67% Incidence of Neutropenia 6% 22% 1. Chou S, Marousek GI. J Virol. 2008;82:246–53; 2. Chou S. Curr Opin Infect Dis. 2015;28:293–9; 3. Krosky PM, et al. J Virol. 2003;77:905–14; 4. Maertens J, et al. N Engl J Med. 2019;381:1136–47; 5. Papanicolaou GA, et al. Clin Infect Dis. 2019;68:1255–64; 6. Prichard MN. Rev Med Virol. 2009;19:215–29; 7. Clin Infect Dis. 2019 Apr 8;68(8):1255-1264; 8. Antimicrob Agents Chemother, 2014;58:128-35; 9. Mehta et al, 2016 American Transplant Congress, Meeting abstract C279; 10. J Heart Lung Transplant. 2019;Vol.38,Issue 12;p.1268-1274; 11. N Engl J Med 2019; 381:1136-47 76 | ODD

TAK-609 Potential To Be The First Product For Cognitive Impairment In Hunter Syndrome In US/EU MECHANISM Recombinant human iduronate-2-sulfatase unique formulated for intrathecal injection directly into the CNS through a surgically implanted port to circumvent the blood brain barrier. PATIENT JOURNEY/ UNMET NEED Significant outstanding unmet need for a treatment that can address cognitive manifestation of the Hunter Syndrome, which affects the vast majority of patients (~60%). • Deficiency of iduronate-2-sulfatase can lead to a build-up glycosaminoglycans (GAGs) that affect the function of cells and tissues within the central nervous system, causing a progressive decline in cognitive abilities. Current therapies do not address cognitive deterioration due to their inability to cross the blood brain barrier • TAK-609 will be first add-on therapy to Elaprase to halt/reduce cognitive decline in Hunter syndrome KEY DATA • In Dec 2017 the pivotal study, despite demonstrating a significant reduction in CSF GAG’s (-74%), failed to meet both primary and secondary endpoints; ad hoc analysis demonstrated potential efficacy in patients initiated on therapy before 6 years of age • A Phase 2/3 open-label extension study is ongoing to further evaluate long-term safety and clinical outcomes of TAK-609 (49 patients treated) (Link to clinicaltrials.gov) MARKET OPPORTUNITY • 1 in 100,000 to 170,000 male births are affected by Hunter Syndrome (~600 patients in the U.S., ~4,600 in marketed territories1). 2/3 of Hunter patients are affected by CNS manifestations. • Global market approximately $745M- $780M2 DEVELOPMENT STATUS & EXPECTED MILESTONES • HGT-HIT-094: A Controlled, Randomized, Two-arm, Open-label, Assessor-blinded, Multicenter Study of Intrathecal Idursulfase-IT Administered in Conjunction With Elaprase® in Pediatric Patients With Hunter Syndrome and Early Cognitive Impairment • SHP609-302: An Open Label Extension of Study HGT-HIT-094 Evaluating Long Term Safety and Clinical Outcomes of Intrathecal Idursulfase Administered in Conjunction With Elaprase® in Patients With Hunter Syndrome and Cognitive Impairment REDUCTION IN CSF GAGS ODD Approval (US) FY22 FY23 FY24FY20 FY21 Approval (EU) The metabolites that accumulate as a result of the enzyme deficiency in Hunter Syndrome are declining on therapy compared to the range of GAG levels of untreated patients (black dotted line) Source: Clinical Study Report Study SHP-609-094/302 (3 year data) 77 | 1. Elaprase universe, it includes Sanofi Genzyme territory (APAC, ANZ, SA), it excludes China and India, from 2020 to 2026 2. MPSII market in total somatic + CNS

TAK-611 Potential As The Only Therapy To Halt Rapid Progression Of Symptomatic Late Infantile MLD MECHANISM Recombinant human arylsulfatase A (rhASA) unique formulated for intrathecal injection directly into the CNS through a surgically implanted port to circumvent the blood brain barrier PATIENT JOURNEY/ UNMET NEED Tremendous unmet need for a treatment that can slow, delay or stop disease progression, because no treatments exist so far. • Metachromatic leukodystrophy (MLD) is characterized by developmental delays, motor skill regression, cognitive impairment, and optic atrophy leading to paralysis and early death • Late Infantile Onset patients (50-60% of prevalent cases) experience rapid motor function decline and death within 5 years of onset • Current standard of care relies on very weak options: palliative care, symptom management KEY DATA In Phase 1 study IDEAMLD, 2/12 children had a motor response with a dose dependent reduction of accumulated sulfatides in cerebrospinal fluid. Delayed motor decline 1.5-2 years vs. natural history. Those 2 patients treated with the highest dose (100mg EOW) maintained most motor function until age 5-6. Ph2b EMBOLDEN study is currently enrolling patient at dose of 150mg every week; topline data is anticipated to be available in FY22 MARKET OPPORTUNITY 0.7-1.4 per 100,000 live births, ~325 - 450 prevalent patients in the U.S.; ~11K worldwide (~2K reachable in total). In the near term, OTL-200 (Libmeldy), an ex-vivo gene therapy (expected EUCAN launch H1 2021 with a price range of EUR 2.5-3m1), and TAK-611 will become available to MLD patients. Global market size approximately $ 500m- $600m DEVELOPMENT STATUS & EXPECTED MILESTONES TAK-611 REDUCES NEUROTOXIC SULFATIDES ODD Sulfatide clearance requires uptake by cells and movement of enzyme into the acidic lysosome to become active Thus reduction of toxic sulfatides indicates TAK-611 is taken up by oligodendrocytes and active in the lysosome Source: Clinical Study Report Study HGT-MLD-070/071 (40 week data) Better Approval (US) FY22 FY23 FY24FY20 FY21 Approval (EU) Ph2b data readout • IDEAMLD: Multicenter, open-label, dose-escalation study designed to evaluate the safety of up to 3 dose levels of TAK-611 administered via an intrathecal drug delivery device every other week for a total of 38 weeks to children with MLD. • EMBOLDEN: Global, Multicenter, open-label, matched historical control study of intrathecal TAK-611 in subjects with late infantile MLD 78 | 1. Source: Orchard Therapeutics.

MECHANISM Recombinant ADAMTS-13 enzyme replacement therapy aiming to reduce the abnormally high von Willebrand factor activity seen in TTP PATIENT JOURNEY/ UNMET NEED • Standard of care with on-demand or prophylactic plasma infusions is highly burdensome. Replacement of ADAMTS13 to achieve sufficient levels is not possible in most cases with SoC. • Reduction of plasma dependency and improvement in short- and long-term morbidity seen as key value drivers KEY DATA The first and only recombinant ADAMTS-13 enzyme replacement therapy in development for congenital Thrombotic Thrombocytopenic Purpura (cTTP) and immune-mediated TTP (iTTP) • Phase 1 study demonstrated evidence for TAK-755 activity in vivo, including effects on VWF multimers, platelet count, and serum LDH. TAK-755 was well tolerated, no serious adverse events occurred, and no anti-ADAMTS-13 antibodies were observed • TAK-755 will allow for ADAMTS-13 substitution that is 3-5 times higher than possible with plasma infusions resulting in peak plasma levels in the normal range. MARKET OPPORTUNITY Congenital TTP: Global epidemiology ~1 per million; Treated patients: <500 in the U.S., 2.5K worldwide Immune TTP: Global epidemiology ~10 per million; patient events: < 2.5K in the U.S., ~14K worldwide Sickle Cell disease epidemiology: ~100K in in the USA and ~150K in EU DEVELOPMENT STATUS & EXPECTED MILESTONES TAK-755 Potential Transformational Therapy In cTTP & iTTP TAK-755 PK PROFILE AND PD EFFECT ON VWF CLEAVAGE AT 40 IU/KG ODD FTD FY22 FY23 FY24FY21 cTTP Approval (US) cTTP Approval (EU/JP) iTTP Ph2 data readout cTTP Ph3 data readout iTTP Ph3 data readout FY25 • TAK-755 therapy may be of benefit in other diseases associated with high von Willebrand Factor (VWF) activity and/or decreased ADAM-13 activity. TAK-755 is also in clinical phase 1/2 for sickle cell disease. • Phase 3: A prospective, randomized, controlled, open-label, multicenter study evaluating the safety and efficacy of TAK- 755 (rADAMTS13) in the prophylactic and on-demand treatment of participants with severe congenital Thrombotic Thrombocytopenic Purpura (cTTP) • Phase 2: A multicenter, randomized, placebo-controlled, double-blind study evaluating the PK, safety, and efficacy of TAK-755 in patients with acquired Thrombotic Thrombocytopenic Purpura (aTTP) Blood (2017) 130 (19): 2055–2063. 79 |

MECHANISM Cholesterol 24-hydroxylase (CH24H) enzyme inhibitor PATIENT JOURNEY/ UNMET NEED Developmental and Epileptic Encephalopathies (DEEs) are highly treatment resistant to multiple antiepileptic drugs, with few FDA-approved therapies • Over 50% of patients suffer from treatment-resistant seizures that can manifest in developmental and/or cognitive delays, communication and behavioral challenges and risk of sudden unexpected death in epilepsy (SUDEP)1 KEY DATA Strong efficacy in DS and a numeric reduction in LGS from Phase 2 ELEKTRA study • Well-tolerated, with a safety profile consistent with the findings of previous studies with no new safety signals identified • Statistically significant reduction in convulsive seizure frequency in DS cohort • Numerical reductions in drop seizure frequency in LGS cohort MARKET OPPORTUNITY • ~50K addressable DEE3 patients in the US • ~70-90K addressable DEE patients in major global market DEVELOPMENT STATUS & EXPECTED MILESTONES • Meet with regulatory agencies and initiate Phase 3 studies in DS and LGS REDUCTION IN SEIZURE FREQUENCY OVER 20 WEEKS OF FULL TREATMENT PERIOD (mITT) 4 ODD in LGSSOTICLESTAT (TAK-935) First-in-class Inhibitor Of Cholesterol 24-hydroxylase (CH24H) Enzyme To Improve Seizure Control In Rare Epileptic Syndromes ODD in DS • Co-development partnership with Ovid Therapeutics2 1. SUDEP: Sudden unexpected death in epilepsy 2. Takeda and Ovid are sharing in the development and commercialization costs of soticlestat and, if successful, will share in the profits on a 50/50 basis 3. DEE: Developmental and epileptic encephalopathies 80 | 4. mITT: modified intent-to-treat 5. Based on Hodges-Lehmann estimation of the median of differences in % change between the two arms

MECHANISM Orexin 2 receptor (OX2R) agonist PATIENT JOURNEY/ UNMET NEED Current treatments do not address the underlying orexin deficiency in NT1 patients • Backbone of care is a combination of wake promoting agents/stimulants for excessive daytime sleepiness (EDS), anti-depressants for cataplexy and sedating agents for disrupted nighttime sleep. • Despite treatment > 90% experience EDS1 and 50% have daily cataplexy making functioning at home, school and work problematic.2 KEY DATA • No cataplexy on TAK-925: Patients on TAK-925, an IV orexin 2 receptor agonist (OX2R), showed no cataplexy attacks during the infusion period3 • In addition, benefits were seen in the MWT4 over 7-days in NT1 and NT25 patients • TAK-925 has published POC data in NT1, NT2, shift work sleep disorder. Data for IH6 and OSA6 will be disclosed in the future. MARKET OPPORTUNITY NT1: Global prevalence 2-6 per 10,000; total adult prevalent population of ~135K in the U.S.; ~700K across key markets (US, EU5, JP, CN)7 DEVELOPMENT STATUS & EXPECTED MILESTONES • TAK-994, the first oral OX2R agonist in Ph 2 is enrolling NT1 and NT2 patients. Final data targeted 2H FY21 • TAK-861, a second oral OX2R agonist will begin clinical testing in 2H FY20 POC NT1: 7-DAY REPEATED DOSING STUDY3 OREXIN 2 RECEPTOR AGONISTS (TAK-925/TAK-994) Transformative Potential In Narcolepsy Type 1 (NT1) And Other Sleep Disorders The lead indication is NT1, and we continue to explore use of OX2R agonists in other medical conditions, where wakefulness is needed and/or orexin pathophysiology plays a role such as Narcolepsy Type 2, Idiopathic Hypersomnia, and other conditions. BTDODD SKGFTD 81 | 1. EDS: Excessive daytime sleepiness; 2. Maski, K et al. 2017. J Clin Sleep Med. Mar 15; 13(3): 419-425 ; 3. Presented at the European Sleep Research Society 2020 Virtual Congress, September 22-24, 2020; 4. MWT: Maintenance of Wakefulness Test; 5. NT2: Narcolepsy Type 2; 6. IH: Idiopathic hypersomnia. OSA: Obstructive sleep apnea.; 7. Diagnosis typically 5-15 years delayed; 8. Observed mean and standard deviation shown. ***: p-value <0.001 comparing to placebo;

MECHANISM Viscous budesonide oral suspension for eosinophilic esophagitis (EoE) PATIENT JOURNEY/ UNMET NEED No U.S.-approved medication exists for EOE • EoE often results in dysphagia (difficulty swallowing) and heartburn, and in adolescents often presents with vomiting and GI pain. Symptoms can represent a significant physical and emotional burden as patients avoid social settings focused on food • Standard of care is food elimination, off-label use of PPIs, and steroids1 • There is often a long delay in diagnosis due to low awareness of the disease, symptom confusion, and patient adaptive behaviors that mask the symptoms of the disease REASON TO BELIEVE Largest EoE clinical trial program globally, including adults and adolescents • Pivotal 12-week study (301 study) showed statistically significant histologic and symptomatic improvement over placebo MARKET OPPORTUNITY >150,000 patients in U.S. and growing rapidly DEVELOPMENT STATUS & EXPECTED MILESTONES 12 WEEK DATA SHOWS SIGNIFICANT HISTOLOGIC AND SYMPTOM RESPONSE TAK-721 On-track To Be The First FDA Approved Agent To Treat Eosinophilic Esophagitis Eosinophilic esophagitis Approval (US)4 FY22 FY23 FY24FY20 FY21 BTDODD 1.0% 53.1% 0 20 40 60 Placebo (n=105) 2 mg BID (n=213) 39.1% 52.6% 0 20 40 60 Placebo (n = 105) 2 mg BID (n=213) Histologic Response at 12 Weeks (peak ≤ 6 eosinophils/hpf2 on biopsy) Symptom Response at 12 Weeks (≥ 30% reduction in DSQ score3) Pr op or ti on o f pa ti en ts (% ) Pr op or ti on o f pa ti en ts (% ) p < 0.001 p = 0.024 82 | 1. Gastroenterology 2020; 158: 1776 – 1786. In patients with EOE, the AGA/JTF recommend topical glucocorticosteroids over no treatment. Swallowed use of glucocorticoids intended for asthma (e.g., home or compounded thickening of budesonide solution, or swallowing fluticasone aerosol). 2. Eos/hpf: eosinophils per high-power field; BID: Twice daily; SOC: Standard of care; NDA: new drug application 3. DSQ score: Dysphagia Symptom Questionnaire patient reported outcome score 4. Approval expected Q4 FY20 or early Q1 FY21 Launch (US)

MECHANISM Tetravalent Dengue Vaccine Candidate based on a live-attenuated dengue serotype 2 virus PATIENT JOURNEY/ UNMET NEED Dengue is endemic in more than 100 countries. Each year, dengue is estimated to cause 390 million infections1. • Severe dengue is a leading cause of serious illness and death in some Asian and Latin American countries2. There is no specific therapy available to treat dengue and care is supportive1. • Only one marketed vaccine exists; however, its use is restricted to individuals 9 to 16 years old and with confirmed prior dengue virus exposure. REASON TO BELIEVE 80.2%: Overall vaccine efficacy (VE) in preventing symptomatic dengue at 12 months follow up (primary endpoint)3. • 90.4%: reduction in dengue-associated hospitalizations at 18 months (secondary endpoint)4. • Similar efficacy regardless of previous dengue exposure (VE: 76.1% and VE: 66.2% in baseline seropositives and seronegatives respectively (secondary endpoint)4. • TAK-003 has been generally well-tolerated with no important safety risks to date3,4,5. MARKET OPPORTUNITY • More than 6 billion people could be at risk for dengue fever by 2080 due to population growth in endemic areas6. • High level of awareness of dengue and high attribution of potential severity of dengue disease. • Estimated 90% of burden in middle income countries7,8. DEVELOPMENT STATUS & EXPECTED MILESTONES • Longer-term data is being collected to fully characterize TAK-003’s safety and efficacy profile. • The potential impact of a booster dose will be assessed during the TIDES study. TAK-003 PH3 DATA: 24 MONTHS FOLLOW-UP5 TAK-003 Potential To Help Address The Fastest Spreading Mosquito-borne Viral Disease 36-month data readout from Ph3 study (H2) First approval in EU FY22 FY23FY20 FY21 First approvals in 1st Wave endemic countries and U.S. Launches in 1st Wave endemic countries, US and EU 2nd Wave countries: First approvals and launches FY24 3rd Wave countries: Expected approvals and launches (FY24 and beyond) Overall Efficacy against Virologically Confirmed Dengue (VCD) 72.7% (67.1, 77.3) Overall Efficacy against Hospitalized VCD 89.2% (82.4, 93.3) Seronegative Seropositive 67.0% (53.6, 76.5) 74.8% (68.6, 79.8) DENV-1 DENV-2 DENV-3 DENV-4 69.0% (57.1, 77.5) 90.8% (85.6, 94.1) 54.4% (34.0, 64.2) 50.4% (-19.3, 79.3) No important safety risks identified 83 | 1. WHO. Dengue and Severe Dengue. https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue 2. Halstead S, Wilder-Smith A. Severe dengue in travelers: pathogenesis, risk and clinical management. J Travel Med. 2019;26(7). 3. Biswal S, et al. Efficacy of a tetravalent dengue vaccine in healthy children and adolescents. N Engl J Med. 2019; Retrieved November 2019 4. Biswal S, et al. Efficacy of a tetravalent dengue vaccine in health children aged 4-16 years: a randomized, placebo-controlled, phase 3 trial. Lancet. 2020. doi:10.1016/S0140- 6736(20)30414-1 5. Biswal S. Takeda’s Tetravalent Dengue Vaccine – Two Years Efficacy Surveillance. Presented at 69th Annual Meeting, American Society of Tropical Medicine and Hygiene; November 2020. 6. Messina, J.P., Brady, O.J., Golding, N. et al. The current and future global distribution and population at risk of dengue. Nat Microbiol 4, 1508–1515 (2019). https://doi.org/10.1038/s41564-019-0476-8 7. Cases: Supplement to Stanaway JD, Shepard DS, Undurraga EA, et al. The global burden of dengue: an analysis from the Global Burden of Disease Study 2013. Lancet Infect Dis 2016; published online Feb 10. http://dx.doi.org/10.1016/S1473-3099(16)00026-8. Accessed Jan14, 2019. 8. Income Classification: World Bank: List of Economies (June 2018). https://datahelpdesk.worldbank.org/knowledgebase/articles/906519-world-bank-country-and-lending-groups

Appendix 2 Epidemiology Data

OVERVIEW OF EPIDEMIOLOGY DATA ONCOLOGY GASTROENTEROLOGY (GI) RARE GENETIC & HEMATOLOGY 85 |

EPIDEMIOLOGY – NINLARO, ALUNBRIG, ADCETRIS & ICLUSIG Product Indication Total Global Eligible Population (FY20) Geographies included R/R 2L+ Multiple Myeloma ~105,0001 Japan, US, EU5, China ALK+ NSCLC ~14,000 [+ ~25,000 in China]2 Japan, US, EU5, [China] HL – Front Line, ASCT Consolidation, 2L+; TCL - PTCL & R/R CTCL ~11,0003 Japan, EU5, China 2L+ CML, ALL ~2,400 US 86 | 1. R/R 2L+ MM label eligible patients; 2. ALK+ tested patients; 3. CD30+ label eligible patients - approved regulatory approval include Stage IV/ITT Front Line Patients and High Risk HL consolidation patients Source: Takeda estimates.

OVERVIEW OF EPIDEMIOLOGY DATA ONCOLOGY GASTROENTEROLOGY (GI) RARE GENETIC & HEMATOLOGY 87 |

EPIDEMIOLOGY ULCERATIVE COLITIS (UC) 770K 755K 453K 83K 1,100K 850K 423K 131K 488K 303K 160K 24K 299K 287K 103K 19K ~2,195K ~1,138K ~257K GEM (incl. China) EUCAN US Japan Diagnosed Prevalence Treated Treated Moderate to Severe Patients on biologic therapies ~2,658K 88 | Source: Takeda estimate. Note: Numbers are rounded.

804K 788K 473K 193K 888K 741K 461K 216K 262K 160K 103K 50K 53K 52K 23K 14K ~473K ~1,060K ~1,740K EPIDEMIOLOGY CROHN’S DISEASE (CD) GEM (incl. China) EUCAN US Japan Diagnosed Prevalence Treated Treated Moderate to Severe Patients on biologic therapies ~2,007K 89 | Source: Takeda estimate. Note: Numbers are rounded.

EPIDEMIOLOGY COMPLEX PERIANAL FISTULA (CPF) 780K 193K 114K 21K 792K 119K 62K 21K 58K 27K 14K 2K EUCAN US Japan Crohn’s Disease (CD) Patients Alofisel Eligible Refractory CPF Patients ~1,630K CD Patients with Perianal Fistula Complex Perianal Fistula (CPF) Patients 90 | Source: Takeda estimate. Note: Numbers are rounded. ~44K ~190K ~339K

14K 6K 6K 1K 10K 5K 2K EPIDEMIOLOGY SHORT BOWL SYNDROME (SBS-IF)-ADULT INDICATION ~8K ~1.7K ~11K Ex-US (mainly EUCAN) US Diagnosed Treated ~24K Diagnosed Eligible1 Access to Gattex/Revestive 91 | 1. Revestive/Gattex Eligible patients: excluding SBS caused by malignancies that occurred less than 5 years ago Source: Takeda estimates. Note: Numbers are rounded.

3K 3K 3K 3K 2K 1K EPIDEMIOLOGY SHORT BOWL SYNDROME (SBS-IF)-PEDIATRIC INDICATION Ex-US (mainly EUCAN) US Diagnosed Treated ~6K Diagnosed Eligible1 Access to Gattex/Revestive ~5K ~4K ~0.2K 92 | 1. Revestive/Gattex Eligible patients: excluding SBS caused by malignancies that occurred less than 5 years ago Source: Takeda estimates. Note: Numbers are rounded.

OVERVIEW OF EPIDEMIOLOGY DATA ONCOLOGY GASTROENTEROLOGY (GI) RARE GENETIC & HEMATOLOGY 93 |

EPIDEMIOLOGY HEREDITARY ANGIOEDEMA 64K 21K 18K Prevalence Diagnosed Treated Global 94 | Source: Takeda estimates. Note: Numbers are rounded. 1. ORE HAE: Global overview of Hereditary Angioedema Epidemiology (http://207.154.195.35/) 2. Dx and Tx to be reviewed with the country * Geographies considered: EUCAN: Canada, Germany, Austria, France, The Netherlands, Belgium, Italy, United Kingdom, Spain, Region Nordics, Israel GEM: China, Russia, Australia, Brazil, Mexico, Colombia, Argentina

EPIDEMIOLOGY HUNTER’S DISEASE: GLOBAL, INDIA/CHINA NOT INCLUDED 5K 2-3K 2K MPS II Patients Prevalence Diagnosed Treated Global 95 | Source: Takeda estimates. Note: Numbers are rounded.

EPIDEMIOLOGY GAUCHER’S DISEASE: GLOBAL, CHINA/INDIA NOT INCLUDED Prevalence Diagnosed ~35K prevalent patients ~9K diagnosed patients (26%) ~26K un-diagnosed patients (74%) 96 | Source: Takeda estimates, US Census Bureau, Shire/CRA developed epi rate (2016). Note: Numbers are rounded.

EPIDEMIOLOGY FABRY’S DISEASE: EX-US REGION, CHINA/INDIA NOT INCLUDED Prevalence Diagnosed ~60K prevalent Fabry patients ~13K diagnosed Fabry patients (21%) ~47K un-diagnosed patients (79%) 97 | Source: Takeda estimates, US Census Bureau, Shire/CRA developed blended epi rate (2016): 1.28,500. Note: Numbers are rounded.

EPIDEMIOLOGY CHRONIC HYPOPARATHYROIDISM US + EUROPE GEM, Japan And China Not Included Prevalent cHypoPT cases ~350k cases of cHypoPT 98 | Sources: Takeda estimates. Note: Numbers are rounded.

EPIDEMIOLOGY HEMOPHILIA A 17K 17K 17K 30K 25K 18K 5K 5K 5K Prevalence Diagnosed Treated 52K *Note: In the graph, prevalence refers to the number of patients with Hemophilia A without inhibitors. Calculated prevalence for US based on occurrence per x population is high as is does not consider high mortality due to concomitant conditions such as AIDS and Hep C. EU5 Japan USHEM A without inhibitors 48K 39K 99 | Sources: Takeda estimates, WFH 2018 Report, Epidemiology of Hemophilia; Pharmametrics, NHF. Note: Numbers are rounded.

Appendix 3 Clinical Trial Summary

LCM1 WAVE 1 WAVE 2 ONCOLOGY ALUNBRIG 1L ALK+ NSCLC mobocertinib 2L NSCLC w/EGFR exon 20 insertion mutation TAK-981 Multiple cancers TAK-169 R/R Multiple myeloma ALUNBRIG 2L ALK+NSCLC H2H with alectinib mobocertinib 1L NSCLC w/EGFR exon 20 insertion mutation TAK-981 Non-Hodgkin’s lymphoma TAK-252 Bispecific solid tumors ICLUSIG TKI res. Chronic phase CML pevonedistat HR-MDS TAK-981 Solid tumors TAK-102 CAR-T solid tumors ICLUSIG FL Ph+ ALL pevonedistat Unfit AML TAK-605 Multiple cancers TAK-940 CAR-T CD19+ Heme malignancy NINLARO Maintenance ND MM post-SCT (MM3) TAK-007 CD19+ Heme malignancies TAK-573 Solid tumors NINLARO Maintenance ND MM no-SCT (MM4) TAK-573 R/R Multiple myeloma NINLARO Maintenance no-SCT (MM6) TAK-676 STING agonist solid tumors RARE GENETIC & HEMATOLOGY ADYNOVATE Pediatric Hemophilia A maribavir R/R CMV infection in HSCT and SOT mezagitamab (TAK-079) ITP, MG VONVENDI vWD Adult prophylaxis, Peds maribavir 1L CMV infection In HSCT TAK-607 Complications of prematurity TAKHZYRO HAE Pediatric TAK-755 cTTP TAK-755 iTTP TAKHZYRO Bradykinin-mediated angioedema TAK-611 MLD (IT) TAK-755 SCD OBIZUR CHAWI surgery TAK-609 Hunter CNS (IT) NEUROSCIENCE TAK-994 Orexin 2-ag NT1 and NT2 WVE 120101/02 Huntington's Disease TAK-925 Narcolepsy NT1 and other sleep disorders TAK-341 Parkinson's Disease soticlestat Rare epilepsies – LGS, DS GI ENTYVIO GvHD Prophylaxis TAK-721 Eosinophilic Esophagitis TAK-951 Post-op nausea & vomiting ENTYVIO UC/CD SC TAK-906 Gastroparesis ENTYVIO Pediatric UC/CD TAK-954 POGD Alofisel Complex perianal fistulas in CD sibofimloc Post-Op CD Vonoprazan H. Pylori China PDT HYQVIA CIDP CoVIg-19 COVID-19 hyperimmune IV globulin HYQVIA Pediatric PID GLASSIA A1P1 deficient patients VACCINES TAK-003 Dengue vaccine TAK-214 Norovirus vaccine TAK-426 Zika vaccine OVERVIEW OF CLINICAL TRIAL SUMMARY 101 | 1. LCM = Life cycle management programs or marketed assets in development seeking new indications, new geographic expansions, fulfillment of regulatory requirements, new formulations/method of use, and/or enhancement in commercial/competitive profile.

OVERVIEW OF CLINICAL TRIAL SUMMARY ONCOLOGY RARE GENETIC & HEMATOLOGY NEUROSCIENCE GASTROENTEROLOGY (GI) PLASMA-DERIVED THERAPIES VACCINES 102 |

ALUNBRIG (BRIGATINIB): ALK INHIBITOR Study NCT02737501 NCT03596866 Indication ALK-positive advanced lung cancer ALK-positive non-small-cell lung cancer (NSCLC) Phase Phase IIIALTA-1L Phase III ALTA-3 # of Patients N = 275 N = 246 Target Patients ALK+ locally advanced or metastatic NSCLC patients who have not previously been treated with an ALK inhibitor Patients with ALK+ locally advanced or metastatic NSCLC who have progressed on crizotinib Arms/Intervention • Arm A: Brigatinib 180 mg QD with 7-day lead-in at 90 mg• Arm B: Crizotinib 250 mg BID • Arm A: Alunbrig 90 mg to 180 mg QD • Arm B: Alecensa 600 mg PO BID with food Primary endpoint and key secondary endpoint(s) Progression-Free Survival (PFS) as assessed by blinded Independent Review Committee (bIRC) Progression-Free Survival (PFS) as assessed by blinded Independent Review Committee (bIRC) Status • Study start date: April 2016 • Primary completion date: June 2019 Publications: • Camidge DR, et al. N Engl J Med 2018;379(21): 2027-2039 • Camidge DR, Kim HR, Ahn MJ, et al. J Clin Oncol 2020;38: 1-13 • Garcia Campelo MR, et al. Ann Oncol 2020;31(suppl 4): 5844 • Popat S, Kim HR, et al. Ann Oncol 2020;31(suppl 4): S840-S841 • Study Start Date: April 2019 • Estimated primary completion date1: FY21 Oncology 103 | 1. The primary endpoint, PFS, is event driven and changes in event rate can lead to a change in the primary completion date.

ICLUSIG (PONATINIB): BCR-ABL INHIBITOR Study NCT02467270 NCT03589326 Indication Chronic myeloid leukemia (CML) Ph+ acute lymphoblastic leukemia (ALL) Phase Phase IIOPTIC Phase III Ph+ALLCON # of Patients N = 276 N = 230 - 320 Target Patients Patients with resistant chronic phase chronic myeloid leukemia Patients with newly-diagnosed Ph+ ALL Arms/Intervention • Ponatinib 45 mg once daily • Ponatinib 30 mg once daily • Ponatinib 15 mg once daily • Cohort A: Ponatinib/reduced intensity chemotherapy until progressive disease (PD) or stem cell transplant (SCT) • Cohort B: Imatinib/reduced intensity chemotherapy until PD or SCT Primary endpoint and key secondary endpoint(s) ≤1% BCR-ABL1 at 12 months (time frame: 12 months) Number of participants with Minimal Residual Disease (MRD) - Negative Complete Remission (CR) [Time frame: From Cycle 1 through Cycle 3 (approximately 3 months) (Cycle length is equal to 28 days) ] Status • Study start date: June 2015• Primary completion date: May 2020 • Study start date: August 2018 • Estimated primary completion date1: FY21 Oncology 104 | 1. The primary endpoint, PFS, is event driven and changes in event rate can lead to a change in the primary completion date.

NINLARO (IXAZOMIB): ORAL PROTEASOME INHIBITOR Study NCT02181413 NCT02312258 Indication Multiple myeloma (MM) maintenance post-stem cell transplant Multiple myeloma (MM) maintenance non-stem cell transplant Phase Phase IIITOURMALINE-MM3 Phase III TOURMALINE-MM4 # of Patients N = 652 N = 761 Target Patients Patients with multiple myeloma following autologous stem cell transplant Patients with newly-diagnosed MM not treated with stem cell transplantation Arms/Intervention Arm A: Ixazomib • Cycles 1-4: Ixazomib 3.0 mg PO days 1, 8, 15 / 28-day cycle • Cycles 5-26: Ixazomib 3.0 or 4.0 mg PO days 1, 8, 15 / 28-day cycle Arm B: Placebo • Cycles 1-4: Placebo 3.0 mg PO days 1, 8, 15 / 28-day cycle • Cycles 5-26: Placebo 3.0 or 4.0 mg PO days 1, 8, 15 / 28-day cycle Arm A: Ixazomib • Cycles 1-4: Ixazomib 3.0 mg PO days 1, 8, 15 / 28-day cycle • Cycles 5-26: Ixazomib 3.0 mg or 4.0 mg PO days 1, 8, 15 / 28-day cycle Arm B: Placebo • Cycles 1-4: Placebo 3.0 mg PO days 1, 8, 15 / 28-day cycle • Cycles 5-26: Placebo 3.0 or 4.0 mg PO days 1, 8, 15 / 28-day cycle Primary endpoint and key secondary endpoint(s) • Primary: Progression Free Survival (PFS) • Secondary: Overall Survival (OS) • Primary: Progression Free Survival (PFS) • Secondary: Overall Survival (OS) Status • Study start date: July 2014 • Primary completion date: April 2018 • Interim OS analysis1: FY21; Final: FY24/25 Publications: • Dimopoulos MA, et al. Lancet. 2019 Jan 19;393(10168): 253-264 • Kaiser M, et al. Ann Hematol. 2020 Aug;99(8): 1793-1804 • Hari P, et al. J Med Econ. 2018 Aug;21(8): 793-798 • Schjesvold F, et al. Eur J Haematol. 2020 May;104(5): 443-458 • Goldschmidt H, et al. Leukemia. 2020 Nov;34(11): 3019-3027 • Paiva B, et al. Presentation at EHA 2020 • Study start date: April 2015 • Primary completion date: August 2019 • Interim OS analysis1: FY22; Final FY24 Publications: • Bringhen S, et al. Presentation at ASH 2020 • Paiva B, et al. Presentation at ASH 2020 • Dimopoulos MA, et al. https://ascopubs.org/doi/full/10.1200/JCO.20.02060 Oncology 105 | 1. A key secondary analysis, OS, is event driven and changes in event rate can lead to a change in the interim and final analysis.

NINLARO (IXAZOMIB): ORAL PROTEASOME INHIBITOR Study NCT03173092 Indication Non-transplant eligible patients with newly diagnosed multiple myeloma Phase Phase IVMM6 # of Patients N = 160 Target Patients Patients with multiple myeloma previously receiving a bortezomib-based induction. In-class (proteasome inhibitor) transition after 3 cycles of bortezomib-based therapy. Arms/Intervention • Ixazomib 4 mg + lenalidomide 25 mg + dexamethasone 40 mg • Transition from a bortezomib based regimen to IRD (ixazomib, lenalidomide, dexamethasone) may allow the long term proteasome inhibition to be maximized while maintaining a manageable safety profile. Primary endpoint and key secondary endpoint(s) Progression Free Survival (PFS). Key secondary endpoints: time to next therapy (TTNT), relative dose intensity (RDI) of the oral regimen, overall survival (OS), electronic patient reported outcomes (ePRO) and actigraphy (activity/sleep) data. Status • Study start date: September 2017• Primary completion date: FY26 Oncology 106 |

MOBOCERTINIB (TAK-788): EGFR/HER2 EXON 20 INHIBITOR Study NCT02716116 NCT04129502 Indication 2L NSCLC exon 20 insertion mutation 1L NSCLC exon 20 insertion mutation Phase Registration enabling Phase IIEXCLAIM Phase III EXCLAIM-2 # of Patients N = 341 N = 318 Target Patients 2L+ NSCLC harboring EGFR in-frame exon 20 insertion mutations 1L NSCLC harboring EGFR in-frame exon 20 insertion mutations Arms/Intervention • Single arm: Mobocertinib 160 mg QD • Arm A: Mobocertinib 160 mg QD• Arm B: Platinum-based chemotherapy Primary endpoint and key secondary endpoint(s) Confirmed ORR assessed by IRC PFS as assessed by blinded Independent Review Committee (IRC) Status • Study start date: April 2016• Primary completion date: May 2020 • Study start date: January 2020 • Estimated primary completion date1: FY21 Oncology 107 | 1. The primary endpoint, PFS, is event driven and changes in event rate can lead to a change in the primary completion date.

PEVONEDISTAT (TAK-924): NEDD8-ACTIVATING ENZYME (NAE) INHIBITOR Study NCT03268954 NCT04090736 Indication HR MDS Unfit AML Phase Phase IIIPANTHER Phase III PEVOLAM # of Patients N = 450 N = 466 Target Patients Patients with higher risk myelodysplastic syndromes (HR MDS), chronic myelomonocytic leukemia or low-blast acute myelogenous leukemia (LB AML) Patients with acute myeloid leukemia (AML) not eligible for INTENSIVE chemotherapy Arms/Intervention • Arm A: Pevonedistat 20 mg/m2 (IV) on days 1, 3, 5; Azacitidine (AZA) 75 mg/m2 (SC) on a 5-on/2-off [weekend]/2-on schedule in 28-day cycles • Arm B: AZA 75 mg/m2 SC on a 5-on/2-off [weekend]/2-on schedule in 28-day cycle • Arm A: Pevonedistat 20 mg/m2 (IV) on days 1, 3, 5; Azacitidine (AZA) 75 mg/m2 (SC) on a 5-on/2-off [weekend]/2-on schedule in 28-day cycles • Arm B: AZA 75 mg/m2 SC on a 5-on/2-off [weekend]/2-on schedule in 28-day cycle (IV AZA can be administered for any patients who have non-tolerated local reactions) Primary endpoint and key secondary endpoint(s) Primary: Event Free Survival (EFS) Secondary: Overall Survival (OS) Overall Survival (OS) Status • Study start date: December 2017• Estimated primary completion date1: FY20/21 • Study start date: August 2019 • Estimated primary completion date2: FY24 Oncology 108 | 1. The primary endpoint, EFS, is event driven and changes in event rate can lead to a change in the primary completion date.2. The primary endpoint, OS, is event driven and changes in event rate can lead to a change in the primary completion date.

TAK-007: CD19 CAR NK Study NCT030563391 Indication Relapsed refractory B-lymphoid malignancies Phase Phase I # of Patients N = 36 Target Patients Patients with relapsed and refractory CD19+ B lymphoid malignances Arms/Intervention • Fludarabine 30 mg/m2 by vein on days -5 to -3 • Cyclophosphamide 300 mg/m2 by vein on days -5 to -3 • Mesna 300 mg/m2 by vein on days -5 to -3 • iC9/CAR.19/IL15-Transduced CB-NK Cells: Infusion of iC9/CAR.19/IL15-transduced CB-NK cells on Day 0 by vein; starting dose: 10E5 • AP1903: If participant has graft-versus-host disease (GvHD) or cytokine release syndrome after the NK cell infusion, they will receive AP1903 0.4 mg/kg administered as an intravenous infusion. Primary endpoint and key secondary endpoint(s) Safety and efficacy Status • Study start date: June 2017 Publication: • Liu E, Marin D, Banerjee P, et al. N Engl J Med 2020;382(6): 545-553 Oncology 109 | 1. Trial managed by MD Anderson Cancer Center

TAK-981: SUMO-ACTIVATING ENZYME1 INHIBITOR Study NCT03648372 NCT04074330 Indication Solid tumors, hematologic malignancies Non-Hodgkin’s lymphoma (NHL) Phase Phase I Phase I/II # of Patients N = 80 N = 130 Target Patients Adult participants with advanced or metastatic solid tumors or relapsed/refractory hematologic malignancies Patients with relapsed/refractory CD-20 positive NHL Arms/Intervention • TAK-981, intravenously, administered as 60 minute-infusion, once on Days 1, 4, 8, and 11 for 2 consecutive weeks, followed by 1 week rest in a 21-day treatment cycle • Phase 1, aNHL/iNHL: TAK-981 (10-160 mg) + rituximab 375 mg/m2 • Phase 2, Cohort A: r/r DLBCL progressed to CAR T-cell therapy • Phase 2, Cohort B: r/r DLBCL with no CAR T-cell prior therapy • Phase 2, Cohort C: r/r FL progressed to systemic therapies Primary endpoint and key secondary endpoint(s) Safety, tolerability and PK Safety, tolerability and RP2D Status • Study start date: October 2018 • Study start date: October 2019 Oncology 110 | 1. SUMO = Small ubiquitin-like modifier

TAK-981: SUMO-ACTIVATING ENZYME1 INHIBITOR Study NCT04381650 Indication Solid tumors Phase Phase Ib/II # of Patients N = 101 Target Patients Patients with select advanced or metastatic solid tumors Arms/Intervention • Escalating doses of TAK-981 with starting dose of 40 mg, intravenous (IV) infusion, on Days 1, 4, 8 and 11 in each 21-day treatment cycle and pembrolizumab 200 mg, IV infusion, as a fixed dose every 3 weeks in 21-day treatment cycle until RP2D is determined (for a maximum of 24 months). • TAK-981 at RP2D as IV infusion on Days 1, 4, 8 and 11 in each 21-day treatment cycle up to disease progression or 12-months and pembrolizumab 200 mg IV infusion as a fixed dose every 3 weeks in 21-day treatment cycle for a maximum of 24 months. Primary endpoint and key secondary endpoint(s) Safety and tolerability Status • Study start date: August 2020 Oncology 111 | 1. SUMO = Small ubiquitin-like modifier

TAK-605: ONCOLYTIC VIRUS ENCODING TRANSGENES FOR FLT3 LIGAND, ANTI-CTLA-4 ANTIBODY, AND IL-12 CYTOKINE Study NCT043010111 Indication Solid tumors Phase Phase I/IIa # of Patients N = 84 Target Patients Patients with advanced solid tumors Arms/Intervention • Arm A: TBio-6517 (TAK-605) dose escalation administered alone by direct injection into tumor(s) x 4. Booster injections of TBio-6517 are permitted for up to 24 months. • Arm B: TBio-6517 and pembrolizumab Dose escalation of TBio-6517 administered in combination with pembrolizumab. TBio-6517 will be directly injected into tumor(s) x 4. Booster injections of TBio-6517 are permitted for up to 24 months. Pembrolizumab will be administered beginning at Day 8 via intravenous (IV) infusion every 3 weeks for up to 24 months. • TBio-6517 and pembrolizumab in MSS-CRC Doses of TBio-6517 will be administered by direct injection into tumor(s) x 4 in combination with pembrolizumab beginning at Day 8 given every 3 weeks for up to 24 months in patients with microsatellite stable colorectal carcinoma (MSS-CRC). Booster injections of TBio-6517 are permitted for up to 24 months. • TBio-6517 and pembrolizumab in TNBC Doses of TBio-6517 will be administered by direct injection into tumor(s) x 4 in combination with pembrolizumab beginning at Day 8 given every 3 weeks for up to 24 months in patients with triple negative breast cancer (TNBC). Booster injections of TBio-6517 are permitted for up to 24 months. Primary endpoint and key secondary endpoint(s) Recommended Phase 2 dose (RP2D) Status • Study start date: August 2020 Oncology 112 | 1. Trial managed by Turnstone Biologics

TAK-573: FIRST-IN-CLASS ANTI-CD38/ATTENUATED IFNα FUSION PROTEIN Study NCT04157517 NCT03215030 Indication Solid tumors Relapsed/refractory multiple myeloma Phase Phase I Phase I/2 # of Patients N = 86 N = 151 Target Patients Patients with locally advanced or metastatic solid tumors Patients with relapsed/refractory multiple myeloma Arms/Intervention • TAK-573 0.1 to 6 milligram per kilogram (mg/kg), infusion, intravenously, once on Day 1 of each 21-days treatment cycle for up to 1 year. Administration of TAK-573 on Day 1 of each 21-days treatment cycle may also be evaluated. • Phase 1 cohort: TAK-573 0.001 to 14 milligram per kilogram (mg/kg), infusion, intravenously, once on Days 1, 8, 15 and 22 of each 28-day treatment cycle up to 2 cycles, followed by once on Days 1 and 15 of each 28-day treatment cycle up to 4 cycles, followed by once on Day 1 of each 28-day treatment cycle until treatment discontinuation. • Phase 2 cohort: TAK-573 TBD as a single agent. Participants in at least 1 cohort will receive TAK-573 TBD and dexamethasone 40 mg, orally, once weekly of each 28-day treatment cycle until treatment discontinuation. Primary endpoint and key secondary endpoint(s) Safety and tolerability Safety and tolerability Status • Study start date: December 2019 • Study start date: October 2017 Oncology 113 |

TAK-676: STING AGONIST Study NCT04420884 Indication Solid tumors Phase Phase I # of Patients N = 76 Target Patients Adult patients with advanced or metastatic solid tumors Arms/Intervention • Arm 1: Dose escalating single agent TAK-676, starting with a safety lead-in at 0.1 mg IV on Days 1, 8, 15 in 21-day treatment cycles, and capping at 2.5 mg IV on Days 1, 8 and 15 in a 21-day cycle. • Arm 2: Dose escalating TAK-676 along the above parameters in combination with fixed dose pembrolizumab at 200 mg IV administered on D1 in a 21-day cycle. Primary endpoint and key secondary endpoint(s) • Primary endpoints: Safety and tolerability • Secondary objectives: Recommended Phase 2 dose (RP2D), overall response rate (ORR) Status • Study start date: July 2020 Oncology 114 |

TAK-169: ANTI-CD38 ANTIBODY-SLTA1 TOXIN Study NCT04017130 Indication Relapsed or refractory multiple myeloma Phase Phase I # of Patients N = 102 Target Patients Patients with relapsed or refractory multiple myeloma Arms/Intervention • Dose escalation arms: TAK-169 50 mcg/kg Once Weekly; TAK-169 100 mcg/kg Once Weekly; TAK-169 200 mcg/kg Once Weekly; TAK- 169 335 mcg/kg Once Weekly; TAK-169 500 mcg/kg Once Weekly; TAK-169 665 mcg/kg Once Weekly; TAK-169 TBD Once Every Two Weeks; • Expansion arms: Daratumumab (R/R) cohorts (once weekly and once every 2 weeks TAK-169 administration) and an anti-CD38 therapy naive cohort (once weekly TAK-169 administration). The starting dose for each expansion cohort may be the MTD/RP2D2 or a recommended dose below the MTD determined during dose escalation after review of the available safety, efficacy, PK, and PD data. Primary endpoint and key secondary endpoint(s) Safety, tolerability, PK and efficacy Status • Study start date: February 2020 Oncology 115 | 1. SLTA = Shiga-like toxin A2. MTD = Maximum tolerated dose. RP2D = Recommended phase 2 dose.

TAK-252: PD1-FC OX40L ARC Study NCT038946181 Indication Advanced solid tumors or lymphomas Phase Phase I # of Patients N = 87 Target Patients Patients with advanced solid tumors or lymphomas Arms/Intervention • TAK-252 (SL-279252) is a first-in-class agonist redirected checkpoint (ARC) fusion protein (FP) consisting of the extracellular domains of human programmed cell death 1 (PD- 1) and OX40L, linked by a central Fc domain (PD1-Fc-OX40L). Primary endpoint and key secondary endpoint(s) Safety, maximum tolerated dose (MTD). Recommended Phase 2 dose (RP2D), preliminary antitumor activity by iRECIST, immunogenicity and PK characterization of TAK-252 Status • Study start date: March 2019 Oncology 116 | 1. Trial managed by Shattuck Labs

TAK-102: GPC3 CAR-T Study NCT044057781 Indication Solid tumors Phase Phase I # of Patients N = 18 Target Patients Adult patients with GPC3-expressing previously treated solid tumors Arms/Intervention • Cohort 1: 1 × 10^7 CAR (+) cells/body [starting dose] • Cohort 2: 1 × 10^8 CAR (+) cells/body • Cohort 3: 1 × 10^9 CAR (+) cells/body Primary endpoint and key secondary endpoint(s) • Primary endpoint: Incidence of dose-limiting toxicities, treatment-emergent adverse events (AEs) and AEs of clinical interest • Primary objective: To evaluate the safety and tolerability of TAK-102 and to determine the recommended Phase 2 dose of TAK-102 Status • Study start date: July 2020 Oncology 117 | 1. In collaboration with Noile-Immune Biotech Inc. Enrollment in Japan.

TAK-940: CD19 CAR-T Study NCT044642001 Indication Relapsed/refractory B-cell cancers Phase Phase I # of Patients N = 30 Target Patients Adult patients with relapsed or refractory B-dell malignancies Arms/Intervention • 19(T2)28z1xx CAR T cells Cohorts of 3-6 patients will be infused with escalating doses of 19(T2)28z1xx CAR T cells to establish the RP2D. There are 4 planned flat-dose levels: 25x10^6, 50 x 10^6, 100 x 10^6, and 200 x 10^6 CAR T cells and one de-escalation dose: 12.5 x 10^6 CAR T cells. A standard 3+3 dose escalation design will be implemented starting from dose 1. Primary endpoint and key secondary endpoint(s) Recommended Phase 2 dose (RP2D) Status • Study start date: August 2020 Oncology 118 | 1. Trial managed by Memorial Sloan Kettering Cancer Center

OVERVIEW OF CLINICAL TRIAL SUMMARY RARE GENETIC & HEMATOLOGY NEUROSCIENCE GASTROENTEROLOGY (GI) ONCOLOGY PLASMA-DERIVED THERAPIES VACCINES 119 |

Study NCT02615691 Indication Hemophilia A Phase Phase III # of Patients N = 120 Target Patients Previously untreated patients (PUPs) < 6 years with severe hemophilia A (FVIII < 1%) Arms/Intervention • Single group assignment Primary endpoint and key secondary endpoint(s) The primary objective is to determine safety including immunogenicity of Adynovate (TAK-660/BAX 855) based on the incidence of inhibitor development to FVIII (≥ 0.6 Bethesda unit (BU)/mL using the Nijmegen modification of the Bethesda assay). Safety 1. To determine the immunogenicity of Adynovate in terms of binding IgG and IGM antibodies to FVIII, PEG-FVIII and PEG 2. To determine the safety of Adynovate based on adverse events (AEs) and serious adverse events (SAEs) Hemostatic Efficacy 3. To assess the efficacy of prophylactic treatment with Adynovate 4. To characterize the efficacy of Adynovate in the control of bleeding episodes Pharmacokinetics 6. To determine the incremental recovery (IR) of Adynovate at baseline and over time 7. To determine half-life of Adynovate at baseline (optional) Status • Study start date: November 2015 Rare Genetic and HematologyADYNOVATE (TAK-660): RECOMBINANT, PEGYLATED ANTIHEMOPHILIC FACTOR 120 |

VONVENDI (TAK-577): RECOMBINANT VON WILLEBRAND FACTOR Study NCT02973087 NCT02932618 Indication Adult Prophylaxis Pediatric On-demand and Elective Surgery Phase Phase III Phase III # of Patients N = 22 N = 27 (On-demand)N = 12 (Elective Surgery) Target Patients Severe von Willebrand Disease Severe von Willebrand Disease Arms/Intervention • Arm A: Transitioning from on-demand• Arm B: Switching from prophylactic treatment with pdVWF • Arm A: On-demand • Arm B: Elective and emergency surgery Primary endpoint and key secondary endpoint(s) • Annual Bleed Rate (ABR) <= subject’s historical ABR for spontaneous bleeding episodes • Key secondary endpoint: Additional efficacy of prophylactic treatment • Hemostatic efficacy and safety of rVWF, with or without ADVATE, in the treatment and control of nonsurgical bleeding events • Key secondary endpoint: Hemostatic efficacy assessed after the last perioperative rVWF infusion Status • Study start date: October 2017• Primary completion date: August 2020 • Study start date: October 2016 • Estimated primary completion date: FY22 Rare Genetic and Hematology 121 |

TAKHZYRO (LANADELUMAB): PLASMA KALLIKREIN (PKAL) INHIBITOR Study NCT04070326 NCT04206605 Indication Hereditary angioedema (HAE) pediatric Non-histaminergic angioedemawith normal C1-Inhibitor Phase Phase IIISPRING Phase III CASPIAN # of Patients N = 20 N = 75 Target Patients Type I and Type II hereditary angioedema, ages 2 to <12 yo Non-histaminergic bradykinin-mediated angioedema (BMA) with normal C1-inhibitor Arms/Intervention • Lanadelumab 150mg; q4wks ages 2 to < 6, q2wks ages 6 to <12 yo • Lanadelumab 300mg q2wks Primary endpoint and key secondary endpoint(s) • Primary: Safety and pharmacokinetics • Key secondary: Clinical outcomes, pharmacodynamics • Primary: Number of investigator-confirmed angioedema attacks during the treatment period of Day 0 through Day 182 • Key secondary: Number of participants achieving attack-free status during the treatment period of Day 0 through Day 182 Status • Study start date: August 2019• Estimated primary completion date: FY22 • Study start date: August 2020 • Estimated primary completion date: FY23 Rare Genetic and Hematology 122 |

MARIBAVIR (TAK-620): ORAL VIRAL PROTEIN KINASE INHIBITOR Study NCT02931539 NCT02927067 Indication Treatment of Resistant/Refractory Post-Transplant Cytomegalovirus (CMV) Infection Treatment of CMV infection in Hematopoietic Stem Cell Transplant Recipients Phase Phase III Phase III # of Patients N = 351 N = 550 Target Patients Treatment of CMV infection refractory or resistant to ganciclovir, valganciclovir, cidofovir or foscarnet in solid organ transplant (SOT) and stem cell transplant patients Treatment of asymptomatic CMV infection in stem cell transplant patients Arms/Intervention Arm A: MaribavirArm B: Investigator-assigned treatment Arm A: Maribavir Arm B: Valganciclovir Primary endpoint and key secondary endpoint(s) • Primary: Confirmed clearance of plasma CMV DNA (CMV viremia clearance) at the end of Study Week 8 • Secondary: Achievement of CMV viremia clearance and resolution or improvement of tissue invasive CMV disease or CMV syndrome for subjects symptomatic at baseline or achievement of clearance of viremia and no symptoms of tissue invasive CMV disease or CMV syndrome for subjects asymptomatic at baseline at the end of Study Week 8, followed by maintenance of this treatment effect for an additional 8 weeks off treatment • Primary: Confirmed clearance of plasma CMV DNA (CMV viremia clearance) at the end of Study Week 8 • Secondary: Maintenance of confirmed CMV viremia clearance achieved at the end of Study Week 8 through Week 16 having received exclusively a study-assigned treatment. Status • Study start date: December 2016 • Estimated primary completion date: FY20 • Papanicolaou GA, et al. Clin Infect Dis. 2019 Apr 8;68(8):1255-1264. • Study start date: April 2017 • Estimated primary completion date: FY21 • Maertens J, et al. N. Engl J Med 2019;381:1136-47. Rare Genetic and Hematology 123 |

TAK-755: REPLACEMENT OF THE DEFICIENT-ADAMTS13 ENZYME Study NCT03393975 NCT03922308 NCT03997760 Indication Congenital Thrombotic Thrombocytopenic Purpura (cTTP) Immune Thrombotic Thrombocytopenic Purpura (iTTP) Sickle Cell Disease Phase Phase III Phase II Phase I # of Patients N = 68 N = 30 N = 56 Target Patients Patients diagnosed with severe cTTP in prophylactic and on-demand treatment Adult patients diagnosed with iTTP Adult patients with sickle cell disease at baseline health and during acute vaso-occlusive crisis (VOC) Arms/Intervention Prophylaxis Treatment Cohort: 6 + 6 months cross over of TAK-755 vs SoC followed by 6 months TAK-755 extension • Arm 1: TAK-755 + SOC • Arm 2: SOC + TAK-755 (Patients are eligible to enter the prophylaxis study upon completion of acute treatment) • Arm 1: TAK-755 High dose + SOC • Arm 2: TAK-755 Low dose + SOC • Arm 3: Placebo + SOC • Part A: TAK-755 administered at baseline health at 3 dose levels and with placebo • Part B: TAK-755 administered during acute VOC at 3 dose levels of 40, 80, and 160 IU/kg. • Placebo will be administered in an equivalent volume of the 3 dose levels of 40, 80, and 160 IU/kg during part A and part B Primary endpoint and key secondary endpoint(s) Incidence of acute TTP episodes in subjects receiving prophylactic treatment with either TAK-755 or SoC ADAMTS-13 activity, ADAMTS-13 binding and inhibitory antibodies, Platelet count, and LDH levels SAEs/AEs, adverse changes in vital signs and laboratory parameters, and incidence of binding and inhibitory antibodies to ADAMTS-13 Status • Study start date: October 2017• Estimated primary completion date: FY22 • Study start date: October 2019 • Study start date: October 2019 Rare Genetic and Hematology 124 |

Study NCT01887938 NCT03771898 Indication Treatment of patients with motor symptoms in Metachromatic Leukodystrophy (MLD) Treatment of patients with motor symptoms in Metachromatic Leukodystrophy (MLD) Phase Phase I/II Extension Trial (Of HGT-MLD-070) Registration Enabling Phase IIb # of Patients N = 23 N = 42 Target Patients Children with Metachromatic Leukodystrophy (MLD) Late Infantile Metachromatic Leukodystrophy (MLD) Arms/Intervention Open Label with 4 Cohorts: • Cohort 1 – 10 mg dose level • Cohort 2 – 30 mg dose level • Cohort 3 – 100 mg dose level • Cohort 4 – 100 mg dose level (Process B) Open Label with 6 Groups: • Group A - GMFC-MLD level of 1 or 2 • Group B - GMFC-MLD level of 3 • Group C - GMFC-MLD level of 4 • Group D - younger siblings of enrolled subjects, and have the same ASA allelic constitution • Group E - GMFC-MLD level of 1 or 2 ( ≥12 to <18 mons of age) • Group F - GMFC-MLD level of 5 or 6 Primary endpoint and key secondary endpoint(s) Primary - Safety will be measured by the following endpoints: • Reporting of treatment-emergent adverse events (TEAEs) • Change from baseline in clinical laboratory testing (serum chemistry including liver function tests, hematology, and urinalysis) • Change from baseline in vital signs, physical examinations, and CSF chemistry (including cell counts, glucose, albumin, and protein) • Determination of the presence of anti-HGT-1110 antibodies in CSF and/or serum Primary - The primary efficacy endpoint is response in Group A, defined as maintenance of gross motor function at 2 years (Week 106), evaluated as no greater than 2 levels decline from baseline in GMFC-MLD. If suitable controls cannot be matched despite the sponsor’s best efforts, change from baseline results of GMFC-MLD at Week 106 may be compared with a prespecified objective threshold to evaluate primary efficacy for this study. Status • Study start date: May 2013 • Study start date: May 2019• Estimated primary completion date: FY22 Rare Genetic and HematologyTAK-611: RHASA1 ENZYME REPLACEMENT THERAPY FOR MLD, INTRATHECAL (IT) 125 | 1. rhASA = recombinant human arylsulfatase A

Study NCT01506141 NCT02412787 Indication Hunter Syndrome with Cognitive Impairment Hunter Syndrome with Cognitive Impairment Phase Phase I/IIHGT-HIT-045 Phase II/III HGT-HIT-094 # of Patients N = 14 N = 56 Target Patients Pediatric participants that completed HGT-HIT-045 with Hunter syndrome and cognitive Impairment Pediatric participants that completed study HGT-HIT-094 to continue receiving Elaprase treatment in conjunction with IdS IT or to continue receiving Elaprase treatment and begin concurrent IT treatment for those that did not receive IdS IT treatment in study HGT-HIT–094. Arms/Intervention All participants will receive Idursulfase-IT once monthly at the dose used in study HGT-HIT-045 via intrathecal drug delivery device (IDDD). All 56 participants will receive 10 mg of IdS IT once every 28 days. Participants who are younger than 3 years of age will receive an adjusted dose of 7.5 mg (>8 months to 30 months of age) and 10 mg (>30 months to 3 years of age). Primary endpoint and key secondary endpoint(s) Extension study of HGT-HIT-045 evaluating long-term safety and clinical outcomes of intrathecal idursulfase in conjunction with intravenous Elaprase An open label extension of study HGT-HIT-094 evaluating long term safety and clinical outcomes of intrathecal idursulfase administered in conjunction with Elaprase Status • Study start date: August 2010, recruitment completed Publication: • Muenzer J, et al. Genet. Med. 2016 Jan; 18(1):73-81. • Study start date: October 2015, recruitment completed Rare Genetic and HematologyTAK-609: CNS REPLACEMENT OF THE DEFICIENT-IDS1 ENZYME, INTRATHECAL (IT) 126 | 1. IdS = iduronate-2-sulfatase

MEZAGITAMAB (TAK-079): ANTI-CD38 ANTIBODY Study NCT04278924 NCT04159805 Indication Persistent/Chronic PrimaryImmune Thrombocytopenia (ITP) Myasthenia Gravis Phase Phase II Phase II # of Patients N = 54 N = 36 Target Patients Patients ≥18 years of age with persistent/chronic primary ITP Patients ≥18 years of age with generalized Myasthenia Gravis Arms/Intervention • Part A: 2 dose groups and placebo added to stable background therapy • Arm A1: Matching placebo (n = 12 patients) • Arm A2: TAK-079 100 mg (n = 12 patients) • Arm A3: TAK-079 300 mg (n = 12 patients) • Part B: Following interim analysis. 1 dose group and placebo (600 mg) added to stable, standard background therapy. • Arm B1: Matching placebo (n = 6 patients) • Arm B2: TAK-079 600 mg (n = 12 patients) • 2 dose groups and placebo added to stable background therapy • TAK-079 300 mg (n = 12 patients) • TAK-079 600 mg (n = 12 patients) • Matching placebo (n = 12 patients) Primary endpoint and key secondary endpoint(s) The primary endpoint is the percentage of patients with TEAEs including Grade 3 or higher events, SAEs, and AEs leading to TAK-079 discontinuation. The primary endpoint is the percentage of patients with TEAEs including Grade 3 or higher events, SAEs, and AEs leading to TAK-079 discontinuation. Status • Estimated study start date: Late FY2020 Study start date: January 2020 Rare Genetic and Hematology 127 |

Study NCT03253263 Indication Disease Complications of Extremely Premature Infants Phase Phase IIb # of Patients N = 477 Target Patients Extremely premature infants (birth>23 weeks to < 28 weeks of gestational age) Arms/Intervention 3 Arms 1:1:1 Ratio • ~159 subjects randomized to continuous IV infusion of SHP607 250 μg/kg/24 hours • ~159 subjects randomized toto continuous IV infusion of SHP607 400 μg/kg/24 hours • ~159 subjects randomized to standard neonatal care Primary endpoint and key secondary endpoint(s) Time to final weaning off respiratory technology support (RTS) from Day 1 (i.e., randomization) through 12 months corrected age (CA) Status • Study start date: May 2019 Rare Genetic and HematologyMECASERMIN RINFABATE (TAK-607): REPLENISHES INSULIN LIKE GROWTH FACTOR-1, IV 128 |

Study NCT02895945 Indication Congenital Hemophilia A with Inhibitors (CHAWI) patients who are undergoing major or minor elective surgical, dental, or other invasive procedures Phase Phase III # of Patients N = 12 Target Patients CHAWI patients Arms/Intervention • Single arm study with individualized loading and subsequent dosing Primary endpoint and key secondary endpoint(s) • Primary endpoint: Global Hemostatic Efficacy Assessment Score • Secondary endpoints: Blood loss, blood transfusions, and bleeding episodes Status • Study start date: May 2017 Rare Genetic and HematologyOBIZUR (TAK-672): RECOMBINANT ANTIHEMOPHILIC FACTOR, PORCINE SEQUENCE 129 |

OVERVIEW OF CLINICAL TRIAL SUMMARY ONCOLOGY RARE GENETIC & HEMATOLOGY NEUROSCIENCE GASTROENTEROLOGY (GI) PLASMA-DERIVED THERAPIES VACCINES 130 |

TAK-994: OREXIN 2R AGONIST, ORAL Study NCT04096560 NCT04551079 Indication Narcolepsy with or without cataplexy (NT1 or NT2) Acute sleep phase delay paradigm in healthy male participants Phase Phase IISPARKLE-1501 Phase I # of Patients N = up to 202 N = 18 Target Patients Patients with Narcolepsy Type 1 (with cataplexy, NT1) or Narcolepsy Type 2 (without cataplexy, NT2) Healthy male participants Arms/Intervention • Part A: Patients with NT1 treated for 28 days (TAK-994 dose 1 or placebo in 2:1 ratio). Second cohort with dose 2 TBD. • Part B: Dose ranging study in NT1 for 56 days (TAK-994 dose 1-3 or placebo in 1:1:1:1 ratio) • Part C: China specific cohort in NT1 for 56 days (TAK-994 or placebo in 2:1 ratio) • Part D: Patients with NT2 treated for 28 days (TAK-994 or placebo in 2:1 ratio). Second cohort with dose 2 TBD. Randomization to 1 of 3 treatment sequences with a washout period of at least 7 days in between each treatment period: • TAK-994 Dose A, Placebo, and TAK-994 Dose B • TAK-994 Dose B, TAK-994 Dose A, and Placebo • Placebo, TAK-994 Dose B, and TAK-994 Dose A Primary endpoint and key secondary endpoint(s) • Maintenance of Wakefulness Test (MWT) • Epworth Sleepiness Scale (ESS) • Weekly Cataplexy Rate (WCR) • Maintenance of Wakefulness Test (MWT) • Safety, PK/PD Status • Study start date: July 2020 • Study start date: September 2020 Neuroscience 131 |

TAK-925: OREXIN 2R AGONIST, IV Study NCT03332784 NCT03748979 Indication Narcolepsy type 1 Narcolepsy type 1 and Narcolepsy type 2 Phase Phase I Phase I # of Patients N = 58 N = 57 Target Patients Patients with narcolepsy type 1 andhealthy volunteers Patients with narcolepsy type 1, patients with narcolepsy type 2 and healthy volunteers Arms/Intervention • Part 1: Healthy participants and healthy elderly participants • Part 2: Patients with narcolepsy type 1: TAK-925 5 mg, 11.2 mg, 44.8mg or placebo with cross-over • Part A: Healthy participants • Part B: TAK-925 (Dose Levels 11mg, 44mg ) vs. placebo in NT1 patients • Part C: TAK-925 (Dose Levels 44mg, 112mg ) vs. placebo in NT2 patients • Part A’: TAK-925 (Dose Levels 112mg) in healthy participants. Primary endpoint and key secondary endpoint(s) Sleep Latency in Maintenance of Wakefulness Test (MWT) Karolinska Sleepiness Scale (KSS) Sleep Latency in Maintenance of Wakefulness Test (MWT) Epworth Sleepiness Scale (ESS) Status • Study start date: November 2017 • Study primary completion date: September 2018 Publication: https://www.professionalabstracts.com/ws2019/iPlanner/#/presenta tion/1832 • Study start date: November 2018 • Study primary completion date: October 2019 Publication: https://onlinelibrary.wiley.com/toc/13652869/2020/29/S1 Neuroscience 132 |

TAK-925: OREXIN 2R AGONIST, IV Study NCT04091425 NCT04091438 Indication Excessive Daytime sleepiness in subjects with Obstructive Sleep Apnea Idiopathic Hypersomnia Phase Phase 1 Phase 1 # of Patients N = 25 N = 40 Target Patients Patients with obstructive sleep apnea who are experiencing excessive daytime sleepiness despite adequate use of CPAP Patients with Idiopathic Hypersomnia (IH) Arms/Intervention • 3 period, 3 treatment crossover: TAK-925 High Dose, Low dose and placebo • 2 period, 2 treatment crossover: TAK-925 and placebo Primary endpoint and key secondary endpoint(s) • Maintenance of Wakefulness Test (MWT) • Karolinska Sleepiness Scale (KSS) • Maintenance of Wakefulness Test (MWT) • Karolinska Sleepiness Scale (KSS) • Safety, PK/PD Status • Study start date: November 2019 • Study primary completion date: April 2020 • Results in-house awaiting publication at a future conference • Study start date: January 2020 Neuroscience 133 |

SOTICLESTAT (TAK-935): CH24H INHIBITOR, ORAL Study NCT036504521 Indication Dravet Syndrome (DS) and Lennox–Gastaut syndrome (LGS) Phase Phase IIELEKTRA # of Patients N = 141 Target Patients Pediatric patients between the ages of 2 and < 18 years of age with the diagnosis of DS or LGS demonstrating ≥3 convulsive or ≥4 drop seizures, respectively, per month during the 3 months immediately prior to screening Arms/Intervention • 51 DS subjects (1:1 soticlestat:placebo randomization ratio) • And 90 LGS subjects (1:1 soticlestat:placebo randomization ratio) Primary endpoint and key secondary endpoint(s) Primary: Percent change from baseline in seizure frequency (convulsive for DS and drop for LGS) Key secondary endpoints: • Clinician’s Clinical Global Impression of Severity and Change • Caregiver Global Impression of Change (GI-C) responses • Plasma 24S-hydroxycholesterol (24HC) levels • Safety and tolerability endpoints Status • Study start date: August 2018 • Study completion date: July 2020 • Press release August 25, 2020: https://www.takeda.com/newsroom/newsreleases/2020/phase-2-elektra-study-of-soticlestat-tak- 935ov935-meets-primary-endpoint-reducing-seizure-frequency-in-children-with-dravet-syndrome-or-lennox-gastaut-syndrome/ Neuroscience 134 | 1. In collaboration with Ovid Therapeutics Inc.

WVE-120101/120102: MHTT ASO Study NCT032258331 NCT032258461 Indication Huntington’s Disease Huntington’s Disease Phase Phase I/IIPRECISION-HD1 Phase I/II PRECISION-HD2 # of Patients N = 60 N = 60 Target Patients Adult patients with early manifest Huntington's disease (HD) who carry a targeted single nucleotide polymorphism (SNP) rs362307 (SNP1) Adult patients with early manifest Huntington's disease (HD) who carry a targeted single nucleotide polymorphism (SNP) rs362331 (SNP2) Arms/Intervention • WVE-120101 (2 mg) or placebo • WVE-120101 (4 mg) or placebo • WVE-120101 (8 mg) or placebo • WVE-120101 (16 mg) or placebo • WVE-120101 (32 mg) or placebo • WVE-120102 (2 mg) or placebo • WVE-120102 (4 mg) or placebo • WVE-120102 (8 mg) or placebo • WVE-120102 (16 mg) or placebo • WVE-120102 (32 mg) or placebo Primary endpoint and key secondary endpoint(s) Primary outcome: Safety Secondary: • Pharmacokinetics (PK), Pharmacodynamics (PD) of single and multiple doses (Concentration of mutant huntingtin (mHTT) protein in CSF) • Clinical effect: Total Functional Capacity (TFC) Other outcome measures: UHDRS, short Problems Behavior Assessment (PBA-s), magnetic resonance Imaging Primary outcome: Safety Secondary: • Pharmacokinetics (PK), Pharmacodynamics (PD) of single and multiple doses (Concentration of mutant huntingtin (mHTT) protein in CSF) • Clinical effect: Total Functional Capacity (TFC) Other outcome measures: UHDRS, short Problems Behavior Assessment (PBA-s), magnetic resonance Imaging Status Study start date: July 2017 Study start date: July 2017 Neuroscience 135 | 1. Trial managed by Wave Life Sciences

TAK-3411: ALPHA-SYNUCLEIN ANTIBODY, IV Study NCT03272165 NCT04449484 Indication Parkinson’s Disease Parkinson’s Disease Phase Phase I Phase I # of Patients N = 48 N = 36 Target Patients Healthy volunteers Patients with Parkinson’s Disease Arms/Intervention • TAK-341 (MEDI1341) IV at a single ascending dose• Placebo IV Three cohorts of 12 patients treated over 8 weeks with three 60 minute IV infusions • Dose A of TAK-341/MEDI1341 over 8 weeks, with 4 weeks intervals • Dose A of TAK-341/MEDI1341 over 8 weeks, with 4 weeks intervals • Matched placebo over 8 weeks, with 4 weeks intervals Primary endpoint and key secondary endpoint(s) • Safety and tolerability • Secondary endpoint: PK and PD (alpha-synuclein concentrations in plasma and CSF) • Safety and tolerability Status • Study start date: October 2017 • Study start date: August 2020 Neuroscience 136 | 1. Trials managed by AstraZeneca

OVERVIEW OF CLINICAL TRIAL SUMMARY ONCOLOGY RARE GENETIC & HEMATOLOGY GASTROENTEROLOGY (GI) NEUROSCIENCE PLASMA-DERIVED THERAPIES VACCINES 137 |

ENTYVIO (VEDOLIZUMAB): GUT-SELECTIVE ANTI-α4β7 INTEGRIN MAB Study NCT03657160 NCT02620046 Indication Graft-versus-Host Disease (GvHD) prophylaxis IV Ulcerative Colitis (UC) or Crohn’s disease (CD) subcutaneous (SC) Phase Phase III Phase III # of Patients N = 558 N = 692 Target Patients Patients undergoing allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in the prophylaxis of intestinal acute GvHD (aGvHD) Patients with UC or CD who received vedolizumab SC in a prior vedolizumab SC study – long-term open-label extension Arms/Intervention • Arm 1: Vedolizumab 300 mg at Days -1 (baseline), +13, +41, +69, +97, +125, and +153 • Arm 2: Placebo at Days -1 (baseline), +13, +41, +69, +97, +125, and +153 • Group A: Vedolizumab SC 108 mg Q2W - patients from studies VISIBLE 1 (NCT02611830) and VISIBLE 2 (NCT02611817) who completed the Maintenance Period (Week 52) or were not randomized into Maintenance Period and achieved response at Week 14 after having received a third vedolizumab IV infusion at Week 6 • Group B: Vedolizumab SC 108 mg QW - patients from studies VISIBLE 1 and VISIBLE 2 who withdrew early from the Maintenance Period due to treatment failure or patients from current study who enrolled on Q2W dosing but experienced treatment failure while on study and were dose escalated to QW dosing. Primary endpoint and key secondary endpoint(s) Intestinal aGvHD-free survival by Day +180 after Allo-HSCT Percentage of participants with study drug related treatment emergent adverse events (AEs) and serious AEs Key secondary endpoints: long term clinical response and remission rates for UC and CD Status • Study start date: February 2019• Estimated primary completion date: FY22 • Study start date: April 2016 GASTROENTEROLOGY (GI) 138 |

ENTYVIO (VEDOLIZUMAB): GUT-SELECTIVE ANTI-α4β7 INTEGRIN MAB Study NCT03196427 Indication Ulcerative Colitis or Crohn’s disease in pediatric patients IV Phase Phase II(Long-term safety study) # of Patients N = 90 Target Patients Pediatric patients with Ulcerative Colitis or Crohn’s disease between 2 to 17 years old at the time of randomization for Study NCT03138655. Arms/Intervention • Arm 1 ( ≥30 kg weight cohort): Vedolizumab 300 mg or 200 mg (Q8W)• Arm 2 ( <30 kg weight cohort): Vedolizumab 150 mg or 100 mg (Q8W) Primary endpoint and key secondary endpoint(s) Percentage of participants with Treatment-Emergent Adverse Events (TEAEs) Status • Phase 2 start date: July 2018 • Study completion date: May 2020 • Pediatric Phase 3 to start 2021 139 | GASTROENTEROLOGY (GI)

Study NCT03279081 Indication Complex perianal fistula(s) in patients with Crohn’s disease Phase Phase IIIADMIRE-CD II # of Patients N = 554 Target Patients Patients with Crohn’s disease who have complex perianal fistula(s), previously treated and have shown an inadequate response to immunosuppressants, anti TNF, ustekinumab Arms/Intervention • Arm 1: Cx601, adult allogeneic expanded adipose-derived stem cells (eASC 120 million cells (5 million cells per milliliter)) administered once by intralesional injection • Arm 2: Placebo-matching eASCs cells administered once by intralesional administration Primary endpoint and key secondary endpoint(s) Primary: Combined Remission, defined as: • The clinical assessment of closure of all treated external openings at week 24, and • Absence of collections >2 cm (in at least 2 dimensions) confirmed by blinded central MRI assessment at Week 24. Key Secondary: • Clinical Remission at weeks 24 and 52 • Time to Clinical Remission at weeks 24 and 52 Status • Study start date: September 2017• Estimated primary completion date: FY22 ALOFISEL/CX601 (DARVADSTROCEL): ALLOGENEIC EXPANDED ADIPOSE-DERIVED STEM CELLS (ASC) 140 | GASTROENTEROLOGY (GI)

Study NCT04198363 Indication Acid related disease (adjunct to Helicobacter pylori eradication) Phase Phase III China # of Patients N = 510 Target Patients Helicobacter pylori (HP)-positive participants who require HP eradication Arms/Intervention • Experimental: Vonoprazan 20 mg in combination with bismuth containing quadruple therapy• Active Comparator: Esomeprazole 20 mg in combination with bismuth containing quadruple therapy Primary endpoint and key secondary endpoint(s) Percentage of Helicobacter pylori positive (HP+) participants with successful HP eradication at week 4 post-treatment Status • Study start date: April 2020• Estimated primary completion date: FY21 VONOPRAZAN: POTASSIUM-COMPETITIVE ACID BLOCKER, ORAL 141 | GASTROENTEROLOGY (GI)

Study NCT03245840 Indication Eosinophilic Esophagitis (EoE) Phase Phase III # of Patients N = 133 Target Patients Subjects with EoE who have completed participation in both the SHP621-301 and SHP621-302 studies – extension study Arms/Intervention Open Label Study:• Budesonide oral suspension (BOS) (0.2 milligrams/mL) 2mg twice daily Primary endpoint and key secondary endpoint(s) To evaluate the long term safety and tolerability of budesonide oral suspension ･# of participants with treatment-emergent adverse events (TEAEs) ･# of participants with clinically relevant changes in physical examinations, vital signs and clinical laboratory assessments ･Change from baseline in bone mineral density (BMD) for adolescents assessed by dual-energy x-ray absorptiometry (DXA) scan ･Change from baseline in adrenocorticotropic hormone (ACTH) stimulation level Status • Study start date: October 2017 TAK-721: GLUCOCORTICOSTEROID, ORAL 142 | GASTROENTEROLOGY (GI)

TAK-951: PEPTIDE AGONIST, SC Study NCT04486950 NCT04557189 Indication Nausea & Vomiting Nausea & Vomiting Phase Phase I Phase IIa # of Patients N = 40 N = 100 Target Patients Healthy participants Surgical patients under general anesthesia with 3 or more Apfel risk factors Arms/Intervention • Cohort 1: TAK-951 20 mcg or matching placebo infusion (intravenous (IV)) over 60 minutes • Cohort 2: TAK-951 (dose TBD) or matching placebo infusion (IV) over 60 minutes • Cohort 3: TAK-951 (dose TBD) or matching placebo infusion (IV) < 60 minutes • Group A: Ondansetron placebo-matching intravenous (IV) injection, once immediately before induction of anesthesia and prophylaxis followed by TAK- 951 4 mg subcutaneous (SC) injection once 30 to 45 mins before the end of surgery; • Group B: Ondansetron IV 4 mg once immediately before induction of anesthesia followed by TAK-951 placebo-matching injection SC administered 30 to 45 minutes before the end of surgery Primary endpoint and key secondary endpoint(s) Safety and tolerability of IV administered TAK-951 in healthy participants Complete response in the immediate postoperative period (time frame: 6 hours post surgery) Percentage of participants with complete response, defined as no emesis (vomiting or retching) and no need for rescue therapy (indicated if vomiting/retching and/or nausea score ≥4 or upon participant's request), will be reported. The severity of nausea will be scored using a self-reported, 11-point numerical Verbal Rating Scale (VRS), where 0 represents "no nausea" and 10 represents the "worst nausea possible." Significant nausea is defined as a VRS score ≥4 Status • Study start date: July 2020 • Study start date: October 2020 143 | GASTROENTEROLOGY (GI)

Study NCT03544229 Indication Gastroparesis Phase Phase II # of Patients N = 205 Target Patients Patients who have symptomatic idiopathic or diabetic gastroparesis. Arms/Intervention • TAK-906 5 mg capsule BID: approximately 25 subjects prior to discontinuation of randomization into this dose arm • TAK-906 25 mg capsule BID: n = 60 • TAK-906 50 mg capsule BID: n = 60 • Placebo capsule BID: n = 60 Primary endpoint and key secondary endpoint(s) To assess the efficacy of treatment with 2 dose levels of TAK-906 in adult subjects with gastroparesis compared with placebo during 12 weeks of treatment Status • Study start date: October 2018 TAK-906: DOPAMINE D2/D3 RECEPTOR ANTAGONIST, ORAL 144 | GASTROENTEROLOGY (GI)

Study NCT03827655 Indication Post-Operative Gastrointestinal Dysfunction (POGD) Phase Phase II # of Patients N = 180 Target Patients Participant is scheduled to undergo a laparoscopic-assisted or open partial small- or large-bowel resection. Arms/Intervention • Regimen 1: Placebo (NS 100 mL infusion over 60 minutes) pre-operation and daily post-operation until return of upper and lower GI function (ie, resolution of POGD) or for up to 10 days. • Regimen 2: TAK-954 (0.1 mg/100 mL infusion over 60 minutes) pre-operation and daily post-operation until return of upper and lower GI function or for up to 10 days. • Regimen 3: TAK-954 (0.5 mg/100 mL infusion over 60 minutes) pre-operation and daily post-operation until return of upper and lower GI function or for up to 10 days. • Regimen 4: TAK-954 (0.1 mg/100 mL infusion over 60 minutes) pre-operation and daily placebo infusions post-operation until return of upper and lower GI function or for up to 10 days. • Regimen 5: TAK-954 (0.5 mg/100 mL infusion over 60 minutes) pre-operation and daily placebo infusions post-operation until return of upper and lower GI function or for up to 10 days. Primary endpoint and key secondary endpoint(s) To assess the efficacy and safety of intravenous (IV) TAK-954 for accelerating the recovery of GI function post-surgery in patients undergoing open or laparoscopic-assisted partial small- or large-bowel resection. Status • Study start date: March 2018 TAK-954: 5-HT4-HYDROXYTRYPTAMINE RECEPTOR AGONIST, IV 145 | GASTROENTEROLOGY (GI)

Study NCT03943446 Indication Prevention of the Recurrence of Postoperative Crohn's Disease (CD) Phase Phase II # of Patients N = 96 Target Patients Documented diagnosis of CD confirmed by endoscopic biopsy before resection or by tissue obtained at resection. Arms/Intervention • Cohort 1: TAK-018 0.30 g Low Dose BID for up to 26 weeks • Cohort 2: TAK-018 1.5 g High Dose BID for up to 26 weeks • Placebo Primary endpoint and key secondary endpoint(s) % of participants with endoscopic recurrence of CD as assessed by Rutgeerts Grading Scale at Week 26 Status • Study start date: August 2020 SIBOFIMLOC (TAK-018): FIMH ANTAGONIST, ORAL 146 | GASTROENTEROLOGY (GI)

OVERVIEW OF CLINICAL TRIAL SUMMARY ONCOLOGY RARE GENETIC & HEMATOLOGY PLASMA-DERIVED THERAPIES NEUROSCIENCE GASTROENTEROLOGY (GI) VACCINES 147 |

HYQVIA (TAK-771): IVIG WITH RECOMBINANT HUMAN HYALURONIDASE, SC Study NCT02549170 NCT02955355 Indication Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) Phase Phase III Phase III # of Patients N = 174 N = 120 Target Patients Adult subjects with a confirmed diagnosis of CIDP and who have remained on a stable dosing regimen of IV immunoglobulin G (IGIV) therapy for at least 12 weeks prior to screening. Adult subjects who have completed Epoch 1 of Study NCT02549170 without CIDP worsening. Arms/Intervention • Epoch 1: SC Treatment Period – Double blind assignment of HYQVIA/HyQvia or 0.25% albumin placebo solution with rHuPH20 6 months or until relapse. • Epoch 2: IV Treatment Period - Open-label phase providing IGIV for subjects who meet relapse criteria during Epoch 1. • Subjects remain on same dosing regimen they were administered in Epoch 1 of study 161403 (1 to 2 g/kg body weight every 4 weeks). The first infusion will be at the subject’s full dose; there will be no ramp-up of dose. Primary endpoint and key secondary endpoint(s) To evaluate the efficacy of HYQVIA/HyQvia as a maintenance therapy for CIDP to prevent relapse of neuromuscular disability and impairment. Safety and tolerability. To evaluate the long-term safety, tolerability, and immunogenicity of HYQVIA/HyQvia. Status • Study start date: April 2016• Estimated primary completion date: FY21/22 • Study start date: December 2016 PDT 148 |

HYQVIA (TAK-771): IVIG WITH RECOMBINANT HUMAN HYALURONIDASE, SC Study NCT03277313 NCT03116347 Indication Primary Immunodeficiency Diseases (PIDD) Primary Immunodeficiency Diseases (PIDD) Phase Phase III Phase IV # of Patients N = 44 N = 42 Target Patients Pediatric subjects with primary immunodeficiency diseases in the US Pediatric subjects with primary immunodeficiency diseases in the EU Arms/Intervention Single-Group: • Epoch 1: HyQvia SC dose and ramp up for all patients; up to 6 weeks duration; patients were previously treated with IVIG or other SC immunoglobulin • Epoch 2: HYQVIA treatment (final dosing); 1-3 years • For IV-pre-treated subjects: every three or four weeks, depending on the subject’s previous IV dosing schedule. • For SC-pre-treated subjects: every three or four weeks, at the discretion of investigator and subject. • Epoch 3: Safety Follow-Up: up to 1 year, if needed Single-Group: • Epoch 1: HyQvia SC dose and ramp up for patients previously not treated with HyQvia • Epoch 2: HyQvia dose once every three or four weeks • For IV-pretreated subjects: every three or four weeks, depending on the subject’s previous IV dosing schedule. • For SC-pretreated subjects: every three or four weeks, at the discretion of investigator and subject • For HyQvia pre-treated subjects: No change in frequency of administration • Epoch 3: Safety Follow-Up: up to 1 year, if needed Primary endpoint and key secondary endpoint(s) Primary: Efficacy - rate of acute serious bacterial infections per participant per year. Secondary: Safety, tolerability, immunogenicity, efficacy, PK, health-related Quality of Life. Primary: Safety Secondary: Tolerability, immunogenicity, efficacy, health-related Quality of Life. Status • Study start date: September 2017• Estimated primary completion date: FY23 • Study start date: June 2017 • Estimated primary completion date: FY23 PDT 149 |

Study NCT02525861 Indication Chronic augmentation and maintenance therapy in adults with clinically evident emphysema due to severe congenital deficiency of Alpha1-Proteinase Inhibitor (A1PI) Phase Phase III/IV # of Patients N = 36 Target Patients A1PI deficient subjects Arms/Intervention • Arm 1: GLASSIA lot with particle loads representing the high end within the normal range observed in GLASSIA lots manufactured• Arm 2: GLASSIA lot with particle loads representing the low end within the normal range observed in GLASSIA lots manufactured Primary endpoint and key secondary endpoint(s) 1. To evaluate the effectiveness of the use of 5-micron in-line filter on the safety and potential immunogenicity of GLASSIA. 2. To determine the effects of weekly IV augmentation therapy with GLASSIA at a dosage of 60 mg/kg BW on antigenic and functional A1PI levels in epithelial lining fluid (ELF) in subjects with congenital A1PI deficiency. 3. To collect additional safety information for GLASSIA. Status • Study start date: April 2016• Primary completion date: July 2020 GLASSIA (TAK-670): HUMAN ALPHA1-PROTEINASE INHIBITOR, IV PDT 150 |

Study NCT045465811 Indication Treatment of COVID-19 in hospitalized patients with moderate disease Phase Phase III # of Patients N = 500 Target Patients Adult hospitalized COVID-19 patients with moderate disease with duration of symptoms ≤ 12 days Arms/Intervention • Arm A: Hyperimmune globulin to SARS-CoV-2 (hIVIG)2 single dose of 400 mg/kg body weight, to a maximum dose of 40 g or 400 mL (i.e. capped at a body weight of 100kg) + remdesivir • Arm B: Placebo (normal saline) + remdesivir Primary endpoint and key secondary endpoint(s) Primary endpoint: Clinical Status at Day 7 According to a 7-point Ordinal Outcome Scale 7. Death 6. End-organ failure 5. Life-threatening end-organ dysfunction; 4. Serious end-organ dysfunction; 3. Moderate end-organ dysfunction; 2. Limiting symptoms due to COVID-19; 1. No limiting symptoms due to COVID-19 (Outcome is reported as the percent of participants in each of 7 categories) Key secondary endpoints: mortality, adverse events, and days of hospitalization Status • Study start date: October 2020 • Estimated primary completion date: Q4FY20 COVIG-19: ANTI-COVID-19 HYPERIMMUNE INTRAVENOUS GLOBULIN PDT 151 | 1. Sponsor: The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH)2. Arm A represents hIVIG produced by four manufacturers (Takeda, CSL, Grifols, and Emergent). The hIVIG products will be pooled for the planned efficacy and safety analyses.

OVERVIEW OF CLINICAL TRIAL SUMMARY ONCOLOGY RARE GENETIC & HEMATOLOGY VACCINESNEUROSCIENCE GASTROENTEROLOGY (GI) PLASMA-DERIVED THERAPIES 152 |

Study NCT02747927 Indication The prevention of dengue disease caused by any dengue virus serotype in individuals 4 years to 60 years of age Phase Phase IIITetravalent Immunization against Dengue Efficacy Study (TIDES) # of Patients N = 20,100 Target Patients Healthy children aged 4 to 16-year-old in dengue-endemic countries in Latin America and Asia Arms/Intervention • Randomized 2:1 to receive either TAK-003 or placebo on Day 1 and Day 90 Primary endpoint and key secondary endpoint(s) • Efficacy: Onset of protection 30 days post 2nd dose in all (seronegative and seropositive) • Primary endpoint: ≥70% efficacy against all symptomatic dengue fever caused by any strain • Secondary endpoints: − ≥70% efficacy individual strains − ≥60% efficacy in seronegatives • Safety: • Comparable to other live attenuated viral vaccines (e.g. MMR, YF, Varicella) • No disease enhancement in partially protected individuals Status • Study start date: September 2016 • Primary completion date: July 2018 • Estimated completion date: FY24/25 (following booster evaluation) • 24 month data presented November 2020 at American Society of Tropical Medicine and Hygiene Annual Meeting Publication: • Biswal S, et al. N Engl J Med. 2019; 381:2009-2019. • Biswal S, et al. Lancet. 2020; 395(10234):1423-1433. VBUTAK-003: LIVE ATTENUATED TETRAVALENT VACCINE FOR PREVENTION OF DENGUE DISEASE 153 |

TAK-214: NOROVIRUS GI.1/GII.4 BIVALENT VIRUS-LIKE PARTICLE VACCINE Study NCT02669121 NCT03039790 Indication For active immunization for the prevention of acute gastroenteritis caused by norovirus (NoV) For active immunization for the prevention of acute gastroenteritis caused by norovirus (NoV) Phase Phase II Phase II # of Patients N = 4176 up to N = 575 Target Patients Healthy adults (18 to 49 years of age) Healthy adults >18 years who received at least one dose of NoV GI.1/GII.4 Bivalent Virus-Like Particle Vaccine in previous studies NOR- 107, NOR-210 and NOR-204 Arms/Intervention • Arm 1: NoV 15µg GI.1/50µg GII.4 bivalent virus-like particle (VLP) vaccine, 0.5 mL intramuscularly (IM), once, on Day 1 • Arm 2: NoV vaccine placebo-matching solution (0.9% sodium chloride), 0.5 mL intramuscularly (IM), once, on Day 1 • No NoV vaccine injection administered. • Long-Term Immunogenicity Follow-up Trial of Adult and Elderly Subjects (followed up to 5y post-primary vaccination). • Vaccine formulation according to parent trials. Primary endpoint and key secondary endpoint(s) • Primary endpoint: Percentage of Participants with Moderate or Severe Acute Gastroenteritis (AGE) Occurring >7 Days After Dosing Due to GI.1 or GII.4 NoV Strains (excluding Co-infection due to Salmonella, Shigella, or Campylobacter) • Key secondary: Percentage of Participants with Moderate or Severe AGE Occurring >7 Days After Dosing Due to Any NoV Strains (including/excluding Co-infection) and Due to GI.1 or GII.4 NoV Strains (including Co-infection) • Primary endpoint: Geometric Mean Blocking Titers 50 percent (%) (GMBT50) of Anti-norovirus GI.1 VLP / GII.4 VLP Antibodies as measured by the histo-blood group antigen (HBGA) blocking assay. • Secondary endpoint: Geometric Mean Titers (GMT) of Anti-norovirus GI.1 VLP / GII.4 VLP Antibodies as measured by total immunoglobulin (pan-Ig) enzyme-linked immunoassay (ELISA). Status • Study start date: February 2016 • Study primary completion date: June 2018 Publication: • Sherwood J, et al. Vaccine 2020; 38(41):6442-6449. • Study start date: February 2017 VBU 154 |

Study NCT03343626 Indication For active immunization for prevention of disease caused by Zika virus (ZIKV) Phase Phase I # of Patients N = 271 Target Patients Healthy Adult Participants aged 18-49-years of age Arms/Intervention • Placebo: TAK-426 placebo-matching injection, intramuscular, once on Days 1 and 29 • Low Dose: PIZV 2 microgram (mcg) (PIZV 0.5 milliliter (mL), 2 mcg antigen, injection, intramuscular, once on Days 1 and 29) • Medium Dose: PIZV 5 mcg (PIZV 0.5 mL, 5 mcg antigen, injection, intramuscular, once on Days 1 and 29) • High Dose: PIZV 10 mcg (PIZV 0.5 mL, 10 mcg antigen, injection, intramuscular, once on Days 1 and 29) Primary endpoint and key secondary endpoint(s) Safety, immunogenicity and dose ranging study Status • Study start date: November 2017 • Presentation at ASTHM 2019 (Htay Htay Han #215, #1948) • https://www.astmh.org/ASTMH/media/2019-Annual-Meeting/ASTMH-2019-Abstract-Book.pdf TAK-426: PURIFIED INACTIVATED ZIKA VIRUS VACCINE PIZV VBU 155 |

Appendix Reconciliation Tables, Glossary

Takeda uses the concept of Underlying Growth for internal planning and performance evaluation purposes. Underlying Growth compares two periods (fiscal quarters or years) of financial results under a common basis and is used by management to assess the business. These financial results are calculated on a constant currency basis using a full year plan rate and exclude the impacts of divestitures and other amounts that are unusual, non-recurring items or unrelated to our ongoing operations. Although these are not measures defined by IFRS, Takeda believes Underlying Growth is useful to investors as it provides a consistent measure of our performance. Takeda uses "Underlying Revenue Growth", "Underlying Core Operating Profit Growth", and "Underlying Core EPS Growth" as key financial metrics. Underlying Revenue represents revenue on a constant currency basis and excluding non- recurring items and the impact of divestitures that occurred during the reporting periods presented. Underlying Core Operating Profit represents Core Operating Profit (as defined below) on a constant currency basis and further adjusted to exclude the impacts of divestitures that occurred during the reporting periods presented. Core Operating Profit represents net profit adjusted to exclude income tax expenses, the share of profit or loss of investments accounted for using the equity method, finance expenses and income, other operating expenses and income, amortization and impairment losses on acquired intangible assets and other items unrelated to Takeda’s core operations, such as purchase accounting effects and transaction related costs. Underlying Core EPS represents net profit based on a constant currency basis, adjusted to exclude the impact of divestitures, items excluded in the calculation of Core Operating Profit, and other non-operating items (e.g. amongst other items, fair value adjustments and the imputed financial charge related to contingent consideration) that are unusual, non-recurring in nature or unrelated to Takeda’s ongoing operations and the tax effect of each of the adjustments, divided by the outstanding shares (excluding treasury shares) as of the end of the comparative period. DEFINITION OF CORE AND UNDERLYING GROWTH 157 |

Billion yen FY2013 FY2014 Growth Revenue 1,691.7 1,778.8 +5.1% Fx effects 6.0 (40.0) Divestments (22.1) (16.0) Underlying Revenue 1,675.7 1,721.9 Underlying Growth +2.8% Operating Profit 139.3 -129.3 — Actos one off 274.1 Amortization of intangibles 119.7 123.8 Impairment of intangibles 23.1 63.5 Disposal of unused property (6.7) (32.8) Restructuring costs 21.7 31.2 Contingent consideration 5.6 (51.3) Litigation costs, etc. 11.6 9.2 Core Earnings 314.2 288.3 -8.2% Fx effects 3.0 13.8 Divestments and other (16.1) (7.3) Underlying Core Earnings 301.1 294.9 Underlying Growth -2.1% RECONCILIATION FROM REPORTED TO CORE/UNDERLYING CORE FY2014 FULL YEAR 158 |

(BN JPY) REPORTED REPORTED TO CORE ADJUSTMENTS CORE CORE TO UNDERLYING CORE ADJ. UNDERLYING CORE Amortization & impairment of intangible assets Other operating income/ expense Shire acquisition related costs Shire purchase accounting adjustments Swiss Tax Reform Teva JV related accounting adjustments Others FX Divestitures Revenue 3,291.2 3,291.2 102.4 -30.5 Cost of sales -1,089.8 199.5 -890.3 -27.9 5.0 Gross Profit 2,201.4 199.5 2,400.9 74.4 -25.5 SG&A expenses -964.7 5.5 2.4 -956.8 -29.0 R&D expenses -492.4 10.4 0.1 -481.9 -8.9 Amortization of intangible assets -412.1 87.0 325.1 — Impairment losses on intangible assets -43.3 43.3 — Other operating income 60.2 -46.0 -14.2 — Other operating expenses -248.7 113.3 135.4 — Operating profit 100.4 130.3 67.3 151.2 527.1 -14.2 962.2 36.5 -25.5 Margin 3.1% 29.2% 28.9% Financial income/expenses -137.2 7.1 14.4 -20.1 -135.7 5.3 Equity income/loss -24.0 32.2 8.2 -0.0 Profit before tax -60.8 130.3 67.3 158.3 541.6 18.0 -20.1 834.7 41.8 -25.5 Tax expense 105.0 -31.7 -10.8 -29.2 -98.2 -94.6 -5.5 -67.5 -232.4 -10.0 5.9 Non-controlling interests -0.0 -0.0 Net profit 44.2 98.7 56.5 129.1 443.4 -94.6 12.5 -87.6 602.2 31.8 -19.6 EPS (yen) 28 387 21 -13 395 Number of shares (millions) 1,557 1,557 1,555 RECONCILIATION FROM REPORTED TO CORE/UNDERLYING CORE FY2019 FULL YEAR 159 | Note: FY2019 Underlying Core results reflect divestiture adjustments applied in FY2019 Underlying calculation which was disclosed on May 13, 2020.

GLOSSARY OF ABBREVIATIONS 160 | PBS phosphate buffered saline PCAB potassium competitive acid blocker Ph+ ALL Philadelphia chromosome-positive acute lymphoblastic leukemia PID primary immunodeficiency PK pharmacokinetics POC proof of concept POGD post-operative gastrointestinal dysfunction POI post-operative ileus PTCL peripheral T-cell lymphoma PTH parathyroid hormone R/R relapsed/refractory RCC renal cell cancer RTK receptor tyrosine kinase sALCL systemic anaplastic large cell lymphoma SBS short bowel syndrome SC subcutaneous formulation SCD sickle cell disease SCT stem cell transplant SCZ schizophrenia SID secondary immunodeficiency SLE systemic lupus erythematosus sq squamous STING stimulator of interferon genes SUMO small ubiquitin-related modifier TESD treatment emergent sexual dysfunction TKI tyrosine kinase inhibitor TRD treatment resistant depression UC ulcerative colitis vWD von Willebrand disease AD Alzheimer’s disease ADC antibody drug conjugate ADHD attention deficit hyperactivity disorder AHA acquired hemophilia A ALK anaplastic lymphoma kinase ALCL anaplastic large-cell lymphoma AML acute myeloid leukemia ASCT autologous stem cell transplant ARD acid-related diseases BLA biologics license application BBB blood brain barrier BMA bradykinin mediated angioedema BTK Bruton's tyrosine kinase BOS budesonide oral suspension CAR-T Chimeric antigen receptor-T CD Crohn's disease CHAWI congenital hemophilia A with inhibitors CIAS cognitive impairment associated with schizophrenia CIDP chronic inflammatory demyelinating polyradiculoneuropathy CLL Chronic lymphocytic leukemia CML chronic myeloid leukemia CMML chronic myelomonocytic leukemia CMV Cytomegalovirus CSF cerebrospinal fluid CNS central nervous system CPF Complex perianal fistulas CRL complete response letter CRPS complex regional pain syndrome CTCL cutaneous T-cell lymphoma cTTP congenital thrombotic thrombocytopenic purpura DAAO D-amino acid oxidase DEE developmental and epileptic encephalopathies DLBCL diffuse large B-cell lymphoma DU duodenal ulcer Dx diagnosis EDS excessive daytime sleepiness EE H erosive esophagitis healing EE M erosive esophagitis maintenance EFI enteral feeding intolerance EGFR epidermal growth factor receptor EOE eosinophilic esophagitis ESCC esophageal squamous-cell carcinoma FL front line FSI first subject in GCC guanylyl cyclase C GERD gastroesophageal reflux disease GI gastrointestinal GnRH gonadotropin-releasing hormone GU gastric ulcer GvHD graft versus host disease HAE hereditary angioedema H2H head to head HCC hepatocellular carcinoma HemA hemophilia A HER2 human epidermal growth factor receptor 2 HL Hodgkin's lymphoma HR MDS higher-risk myelodysplastic syndromes IBD inflammatory bowel disease IND investigational new drug iNHL Indolent non-Hodgkin’s lymphoma I/O immuno-oncology iTTP immune thrombotic thrombocytopenic purpura IV intravenous iPSC induced pluripotent stem cells L-ASA low dose aspirin LBD Lewy body dementia LB AML low-blast acute myeloid leukemia LSD1 Lysine specific demethylase 1 LCM lifecycle management mAb monoclonal antibody MAOB monoamine oxidase B MG myesthenia gravis MLD metachromatic leukodystrophy MM multiple myeloma NAE NEDD8 activating enzyme ND newly diagnosed NDA new drug application Neg negative NERD non-erosive reflux disease NHL non-Hodgkin’s lymphoma NK natural killer NME new molecular entity NSCLC non-small cell lung cancer NSCT non stem cell transplant NS negative symptoms NT1 Narcolepsy Type 1 ORR overall response rate PARP poly (ADP-ribose) polymerase Regional Abbreviations: CN: China; EU: Europe; JP: Japan; US: United States of America