Takeda Pharmaceutical Co. Ltd. · TSE:4502
Takeda Pharmaceutical — Investor Day (November 2019)
149 slides from Takeda Pharmaceutical's investor day presentation, Nov 21, 2019
Slide 1: Takeda R&D Investor Day 2019
TAKEDA R&D INVESTOR DAY 2019 Tokyo, Japan November 21, 2019
Slide 2: R&D Day Agenda – Tokyo, November 21, 2019
R&D DAY AGENDA – TOKYO, NOVEMBER 21, 2019 TIME AGENDA Welcome and Introduction of Presenters 11:00 – 11:05 Ayako Iwamuro, Investor Relations, Global Finance Realizing the Potential of Plasma‐derived Therapies 11:05 – 11:45 Julie Kim, President, Plasma‐Derived Therapies Business Unit A New Dedicated
Slide 3: Important Notice
IMPORTANT NOTICE For the purposes of this notice, “presentation” means this document, any oral presentation, any question and answer session and any written or oral material discussed or distributed by Takeda Pharmaceutical Company Limited (“Takeda”) regarding this presentation. This presentation (i
Slide 4: Slide 4
Slide 5: People Dedicated to Bringing Better Health to Patients
PEOPLE DEDICATED TO BRINGING BETTER HEALTH TO PATIENTS | 4
Slide 6: Global locations: Zurich, Tokyo, Greater Boston, Singapore
ZURICH TOKYO Takeda Global HQ GREATER BOSTON SINGAPORE AREA Global Hub 5
Slide 7: Research and manufacturing sites
GREATER TOKYO BOSTON Takeda AREA Global HQ Global Hub 3 36 RESEARCH MANUFACTURING SITES SITES 6
Slide 8: Countries of operation
GREATER TOKYO BOSTON Takeda AREA Global HQ Global Hub COUNTRIES 27 7
Slide 9: Integrity
INTEGRITY AN Perseverance (AE) (Ee) TAKEDA-ISM
Slide 10: Takeda-ism: Integrity, Fairness, Honesty, Perseverance
ih NE Perseverance i “SIE \ ( EB INTEGRITY Fairness Honesty TAKEDA-ISM |:
Slide 11: Patient
PATIENT
Slide 12: Takeda-ism
ih NE Perseverance i “SIE \ ( EB INTEGRITY Fairness Honesty TAKEDA-ISM |
Slide 13: Innovation
INNOVATION © &VY) 2° PATIENTS w= ACCESS TO Ro MEDICINE ams) SOCIETY Ww) fm, CORPORATE SOCIAL GOVERNMENT RESPONSIBILITY AGENCIES
Slide 14: Trust / Reputation
| ‘ \ A TRUST / |REPUTATION 92 | 4S1F \ ( Ee Fairness Honesty Perseverance TAKEDA-ISM J INTEGRITY
Slide 15: Fee
Fee rH: = pila
Slide 16: Long-term value for patients, society and investors
LONG-TERM VALUE FOR PATIENTS, SOCIETY AND INVESTORS
Slide 17: Science-driven company with a focused mind
SCIENCE DRIVEN COMPANY WITHA FOCUSED MIND __ BRINGIN >> INNOVATIOF -TO PATIENTS
Slide 18: Positioned for Sustainable Revenue Growth
Positioned for Sustainable Revenue Growth Potential Wave 2 pipeline not included WAVE 1 Vyvanse i) PIPELINE” Velcade WAVE 1 Entyvio Azilva PIPELINE Hemophilia} 14 GLOBAL 14 BRANDS GLOBAL BRANDS 2018 2024 2029 PRO-FORMA REVENUE Note: The above chart represents conceptual changes in revenue through 20
Slide 19: Slide 19
Slide 20: R&D Day Agenda
R&D DAY AGENDA – TOKYO, NOVEMBER 21, 2019 TIME AGENDA Welcome and Introduction of Presenters 11:00 – 11:05 Ayako Iwamuro, Investor Relations, Global Finance Realizing the Potential of Plasma‐derived Therapies 11:05 – 11:45 Julie Kim, President, Plasma‐Derived Therapies Business Unit A New Dedicated
Slide 21: Translating Science into Highly Innovative Life-Changing Medicines
TRANSLATING SCIENCE INTO HIGHLY INNOVATIVE LIFE‐CHANGING MEDICINES Andy Plump MD, PhD President R&D Takeda Pharmaceutical Company Limited Tokyo November 21, 2019
Slide 22: What You Will Hear Today
WHAT YOU WILL HEAR TODAY 132 Our portfolio We are investing in We have cultivated and pipeline will novel mechanisms an environment of drive growth and and capabilities for empowerment, offset key patent a sustainable accountability and expirations future agility 21
Slide 23: Positioned to Deliver Near-Term and Sustained Growth
WE ARE POSITIONED TO DELIVER NEAR‐TERM & SUSTAINED GROWTH WAVE 11 WAVE 22 TARGET CLINICAL‐STAGE NMEs PLATFORMS APPROVAL FY20 FY21 FY22 FY23 FY24 FY25 AND BEYOND TAK‐7883 TAK‐007 TAK‐924 TAK‐164 TAK‐252 2L NSCLC Hematologic AML GI malignancies Solid tumors TARGETED malignancies CELL THERAPY INNATE NE
Slide 24: 2019: A Watershed Year for Takeda
2019: A WATERSHED YEAR FOR TAKEDA INTEGRATION OF SHIRE EXPANSION OF OUR GLOBAL BRANDS UNPRECEDENTED NMEs • 18 assets added to the clinical pipeline* • VARSITY study demonstrated head‐to‐head • 17 NMEs in Phase 2 and Phase 3 superiority of Entyvio vs adalimumab and • Creation of a Rare Diseases Thera
Slide 25: Patient-Driven and Science-First in Core Areas
PATIENT‐DRIVEN AND SCIENCE‐FIRST IN 3 CORE AREAS INNOVATIVE BIOPHARMA ONCOLOGY RARE DISEASES NEUROSCIENCE GASTROENTEROLOGY PLASMA DERIVED THERAPIES VACCINES BUSINESS UNIT Complementing our Differentiated rare disease focus Dengue vaccine 24
Slide 26: We Are Doing More for Our Patients
WE ARE DOING MORE FOR OUR PATIENTS 8 ~40 ~4,500 POTENTIAL BIC/FIC NMEs IN NEW MOLECULAR R&D EMPLOYEES PIVOTAL STUDIES1 ENTITY CLINICAL GLOBALLY STAGE ASSETS PIPELINE WITH DIVERSIFIED ~70% ~50% ORPHAN DRUG MODALITIES 2 200+ DESIGNATION IN RESEARCH ACTIVE PARTNERSHIPS 1. BIC/FIC Best‐In‐Class/First‐In
Slide 27: Taking Courageous Risks to Make a Critical Difference
WE ARE TAKING COURAGEOUS RISKS TO MAKE A CRITICAL DIFFERENCE “There is a considerable need for improved treatments for Accelerated programs Cell Tx 5 individuals with NT1, which is Gene Tx caused by the loss of orexin‐ Biologics producing neurons in the brain” NME stage‐ups since FY18 Peptides ~70%
Slide 28: Cultivating the Best Science Through Differentiated Partnerships
WE ARE CULTIVATING THE BEST SCIENCE THROUGH DIFFERENTIATED PARTNERSHIPS… Select partnerships* Access to Innovation RESEARCH IN‐LICENSE Risk‐Sharing COLLABORATIONS ~ 110 ~ 50 Expanding Capacity JOINT NEWCO DEVELOPMENT FORMATION ~ 20 ~ 20 Total Value in Public & Private Equity >$1B * Externalizations
Slide 29: Nurturing Innovation Wherever It Occurs
WE ARE NURTURING INNOVATION WHEREVER IT OCCURS CHARACTERISTICS TAKEDA PARTNER‐SOURCED TAKEDA GREATER VALIDATION TAK‐925, TAK‐994 Narcolepsy TAK‐573 Multiple Myeloma DEVELOPS & AND / OR LOWER COMMERCIALIZES DEVELOPMENT COST TAK‐951 Vomiting Syndromes CD19 1XX (CAR‐T) TAK‐924 Myelodysplastic Syndrome
Slide 30: Driving Higher Return on $4.5B Annual R&D Investment
TO DRIVE HIGHER RETURN ON OUR $4.5B ANNUAL R&D INVESTMENT PRIORITIZED R&D PORTFOLIO FLEXIBLE R&D FUNDING MODEL BALANCED SPEND TARGETED POPULATIONS PARTNERSHIP MODEL Minimize internal spend and Smaller trials, lower costs, potential Success driven milestone infrastructure longer exclusivity payments
Slide 31: A Research Engine Fueling a Sustainable Pipeline
A RESEARCH ENGINE FUELING A SUSTAINABLE PIPELINE POTENTIAL NME PIVOTAL STUDY STARTS BY YEAR IMPROVED PRODUCTIVITY • Research momentum building with a projected ~18 portfolio Projected Clinical ReplenishmentResearch entries in FY19 Pipeline Engine • Productivity likely to increase with 11 expansion o
Slide 32: Pipeline Investments Supporting Near-Term Growth Wave
PIPELINE INVESTMENTS SUPPORTING NEAR‐TERM GROWTH WAVE 1 INNOVATIVE EXPANSIONS NEW MOLECULAR ENTITIES
Slide 33: Driving Expansion of Our Global Brands
WE ARE DRIVING EXPANSION OF OUR GLOBAL BRANDS SELECT GLOBAL GROWTH BRANDS TAU Therapies New Indications / Geographic Expansions Target (FY) Alunbrig 1L Non Small Cell Lung Cancer 2020 ONC Ninlaro ND MM Maintenance (non‐SCT and post‐SCT) 2020 / 2022 Entyvio Bradykinin Mediated Angioedema 2024 Rare *
Slide 34: Wave 1 NMEs Potential >$10B Aggregate Peak Sales
WAVE 1 NEW MOLECULAR ENTITIES HAVE POTENTIAL TO DELIVER >$10B AGGREGATE PEAK SALES… TARGET APPROVAL1 FY20 FY21 FY22 FY23 FY24 2 TAK‐007 TAK‐788 Hematologic TAK‐924 2L NSCLC malignancies AML ONCOLOGY TAK‐9242 TAK‐788 HR‐MDS 1L NSCLC 14 potential NME launches which TAK‐620 TAK‐611 TAK‐607 CMV infect.
Slide 35: Expected to Deliver Life-Changing Medicines
…AND ARE EXPECTED TO DELIVER LIFE‐CHANGING MEDICINES POTENTIAL FIRST‐IN‐CLASS OR BEST‐IN‐CLASS NMEs TARGET ADDRESSABLE ADDRESSABLE PRODUCT MECHANISM INDICATION APPROVAL DATE POPULATION POPULATION (FY)1 (IN US)2 (WW)2,3 TAK‐788 EGFR inhibitor (exon 20) NSCLC – 2L / 1L 20214 / 2023 ~2k ~20 ‐ 30k pevon
Slide 36: In Summary: Robust Near-Term Growth
IN SUMMARY: ROBUST NEAR‐TERM GROWTH TAK‐609 Hunter CNS (IT) Potential NME Approval Eosinophilic TAK‐721 TAK‐003 Dengue vaccine Esophagitis1 Potential Global Brand Extension UC/CD, CN maribavir ENTYVIO CMV transplant sc UC/CD, US, EU, JP2 TAK‐620 Potential Regional Brand Extension NDMM nSCT, US, pevo
Slide 37: Sustained Growth Beyond FY25 Wave
SUSTAINED GROWTH BEYOND FY25 WAVE 2 NOVEL MECHANISMS NEXT‐GENERATION PLATFORMS
Slide 38: Clinical Pipeline of Novel Mechanisms
DRIVEN BY A CLINICAL PIPELINE OF NOVEL MECHANISMS… TARGET APPROVAL1 FY25 AND BEYOND TAK‐164 TAK‐252 GI malignancies Solid tumors ONCOLOGY TAK‐573 TAK‐981 R/R MM Multiple cancers TAK‐0792 TAK‐754 TAK‐755 MG, ITP HemA iTTP, SCD RARE Immunology Rich early Hematology DISEASES Metabolic TAK‐531 Hunter CN
Slide 39: Next-Generation Platforms
…AND WITH OUR NEXT‐GENERATION PLATFORMS TARGET APPROVAL FY25 AND BEYOND CELL THERAPIES AND TARGETED INNATE IMMUNE NEXT‐GEN CHECKPOINT IMMUNE ENGAGERS MODULATION MODULATORS Attenukine Agonist‐redirected checkpoints CAR‐T GammaDelta Teva MSKCC, Noile‐ CAR‐T Shattuck ONCOLOGY Immune GammaDelta Tx STING
Slide 40: Investing in Capabilities to Position Us for Success
INVESTING IN CAPABILITIES TO POSITION US FOR SUCCESS • 5 clinical programs by end of FY20 Cell Therapy • Disruptive platforms, including off‐the‐ shelf cell‐therapies • World‐class gene therapy manufacturing Gene Therapy • Accessing innovation through partnerships (e.g. Stridebio, Ambys) • Accelerat
Slide 41: Committed to Our People
COMMITTED TO OUR PEOPLE 40
Slide 42: Living Our Values Throughout the Integration Process
LIVING OUR VALUES THROUGHOUT THE INTEGRATION PROCESS December 2018 Leadership Team and Proposed R&D Operating Model Announced April 2019 Prioritization of Combined Pipeline and Portfolio August 2019 R&D Employees Informed of Employment Status* 41 * Where legally cleared
Slide 43: Strong Leadership Executing on Our Vision
STRONG LEADERSHIP EXECUTING ON OUR VISION ASIT PARIKH PHIL ROWLANDS DAN CURRAN EMILIANGELO RATTI SARAH SHEIKH New hire Head, Gastroenterology Head, Oncology Head, Rare Diseases Head, Neuroscience Head, Neuroscience Therapeutic Area Unit Therapeutic Area Unit Therapeutic Area Unit Therapeutic Area Un
Slide 44: Our Commitment to Our People Is Being Recognized
OUR COMMITMENT TO OUR PEOPLE IS BEING RECOGNIZED 43
Slide 45: Positioned to Deliver Near-Term and Sustained Growth
WE ARE POSITIONED TO DELIVER NEAR‐TERM & SUSTAINED GROWTH WAVE 11 WAVE 22 TARGET CLINICAL‐STAGE NMEs PLATFORMS APPROVAL FY20 FY21 FY22 FY23 FY24 FY25 AND BEYOND TAK‐7883 TAK‐007 TAK‐924 TAK‐164 TAK‐252 2L NSCLC Hematologic AML GI malignancies Solid tumors TARGETED malignancies CELL THERAPY INNATE NE
Slide 46: R&D Day Agenda
R&D DAY AGENDA – TOKYO, NOVEMBER 21, 2019 TIME AGENDA Welcome and Introduction of Presenters 11:00 – 11:05 Ayako Iwamuro, Investor Relations, Global Finance Realizing the Potential of Plasma‐derived Therapies 11:05 – 11:45 Julie Kim, President, Plasma‐Derived Therapies Business Unit A New Dedicated
Slide 47: Takeda Oncology: Innovative Cell Therapies and New Frontiers in Immuno-Oncology
TAKEDA ONCOLOGY: INNOVATIVE CELL THERAPIES & NEW FRONTIERS IN IMMUNO‐ONCOLOGY Chris Arendt, PhD Head of Oncology Drug Discovery Unit Takeda Pharmaceutical Company Limited Tokyo November 21, 2019
Slide 48: A Curative-Intent Immuno-Oncology Pipeline Is Taking Shape
A CURATIVE‐INTENT IMMUNO‐ONCOLOGY PIPELINE IS TAKING SHAPE WAVE 1 WAVE 2 NMEs that complement our global brands Leading platforms in immuno‐oncology and cell therapies Hematologic Hematologic Immuno‐Oncology Malignancies TAK‐924 Malignancies FY21 target approval TAK‐007 FY23 target approval Lung Can
Slide 49: Partnerships Drive Our Differentiated Early Clinical Pipeline
PARTNERSHIPS DRIVE OUR DIFFERENTIATED EARLY CLINICAL PIPELINE Unique Differentiated Partnership Portfolio Model • Innovative, disruptive platforms • Harness innate immunity • Agility in ‘open lab’ model • Eye towards solid tumors 48
Slide 50: First Breakthroughs in Cancer Immunotherapy Target T Cells
THE FIRST BREAKTHROUGHS IN CANCER IMMUNOTHERAPY TARGET T CELLS T CELL CHECKPOINT INHIBITORS FIRST‐GEN CAR‐Ts PD‐1 T cell CAR T cell CTLA‐4 Cancer cell death 49 Adapted from Chen & Mellman, Immunity 2013
Slide 51: Focus on Novel Mechanisms in the Cancer-Immunity Cycle
OUR FOCUS IS ON NOVEL MECHANISMS IN THE CANCER‐IMMUNITY CYCLE 2 Novel‐scaffold immune checkpoint platforms Next‐gen cell therapy & 3 immune engager platforms 1 Innate immuno‐ modulation Cancer cell death 50 Adapted from Chen & Mellman, Immunity 2013
Slide 52: Emerging Strength in Targeted Innate Immune Modulation
EMERGING STRENGTH IN TARGETED INNATE IMMUNE 1 MODULATION HIGH UNMET Patients refractory/ unresponsive to current NEED immunotherapies OUR Systemic therapies leveraging innate immunity to DIFFERENTIATED enhance response breadth, depth & durability APPROACH Cancer cell death PLATFORM PARTNER MECHANISM
Slide 53: Attenukine Platform Elicits Direct Tumor Kill and Immune Activation
ATTENUKINETM PLATFORM ELICITS BOTH DIRECT 1 TUMOR KILL AND IMMUNE ACTIVATION TARGETED ATTENUATED TYPE I IFN PAYLOAD TAK‐573 POM IN ONGOING PHASE 1 R/R MM STUDY TAK‐573 Activation of CD8+ T cells in bone marrow Binds CD38 Immunomodulation in Baseline preclinical models Cycle 1 Day 16 Cycle 2 Day 2 7.
Slide 54: Novel Scaffold Next-Generation Checkpoint Modulators
2 NOVEL SCAFFOLD NEXT‐GENERATION CHECKPOINT MODULATORS HIGH UNMET Current checkpoint modulators fail to improve NEED overall survival in majority of patients OUR New classes of checkpoint inhibitors designed DIFFERENTIATED to increase breadth and depth of responses APPROACH Cancer cell death PLATFOR
Slide 55: Bringing Novel Cell Therapy Platforms to the Clinic by End of FY20
BRINGING 5 NOVEL CELL THERAPY PLATFORMS 3 TO THE CLINIC BY THE END OF FY20 HIGH UNMET Current CAR‐T therapies have significant NEED challenges & fail to address solid tumors OUR Leverage novel cell platforms & engineering to DIFFERENTIATED address shortcomings in liquid & solid tumors APPROACH Cance
Slide 56: Network of Top Innovators Fueling Takeda's Cell Therapy Engine
A NETWORK OF TOP INNOVATORS IS 3 FUELING TAKEDA’S CELL THERAPY ENGINE CUTTING‐EDGE ENGINEERING & CELL PLATFORMS IPSC T cell Armored Next‐gen IPSC CAR‐NK expertise platform CAR‐Ts CARs CAR‐Ts platform Shinya Adrian Koji Michel Shin Katy Yamanaka Hayday Tamada Sadelain Kaneko Rezvani 2019 2016 2017
Slide 57: Transformative CAR-NK Partnership
TAKEDA IS EMBARKING ON A TRANSFORMATIVE CAR‐NK 3 PARTNERSHIP THAT COULD ENTER PIVOTAL TRIALS IN 2021 IL‐15 Activating NK CAR NK receptor Platform Multiple mechanisms of tumor killing Potentiation of innate & adaptive immunity CAR19 56
Slide 58: Four Novel Off-the-Shelf CAR-NK Therapies in Development
3 FOUR NOVEL, OFF‐THE‐SHELF CAR‐NK THERAPIES IN DEVELOPMENT PATIENT VALUE PROPOSITION PLATFORM VALUE INFLECTIONS Rapid and deep responses with a short‐time‐to‐treatment, FY safe, off‐the‐shelf CAR‐NK available in outpatient & Ongoing maturation of clinical data: Efficacious dose, community settings
Slide 59: Dramatic Complete Response in First Patient Treated
3 DRAMATIC COMPLETE RESPONSE IN FIRST PATIENT TREATED 47‐YEAR OLD MALE WITH RELAPSED TRANSFORMED KINETICS OF CAR‐NK VERSUS ENDOGENOUS T AND B DOUBLE‐HIT (C‐MYC / BCL‐2) DLBCL CELLS IN PERIPHERAL BLOOD CAR‐NK cells % positive cells Days post‐CAR‐NK infusion T cells X1000/ml of blood B cells Baseline
Slide 60: Impressive Responses in Other Heavily Pretreated Patients
3 IMPRESSIVE RESPONSES IN OTHER HEAVILY PRETREATED PATIENTS 61‐YEAR OLD MALE CLL/RICHTER’S TRANSFORMATION 60‐YEAR OLD FEMALE WITH CLL / ACCELERATED CLL (5 PRIOR LINES OF THERAPY) (5 PRIOR LINES OF THERAPY) CAR‐NK Baseline scan Day 30 post CAR19‐NK Baseline scan Day 30 post CAR19‐NK CR in Richter’s;
Slide 61: CAR-NK Cells Persist and Do Not Trigger CRS
CAR‐NK CELLS PERSIST IN PATIENTS AND DO NOT TRIGGER 3 CYTOKINE RELEASE SYNDROME (CRS) CAR‐NK CELLS PERSIST UP TO 4 MONTHS POST INFUSION IL‐6 LEVLS POST CAR‐NK INFUSION DO NOT INDICATE CRS Median IL‐6 level in grade 2‐5 CRS post‐CAR‐T treatment* g of genomic DNA IL‐6 (pg/ml) Vector transgene copy p
Slide 62: CAR-NK Efficacy and Toxicity
3 CAR‐NK EFFICACY & TOXICITY TREATING MULTPLE DIAGNOSES Lines of CRS / Complete Diagnosis HLA Match Treatment Neurotox Response DLBCL ‐ Relapsed transformed double‐hit 3 Partial match None Incl. ASCT Dose DLBCL ‐ Refractory 7 Partial match None PD Level 1 CLL 4 Partial match None Incl. ibrutinib &
Slide 63: Fast-to-Clinic Cell Therapy Engine
FAST‐TO‐CLINIC CELL THERAPY ENGINE WILL MAXIMIZE 3 LEARNINGS ON MULTIPLE ‘DISRUPTIVE’ PLATFORMS 5 CLINICAL‐STAGE PROGRAMS EXPECTED BY END OF FY20 FY19 FY20 FY21+: Other cell Cytokine + therapy TAK‐007 Off‐the‐shelf TAK‐102 chemokine CAR‐NK product candidates armed CAR‐T CD19 1XX‐CAR‐T Next‐gen CART
Slide 64: Rich Early Clinical Oncology Pipeline
A RICH AND POTENTIALLY TRANSFORMATIVE EARLY CLINICAL 3 ONCOLOGY PIPELINE PLATFORM PARTNER(S) MECHANISM‐OF‐ACTION PROGRAMS PRECLINICAL PH1 TAK‐676 (STING agonist) STING agonism • Innate‐to‐adaptive priming UNDISCLOSED Targeted STING agonist TARGETS TAK‐981 SUMOylation • Innate immune enhancer TAK‐981
Slide 65: NME Milestones Achieved in FY19 and Looking Ahead
NME MILESTONES ACHIEVED IN FY19 AND LOOKING AHEAD TO OTHER POTENTIAL MILESTONES1 THROUGH FY20 PIVOTAL STUDY STARTS, APPROVALS MLD PEVONEDISTAT AML EoE TAK‐611 TAK‐721 Ph 2 start2 TAK‐924 Ph 3 start Approval cTTP 1L NSCLC Huntington’s Disease TAK‐755 TAK‐788 mHTT ASO Ph 3 start Ph 3 start Pivot
Slide 66: Summary
SUMMARY 132 Total transformation Differentiated Multiple near‐term of preclinical & early opportunities in IO catalysts informing clinical pipeline leveraging innate momentum towards immunity & cell solid tumors therapies 65
Slide 67: R&D Day Agenda
R&D DAY AGENDA – TOKYO, NOVEMBER 21, 2019 TIME AGENDA Welcome and Introduction of Presenters 11:00 – 11:05 Ayako Iwamuro, Investor Relations, Global Finance Realizing the Potential of Plasma‐derived Therapies 11:05 – 11:45 Julie Kim, President, Plasma‐Derived Therapies Business Unit A New Dedicated
Slide 68: TAK-788: Fast-to-Patient Strategy for NSCLC with EGFR Exon 20 Insertions
TAK‐788: PURSUING A FAST‐TO‐PATIENT STRATEGY FOR NSCLC PATIENTS WITH EGFR EXON 20 INSERTIONS Rachael L Brake, PhD Global Program Leader, Oncology Takeda Pharmaceutical Company Limited Tokyo November 21, 2019
Slide 69: The Size of the Lung Cancer Challenge Is Vast
THE SIZE OF THE LUNG CANCER CHALLENGE IS VAST Survival of Lung cancer is amongst 228,0001 the lowest of all cancers New Lung cancer cases / year Male Female 1 10% 13% 143,000 survival survival Lung cancer deaths/ yr More than breast, colon, and prostate cancer combined 5 yr survival estimates among
Slide 70: Exon Insertions Are a Rare Subset of EGFR Mutant NSCLC
EXON 20 INSERTIONS ARE A RARE SUBSET OF EGFR MUTANT NSCLC Non‐Sq NSCLC EGFR Exon 20 insertions 1 200,000 pts/yr 2,000 pts/yr2 EGFR Sensitizing Mutations 19.4% No Mutations 1.2% EGFR exon18 4% UMD 12.0% EGFR exon19 45% EGFR exon21 41% Other Drivers 2.9% Insertion variants PTEN loss 0.7% CDKN2A loss 1
Slide 71: No Effective Therapy for EGFR Exon Insertions
PATIENTS WITH EGFR EXON 20 INSERTIONS HAVE NO EFFECTIVE THERAPY POOR RESPONSE TO EXISTING TKIs 1 POOR RESPONSE TO ANTI PD‐1/PDL‐1 THERAPY 2 EGFR exon 20 insertions do not demonstrate EGFR exon 20 ins patients demonstrate limited significant PFS benefit with 1st and 2nd gen EGFR TKIs benefit to anti
Slide 72: Overcoming the Drug Development Challenge in Exon Insertions
OVERCOMING THE DRUG DEVELOPMENT CHALLENGE IN EXON 20 INSERTIONS EGFR exon 20 NPG insertion L858R EGFR mutation Wild type EGFR Wild type EGFR Classical EGFR mutation L858R TAK‐788 TAK‐788 EGFR exon 20 insertion EGFR D770 ins NPG EGFR exon 20 insertion mutations Classical EGFR mutations have a similar
Slide 73: TAK-788 Proof of Concept Data
TAK‐788 PROOF OF CONCEPT DATA IN EGFR EXON 20 INSERTIONS • Confirmed ORR: 12/28 patients: 43% (24.5‐62.8%) • Median PFS: 7.3 months (4.4 mo ‐ NR) ANTITUMOR ACTIVITY IN EGFR EXON 20 INS AT 160 MG DAILY SAFETY SUMMARY IN PATIENTS TREATED WITH TAK‐788 All Patients 80 N (%) 160 mg qd (n=72) 60 40 Treatm
Slide 74: Encouraging Efficacy and Safety Observed with TAK-788
ENCOURAGING EFFICACY AND SAFETY HAS BEEN OBSERVED WITH TAK‐788 Select signs of efficacy TAK‐788 1 Poziotinib 2 Afatinib 3 Osimertinib 4 Clinical feature n=28 n=50 n=23 n=15 ITT confirmed ORR (%) 43% NR 8.7% 0% Evaluable confirmed ORR (%) NR 43% NR NR ITT median PFS (months) 7.3 5.5 2.7 3.5 Select tr
Slide 75: Stronger Diarrhea Management Should Enhance Efficacy
STRONGER DIARRHEA MANAGEMENT SHOULD = ENHANCED EFFICACY Average time on TAK‐788 June 2016 7.9 months Feb 2019 new trial FIRST IN HUMAN Time on Diarrhea Diarrhea Treatment (Mo) management very Comprehensive Grade 3 4.6 late ‐ medicate diarrhea management when at Grade 2 Grade 2 9.8 Grade 1 12.7 guide
Slide 76: 2021: Expected First Approval in EGFR Exon Insertions
2021: EXPECTED FIRST APPROVAL IN EGFR EXON 20 INSERTIONS ∙ Single arm Phase 2 trial ∙ Supporting data generation ∙ Refractory EGFR Exon 20 insertion patients ∙ Real world evidence (RWE) data collection • Previously treated, ≤2 systemic anticancer chemotherapy RWE will be used to assess the benefit o
Slide 77: New Activation: Trial for Newly Diagnosed Patients
NEW ACTIVATION: A TRIAL FOR NEWLY DIAGNOSED PATIENTS ∙ Randomized, controlled, Phase 3 trial ∙ Treatment‐naïve EGFR exon 20 insertion patients • Advanced or metastatic • Treatment‐naïve patients diagnosed with NSCLC harboring EGFR exon 20 insertion mutations R ‐2 1:1 TAK‐788 at 160 mg qd Platinum do
Slide 78: Summary
SUMMARY 132 NSCLC patients with TAK‐788 is the first The EXCLAIM trial in EGFR Exon 20 insertions purposely designed refractory patients are underserved with inhibitor and clinical could lead to the first the current available proof‐of‐concept has approval of TAK‐788 therapies demonstrated efficacy
Slide 79: Pevonedistat (TAK-924): Potential New Treatment for HR-MDS and AML
PEVONEDISTAT (TAK‐924): A POTENTIAL NEW TREATMENT FOR HR‐MDS AND AML Phil Rowlands, PhD Head Oncology Therapeutic Area Unit Takeda Pharmaceutical Company Limited Tokyo November 21, 2019
Slide 80: Building on Takeda Oncology Foundation in Hematologic Malignancies
BUILDING ON THE TAKEDA ONCOLOGY FOUNDATION IN HEMATOLOGIC MALIGNANCIES Next Generation Cell therapies Type I IFN I/O Novel checkpoints GROWING MDS/AML LEADERSHIP Phase 3 POSITION IN pevonedistat HEMATOLOGIC MALIGNANCIES Lymphoma Chronic Myeloid Leukemia Improving Patient Outcomes in Multiple Myeloma
Slide 81: HR-MDS and AML Have Limited Treatment Options
HIGH RISK MYELODYSPLASTIC SYNDROME (HR‐MDS) AND ACUTE MYELOID LEUKEMIA (AML) HAVE LIMITED TREATMENT OPTIONS CONTINUUM OF HR‐MDS AND AML CLINICAL TREATMENT BM failure → cytopenias Clinical treatment goals: Blasts • Fatigue (anemia) Alleviate cytopenias 20% 30% • Infection (neutropenia) Improve patien
Slide 82: Current Standard of Care Is Inadequate for HR-MDS
CURRENT STANDARD OF CARE IS INADEQUATE FOR HR‐MDS PATIENTS MDS SURVIVAL BY PROGNOSTIC RISK • No new treatments have been approved for MDS in over a decade • Transplant ineligible patients treated with first line therapy: Median OS = 15mo; 2yr OS rate 35% Survival (probability) • Economic burden is s
Slide 83: Pevonedistat: A First-in-Class NAE Inhibitor
PEVONEDISTAT: A UNIQUE FIRST‐IN‐CLASS NAE INHIBITOR • Pevonedistat is a small molecule inhibitor of NAE (NEDD‐8 activating enzyme), a protein involved in the ubiquitin‐proteasome system • NAE acts upstream of the proteasome and catalyzes the first step in the neddylation pathway Amir T. Fathi Blood
Slide 84: Encouraging Responses in AML with Pevonedistat + Azacitidine
ENCOURAGING RESPONSES IN AML PATIENTS TREATED WITH PEOVNEDISTAT + AZACITIDINE 60% ORR with a trend towards improved survival in secondary AML Response rates not influenced by AML genetic risk or leukemia burden Initial data drove interest to move to registration Ronan T Swords et al. Blood 2016;128:
Slide 85: Phase 2 Study in HR-MDS
A PHASE 2 STUDY IN HR‐MDS TO CONFIRM THE RISK / BENEFIT PROFILE OBSERVED IN AML Phase 2, Randomized, Open‐label, Global, Multicenter Study Comparing Pevonedistat Plus Azacitidine vs. Azacitidine in Patients with Higher‐Risk MDS, CMML, or Low‐Blast AML • Mature OS data will be n = 117 available in No
Slide 86: Phase 3 PANTHER Study
THE PHASE 3 PANTHER STUDY WAS INITIATED AT RISK TO ACCELERATE DEVELOPMENT Phase 3, Randomized controlled trial of Pevonedistat Plus Azacitidine Versus Single‐Agent Azacitidine as First‐Line Treatment for Patients with Higher risk‐MDS/CMML, or Low‐blast AML n = 450 • Completed global enrollment Pevon
Slide 87: Expanding Patient-Centric Development of Pevonedistat
EXPANDING PATIENT‐CENTRIC DEVELOPMENT OF PEVONEDISTAT Continuum of disease HR‐MDS NEW STUDIES IN UNFIT AML Ph2 (P2001) Ph3 (P3001) Ph3 PEVOLAM Potential Utilizing partnership approval in FY21* pevo + aza vs. aza (PETHEMA) for Currently enrolling patients efficient development Ph2 (P2002) Combo Uniqu
Slide 88: Summary
SUMMARY 132 Unmet need in High‐ Pevonedistat is a The Ph2 HR‐MDS trial risk MDS and AML selective first‐in‐class has reached the remain high with few inhibitor with updated OS endpoint treatment options potential to be first data readout and the new therapy in over PANTHER Ph3 trial a decade for HR‐
Slide 89: R&D Day Agenda
R&D DAY AGENDA – TOKYO, NOVEMBER 21, 2019 TIME AGENDA Welcome and Introduction of Presenters 11:00 – 11:05 Ayako Iwamuro, Investor Relations, Global Finance Realizing the Potential of Plasma‐derived Therapies 11:05 – 11:45 Julie Kim, President, Plasma‐Derived Therapies Business Unit A New Dedicated
Slide 90: Rare Diseases & Gene Therapy
RARE DISEASES & GENE THERAPY Dan Curran, MD Head Rare Diseases Therapeutic Area Unit Takeda Pharmaceutical Company Limited Tokyo November 21, 2019
Slide 91: Rare Diseases: An Opportunity to Transform Treatment
RARE DISEASES: AN OPPORTUNITY TO TRANSFORM TREATMENT HIGH UNMET NEED SCIENTIFIC AND REGULATORY ADVANCES Diseases are genetic Distinct rare diseases1 7,000 80% in origin Recombinant 350 Transformative engineering & delivery Patients worldwide million therapies of proteins and nucleic acids 2 Orphan d
Slide 92: Rare Disease Market Expected to Double in Size
RARE DISEASE MARKET IS EXPECTED TO DOUBLE IN SIZE GLOBAL ORPHAN DRUG1 SALES EXCLUDING ONCOLOGY2, USD BN % share of global, branded Rx sales 7% 11% 17% • Orphan drugs expected to make 124 up ~17% of global branded Rx sales by 2024 12% • Growth driven by advances in new CAGR modalities and new indicat
Slide 93: Takeda Is the Leader in Rare Diseases
TAKEDA IS THE LEADER IN RARE DISEASES PATIENT IMPACT SCIENCE & INNOVATION CAPABILITIES AND SCALE • Foundation of >30 year history • Multiple opportunities for • Engagement with key of leadership in rare diseases transformational therapies stakeholders within the across therapeutic areas ecosystem e.
Slide 94: Strategy to Transform and Cure Rare Diseases
OUR STRATEGY IS TO TRANSFORM AND CURE RARE DISEASES As the global leader in Rare Diseases, we aspire to provide transformative and curative treatments to our patients Transformative Curative Programs with transformative Emerging early pipeline of AAV potential in devastating gene therapies to redefi
Slide 95: Positioned to Deliver Near-Term and Sustained Growth
WE ARE POSITIONED TO DELIVER NEAR‐TERM & SUSTAINED GROWTH WAVE 11 WAVE 22 TARGET CLINICAL‐STAGE NMEs PLATFORMS APPROVAL FY20 FY21 FY22 FY23 FY24 FY25 AND BEYOND TAK‐620 TAK‐607 TAK‐7883 TAK‐007 TAK‐924 TAK‐164 CMV infect. in TAK‐252 2L NSCLC Hematologic AML GI malignancies Solid tumors Complications
Slide 96: Potential Approvals of Transformative Therapies
POTENTIAL APPROVALS OF TRANSFORMATIVE THERAPIES WAVE 11 Phase 3 Phase 3 Phase 3 Phase 2 Phase 2Phase 1/2 Phase 2b TAK‐721 TAK‐620 TAK‐755 TAK‐611 TAK‐935 Orexin TAK‐607 Eosinophilic Cytomegalovirus Congenital Metachromatic Developmental Narcolepsy Type 1 Complications of Esophagitis (CMV) infection
Slide 97: Selected Transformative Programs
SELECTED TRANSFORMATIVE PROGRAMS Potential first treatment of CMV infection in transplant patients in over 10 years. TAK‐620 Inhibitor of protein kinase UL97. Potential best‐in‐class therapy for Thrombotic Thrombocytopenic Purpura (TTP). TAK‐755 Recombinant ADAMTS13. Potential first pharmacologic th
Slide 98: TAK-620: Potential Best in Class Treatment for Post-Transplant CMV
TAK‐620: POTENTIAL BEST IN CLASS TREATMENT FOR POST‐ TRANSPLANT CMV INFECTION BURDEN OF CMV INFECTION IN TRANSPLANT RECIPIENTS TAK‐620: NOVEL MOA TARGETING PROTEIN KINASE UL97 CMV infection is the most common 1 post‐transplant viral infection1 2 Affects >25% of transplants 4 5 CMV infection can be f
Slide 99: TAK-620 Addresses Unmet Need in First-Line and R/R Settings
TAK‐620 ADDRESSES UNMET NEED IN BOTH FIRST‐LINE AND RESISTANT / REFRACTORY SETTING CMV Failure First‐Line: Newly Resistant/ Transplant treatment Viremia First‐Line diagnosed CMV Refractory (R/R) CMV TAK‐620: Ph 3 Study 303 ~100K ~30K ~5K Solid organ transplant (SOT) patients1,2: TAK‐620: Ph 3 Study
Slide 100: TAK-620 Similar Efficacy and Better Safety vs SOC in Phase 2
TAK‐620 DEMONSTRATED SIMILAR EFFICACY AND BETTER SAFETY VERSUS SOC IN A PHASE 2 STUDY IN FIRST‐LINE PATIENTS DEMONSTRATED SIMILAR ANTI‐VIRAL ACTIVITY TO NEUTROPENIA WAS TREATED WITH GROWTH FACTORS MORE VALGANCICLOVIR (VGV) ACROSS ALL DOSES1 OFTEN IN THE VGV ARM (15%) VS. TAK‐620 ARM (7%)2 TAK‐620: T
Slide 101: TAK-620 Breakthrough Designation in R/R CMV
TAK‐620: GRANTED BREAKTHROUGH DESIGNATION IN RESISTANT OR REFRACTORY CMV INFECTION Efficacy in seriously ill R/R CMV in SOT and HSCT recipients with 1 multiple risk factors predictive of poor outcomes TAK‐620 Dose: 400 mg, 800 mg, 1200 mg BID1 Primary efficacy endpoint All doses (Total N = 120) Hist
Slide 102: TAK-620: Two Ongoing Pivotal Studies
TAK‐620: TWO ONGOING PIVOTAL STUDIES; EXPECT FIRST APPROVAL IN RESISTANT OR REFRACTORY CMV IN 2021 TAK‐620 PHASE 3 STUDY 303 TAK‐620 PHASE 3 STUDY 302 Resistant/Refractory CMV Patients with SOT or HSCT HSCT Recipients With First CMV Infection 2:1 Randomization 1:1 Randomization TAK‐620 400mg BID Inv
Slide 103: Selected Transformative Programs
SELECTED TRANSFORMATIVE PROGRAMS Potential first treatment of CMV infection in transplant patients in over 10 years. TAK‐620 Inhibitor of protein kinase UL97. Potential best‐in‐class therapy for Thrombotic Thrombocytopenic Purpura (TTP). TAK‐755 Recombinant ADAMTS13. Potential first pharmacologic th
Slide 104: Congenital and Immune TTP Burden
CONGENITAL AND IMMUNE TTP HAVE SUBSTANTIAL MORTALITY AND MORBIDITY BURDEN DUE TO INADEQUATE SOC CONGENITAL TTP (cTTP) • Sub‐therapeutic dose with plasma infusions • Patients still experience ischemic injury of brain, kidneys and heart • Poor long‐term outcomes IMMUNE TTP (iTTP) • ~30% relapse rate w
Slide 105: TAK-755 Addresses Underlying Cause of TTP
TAK‐755 DIRECTLY ADDRESSES UNDERLYING CAUSE OF TTP TAK‐755 REPLACES ADAMTS13, DEFICIENCY OF WHICH LEADS TO TTP Platelet Von Willebrand Factor (VWF) Normal ADAMTS13: clotting Cleaves VWF multimers that mediate cascade platelet aggregation and clotting Blood vessel ADAMTS13 deficiency: TTP Formation o
Slide 106: TAK-755: Potential Transformative Therapy for TTP
TAK‐755: POTENTIAL TRANSFORMATIVE THERAPY FOR TTP TAK‐755 PHASE I, OPEN‐LABEL, DOSE TAK‐755 PK PROFILE AND PD EFFECT ON ESCALATION STUDY IN cTTP1 VWF CLEAVAGE AT 40 IU/KG 100% Mean FRETS ADAMTS13 Activity 100% 176 kDa VWF Cleavage Product • Administered as a single dose 90% 90% 80% 80% (%) TTP diagn
Slide 107: TAK-755: Ongoing Phase 3 Congenital TTP Study
TAK‐755: ONGOING PHASE 3 CONGENITAL TTP STUDY TAK‐755 PHASE 3 PROPHYLAXIS STUDY cTTP patients (N = 26 – 42) 1:1 Randomization • All patients roll over to a 6 month TAK‐755 extension TAK‐755 40 IU/kg SOC Every other week1 • Phase 3 study has a cohort of acute cTTP Tx duration: 6 months patients who r
Slide 108: TAK-755 Immune TTP Phase 2 Study Design
TAK‐755 IMMUNE TTP PHASE 2 STUDY DESIGN Primary or relapse acute iTTP episode (N=30) PEX Day 1 1:1:1 Randomization Placebo TAK‐755 Low dose TAK‐755 High dose + + + SOC SOC SOC Remission Phase Placebo or TAK‐755 Primary endpoints: PK/PD EXPECTED 2020 2021 2023 2025 MILESTONES (FY) 2H: Ph 2 Readout 2H
Slide 109: Selected Transformative Programs
SELECTED TRANSFORMATIVE PROGRAMS Potential first treatment of CMV infection in transplant patients in over 10 years. TAK‐620 Inhibitor of protein kinase UL97. Potential best‐in‐class therapy for Thrombotic Thrombocytopenic Purpura (TTP). TAK‐755 Recombinant ADAMTS13. Potential first pharmacologic th
Slide 110: Extremely Premature Infants Experience Considerable Morbidity
EXTREMELY PREMATURE INFANTS EXPERIENCE CONSIDERABLE MORBIDITY ~80,000‐90,000 0 Therapies Extremely preterm for prevention of babies (<28 wks complications of gestational age) born prematurity WW2,3 ~40% have lung ~$200,000 1 Morbidity (%) by birth year, US data complications hospitalization 100% in
Slide 111: TAK-607 Replenishes IGF-1
TAK‐607 REPLENISHES IGF‐1, A FETAL GROWTH FACTOR THAT IS DECREASED IN PRETERM INFANTS TAK‐607: IGF‐1 / IGFBP‐31 COMPLEX IGF‐1 LEVELS ARE LOW IN PRETERM INFANTS2 • IGF‐1 is an important fetal growth factor supplied by the mother that is involved in the IGF‐1 in normal in utero fetus development of mu
Slide 112: TAK-607: Phase 2 Study Informed Dose and Endpoint Selection
TAK‐607: PHASE 2 STUDY INFORMED DOSE AND ENDPOINT SELECTION ROP‐2008‐01: RANDOMIZED, CONTROLLED PHASE 2 STUDY OF TAK‐607 TAK‐607 IMPACTED BPD AND IVH2 • Pre‐term infants with a gestational age (GA) <28 weeks (N = 120) 100 Standard of care IGF‐1/IGFBP‐3 • Assessed outcomes in ITT and “evaluable” sets
Slide 113: TAK-607: FOOTPRINTS Study Design
TAK‐607: FOOTPRINTS STUDY DESIGNED TO DEMONSTRATE REDUCTION IN THE COMPLICATIONS OF PREMATURITY Open label, 1:1:1 Randomization Treatment Post Treatment (N = 200/arm) (2‐7 wks based on GA) Follow‐up period TAK‐607 250 μg/kg/24 h Rx: Day 1 Rx End: 29 wk + Primary endpoint: continuous IV 6 d PMA 12 mo
Slide 114: NME Milestones Achieved in FY19 and Looking Ahead
NME MILESTONES ACHIEVED IN FY19 AND LOOKING AHEAD TO OTHER POTENTIAL MILESTONES1 THROUGH FY20 PIVOTAL STUDY STARTS, APPROVALS MLD PEVONEDISTAT AML EoE TAK‐611 TAK‐721 Ph 2 start2 TAK‐924 Ph 3 start Approval cTTP 1L NSCLC Huntington’s Disease TAK‐755 TAK‐788 mHTT ASO Ph 3 start Ph 3 start Pivot
Slide 115: We Aim to Provide Curative Therapy
WE AIM TO PROVIDE CURATIVE THERAPY As the global leader in Rare Diseases, we aspire to provide transformative and curative treatments to our patients Transformative Curative Programs with transformative Emerging early pipeline of AAV potential in devastating gene therapies to redefine disorders with
Slide 116: Building a World Class Gene Therapy Engine
BUILDING A WORLD CLASS GENE THERAPY ‘ENGINE’ TOP TIER GMP GENE THERAPY GENE THERAPY MANUFACTURING AAV1 PLATFORM PIPELINE TAKEDA THERAPEUTIC AREAS Preclinical Clinical Development Development Liver expression 3+ Research NextGen TAK‐748 TAK‐754 • Strong capabilities Candidates Hem A Hem B Hem A in li
Slide 117: Applying Cell Therapy Playbook to Build Gene Therapy Pipeline
WE WILL APPLY OUR CELL THERAPY PLAYBOOK AND UNIFYING CAPABILITIES TO BUILD A GENE THERAPY PIPELINE Select Cell Therapy Cell To Gene Therapy Partnerships/Acquisitions Unifying Capabilities • Viral expertise • Manufacturing Acquisition 2016 2017 2018 2019 2020 2021 2022+ Focus of Future Gene Therapy P
Slide 118: Summary
SUMMARY 132 Takeda has the We have a leading late We are building cutting ‐ capabilities, scale, and stage portfolio of edge capabilities in gene innovative platforms to transformative programs therapy that aim to extend our leadership in that will establish or deliver ‘cures’ in Rare Diseases re‐de
Slide 119: R&D Day Agenda
R&D DAY AGENDA – TOKYO, NOVEMBER 21, 2019 TIME AGENDA Welcome and Introduction of Presenters 11:00 – 11:05 Ayako Iwamuro, Investor Relations, Global Finance Realizing the Potential of Plasma‐derived Therapies 11:05 – 11:45 Julie Kim, President, Plasma‐Derived Therapies Business Unit A New Dedicated
Slide 120: OX2R Agonists for the Treatment of Narcolepsy Type 1
OX2R AGONISTS FOR THE TREATMENT OF NARCOLEPSY TYPE 1 Deborah Hartman, PhD Global Program Leader, Neuroscience Takeda Pharmaceutical Company Limited Tokyo November 21, 2019
Slide 121: Narcolepsy Type 1 Is a Rare, Acquired Chronic Neurological Disorder
NARCOLEPSY TYPE 1 IS A RARE, ACQUIRED CHRONIC NEUROLOGICAL DISORDER 3M ~50% 15Y Estimated global Estimated Mean diagnostic population affected by diagnostic rate for delay3 NT11 NT1 in US, EU, JP2 When I'm awake, sleep is constantly • Psychosocially devastating effects intruding on that part of my l
Slide 122: Narcolepsy Type 1 Distinguished by Cataplexy and Low Orexin
NARCOLEPSY TYPE 1 IS DISTINGUISHED BY THE PRESENCE OF CATAPLEXY AND LOW OREXIN LEVELS Other hypersomnia disorders <110 pg/mL • Idiopathic Hypersomnia It’s not just about sleep, it’s • Residual Excessive about quality of wakefulness Daytime Sleepiness … it’s really about partnership in Obstructive wi
Slide 123: Narcolepsy Type 1 Caused by Loss of Orexin-Producing Neurons
NARCOLEPSY TYPE I IS CAUSED BY PROFOUND LOSS OF OREXIN‐PRODUCING NEURONS OREXIN mRNA LABELLING OF ACTIVATION OF OREXIN 2 RECEPTOR (OX2R) POSTMORTEM HYPOTHALAMIC SECTIONS LEADS TO AROUSAL AND PROMOTES WAKEFULNESS3 Orexin neuropeptides Post‐synaptic neurons with Downstream signalling Healthy control N
Slide 124: TAK-925 Reduces Narcolepsy-Like Symptoms in Mouse Model
TAK‐925, A SELECTIVE OX2R AGONIST, REDUCES NARCOLEPSY‐LIKE SYMPTOMS IN AN OREXIN‐DEFICIENT MOUSE MODEL TAK‐925 FULLY RESTORED TAK‐925 ELIMINATED SLEEP / TAK‐925 ABOLISHED WAKEFULNESS WAKE TRANSITIONS CATAPLEXY‐LIKE EPISODES Wakefulness time of NT1 mouse model Hypnogram of sleep/wake transitions Cata
Slide 125: TAK-925 Maintains Wakefulness in Early Proof of Concept Study
TAK‐925 SHOWED PROMISING ABILITY TO MAINTAIN WAKEFULNESS IN AN EARLY PROOF OF CONCEPT STUDY IN NT1 PATIENTS SLEEP LATENCY IN THE MAINTENANCE OF WAKEFULNESS TEST (MWT): SLEEP LATENCY IN THE MAINTENANCE OF WAKEFULNESS TEST (MWT): CURRENT TREATMENTS TAK‐925 (N=14) (single dose nine hour continuous IV i
Slide 126: TAK-925 Reduced Subjective Sleepiness
TAK‐925 ALSO REDUCED SUBJECTIVE SLEEPINESS IN THIS EARLY PROOF OF CONCEPT STUDY IN NT1 KAROLINSKA SLEEPINESS SCALE VALUES DURING AND AFTER ADMINISTRATION OF TAK‐925 (single dose nine hour continuous IV infusion during the day) Mean (SD) Placebo 9 TAK-925 5 mg 8 TAK-925 11.2 mg End of infusion TAK-92
Slide 127: TAK-925 Maintained Wakefulness in Sleep-Deprived Healthy Adults
TAK‐925 MAINTAINED WAKEFULNESS IN SLEEP‐DEPRIVED HEALTHY ADULTS IN A SECOND PHASE 1 STUDY SLEEP LATENCY IN THE MAINTENANCE OF WAKEFULNESS TEST (MWT) IN SLEEP‐DEPRIVED HEALTHY ADULTS1 *** 40 39 30 *** 25 Results suggest potential 20 therapeutic use of TAK‐925 in other hypersomnia disorders Average mi
Slide 128: Leading Innovation in Orexin Biology and Expanding Indications
WE ARE COMMITTED TO LEADING INNOVATION IN OREXIN BIOLOGY AND EXPANDING THERAPEUTIC INDICATIONS FOR OX2R AGONISTS Rare primary hypersomnia disorders Top priority Other hypersomnia disorders Additional opportunities for expansion Idiopathic Hypersomnia Narcolepsy Residual EDS Type II in Obstructive •
Slide 129: TAK-994 Oral OX2R Agonist Progressing to Narcolepsy Type 1 Studies
TAK‐994 IS AN ORAL OX2R AGONIST PROGRESSING TO STUDIES IN NARCOLEPSY TYPE 1 TAK‐994‐1501 PROOF OF CONCEPT STUDY IN NARCOLEPSY TYPE 1 • Multi‐center, placebo‐controlled trial in North America and Japan • Enrollment target: 72 adults • Duration of treatment: 28 days dosing • Exploratory outcome measur
Slide 130: Digital Technologies Enhancing OX2R Agonist Development
DIGITAL TECHNOLOGIES ARE ENHANCING THE DEVELOPMENT OF OX2R AGONISTS FOR SLEEP DISORDERS TRADITIONAL CLINICAL INSTRUMENTS DO NOT FULLY MEASURE DIGITAL MEASURES WILL FURTHER CHARACTERIZE SLEEP SYMPTOMS OF SLEEP DISORDERS ARCHITECTURE AND SUPPORT CLINICAL TRIAL ASSESSMENTS Hand‐scored Automated analysi
Slide 131: Aspire to Bring Transformative OX2R Agonist Solution to Narcolepsy Type 1
WE ASPIRE TO BRING A POTENTIALLY TRANSFORMATIVE OX2R AGONIST SOLUTION TO INDIVIDUALS WITH NARCOLEPSY TYPE 1 • Achieved early Proof of Concept for NT1 • Awarded Breakthrough Therapy Designation TAK‐925 • Awarded Sakigake Designation • Launched formulation development activities TAK‐994, first oral OX
Slide 132: Summary
SUMMARY 132 TAK‐925 has achieved TAK‐925 has TAK‐994 is an oral early Proof‐of‐Concept demonstrated potential OX2R agonist for OX2R agonists in of OX2R agonists for progressing to studies Narcolepsy Type 1 treatment of other in Narcolepsy Type 1 sleep‐related disorders 131
Slide 133: R&D Day Agenda
R&D DAY AGENDA – TOKYO, NOVEMBER 21, 2019 TIME AGENDA Welcome and Introduction of Presenters 11:00 – 11:05 Ayako Iwamuro, Investor Relations, Global Finance Realizing the Potential of Plasma‐derived Therapies 11:05 – 11:45 Julie Kim, President, Plasma‐Derived Therapies Business Unit A New Dedicated
Slide 134: Therapeutic Area Focus in GI with Spotlight on Celiac Disease
THERAPEUTIC AREA FOCUS IN GI WITH SPOTLIGHT ON CELIAC DISEASE Asit Parikh, MD, PhD Head Gastroenterology Therapeutic Area Unit Takeda Pharmaceutical Company Limited Tokyo November 21, 2019
Slide 135: We Target Unmet Needs That Align with Our Strengths
WE TARGET UNMET NEEDS THAT ALIGN WITH OUR STRENGTHS AREAS OF FOCUS GI WW RX SALES 2018 (USD BN) TAKEDA GI DISEASE AREAS Total = $57Bn High unmet medical need Other GI inflammation GI GI Potential to advance SoC Cancers 3.9 through innovative science – by being first or best in class 18.2 12.2 GI mot
Slide 136: Strengthening Entyvio by Continuously Improving Value for Patients
WE STRENGTHEN ENTYVIO BY CONTINUOUSLY IMPROVING VALUE FOR PATIENTS COMPETITIVE POSITIONING EXPANDED PATIENT POPULATIONS GEOGRAPHIC EXPANSION VARSITY: 1st Head‐to‐Head study in IBD (UC) Entyvio Subcutaneous Development Entyvio IV • Vedolizumab was superior to adalimumab on • Positive VISIBLE UC and C
Slide 137: Positioned to Deliver Near-Term and Sustained Growth
WE ARE POSITIONED TO DELIVER NEAR‐TERM & SUSTAINED GROWTH WAVE 11 WAVE 22 TARGET CLINICAL‐STAGE NMEs PLATFORMS APPROVAL FY20 FY21 FY22 FY23 FY24 FY25 AND BEYOND TAK‐7883 TAK‐007 TAK‐924 TAK‐164 TAK‐252 2L NSCLC Hematologic AML GI malignancies Solid tumors TARGETED malignancies CELL THERAPY INNATE NE
Slide 138: TAK-721: On Track to Be First FDA Approved Agent for EoE
TAK‐721: ON TRACK TO BE THE FIRST FDA APPROVED AGENT TO TREAT EOSINOPHILIC ESOPHAGITIS (EOE) INDUCTION DATA SHOWS SIGNIFICANT ADDRESSES SIGNIFICANT UNMET NEED HISTOLOGIC AND SYMPTOM RESPONSE • Chronic, allergic, inflammatory condition of the esophagus Results presented at presidential plenary at ACG
Slide 139: Celiac Disease: High Unmet Need Area with No Therapies
CELIAC DISEASE IS AN EXAMPLE OF A HIGH UNMET NEED AREA WITH NO THERAPIES ~1% ~40% ~1M Estimated Patients still suffer from Global population global, eligible symptoms despite being affected by celiac1 patient on a gluten‐free diet population2 • Overlooked disease, growing prevalence • Chronic sympto
Slide 140: Focusing on Narrowest Population with High Unmet Need
WE ARE FOCUSING ON THE NARROWEST POPULATION WITH HIGH UNMET NEED 20% Moderate Our focus: • Niche patient segment with the highest unmet 40% Uncontrolled* on GFD need • Severe symptoms with villous atrophy 18% Severe • Continue to suffer 60% despite the GFD and are highly likely to take a Controlled
Slide 141: Our Approach to Treating Celiac Disease
OUR APPROACH TO TREATING CELIAC DISEASE TREATMENT OPPORTUNITIES FOR CELIAC DISEASE 1 1 Enzymatic digestion of gluten Kuma062 promises greatly increased 3 Microbiome Modulation enzymatic efficiency and improved 2 Reduce intestinal permeability formulation over predecessors 2 3 Microbiome modulation 4
Slide 142: Kuma062: Highly Potent Oral Glutenase
KUMA062: A HIGHLY POTENT ORAL GLUTENASE THAT COULD CHANGE THE STANDARD OF CARE IN CELIAC DISEASE CLINICAL DATA SHOWS KUMA062 CAN DEGRADE ABOUT KUMA062 >95% OF INGESTED GLUTEN • Kuma062 is an oral, computationally‐engineered super glutenase • Enhanced catalytic activity compared to other glutenases G
Slide 143: TAK-101: Potential Best-in-Class IV Therapy for Celiac Disease
TAK‐101: POTENTIAL BEST‐IN‐CLASS, INTRAVENOUS THERAPY FOR CELIAC DISEASE DESIGNED TO MODIFY T CELL RESPONSE ABOUT TAK‐101* TAK‐101 REDUCES IMMUNE ACTIVATION AFTER GLUTEN EXPOSURE • Biodegradable polymer encapsulating antigen Interferon‐gamma ELISPOT measurement of gluten‐responsive T cells • Designe
Slide 144: Leading the Science in Celiac Disease with AI-Based Tool
WE ARE LEADING THE SCIENCE IN CELIAC DISEASE WITH A NEW AI ‐ BASED TOOL AND INGESTIBLE DEVICE PIONEERING AT BOUNDARIES INNOVATIVE USE PRECISION OF CLINICAL MEDICINE OF TECHNOLOGY MEASUREMENT USING AI • Innovative, non‐invasive, patented • Ingestible high resolution camera pill • Pioneering Automated
Slide 145: Takeda Is the Best Company to Bring Celiac Therapies to Patients
TAKEDA IS THE BEST COMPANY TO BRING CELIAC THERAPIES TO PATIENTS World‐class, fully connected GI commercial infrastructure across 65+ countries that supports $6bn+ revenues • Extensive GI clinical footprint • Strong reputation for scientific excellence • Lauded for calculated risk‐taking by the GI c
Slide 146: NME Milestones Achieved in FY19 and Looking Ahead
NME MILESTONES ACHIEVED IN FY19 AND LOOKING AHEAD TO OTHER POTENTIAL MILESTONES1 THROUGH FY20 PIVOTAL STUDY STARTS, APPROVALS MLD PEVONEDISTAT AML EoE TAK‐611 TAK‐721 Ph 2 start2 TAK‐924 Ph 3 start Approval cTTP 1L NSCLC Huntington’s Disease TAK‐755 TAK‐788 mHTT ASO Ph 3 start Ph 3 start Pivot
Slide 147: Summary
SUMMARY 132 We have built an We are well We have multiple industry‐leading positioned to bring milestones, including portfolio rooted in the first therapies to expected key approvals unparalleled scientific celiac patients that in the next 2 years that excellence and could change the will be transfo
Slide 148: R&D Day Agenda
R&D DAY AGENDA – TOKYO, NOVEMBER 21, 2019 TIME AGENDA Welcome and Introduction of Presenters 11:00 – 11:05 Ayako Iwamuro, Investor Relations, Global Finance Realizing the Potential of Plasma‐derived Therapies 11:05 – 11:45 Julie Kim, President, Plasma‐Derived Therapies Business Unit A New Dedicated
Slide 149: Panel Q&A Session
Panel Q&A Session © 2019 Takeda Pharmaceutical Company Limited. All rights reserved