Takeda Pharmaceutical Co. Ltd. · TSE:4502
Takeda Pharmaceutical — 43rd Annual J.P. Morgan Healthcare Conference (January 2025)
189 slides from Takeda Pharmaceutical's conference presentation, Jan 14, 2025
Slide 1: Takeda Pharmaceutical Company - 43rd Annual J.P. Morgan Healthcare Conference
TSE: 4502 Takeda Pharmaceutical Company 43rd Annual J.P. Morgan Healthcare Conference Christophe Weber President & CEO January 14th, 2025
Slide 2: 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 3: Better health for people, brighter future for the world
Better health for people, brighter future for the world Our vision is to discover and deliver life-transforming We are guided by our values of Takeda-ism which treatments, guided by our commitment to: incorporate Integrity, Fairness, Honesty, and Perseverance, with Integrity at the core. PATIENT PEO
Slide 4: A global, innovation driven biopharmaceutical company
A global, innovation driven biopharmaceutical company FY2023 REVENUE Global Footprint Aligned With Key Market Opportunities 15% GROWTH & EMERGING 51% ¥4.3T MARKETS U.S. GLOBAL HEADQUARTERS TOKYO, JAPAN KEY BUSINESS AREAS 23% GLOBAL HUB CAMBRIDGE, MA, USA 6 REPRESENT ~94% OF REVENUE GI, RARE DISEASES
Slide 5: Our late-stage pipeline has significant revenue potential
Our late-stage pipeline has significant revenue potential Late-Stage Pipeline Peak Revenue Potential of $10 - 20B Oveporexton (TAK-861) Zasocitinib (TAK-279) Rusfertide (TAK-121) Narcolepsy Type 1 Psoriasis & Ulcerative Colitis Polycythemia Vera Psoriatic Arthritis & Crohn’s Disease Potential for $2
Slide 6: Late-stage programs have significant value potential; phase 3 data expected in 2025
Late-stage programs have significant value potential; oveporexton, zasocitinib, rusfertide phase 3 data expected in 2025 Three Phase 3 Data Readouts Over the Next 12 Months Target Filing Dates by Indication • Oveporexton in Narcolepsy Type 1 FY25 / FY26 • Zasocitinib in Psoriasis Oveporexton (TAK-86
Slide 7: Oveporexton's optimized dosing regimen is critical to deliver efficacy
Oveporexton (TAK-861)’s optimized dosing regimen is critical to deliver transformative efficacy while minimizing adverse events TAK-861 BID profile mimics natural diurnal orexin tone Diurnal fluctuation of orexin levels in Long-acting orexin 2 receptor (OX2R) agonist monkey CSF Takeda’s novel method
Slide 8: Oveporexton development evaluating full spectrum of NT1 symptoms
Oveporexton development evaluating full spectrum of NT1 symptoms with established and novel endpoints defining a new treatment class Daytime Symptoms Nighttime Symptoms Excessive Daytime Cataplexy Cognitive Symptoms Disrupted Nighttime Sleep, Hallucinations, Sleepiness (EDS) Disturbing Dreams Sleep
Slide 9: Oveporexton normalization of wakefulness (MWT) in Ph2b
Oveporexton demonstrated normalization of wakefulness at 8 weeks, and maintained over an additional 6 months in Ph2b study Maintenance of Wakefulness Test (MWT): daytime polysomnographic procedure which quantifies wake tendency by measuring ability to remain awake during soporific circumstances (sle
Slide 10: Oveporexton normalization of wakefulness (ESS) in Ph2b
Oveporexton demonstrated normalization of wakefulness at 8 weeks, and maintained over an additional 6 months in Ph2b study Epworth Sleepiness Scale (ESS): short self-assessment to identify how likely to fall asleep during daytime, measured by eight questions. Total score range 0-24 (each question 0-
Slide 11: Oveporexton sustained reduction in cataplexy events
Oveporexton demonstrated sustained reduction in cataplexy events over an additional 6 months Weekly Cataplexy Rate (WCR): average number of cataplexy events per week WCR • Oveporexton showed statistically significant and 25 clinically meaningful reduction in cataplexy events 20 compared to placebo I
Slide 12: Oveporexton improved cognitive symptoms in NT1 patients
Oveporexton improved cognitive symptoms in NT1 patients, offering a unique advantage over standard of care Psychomotor Vigilance Test (PVT): simple 10 min reaction performance task to measure sustained attention (test counts # of lapses in attention) Number of PVT lapses at week 8 • Oveporexton resu
Slide 13: Oveporexton on track to be the first orexin agonist
Oveporexton on track to be the first orexin agonist with potential to transform NT1 treatment paradigm, starting in the U.S. 10-20% 5-10% ~95-120k Improvement in Increase in 30-50% Prevalent NT1 diagnosis rate treatment rate Preference patients in U.S.1 (currently ~50%) (currently ~75%) Share Improv
Slide 14: Late-stage programs have significant value potential
Late-stage programs have significant value potential; oveporexton, zasocitinib, rusfertide phase 3 data expected in 2025 Three Phase 3 Data Readouts Over the Next 12 Months Target Filing Dates by Indication • Oveporexton in Narcolepsy Type 1 FY25 / FY26 • Zasocitinib in Psoriasis Oveporexton (TAK-86
Slide 15: Zasocitinib exhibits greater and longer TYK2 inhibition versus deucravacitinib
Zasocitinib exhibits greater and longer TYK2 inhibition versus deucravacitinib and no inhibition of JAK1/3 Zasocitinib 30 mg QD Deucravacitinib 6 mg QD JAK1/3 IC50 was not achieved at max concentration tested, 30,000 nM1 Greater and Longer Inhibition JAK safety margin Zasocitinib at 30mg QD is signi
Slide 16: Zasocitinib in psoriasis: complete skin clearance at 12 weeks
Zasocitinib in psoriasis (PsO): One-third of patients achieved complete skin clearance at 12 weeks with 30 mg once daily PASI Score @ 12 weeks Ph2b PsO study results 100% 90% 80% *** *** achieving PASI scores Proportion of patients 70% 68% 67% 60% PASI 75 *** *** *** 50% 44% 45% 46% *** PASI 90 40%
Slide 17: Zasocitinib peak sales potential up to $6B in PsO and PsA
Zasocitinib peak sales potential for up to $6B in PsO and PsA, with potential for additional indications including Crohn’s & UC U.S. PsO + PsA Market Evolution over next ~10 yrs Global Peak Diagnosed Advanced Zasocitinib Revenue Plus Plus Oral Potential potential PsO & PsA Therapy 1st Choice Crohn’s
Slide 18: Late-stage programs have significant value potential
Late-stage programs have significant value potential; oveporexton, zasocitinib, rusfertide phase 3 data expected in 2025 Three Phase 3 Data Readouts Over the Next 12 Months Target Filing Dates by Indication • Oveporexton in Narcolepsy Type 1 FY25 / FY26 • Zasocitinib in Psoriasis Oveporexton (TAK-86
Slide 19: Rusfertide is a hepcidin mimetic for managing polycythemia vera
Rusfertide is a hepcidin mimetic for managing polycythemia vera Rusfertide helps address the overproduction of red blood cells MOA of Rusfertide (RBCs) in patients with polycythemia vera (PV) through, Leveraging Hepcidin Mimetic to Target Excessive RBC Production Restricting availability of iron by
Slide 20: Rusfertide rapid, sustained and durable hematocrit control
Rusfertide demonstrated rapid, sustained & durable hematocrit control REVIVE Study: PV patients requiring frequent phlebotomy + cytoreductives; 90% phlebotomy free 47 Hematocrit Results1 (Mean ± 1 SEM) Placebo • Rapid, Sustained and N = 582, 1:1 randomization Rusfertide 46 Durable hematocrit control
Slide 21: Rusfertide expected to be used at each step of the treatment landscape
Rusfertide aims to deliver rapid, consistent & sustained HCT control and is expected to be used at each step of the treatment landscape Patients are often on polytherapy and will cycle through various treatments ~155k diagnosed ~41K ~26K ~6K ~3K Phlebotomy And/Or Hydroxy Urea And/Or And/Or Ropeg- pa
Slide 22: Late-stage programs have significant value potential
Late-stage programs have significant value potential; oveporexton, zasocitinib, rusfertide phase 3 data expected in 2025 Three Phase 3 Data Readouts Over the Next 12 Months Target Filing Dates by Indication • Oveporexton in Narcolepsy Type 1 FY25 / FY26 • Zasocitinib in Psoriasis Oveporexton (TAK-86
Slide 23: Mezagitamab designed for rapid, selective, safe depletion of immune cells
Mezagitamab is designed for rapid, selective, safe and sustained depletion of immune cells Rapid and robust antibody reduction Selective targeting observed in multiple indications1 Plasma cell of CD38 directly • IgG up to 41% depletes long and CD38 • IgA up to 70% short-lived plasma • Gd-IgA1 up to
Slide 24: Mezagitamab in IgA nephropathy POC study
Mezagitamab in IgA nephropathy POC study was well tolerated and showed rapid, sustained best-in-class UPCR reduction Mezagitamab IgAN Phase 1 data1 Best-in-Class Efficacy Rapid and sustained reduction in proteinuria (UPCR) Start Tx End of Tx • Mezagitamab demonstrated rapid and Weeks 0 8 24 36 susta
Slide 25: Mezagitamab potential transformative profile in auto-immune diseases
Mezagitamab has potential to deliver a transformative profile, addressing the root cause in auto-immune diseases IgAN ambition • 1st anti-CD38 choice • Stop progression of disease (eGFR stabilization) with sustained kidney protection off-treatment • Promise of treatment holiday (half of year) Peak R
Slide 26: Fazirsiran mechanism of action stops production of Z-AAT
Fazirsiran mechanism of action stops the production of Z-AAT, directly addressing the pathology in AATD liver disease Fazirsiran is a liver-targeted, 1 double-stranded siRNA1-3 Nucleus Cytoplasm SERPINA1 1 Fazirsiran Z allele Fazirsiran leads to 2 Z-AAT mRNA degradation1,2 Z-AAT mRNA 2 Z-AAT protein
Slide 27: Fazirsiran Ph2 placebo-controlled study reducing Z-AAT
Fazirsiran Ph2 placebo-controlled study demonstrates transformative potential in reducing Z-AAT Serum Z-AAT concentration Liver Z-AAT concentration 20 40 9 % change from baseline to week 48+ in liver 26 % change from baseline in mean serum 4 0 20 0 -20 -20 Z-AAT -40 Z-AAT -40 -60 -60 -62 -80 -74 -80
Slide 28: Fazirsiran poised to benefit from advancements in MASH
Fazirsiran poised to benefit from advancements in MASH & potential diagnosis acceleration upon availability of effective AATD treatment ~35% ~10-15% No ~250k of Pi*ZZ of AATD-LD available Pi*ZZ prevalent patients patients are treatment patients globally1 develop diagnosed in AATD-LD AATD-LD2 today3
Slide 29: Elritercept potentially best-in-class treatment for anemia-associated diseases
Elritercept is a potentially best-in-class treatment for anemia-associated diseases Elritercept has the potential to address significant clinical unmet need that persists despite currently available Elritercept anemia-associated LR-MDS treatments Erythrocytes (RBCs) • Potent inhibitor of both Activi
Slide 30: Elritercept strong responses across AA LR-MDS segments
Elritercept demonstrated strong responses across AA LR-MDS segments, supporting the potential to treat a broad proportion of patients EPO < 500 U/L2 % Responders1 All (N=71) HTB (N=39) • Response rates in patients with Overall Response3 60.6% 56.4% high transfusion burden (HTB) were similar to those
Slide 31: Elritercept targeting initial indication in 2L+
Elritercept is a potential best-in-class treatment for AA LR-MDS targeting initial indication in 2L+ with the aim to expand quickly into 1L Anemia Associated with LR-MDS RS+ (30%) RS- (70%) 1L Potential Potential expansion expansion to 1L to 1L 2L Elritercept target indications 3L Initial indication
Slide 32: Late-stage programs have significant value potential
Late-stage programs have significant value potential; oveporexton, zasocitinib, rusfertide phase 3 data expected in 2025 Three Phase 3 Data Readouts Over the Next 12 Months Target Filing Dates by Indication • Oveporexton in Narcolepsy Type 1 FY25 / FY26 • Zasocitinib in Psoriasis Oveporexton (TAK-86
Slide 33: Committed to growth & shareholder returns
Committed to growth & shareholder returns Revenue Growth Pipeline Acceleration Margin Improvement Shareholder Returns • Growth & Launch Products • Accelerating late-stage • Targeting Core Operating • Strong cashflow outlook represent ~50% of revenue assets with potential to Profit margin improvement
Slide 34: APPENDIX: Takeda R&D Day 2024 Presentation Slides
APPENDIX: Takeda R&D Day 2024 Presentation Slides Presented December 13, 2025
Slide 35: Takeda R&D Day 2024
Takeda R&D Day 2024 Focus on Late-stage Pipeline & Market Opportunity Friday, December 13th, 2024 Tokyo This material is prepared and distributed solely for the purpose of providing information about Takeda's management or business to shareholders, investors, and analysts, and is not intended to ind
Slide 36: 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 37: Today's Agenda
Today’s Agenda TIME (JST) AGENDA 8:30-8:40 A Global, Innovation-driven Biopharmaceutical Company Christophe Weber, President & CEO 8:40-9:00 R&D Strategy and Pipeline Highlights Andy Plump, President Research & Development 9:00-9:50 Neuroscience: Deep-dive on Orexin Franchise Sarah Sheikh, Head of N
Slide 38: Better health for people, brighter future for the world
Better health for people, brighter future for the world Our vision is to discover and deliver life-transforming We are guided by our values of Takeda-ism which treatments, guided by our commitment to: incorporate Integrity, Fairness, Honesty, and Perseverance, with Integrity at the core. PATIENT PEO
Slide 39: A global, innovation-driven biopharmaceutical company
A global, innovation-driven biopharmaceutical company FY2023 REVENUE Global Footprint Aligned With Key Market Opportunities 15% GROWTH & EMERGING 51% ¥4.3T MARKETS U.S. GLOBAL HEADQUARTERS TOKYO, JAPAN KEY BUSINESS AREAS 23% GLOBAL HUB CAMBRIDGE, MA, USA 6 REPRESENT ~94% OF REVENUE GI, RARE DISEASES
Slide 40: Committed to growth & shareholder returns
Committed to growth & shareholder returns Revenue Growth Pipeline Acceleration Margin Improvement Shareholder Returns • Growth & Launch Products • Accelerating late-stage • Targeting Core Operating • Strong cashflow outlook represent ~50% of revenue assets with potential to Profit margin improvement
Slide 41: Our late-stage pipeline has significant revenue potential
Our late-stage pipeline has significant revenue potential Late-Stage Pipeline Peak Revenue Potential of $10 - 20B Oveporexton (TAK-861) Zasocitinib (TAK-279) Rusfertide (TAK-121) Narcolepsy Type 1 Psoriasis & Ulcerative Colitis Polycythemia Vera Psoriatic Arthritis & Crohn’s Disease Potential for $2
Slide 42: Late-stage programs have significant value potential
Late-stage programs have significant value potential; oveporexton, zasocitinib, rusfertide phase 3 data expected in 2025 Three Phase 3 Data Readouts Over the Next 12 Months Target Filing Dates by Indication • Oveporexton in Narcolepsy Type 1 FY25 / FY26 • Zasocitinib in Psoriasis Oveporexton (TAK-86
Slide 43: R&D Strategy and Pipeline Highlights
R&D Strategy and Pipeline Highlights Accelerating Our Late-Stage Pipeline to Transform Patients’ Lives and Deliver Significant Value to Takeda Andy Plump President, Research & Development
Slide 44: R&D Strategy
We discover, develop and deliver life-transforming medicines for rare and more prevalent diseases across our focused therapeutic areas R&D STRATEGY INNOVATIVE BIOPHARMA DATA SCIENCES & OPERATIONAL EXCELLENCE ONCOLOGY NEUROSCIENCE GASTROINTESTINAL AND THERAPEUTIC AREA UNIT THERAPEUTIC AREA UNIT INFLA
Slide 45: Our scale, focus, and capabilities have advanced significantly since FY2015
Our scale, focus, and capabilities have advanced significantly since FY2015 FY2015 FY2024 Regional Development and Launch Capability Global Development, Global Launch Capability 10 Therapeutic Areas, Small Molecule Focus 3 Therapeutic Areas, 4 Key Modalities R&D Investment 346 bn JPY R&D Investment
Slide 46: Late-stage programs have significant value potential
Late-stage programs have significant value potential; oveporexton, zasocitinib, rusfertide phase 3 data expected in 2025 Three Phase 3 Data Readouts Over the Next 12 Months Target Filing Dates by Indication • Oveporexton in Narcolepsy Type 1 FY25 / FY26 • Zasocitinib in Psoriasis Oveporexton Narcole
Slide 47: Strong global development, regulatory and launch expertise
We have built strong global development, regulatory and launch expertise FY2021 FY2022 FY2023 FIRST NME APPROVALS KEY LCM APPROVALS U.S. SC in UC and Crohn’s2 CIDP maintenance MAJOR MARKET 15 7 25 APPROVALS1 13 1.Major Markets: US, EU, Japan or China 2.U.S. approval for Entyvio SC was in September 2
Slide 48: Rigorous prioritization to deliver high value late-stage pipeline
Rigorous prioritization to deliver our high value late-stage pipeline GLOBAL NMEs1 % OF EXTERNAL SPEND3 Q4 FY21 Q2 FY24 100% 4 Ph3 Trials2 14 Ph3 21% 18% LCM Trials2 3 1 6 Late-Stage Early-Stage 31% 51% Investing in Robust 17 8 Late-Stage Pipeline 12 6 FY25+ Phase 1 Phase 2 Phase 3 Filed 48% 31% Pro
Slide 49: Future Fit development model
Future Fit development model: delivering improved speed, quality and efficiencies across the pipeline Execute Clinical Trials with top tier industry performance Research Development Preclinical Ph 1 Ph 2 Ph 3 Filing Launch Study level: 3 core elements that can be optimized Study & Recruitment & Clos
Slide 50: Future Fit has accelerated zasocitinib and oveporexton
Future Fit and prioritization has led to significant acceleration for zasocitinib and oveporexton Psoriasis: Time to recruit pivotal trials Latitude-Psoriasis 1 – 308 days (N=693) Zasocitinib ~ 7 months ahead of plan Latitude-Psoriasis 2 – 294 days (N=1108) Study 1 – 363 days (N=666) Competitor Oral
Slide 51: Late-stage programs have significant value potential
Late-stage programs have significant value potential; oveporexton, zasocitinib, rusfertide phase 3 data expected in 2025 Three Phase 3 Data Readouts Over the Next 12 Months Target Filing Dates by Indication • Oveporexton in Narcolepsy Type 1 FY25 / FY26 • Zasocitinib in Psoriasis Oveporexton Acceler
Slide 52: Right modalities and resourcing; research engine
Right modalities and resourcing from project inception; Research engine to fuel our sustainable pipeline Sustainable acceleration of First-in-Human, and BLA/NDA First Filing Preclinical stage: 3 core elements for optimization Accelerate Delivery to Clinic Driving Efficiency with Real-Time Apply Digi
Slide 53: Our sustainable pipeline provides opportunities across therapeutic areas
Our sustainable pipeline provides opportunities across all our therapeutic areas EARLY-STAGE PROGRAMS / SELECT LCMs TAK-227 TAK-101 TAK-007 Celiac Disease Celiac Disease Autoimmune Disease1 GASTROINTESTINAL AND INFLAMMATION zamaglutenase TAK-004 ADZYNMA® Celiac Disease Nausea & Vomiting iTTP TAK-360
Slide 54: Partnering to expand our pipeline
Partnering to expand our pipeline and maximize R&D investment Acquisitions Late-stage/Commercialization Zasocitinib1 GammaDelta FRUZAQLA Rusfertide Takeda Development Partner Development/Takeda Commercialization In-licensing Options2 Elritercept Fazirsiran Olverembatinib ACI-24.060 Takeda Developmen
Slide 55: Late-stage programs have significant value potential
Late-stage programs have significant value potential; oveporexton, zasocitinib, rusfertide phase 3 data expected in 2025 Three Phase 3 Data Readouts Over the Next 12 Months Target Filing Dates by Indication • Oveporexton in Narcolepsy Type 1 FY25 / FY26 • Zasocitinib in Psoriasis Oveporexton Narcole
Slide 56: Neuroscience: Deep-dive on Orexin Franchise
Neuroscience: Deep-dive on Orexin Franchise Sarah Sheikh Ramona Sequeira Head of Neuroscience Therapeutic Area Unit & President, Global Portfolio Division Global Development
Slide 57: Recent scientific advancements & regulatory momentum in Neuroscience
Recent scientific advancements & regulatory momentum heralds a new era in Neuroscience High Unmet Need Growing Scientific Understanding Innovative Regulatory Approaches • Enhanced understanding of underlying Evidenced by Numerous Estimated to be 9 million deaths per pathophysiology year due to neuro
Slide 58: Vision to be a leader in neuroscience
Our vision is to be a leader and partner in neuroscience by discovering and delivering life-changing medicines for people and society Strategically focused on three core areas OREXIN NEURODEGENERATION RARE NEUROLOGY Transform care for Address the leading Address the devastating rare sleep disorders
Slide 59: Leading Orexin Franchise
Leading Orexin Franchise Better Health, Brighter Future
Slide 60: Takeda pioneering the field of orexin therapeutics
Takeda pioneering the field of orexin therapeutics – franchise leading with oveporexton, a potential first-in-class treatment for NT1 Oveporexton (TAK-861): TAK-360 and beyond: First & Fast3 in NT1 Additional assets/indications • The most advanced orexin agonist – • TAK-360: Accelerated development
Slide 61: NT1 patients face daytime and nighttime debilitating symptoms
NT1 patients face daytime and nighttime debilitating symptoms impacting daily function Daytime Symptoms Nighttime Symptoms Excessive Daytime Cataplexy Cognitive Symptoms Disrupted Nighttime Sleep, Hallucinations, Sleepiness (EDS) Disturbing Dreams1 Sleep Paralysis These symptoms may have significant
Slide 62: NT1 pathophysiology is caused by loss of orexin neurons
NT1 pathophysiology is caused by loss of orexin neurons Healthy orexin neurons with 01 Healthy normal postsynaptic downstream Individual neurotransmitter activity OX2R Orexin Reduced availability of orexin as orexin 02 Individual with neurons are lost, reducing downstream Narcolepsy type 1 neurotran
Slide 63: Comprehensive approach to evaluate full spectrum of NT1 symptoms
Comprehensive approach to evaluate full spectrum of NT1 symptoms with established and novel endpoints defining a new treatment class Daytime Symptoms Nighttime Symptoms Excessive Daytime Cataplexy Cognitive Symptoms Disrupted Nighttime Sleep, Hallucinations, Sleepiness (EDS) Disturbing Dreams1 Sleep
Slide 64: Oveporexton phase 2 program foundation for phase 3
The extensive oveporexton (TAK-861) phase 2 program laid solid foundation for phase 3 program Ph2b TAK-861 2001 (NT1) N=112 TAK-861 0.5 mg twice daily ~3 hours apart Key Efficacy Measures • MWT TAK-861 2 mg twice daily ~3 hours apart • ESS • WCR TAK-861 2 mg followed by 5 mg ~3 hours apart Long Term
Slide 65: Optimized dosing regimen critical to efficacy
Optimized dosing regimen critical to deliver transformative efficacy while minimizing adverse events TAK-861 BID profile mimics natural diurnal orexin tone Diurnal fluctuation of orexin levels in Long-acting orexin 2 receptor (OX2R) agonist monkey CSF Takeda’s novel method enabling accurate measurem
Slide 66: Normalization of wakefulness (MWT)
Oveporexton (TAK-861) demonstrated normalization of wakefulness (MWT) at 8 weeks and maintained over an additional 6 months The Maintenance of Wakefulness Test (MWT): daytime polysomnographic procedure which quantifies wake tendency by measuring ability to remain awake during soporific circumstances
Slide 67: Normalization of wakefulness (ESS)
Oveporexton (TAK-861) demonstrated normalization of wakefulness (ESS) at 8 weeks and maintained over an additional 6 months The Epworth Sleepiness Scale (ESS): short self-assessment to identify how likely to fall asleep during daytime, measured by eight questions. Total score range 0-24 (each questi
Slide 68: Sustained reduction in cataplexy events
Oveporexton (TAK-861) demonstrated sustained reduction in cataplexy events over an additional 6 months Weekly Cataplexy Rate (WCR): average number of cataplexy events per week WCR Cataplexy 25 • Oveporexton showed statistically significant 20 and clinically Improvement meaningful reduction in Median
Slide 69: Improved cognitive symptoms in NT1 patients
Oveporexton (TAK-861) improved cognitive symptoms in NT1 patients, offering a unique advantage over standard of care Psychomotor Vigilance Test (PVT): simple 10 min reaction performance task to measure sustained attention (test counts # of lapses in attention) Number of PVT lapses at week 8 Cognitiv
Slide 70: Substantial improvements in nighttime symptoms
NT1 patients reported substantial improvements in nighttime symptoms with oveporexton (TAK-861) Sleep diary: daily recording of last night's sleep quality and disturbances (difficulty falling or staying asleep, nightmares as well as sleep paralysis and hallucinations) Nights Per Week With Disturbing
Slide 71: Sustained improvements in Narcolepsy Severity Score
Patient reported symptoms demonstrated sustained improvements in Narcolepsy Severity Score (NSS-CT) in participants with NT1 NSS: validated, self-administered, 15-item scale evaluating severity, frequency and impact of 5 narcolepsy symptoms (sleepiness, cataplexy, sleep paralysis, hallucinations and
Slide 72: Oveporexton well tolerated over additional 6 months
Oveporexton (TAK-861) was well tolerated by participants with NT1 over an additional 6 months of treatment Oveporexton was well tolerated by NT1 participants with no serious treatment-related TEAEs or discontinuations due to TEAEs in the Ph2b trial and LTE. The most common TEAEs observed were insomn
Slide 73: Oveporexton Ph3 NT1 studies on track to readout in CY2025
Oveporexton (TAK-861) Ph3 NT1 studies on track to readout in CY2025 Oveporexton (TAK-861) Dose 1 Primary Endpoint: 1 Oveporexton (TAK-861) Dose 2 • MWT @ wk 12 N = 152 Secondary Endpoints including: Placebo • ESS @ wk 12 • WCR @ wk 12 • PVT @ wk 12 • Safety/Tolerability 2 Oveporexton (TAK-861) Dose
Slide 74: Oveporexton potential best-in-class, transformative profile
Oveporexton (TAK-861) with potential best-in-class, transformative profile addressing NT1 symptoms holistically • Positioned to be first orexin agonist with potentially • Oveporexton was well tolerated by NT1 participants transformative profile: with no serious treatment-related TEAEs or • Statistic
Slide 75: TAK-360 and beyond
TAK-360 and beyond Additional assets/indications
Slide 76: NT1, NT2 and IH are central disorders of hypersomnolence
Narcolepsy type 1 (NT1), narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH) are all central disorders of hypersomnolence with significant unmet need Orexin deficiency is NT1 NT2 IH cause of NT1; unknown Excessive Daytime pathophysiology Sleepiness for NT2/IH Cognitive Symptoms Common challenge:
Slide 77: TAK-360: next-generation orexin agonist for NT2 and IH
TAK-360: next-generation orexin agonist for NT2 and IH and potentially other indications in patients with normal orexin levels Higher doses (>3X) of an Distinct structure -- target profile supported by 01 OX2R agonist necessary pre-clinical data for orexin normal populations Potent - greater flexibi
Slide 78: Takeda pioneering the field of orexin therapeutics
Takeda pioneering the field of orexin therapeutics – franchise leading with oveporexton, a potential first-in-class treatment for NT1 Oveporexton (TAK-861): TAK-360 and beyond: First & Fast3 in NT1 Additional assets/indications • The most advanced orexin agonist – • TAK-360: Accelerated development
Slide 79: Orexin Franchise Market Opportunity
Unlocking the full value Orexin Franchise of orexin and potentially Market Opportunity transforming patient care in sleep and beyond
Slide 80: Narcolepsy is a life-altering condition with significant burden
Narcolepsy is a life-altering condition with a significant burden – expanding far beyond symptoms EDS or cataplexy True burden of narcolepsy is often unrecognized are just the tip of the iceberg and underappreciated - leaving patients vulnerable to isolation and stigma Functional impairments Work &
Slide 81: Patients with narcolepsy face challenges at each step of their journey
Patients with narcolepsy face significant challenges at each step of their journey – starting with one of the longest diagnosis delays Symptom Onset Pre-Referral Testing & Diagnosis Treatment Start & Adjustments Management of Narcolepsy • Patients undergo trial & • Lack of patient-centric goals & er
Slide 82: Significant unmet needs remain today
Significant unmet needs remain today - with no treatment options addressing the underlying cause and holistic burden of NT1 Diagnosis Symptom delays Diagnosis rate dismissal >10-15 years <50% Discontinuation Add-on Residual rate Treatment rate3 polypharmacy symptoms ~25% >60% >80%1 ~75% Low disease
Slide 83: Oveporexton potential to address overall disease burden
Oveporexton (TAK-861) has the potential to address the overall disease burden important to patients with NT1 Potential first-in-class orexin agonist addressing broader disease burden and functional impacts • High treatment satisfaction • Sustained normalization of core Excessive symptoms and signifi
Slide 84: Takeda advancing solutions for holistic transformation of narcolepsy care
Takeda is advancing multiple industry-leading solutions to support a holistic transformation of narcolepsy patient care Takeda Orexin Franchise Focus Uncovering the True Advancing & Redefine Burden of Narcolepsy Accelerating Diagnosis Treatment Outcomes Evidence generation Industry-leading Capturing
Slide 85: Oveporexton on track to be first orexin agonist
Oveporexton – On track to be the first orexin agonist with potential to transform NT1 treatment paradigm, starting in the U.S. ~95-120k 10-20% 5-10% 30-50% Prevalent NT1 Diagnosis rate Treatment Preference patients1 Optimization rate increase Share Improve rate, speed and Redefine treatment Deliver
Slide 86: Tailored portfolio to unlock full value of orexin
Tailored portfolio of potentially transformative treatments to unlock full value of orexin Additional Opportunities: TAK-360: Accelerated Sleep-Wake Oveporexton: Development Respiratory conditions Tailored to address unique $2-3B NT1 PEAK REVENUE POTENTIAL unmet needs in NT2 & IH Metabolic disorders
Slide 87: Unlocking the full value of orexin with a multi-asset franchise
Takeda is unlocking the full value of orexin with a multi-asset, multi-indication franchise – Leading with oveporexton (TAK-861), peak revenue potential $2-3B Oveporexton is on track to become the 1st and potentially best-in-class, transformative treatment indicated for NT1 Unprecedented Ph2 and LTE
Slide 88: Today's Agenda
Today’s Agenda TIME (JST) AGENDA 8:30-8:40 A Global, Innovation-driven Biopharmaceutical Company Christophe Weber, President & CEO 8:40-9:00 R&D Strategy and Pipeline Highlights Andy Plump, President Research & Development 9:00-9:50 Neuroscience: Deep-dive on Orexin Franchise Sarah Sheikh, Head of N
Slide 89: Gastrointestinal & Inflammation: Zasocitinib, Rusfertide, Mezagitamab, Fazirsiran
Gastrointestinal & Inflammation (GI&I): Deep-dive on Zasocitinib, Rusfertide, Mezagitamab, and Fazirsiran Chinwe Ukomadu Ramona Sequeira Head of GI&I Therapeutic, Area Unit President, Global Portfolio Division
Slide 90: GI & Inflammation portfolio designed to deliver high-value therapies
The GI & Inflammation portfolio is designed to deliver high-value therapies in the next 5 years and over the long-term to ensure strong & sustainable growth Large portfolio 11 unique drugs being developed to treat 13 diseases, with more of differentiated programs poised to enter the clinic over the
Slide 91: Late-stage programs have significant value potential
Late-stage programs have significant value potential; oveporexton, zasocitinib, rusfertide phase 3 data expected in 2025 Three Phase 3 Data Readouts Over the Next 12 Months Target Filing Dates by Indication • Oveporexton in Narcolepsy Type 1 FY25 / FY26 • Zasocitinib in Psoriasis Oveporexton Narcole
Slide 92: Zasocitinib (TAK-279)
Zasocitinib (TAK-279) Next-generation TYK2 Inhibitor, potential to be the 1st choice advanced therapy
Slide 93: TYK2 is the fundamental regulator of immune signaling pathways
TYK2 is the fundamental regulator of immune signaling pathways including IL-23 and IFN α/β which play a critical role in inflammatory diseases IL-23 IL-12 IFN-α/β • IL-23 & INF α/β signaling plays a role in several inflammatory diseases such as, • PsO, PsA, UC, Crohn’s and others • TYK2 regulates th
Slide 94: Genetic alteration in TYK2 protects against inflammatory diseases
Studies suggest that genetic alteration in TYK2 function protects against inflammatory diseases, without significant adverse outcomes People with One Altered Copy of TYK2 A common genetic alteration in the TYK2 Multiple Sclerosis gene has been identified and results in an ~80% reduction of TYK2 sign
Slide 95: Zasocitinib's high selectivity
Zasocitinib’s high selectivity supports the evaluation of a range of doses without concern of JAK1/2/3 inhibition Zasocitinib binds to the regulatory domain of TYK2 allowing it to demonstrate exquisite selectivity, unlike traditional kinase inhibitors IL-23 IL-12 IFN-α/β Highly Selective Supports th
Slide 96: Zasocitinib greater and longer TYK2 inhibition versus deucravacitinib
Zasocitinib exhibits greater and longer TYK2 inhibition versus deucravacitinib and no inhibition of JAK1/3 Zasocitinib 30 mg QD Deucravacitinib 6 mg QD JAK1/3 IC50 was not achieved at max concentration tested, 30,000 nM1 Greater and Longer Inhibition JAK safety margin Zasocitinib at 30mg QD is signi
Slide 97: Unmet need for a simple, safe and effective oral treatment in psoriatic disease
Despite numerous treatment options available to patients with psoriatic diseases there is still unmet need for a simple, safe and effective oral treatment • Psoriasis is estimated to affect Scalp • Psoriatic arthritis is a chronic, progressive, >60 million adults1 inflammatory disease of the joints
Slide 98: One-third of patients achieved complete skin clearance
One-third of patients achieved complete skin clearance at 12 weeks with 30 mg once daily of zasocitinib PASI Score @ 12 weeks Ph2b PsO study results 100% 90% 80% *** *** achieving PASI scores Proportion of patients 70% 68% 67% 60% PASI 75 *** *** *** 50% 44% 45% 46% *** PASI 90 40% 33% 30% *** PASI
Slide 99: No evidence of JAK-related safety signals
No evidence of JAK-related safety signals, consistent with zasocitinib’s exquisite selectivity Zasocitinib Zasocitinib Zasocitinib Zasocitinib Ph2b PsO study results Placebo 2 mg once daily 5 mg once daily 15 mg once daily 30 mg once daily AE, n (%) (n=52) (n=50) (n=52) (n=53) (n=52) Deaths 0 0 0 0
Slide 100: Strong efficacy in Ph2b PsA study
Strong efficacy across joint and skin endpoints demonstrated in Ph2b PsA study PASI 75 Response at Week 121 ACR 20, ACR 50, ACR 70 Response at Week 121 Ph2b Study Results Ph2b Study Results 100 Response rate, % (95% CI) 100% * 80 45.7% 90% 60 25.6% 28.3% 80% 40 15.4% Response Rate (%) 70% 20 * * 0 6
Slide 101: Safety data from psoriatic arthritis Ph2b study
Safety data from psoriatic arthritis Ph2b study supports that zasocitinib is generally well tolerated with a balanced benefit-risk profile Placebo Zasocitinib 5 mg QD Zasocitinib 15 mg QD Zasocitinib 30 mg QD Ph2b PsA study results (n=72) (n=71) (n=75) (n=72) n (%) n (%) n (%) n (%) Any TEAEs 39 (54
Slide 102: Pivotal Ph3 studies in PsO and head-to-head plans
Completed enrollment ahead of schedule in two pivotal Ph3 studies in PsO with plans to begin head-to-head study versus deucravacitinib LATITUDE-PsO-3001 Zasocitinib 30mg QD Co-primary Endpoint: Moderate-to-Severe Patients PASI-75 at week 16 n=600 Apremilast 30mg BID sPGA of clear (0) or almost clear
Slide 103: Zasocitinib advanced into phase 3 for psoriatic arthritis
Takeda has advanced zasocitinib into phase 3 for psoriatic arthritis Primary Endpoint: Zasocitinib 15mg QD ACR20 at week 16 LATITUDE-PsA-3001 n=1088 Zasocitinib 30mg QD Key Secondary Endpoint: Randomization 1:1:1:1 PASI-75 at week 16 Apremilast 30mg BID MDA at week 16 Placebo Primary Endpoint: LATIT
Slide 104: More than 5 million patients globally suffer from IBD
More than 5 million patients globally suffer from IBD IBD is a chronic inflammatory condition which includes two subtypes: Ulcerative Colitis (UC) & Crohn’s Disease IBD patients experience diarrhea, abdominal pain, and, in the case of UC, perianal bleeding Patients experience morbidity from prolonge
Slide 105: Zasocitinib scientific rationale in IBD
Zasocitinib has strong scientific rationale to support exploration in IBD Genetic analysis has identified an alteration in Animal models of colitis demonstrate a 1 the TYK2 gene that is highly protective against 3 significant reduction in disease activity at high inflammatory diseases, including Cro
Slide 106: Zasocitinib phase 2b studies in IBD
Takeda is currently evaluating zasocitinib in phase 2b studies in IBD Primary Endpoint: Endoscope response based on SES-CD at Zasocitinib Dose 1 week 12 LATITUDE-CD-2001 Moderate-to-severe patients Zasocitinib Dose 2 Key Secondary Endpoint: n=268 Clinical remission based on CDAI at week 12 Randomiza
Slide 107: Zasocitinib development timeline
With a deep history in inflammation, Takeda is uniquely placed to advance zasocitinib PHASE 2b START PHASE 2b READOUT PHASE 3 FILING Ph3 Start FY2023 Psoriasis Ph2b March 2023 Target FY2026 Zaso vs Deucra Start FY2025 Psoriatic Arthritis Ph2b September 2023 Target Ph3 Start FY2024 Target FY28/29 Cro
Slide 108: Zasocitinib Market Opportunity
Well-positioned to be the first-choice Zasocitinib advanced therapy for Market Opportunity psoriatic disease patients, leading the next-generation orals
Slide 109: PsO is much more than just a rash
PsO is much more than just a rash; patients are really suffering The visible plaques, social stigma and higher risk of comorbidities negatively impact patients’ QoL1 Associated comorbidities “Psoriasis first spread over my entire body and then onto my face. For me personally facial psoriasis was the
Slide 110: 30% of PsO patients develop PsA
30% of PsO patients develop PsA, which comes with an even higher burden of disease Patients experience unbearable symptoms… … with a significant impact on QoL Irreversible joint damage, Social withdrawal from Inability to perform potentially leading to Chronic pain Fatigue Skin lesions activities “n
Slide 111: Significant growth of advanced therapies in PsO and PsA markets
We expect significant growth of advanced therapies in both PsO and PsA markets, both already large at $23B and $7B worldwide, respectively US Moderate-to-Severe PsO AT Market Projection2 Significant headspace for growth of advanced 2M pts therapy segment in PsO • WW PsO Advanced Therapy (AT) Market
Slide 112: Growth of advanced therapies driven by improved oral options
This growth of advanced therapies is driven by improved oral options Oral share is expected to double in both PsO and PsA US Moderate to Severe PsO and Active PsA Oral Market Projection1 1.4M AT “ Orals treated pts are where the market is going. It's where all the companies are investing. 900K AT tr
Slide 113: Redefine what is possible with an oral therapy in psoriatic disease
Zasocitinib aims to… REDEFINE WHAT IS POSSIBLE WITH AN ORAL THERAPY IN PSORIATIC DISEASE
Slide 114: Patients seeking safe and effective oral treatment options
Patients are seeking safe and effective oral treatment options when topical and conventional treatments aren't enough WHAT PATIENTS TELL US THEY WANT Zasocitinib Apremilast Deucravacitinib Clear skin Safety data Well-tolerated Once daily oral / easy to take Target profile based on Ph2b results Zasoc
Slide 115: Zasocitinib designed for efficacy, safety and simple treatment
Zasocitinib was designed to provide both efficacy & safety, along with a simple and easy treatment experience A next-generation, highly selective and potent TYK2 inhibitor A simple & easy treatment experience • Once daily oral treatment • Well-tolerated • Can be taken any time of the day without reg
Slide 116: PsO & PsA combine for up to $6B of peak revenue
PsO & PsA combine for up to $6B of peak revenue, with the potential for additional indications including Crohn’s & UC US PsO + PsA Market Evolution over next ~10 yrs Global Peak Diagnosed Advanced Revenue Plus Plus Oral Zasocitinib Potential PsO & PsA Therapy potential st treated 1 Choice Crohn’s ad
Slide 117: Unique opportunity for zasocitinib
Unique opportunity for zasocitinib Large, growing market in PsO/PsA with only ~30-50% of moderate-to-severe patients currently on advanced therapy Opportunity for improved oral options to expand the use of advanced therapy and more than double the share of AT patients on orals As a next-generation,
Slide 118: Rusfertide: Advancing Polycythemia Vera Treatment
Rusfertide: Advancing Polycythemia Vera (PV) Treatment for Superior Hematocrit Control
Slide 119: Elevated hematocrit is the hallmark of polycythemia vera
Elevated hematocrit is the hallmark of polycythemia vera (PV) and its clinical challenges PV – Rare Myeloproliferative Neoplasm Characterized by Excessive Production of Red Blood Cells1 FERROPORTIN PV is a rare transports iron Elevated myeloproliferative neoplasm Hematocrit characterized by elevated
Slide 120: Significant unmet need in polycythemia vera treatment
There remains significant unmet need in polycythemia vera treatment Inconsistent HCT Control Increased Risk of Thrombotic Events Significant Burden • Consistent HCT <45% is critical, as • 34-41% of patients experience • PV impacts daily activities and uncontrolled HCT is associated thrombotic events
Slide 121: Mechanistic rationale of rusfertide
Mechanistic rationale of rusfertide in managing polycythemia vera Rusfertide helps address the overproduction of red blood cells MOA of Rusfertide (RBCs) in patients with polycythemia vera (PV) through, Leveraging Hepcidin Mimetic to Target Excessive RBC Production Restricting availability of iron b
Slide 122: Clinical efficacy of rusfertide: durable hematocrit control
Clinical efficacy of rusfertide: rapid, sustained and durable hematocrit control REVIVE Study: PV patients requiring frequent phlebotomy + cytoreductives; 90% phlebotomy free 47 Hematocrit Results1 (Mean ± 1 SEM) Placebo N = 582, 1:1 randomization • Rapid, Sustained and Rusfertide 46 Durable hematoc
Slide 123: REVIVE favorable long-term safety profile
REVIVE demonstrated a favorable long-term safety profile Most common (≥20%) TEAEs • Injection site reactions, fatigue, COVID-19, pruritus, arthralgia, dizziness, nausea, anemia, and headache – Grade 3 TEAEs occurred in 25.7% of patients and there were no Grade 4 or 5 TEAEs Patients in REVIVE were el
Slide 124: Rusfertide phase 3 ongoing: data readout CY2025
Rusfertide phase 3 ongoing: target data readout CY2025 Verify Study (Ph3) Design Primary endpoint: Response Rate at wk 20 to wk 32 (inclusive) Part 1A: Double-Blind1, 2 Part 1B: Open-Label1, 2 vs placebo N = 250 Duration - 32 weeks Duration - 20 weeks • Response is the absence of PHL eligibility Ran
Slide 125: Rusfertide Market Opportunity
Advancing care in Rusfertide polycythemia vera by Market Opportunity targeting critical unmet needs
Slide 126: Patient journey in PV identifies unmet need
Patient Journey in PV identifies unmet need in current treatment paradigm as patients cycle through options with inconsistent HCT and tolerability Cycling on through treatments 2L/3L options often add-on to PHL Ongoing Management Initial Treatment • Introduces 2L/3L treatments if not Presentation an
Slide 127: Rusfertide expected use across treatment landscape
Rusfertide aims to deliver rapid, consistent & sustained HCT control and is expected to be used at each step of the treatment landscape Patients are often on polytherapy and will cycle through various treatments ~155k diagnosed ~41K ~26K ~6K ~3K Phlebotomy And/Or Hydroxy Urea And/Or And/Or Ropeg- pa
Slide 128: Unlocking the full potential of rusfertide
Unlocking the full potential of rusfertide for polycythemia vera patients Advancing Care In The PV Space By Targeting Critical Unmet Needs Approximately 155,000 patients diagnosed with PV with only 78,000 currently being treated Hematocrit control (<45%) is the primary goal of physicians in treating
Slide 129: Mezagitamab (TAK-079)
Mezagitamab (TAK-079) Transformative Potential for Chronic Auto-immune Diseases
Slide 130: Mezagitamab: new unique anti-CD38 antibody
Mezagitamab: New unique anti-CD38 antibody with disease modifying potential providing rapid, safe, selective & sustained depletion of disease-causing immune cells 01 02 03 Potential best-in-class Pipeline Proof of concept anti-CD38 agent in a product in ITP and IgAN Leadership in Potential for multi
Slide 131: Mezagitamab rapid, selective depletion of immune cells
Mezagitamab is designed for rapid, selective, safe and sustained depletion of immune cells Rapid and robust antibody reduction Selective targeting observed in multiple indications1 Plasma cell of CD38 directly • IgG up to 41% depletes long and CD38 • IgA up to 70% short-lived plasma • Gd-IgA1 up to
Slide 132: Understanding IgA Nephropathy pathophysiology
Understanding IgA Nephropathy (IgAN) pathophysiology and the consequences for patients 4-hit model of IgAN pathophysiology1-3 Gd-IgA Plasma cells produce Hit 1 circulating galactose- • IgAN is a chronic progressive deficient (Gd-) IgA1 IgA plasma cell autoimmune mediated kidney disease usually diagn
Slide 133: Mezagitamab addresses the root causes of IgAN
Mezagitamab addresses the root causes of IgAN, thereby delivering a sustained disease-modification (including off-treatment) 4-hit model of IgAN pathophysiology1-3 Mezagitamab targets the initial steps in Hit 1 IgAN pathophysiology (Hit 1 and 2)1-3 Mezagitamab Mezagitamab • Binding to CD38, mezagita
Slide 134: Unmet need in IgAN: disease modifying treatment
Unmet need in IgAN is for a transformative disease modifying treatment that preserves kidney function The primary goal of IgAN treatment is to halt the chronic kidney injury thereby preserving renal function (eGFR) Unmet needs remain Time (year) Mezagitamab’s Need for disease modifying treatment 0 1
Slide 135: Mezagitamab POC study in IgA nephropathy
Mezagitamab in POC study was well tolerated and showed rapid, sustained best-in-class UPCR reduction in patients with IgA nephropathy Mezagitamab IgAN Phase 1 data1 Best-in-Class Efficacy Rapid and sustained reduction in proteinuria (UPCR) Start Tx End of Tx • Mezagitamab demonstrated rapid and Week
Slide 136: Potential best in class anti-CD38 agent in IgAN
Potential best in class (anti-CD38) disease modifying agent in IgAN Disease Modifying Potential Not Disease Modifying Targeting Mezagitamab Targeting B-cells Plasma Cells Corticosteroid Anti-APRIL Anti-CD38 Stabilizing renal Complement inhibitors Anti-APRIL/BLyS ETA(AT1) inhibitors function ACE/ARB
Slide 137: Understanding immune thrombocytopenia
Understanding immune thrombocytopenia (ITP) and its consequences for patients ITP pathophysiology1-8 Plasma cell • ITP is a rare chronic disorder characterized by an autoimmune response against platelets and Autoantibodies against platelets and megakaryocytes megakaryocytes leading to low platelet c
Slide 138: Mezagitamab addresses the root causes of ITP
Mezagitamab addresses the root causes of ITP, delivering a sustained disease-modifying treatment Plasma cell • Binding to CD38, mezagitamab Mezagitamab depletes IgG producing plasma cells • This suppresses the production of the IgG autoantibodies and leads to a profound and sustained reduction in le
Slide 139: Current ITP treatments leave clinical unmet needs
Current ITP treatments leave clinical unmet needs The primary goal of ITP treatment is to quickly and sustainably restore safe levels of platelets Patients want new novel 1 Stable platelet count over time treatments that deliver Platelet counts (109/L) • Durable platelet response • Long-term remissi
Slide 140: Mezagitamab improvement in platelet response in ITP
Mezagitamab demonstrated rapid and sustained improvement in multiple efficacy measures of durable platelet response in patients with immune thrombocytopenia Mezagitamab ITP Phase 2b data1 Robust and Sustained Efficacy and Favorable Safety1 Platelet response (PR) Complete PR 100 PC ≥50,000/µL and ≥20
Slide 141: ITP phase 3 pivotal study
ITP phase 3 pivotal study – expected to start Q4 FY2024 Mode of action permits cyclic dosing thus allowing patients to have extended treatment free periods Primary Endpoint: Inclusion criteria: Durable platelet response ITP pts with insufficient • Response is, platelet count ≥50,000/μL response or i
Slide 142: Mezagitamab Market Opportunity
Well positioned to be the best-in-class anti-CD-38 Mezagitamab agent to transform the Market Opportunity IgAN and ITP markets by setting new standard for patients
Slide 143: Mezagitamab: transformative approach to autoimmune diseases
Mezagitamab: a transformative approach to combat autoimmune diseases Disease modifying Dosing holiday enhances Targets plasma cells treatment potential potential for safety and The direct source of auto-antibodies convenience Rapid and sustained disease Subcutaneous dosing with extended production r
Slide 144: IgAN progressive loss of kidney function
IgAN patients often experience progressive and irreversible loss of kidney function leading to end stage kidney disease ILLUSTRATIVE PATIENT EXPERIENCE WITH IgAN 1 2 3 4 …First visible symptoms …Diagnosis … Progressive loss of renal function …End stage kidney disease Blood in urine often in teens or
Slide 145: Mezagitamab potential to stop IgAN progression
Mezagitamab has the potential to stop the disease progression and address the root cause of the disease in IgAN ~1.5M No diagnosed ~90% ~55% approved IgAN patients treatment treated with Progressing stopping G7+ China current SOC despite SOC2 the disease ~200K in the progression US1 Establish the CD
Slide 146: ITP current therapies leave many patients struggling
In ITP, current therapies leave many patients struggling with their disease and looking for improved treatment options in 3L ILLUSTRATIVE PATIENT EXPERIENCE WITH ITP …Newly Diagnosed ITP …Persistent / Chronic ITP …Refractory to 2 lines (0-3 months post Dx) (>3 months post Dx) of therapies 1 2 3 …Dia
Slide 147: Need for effective treatment in ITP creates opportunity
The need for effective treatment for patients not responding well to current standard of care in ITP creates an opportunity for mezagitamab >200k diagnosed ~20% with ITP patients inadequate Need for globally / response to effective 2 lines of options ~50K in the US1 therapies2 Differentiate mezagita
Slide 148: Potential transformative profile in auto-immune diseases
Potential to deliver a transformative profile, addressing the root cause in auto-immune diseases IgAN ambition • 1st anti-CD38 choice • Stop progression of disease (eGFR stabilization) with sustained kidney protection off-treatment Global Peak Revenue Plus • Promise of treatment holiday (half of yea
Slide 149: Unlocking the full potential of mezagitamab - summary
Unlocking the full potential of mezagitamab in autoimmune diseases – Summary Slide Mezagitamab is well positioned to be the best-in-class anti-CD38 agent with disease modifying potential and treatment holiday to transform the IgAN and ITP treatment by setting new standard for patients POC studies de
Slide 150: Fazirsiran
Fazirsiran The potential of a transformative therapy for patients living with Alpha-1 Antitrypsin Deficiency Liver Disease (AATD-LD)
Slide 151: No treatment options available for AATD liver disease
There are no treatment options available to Alpha-1 Antitrypsin Deficiency liver disease (AATD-LD) patients today AAT Deficiency (AATD), a genetic disease, often results in a misfolded AAT protein and increases risk of liver and lung disease AATD-LD is caused by to the AATD-LD is a largely Fazirsira
Slide 152: Z-AAT polymer accumulation causes fibrosis and end stage liver disease
Z-AAT polymer accumulation is known to cause fibrosis and end stage liver disease FIBROSIS Hepatocellular Inflammation injury and cell stress CIRRHOSIS Accumulation of aggregated misfolded Z-AAT polymers within hepatocytes causes ER (proteotoxic) stress which over time HCC leads to chronic liver inj
Slide 153: Fazirsiran mechanism of action
Fazirsiran’s mechanism of action stops the production of Z-AAT, directly addressing the pathology in AATD liver disease Fazirsiran is a liver-targeted, 1 double-stranded siRNA1-3 Nucleus Cytoplasm SERPINA1 1 Fazirsiran Z allele Fazirsiran leads to 2 Z-AAT mRNA degradation1,2 Z-AAT mRNA 2 Z-AAT prote
Slide 154: Ph2 study to demonstrate reduction of liver Z-AAT
Ph2 study intended to demonstrate reduction of liver Z-AAT AROAAT2002: Ph2 study design1,2 6-month study arms FAZIRSIRAN COHORT 1 200mg/mL (SC) FAZIRSIRAN COHORT 1b 100mg/mL (SC) Cohort 1 (n = 4) Primary Endpoint: Dosing • Change from baseline in Schedule Q12 W thereafter up to Cohort 1b (n = 4) Day
Slide 155: Ph2 POC study reductions in serum and liver Z-AAT
Ph2 POC study showed that fazirsiran treatment leads to significant reductions in serum and liver Z-AAT concentrations Primary endpoint: Change from baseline in liver Z-AAT Change from baseline serum Z-AAT 100 Median relative change 0% 90 -83.3% Fazirsiran 200 mg Cohort 1 (N=4) (95% CI -89.7 to -76.
Slide 156: Randomized dose ranging placebo-controlled study
Randomized dose ranging placebo-controlled study that laid the foundation for Ph3 development AROAAT2001 (SEQUOIA): Ph2 study design1,2 FAZIRSIRAN 25mg/mL (SC) Primary Endpoint: N = 40 • Percent change in serum Z-AAT FAZIRSIRAN 100mg/mL (SC) @ wk 16 Fibrosis <F4 or no fibrosis (based on FAZIRSIRAN 2
Slide 157: Ph2 placebo controlled study reducing Z-AAT
Ph2 Placebo controlled study demonstrates fazirsiran’s transformative potential in reducing Z-AAT Serum Z-AAT concentration Liver Z-AAT concentration 20 40 9 % change from baseline to week 48+ in liver 26 % change from baseline in mean serum 4 0 20 0 -20 -20 Z-AAT -40 Z-AAT -40 -60 -60 -62 -80 -74 -
Slide 158: Strong safety profile demonstrated in Ph2
Strong safety profile demonstrated in Ph2, with no TEAE-related discontinuations, dose interruptions, or study withdrawals Treatment emergent adverse events (TEAE) AROAAT2001 (NCT03945292; Phase 2) 1 Incidence, n (%) Fazirsiran 25 mg Fazirsiran 100 mg Fazirsiran 200 mg Placebo (n=9) (n=8) (n=9) (n=1
Slide 159: Fazirsiran Ph3 ongoing: target filing FY2028
Fazirsiran Ph3 ongoing: target filing FY2028 Redwood Study (Ph3) Design1 Primary Endpoint: • ≥ 1 point reduction in fibrosis score (F2-F3) by liver biopsy @ wk 106 n=160 FAZIRSIRAN 200mg/mL (SC) Secondary Endpoint include: Randomization 1:1 • Percent change in total liver Z-AAT Includes stage F2 – F
Slide 160: Fazirsiran Market Opportunity
Well positioned to be the first Fazirsiran available treatment indicated for AATD associated Liver Market Opportunity Disease
Slide 161: Fazirsiran opportunity to offer transformative therapy for AATD-LD
Fazirsiran represents an opportunity to offer hope in the form of a transformative therapy for patients living with AATD-LD I had lived a perfectly healthy life for 50 years when I suddenly became “ unwell with several subtle changes, then suddenly became jaundiced. I was diagnosed with Alpha-1 Anti
Slide 162: AATD-LD asymptomatic progression with higher risks
AATD-LD, an asymptomatic disease progression coupled with higher risks for cancer and liver transplant ILLUSTRATIVE PATIENT EXPERIENCE WITH AATD -LD Silently progressive liver disease End stage liver disease Undiagnosed +10 years +1 year Diagnosed +6 months +1 year Potential elevated LFTs Referral t
Slide 163: AATD-LD significant unmet needs
AATD-LD has significant unmet needs anchored around the lack of available treatments, low awareness & low diagnostic rates There are no treatments available to slow or stop progression to end-stage liver disease and liver failure in Low AATD patients ent Aw tm rea ar ene No T Disease awareness is lo
Slide 164: AATD-LD market and Fazirsiran's potential
The AATD-LD market & Fazirsiran's potential are poised to benefit from the advancements in MASH & diagnosis acceleration upon availability of an effective treatment in AATD ~35% ~10-15% No ~250k of Pi*ZZ of AATD-LD available Pi*ZZ prevalent patients patients are treatment patients globally1 develop
Slide 165: Fazirsiran: first potential treatment for AATD-LD
Fazirsiran (TAK-999): The 1st Potential Treatment for AATD-LD with global peak revenue opportunity of $1-3B Fazirsiran is on track to be the 1st available treatment indicated for AATD associated liver disease Strong Phase 2 clinical data demonstrates Fazirsiran reduces Z-AAT, reverses fibrosis, and
Slide 166: Today's Agenda
Today’s Agenda TIME (JST) AGENDA 8:30-8:40 A Global, Innovation-driven Biopharmaceutical Company Christophe Weber, President & CEO 8:40-9:00 R&D Strategy and Pipeline Highlights Andy Plump, President Research & Development 9:00-9:50 Neuroscience: Deep-dive on Orexin Franchise Sarah Sheikh, Head of N
Slide 167: Oncology: Deep dive on Elritercept
Oncology: Deep dive on Elritercept – newly announced BD deal P.K. Morrow Teresa Bitetti Head of Oncology Therapeutic Area Unit President, Global Oncology Business Unit Please refer to the Important Notice at the start of this presentation for more information about the Elritercept license agreement
Slide 168: Late-stage programs have significant value potential
Late-stage programs have significant value potential; oveporexton, zasocitinib, rusfertide phase 3 data expected in 2025 Three Phase 3 Data Readouts Over the Next 12 Months Target Filing Dates by Indication • Oveporexton in Narcolepsy Type 1 FY25 / FY26 • Zasocitinib in Psoriasis Oveporexton Narcole
Slide 169: Oncology strategy leveraging internal and external innovation
Oncology strategy is focused on leveraging internal and external innovation to address unmet medical need We aspire to cure cancer with inspiration from patients and Vision innovation from everywhere • ENRICH mid- and late-stage pipeline through internal and external innovation, and create a robust,
Slide 170: Oncology R&D focus on three disease areas and four modalities
Oncology R&D efforts focus on three disease areas and four modalities Oncology Disease Areas Modalities Small Molecules Heme ALL, AML/MDS, CML/MF Complex Biologics GI CRC, Gastric, Pancreatic, HCC Antibody–drug conjugates (ADCs) Thoracic NSCLC, SCLC, SCCHN Gamma Delta Cell Therapies ALL: Acute Lymph
Slide 171: Recent business development transactions enhance Oncology strategy
Recent business development transactions enhance realization of Takeda’s Oncology strategy Aligning our disease focus, exploring diverse modalities and addressing high unmet patient needs Fruzaqla® (Fruquintinib) Mirvetuximab soravtansine-gynx In-licensing of fruquintinib1 from HUTCHMED Licensing ag
Slide 172: Elritercept
Elritercept Potentially best-in-class activin inhibitor for treatment of anemia associated with hematologic diseases, including myelodysplastic syndromes (MDS) & myelofibrosis (MF) Elritercept is included for reference only. Takeda entered into an exclusive license agreement with Keros for global ri
Slide 173: Elritercept foundational opportunity for Oncology strategy
Elritercept represents a foundational opportunity to further realize Takeda’s Oncology strategy and grow our footprint in hematologic cancers 01 02 03 Best-in-Class Potential Pipeline in a Molecule Strong Strategic Fit Differentiated Potential to help patients Strong strategic fit into our mechanism
Slide 174: High unmet need remains for MDS patients
High unmet need remains for MDS patients despite advances In MDS, overactivation of the TGF-β superfamily (e.g., MDS comprises several bone marrow disorders characterized Activin A and B) blocks Activin by ineffective hematopoiesis and peripheral cytopenias, which hematopoiesis A+B may arise from ov
Slide 175: Elritercept potentially best-in-class for anemia-associated diseases
Elritercept is a potentially best-in-class treatment for anemia-associated diseases Elritercept has the potential to address significant clinical unmet need that persists despite currently available Elritercept anemia-associated LR-MDS treatments Erythrocytes (RBCs) • Potent inhibitor of both Activi
Slide 176: Elritercept strong responses across AA LR-MDS segments
Elritercept demonstrated strong responses across AA LR-MDS segments, supporting the potential to treat a broad proportion of patients EPO < 500 U/L2 % Responders1 All (N=71) HTB (N=39) • Response rates in patients with Overall Response3 60.6% 56.4% high transfusion burden (HTB) were similar to those
Slide 177: Elritercept prolonged and durable transfusion independence
Elritercept resulted in prolonged and durable transfusion independence (TI) in Ph2 study Longest TI interval in mITT24 participants who achieved TI ≥ 8 wks from baseline through Wk 24** 1.0 Duration of TI Probability of Maintaining TI Median (95% CI), weeks 134.1 (23.0, NE) Participants with ongoing
Slide 178: Elritercept safety profile and QoL improvements
Elritercept showed a generally well tolerated safety profile and has resulted in improvements in QoL in AA LR-MDS patients Majority of the treatment-emergent adverse events (TEAEs) were mild to moderate (Gr 1-2) Safety Investigator and sponsor assessed that there were no treatment related fatal adve
Slide 179: Elritercept Ph3 in 2L+ AA LR-MDS
Elritercept Ph3 in 2L+ AA LR-MDS – Target study start FY2024 RENEW Ph3 Study Design Primary endpoint N = 225 Elritercept + BSC* • TI ≥ 8 weeks within the first Randomization 2:1 24 weeks (ITT population) Placebo + BSC* Secondary endpoint Stratification • Safety/tolerability • Transfusion Burden (hig
Slide 180: Elritercept benefit across hematologic indications
Elritercept is a molecule that has the potential to benefit patients across a wide portfolio of hematologic indications • Potential best-in-class asset, based on Ph2 results, showing strong Anemia- efficacy across heme lineages, and a generally well tolerated safety Associated profile (AA) LR-MDS •
Slide 181: Elritercept Commercial Opportunity
Well positioned to be the best-in-class agent for Elritercept treating anemia Commercial Opportunity associated with LR-MDS across treatment lines Please refer to the Important Notice at the start of this presentation for more information about the Elritercept license agreement
Slide 182: LR-MDS large growing space with unmet medical need
LR-MDS is a large growing space with significant unmet medical need Transfusion Dependent LR-MDS Patients 50k+ Incident1 MDS patients (US, EU-42 RS+ (30%) RS- (70%) and JP) • ~40% of patients will not 1L ESA ESA respond to ESA in 1L and will progress within a year luspatercept luspatercept3 37k+ • M
Slide 183: Elritercept profile potential best-in-class
Elritercept profile has the potential to be best-in-class based on Ph2 data Key Unmet Needs Emerging Elritercept Profile1 Transfusion independence and time to response Nearly half of patients achieved TI ≥8 weeks Faster onset of action Broad activity across patient segments Strong efficacy and
Slide 184: Elritercept targeting initial indication in 2L+
Elritercept is a potential best-in-class treatment for AA LR-MDS targeting an initial indication in 2L+ with the aim to expand quickly into 1L Anemia Associated with LR-MDS RS+ (30%) RS- (70%) 1L Potential Potential expansion expansion to 1L to 1L 2L Elritercept target indications 3L Initial indicat
Slide 185: Elritercept: potential to benefit wide range of MDS and MF patients
Elritercept: Potential to benefit a wide range of patients with MDS and MF Strong strategic fit with existing hematology-oncology disease area focus Differentiated mechanism of action impacting early and late haematopoiesis Ph3 ready asset with lead indication in 2L+ AA LR-MDS and potential expansio
Slide 186: Late-stage programs have significant value potential
Late-stage programs have significant value potential; oveporexton, zasocitinib, rusfertide phase 3 data expected in 2025 Three Phase 3 Data Readouts Over the Next 12 Months Target Filing Dates by Indication • Oveporexton in Narcolepsy Type 1 FY25 / FY26 • Zasocitinib in Psoriasis Oveporexton Narcole
Slide 187: Glossary of Abbreviations - 1
Glossary of Abbreviations - 1 Regional Abbreviations: CN: China; EU: Europe; JP: Japan; U.S.: United States of America AA anemia-associated CRC colorectal cancer HCC hepatocellular carcinoma AATD α1-antitrypsin deficiency CRPC castrate-resistant prostate cancer HCP healthcare professional AATD LD α1
Slide 188: Glossary of Abbreviations - 2
Glossary of Abbreviations - 2 Regional Abbreviations: CN: China; EU: Europe; JP: Japan; U.S.: United States of America LS least square PASI psoriasis area and severity index SID secondary immunodeficiency LTB low transfusion burden PC platelet count SOC standard of care LTE long-term extension PDT p
Slide 189: Takeda Investor Relations
Takeda Investor Relations: takeda.ir.contact@takeda.com © 2025 Takeda Pharmaceutical Company Limited. All rights reserved.
Takeda Pharmaceutical Company — 43rd Annual J.P. Morgan Healthcare Conference (January 2025) on 6ix