Takeda Pharmaceutical Co. Ltd. · TSE:4502
Takeda Pharmaceutical — Investor Day (December 2024)
159 slides from Takeda Pharmaceutical's investor day presentation, Dec 13, 2024
Slide 1: Takeda R&D Day 2024: Focus on Late-stage Pipeline & Market Opportunity
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 2: Important Notice and Forward-Looking Statements
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 (including any oral
Slide 3: 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 4: Better health for people, brighter future for the world
Better health for people, brighter future for the world PATIENT PEOPLE PLANET Our vision is to discover and deliver life-transforming treatments, guided by our commitment to: We are guided by our values of Takeda-ism which incorporate Integrity, Fairness, Honesty, and Perseverance, with Integrity at
Slide 5: A global, innovation-driven biopharmaceutical company
15% GROWTH & EMERGING MARKETS 23% EUROPE & CANADA 11% JAPAN 51% U.S. FY2023 REVENUE ¥4.3T ~$28.2B1 A global, innovation-driven biopharmaceutical company 80PRESENCE IN APPROX COUNTRIES & REGIONS Global Footprint Aligned With Key Market Opportunities GLOBAL HEADQUARTERS TOKYO, JAPAN GLOBAL HUB CAMBRID
Slide 6: Committed to growth & shareholder returns
Committed to growth & shareholder returns Revenue Growth Pipeline Acceleration • Accelerating late-stage assets with potential to generate significant value • Three new molecular entities with Phase 3 data readouts expected by end of CY2025 Margin Improvement Shareholder Returns • Strong cashflow ou
Slide 7: Our late-stage pipeline has significant revenue potential
7 Please refer to the Important Notice at the start of this presentation for more information about peak revenue estimates Elritercept is included for reference only. Takeda entered into an exclusive license agreement with Keros for global rights, in all territories outside of mainland China, Hong K
Slide 8: Late-stage programs have significant value potential; three Phase 3 readouts
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 1. Our partner Protagonist Therapeutics is responsible for Phase 3 development of Rusfertide and has stated Phase 3 data may be
Slide 9: R&D Strategy and Pipeline Highlights
R&D Strategy and Pipeline Highlights Andy Plump President, Research & Development Accelerating Our Late-Stage Pipeline to Transform Patients’ Lives and Deliver Significant Value to Takeda
Slide 10: We discover, develop and deliver life-transforming medicines
We discover, develop and deliver life-transforming medicines for rare and more prevalent diseases across our focused therapeutic areas R&D STRATEGY INNOVATIVE BIOPHARMA ONCOLOGY THERAPEUTIC AREA UNIT NEUROSCIENCE THERAPEUTIC AREA UNIT GASTROINTESTINAL AND INFLAMMATION (GI2) THERAPEUTIC AREA UNIT DAT
Slide 11: Global Development, Global Launch Capability
Global Development, Global Launch Capability 3 Therapeutic Areas, 4 Key Modalities R&D Investment 770 bn JPY1 Robust, High Value Late-Stage Pipeline Our scale, focus, and capabilities have advanced significantly since FY2015 Shire Integration R&D Transformation Enhance R&D Productivity Invest Data S
Slide 12: 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 Late-Stage Peak Revenue Potential >70% PTRS2 to approval $10 - 20B Fazirsiran AATD Liver Disease Elritercept Myelodysplastic Sy
Slide 13: Strong global development, regulatory and launch expertise
We have built strong global development, regulatory and launch expertise FY2021 FY2022 FY2023 FIRST NME APPROVALS MAJOR MARKET APPROVALS1 CIDP maintenance U.S. SC in UC and Crohn’s2 KEY LCM APPROVALS 25715 1.Major Markets: US, EU, Japan or China 2.U.S. approval for Entyvio SC was in September 2023 f
Slide 14: Rigorous prioritization to deliver our late-stage pipeline
Rigorous prioritization to deliver our high value late-stage pipeline GLOBAL NMEs1 % OF EXTERNAL SPEND3 1.Lead indication only, no regional assets/expansions 2.Phase 3 trials ongoing or planned that support the development of the NMEs 3.External spend refers to direct pipeline spend in R&D Business
Slide 15: Execute Clinical Trials with top tier industry performance
Execute Clinical Trials with top tier industry performance Future Fit development model: delivering improved speed, quality and efficiencies across the pipeline Preclinical Ph 1 Ph 2 Ph 3 Filing Launch Research Development Study level: 3 core elements that can be optimized Closeout & Reporting Recru
Slide 16: Future Fit has led to acceleration for zasocitinib and oveporexton
Future Fit and prioritization has led to significant acceleration for zasocitinib and oveporexton ~8 yearsAverage Sleep Medication Development1,2 Study 2 – 503 days (N=1020) Study 2 – 409 days (N=413) Latitude-Psoriasis 1 – 308 days (N=693) Zasocitinib Psoriasis: Time to recruit pivotal trials Latit
Slide 17: 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 Late-Stage Peak Revenue Potential >70% PTRS2 to approval $10 - 20B Fazirsiran AATD Liver Disease Elritercept Myelodysplastic Sy
Slide 18: Sustainable acceleration of First-in-Human and first filing
Sustainable acceleration of First-in-Human, and BLA/NDA First Filing Preclinical stage: 3 core elements for optimization Apply Digital Accelerators Driving Efficiency with Real-Time Decision Support Accelerate Delivery to Clinic (Fast to First-in-Human) Building unified digital infrastructure and th
Slide 19: Our sustainable pipeline provides opportunities across therapeutic areas
EARLY-STAGE PROGRAMS / SELECT LCMs SELECT OPTIONS5 NEUROSCIENCE zamaglutenase Celiac Disease Orphan Drug Designation potential (in any region / indication for a given asset) TAK-594 Frontotemporal Dementia TAK-341 MSA GASTROINTESTINAL AND INFLAMMATION TAK-101 Celiac Disease TAK-227 Celiac Disease da
Slide 20: Partnering to expand our pipeline
Partnering to expand our pipeline and maximize R&D investment Acquisitions Late-stage/Commercialization In-licensing Zasocitinib1 Takeda Development FRUZAQLA Partner Development/Takeda Commercialization Fazirsiran Olverembatinib Shared Development Partner Development with Opt-in Rights RusfertideGam
Slide 21: 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 Late-Stage Peak Revenue Potential >70% PTRS2 to approval $10 - 20B Fazirsiran AATD Liver Disease Elritercept Myelodysplastic Sy
Slide 22: Neuroscience: Deep-dive on Orexin Franchise
Neuroscience: Deep-dive on Orexin Franchise Sarah Sheikh Head of Neuroscience Therapeutic Area Unit & Global Development Ramona Sequeira President, Global Portfolio Division
Slide 23: Recent scientific advancements herald a new era in Neuroscience
High Unmet Need Recent scientific advancements & regulatory momentum heralds a new era in Neuroscience Growing Scientific Understanding Innovative Regulatory Approaches BBB Shuttle Technology • Enhanced understanding of underlying pathophysiology • Identification & validation of previously undruggab
Slide 24: Our vision is to be a leader and partner in neuroscience
Our vision is to be a leader and partner in neuroscience by discovering and delivering life-changing medicines for people and society NEURODEGENERATION RARE NEUROLOGY Strategically focused on three core areas OREXIN Transform care for rare sleep disorders and orexin-related conditions Leverage Taked
Slide 25: Leading Orexin Franchise
Leading Orexin Franchise Better Health, Brighter Future
Slide 26: Takeda pioneering the field of orexin therapeutics
• TAK-360: Accelerated development in NT2 & IH • New chemistry and profile • Fast track designation received in U.S. • Target Ph2 start FY2024 in NT2/IH • Exploration of indications pertinent to orexin biology: sleep-wake, respiration and metabolism • Tailored assets/profiles (e.g., TAK-9252 and oth
Slide 27: NT1 patients face debilitating daytime and nighttime symptoms
Nighttime Symptoms Excessive Daytime Sleepiness (EDS) Cataplexy Hallucinations, Sleep Paralysis Disrupted Nighttime Sleep, Disturbing Dreams1 NT1 patients face daytime and nighttime debilitating symptoms impacting daily function Cognitive Symptoms Daytime Symptoms 1 Sateia MJ. Chest 2014;146:1387–94
Slide 28: OX2R agonist may restore downstream neurotransmitter activity
OX2R Orexin Downstream Neurotransmitter OX2R Agonist Mahoney CE, et al. Nat Rev Neurosci. 2019;20(2):83-93; Chastain EM, et al. Biochim Biophys Acta. 2011;1812:265–274; Nishino S. Sleep Med. 2007;8(4):373-399; Saper CB, et al. Trends Neurosci. 2001;24(12):726-731; Yoshida Y, et al. Eur J Neurosci. 2
Slide 29: Comprehensive approach to evaluate full spectrum of NT1 symptoms
Sleep Diary, PSG ESS: Epworth Sleepiness Scale; MWT: Maintenance of Wakefulness Test; NSS-CT: Narcolepsy severity scale; PVT: Psychomotor Vigilance Task; WCR: Weekly cataplexy rate; FINI: Functional Impacts of Narcolepsy Instrument; CGI-C: Clinical Global Impression of Change; PGI-C: Patient Clinica
Slide 30: Extensive oveporexton Phase 2 program
*Randomized to active arms The extensive oveporexton (TAK-861) phase 2 program laid solid foundation for phase 3 program 95% of participants that completed the placebo-controlled study enrolled in the LTE TAK-861 0.5 mg twice daily ~3 hours apart TAK-861 2 mg twice daily ~3 hours apart TAK-861 2 mg
Slide 31: Optimized dosing regimen critical to efficacy and tolerability
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 monkey CSF Long-acting orexin 2 receptor (OX2R) agonist 7:0 0 8:0 0 12 :00 17 :00 19 :00 21 :00 23 :00 3
Slide 32: Normalization of wakefulness (MWT) at 8 weeks, maintained
Oveporexton (TAK-861) demonstrated normalization of wakefulness (MWT) at 8 weeks and maintained over an additional 6 months • Oveporexton normalized sleep latency on MWT • Sustained improvements in wakefulness in NT1 patients over an additional 6 months of treatment The Maintenance of Wakefulness Te
Slide 33: Normalization of wakefulness (ESS) at 8 weeks, maintained
0 5 10 15 20 25 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 M ea n (S EM ) E SS to ta l s co re Week TAK-861 0.5/0.5 mg TAK-861 2/2 mg TAK-861 2/5 mg TAK-861 7 mg QD Oveporexton (TAK-861) demonstrated normalization of wakefulness (ESS) at 8 weeks and maintained over an additional 6 months N or
Slide 34: Sustained reduction in cataplexy events
Oveporexton (TAK-861) demonstrated sustained reduction in cataplexy events over an additional 6 months IQR: Interquartile Range 0 5 10 15 20 25 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 M ed ia n (IQ R) W CR Week TAK-861 0.5/0.5 mg TAK-861 2/2 mg TAK-861 2/5 mg TAK-861 7 mg QD Weekly Cataplex
Slide 35: Improved cognitive symptoms in NT1 patients
Oveporexton (TAK-861) improved cognitive symptoms in NT1 patients, offering a unique advantage over standard of care Linear mixed effects model with square root transformation, presented on the original scale. *p<0.05; **p<0.01; ***p≤0.001. 0 2 4 6 8 10 12 14 16 18 20 LS m ea n (S E) P VT la ps es *
Slide 36: Substantial improvements in nighttime symptoms
NT1 patients reported substantial improvements in nighttime symptoms with oveporexton (TAK-861) 0 0.5 1 1.5 2 2.5 3 3.5 4 Baseline Week 8 N ig ht s p er w ee k Placebo 2mg/2mg 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 Baseline Week 8 N ig ht s p er w ee k Placebo 2mg/2mg *** * Sleep diary: daily recording of
Slide 37: Sustained improvements in Narcolepsy Severity Score
Patient reported symptoms demonstrated sustained improvements in Narcolepsy Severity Score (NSS-CT) in participants with NT1 0 5 10 15 20 25 30 35 40 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 M ea n (S EM ) N SS -C T to ta l s co re Week TAK-861 0.5/0.5 mg TAK-861 2/2 mg TAK-861 2/5 mg TAK-86
Slide 38: Oveporexton well tolerated by NT1 participants
Oveporexton was well tolerated by NT1 participants with no serious treatment-related TEAEs or discontinuations due to TEAEs in the Ph2b trial and LTE. ~90% of patients continuing in LTE - will provide long term data for benefit-risk. The most common TEAEs observed were insomnia, urinary urgency and
Slide 39: Ph3 NT1 studies on track to readout in CY2025
N = 152 Oveporexton (TAK-861) Dose 1 Placebo Oveporexton (TAK-861) Dose 2 N = 93 Oveporexton (TAK-861) Dose 2 Placebo Oveporexton (TAK-861) Ph3 NT1 studies on track to readout in CY2025 LTE Ph2 completed Q4 FY2023 Ph3 start Q2 FY2024 Ph3 readout CY2025 Potentially transformative profile at launch Pr
Slide 40: Oveporexton positioned as first orexin agonist with transformative profile
• Positioned to be first orexin agonist with potentially transformative profile: • Statistically significant and clinically meaningful improvements in daytime and nighttime NT1 symptoms after 8 weeks of administration returning patients to normative range • Sustained improvements over an additional
Slide 41: TAK-360 and beyond
TAK-360 and beyond Additional assets/indications
Slide 42: Symptoms across NT1, NT2 and IH
Based on Article Reviewed: 1. Sturzenegger C et al. J Sleep Res 2004;13:395–406; 2. Roth T et al. J Clin Sleep Med 2013;9:955–65; 3. Scammell T. Ann Neurol 2003;53:154–66; 4. Black J et al. Sleep Med 2016;24:57–62; 5. Maski K et al. Sleep 2020;43:zsaa066; 6. Trotti LM. Sleep Med Rev 2017;35:76–84; 7
Slide 43: TAK-360: next-generation orexin agonist for NT2 and IH
Higher doses (>3X) of an OX2R agonist necessary for orexin normal populations Best in class development guided by models using extensive OX2R agonism data across multiple assets TAK-360 Distinct structure -- target profile supported by pre-clinical data01 02 Potent - greater flexibility in dosing or
Slide 44: Takeda pioneering the field of orexin therapeutics
• TAK-360: Accelerated development in NT2 & IH • New chemistry and profile • Fast track designation received in U.S. • Target Ph2 start FY2024 in NT2/IH • Exploration of indications pertinent to orexin biology: sleep-wake, respiration and metabolism • Tailored assets/profiles (e.g., TAK-9252 and oth
Slide 45: Orexin Franchise Market Opportunity
Orexin Franchise Market Opportunity Unlocking the full value of orexin and potentially transforming patient care in sleep and beyond
Slide 46: EDS or cataplexy are just the tip of the iceberg
EDS or cataplexy are just the tip of the iceberg Functional impairments Work & school impacts Daily activities Quality of life Relationships Family life Stigma Mood True burden of narcolepsy is often unrecognized and underappreciated - leaving patients vulnerable to isolation and stigma Impact of na
Slide 47: Patients with narcolepsy face challenges at each step of their journey
Testing & DiagnosisPre-Referral Treatment Start & Adjustments Patients with narcolepsy face significant challenges at each step of their journey – starting with one of the longest diagnosis delays Symptom Onset • Spinning across specialties with misdiagnosis of depression, ADHD, anxiety with increas
Slide 48: Significant unmet needs remain today
Symptom dismissal Diagnosis delays >10-15 years Discontinuation rate ~25% Add-on polypharmacy >60% Low disease awareness Undervalued disease burden Residual symptoms >80%1 Diagnosis rate <50% Low treatment expectations Treatment rate3 ~75% Significant unmet needs remain today - with no treatment opt
Slide 49: Potentially transformative profile as first treatment addressing orexin deficiency
Potentially transformative profile as the first treatment addressing orexin deficiency, the cause of NT1, and eliminating the need for polypharmacy TAK-861 Patient Satisfaction Cataplexy Safety and Tolerability Functioning & Quality of Life Nighttime Symptoms Cognition Excessive Daytime Sleepiness •
Slide 50: Takeda Orexin Franchise Focus
Takeda Orexin Franchise Focus Voice of the Patient Capturing patient-centric outcomes of daily living Industry-leading digital initiatives Evidence generation & real-world data Uncovering the True Burden of Narcolepsy Advancing & Accelerating Diagnosis Redefine Treatment Outcomes “Being half-awake i
Slide 51: 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. Redefine treatment outcomes with new MOA Improve rate, speed and accuracy, of NT1 diagnosis utilizing digital tools Uncover the true burden of narcolepsy Deliver transformat
Slide 52: Tailored portfolio to unlock full value of orexin
Tailored portfolio of potentially transformative treatments to unlock full value of orexin Oveporexton: $2-3B NT1 PEAK REVENUE POTENTIAL TAK-360: Accelerated Development Tailored to address unique unmet needs in NT2 & IH Strong foundation of Takeda capabilities in maximizing global launches and adva
Slide 53: Unlocking the full value of orexin: peak revenue potential $2-3B
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 Global peak revenue potential: $2-3B Oveporexton is on track to become the 1st and potentially best-in-class, transformative treatment indica
Slide 54: 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 55: Gastrointestinal & Inflammation: Zasocitinib, Rusfertide, Mezagitamab, Fazirsiran
Gastrointestinal & Inflammation (GI&I): Deep-dive on Zasocitinib, Rusfertide, Mezagitamab, and Fazirsiran Chinwe Ukomadu Head of GI&I Therapeutic, Area Unit Ramona Sequeira President, Global Portfolio Division
Slide 56: The GI & Inflammation portfolio is 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 11 unique drugs being developed to treat 13 diseases, with more programs poised to enter the clinic over the next year Large portfolio of diffe
Slide 57: 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 Late-Stage Peak Revenue Potential >70% PTRS2 to approval $10 - 20B Fazirsiran AATD Liver Disease Elritercept Myelodysplastic Sy
Slide 58: Zasocitinib (TAK-279) Next-generation TYK2 Inhibitor
Zasocitinib (TAK-279) Next-generation TYK2 Inhibitor, potential to be the 1st choice advanced therapy
Slide 59: 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 JAK TYK2 IL-23 Downstream proinflammatory signaling (e.g. IL-17, TNFα) IFN-α/β IL-12 Adapted from Shang et al, 2022 and Muramoto et al, 2022. IFN, interferon
Slide 60: Genetic alteration in TYK2 protects against inflammatory diseases
0 0.2 0.4 0.6 0.8 1 1.2 Psoriasis Crohn's Disease Ulcerative Colitis Ankylosing Spondylitis Multiple Sclerosis 0 0.2 0.4 0.6 0.8 1 1.2 Psoriasis Crohn's Disease Ulcerative Colitis Ankylosing Spondylitis Multiple Sclerosis People with One Altered Copy of TYK2 People with Two Altered Copies of TYK2 St
Slide 61: Zasocitinib's high selectivity supports a range of doses
Zasocitinib’s high selectivity supports the evaluation of a range of doses without concern of JAK1/2/3 inhibition 1. Leit S, et al. J Med Chem. 2023;66:10473-10496. 2. Mehrotra S, et al. Poster presentation at: European Society for Dermatological Research (ESDR) Conference 2024; 4–7 September 2024;
Slide 62: Greater and longer TYK2 inhibition versus deucravacitinib
Zasocitinib exhibits greater and longer TYK2 inhibition versus deucravacitinib and no inhibition of JAK1/3 1. The maximum concentration evaluated was 30 000 nM 2. JAK1/3 IC50 is based on IL-2 pSTAT5 3. TYK2 IC50 is based on IL-12/IL-18-dependent production of IFN-γ; S Mehrotra, Y Sano, P Halkowycz,
Slide 63: 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 >60 million adults1 • Lesions are painful, disfiguring, and disabling • Lesions can occur anywhere on the body
Slide 64: One-third of patients achieved complete skin clearance with 30 mg
One-third of patients achieved complete skin clearance at 12 weeks with 30 mg once daily of zasocitinib PASI 100 PASI 90 PASI 75 6% 18% *** 44% *** 68% *** 67% 0% * 8% *** 21% *** 45% *** 46% 0% 2% * 10% ** 15% *** 33% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Placebo (n=52) Zasocitinib 2 mg once
Slide 65: No evidence of JAK-related safety signals
No evidence of JAK-related safety signals, consistent with zasocitinib’s exquisite selectivity AE, n (%) Placebo (n=52) Zasocitinib 2 mg once daily (n=50) Zasocitinib 5 mg once daily (n=52) Zasocitinib 15 mg once daily (n=53) Zasocitinib 30 mg once daily (n=52) Deaths 0 0 0 0 0 SAEs 0 0 0 1 (1.9) 0
Slide 66: Strong efficacy across joint and skin endpoints in Ph2b PsA
Strong efficacy across joint and skin endpoints demonstrated in Ph2b PsA study ACR 20, ACR 50, ACR 70 Response at Week 121 Ph2b Study Results PASI 75 Response at Week 121 Ph2b Study Results 15.4% 25.6% 28.3% * 45.7% 0 20 40 60 80 100 Re sp on se ra te , % (9 5% C I) Placebo (n=39) TAK-279 5mg QD (N=
Slide 67: Safety data from PsA Ph2b study
Safety data from psoriatic arthritis Ph2b study supports that zasocitinib is generally well tolerated with a balanced benefit-risk profile Placebo (n=72) Zasocitinib 5 mg QD (n=71) Zasocitinib 15 mg QD (n=75) Zasocitinib 30 mg QD (n=72) n (%) n (%) n (%) n (%) Any TEAEs 39 (54.2) 42 (59.2) 45 (60.0)
Slide 68: Pivotal Ph3 studies in PsO completed enrollment
Completed enrollment ahead of schedule in two pivotal Ph3 studies in PsO with plans to begin head-to-head study versus deucravacitinib Zasocitinib 30mg QDLATITUDE-PsO-3001 Moderate-to-Severe Patients n=600 Randomization 3:1:1 Co-primary Endpoint: PASI-75 at week 16 sPGA of clear (0) or almost clear
Slide 69: Zasocitinib advanced into Phase 3 for psoriatic arthritis
Takeda has advanced zasocitinib into phase 3 for psoriatic arthritis LATITUDE-PsA-3001 n=1088 Randomization 1:1:1:1 Primary Endpoint: ACR20 at week 16 Key Secondary Endpoint: PASI-75 at week 16 MDA at week 16 Zasocitinib 15mg QD Placebo Zasocitinib 30mg QD Apremilast 30mg BID LATITUDE-PsA-3002 n=600
Slide 70: Patients with IBD need safe, efficacious & convenient therapies
Patients are in need of safe, efficacious & convenient novel therapies More than 5 million patients globally suffer from IBD Mortality rates for IBD range from 1.4 to 5 times the general population 1.4-5x 90% of Crohn’s disease patients experience relapse within 10 years 75% of IBD patients do not a
Slide 71: Strong scientific rationale to explore zasocitinib in IBD
3.2 2.5 1.2 0.9 0 1 2 3 4 Placebo Zasocitinib Low Dose Zasocitinib High Dose Biologic Positive Control Zasocitinib has strong scientific rationale to support exploration in IBD Genetic analysis has identified an alteration in the TYK2 gene that is highly protective against inflammatory diseases, inc
Slide 72: Zasocitinib Phase 2b studies in IBD
Takeda is currently evaluating zasocitinib in phase 2b studies in IBD LATITUDE-CD-2001 Moderate-to-severe patients n=268 Randomization 1:1:1:1 Primary Endpoint: Endoscope response based on SES-CD at week 12 Key Secondary Endpoint: Clinical remission based on CDAI at week 12 Clinical response based o
Slide 73: Zasocitinib development timeline
PHASE 2b START PHASE 2b READOUT PHASE 3 FILING Psoriasis Ph2b March 2023 Ph3 Start FY2023 Zaso vs Deucra Start FY2025 Target FY2026 Psoriatic Arthritis Ph2b September 2023 Target Ph3 Start FY2024 Target FY28/29 Crohn’s Disease Ph2b March 2024 Target FY2026 Ulcerative Colitis Ph2b June 2024 Target FY
Slide 74: Zasocitinib Market Opportunity
Zasocitinib Market Opportunity Well-positioned to be the first-choice advanced therapy for psoriatic disease patients, leading the next-generation orals
Slide 75: PsO is much more than just a rash
PsO is much more than just a rash; patients are really suffering 1. The total body inflammatory burden increases the risk of medical comorbidities, including CVD, diabetes and obesity. Symptoms can restrict patients to stay home increasing feeling of disconnect and also cause frustration and embarra
Slide 76: 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 Social withdrawal from activities Inability to perform “normal” daily tasks Rheumatologists are forced to make difficult trade-offs; more agg
Slide 77: Significant headspace for growth of advanced therapy in PsO
Significant headspace for growth of advanced therapy segment in PsO • WW PsO Advanced Therapy (AT) Market ~$23B1 in 2023 • In the US, only 34% of patients are being treated with an advanced therapy • This is even less worldwide, at only 30% • AT penetration is projected to grow to ~45% Similar growt
Slide 78: Growth of advanced therapies driven by improved oral options
This growth of advanced therapies is driven by improved oral options 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 900K AT treated pts 33% of AT 16% of AT 1.4M AT treated pts US Moderate to Severe PsO and Active PsA Oral Market Projection1 Biologic AT segment Oral AT segment “ Orals are whe
Slide 79: Redefine what is possible with an oral therapy in psoriatic disease
REDEFINE WHAT IS POSSIBLE WITH AN ORAL THERAPY IN PSORIATIC DISEASE Zasocitinib aims to…
Slide 80: Patients are seeking safe and effective oral treatment options
Patients are seeking safe and effective oral treatment options when topical and conventional treatments aren't enough Clear skin Safety data Well-tolerated Once daily oral / easy to take WHAT PATIENTS TELL US THEY WANT Zasocitinib has the potential to be the first oral treatment option that can addr
Slide 81: 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 Favorable safety profile Biologic-like efficacy • Once daily oral treatment • Well-tolerate
Slide 82: 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 Global Peak Revenue Potential PsO and PsA $3 - 6B Plus Crohn’s & UC Plus potential additional indications Diagnosed PsO & PsA Patients Advanced Therapy Treated Oral treated Zasocitin
Slide 83: 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, highly selective TYK2 inhibitor, Za
Slide 84: Rusfertide: Advancing Polycythemia Vera Treatment
Rusfertide: Advancing Polycythemia Vera (PV) Treatment for Superior Hematocrit Control
Slide 85: 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 transports iron HEPCIDIN Inhibits ferroportin serum iron Transferrin delivers iron EXCESSIVE RBC PRODU
Slide 86: Significant unmet need in polycythemia vera treatment
There remains significant unmet need in polycythemia vera treatment Increased Risk of Thrombotic Events Significant BurdenInconsistent HCT Control • Consistent HCT <45% is critical, as uncontrolled HCT is associated with ~4 times higher risk of death from cardiovascular causes or thrombotic events1
Slide 87: Mechanism of action of rusfertide
MOA of Rusfertide Mechanistic rationale of rusfertide in managing polycythemia vera Rusfertide helps address the overproduction of red blood cells (RBCs) in patients with polycythemia vera (PV) through, Restricting availability of iron by closing the ferroportin channel, which reduces serum iron Dec
Slide 88: Rapid, sustained and durable hematocrit control
38 39 40 41 42 43 44 45 46 47 1 5 9 1 3 1 7 2 1 2 5 2 9 3 3 3 7 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 10 0 10 4 10 8 11 2 11 6 12 0 12 4 12 8 13 2 13 6 14 0 14 4 14 8 15 2 15 6 16 0 16 4 16 8 17 2 17 6 18 0 18 4 18 8 Placebo Rusfertide M ea n (± SE M ) H em at oc rit (% ) Week 0.5 yrs 1 yr 1.
Slide 89: REVIVE favorable long-term safety profile
REVIVE demonstrated a favorable long-term safety profile • 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 Most common (≥20%) TEAEs • 18 patients (26%) experi
Slide 90: Rusfertide Phase 3 ongoing: data readout CY2025
Rusfertide phase 3 ongoing: target data readout CY2025 N = 250 Randomization 1:1 INCLUSION CRITERIA ≥3 PHL3 due to inadequate HCT control in 28 weeks before randomization OR ≥5 PHL due to inadequate HCT control within 1 year prior to randomization Part 1B: Open-Label1, 2 Duration - 20 weeks (Weeks 3
Slide 91: Rusfertide Market Opportunity
Rusfertide Market Opportunity Advancing care in polycythemia vera by targeting critical unmet needs
Slide 92: 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 Initial Presentation: Routine blood work or thrombotic event Work Up: Blood tests prompt a referral to Hematology/Oncologist Diagnosis: Hem/Onc diagnoses
Slide 93: Rusfertide expected to be used at each step of treatment landscape
Rusfertide aims to deliver rapid, consistent & sustained HCT control and is expected to be used at each step of the treatment landscape Engaging with key stakeholders to promote use of Rusfertide Working broad access and inclusion in guidelines Driving awareness of the unmet needs in PV Exploring di
Slide 94: 155,000 diagnosed PV patients, only 8,000 treated
Approximately 155,000 patients diagnosed with PV with only 78,000 currently being treated Unlocking the full potential of rusfertide for polycythemia vera patients Advancing Care In The PV Space By Targeting Critical Unmet Needs Hematocrit control (<45%) is the primary goal of physicians in treating
Slide 95: Mezagitamab (TAK-079)
Mezagitamab (TAK-079) Transformative Potential for Chronic Auto-immune Diseases
Slide 96: Potential best-in-class anti-CD38 agent
Potential best-in-class anti-CD38 agent Leadership in immune modulation Pipeline in a product Proof of concept in ITP and IgAN Potential for multiple indications in auto- immune diseases Setting new standard for ITP and IgAN patients Mezagitamab: New unique anti-CD38 antibody with disease modifying
Slide 97: Rapid, selective, safe and sustained depletion of immune cells
Mezagitamab is designed for rapid, selective, safe and sustained depletion of immune cells Rapid and robust antibody reduction observed in multiple indications1 • IgG up to 41% • IgA up to 70% • Gd-IgA1 up to 62% -80 -60 -40 -20 0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 Ig G , I gA , a n
Slide 98: IgA Nephropathy pathophysiology
Understanding IgA Nephropathy (IgAN) pathophysiology and the consequences for patients Hit 2 Hit 3 Hit 4 Hit 1 Plasma cells produce circulating galactose- deficient (Gd-) IgA1 Other plasma cells produce IgG & IgA autoantibodies against Gd-IgA1 Deposition of pathogenic immune-complexes in kidney lead
Slide 99: Mezagitamab addresses the root causes of IgAN
Mezagitamab addresses the root causes of IgAN, thereby delivering a sustained disease-modification (including off-treatment) Mezagitamab targets the initial steps in IgAN pathophysiology (Hit 1 and 2)1-3 • Binding to CD38, mezagitamab depletes IgA and IgG producing plasma cells • This suppresses the
Slide 100: Unmet need in IgAN for a disease modifying treatment
Unmet need in IgAN is for a transformative disease modifying treatment that preserves kidney function Need for disease modifying treatment that, • Stops the chronic kidney damage • Prevents the progressive loss of renal function (eGFR) • Is safe and well-tolerated • Allows for convenient dosing and
Slide 101: Mezagitamab POC: best-in-class UPCR reduction in IgAN
Mezagitamab in POC study was well tolerated and showed rapid, sustained best-in-class UPCR reduction in patients with IgA nephropathy • Mezagitamab demonstrated rapid and sustained reduction of serum IgA, IgG and gd- IgA1 over time during the treatment period • Urinary protein creatine ratio (UPCR)
Slide 102: Potential best in class disease modifying agent in IgAN
Potential best in class (anti-CD38) disease modifying agent in IgAN Not Disease Modifying Targeting B-cells Targeting Plasma Cells Stabilizing renal function Efficacy maintained off-treatment NOT targeting memory B cells Best-in-class antibody reduction Mezagitamab Disease Modifying Potential Cortic
Slide 103: Understanding ITP and its consequences for patients
Understanding immune thrombocytopenia (ITP) and its consequences for patients • ITP is a rare chronic disorder characterized by an autoimmune response against platelets and megakaryocytes leading to low platelet count in the blood • ITP patients have an increased risk of bleeding, including risk of
Slide 104: Mezagitamab addresses the root causes of ITP
Mezagitamab addresses the root causes of ITP, delivering a sustained disease-modifying treatment • Binding to CD38, mezagitamab depletes IgG producing plasma cells • This suppresses the production of the IgG autoantibodies and leads to a profound and sustained reduction in levels of pathogenic auto-
Slide 105: Primary goal of ITP treatment is to restore safe platelet levels
The primary goal of ITP treatment is to quickly and sustainably restore safe levels of platelets Current ITP treatments leave clinical unmet needs Stable platelet count over time1 Pl at el et c ou nt s ( 10 9 / L) Patients want new novel treatments that deliver • Durable platelet response • Long-ter
Slide 106: Rapid and sustained platelet response in ITP
Mezagitamab demonstrated rapid and sustained improvement in multiple efficacy measures of durable platelet response in patients with immune thrombocytopenia 23.1 0.0 66.7 55.6 62.5 50.0 90.9 81.8 0 20 40 60 80 100 Re sp on de rs % Placebo combined Meza 100mg Meza 300mg Meza 600mg Visit (weeks) Plate
Slide 107: ITP pivotal study expected to start Q4 FY2024
ITP phase 3 pivotal study – expected to start Q4 FY2024 8-week blinded treatment period Mezagitamab 600mg SC weekly (plus background standard therapy) Placebo SC weekly (plus background standard therapy) Dosing-free period 8-week blinded treatment period Target filing in ITP – FY28/29 Mode of action
Slide 108: Mezagitamab Market Opportunity
Mezagitamab Market Opportunity Well positioned to be the best-in-class anti-CD-38 agent to transform the IgAN and ITP markets by setting new standard for patients
Slide 109: Dosing holiday enhances safety and convenience
Dosing holiday enhances potential for safety and convenience Subcutaneous dosing with extended treatment-free periods Mezagitamab: a transformative approach to combat autoimmune diseases Targets plasma cells The direct source of auto-antibodies production Disease modifying treatment potential Rapid
Slide 110: IgAN patients experience progressive loss of kidney function
IgAN patients often experience progressive and irreversible loss of kidney function leading to end stage kidney disease 1 2 3 4 …First visible symptoms Blood in urine … Progressive loss of renal function and irreversible kidney damage …End stage kidney disease Need for dialysis and kidney transplant
Slide 111: Potential to stop disease progression in IgAN
Mezagitamab has the potential to stop the disease progression and address the root cause of the disease in IgAN Establish the CD38 class as a new transformative approach to combat IgAN disease, a plasma cell driven disease ~1.5M diagnosed IgAN patients G7+ China ~200K in the US1 ~55% Progressing des
Slide 112: Current ITP therapies leave many patients struggling
In ITP, current therapies leave many patients struggling with their disease and looking for improved treatment options in 3L 1 2 3 Efficacy of 3L agents are limited ILLUSTRATIVE PATIENT EXPERIENCE WITH ITP …Newly Diagnosed ITP (0-3 months post Dx) …Persistent / Chronic ITP (>3 months post Dx) …Refra
Slide 113: 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 Redefine what success looks like >200k diagnosed ITP patients globally / ~50K in the US1 Need for effective options ~20% with inadequate response to 2 lines of
Slide 114: Potential transformative profile in IgAN and ITP
Potential to deliver a transformative profile, addressing the root cause in auto-immune diseases ITP ambition • 1st choice in patients not responding well to current standard of care • Sustained platelet restoration with treatment- free remission periods • Favorable safety and tolerability profile G
Slide 115: Unlocking the full potential of mezagitamab – Summary
Unlocking the full potential of mezagitamab in autoimmune diseases – Summary Slide Global peak revenue potential: $1-3B with IgAN and ITP alone with potential upside through new indications Mezagitamab is well positioned to be the best-in-class anti-CD38 agent with disease modifying potential and tr
Slide 116: Fazirsiran: Alpha-1 Antitrypsin Deficiency Liver Disease
Fazirsiran The potential of a transformative therapy for patients living with Alpha-1 Antitrypsin Deficiency Liver Disease (AATD-LD)
Slide 117: AATD-LD is a progressive chronic liver disease with no approved treatments
AATD-LD is a largely asymptomatic and progressive chronic liver disease that has no approved treatments2 Fazirsiran treatment reduces/eliminates Z-AAT production, removing the trigger for fibrosis thereby preventing progression to end-stage liver disease3, 4 AATD-LD is caused by to the aggregation o
Slide 118: 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 ER: endoplasmic reticulum; HCC: hepatocellular carcinoma; Z-AAT: alpha-1 antitrypsin produced by the Pi*Z SERPINA1 allele 1. Teckman JH. COPD. 2013;10(Suppl 1):35-43; 2. Strnad P, et al. N Engl J Med. 2020;382(15):1443
Slide 119: Fazirsiran mechanism of action stops production of Z-AAT
Fazirsiran’s mechanism of action stops the production of Z-AAT, directly addressing the pathology in AATD liver disease AAT, alpha-1 antitrypsin; AATD, alpha-1 antitrypsin deficiency; DNA, deoxyribonucleic acid; GalNAc, N-acetylgalactosamine; mRNA, messenger ribonucleic acid; siRNA, small-interferin
Slide 120: Ph2 study design to demonstrate reduction of liver Z-AAT
Ph2 study intended to demonstrate reduction of liver Z-AAT Cohort 1 (n = 4) Cohort 1b (n = 4) Cohort 2 (n = 8) Includes stage F1 – F3 patients Primary Endpoint: • Change from baseline in liver Z-AAT @ wk 24/48 Secondary Endpoints include: • Change from baseline in serum Z-AAT • Treatment emergent AE
Slide 121: Significant reductions in serum and liver Z-AAT
0 10 20 30 40 50 60 70 80 90 100 61 9 Ph2 POC study showed that fazirsiran treatment leads to significant reductions in serum and liver Z-AAT concentrations CI: confidence interval; Z-AAT: alpha-1 antitrypsin produced by the Pi*Z SERPINA1 allele Strnad P, et al. N Engl J Med. 2022;387(6):514-24; *We
Slide 122: Randomized dose ranging placebo-controlled Ph2 study
Randomized dose ranging placebo-controlled study that laid the foundation for Ph3 development N = 40 Fibrosis <F4 or no fibrosis (based on previous liver biopsy) Primary Endpoint: • Percent change in serum Z-AAT @ wk 16 Secondary Endpoints include: • Change from basline in serum and liver Z-AAT • Tr
Slide 123: Ph2 placebo controlled study shows reduction in Z-AAT
‡N=40 to Week 16; Reference: Fazirsiran SEQUOIA Topline Results. Arrowhead Pharmaceuticals website. https://ir.arrowheadpharma.com/static-files/ffc86cc4-7005-4f02-a538-ebcf0ed7de0a. Ph2 Placebo controlled study demonstrates fazirsiran’s transformative potential in reducing Z-AAT 4 -62 -86 -92 9 -74
Slide 124: Strong safety profile demonstrated in Ph2
Strong safety profile demonstrated in Ph2, with no TEAE-related discontinuations, dose interruptions, or study withdrawals AAT: alpha-1 antitrypsin; PFT: pulmonary function test; TEAE: treatment-emergent adverse event; 1. Clark VC, et al. Gastroenterology. 2024; 2:S0016-5085(24)05181-3. online ahead
Slide 125: Fazirsiran Ph3 ongoing: target filing FY2028
Fazirsiran Ph3 ongoing: target filing FY2028 n=160 Randomization 1:1 Includes stage F2 – F4 patients Day 1 Wk 4 Wk 16 Q12 W thereafter up to 196 wks Dosing Schedule FAZIRSIRAN 200mg/mL (SC) PLACEBO Biopsy Wk 106 Biopsy Wk 202 Primary Endpoint Redwood Study (Ph3) Design1 Biopsy @ baseline Primary End
Slide 126: Fazirsiran Market Opportunity
Fazirsiran Market Opportunity Well positioned to be the first available treatment indicated for AATD associated Liver Disease
Slide 127: Opportunity to offer hope for patients living with AATD-LD
Fazirsiran represents an opportunity to offer hope in the form of a transformative therapy for patients living with AATD-LD Source: American Liver Foundation: https://liverfoundation.org/about-your-liver/patient-stories/linda-k/ I had lived a perfectly healthy life for 50 years when I suddenly becam
Slide 128: AATD-LD patients have higher risk of cancer and liver transplant
Patients living with AATD-LD have 20x risk of cancer1 & 40x risk of liver transplant2 AATD-LD, an asymptomatic disease progression coupled with higher risks for cancer and liver transplant ILLUSTRATIVE PATIENT EXPERIENCE WITH AATD -LD End stage liver diseaseSilently progressive liver disease Referra
Slide 129: AATD-LD significant unmet needs
AATD-LD has significant unmet needs anchored around the lack of available treatments, low awareness & low diagnostic rates AATD Liver Disease Cycle of Unmet Needs There are no treatments available to slow or stop progression to end-stage liver disease and liver failure in AATD patients Disease aware
Slide 130: AATD-LD market poised to benefit from MASH advancements
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 Accelerate adoption of diagnosis in AATD-LD upon approval of Fazirsiran Elevate awareness on AATD-LD & prognosis Advancement in
Slide 131: Fazirsiran on track to be first treatment for AATD-LD
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 restores liver health Fazirsiran has been granted Breakthrough Therapy Designation by the FDA and Orphan Des
Slide 132: 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 133: Oncology: Deep dive on Elritercept
Oncology: Deep dive on Elritercept – newly announced BD deal P.K. Morrow Head of Oncology Therapeutic Area Unit Please refer to the Important Notice at the start of this presentation for more information about the Elritercept license agreement Teresa Bitetti President, Global Oncology Business Unit
Slide 134: 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 Late-Stage Peak Revenue Potential >70% PTRS2 to approval $10 - 20B Fazirsiran AATD Liver Disease Elritercept Myelodysplastic Sy
Slide 135: Oncology strategy focused on 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 innovation from everywhere Areas of Focus Vision • ENRICH mid- and late-stage pipeline through internal and external innovation, and c
Slide 136: Oncology R&D focus on three disease areas and four modalities
Thoracic NSCLC, SCLC, SCCHN CRC, Gastric, Pancreatic, HCCGI ALL, AML/MDS, CML/MFHeme Complex Biologics Antibody–drug conjugates (ADCs) Small Molecules Gamma Delta Cell Therapies Oncology Disease Areas Modalities ALL: Acute Lymphoblastic Leukemia, AML: Acute Myeloid Leukemia, CML: Chronic Myeloid Leu
Slide 137: Recent business development transactions enhance Oncology strategy
Recent business development transactions enhance realization of Takeda’s Oncology strategy Fruzaqla® (Fruquintinib) In-licensing of fruquintinib1 from HUTCHMED Takeda leads development and commercialization globally (ex-China, Hong Kong and Macau) Mirvetuximab soravtansine-gynx Licensing agreement w
Slide 138: Elritercept: Potentially best-in-class activin inhibitor
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 139: Elritercept represents a foundational opportunity in Oncology
Elritercept represents a foundational opportunity to further realize Takeda’s Oncology strategy and grow our footprint in hematologic cancers 1. Feigenson, M et al. European Hematology Association. 2001. MDS: Myelodysplastic Syndrome, MF: Myelofibrosis Please refer to the Important Notice at the sta
Slide 140: Overactivation of TGF-β superfamily blocks hematopoiesis in MDS
In MDS, overactivation of the TGF-β superfamily (e.g., Activin A and B) blocks hematopoiesis Activin A + B High unmet need remains for MDS patients despite advances 1. Jain, et al. Haematologica. 2024 AA: Anemia-Associated; QoL: Quality of Life.; TGF-β: Transforming Growth Factor Beta. Diez-Campelo,
Slide 141: Elritercept inhibits Activin A and B
White Blood Cells Platelets Erythrocytes (RBCs) Elritercept Elritercept inhibits Activin A and B, restoring a balanced early and late hematopoiesis process Elritercept is a potentially best-in-class treatment for anemia-associated diseases Diez-Campelo, et al. ASH. 2023. LR-MDS: Low-Risk Myelodyspla
Slide 142: Strong responses across AA LR-MDS segments
% Responders1 EPO < 500 U/L2 All (N=71) HTB (N=39) Overall Response3 60.6% 56.4% Modified IWG 2006 HI-E4 52.1% 53.8% RS+ 55.8% 53.3% RS- 42.1% 55.6% TI ≥8 weeks5 26/55 (47.3%) 15/39 (38.5%) RS+ 21/41 (51.2%) 12/30 (40%) RS- 5/14 (35.7%) 3/9 (33.3%) Elritercept demonstrated strong responses across AA
Slide 143: Prolonged and durable transfusion independence in Ph2
0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 10 0 10 4 10 8 11 2 11 6 12 0 12 4 12 8 13 2 13 6 14 0 14 4 14 8 0.0 0.2 0.4 0.6 0.8 1.0 Longest TI interval in mITT24 participants who achieved TI ≥ 8 wks from baseline through Wk 24** TI Duration (Wks) Pr ob ab ili ty o f M ai
Slide 144: Well tolerated safety profile and improved QoL
Elritercept showed a generally well tolerated safety profile and has resulted in improvements in QoL in AA LR-MDS patients Giagounidis, et al. ASH. 2024. Data cutoff 30Aug2024. AA: Anemia-Associated; Gr: Grade; QoL: Quality of Life; TI: Transfusion Independence Patients who achieved TI ≥24 weeks sho
Slide 145: RENEW Ph3 study design in 2L+ AA LR-MDS
N = 225 Randomization 2:1 Elritercept Ph3 in 2L+ AA LR-MDS – Target study start FY2024 Primary endpoint • TI ≥ 8 weeks within the first 24 weeks (ITT population) Secondary endpoint • Safety/tolerability Elritercept + BSC* Placebo + BSC* *Best Supportive Care includes Red Blood Cell transfusions, as
Slide 146: Potential benefit across hematologic indications
AA Myelofibrosis • Potential best-in-class asset, based on Ph2 results, showing strong efficacy across heme lineages, and a generally well tolerated safety profile • Potential to treat a broad range of patients with Low-Risk MDS, across lines of therapy, agnostic of RS status and transfusion burden
Slide 147: Elritercept Commercial Opportunity
Elritercept Commercial Opportunity Well positioned to be the best-in-class agent for treating anemia 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 148: LR-MDS is a large growing space with unmet medical need
LR-MDS is a large growing space with significant unmet medical need MDS sales currently estimated at $2B+ with estimated growth to $6B+ by 2030 Majority of sales coming from lower-risk6,7 1. Per annum 2. Germany, France, Italy, Spain 3. Luspatercept indicated for 1L treatment however use in RS- pati
Slide 149: Elritercept profile potential to be 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 Improved tolerability Generally well tolerated safety profile
Slide 150: Elritercept target indications and peak revenue potential
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%) Elritercept peak revenue potential $2 – 3B 1L 2L 3L Initial indication 2L+ LCM indication Elritercept targe
Slide 151: Elritercept global peak revenue potential $2-3B
Global peak revenue potential: $2-3B Differentiated mechanism of action impacting early and late haematopoiesis Strong strategic fit with existing hematology-oncology disease area focus Ph3 ready asset with lead indication in 2L+ AA LR-MDS and potential expansion opportunities in earlier lines, MF a
Slide 152: 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 Late-Stage Peak Revenue Potential >70% PTRS2 to approval $10 - 20B Fazirsiran AATD Liver Disease Elritercept Myelodysplastic Sy
Slide 153: Q&A Session
Q&A SESSION CHINWE UKOMADU Head of GI&I Therapeutic Area Unit SARAH SHEIKH Head of Neuroscience Therapeutic Area Unit & Global Development P.K. MORROW Head of Oncology Therapeutic Area Unit ANDY PLUMP Director; President, Research & Development CHRISTOPHE WEBER Representative Director; President & C
Slide 154: Appendix
APPENDIX
Slide 155: Consolidated Development Pipeline by Phase
PHASE 2 (11 NMEs + 2 LCM)PHASE 1 (5 NMEs) ONCOLOGY Consolidated Development Pipeline by Phase NEUROSCIENCE dazostinag Solid Tumors4 TAK-012 Acute myeloid leukemia3 ACI-24.0606 Alzheimer’s Disease zamaglutenase Celiac Disease ADZYNMA® iTTP TAK-500 Solid Tumors3 1. TAK-007 Phase 1 trial in autoimmune
Slide 156: Consolidated Development Pipeline by Phase
Orphan Drug Designation potential (in any region / indication for a given asset) FILED (2 NME + 11 LCMs)PHASE 3 (6 NMEs + 13 LCMs) NME LCMAPPROVED CABOMETYX® mCRPC combo w/atezolizumab (JP) maralixibat PFIC (JP) Prothromplex DOAC Reversal (US) HYQVIA® PID, SID (JP) ADCETRIS® FL HL BrECADD (EU) HYQVI
Slide 157: Glossary of Abbreviations - 1
157 Regional Abbreviations: CN: China; EU: Europe; JP: Japan; U.S.: United States of America Glossary of Abbreviations - 1 AA anemia-associated AATD α1-antitrypsin deficiency AATD LD α1-antitrypsin deficiency associated liver disease ACE/ARB angiotensin converting enzyme / angiotensin receptor block
Slide 158: Glossary of Abbreviations - 2
158 Regional Abbreviations: CN: China; EU: Europe; JP: Japan; U.S.: United States of America Glossary of Abbreviations - 2 LS least square LTB low transfusion burden LTE long-term extension MASH Metabolic dysfunction-associated steatohepatitis mCRC metastatic colorectal cancer mCRPC metastatic castr
Slide 159: Takeda Investor Relations
© 2024 Takeda Pharmaceutical Company Limited. All rights reserved. Takeda Investor Relations: takeda.ir.contact@takeda.com