Takeda Pharmaceutical Co. Ltd. · TSE:4502
Takeda Pharmaceutical — World Sleep Congress 2025
94 slides from Takeda Pharmaceutical's conference presentation, Sep 8, 2025
Slide 1: Takeda's Leading Orexin Franchise: Oveporexton Phase 3 Data & Commercial Readiness
Ready to translate Takeda’s Leading Orexin Franchise Oveporexton Phase 3 Data & Commercial Readiness World Sleep Congress 2025 September 8th, 2025 This material is prepared and distributed solely for the purpose of providing information about Takeda's management or business to shareholders, investor
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: Pioneering Orexin science and catalyzing a potential new era of care in NT1
Pioneering Orexin science and catalyzing a potential new era of care for patients with narcolepsy type 1 (NT1) with oveporexton 1 2 3 Oveporexton is designed to Ph3 results demonstrated Orexin deficiency is the root treat the root cause of NT1 and oveporexton’s potential to cause of NT1 has the pote
Slide 4: NT1 patients face debilitating daytime and nighttime symptoms
NT1 patients face debilitating daytime and nighttime symptoms often 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 signi
Slide 5: NT1 pathophysiology is caused by the loss of orexin neurons
NT1 pathophysiology is caused by the loss of orexin neurons Downstream signaling Healthy Individual: Healthy orexin neurons with normal postsynaptic downstream orexin neurotransmitter activity Patient with NT1: Reduced availability of orexin as orexin neurons are lost, reducing downstream neurotrans
Slide 6: Optimized dosing regimen critical to deliver efficacy while minimizing adverse events
Optimized dosing regimen critical to deliver potentially transformative efficacy while minimizing adverse events Oveporexton 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 a
Slide 7: Comprehensive approach to evaluate broad spectrum of NT1 symptoms
Comprehensive approach to evaluate broad spectrum of NT1 symptoms with established and novel endpoints Daytime Symptoms Nighttime Symptoms Excessive Daytime Cataplexy Cognitive Symptoms Disrupted Nighttime Sleep, Hallucinations, Sleepiness (EDS) Disturbing Dreams Sleep Paralysis MWT, ESS, KSS WCR PV
Slide 8: Oveporexton Phase 3 Results
Oveporexton Phase 3 Results Better Health, Brighter Future
Slide 9: Global placebo controlled randomized Ph3 NT1 studies
Global placebo controlled randomized Oveporexton Ph3 NT1 studies conducted across 19 countries enrolling 273 subjects 12-week treatment period Placebo (N=41) Primary Endpoint @ 12wks: Randomization TAK-861-3001 Long Term • MWT N=168 Oveporexton: 1 mg BID (N = 61) 2:3:3 Extension Secondary Endpoints
Slide 10: Oveporexton could establish a new standard of care in NT1
Oveporexton could establish a new standard of care in NT1 addressing the broad spectrum of symptoms Majority of NT1 patients within Generally well tolerated normative ranges (MWT, ESS, NSS-CT) Excessive Safety and daytime tolerability sleepiness Normalization of daily functioning and Significant & c
Slide 11: Improved sleep latency on MWT
Oveporexton significantly improved sleep latency on MWT at 12 weeks with majority of patients within normative range The Maintenance of Wakefulness Test (MWT): daytime polysomnographic procedure which quantifies wake tendency by measuring ability to remain awake during soporific circumstances (sleep
Slide 12: Improved subjective sleepiness on ESS
Oveporexton significantly improved subjective sleepiness at 12 weeks with majority of patients within normative range 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 question 0-3
Slide 13: Reduced weekly cataplexy rate over 12 weeks
Oveporexton significantly reduced weekly cataplexy rate over 12 weeks Cataplexy: sudden loss of muscle tone and strength, often caused by an emotional stimulus; defining symptom of NT1 Incidence Rate Ratio (IRR): incidence rate for the treatment arms over the placebo incidence rate (lower IRR indica
Slide 14: Rapid reduction in cataplexy sustained over 12 weeks
Oveporexton demonstrated rapid reduction in cataplexy, sustained over 12 weeks Weekly Cataplexy Rate (WCR): number of cataplexy events per week The First Light (3001) Weekly Cataplexy Rate (WCR) • Reduction in median WCR from baseline sustained over the entire duration of the study • 79% 1 mg/1 mg (
Slide 15: Improved symptoms across NT1 spectrum and overall severity
Oveporexton improved symptoms across NT1 spectrum and reduced the overall symptom severity Narcolepsy Severity Scale for Clinical Trials (NSS-CT): validated, self-administered, 15-item scale evaluating severity, frequency and impact of 5 narcolepsy symptoms (sleepiness, cataplexy, sleep paralysis, h
Slide 16: Improved nighttime symptoms at week 12
Oveporexton improved nighttime symptoms at week 12 The First Light (3001) The Radiant Light (3002) Nighttime symptoms (NSS-CT) 6 6 • ~85% of patients treated 5 5 with oveporexton with no Hallucinations 4 4 hallucinations or sleep Improvement domain scores How frequently do you Mean (SD) 3 3 paralysi
Slide 17: Improved sustained attention throughout the day
Oveporexton significantly improved sustained attention throughout the day with ~70% patients within normative range Psychomotor Vigilance Test (PVT): simple 10 min reaction performance task to measure sustained attention (test counts # of lapses in attention). Normative levels: PVT lapses ≤ 6 90 The
Slide 18: Improved overall functioning and quality of life
Oveporexton significantly improved overall functioning and quality of life Oveporexton treatment resulted in More than 80% of patients reporting no group mean EQ-5D-5L index scores problems on ‘Usual Activities’ on EQ-5D-5L reaching normative values (compared to 30% of placebo patients) SF-36 mental
Slide 19: Oveporexton was generally well tolerated
Oveporexton was generally well tolerated The First Light (3001) The Radiant Light (3002) Adverse Events Placebo 1 mg/1 mg 2 mg/2 mg Placebo 2 mg/2 mg (n=41) (n=60) (n=66) (n=35) (n=70) • No treatment-related serious TEAEs Any TEAE, n (%) 22 (53.7) 52 (86.7) 59 (89.4) 15 (42.9) 60 (85.7) • Most commo
Slide 20: Potential to establish a new era of care with transformative efficacy
Oveporexton has the potential to establish a new era of care with transformative efficacy Oveporexton demonstrated transformative efficacy profile at 12 weeks with BID dosing • Significant and clinically meaningful improvements across all NT1 symptoms • Majority of NT1 patients within normative rang
Slide 21: Takeda is pioneering orexin therapeutics with a potentially transformative franchise
Takeda is pioneering the field of orexin therapeutics with a potentially transformative franchise • Global filings on track to start FY25 Oveporexton: • Breakthrough designation received in USA and China NT1 • Potential first-in-class potential treatment for NT1 • Novel chemistry and profile for ore
Slide 22: Oveporexton Market Opportunity & Commercialization
Oveporexton Market Opportunity & Commercialization 22
Slide 23: No time or energy for what matters most
No time or energy for what matters most: coping through most aspects of life Limited hours of functional “wakefulness” make “I’m angry with my own body. It meaningful activities like work, becomes a self-detrimental family care, or exercise often emotional state” difficult and at times Person with N
Slide 24: Long, exhausting NT1 patient journey fraught with roadblocks
Long, exhausting NT1 patient journey is fraught with roadblocks hindering accurate & timely diagnosis, often followed by lifetime of treatment trade-offs A PATIENT’S JOURNEY TO DIAGNOSIS CAN TAKE DECADES Symptom Testing & Treatment & Onset Diagnosis Adjustment In the US, patients can spend >50% poly
Slide 25: Patients rely on symptomatic treatments with residual symptoms
Patients rely on symptomatic treatments, which often lead to persistent breakthrough or residual symptoms and suboptimal disease management Current standard of care does not target Orexin deficiency, the underlying cause of NT1 75% of U.S. diagnosed patients are treated, but both branded and generic
Slide 26: Many patients continue to experience symptoms despite treatment
Despite treatment, many patients continue to experience symptoms and need to cope with the continued impact of NT1 on many aspects of their lives Half as likely to have 82% feel restricted in 3.5x more likely to be children1,2 jobs they can pursue3 clinically depressed4 26 Sources: 1. Peter-Derex et
Slide 27: Development program designed to demonstrate transformative efficacy of an Orexin therapy
Pioneering a potential paradigm shift with a development program designed to demonstrate the transformative efficacy of an Orexin therapy oveporexton MWT PVT PGI-C FINI Maintenance of Psychomotor Patient Global Functional Impacts of Wakefulness Test Vigilance Test Impression of Change Narcol
Slide 28: Oveporexton is poised to redefine treatment outcomes
Oveporexton is poised to redefine treatment outcomes that matter most to patients Excessive Safety and daytime tolerability sleepiness Functioning You recover the life you Being able to laugh and be sad & QoL Cataplexy freely, I feel like I’ve become a Oveporexton want….You also make up for lost tim
Slide 29: Oveporexton: A New Era of Care
Designed to treat the root cause OVEPOREXTON of NT1, OREXIN deficiency Aspiration: Potential to be a transformative OREXIN therapy A New Era Of Care Transformative efficacy demonstrated across a broad spectrum of NT1 symptoms 29
Slide 30: Takeda is leveraging neuroscience and rare expertise to advance oveporexton
Takeda is leveraging its neuroscience and rare expertise to advance oveporexton towards the market*, preparing for a seamless patient and HCP experience ASPIRING TO A NEW ERA OF CARE FOR NT1 PATIENTS: EDUCATION & AWARENESS OF ENABLING ACCESS TO ADVANCING & ACCELERATING NT1 TRUE BURDEN AND ROLE OF TR
Slide 31: Successful launch of oveporexton will unlock a new era of care in NT1
Successful launch of oveporexton* will unlock the potential of a new era of care in NT1, starting in the US ~95-120k Uncovering the true Prevalent U.S. NT1 patients1 burden of narcolepsy Improving rate, speed and 10-20% accuracy of NT1 diagnosis Diagnosis Rate Optimization utilizing digital tools To
Slide 32: Takeda is the leader in Orexin biology
Takeda is the leader in Orexin biology, aiming to transform patient outcomes Sleep-Wake Respiratory Tailored Orexin conditions Assets For Additional Metabolic Indications disorders TAK-360: Accelerated Mood Development And beyond Oveporexton: Tailored to address unique unmet needs in NT2 & IH $2-3B+
Slide 33: Pioneering Orexin science and catalyzing a potential new era of care
Pioneering Orexin science and catalyzing a potential new era of care for patients with narcolepsy type 1 (NT1) with oveporexton 1 2 3 Oveporexton is designed to Ph3 results demonstrated Orexin deficiency is the root treat the root cause of NT1 and oveporexton’s potential to cause of NT1 has the pote
Slide 34: Q&A Session
ANDY PLUMP JULIE KIM Director; President, President; U.S. Business Unit & Q&A Research & Development Interim Head of Global Portfolio Division Session SARAH SHEIKH HEATHER DEAN Head of Neuroscience Senior Vice President; Therapeutic Area Unit & Head Neuroscience U.S. Business Unit Global Development
Slide 35: Glossary of Abbreviations
Glossary of Abbreviations Regional Abbreviations: CN: China; EU: Europe; JP: Japan; U.S.: United States of America AE adverse event IH idiopathic hypersomnia PK pharmacokinetics AI artifcial inetlligence IND investigational new drug PMDA Japan’s Pharmaceuticals and Medical Devices Agency ASN America
Slide 36: Medical Presentation as presented at World Sleep 2025
Medical Presentation as presented at World Sleep 2025
Slide 37: Efficacy and safety of a multi-dose study of oveporexton in NT1 (Mignot)
Emmanuel Mignot, MD, PhD, USA The First Light: Efficacy and safety of a multi-dose study of oveporexton (TAK-861), an oral orexin receptor 2 agonist, for the treatment of narcolepsy type 1 WSC 2025, Singapore | September 5-10, 2025 | O-09 | This presentation is intended for health care professionals
Slide 38: Contributors
Contributors Emmanuel Mignot,1,* Isabelle Arnulf,2,* Giuseppe Plazzi,3,4 Rafael del Rio Villegas,5,6 Ramin Khatami,7,8 Gert Jan Lammers,9,10 Mitsutaka Taniguchi,11 Harisha Kadali,12 Yeting Du,12 Samuel Hsiao,12 Tina Olsson,12 Sarah Sheikh,12 Christian von Hehn,12 Mark R. Etherton,12,† Yves Dauvillie
Slide 39: Disclosures
Disclosures Disclosures • Emmanuel Mignot received consulting fees from Ambulatory Monitoring, Jazz Pharmaceuticals, and Takeda; research grant or trials to Stanford from Apple, Avadel, Eisei, Jazz Pharmaceuticals, and Takeda; travel funding from Harmony Biosciences, Paladin Labs, and Takeda; and st
Slide 40: Background
Background Narcolepsy type 1 (NT1) is a chronic, rare, neurologic disorder Excessive of hypersomnolence characterized by a range of debilitating daytime Functioning symptoms.1-3 sleepiness NT1 is caused by loss of the orexin-producing neurons in the Quality brain, which regulate wakefulness, sleep,
Slide 41: Oveporexton development
Oveporexton development First in Phase 2 Phase 3 Phase 3 human start start results 2021 2023 2024 2025 Balanced efficacy and on- Early-phase clinical trials showed Here, we report the first data from target/off-target tolerability significant and meaningful The First Light phase 3 study and safety1
Slide 42: The First Light study design
The First Light study design • Randomized, double-blind, placebo-controlled, phase 3 study of twice-daily doses of oral oveporexton, an orexin receptor 2 agonist, conducted across Europe, Japan, and North America. Inclusion criteria†: • Participants aged 16–70 years Placebo‡ • ICSD-3/ICSD-3 TR diagn
Slide 43: Participant disposition
Participant disposition Randomized (n=168) • 168 participants Placebo Oveporexton 1 mg/1 mg Oveporexton 2 mg/2 mg randomized. (n=41) (n=61) (n=66) • 157 completed 12 weeks n=5 (12.2%) n=4 (6.6%) n=2 (3.0%) • 150/157 (>95%) of Adverse event: 1 (2.4%)* Discontinued Protocol deviation: 2 (4.9%) Adverse
Slide 44: Participant characteristics at baseline
Participant characteristics at baseline Oveporexton Oveporexton Placebo 1 mg/1 mg 2 mg/2 mg (n=41) (n=61) (n=66) Mean (SD) age, years 30.9 (12.7) 33.5 (11.8) 29.7 (9.6) Female, n (%) 24 (58.5) 28 (45.9) 46 (69.7) Demographics Race, n (%) and disease Asian 6 (14.6) 10 (16.4) 10 (15.2) Black/African A
Slide 45: Improved mean sleep latency versus placebo
Oveporexton significantly improved mean sleep latency at 12 weeks compared with placebo, with majority of participants within the normative range Maintenance of Wakefulness Test (MWT) LS mean difference from placebo in change from baseline at week 12 (primary endpoint) Oveporexton LS mean (95% CI) A
Slide 46: Improved subjective sleepiness versus placebo
Oveporexton significantly improved subjective sleepiness at 12 weeks compared with placebo, with majority of participants within the normative range Epworth Sleepiness Scale (ESS) LS mean difference from placebo in change from baseline at week 12 Oveporexton LS mean (95% CI) Adjusted P-value* 1 mg/1
Slide 47: Reduced WCR and increased cataplexy-free days
Oveporexton significantly reduced WCR over 12 weeks versus placebo and increased the number of cataplexy-free days for both doses Weekly Cataplexy Rate (WCR) 60 Placebo • Median cataplexy-free Oveporexton 1 mg/1 mg days/week increased 50 from 0 days at Median (IQR) WCR Oveporexton 2 mg/2 mg baseline
Slide 48: Oveporexton was generally safe and well tolerated
Oveporexton was generally safe and well tolerated Safety population Oveporexton Oveporexton Placebo 1 mg/1 mg 2 mg/2 mg • Most TEAEs were mild to moderate in severity Participants with: (n=41) (n=60) (n=66) and on-target events. Any TEAE, n (%) 22 (53.7) 52 (86.7) 59 (89.4) • No treatment-related se
Slide 49: Conclusions
Conclusions • This is the first report of phase 3 clinical data with an orexin receptor 2 agonist in people with NT1. • In The First Light phase 3 study, twice-daily 1 mg and 2 mg doses of oral oveporexton resulted in statistically significant and clinically meaningful improvements versus placebo ov
Slide 50: Questions
vo september 310 ZOZD ORLD SLEEP Singapore Questions
Slide 51: Efficacy and safety of oveporexton for NT1 (Dauvilliers)
Yves Dauvilliers, MD, PhD, France The Radiant Light: Efficacy and safety of oveporexton (TAK-861), an oral orexin receptor 2 agonist, for the treatment of narcolepsy type 1 WSC 2025, Singapore | September 5-10, 2025 | O-09 | This presentation is intended for health care professionals only. The Radia
Slide 52: Contributors
Contributors Yves Dauvilliers,1,2,3 Jakub Antczak,4 Erik Buntinx,5 Rafael del Rio Villegas,6,7 Seung-Chul Hong,8 Sheila Sivam,9 Shuqin Zhan,10 Elena Koundourakis,11 Rachel Neuwirth,11 Tina Olsson,11 Sarah Sheikh,11 Philipp von Rosenstiel,11 Baiyun Yao,11 Alice Cai,11,* Giuseppe Plazzi12,13,* 1 Sleep
Slide 53: Disclosures
Disclosures Disclosures • Yves Dauvilliers received funds for seminars, board engagements, and travel to conferences from Avadel, Bioprojet, Idorsia, Jazz Pharmaceuticals, Orexia, and Takeda. • Jakub Antczak has no disclosures to declare. • Erik Buntinx received consultancy fees from Alkermes, Eli L
Slide 54: Oveporexton development
Oveporexton development First in Phase 2 Phase 3 Phase 3 human start start results 2021 2023 2024 2025 Balanced efficacy and on- Early-phase clinical trials showed Here, we report the first data from target/off-target tolerability significant and meaningful The Radiant Light phase 3 study and safety
Slide 55: The Radiant Light study design
The Radiant Light study design • Randomized, double-blind, placebo-controlled, phase 3 study of 2 mg twice-daily oral oveporexton, an orexin receptor 2 agonist, conducted across Asia, Australia, and Europe. Inclusion criteria: • Participants aged 16–70 years • ICSD-3/ICSD-3 TR diagnosis of NT1 suppo
Slide 56: Participant disposition
Participant disposition Randomized (n=105) • 105 participants Placebo Oveporexton 2 mg/2 mg were randomized. (n=35) (n=70) • 101 completed 12 n=3 (4.3%) weeks Discontinued n=1 (2.9%) Adverse event: 2 (2.9%)* study drug Withdrawal by participant: 1 (2.9%) Withdrawal by participant: 1 (1.4%) • 100/101
Slide 57: Participant characteristics at baseline
Participant characteristics at baseline Oveporexton Placebo 2 mg/2 mg (n=35) (n=70) Mean (SD) age, years 34.0 (13.1) 29.1 (9.6) Female, n (%) 13 (37.1) 37 (52.9) Demographics Race, n (%) 7 (20.0) 14 (20.0) and disease Asian Black/African American 0 0 characteristics White 19 (54.3) 28 (40.0) were ge
Slide 58: Improved mean sleep latency versus placebo
Oveporexton significantly improved mean sleep latency at 12 weeks compared with placebo, with majority of participants within the normative range Maintenance of Wakefulness Test (MWT) LS mean difference from placebo in change from baseline at week 12 (primary endpoint) Oveporexton LS mean (95% CI) A
Slide 59: Improved subjective sleepiness versus placebo
Oveporexton significantly improved subjective sleepiness at 12 weeks compared with placebo, with majority of participants within the normative range Epworth Sleepiness Scale (ESS) LS mean difference from placebo in change from baseline at week 12 25 Oveporexton LS mean (95% CI) Adjusted P-value* 2 m
Slide 60: Reduced WCR and increased cataplexy-free days
Oveporexton significantly reduced WCR over 12 weeks versus placebo and increased the number of cataplexy-free days Weekly Cataplexy Rate (WCR) 70 Placebo • Median cataplexy-free 60 Oveporexton 2 mg/2 mg days/week increased Median (IQR) WCR 50 from 0 days at (any events) 40 baseline to 5 days at week
Slide 61: Oveporexton was generally safe and well tolerated
Oveporexton was generally safe and well tolerated Oveporexton Placebo 2 mg/2 mg • Most TEAEs were mild to moderate in severity Participants with: (n=35) (n=70) and on-target events. Any TEAE, n (%) 15 (42.9) 60 (85.7) • No treatment-related serious TEAEs. Mild 9 (25.7) 38 (54.3) • The most common TE
Slide 62: Conclusions
Conclusions • The first results from The Radiant Light phase 3 study in Asia, Australia, and Europe are consistent with those from The First Light study in Europe, Japan, and North America1 and with the 8-week phase 2 TAK-861-2001 study in participants with NT1.2 • Oveporexton 2 mg/2 mg demonstrated
Slide 63: Questions
vo september 310 ZOZD ORLD SLEEP Singapore Questions
Slide 64: Effect of oveporexton on severity of symptoms in NT1 (Barateau)
Lucie Barateau, MD, PhD, France Effect of oral orexin receptor 2 agonist oveporexton (TAK-861) on the severity of symptoms in individuals with narcolepsy type 1: Results from two phase 3 studies WSC 2025, Singapore | September 5-10, 2025 | O-09 | This presentation is intended for health care profess
Slide 65: Contributors
Contributors Lucie Barateau,1,2,3 Isabelle Arnulf,4,5,6 Yves Dauvilliers,1,2,3 Claudio Liguori,7,8 Fabio Pizza,9,10 Oliver Sum-Ping,11 Ellie Stukalin,12 Tina Olsson,12 Philipp von Rosenstiel12 1 Sleep-Wake Disorders Center, Department of Neurology, Gui-de-Chauliac Hospital, CHU, Montpellier, France;
Slide 66: Disclosures
Disclosures Disclosures • Lucie Barateau received funds for travel to conferences from Bioprojet and Idorsia and for board engagement from Bioprojet, Idorsia, Jazz Pharmaceuticals, and Takeda. • Isabelle Arnulf has no disclosures to declare. • Yves Dauvilliers received funds for seminars, board enga
Slide 67: Background
Background • In The First Light (Europe, Japan, and North America) and The Radiant Light (Asia, Australia, and Europe) phase 3 studies, twice-daily oral doses of 1 mg and 2 mg oveporexton, an orexin receptor 2 agonist, given at least 3 h apart demonstrated statistically significant and clinically me
Slide 68: Narcolepsy Severity Scale for Clinical Trials (NSS-CT)
Narcolepsy Severity Scale for Clinical Trials (NSS-CT) • The NSS-CT is a validated, self-administered, 15-item scale evaluating severity, frequency, and impact of the spectrum of narcolepsy symptoms, with domains for sleepiness, cataplexy, sleep paralysis, hallucinations, and disrupted nocturnal sle
Slide 69: The First Light & The Radiant Light study designs
The First Light & The Radiant Light study designs • 2 randomized, double-blind, placebo-controlled, phase 3 studies of twice-daily oral oveporexton, an orexin receptor 2 agonist, conducted across Asia, Australia, Europe, and North America. The First Light 12 weeks The Radiant Light 12 weeks Placebo†
Slide 70: Disease characteristics similar across groups at baseline
Disease characteristics were generally similar across groups at baseline The First Light The Radiant Light Oveporexton Oveporexton Oveporexton Placebo 1 mg/1 mg 2 mg/2 mg Placebo 2 mg/2 mg (n=41) (n=61) (n=66) (n=35) (n=70) Mean (SD) age, years 30.9 (12.7) 33.5 (11.8) 29.7 (9.6) 34.0 (13.1) 29.1 (9.
Slide 71: Changes in NSS-CT total score versus placebo
Oveporexton resulted in statistically significant and clinically meaningful changes in NSS-CT total score versus placebo Narcolepsy Severity Scale for Clinical Trials (NSS-CT) The First Light The Radiant Light 57 57 50 50 Very severe LS mean (95% CI) change Mean (SD) NSS-CT total score from baseline
Slide 72: Most participants achieved mild or moderate symptom severity
Most participants achieved mild or moderate symptom severity over 12 weeks of oveporexton Narcolepsy Severity Scale for Clinical Trials (NSS-CT) The First Light The Radiant Light Baseline Week 12 Baseline Week 12 100 4.9 1.6 3 100 4.3 Across both studies, 8.8 >70% of participants NSS-CT category (%
Slide 73: PGI-S: no or mild symptoms at week 12
The First Light: Most oveporexton-treated participants reported no or mild symptoms at week 12 versus placebo Patient Global Impression of Symptom Severity (PGI-S) Baseline Week 12 69% of participants 1.6 1.5 100 6.6 100 8.8 treated with 13.9 12.5 90 90 oveporexton overall PGI-S category (% particip
Slide 74: PGI-S: no or mild symptoms at week 12
The Radiant Light: Most oveporexton-treated participants reported no or mild symptoms at week 12 versus placebo Patient Global Impression of Symptom Severity (PGI-S) Baseline Week 12 100 2.9 100 79% of participants 5.7 11.8 90 90 16.4 treated with PGI-S category (% participants) PGI-S category (% pa
Slide 75: Improvements in PGI-C at week 12 versus placebo
Oveporexton resulted in statistically significant improvements in PGI-C at week 12 versus placebo* Patient Global Impression of Change (PGI-C) The First Light The Radiant Light 100 100 Across both studies, 2.9 11.8 74–97% of 90 22.2 90 PGI-C category (% participants) PGI-C category (% participants)
Slide 76: Oveporexton was generally safe and well tolerated
Oveporexton was generally safe and well tolerated The First Light The Radiant Light Oveporexton Oveporexton Oveporexton Placebo 1 mg/1 mg 2 mg/2 mg Placebo 2 mg/2 mg (n=41) (n=60) (n=66) (n=35) (n=70) Any TEAE, n (%) 22 (53.7) 52 (86.7) 59 (89.4) 15 (42.9) 60 (85.7) Mild 14 (34.1) 26 (43.3) 34 (51.5
Slide 77: Conclusions
Conclusions • In The First Light and The Radiant Light phase 3 studies, twice-daily 1 mg and 2 mg doses of oral oveporexton significantly improved disease severity as assessed with the NSS-CT, PGI-S, and PGI-C scales versus placebo in participants with NT1 over 12 weeks. • Oveporexton was generally
Slide 78: Questions
vo september 310 ZOZD ORLD SLEEP Singapore Questions
Slide 79: Effect of oveporexton on quality of life in NT1 (Sivam)
Sheila Sivam, MD, PhD, Australia Effect of the oral orexin receptor 2 agonist oveporexton (TAK-861) on quality of life in individuals with NT1 over 12 weeks WSC 2025, Singapore | September 5-10, 2025 | O-09 | This presentation is intended for health care professionals only.
Slide 80: Contributors
Contributors Sheila Sivam,1 Samuel Hsiao,2 Yeting Du,2 Heather Romero,2 Tina Olsson2 1 Woolcock Institute of Medical Research and Royal Prince Alfred Hospital, Sydney, NSW, Australia; 2 Takeda Development Center Americas, Inc., Cambridge, MA, USA WSC 2025, Singapore | September 5-10, 2025 | O-09 | T
Slide 81: Disclosures
Disclosures Disclosures • Sheila Sivam has received funding to attend clinical trial related investigator meetings or speaker fees from Avadel, Somnomed, Takeda, Teva, and Vertex Pharmaceuticals. • Samuel Hsiao, Yeting Du, Heather Romero, and Tina Olsson are employees of Takeda Development Center Am
Slide 82: Background
Background • In The First Light (Europe, Japan, and North America) and The Radiant Light (Asia, Australia, and Europe) phase 3 studies, twice-daily oral doses of 1 mg and 2 mg oveporexton, an orexin receptor 2 agonist, given at least 3 h apart demonstrated statistically significant and clinically me
Slide 83: The First Light & The Radiant Light study designs
The First Light & The Radiant Light study designs • 2 randomized, double-blind, placebo-controlled, phase 3 studies of twice-daily oral oveporexton, an orexin receptor 2 agonist, conducted across Asia, Australia, Europe, and North America. The First Light 12 weeks The Radiant Light 12 weeks Placebo†
Slide 84: Short Form-36 Survey (SF-36)
Short Form-36 Survey (SF-36) • SF-36 is a patient-reported assessment of quality of life and overall health status.1 Physical Mental • 36 items: 35 items constitute the Component Component Health domain scales Items, n Summary* Summary* domain scores, and 1 general Physical Functioning (PF) 10 healt
Slide 85: Improved SF-36 Mental Component Summary over 12 weeks
Oveporexton significantly improved patient-reported QoL on the SF-36 Mental Component Summary over 12 weeks Short Form-36 Survey (SF-36) The First Light The Radiant Light LS mean difference from placebo in change from LS mean difference from placebo in change from baseline at week 12 baseline at wee
Slide 86: Improved SF-36 Physical Component Summary over 12 weeks
Oveporexton significantly improved patient-reported QoL on the SF-36 Physical Component Summary over 12 weeks Short Form-36 Survey (SF-36) The First Light The Radiant Light LS mean difference from placebo in change from LS mean difference from placebo in change from baseline at week 12 baseline at w
Slide 87: Improved SF-36 domain scores across multiple domains
Oveporexton improved SF-36 domain scores over multiple domains at 12 weeks versus placebo in both studies Short Form-36 Survey (SF-36) The First Light Physical The Radiant Light Physical Functioning Functioning 100 100 80 Vitality 80 Vitality Bodily Pain Bodily Pain 60 Changes from baseline 60 40 to
Slide 88: EuroQol-5 Dimension-5 Level (EQ-5D-5L)
EuroQol-5 Dimension-5 Level (EQ-5D-5L) • EQ-5D-5L is a patient-reported assessment of quality of life and overall health status. • 5 dimensions are rated on 5-point Likert scale, from “No problems” to 5 severity levels “Unable/extreme.” EQ-5D scores Items, n (dimension scores)* • 1-item VAS scored f
Slide 89: Improved EQ-5D-5L Index scores at 12 weeks
Oveporexton significantly improved patients’ EQ-5D-5L Index scores at 12 weeks versus placebo EuroQol-5 Dimension-5 Level (EQ-5D-5L) The First Light The Radiant Light LS mean difference from placebo in change from BL at week 12 LS mean difference from placebo in change from BL at week 12 Oveporexton
Slide 90: Improved EQ-5D-5L VAS scores at 12 weeks
Oveporexton significantly improved patients’ self-rated EQ-5D-5L VAS scores at 12 weeks versus placebo EuroQol-5 Dimension-5 Level (EQ-5D-5L) The First Light The Radiant Light LS mean difference from placebo in change from BL at week 12 LS mean difference from placebo in change from BL at week 12 Ov
Slide 91: Improved EQ-5D-5L domain scores
Oveporexton improved patients’ self-rated EQ-5D-5L domain scores at 12 weeks versus placebo EuroQol-5 Dimension-5 Level (EQ-5D-5L) The First Light Self-care Mobility Pain/Discomfort Anxiety/Depression Usual Activities 100% 80% Patients 60% 40% 20% 0% Placebo 1/1 mg 2/2 mg Placebo 1/1 mg 2/2 mg Place
Slide 92: Oveporexton was generally safe and well tolerated
Oveporexton was generally safe and well tolerated The First Light The Radiant Light Oveporexton Oveporexton Oveporexton Placebo 1 mg/1 mg 2 mg/2 mg Placebo 2 mg/2 mg (n=41) (n=60) (n=66) (n=35) (n=70) Any TEAE, n (%) 22 (53.7) 52 (86.7) 59 (89.4) 15 (42.9) 60 (85.7) Mild 14 (34.1) 26 (43.3) 34 (51.5
Slide 93: Conclusions
Conclusions • In The First Light and The Radiant Light phase 3 studies, twice-daily 1 mg and 2 mg doses of oral oveporexton showed significant improvements in HRQoL over 12 weeks versus placebo in participants with NT1. • Oveporexton was generally safe and well tolerated. • These results are consist
Slide 94: Questions
vo september 310 ZOZD ORLD SLEEP Singapore Questions
Takeda Pharmaceutical Company — World Sleep Congress 2025 on 6ix