oveporexton (TAK-861) / Takeda - LARVOL DELTA

Takeda Delivers Strong Third-Quarter FY2024 Results; Raises Full Year Outlook, Forecasting Revenue and Core Operating Profit Margin Growth (Businesswire) - "Among the multiple late-stage programs presented, the company expects...Phase 3 data readouts in the calendar year 2025 with filings anticipated in FY2025-FY2026 for the following programs and indications: oveporexton (TAK-861) for the treatment of narcolepsy type 1; zasocitinib for the treatment of psoriasis...Moreover, five additional indication filings for late-stage programs are on pace for FY2027-FY2029. zasocitinib for the treatment of psoriatic arthritis; mezagitamab for treatments of immune thrombocytopenia (ITP), a rare immune-mediated bleeding disorder, and immunoglobulin A nephropathy (IgAN), a chronic progressive autoimmune mediated kidney disease; fazirsiran for the treatment of alpha-1 antitrypsin deficiency-associated liver disease, and elritercept for the treatment of anemia associated with myelodysplastic syndrome."

Filing • P3 data • Alpha-1 Antitrypsin Deficiency • Anemia • IgA Nephropathy • Immune Thrombocytopenic Purpura • Narcolepsy • Psoriasis • Psoriatic Arthritis

A Study of TAK-861in People With Narcolepsy Type 1 (clinicaltrials.gov) - P3 | N=93 | Recruiting | Sponsor: Takeda | Not yet recruiting ➔ Recruiting

Enrollment open • Cataplexy • Narcolepsy • Sleep Disorder

A Study of TAK-861 for the Treatment of Selected Central Hypersomnia Conditions (clinicaltrials.gov) - P2/3 | N=500 | Recruiting | Sponsor: Takeda | Trial completion date: Jun 2028 ➔ Feb 2028 | Trial primary completion date: Jun 2028 ➔ Feb 2028

Trial completion date • Trial primary completion date • Narcolepsy • Sleep Disorder

TAK-861, a potent, orally available orexin receptor 2-selective agonist, produces wakefulness in monkeys and improves narcolepsy-like phenotypes in mouse models. (PubMed, Sci Rep) - "We discovered a parenteral orexin receptor 2 (OX2R) agonist, danavorexton, and an orally available OX2R agonist, TAK-994; both improving NT1 phenotypes in mouse models and individuals with NT1. Compared with modafinil, TAK-861 induces highly correlated brain-wide neuronal activation in orexin-tTA;TetO DTA mice, suggesting efficient wake-promoting effects. Thus, TAK-861 has potential as an effective treatment for individuals with hypersomnia disorders including narcolepsy, potentially with a favorable safety profile."

Journal • Preclinical • Cataplexy • Excessive Daytime Sleepiness • Hepatology • Narcolepsy • Sleep Disorder • ATXN3

A Study of TAK-861 for the Treatment of Narcolepsy Type 1 (clinicaltrials.gov) - P3 | N=152 | Recruiting | Sponsor: Takeda | Not yet recruiting ➔ Recruiting

Enrollment open • Cataplexy • Narcolepsy • Sleep Disorder

A Study of TAK-861 for the Treatment of Selected Central Hypersomnia Conditions (clinicaltrials.gov) - P2/3 | N=500 | Recruiting | Sponsor: Takeda | N=160 ➔ 500 | Trial completion date: Dec 2026 ➔ Jun 2028 | Trial primary completion date: Dec 2026 ➔ Jun 2028

Enrollment change • Trial completion date • Trial primary completion date • Narcolepsy • Sleep Disorder

A Study of TAK-861in People With Narcolepsy Type 1 (clinicaltrials.gov) - P3 | N=93 | Not yet recruiting | Sponsor: Takeda

New P3 trial • Cataplexy • Narcolepsy • Sleep Disorder

A Study of TAK-861 for the Treatment of Narcolepsy Type 1 (clinicaltrials.gov) - P3 | N=152 | Not yet recruiting | Sponsor: Takeda

New P3 trial • Cataplexy • Narcolepsy • Sleep Disorder

Efficacy and Safety of TAK-861, an Oral Orexin Receptor 2 Agonist, in Individuals with Narcolepsy Type 1: Results From a Phase 2 Study (SLEEP 2024) - P2 | "In this Phase 2 study, TAK-861 showed significant and clinically meaningful improvements versus placebo on objective and subjective measures of sleepiness and cataplexy frequency. TAK-861 was generally well tolerated in participants with NT1 over 8 weeks"

Clinical • Late-breaking abstract • P2 data • Cataplexy • CNS Disorders • Excessive Daytime Sleepiness • Insomnia • Narcolepsy • Sleep Disorder

Effect of Oral Orexin Receptor 2 Agonist TAK-861 on the Severity of Symptoms in Individuals with Narcolepsy Type 1: Results from a Phase 2 Study (SLEEP 2024) - P2 | "In this Phase 2 study, TAK-861 showed significant and clinically meaningful improvements in NSS-CT and improvements in PGI and CGI versus placebo in participants with NT1 over 8 weeks."

Clinical • Late-breaking abstract • P2 data • Cataplexy • CNS Disorders • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

A Study of TAK-861 in Participants With Narcolepsy Type 2 (clinicaltrials.gov) - P2 | N=71 | Completed | Sponsor: Takeda | Active, not recruiting ➔ Completed | Trial completion date: Oct 2024 ➔ Dec 2023 | Trial primary completion date: May 2024 ➔ Dec 2023

Trial completion • Trial completion date • Trial primary completion date • Cataplexy • Narcolepsy • Sleep Disorder

A Study of TAK-861 in Participants With Narcolepsy Type 1 (clinicaltrials.gov) - P2 | N=112 | Completed | Sponsor: Takeda | Active, not recruiting ➔ Completed | Trial completion date: May 2024 ➔ Dec 2023 | Trial primary completion date: May 2024 ➔ Dec 2023

Trial completion • Trial completion date • Trial primary completion date • Cataplexy • Narcolepsy • Sleep Disorder • HLA-DQB1

A Study of TAK-861 in Participants With Narcolepsy Type 2 (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: Takeda | Recruiting ➔ Active, not recruiting

Enrollment closed • Cataplexy • Narcolepsy • Sleep Disorder

A Study of TAK-861 in Participants With Narcolepsy Type 1 (clinicaltrials.gov) - P2 | N=100 | Active, not recruiting | Sponsor: Takeda | Recruiting ➔ Active, not recruiting

Enrollment closed • Cataplexy • Narcolepsy • Sleep Disorder • HLA-DQB1

Safety, tolerability, pharmacodynamics, and pharmacokinetics of oral TAK-861 in an acute sleep phase delay paradigm in healthy male subjects (WSS 2023) - "HD and LD TAK-861 demonstrated significant and dose-dependent improvements in measures of wakefulness compared with placebo, with no serious or severe adverse events.Acknowledgements: Funded by Takeda Development Center Americas, Inc."

Clinical • PK/PD data • CNS Disorders • Delayed Sleep Phase Disorder • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

Discovery of a highly potent and orally available orexin 2 receptor-selective agonist, TAK-861, as a novel therapeutic agent for narcolepsy and other hypersomnia disorders (WSS 2023) - "We have previously discovered a parenteral OX2R agonist, danavorexton, and an orally available OX2R agonist, TAK-994, which improved NT1-like phenotypes in mouse models and showed promising therapeutic effects in NT1 patients. Compared with TAK-994, the novel orally available OX2R-selective agonist TAK-861 showed approximately 10-fold higher potency in OX2R activation, better selectivity over OX1R, and 10-fold lower effective dosage for arousal in both mice and monkeys.Acknowledgements: This work was conducted by Takeda Pharmaceutical Company Limited."

Cataplexy • CNS Disorders • Excessive Daytime Sleepiness • Hepatology • Narcolepsy • Sleep Disorder

A Study of TAK-861 for the Treatment of Selected Central Hypersomnia Conditions (clinicaltrials.gov) - P2/3 | N=160 | Recruiting | Sponsor: Takeda | Not yet recruiting ➔ Recruiting

Enrollment open • Narcolepsy • Sleep Disorder

A Study of TAK-861 for the Treatment of Selected Central Hypersomnia Conditions (clinicaltrials.gov) - P2/3 | N=160 | Not yet recruiting | Sponsor: Takeda

New P2/3 trial • Narcolepsy • Sleep Disorder

"AFTER 8+ MONTHS: How I finally figured out the structure of TAK-861, a 2nd gen oral Ox2R agonist for narcolepsy by @TakedaPharma. Currently in ph2! $TAK A long & winding road, w some PEARLS gathered along the way TL;DR... 🧵 1/10" (@victoriacyanide)

Narcolepsy • Sleep Disorder

"TAK-861 by @TakedaPharma $TAK https://t.co/oEXPYWaX8b" (@victoriacyanide)

A Study to Evaluate the Efficacy, Safety, and Tolerability of TAK-861 for the Treatment of Narcolepsy With Cataplexy Un estudio para evaluar la eficacia, seguridad y tolerabilidad de TAK-861 para el tratamiento de la narcolepsia con cataplejía (clinicaltrialsregister.eu) - P2 | N=100 | Ongoing | Sponsor: Takeda Development Center Americas, Inc.

New P2 trial • Cataplexy • Narcolepsy • Sleep Disorder • HLA-DQB1

A Study of TAK-861 in Participants With Narcolepsy Type 1 (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Takeda | Not yet recruiting ➔ Recruiting

Enrollment open • Cataplexy • Narcolepsy • Sleep Disorder • HLA-DQB1

A Study of TAK-861 in Participants With Narcolepsy Type 2 (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Takeda | Not yet recruiting ➔ Recruiting

Enrollment open • Cataplexy • Narcolepsy • Sleep Disorder

A Study of TAK-861 in Participants With Narcolepsy Type 2 (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Takeda

New P2 trial • Cataplexy • Narcolepsy • Sleep Disorder

A Study of TAK-861 in Participants With Narcolepsy Type 1 (clinicaltrials.gov) - P2 | N=100 | Not yet recruiting | Sponsor: Takeda

New P2 trial • Cataplexy • Narcolepsy • Sleep Disorder • HLA-DQB1