Small Molecule · SEP-363856

Ulotaront (SEP-363856)

Phase 2/3Otsuka Pharmaceutical Co., Ltd. (4578)

Orally active TAAR1 agonist with 5-HT1A agonism and no appreciable D2 or 5-HT2A activity. Schizophrenia Phase 3 (DIAMOND) failed in 2023; advanced into Phase 2/3 programs in generalized anxiety disorder (lead) and adjunctive major depressive disorder (now under Otsuka).

Also known as: SEP-363856, SEP-856, ulotaront

Data current as of

Key facts

Modality
Small molecule
Chemical class
thienopyran, amine
Chemistry
Single enantiomer
Mechanism
TAAR1 agonist
Highest phase
Phase 2/3
Lead indication
Generalized anxiety disorder
Developer
Otsuka Pharmaceutical Co., Ltd. (4578)
Trials
2 tracked · 160 sites

Mechanism of action#

Dual TAAR1 agonist / 5-HT1A agonist with no appreciable D2 or 5-HT2A activity.

10 nM100 nM1 µMTAAR1TAAR1 — agonist — EC50 38 nMEC50 38 nM5-HT1A5-HT1A — agonist — Ki 284 nMKi 284 nM
Binding affinity on a log scale — further left is more potent. Values from the sourced literature (see table).
TargetActionAffinity
TAAR1primaryTAAR1AgonistEC50 38 nMⓘ
5-HT1AHTR1AAgonistKi 284 nMⓘ

Formulations#

FormulationRouteRegimenPharmacokinetics
Ulotaront oral
Oral doses studied 10-100 mg (dose-proportional PK); 25 mg single oral dose in the CYP2D6 healthy-subject study; once-daily dosing supported by PK.
OralOnce dailyt½ 7 h · Tmax 2 h

Development timeline#

20222023202420252026TodayPhase 2/36 Nov 2025 — phase change — Phase 2/3 adjunctive MDD study reached completion; topline results not yet disclosed.26 Sept 2025 — phase change — Phase 2/3 GAD study (NCT05729373) reached completion; topline results not yet disclosed.15 Mar 2024 — phase change — Sumitomo Pharma amended its worldwide license; Otsuka took over ulotaront (incl. GAD/MDD) and decided to continue development.15 Mar 2024 — Licensing deal — Otsuka and Sumitomo revise the license agreement; Otsuka gains exclusive worldwide rights to ulotaront8 Mar 2023 — phase change — First patient randomized in the Phase 2/3 GAD study (NCT05729373).9 Nov 2022 — phase change — Phase 2/3 adjunctive MDD study (NCT05593029) started.30 Sept 2021 — Licensing deal — Otsuka in-licenses ulotaront (SEP-363856) in a worldwide collaboration with Sumitomo Dainippon Pharma and Sunovion
Phase change Readout Event UpcomingHover a marker for details.
Phase 2/3Sept 2021 – Nov 2025
  1. Phase 2/3 adjunctive MDD study reached completion; topline results not yet disclosed.Major depressive disorder
  2. Phase 2/3 GAD study (NCT05729373) reached completion; topline results not yet disclosed.Generalized anxiety disorder
  3. Sumitomo Pharma amended its worldwide license; Otsuka took over ulotaront (incl. GAD/MDD) and decided to continue development.Generalized anxiety disorder↗
  4. Licensing dealOtsuka and Sumitomo revise the license agreement; Otsuka gains exclusive worldwide rights to ulotaront↗
  5. First patient randomized in the Phase 2/3 GAD study (NCT05729373).Generalized anxiety disorder
  6. Phase 2/3 adjunctive MDD study (NCT05593029) started.Major depressive disorder
  7. Licensing dealOtsuka in-licenses ulotaront (SEP-363856) in a worldwide collaboration with Sumitomo Dainippon Pharma and Sunovion↗

Ulotaront (SEP-363856) for Generalized anxiety disorder#

Phase 2/3CompletedGeneralized anxiety disorder indication →

Phase 2/3 ulotaront monotherapy in generalized anxiety disorder (SEP361-226 / NCT05729373, n=434, HAM-A primary), completed 26 Sep 2025; topline pending. A Phase 2/3 adjunctive MDD program (NCT05593029, n=929) also completed (Nov 2025). Otsuka committed to continuing GAD/MDD development after the 2023 schizophrenia Phase 3 failure.

Ulotaront (SEP-363856) for Major depressive disorder#

Phase 2/3CompletedMajor depressive disorder indication →

Adjunctive ulotaront for major depressive disorder — second mood indication after the lead GAD program. Phase 2/3 study (NCT05593029, n=929) completed Nov 2025; topline pending.

Clinical trials#

NCT05729373SEP361-226Phase 2/3Completedn=434

Phase 2/3 Study of SEP-363856 in Generalized Anxiety Disorder

Started Mar 2023· Primary completion Sept 2025· 83 sites across 8 countries

United StatesJapanBulgariaSpain

NCT05593029382-201-00001Phase 2/3Completedn=929

Phase 2/3 Trial of SEP-363856 as Adjunctive Therapy in Major Depressive Disorder

Started Nov 2022· Primary completion Nov 2025· 77 sites across 7 countries

United StatesGermanyPolandBulgaria

Conference coverage#

SEP-363856 appears in 2 CNS Pulse conference abstracts:

Sources#

  1. A Phase I, Open-Label, Fixed Sequence Study to Investigate the Effect of CYP2D6 Inhibition on the Pharmacokinetics of Ulotaront in Healthy Subjects — Clinical Pharmacokinetics (PMC)
  2. Otsuka and Sumitomo Revise License Agreement - Otsuka holds exclusive rights to develop, manufacture, and commercialize ulotaront and SEP-380135 worldwide — Otsuka Pharmaceutical Co., Ltd.
  3. Sumitomo Dainippon Pharma and Otsuka Announce a Worldwide Collaboration and License Agreement for Four Psychiatry and Neurology Compounds — Otsuka Pharmaceutical Co., Ltd.
  4. Sumitomo→Otsuka license amendment (ulotaront) — Sumitomo Pharma
  5. Ulotaront adjunctive MDD Phase 2/3 (NCT05593029) — ClinicalTrials.gov
  6. Ulotaront Phase 2/3 GAD (NCT05729373) — ClinicalTrials.gov
  7. Ulotaront: A TAAR1 Agonist for the Treatment of Schizophrenia (synthesis/med-chem) — ACS Med Chem Lett (PMC)