Small Molecule · ITI-1284

ITI-1284 (deulumateperone)

Phase 2Intra-Cellular Therapies, Inc. (ITCI)

Deuterated form of lumateperone (the Caplyta active moiety) and a new chemical entity, formulated as an orally disintegrating tablet for sublingual administration. Deuteration (replacing select hydrogen atoms with deuterium) is intended to slow metabolism and extend the half-life relative to lumateperone. Like lumateperone, it is a multi-target agent: a high-affinity serotonin 5-HT2A antagonist with moderate dopamine D2 (and D1) receptor activity and serotonin-transporter (SERT) inhibition. Developed by Intra-Cellular Therapies, which was acquired by Johnson & Johnson (closed 2 Apr 2025); ITI-1284 is in Phase 2 development for generalized anxiety disorder (both adjunctive and monotherapy) as well as Alzheimer's-related psychosis and agitation (separate programs).

Also known as: ITI-1284, ITI-1284-ODT-SL, deulumateperone, 2102683-75-8

Data current as of

Modality
Small molecule
Chemical class
pyridopyrroloquinoxaline, butyrophenone
Chemistry
Single enantiomer · Deuterated
Mechanism
5-HT2A antagonist
Highest phase
Phase 2
Lead indication
Alzheimer's disease
Developer
Intra-Cellular Therapies, Inc. (ITCI)
Trials
4 tracked · 4 recruiting · 263 sites
Next catalyst
Mid-2027 — Topline data (Generalized anxiety disorder)

Mechanism of action

Multi-target small molecule; a deuterated analogue of lumateperone with the same receptor pharmacophore. Acts as a high-affinity serotonin 5-HT2A receptor antagonist with comparatively lower-affinity activity at dopamine D2 receptors (functionally described by the developer as a presynaptic partial agonist / postsynaptic antagonist, a 'dopamine receptor phosphoprotein modulator'), inhibition of the serotonin transporter (SERT), and additional D1-receptor / glutamatergic modulation. No ITI-1284-specific binding constants have been published; deuteration is a metabolic (pharmacokinetic) modification that is not expected to alter target affinities, so the target identities are inherited from lumateperone (IUPHAR ligand 9099). The anxiolytic rationale rests on this combined 5-HT2A antagonism plus low/region-selective D2 occupancy and SERT inhibition.

TargetActionAffinity
5-HT2AprimaryHTR2AAntagonist—ⓘ
D2DRD2Antagonist—ⓘ
SERTSLC6A4Inhibitor—ⓘ

Formulations

FormulationRouteRegimenPharmacokinetics
ITI-1284 ODT-SLZydis orally disintegrating tablet (Catalent)
10 mg or 20 mg sublingual orally disintegrating tablet, once daily
SublingualOnce daily—

Development timeline

Phase 2Feb 2024 – Oct 2027
  1. UpcomingAnticipated Phase 2 topline for ITI-1284 in agitation associated with Alzheimer's dementia (NCT06651567); primary completion targeted October 2027.Agitation in Alzheimer's disease
  2. UpcomingAnticipated Phase 2 topline for ITI-1284 in psychosis associated with Alzheimer's disease (NCT06540833); primary completion targeted September 2027.Alzheimer's disease
  3. UpcomingAnticipated Phase 2 topline for monotherapy ITI-1284 in GAD (NCT06701903); primary completion targeted June 2027.Generalized anxiety disorder
  4. UpcomingAnticipated Phase 2 topline for adjunctive ITI-1284 in GAD (NCT06480383); primary completion targeted June 2027.Generalized anxiety disorder
  5. Intra-Cellular Therapies FY2024 corporate update reports patient enrollment ongoing in the Phase 2 program evaluating ITI-1284 in agitation associated with Alzheimer's disease (alongside the Phase 2 Alzheimer's psychosis program).Agitation in Alzheimer's disease↗
  6. Second GAD trial started: monotherapy Phase 2 study NCT06701903 (ITI-1284 10 mg / 20 mg sublingual vs placebo, n~570).Generalized anxiety disorder
  7. Phase 2 agitation-in-Alzheimer's-dementia trial started: NCT06651567 (ITI-1284 10-20 mg sublingual ODT once daily vs placebo, flexible-dose, n~320; primary endpoint CMAI total score at Week 12). Actual study start per ClinicalTrials.gov.Agitation in Alzheimer's disease
  8. Phase 2 Alzheimer's-disease psychosis trial started: NCT06540833, a multicenter, randomized, double-blind, placebo-controlled, flexible-dose study of ITI-1284 10 mg / 20 mg once-daily sublingual ODT vs placebo (n=370), 6-week treatment, primary outcome BEHAVE-AD psychosis subscale at Week 6.Alzheimer's disease
  9. First GAD trial started: adjunctive Phase 2 study NCT06480383 (ITI-1284 10 mg / 20 mg sublingual vs placebo in patients with inadequate response to GAD treatment, n~705).Generalized anxiety disorder
  10. Intra-Cellular Therapies announced (FY2023 corporate update) that it had initiated Phase 2 programs evaluating ITI-1284, including in psychosis associated with Alzheimer's disease, with patient enrollment anticipated to commence in 2Q 2024.Alzheimer's disease↗
  11. Intra-Cellular Therapies announced (FY2023 corporate update) that it had initiated Phase 2 programs evaluating ITI-1284 in generalized anxiety disorder (GAD), with patient enrollment anticipated in 1H 2024.Generalized anxiety disorder↗

ITI-1284 (deulumateperone) for Alzheimer's disease

Phase 2RecruitingAlzheimer's disease indication →

Phase 2 program of ITI-1284 (deulumateperone), an orally disintegrating sublingual tablet, in psychosis associated with Alzheimer's disease. A single multicenter, randomized, double-blind, placebo-controlled, flexible-dose Phase 2 trial is recruiting (NCT06540833, n=370): ITI-1284 10 mg or 20 mg once daily vs placebo over a 6-week treatment period in patients with biomarker-confirmed Alzheimer's disease and psychosis, with the BEHAVE-AD psychosis subscale at Week 6 as the primary outcome. Intra-Cellular Therapies announced initiation of the Phase 2 ITI-1284 psychosis program in its FY2023 corporate update (Feb 2024) and commenced enrollment in 3Q 2024; the trial started 15 Aug 2024 with primary completion targeted for September 2027. No topline results have been reported and no FDA designations have been disclosed for this indication. is_lead_indication=false: AD-related psychosis is one of several ITI-1284 Phase 2 indications (alongside Alzheimer's agitation and generalized anxiety disorder), with no AD-psychosis-specific lead designation, and the parent compound lumateperone is approved in other indications.

Readouts

  • 2H 2027AnticipatedTopline dataNCT06540833

    Anticipated Phase 2 topline for ITI-1284 in psychosis associated with Alzheimer's disease (NCT06540833); primary completion targeted September 2027.

ITI-1284 (deulumateperone) for Generalized anxiety disorder

Phase 2RecruitingGeneralized anxiety disorder indication →

Phase 2 program of ITI-1284 (deulumateperone), an orally disintegrating sublingual tablet, in generalized anxiety disorder. Two randomized, double-blind, placebo-controlled multicenter Phase 2 trials are recruiting at 10 mg and 20 mg once-daily doses: an adjunctive study in patients with inadequate response to GAD treatment (NCT06480383, n~705, started Aug 2024) and a monotherapy study (NCT06701903, n~570, started Nov 2024), both with primary completion targeted for June 2027. Intra-Cellular Therapies announced initiation of the Phase 2 GAD program in its Feb 2024 corporate update. No topline GAD results have been reported and no FDA designations have been disclosed for the GAD indication. is_lead_indication=false: GAD is one of several ITI-1284 Phase 2 indications (alongside Alzheimer's-related psychosis and agitation), with no GAD-specific lead designation, and the parent compound lumateperone is approved in other indications.

Readouts

  • Mid-2027AnticipatedTopline dataNCT06701903

    Anticipated Phase 2 topline for monotherapy ITI-1284 in GAD (NCT06701903); primary completion targeted June 2027.

  • Mid-2027AnticipatedTopline dataNCT06480383

    Anticipated Phase 2 topline for adjunctive ITI-1284 in GAD (NCT06480383); primary completion targeted June 2027.

ITI-1284 (deulumateperone) for Agitation in Alzheimer's disease

Phase 2RecruitingAgitation in Alzheimer's disease indication →

Phase 2 program of ITI-1284 (deulumateperone), a sublingual orally disintegrating tablet, in agitation associated with Alzheimer's dementia. One multicenter, randomized, double-blind, placebo-controlled, flexible-dose Phase 2 trial is recruiting (NCT06651567, n~320, started 22 Oct 2024): ITI-1284 10-20 mg once-daily sublingual vs placebo over a 12-week double-blind treatment period, with the Cohen-Mansfield Agitation Inventory (CMAI) total score at Week 12 as the primary endpoint and primary completion targeted for October 2027. Intra-Cellular Therapies' FY2024 corporate update (Feb 2025) reported enrollment ongoing in the Phase 2 agitation-in-AD program. No topline results have been reported and no FDA designations have been disclosed for this indication. is_lead_indication=false: agitation in Alzheimer's dementia is one of several ITI-1284 Phase 2 indications (alongside generalized anxiety disorder and Alzheimer's-related psychosis), with the parent compound lumateperone already approved in other indications.

Readouts

  • Q4 2027AnticipatedTopline dataNCT06651567

    Anticipated Phase 2 topline for ITI-1284 in agitation associated with Alzheimer's dementia (NCT06651567); primary completion targeted October 2027.

Clinical trials

NCT06701903Phase 2Recruitingn=570

A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety, and Tolerability of ITI-1284 as Monotherapy Treatment in Patients With Generalized Anxiety Disorder

Started Nov 2024· Primary completion Jun 2027· 📍 60 sites across 6 countries (United States, Bulgaria, Serbia, Poland)

NCT06651567Phase 2Recruitingn=320

A Multicenter, Randomized, Double-blind, Placebo-controlled, Flexible-dose Study of the Efficacy, Safety, and Tolerability of ITI-1284 in Patients With Agitation Associated With Alzheimer's Dementia

Started Oct 2024· Primary completion Oct 2027· 📍 69 sites across 8 countries (United States, Bulgaria, Czechia, Slovakia)

NCT06540833Phase 2Recruitingn=370

A Multicenter, Randomized, Double-blind, Placebo-controlled, Flexible-dose Study to Assess the Efficacy, Safety, and Tolerability of ITI-1284 in Patients With Psychosis Associated With Alzheimer's Disease

Started Aug 2024· Primary completion Sept 2027· 📍 65 sites across 9 countries (United States, Bulgaria, Slovakia, Romania)

NCT06480383Phase 2Recruitingn=705

A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety, and Tolerability of ITI-1284 as an Adjunctive Treatment in Patients With Generalized Anxiety Disorder Who Have an Inadequate Response to Generalized Anxiety Disorder Treatment

Started Aug 2024· Primary completion Jun 2027· 📍 69 sites across 6 countries (United States, Bulgaria, Serbia, Poland)

Related compounds

Other 5-HT2A compounds

More from Intra-Cellular Therapies, Inc.

Identifiers

Sources

  1. Intra-Cellular Therapies Announces Expansion of its Pipeline with the Introduction of a New Molecular Entity, ITI-1284 — Intra-Cellular Therapies (GlobeNewswire)
  2. Intra-Cellular Therapies FY2023 corporate update - initiation of Phase 2 ITI-1284 GAD program — Intra-Cellular Therapies, Inc. (GlobeNewswire)
  3. Intra-Cellular Therapies reports fourth quarter and full-year 2024 financial results - enrollment ongoing in Phase 2 ITI-1284 agitation-in-AD program — Intra-Cellular Therapies, Inc. (GlobeNewswire)
  4. ITI-1284 as adjunctive treatment in generalized anxiety disorder (Phase 2, NCT06480383) — ClinicalTrials.gov
  5. ITI-1284 as monotherapy treatment in generalized anxiety disorder (Phase 2, NCT06701903) — ClinicalTrials.gov
  6. ITI-1284 in agitation associated with Alzheimer's dementia (Phase 2, NCT06651567) — ClinicalTrials.gov
  7. ITI-1284 in patients with psychosis associated with Alzheimer's disease (Phase 2, NCT06540833) — ClinicalTrials.gov
  8. Lumateperone (ligand 9099) - binding data at 5-HT2A, D2, and SERT — IUPHAR/BPS Guide to Pharmacology