LB-102 · program
LB-102 (N-methylamisulpride) for Bipolar depression
Indications for LB-102: Schizophrenia · Phase 3 Bipolar depression · Phase 2 Major depressive disorder · Unknown
Lifecycle-expansion indication for LB-102 (N-methylamisulpride), pursued on the strength of the positive Phase 2 NOVA-1 schizophrenia result. The Phase 2 ILLUMINATE-1 trial (NCT07494305) began on 23-Jan-2026 (initiation announced 26-Jan-2026): a U.S.-only, randomized, double-blind, placebo-controlled, multicenter, 6-week outpatient study in ~320 adults with bipolar I depression (major depressive episodes associated with bipolar I disorder) at ~30 U.S. sites. Patients are randomized 1:1 to once-daily LB-102 (fixed-flexible 25 mg for weeks 1-3, may up-titrate to 50 mg at week 4) or placebo. Primary endpoint is change from baseline in MADRS-10 at Week 6 (pooled LB-102 vs placebo); secondary endpoints include MADRS-6, CGI-BP, cognition, anhedonia, treatment-emergent mania (YMRS), and safety/tolerability. Topline results are anticipated in 1Q 2028. Mechanistic rationale: D2 antagonism for mood/psychotic control plus D3 and 5-HT7 antagonism for potential antidepressant and procognitive effects.
Development timeline
- UpcomingPhase 2 ILLUMINATE-1 topline (MADRS-10 change at Week 6) in bipolar I depression anticipated in 1Q 2028.↗
- Phase 2 ILLUMINATE-1 (NCT07494305) initiated in bipolar I depression, expanding the LB-102 development program beyond schizophrenia. ~320 patients with bipolar I depression at ~30 U.S. sites; once-daily LB-102 (25 mg/50 mg fixed-flexible) vs placebo 1:1 over 6 weeks; primary endpoint MADRS-10 change at Week 6; topline anticipated 1Q 2028. CT.gov actual start date 2026-01-23; initiation announced by the company 2026-01-26.↗
Readouts
- 1Q 2028AnticipatedTopline dataNCT07494305
Phase 2 ILLUMINATE-1 topline (MADRS-10 change at Week 6) in bipolar I depression anticipated in 1Q 2028. ↗
Clinical trials in Bipolar depression
NCT07494305Phase 2Recruitingn=320
A Randomized, Double Blind, Placebo Controlled, Multicenter Study to Assess the Efficacy and Safety of LB-102 in the Treatment of Adult Patients With Major Depressive Episodes Associated With Bipolar I Disorder (ILLUMINATE-1)
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| LB-102 long-acting injectablelong-acting injectable (LAI) Long-acting injectable formulation planned for global development (route/schedule not yet disclosed) | Subcutaneous depot (LAI) | — | — |
Mechanism of action
Selective antagonist of dopamine D2 and D3 receptors and serotonin 5-HT7 receptors. LB-102 retains high-affinity D2/D3 antagonism (Ki = 0.8 nM at each) and 5-HT7 antagonism (Ki = 31 nM); like its parent amisulpride it is a racemate with enantiomer-divergent polypharmacy (the S-enantiomer preferentially engages D2/D3, the R-enantiomer preferentially engages 5-HT7). N-methylation increases lipophilicity and passive membrane diffusion, giving better brain penetration than amisulpride and enabling once-daily oral dosing at 5-8 fold lower systemic exposure while still achieving the 60-80% striatal dopamine receptor occupancy associated with antipsychotic efficacy.
| Target | Action | Affinity |
|---|---|---|
| D2primaryDRD2 | Antagonist | Ki 0.8 nMⓘ |
| 5-HT7HTR7 | Antagonist | Ki 31 nMⓘ |
| D3DRD3 | Antagonist | Ki 0.8 nMⓘ |
← Full LB-102 compound page (identity, identifiers, all indications)
Sources
- Antipsychotic Efficacy and Safety of LB-102 in the Treatment of Adults With Acute Schizophrenia: A Randomized Clinical Trial (NOVA-1) — JAMA Psychiatry (PMC)
- ILLUMINATE-1: Phase 2 study of LB-102 in adults with major depressive episodes associated with bipolar I disorder (NCT07494305) — ClinicalTrials.gov
- LB Pharmaceuticals Announces Positive Topline Results from Phase 2 Trial of LB-102 in Schizophrenia — LB Pharmaceuticals (GlobeNewswire)
- LB Pharmaceuticals Initiates Phase 2 ILLUMINATE-1 Trial in Bipolar Depression, Expanding LB-102 Development Program — LB Pharmaceuticals (GlobeNewswire)