LB-102 (N-methylamisulpride)

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.

Formulations

LB-102 (N-methylamisulpride) for Schizophrenia

Phase 3ActiveSchizophrenia indication →

Lead indication. The Phase 2 NOVA-1 study (NCT06179108, n=359 acute schizophrenia) met its primary endpoint on 08-Jan-2025: statistically significant placebo-adjusted reduction in PANSS total score at Week 4 across all dose levels (50 mg, 75 mg, 100 mg), with low EPS, limited prolactin-related adverse events, minimal QTc prolongation, and ~2 kg placebo-adjusted weight gain; published in JAMA Psychiatry (Apr 2026). LB Pharmaceuticals advanced LB-102 into the pivotal Phase 3 NOVA-2 trial (NCT07363577), which began recruiting 25-Mar-2026: ~456 patients with acute schizophrenia at ~25 U.S. sites, 50 mg / 100 mg / placebo (1:1:1) over 6 weeks, primary endpoint PANSS total change at Week 6, topline expected 2H 2027.

LB-102 (N-methylamisulpride) for Bipolar depression

Phase 2RecruitingBipolar depression indication →

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.

LB-102 (N-methylamisulpride) for Major depressive disorder

UnknownActiveMajor depressive disorder indication →

Planned (not yet initiated) adjunctive MDD program. Per LB Pharmaceuticals' SEC 10-K (FY2025, filed Mar 2026): 'We are planning a Phase 2 trial that will evaluate LB-102 as an adjunctive therapy in MDD. We plan to initiate this trial in early 2027 and expect to report topline data in the first half of 2029.' Planned design: a two-arm, six-week, outpatient, multi-center, randomized, double-blind, placebo-controlled, fixed- and flexible-dose trial evaluating two doses of LB-102 (15 mg and 25 mg once daily) added to standard antidepressant therapy in approximately 380 patients with MDD who have an inadequate response after 1-2 prior antidepressant trials, at approximately 50 sites in the U.S. and Europe. Patients randomized 1:1 to LB-102 (pooled across dose) vs placebo on top of ongoing antidepressant therapy; primary endpoint MADRS-10 at Week 6; secondary endpoints CGI-I/CGI-S, anhedonia, function, cognition, and safety/tolerability. As of June 2026 no MDD trial is registered on ClinicalTrials.gov and enrollment has not begun, so phase is tracked as 'unknown' (planning stage) rather than phase_2.

Clinical trials