LB-102 · program

LB-102 (N-methylamisulpride) for Schizophrenia

Phase 3ActiveLB Pharmaceuticals Inc. (LBRX)

Indications for LB-102: Schizophrenia · Phase 3 Bipolar depression · Phase 2 Major depressive disorder · Unknown

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.

Data current as of

Development timeline

Phase 3Mar 2026 – Dec 2027
  1. UpcomingPivotal Phase 3 NOVA-2 topline (PANSS total at Week 6) anticipated in 2H 2027.↗
  2. Pivotal Phase 3 NOVA-2 (NCT07363577) initiated and recruiting: ~456 patients with acute schizophrenia at ~25 U.S. sites; 50 mg / 100 mg / placebo over 6 weeks; primary endpoint PANSS total change at Week 6; topline expected 2H 2027.↗
Phase 2Jan 2025
  1. metPhase 2 NOVA-1 met its primary endpoint: significant PANSS total reduction at Week 4 at all LB-102 doses vs placebo, with favorable short-term safety.↗

Readouts

  • 2H 2027AnticipatedTopline dataNCT07363577

    Pivotal Phase 3 NOVA-2 topline (PANSS total at Week 6) anticipated in 2H 2027. ↗

  • 2025-01-08ReportedTopline datametNCT06179108

    Phase 2 NOVA-1 met its primary endpoint: significant PANSS total reduction at Week 4 at all LB-102 doses vs placebo, with favorable short-term safety. ↗

Clinical trials in Schizophrenia

NCT07363577LB-102-008Phase 3Recruitingn=456

A Randomized, Double-blinded, Placebo-controlled, Multicenter Study to Evaluate the Antipsychotic Efficacy and Safety of LB-102 in the Treatment of Adult Patients With Acute Schizophrenia (NOVA-2)

Started Mar 2026· Primary completion Jun 2027· 📍 13 sites across 1 country (United States)

NCT06179108LB-102-003Phase 2Completedn=359

A Randomized, Double-blinded, Placebo-controlled, Multicenter Study to Evaluate the Antipsychotic Efficacy and Safety of LB-102 in the Treatment of Adult Patients With Acute Schizophrenia (NOVA-1)

Started Nov 2023· Primary completion Dec 2024· 📍 25 sites across 1 country (United States)

metprimaryPANSS total score change from baseline to Week 4 — LB-102 50 mg vs placebo — LS mean change -14.3 (vs placebo -9.3); Hedges g=0.61 (<0.001)

Statistically significant placebo-adjusted PANSS reduction (~5.0 points) at the 50 mg dose.

metsecondaryClinical Global Impressions-Severity (CGI-S) change from baseline

All LB-102 dose groups showed significantly greater improvement in CGI-S than placebo. Safety: EPS 0-2.8%, prolactin-related clinical events 6.5-8.3%, no clinically meaningful QTc prolongation, ~2 kg placebo-adjusted weight gain.

metprimaryPANSS total score change from baseline to Week 4 — LB-102 100 mg vs placebo — LS mean change -16.1 (vs placebo -9.3); Hedges g=0.83 (0.002)

Statistically significant placebo-adjusted PANSS reduction (~6.8 points) at the 100 mg dose (smaller arm, n=36).

metprimaryPANSS total score change from baseline to Week 4 — LB-102 75 mg vs placebo — LS mean change -14.0 (vs placebo -9.3); Hedges g=0.41 (0.002)

Statistically significant placebo-adjusted PANSS reduction (~4.7 points) at the 75 mg dose.

Formulations

FormulationRouteRegimenPharmacokinetics
LB-102 oral
50 mg, 75 mg, and 100 mg once-daily oral doses studied (Phase 2 NOVA-1); Phase 1 well-tolerated up to 150 mg/day
OralOnce daily—
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 (compound-wide)

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.

TargetActionAffinity
D2primaryDRD2AntagonistKi 0.8 nMⓘ
5-HT7HTR7AntagonistKi 31 nMⓘ
D3DRD3AntagonistKi 0.8 nMⓘ

← Full LB-102 compound page (identity, identifiers, all indications)

Sources

  1. Antipsychotic Efficacy and Safety of LB-102 in the Treatment of Adults With Acute Schizophrenia: A Randomized Clinical Trial (NOVA-1) — JAMA Psychiatry (PMC)
  2. LB Pharmaceuticals Announces Positive Topline Results from Phase 2 Trial of LB-102 in Schizophrenia — LB Pharmaceuticals (GlobeNewswire)
  3. LB Pharmaceuticals Initiates Pivotal Phase 3 Trial (NOVA-2) for LB-102 in Patients with Schizophrenia — LB Pharmaceuticals (GlobeNewswire)
  4. NOVA-1: Phase 2 study of LB-102 in adults with acute schizophrenia (NCT06179108) — ClinicalTrials.gov
  5. NOVA-2: Pivotal Phase 3 study of LB-102 in adults with acute schizophrenia (NCT07363577) — ClinicalTrials.gov