Phase 2 Trial of LB-102 for Schizophrenia Shows Positive Impact on Cognitive Performance

Phase 2 post hoc analysis of LB-102 for treatment of schizophrenia showed positive results on cognitive performance in patients.¹ LB Pharmaceuticals presented this new analysis of the NOVA-1 clinical trial at the 2026 Schizophrenia International Research Society meeting in Florence, Italy.

“There remains significant unmet need for new schizophrenia therapies that offer patients the potential for improvements in cognitive symptoms that drive functional impairment,” said Anna Eramo, MD, chief medical officer of LB Pharmaceuticals.¹ She continued, “this new analysis provides additional insights into the potential of LB-102 to offer differentiated improvement in cognitive performance that is independent of its effect on overall schizophrenia symptoms.”

Analysis of the phase 2 trial assessed whether improvement in cognitive performance found was a direct effect or indirect consequence of the effect of LB-102. The analysis confirmed that cognitive performance improvement was statistically significant and directly related to LB-102. Based on measurement of the Global Cognition composite score, analysis showed improved cognitive performance was a direct effect of LB-102.

Generally, the phase 2 trial showed statistically significant effects of LB-102 compared with placebo at all doses tested. The medication showed rapid onset at week 1, and sustained benefit through trial endpoints. LB-102 was generally well-tolerated and safe, potentially with a class-leading safety profile of low rates of extrapyramidal symptoms, minimal sedation, and gastrointestinal adverse effects. Overall, a dose-dependent and statistically significant improvement in the Global Cognition composite score was found at all dose levels. The patient population was not enriched for severe cognitive impairment at baseline.

LB-102 is a once-daily, oral, investigational small molecule. The drug is a selective antagonist of D2, D3 5HT7 receptors and is currently being developed as a potential first benzamide antipsychotic in the United States. LB-102 is also being evaluated for treatment of bipolar depression, and a phase 2 trial for adjunctive treatment of major depressive disorder is currently planned.² In another recent evaluation, LB-102 was found to have striatal dopamine occupancy in the desirable 60-80% range over 24 hours, consistent with known dopamine antagonists that successfully treat schizophrenia.³

Eramo also noted that “based on these robust data, we are prospectively evaluating cognitive performance as a secondary endpoint in our recently initiated pivotal Phase 3 trial (NOVA-2) of LB-102 in patients with acute schizophrenia, our planned open label extension trial in patients with schizophrenia, as well as our ongoing and planned trials in bipolar 1 depression and adjunctive MDD.”¹ The phase 3 trial of LB-102 for treatment of schizophrenia was recently initiated, with anticipated results in late 2027.²

References

1. LB Pharmaceuticals presents new analysis from the phase 2 NOVA-1 trial highlighting LB-102’s potential impact on cognitive performance at the 2026 Annual Congress of the Schizophrenia International Research Society (SIRS). Press release. March 27, 2026. Accessed March 27, 2026. https://ir.lbpharma.us/press_releases/lb-pharmaceuticals-presents-new-analysis-from-the-phase-2-nova-1-trial-highlighting-lb-102s-potential-impact-on-cognitive-performance-at-the-2026-annual-congress-of-the-schizophrenia-int/

2. Kuntz L. New pivotal phase 3 trial: LB-102 for treatment of schizophrenia. Psychiatric Times. March 25, 2026. https://www.psychiatrictimes.com/view/new-pivotal-phase-3-trial-lb-102-for-treatment-of-schizophrenia

3. Wong DF, Chand GB, Caito N, et al. PET clinical study of novel antipsychotic LB-102 demonstrates unexpectedly prolonged dopamine receptor target engagement. Neuropsychopharm. 2025;50:372-377.