New Pivotal Phase 3 Trial: LB-102 for Treatment of Schizophrenia

LB Pharmaceuticals today announced the initiation of its pivotal phase 3 NOVA-2 trial evaluating the efficacy and safety of LB-102 as a treatment for schizophrenia.¹ LB-102, a novel, once-daily, oral investigational small molecule, is a selective antagonist of D2, D3, and 5HT-7 receptors. It is the first potential benzamide in the US for the treatment of neuropsychiatric disorders.

The phase 3 trial is a multi-center, randomized, double-blind, placebo-controlled trial that is designed to enroll approximately 460 participants with acute exacerbation of schizophrenia at approximately 25 sites in the US. Participants will be randomly assigned 1:1:1 to receive 50 mg or 100 mg of LB-102 or placebo for 6 weeks. The primary endpoint is the change from baseline in Positive and Negative Syndrome Scale (PANSS) total score at eeek 6. Secondary endpoints include Clinical Global Impression-Severity, PANSS positive and negative subscales, Marder factor scores, cognitive performance, and Personal and Social Performance scale.

“There remains significant unmet need for new schizophrenia therapies that provide patients rapid relief from positive symptoms, minimize burdensome adverse effects, and offer potential for improving negative and cognitive symptoms that drive functional impairment. In our robust NOVA-1 trial, LB-102 demonstrated a statistically significant benefit vs placebo in PANSS total score at all doses studied, including rapid onset of effect at week 1 and sustained benefit through the endpoint of the trial, a potentially class-leading safety profile with low rates of EPS (including akathisia), minimal sedation and few GI side effects, as well as effects on negative symptoms and cognitive performance,” said Anna Eramo, MD, the chief medical officer of LB Pharmaceuticals. “Our phase 3 trial, NOVA-2, is designed to further elucidate the potential multidimensional benefits of LB-102 across the positive, negative, and cognitive symptom domains of schizophrenia.”

LB Pharmaceuticals also plans to initiate an open label extension trial with approximately 900 participants. Those who complete NOVA-2 will be able to continue in the open label extension trial, but investigators will also enroll de novo patients. This open-label trial will characterize the long-term safety of LB-102 and explore the effects of LB-102 on negative symptoms of schizophrenia and cognitive performance.

“The initiation of the NOVA-2 trial marks a major milestone and underscores our strong and continued focus on execution,” said Heather Turner, the chief executive officer of LB Pharmaceuticals. “NOVA-2 is designed to build on the compelling clinical activity and safety profile that LB-102 has demonstrated to date. Based on positive results and prior FDA feedback, we believe NOVA-2, together with the open label extension trial, and data from our phase 2 (NOVA-1) trial, will support the potential US approval of LB-102 for the treatment of schizophrenia. We believe that LB-102 has the potential to become a mainstay of psychiatric practice by offering patients a balanced clinical benefit and tolerability profile. With our broad development program in both psychosis and mood disorders, we are focused on unlocking the full potential of LB-102.”

Investigators anticipate topline results from NOVA-2 in the second half of 2027. If results are positive, LB Pharmaceuticals expects to hold a pre-NDA meeting with FDA following their release.

LB-102 is also being evaluated for the treatment of bipolar depression in the phase 2 ILLUMINATE-1 clinical trial.² A phase 2 trial in adjunctive treatment of major depressive disorder is planned but not yet initiated. Investigators see additional expansion opportunities for LB-102 in the treatment of negative symptoms of schizophrenia, Alzheimer disease psychosis and agitation, and other neuropsychiatric diseases.

References

1. LB Pharmaceuticals initiates pivotal phase 3 trial (NOVA-2) for LB-102 in patients with schizophrenia. News release. March 25, 2026. Accessed March 26, 2026. https://www.globenewswire.com/news-release/2026/03/25/3262125/0/en/LB-Pharmaceuticals-Initiates-Pivotal-Phase-3-Trial-NOVA-2-for-LB-102-in-Patients-with-Schizophrenia.html

2. LB Pharmaceuticals initiates phase 2 ILLUMINATE-1 trial in bipolar depression, expanding LB-102 development program. News release. January 26, 2026. Accessed March 26, 2026. https://ir.lbpharma.us/press_releases/lb-pharmaceuticals-initiates-phase-2-illuminate-1-trial-in-bipolar-depression-expanding-lb-102-development-program/