LB Pharmaceuticals has announced the initiation of its phase-III trial (NOVA-2) evaluating the efficacy and safety of LB-102 as a treatment for schizophrenia. LB-102, a novel, once-daily, oral investigational small molecule, is a selective antagonist of D2, D3 and 5HT-7 receptors that is being advanced as a potential first benzamide in the US for the treatment of neuropsychiatric disorders.

“The initiation of the NOVA-2 trial marks a major milestone and underscores our strong and continued focus on execution. 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-II (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 programme in both psychosis and mood disorders, we are focused on unlocking the full potential of LB-102,” said Heather Turner, Chief Executive Officer (CEO), LB Pharmaceuticals.

The phase-III trial (NCT07363577) is a multi-centre, randomised, double-blind, placebo-controlled trial evaluating the efficacy and safety of LB-102 for the treatment of schizophrenia. The trial is designed to enroll approximately 460 patients with acute exacerbation of schizophrenia at approximately 25 sites in the US. Patients will be randomised 1:1:1 to receive either 50 mg or 100 mg of LB-102 or placebo for six weeks. The primary endpoint is the change from baseline in Positive and Negative Syndrome Scale (PANSS) total score at week 6. Secondary endpoints include Clinical Global Impression-Severity (CGI-S), PANSS positive and negative subscales, Marder factor scores, cognitive performance and Personal and Social Performance (PSP) scale.

“There remains significant unmet need for new schizophrenia therapies that provide patients rapid relief from positive symptoms, minimise 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 versus 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. Our phase-III trial, NOVA-2, is designed to further elucidate the potential multi-dimensional benefits of LB-102 across the positive, negative and cognitive symptom domains of schizophrenia,” added Anna Eramo, MD, Chief Medical Officer (CMO), LB Pharmaceuticals.

The company also plans to initiate an approximately 900-patient open label extension trial. Patients who complete NOVA-2 will be able to continue in the open label extension trial that will also enroll de novo patients. This open-label trial is expected to characterise the long-term safety of LB-102 as well as further explore the effects of LB-102 on negative symptoms and cognitive performance.

Topline results from NOVA-2 are anticipated in the second half of 2027, and, if positive, the company expects to hold a pre-NDA meeting with FDA thereafter.