Phase 2 Trial Initiated: LB-102 for Bipolar Depression

LB Pharmaceuticals today announced the initiation of a phase 2 trial evaluating the efficacy and safety of LB-102 in patients with bipolar depression. LB-102 is a novel, once-daily, oral investigational small molecule, and a potent and selective antagonist of D2, D3, and 5HT7 receptors. LB-102 is being advanced as the potential first benzamide antipsychotic in the US for the treatment of neuropsychiatric disorders.¹

“Our year is off to a strong start and the initiation of this phase 2 trial in patients with bipolar depression marks an important step in our strategy to expand the potential of LB-102 for the treatment of mood disorders,” said Heather Turner, the chief executive officer of LB Pharmaceuticals.

The phase 2 trial is a multi-center, randomized, double-blind, placebo-controlled trial with fixed- and flexible-doses and is designed to evaluate the efficacy and safety of 2 doses (25 mg and 50 mg once daily) of LB-102 for the treatment of bipolar depression. The 2-arm, 6-week, outpatient trial is expected to enroll approximately 320 participants with bipolar 1 depression at approximately 30 sites in the US. Participants will be randomly assigned 1:1 to receive either LB-102 or placebo. The primary endpoint is the Montgomery–Åsberg Depression Rating Scale (MADRS)-10 at week 6. The primary statistical analysis will compare results from all participants receiving LB-102, regardless of dose, with placebo. Secondary endpoints include MADRS-6, and CGI-BP, cognition, and anhedonia, as well as safety and tolerability. Topline results from the trial are anticipated in the first quarter of 2028.

“We believe LB-102’s pharmacologic profile, including selective D2, D3, and 5HT7 receptor antagonism and favorable tolerability observed in prior clinical trials, aligns well with the critical unmet needs in bipolar depression. Significant opportunity exists for new therapies that can offer early onset of effect, reduced side effects such as sedation and extrapyramidal symptoms (EPS; including akathisia), and improvement in anhedonia and cognitive deficits, all of which can impact a patient’s ability to function,” said Anna Eramo, the chief medical officer of LB Pharmaceuticals.

In January 2025, investigators shared positive data from a 4-week placebo-controlled, double-blinded, phase 2 trial in participants with acute schizophrenia. In this trial, LB-102 demonstrated statistically significant benefit compared with placebo at all doses studied, including rapid and sustained benefit, a potentially class-leading safety profile with low rates of EPS, minimal sedation, and few gastrointestinal adverse effects, as well as significant effects on cognition and negative symptoms. These data indicate that LB‑102 has potential to address multiple dimensions of neuropsychiatric illness. LB-102 is now advancing into a phase 3 clinical trial for schizophrenia.^2,3

“We believe the compelling results from our phase 2 trial in acute schizophrenia, the heritage of clinical and real-word experience with amisulpride in the treatment of mood disorders, and our innovative fixed-flexible dose trial design can significantly derisk this program. We look forward to a number of late-stage clinical catalysts, including results from this phase 2 trial in the first quarter of 2028, as well as from our planned phase 3 trial in schizophrenia which remains on track to initiate this quarter with results expected in the second half of 2027,” concluded Turner.

References

1. LB Pharmaceuticals initiates phase 2 ILLUMINATE-1 trial in bipolar depression, expanding LB-102 development program. News release. January 26, 2026. Accessed January 26, 2026. https://www.globenewswire.com/news-release/2026/01/26/3225570/0/en/LB-Pharmaceuticals-Initiates-Phase-2-ILLUMINATE-1-Trial-in-Bipolar-Depression-Expanding-LB-102-Development-Program.html

2. LB Pharmaceuticals announces positive topline results from phase 2 trial of LB-102 in schizophrenia. News release. January 8, 2025. Accessed January 26, 2026. https://www.globenewswire.com/news-release/2025/01/08/3006104/0/en/LB-Pharmaceuticals-Announces-Positive-Topline-Results-from-Phase-2-Trial-of-LB-102-in-Schizophrenia.html

3. Kuntz L. LB-102 for schizophrenia sees positive phase 2 topline results. Psychiatric Times. January 8, 2025. https://www.psychiatrictimes.com/view/lb-102-sees-positive-phase-2-topline-results