LB Pharmaceuticals (NASDAQ:LBRX) outlined its clinical and commercial plans for LB-102, an investigational antipsychotic designed as a structural modification of amisulpride, during its first R&D Day in New York. The company said it expects three clinical readouts over the next three years, beginning with Phase III schizophrenia data in the first half of 2027.
Heather Turner, LB Pharmaceuticals’ chief executive officer, said the company is pursuing treatments for schizophrenia, bipolar disorder and major depressive disorder, which she described as conditions with substantial unmet need. Turner said LB-102 was engineered to address limitations of amisulpride, a widely used generic antipsychotic outside the United States that was not approved in the U.S. as an antipsychotic.
According to Turner, amisulpride has limited blood-brain-barrier penetration, requires relatively high doses and is generally administered twice daily. LB-102 is intended to retain amisulpride’s selective activity at D2, D3 and 5-HT7 receptors while enabling lower-dose, once-daily administration.
Phase II Results and Phase III Plan
Susan Kozauer, LB Pharmaceuticals’ chief medical officer, reviewed results from the completed Phase II NOVA-1 study in patients experiencing an acute exacerbation of schizophrenia. The four-week inpatient study enrolled 359 patients at 25 U.S. sites and compared 50 mg, 75 mg and 100 mg doses of LB-102 with placebo.
Kozauer said all three dose levels showed statistically superior clinical activity versus placebo on the primary endpoint, a change in the Positive and Negative Syndrome Scale, or PANSS, total score through day 28. The company reported that treatment effects were observed by week one and sustained through the trial.
The company highlighted results in several symptom domains, including positive symptoms, negative symptoms and cognition. Kozauer said the 50 mg dose produced a statistically significant improvement on the PANSS negative-symptom subscale, while cognitive testing using CogState showed a dose-dependent effect. She added that analyses conducted by the company indicated the cognitive findings were not closely correlated with improvement in overall PANSS scores.
LB Pharmaceuticals also emphasized the safety profile observed in NOVA-1. Kozauer said most adverse events were mild or moderate and generally similar to placebo. The company reported low rates of extrapyramidal symptoms, or EPS, negligible sedation, minimal QTc prolongation and low discontinuation rates. She noted that tardive dyskinesia typically emerges after longer exposure periods and said the company’s planned long-term data may provide additional information.
The ongoing Phase III NOVA-2 study is designed to enroll approximately 460 patients across 25 U.S. sites. It is evaluating 50 mg and 100 mg doses of LB-102 in a six-week inpatient trial, with change from baseline in PANSS total score at day 42 as the primary endpoint. Secondary measures include positive- and negative-symptom subscales, cognition and functioning.
Turner said the company sought to retain key elements of the NOVA-1 design in NOVA-2, including use of the same contract research organization and overlap in study sites and personnel. Patients in NOVA-2 may enter NOVA-3, a 52-week open-label safety and tolerability study that will also enroll new patients.
Preclinical Research on EPS and Symptom Domains
Roger McIntyre, professor of psychiatry at the University of Toronto, presented preclinical research that he said may help explain the low EPS rates reported in the Phase II study. McIntyre disclosed that he has a financial relationship with LB Pharmaceuticals and was presenting on the company’s behalf.
McIntyre described mouse studies measuring c-Fos activation in the associative and motor regions of the striatum. He said the data suggested LB-102 had greater relative activity in the associative striatum, which is associated with psychotic symptoms, than in the motor striatum, which is linked to movement-related side effects. He said this regional selectivity could provide a potential explanation for the clinical EPS profile but noted that the findings would require replication.
He also discussed preclinical evidence suggesting that lower doses of LB-102 may preferentially engage presynaptic D2/D3 autoreceptors. McIntyre said that mechanism may increase dopamine release in brain areas relevant to negative symptoms, mood and cognition, potentially supporting the company’s planned studies in mood disorders.
Additional Programs and Commercial Preparation
LB Pharmaceuticals said it is also conducting the Phase II ILLUMINATE-1 study in bipolar depression, with data expected in 2028. A Phase II study of LB-102 as an adjunctive treatment for major depressive disorder is slated to begin early next year, with a readout expected in 2029.
Gad Soffer, the company’s chief operating and business officer, said dose selection for the development program was based on modeling that mapped LB-102 dopamine receptor occupancy to dosing experience with amisulpride. The planned adjunctive major depressive disorder study will evaluate 15 mg and 25 mg doses, while the bipolar depression study will evaluate 25 mg and 50 mg doses, according to the company.
Kaya Pai Panandiker, chief commercial officer, said LB Pharmaceuticals’ market research with clinicians, patients and payers identified clinical response, tolerability and simplicity of use as central considerations in treatment decisions. She said the company is building its commercial strategy, engaging with clinicians and patient advocacy groups, and assessing payer evidence requirements ahead of potential future launch activity.
Turner said all currently planned trials are fully funded and that the company has cash expected to extend beyond the second quarter of 2029. She also said a relapse-prevention study would be required following a potential approval and would be important in discussions with payers regarding long-term outcomes.
About LB Pharmaceuticals (NASDAQ:LBRX)
LB Pharmaceuticals, Inc is a clinical-stage biopharmaceutical company focused on developing treatments for neuropsychiatric disorders. The company’s lead product candidate, LB-102, is an investigational oral therapy being developed for schizophrenia and potentially other conditions involving serious disturbances in mood, thought and behavior.
LB-102 is designed as a prodrug of amisulpride, an antipsychotic compound that has been approved in certain markets outside the United States but is not approved by the U.S.
