N-methyl amisulpride (LB-102) / LB Pharma - LARVOL DELTA

LB-102 for cognitive impairment in schizophrenia: exploratory post hoc analyses from a randomised, double-blind, placebo-controlled phase 2 study (ECNP 2025) - P2 | "359 participants were randomised to receive placebo (n=108), LB-102 50 mg (n=107), LB-102 75 mg (n=108), or LB-102 100 mg (n=36). LB-102 met the primary endpoint, with least-squares mean change from baseline to week 4 in PANSS total score of -9.3 (placebo), -14.3 (50 mg, p=0.0009; effect size=0.61), -14.0 (75 mg, p=0.0022; effect size=0.41), and -16.1 (100 mg, nominal p=0.0017; effect size=0.83). An exploratory post hoc analysis was conducted to evaluate the impact of LB-102 on cognition."

Clinical • P2 data • Retrospective data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia

LB-102 for acute schizophrenia in adults: efficacy and safety from a large phase 2 clinical trial (ECNP 2025) - P2 | "Of 359 participants randomized (placebo, n=108; 50mg, n=107; 75mg, n=108; 100mg, n=36), 261 (73%) completed the trial. LB-102 met the primary endpoint, with 50mg and 75mg statistically superior to placebo (Hochberg multiplicity correction). Least-squares mean (LSM) changes from baseline to week 4 in PANSS total score were –9.3 (placebo), –14.3 (50mg, p=0.0009 vs placebo; effect size=0.61), –14.0 (75 mg, p=0.0022; effect size=0.41), and –16.1 (100mg, nominal p=0.0017; effect size=0.83)."

Clinical • P2 data • CNS Disorders • Insomnia • Mood Disorders • Psychiatry • Schizophrenia • Sleep Disorder

LB-102 for acute schizophrenia in adults: Results from the phase 2 clinical trial (NOVA1) with a focus on Negative Symptoms (ECNP 2025) - P2 | "359 participants were randomised (placebo, n=108; 50mg, n=107; 75mg, n=108; 100mg, n=36), with 261 (73%) completing the trial. LB-102 met the primary endpoint, with least-squares mean (LSM) changes from baseline to week 4 in PANSS total score being -9.3 (placebo), -14.3 (50mg, p=0.0009; effect size=0.61), -14.0 (75mg, p=0.0022; effect size=0.41), and -16.1 (100mg, nominal p=0.0017; effect size=0.83). The effect on PANSS Negative Subscore at week 4 was -1.1 (placebo), -2.2 (50mg, Δ -1.08, p=0.0116 vs placebo), -1.7 (75mg, Δ -0.61, p=0.1633), and -1.8 (100mg, Δ -0.7, p=0.2632)."

Clinical • P2 data • CNS Disorders • Psychiatry • Schizophrenia

New Developments in the Treatments of Psychosis (WFSBP 2025) - "Objective: Despite the discovery of chlorpromazine over 70 years ago and substantial pharmacologic advances, postsynaptic dopamine blockade has remained the sole mechanism of action of approved drugs for schizophrenia... Newly/recently approved agents include vesicular monoamine transporter-2 inhibitors valbenazine and deutetrabenazine for tardive dyskinesia and, possibly, residual positive symptoms; olanzapine/samidorphan combination, lumateperone, new formulations, including subcutaneous injections, and ultra-long-acting injectable antipsychotics. Agents in development that have at least one positive phase 1B, 2 or 3 trial include the trace amine-associated receptor-1 (TAAR1) ulotaront, M1/M4 muscarinic agonist xanomeline plus peripherally restricted anticholinergic trospium, the M4 muscarinic positive allosteric modulator emraclidine, as well as multiple other muscarinic receptor modulators for total psychopathology, methylated amisulpride (LB-102), and evenamide, a..."

CNS Disorders • Movement Disorders • Psychiatry • Schizophrenia

Randomized, Double-blinded, Placebo-controlled, Evaluating the Treatment With LB-102 in Patients With Acute Schizophrenia (clinicaltrials.gov) - P2 | N=359 | Completed | Sponsor: LB Pharmaceuticals Inc. | Active, not recruiting ➔ Completed | Trial completion date: May 2025 ➔ Dec 2024

Trial completion • Trial completion date • CNS Disorders • Psychiatry • Schizophrenia

LB Pharmaceuticals Announces Key Executive Appointments to Support Growth and Late-Stage Development of LB-102 (GlobeNewswire) - "LB Pharmaceuticals Inc...today announced the appointment of Gad Soffer as Chief Business Officer (CBO) and Richard Silva, Ph.D., as Senior Vice President of Technical Operations. These leadership additions strengthen LB Pharma’s executive team as the company advances its lead asset, LB-102, toward Phase 3 clinical development in schizophrenia and explores additional neuropsychiatric indications."

Clinical • CNS Disorders • Schizophrenia

Randomized, Double-blinded, Placebo-controlled, Evaluating the Treatment With LB-102 in Patients With Acute Schizophrenia (clinicaltrials.gov) - P2 | N=350 | Active, not recruiting | Sponsor: LB Pharmaceuticals Inc. | Trial completion date: Jan 2025 ➔ May 2025

Trial completion date • CNS Disorders • Psychiatry • Schizophrenia

Segal Trials Leads Phase 2 Schizophrenia Trial of LB-102 Toward Primary Endpoint (Businesswire) - P2 | N=350 | NCT06179108 | Sponsor: LB Pharmaceuticals Inc. | "Segal Trials...has released enrollment performance metrics from their participation in NOVA - a Phase 2 dose finding trial in adult patients with acute schizophrenia evaluating LB-102, a once-daily orally administered small molecule and potential first-in-class benzamide antipsychotic...the study’s positive topline results were presented at the 43rd Annual J.P. Morgan Healthcare Conference on January 13th. Having met its primary endpoint, the study showed LB-102 to be efficacious, generally safe, and well-tolerated over the course of the 4 week treatment period....In accordance with the positive topline results, LB Pharmaceuticals plans to engage with the U.S. Food & Drug Administration (FDA) to finalize Phase 3 trial design by early 2026."

FDA event • P2 data • CNS Disorders • Schizophrenia

Negative Symptoms in Schizophrenia: An Update on Research Assessment and the Current and Upcoming Treatment Landscape. (PubMed, CNS Drugs) - "With the caveat that no compounds are definitively proven as gold-standard treatments for broadly defined negative symptoms, the evidence base supports several potentially beneficial off-label and investigational medications for treating negative symptoms in schizophrenia, such as monotherapy with cariprazine, olanzapine, clozapine, and amisulpride, or adjunctive use of memantine, setrons such as ondansetron, minocycline, and antidepressants. Among investigational medications, NMDAR agonists, muscarinic agonists, and LB-102 remain under study. Suggestions for future research include reducing placebo effects by designing studies with a smaller number of high-quality study sites, potentially increasing the use of more precise rating scales for negative symptoms, and focused studies in people with predominant negative symptoms."

Journal • Review • CNS Disorders • Psychiatry • Schizophrenia

PET clinical study of novel antipsychotic LB-102 demonstrates unexpectedly prolonged dopamine receptor target engagement. (PubMed, Neuropsychopharmacology) - P1 | "LB-102 was generally safe and well-tolerated at all doses. Results of this study were used to inform dosing in a subsequent Phase 2 clinical study in schizophrenia patients."

Journal • CNS Disorders • Mental Retardation • Psychiatry • Schizophrenia • DRD2

Randomized, Double-blinded, Placebo-controlled, Evaluating the Treatment With LB-102 in Patients With Acute Schizophrenia (clinicaltrials.gov) - P2 | N=350 | Active, not recruiting | Sponsor: LB Pharmaceuticals Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Psychiatry • Schizophrenia

Randomized, Double-blinded, Placebo-controlled, Evaluating the Treatment With LB-102 in Patients With Acute Schizophrenia (clinicaltrials.gov) - P2 | N=350 | Recruiting | Sponsor: LB Pharmaceuticals Inc. | Trial completion date: Dec 2025 ➔ Jan 2025 | Trial primary completion date: Sep 2025 ➔ Oct 2024

Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

LB-102, A Novel Benzamide for the Treatment of Schizophrenia: Safety and Dopamine Receptor Occupancy Data from Two Clinical Studies (ASCP 2024) - P1, P2 | "LB-102 was safe and well-tolerated up to 150 mg/day and showed dopamine RO in the desired 60 to 80% rage under steady-state conditions at 50 mg/day. Unlike most SCZ treatments, dopamine RO of LB-102 was consistent 24 h post dose; consistent dopamine RO may be one of the contributing factors to the greater efficacy of long-acting injections in treating SCZ. A large Phase 2 clinical study, LB-102-003 (NCT06179108), is currently enrolling 350 schizophrenia patients at 25 sites in the USA."

Clinical • CNS Disorders • Dystonia • Psychiatry • Schizophrenia

Randomized, Double-blinded, Placebo-controlled, Multicenter Study to Evaluate LB-102 in the Treatment of Adult Patients With Acute Schizophrenia (clinicaltrials.gov) - P2 | N=350 | Recruiting | Sponsor: LB Pharmaceuticals Inc.

New P2 trial • CNS Disorders • Psychiatry • Schizophrenia

Pre-clinical evaluation of cognitive properties of LB-102 and enantiomers (ECNP 2023) - "Data from this study will inform which enantiomeric mixture of LB-102 to move into clinical development in disorders related to cognition."

Preclinical • CNS Disorders • Psychiatry • Schizophrenia

A randomized, double-blind, placebo controlled, phase 1 study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of LB-102, a selective dopamine D/5-HT inhibitor. (PubMed, Psychopharmacology (Berl)) - "There were four instances of EPS (acute dystonia), typically associated with dopamine receptor occupancy in excess of 80%, one at 100 mg QD, one at 75 mg BID, and two at 100 mg BID. A phase 2 clinical study of LB-102 in schizophrenia patients with PANSS as primary endpoint is being planned."

Clinical • Journal • P1 data • PK/PD data • CNS Disorders • Dystonia • Movement Disorders • Psychiatry • Schizophrenia

Receptor Occupancy of LB-102 Using Positron Emission Tomography (PET) in Healthy Volunteers (clinicaltrials.gov) - P1; N=16; Completed; Sponsor: LB Pharmaceuticals Inc.; Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Psychiatry • Schizophrenia

PET Clinical Study of Novel Antipsychotic LB-102 Demonstrates Unexpectedly Prolonged Dopamine Receptor Target Engagement (ACNP 2021) - P1 | "Results from this study demonstrated that striatal dopamine RO in the desired range of 60 ~ 75% can be achieved with once daily dosing of 100 mg LB-102, a dose that was well-tolerated in our Phase 1 clinical study. Due to slow CNS exchange kinetics, with a single dose of 100 mg, sustained (>50 %) dopamine receptor occupancy persists for as long as 48 hours post-dose. Notably, our phase 1 clinical study revealed that for a given dose, LB-102 plasma exposure of LB-102 is 2.5 X greater than what is reported for amisulpride."

Clinical • Alzheimer's Disease • CNS Disorders • Depression • Pain • Psychiatry • Schizophrenia

PET Clinical Study of Novel Antipsychotic LB-102 Demonstrates Unexpectedly Prolonged Dopamine Receptor Target Engagement (ACNP 2021) - P1 | "Results from this study demonstrated that striatal dopamine RO in the desired range of 60 ~ 75% can be achieved with once daily dosing of 100 mg LB-102, a dose that was well-tolerated in our Phase 1 clinical study. Due to slow CNS exchange kinetics, with a single dose of 100 mg, sustained (>50 %) dopamine receptor occupancy persists for as long as 48 hours post-dose. Notably, our phase 1 clinical study revealed that for a given dose, LB-102 plasma exposure of LB-102 is 2.5 X greater than what is reported for amisulpride."

Clinical • Alzheimer's Disease • CNS Disorders • Depression • Pain • Psychiatry • Schizophrenia

Receptor Occupancy of LB-102 Using Positron Emission Tomography (PET) in Healthy Volunteers (clinicaltrials.gov) - P1; N=16; Active, not recruiting; Sponsor: LB Pharmaceuticals Inc.; Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Psychiatry • Schizophrenia

Receptor Occupancy of LB-102 Using Positron Emission Tomography (PET) in Healthy Volunteers (clinicaltrials.gov) - P1; N=16; Recruiting; Sponsor: LB Pharmaceuticals Inc.; Trial completion date: May 2021 ➔ Oct 2021; Trial primary completion date: Apr 2021 ➔ Sep 2021

Clinical • Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

Psychotherapy Said to Be Key To Successful Psychosis Treatment - "'When luminaries like John Kane, Cristoph Correll...were willing to join us in the earliest days, it shows that the psychiatric community wants this drug in the United States.'"

Media quote • Schizophrenia

LB Pharmaceuticals Announces the Initiation of Patient Dosing in Open Label Phase 1b Imaging Study of LB-102 (Businesswire) - "LB Pharmaceuticals Inc...announced today the administration of the first dose of LB-102 in a Phase 1b clinical trial (Clinical Trials Identifier NCT04588129). This clinical study is designed to evaluate the dopamine receptor occupancy of LB-102 in healthy subjects using positron emission tomography (PET)."

Trial status • CNS Disorders • Schizophrenia

Receptor Occupancy of LB-102 Using Positron Emission Tomography (PET) in Healthy Volunteers (clinicaltrials.gov) - P1; N=16; Recruiting; Sponsor: LB Pharmaceuticals Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • CNS Disorders • Psychiatry • Schizophrenia

Safety and Tolerability of Single and Multiple Doses of LB-102 in Healthy Adults (clinicaltrials.gov) - P1; N=64; Completed; Sponsor: LB Pharmaceuticals Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion • CNS Disorders • Psychiatry • Schizophrenia