We are a clinical-stage biopharmaceutical company developing novel therapies for
the treatment of schizophrenia, bipolar depression, and other neuropsychiatric
diseases. We are building a pipeline that leverages the broad therapeutic
potential of our lead product candidate, LB-102, which we believe has the
potential to be the first benzamide antipsychotic drug approved for
neuropsychiatric disorders in the United States. LB-102 is a new chemical entity
and a methylated derivative of amisulpride, a second-generation antipsychotic
drug approved in over 50 countries, not including the United States, because the
development and regulatory requirements of the U.S. Food and Drug
Administration, or FDA, for amisulpride were incompatible with patent coverage
on the drug. Amisulpride is a generic drug that has been extensively used in
clinical practice following its initial approval in France in the 1980s,
generating at least two million monthly prescriptions in 2023 in a subset of 16
continental European countries. Among these European prescriptions for
amisulpride, our data suggest that approximately 60% are for schizophrenia and
schizoaffective disorders, approximately 20% are for mood disorders,
approximately 14% are for anxiety, and the remainder are for a variety of other
indications. We developed LB-102 in order to address the limitations of
amisulpride with a differentiated therapeutic profile and strong intellectual
property protection. We believe LB-102’s mechanism of action, data from our
recently completed Phase 2 trial of LB-102 in acute schizophrenia, and the
legacy of clinical experience with amisulpride support the continued development
of LB-102 in schizophrenia and bipolar depression. If successful in treating
bipolar depression, we may also develop LB-102 in the treatment of major
depressive disorder, or MDD. In the future, we may also develop LB-102 for the
treatment of other neuropsychiatric disorders, including schizophrenia with
predominantly negative symptoms, Alzheimer’s disease-related agitation and
psychosis, manic episodes associated with bipolar disorder, and cognitive
impairment associated with schizophrenia, or CIAS. We believe that LB-102, if
approved, can become a mainstay of psychiatric practice by offering a
potentially attractive alternative to branded and generic therapeutics for the
treatment of schizophrenia, bipolar depression, and other neuropsychiatric
diseases.
Our product candidate, LB-102, is a Phase 3-ready oral, small molecule for the
treatment of acute schizophrenia, defined as a sudden and severe episode of
psychotic symptoms, characterized by hallucinations, delusions, and other
positive symptoms. Schizophrenia is a chronic, severe, complex, and debilitating
psychiatric disorder that affects approximately 1% of the U.S. population and is
a leading cause of disability. Symptoms are divided into three categories:
(i) psychotic or positive symptoms, which include delusions, hallucinations,
thought disorder, and movement disorder; (ii) negative symptoms, which include
lack of motivation, interest, or enjoyment in daily activities, withdrawal from
social life, and difficulty showing emotions; and (iii) cognitive symptoms,
which encompass problems with attention, concentration, and memory. The disease
is associated with increased mortality, with approximately 5% of schizophrenia
patients dying by suicide, and average overall life expectancy decreasing by as
much as 29 years compared to the general population. There is currently no cure
for schizophrenia, which means the disease must be managed with life-long
therapy, increasing the importance of therapies that can improve compliance
rates and dosing challenges.
In January 2025, we announced positive data from our four-week
placebo-controlled, double-blinded, Phase 2 trial in the United States, which
assessed the safety and efficacy of LB-102 in patients with acute schizophrenia.
Results from the trial demonstrated (i) statistically significant clinical
activity at all LB-102 doses tested; (ii) a significant average change in
overall symptoms (effect size); (iii) a potentially class-leading tolerability
profile among D2/D3 antagonists and partial agonists; and (iv) a potentially
differentiated impact on cognition as measured by CogState Computerized
Schizophrenia Battery of Tests. The trial achieved its primary endpoint of
change in the Positive and Negative Syndrome Scale, or PANSS, a 30-item scale
that measures the severity of schizophrenia symptoms, from baseline to Week 4. A
statistically significant decrease in symptoms was observed for all three dose
cohorts (50 mg, 75 mg, and 100 mg) compared to placebo. Additionally, our Phase
2 trial data showed a statistically significant impact on negative symptoms
versus placebo at the 50 mg dose even though the inclusion criteria enriched for
patients experiencing predominantly positive symptoms of schizophrenia. An
exploratory post-hoc analysis of our Phase 2 data on the treatment effect in
patients with negative symptoms at baseline (i.e., those patients with a PANSS
Negative Subscore greater than or equal to 24) yielded similar results with a
statistically significant impact on negative symptoms versus placebo at the 50
mg dose. LB-102 was generally well tolerated in the clinical trial, with adverse
events being mostly transient and mild to moderate in severity. If replicated in
our planned Phase 3 trial, we believe this tolerability profile has the
potential to be class-leading among D2/D3 antagonists and partial agonists
specifically with respect to the rate of sedation and extrapyramidal symptoms,
or EPS, a group of movement disorders including involuntary movements, muscle
stiffness, and tremors, that, together with sedation, are quite burdensome to
patients and can result in discontinuation of treatments. The impact of LB-102
on cognitive function was also evaluated as an exploratory endpoint in this
trial. After four weeks of treatment with LB-102, a robust, dose-dependent, and
significant treatment effect size was identified in a post-hoc analysis in the
completer population for all doses of LB-102 compared with placebo.
We designed our Phase 2 acute schizophrenia trial to be potentially
registrational by including a large sample size (n=359), robust statistical
analyses, as well as numerous sensitivity analyses. Based on positive
end-of-Phase 2 feedback from the FDA, as well as historical precedent, we
believe that our Phase 2 acute schizophrenia trial may serve as one of the two
pivotal trials required for approval of a new drug application, or NDA, in the
United States. As a result, we believe there is a viable path to approval of
LB-102 in the United States for the treatment of schizophrenia with a single,
six-week Phase 3 trial alongside other planned NDA-enabling studies. However,
there is no guarantee that our Phase 2 trial may serve as one of the two pivotal
trials required for FDA approval, and in such case, we may be required to
conduct an additional pivotal trial in acute schizophrenia. The adequacy of our
Phase 2 trial to support registration will be a matter of review by the FDA at
the time of NDA submission and will depend on the totality of the data included
in our submission, including the results of our planned Phase 3 trial. We are
planning to initiate a six-week Phase 3 trial of LB-102 in acute schizophrenia
patients in the first quarter of 2026, which we believe, if positive, could be
sufficient to support a regulatory application for approval in the United States
along with our completed Phase 2 trial and other planned NDA-enabling studies.
The Phase 3 trial is anticipated to be a three-arm, inpatient, double-blinded,
placebo-controlled, oral once-daily dose of LB-102 in patients with acute
schizophrenia, with a six-week treatment duration. We plan to study the effects
of 50 mg LB-102 or 100 mg LB-102 versus placebo in this trial, and patients will
be randomized in a 1:1:1 ratio across the three arms of the trial. The sample
size will be approximately 400 patients, and we plan to conduct this trial at
approximately 25 sites entirely in the United States. The primary endpoint of
the trial is anticipated to be change from baseline in PANSS at Day 42. We
expect to disclose topline data from this Phase 3 trial in the second half of
2027 and, if positive, meet with the FDA in the first quarter of 2028 to discuss
the potential for submission of an NDA.
In addition to our clinical development program in schizophrenia, we plan to
leverage our expertise in neuropsychiatry and the unique mechanism of action of
LB-102 to develop our product candidate in other indications, starting with
bipolar depression. Most people living with bipolar depression experience
dramatic shifts in mood, energy, and behavior, alternating between manic and
depressive states. It is estimated that 2.8%, or approximately seven million
Americans, experience bipolar disorder in a year, and approximately 40 million
people live with bipolar disorder worldwide. Our initial Phase 2 trial will
explore the utility of LB-102 in controlling the depressive symptoms of the
disease. We plan to initiate this potentially registrational Phase 2 trial in
bipolar depression in the first quarter of 2026, with topline data expected in
the first quarter of 2028.
We believe LB-102’s strong antagonism of the D2, D3, and 5HT7 receptors makes it
well suited for treating bipolar depression, providing potential to control
psychosis and mania through its effects on D2 and potential for antidepressive
and pro-cognitive effects through its antagonism of 5HT7 and D3. Our Phase 2
trial of LB-102 in acute schizophrenia demonstrated strong antipsychotic
activity and suggests opportunities for potential differentiation in bipolar
depression given the observed tolerability profile (low rates of EPS, sedation,
and gastrointestinal side effects) and positive impact on cognition. Amisulpride
is approved for the treatment of dysthymia, a form of depression, in certain
countries outside of the United States and has been shown to be as effective as
certain approved agents for MDD and dysthymia. We believe that results in
dysthymia and MDD provide strong scientific and clinical rationale for
development of LB-102 in the treatment of depressive episodes associated with
bipolar disorder or bipolar depression because episodes of major depression,
whether unipolar (as in MDD) or bipolar (as in bipolar depression), are
typically characterized by a similar imbalance in the neurotransmitters
serotonin, noradrenaline, and dopamine, regardless of the underlying
pathophysiology of the disease. There is wide use of amisulpride in bipolar
disorder with approximately 3.4% of at least two million monthly prescriptions
written for this indication in a select group of European countries including
Germany, France, Italy, Spain, and several others. A non-racemic form of
amisulpride also showed antidepressant activity in two independent third-party,
placebo-controlled bipolar depression trials with an approximately 17- to
18-point reduction in Montgomery–Åsberg Depression Rating Scale, or MADRS, from
baseline observed across these studies. Additionally, among the four
antipsychotics approved for schizophrenia and MDD or treatment resistant
depression that were also studied in late-stage bipolar depression trials
(quetiapine, cariprazine, aripiprazole, and olanzapine), three out of four, or
75%, generated positive data for the treatment of bipolar depression. Our
planned Phase 2 trial for bipolar depression will utilize a fixed-flexible dose
of LB-102. This trial design allows us to evaluate two doses of LB-102 in the
trial, thereby increasing the chances for a patient to derive clinical benefit
from treatment with LB-102, while retaining the advantages of a two-arm trial,
which is known to mitigate the risk of a high placebo rate. Additionally,
flexible dose trials typically have better signal detection than fixed dose
trials for depression, as flexible dose trials lower the magnitude of symptom
reduction with placebo. We believe LB-102 has the potential to provide improved
tolerability and clinical activity in bipolar depression compared to currently
available treatments worldwide, which are associated with troubling adverse
events and insufficient efficacy for certain symptoms, including cognitive
impairment associated with the disease.
We are also developing a long-acting injectable, or LAI, formulation of LB-102,
which may improve compliance, a common issue in patients with schizophrenia and
bipolar disorder. We believe an effective LAI form of LB-102 has the potential
to benefit patients worldwide, as relatively few approved agents are available
as long-acting formulations and there are no benzamide class LAIs currently
available or in development worldwide. The American Psychiatric Association
recommends injectable formulations in circumstances where doing so will improve
adherence, decrease mortality, reduce hospitalization risk, and decrease
treatment discontinuation rates. We have commenced LAI formulation development
and expect to continue these efforts in 2026.
The U.S. market for branded antipsychotic drugs was approximately $12 billion as
of 2024. Despite the widespread use of generic antipsychotic drugs, several of
these branded drugs each generate U.S. sales in excess of $1 billion annually.
Additionally, while available therapeutics to treat schizophrenia and bipolar
depression demonstrate clinical benefit, a significant unmet need remains for a
treatment that balances tolerability with clinically meaningful efficacy for the
chronic management of symptoms related to both psychosis and mood disorders.
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LB Pharmaceuticals Inc was incorporated under the laws of the State of Delaware
in September 2015. Our principal executive office is located at One Pennsylvania
Plaza, Suite 1025, New York, NY 10119. Our telephone number is (212) 605-0300.
Our website address is https://lbpharma.us.
