Company: LBRX
Filing Date: 2025-07-23
Form Type: DRS/A
Source: 0000950123-25-006557
Chunk: 178

Company: LB PHARMACEUTICALS INC
Filing Date: 2025-07-23
Form: DRS/A
Chunk 178
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, and glutamate. Specifically, schizophrenia is associated with an imbalance of dopaminergic pathways at the D receptor subtype. Increased dopamine activity in certain parts
of the brain can contribute to positive symptoms of schizophrenia. In contrast, reduced dopamine activity in other parts of the brain may cause negative and cognitive symptoms. Detailed understanding of the specific changes in dopamine signaling
that lead to schizophrenia is limited by the relative inaccessibility of methods to assess signaling pathways in the brain, the heterogeneity of psychological responses, and the lack of highly translatable animal models. Since the 1970s, clinical
trials with haloperidol, risperidone, and olanzapine, among others, have conclusively demonstrated that antagonism of the dopamine Dreceptor can improve symptoms of schizophrenia.

Schizophrenia with Predominantly Negative Symptoms

Negative symptoms are a core component of schizophrenia and are distinct from positive symptoms. They account for a large part of the long-term
morbidity and poor functional outcomes. It is estimated that up to 60% of people with schizophrenia may have predominantly negative symptoms that are clinically relevant and require treatment equating to approximately 1.3 million people in the
United States. In a meta-analysis for 20 placebo-controlled trials of second generation antipsychotic drugs, 62% of patients were experiencing predominantly negative symptoms and after six weeks of treatment,
one-third of patients continued to experience negative symptoms on active treatment. Negative symptoms are linked to worse functional outcomes in occupational and academic performance, household integration,
social functioning, participation in activities and quality of life.

People living with negative symptoms of schizophrenia are considered
to have a higher burden of illness, which may be partially attributed to the limited number of effective treatment options for this population. To date, there are no FDA approved treatments for predominantly negative symptoms in schizophrenia.

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Cognitive Impairment Associated with Schizophrenia

CIAS is a major burden for patients and negatively impacts many aspects of a patient’s life. Cognitive impairment is a core feature and
leading cause of functional disability in schizophrenia and other neuropsychiatric disorders. Antipsychotic drugs are the standard-of-care treatment for schizophrenia
but typically only address positive symptoms. So far there are no approved pharmacotherapies for the treatment of CIAS. More than 80% of people with schizophrenia have cognitive symptoms of some kind, equating to approximately 1.8 million
patients in the United States.

Limitations of Current Treatments for Schizophrenia

Antipsychotic drugs