Company: LBRX
Filing Date: 2025-08-22
Form Type: S-1
Source: 0001193125-25-186467
Chunk: 182

Company: LB PHARMACEUTICALS INC
Filing Date: 2025-08-22
Form: S-1
Chunk 182
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 it is estimated that 13% to 48% of patients continue to have residual symptoms. At this point, the patient may experience cycles of active disease, characterized by positive 119

symptoms, and periods of stability, potentially with persistent negative symptoms. A meta-study showed that 55% of people with schizophrenia required hospitalization over an average follow-up of seven years after their first episode. With each relapse, the disease worsens, and the patient typically is unable to recover to the same level of health as prior to the active episode. Over years of
experiencing these cycles, most patients deteriorate, experiencing worsening symptoms and health outcomes. A therapy that reduces the number of relapses a patient experiences has the potential to provide a significant and life-long benefit. The
figure below depicts a graphic illustration of these phases.

Pathophysiology of Schizophrenia

One of the main hypotheses for the pathophysiology leading to schizophrenia is an imbalance in neurochemical signaling in the brain, including
serotonin, dopamine, 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. Negative symptoms are linked to worse
functional outcomes in occupational and academic performance, household integration, social functioning, participation in activities