Reviva Pharmaceuticals Holdings, Inc. has presented the foundational preclinical data that supported the initial clinical development of its novel serotonin-dopamine stabilizer brilaroxazine at the 78th Annual Scientific Convention of the Society of Biological Psychiatry (SOBP) in San Diego. The Company also announced acceptance of this data for publication in Medical Research Archives. Limitations of current antipsychotics, predominantly dopamine or dopamine and serotonin receptor selective compounds, include refractory response, suboptimal effectiveness of major symptoms, adherence, and neurological and cardiometabolic side effects.

Preclinical studies in three different translational rodent models capturing the heterogeneity in symptom cluster and severity were used to evaluate the potential of brilaroxazine to address the major symptom domains among patients with schizophrenia. Key highlights from the poster presentation and publication support brilaroxazine's differentiated profile: Brilaroxazine demonstrated significant antipsychotic effects on pharmacologic-induced behaviors associated with psychosis and schizophrenia in three standard translational rodent models: Apomorphine-induced (dopamine agonism) climbing rodent models represent symptoms of acute schizophrenia: Brilaroxazine lowered climbing scores at all time points across doses with ~5-fold reduction vsapomorphine control; Apomorphine-induced prepulse inhibition (PPI) rodent models represent psychotic behaviors, in particular for negative symptoms and cognitive deficits: Significant dose-dependent reversal of PPI deficits with brilaroxazine vs vehicle control at the 3-, 10-, and 30-mg/kg doses; NMDA-induced (a surrogate model for dopamine and serotonin systems) rodent models provide overall assessments of symptoms and in particular locomotion for positive symptoms and stereotypy for negative symptoms: Brilaroxazine significantly decreased dizocilpine-induced hyperlocomotion and stereotypy behaviors in a dose-dependent manner across the 3-, 10-, and 30-mg/kg doses. Preclinical data reinforce the efficacy profile of brilaroxazine seen in the clinical trials Phase 1B in patients with stable schizophrenia, and Phase 2 in patients with acute schizophrenia and schizoaffective disorders.

Differentiated efficacy demonstrated in patients with schizophrenia possibly attributed to the multimodal effects of brilaroxazine that involves critical dopamine and serotonin targets and influence on pro-inflammatory cytokine release.