Reviva Pharmaceuticals Holdings, Inc. announced positive data from its recently completed clinical drug-drug interaction (DDI) study investigating the potential effect of CYP3A4 enzyme on brilaroxazine in healthy subjects. The CYP3A4 enzyme plays a pivotal role in helping the body metabolize and remove small foreign molecules and is primarily found in the liver and intestine. DDI evaluation is a critical clinical pharmacology study required by theU.S. Food and Drug Administration (FDA) and other regulatory agencies globally for approving a new drug to market.

Brilaroxazine is a serotonin/dopamine modulator in late-stage clinical development for the treatment of schizophrenia. Following FDA guidelines, the DDI clinical study was designed to evaluate the drug interaction effect of a strong CYP3A4 inhibitor or inducer when co-administered with brilaroxazine in healthy volunteers. A strong CYP3A4 inhibitor, itraconazole, slightly increased brilaroxazine C(max), AUC(last) and AUC(inf) by 6, 16 and 13%, respectively, in healthy volunteers (N=11).

Similarly, a strong CYP3A4 inducer, phenytoin, in healthy volunteers (N=16) decreased brilaroxazine C(max), AUC(last) and AUC(inf) by 33, 56 and 53%, respectively. Reviva believes that brilaroxazine'sclinical safety is further reinforced with the positive results of this DDI study, which found no clinically significant double-blind, placebo- controlled, multicenter study designed to assess the safety and efficacy of brilaroxazine in approximately 400 patients with acute schizophrenia compared to placebo. Brilaroxazine will be administered at fixed doses of 15 mg or 50 mg once daily for 28 days.

A 52-week open-label extension study with flexible doses of 15 mg, 30 mg, or 50 mg will further evaluate the long-term expected in mid-2023. About DDI Clinical Studies Drug-drug interaction (DDI) clinical studies are an imperative step in the new drug approval process. DDI studies help identify potential adverse reactions that may be caused by interactions between multiple drugs, leading to unintended reactions, toxic side effects, or in some cases, a lack of therapeutic efficacy.

With the rise in polypharmacy to treat comorbidities, alongside prevalent substance abuse, drug-drug interactions have become a critical factor to consider when treating schizophrenia. Approximately 50% of prescribed drugs and over 25% of antipsychotics currently on the market are known to cause drug interactions with CYP3A4 inhibitors and can lead to side effects. Findings from DDI studies help to inform drug labeling that is then used by healthcare providers to aid in therapeutic decision-making.

About Brilaroxazine Brilaroxazine (RP5063) is a new chemical entity with potent affinity and selectivity against key serotonin and dopamine receptors implicated in schizophrenia and its comorbid symptoms.