Reviva Pharmaceuticals FY Conference Summary Company Overview - **Company**: Reviva Pharmaceuticals (NasdaqCM: RVPH) - **Focus**: Late-stage pharmaceutical company developing next-generation therapies for neurodysfunction diseases, particularly schizophrenia [2][21] Key Points on Schizophrenia and Unmet Needs - **Prevalence**: Approximately 24 million people globally suffer from schizophrenia, which is a lifelong condition for most patients [3] - **Treatment Challenges**: - Around 30% of patients do not respond to current treatments - High treatment discontinuation rates: 30%-45% in the short term and up to 80% in the long term - Relapse rates are significant, with 25% of patients experiencing relapse within a year, increasing to 90% in the long run [4] Brilaroxazine Development - **Lead Molecule**: Brilaroxazine, currently in development for schizophrenia, with potential for other indications like bipolar disorder and ADHD [2] - **Clinical Trials**: - Completed multiple trials, treating nearly 900 patients - Pivotal trial design included acute treatment for one month and stable treatment for one year, involving around 850 patients [5][11] Efficacy Data - **Primary Endpoint**: Brilaroxazine showed a statistically significant improvement of around 10 points compared to placebo, indicating robust efficacy [6] - **Negative Symptoms**: - Significant improvement in negative symptoms, a critical unmet need in schizophrenia treatment - Data from the Marder factor indicated early onset of action and progressive improvement [9][10] - **Long-term Efficacy**: - Sustained efficacy over one year with a reduction in PANS score by nearly 50 points for patients transitioning from acute to long-term treatment [11] - Less than 1% of patients reported relapse or near relapse symptoms during long-term treatment [14] Safety and Tolerability - **Safety Profile**: - No serious drug-related adverse events reported - Common side effects included headaches and sleep disturbances, occurring in less than 5% of patients [15][16] - **Endocrine Effects**: - Prolactin levels decreased to normal, avoiding common side effects associated with other antipsychotics [17][18] - **Cardiac Safety**: No QTc prolongation or significant cardiac side effects observed [19] Regulatory Path and Future Plans - **NDA Submission**: - Completed trials required for NDA filing; however, FDA recommended an additional phase three study - Anticipated initiation of the second trial in early Q2 2027, with NDA submission expected in Q4 2027 [20][21] - **Funding Needs**: Company requires approximately $50 million to complete the second study and submit the NDA [21] Competitive Landscape - **Market Comparison**: Brilaroxazine's efficacy data is competitive with leading antipsychotics, some of which have over $1 billion in sales [19][20] Conclusion Reviva Pharmaceuticals is positioned to address significant unmet needs in schizophrenia treatment with Brilaroxazine, demonstrating promising efficacy and safety data. The company is preparing for further clinical trials and regulatory submissions to bring this innovative therapy to market.

Efficacy of Brilaroxazine - Brilaroxazine demonstrated a significant decrease of 18 points in PANSS total score at Week 52 compared to baseline (p ≤ 0.0001) [41] - There was a 5-point decrease in PANSS positive symptoms score at 12 months with brilaroxazine pooled (15, 30 & 50 mg) vs baseline (p ≤ 0.001) [47] - Brilaroxazine showed a 4.4-point decrease in PANSS negative symptoms score at 12 months compared to baseline (p ≤ 0.001) [50] - 58.5% of patients showed >1-point improvement on the CGI-S scale at 12 months with brilaroxazine pooled (15, 30, & 50 mg) vs baseline (p ≤ 0.001) [69] Safety and Tolerability of Brilaroxazine - In the 52-week open-label trial, 37.2% of patients experienced any treatment emergent adverse event (TEAE) [84] - The pooled brilaroxazine dose group reported a mild weight gain of 1.52 kg [104] - There was a decrease in cholesterol of -8.3 mg/dL overall (p=0.030) and LDL cholesterol of -8.0 mg/dL overall (p=0.0093) in the 12-month OLE trial [90] - A clinically significant decrease in serum prolactin levels of -12.50 ug/L overall was observed from baseline to week-52/EOT [94] - There was an improvement in thyroid (T3) hormone levels of 0.044 ug/L overall (P ≤ 0.05) [97] Trial Design and Demographics - The RECOVER open-label extension (OLE) trial enrolled 446 patients with stable schizophrenia [37]

Core Insights - Reviva Pharmaceuticals announced positive results from the Phase 3 RECOVER open-label extension study of brilaroxazine for schizophrenia, demonstrating sustained efficacy and a well-tolerated safety profile over one year [1][2][5] Efficacy and Safety - Brilaroxazine showed robust broad-spectrum efficacy across all major symptom domains of schizophrenia, with a statistically significant reduction in PANSS total score of -18.1 at 12 months [3][4] - The treatment was generally well-tolerated, with a discontinuation rate of 35%, primarily due to withdrawal of consent and loss to follow-up [1][9] - Improvements in multiple neuroinflammatory markers were observed, suggesting enhanced efficacy and reduced side effects [1][2][9] Clinical Data - The study included a pooled analysis of 446 patients receiving doses of 15 mg, 30 mg, and 50 mg, showing dose-dependent efficacy [2][4] - Key findings included a reduction in negative symptoms by -4.4 at 12 months and significant improvements in personal and social performance scores [3][4] - The treatment also demonstrated a low incidence of treatment-emergent adverse events, with most being mild or moderate in severity [9][10] Future Development - Reviva aims to advance brilaroxazine towards regulatory submission, with plans to explore its use in other neuropsychiatric conditions such as bipolar disorder and major depressive disorder [10][11] - The company has received Orphan Drug Designation from the FDA for brilaroxazine in treating pulmonary arterial hypertension and idiopathic pulmonary fibrosis [11][12]