Newron Pharmaceuticals S.p. A presented additional results from the international, randomized, double-blind, placebo-controlled study 008A that evaluated the efficacy and safety of evenamide (30 mg bid) as add-on treatment in 291 patients not benefitting from their second-generation antipsychotic medication, including clozapine. Initial top line data announced on 30thApril 2024 demonstrated that the study met its primary endpoint, an improvement of the Positive and Negative Syndrome Scale (PANSS) Total Score as well as the key secondary endpoint, an improvement of the Clinical Global Impression of Severity (CGI-S), in the a-priori defined regulatory analysis. Additional analyses for the secondary endpoints indicate significant effects achieved at the endpoint (Day 29), on all the following measures: PANSS total: Proportion of patients with a clinically relevant improvement (more than 20% improvement from baseline); p-value < 0.05; Clinical Global Impression of Change (CGI-C): Mean rating at endpoint; evenamide 3.3 versus placebo 3.5; p-value < 0.001; Clinical Global Impression of Change (CGI-C): Proportion of patients rated as showing any improvement; p-value < 0.05; Clinical Global Impression of Change (CGI-C): Proportion of patients rated as at least ?much improved?; evenamide: 31.3% versus placebo: 17.3%; p-value = 0.006; PANSS Positive subscale: Mean change from baseline; p-value < 0.05; PANSS Negative subscale: Mean change from baseline; p-value < 0.05.

The sensitivity analyses for the PANSS total (primary endpoint) and CGI-S (secondary endpoint) confirmed a statistically significant improvement for evenamide irrespective of the population analyzed and the statistical methods used; some examples are provided below: PANSS total worst observation carried forward (WOCF) ANCOVA p-value = 0.008; PANSS total Multiple Imputation (MI) ANCOVA: p-value = 0.006; CGI-S Multiple Imputation (MI) ANCOVA: p-value = 0.014. In the study, the addition of 30 mg (bid) of evenamide to the patients? current antipsychotic medication was very well tolerated, with a similar profile to placebo with no increases in EPS, weight gain, blood glucose, metabolic syndrome, sexual dysfunction, CNS or cardiac effects, or laboratory abnormalities.

Study 008A is the first well-designed study demonstrating efficacy of an adjunctive treatment in benefiting patients who do not respond to their current antipsychotic. Evenamide also is the first glutamate modulator to demonstrate efficacy in inadequately responding patients with schizophrenia in a placebo-controlled study.