Oryzon Genomics, S.A. announced the enrollment of the first patient in the EVOLUTION Phase IIb clinical trial with vafidemstat in patients with schizophrenia, at the Vall d?Hebr?n Hospital in Barcelona, Spain. EVOLUTION is a multicenter, double-blind, randomized, placebo-controlled, 24-week Phase IIb trial to evaluate the efficacy and safety of vafidemstat in adult schizophrenia patients under stable antipsychotic therapy. The trial has two primary independent objectives: to assess the effect of vafidemstat on negative symptoms of schizophrenia, and to assess improvement on cognitive impairment associated with schizophrenia (CIAS). To accommodate this second ambitious primary objective, patients will be treated for 6 months. EVOLUTION includes multiple primary and secondary endpoints focusing on negative and positive symptoms, as well as cognition. The trial will be conducted in 6-10 sites in Spain and aims to include 100 patients in total, with 50 patients in each arm. An interim analysis is foreseen to adjust the final number of patients needed to assess efficacy. EVOLUTION?s scientific rationale is based on vafidemstat?s ability to inhibit LSD1, reducing aggression, enhancing sociability and mitigating social withdrawal, as demonstrated in several preclinical models. Importantly, EVOLUTION builds on clinical data from the Phase IIa REIMAGINE trial, where vafidemstat reduced agitation-aggression in patients with attention deficit hyperactivity disorder, autism spectrum disorder and borderline personality disorder and showed positive global effects across these psychiatric disorders after 2 months of treatment. Vafidemstat has shown a favorable safety and tolerability profile in multiple Phase I/II clinical trials, with over 300 subjects treated, some for up to 24 months. Vafidemstat has not been associated with sedation, weight gain or extrapyramidal side effects, which are common in current antipsychotic therapy, nor with any other adverse events.