ORYZON enrolls first patient in EVOLUTION, a Phase IIb clinical trial with vafidemstat in schizophrenia

Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company leveraging epigenetics to develop therapies in diseases with strong unmet medical need, announced today the enrollment of the first patient in the EVOLUTION Phase IIb clinical trial with vafidemstat in patients with schizophrenia, at the Vall d’Hebrón Hospital in Barcelona, Spain.

EVOLUTION (EudraCT No.: 2021-000350-26) is a multicenter, double-blind, randomized, placebocontrolled, 24-week Phase IIb trial to evaluate the efficacy and safety of vafidemstat in adult schizophreniapatients 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 patientsin total, with 50 patientsin each arm. An interim analysis is foreseen to adjust the final number of patients needed to assess efficacy.

Oryzon’s Chief Medical Officer for CNS, Dr. Michael Ropacki, said: “We are excited for the first patient in (FPI) in EVOLUTION, our Phase IIb trial focused on the negative symptoms and cognitive impairments associated with schizophrenia. Considering the significant side effect profiles of atypical antipsychotics used to treat schizophrenia, vafidemstat holds tremendous potential to be a safe, effective, and welltolerated treatment option to treat the underlying cognitive dysfunction and negative symptoms of 

schizophrenia.”

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 (see Maes et al., PLOS ONE 2020 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233468). 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.

More information and contact in the file attached.