ORYZON Enrolls First Patient in EVOLUTION, a Phase IIb Clinical Trial With Vafidemstat in Schizophrenia

• Primary objectives: to assess the effect of vafidemstat to address negative and cognitive symptoms in schizophrenia
• Phase IIb adaptive trial planning to enroll 100 patients
• Second Phase IIb study of vafidemstat in CNS disorders

MADRID, Spain and CAMBRIDGE, Mass., Nov. 17, 2021 (GLOBE NEWSWIRE) -- 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, 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.

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 well-tolerated 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.

About Oryzon
Founded in 2000 in Barcelona, Spain, Oryzon (ISIN Code: ES0167733015) is a clinical stage biopharmaceutical company considered as the European champion in Epigenetics. Oryzon has one of the strongest portfolios in the field. Oryzon’s LSD1 program has rendered two compounds, vafidemstat and iadademstat, in Phase II clinical trials. In addition, Oryzon has ongoing programs for developing inhibitors against other epigenetic targets. Oryzon has a strong technological platform for biomarker identification and performs biomarker and target validation for a variety of malignant and neurological diseases. Oryzon has offices in Spain and the United States. Oryzon is one of the most liquid biotech stocks in Europe with +90 M shares negotiated in 2020 (ORY:SM / ORY.MC / ORYZF US OTC mkt). For more information, visit www.oryzon.com

About Vafidemstat
Vafidemstat (ORY-2001) is an oral, CNS optimized LSD1 inhibitor. The molecule acts on several levels: it reduces cognitive impairment, including memory loss and neuroinflammation, and at the same time has neuroprotective effects. In animal studies vafidemstat not only restores memory but reduces the exacerbated aggressiveness of SAMP8 mice, a model for accelerated aging and Alzheimer’s disease (AD), to normal levels and also reduces social avoidance and enhances sociability in murine models. In addition, vafidemstat exhibits fast, strong and durable efficacy in several preclinical models of multiple sclerosis (MS). Oryzon has performed two Phase IIa clinical trials in aggressiveness in patients with different psychiatric disorders (REIMAGINE) and in aggressive/agitated patients with moderate or severe AD (REIMAGINE-AD), with positive clinical results reported in both. Additional finalized Phase IIa clinical trials with vafidemstat include the ETHERAL trial in patients with Mild to Moderate AD, where a significant reduction of the inflammatory biomarker YKL40 has been observed after 6 and 12 months of treatment, and the pilot, small scale SATEEN trial in Relapse-Remitting and Secondary Progressive MS, where anti-inflammatory activity has also been observed. Vafidemstat has also been tested in a Phase II in severe Covid-19 patients (ESCAPE) assessing the capability of the drug to prevent ARDS, one of the most severe complications of the viral infection, where it showed significant anti-inflammatory effects in severe Covid-19 patients. Currently, vafidemstat is in two Phase IIb trials in borderline personality disorder (PORTICO) and in schizophrenia patients (EVOLUTION). The company is also deploying a CNS precision medicine approach with vafidemstat in genetically-defined patient subpopulations of certain CNS disorders.

About Schizophrenia
Schizophrenia is a severe mental disorder characterized by positive symptoms such as delusions and hallucinations, negative symptoms including amotivation and social withdrawal, and cognitive symptoms such as deficits in working memory and cognitive flexibility. While new antipsychotics are available to improve the positive symptoms, no approved medications are available yet for the negative symptoms and cognitive impairment that are the most debilitating aspects of this disease. Prevalence of schizophrenia and related psychotic disorders in the US range between 0.25% and 0.64% of the population.

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