ORYZON enrolls first patient in the US in PORTICO, a Phase IIb clinical trial with vafidemstat in Borderline Personality Disorder

18 October 2021

Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company leveraging epigenetics to developtherapies in diseases with strong unmet medical need, announced today the enrollment of the first patient in the US in its Phase IIb clinical trial with vafidemstat, a selective inhibitor of the epigenetic target LSD1, in Borderline Personality Disorder (BPD) patients.

PORTICO (ClinicalTrials.gov Identifier NCT04932291) is a multicenter, double-blind, randomized, placebo-controlled Phase IIb trial to evaluate the efficacy and safety of vafidemstat in BPD patients. The two primary independent objectives of the trial are a reduction of aggression and agitation and an overall improvement of BPD. The study aims to include 156 patients in total, with 78 patients in each arm, and has an adaptive design with a pre-defined interim analysis to adjust the sample size in case of excessive variability around the endpoints or an unexpectedly high placebo rate. The study is already approved in Europe by the Spanish, German and Bulgarian Medicine Agencies.

Dr. Michael Ropacki, Oryzon's CNS Chief Medical Officer, stated: "We are extremely excited that the global PORTICO trial has achieved first patient in (FPI) in the United States, in collaboration with Adams Clinical of Boston, Massachusetts. Vafidemstat offers tremendous potential to be a safe, effective, and well-tolerated treatment option in Borderline Personality Disorder, a population with high unmet medical need, but no approved safe or effective pharmacologic treatments."

PORTICO builds on clinical data from the Phase IIa REIMAGINE trial, where vafidemstat reduced agitation-aggression in patients with attention deficit and hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and BPD after 2 months of treatment, and from the Phase IIa REIMAGINE-AD trial, where vafidemstat reduced agitation-aggression in patients with severe and moderate Alzheimer's disease after 6 months of treatment. Vafidemstat has proven to be safe and well-tolerated across multiple clinical trials in more than 300 treated subjects, some on continuous therapy for up to 24 months. PORTICO's scientific rationale is based on vafidemstat' s ability to inhibit selectively LSD1 and modulate aggression and sociability, as tested in several preclinical models

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

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 https://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 preliminary 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 months of treatment, and the pilot, small scale SATEEN trial in Relapse-Remitting and Secondary Progressive MS. A Phase IIb trial in borderline personality disorder (PORTICO) has been recently authorized and the company is preparing a Phase IIb trial in schizophrenia patients (EVOLUTION). Vafidemstat is also being explored 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.

Contact information: in the file attached