ORYZON presents blinded aggregate safety data from vafidemstat’s ongoing Phase IIb PORTICO trial in Borderline Personality Disorder

Oryzon Genomics, S.A., a clinical-stage biopharmaceutical company leveraging epigenetics to develop therapies in diseases with strong unmet medical need, announced today that the company presented an update on vafidemstat’s ongoing Phase IIb PORTICO trial in borderline personality disorder (BPD) at the 36th European College of Neuropsychopharmacology (ECNP) Congress, held on October 7-10 in Barcelona, Spain.

Oryzon presented a poster communication entitled “PORTICO – Double-blind, randomized placebo-controlled, adaptive phase IIb trial with vafidemstat in borderline personality disorder – aggregated baseline characteristics, demographics and safety”, which was presented by Dr. Michael Ropacki, Oryzon’s CMO for CNS.

PORTICO enrolled the last patient in July 2023. The data presented at ECNP-2023 correspond to the analysis of aggregated blinded safety data cut as of August 23, 2023. As of September 2023, PORTICO randomized 210 participants, and 131 of the originally planned participants (N = 150) already completed the trial. Results obtained confirm that PORTICO enrolled a representative real-world BPD population allowing common comorbidities and concomitant medications that are typically exclusionary in other BPD trials, as well as allowed subjects to receive psychotherapy during the trial. The screen failure and dropout rates were lower than in the most recent BPD clinical trial. Finally, the aggregated blinded safety data on the fully enrolled sample supports that vafidemstat has been extremely safe and well-tolerated, with a low number of discontinuations (2%) due to treatment-emergent adverse events (TEAEs) and 0% due to serious TEAEs (STEAEs). Only one serious TEAE deemed severe was reported, which fully recovered/resolved during the study.

Dr. Ropacki stated: “PORTICO is a global BPD clinical trial evaluating vafidemstat that enrolled a real-world representative BPD population. It is hoped that the PORTICO efficacy results, expected early next year, together with the excellent safety profile observed to-date will support vafidemstat as a potential effective new treatment option in a population with high unmet need and no approved drug therapy”.

PORTICO (EudraCT No.: 2020-003469-20, ClinicalTrials.gov Identifier NCT04932291) is a global double blind, randomized, placebo-controlled, adaptive 14-week Phase IIb trial evaluating the efficacy and safety of vafidemstat in a BPD population. The trial has multiple primary endpoints: reduction of agitation and aggression and overall disease improvement in BPD severity. The trial recruited patients in the US, Germany, Spain, Bulgaria and Serbia, and aims to analyze 150 patients who complete the trial, randomized in two arms at a 1:1 ratio.

The trial is fully recruited and last patient out is expected before the end of 2023. Topline results are expected in Q1 2024, followed by a full data presentation at a psychiatric conference, as well as in a peer-reviewed journal publication.

A copy of the poster is available here

For more information about ECNP-2023, please visit ECNP-2023 website

About Oryzon

Founded in 2000 in Barcelona, Spain, Oryzon (ISIN Code: ES0167733015) is a clinical stage biopharmaceutical company and the European leader in epigenetics, with a strong focus on personalized medicine in CNS disorders and oncology. Oryzon’s team is composed of highly qualified professionals from the pharma industry located in Barcelona, Boston and San Diego. Oryzon has an advanced clinical portfolio with two LSD1 inhibitors, vafidemstat in CNS and iadademstat in oncology, in several Phase II clinical trials. The company has other pipeline assets directed against other epigenetic targets. In addition, Oryzon has a strong platform for biomarker identification and target validation for a variety of malignant and neurological diseases. 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 and is preparing a clinical trial in Kabuki Syndrome patients. The company is also exploring the clinical development of vafidemstat in other neurodevelopmental syndromes.

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