ORYZON to Present Final Data From PORTICO Phase IIb Trial of Vafidemstat in Borderline Personality Disorder at 37th ECNP Conference

Oryzon Genomics, S.A., a clinical-stage biopharmaceutical company specializing in epigenetics, recently announced that it will present the final data from its Phase IIb PORTICO trial at the 37th European College of Neuropsychopharmacology (ECNP) annual conference. The event will take place in Milan, Italy, from September 21-23, 2024. Dr. Michael Ropacki, Oryzon’s Chief Medical Officer and Head of CNS Clinical Development, will deliver the presentation on September 23rd during the ECNP New Medication Symposium. The presentation is titled “Final Results: PORTICO a double-blind, randomized placebo-controlled, adaptive phase IIb trial to assess vafidemstat’s efficacy in treating borderline personality disorder”.

The PORTICO trial was a global double-blind, randomized, placebo-controlled, adaptive 14-week Phase IIb study that evaluated the efficacy and safety of vafidemstat in patients with Borderline Personality Disorder (BPD). The trial had two primary objectives: to measure the reduction of agitation and aggression, and to assess overall disease improvement. Secondary objectives also included measuring these improvements through different scales. The study was conducted across 27 clinical sites, including 14 in the U.S. and 13 in Europe, encompassing countries like Germany, Spain, Bulgaria, and Serbia. A total of 210 patients were enrolled in the trial and randomized into two groups.

In January, Oryzon released the topline data from the PORTICO trial. The primary endpoints, which were overall disease improvement as measured by the Borderline Personality Disorder Checklist (BPDCL) and improvement in agitation/aggression using the Clinical Global Impression – Severity Agitation/Aggression (CGI-S A/A), did not achieve statistical significance. However, notable statistical significance was observed in two secondary endpoints: overall disease improvement measured by the Borderline Evaluation of Severity (BEST) at weeks 8-12, and reduction of agitation/aggression measured by the State-Trait Anger Expression Inventory 2 (STAXI-2) Trait Anger at weeks 8-12. Vafidemstat was found to be safe and well-tolerated, consistent with its safety profile to date.

The final analysis revealed substantial improvements in most of the measures compared to the January data. Following the ECNP presentation, the results will be published in a peer-reviewed medical journal. Oryzon has also requested an End-Of-Phase 2 meeting with the FDA to discuss the design of a registrational Phase III trial for vafidemstat in BPD.

Founded in 2000 in Barcelona, Spain, Oryzon is a leader in epigenetics with a focus on personalized medicine for CNS disorders and oncology. The company has a skilled team based in Barcelona, Boston, and San Diego. Oryzon’s portfolio includes two LSD1 inhibitors, vafidemstat for CNS disorders and iadademstat for oncology, both in several Phase II clinical trials. The company also has assets targeting other epigenetic markers like HDAC-6, with ORY-4001 identified as a clinical candidate for neurological disorders such as CMT and ALS. Oryzon excels in biomarker identification and target validation for various malignant and neurological diseases.

Vafidemstat (ORY-2001) is an oral LSD1 inhibitor optimized for CNS conditions. It mitigates cognitive impairment, including memory loss and neuroinflammation, and also offers neuroprotective effects. In animal studies, the drug has demonstrated the ability to restore memory and reduce aggressiveness and social avoidance. It has shown strong efficacy in preclinical models of multiple sclerosis (MS). Clinical trials such as REIMAGINE and REIMAGINE-AD have reported positive results in reducing aggression in psychiatric and Alzheimer's disease patients, respectively. Other Phase II trials, including ETHERAL for Alzheimer's disease and SATEEN for multiple sclerosis, have also shown promising results. Vafidemstat is currently being investigated in two Phase IIb trials for neuropsychiatric disorders: EVOLUTION for schizophrenia and PORTICO for BPD. An End-of-Phase II meeting with the FDA is planned to discuss a Phase III trial for BPD. The company is also exploring vafidemstat's use in genetically-defined CNS disorders and is preparing a clinical trial for Kabuki Syndrome.

Borderline Personality Disorder (BPD) is a severe psychiatric condition affecting 0.5 to 1.6% of the population, characterized by emotional instability, impulsivity, and unstable relationships. Up to 10% of BPD patients die by suicide. While psychotherapy is the primary treatment, no FDA-approved medications exist for BPD, leading to the use of off-label drugs for symptom management. Approximately 1.4 million BPD patients in the U.S. are treated with off-label medications.