Oryzon defines Phase III Trial endpoints for Agitation and Aggression in BPD with input from new Clinical Advisory Board

Oryzon Genomics S.A (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company and a European leader in epigenetics, today announced that it has established the primary and key secondary endpoints for its planned Phase III clinical trial evaluating vafidemstat in Borderline Personality Disorder (BPD). This milestone was reached in collaboration with Oryzon’s newly formed Clinical Advisory Board (CAB), composed of leading experts in psychiatry research and clinical trials for psychiatric disorders.

The CAB’s insights have been instrumental in ensuring that the Phase III protocol aligns with FDA expectations and incorporates well-validated, widely recognized assessment scales to measure agitation and aggression in BPD patients. This development follows the successful completion of the Phase IIb PORTICO trial, which received positive feedback from the FDA, and positions Oryzon to submit the Phase III protocol for regulatory review in the first half of 2025.

“We are honored to collaborate with such a distinguished panel of experts as we advance vafidemstat into Phase III development,” said Dr. Carlos Buesa, Chief Executive Officer of Oryzon. “Their expertise in psychiatric disorders and clinical trial methodology strengthens our program and ensures that we are wellprepared for the next regulatory interactions. Addressing aggression and agitation in BPD remains an urgent medical need, and we are committed to delivering innovative solutions for these patients.”

Oryzon’s Clinical Advisory Board Members:

Oryzon’s CAB includes internationally recognized leaders in psychiatry and clinical trial research:

• Dr. Alan F. Schatzberg, Kenneth T. Norris, Jr. Professor of Psychiatry and Behavioral Sciences at Stanford University School of Medicine, former Chair of the Department (1991–2010), and current Director of the Stanford Mood Disorders Center. A past President of the American Psychiatric Association (2009–2010), he is a leading expert in mood disorders, particularly the neurobiology and treatment of depression.
• Dr. Eric Hollander, Professor of Psychiatry and Director of the Autism and Obsessive Compulsive Spectrum Program at Albert Einstein College of Medicine and Montefiore Medical Center, is a leading authority on obsessive-compulsive and related disorders. He has received multiple NIMH grants to develop treatments for BPD, with a research focus on the neurobiology of aggression and affective instability in BPD.
• Dr. Sarah Fineberg, Assistant Professor of Psychiatry at Yale University School of Medicine, specializes in the neurobiology of BPD. Her research explores social cognition and decision-making using computational psychiatry and neuroimaging. She has led clinical trials testing novel interventions for BPD, including sub-anesthetic ketamine for BPD and real-time fMRI neurofeedback.
• Dr. Emil F. Coccaro, George T. Harding III, M.D., Endowed Professor in the Department of Psychiatry and Behavioral Health at The Ohio State University Wexner Medical Center, is a leading expert in the neurobiology of aggression and impulsivity. His work has significantly advanced the understanding and treatment of impulsive aggression in BPD through pharmacological interventions.

“These are the right experts to help us shape a Phase III program that is both scientifically rigorous and clinically meaningful,” added Dr. Buesa. “It is particularly reassuring that their expert medical opinion and years of practice recognize aggression as one of the most debilitating aspects of many psychiatric disorders, and particularly in borderline personality disorder. Their contributions have been instrumental in defining the primary and secondary endpoints, that will generate robust data for regulatory submissions.”

Next Steps in Vafidemstat’s Development

Oryzon remains committed to progressing vafidemstat as a potential first-in-class treatment for agitation and aggression in BPD. Following the FDA’s feedback on the PORTICO trial results, Oryzon plans to submit the Phase III protocol in the first half of 2025, with trial initiation expected soon after, pending regulatory approval and securing the necessary funding.

Beyond BPD, vafidemstat is being evaluated in a Phase IIb trial for the treatment of negative symptoms in schizophrenia (EVOLUTION trial) and is part of Oryzon’s broader CNS precision medicine approach. The company is also exploring additional applications in genetically defined subpopulations and neurodevelopmental disorders.