Oryzon Genomics, a leading European epigenetics-focused biopharmaceutical company, has announced a significant step forward in addressing the critical unmet medical need in Borderline Personality Disorder (BPD). The company has submitted the clinical trial protocol for its Phase III PORTICO-2 trial to the U.S. Food and Drug Administration (FDA), aiming to initiate a registrational study to evaluate vafidemstat in BPD patients. This submission was made possible through extensive interactions with the FDA and contributions from internationally recognized psychiatric experts. The decision to advance to Phase III is rooted in the encouraging results from the preceding Phase IIb PORTICO study, where vafidemstat demonstrated clinically meaningful reductions in secondary endpoints related to aggression and overall BPD improvement. Given that aggression is a pervasive and debilitating symptom in BPD, often leading to self-harm and high suicide rates, it will serve as the primary endpoint in the PORTICO-2 trial, measured by the patient-reported STAXI-2 Trait Anger scale, with the clinician-rated Overt Aggression Scale-Modified (OAS-M) as a key secondary endpoint. Additional secondary endpoints will assess broader improvements in BPD symptomatology and quality of life.

Vafidemstat (ORY-2001) is an orally active LSD1 inhibitor with a novel epigenetic mechanism of action. This compound has consistently shown a favorable safety and tolerability profile across numerous clinical studies, including previous Phase IIa trials in aggression across various psychiatric disorders (REIMAGINE) and in aggressive/agitated Alzheimer's patients (REIMAGINE-AD), both yielding positive clinical outcomes. Beyond BPD, vafidemstat's potential to manage aggression is also being explored in other neurodevelopmental and neurodegenerative disorders, with a new trial in Autism Spectrum Disorder (ASD) planned.

The PORTICO-2 trial will be a randomized, double-blind, placebo-controlled, multi-center study, planning to enroll approximately 350 BPD patients. BPD affects 1-2% of the general population and is characterized by severe emotional instability, impulsivity, and high rates of self-harm and suicide attempts. Currently, there are no FDA-approved pharmacological treatments specifically for BPD, highlighting the urgent necessity for effective therapeutic options like vafidemstat. Oryzon, founded in 2000, maintains a strong focus on personalized medicine in CNS disorders and oncology, with an advanced clinical portfolio that includes vafidemstat in CNS and iadademstat in oncology.