ORYZON announces submission of Phase III protocol to FDA to initiate PORTICO-2 trial of vafidemstat in Borderline Personality Disorder (BPD) patients

Oryzon Genomics S.A., (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company and a European leader in epigenetics, announced today that it has submitted the clinical trial protocol for its Phase III PORTICO-2 trial to the U.S. Food and Drug Administration (FDA) to initiate a registrational trial to evaluate vafidemstat in patients with Borderline Personality Disorder (BPD). The PORTICO-2 trial builds upon the encouraging results observed in the previous PORTICO Phase IIb study, where vafidemstat demonstrated significant and clinically meaningful reductions in secondary endpoints measuring aggression and overall BPD improvement. Aggression is a key symptom domain in BPD that currently represents a major unmet medical need and will be the primary endpoint in PORTICO-2. Vafidemstat, an orally active LSD1 inhibitor with a novel epigenetic mechanism of action, has shown a favorable safety and tolerability profile across multiple clinical studies.

"The submission of PORTICO-2 to the FDA marks a major step forward for Oryzon and for the field of neuropsychiatry of personality disorders," said Carlos Buesa, Chief Executive Officer of Oryzon. "Borderline Personality Disorder is a highly disabling condition with no approved pharmacological treatments. With its novel epigenetic mechanism, vafidemstat has the potential to become the first targeted therapy specifically addressing aggression and overall improvement in BPD, offering real hope for patients and clinicians confronting this serious disorder. Vafidemstat has also the potential to manage aggression in other neurodevelopmental and neurodegenerative disorders, and we are planning to explore it in a new trial in aggression in ASD."

The Phase III protocol was developed through multiple interactions and constructive exchanges with the FDA. Its final design was further refined with the scientific contribution of internationally recognized psychiatric experts, including Dr. Alan Schatzberg (Stanford University), Dr. Eric Hollander (Albert Einstein Medical School), Dr. Emil Coccaro (Ohio State University Wexner Medical Center), and Dr. Sarah Fineberg (Yale University).

PORTICO-2 will employ two clinical outcome measures for aggression: the STAXI-2 Trait Anger scale (patient-reported) as the primary endpoint, and the Overt Aggression Scale-Modified (OAS-M) (clinicianrated) as key secondary endpoint. Additional secondary endpoints will evaluate broader clinical improvements in BPD symptomatology and quality of life.

A dedicated Key Opinion Leader (KOL) webinar is planned in the coming weeks to discuss the PORTICO-2 study design, the substantial unmet medical need in BPD, and the role of aggression as a clinical target. Details will be announced in a further communication.

PORTICO-2 will be a randomized, double-blind, placebo-controlled, multi-center study to assess both the efficacy and safety of vafidemstat in BPD patients, and aims to randomize 350 patients

BPD affects approximately 1-2% of the general population and is characterized by pervasive emotional instability, impulsivity, interpersonal dysfunction, unstable self-image and frequent episodes of aggression and self-harm. More than 75% of BPD patients attempt suicide, and the rate of completed suicide has been estimated to be approximately 10%, 50-times higher than in the general population. Currently, there are no FDA-approved medications specifically indicated for the treatment of BPD, underscoring the urgent need for novel therapeutic approaches.

Additional exploratory data from earlier Phase IIa studies suggest that vafidemstat may also reduce aggression in other patient populations, including Autism Spectrum Disorder (ASD), AttentionDeficit/Hyperactivity Disorder (ADHD), and Alzheimer's Disease (AD). The company is planning to explore this further in a new trial in aggression in ASD to be conducted within the activities of the Med4Cure IPCEI-EU Grant.