Oryzon Publishes Key PMS Study, Advancing Vafidemstat Research For Precision Psychiatry

Oryzon Genomics, a clinical-stage biopharmaceutical company specializing in epigenetic therapies, has published the final results of an observational study on Phelan-McDermid syndrome (PMS) in Frontiers in Psychiatry. The study aimed to psychometrically characterize individuals with PMS who carry deletions or pathogenic variants in the SHANK3 gene. The collected data will serve as a foundation for future precision psychiatry clinical trials evaluating the potential of vafidemstat in this patient group.

Dr. Jordi Xaus, Oryzon’s CSO, said in a statement, “The publication of these results in this prestigious clinical psychiatry journal marks a critical first step toward establishing vafidemstat as a novel personalized medicine therapy for relevant psychiatric indications. In recent years, a range of monogenic rare neurodevelopmental disorders linked to alterations in the epigenetic machinery and other key neuronal genes have been identified as potential targets for precision medicine. The use of LSD1 inhibitors has been shown to partially or fully rescue the complex phenotypes caused by these genetic mutations. Vafidemstat is currently the only LSD1 inhibitor in clinical development in CNS and represents a promising opportunity for these patients.”

Agitation and aggression are common symptoms in PMS, and vafidemstat has previously shown effectiveness in reducing these behaviours in patients with Autism Spectrum Disorder (ASD), Attention Deficit Hyperactivity Disorder (ADHD), and Borderline Personality Disorder (BPD). In the study, 30 PMS patients underwent psychometric evaluations using various standardized scales, leading to the identification of three patient clusters with distinct cognitive and behavioral profiles. The study found that deletion size in SHANK3 correlated with certain psychometric scores, providing valuable insights into the condition’s variability.

Dr Julian Nevado, first author of the study and Head of Structural and Functional Genomics at INGEMM commented, “There is currently no treatment approved specifically for Phelan-McDermid syndrome. This study is a proof of concept that highlights the importance of patient stratification in PMS. Selecting PMS patients for a clinical trial based on their distinctive clinical and genetic characteristics will be essential in the era of personalized precision medicine.”

The psychiatric drug vafidemstat builds clinical data through Phase III and Phase IIb trials operated by Oryzon for BPD and schizophrenia treatment, respectively. The company performs searches regarding vafidemstat assessments for rare monogenic neurodevelopmental disorders like PMS and Kabuki Syndrome. The research results will help identify appropriate patients for future trials, thereby strengthening precision medicine applications in treating Central Nervous System disorders.