Oryzon announces publication of study on Phelan-McDermid Syndrome (PMS) patients, a form of autism, paving the way for a novel personalized medicine approach with vafidemstat

Oryzon Genomics S.A., (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company leveraging epigenetics to develop therapies in diseases with strong unmet medical need, announced today that the final results of an observational clinical study aimed at psychometrically characterizing individuals with Phelan-McDermid syndrome (PMS) carrying deletions or pathogenic variants in SHANK3 have been published online in the journal Frontiers in Psychiatry. The purpose of this study was to gather data that could serve as a foundation for a future precision psychiatry clinical trial involving vafidemstat for this patient population.

Agitation and aggression are key components of PMS, and vafidemstat has demonstrated efficacy in reducing agitation and aggression in a basket trial involving patients with Autism Spectrum Disorder (ASD), Attention Deficit Hyperactivity Disorder (ADHD), and Borderline Personality Disorder (BPD). This characterization paves the way for addressing these symptoms in a subset of PMS patients, further expanding the potential application of vafidemstat in reducing aggression in this specific patient population.

Dr. Jordi Xaus, Oryzon’s CSO, stated, “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.

In this pilot study, we clinically characterized the profile of 30 subjects, all diagnosed of molecularly confirmed PMS, by applying different psychometric scales, including Repetitive Behavior Questionnaire (RBQ), Vineland Adaptive Behavior Scales, ADOS-2, the Battelle developmental inventory screening test and the Behavior Problems Inventory (BPI).

As reported in the publication, unsupervised hierarchical clustering of the collected psychometric data identified three groups of patients, with different cognitive, aggression and behavioral profile scores. Statistically significant differences in deletion sizes were detected comparing the three clusters (corrected by gender), and the size of the deletion appears to be correlated with some of the assayed scores.

A link to access the online publication can be found here.

Oryzon is developing vafidemstat in prevalent multifactorial psychiatric indications like BPD, with a Phase III trial in preparation, or schizophrenia, with the ongoing EVOLUTION Phase IIb trial, but is also committed to exploring the potential of vafidemstat in rare monogenic psychiatric and neurodevelopmental disorders such as PMS or Kabuki Syndrome. In the Phase IIb PORTICO trial in BPD, vafidemstat demonstrated nominal statistical significance in reducing agitation and aggression, also a relevant feature of some PMS patients and a significant caregiver burden that often results in sedation or institutionalization of these PMS patients.

This published study provides relevant data for patient inclusion in a future clinical study exploring vafidemstat actionability for SHANK3-associated psychiatric disorders, including PMS, constituting a good example of how precision medicine may open new avenues to understand and treat Central Nervous System (CNS) disorders, pioneering individual management in PMS.