Oryzon Gains Ema Cta For Vafidemstat Phase Ii Pms Study

With no approved pharmacologic treatment on the market for Phelan-McDermid Syndrome, Oryzon Genomics has secured a Clinical Trial Authorisation from the European Medicines Agency to advance vafidemstat into the HOPE-2 Phase IIa study, a development that places the LSD1 inhibitor at the centre of an unmet-need indication where regulatory pathways for rare neurodevelopmental disorders are under active scrutiny.

HOPE-2 is a single-centre, single-arm, open-label study enrolling 12 adult patients with PMS, a severely disabling neurodevelopmental disorder caused by deletions or pathogenic mutations in the SHANK3 gene. The primary endpoint is safety and tolerability over a 12-week treatment period, with secondary endpoints covering anger and aggression via the Aberrant Behavior Checklist Irritability Subscale and the Clinical Global Impression of Severity, alongside broader disease measures including the Phelan-McDermid Syndrome Assessment of Severity and Repetitive Behavior Scale-Revised. An investigator-assessed extension to week 24 is permitted based on clinical benefit.

For regulatory affairs teams tracking EMA's rare disease framework, the CTA authorisation carries structural context: HOPE-2 is partially funded through Oryzon's VANDAM project under Med4Cure, an Important Project of Common European Interest on Health. That funding designation signals alignment with EU-level rare disease priorities and may inform how similar orphan-indication CTAs are scoped and reviewed going forward.

PMS affects an estimated 1 in 7,300 people in the United States, with no approved therapy specifically targeting the aggression phenotype that characterises the condition. Current off-label management carries documented efficacy limitations and safety concerns, a gap that regulatory reviewers will weigh against vafidemstat's preclinical data, which includes reversal of social behaviour and aggression phenotypes in SHANK3-deficient mouse models. Oryzon cites supportive clinical signals from the REIMAGINE Phase IIa trial in autism spectrum disorder as additional basis for the programme.

Oryzon will work with the Spanish Phelan-McDermid Syndrome Association on participant identification, a patient-organisation collaboration that aligns with EMA expectations for rare disease trial feasibility planning.

Enrolment progress and the 12-week primary safety readout will serve as the first measurable checkpoint for regulatory teams assessing whether vafidemstat's LSD1 inhibition profile translates from ASD models to a defined genetic subpopulation.

Source: Oryzon Genomics via company press release, 28 September 2026.