Neuren launches historic Phase 3 trial for untreatable childhood disorder
Neuren Pharmaceuticals (ASX: NEU) has announced the commencement of dosing in the Neuren PMS Phase 3 trial, marking the first Phase 3 trial ever conducted for Phelan-McDermid syndrome globally. The first participant has completed a 4-week screening period and commenced the 13-week period of twice-daily dosing in the Koala Phase 3 clinical trial of NNZ-2591.
The trial represents a critical milestone for patients with Phelan-McDermid syndrome, a rare genetic disorder for which zero approved treatments currently exist. Koala is a randomised, double-blind, placebo-controlled clinical trial evaluating the safety and efficacy of NNZ-2591 in approximately 160 children aged 3 to 12 years with PMS.
The Neuren PMS Phase 3 trial positions the company as first-mover in an orphan disease space with no competition and regulatory tailwinds already secured through multiple FDA designations.
What is Phelan-McDermid syndrome?
Phelan-McDermid syndrome is a genetic disorder caused by a deletion or other change in the 22q13 region of chromosome 22, which includes the SHANK3 gene, or a mutation of the gene. The SHANK3 gene produces a protein that supports the structure of synapses between neurons in the brain. When this gene is damaged or missing, brain development and function are severely impacted.
The condition is estimated to affect between 1 in 8,000 and 1 in 15,000 people. Currently, there are no medications, drugs, or therapies specifically approved for PMS, creating an overwhelming unmet medical need.
The syndrome has severe quality of life impacts on patients and their families. Key characteristics include:
- Moderate to severe developmental and intellectual impairment
- Delayed or absent speech
- Symptoms of autism
- Low muscle tone and motor delays
- Mild to severe epilepsy
- Behavioural problems
- Difficulties with socialisation, activities of daily living and self-care
For investors, the severity of symptoms combined with zero treatment options creates strong commercial potential if NNZ-2591 succeeds in demonstrating efficacy and safety.
Trial momentum builds with strong family interest
Early recruitment data suggests significant community engagement with the trial. To date, 25 families have been referred to the two currently activated trial sites. An additional 37 families are already on waitlists for a trial site in a convenient geographical location.
Site activation is progressing rapidly. Two additional sites are expected to activate in February, with 20 more across the US progressing towards activation during the first half of 2026. More participants are scheduled to start dosing or screening during February and March.
| Metric | Current Status | Near-Term | H1 2026 Target |
|---|---|---|---|
| Families referred | 25 | Growing | Expanding |
| Waitlist families | 37 | Adding | Multiple sites |
| Active sites | 2 | 4 (February) | 22+ |
Jon Pilcher, CEO
“We are excited to have started the treatment phase of our Koala Phase 3 study and are very encouraged by the level of interest in the PMS community. We are proud to be the presenting sponsor of the PMSF Family Conference in July and we anticipate strong momentum for Koala as trial sites around the US progressively activate during the first half of this year.”
Regulatory designations de-risk the pathway
NNZ-2591 has secured Fast Track, Rare Pediatric Disease, and Orphan Drug designations from the US Food and Drug Administration.
These designations provide incentives to encourage development of therapies for rare and serious diseases. For investors, these regulatory advantages reduce execution risk and improve the commercial opportunity if the trial succeeds.
Strategic community engagement strengthens position
Neuren continues its commitment to the PMS community as the Presenting Sponsor of the 2026 Phelan-McDermid Syndrome Foundation Family Conference, “The Climb We Make Together”, which will take place in Colorado in July 2026.
Strong relationships with patient advocacy groups support trial recruitment and build brand equity ahead of potential commercialisation. For rare disease drug developers, community engagement is essential to identifying patients, understanding their needs, and establishing trust with families who may participate in clinical trials.
The conference timing in mid-2026 aligns with the trial recruitment phase, positioning Neuren to maintain engagement with families as additional sites activate across the US.
What comes next for Neuren’s NNZ-2591 programme
The first half of 2026 will see multiple site activations and recruitment momentum building across the US. The trial is registered as NCT07281079 on ClinicalTrials.gov.
NNZ-2591 has platform potential across multiple orphan indications, amplifying the commercial opportunity beyond PMS alone. Positive results have already been achieved in Phase 2 clinical trials in Phelan-McDermid syndrome, Pitt Hopkins syndrome, and Angelman syndrome. Each programme has been granted orphan drug designation in the United States and the European Union.
For investors, the breadth of the NNZ-2591 development programme represents multiple shots on goal in rare paediatric neurodevelopmental disorders, each with significant unmet need and no approved treatments. Success in the Neuren PMS Phase 3 trial could validate the compound’s mechanism across this broader patient population.
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