Pitt Hopkins Syndrome

Pitt Hopkins syndrome (PTHS) is a neurodevelopmental condition affecting both males and females, caused by the loss of one copy or a mutation of the TCF4 gene on chromosome 18. The incidence of PTHS is not known, however it has been estimated as between 1 in 11,000 and 1 in 41,000 people.

Characteristics of PTHS are developmental delay with moderate-to-severe intellectual disability and behavioral differences, hyperventilation and/or breath-holding while awake, seizures, gastrointestinal issues, lack of speech, sleep disturbance, stereotypic hand movements and distinctive facial features. Some individuals with PTHS are diagnosed with autism.

NNZ-2591 was tested in the tcf4 mutation mouse model, which exhibits features of PTHS in humans, comparing normal mice and mice with a disrupted tcf4 gene. In the mice with a disrupted gene, treatment with NNZ-2591 for 6 weeks normalized the deficits in all the tests of hyperactivity, daily living, learning and memory, sociability, motor performance and stereotypy.

On 27 May 2024, Neuren announced top-line results from a Phase 2 clinical trial of NNZ-2591 in children with PTHS. Significant improvement was observed by both clinicians and caregivers from treatment in all four efficacy measures specifically designed for Pitt Hopkins syndrome. Improvements were seen in clinically important aspects of PTHS.

Neuren has been granted Orphan Drug designation by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for NNZ-2591 to treat PTHS.