Neuren Pharmaceuticals (NEU) Study Result summary

Study design and patient population

• Phase 2 open-label trial of NNZ-2591 in Angelman syndrome enrolled 16 children aged 3–17 years at three Australian sites, focusing on safety, tolerability, and pharmacokinetics as primary endpoints.

• Participants had severe developmental impairment, with a mean age of 10.1 years and low developmental quotient scores.

• The study included frequent clinic and home visits, with a demanding protocol for participants and families.

• 13 of 16 subjects completed the study; discontinuations were due to compliance, protocol deviation, or COVID-19-related events.

• NNZ-2591 was administered as an oral liquid with dose escalation up to 12 mg/kg over 6 weeks, followed by a 13-week treatment and two-week post-treatment follow-up.

Safety and tolerability

• NNZ-2591 was safe and well-tolerated, with no serious adverse events or meaningful trends in lab values, ECGs, or other safety parameters.

• Most adverse events were mild to moderate and not drug-related; somnolence was mild and related in two cases.

• Common adverse events included viral infections, nasopharyngitis, seizures, insomnia, and mild gastrointestinal symptoms.

• Seizures occurred in four subjects, consistent with Angelman syndrome, and were not drug-related.

• One discontinuation occurred due to a COVID-19-related adverse event.

Efficacy results

• Statistically significant and clinically meaningful improvements were observed in both clinician and caregiver global impression scores (CGI-I, CIC), with greatest gains in communication, behavior, cognition, and motor abilities.

• 11 of 13 children improved on clinician-rated CGI-I (mean 3.0, p=0.0010); 8 of 12 improved on caregiver CIC (mean 3.2, p=0.0273); all 8 children aged 3–12 improved on both measures (mean CGI-I 2.8, mean CIC 2.6, both p=0.0078).

• Four subjects improved by one point on the Clinical Global Impression of Severity after 13 weeks.

• Bayley-4 developmental scales showed improvement in cognitive, motor, and communication domains in over 50% of children despite the short trial duration.

• Clinician and caregiver testimonials highlighted better sleep, focus, communication, balance, and reduced behavioral issues.