Neuren Pharmaceuticals revealed top-line results from its Phase 2 clinical trial of NNZ-2591 in children with Pitt Hopkins syndrome (PTHS). This trial demonstrated statistically significant improvements from baseline across all four efficacy measures, assessed by both clinicians and caregivers (Wilcoxon signed rank test p<0.05). These measures were specifically designed to address the core characteristics of PTHS, a severely debilitating condition with no approved treatments.

Key Findings:

• Clinically Meaningful Improvements: Both clinician and caregiver global efficacy measures showed significant improvements:
  • Clinical Global Impression of Improvement (CGI-I): Mean score of 2.6, with 9 out of 11 children showing improvement.
  • Caregiver Overall Impression of Change (CIC): Mean score of 3.0, with 8 out of 11 children showing improvement.
• Core Symptom Improvements: Notable advancements in communication, social interaction, cognition, and motor abilities were observed.
• Safety Profile: NNZ-2591 was safe and well-tolerated, with no serious or severe adverse events and no meaningful trends in laboratory values or other safety parameters during treatment.

Neuren CEO Jon Pilcher commented, "We are very excited about the results of this first clinical trial in Pitt Hopkins patients. This underserved community has such urgent unmet needs, and we are now closer to our goal of developing the first approved treatment. We are very grateful to everyone involved in this groundbreaking trial."

Dr. Elliott Sherr, Professor of Neurology and Pediatrics at the University of California San Francisco, and trial investigator, stated, "I am optimistic about the results in the PTHS-specific measures. The mechanism of action of NNZ-2591 supports this response in PTHS and its potential in other neurodevelopmental disorders."

Dr. Nancy Jones, Neuren Vice President of Clinical Development, added, "The consistent results on the PTHS-specific assessments affirm the need for syndrome-specific measurements in severe neurodevelopmental disorders."

Study Design: The open-label Phase 2 trial included 16 children aged 3 to 17 years (mean age 9 years) at five hospitals in the United States. The study examined safety, tolerability, pharmacokinetics, and efficacy over 13 weeks of treatment with NNZ-2591, administered as an oral liquid dose twice daily. The primary endpoints were safety, tolerability, and pharmacokinetics, with secondary endpoints including efficacy measures specifically designed for PTHS.

Safety and Tolerability: NNZ-2591 demonstrated a good safety profile, with all Treatment Emergent Adverse Events (TEAEs) being mild to moderate and mostly unrelated to the study drug. No serious TEAEs or meaningful trends in safety parameters were observed.

Efficacy Results:

• Global Measures: 9 out of 11 children showed improvement in the CGI-I, with a mean score of 2.6. Similarly, 8 out of 11 children showed improvement in the CIC, with a mean score of 3.0.
• Symptom Severity: 6 out of 11 children improved in the CGI-S, with notable reductions in severity scores.
• Top Concerns: 8 out of 11 children showed improvement in the Caregiver Top 3 Concerns overall score.

Conclusion: The positive results from this Phase 2 trial bolster confidence in NNZ-2591's potential relevance for treating multiple neurodevelopmental disorders. Neuren Pharmaceuticals remains committed to advancing this promising treatment to address the urgent needs of the PTHS community and beyond.