OPERATING REVIEW CONTINUED Positive results in Phelan-McDermid syndrome Phase 2 trial In December 2023, Neuren announced positive top-line results from the Phase 2 clinical trial of NNZ-2591 in children with Phelan-McDermid syndrome. NNZ-2591 was well tolerated and demonstrated a good safety profile. There was only one serious treatment emergent adverse event (TEAE) of gastroenteritis, which was not related to study drug and occurred during the safety follow-up period after end of treatment. Three subjects discontinued due to TEAEs, two testing positive for COVID-19 and one due to seizures that were not related to study drug. No clinically significant changes in laboratory values, electrocardiogram (ECG) or other safety parameters were observed during treatment. TEAEs occurring in two or more subjects are listed in the following table: Event N=18 n (%) Event N=18 n (%) Constipation 2 (11.1) Somnolence 3 (16.7) Diarrhea 2 (11.1) Pyrexia 3 (16.7) Nausea 2 (11.1) Fatigue 2 (11.1) Vomiting 2 (11.1) Aggression 2 (11.1) COVID-19 3 (16.7) Insomnia 2 (11.1) Nasopharyngitis 2 (11.1) Decreased Appetite 3 (16.7) Otitis Media 2 (11.1) Rhinorrhea 2 (11.1) Psychomotor Hyperactivity 4 (22.2) Significant improvement was observed by both clinicians and caregivers from treatment, across multiple efficacy measures. Improvements were consistently seen across many of the core PMS characteristics. The results for the global efficacy measures rated by both clinicians and caregivers showed a level of improvement typically considered clinically meaningful. 16 out of 18 children showed improvement measured by the Clinical Global Impression of Improvement (CGI-I), an assessment by the clinician of the child’s overall status compared with baseline. The mean CGI-I score was 2.4. 10 children received a score of either 1 (“very much improved”) or 2 (“much improved”). 15 out of 18 children showed improvement measured by the Caregiver Overall Impression of Change (CIC), an assessment by the caregiver of the child’s overall status compared with baseline. The mean CIC score was 2.7. Seven children received a score of either 1 (“very much improved”) or 2 (“much improved”). CGI-I and CIC are 7 point scales in which scores of 1, 2 or 3 indicate improvement. Efficacy endpoints summary 30 • Statistically significant improvement vs baseline in 10/14 efficacy endpoints • Mean CGI-I of 2.4 and Median of 2.0 with p-value <0.0001 • Mean CIC of 2.7 and Median of 3.0 with p-value =0.0003 Global Behaviour GI Health Quality of Life Symptom Specific Sleep CGI-I <0.0001 CIC 0.0003 CGI-S 0.0156 Aberrant Behavior Checklist-2 total 0.0013 Behavior Problems Inventory total frequency 0.0326 Vineland Adaptive Behavior Scales Composite 0.1710 GIHQ total frequency 0.0013 Efficacy measures and p-values1 (Total/Overall scores) PMS Clinician Domain Specific Rating Scale total 0.0156 Caregiver Top 3 Concerns total 0.0005 QL InventoryDisability total 0.0066 Impact of Childhood Neurologic Disability 0.1094 CSHQ total 0.0191 MB-CDI Total Vocabulary 0.0647 ORCA T-Score 0.0714 Communication 1 Wilcoxon signed rank test 1 Wilcoxon signed rank test Neuren Pharmaceuticals Limited Annual Report 2023 10
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