OPERATING REVIEW CONTINUED 1 NEU-2591-PMS-001: An Open-Label Study of the Safety, Tolerability, and Pharmacokinetics of Oral NNZ-2591 in Phelan-McDermid Syndrome – 13 weeks treatment of patients age 3-12 years at 4 US sites 2 Wilcoxon signed rank test – p-values are nominal without type 1 error control 3 Based on post hoc analysis of overall VABS-3 secondary endpoint The Koala trial co-primary endpoints will be the change from baseline in the Receptive Communication sub-domain of the Vineland Adaptive Behavior Scales, Third Edition (VABS-3 Receptive-Raw Score) and the overall score in the Phelan-McDermid Syndrome Assessment of Change (PMSA-C, previously referred to as CGI-I in Neuren’s Phase 2 trial). Both measures were robustly positive with clinically meaningful improvement in Neuren’s Phase 2 open-label clinical trial. 16 out of 18 children showed improvement measured by the VABS-3 Receptive-Raw Score, with mean improvement of 7.5 from a mean baseline of 29.0 (Wilcoxon signed rank test p=0.0001) and 16 out of 18 children showed improvement from baseline measured by the PMSA-C with a mean score of 2.4 (Wilcoxon signed NNZ-2591 was safe and well tolerated in Phase 2, with no clinically meaningful changes in safety parameters during treatment. Co-primary Endpoints in Phase 2 Results1 Phelan-McDermid Syndrome Assessment of Change (PMSA-C), previously referred to as CGI-I in Phase 2 16/18 subjects showed improvement Mean score: 2.4 (P < 0.00012) Receptive Communication sub-domain of the Vineland Adaptive Behavior Scales, 3rd Edition (VABS-3 Receptive-Raw Score) 16/18 subjects showed improvement Mean improvement: 7.5 (from baseline of 29.0)3 (P = 0.00012)3 Key Secondary Endpoint in Phase 2 Results1 Caregiver Impression of Change (CIC) score 15/18 subjects showed improvement Mean score: 2.7 (P < 0.00032) rank test p<0.0001). The endpoints pair the caregiver’s assessment of change in one important symptom area with the clinician’s assessment of change across multiple aspects of PMS. Communication is one of the most impactful health concerns in PMS reported by caregivers. Receptive communication, as measured by VABS-3 Receptive-Raw Score, is the ability to receive and understand non-verbal and verbal interactions which is a foundational skill for the development of learning, social interaction, and speech. The results of Neuren’s Phase 2 clinical trial have been published in the journal Neurology Genetics (NNZ-2591 in Children and Adolescents With Phelan-McDermid Syndrome | Neurology Genetics). Neuren Pharmaceuticals Limited Annual Report 2025 12
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