NNZ-2591 FOR MULTIPLE NEURODEVELOPMENTAL DISORDERS In July and August 2022, Neuren announced the commencement of Phase 2 clinical trials of its second drug candidate NNZ2591 for Phelan-McDermid syndrome (PMS), Angelman syndrome (AS) and Pitt Hopkins syndrome (PTHS) after receiving in March 2022 approval from the FDA for Investigational New Drug (IND) applications to conduct the trials. In December 2022, Neuren submitted an IND application to the FDA for approval to proceed with a Phase 2 trial in Prader-Willi syndrome (PWS) and received approval from the FDA in January 2023. There are currently no approved therapies for these debilitating neurodevelopmental disorders, other than human growth hormone to treat some aspects of PWS. The estimated number of potential patients being targeted across these four disorders is more than five times larger than Rett syndrome. Neuren retains all global rights to NNZ-2591. Five times larger opportunity for NNZ-2591 Potential patients Disorder Gene mutation Published prevalence estimates US1 Europe1 Asia1, 2 Phelan-McDermid SHANK3 1/8,000 to 1/15,000 males and females 22,000 28,000 81,000 Angelman UBE3A 1/12,000 to 1/24,000 males and females 14,000 18,000 52,000 Pitt Hopkins TCF4 1/34,000 to 1/41,000 males and females 7,000 9,000 25,000 Prader-Willi 15q11-q13 1/10,000 to 1/30,000 males and females 13,000 16,000 47,000 56,000 71,000 205,000 1 Estimates derived by applying the mid-point of the prevalence estimate range to the populations under 60 years 2 Asia comprises Japan, Korea, Taiwan, Israel and urban populations of China and Russia Phase 2 trials in AS, PMS and PTHS – results expected from H2 2023 The open label Phase 2 trials are each enrolling up to 20 children to examine safety, tolerability, pharmacokinetics and efficacy over 13 weeks of treatment with NNZ-2591. All subjects receive NNZ-2591 as an oral liquid dose daily, with escalation in two stages up to the target dose during the first 6 weeks of treatment, subject to independent review of safety and tolerability data. The trials are enrolling subjects in three age groups. Safety and tolerability data in the oldest age group must be independently reviewed before proceeding with dosing in the second age group and then safety and tolerability data in the second age group must be independently reviewed before proceeding with dosing in the youngest age group. The study begins with 4 weeks of observation to thoroughly examine baseline characteristics prior to treatment, against which safety and efficacy are assessed for each child. This is followed by the treatment period of 13 weeks. A follow-up assessment is made 2 weeks after the end of treatment. OPERAT I NG REV I EW CON T I NU E D Angelman Phelan-McDermid Pitt Hopkins n subjects Up to 20 Up to 20 Up to 20 Age range 3 to 17 3 to 12 3 to 17 (Sequential enrolment in three age groups following DSMC review) Location Australia US US Baseline observation Week 0 Week 4 Week 10 Week 17 Week 19 Up-titration NNZ-2591 treatment Follow-up Phase 3 preparation Non-clinical toxicity studies and optimisation of drug product and drug substance manufacturing Neuren Pharmaceuticals Limited Annual Repor t 2022 8
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