Neuren Pharmaceuticals Annual Report 2022

OPERAT I NG REV I EW CON T I NU E D In December 2022, Neuren announced that the first subject in the oldest age group had completed treatment in the AS trial and in the PMS trial. Each subject was successfully escalated up to the target dose following safety and tolerability reviews by an independent data and safety monitoring committee (DSMC). No serious adverse events were reported and no dose modifications were required. Most of the adverse events reported were mild and not considered to be related to study drug. There were no clinically relevant observations in safety laboratory measurements or cardiac tests. A series of top-line results announcements from the trials are anticipated, commencing with Phelan-McDermid syndrome in H2 2023. The overall aim of these first trials is to expedite the generation of data that will enable the subsequent trials to be designed as registration trials. The primary aim is to confirm the safety and pharmacokinetics of NNZ-2591 in pediatric patients. However, each trial will also assess the treatment impact across multiple efficacy measures to generate data to select the best primary efficacy endpoint or endpoints for the registration trials. The trials maximise the opportunity to demonstrate effects by focusing on pediatric patients and treating them for 13 weeks. Preparation for Phase 3 In order to expedite the overall development plan, in parallel with conducting the Phase 2 trials Neuren is executing the additional development work required to be ready for Phase 3 development. This includes non-clinical toxicity studies to support longer clinical trials and commercial use of the product, as well as optimisation of the drug product and drug substance manufacturing arrangements. Strong foundations for Phase 2 trials In designing and executing the NNZ-2591 development program, Neuren has been able to leverage the extensive and highly relevant experience the management team has gained from the trofinetide Rett syndrome program across manufacturing, nonclinical, clinical and regulatory. Neuren has meticulously built strong foundations in each of these areas to enable Phase 2 trials in multiple indications. Clear and consistent efficacy in mouse models of all four disorders The studies in these models compared normal mice (“wild type”) and mice with a disrupted gene (“knockout”). The knockout mice exhibit behavioural and biochemical deficits that mimic each disorder in humans. The wild type mice and the knockout mice were each treated with placebo and NNZ-2591. In all four models, treatment with NNZ-2591 for 6 weeks eliminated all the deficits so that the knockout mice were indistinguishable from the wild type mice. Treatment had no impact on the wild type mice which is important from a safety point of view. Following review of the data from the mouse models and the mechanistic rationale for treatment, FDA granted Orphan Drug designation for NNZ-2591 in each of the four disorders. Neuren Pharmaceuticals Limited Annual Repor t 2022 9

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