Optimum dose identified In the PMS model, the effect of four escalating dose levels was investigated. The results of this dose ranging study were consistent across all 8 behavioral tests and the incidence of seizures, demonstrating that the second highest dose was the optimum dose level in the mouse model. Comparison with human pharmacokinetic data from the Phase 1 clinical trial has informed the equivalent human dose for the clinical trials in patients. A further observation was that the optimum dose in this 6-week study showed better efficacy than the same dose in an earlier study for 3 weeks, indicating that efficacy increases with treatment duration. OPTIMUM DOSE IN MOUSE MODEL OF PHELANMCDERMID 9 Memory Learning Sociability WT + vehicle KO + vehicle KO + x mg/kg KO + 2x mg/kg KO + 4x mg/kg KO + 8x mg/kg 0% 60% 50% 30% 10% 10% Incidence of seizures OPTIMUM DOSE IN MOUSE MODEL OF PHELANMCDERMID 10 Motor function Anxiety Repetitive behavior Daily living Daily living OPTIMUM DOSE IN MOUSE MODEL OF PHELANMCDERMID 10 Motor function Anxiety Repetitive behavior Daily living Daily living DOSE IN MOUSE MODEL OF PHELAN9 Learning Sociability e KO + vehicle KO + x mg/kg KO + 2x mg/kg KO + 4x mg/kg KO + 8x mg/kg 60% 50% 30% 10% 10% Incidence of seizures OPTIMUM DOSE IN MOUSE MODEL OF PHELANMCDERMID 10 Motor function Anxiety Repetitive behavior Daily living Daily living OPTIMUM DOSE IN MOUSE MODEL OF PHELANMCDERMID 10 Motor function Anxiety Repetitive behavior Daily living Daily living OPERATING REVIEW CONTINUED Neuren Pharmaceuticals Limited Annual Report 2025 15
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