• FDA provided feedback on Neuren's plans for NNZ-2591 in hypoxic ischemic encephalopathy (HIE) and Pitt Hopkins syndrome (PTHS)
• FDA generally accepted Neuren's proposed IND-opening clinical study for HIE but requested additional animal data
• For PTHS, FDA indicated a PTHS-specific clinical global impression (CGI) scale may be used as a co-primary endpoint

Neuren Pharmaceuticals received feedback from the US FDA on its plans to develop NNZ-2591 for the treatment of hypoxic ischemic encephalopathy (HIE) and Pitt Hopkins syndrome (PTHS). For the HIE program, the FDA generally accepted Neuren's plan to submit an IND application and conduct an initial clinical study to evaluate the pharmacokinetics, tolerability and safety of NNZ-2591 in neonates and infants with HIE. However, the FDA requested that Neuren provide additional juvenile animal study data to support NNZ-2591 dosing in neonatal participants prior to initiating the clinical study. Neuren plans to generate this data before submitting the IND application and commencing the clinical study later in 2026. For the PTHS program, the FDA feedback indicated that in a controlled trial to demonstrate efficacy of NNZ-2591, a PTHS-specific clinical global impression (CGI) scale may be used as a co-primary endpoint if it is accompanied by an observer-reported functional outcome measure. Neuren is currently assessing alternative trial designs and endpoint analysis methodologies to accommodate the fact that PTHS is significantly more rare and generally more profoundly disabling than Phelan McDermid syndrome, for which a similar approach is being implemented in Neuren's ongoing Phase 3 trial. A further interaction with the FDA will likely be required to finalize this assessment, but Neuren still intends to initiate the next trial in 2026.