Neuren Pharmaceuticals Annual Report 2023

A redacted version of the expanded licence agreement between Neuren and Acadia was filed with the US Securities and Exchange Commission as a material contract exhibit to Acadia’s 2023 10-K Annual Report, which is available to view via the SEC Filings section of Acadia’s website. Following the expansion of the partnership with Acadia for trofinetide to worldwide, Acadia is now advancing in key markets outside North America. For Europe, Acadia is engaging with the European Medicines Agency (EMA) in Q1 2024, with a potential Marketing Authorisation Application filing in H1 2025. For Japan, Acadia is engaging with the regulator, Pharmaceuticals and Medical Devices Agency (PMDA) in 2024. There is urgent unmet need for a treatment for Rett syndrome around the world, evidenced by communications received from families, patient support groups and physicians. The estimated number of potential patients and currently identified patients is shown in the table below. Neuren expects rates of diagnosis to increase with greater awareness and accelerate with the availability of a treatment. Europe Japan Other Potential Rett patients 9,000 – 14,0001 1,000 – 2,0001 ~30,0002 Currently identified Rett patients ~4,0002 ~800 – 1,0002 ~2,0002 1 Acadia estimates 2 Neuren estimates based on prevalence studies and patient organisations About Rett syndrome Rett syndrome is a seriously debilitating and life-threatening neurological disorder. It is first recognized in infancy and seen predominantly in girls, but can occur very rarely in boys. At diagnosis, Rett syndrome has often been misdiagnosed as autism, cerebral palsy, or non-specific developmental delay. Most cases of Rett syndrome are caused by mutations on the X chromosome on a gene called MECP2. Rett syndrome strikes all racial and ethnic groups and has been estimated to occur worldwide in 1 of every 10,000 to 15,000 female births, causing problems in brain function that are responsible for cognitive, sensory, emotional, motor and autonomic function. These problems can include learning, speech, sensory sensations, mood, movement, breathing, cardiac function, and even chewing, swallowing, and digestion. Rett syndrome symptoms appear after an early period of apparently normal or near normal development until six to eighteen months of life, when there is a slowing down or stagnation of skills. A period of regression then follows, with loss of communication skills and purposeful hand use, loss or impairment of walking, and the onset of stereotypic hand movements. Other problems frequently include seizures and erratic breathing patterns, an abnormal side-to-side curvature of the spine (scoliosis), and sleep disturbances. OPERATING REVIEW CONTINUED i Development and commercialisation outside North America In July 2023 Neuren and Acadia expanded their partnership for trofinetide from North America to worldwide. Neuren received US$100 million up-front and is eligible to receive milestone payments and royalties related to development and commercialization of trofinetide outside North America as set out in the table below. Trofinetide Payment Upon 1st commercial sale for Rett in Europe US$35m Upon 1st commercial sale for Rett in Japan US$15m Upon 1st commercial sale for second indication in Europe US$10m Upon 1st commercial sale for second indication in Japan US$4m Total development milestones US$64m Europe Up to US$170m Japan Up to $110m Rest of World Up to US$83m Total sales milestones on achievement of escalating annual net sales thresholds Up to US$363m Tiered royalties on net sales Mid-teen to low twenties per cent Neuren Pharmaceuticals Limited Annual Report 2023 8

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