US$10m upfront in 2018 US$10m in2022 followingacceptanceof NDAfor review US$40m in2023following1st commercialsalein the US US$50m In 2024 one third share of Priority Review Voucher awardedtoAcadia (soldfor US$150m) US$55m Milestone payments related to Fragile X U Tiered Royalty Rates (% of net sales) Annual Net Sales Rates ≤US$250m 10% >US$250m, ≤US$500m 12% >US$500m, ≤US$750m 14% >US$750m 15% Sales Milestones Net Salesin one calendar year US$m ≥US$250m 50 ≥US$500m 50 ≥US$750m 100 ≥US$1bn 150 U U North America US$100m upfront in 2023 US$35m following 1st commercial sale in Europe US$15m following 1st commercial sale in Japan US$10m following 1st commercial sale of a 2nd indication Europe US$4m following 1st commercial sale of a 2nd indication Japan Sales milestones On achievement of escalating annual net sales thresholds: Europe: up to US$170m Japan: up to US$110m RoW :upto US$83m Tiered royalties Mid- teens to low- 20s%of net sales Outside North America U U OPERATING REVIEW CONTINUED NEUREN’S ATTRACTIVE ECONOMICS FROM DAYBUE (TROFINETIDE) IN NORTH AMERICA In 2024, Neuren earned income from DAYBUE of A$213 million. In addition to royalties of A$56 million, Neuren received a sales milestone payment of A$80.5 million earned on achievement of the first in a series of four thresholds of total annual net sales of DAYBUE in North America, due to net sales for 2024 exceeding US$250 million. Neuren also earned A$76.5 million from Acadia, being one third of the market value of the Rare Pediatric Disease Priority Review Voucher (PRV) that was awarded to Acadia by the FDA upon marketing authorisation of DAYBUE. Acadia completed the sale of the PRV for US$150 million in December 2024. Neuren is eligible to receive ongoing royalties on net sales of trofinetide in North America, plus milestone payments of up to US$350m on achievement of a series of four thresholds of total annual net sales. No royalties or similar costs are payable by Neuren to third parties, which means Neuren’s revenue from Acadia flows through to pre-tax profit. The royalty rates and sales milestone payments are related to the total amount of annual net sales of trofinetide in all indications in North America, as set out in the following tables: US$10m upfront in 2018 US$10m in2022 followingacceptanceof NDAfor review US$40m in2023following1st commercialsalein the US US$50m In 2024 one third share of Priority Review Voucher awardedtoAcadia (soldfor US$150m) US$55m Milestone payments related to Fragile X U Tiered Royalty Rates (% of net sales) Annual Net Sales Rates ≤US$250m 10% >US$250m, ≤US$500m 12% >US$500m, ≤US$750m 14% >US$750m 15% Sales Milestones Net Salesin one calendar year US$m ≥US$250m 50 ≥US$500m 50 ≥US$750m 100 ≥US$1bn 150 U U North America US$100m upfront in 2023 US$35m following 1st commercial sale in Europe US$15m following 1st commercial sale in Japan US$10m following 1st commercial sale of a 2nd indication Europe US$4m following 1st commercial sale of a 2nd indication Japan Sales milestones On achievement of escalating annual net sales thresholds: Europe: up to US$170m Japan: up to US$110m RoW :upto US$83m Tiered royalties Mid- teens to low- 20s%of net sales Outside North America U U In October 2024, Health Canada approved Acadia’s New Drug Submission for DAYBUE and Acadia anticipates first sales in Q3 2025, pending price negotiations. Canada net sales will be added to US net sales to give total net sales for calculation of Neuren’s North America royalties and sales milestone payments. In Canada, the prevalence of Rett Syndrome is estimated to be 600 to 900 patients. LONG TERM GROWTH OPPORTUNITY FOR TROFINETIDE THROUGH GLOBAL EXPANSION 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. 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. In January 2025, Acadia submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for trofinetide for the treatment of Rett syndrome in adults and pediatric patients two years of age and older. Acadia anticipates potential approval in Q1 2026. If granted marketing authorization, trofinetide will be the first and only approved therapy for Rett syndrome in the European Union. In the meantime, Acadia anticipates initiating Managed Access Programs in Europe in Q2 2025, which will provide valuable real-world experience of treatment for European families and physicians in advance of full commercial launch. Neuren Pharmaceuticals Limited Annual Report 2024 7
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