Ann: 2024 Annual Report to shareholders, page-5

Good report. One new statement, regarding the recent announcement of NNZ-2591 in hypoxic-ischemic encephalopathy (‘HIE’), answers a question posed in the previous thread. The company says ‘NNZ-2591 can potentially provide a highly differentiated form of treatment continuing beyond acute treatment in the neonatal intensive careunit to target both the acute effects and the long term neurodevelopmental impairments resulting from HIE’. No further clarification about mouse models or the commercial reasons for targeting HIE over other disorders.

Some other highlights:

NNZ-2591:

• During 2024, the positive Phase 2 trial results for Pitt Hopkins syndrome and Angelman syndrome were consistent with the Phelan-McDermid syndrome results, validating the company’s thesis that NNZ-2591 can potentially have a broad impact on neurodevelopmental conditions.
• Company very pleased with the outcome of the End of Phase 2 Meeting with the FDA for Phelan-McDermid syndrome, enabling it to move straight to Phase 3 with a similar program to the successful DAYBUE program in Rett syndrome.
• Company believes that the success of Daybue de-risks the NNZ-2591 programs, given the similarities in clinical profile, scientific rationale, trial design and endpoints.
• Type C Meeting with the FDA, scheduled in early April 2025, to seek alignment on the primary efficacy endpoints in the Phase 3 clinical trial.
• Transitioning Neuren’s capabilities from Phase 2 development to Phase 3 development. In parallel with the FDA interaction, Neuren is continuing the extensive preparations for the trial, planning for mid-2025 commencement.

Daybue:

• Company’s view that share price impacted negatively by momentum trading, initially triggered by a switch to negative sentiment about Daybue sales.
• Neuren maintains that the launch has been very successful and better than comparators, with net sales reaching US$348 million in the first full year of sales.
• Acadia has committed substantial additional resources to expand Daybue in the USA and has forecast continued growth in 2025.
• More than 60% of patients currently on therapy have now been treated for more than 12 months…. sales have become much more predictable.
• There are still 70% of the expanding pool of diagnosed patients in the US who have not yet tried treatment. This, together with the coming expansion into Canada, Europe, Japan and potentially other countries, provides substantial upside and a long-term growth opportunity for Neuren.
• The number of diagnosed Rett patients in the US has grown from approximately 4,500 at the launch of DAYBUE to between 5,500 and 5,800. Prevalence studies suggest the total number of patients may be 6,000 to 9,000.
• In Q4 2024 discontinuations improved by approximately 15% compared with Q3.

Finances:

• Net sales of Daybue in 2024 were US$348.4 million, with sequential growth in each quarter and record net sales of US$96.7 million in Q4 2024. These sales generated royalty income for Neuren in 2024 of A$56 million.
• 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 sold the PRV for US$150 million in December 2024.
• Adjusted pro-forma cash position at 31 December 2024 was A$359m.
• Neuren’s 19 person workforce all work from home and no office or other facility is maintained. In 2024, Neuren had zero Scope 1 and 2 emissions.