Neuren Pharmaceuticals Ltd.

Acadia Pharmaceuticals on Sunday said the EMA's Committee for Medicinal Products for Human Use (CHMP) — ahead of issuing a formal opinion later this month — orally delivered a negative trend vote regarding a marketing filing for trofinetide to treat Rett syndrome, a rare neurodevelopmental condition. The news sent the company's stock tumbling nearly 4.4% in after hours trading.Although details of the oral feedback were not specified, Acadia noted it will seek a re-examination once the CHMP's opinion on the IGF-1 analogue — which is already approved in the US, Canada and Israel under the brand name Daybue — is formally adopted. The company has 15 days to request the re-examination upon receiving the opinion, with the EMA committee having 60 days to conclude its review."While the negative trend vote is disappointing and not what we hoped for, we believe the strong data that supported the approval [in other countries]…speak to the meaningful benefits that trofinetide can deliver," said Catherine Owen Adams, chief executive of Acadia.The marketing application submitted to the European regulator last year, backed by the Phase III LAVENDER study evaluating trofinetide versus placebo in 187 girls and young women aged five to 20 years with Rett syndrome. Results showed the trial met both co-primary endpoints — change from baseline in the Rett Syndrome Behaviour Questionnaire (RSBQ) total score and Clinical Global Impression–Improvement (CGI-I) scale score at week 12 — alongside the key secondary endpoint measuring communication and social behaviour improvements.Acadia initially bagged North American rights to the therapy from Neuren Pharmaceuticals in 2018 and subsequently secured the entire global rights in 2023.

Key points: Fast track designation from the FDA for Neuren’s NNZ-2591 across three programs Launch of phase 3 "Koala" trial, last step to filing for approval Strong financial position supported by DAYBUE sales in the US Increased focus on growth and further clinical milestones for NNZ-2591 Fast track designation from the FDA for Neuren’s NNZ-2591 across three programs Launch of phase 3 "Koala" trial, last step to filing for approval Strong financial position supported by DAYBUE sales in the US Increased focus on growth and further clinical milestones for NNZ-2591 Neuren Pharmaceuticals chief executive Jon Pilcher expresses optimism as the company secures fast track designation from the US Food and Drug Administration for its treatment targeting a rare genetic disorder, Phelan-McDermid Syndrome. Pilcher states that the FDA’s decision reflects the serious nature of the condition and the current lack of approved therapies, adding that enhanced engagement with the US regulator could lead to a more expedited review process. He emphasises how this designation now extends across three programs for Neuren’s lead treatment, NNZ-2591, highlighting the company’s strengthened position in the clinical landscape. Pilcher says the launch of the phase 3 "Koala" clinical trial for NNZ-2591 marks a significant milestone, coinciding with Phelan-McDermid Syndrome Awareness Day. With an agreement in place for rapid filing should results prove positive, he notes the "Koala" trial brings an "Aussie flavour" to an international clinical effort, aiming to resonate with patient communities and their families. Pilcher also points to Neuren’s active engagement at the Canaccord Drug and Device Investor Conference in Noosa, uniting leading biotech firms and fund managers for in-depth sector interaction. Turning to commercial progress, Pilcher provides an update on DAYBUE, Neuren’s first approved drug in the United States. He points to strong quarterly performance and growth potential, with only a third of eligible patients currently accessing treatment, leaving room for expansion. Pilcher describes Neuren’s financials as robust, driven by DAYBUE revenue, providing the foundation for continued investment and potential upside if NNZ-2591 succeeds in multiple indications.

Melbourne, Australia: 20 October 2025 Neuren Pharmaceuticals (ASX: NEU) today announced that the US Food and Drug Administration (FDA) has granted Fast Track designation for NNZ-2591 for the treatment of Phelan-McDermid syndrome (PMS). Fast Track is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. Currently there are no FDA-approved treatments for PMS. Neuren recently initiated “Koala”, a Phase 3 randomized double-blind placebo-controlled clinical trial evaluating NNZ-2591 treatment in children aged 3 to 12 years with PMS. Alignment was reached with the FDA on the single Phase 3 trial design and endpoints to support a New Drug Application. Neuren CEO Jon Pilcher commented: “As we approach Phelan-McDermid Syndrome Awareness Day on 22 October, we are very pleased to announce Fast Track designation for our NNZ-2591 program. Neuren’s Koala trial is the first ever Phase 3 clinical trial for PMS, which we hope may lead to a muchneeded treatment for this community. We encourage all initiatives to increase awareness and diagnosis of PMS and applaud the leadership of both the Phelan-McDermid Syndrome Foundation and CureSHANK.” Fast Track designation has also been granted for NNZ-2591 in Angelman syndrome (AS), which means that Neuren now has Fast Track for NNZ-2591 across all of PMS, Pitt Hopkins syndrome and AS. About FDA Fast Track designation Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. A drug that receives Fast Track designation is eligible for some or all of the following: • More frequent meetings with FDA to discuss the drug's development plan and ensure collection of appropriate data needed to support drug approval • More frequent written communication from FDA about such things as the design of the proposed clinical trials and use of biomarkers • Eligibility for Accelerated Approval and Priority Review, if relevant criteria are met • Rolling Review, which means that a drug company can submit completed sections of its New Drug Application (NDA) for review by FDA, rather than waiting until every section of the NDA is completed before the entire application can be reviewed. NDA review usually does not begin until the drug company has submitted the entire application to the FDA. About Phelan-McDermid syndrome Phelan-McDermid syndrome (PMS) is caused by a deletion or other change in the 22q13 region of chromosome 22, which includes the SHANK3 gene, or a mutation of the gene. PMS is also known as 22q13 deletion syndrome. The SHANK3 gene codes for the SHANK3 protein, which supports the 2 of 2 structure of synapses between neurons in the brain. It is estimated that between 1 in 8,000 and 1 in 15,000 people have PMS. There are no medications, drugs, or therapies specifically for PMS, which has an overwhelming unmet medical need. PMS has severe quality of life impacts on those living with it, as well as on parents and siblings. The most common characteristics are moderate to severe developmental and intellectual impairment and developmental delay, delayed or absent speech, symptoms of autism, low muscle tone, motor delays, mild to severe epilepsy, behavioural problems and difficulties with socialization, activities of daily living and self-care. Further information about PMS is available at: www.pmsf.org and www.cureshank.org About Neuren Neuren is developing new drug therapies to treat multiple serious neurological disorders that emerge in early childhood and have no or limited approved treatment options. DAYBUE™ (trofinetide) is approved by the US Food and Drug Administration (FDA) and Health Canada for the treatment of Rett syndrome. Neuren has granted an exclusive worldwide licence to Acadia Pharmaceuticals Inc. for the development and commercialisation of trofinetide. Neuren’s second drug candidate, NNZ-2591, is in development for multiple neurodevelopmental disorders, with positive results achieved in Phase 2 clinical trials in Phelan-McDermid syndrome, Pitt Hopkins syndrome and Angelman syndrome. Recognising the urgent unmet need, each program has been granted “orphan drug” designation in the United States and the European Union. Orphan drug designation provides incentives to encourage development of therapies for rare and serious diseases. Forward-looking Statements This announcement contains forward-looking statements that are subject to risks and uncertainties. Such statements involve known and unknown risks and important factors that may cause the actual results, performance or achievements of Neuren to be materially different from the statements in this announcement. Source: Neuren