Neuren Pharmaceuticals (ASX:NEU) used a company webcast to outline a newly approved on-market share buyback and to review several updates released the prior week spanning its Daybue (trofinetide) royalty stream and the NNZ-2591 development pipeline.
Board approves up to 5% on-market buyback
Board member Patrick said the board approved an on-market buyback of up to 5% of shares on issue, citing the company’s “very strong cash position” supported by growing cash flows from the Daybue franchise. He emphasized that NNZ-2591 programs in Phelan-McDermid syndrome (PMS), Pitt Hopkins syndrome, and hypoxic-ischemic encephalopathy (HIE) “all are and will remain well-funded alongside the buyback.”
Management reiterated during Q&A that the buyback is not intended to displace spending on development plans and that the pace of repurchases will be at the company’s discretion as it monitors other opportunities.
European trofinetide update: CHMP “trend vote” and next steps
Management reviewed Acadia’s disclosure that it had been informed of a negative “trend vote” by the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) following an oral explanation. Neuren explained that the trend vote is an informal committee vote taken after the oral explanation, with a formal CHMP opinion expected to be adopted at the end of February.
If the formal opinion is negative, management said Acadia has indicated it would request a reexamination. The webcast outlined the steps described: a 15-day window to request reexamination, 60 days to submit grounds, and an additional 60 days for CHMP to reexamine. Neuren also said different rapporteurs are appointed for the reexamination process.
Management characterized the development as a “really bad outcome” for the Rett community in Europe, noting that Daybue has been on the U.S. market for about 2.5 years, with more than 1,000 patients on therapy and more than 300 contributing to Acadia’s LOTUS real-world study. They also pointed out that approvals have been granted in the U.S., Canada, and Israel based on the same data.
Daybue franchise: guidance, persistence trends, and Daybue Stix launch
While acknowledging disappointment around Europe, management stressed that the primary value driver remains the U.S. market, along with international named patient programs in regions including Europe, the Middle East, and South America.
Neuren referenced Acadia’s previously issued net sales guidance of $385 million to $400 million for the year and said Neuren’s royalty guidance based on that range is AUD 63 million to AUD 66 million, which management described as a 100% margin to Neuren.
Management also highlighted improving persistence data, saying the proportion of patients remaining on treatment at 12 months has increased to 55% from 50%. They added that diagnosed patient estimates have risen over time, with the latest figure cited as about 6,000.
Another focus was the upcoming launch of Daybue Stix, a powder formulation intended as an alternative to the liquid. Management said the powder allows families to reconstitute the medication in different flavors and volumes and excludes some ingredients present in the liquid formulation that some families dislike. They said the initial rollout will be limited in the first quarter to U.S. Centers of Excellence, with broader launch thereafter, and cautioned that meaningful impact is not expected in 2025 and likely not in early 2026.
NNZ-2591 pipeline: FDA feedback and PMS phase 3 dosing begins
Neuren reviewed FDA feedback received for HIE and Pitt Hopkins syndrome. For HIE, management said the FDA was broadly supportive of the company’s approach to open an IND with a one-month pharmacokinetics and safety study in neonates and infants, including the proposed doses, while requesting additional juvenile animal data before commencing the study. Management said the company will conduct the requested work and that the FDA encouraged a subsequent meeting to discuss a planned phase 2/3 registrational study, including endpoints, population, and safety monitoring.
For Pitt Hopkins syndrome, Neuren said written FDA responses indicated a pathway similar to PMS, using a syndrome-specific CGI scale paired with a co-primary observer-reported functional outcome measure. Management said the challenge in Pitt Hopkins is that functional measures not designed for the syndrome may be less sensitive in a more severely impaired population, potentially driving impractically large sample sizes. The company said it is evaluating alternatives, including different analytical approaches such as responder analyses and other trial designs, and expects further FDA interaction. Neuren’s stated target is to initiate both HIE and Pitt Hopkins studies late in the year.
Neuren also noted that the Rare Pediatric Disease Priority Review Voucher (PRV) program was reauthorized by the U.S. Congress through 30 September 2029. Management said Neuren holds the necessary designation across three indications (PMS, Pitt Hopkins, and Angelman) but can receive only one PRV per drug, with PMS expected to be first. They referenced Acadia’s sale of a PRV for $150 million following Daybue approval, from which Neuren received $50 million under its agreement, and noted that a PRV has recently sold for $200 million, though they said it is unclear if that reflects a new market price.
Finally, management said Neuren achieved first patient dosing in its PMS phase 3 “Koala” trial, which they described as the company’s most important NNZ-2591 program. The randomized, placebo-controlled portion includes a 4-week screening period followed by 13 weeks of treatment (1:1 drug vs. placebo), after which all participants can enter a 12-month open-label period. Neuren aims to enroll approximately 160 patients to power the co-primary endpoints. The company said it currently has two active U.S. trial sites, with additional sites expected to open progressively through the first half of the year, and cited family referral and waitlist figures discussed in its prior announcement. Management reiterated it is not providing formal timelines yet, but pointed to Acadia’s Rett phase 3 trial as a benchmark of roughly two years from study start to results.
About Neuren Pharmaceuticals (ASX:NEU)
Neuren Pharmaceuticals Limited, a biopharmaceutical company, develops drugs for the treatment of neurological disorders. It develops and commercializes DAYBUE (trofinetide), which has been registered to treat Rett syndrome in adults and pediatric patients 2 years of age and older, as well as in Phase 2 clinical trial to treat Fragile X syndrome. The company also develops NNZ-2591, which has completed Phase 2 clinical trial for the treatment of Phelan-McDermid, and in Phase 2 clinical trial for the treatment of Angelman, Pitt Hopkins, and Prader-Will syndromes.
