On October 27, 2022 Neuren Pharmaceuticals (ASX: NEU) reported its quarterly activity and cash flow report for Q3 2022 (Press release, Neuren, OCT 27, 2022, View Source;[email protected] [SID1234622510]).
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Neuren CEO Jon Pilcher commented: "Neuren continued to achieve the planned milestones during the quarter, remaining on track for the transforming catalysts still to come, notably the FDA target action date for trofinetide in Rett syndrome on 12 March 2023, followed by Phase 2 results for NNZ-2591 in multiple indications.
"Commentary on events since 30 June and outlook
Trofinetide for Rett syndrome In September 2022 the US Food and Drug Administration (FDA) accepted for review the New Drug Application (NDA) for trofinetide to treat Rett syndrome in adults and pediatric patients two years of age and older, that was submitted in July by Neuren’s North America partner Acadia Pharmaceuticals (Nasdaq: ACAD). The FDA granted a Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) action date of 12 March 2023. The FDA also informed Acadia that at that time they were not planning to hold an Advisory Committee meeting. The trofinetide program has Orphan Drug, Fast Track and Rare Pediatric Disease designations from the FDA. If approved, trofinetide will be the first drug for the treatment of Rett syndrome.
Acadia has exclusive rights to develop and commercialize trofinetide in North America, which is fully funded by Acadia.
Acceptance of the NDA earned a milestone payment of US$10 million from Acadia, which Neuren received in October. In 2023, if the NDA is approved by the FDA, Neuren expects to earn revenue for Rett syndrome in the US alone of A$112 million plus royalties. The next potential milestone payment to Neuren would be US$40 million (A$61 million at an assumed exchange rate of 0.65), payable following the first commercial sale of trofinetide in the United States. Subsequently, Neuren is eligible to receive double-digit percentage royalties on net sales of trofinetide in North America, plus milestone payments of up to US$350 million (A$538 million) on achievement of a series of four thresholds of total annual net sales, plus one third of the market value of a Rare Pediatric Disease Priority Review Voucher if awarded by the FDA upon approval of the NDA, with the one third share estimated by Neuren as US$33 million (A$51 million). No royalties or similar costs are payable by Neuren to third parties, which means that Neuren’s revenue from Acadia will flow through to pre-tax profit.
Neuren retains all rights to trofinetide for all countries outside North America and has a fully paid-up, irrevocable licence for use in those countries to all data generated by Acadia. Rett syndrome is a devastating condition with no approved therapies and there is urgent unmet need around the world for a treatment. Neuren has received strong interest for potential commercial partnerships and discussions are continuing under a process to secure the optimum outcome for shareholders and for patients. NNZ-2591 for multiple neurodevelopmental disorders During Q3 Neuren commenced its Phase 2 clinical trials of NNZ-2591 in each of Angelman syndrome (AS), Phelan-McDermid syndrome (PMS) and Pitt Hopkins syndrome (PTHS).
The open label Phase 2 trials will each enrol up to 20 children to examine safety, tolerability, pharmacokinetics and efficacy over 13 weeks of treatment with NNZ-2591. All subjects will receive NNZ-2591 as an oral liquid dose twice daily, with titration up to the target mg/kg dose during the first 6 weeks of treatment, subject to safety and tolerability. The treatment period is preceded by 4 weeks of observation to thoroughly examine the baseline characteristics prior to treatment, against which safety and efficacy will be assessed for each child. A follow-up assessment will be made 2 weeks after end of treatment. For each trial there are three age cohorts. Safety and tolerability is assessed in the oldest cohort before proceeding with the middle cohort and then safety and tolerability is assessed in the middle cohort before proceeding with the youngest cohort.
Neuren is also planning a Phase 2 trial in a fourth disorder, Prader-Willi syndrome, with an Investigational New Drug (IND) Application to be submitted to the FDA in Q4 2022. Neuren has Orphan Drug designation from the FDA for NNZ-2591 in all four syndromes, which are serious neurodevelopmental disorders with no approved medicines. The estimated number of potential patients being targeted across these four disorders is more than five times larger than Rett syndrome. Neuren retains all global rights to NNZ-2591. The overall aim of these first trials in patients is to expedite the generation of data that will enable the subsequent trials to be designed as registration trials. Prioritising fast enrolment of subjects, the AS trial is being conducted in Australia, whilst the PMS and PTHS trials are being conducted in the US.
In order to expedite the overall development plan, in parallel with conducting the Phase 2 trials Neuren is executing the additional development work required to be ready for Phase 3 development. This includes non-clinical toxicity studies to support longer clinical trials and commercial use of the product, as well as optimisation of the drug product and drug substance manufacturing arrangements. Neuren is well funded from current cash reserves to execute the Phase 2 trials and Phase 3 preparation, notwithstanding the anticipated material cash flows from trofinetide. Investor relations In September, Neuren was added into the S&P/ASX 300 index. Since 30 June, Neuren has presented at the healthcare conferences of Evans & Partners, Euroz Hartleys and Goldman Sachs, as well as at the ASX Small and Mid-Cap conference. Presentations are scheduled at the Wilsons and Bell Potter healthcare conferences. Neuren will also present at the Jefferies London Healthcare Conference in November.
Human resources In July, Neuren’s skills and experience in pediatric neurology and orphan drug development were further enhanced by the appointment of Liza Squires M.D. to the new position of Chief Medical Officer, based in the United States. Dr Squires is a board-certified physician in General Pediatrics and Neurology with Special Competence in Child Neurology. Over the past 20 years, she has held positions of increasing responsibilities in both early and late-stage development at Johnson and Johnson, Shire Pharmaceuticals, Lumos Pharma, Aevi Genomic Medicine and Origin Biosciences. She has led and contributed to multiple New Drug Applications resulting in global regulatory approvals and has extensive experience in orphan drug development.Financials Cash reserves at 30 September 2022 were $27.3 million, compared with $31.1 million at 30 June 2022. In Q3 net cash of $4.0 million was used in operating activities, with R&D payments of $2.8 million mainly relating to the NNZ-2591 Phase 2 clinical trials and the foundational work to prepare for Phase 3 development of NNZ-2591 across multiple indications.
The carrying value in AUD of USD cash held to mitigate exchange rate risk for USD expenditure increased by $0.2m for the quarter, due to the strengthening of the USD against the AUD. Payments to related parties of approximately $194,000 comprised the Managing Director’s executive remuneration and non-executive directors’ fees.