NNZ-2591

Acadia Pharmaceuticals committed a lot of money for rights to Daybue, which in the biotech’s hands became the first FDA-approved drug for the rare neurological disorder Rett syndrome. That approval came with a regulatory fast pass for a future drug, and Acadia is now capitalizing on it with a deal to sell the voucher for $150 million. The San Diego-based biotech did not disclose the buyer of the priority review voucher. But when the deal closes, $50 million of the proceeds from that sale will go to Neuren Pharmaceuticals, the company that licensed Daybue to Acadia. A priority review voucher shaves the standard 10-month review for a drug down to six months. The FDA created the program in 2012 to incentivize drug development in rare or neglected diseases. The FDA awards vouchers to companies that win regulatory approval for a drug that treats a rare disease. That company may apply the voucher toward speedier review of a different drug in the future, but most voucher holders monetize them by selling the regulatory fast pass to larger companies. Voucher buyers hope the investment pays for itself and then some by enabling them to reach the market sooner with a new drug that has blockbuster potential. However, the FDA has decided to wind down the program starting next month, putting vouchers in high demand. The $150 million price tag for Acadia’s voucher is notably higher than the $100 million that has been the typical price for voucher sales. Sponsored Post The Future of Hospitals and Pharma Companies Will Depend on Strength of Healthcare Analytics Insights PurpleLab® stands out from others in this sector by providing its data analytics services to several different groups of users across healthcare and pharma companies. By Stephanie Baum The prospect of a priority review voucher was contemplated by Acadia’s licensing deal for Daybue. The peptide, known in development as trofinetide, was initially developed by Australia-based Neuren Pharmaceuticals. In 2018, Acadia licensed North American rights to the drug candidate, agreeing to pay $10 million up front and up to $455 million in milestone payments, according to Acadia regulatory filings. The terms of the licensing agreement also require Acadia to pay Neuren one third of the value of the priority review voucher at the time it is sold or used. Last year, the FDA approved Daybue for treating Rett syndrome in adults and in children age 2 and older. With that approval, Acadia was awarded a priority review voucher. But Acadia has also positioned itself to capture more of the value of its new product. Months after FDA approval of Daybue, Acadia secured rights to the drug in the rest of the world by paying Neuren $100 million up front. The deal includes global rights to NNZ-2591, which Neuren was developing for Rett syndrome and Fragile X syndrome. In its report of third quarter 2024 financial results posted on Wednesday, Acadia said Daybue accounted for $251.7 million in sales in the first nine months of this year, up from $90.1 million in the same period in 2023. Acadia forecasts 2024 sales of this product will be in the range of $340 million to $350 million. The company’s cash position at the end of the third quarter was about $565 million. The company said proceeds from the voucher sale will support commercial operations, R&D programs in central nervous system and rare disease, and future business development. Image: TAW4, Getty Images

Highlights: Statistically significant improvement from baseline assessed by both clinicians and caregivers in all four efficacy measures specifically designed for Pitt Hopkins syndrome (Wilcoxon signed rank test p<0.05) Clinician and caregiver global efficacy measures showed a level of improvement considered clinically meaningful: - Clinical Global Impression of Improvement (CGI-I) - mean score of 2.6, with 9 out of 11 children showing improvement assessed by clinicians - Caregiver Overall Impression of Change (CIC) – mean score of 3.0, with 8 out of 11 children showing improvement assessed by caregivers Improvements were seen in clinically important aspects of Pitt Hopkins syndrome, including communication, social interaction, cognition and motor abilities NNZ-2591 was safe and well tolerated, with no serious or severe adverse events and no meaningful trends in laboratory values or other safety parameters during treatment Second positive Phase 2 trial result further strengthens confidence in NNZ-2591's potential relevance for multiple neurodevelopmental disorders MELBOURNE, Australia, May 27, 2024 /PRNewswire/ -- Neuren Pharmaceuticals (ASX: NEU) today announced top-line results from its Phase 2 clinical trial of NNZ-2591 in children with Pitt Hopkins syndrome (PTHS). Statistically significant improvement from baseline was observed by both clinicians and caregivers from treatment, across all 4 efficacy measures that were specifically designed to assess the core characteristics of PTHS. There are no approved treatments for PTHS despite its severely debilitating impact on the lives of patients, as well as their parents and siblings. Neuren CEO Jon Pilcher commented "We are very excited about the results of this first clinical trial in Pitt Hopkins patients. This underserved community has such urgent unmet need and we can now continue towards our goal of developing a first approved treatment. We are very grateful to the people in the Pitt Hopkins community and at the trial sites in the United States who enabled the successful completion of this extremely challenging, but groundbreaking trial." Elliott Sherr, M.D., Ph.D., Professor of Neurology and Pediatrics at the University of California San Francisco, and Director, Brain Development Research Program was an investigator in the trial. Dr Sherr commented: "I am optimistic about the results in the PTHS specific measures. The mechanism of action of NNZ-2591 supports this response seen in PTHS and its potential in other highly impactful neurodevelopmental disorders." Dr. Nancy Jones, Neuren Vice President of Clinical Development commented: "The consistent results on the PTHS specific assessments affirm the need for syndrome specific measurements in severe neurodevelopmental disorders where measures that were developed for broader populations may not be as appropriate. Neuren appreciates the collaboration of Dr. Cassandra Newsom, Associate Professor at the University of Alabama, Birmingham (an investigator in the trial), the Pitt-Hopkins Research Foundation, and others who contributed to the development of these important measures." Study design The open label Phase 2 trial in 16 children aged 3 to 17 years (mean age 9 years) at five hospitals in the United States examined safety, tolerability, pharmacokinetics and efficacy over 13 weeks of treatment with NNZ-2591. NNZ-2591 was administered to all subjects as an oral liquid dose twice daily, with escalation in two stages up to the target dose of 12 mg/kg during the first 6 weeks of treatment, subject to independent review of safety and tolerability data. The study commenced with at least 4 weeks of screening and observation to thoroughly define baseline characteristics prior to treatment, followed by the treatment period of 13 weeks. A follow-up assessment was made 2 weeks after the end of treatment. The primary endpoints of this first trial in children with PTHS were safety, tolerability and pharmacokinetics. Secondary endpoints included four efficacy measures specifically designed for PTHS assessed by clinicians and by caregivers, as well as ten efficacy measures that were not designed for use in PTHS but have been used in other neurodevelopmental conditions. Safety and tolerability NNZ-2591 was well tolerated and demonstrated a good safety profile. All Treatment Emergent Adverse Events (TEAEs) were mild to moderate and most were considered not related to study drug. There were no Serious TEAEs and no meaningful trends in laboratory values, electrocardiogram (ECG) or other safety parameters were observed during treatment. 11 subjects completed the trial. One subject discontinued because they were unable to complete the safety monitoring procedures required by the study protocol. Four subjects discontinued due to TEAEs, all of which resolved. For two of those subjects the TEAEs (COVID-19 and mild vomiting/diarrhea/lethargy) were considered not related to study drug and for two subjects the TEAEs (moderate constipation/self-injury/abdominal distention/fatigue and mild sleep disorder/constipation) were considered related to study drug. Efficacy The mean improvement from baseline was statistically significant (Wilcoxon signed rank test p<0.05) for each of the four efficacy measures that were specifically designed for Pitt Hopkins syndrome, whether calculated for the subjects that completed the study (n=11), or including discontinued subjects (n=15). Changes from baseline were not statistically significant for the efficacy measures that were not designed for use in PTHS but have been used in other neurodevelopmental conditions. Results for efficacy measures specifically designed for Pitt Hopkins syndrome The results for the global measures rated by both clinicians and caregivers showed a level of improvement considered clinically meaningful. 9 out of 11 children that completed the trial showed improvement measured by the PTHS Clinical Global Impression of Improvement (CGI-I), an assessment by the clinician of the child's overall status compared with baseline. The mean CGI-I score was 2.6. Five children received a score of either 1 ("very much improved") or 2 ("much improved"). 8 out of 11 children that completed the trial showed improvement measured by the PTHS Caregiver Overall Impression of Change (CIC), an assessment by the caregiver of the child's overall status compared with baseline. The mean CIC score was 3.0. Four children received a score of 2 ("much improved"). 6 out of 11 children that completed the trial showed improvement measured by the PTHS Clinical Global Impression of Severity (CGI-S), an assessment by the clinician of the child's overall severity of illness, compared with the assessment at baseline. The CGI-S score improved from 6 to 5 for 3 children and from 5 to 4 for 3 children. 8 out of 11 children that completed the trial showed improvement measured by the Caregiver Top 3 Concerns overall score, an individualised assessment by the caregiver of their child's most concerning symptoms. Language/Communication was the most commonly chosen concern. Detailed results are available in the full announcement and investor presentation: About Pitt Hopkins syndrome Pitt Hopkins syndrome (PTHS) is a neurodevelopmental condition caused by the loss of one copy or a mutation of the TCF4 gene on chromosome 18. The incidence of PTHS has been estimated at between 1 in 34,000 and 1 in 41,000 people. Characteristics of PTHS are a range of developmental delay with moderate-to-severe intellectual disability and behavioral differences, hyperventilation and/or breath-holding while awake, seizures, gastrointestinal issues, lack of speech, sleep disturbance, stereotypic hand movements and distinctive facial features. Some individuals with PTHS are diagnosed with autism. Further information about PTHS is available at: 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. Recognising the urgent unmet need, all programs have been granted "orphan drug" designation in the United States. Orphan drug designation provides incentives to encourage development of therapies for rare and serious diseases. DAYBUE™ (trofinetide) is approved by the US Food and Drug Administration (FDA) for the treatment of Rett syndrome in adult and pediatric patients two years of age and older. 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 Phase 2 development for multiple neurodevelopmental disorders, with positive results achieved in Phase 2 clinical trials in Phelan-McDermid syndrome and Pitt Hopkins syndrome. ASX Listing Rules information This announcement was authorized to be given to the ASX by the board of directors of Neuren Pharmaceuticals Limited, Suite 201, 697 Burke Road, Camberwell, VIC 3124 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 Pharmaceuticals Ltd