2023 Neuren Pharmaceuticals Update
Neuren Pharmaceuticals is developing treatments for neurodevelopmental disorders, with two compounds in development: Trofinetide and NNZ-2591. Trofinetide has been approved for the treatment of Rett syndrome in the United States, while NNZ-2591 is in Phase 2 development for neurodevelopmental disorders, specifically Angelman Syndrome. NNZ-2591 is a novel synthetic analog of cyclic glycine proline, a metabolite of insulin-like growth factor I (IGF-1), a growth hormone responsible for managing the growth and development of brain cells. NNZ-2591 has shown to improve the abnormal function of brain cells and rescue abnormal morphology and density of dendritic spines. In a mouse model of Angelman syndrome, treatment with NNZ-2591 was able to fully rescue the phenotype. The Phase 1 study in healthy adults showed good safety results, with all adverse events being mild or moderate and resolving during the trial. The Phase 2 study is currently open for enrolment, with top line results expected next year. The study aims to evaluate safety, pharmacokinetics, and clinical response to the drug.
Hello, everyone. My name is Nancy Jones, the Vice President of Chemical Development at Neuren Pharmaceuticals. I’m delighted to join you today via this recorded presentation to provide an update on our clinical development programme for Angelman Syndrome. Neuren is a specialty pharmaceutical company, specifically focused on the development of treatments for neurodevelopmental disorders. We have two compounds in development, Trofinetide and NNZ-2591.
Trofinetide and NNZ-2591
Trofinetide has been approved for the treatment of Rett syndrome in the United States, in partnership with Acadia Pharmaceuticals in North America. It is available in the United States as Daybue. NNZ-2591, on the other hand, is in Phase 2 development for neurodevelopmental disorders, and it is NNZ-2591 that’s being developed for Angelman Syndrome.
NNZ-2591: A Novel Neurobiological Therapy
NNZ-2591 is a novel neurobiological therapy. Specifically, it is a novel synthetic analog of cyclic glycine proline, a metabolite of insulin-like growth factor I, or IGF-1. IGF-1 is a growth hormone that occurs in your body and is present in the brain. It is responsible for managing the growth and development of the cells in the brain. NNZ-2591 has the same molecular structure as IGF-1, with one small change that gives it properties that make it better to be used as a medication.
Properties of NNZ-2591
NNZ-2591 is orally available and comes in a liquid formulation. It has 100% oral bioavailability, meaning all the drug is able to be used and absorbed. It crosses the blood-brain barrier and has good pharmacokinetic properties, which refers to how the drug is used and absorbed by the body.
Progress in Clinical Development Program
We have completed several steps in our clinical development programme, with ongoing work in other areas. From our preclinical work, we have been able to show what NNZ-2591 does at the molecular level. It improves the abnormal function of brain cells, specifically microglia cells, and rescues abnormal morphology and density of dendritic spines.
Animal Model Study
From an animal model study, which was a mouse model of Angelman syndrome, we found that treatment was able to fully rescue the phenotype in this mouse model. This included seizures, as well as behaviours that are similar to symptoms seen in individuals with Angelman.
We have completed the Phase 1 study, which is the first study you do to look at safety and also sort of targeting the dose. This study was in healthy adults. The safety results from this study were good. Adverse events were all mild or moderate and resolved during the trial. There were no serious adverse events or severe adverse events, and no clinically significant findings on lab tests, vital signs, or cardiac tests.
Phase 2 Study
Currently, we are at Phase 2, and we have enrolment open in our Phase 2 study, with top line results expected next year. The Phase 2 study is 13 weeks of treatment, and it’s an open-label study, which means everyone is getting NNZ-2591. The primary aim is to evaluate safety, and then also looking at pharmacokinetics. But we’re also looking at the clinical response to the drug, or sort of the signs of efficacy.
Inclusion and Exclusion Criteria
This trial is looking at ages 3 to 17 in both males and females, with individuals that have a diagnosis of AS with the confirmed genetic etiology, minimum weight at screening, and of course the ability to swallow the liquid study medication, and then a stable seizure profile and treatment regimen.
Study Sites and Further Information
The study sites are all in Australia, so we have three sites, one in Brisbane, one in Melbourne, and one in Sydney. For more information, visit our study-specific website, angelmanstudy.com.au, or search Neuren and Angelman on clinicaltrials.gov. You can also sign up for updates about the study on the Neuren website, neurenpharma.com, under News and Reports, then click on Email Alerts.
Thank you very much for your attention, and enjoy the rest of the conference.
- Title: 2023 Neuren Pharmaceuticals Update
- Author(s): Nancy Jones
- Author(s)’ affiliation: Neuren Pharmaceuticals
- Publication date: 2023-07-07
- Collection: 2023 ASF Virtual Conference