NNZ-2591 as a Treatment for Angelman Syndrome

Quick Overview

Dr. Nancy Jones, Vice President of Clinical Development at Neuren Pharmaceuticals, presented their clinical trial for NNZ-2591 as a treatment for Angelman syndrome at the 2022 FAST Science Summit. Neuren Pharmaceuticals is a specialty biopharmaceutical company focused on developing treatments for neural developmental disorders. NNZ-2591 is a synthetic analog of a metabolite of insulin-like growth factor one (IGF-1) and is being developed as a neurobiological therapy for Angelman syndrome. Preclinical studies have shown that NNZ-2591 can improve the function and morphology of brain cells, as well as rescue abnormal signaling and improve the bioavailability of IGF-1. A Phase 1 study in healthy volunteers showed a good safety profile, and a Phase 2 study in Angelman syndrome patients is currently ongoing. The study aims to evaluate safety, pharmacokinetics, and efficacy measures related to communication, motor skills, behavior, GI issues, sleep, seizures, and daily function. Enrollment has started at three study sites in Australia, and top-line results are expected in the first half of next year.

Introduction

Dr. Nancy Jones, Vice President of Clinical Development at Neuren Pharmaceuticals, presented an update on their clinical trial for NNZ-2591 as a treatment for Angelman syndrome at the 2022 FAST Science Summit. Neuren Pharmaceuticals is a specialty biopharmaceutical company focused on developing treatments for neural developmental disorders. In her presentation, Dr. Jones provided background information on Neuren and their milestones in the program, as well as details about NNZ-2591 and its potential as a neurobiological therapy for Angelman syndrome.

Neuren Pharmaceuticals and Milestones

Neuren Pharmaceuticals is a small biopharmaceutical company based in Australia. They are dedicated to developing treatments for rare genetic disorders with unmet medical needs. Currently, Neuren has two drugs in development: Trofinetide and NNZ-2591. Trofinetide, being developed for Rett syndrome, has completed a Phase 3 pivotal trial with positive results and has been submitted to the FDA for review. NNZ-2591, the focus of Dr. Jones’ presentation, is being developed for four rare neurodevelopmental disorders, including Angelman syndrome.

NNZ-2591: A Neurobiological Therapy

NNZ-2591 is a novel synthetic analog of a metabolite of insulin-like growth factor one (IGF-1) called cyclic glycine proline (cGP). IGF-1 is a growth hormone produced in the body, including the brain, and is responsible for the growth and development of neurons and supporting cells. NNZ-2591 has the same molecular structure as cGP but with a slight chemical change that makes it more suitable for use as a medication. It is orally available, has 100% oral bioavailability, crosses the blood-brain barrier, and has good pharmacokinetic properties.

Preclinical Studies and Animal Model Study

Preclinical studies have shown that NNZ-2591 can improve the function of brain cells called microglia, which support and maintain the structure and connectivity of neurons. It also improves abnormal morphology and density of dendritic cell spines, which receive messages from other neurons. Additionally, NNZ-2591 improves impaired signaling between cells and increases the bioavailability of IGF-1. An animal model study demonstrated that NNZ-2591 fully rescued the phenotype, including seizures, in mice with Angelman syndrome.

Clinical Trials

Neuren Pharmaceuticals has completed a Phase 1 study of NNZ-2591 in healthy adult volunteers, which showed a good safety profile with mild or moderate adverse events that resolved during the study. The drug’s pharmacokinetic profile was predictable and systematic. Currently, Neuren is conducting a Phase 2 open-label study in individuals with Angelman syndrome. The study involves 13 weeks of treatment with twice-daily dosing, and the primary aim is to evaluate safety and pharmacokinetics, with secondary measures of efficacy. Enrollment has begun, and top-line results are expected in the first half of next year.

Study Details and Sites

The Phase 2 study includes a screening period of four to six weeks, a 13-week treatment period, and a two-week follow-up. It is open to pediatric participants aged three to 17 across different genetic etiologies of Angelman syndrome. Three study sites in Australia (Brisbane, Melbourne, and Sydney) are currently open for enrollment. The study-specific website and clinicaltrials.gov provide more detailed information about the study and its inclusion-exclusion criteria.

Acknowledgments

Dr. Jones expressed gratitude to the families and individuals participating in the study, as well as FAST Australia and the FAST Global community for their support. The study’s design was influenced by interactions with the ABOM group and advocacy groups. Dr. Jones thanked everyone for their contributions in making the study possible.