Clinical Development Update: NNZ-2591 as a Treatment for Angelman Syndrome

Quick Overview

Neuren Pharmaceuticals provided an update on their drug NNZ-2591, which aims to improve impaired connections and signaling between brain cells in individuals with Angelman syndrome. Neuren is a specialty pharmaceutical company focused on rare genetically based disorders, particularly neurodevelopmental disorders. They have two drugs in development, Trofinetide and NNZ-2591. Trofinetide recently received FDA approval for the treatment of Rett syndrome. NNZ-2591 is a neurobiological therapy that replicates the functions of insulin-like growth factor one (IGF-1) in the brain. Preclinical and Phase 1 studies have shown positive results, and a Phase 2 study is currently ongoing to assess safety, pharmacokinetics, and efficacy in individuals with Angelman syndrome. The study is expected to be completed next year, and results will inform the design of pivotal Phase 3 trials. Interested individuals can find more information on the study-specific website and sign up for email alerts on Neuren Pharmaceuticals’ webpage.

Introduction

Dr. Nancy Jones, Vice President of Clinical Development from Neuren Pharmaceuticals, provided an update on NNZ-2591 during the 2023 FAST Science Summit. NNZ-2591 aims to improve the impaired connections and signaling between brain cells. Dr. Jones gave an overview of Neuren Pharmaceuticals, discussed the Phase 2 program for NNZ-2591, and shared the progress and future plans for the treatment.

Neuren Pharmaceuticals and NNZ-2591

Neuren Pharmaceuticals is a specialty pharmaceutical company focused on rare genetically based disorders, particularly neurodevelopmental disorders. They have two drugs in development, Trofinetide and NNZ-2591. Trofinetide recently received FDA approval for the treatment of Rett syndrome in the United States. Neuren Pharmaceuticals is now focusing on NNZ-2591 and its potential as a treatment for Angelman syndrome.

NNZ-2591: A Neurobiological Therapy

NNZ-2591 is a neurobiological therapy that aims to improve the function of brain cells and the connections between them. It is a synthetic analog of a metabolite of insulin-like growth factor one (IGF-1). IGF-1 is responsible for the growth and maintenance of brain cells. NNZ-2591 replicates the functions of IGF-1 and has properties that regulate the amount of IGF-1, reduce neural inflammation, normalize microglia function, and help with synaptic maintenance. Importantly, NNZ-2591 only affects abnormal cells and has no negative effects on normal cells.

Preclinical and Phase 1 Studies

Neuren Pharmaceuticals has completed preclinical and Phase 1 studies for NNZ-2591. The preclinical studies showed that NNZ-2591 can improve the structure and function of brain cells, as well as levels of IGF-1. In mouse models, improvements were observed across a range of symptoms. The Phase 1 study demonstrated a good safety profile and tolerability of NNZ-2591.

Phase 2 Study

The Phase 2 study for NNZ-2591 is currently ongoing. It is an open-label study, meaning that all participants receive the treatment. The study lasts for 13 weeks, with a baseline observation period of four weeks and a follow-up period after the treatment. The study involves oral dosing and a liquid formulation taken twice a day. It includes in-clinic visits and in-home nursing visits.

Study Objectives and Criteria

The primary aim of the Phase 2 study is to assess the safety and pharmacokinetics of NNZ-2591. Efficacy is also being evaluated, with a focus on a range of outcomes related to communication, motor skills, behavior, sleep, seizures, gastrointestinal issues, and daily function. The study includes participants aged three to 17 with various genetic etiologies and specific body weight and seizure profile requirements. Eligibility is determined through assessments, review of current medications, and medical history.

Study Progress and Future Plans

The Phase 2 study is still ongoing, with participants enrolling and completing their treatment. The results will be reported once all enrolled participants have completed the study, expected next year. The design and inclusion criteria for the Phase 3 pivotal program will be determined based on the Phase 2 study results. Follow-up studies may include additional locations. Updates and announcements regarding the study can be found on Neuren Pharmaceuticals’ website.

Conclusion

Dr. Nancy Jones expressed gratitude to the community for their support of the study. She acknowledged the support from organizations such as FAST in Australia, the Angelman Syndrome Association in Australia, Global FAST, and the Angelman Syndrome Foundation. Dr. Jones concluded by looking forward to answering questions during the panel discussion.

For more information about the study, visit the study-specific website or sign up for email alerts on Neuren Pharmaceuticals’ webpage.