The Use of the NNZ-2591 Compound as a Potential Therapeutic for Angelman Syndrome

Quick Overview

Dr. Larry Glass from Neuren Pharmaceuticals presented at the 2019 FAST Science Summit about the potential therapeutic use of the NNZ-2591 compound for Angelman syndrome. Neuren Pharmaceuticals is a New Zealand company focused on rare and orphan neurodevelopmental disorders. NNZ-2591 is an analog of cyclic GP, a metabolite of IGF-1, and is being targeted for synaptopathies such as Angelman syndrome. The compound has shown efficacy in various models and has a good safety profile. Neuren Pharmaceuticals plans to start Phase 2 trials in 2020 and will focus on a pediatric population. The dosage form will likely be a flavored liquid administered twice a day. The company aims to determine the magnitude of the response and validate outcome measures in the Phase 2 trial, as well as confirm the optimal dose for a pivotal trial.

Introduction

Dr. Larry Glass from Neuren Pharmaceuticals presented at the 2019 FAST Science Summit about the potential use of the NNZ-2591 compound as a therapeutic for Angelman syndrome. Neuren Pharmaceuticals is a New Zealand company focused on rare and orphan neurodevelopmental disorders. Dr. Glass has extensive experience in translational research and has been with Neuren Pharmaceuticals since 2004.

Background

Neuren Pharmaceuticals is currently developing two analogs of IGF-1 derivatives, including Trofinetide (NNZ-2566) and NNZ-2591. Trofinetide is in Phase 3 clinical trials for Rett syndrome and has shown positive results in Phase 2 trials for Fragile X syndrome. Neuren Pharmaceuticals has orphan designation and fast track designation for Trofinetide in the US and Europe.

NNZ-2591 and Synaptopathies

NNZ-2591 is an analog of cyclic GP, a metabolite of IGF-1. Neuren Pharmaceuticals is targeting synaptopathies, which are conditions characterized by pathologic changes in synapses due to genetic changes. Angelman syndrome, Phelan-McDermid syndrome, and Pitt-Hopkins syndrome are among the synaptopathies being targeted. NNZ-2591 has orphan designation for all three syndromes in the US.

Mechanism of Action

IGF-1 and its metabolites play important roles in brain development and synaptic plasticity. NNZ-2591 reduces the expression of inflammatory cytokines and normalizes microglia, which are critical for pruning weak synapses and allowing strong synapses to grow. It also regulates the bioavailability of IGF-1, which can fix both hyperconnectivity and hypoconnectivity in synapses. NNZ-2591 has shown efficacy in various models, including the SHANK3 model for Phelan-McDermid syndrome.

Clinical Trials and Future Plans

Neuren Pharmaceuticals plans to start Phase 2 trials for NNZ-2591 in 2020 for Angelman syndrome and other synaptopathies. The company is also planning to conduct a pediatric study for NNZ-2591. The first Phase 2 trial will help determine the magnitude of the response and validate outcome measures. Neuren Pharmaceuticals aims to confirm the optimal dose for a pivotal trial.

Conclusion

Neuren Pharmaceuticals is developing NNZ-2591 as a potential therapeutic for Angelman syndrome and other synaptopathies. The compound has shown promising results in preclinical models and is expected to enter Phase 2 trials in 2020. Neuren Pharmaceuticals is committed to advancing research and development in the field of rare and orphan neurodevelopmental disorders.