NNZ-2591 as a Potential Treatment for Angelman Syndrome
Neuron Pharmaceuticals is developing NNZ-2591 as a potential treatment for Angelman Syndrome, a rare neurodevelopmental disorder. NNZ-2591 is a synthetic analog of a metabolite called cyclic glycin-proline (cGP), which helps maintain the bioavailability of insulin growth factor-1 (IGF-1) in the brain. Preclinical studies have shown that NNZ-2591 can correct impairments in synaptic dysfunction and improve behavioral symptoms in a mouse model of Angelman Syndrome. A Phase 1 study in healthy adults demonstrated good safety and tolerability, as well as predictable pharmacokinetics. Neuron Pharmaceuticals is now preparing for a Phase 2 study in Angelman Syndrome patients to further evaluate safety and clinical response. The company has submitted an investigational new drug application to the FDA and is in the process of finalizing study preparations. More information can be found on clinicaltrials.gov and the Neuron Pharmaceuticals website.
Larry Glass and Nancy Jones from Neuron Pharmaceuticals provided an update on the clinical development program for Angelman syndrome during the 2021 FAST Science Summit. Neuron Pharmaceuticals is a biopharmaceutical company focused on rare neurodevelopmental disorders with high unmet medical needs. They have two compounds in development, Trofinetide and NNZ-2591. While Trofinetide is being developed for Fragile X syndrome and Rett syndrome, NNZ-2591 is specifically being developed for Angelman syndrome.
Drug Development Stages
The drug development process involves several key stages, starting with preclinical studies and animal model studies. This is followed by three major phases of clinical trials: Phase 1 (safety and dosing), Phase 2 (safety and efficacy), and Phase 3 (confirming efficacy and safety). Once Phase 3 studies are completed and data is obtained, a new drug application can be submitted for approval. Neuron Pharmaceuticals has completed animal model studies, IND-enabling studies, and a Phase 1 study in healthy adults. They are now preparing for a Phase 2 study in Angelman syndrome.
Different Approaches to Drug Development
When developing a new treatment, there are two major approaches: repurposing existing drugs or developing novel drugs. Repurposing involves using drugs already on the market for other indications or testing existing supplements. Novel drug development focuses on creating new molecules. Neuron Pharmaceuticals is developing NNZ-2591 as a neurobiological therapy, which falls under the category of downstream treatments that address impairments in the neurobiological system.
How NNZ-2591 Works
NNZ-2591 is a synthetic analog of a metabolite called cyclic glycin-proline (cGP), which is produced by supporting cells in the brain. It helps maintain the bioavailability of insulin growth factor 1 (IGF-1), an essential growth factor in the brain. NNZ-2591 has a molecular structure similar to cGP but with one small change that makes it more suitable for use as a medication. It has good pharmacokinetic properties, crosses the blood-brain barrier, and is 100% bioavailable. NNZ-2591 is available as an oral liquid formulation.
Potential Benefits for Angelman Syndrome
In preclinical studies, NNZ-2591 has shown the ability to correct impairments associated with synaptic dysfunction, which is common in disorders like Angelman syndrome. It improves signaling between brain cells, reduces inflammatory signaling molecules, and increases the availability of IGF-1. NNZ-2591 has been tested in a mouse model of Angelman syndrome and successfully normalized the behavioral impairments associated with the condition.
Neuron Pharmaceuticals conducted a Phase 1 study of NNZ-2591 in healthy adults to assess safety, tolerability, and pharmacokinetics. The study involved single-dose and seven-day twice-daily dosing, with participants receiving either NNZ-2591 or a placebo. The study showed a good safety and tolerability profile, with no severe or serious adverse events. NNZ-2591 demonstrated predictable pharmacokinetics. The next step is a Phase 2 study in Angelman syndrome, which will focus on safety, pharmacokinetics, and clinical response. The results will inform the design of larger Phase 3 trials.
The Phase 3 study of NNZ-2591 in Angelman syndrome will be conducted in Australia, recruiting up to 22 children aged three to 17. The study will involve 13 weeks of open-label treatment with the oral liquid formulation of NNZ-2591. Neuron Pharmaceuticals has submitted an investigational new drug application to the FDA and is currently responding to feedback on the protocol design. More information about the study can be found on clinicaltrials.gov by searching for “Neuren and Angelman.” Updates will also be posted on the Neuron Pharmaceuticals website.
In conclusion, NNZ-2591 shows promise as a potential treatment for Angelman syndrome. The preclinical studies and Phase 1 trial have provided positive results, and Neuron Pharmaceuticals is moving forward with a Phase 2 study to further evaluate its safety, pharmacokinetics, and clinical response. The ultimate goal is to improve the lives of individuals with Angelman syndrome and address the unmet medical needs in this rare neurodevelopmental disorder.
- Title: NNZ-2591 as a Potential Treatment for Angelman Syndrome
- Author(s): Larry Glass, Nancy Jones
- Author(s)’ affiliation: Neuren Pharmaceuticals
- Publication date: 2022-01-04
- Collection: 2021 FAST Science Summit