NNZ-2591 is an analogue of cyclic glycine proline (cGP), a peptide (small protein) that naturally exists in the brain and is important for the development of neurons. The investigational therapy is designed to restore the normal connectivity and signaling between brain cells for conditions in which they are impaired, such as Angelman syndrome.
In a mouse model of Angelman syndrome, treatment with NNZ-2591 improved cognition and motor function, reduced anxiety, and eliminated seizures. NNZ-2591 also has shown brain-protecting and memory-enhancing effects in animal models of multiple neurological conditions, including fragile X syndrome, Parkinson’s disease, multiple sclerosis, Pitt Hopkins syndrome and Phelan-McDermid syndrome.
The U.S. Food and Drug Administration (FDA) has granted NNZ-2591 orphan drug designation as a potential Angelman syndrome treatment. The FDA also has given NNZ-2591 orphan drug designation as a potential treatment for Pitt Hopkins syndrome and Phelan-McDermid syndrome. Currently, there are no medications approved by the FDA to treat any of those three disorders.
Neuren is currently funding a Phase 1 clinical trial (NCT04379869) that is planning to assess multiple doses of NNZ-2591 in about 30 healthy volunteers (i.e., without Angelman syndrome or other known health conditions). The goal of this study is to determine the investigational medicine’s safety and tolerability, as well as its pharmacokinetic profile (how the medication moves through and is processed by the body).
The Phase 1 study is recruiting participants in Australia; additional information is available here.
A contract manufacturer produced NNZ-2591 for use in this ongoing Phase 1 clinical trial. Neuren announced that the same contract manufacturer also will be making the investigational medicine for use in upcoming Phase 2 clinical trials.
Neuren is planning to start Phase 2 trials in Angelman syndrome, Phelan-McDermid syndrome, and Pitt Hopkins syndrome in 2021.
“We have made excellent progress in the optimisation and scale up of the manufacturing process for NNZ-2591,” Jon Pilcher, CEO of Neuren Pharmaceuticals, said in a press release. “This investment is another important stepping-stone towards the Phase 2 trials in 2021, in which we aim to confirm the potential of NNZ-2591 to address the urgent unmet need in three serious childhood disorders.”