First Patient Dosed in Neuraly’s NLY01 Trial Testing Safety, Efficacy

The first patient has been dosed in a Phase 2 study testing NLY01, an investigational compound with a new mechanism of action designed to stall the progression of Parkinson’s disease.

NLY01, being developed by Neuraly, could prevent nerve cell loss in the brain by stopping the toxic activation of immune cells. The results of the trial are expected within two years.

“Current therapies for Parkinson’s disease provide only temporary symptomatic improvement and fail to slow or halt the relentless progression of the disease,” Seulki Lee, PhD, Neuraly’s president and CEO said in a press release.

“The initiation of this Phase 2 study is an important milestone in the ongoing advancement of NLY01 which we believe has the potential to be a ground-breaking therapy for Parkinson’s patients based on results we have seen to date in preclinical trials,” Lee said.

Initially developed by researchers at Johns Hopkins University, NLY01 is being pursued as a disease-modifying agent for neurodegenerative disorders including Parkinson’s and Alzheimer’s disease.

It consists of a brain-penetrating, long-acting activator of the glucagon-like peptide 1 receptor (GLP-1R). Specifically, it is a form of exenatide, a small protein that activates GLP-1R (exendin-4), which has an extended lifetime in the body.

GLP-1R activators, or agonists, are a class of glucose-lowering therapies that enhance the secretion of insulin in the pancreas. For this reason, they include approved medications to help control blood sugar levels in people with type 2 diabetes — such as Byetta (short-acting exenatide), Bydureon (extended-release exenatide) and Victoza (liraglutide).

There is growing evidence that this class of compounds also work as neuroprotective agents with potential benefits for neurodegenerative diseases.

Preclinical studies in mouse models of Alzheimer’s and Parkinson’s have shown that NLY01 binds to overabundant GLP-1R, blocking the activation of microglia — brain-resident immune cells whose overactivation can result in damaging inflammatory responses in the brain.

By blocking glial activation and inflammatory signalling molecules (small proteins called cytokines), NLY01 prevented nerve cell death, slowed disease progression, improved motor and cognitive functions, and extended the animals’ lifespan.

A first-in-human Phase 1 study (NCT03672604), in which NLY01 was given via under-the-skin (subcutaneous) injections to healthy volunteers, found the treatment to be well-tolerated.

A once-weekly dosing of the compound was sufficient to provide nearly continuous therapeutic concentrations of NLY01 in the blood. This treatment achieved three times higher concentrations than short-acting forms of GLP-1R agonists, which are often limited by side effects.

The ongoing Phase 2 trial (NCT04154072) is looking to enroll 240 patients, ages 30–80, in the U.S. and Canada. Its goal is to assess the safety, tolerability, and efficacy of 36 weeks of treatment with NLY01 in individuals with early untreated Parkinson’s disease

Participants will be randomly assigned to 2.5 mg or 5.0 mg of NLY01 or a placebo.

The study’s primary goal is to understand NYL01’s capacity to improve motor function by assessing changes in the Unified Parkinson’s Disease Rating Scale (UPDRS) part 2 and 3.

Enrollment is currently ongoing at different sites in the U.S. More information is available here.

“Inhibition of pathological glial activation has the potential to prevent neuronal cell death and this has the potential to lead to novel treatments for Parkinson’s and other neurodegenerative diseases,” said Viktor Roschke, PhD, chief scientific officer of Neuraly.

“Numerous attempts to develop therapies for Parkinson’s have failed, partly due to poorly understood mechanisms of neurodegeneration. Our knowledge of how and why susceptible neuronal cells in the brain die in this disease provided us with the foundation for developing NLY01,” Roschke said. “We are excited to initiate this Phase 2 study and continue to explore this new opportunity to treat Parkinson’s disease and potentially forestall the progressive decline in function that occurs with available therapies.”