Dosing begins in Phase 1 safety study of new LRRK2 inhibitor

Therapy blocks the enzyme whose mutated gene is a common cause of Parkinson's

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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Dosing has begun in a Phase 1 clinical trial of healthy volunteers to evaluate the safety and pharmacological properties of NEU-723, Neuron23’s oral investigational treatment for Parkinson’s disease.

The small molecule candidate therapy is designed to block LRRK2, an enzyme coded by a gene of the same name whose mutations are one of the most common genetic causes of Parkinson’s.

“We are excited to begin this clinical trial of NEU-723, marking our first program to enter clinical development and only the second LRRK2 small molecule currently in the clinic for the modification of Parkinson’s disease,” said Nancy Stagliano, PhD, Neuron23’s CEO, in a company press release. “A best-in-class LRRK2 inhibitor for Parkinson’s disease, NEU-723 has been shown in preclinical studies to have strong disease-modifying potential with a higher therapeutic index than other candidates in development.”

A feature of Parkinson’s disease is the progressive loss of dopaminergic neurons, the nerve cells in the brain that produce the chemical messenger dopamine. This leads to the condition’s hallmark motor symptoms, tremors and slow movements, and nonmotor symptoms, such as cognitive impairment, constipation, and sleep disturbances.

Current Parkinson’s treatments mainly target motor symptoms by increasing dopamine levels, but don’t alter the disease’s progression.

“Parkinson’s disease is one of the most devastating neurodegenerative diseases, with no cure and no existing therapies that modify the progression of the disease,” said Sam Jackson, MD, chief medical officer of Neuron23.

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Parkinson’s risk is thought to arise through a combination of genetic and environmental factors. Most cases occur in people without a family history, but mutations in the LRRK2 gene ­have been associated with both familial and sporadic Parkinson’s.

These mutations are known to increase the activity of the encoded LRRK2 enzyme, which is thought to trigger the abnormal activation of certain immune cells in the brain, leading to damage to dopaminergic neurons. Blocking LRRK2’s action with NEU-723, which can access the brain, may protect neurons and slow or halt the disease.

The first-in-human Phase 1 trial (NCT05633745) is testing single and multiple ascending doses of NEU-723 versus a placebo in up to 64 healthy adults, ages 18-80. The multiple dosing group will receive either the therapy or a placebo for seven days.

In addition to safety and tolerability, the study will investigate NEU-723’s pharmacokinetic properties — how it’s absorbed into the bloodstream, the levels it reaches and how long it lasts, and how it’s cleared from the body.

Neuron23 has recently partnered with QIAGEN to develop a companion diagnostic to identify Parkinson’s patients who are likely to respond to an LRRK2 blocker like NEU-723, even though they don’t carry an LRRK2 variant.

“The combination of best-in-class clinical candidates with a first-of-its-kind companion diagnostic places Neuron23 in a leadership position in Parkinson’s disease,” Stagliano said.

Another LRRK2-based candidate for Parkinson’s, NEU-411, is expected to enter clinical assessment this year, according to Neuron23.

“We look forward to advancing this clinical trial along with our entire LRRK2 program and pipeline with the goal of treating the right patients with the right medicines,” Jackson said.