Aptinyx’s Investigational Parkinson’s Therapy NYX-458 Enters Phase 1 Clinical Testing

Iqra Mumal, MSc avatar

by Iqra Mumal, MSc |

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Aptinyx has launched a Phase 1 clinical trial of NYX-458, a potential treatment for cognitive impairment in Parkinson’s disease patients.

The randomized, double-blind, placebo-controlled trial will be conducted in roughly 62 healthy volunteers to evaluate the safety, tolerability, and pharmacokinetics of the compound. Pharmacokinetics refers to a drug’s absorption, bioavailability, distribution, metabolism, and excretion in the body.

Patients will receive both single and repeat dosing of NYX-458 at multiple dose levels to determine the optimal dosage for future Phase 2 studies. The company is planning studies to test the effectiveness of the investigational therapy next year.

“Based on the compelling preclinical evidence of NYX-458 in reversing cognitive impairment, we are excited to initiate this first-in-human study and advance NYX-458 as a potential treatment for this very common and highly limiting, but poorly treated, symptom of Parkinson’s disease,” Torsten Madsen, MD, PhD, chief medical officer of Aptinyx, said in a press release.

NYX-458 is a small molecule therapy that functions by regulating the activity of N-methyl-D-aspartate (NMDA) receptors, which are found in nerve cells, enhancing synaptic plasticity and improving nerve cell communication. Synapses are the junctions between two nerve cells that allow them to communicate; synaptic plasticity refers to the ability of synapses to strengthen or weaken over time.

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Synaptic plasticity contributes to learning, memory, and cognition, all of which are often impaired in Parkinson’s patients.

Earlier this year, Aptinyx presented positive preclinical data of NYX-458 during the 2018 Advances in Alzheimer’s and Parkinson’s Therapies Focus Meeting in Torino, Italy.

The study, which was conducted in a non-human primate model of Parkinson’s disease, showed that NYX-458 significantly increased attention, improved cognitive flexibility, and enhanced working memory as quickly as two hours after the administration of a single oral dose. Those effects were maintained for up to three weeks. No major safety or tolerability issues were observed.

“… NYX-458 has the potential to be a meaningful therapy for patients suffering from some of the most devastating symptoms of Parkinson’s disease,” Cassia Cearley, PhD, vice president of research at Aptinyx, said in a press release at the time. “These results in a relevant and highly translatable model warrant the advancement of NYX-458 into clinical studies.”

So far, Aptinyx’s chemistry and discovery platform has generated three therapeutic candidates, NYX-2925, NYX-783, and NYX-458, currently in clinical development for the treatment of various nervous system disorders. This platform is unique in that it discovers compounds that work to regulate — rather than block or over-activate — NMDA receptors to enhance synaptic plasticity, which is the foundation of nerve cell communication.


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