Patient Dosing Begins in Phase 1/2a Trial of Oral NMD670

Patient dosing has begun in a Phase 1/2a clinical trial of NMD670, an investigational oral therapy by NMD Pharma aiming to improve motor abilities and quality of life for people with myasthenia gravis (MG).

“We are pleased to announce the dosing of the first myasthenia gravis patient today with our lead development candidate, NMD670. This represents a significant milestone in this study and for NMD Pharma,” Thomas Holm Pedersen, the company’s CEO, said in a press release.

NMD670 is an oral small molecule that helps muscles contract by blocking the activity of the CIC-1 chloride ion channel, a cell surface protein that normally transmits inhibitory nerve signals that prevent muscle contraction.

Muscles rely on excitatory and inhibitory nerve signals to contract and relax in a healthy manner. In people with MG, however, the body produces self-reactive antibodies that attack acetylcholine receptors (AChRs). This reduces excitatory signals telling muscles to contract, but not inhibitory signals telling them to relax, causing these signals to become proportionally stronger. The result is muscle weakness and impaired muscle function.

NMD670, by blocking inhibitory signals, aims to restore a balance between muscle contraction and relaxation.

“The pre-clinical data generated by NMD Pharma demonstrates the potential of CIC-1 inhibition in strengthening neuromuscular transmission in myasthenia gravis and I am hopeful that we can replicate those promising pre-clinical results in patients,” said Geert Jan Groeneveld, MD, PhD, the trial’s principal investigator.

The safety and tolerability of NMD670 are being investigated in a Phase 1/2a trial (CHDR1948) involving about 79 adults, including healthy volunteers and people with generalized MG.

Participants will be randomly assigned to either a single or repeated doses of NMD670, or to a placebo.

In addition to safety and tolerability, the study — taking place in Leiden, the Netherlands — aims to assess the medication’s pharmacokinetics, or how it moves into, through, and out of the body, and its pharmacodynamics, meaning the effects it has on the body.

The first healthy volunteer was dosed late last year. NMD Pharma now reported that healthy male and female volunteers have received single doses of NMD670, and that safety, tolerability, and pharmacokinetic endpoints have been assessed.

The study will now proceed with single doses of NMD670 being given to MG patients, and repeated doses (daily doses for a period of 10 days) to healthy volunteers. The trial is expected to finish in December.

“Myasthenia gravis is a debilitating autoimmune disease which can lead to life-threatening symptoms,” Groeneveld said. “There is a real unmet need for a therapy to help relieve these symptoms and so it is particularly exciting that this trial has now moved into patients.”

NMD670 is also being evaluated for its potential in treating other neuromuscular disorders.