Promising findings seen in healthy volunteer study of Axoltis’ NX210c

Two clinical trials are planned to study therapy in ALS, Parkinson's disease

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

Share this article:

Share article via email
Multiple hands are seen giving the thumbs up sign against the backdrop of a black circle.

Axoltis Pharma‘s new treatment candidate for amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases was deemed safe and well tolerated at multiple doses in healthy volunteers who participated in a Phase 1b trial.

Findings from the trial and preclinical studies also indicate NX210c is working as intended, boosting neuroprotection and neuronal communication and repairing the blood-brain barrier (BBB), the highly selective membrane that prevents microbes and other harmful molecules in circulation from entering the brain and spinal cord.

“This trial confirms the excellent safety and tolerability profile of NX210c. Moreover, we are excited to observe significant pharmacodynamic effects on blood and [spinal] fluid biomarkers, especially those important for BBB integrity, neuroprotection and neurotransmission,” Annette Janus, MD, neurologist and chief medical officer at Axoltis, said in a company press release. Pharmacodynamic effects are the effects of a compound on the body.

The company plans to launch two clinical trials in 2024 to study NX210c in people with neurodegenerative conditions — a Phase 2 trial in ALS and a Phase 1b trial in Parkinson’s disease.

“The results are very promising and provide a strong foundation to build on the NX210c drug development strategy,” Janus said.

A hallmark feature of aging and many neurodegenerative conditions is a loss of integrity of the BBB. This lets unwanted compounds in the blood reach the brain and spinal cord and contribute to inflammation and nerve damage. In ALS, damage to this barrier is believed to occur in the earliest stages of disease, possibly before overt clinical signs are evident.

Neuronal inflammation and impaired nerve communication are also features of the disease, leading to symptoms such as trouble walking and speaking, and breathing difficulties.

Recommended Reading
Illustration of intranasal spray.

Intranasal formulation helps edaravone reach brain: Early study

What is NX210c and how does it work?

NX210c is a small protein fragment derived from SCO-spondin, a protein important for processes such as nerve cell survival, maturation, and growth during embryonic development. It is mostly lost in later developmental stages.

By providing patients with the functional part of SCO-spondin, NX210c should exert neuroprotective effects, boost the communication between nerve cells, and promote the integrity of the BBB.

The molecule was tested in a Phase 1b clinical trial (NCT05827653) in 29 healthy participants, ages 55 and older, who were randomly assigned to one of two doses of NX210c — 5 mg/kg or 10mg/kg — or a placebo, given as a 10-minute intravenous (into-the-vein) infusion, three times a week for four weeks.

The trial was conducted at the Center for Human Drug Research in the Netherlands. Its main goal was to evaluate the compound’s safety and tolerability, and a secondary measure examined its pharmacokinetics, or movement into, through, and out of the body.

A number of disease biomarkers were also examined, including MRI biomarkers to assess BBB integrity and cerebral blood flow, along with blood and spinal fluid biomarkers of BBB integrity and neuroinflammation.

NX210c was safe and well tolerated at both doses, with only mild side effects reported. The most common treatment-emergent side effects were headache and somnolence. Its neurologic safety profile was also validated using NeuroCart, which can conduct a battery of nervous system tests.

The findings follow positive tolerability findings from a Phase 1 trial with 39 healthy people who received single ascending doses.

“We are very pleased with our preclinical and clinical studies, which strengthen Axoltis’ position to become a key leader in BBB repair. Among our target applications is the initiation of a Phase 2 trial for NX210c in patients living with amyotrophic lateral sclerosis, as BBB deterioration may be a trigger in the progression of this terrible disease,” said Yann Godfrin, PhD, CEO of Axoltis.

Under a partnership with InSilicoTrials, Axoltis will conduct further virtual modeling to evaluate and optimize NX210c for other neurodegenerative diseases.