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<a href="https://www.axoltis.com/">Axoltis Pharma</a>&#8216;s new treatment candidate for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (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 <a href="https://www.axoltis.com/wp-content/uploads/2023/12/231212-Axoltis-results-EN.pdf">company press release</a>. 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 <a href="https://parkinsonsnewstoday.com/what-is-parkinsons-disease/">Parkinson&#8217;s disease</a>.
“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 <a href="https://journals.sagepub.com/doi/10.1177/0271678X231153281">in the earliest stages of disease</a>, possibly before overt clinical signs are evident.
Neuronal inflammation and impaired nerve communication are also features of the disease, leading to <a href="https://alsnewstoday.com/als-symptoms/">symptoms</a> such as trouble walking and speaking, and breathing difficulties.
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<h3>What is NX210c and how does it work?</h3>
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 <a href="https://clinicaltrials.gov/study/NCT05827653?intr=NCT05827653&amp;rank=1">Phase 1b clinical trial (NCT05827653)</a> 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&#8217;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 <a href="https://chdr.nl/clinical-studies-development/methods-biomarkers/central-nervous-system/neurocart">NeuroCart</a>, which can conduct a battery of nervous system tests.
The findings follow <a href="https://alsnewstoday.com/news/potential-als-therapy-nx210c-be-tested-insilico-axoltis-teamup/">positive tolerability findings</a> 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.

Promising findings seen in healthy volunteer study of Axoltis’ NX210c

<a href="https://insilicotrials.com">InSilicoTrials</a> and <a href="https://www.axoltis.com">Axoltis Pharma</a> are teaming up to advance the development of NX210c, the latter’s lead candidate for treating <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) and other neurodegenerative diseases.
Axoltis will use InSilicoTrials’ <a href="https://insilicotrials.com/platform2/">simulation platform</a> to see how well NX210c works in virtual simulations that mimic brain and spinal cord features of people with neurological conditions, including ALS, <a href="https://parkinsonsnewstoday.com/what-is-parkinsons-disease/">Parkinson’s disease</a>, and <a href="https://multiplesclerosisnewstoday.com/multiple-sclerosis-overview/">multiple sclerosis</a>.
“This partnership represents an exciting synergy between cutting-edge simulation technologies and innovative biotechnological advancements,” Luca Emili, CEO of InSilicoTrials, said in a <a href="https://www.prnewswire.co.uk/news-releases/insilicotrials-and-axoltis-pharma-collaborate-to-advance-therapeutic-solutions-for-neurological-disorders-301886792.html">company press release</a>. “Together, we aim to unlock new insights and develop groundbreaking treatments that will positively impact the lives of patients with neurologic impairments worldwide.&#8221;
InSilicoTrials’s platform combines artificial intelligence (AI) and software tools to develop potential treatments faster while cutting the costs associated with time-consuming and often expensive clinical trials.
It will assess the best dosing regimens of NX210c based on how it impacts brain health and the levels of certain biomarkers, and how safe and effective it might be in a wide range of neurological and neurodegenerative conditions.
“We are very delighted to initiate this collaboration with InSilicoTrials and have the opportunity to optimize and accelerate our next clinical steps,” Yann Godfrin, PhD, CEO of Axoltis, said. “Integrating their industry-leading AI and computational modeling solutions in the development plan of our promising disease-modifying drug will allow us to address the pressing challenges faced by individuals suffering from neurological disorders.&#8221;
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<h3>What is NX210c and how does it work?</h3>
A Phase 2 clinical trial of NX210c in people with ALS is <a href="https://www.axoltis.com/pipeline/">expected to start in the coming years</a>. Multiple, increasing doses of the therapy are being evaluated in healthy elderly people in a <a href="https://classic.clinicaltrials.gov/ct2/show/NCT05827653">Phase 1 trial (NCT05827653)</a>. That study is expected to enroll people with <a href="https://alzheimersnewstoday.com/what-is-alzheimers-disease/">Alzheimer’s disease</a>.
Several neurodegenerative diseases, including ALS, share features such as blood-brain barrier (BBB) leakage, neuronal communication problems, and neuron death. The blood-brain barrier is a highly selective membrane that prevents microbes and other harmful molecules in circulation from entering the brain and spinal cord.
In ALS, motor neurons — nerve cells that control voluntary movements — are affected, causing <a href="https://alsnewstoday.com/symptoms-of-als/">muscle weakness</a> and other symptoms.
NX210c is a lab-made small peptide (small protein) derived from SCO-spondin, a protein involved in several developmental processes, including neuronal survival, maturation, and growth. NX210c corresponds to the specific domain of SCO-spondin that mainly exerts its beneficial effects.
According to Axoltis, NX210c has <a href="https://www.axoltis.com/our-product/properties/">three main properties</a> that make it a promising candidate for treating neurodegenerative conditions: it&#8217;s neuroprotective, it boosts neuronal communication, and it improves the integrity of the blood-brain barrier.
It helps neurons in the brain <a href="https://www.mdpi.com/1422-0067/23/16/8867">communicate better</a> by increasing the transmission of glutamate signals, earlier work in lab-grown neurons and mice has shown. At the same time, it <a href="https://www.sciencedirect.com/science/article/pii/S0306452221000701">protects neurons</a> against damage caused by glutamate overload.
Glutamate is a chemical messenger molecule used by neurons to communicate with each other and plays a crucial role in learning, memory, and brain function. Glutamate signaling <a href="https://alsnewstoday.com/news/reduced-editing-efficiency-mrna-molecule-als-may-be-biomarker/">is abnormal in ALS</a>, suggesting a potential role in the disease.
By acting on the connections between BBB cells, NX210c is thought to help prevent leakage into the brain, including the entry of the <a href="https://alsnewstoday.com/causes-of-als/">overactive immune cells</a> known to contribute to neuroinflammation in ALS.
In a previous Phase 1 trial with 39 healthy people, the related peptide NX210 was found to be <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338184/">safe and well tolerated</a> when given as single ascending doses into the bloodstream. It also was rapidly eliminated from the bloodstream.
The therapy received orphan drug status in the U.S. for ALS and in Europe for treating spinal cord injury. The designation is meant to accelerate a therapy’s clinical development and regulatory review.

Tag: Axoltis Pharma

Promising findings seen in healthy volunteer study of Axoltis’ NX210c

InSilicoTrials, Axoltis partner to work on potential ALS therapy