InSilicoTrials, Axoltis partner to work on potential ALS therapy

Effort will explore how well NX210c works in virtual brain, spinal simulations

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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InSilicoTrials and Axoltis Pharma are teaming up to advance the development of NX210c, the latter’s lead candidate for treating amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases.

Axoltis will use InSilicoTrials’ simulation platform to see how well NX210c works in virtual simulations that mimic brain and spinal cord features of people with neurological conditions, including ALS, Parkinson’s disease, and multiple sclerosis.

“This partnership represents an exciting synergy between cutting-edge simulation technologies and innovative biotechnological advancements,” Luca Emili, CEO of InSilicoTrials, said in a company press release. “Together, we aim to unlock new insights and develop groundbreaking treatments that will positively impact the lives of patients with neurologic impairments worldwide.”

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.”

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What is NX210c and how does it work?

A Phase 2 clinical trial of NX210c in people with ALS is expected to start in the coming years. Multiple, increasing doses of the therapy are being evaluated in healthy elderly people in a Phase 1 trial (NCT05827653). That study is expected to enroll people with Alzheimer’s disease.

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 muscle weakness 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 three main properties that make it a promising candidate for treating neurodegenerative conditions: it’s neuroprotective, it boosts neuronal communication, and it improves the integrity of the blood-brain barrier.

It helps neurons in the brain communicate better by increasing the transmission of glutamate signals, earlier work in lab-grown neurons and mice has shown. At the same time, it protects neurons 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 is abnormal in ALS, 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 overactive immune cells 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 safe and well tolerated 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.