Axoltis Pharma has announced topline results of SEALS, its phase 2 clinical trial evaluating the effect of NX210c in patients with amyotrophic lateral sclerosis (ALS).
The drug candidate has three properties relevant for treating neurodegenerative diseases: blood brain barrier (BBB) restoration, neuroprotection and enhancement of neurotransmission.
Between October 2024 and October 2025, 82 ALS patients at 16 French clinical sites were enrolled in the SEALS study. Patients were stratified by low and high serum neurofilament light chain (NfL) concentration and randomised (3:3:2) in three arms to receive NX210c at either one of two dose levels (5 mg/kg or 10 mg/kg) or placebo, administered as 10‑minute intravenous infusions 3 times weekly for 4 weeks.
While NX210c did not meet the primary endpoint of change from baseline to week-6 in NfL or albumin quotient between cerebrospinal fluid and blood (Qalb), the company said consistent positive trends were observed in secondary and exploratory assessed parameters.
In post-hoc analyses, the decline rate of clinical function, assessed by the Harmonized Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) slope, was substantially reduced versus placebo at week 6. This effect was consistently stronger at week 10. The effect on the decline rate was also maintained at month 4.
Benefits were especially observed in motor function subscale, with an average reduction of about 64% for 5mg/kg, p<0.05 and 33% for 10mg/kg for weeks 6 and 10, and still observable at month 4 with an average reduction of 42% for 5mg/kg and 18% for 10mg/kg. The decline of the respiratory subscale was also substantially attenuated at week 10, with an average reduction of 59% for 5mg/kg and 91% for 10mg/kg with p=0.066, and at month 4 with an average reduction of 53% for 5mg/kg and 84% for 10mg/kg with p<0.05.
At week 6, a trend to dose response in serum NfL was observed, which was even more pronounced at month 4. In that same month, 25.4% of the patients in the active dose arms had a decrease in serum NfL of more than 10% from pre-dose while only 11.8% of the patients in the placebo arm did.
The percentage change from pre-dose of plasma claudin-5, a resident tight-junction protein mainly expressed in the endothelial cells of the neurovascular unit that acts as a gate keeper of the BBB, was significantly reduced at 10mg/kg vs placebo arm at end of treatment with a dose-effect relationship. This effect was maintained at month 4. Claudin-5 is released in the blood stream in case of BBB dysfunction. Therefore, observing a decrease in its circulating levels serves as a promising proxy for barrier recovery.
The SEALS trial confirmed the safety and tolerability profile of NX210c in ALS patients with no drug accumulation, and pharmacological parameters have already been observed in phase 1.
“These results are promising and contribute to generating evidence that NX210c’s properties are beneficial in neurodegenerative diseases, especially ALS. These findings support advancing NX210c to the next stages of clinical development. We are very grateful to all the patients participating in the SEALS study, their caregivers, the investigators and their team, the service providers and our team,” said Annette Janus, neurologist and chief medical officer at Axoltis Pharma.
“The observed effect of NX210c in reducing plasma claudin-5 opens new avenues for the use of NX210c to treat a broad range of indications where blood brain barrier dysfunction is observed, among them Alzheimer’s disease, Parkinson’s disease and multiple sclerosis,” said Yann Godfrin, CEO at Axoltis.
Axoltis is exploring the next clinical steps for NX210c in ALS. Additional analyses are under way, including a 10-month follow-up of the patients, the PKPD relationship, to determine the potential optimal regimen of treatment repetition able to sustain the clinical effects.
The results will be presented in more detail during Neuroscience 2026, the annual meeting of the Society for Neuroscience, in Washington, DC, in November.
“These results represent an important milestone for Axoltis and provide a strong foundation for the next stages of clinical development,” said Gilles Avenard, chairman of Axoltis’ board.
“We will engage with the regulatory health authorities to define a clear and streamlined development pathway and to determine the most appropriate next steps.”