Axoltis reports Phase 2 SEALS results for NX210c in ALS, with post-hoc analyses showing slower ALSFRS-R decline and reduced plasma claudin-5.
Written By: Kirti Kumbhar, M. Pharm (QA)
Reviewed By: Pharmacally Editorial Team
Axoltis Pharma has reported topline results from the Phase 2 SEALS trial evaluating NX210c in patients with amyotrophic lateral sclerosis (ALS). Although NX210c did not meet the study’s primary endpoint, post-hoc analyses showed slower rates of functional decline compared with placebo at weeks 6 and 10, with the effect remaining observable at month 4.
NX210c is a 12-amino-acid cyclic peptide derived from a conserved and repeated sequence of SCO-spondin. Axoltis is developing the candidate for neurodegenerative and trauma-related disorders based on proposed blood-brain barrier (BBB) restoration, neuroprotection and improved neurotransmission. NX210c has received Orphan Drug Designation from both the U.S. Food and Drug Administration and European Medicines Agency for ALS.
Between October 2024 and October 2025, 82 patients were enrolled across 16 clinical sites in France. Patients were stratified by low or high serum neurofilament light chain (NfL) concentration and randomized in a 3:3:2 ratio to NX210c 5 mg/kg, NX210c 10 mg/kg or placebo. Treatment was administered as a 10-minute intravenous infusion three times weekly for four weeks.
The primary endpoint assessed change from baseline to week 6 in serum NfL or the cerebrospinal fluid-to-blood albumin quotient (Qalb). NX210c did not meet this endpoint, although positive trends were observed across secondary and exploratory assessments.
Post-Hoc Analysis Showed Slower ALSFRS-R Decline
A post-hoc analysis evaluated clinical function using the slope of the Harmonized Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R).
At week 6, the ALSFRS-R decline rate was -0.67 points/month with NX210c 5 mg/kg, -0.90 with 10 mg/kg and -1.14 with placebo. These values corresponded to average reductions in the rate of decline of 41% and 21%, respectively, compared with placebo.
At week 10, decline rates were -0.77 points/month for 5 mg/kg, -1.06 for 10 mg/kg and -1.57 for placebo. The corresponding reductions were 51% for 5 mg/kg, with p<0.05, and 32% for 10 mg/kg.
At month 4, the decline rates were -1.01, -1.08 and -1.59 points/month for the 5 mg/kg, 10 mg/kg and placebo groups, respectively. This corresponded to reductions of 36% and 32% versus placebo.
Motor function showed an average reduction in the rate of decline of approximately 64% with 5 mg/kg, with p<0.05, and 33% with 10 mg/kg across weeks 6 and 10. At month 4, the reductions remained observable at 42% and 18%, respectively.
Respiratory function also showed attenuated decline. At week 10, the reported reductions were 59% with 5 mg/kg and 91% with 10 mg/kg, with p=0.066. At month 4, the corresponding reductions were 53% and 84%, with p<0.05.
NfL and Claudin-5 Findings
Serum NfL showed a trend toward a dose response at week 6 that became more pronounced at month 4. At month 4, 25.4% of patients receiving an active NX210c dose had a reduction in serum NfL of more than 10% from predose, compared with 11.8% of patients receiving placebo.
The study also assessed plasma claudin-5, a tight-junction protein mainly expressed in endothelial cells of the neurovascular unit and involved in maintaining the BBB. The percentage change from predose was significantly reduced with NX210c 10 mg/kg versus placebo at the end of treatment (p<0.001), with a dose-effect relationship. The effect remained observable at month 4, although the p-value for the 10 mg/kg group was 0.069.
Axoltis described circulating claudin-5 reduction as a promising proxy for BBB barrier recovery. The finding provides biological evidence consistent with the proposed BBB-related activity of NX210c, rather than establishing clinical efficacy on its own.
Safety and Next Development Steps
NX210c showed a good safety and tolerability profile in the SEALS trial, with no drug accumulation reported. Earlier Phase 1b multiple ascending-dose data reported in 2023 also showed that NX210c was well tolerated.
Axoltis is evaluating the next clinical steps for NX210c in ALS. Additional analyses include a 10-month patient follow-up and assessment of the pharmacokinetic/pharmacodynamic relationship to help determine a potential treatment-repetition regimen.
Detailed SEALS results are scheduled to be presented on November 15, 2026, during Neuroscience 2026, the annual meeting of the Society for Neuroscience, being held in Washington, DC, from November 14–18.
The company also plans to engage with regulatory health authorities regarding the development pathway and next steps for NX210c.
Reference
Axoltis Pharma announces topline Phase 2 results for NX210c in Amyotrophic Lateral Sclerosis, axoltis pharma, 15 September 2026
ALS Phase II Study of NX210c (SEALS), ClinicalTrials.gov ID NCT06365216
About the Writer
Kirti Kumbhar (LinkedIn) is an M.Pharm graduate with experience in Quality Assurance at Lupin Limited and a strong interest in clinical research, regulatory affairs, and Trial Master File (TMF) management. She has developed knowledge of regulatory documentation, quality systems, compliance, and healthcare research through her professional experience. Passionate about clinical development and continuous learning, Kirti is committed to supporting high-quality healthcare documentation, regulatory excellence, and research-driven healthcare advancements.