NX210c / Axoltis Pharma, Godfrin Life-Sci - LARVOL DELTA

Axoltis misses the mark in phase 2 ALS study, but will persevere with the synthetic peptide (FierceBiotech) - "At six weeks, patients did not show a significant change from baseline in blood neurofilament light chain (NfL), a test used to evaluate leakage of NfL protein into the bloodstream when nerve cells are injured. While there was a trend of a decrease of NfL in the blood in 25.4% of patients in the NX210c arms of the study compared to 11.8% among the placebo-takers after four months, these results were not significant....Benefits in motor function scale, measured using the harmonized revised amyotrophic lateral sclerosis functional rating scale, were observed with 64% and 33% reductions in patients treated with 5 mg/kg and 10 mg/kg NX210c, respectively."

P2 data • Amyotrophic Lateral Sclerosis

NX210c, A Promising Drug Candidate For Neurodegenerative Diseases (ENCALS 2026) - P2 | "This likewise guided selection of NfL and the quotient of cerebrospinal fluid to blood albumin blood (Qalb) as primary endpoints in the trial. Conclusion NX210c is a promising drug candidate that may offer a novel therapeutic strategy for neurodegenerative disease involving BBB breakdown, including ALS."

CNS Disorders • CLDN5 • NEFL • SPON1

SEALS: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study Evaluating Efficacy And Safety Of NX210c In Amyotrophic Lateral Sclerosis (ALS) Patients: Topline Results (ENCALS 2026) - "Based on the first 50 subjects, DSMB concluded safety and tolerability satisfactory. Results of NfL, Qalb and clinical endpoints for the initial post-treatment follow-up period will be presented.Conclusion Topline results will unveil the impact of NX210c in ALS and how its properties may be potentially applicable to other CNS diseases."

Clinical • P2 data • Amyotrophic Lateral Sclerosis • CNS Disorders • CLDN5

Augmented Placebo Control Using Synthetic Patient Profiles In ALS Clinical Trials: A Methodological Framework (ENCALS 2026) - P2 | "We present a methodological framework integrating synthetic placebo patient profiles into treatment effect estimation, applied in the SEALS study evaluating NX210c in patients with ALS (ID: NCT06365216).Material and methods Synthetic placebo profiles are generated using disease progression and biomarker models from external ALS datasets, including clinical trial populations and patient registries...Design paper, no results are presented.Conclusion This framework aims to enhance the efficiency and interpretability of treatment effect estimation while maintaining trial validity. By leveraging external knowledge through synthetic data and prognostic modeling, augmented placebo approaches may optimize evidence generation in rare disease trials, such as ALS, while limiting reliance on large placebo groups."

Clinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Rare Diseases • NEFL

NX210c Demonstrates Therapeutic Potential to Restore Blood-Brain Barrier in a QSP Model of Relapsing-Remitting Multiple Sclerosis. (PubMed, Int J Mol Sci) - "Particularly when administered alongside one of five commonly used MS therapies (interferon β-1a, teriflunomide, cladribine, natalizumab, ocrelizumab), in the highly active subpopulation, the model on average predicted a reduction in relapse frequency in the 10 mg NX210c-treated group versus untreated group from four to no relapses over two years. These findings suggest that NX210c may enhance therapeutic efficacy in RRMS by promoting BBB restoration and modulating immune responses, offering a promising avenue for combination treatment strategies."

Journal • CNS Disorders • Inflammation • Multiple Sclerosis • IFNB1

SEALS: ALS Phase II Study of NX210c (clinicaltrials.gov) - P2 | N=80 | Active, not recruiting | Sponsor: Axoltis Pharma | Recruiting ➔ Active, not recruiting | Trial completion date: Feb 2026 ➔ Sep 2026

Enrollment closed • Trial completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

Administration of a Novel Peptide Derived From Thrombospondin Repeat Sequences Enhances Recovery after Cervical Spinal Cord Injury. (PubMed, J Neurotrauma) - "Furthermore, for animals that were treated daily with NX210c starting 8 h post-injury, histological analysis demonstrated greater white and gray matter preservation and reduced cavity size, along with the upregulation of neuronal markers. To conclude, NX210c mitigates various aspects of SCI, including motor function and tissue preservation, with preferential results being obtained with the delayed initial administration of NX210c at 8 h post-injury."

Journal • CNS Disorders • Orthopedics • SPON1 • THBS1

Axoltis Pharma, a French BioTech company dedicated to developing novel therapeutic solutions for neurodegenerative diseases, today announces the closing of a €18 million ($20.9 million) Series A funding round in order to develop its lead drug candidate, currently in phase 2 clinical trials in patients with ALS/Lou Gehrig’s disease. (EU-Startups) - "It is here that the company looks to make progress as they develop NX210c, a cyclic peptide of 12 amino acids designed from the most conserved and repeated sequence of SCO-spondin, a glycoprotein that plays a crucial role in the development of the central nervous system during embryogenesis....The funds obtained will also help the company pursue research into other neurological indications where the properties of NX210c could deliver a significant impact, notably in repairing the blood-brain barrier."

Financing • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • Parkinson's Disease

Smart zwitterionic biodegradable hydrogel for sustained peptide delivery: Application to the neurotherapeutic peptide NX210c. (PubMed, Biomater Adv) - "These results highlight the hydrogel's potential as a patient-friendly, clinically translatable platform for therapeutic peptides requiring sustained release. Future studies will focus on the evaluation of its therapeutic efficiency."

Journal • CNS Disorders • SPON1

Safety, Tolerability and Pharmacokinetic-Pharmacodynamic Relationship of NX210c Peptide in Healthy Elderly Volunteers: Randomized, Placebo-Controlled, Double-Blind, Multiple Ascending Dose Study. (PubMed, Neurol Ther) - "Multiple doses of NX210c exhibited a good safety profile, showed non-cumulative pharmacokinetics, and exerted pharmacodynamic effects on biomarkers linked to BBB integrity. The effects of NX210c on claudin-5 and biomarkers influencing BBB integrity-and the overarching brain protection it offers-provide a novel therapeutic strategy targeting an underlying driver of neurodegenerative conditions for which disease-modifying treatments are limited or not available."

Journal • PK/PD data • CNS Disorders • Inflammation • CLDN5 • NEFL • SPON1

CHDR2235: MAD Study of NX210c (clinicaltrials.gov) - P1 | N=29 | Completed | Sponsor: Axoltis Pharma | Recruiting ➔ Completed

Trial completion • Alzheimer's Disease • CNS Disorders

NX210c for recovering Blood Brain Barrier integrity in ALS patients: in silico modelling complements statistical analysis of fluid biomarkers for dose selection and design of a phase II study (ALS-MND 2024) - "Safety results of 29 subjects showed NX210c has a good safety profile with all but one of the treatment emergent adverse events being mild (1 moderate) and no significant neurotoxicity. Statistical analysis of blood and cerebrospinal fluid (CSF) biomarkers demonstrated significance or trend(s) for change. Further PK/PD modelling methods identified relationships between NX210c PK and plasma biomarkers, with claudin-5, homocysteine, neurofilament light chain and SPARC-like protein 1 (SPARCL1) among them."

Biomarker • Clinical • P2 data • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation • CLDN5 • NEFL • SPARCL1 • SPON1

SEALS: ALS Phase II Study of NX210c (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: Axoltis Pharma | Not yet recruiting ➔ Recruiting

Enrollment open • Amyotrophic Lateral Sclerosis • CNS Disorders • NEFL

NX210c drug candidate peptide strengthens mouse and human blood-brain barriers. (PubMed, Fluids Barriers CNS) - "In summary, we have gathered preclinical data showing the capacity of NX210c to strengthen BBB integrity. Through this property, NX210c holds great promises of being a disease-modifying treatment for several neurological disorders with high unmet medical needs."

Journal • Preclinical • CNS Disorders • Inflammation • CLDN5 • OCLN • SPON1

Nx210c peptide: a promising drug candidate for neurodegenerative diseases and injuries (Neuroscience 2024) - P2 | "A good safety and tolerability profile of NX210c and pharmacological effects on BBB repair and neuroprotection were demonstrated in a phase Ib study in healthy elderly volunteers (2023). Altogether, this extensive package supports the planned phase II clinical trial evaluating NX210c efficacy in ALS patients (NCT06365216)."

CNS Disorders • CLDN5 • OCLN • SPON1

Randomized, placebo-controlled, multiple ascending dose study of NX210c safety/tolerability and PK/PD in the elderly (EAN 2024) - "NX210c demonstrated a good safety profile following multiple doses in HEV and showed a PD relationship for biomarkers relevant to the BBB, including a reduction of plasma claudin-5. As BBB disruption is a driving feature of NDD, NX210c effect on target biomarkers may represent an important disease-modifying treatment for several neurological disorders and warrants further study in patients with NDD."

Clinical • PK/PD data • CNS Disorders • CLDN5

SEALS: ALS Phase II Study of NX210c (clinicaltrials.gov) - P2 | N=80 | Not yet recruiting | Sponsor: Axoltis Pharma

New P2 trial • Amyotrophic Lateral Sclerosis • CNS Disorders • NEFL

CHDR2235: MAD Study of NX210c (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Axoltis Pharma | Trial completion date: Oct 2023 ➔ Dec 2024 | Trial primary completion date: Oct 2023 ➔ Dec 2024

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders

NX210C PEPTIDE: A PROMISING DRUG CANDIDATE FOR BLOOD-BRAIN BARRIER REPAIR IN PARKINSON'S DISEASE (ADPD 2024) - "NX210c is a promising drug candidate for modifying PD course, notably by reducing BBB leakage. Therefore, we are now evaluating if NX210c promotes BBB repair in a PD mouse model."

CNS Disorders • Movement Disorders • Parkinson's Disease • CLDN5 • OCLN • SPON1

NX210C PEPTIDE: A PROMISING DRUG CANDIDATE FOR NEUROPROTECTION IN PARKINSON'S DISEASE (ADPD 2024) - "NX210c is a promising drug candidate for reducing neuropathological changes in PD, notably the loss of dopaminergic neurons."

CNS Disorders • Movement Disorders • Parkinson's Disease • SPON1

NX210c drug candidate peptide improves motor function and prolongs survival in the SOD1G93A mouse model of ALS (ALS-MND 2023) - "The orientation, travel and total times during the static rods test were higher in SOD1G93A mice compared with WT mice from 16 weeks old until disease end-stage (p < 0.001). A dose-dependent improvement of motor performances was observed in SOD1G93A mice treated with NX210c. More particularly, the peptide at 10 mg/kg reduced ALS-induced increased orientation and travel times from 16 weeks old (WT: 1.3 and 3.2s, vehicle SOD1G93A: 24.5s and 26.6s and 5.4s, NX210c SOD1G93A: 2.6 and 4.8s for orientation and travel times, respectively; p < 0.01) until disease end-stage on the largest diameter rod."

Preclinical

NX210c drug candidate peptide improves motor function and prolongs survival in the SOD1G93A mouse model of ALS (Neuroscience 2023) - "Overall, NX210c is a new promising drug candidate and its solid preclinical package (mechanism of action, proof of concept in ALS) should support the clinical development of NX210c in ALS patients. In addition, we have gathered several proofs of concept showing that NX210c restores cognitive functions (Lemarchant et al., 2022; Le Douce et al., 2021), which may represent a supplementary beneficial effect of NX210c for ALS patients, since 35% of them suffer from cognitive or behavioral impairments, with an additional 15% having FTD."

Preclinical • CNS Disorders • SPON1

NX210c drug candidate peptide strengthens the blood-brain barrier (Neuroscience 2023) - "Through this property, NX210c may represent a breakthrough treatment for neurological diseases. Finally, a clinical phase 1b evaluating the safety, tolerability and pharmacodynamic effects (including BBB integrity) of multiple ascending doses of NX210c in elderly healthy volunteers is ongoing."

CNS Disorders • CLDN5 • OCLN • SPON1

A randomized, placebo-controlled, double-blind, multiple ascending dose (MAD) study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of NX210c peptide in healthy elderly volunteers (Neuroscience 2023) - "NX210c demonstrated a good safety profile following multiple doses in healthy elderly volunteers in both doses tested. These preliminary results are very promising for further clinical development in patients suffering from neurodegenerative diseases."

Clinical • PK/PD data • CNS Disorders • Pain • SPON1

CHDR2235: MAD Study of NX210c (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Axoltis Pharma | Trial completion date: Apr 2023 ➔ Oct 2023 | Trial primary completion date: Apr 2023 ➔ Oct 2023

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders