Axoltis Pharma announces topline Phase 2 results for NX210c in Amyotrophic Lateral Sclerosis
- Post-hoc analysis shows substantial reduction in ALSFRS-R decline rate versus placebo at week 6; sustained at month 4 follow-up
- Target engagement confirmed by significant reduction in plasma claudin-5, supporting restoration process at blood brain barrier
- Good safety and tolerability profile in ALS patients
- Detailed presentation of results will be given on November 15, 2026 at Neuroscience 2026, annual meeting of the Society for Neuroscience
- Results support continuation of NX210c clinical development
Lyon and Clermont-Ferrand, France, September 15, 2026 – Axoltis Pharma, a biotech
company dedicated to developing novel therapeutic solutions for neurodegenerative
diseases, today announces the topline results of SEALS, its Phase 2 clinical trial evaluating
the effect of NX210c in patients with Amyotrophic Lateral Sclerosis (ALS). This 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 spread across 16 French clinical
sites were enrolled in the SEALS study. Patients were stratified by low and high serum
neurofilament light chain (NfL) concentration and randomized (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), 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 (-0.67 point/month for 5mg/kg arm, -0.9 for 10mg/kg
and -1.14 for placebo corresponding to an average reduction of 41% for 5mg/kg and 21%
for 10mg/kg) at week 6. This effect was consistently stronger at week 10 (-0.77 point/month
for 5mg/kg arm, -1.06 for 10mg/kg and -1.57 for placebo corresponding to an average
reduction of 51% for 5mg/kg with p<0.05 and of 32% for 10mg/kg). The effect on the decline
rate was also maintained at month 4 (-1.01 point/month for 5mg/kg arm, -1.08 for 10mg/kg
and -1.59 for placebo corresponding to an average reduction of 36% for 5mg/kg and 32%
for 10mg/kg).
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 predose while only 11.8% of the patients
in the placebo arm did.
The percentage change from predose 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 (p<0.001) at 10mg/kg vs placebo arm at end
of treatment with a dose-effect relationship. This effect was maintained at month 4 (p=0.069
for 10mg/kg arm). 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 good 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 Dr. 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
underway, 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 (USA) on November 14 -18.
“These results represent an important milestone for Axoltis and provide a strong foundation
for the next stages of clinical development,” said Dr. 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.”
“The execution of the SEALS clinical study has been a success thanks to the FILSLAN (Filière
de Santé Maladies Rares SLA et Maladies du Neurone Moteur) and ACT4ALS/MND
networks, the invaluable support of ARSLA, Les Invincibles, the Swiss ALS Foundation, the
Auvergne-Rhône-Alpes Region and Bpifrance, as well as the backing of Axoltis’ investors.
We are deeply grateful to them all,” added Dr. Godfrin.
About NX210c
Axoltis is developing 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. NX210c is a
novel drug candidate for neurodegenerative or trauma-related disorders, with blood-brain
barrier repair, neuroprotective and neurotransmission improvement properties. NX210c is
protected by eight patents fully owned by Axoltis Pharma, including the composition of
matter, which is covered in several countries. The FDA and the EMA have granted Orphan
Drug Designation for NX210c in ALS. In 2023, the safety data collected in a Phase 1b multiple
ascending dose study showed NX210c to be well-tolerated. The full results of SEALS, a Phase
2 clinical trial in ALS patients, are expected by the end of 2026.
www.axoltis.com/product
About Axoltis Pharma
Axoltis Pharma, a French biopharma company, develops innovative drugs for
neurodegenerative and neurotraumatic diseases with a high unmet medical need.
Headquartered in Clermont-Ferrand with offices in Lyon, France, Axoltis has established
several partnerships with internationally recognized academic and private labs to develop
its lead product, NX210c. The team is highly experienced in drug development, especially
for neurological applications.
www.axoltis.com
