Company: NCEL
Filing Date: 2025-05-16
Form Type: 20-F
Source: 0001213900-25-044868
Chunk: 205

Company: NewcelX Ltd.
Filing Date: 2025-05-16
Form: 20-F
Item: Item 4
Chunk 205
---
in hematological parameters or blood chemistry.

PMID: 32848579: Rising Stars: Astrocytes as a Therapeutic Target
for ALS Disease

This paper describes the role of Astrocytes malfunction
in several neurodegenerative diseases and specifically in ALS. Astrocytes impaired biological functionality were implicated in multiple
neurodegenerative diseases, including ALS, FTD, Parkinson’s, and Alzheimer’s. In ALS
disease patients, A1 reactive astrocytes were found to play a key role in the pathology of ALS disease and death of motor neurons, via
loss or gain of function or acquired toxicity. The contribution of astrocytes to the maintenance of motor neurons by diverse mechanisms
makes them a promising therapeutic candidate for the treatment of ALS. Therapeutic approaches targeting at modulating the function of
endogenous astrocytes or replacing lost functionality by transplantation of healthy astrocytes, may contribute to the development of therapies
which might slow down or even halt the progression ALS diseases. The proposed mechanisms by which astrocytes can potentially ameliorate
ALS progression and the status of ALS clinical studies involving astrocytes are discussed.

In the Phase 1/2a trial of
AstroRx®, when applied to humans, these effects were not observed at 6- and 12-month follow-up time points. As so, Kadimastem
believes that it is more likely that AstroRx®astrocytes will be more effective in treating diseases than single-molecule
based drugs, e. g. Riluzole (assumed to improve glutamate uptake and to reduce excitotoxicity), or Edaravone (a reactive oxygen species,
reducing oxidative stress). AstroRx®astrocytes’ activity may include both drugs’ modes of action, in addition
to secretion of multiple neurotrophic factors that act through multiple pathways. Importantly, this astroglial-based approach should
be therapeutic regardless of the etiology of the ALS - familial (independent of genotype) as well as sporadic - because
it attacks final common molecular pathways of MN demise, which contrasts with some present genetic approaches.

Mode of Action: AstroRx®is based on differentiated clinical grade cells derived from embryonic stem cells it received under licensing agreements and
technologies developed by it to expand pluripotent stem cells and differentiate them into cells supporting the central nervous
system (astrocytes), and then transplant them into patients. In healthy individuals, astrocytes support neuronal health