Company: NCEL
Filing Date: 2025-03-31
Form Type: F-4/A
Source: 0001213900-25-026428
Chunk: 268

Company: NewcelX Ltd.
Filing Date: 2025-03-31
Form: F-4/A
Chunk 268
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 astrocytes) that have differentiated from pluripotent stem cells, thereby returning to the recipient the motoneuron -supportingenvironment. It is assumed that this procedure will moderate the mortality rate of the neurons, and maybe even stop it, so that the quality of life and life expectancy of the patients will improve. Astrocyte function in neuronal support is also impaired in other neurodegenerative diseases such as multiple sclerosis, progressive multiple sclerosis, frontotemporal dementia (FTD), Alzheimer’s, Parkinson’s and glaucoma. 135 Mechanism of Action:AstroRx ®were demonstrated to promote neuroprotection and to maintain homeostasis by several mechanism including reuptake of excessive glutamate, neutralizing oxidative stress, immunomodulation and secretion of a variety of potent neurotrophic factors. For example, disruption of the astrocytic TNFR1 — GDNF axis accelerates MN degeneration and disease progression, as the levels of the protective agents for MNs, glial -derivedneurotrophic factor (GDNF), are reduced. AstroRx were tested in vitro, in vivo (animal studies) and on human subjects, as described in the following peer reviewed papers: PMID: 36788520 PMID: 29871694 PMID: 32848579. In the Phase 1/2a trial of AstroRx, when applied to humans, these effects were not observed at 6- and 12 -monthfollow -uptime points. As so, Kadimastem believes that it is more likely that AstroRx ®astrocytes will be more effective in treating diseases than single -moleculebased 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 -basedapproach 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; this 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 (astrocy