Company: NCEL
Filing Date: 2025-02-10
Form Type: F-3
Source: 0001213900-25-011823
Chunk: 19

Company: NewcelX Ltd.
Filing Date: 2025-02-10
Form: F-3
Chunk 19
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 also impaired in other neurodegenerative diseases
such as multiple sclerosis, progressive multiple sclerosis, frontotemporal dementia (FTD), Alzheimer’s, Parkinson’s and glaucoma.

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. In addition, disruption
of the astrocytic TNFR1–GDNF axis accelerates MN degeneration and disease progression, as the levels of the protective agents for
MNs, glial-derived neurotrophic factor (GDNF), are reduced. 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 (an 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; 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 (astrocytes),
and then transplant them into patients. In healthy individuals, the role of astrocytes is to support the health of neurons and their proper
functioning by secreting growth inducers on them and monitoring, eliminating toxic substances and reducing environmental stress (such
as free radicals and excessively high levels of glutamate and potassium).

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Strengths Kadimastem’s vision is to act to find cell therapy treatments for incurable diseases that impair patients’ life expectancy and quality of life, such as ALS. The strategy is to replace the functionality of malfunctioning cells even within some distance from the original tissue/organ that is difficult or impossible to replace. The activity of malfunctioning astrocytes can be restored using