Company: NCEL
Filing Date: 2025-03-03
Form Type: F-4/A
Source: 0001213900-25-018981
Chunk: 263

Company: NewcelX Ltd.
Filing Date: 2025-03-03
Form: F-4/A
Chunk 263
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 in the disease, there is involvement of malfunctioning astrocytes in the pathogenesis and progression of ALS. This notion supports the rationale that transplantation of healthy human astrocytes into the CNS of ALS patients may compensate for the malfunctioning astrocytes and rescue remaining MNs by supply supportive factors, clues and functions. The product AstroRx ®is composed of healthy human astrocytes derived from hESCs which allows ready scale -upof large numbers of donor cells. AstroRx ®cells are manufactured in compliance with GMP guidelines. Once manufactured, the cells are resuspended in PlasmaLyte A (a physiological solution) to formulate the AstroRx ®product. The product is loaded into a syringe and delivered to the physician at point -of-carefor intrathecal injection, or IT injection, into the CSF of ALS patient following minimally invasive lumbar puncture, or LP. Kadimastem’s Solution The cell therapy Kadimastem is developing to treat ALS, AstroRx ®, is based on the transplantation of allogeneic glial cells (mainly cells that support the CNS, or 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. 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. 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,