Company: NCEL
Filing Date: 2025-07-29
Form Type: F-4/A
Source: 0001213900-25-068765
Chunk: 409

Company: NewcelX Ltd.
Filing Date: 2025-07-29
Form: F-4/A
Chunk 409
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 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, or FTD, Alzheimer’s, Parkinson’s and glaucoma. Mechanism of Action:AstroRx ®was demonstrated to promote neuroprotection and to maintain homeostasis through several mechanisms 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, 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: Safety and efficacy of first -in-man intrathecal injection of human astrocytes (AstroRx ® ) in ALS patients: phase I/IIa clinical trial results. This paper describes the results of Phase 1/2a NCT03482050 clinical trial (further described on page 207). PMID: 29871694: Safety and efficacy of human embryonic stem cell -derived astrocytes following intrathecal transplantation in SOD1 G93A and NSG animal models. This paper describes the development of good manufacturing practice -gradeprotocol for generation of astrocytes from human embryonic stem cells (AstroRx ®), their in vitro function, their efficacy in ALS animal model (hSOD1 G93Atransgenic mice) and their 205 safety and biodistribution in a 9 -monthstudy conducted in immunodeficient NSG mice under good laboratory practice conditions. In vitro, AstroRx ®possess the activities of functional healthy astrocytes, including glutamate uptake, promotion of axon outgrowth and protection of MNs from oxidative stress. A secretome analysis shows that AstroRx ®also secretes several inhibitors of metalloproteases as well as a variety of neuroprotective factors (e.g. TIMP -1, TIMP -2, OPN, MIF and Midkine). Intrathecal injections of the AstroRx ®into transgenic hSOD1 G93Amice and rats significantly delayed disease onset and improved motor performance compared to sham -in