Company: NCEL
Filing Date: 2025-05-16
Form Type: 20-F
Source: 0001213900-25-044868
Chunk: 216

Company: NewcelX Ltd.
Filing Date: 2025-05-16
Form: 20-F
Item: Item 4
Chunk 216
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carried out under laboratory conditions, in several stages, by adding chemical and/or biological agents in controlled timings to the pluripotent
stem cell culture. Induction of differentiation processes of pluripotent stem cells into islet-like cell clusters, under laboratory conditions
is conducted in a stirred suspension bioreactor under conditions that mimic the development of the pancreatic islets.

Enrichment: Kadimastem
has developed an enrichment technology which it believes improves safety and efficacy of IsletRx cells. The IsletRx cells are enriched
for insulin secreting cells, designated as IsletRxPlus, and formulated as the drug substance.

Delivery: Several
delivery strategies were developed to obviate the need for life-long immunosuppressive treatment while enabling the long-term function
of IsletRxPlus cells. These strategies include immune tolerance, microencapsulation in polymer, and scaffolding using electrospinning
of polycaprolactone. The cellular component in all products is the same, IsletRxPluscells.

Products description

iTOL-102Human pluripotent (embryonic)
stem cell-derived pancreatic islet-like cell clusters (IsletRxPlus); mixed with SA-FasL Microgels (iTOL-100), intended for
omental implantation. The iTOL100 enables implanting of IsletRxPluscells without the need of chronic immunosuppression treatment.
Thus, IsletRxPluscells are in direct contact with the omental vasculature, ensuring proper engraftment and function. Preclinical
efficacy studies using iTOL-102 demonstrated prolonged anti-diabetic effect, with physiological secretion of human insulin in a glucose
dependent manner. These results, along with the proof of concept, or POC, studies with an iTOL100 component, have led to submission of
a Pre-IND package.

Encap-IsletRx PlusHuman pluripotent
(embryonic) stem cell-derived pancreatic islet-like cell clusters (IsletRxPlus); encapsulated in alginate microgels, intended
for intra-periotenal implantation. The alginate microencapsulation enables implanting of IsletRxPluscells without the need
of chronic immunosuppression treatment. Still, IsletRxPluscells are not in direct contact with the vasculature, and may suffer
from hypoxia and loss of function due to fibrosis. The retrievability of microencapsulated IsletRxPluscells is a regulatory