Company: NCEL
Filing Date: 2025-02-05
Form Type: F-3
Source: 0001213900-25-010223
Chunk: 29

Company: NewcelX Ltd.
Filing Date: 2025-02-05
Form: F-3
Chunk 29
---
Rx cells without the need of chronic immunosuppression treatment.
Thus, IsletRx cells 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 Plus Human pluripotent
(embryonic) stem cell-derived pancreatic islet-like cell clusters (IsletRx); encapsulated in alginate microgels, intended
for intra-periotenal implantation. The alginate microencapsulation enables implanting of IsletRx cells without the need
of chronic immunosuppression treatment. Still, IsletRx cells are not in direct contact with the vasculature, and may suffer
from hypoxia and loss of function due to fibrosis. The retrievability of microencapsulated IsletRx cells is a regulatory
concern, as there is very limited data about the safety of stem cells-derived islets. Preclinical efficacy studies using Encap-IsletRx
demonstrated prolong anti-diabetic effect, with physiological secretion of human insulin in a glucose dependent manner.

<div align='center'>17</div>

In-Scaffold-IsletRx Plus Human
pluripotent (embryonic) stem cell-derived pancreatic islet-like cell clusters (IsletRx); encapsulated in alginate microgels
embedded in electro spun polycaprolactone membrane, intended for subcutaneous implantation. The alginate microencapsulation enables implanting
of IsletRx cells without the need of chronic immunosuppression treatment. The embedding of the microcapsules in a membrane
makes it a retrievable solution and obviates the regulatory concern. POC studies using In-Scaffold-IsletRx demonstrated
that microencapsulated IsletRx cells maintain their identity and capability to secrete insulin in immunodeficient mice.
Next planned studies aim to test the anti-diabetic effect of this delivery method.

These delivery options are in various development
stages. The most advanced is iTOL-102, currently at the pre-IND stage. Preclinical development studies were conducted to support regulatory
submissions for iTOL-102 (pre-IND) and