Company: NCEL
Filing Date: 2025-05-16
Form Type: 20-F
Source: 0001213900-25-044868
Chunk: 217

Company: NewcelX Ltd.
Filing Date: 2025-05-16
Form: 20-F
Item: Item 4
Chunk 217
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concern, as there is very limited data about the safety of stem cells-derived islets. Preclinical efficacy studies using Encap-IsletRxPlusdemonstrated prolong anti-diabetic effect, with physiological secretion of human insulin in a glucose dependent manner.

In-Scaffold-IsletRx PlusHuman
pluripotent (embryonic) stem cell-derived pancreatic islet-like cell clusters (IsletRxPlus); encapsulated in alginate microgels
embedded in electro spun polycaprolactone membrane, intended for subcutaneous implantation. The alginate microencapsulation enables implanting
of IsletRxPluscells 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-IsletRxPlusdemonstrated
that microencapsulated IsletRxPluscells 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. Kadimastem expects to submit a pre-IND package in the
second quarter of 2025.

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 Encap-IsletRxPlus(INTERACT).

Drug administration strategies

The use of allogeneic islets in clinical settings
requires to ensure their long-term function in the patient without being destroyed by patient’s immune system Kadimastem utilizes
several technologies to protect the islets from the recipient’s immune system, which will eliminate the implant rejection risk,
without the need to administer immunosuppressive drugs to weaken the patient’s immune system and ensure long term function of IsletRxPlus
cells.

iTOL-102

iTOL-102 are human pluripotent (embryonic) stem-cell
derived islet-like clusters mixed with iTOL-100 (biotinylated PEG microgels with surface bound SA-FasL). iTOL-102 consists of IsletRxPlus
cells and iTOL-100 prepared for delivery into the omentum, a part of the stomach of diabetic patients. The therapeutic goal for iTOL-102
is to provide an easily administered, low risk, treatment