Company: DRTSW
Filing Date: 2025-03-12
Form Type: 20-F
Source: 0001213900-25-023187
Chunk: 144

Company: Alpha Tau Medical Ltd.
Filing Date: 2025-03-12
Form: 20-F
Item: Item 4
Chunk 144
---
 a single Alpha DaRT source was used for the treatment of a tumor, despite that the alpha-emitting atoms
released from this single source would not be expected to cover the whole tumor. The purpose of using a single source is to avoid a complete
response of the tumor only by virtue of the direct impact of the alpha radiation. Deliberately under-dosing Alpha DaRT enables the investigation
of the combination and potential synergy between Alpha DaRT and the drug.

GBM-bearing mice were also
treated with Alpha DaRT in combination with the anti-angiogenic agent Avastin (bevacizumab), where Avastin was injected 3 times per week
for 3 weeks from day 5 after insertion of the Alpha DaRT. The combination treatment prevented tumor regrowth following treatment, and
tumor size was stable for a longer period than in either of the treatments alone. Additionally, in the mice treated with the combination
or with Alpha DaRT, 4 of 14 or 3 of 13 mice, respectively, saw their tumors disappear completely without late relapse, potentially indicating
an ability to prevent GBM recurrence. We have seen evidence that the Avastin-induced decrease in angiogenesis may reduce the clearance
of radioisotopes from the tumor, consequently expanding the “effective range” of Alpha DaRT in the tumor.

Alpha DaRT as a Potential Immunostimulator

Radiation is traditionally
considered to produce damage-associated molecular patterns, or DAMPs, that activate dendritic cells; in the presence of an antigen this
may lead to specific T cell responses. During the escape phase, melanoma cells acquire deficient antigen presentation machinery, masking
them from the immune system.

A published third-party study
recently reported that, apart from the potential to efficiently kill tumor cells relative to other radiation types, alpha-emitting radium
significantly enhanced T cell-mediated tumor lysis that was accompanied by augmented protein expression of MHC-I and calreticulin, molecules
that are essential for efficient antigen presentation and immune activation.

The figure below illustrates
the potential effect of irradiation to release antigens from the tumor, which, in turn, may be able to harness the dendritic cells to
generate T cell response to detect and target the specific tumor cells for destruction. Tumor antigens released by irradiated tumor cells
can be taken up by antigen-presenting cells, or APCs, such as dendritic cells and phagocytic cells. The APCs may