Company: DRTSW
Filing Date: 2025-03-12
Form Type: 20-F
Source: 0001213900-25-023187
Chunk: 146

Company: Alpha Tau Medical Ltd.
Filing Date: 2025-03-12
Form: 20-F
Item: Item 4
Chunk 146
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 DaRT, providing further evidence of immune response.

As seen in the figure below,
mice bearing breast DA3 tumors demonstrated the least tumor development when treated with the Alpha DaRT together with CpG (as compared
to phosphate-buffered saline, or PBS).

In addition, as seen in the
figures below, the combination of sildenafil (A) or cyclophosphamide (B) with Alpha DaRT, led to greater tumor growth inhibition compared
to any of the monotherapy groups.

As can be seen in the figure
below showing survival curves for the different groups, the combination of cyclophosphamide, sildenafil, CpG and Alpha DaRT led to 51%
long-term tumor rejection of the CT26 bearing mice, while the combination of cyclophosphamide, sildenafil, CpG and an inert source in
lieu of Alpha DaRT mostly led to tumor recurrence.

In addition, as shown in the
figure below, when repeating the previously described challenge tests four months after a previous treatment, the previous treatment that
included Alpha DART and immunomodulation (CpG, cyclophosphamide and sildenafil) led to the most meaningful tumor inhibition.

It was observed that the anti-tumor
immune memory evidenced following combination treatment (Alpha DaRT and immunomodulators) was specific to CT26 tumor cells and did not
provide any protection against other tumor cell lines. In addition, this specific anti-tumor immune memory was transferable to naïve
mice, as splenocytes isolated from treated mice were able to protect naïve mice from the CT26 tumor cells, yet not from other tumor
cells.

In a range of tumors, including
triple negative breast cancer, pancreatic and squamous cell carcinoma, a synergy in tumor/metastases development was observed between
Alpha DaRT and the delivery of viral dsRNA into the cytoplasm of tumor cells by intratumoral injection of polyIC complexed with polyethylenimine,
or PEI.

As shown in the figure below,
under neoadjuvant settings and following long-term follow-up in mice with 4T1 breast tumors, it was observed that metastases were not
formed in the lungs of 75% of studied mice which underwent the combined before surgery treatment, while metastases-related death was observed
in the other animals.

In light of the observed potential
of Alpha DaRT to induce antigen-specific immune memory and to demonstrate synergy with immunomodulation, we have investigated the