Company: DRTSW
Filing Date: 2025-03-12
Form Type: 20-F
Source: 0001213900-25-023187
Chunk: 147

Company: Alpha Tau Medical Ltd.
Filing Date: 2025-03-12
Form: 20-F
Item: Item 4
Chunk 147
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 use
of the Alpha DaRT in combination with an inhibitor of programmed cell death protein 1, or PD1. As there are many patients who do not demonstrate
a response to such therapies, we wish to understand whether the Alpha DaRT may demonstrate immunostimulatory traits that can potentially
enhance response rates or efficacy of response to anti-PD1 therapies, thereby offering a potential mechanism for reducing recurrence rates
or enhancing systemic effects in addition to the local therapeutic effect.

Recent data supports this
hypothesis, shown in the figure below, in mice bearing SCC tumors which were treated with the Alpha DaRT, and then a PD1 inhibitor was
injected 4 times from day 2 to day 12 after Alpha DaRT treatment. Alpha DaRT demonstrated the potential to increase the response of tumors
otherwise unresponsive to a PD-1 inhibitor, where the tumor growth of SCC tumors in mice was meaningfully inhibited in mice that received
both the Alpha DaRT as well as a PD-1 inhibitor, as compared to mice that received either the Alpha DaRT or the PD-1 inhibitor alone.
Whereas anti-PD-1 therapy did not affect tumor progression on its own, adding anti-PD-1 therapy to Alpha DART further increased the growth
retardation induced by Alpha DaRT, suggesting that Alpha DART may induce responsiveness to anti-PD-1 therapy.

Furthermore, as shown below
both graphically and in representative immunohistochemistry cryo-sections, it was observed that the density of tumor-infiltrating lymphocytes
(CD3+ TILs) in the tumor, which is often used to define a “hot tumor” and as a predictor for treatment response, is higher
in the combination treatment relative to anti-PD-1 alone, further suggesting that Alpha DART may activate T-cell function when used with
anti-PD-1 therapy.

  anti PD-1      Alpha DaRT + anti PD-1  

Similar effects were seen
with respect to the density of the lymphocyte effector sub population (CD8+ TILs) and Granzyme B, a serine protease most commonly found
in the granules of natural killer cells and cytotoxic T cells, as seen in the figures below.

In the pancreatic tumor model,
as seen below in the figure of average tumor volume measured at day 14 after treatment, a similar trend was observed in response to the
combination of Alpha DaRT with anti-PD1, which