Company: INMB
Filing Date: 2025-03-27
Form Type: 10-K
Source: 0001013762-25-003354
Chunk: 17

Company: Inmune Bio, Inc.
Filing Date: 2025-03-27
Form: 10-K
Item: Item 1
Chunk 17
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 A cocktail of three cytokines, IL12, IL15 and IL18 can be used to convert
a resting NK cell to cytokine induced memory like NK cells (“CIML”) [Fehneger 2016] or by INKmune priming with INB16 (TpNK
– tumor primed NK cells). Although the intracellular biology of these two strategies has yet to be worked out, they do not appear
to be identical. In summary, INKmune converts resting NK cells into tumor killing memory like NK cells that function well in the hostile
environment of the TME. (Figure 1 below).

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The ability of NK cells to
kill tumor cells depends on the strength and duration of the cell-cell interaction. This is called avidity. The higher the avidity the
greater the tumor cell killing. Cytokine stimulation may increase avidity of NK binding to some cancer cells whereas, in all experiments
to date, INKmune priming enhances NK binding to all cancer cells tested. The relative increase in avidity to specific cancer cells is
cytokine specific; as shown below, IL15 increases NK avidity for the ovarian cancer line SKOV-3 whereas IL2 has a limited effect. IL15
primed NK cells lyse SKOV-3 cells whereas IL2 primed NK do not. INKmune primed NK (TpNK) showed the highest avidity for the tumor cells
and the highest level of cytotoxicity. It is likely that the use of multiple cytokines will achieve the same level of avidity and cytotoxicity
as INKmune but studies with multiple cytokines have not yet been performed (Figure below).

We have demonstrated TpNK killing of many tumor types in laboratory studies.
Tumor priming is effective regardless of the source of the NK cells (normal volunteers or patients with cancer) and in many types of tumors
– both cell lines and primary tumors from patients. The principle of TpNK killing has also been demonstrated in two Phase I trials
in patient with acute myelogenous leukemia (“AML”). These trials were not supported by us and used a first-generation personalized
cell therapy product and treatment strategy that is different from the INKmune product and treatment strategy. In these trials, haplo-identical
NK cells obtained from a first degree relative by leukapheresis were primed ex-vivo using a lysate of the parent cell line from which