Company: INMB
Filing Date: 2025-03-27
Form Type: 10-K
Source: 0001013762-25-003354
Chunk: 5

Company: Inmune Bio, Inc.
Filing Date: 2025-03-27
Form: 10-K
Item: Item 1
Chunk 5
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 Components of the innate immune system include cytokines, chemokines, macrophages,
neutrophils and NK cells, among others.

The adaptive immune system
is often initially triggered by the innate immune system, mounts a delayed response against diseased cells and plays a role protecting
against re-infection. An adaptive immune response is highly specific to a pathogen or antigen and is developed or learned from prior exposure.
Key components of the adaptive immune system include antibodies which bind to antigens and mark them for destruction by other immune cells,
B-cells which produce these antibodies upon exposure to antigens, and T-cells which attack and eliminate the diseased cells.

The biopharmaceutical industry
has made significant advances in harnessing specific components of innate and adaptive immune systems for therapeutic use. Some of these
approaches are summarized below.

Cytokines. Tumor
Necrosis Factor alpha (“TNF”) is the focus of XPro and INB03. TNF biology has four elements that include two cytokines, soluble
TNF and trans-membrane TNF (“sTNF” and “tmTNF,” respectively), and two receptors, TNF Receptor 1 and 2 (“TNFR1”
and “TNFR2”). The biology of TNF ligation of TNFR varies dramatically based on what elements of the TNF system that are used.
sTNF binding to TNFR1 is responsible for inflammation and cell death while sTNF binding to TNFR2 promotes proliferation of regulatory
T cells (“Treg”). In patients with advanced cancers, increased sTNF is not favorable to long-term survival because it promotes
epithelial-mesenchymal transformation and metastasis while making the tumor microenvironment more immunosuppressive promoting resistance
to therapy. In the CNS, sTNF promotes neuronal cell death, demyelination and synaptic pruning while tmTNF promotes nerve cell survival,
improves synaptic function and stimulates remyelination. In brief, sTNF is the “bad” TNF and tmTNF is the “good”
TNF. In patients with cancer, infection or neurologic disease, blockade of tmTNF function has negative consequences such as immunosuppression,
increased infection, synaptic dysfunction and demyelination.

One of the early applications
of immunotherapy is the use of cytokines, including interferons and interleukin-2 (“IL-2”). Interferons are molecules that
inhibit