Company: INMB
Filing Date: 2025-03-27
Form Type: 10-K
Source: 0001013762-25-003354
Chunk: 211

Company: Inmune Bio, Inc.
Filing Date: 2025-03-27
Form: 10-K
Item: Item 1A
Chunk 211
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 TRD. In each case, we believe
neutralizing sTNF is a cornerstone to the treatment of these diseases.

We believe the DN-TNF platform
can be used to treat selected neurodegenerative diseases by reducing neuroinflammation without immunosuppression. The Company believes
the core pathology of cognitive decline is a combination of neurodegeneration and synaptic dysfunction. Neurodegeneration is nerve cell
death that may include demyelination. Synaptic dysfunction means the connections between nerve cells stop working efficiently and may
decrease in number. The combination of neurodegeneration and synaptic dysfunction causes cognitive decline and behavioral changes associated
with Alzheimer’s disease (“AD”). XPro completed a Phase I trial treating patients with Alzheimer’s disease that
was partially funded by a Part-the-Clouds Award from the Alzheimer’s Association. We believe XPro targets activated microglia and
astrocytes of the brain that produce sTNF that promotes nerve cell loss, synaptic dysfunction and prevents myelin repair - key elements
in the development of dementia. In animal models, elimination of sTNF prevents nerve cell dysfunction, reverses synaptic pruning and promotes
myelin repair. The Phase I trial in patients with biomarkers of inflammation with AD has been completed. The open label, dose escalation
trial was designed to demonstrate that XPro can safely decrease neuroinflammation in patients with ADi. ADi is the term used to delineate
patients with AD with biomarkers of inflammation. The endpoints of the trial were measures of neuroinflammation and neurodegeneration
in blood and cerebral spinal fluid by measuring changes in inflammatory cytokine levels in the CNS and using MRI-DTI to measure brain
microstructural changes. XPro, at the 1mg/kg/week dose, decreased inflammatory cytokines in the CSF in the brain demonstrating that XPro
can decrease neuroinflammation in patients with AD. We also studied downstream benefits of decreasing neuroinflammation by measuring changes
in the CSF proteome and quantifying changes in novel white matter MRI biomarkers. XPro significantly decreases biomarkers of neurodegeneration as
measured by changes in the CSF proteome including neurofilament light chain, phospho Tau 217 and VILIP-1; decreases of 84%, 46% and 91%
respectively after 3 months of therapy. Three months of XPro therapy improved measures of synaptic function, as measured in the CSF proteome
including a 222%