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DKN-01 –
an anti-DKK1
antibody

DKN-01 binds and removes free DKK1 from the TME:

Reduces cell proliferation

Blocks signaling through CKAP4 and PI3K to downregulate Akt

Suppresses
MDSC cells

B-catenin dependent Wnt signaling reprograms MDSCs and reduces immunosuppressive activity

Reduces angiogenesis

Reduces blood vessel formation, upregulates key cytokines, IFNy, IL-15 and IL-33

Activates
NK cells

Upregulates NK cell ligands on tumor, production of Granzyme B by activated NK cells

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DKN-01 + anti-PD1

DKN-01 stimulates innate
immune system:

Stimulates activity
of NK cells
Induces
pro-inflammatory
tumor microenvironment
Upregulates PD-L1 (the target for PD-1 antibodies)

Anti-PD1 stimulate
CD8 T cell adaptive immunity:

Enhances tumor microenvironment for immune cells
to target and clear
the tumor
Activates
CD8 T cells
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DKK1 expression determined using RNAscope

Chromogenic in situ
hybridization RNAscope

The biopsy sample is stained to identify DKK1 mRNA Pathologist determines histology score (H-Score), measuring DKK1 expression rather than protein itself.

Each red dot is an individual mRNA for DKK1.
Amount of cells and intensity of staining is converted to H-Score.

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