DKN-01 –
an anti-DKK1
antibody
![](https://www.leaptx.com/wp-content/uploads/2022/01/diagram-img-01@2x.jpg)
Single agent and combination activity demonstrated in three different tumor types. Well tolerated as monotherapy and in combination with chemotherapy or checkpoint inhibitors.
DKN-01 binds and removes free DKK1 from the TME:
![](https://www.leaptx.com/wp-content/uploads/2022/01/scheme-art-01.png)
Reduces cell proliferation
Blocks signaling through CKAP4 and PI3K to downregulate Akt
![](https://www.leaptx.com/wp-content/uploads/2022/01/scheme-art-02.png)
Suppresses
MDSC cells
B-catenin dependent Wnt signaling reprograms MDSCs and reduces immunosuppressive activity
![](https://www.leaptx.com/wp-content/uploads/2022/01/scheme-art-03.png)
Reduces angiogenesis
Reduces blood vessel formation, upregulates key cytokines, IFNy, IL-15 and IL-33
![](https://www.leaptx.com/wp-content/uploads/2022/01/scheme-art-04.png)
Activates
NK cells
Upregulates NK cell ligands on tumor, production of Granzyme B by activated NK cells
![](https://www.leaptx.com/wp-content/uploads/2022/01/diagram-img-05@2x-265x300.png)
DKN-01 + anti-PD1
DKN-01 stimulates innate
immune system:
![](https://www.leaptx.com/wp-content/uploads/2022/01/scheme-art-05.png)
Stimulates activity
of NK cells
![](https://www.leaptx.com/wp-content/uploads/2022/01/scheme-art-06.png)
Induces
pro-inflammatory
tumor microenvironment
![](https://www.leaptx.com/wp-content/uploads/2022/01/scheme-art-07.png)
Upregulates PD-L1 (the target for PD-1 antibodies)
Anti-PD1 stimulate
CD8 T cell adaptive immunity:
![](https://www.leaptx.com/wp-content/uploads/2022/01/scheme-art-08.png)
Enhances tumor microenvironment for immune cells
to target and clear
the tumor
![](https://www.leaptx.com/wp-content/uploads/2024/03/icon_cell_CD8.png)
Activates
CD8 T cells
![](https://www.leaptx.com/wp-content/uploads/2022/01/diagram-img-06@2x-525x556.png)
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.