Next-Generation Cytokine Therapy

The Diakine™ platform is a next-generation cytokine therapy created to treat inflammatory disease and cancer based on each patient’s individual immune response.

Anti-inflammatory Cytokine

Interleukin-4 is an additional anti-inflammatory

cytokine that specifically suppresses T cell

activation while also suppressing macrophage

and monocyte inflammatory responses.

scFv Scaffold

The scFv scaffold is used to enrich inflamed

tissue with the anti-inflammatory cytokines

targeting MAdCAM for Crohn’s and colitis,

VEGFR2 for Psoriasis and Rheumatoid

Arthritis, or CD14 for sepsis.

Targeting System

The complementarity determining regions

(CDR’s) from other antibodies are grafted into

the scFv scaffold sequence to confer specificity

for targets expressed in inflamed tissue or on

inflammatory cells (e.g., CD14, MAdCAM,

VEGFR2 receptors).

Anti-inflammatory Cytokine

Interleukin-10 is a potent anti-inflammatory

cytokine and the low affinity variant developed

by Deka does not activate T cells

at any dose.

Linkers

Each protein subunit of the Diakine™ (e.g. interleukin-4,

interleukin-10, variable heavy and variable light chain)

is linked in series as a single chain via simple and flexible

protein linkers. Due to the orientation of the amino and carboxy

termini of each protein, the Diakine™ exhibits

a three-dimensional structure and stability similar to antibodies.

Our Anti-Inflammatory Platform

The Diakine™ platform is also developed for inflammatory disease. These Diakines™ combine two potent anti-inflammatory cytokines, Interleukin-10 and Interleukin-4. Deka has developed a low affinity form of Interleukin-10 that is anti-inflammatory and does not stimulate T cells. IL-4 is also an anti-inflammatory cytokine that specifically blocks inflammatory T cell activation.

These Diakine™ combinations are targeted to specific tissue markers that are increased in inflammatory disease, to achieve higher drug concentrations in the affected (inflamed) tissues.

Our Oncology Platform

The different Diakines™  are composed of a disease-targeting scaffold that links together the combination of cytokines that safely stimulate the immune system to destroy cancer cells.

Cytokines are naturally occurring, small proteins that control the immune system. Using single cytokines to treat cancer can be effective, but is often toxic.

The Diakine™ platform combines the potent anti-cancer function of stimulatory cytokines like interleukin-2, with the inflammation-controlling function of a cytokine like interleukin-10, and targets these cytokines to the tumor, using a human single-chain variable antibody fragment.

By combining the natural functions of two different cytokines, the Diakine™ platform can increase anti-cancer immunostimulatory function while reducing risk of toxic side effects – maximizing the overall potential of the immune system to fight cancer.

Stimulatory Cytokine

Stimulatory cytokine (e.g., interleukin-2,

interleukin-12, interferon alpha) are small

proteins that can activate immune cells

(e.g., T and NK cells) to selectively destroy

cancer cells, but can also cause toxic

inflammation.

scFv Scaffold

The single chain variable fragment (scFv)

scaffold is used to enrich the DiakineTM in

the tumor microenvironment. The scFv is

comprised of a variable heavy and variable

light chain derived from a human antibody.

Targeting System

The complementarity determining regions

(CDR’s) from other antibodies are grafted

into the scFv scaffold sequence to confer

specificity for tumor antigens

(e.g., EGFR, HER2, VEGFR receptors).

Anti-inflammatory Cytokine

Interleukin-10 is nature’s anti-inflammatory

cytokine, which at certain doses can also

activate  anti-cancer T cells. By individually

coupling  the stimulatory cytokines with

IL-10, each  DiakineTM controls toxic

inflammation,  while potently activating

the patient’s immune system to seek out

and destroy tumors.

Linkers

Each protein subunit of the DiakineTM

(e.g. interleukin-2, interleukin-10, variable heavy

and variable light chain) is linked in series as

a single chain via simple and flexible

protein linkers. Due to the orientation of the amino and carboxy

termini of each protein, the DiakineTM exhibits

a three-dimensional structure and stability similar to antibodies.

Our Anti-Inflammatory Platform

The Diakine™ platform is also developed for inflammatory disease. These Diakines™ combine two potent anti-inflammatory cytokines, Interleukin-10 and Interleukin-4. Deka has developed a low affinity form of Interleukin-10 that is anti-inflammatory and does not stimulate T cells. IL-4 is also an anti-inflammatory cytokine that specifically blocks inflammatory T cell activation.

These Diakines™ combine two potent anti-inflammatory cytokines that are targeted to specific tissue markers that are increased in inflammatory disease, to achieve higher drug concentrations in the affected (inflamed) tissues.

Our Oncology Platform

The different Diakines™ are composed of a disease-targeting scaffold that links together the combination of cytokines that safely stimulate the immune system to destroy cancer cells .

Cytokines are naturally occurring, small proteins that control the immune system. Using single cytokines to treat cancer can be effective but is often toxic.

The Diakine™ platform combines the potent anti-cancer function of stimulatory cytokines like interleukin-2, with the inflammation-controlling function of a cytokine like interleukin-10, and targets these cytokines to the tumor, using a human single-chain variable antibody fragment.

By combining the natural functions of two different cytokines, the Diakine™ platform can increase anti-cancer immunostimulatory function while reducing risk of toxic side effects – maximizing the overall potential of the immune system to fight cancer.

Our Precision Medicine

People respond differently to various cytokine combinations. Drawing from years of research, we are now able to determine underlying cellular reactions that help us predict each patient’s immune response to different Diakines™. 

When testing for inflammatory disease, we use a different in-vitro assay with Toll-like receptor agonists measuring stimulated monocytes secretion and response to IL-10 to determine who will potentially benefit the most from treatment with an anti-inflammatory Diakine™. 

For cancer, we have reduced the complexities of anti-cancer immunity to an in-vitro assay that assesses the induced secretion of IFN-gamma by CD8+ T cells after exposure to each Diakine™. This test permits the evaluation of each patient’s immune response to the different combinations of cytokines, which has the potential to predict treatment response.

Our mission is to continue to develop simple genetic tests to enable treating physicians to choose the most effective Diakine™ for each patient.

Our Manufacturing

The unique structure of the Diakine™ scaffold provides stability under extreme conditions, like high temperatures and a large pH range. This permits higher manufacturing titers that in turn drive down manufacturing costs to a level that is typically unachievable with single cytokines. The targeting of Diakines™ to the diseased tissue permits less frequent dosing and lower overall dose levels.

Diakine™ therapies are a promising and cost-effective way to treat a wide range of inflammatory diseases and cancer.

Collaboration is part of our ethos.

Deka’s targeted Diakine™ therapies are designed to be customized and provide complementary functions with other established modalities to increase their therapeutic potential.

Similar to the fundamental premise of the Diakine™, we believe that collaboration makes us better, and Deka is always welcoming new partners to advance medicine and improve the lives of patients.