Model ES014 - Anti-CD39xTGF-ß BsAb Dual-Acting Molecule

The combined removal of immune suppression and immune stimulating effects of ES014 were recently demonstrated in a PD-1 antibody non-responsive in vivo animal model where tumor growth was significantly inhibited after treatment. ES014 received FDA IND clearance in May 2022.

• Solid tumors frequently express TGF-β, which suppresses T cell activation and induces CD39 expression, the rate-limiting enzyme in the adenosine pathway
• The anti-CD39 target is designed to selectively direct ES014 to the TME where the anti-TGF-β activity promotes immune-favorable T cell activation and cytokine release, while avoiding or minimizing systemic immunotoxicity
• ES014’s anti-CD39 activity further aims to reverse TME immunosuppression by reducing suppressive adenosine, while maintaining high levels of immune-stimulatory extracellular ATP

• Unique MOA: Simultaneously targets two major TME immunosuppressive pathways
• Designed to effectively promote T cell function and activation as well as reverse immunosuppression in the TME
• Superior anti-tumor activity in PD-(L)1 non-responsive in vivo model

In vitro:

• Inhibits CD39 expression and reverses Treg cell differentiation
• Effectively promotes T cell survival and expansion by anti- CD3/CD28 stimulation
• Promotes IL-2 and IFN-γ cytokine production leading to higher T cell activation

In vivo:

• Significantly anti-tumor activity in SK-MEL-5 anti-PD-1 resistant model