ES014: Clinical-Stage First-in-Class Anti-CD39xTGF-β BsAb
ES014 is a first-in-class anti-CD39xTGF-β bispecific antibody (bsAb) that simultaneously targets the adenosine and TGF-β pathways, two major immunosuppressive mechanisms in the tumor microenvironment (TME).
Solid tumors frequently express TGF-β, which suppresses T cell activation and induces CD39 expression, the rate-limiting enzyme in the ATP-adenosine pathway. The anti-CD39 target is designed to selectively direct ES014 to the TME where the anti-TGF-β activity promotes effector T cell function and immune activation, 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.
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 and Elpiscience plans to initiate a first-in-human trial for patients with advanced solid tumors in the U.S. in the second half of 2022.
Mechanism of Action
In vitro and In vivo Properties
Clinical Plan Highlights