欧洲杯买球网游戏: Clinical-Stage First-in-Class Anti-CD39xTGF-β BsAb

欧洲杯买球网游戏 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 欧洲杯买球网游戏 to the TME where the anti-TGF-β activity promotes effector T cell function and immune activation, while avoiding or minimizing systemic immunotoxicity. 欧洲杯买球网游戏’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 欧洲杯买球网游戏 were recently demonstrated in a PD-1 antibody non-responsive in vivo animal model where tumor growth was significantly inhibited after treatment. 欧洲杯买球网游戏 received FDA IND clearance in May 2022, and China CDE IND approval in December 2022.

Mechanism of Action

• 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 欧洲杯买球网游戏 to the TME where the anti-TGF-β activity promotes immune-favorable T cell activation and cytokine release, while avoiding or minimizing systemic immunotoxicity
• 欧洲杯买球网游戏’s anti-CD39 activity further aims to reverse TME immunosuppression by reducing suppressive adenosine, while maintaining high levels of immune-stimulatory extracellular ATP

Key Differentiation

• 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 and In vivo Properties

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

Publications

• 欧洲杯买球网游戏 achieved a strong single agent anti-tumor efficacy in a PD-(L)1 unresponsive mouse model. SITC 2021, P792

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