Our Science

Trishula is dedicated to improving the outcomes for people with cancer. TTX-030 is a first-in-class antibody that inhibits the activity of CD39. TTX-030 targets the ATP-adenosine pathway and inhibition of CD39 is believed to modulate immune suppression within the tumor microenvironment, thus increasing anti-tumor immunity.

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The clinical development plan for TTX-030, a novel immunotherapy, is focused on restoring and bolstering immune responses in the tumor microenvironment.

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See clinical trials: TTX-030-001 (NCT03884556) and TTX-030-002 (NCT04306900)

ATP and Adenosine in the Tumor Microenvironment

Tumors employ various strategies to create an environment that reduces the immune system’s ability to detect and fight cancer.

The ATP-adenosine pathway plays a key role in establishing an immunosuppressive tumor microenvironment (TME) by driving the conversion of proinflammatory, extracellular ATP to immunosuppressive adenosine. Trishula’s TTX-030 aims to reverse this process in two ways:

  1. By inhibiting the production of adenosine in the TME, TTX-030 prevents the adenosine-mediated inhibition of immune effector cells (including T cells, B cells, NK cells and myeloid cells).
  2. By maintaining high levels of extracellular ATP, TTX-030 enables the stimulation of dendritic and myeloid-derived cells necessary to support innate and adaptive immunity.

This dual mechanism of action is designed to reverse the immunosuppressive conditions within the TME and restore the immune system’s anti-tumor capabilities.

TTX-030, A NOVEL, FIRST-IN-CLASS, ANTI-CD39 ANTIBODY

TTX-030 is an antibody that inhibits the activity of CD39, the rate-limiting enzyme in the conversion of ATP to adenosine in the tumor microenvironment.

TTX-030 is being studied in phase 1/1b clinical trials as a monotherapy and in combination with anti-PD-1 immunotherapy and standard chemotherapy in adults with advanced cancer (NCT03884556 and NCT04306900)

Publications

Moesta AK, Li XY, Smyth MJ. Targeting CD39 in cancer. Nat Rev Immunol. 2020; 20(12):739-755.

Spatola B et al. Fully human anti-CD39 antibody potently inhibits ATPase activity in cancer cells via uncompetitive allosteric mechanism. mAbs. 2020; 12(1):1838036.

Yan J et al. Control of metastases via myeloid CD39 and NK cell effector function. Cancer Immunol Res 2020; 8(3):356-367.

Li XY et al. Targeting CD39 in Cancer Reveals an Extracellular ATP- and Inflammasome-Driven Tumor Immunity. Cancer Discovery. 2019; 9(12):1754-1773