Tizona Therapeutics, Inc., a clinical stage, privately held company developing first-in-class cancer immunotherapies, announced today the online publication of an article in Cancer Discovery describing novel mechanisms to more potently modulate the adenosine pathway and activate anti-tumor immune responses using antibodies that block CD39.
The paper, “Targeting CD39 in Cancer Reveals an Extracellular ATP and Inflammasome-driven Tumor Immunity”, found that blocking CD39 enzymatic activity with an anti-CD39 antibody facilitated immune cell infiltration into T cell-poor tumors and rescued anti-PD-1 resistance. This activity was shown to be mediated by ATP’s signaling of the P2X7 receptor and consequent stimulation of the inflammasome. Stimulating inflammasome-driven anti-tumor immunity through the preservation of ATP coupled with preventing the production of immune suppressive adenosine is only achieved through targeting CD39.
TTX-030, a first-in-class anti-CD39 antibody discovered at Tizona, is currently being evaluated in collaboration with AbbVie in a Phase 1/1b clinical study as a monotherapy and in combination with an approved anti-PD-1 agent and standard chemotherapy in adults with advanced cancer (NCT03884556).
“Targeting CD39 is a promising approach to modulate the adenosine pathway within the tumor microenvironment to both stimulate the immune system and counter immune suppression,” said Scott Clarke, CEO of Tizona. “This paper provides additional evidence that CD39 is a key immune regulatory switch in the TME, and we are excited to develop TTX-030, our first-in-class anti-CD39 antibody, with the potential to transform outcomes for people with cancer.”
About TTX-030, the Adenosine Axis, and the Tumor Microenvironment
TTX-030 is a monoclonal antibody that inhibits the activity of CD39, a cell surface enzyme upregulated on tumors, exhausted T cells, as well as many suppressive cell types. It catalyzes the conversion of ATP to AMP, the first step in the generation of adenosine. By blocking the action of CD39, TTX-030 prevents the formation of immune suppressive extracellular adenosine, which would otherwise inhibit effector cells in the TME. In addition to preventing the formation of suppressive adenosine, TTX-030 also prevents the degradation of ATP, preserving ATP’s ability to stimulate dendritic and myeloid-derived cells responsible for innate immunity and the immune cell priming necessary for adaptive immunity.
About Tizona Therapeutics, Inc.
Tizona is a privately held, clinical-stage immunotherapy company that develops first-in-class medicines to deliver transformational benefits to people with cancer. Tizona addresses cancer progression and relapse by applying novel human biological insights to develop biotherapeutics that stimulate the immune system and counter immune suppression.
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Source: Tizona Therapeutics, Inc.