The successful development of immunotherapies represents one of the most important and exciting breakthroughs in cancer. Recent approvals of checkpoint inhibitors provide evidence that the immune system is capable of recognizing cancerous cells and eradicating them. These checkpoint inhibitors can achieve complete, durable remissions and help patients live longer. Yet, despite this progress, existing immunotherapies are effective in a relatively small number of patients and types of cancer.
Tizona’s therapies are designed to modulate the activity of immunosuppressive cells by targeting the cell types and biological mechanisms responsible for immune suppression in the tumor microenvironment:
The ATP-adenosine pathway regulates immune activity in the tumor microenvironment (TME) by controlling the inflammatory and suppressive activities of immune cells. High concentrations of extracellular ATP increase inflammatory activities of dendritic and myeloid-derived cells responsible for innate immunity and immune cell priming necessary for adaptive immunity. Inversely, high concentrations of extracellular adenosine increase the suppressive activities of nearly all immune cells in the microenvironment, including T cells, dendritic cells, macrophages, myeloid-derived suppressor cells and natural killer cells.
CD39 is the enzyme responsible for the initial steps in conversion of extracellular ATP to adenosine in the TME. CD39 expression is found on both tumor cells and tumor infiltrating leukocytes as immune evasion strategies and in response to hypoxia. Large and hypoxic tumors frequently become immune suppressive due to the breakdown of excessive ATP released from dying tumor cells to immune suppressive adenosine by CD39. CD39 expression in the TME, therefore, acts as a switch: low ATP and high adenosine lead to immune suppression when CD39 activity is present and high extracellular ATP and low extracellular adenosine lead to immune activation when CD39 is inhibited.
Tizona Therapeutics is advancing an anti-CD39 antibody that inhibits the breakdown of ATP by CD39. The company is on track to file an Investigational New Drug application for the CD39 program in late 2018.
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At Tizona, we are developing cancer immunotherapy treatments that have the potential to be first- and best-in-class therapies, and core components of innovative combination treatments. We have successfully built a talented and experienced research and development team, and are interested in collaborations with pharmaceutical and biotech companies as well as academic institutions around the world to jointly discover and develop products that will bring meaningful treatment options to cancer patients.
Currently we are engaged in partnering/in-licensing discussions related to our existing programs. If you would like additional information on partnering with Tizona, please contact our business development team at firstname.lastname@example.org
QIMR Berghofer Medical Research Institute
Beth Israel Deaconess Medical Center
Brigham and Women’s Hospital
Dana-Farber Cancer Institute
St. Jude Children’s Research Hospital
University of Turku