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AbbVie and immunotherapy company Tizona Therapeutics will join forces to develop and commercialize CD39-targeted therapeutics to treat cancer.
On Jan. 3, 2019, AbbVie announced a collaboration with Tizona Therapeutics, a privately held immunotherapy company, to develop and commercialize CD39-targeted therapeutics, including TTX-030, an antibody for the treatment of cancer.
Under the terms of the agreement, Tizona has received an upfront payment of $105 million for the exclusive option to license the CD39 program, including TTX-030. In addition, AbbVie has made an equity investment in Tizona. Tizona will lead clinical development through completion of Phase Ib studies, after which AbbVie has an exclusive option to lead global development and commercial activities. Tizona retains an option to co-develop and co-promote in the United States and is eligible for success-based development and commercial milestones and tiered royalties on net sales.
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 as an immune evasion strategy. 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 tumor microenvironment (TME). In addition to preventing the formation of suppressive adenosine, TTX-030 prevents the degradation of ATP, preserving its ability to stimulate dendritic and myeloid-derived cells responsible for innate immunity and immune cell priming necessary for adaptive immunity.
According to AbbVie, the ATPÂadenosine axis has recently emerged as a key immune regulatory switch in the TME by controlling the inflammatory and suppressive activities of immune cells. CD39 is the enzyme responsible for the initial steps in the conversion of immune stimulatory extracellular ATP to immune suppressive adenosine in the TME. Inhibition of CD39 with TTX-030 represents a new approach to targeting this pathway.
"Immuno-oncology is one of AbbVie's key focus areas in our mission to discover and develop medicines that drive transformational improvements in cancer treatment," said Mo Trikha, PhD, vice president, head of Oncology Early Development, AbbVie, in a company press release. "Exploring the tumor microenvironment as a source of targets that can be modulated to inhibit cancer growth holds tremendous promise. The Tizona team has generated compelling preclinical data for their TTX-030 program, and we look forward to a productive collaboration focused on rapidly advancing this novel first-in-class antibody."
"Tumors employ various strategies to create a tolerogenic microenvironment, which reduces the immune system's ability to detect and fight cancer," said Courtney Beers, PhD, vice president, Immunology, Tizona, in the release. "Preclinical research shows that inhibiting CD39 may hold the key to restoring and bolstering immune responses against tumors. In AbbVie, we have a partner who shares our passion for science and commitment to delivering breakthrough innovation to patients with cancer. We look forward to advancing this exciting program."
AbbVie reports that FDA has accepted an investigational new drug application for TTX-030.