Tolero Pharmaceuticals Presents Data Demonstrating AXL Inhibition Leads to a Reversal of a Mesenchymal Phenotype Sensitizing Cancer Cells to Targeted Agents and Immuno-Oncology Therapies
Poster presented at the AACR Annual Meeting 2016
SALT LAKE CITY, UT - April 18, 2016 - Tolero Pharmaceuticals, Inc., a clinical-stage company developing treatments for oncology and hematologic diseases, today announced the presentation of positive preclinical data on TP-0903, an AXL kinase inhibitor. In the data presented, Tolero demonstrated that the AXL inhibitor, TP-0903, sensitized cancer cells to various immuno-oncology agents including an immune checkpoint inhibitor. The data were presented in a poster entitled "AXL inhibition leads to a reversal of a mesenchymal phenotype sensitizing cancer cells to targeted agents and immune-oncology therapies," at the American Association for Cancer Research (AACR) Annual Meeting 2016 in New Orleans, Louisiana.
AXL expression promotes a mesenchymal phenotype in cancer cells that is associated with drug resistance and escape from immune surveillance. The preclinical study demonstrated that TP-0903 inhibits AXL kinase, leading to a reversal of the mesenchymal phenotype that can then restore sensitivity to targeted agents and offers the potential for an enhanced immunogenic response to the tumor. The enhanced immunogenic response is facilitated by AXL’s role in promoting the removal of cellular debris from apoptotic cells. In cancer cells undergoing apoptosis, the inhibition of AXL causes the accumulation of tumor-associated antigens and this is believed to enhance the activity of other immune-oncology agents.
"Increasing the immunogenicity of a tumor is a major next step in the development of the entire field of immuno-oncology agents," said Steven L. Warner, Ph.D., Vice President of Discovery and Development at Tolero. "Our data suggest that AXL represents a novel mechanism by which cancer cells further escape being targeted by the immune system and that TP-0903 provides an approach to reverse this mechanism. We look forward to evaluating this molecule in cancer patients, particularly in combination with immune-targeting agents."
About TP-0903 and AXL Kinase Inhibitors
TP-0903 is a small molecule inhibitor of AXL kinase. AXL, along with other members of the TAM family of kinases, are key regulators of the mesenchymal phenotype of cancer cells. Mesenchymal cancer cells have increased invasion and migratory properties, enhanced cell survival characteristics in stressed environments, and critically, increased resistance to both targeted and traditional chemotherapies. Consequently, targeting AXL kinase with TP-0903 is an attractive way to overcome resistance to chemotherapy by targeting mesenchymal cancer cell populations.
Tolero Pharmaceuticals is a clinical stage biopharmaceutical company developing treatments to improve and extend the lives of patients with cancer and blood diseases. Our diverse pipeline targets important biological drivers of blood disorders to treat leukemias and anemia as well as important targets of drug resistance and transcriptional control.
Tolero Pharmaceuticals, Inc.
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