Tolero Pharmaceuticals Presents Positive Preclinical Data That Inhibition Of AXL Kinase Restores Tumor Response To Retinoic Acid

-- Poster presented at the 20^th Congress of European Hematology Association--

SALT LAKE CITY--(BUSINESS WIRE)--Tolero Pharmaceuticals, Inc., a clinical-stage company developing treatments for serious hematological diseases, today announced that it presented positive preclinical data on TP-0903, an AXL kinase inhibitor, on June 12, 2015, at the 20^th Congress of European Hematology Association (EHA) in Vienna, Austria. In the data presented, TP-0903 affected the upregulation of CYP26, an enzyme that is induced by and leads to the metabolism of retinoic acid. This mechanism drives resistance to retinoic acid treatment and limits its effectiveness in treating patients with many types of cancer. Retinoic acid regulates cell growth and differentiation and is now the standard of care in acute promyelocytic leukemia (APL) with around 90% of patients attaining complete and durable remissions. The use of retinoic acid targeted treatments outside of APL are limited by the strong response of tumors up-regulating CYP26 enzymes in response to treatment and causing the elimination of the drug by inducing its metabolism by CYP26 enzymes.

“As we make great strides in developing new treatments for patients with cancer by finding and exploiting the weaknesses in cancer cells, cancer cells find mechanisms by which to evade treatments, creating resistance to many of our old as well as new therapies”

“As we make great strides in developing new treatments for patients with cancer by finding and exploiting the weaknesses in cancer cells, cancer cells find mechanisms by which to evade treatments, creating resistance to many of our old as well as new therapies,” said David J. Bearss, PhD, CEO of Tolero. “The data presented at EHA suggest that TP-0903 represents a novel mechanism by which patients could potentially overcome resistance to retinoic acid treatment and opens up the possibility of combining TP-0903 with drugs targeting the retinoic acid pathway. We look forward to advancing TP-0903 into clinical studies in the near future.”

In the data presented at EHA, retinoic acid treatment of multiple leukemia cell lines increased levels of CYP26, however, in the presence of TP-0903, this increase was inhibited. TP-0903 also inhibited CYP26 expression in the absence of retinoic acid. In animal models of leukemia, TP-0903 as a single agent, strongly inhibited tumor volumes by up to 100% at multiple dose levels and treatment schedules. These data support the continued development of TP-0903 as a single agent as well as an adjuvant to retinoic acid in potentially many cancer types.

About AXL Kinase Inhibitors

AXL and other TAM family members are known to be involved in maintaining a mesenchymal phenotype in cancer cells. Mesenchymal cells have increased invasion and migratory properties, enhanced cell survival in stressed environments, and increased resistance to targeted therapies. In fact, AXL overexpression is a reoccurring theme observed in multiple tumor types that have acquired resistance to various agents.

About TP-0903

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 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.

About Tolero

Tolero Pharmaceuticals is a clinical stage biopharmaceutical company developing treatments to improve and extend the lives of patients with serious oncological and hematological 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. www.toleropharma.com