Tolero Pharmaceuticals Presents Clinical Data of AXL Kinase Inhibitor TP-0903 Showing its Ability to Enhance Host Immune Responses to Tumors
SALT LAKE CITY, Nov. 15, 2018 /PRNewswire/ -- Tolero Pharmaceuticals, Inc., a clinical-stage company focused on developing novel therapeutics for hematological and oncological diseases, today announced the presentation of clinical and preclinical data supporting the development of TP-0903 for the treatment of patients with solid tumors. TP-0903 is an oral, small molecule inhibitor of the AXL receptor tyrosine kinase. Key findings from syngeneic mouse models suggest that TP-0903 has immune activating potential leading to enhanced host immune responses in tumor models.
The data will be presented at the 2018 EORTC-NCI-AACR Molecular Targets and Cancer Therapeutics Symposium in Dublin. Posters will be on display from 10:00 a.m. to 2:00 p.m. GMT on Nov. 16 in the Exhibition Hall of the Convention Centre Dublin.
"There is a significant need to develop new cancer therapeutic solutions aimed at strengthening the body's own immune response," said David J. Bearss, Ph.D., Chief Executive Officer of Tolero Pharmaceuticals, Inc. "AXL kinase is an important oncolytic target; we are encouraged by the findings of TP-0903 showing the inhibition of AXL kinase, demonstrating enhanced host immunity. We look forward to further developments of TP-0903 in counteracting AXL-mediated effects."
The data show that TP-0903 treatment alters tumors by suppressing the mesenchymal phenotype of the cancer cells and favoring a tumor microenvironment amenable to an immune response. Preclinical models in immune competent animals show modulation of immune cell populations, including neutrophils, regulatory T-cells, and dendritic cells, in the tumors. Additionally, the predictive power of soluble AXL levels in the serum of cancer patients as a biomarker to select patients likely to benefit from TP-0903 treatment will be presented.
Recent data suggest that AXL kinase is involved in tumor cell proliferation and development of resistance to chemotherapeutics. TP-0903 is an AXL receptor tyrosine kinase inhibitor, which has showed nanomolar activity in biochemical assays. In this preclinical study, the immune modulating capabilities were assessed using immunohistochemical and real-time PCR techniques in syngeneic mouse models of solid tumors.
The associated abstract #413, PB-076, is available on the EORTC-NCI-AACR meeting program website.
TP-0903 is an investigational oral, small molecule inhibitor of the AXL receptor tyrosine kinase (RTK), which has demonstrated effectiveness in cell-based and animal models of human cancers. The first-in-human Phase 1/1b study is underway identifying the safety and tolerability profile of TP-0903. In addition, the study is analyzing the pharmacodynamics of TP-0903 by assessing biomarkers in patients' samples before and after treatment with TP-0903, including markers of immune suppression.
About AXL Kinase
AXL belongs to the TAM (Tyro3, AXL and Mer) family of receptor tyrosine kinases and is overexpressed in many human cancers. It plays a key role in tumor cell proliferation, survival, metastasis, cellular adhesion and avoidance of the immune response. The overexpression of AXL is associated with a poor patient prognosis and drug resistance.1,2
About Tolero Pharmaceuticals, Inc.
Tolero Pharmaceuticals is a clinical-stage biopharmaceutical company researching and developing treatments to improve and extend the lives of patients with hematological and oncological diseases. Our diverse pipeline targets important biological drivers of blood disorders to treat leukemias, anemia, and solid tumors, as well as targets of drug resistance and transcriptional control. Tolero Pharmaceuticals is based in the United States and is an indirect, wholly-owned subsidiary of Sumitomo Dainippon Pharma Co., Ltd., a pharmaceutical company based in Japan.
Additional information about the company and its product pipeline can be found at www.toleropharma.com.
Tolero Pharmaceuticals Forward-Looking Statements
This press release contains "forward-looking statements", as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. The forward-looking statements in this press release are based on management's assumptions and beliefs in light of information presently available, and involve both known and unknown risks and uncertainties, which could cause actual outcomes to differ materially from current expectations. Any forward-looking statements set forth in this press release speak only as of the date of this press release. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. Information concerning pharmaceuticals (including compounds under development) contained within this material is not intended as advertising or medical advice.
1. Park IK, Mundy-Bosse B, Whitman SP, et al. Receptor tyrosine kinase Axl is required for resistance of leukemic cells to FLT3-targeted therapy in acute myeloid leukemia. Leukemia. 2015;29(12):2382-2389.
2. Soh KK, Bahr BL, Bearss JJ, et al. Inhibition of Axl kinase reverses the mesenchymal phenotype in leukemic cells through the disruption of retinoic signaling [Abstract]. Blood. 2015;126:3253.
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