Tolero Pharmaceuticals Announces First Patient Dosed with Investigational Agent TP-0903 in Phase 1/2 Study in Patients with Previously Treated Chronic Lymphocytic Leukemia andSmall Lymphocytic Lymphoma

SALT LAKE CITY, June 12, 2019 /PRNewswire/ -- Tolero Pharmaceuticals, Inc., a clinical-stage company focused on developing novel therapeutics for hematological and oncological diseases, today announced that the first patient has been dosed in a Phase 1/2 study evaluating the investigational agent TP-0903, an AXL receptor tyrosine kinase (RTK) inhibitor, in patients with previously treated chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). The open-label, dose-escalation, safety, pharmacokinetics, and pharmacodynamic study will evaluate the dose-limiting toxicities and clinical activity of oral TP-0903 administered in patients with previously treated CLL/SLL, as monotherapy or in combination with ibrutinib.

"Although there have been significant advances in the treatment of CLL and SLL in recent years, there remains an area of clinical unmet need for patients who have had disease progression or relapse with available therapies." said David J. Bearss, Ph.D., Chief Executive Officer of Tolero Pharmaceuticals. "The initiation of this study will allow us to learn more about the clinical profile of TP-0903 and the role of AXL receptor tyrosine kinase (RTK) inhibition in patients with previously treated CLL and SLL."

The primary outcome measures of the Phase 1 study are to determine dose-limiting toxicities and the incidence of treatment-emergent adverse events of oral TP-0903 administered once daily for 28 days in patients with previously treated CLL/SLL. Secondary outcome measures of the Phase 1 study include pharmacokinetics. The recommended Phase 2 dose (RP2D) will be determined in Phase 1 of the study. Phase 2 of the study will begin after the completion of Phase 1. The primary outcome measure of Phase 2 will be to determine the objective response rate according to guidelines set forth by the 2018 International Workshop on CLL. Secondary outcome measures of the Phase 2 study include assessment of duration of response and rate of overall survival.

In Phases 1 and 2 of the study, patients will be assigned to one of two defined patient groups. Patients in Group 1, which includes those who are intolerant to or have progressed on B-cell receptor antagonists and/or BCL-2 antagonists, will receive TP-0903 monotherapy. Patients in Group 2, which includes those who have progression of disease on ibrutinib and the treating provider considers continuation of ibrutinib therapy to be in the best interest of the patient, will receive combination therapy of TP-0903 and ibrutinib. Additional information on this trial, including comprehensive inclusion and exclusion criteria, can be accessed at (NCT03572634).

About TP-0903
TP-0903 is an investigational oral AXL receptor tyrosine kinase (RTK) inhibitor under evaluation in a Phase 1/2 study in patients with CLL/SLL (NCT03572634) and a Phase 1b study in patients with advanced solid tumors (NCT02729298). Tolero is exploring parallel clinical development paths for TP-0903 in both solid and hematologic malignancies.

About AXL Kinase
AXL belongs to the TAM (Tyro3, AXL and Mer) family of receptor tyrosine kinases and is overexpressed in many human cancers.(1) 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.(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

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) 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.
(2) 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.

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SOURCE Tolero Pharmaceuticals, Inc.