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Tolero Pharmaceuticals Advances Investigational Agent TP-0903 into Phase 1b Expansion Stage of Study in Patients with Advanced Solid Tumors

SALT LAKE CITY, May 30, 2019 /PRNewswire/ -- Tolero Pharmaceuticals, Inc., a clinical-stage company focused on developing novel therapeutics for hematological and oncological diseases, today announced the initiation of the Phase 1b expansion stage of its ongoing Phase 1 study evaluating the investigational agent TP-0903, an AXL receptor tyrosine kinase (RTK) inhibitor, in patients with advanced solid tumors. The maximum tolerated dose (MTD) of TP-0903 was established during the Phase 1a portion of the study, allowing the study to advance to the Phase 1b stage. AXL inhibition by TP-0903 has shown to have anti-tumor activity and to reverse mesenchymal phenotype, leading to immune surveillance inhibition in preclinical models resistant to targeted agents including immunotherapeutics.1 

The Phase 1b stage of the study will enroll additional patients with specific solid tumor types, including advanced solid tumors with progressive disease post immunotherapy, EGFR positive non-small cell lung cancer progressed following TKI therapies, colorectal carcinoma (BRAF-, KRAS-, or NRAS-mutated), platinum refractory or resistant recurrent ovarian carcinoma, and BRAF-mutated melanoma progressed following immunotherapy or combination BRAF/MEK inhibitor.  

"This milestone marks an important step forward in the clinical development of TP-0903 as a potential treatment option for patients with advanced solid tumors," said David J. Bearss, Ph.D., Chief Executive Officer of Tolero Pharmaceuticals, Inc. "We believe this study may further our understanding of the anti-tumor activity of TP-0903 in these tumor types."

The primary outcome measures of the interventional, open-label, non-randomized, dose-escalation study is to assess the incidence of dose-limiting toxicities and treatment emergent adverse events of oral TP-0903 administered once daily in patients with advanced solid tumors. Secondary outcome measures include pharmacokinetics, activity on predictive biomarkers and objective response rate of TP-0903. The Phase 1b stage of the study is expected to enroll up to 20 patients in each of the five additional cohorts, for a total of up to 100 additional patients enrolled. Ten patients in each of the five expansion cohorts will undergo pre- and post-dose tumor biopsies.

The study is being conducted in the United States. Additional information on this trial, including comprehensive inclusion and exclusion criteria, can be accessed at www.ClinicalTrials.gov (NCT02729298).

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 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.

References

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.