Tolero Pharmaceuticals Presents Preliminary Findings from Phase 1 Study Evaluating Investigational Agent TP-0903 in Patients with Advanced Solid Tumors at ESMO 2019

SALT LAKE CITY, Sept. 28, 2019 /PRNewswire/ -- Tolero Pharmaceuticals, Inc., a clinical-stage company focused on developing novel therapeutics for hematological and oncological diseases, today presented new data from the ongoing Phase 1 study evaluating the maximum tolerated dose (MTD) of the oral investigational agent TP-0903, an AXL receptor tyrosine kinase (RTK) inhibitor, in patients with advanced solid tumors. These results were presented in a poster presentation at the 2019 European Society for Medical Oncology (ESMO) meeting, being held September 27-October 1, 2019, in Barcelona, Spain.

Preliminary findings of the Phase 1a dose-escalation part of the study indicate that TP-0903 was well tolerated with a manageable safety profile. In the study, 34 of 38 total patients were evaluable and received escalating doses of oral TP-0903 from 1.5 to 37 mg/m² and 50 mg flat dosing once-daily in 21 of 28-day cycles. Fifteen patients remained on the study for more than four cycles, despite advanced disease and several previous therapies. To date, 37 percent (n=14) of all patients in the dose-escalation part experienced a best response of stable disease and one patient experienced a partial response. The most frequently observed adverse events of Grade 3 or higher included diarrhea, anemia, hyponatremia, thrombocytopenia, and vomiting. A combination of thrombocytopenia and gastrointestinal toxicities was observed as a dose-limiting toxicity (DLT).¹ The results of pharmacodynamic correlative studies as the time on therapy and best response to therapy will be presented in the future.

"TP-0903 inhibits the AXL receptor tyrosine kinase, an important oncologic target that is upregulated and activated in many solid tumors. AXL activation is often correlated with drug resistance to chemotherapy, targeted cancer therapeutics and immuno-oncology agents," said David J. Bearss, Ph.D., Chief Executive Officer of Tolero Pharmaceuticals, Inc.² "We are encouraged by these preliminary findings on TP-0903 as they lay the foundation for further clinical research and development in various tumor types. We look forward to learning more about the potential activity of TP-0903 as we continue to advance the Phase 1b part of the study."

The Phase 1b part of the study is evaluating the safety and clinical activity of TP-0903 in 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. The recommended Phase 2 dose for TP-0903 being assessed in the Phase 1b part of this study is a 50 mg flat dose. TP-0903 is now being evaluated at a dose of 50 mg in combination with immuno-oncology agents as well as EGFR inhibitory agents.¹

Below are the details for the Tolero presentation:

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 1a/b 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.³ 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.⁴

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. With the support of our parent company, Sumitomo Dainippon Pharma, we work closely together with Boston Biomedical, Inc., and Sumitomo Dainippon Pharma's Cancer Institute to achieve a common goal - expediting the discovery, development and commercialization of novel treatment options with the aim of improving patient outcomes.

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
¹Sarantopoulos J, Fotopoulos G, Tsai F, et al. A Phase 1a/b first-in-human, open-label, dose-escalation, safety, PK and PD study of TP-0903 in solid tumors. ESMO 2019; Abstract 460P.
²Antony J and Y-J Huang R, AXL-Driven EMT State as a Targetable Conduit in Cancer. Cancer Res. 2017;77(14):3725-3732
³Soh 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.
⁴Park 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.