Tolero Pharmaceuticals to Present New Data Evaluating Investigational Agents TP-0903 and TP-0184 at AACR Annual Meeting 2019
SALT LAKE CITY, Feb. 27, 2019 /PRNewswire/ -- Tolero Pharmaceuticals, Inc., a clinical-stage company focused on developing novel therapeutics for hematological and oncological diseases, today announced that new data from five abstracts on the company's pipeline of investigational agents will be presented at the American Association for Cancer Research (AACR) Annual Meeting, taking place March 29-April 3, 2019 in Atlanta, Georgia. Data to be presented includes preclinical studies evaluating the anti-tumor activity of TP-0903, an investigational oral, small molecule inhibitor of the AXL receptor tyrosine kinase, in advanced ovarian cancer, colorectal cancer, EGFR positive non-small cell lung cancer and breast cancer models. Additionally, data will be presented on the evaluation of activin A receptor type 1 (ACVR1) gene mutations as potential clinical biomarkers for the small molecule ACVR1 inhibitor TP-0184.
"We are encouraged by the range of data to be presented in multiple presentations on our early-stage pipeline assets, TP-0903 and TP-0184, at the 2019 AACR Annual Meeting," said David J. Bearss, Ph.D., Chief Executive Officer of Tolero Pharmaceuticals. "The data provides additional support for the continued clinical evaluation of these investigational agents and advance our understanding of their mechanisms of action and the potential of targeting these mechanisms in multiple tumor types."
Below are the details for the Tolero presentations:
Abstract Title
Details
Presenter
---
The AXL Kinase
Inhibitor, TP-
0903, Demonstrates
Efficacy in
Preclinical Models
of Colorectal
Cancer Independent
of KRAS Mutation
Status
Abstract #2197
Ryan Mangelson, Tolero Pharmaceuticals
April 1, 1:00-5:00PM,
Poster Presentation
---
Targeting AXL kinase
with TP-0903
successfully
reverses the
mesenchymal
phenotype and
extends survival in
preclinical models
of advanced ovarian
cancer
Abstract #2646
Nozomi Tomimatsu, Sumitomo Dainippon Pharma
April 1, 1:00-5:00PM,
Poster Presentation
---
TP-0903, a potent
AXL receptor
tyrosine kinase
inhibitor, enhances
the activity of
anti-PD-1 therapy
in a metastatic
preclinical
syngeneic model of
breast cancer
Abstract #1468
Yuka Kumagai, Sumitomo Dainippon Pharma
April 2, 1:00-5:00PM,
Poster Presentation
---
Evaluation of
genetic modulation
of ACVR1 (aka ALK2)
kinase gene as a
clinical biomarker
of the ACVR1
inhibitor TP-0184
Abstract #3166
Mark Wade, Tolero Pharmaceuticals
April 2, 8:00AM-12:00PM,
Poster Presentation
---
The potent AXL
kinase inhibitor,
TP-0903, is active
in pre-clinical
models of EGFR
positive non-small
cell lung cancer
Abstract #3804
Cliff Whatcott, Tolero Pharmaceuticals
April 2, 1:00-5:00PM,
Poster 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 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 TP-0184
TP-0184 is small molecule inhibitor of activin A receptor type 1 (ACVR1), which is involved in the transforming growth factor beta (TGF ) signaling pathway. ACVR1, also known as activin receptor-like kinase 2 (ALK2), is mutated in multiple types of cancers, including diffuse intrinsic pontine glioma (DIPG), a malignancy with high morbidity and mortality affecting the pediatric population.(3-5) ACVR1 mutations are present in approximately 1-4 percent of solid tumors and, more commonly, in 32 percent of diffuse intrinsic pontine gliomas (DIPGs), a brain cancer with high morbidity and mortality afflicting the pediatric population.(4-7) There is currently no approved therapy for the treatment of DIPG. ACVR1 is also involved in regulation of iron hemostasis, through transcriptional activation of hepcidin and reduction of bioavailable iron, which is associated with anemia of chronic inflammation.(6) TP-0184 is currently being evaluated in a Phase 1 clinical trial in advanced solid tumors (NCT03429218).
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.
3. Peterson P, Kim W, Haws H, et al. The ALK-2 inhibitor, TP-0184,
demonstrates high distribution to the liver contributing to significant
preclinical efficacy in mouse models of anemia of chronic disease
[Abstract]. Blood. 2016;128:263.
4. Taylor KR, Mackay A, Truffaux N, et al. Recurrent activating ACVR1
mutations in diffuse intrinsic pontine glioma. Nature Genetics. 2014; 46;
457-461. doi:10.1038/ng.2925
5. Wu G, Diaz AK, Paugh BS, et al. The genomic landscape of diffuse
intrinsic pontine glioma and pediatric non-brainstem high-grade glioma.
Nature Genetics. 2014;46(5):444-450. doi:10.1038/ng.2938.
6. Steinbicker AU, Bartnikas TB, Lohmeyer LK, et al. Perturbation of
hepcidin expression by BMP type I receptor deletion induces iron overload
in mice. Blood. 201; 118(15):4224-4230. doi:10.1182/blood-2011-03-339952.
7. Martelotto LG, Baslan T, Kendall J, et al. Whole-genome single-cell copy
number profiling from formalin-fixed paraffin-embedded samples. Nat Med.
2017; 23(3): 376-385.
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