Tolero Pharmaceuticals Announces First Patient Dosed with Investigational Agent TP-0184, an Activin A Receptor Type 1 (ACVR1) Inhibitor, in Phase 1 Study of Patients with Advanced Solid Tumors

Wednesday, July 25, 2018 Drug News
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SALT LAKE CITY, July 25, 2018 /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 study evaluating investigational agent TP-0184, an activin A receptor type 1 (ACVR1) inhibitor, in patients with advanced
solid tumors. The Phase 1, open-label, dose-escalation study will evaluate the safety, pharmacokinetics, and pharmacodynamics of TP-0184 administered orally daily for the first 21 days of a 28-day cycle across a range of doses.

"The initiation of this study of TP-0184 represents an important milestone for Tolero Pharmaceuticals, as it marks the second investigational agent from our development program to enter the clinical research stage this year," said David J. Bearss, Ph.D., Chief Executive Officer of Tolero Pharmaceuticals, Inc. "We look forward to understanding more about the profile of TP-0184 and its role in inhibiting ACVR1, which is mutated in approximately 1-4 percent of solid tumors and 32 percent of diffuse intrinsic pontine gliomas (DIPGs), an aggressive form of pediatric brain cancer."

The primary objective of the Phase 1 study is to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of TP-0184 orally administered daily for 21 days, over a range of doses in patients with advanced solid tumors. Secondary objectives in the study are to evaluate the pharmacokinetics and pharmacodynamics of TP-0184, observe patients for any evidence of antitumor activity of TP-0184 by objective radiographic assessment, and establish the recommended Phase 2 dose for future studies with TP-0184. The trial is being conducted at sites in the United States. Additional information on this trial, including comprehensive inclusion and exclusion criteria, can be accessed at www.ClinicalTrials.gov (NCT03429218).

About TP-0184 TP-0184 is small molecule inhibitor of ACVR1, an activin A receptor type 1 (ACVR1) inhibitor, 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.1,2,3 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.4,5 There is currently no approved therapy for the treatment of DIPG. ACVR1 is also involved in regulation of iron hemostasis, through stabilization of hepcidin and reduction of bioavailable iron, which is associated with anemia of chronic inflammation.4 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 oncological and hematological 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.

References1 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;128:263.2 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.29253 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.2938.4 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-2011-03-339952.5 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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SOURCE Tolero Pharmaceuticals, Inc.



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