Tolero Pharmaceuticals advances investigational agent alvocidib into second stage of phase 2 Zella 201 study in patients with relapsed refractory MCL-1–dependent AML
SALT LAKE CITY, July 23, 2018 — Tolero Pharmaceuticals, Inc., a clinical-stage company focused on developing novel therapeutics for hematological and oncological diseases, today announced that it has initiated the second stage of the Phase 2 Zella 201 study evaluating the efficacy and safety of alvocidib, a potent CDK9 inhibitor, in combination with cytarabine and mitoxantrone (ACM) in patients with relapsed or refractory MCL-1-dependent acute myeloid leukemia (AML). During Stage 2 of the study, patients will be randomized to receive the ACM regimen or cytarabine and mitoxantrone alone.
“The advancement of this study marks an important milestone for our company as we continue to progress the Phase 2 clinical program for alvocidib,” said David J. Bearss, Ph.D., Chief Executive Officer of Tolero Pharmaceuticals, Inc. “We believe the second stage of this study will deepen our understanding of the activity of alvocidib in relapsed or refractory MCL-1-dependent acute myeloid leukemia. This will allow us to build upon preliminary clinical data from the Stage 1 of the Zella 201 study that were recently presented at the 23rd Annual Congress of the European Hematology Association.”
The randomized, open-label Stage 2 of the Zella 201 study is expected to enroll 106 patients. The primary endpoint of the study is the rate of complete remission. The study also includes secondary endpoints evaluating overall survival, event-free survival, complete remission with incomplete recovery, complete remission without platelet recovery and response duration.
Alvocidib is an investigational small molecule inhibitor of cyclin-dependent kinase 9 (CDK9) currently being evaluated in a Phase 2 study, Zella 201, in patients with relapsed or refractory MCL-1-dependent acute myeloid leukemia, AML, in combination with cytarabine and mitoxantrone (NCT02520011). Alvocidib is also being evaluated in Zella 101, a Phase 1 clinical study evaluating the maximum tolerated dose, safety and clinical activity of alvocidib in combination with (7+3) in newly diagnosed patients with AML (NCT03298984).
About CDK9 Inhibition and MCL-1
MCL-1 is a member of the apoptosis-regulating BCL-2 family of proteins.1 In normal function, it is essential for early embryonic development and for the survival of multiple cell lineages, including lymphocytes and hematopoietic stem cells.2 In MCL-1–dependent AML, MCL-1 inhibits apoptosis and sustains the survival of leukemic blasts, which may lead to relapse or resistance to treatment.1,3 The expression of MCL-1 in leukemic blasts is regulated by cyclin-dependent kinase 9 (CDK9).4,5 Because of the short half-life of MCL-1 (2-4 hours), the effects of targeting upstream pathways are expected to reduce MCL-1 levels rapidly.4 Inhibition of CDK9 has been shown to block MCL-1 transcription, resulting in the rapid downregulation of MCL-1 protein, thus restoring the normal apoptotic regulation.1
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.
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5 Ocana A, Pandiella A. Targeting oncogenic vulnerabilities in triple negative breast cancer: biological bases and ongoing clinical studies. Oncotarget. 2017;8(13):22218-22234