Tolero Pharmaceuticals Presents Findings from Phase 1 Zella 101 Clinical Study Evaluating Investigational Agent Alvocidib in Patients with Newly Diagnosed Acute Myeloid Leukemia at Virtual EHA Annual Congress 2020

SALT LAKE CITY, Utah, June 12, 2020 /PRNewswire/ -- Tolero Pharmaceuticals, Inc., a clinical-stage company focused on developing novel therapeutics for hematological and oncological diseases, today presented data from the completed Phase 1 Zella 101 study evaluating the investigational agent alvocidib, a potent CDK9 inhibitor, in adult patients with newly diagnosed acute myeloid leukemia (AML). These results were presented in a poster presentation at the 25th European Hematology Association (EHA) Virtual Congress, being held June 11-14, 2020.

Updated findings from the Phase 1, dose-escalation, safety and biomarker study of alvocidib followed by cytarabine and daunorubicin (7+3) induction therapy showed encouraging clinical activity and a tolerable safety profile in adults with newly diagnosed AML. In the study, 71% (n=22 of 31) of evaluable patients achieved complete remission (CR), with an overall response rate (ORR) of 77% (n=24 of 31). Additionally, an exploratory cohort of the study found that 89% (n=8 of 9) of patients achieved measurable residual disease (MRD)-negativity. At a median of 9.2 months follow-up, overall survival was not reached, with 62% of patients alive at data cut-off.¹

The maximum tolerated dose of alvocidib was determined to be 30 mg/m² IV bolus followed by 60 mg/m² IV over 4 hours and no dose-limiting toxicities (DLTs) were observed. The most frequently observed treatment-emergent, nonhematologic adverse events of Grade 3 or higher were diarrhea, tumor lysis syndrome and hypocalcemia, which all resolved with supportive care.¹

"AML is an aggressive blood cancer which can progress rapidly and remains difficult to treat. We are pleased with the clinical responses, including overall survival, observed in newly diagnosed AML patients treated with alvocidib followed by standard induction therapy. In addition, the high level of MRD-negativity, a meaningful indicator of durable response, is particularly encouraging," said David J. Bearss, Ph.D., Chief Executive Officer, Tolero Pharmaceuticals, and Chief Scientific Officer and Global Head of Research, Global Oncology. "We are excited to continue the advancement of this program and further investigate the potential role of alvocidib in contributing to a durable complete remission and achievement of MRD-negativity."

Below are the details for the presentation:

About Alvocidib

Alvocidib is an investigational small molecule inhibitor of cyclin-dependent kinase 9 (CDK9) currently being evaluated in the ongoing Phase 2 Zella 202 study in patients with acute myeloid leukemia (AML) who have either relapsed from or are refractory to venetoclax in combination with azacitidine or decitabine (NCT03969420). Alvocidib is also being evaluated in Zella 102, a Phase 1b/2 study in patients with myelodysplastic syndromes (MDS) in combination with azacitidine or decitabine (NCT03593915) and in a Phase 1 study in patients with relapsed or refractory AML in combination with venetoclax (NCT03441555).

About CDK9 Inhibition and MCL-1

MCL-1 is a member of the apoptosis-regulating BCL-2 family of proteins.² In normal function, it is essential for early embryonic development and for the survival of multiple cell lineages, including lymphocytes and hematopoietic stem cells.³ MCL-1 inhibits apoptosis and sustains the survival of leukemic blasts, which may lead to relapse or resistance to treatment.^2,4 The expression of MCL-1 in leukemic blasts is regulated by cyclin-dependent kinase 9 (CDK9).^5,6 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.⁵ 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.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. Tolero has a diverse pipeline that 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. Tolero works closely with its parent company, Sumitomo Dainippon Pharma, and Boston Biomedical, Inc., also a wholly owned subsidiary, to advance a pipeline of innovative oncology treatments. The organizations apply their expertise and collaborate to achieve a common objective - expediting the discovery, development and commercialization of novel treatment options.

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 Zeidner, Joshua et al. "Alvocidib Followed by 7+3 Induction in Newly Diagnosed AML Achieves High Rates of MRD-Negative CR: Results of a Phase 1 Dose Escalation Study." 25th European Hematology Association (EHA) Virtual Annual Congress. 12 June 2020. Poster presentation 551

² Thomas D, Powell JA, Vergez F, et al. Targeting acute myeloid leukemia by dual inhibition of PI3K signaling and Cdk9-mediated Mcl-1 transcription. Blood. 2013;122(5):738-748.

³ Perciavalle RM, Opferman JT. Delving deeper: MCL-1's contributions to normal and cancer biology. Trends Cell Biol. 2013;23(1):22-29.

⁴ Glaser SP, Lee EF, Trounson E, et al. Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia. Genes Dev. 2012;26(2):120-125.

⁵ Chen R, Keating MJ, Gandhi V, Plunkett W. Transcription inhibition by flavopiridol: mechanism of chronic lymphocytic leukemia cell death. Blood. 2005;106(7):2513-2519.

⁶ Ocana A, Pandiella A. Targeting oncogenic vulnerabilities in triple negative breast cancer: biological bases and ongoing clinical studies. Oncotarget. 2017;8(13):22218-22234

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SOURCE Tolero Pharmaceuticals, Inc.