Sumitomo Dainippon Pharma Oncology Presents Findings from Phase 2 Zella 201 Clinical Study Evaluating Investigational Agent Alvocidib in Patients with Acute Myeloid Leukemia at 62nd ASH Annual Meeting

CAMBRIDGE, Mass., Dec. 5, 2020 /PRNewswire/ -- Sumitomo Dainippon Pharma Oncology, Inc., a developer of novel cancer therapeutics, today presented new data from the Phase 2 Zella 201 study evaluating the investigational agent alvocidib, a potent CDK9 inhibitor, in patients with MCL-1 dependent acute myeloid leukemia (AML). These results were presented at the 62^nd American Society of Hematology Annual Meeting, being held virtually December 5-8, 2020.

Preliminary findings from the open-label, randomized, multicenter study indicated that alvocidib was well tolerated with a manageable safety profile in combination with cytarabine and mitoxantrone in an exploratory arm of patients with newly diagnosed, high-risk MCL-1 dependent AML. Alvocidib in combination showed preliminary signs of clinical activity in the study, with 62% (n=8 of 13) of evaluable patients achieving complete remission/complete remission with incomplete count recovery. Of the patients that responded, 75% (n=6 of 8) achieved complete remission after the first treatment cycle. Although all patients included in this cohort were determined to be MCL-1 dependent, there was no association of complete remission with increasing MCL-1 dependence. The most frequently observed treatment-emergent non-hematologic adverse events of Grade 3 or higher were diarrhea, tumor lysis syndrome, hypocalcemia, sepsis and hypotension.¹

Sumitomo Dainippon Pharma Oncology (SDP Oncology) will also be presenting details regarding the trial design of a Phase 1 study evaluating TP-3654, a PIM kinase inhibitor, in patients with intermediate-2 and high-risk primary or secondary myelofibrosis. In addition, SDP Oncology and its parent company, Sumitomo Dainippon Pharma Co. Ltd., will be presenting Phase 1 data evaluating alvocidib in combination with cytarabine and mitoxantrone in patients with relapsed/refractory AML or cytarabine and daunorubicin in patients with newly diagnosed AML. Finally, preclinical data evaluating how dubermatinib (TP-0903), an oral AXL kinase inhibitor, modulates CART19 will be presented.

"These findings presented at the ASH Annual Meeting represent the first data evaluating the clinical activity of alvocidib in patients with newly diagnosed, high-risk, MCL-1-dependent AML," said Patricia S. Andrews, CEO and Global Head of Oncology, SDP Oncology. "The completion of this study marks a milestone for SDP Oncology as we continue to learn more about the optimal patient population that may benefit from alvocidib. The breadth of updates we presented at ASH 2020 from across our pipeline demonstrate our commitment to advancing purposeful science by transforming new discoveries into meaningful therapeutic options for patients with cancer."

Below are the details for the SDP Oncology and Sumitomo Dainippon Pharma presentations:

For more information about SDP Oncology's pipeline and clinical trials, please visit the company's virtual booth at the ASH Annual Meeting here.

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 TP-3654

TP-3654 is an investigational second-generation selective PIM kinase inhibitor currently under evaluation in a Phase 1 study in patients with myelofibrosis (NCT04176198) and a Phase 1 study in patients with advanced solid tumors (NCT03715504).

About PIM Kinase

PIM kinases are major effectors of JAK/STAT proliferative signaling downstream of multiple growth factors and cytokines.⁷ PIM is overexpressed in cancers and it may enhance the ability of fibroblasts to differentiate into myofibroblasts.⁷

About Dubermatinib (TP-0903)

Dubermatinib is an investigational oral AXL receptor tyrosine kinase (RTK) inhibitor under evaluation in a Phase 1a/b study in patients with advanced solid tumors (NCT02729298) and an ongoing study in collaboration with the Leukemia & Lymphoma Society as part of the Beat AML Clinical Trial (NCT03013998). SDP Oncology is exploring parallel clinical development paths for dubermatinib 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.⁸ 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.⁹

About Sumitomo Dainippon Pharma Oncology

Sumitomo Dainippon Pharma Oncology, Inc., is a wholly owned subsidiary of Sumitomo Dainippon Pharma Co., Ltd. As a global oncology organization with teams in the U.S. and Japan, SDP Oncology is relentlessly committed to advancing purposeful science by transforming new discoveries into meaningful treatments for patients with cancer. The company's robust and diverse pipeline of preclinical and advanced-stage assets spans multiple areas, including oncogenic pathways, survival mechanisms and novel protein interactions, which aim to address unmet clinical needs in oncology.

For more information, visit www.sdponcology.com.

About Sumitomo Dainippon Pharma

Sumitomo Dainippon Pharma is among the top-10 listed pharmaceutical companies in Japan, operating globally in major pharmaceutical markets, including Japan, the U.S., China and the European Union. Sumitomo Dainippon Pharma aims to create innovative pharmaceutical products in the Psychiatry & Neurology area, the Oncology area and Regenerative medicine/Cell therapy field, which have been designated as the focus therapeutic areas. Sumitomo Dainippon Pharma is based on the merger in 2005 between Dainippon Pharmaceutical Co., Ltd., and Sumitomo Pharmaceuticals Co., Ltd. Today, Sumitomo Dainippon Pharma has more than 6,000 employees worldwide. Additional information about Sumitomo Dainippon Pharma is available through its corporate website at www.ds-pharma.com.

Disclaimer Regarding 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. 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, J, Lee, D, Fine, G, et al. Zella 201: A Biomarker-Guided Phase II Study of Alvocidib Followed by Cytarabine and Mitoxantrone in MCL-1 Dependent Acute Myeloid Leukemia (AML): Results of Newly Diagnosed High-Risk Exploratory Arm. 62nd American Society of Hematology (ASH) Annual Meeting. 5 December 2020. Abstract 1045.
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
7. Zemskova MY, Song JH, Cen B, et al. Regulation of prostate stromal fibroblasts by the PIM1 protein Kinase. Cell Signaling. 2017;27(1):135-146.
8. 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.
9. 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.

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