Sumitomo Pharma Oncology Receives Orphan Drug Designation for TP-1287, an Investigational Oral CDK9 Inhibitor for the Treatment of Ewing Sarcoma

CAMBRIDGE, Mass., April 10, 2023 /PRNewswire/ -- Sumitomo Pharma Oncology, Inc., a clinical-stage company focused on novel cancer therapeutics, today announced the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation for TP-1287, an investigational oral CDK9 inhibitor, for the treatment of Ewing sarcoma.

"We are delighted to have received this designation for TP-1287 which underscores the need for additional treatment options for patients with Ewing sarcoma," said Patricia S. Andrews, Chief Executive Officer and Global Head of Oncology, Sumitomo Pharma Oncology, Inc. "We recognize the unmet need for novel treatments in this disease state and are excited to contribute to the advancement of this research with the goal of helping to improve patient outcomes."

The FDA's Orphan Drug Designation is granted to investigational therapies addressing rare medical diseases or conditions that affect fewer than 200,000 people in the United States.¹ Ewing sarcoma is a rare type of cancer that occurs in bones or in the soft tissue around the bones. The disease occurs when a cell develops changes in its DNA that cause the cell to multiply quickly, resulting in a tumor of abnormal cells that is capable of invading and destroying healthy body tissue. The abnormal cells can break away and metastasize throughout the body. Ewing sarcoma can occur at any age, but it is more likely to occur in children and teenagers.²

"TP-1287 exhibits potent inhibition of intracellular kinases including CDK9. Inhibition of CDK9 leads to downregulation of key antiapoptotic proteins such as MCL-1, which in turn has been shown to inhibit tumor growth in preclinical models of hematologic malignancies and several tumor types,"^3-6 detailed Jatin J. Shah, M.D., Chief Medical Officer of Sumitomo Pharma Oncology, Inc.

TP-1287 was also granted Rare Pediatric Disease Designation from the FDA for the treatment of Ewing sarcoma. A rare pediatric disease is one that is serious or life-threatening in which the serious or life-threatening manifestations primarily affect patients from birth to 18 years old.⁷

TP-1287 is currently being evaluated in a Phase 1, first-in-human study of oral TP-1287 in patients with advanced metastatic or progressive solid tumors who are refractory to, or intolerant of, established therapy known to provide clinical benefit for their condition, which is being conducted in the United States. To learn more about the study and eligibility for enrollment, visit clinicaltrials.gov (NCT03604783).

This is the fourth Orphan Drug Designation Sumitomo Pharma Oncology, Inc. has received in the last year. DSP-5336, the company's proprietary investigational small molecule inhibitor against the binding of menin and mixed-lineage leukemia (MLL) protein, was granted Orphan Drug Designation for the treatment of acute myeloid leukemia (NCT04988555). TP-3654, the company's proprietary investigational oral inhibitor of PIM kinases, was granted Orphan Drug Designation for the treatment of myelofibrosis (NCT04176198). DSP-0390, an investigational emopamil-binding protein (EBP) inhibitor, was also granted Orphan Drug Designation for the treatment of brain cancer (NCT05023551). These designations showcase the strength and diversity of SMP Oncology's pipeline and commitment to oncology research and development.

About TP-1287
TP-1287 is an investigational oral phosphate prodrug of the CDK9 inhibitor alvocidib.⁸ TP-1287 is hydrolyzed enzymatically to yield alvocidib.^8,9 Alvocidib binds at the ATP-binding site of CDK9, stopping phosphorylation by CDK9.³ This binding prevents productive transcription and causes reduction of messenger RNA (mRNA) in genes such as c-MYC and MCL-1.³ Downregulation of c-MYC and MCL-1 transcription leads to apoptosis in a variety of tumor cells.³ TP-1287 is currently being evaluated in a Phase 1, open-label, dose-escalation, dose-expansion, safety, pharmacokinetics and pharmacodynamic study, with a purpose of determining the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of oral TP-1287 in patients with advanced metastatic or progressive solid tumors who are refractory to, or intolerant of, established therapy known to provide clinical benefit for their condition (NCT03604783).

About Sumitomo Pharma Oncology, Inc.
Sumitomo Pharma Oncology, Inc. is a wholly owned subsidiary of Sumitomo Pharma Co., Ltd. As a global oncology organization with teams in the U.S. and Japan, SMP Oncology is committed to the goal of advancing purposeful science by transforming new discoveries into meaningful treatments for patients with cancer. SMP Oncology's robust and diverse pipeline of preclinical and clinical-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.oncology.sumitomo-pharma.com.

About Sumitomo Pharma Co., Ltd.
Sumitomo Pharma Co., Ltd. is among the top-ten listed pharmaceutical companies in Japan, operating globally in major pharmaceutical markets, including Japan, the U.S., China, and other Asian countries with about 7,000 employees worldwide. Sumitomo Pharma Co., Ltd. defines its corporate mission as "To broadly contribute to society through value creation based on innovative research and development activities for the betterment of healthcare and fuller lives of people worldwide." Additional information about Sumitomo Pharma Co., Ltd. is available through its corporate website at https://www.sumitomo-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. Office of the Commissioner. Rare Diseases at FDA. U.S. Food and Drug Administration. https://www.fda.gov/patients/rare-diseases-fda
2. Mayo Foundation for Medical Education and Research. Ewing sarcoma. Mayo Clinic. Accessed March 3, 2023. https://www.mayoclinic.org/diseases-conditions/ewing-sarcoma/symptoms-causes/syc-20351071
3. Boffo S, Damato A, Alfano L, Giordano A. CDK9 inhibitors in acute myeloid leukemia. J Exp Clin Cancer Res. 2018;37(1):36. doi:10.1186/s13046–018–0704–8 
4. Yin T, Lallena MJ, Kreklau EL, et al. A novel CDK9 inhibitor shows potent antitumor efficacy in preclinical hematologic tumor models. Mol Cancer Ther. 2014;13(6):1442-1456. doi:10.1158/1535-7163.MCT-13-0849 
5. Huang H, Weng H, Zhou H, Qu L. Attacking c-Myc: targeted and combined therapies for cancer. Curr Pharm Des. 2014;20:6543-6554. doi:10.2174/1381612820666140826153203 
6. George B, Richards DA, Edenfield WJ, et al. [Abstract 3611] A phase I, first-in-human, open-label, dose-escalation, safety, pharmacokinetic, and pharmacodynamic study of oral TP-1287 administered daily to patients with advanced solid tumors. Journal of Clinical Oncology. 2020; 38(suppl 15): 3611. doi: 10.1200/JCO.2020.38.15_suppl.3611
7. Office of the Commissioner. Rare Pediatric Disease (RPD) Designation and Voucher Programs. U.S. Food and Drug Administration. https://www.fda.gov/industry/medical-products-rare-diseases-and-conditions/rare-pediatric-disease-rpd-designation-and-voucher-programs
8. Kim W, Haws H, Peterson P, et al. [Abstract 5133] TP-1287, an oral prodrug of the cyclin-dependent kinase-9 inhibitor alvocidib. Cancer Res. 2017;77(suppl 13):5133. doi:10.1158/1538-7445.AM2017-5133 
9. Alvocidib prodrug TP-1287. In: NCI Dictionaries: Drug Dictionary. National Cancer Institute. Accessed November 30, 2022. https://www.cancer.gov/publications/dictionaries/cancer-drug/def/alvocidib-prodrug-tp-1287 

SOURCE Sumitomo Pharma Oncology, Inc.