We began 16 years ago to create a drug that targeted an ideal Achilles' heel in Ewing sarcoma. This target was EWS-FLI1, which is only found in Ewing sarcoma tumor cells and has been called 'undruggable'. Now, TK216 demonstrates that not only is EWS-FLI1 druggable, but that the potential of TK216 inhibiting a broader range of tumors driven by similar oncogenes is a real unexpected benefit.

— Dr. Jeffrey Toretsky, Georgetown University —

ets-Family Transcription Factor Inhibitor

TK216 is a small molecule that inhibits the biological activity of ets-family transcription factor oncoproteins in a variety of tumor types, stopping cancer cell growth and tumor formation. Following the successful filing of an Investigational New Drug (IND) application in the U.S., we are opening a phase 1 study of TK216 to begin in the second quarter of 2016 in patients with relapsed Ewing sarcoma (ES), a rare bone cancer that strikes children and young adults with a typical onset between 10 and 25 years of age.

Targeting Known Oncogenes

The ets-transcription factor family includes four members implicated as oncogenes, or genes that have been identified as initiators of cancer. While they are active in embryogenesis, the ets-family transcription factor proteins are not commonly expressed after birth, presenting an ideal target for researchers hoping to exclusively affect cancer cell growth. In Ewing sarcoma (ES), the cancer is caused by a single and well-characterized genetic mutation that leads to a chimeric ets protein, which enables patients to be easily identified with DNA-based testing. The ets-family transcription factor proteins are also expressed in various other cancers, including acute myeloid leukemia, glioblastoma and prostate cancer.

Ewing Sarcoma Has High Unmet Medical Need

We are initially advancing TK216 in development for ES because of the tremendous need for new, targeted therapies for this devastating disease and the hope that it can be made available for patients with an expedited approval pathway. In the last 30 years, no new therapies have been approved specifically for ES. Despite advances in chemotherapy and local control measures, many patients have very poor outcomes. We are planning subsequent studies to investigate TK216 in patients with other cancers whose tumors carry mutant or overexpressed levels of ets-family oncogenes.

Collaboration with Georgetown University

TK216 was developed based on the discoveries of Jeff A Toretsky, MD, at Georgetown University, who identified a small molecule that was shown to kill Ewing sarcoma cells and inhibit growth of tumors in preclinical studies. Oncternal scientists developed and tested a large series of derivatives of the research molecule, and, after extensive evaluation, TK216 was selected as our lead product candidate. TK216 has been extensively evaluated in preclinical studies, where it has been shown to kill ES cells. We continue to collaborate with Dr. Toretsky and his colleagues in order to advance the research underlying the molecular pathways of TK216 and optimize its development across multiple tumor types.

We are recruiting patients

  • With CLL for a Phase 1 study of Cirmtuzumab, our anti-ROR1 monoclonal antibody
  • With Ewing sarcoma for a Phase 1 study of TK216, our small molecule inhibitor of ets-family transcription factor oncoproteins
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