On February 15, 2023 Aprea Therapeutics, Inc. (Nasdaq: APRE), a biopharmaceutical company focused on developing novel synthetic lethality-based cancer therapeutics targeting DNA damage response (DDR) pathways, reported that it received an award notification from the National Cancer Institute (NCI) for the development of a first-in-class combination of DNA damage response inhibitors for the treatment of high-grade serous ovarian cancer (HGSOC) (Press release, Aprea, FEB 15, 2023, View Source [SID1234627250]). Total funding under the award is up to $1,996,571 over a period of two years, subject to the availability of funds and satisfactory progress of the project over such period.

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HGSOC is a devastating disease responsible for the deaths of about 125,000 women worldwide each year and has low survival rates. Approximately 50% of HGSOCs harbor genetic mutations in BRCA1, BRCA2, or other genes that cause defects in homologous recombination (HR). Another large fraction of HGSOCs exhibit amplification of the cell proliferation regulator Cyclin E1 (CCNE1). To develop a potential therapy for this disease, Aprea Therapeutics is initiating a first-in-human clinical trial of a new highly selective ataxia–telangiectasia and Rad3 related (ATR) inhibitor, ATRN-119. In addition, Aprea Therapeutics has also developed a highly potent and selective WEE1 inhibitor, ATRN-W1051, with a differentiated structure and potentially preferable pharmacokinetic properties. In pre-clinical studies, ATRN-W1051 has demonstrated anti-proliferative activity against a variety of cancer cell lines and shown the potential to inhibit the growth of genetically-defined HGSOC tumors in xenograft models. Notably, the combination of these two agents is a potential treatment for women with CCNE1-amplified HGSOC.

"We are honored and grateful to receive this competitive award to support our scientific approach and compelling opportunities within our pipeline. This award validates our efforts to bring new and effective therapies to cancer patients carrying genetically defined cancers with high unmet medical needs," said Oren Gilad, Ph.D., President, and Chief Executive Officer of Aprea Therapeutics. "A growing body of scientific evidence provides exciting development opportunities for our ATR and WEE1 inhibitors, and the studies proposed in this grant have the potential to provide additional support in validating our findings and progressing these studies towards a clinical trial."

A portion of the work will be carried out at the laboratories of University of Pennsylvania Perelman School of Medicine researchers Drs. Fiona Simpkins, Professor of Obstetrics and Gynecology, and Eric Brown, Associate Professor of Cancer Biology.

This grant will support an evaluation of the in vivo and in vitro activity and tolerability of ATRN-119 and ATRN-W1051 using a library of cell lines and patient-derived xenograft models of HGSOC that express varying levels of CCNE1. These studies could potentially identify mechanistically relevant biomarkers of sensitivity to ATRN-W1051 and may inform future clinical trial protocols using ATRN-119 combination and ATRN-W1051 for the treatment of HGSOC.

Disclosure:
Dr. Simpkins is a member of the Aprea Therapeutics Scientific Advisory Board and affiliated with the University of Pennsylvania. Dr. Brown is a Scientific Consultant for Aprea Therapeutics and owns equity interest in the company in addition to serving on the Scientific Advisory Board.

Research content supported by the National Cancer Institute of the National Institutes of Health under Award Number R44CA278078 is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.