Onconic Therapeutics, the new drug development subsidiary of JEIL PHARMACEUTICAL, said on the 12th that research results confirming that the next-generation anticancer drug candidate "Nesuparib (JPI-547)" may overcome resistance to existing cancer drugs were published in the international journal British Journal of Cancer.
Nesuparib is a next-generation dual-inhibition anticancer drug candidate that simultaneously inhibits "PARP," which blocks cancer cells' DNA damage repair, and "Tankyrase," which is involved in cancer growth. It is drawing attention as a potential solution to resistance, a limitation cited for existing PARP inhibitors.
Earlier, Nesuparib received orphan drug designation (ODD) from the U.S. Food and Drug Administration (FDA) in 2021 as a treatment for pancreatic cancer, and in Mar. this year it additionally obtained orphan drug designation for gastric cancer and gastroesophageal junction cancer.
This study was conducted by a research team led by Professor Moon Yong-hwa of the Division of Medical Oncology at Bundang CHA Hospital. The team built resistance models to existing PARP inhibitors using BRCA1/2 gene-mutant breast and ovarian cancer cells and patient-derived tumor xenograft animal models (PDTX), and then analyzed the efficacy of Nesuparib.
The study found that Nesuparib showed stronger tumor-suppressing effects than "Olaparib," a first-generation PARP inhibitor. Notably, it markedly suppressed tumor growth with monotherapy even in resistance models where existing PARP inhibitors did not work. In some animal models, cases were observed where tumors disappeared completely.
The researchers cited the "RAD51" pathway, a protein involved in DNA repair, as the reason. In cancer cells that developed resistance to existing PARP inhibitors, RAD51 expression increased, tending to reactivate the cells' DNA repair function, but Nesuparib simultaneously inhibited Tankyrase and PARP to block this pathway, they said.
In addition, analysis of ovarian and breast cancer patient data showed that the group with high RAD51 expression had a higher risk of recurrence and tended to have lower survival rates. The team assessed that RAD51 could potentially be used as a biomarker to predict resistance to PARP inhibitors. However, the company said that because this study is at the preclinical stage, additional validation in actual patients is needed.
Onconic Therapeutics is also conducting clinical development for ovarian cancer. The company is conducting a phase 2 ovarian cancer trial based on combination therapy of Celltrion's anticancer drug "Vegzelma" and Nesuparib. The study evaluates the potential for a new re-maintenance therapy in patients who relapsed after PARP inhibitor maintenance therapy.
The phase 2 results have been selected for abstract presentation at the European Society for Medical Oncology (ESMO) and are scheduled to be presented next month in Copenhagen, Denmark.
A company official said, "Nesuparib is in phase 2 trials for intractable diseases including pancreatic cancer not only in BRCA-mutant cancers, which were the restriction criteria for existing PARP inhibitors, but also in patient groups without BRCA mutations," adding, "At the American Society of Clinical Oncology (ASCO 2026), we plan to disclose pancreatic cancer clinical data."