The potent quadruplex-binding compound QN302 shows anti-tumor activity as a monotherapy in an orthotopic in vivo model of pancreatic cancer

Abstract The compound QN-302, a tetra-substituted naphthalene diimide derivative has single-digit nM anti-proliferative activity in a panel of human pancreatic cancer (PDAC) cell lines (Ahmed et al., ACS Med Chem Lett, 2020, 11, 1634-1644). It has significant anti-tumor activity in the MIA-PACA2 xenograft model for PDAC and in the genetic KPC model. We now report that this compound also shows significant mono-therapy anti-tumor activity in an orthotopic model for PDAC. Female athymic nude mice bearing orthotopically implanted pancreatic BxPC-3 cells were dosed with 1 x weekly IV QN-302 at 0.5 and 1.0 mg/kg, over a period of 21 days. A separate group of mice was treated with Gemcitabine twice weekly IV during this period, at a dosage of 15 mg/kg. Blood samples from animals were collected on a weekly basis and were used to detect and quantify circulating tumor DNA as a method of following treatment efficacy. In line with previous studies QN-302 was well-tolerated at 0.5 and 1.0 mg/kg with no adverse effects on animal health or behavior noted during the study. Circulating tumor DNA levels were significantly less than vehicle controls in gemcitabine-treated animals from day 7 and QN-302 (1.0 mg/kg) treated animals from day 14 of treatment. Survival was significantly increased in gemcitabine and QN-302 (1.0 mg/kg) QW treatment groups. Statistically significant efficacy was observed in gemcitabine and QN-302 (1.0 mg/kg) treated animals. Examination of blood chemistry and biochemistry of treated animals did not indicate any adverse effects due to QN-302. This orthotopic model is the 4th in vivo study in a pancreatic cancer model showing anti-tumor activity for QN-302, further confirming the potential of this compound for human disease. QN-302 is currently in an advanced stage of pre-IND development by Qualigen Inc. Citation Format: Nicole Williams, Danielle Santos, Jenny Worthington, Ahmed Ahmed, Tariq Arshad, Stephen Neidle. The potent quadruplex-binding compound QN-302 shows anti-tumor activity as a monotherapy in an orthotopic in vivo model of pancreatic cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6240.