Qualigen Therapeutics announces four poster presentations on QN-302

Qualigen Therapeutics announces data from the Company’s four posters regarding its’ lead program, QN-302, was presented at the American Association for Cancer Research Annual Meeting 2023 held April 14-19 in Orlando, FL. Abstract #390 – "A comparison of the activity of the quadruplex-targeting experimental drugs QN-302 and CX-5461 in wild-type and gemcitabine-resistant pancreatic cancer cell lines" Ahmed Ahmed, Tariq Arshad, and Stephen Neidle – Results demonstrated that QN-302, retains potency in the two gemcitabine resistant cell lines. Up-regulated G4 genes in the resistant line are down-regulated by QN-302. The retention of QN-302 activity in chemo-resistant PDAC cell lines suggests that it may potentially offer significant advantage in the clinic over gemcitabine-based therapies. Gemcitabine either alone or in combination is still among the standard of care for current PDAC treatment. Resistance to gemcitabine is common and is a major contributor to the poor outcomes for most PDAC patients. Abstract #4981 – "The potent quadruplex-binding compound QN-302 down-regulates the S100P gene in vitro and in vivo models of pancreatic cancer: a potential therapeutic target and biomarker for PDAC" Nicole Williams, Jenny Worthington, Ahmed Ahmed, Tariq Arshad and Stephen Neidle – The poster highlighted that QN-302 showed lower expression of the S100P gene on xenograft models following dosing either twice or four times weekly with QN-302. S100P is elevated in human PDAC. Investigators posit that S100P may be a potential biomarker for QN-302 therapy as it contains a G4 in its promoter region and binds QN-302. Abstract #6240 – "The potent quadruplex-binding compound QN-302 shows anti-tumor activity as a monotherapy in an orthotopic in vivo model of pancreatic cancer" Nicole Williams, Danielle Santos, Jenny Worthington, Ahmed Ahmed, Tariq Arshad and Stephen Neidle – Study authors identify orthotopic study as the fourth in vivo pancreatic cancer model showing anticancer activity for QN-302, further confirming its potential for human cancer treatment. Abstract #3098 – "Structure-based design rules for potent quadruplex-binding compounds based on the naphthalene diimide core" Stephen Neidle – The study author concluded that the available data indicates that G4 affinity is necessary but insufficient for cellular activity. The ND core contributes little to G4 affinity. Charged side chains are important for strong G4 binding and cellular activity; greater than2 cationic side chains are required for both G4 binding and activity. Four highly cationic side chains reduce cellular activity but enhance G4 affinity – less basic morpholine groups enhance it. Molecular modeling suggests that enhancing the ND core with a planar hydrophobic group could increase G4 affinity and enhance cellular uptake. Four basic side chains, two of which are morpholino, are used to optimize the series without excess basicity. Docking QN-302 into the G4-duplex structure indicates that the phenyl substituent is well stacked on a G of the quartet, as predicted.