FDA Grants Orphan Drug Designation to Investigational G4 Transcription Inhibitor for Pancreatic Cancer

The FDA grants orphan drug designation to investigational G-quadruplex transcription inhibitor QN-302 for pancreatic cancer.

The FDA has granted orphan drug designation to QN-302 for the management of pancreatic cancer, according to a press release from Qualigen Therapeutics.1

Following the agent's orphan drug designation, QN-302’s manufacturers intend to submit an investigational new drug application to the FDA to proceed to a clinical phase 1 clinical trial in 2023.

QN-302 is an investigational small molecule selective transcription inhibitor that binds to G-quadruplexes (G4s) prevalent in cancer cells, potentially inhibiting cancer cell growth by stabilizing the G4s.

Previously, investigators shared preclinical data on QN-302 in 2 poster sessions during the American Academy of Cancer Research (AACR) 8th Special Conference on Pancreatic Cancer, which included findings related to the agent’s safety, tolerability, and efficacy.2

Data from the first poster presentation indicated that treatment with QN-302 did not result in toxicological adverse effects (AEs) in pancreatic ductal adenocarcinoma (PDAC) cells in mouse models at therapeutic doses.

Based on in vitro tests, QN-302 inhibited acetylcholinesterase (AChE) levels by 53% and muscarinic receptor (M2) levels by 70% at 1 µM. Additionally, when mice received 1 mg/kg of QN-302, investigators reported no changes in in AChE or M2 levels. Due to the lack of change, investigators determined that it was unlikely for there to be an issue binding to either receptor.

A histological assessment of QN-302 performed in mice indicated that the agent dealt no damage to heart tissue or kidney tissue, and investigators observed no abnormal behavioral effects. Animals that received treatment with QN-302 demonstrated normal morphology of the myocardium and normal distribution of cardiomyocytes. Additionally, investigators reported no significant AEs related to heart rate, even at dose levels in excess of the therapeutic dose.

In the second poster session at AACR, an RNA-sequencing analysis of QN-302 in MIA-PACA2 cells, investigators reported a pattern of susceptible genes in cancer-related pathways. The analysis indicated that S100P was the among the most highly down-regulated genes and had a 45-fold overexpression in tumor material from human patients.

Data from the analysis align with a published set of 229 genes associated with human PDAC, including the SPARC, CX3CL1, and S100P genes. The G4 promoter observed in the S100P gene strongly suggests that the G4 structure could serve as a binding site for QN-302.


  1. Qualigen Therapeutics receives orphan drug designation from the U.S. Food and Drug Administration for QN-302, a G-quadruplex (G4) transcription inhibitor for the intended indication of pancreatic cancer. News release. Qualigen Therapeutics. January 10, 2023. Accessed January 16, 2023. bit.ly/3WeSPUI
  2. QLGN: encouraging preclinical data presented for QN-302 and RAS inhibitor. News release. Qualigen Therapeutics. December 1, 2022. Accessed January 16, 2023. yhoo.it/3kgUL1M