Quarfloxin Enters Phase II Clinical Trial

Armen Hareyan's picture

Cylene Pharmaceuticals has initiated a single-agent Phase II clinical trial of its lead Ribosomal RNA Biogenesis Inhibitor, quarfloxin (CX-3543), in patients with chronic lymphocytic leukemia.

Quarfloxin (CX-3543) is a small molecule that selectively targets a DNA protein complex that is amplified in cancer cells, leading to inhibition of ribosomal RNA biogenesis and induction of apoptotic cell death. In vitro tests have shown CLL cells taken from patients to be very sensitive to the apoptotic effects of Quarfloxin. In this open-label trial, CX-3543 will be administered to patients with CLL whose leukemia has progressed on prior treatment with a purine analog and a monoclonal antibody. This study is expected to enroll up to 25 patients at several leading cancer centers, including the Tower Oncology Group in Los Angeles, California, South Texas Accelerated Research Therapeutics (START) in San Antonio, Texas, and the Mayo Clinic Arizona in Scottsdale, Arizona.


"We are very pleased with the progress of our proprietary Ribosomal RNA Biogenesis Inhibition program. The initiation of the Company's first Phase II trial with our lead molecule is an important milestone for Cylene," said Dr. William Rice, President and Chief Executive Officer of Cylene Pharmaceuticals.

"Because quarfloxin has demonstrated potent in vivo efficacy against a broad range of tumors and a considerable therapeutic window in animal xenograft models, we also plan on initiating additional Phase II studies in other cancer indications," added Dr. Daniel Von Hoff, Cylene's Co-Founder and Vice President, Medical Affairs. "Moreover, quarfloxin appears to have promise in combination with other compounds, and it has been well-tolerated in patients with no substantial toxicities."

Quarfloxin is a ground-breaking small-molecule targeted cancer therapeutic derived from the validated fluoroquinolone class of drugs. Rationally designed to selectively inhibit ribosomal RNA (rRNA) Biogenesis in cancer cells, quarfloxin disrupts the interaction between the Nucleolin protein and a G-quadruplex DNA structure in the ribosomal DNA (rDNA) template, a critical interaction for rRNA Biogenesis and one that is amplified in cancer cells. As a result, quarfloxin, selectively induces apoptotic cell death in cancers. Many commercialized cancer therapeutics act indirectly on rRNA Biogenesis through upstream modulators, but quarfloxin is the first agent to directly target this cancer-specific aberrant cell function.