First patients dosed in Phase 1a clinical trial of UCL-backed G-Quadruplex (G4) targeting treatment for solid tumors, including pancreatic cancer
A new treatment for G4-targeted solid tumors including pancreatic cancer has been administered to patients for the first time in a Phase 1a clinical trial. Over 50,000 people will die of pancreatic cancer in the USA in 2023 (American Cancer Society estimate) and over 9,000 people in the UK. This deadly cancer has a 5-year survival rate of just 7%. Patients at a clinical cancer center in Michigan, USA, have been dosed with the experimental drug QN-302, a potential first-in-class novel treatment for advanced or metastatic solid tumors.
This latest development follows the US Food and Drug Administration (FDA) giving clearance for QN-302 in July 2023 to proceed to this initial clinical trial stage.
The QN-302 treatment has reached this major milestone in its development cycle due to the combined efforts in one of the world’s top universities, University College London (UCL), together with drug discovery specialists Sygnature Discovery, and the clinical-stage therapeutics company Qualigen Therapeutics Inc as well as a network of consultants and contract research organizations.
QN-302 has been conceived to work by selectively stabilizing G-quadruplex complexes prevalent in the promoter region of cancer-related genes in many tumor types, impeding the function of these cancer genes, and may therefore potentially offer a tumor-selective clinical approach to treatment.
It was conceived, invented and developed by Professor Stephen Neidle and his team in the School of Pharmacy at University College London with the involvement of Sygnature Discovery scientists. Following on from their exclusive license agreement with UCL in January 2022, subsequent preclinical and clinical development was undertaken by Qualigen Therapeutics Inc. In January 2023, QN-302 received Orphan Drug Designation by the FDA for the potential treatment of pancreatic cancer.
The Phase 1a clinical trial involves a small group of patients who will be given carefully monitored doses of the drug. Reaching this stage is a crucial point in the drug’s development bringing it one step closer to becoming available for patients with advanced or metastatic solid tumors such as pancreatic cancer.
The QN-302 Phase 1 clinical trial is a multi-site, open-label, dose-escalation and dose expansion, safety, pharmacodynamic and pharmacokinetic study of intravenous QN-302 in patients with advanced or metastatic solid tumors. A total of up to 36 patients will be enrolled in the dose escalation (Phase 1a) portion of the study.
Dr. Matthew McConville, Associate Principal Scientist at Sygnature Discovery was project leader during the collaboration with UCL when QN-302 was first developed. He said:
“This was an integrated project where we were tasked with planning the lead optimization (LO), primarily including compound design and synthesis route optimization and scale-up, cellular assays and biophysical measurements.
“The chemical matter for this project provided significant challenges for synthesis and purification but optimization of these processes allowed parallel technologies to speed up the LO phase towards the discovery of QN-302.
“It is amazing to now see the treatment hit such a significant milestone in its development.”
The QN-302 Phase 1 clinical trial will be conducted at leading oncology clinics and medical centers in the United States. In addition to the first site at START Midwest in Grand Rapids, Michigan, Qualigen is expected to activate additional sites in Q4 this year. They anticipate providing an update on safety and preliminary efficacy of the Phase 1a study in the first half of 2024.
Professor Stephen Neidle said:
“This significant milestone in the development of QN-302 could not have been achieved without the outstanding partnership work with Sygnature Discovery and Qualigen Therapeutics, which highlighted the best aspects of industry and academia collaboration. Early indications are that QN-302 has the potential to make significant inroads in the treatment of pancreatic and other hard-to-treat human cancers.”
The initial work at UCL on this revolutionary approach to cancer therapy was made possible with backing especially from the UCL Technology Fund and the UK Pancreatic Cancer Research Fund. It built on an extensive body of previous work in this field by Professor Stephen Neidle and his colleagues.
“The initiation of the QN-302 Phase 1a clinical trial represents a significant milestone for Qualigen Therapeutics and demonstrates further progress toward our goal to offer patients new treatment options for devastating diseases, such as pancreatic cancer and other advanced solid tumors,” commented Tariq Arshad, M.D., M.B.A., Qualigen Therapeutics’ Chief Medical Officer.
“We are grateful for the support of our CRO, TD2, as well as study sites, investigators, and patients and families who are all working together to explore the potential of QN-302 as a novel treatment for G-quadruplex-targeted tumors. We look forward to continuing these close partnerships as we enroll additional patients in our Phase 1a study.”
The first clinical site for Phase 1 is located at START Midwest in Grand Rapids, Michigan. It is hoped that the treatment will be able to progress to a Phase 2 study in due course based on the success of the initial trial.
About Sygnature Discovery
Sygnature Discovery is a world-leading integrated drug discovery Contract Research Organisation based in the UK and Canada with headquarters in Nottingham (UK). Additional sites are located in Alderley Park, Macclesfield and Glasgow (UK), and Montreal and Quebec City (Canada). Its team of over 1,000 employees, which includes 900 scientists, partners with global pharma, biotech and NFP organisations. Since 2004, Sygnature Discovery has delivered over 40 novel pre-clinical and 22 clinical compounds, with its scientists named on over 170 patents. Therapeutic areas of expertise include oncology, inflammation and immunology, neuroscience, metabolic diseases, infectious diseases, fibrotic diseases and more.
About Qualigen Therapeutics, Inc.
Qualigen Therapeutics, Inc. is a clinical-stage therapeutics company focused on developing treatments for adult and pediatric cancer. Our investigational QN-302 compound is a small molecule selective transcription inhibitor with strong binding affinity to G4s prevalent in cancer cells; such binding could, by stabilizing the G4s against “unwinding,” help inhibit cancer cell proliferation. The investigational compounds within Qualigen’s family of Pan-RAS oncogene protein-protein interaction inhibitor small molecules are believed to inhibit or block the binding of mutated RAS genes’ proteins to their effector proteins, thereby leaving the proteins from the mutated RAS unable to cause further harm. In theory, such mechanism of action may be effective in the treatment of about one quarter of all cancers, including certain forms of pancreatic, colorectal, and lung cancers.