- Clinical Trials
Our lead drug candidate, REQORSA® Immunogene Therapy (quaratusugene ozeplasmid) for non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), is designed to interrupt cell signaling pathways that cause replication and proliferation of cancer cells, target and kill cancer cells, and stimulate the natural immune responses against cancer. REQORSA is an immunogene therapy in that it combines features of gene therapy and immunotherapy. It up-regulates TUSC2 expression in the cell, and also increases the anti-tumor immune cell population and down-regulates PD-L1, thereby potentially boosting the immune response to cancer.
In 2020, the FDA granted Fast Track Designation for REQORSA in combination with AstraZeneca’s Tagrisso® (osimertinib) in late-stage NSCLC patients with EFGR mutations whose tumors progressed after treatment with Tagrisso. In 2021, the FDA granted Fast Track Designation for REQORSA in combination with Merck & Co’s Keytruda® (pembrolizumab) in late-stage NSCLC patients whose disease progressed after treatment with Keytruda. In 2023, the FDA granted Fast Track Designation for REQORSA in combination with Genentech, Inc.’s Tecentriq® in patients with extensive-stage small cell lung cancer (ES-SCLC) who did not develop tumor progression after receiving Tecentriq and chemotherapy as initial standard treatment. The FDA also granted Orphan Drug Designation for REQORSA for the treatment of SCLC.
REQORSA consists of the TUSC2 gene expressing plasmid encapsulated in non-viral nanoparticles made from lipid molecules (our ONCOPREX® Nanoparticle Delivery System) with a positive electrical charge. REQORSA is injected intravenously and specifically targets cancer cells, which generally have a negative electrical charge. REQORSA is designed to deliver the functioning TUSC2 gene to cancer cells while minimizing their uptake by normal tissue.
Tumor biopsy studies conducted at MD Anderson show that, in three patients, the uptake of TUSC2 in tumor cells after REQORSA treatment was 10 to 33 times the uptake in normal cells. We believe that REQORSA is the first systemic gene therapy to be used for cancer in humans.
Unlike many other gene therapies, REQORSA is administered intravenously and it does not need to integrate into the patient’s DNA. Many other gene therapies require complex procedures that result in permanent changes in a patient’s DNA, including the removal of cells from a patient and the modification of those cells which are then reinfused into the patient.
Multimodal Mechanism of Action
Many approved cancer therapeutics target only single molecules or a single specific genetic abnormality related to driving the proliferation and survival of cancer cells. In contrast, REQORSA has been shown to have a multimodal mechanism of action whereby it interrupts cell signaling pathways that cause replication and proliferation of cancer cells, re-establishes pathways for programmed cell death (apoptosis) in cancer cells, and modulates the immune response against cancer cells. REQORSA also has been shown to be complementary with targeted drugs and immunotherapies.
Overcoming Drug Resistance
Resistance to targeted drugs and checkpoint inhibitors develop through activation of alternate bypass pathways. For example, when PD-1 is blocked, the TIM-3 checkpoint is up-regulated. We believe that REQORSA’s multimodal activity will block emerging bypass pathways, thereby potentially reducing the probability that drug resistance develops.
Our preclinical and clinical data indicate that REQORSA is well tolerated and may be effective alone or in combination with targeted small molecule therapies. Preclinical data indicate that REQORSA may also be effective with immunotherapies, and in a three-drug combination with immunotherapy and chemotherapy. These data suggest that REQORSA, when combined with other therapies, may be effective in a large population of lung cancer patients.
Tagrisso® is a registered trademark of AstraZeneca.