Reqorsa® Gene Therapy

Genprex’s lead drug candidate, Reqorsa® Gene Therapy (quaratusugene ozeplasmid) for non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), consists of the TUSC2 gene expressing plasmid encapsulated in non-viral nanoparticles made from lipid-based molecules in a lipoplex form (Genprex’s ONCOPREX 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. 

REQORSA has 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, or apoptosis, in cancer cells, and modulates the immune response against cancer cells.

Combination Therapies

REQORSA also has been shown to be complementary with targeted drugs and immunotherapies. 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.

Our strategy is to develop REQORSA in combination with currently approved therapies, and we believe that REQORSA’s unique attributes position it to provide treatments that improve on these current therapies for patients with NSCLC, SCLC, and possibly other cancers.

Overcoming Drug Resistance

Resistance to targeted drugs and checkpoint inhibitors often develops 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.

Why Tumor Suppressor Genes?

Mutations that lead to cancer are usually present in two major classes of genes: oncogenes, which are involved in functions such as signal transduction and transcription; and tumor suppressor genes, which play multiple roles in governing cell growth and proliferation.

The most common genetic alterations present in lung cancer are in tumor suppressor genes.  No targeted small molecule drugs have successfully been developed against tumor suppressor gene mutations in NSCLC or SCLC.

Why TUSC2?

The TUSC2 gene, which is the key component of REQORSA, plays a vital role in cancer suppression and normal cell regulation. Normal TUSC2 function is often inactivated early in cancer development, making TUSC2 a potential target for all stages of cancer, including metastatic disease. 

The TUSC2 protein is reduced or absent in approximately 82% of NSCLCs and in 100% of SCLCs. In patients with NSCLC, the loss of TUSC2 expression has been associated with significantly worse overall survival than when TUSC2 expression is not decreased.

Data from preclinical studies suggest that TUSC2, the active agent in REQORSA, could be effective against other types of cancer, including glioblastoma, head and neck, breast (including triple-negative breast cancer), renal cell (kidney), thyroid, and soft tissue sarcoma, as well as NSCLC and SCLC.

Read more about our REQORSA program in our latest Investor Presentation deck.

To learn more about scientific evidence and studies supporting REQORSA and the TUSC2 gene, please refer to our Clinical Trials and TUSC2 Bibliography pages.