On February 13, 2025 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported that its research collaborators at a major cancer research center in Houston, Texas have published a new study in eLife titled, "NPRL2 gene therapy induces effective antitumor immunity in KRAS/STK11 mutant anti-PD1 resistant metastatic non-small cell lung cancer (NSCLC) in a humanized mouse model (Press release, Genprex, FEB 13, 2025, View Source [SID1234650250])."
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"We are thrilled by the continued advancements of our academic partners on the NPRL2 gene therapy, which supports the therapeutic potential of our non-viral Oncoprex Delivery System to deliver the NPRL2 tumor suppressor gene therapy," said Ryan Confer, President and Chief Executive Officer at Genprex. "These data indicate the single agent potential of NPRL2 in lung cancer. They also demonstrate that the Oncoprex Delivery System used in Reqorsa Gene Therapy with the TUSC2 tumor suppressor gene is a platform and can be used with other tumor suppressor genes, such as NPRL2. We are pleased that these positive data also support the therapeutic potential of NPRL2 gene therapy in NSCLC and positions Genprex for the expansion of our clinical development pipeline."
The studies used the Company’s non-viral ONCOPREX Delivery System in KRAS/STK11 double mutant anti-PD1 resistant metastatic NSCLC xenografts in humanized mouse models. The ONCOPREX Delivery System is a novel non-viral approach utilizing lipid nanoparticles to deliver tumor suppressor genes that have been deleted during the course of cancer development. The platform allows for the intravenous delivery of various tumor suppressor genes to achieve a therapeutic effect without the risk of toxicity often associated with viral delivery systems.
In the published study, humanized mice were treated with NPRL2 gene therapy, immunotherapy pembrolizumab (Keytruda), or the combination. A dramatic antitumor effect was mediated by NPRL2 treatment alone, whereas pembrolizumab alone was ineffective, and the combination added little to NPRL2 treatment alone.
A significant antitumor effect was also found in non-humanized NSG mice, although the antitumor effect was greater in humanized mice, suggesting that the effects of NPRL2 gene therapy are achieved through the immune system. This is consistent with a more detailed analysis showing that NPRL2 gene therapy induces antitumor activity against KRAS/STK11 mutant anti-PD1 resistant tumors through dendritic cell mediated antigen presentation and cytotoxic immune cell activation. KRAS/STK11 mutant tumors are particularly resistant to treatment, and demonstrating efficacy in this setting suggests that a wide variety of lung cancers could potentially be targeted. This potentially would include the approximately 30% of NSCLCs that have KRAS mutations.
About Reqorsa Gene Therapy
REQORSA (quaratusugene ozeplasmid) consists of a plasmid containing the TUSC2 gene encapsulated in non-viral lipid-based nanoparticles in a lipoplex form (the Company’s Oncoprex Delivery System), which has a positive charge. REQORSA is injected intravenously and specifically targets cancer cells. REQORSA is designed to deliver the functioning TUSC2 gene to negatively charged cancer cells while minimizing uptake by normal tissue. Laboratory studies conducted at MD Anderson show that the uptake of TUSC2 in tumor cells in vitro after REQORSA treatment was 10 to 33 times the uptake in normal cells.