On April 9, 2024 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 presented positive preclinical data for Reqorsa Immunogene Therapy (quaratusugene ozeplasmid) and NPRL2 gene therapy, which both utilize the Company’s non-viral Oncoprex Delivery System for the treatment of lung cancer (Press release, Genprex, APR 9, 2024, View Source [SID1234641934]). These studies were presented at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, which is being held April 5-10, 2024 in San Diego, California.
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"We continue to expand our growing body of preclinical evidence supporting REQORSA’s therapeutic potential to treat a variety of cancers, as well as the therapeutic potential of our non-viral delivery system to deliver tumor suppressor genes for the treatment of cancer," said Rodney Varner, Chairman, President and Chief Executive Officer at Genprex. "We are especially delighted to have three preclinical studies presented at one of the largest professional cancer research meetings among the world’s top oncologists and the cancer research community."
Featured Genprex-supported posters presented at AACR (Free AACR Whitepaper) 2024 include:
Title: "Quaratusugene ozeplasmid mediated TUSC2 upregulation in EML4-ALK bearing Non-Small Cell Lung Carcinoma can induce cellular apoptosis"
Session Category: Molecular/Cellular Biology and Genetics
Session Title: Apoptosis and Ferroptosis
Session Date and Time: Sunday, April 7 from 1:30 p.m. – 5:00 p.m. PT
Location: Poster Section 15
Poster Board Number: 7
Abstract Presentation Number: 351
Title: "Mechanism of NPRL2 gene therapy induced anti-tumor immunity in KRAS/STK11mt aPD1 resistant metastatic NSCLC"
Session Category: Immunology
Session Title: Inflammation, Host Factors, and Epigenetic Influences on Cancer Development and Treatment
Session Date and Time: Monday, April 8 from 9:00 a.m. – 12:30 p.m. PT
Location: Poster Section 5
Poster Board Number: 18
Abstract Presentation Number: 1420
Title: "Tumor Suppressor Gene TUSC2 suppresses energy metabolism in lung cancer cells with opposite effects in normal bronchial epithelial cells"
Session Category: Experimental and Molecular Therapeutics
Session Title: Cancer Biology and Metastasis
Session Date and Time: Monday, April 8 from 1:30 p.m. – 5:00 p.m. PT
Location: Poster Section 22
Poster Board Number: 6
Abstract Presentation Number: 3158
In the first poster, entitled "Quaratusugene ozeplasmid mediated TUSC2 upregulation in EML4-ALK bearing Non-Small Cell Lung Carcinoma can induce cellular apoptosis," researchers reported that REQORSA induced apoptosis in alectinib resistant EML4-ALK positive non-small cell lung cancer (NSCLC) cell lines. Alectinib is an ALK-inhibitor commonly used to treat patients with ALK rearrangements such as EML4-ALK positive NSCLCs. This research suggests that REQORSA may be an effective treatment in patients progressing on alectinib.
The second poster, entitled, "Mechanism of NPRL2 gene therapy induced anti-tumor immunity in KRAS/STK11mt aPD1 resistant metastatic NSCLC" detailed a humanized mouse model study in which the researchers investigated the anti-tumor immune responses to NPRL2 gene therapy in pembrolizumab resistant KRAS/STK11mt NSCLC. In the study, lung metastases in humanized mice were treated through I.V. injection of NPRL2 nanoparticles, made with the ONCOPREX Delivery System, with or without pembrolizumab. The study found that the NPRL2 treatment by itself led to a marked decrease in the size of lung metastases but pembrolizumab had no effect. Additionally, a greater anti-tumor effect was seen in humanized compared to non-humanized mice, demonstrating that immune cells play a role in the effects of the NPRL2 nanoparticle therapy. Study findings suggest that NPRL2 gene therapy induces anti-tumor activity against KRAS/STK11mt tumors through dendritic cell-mediated antigen presentation and cytotoxic immune cell activation. The Company believes this data could support the potential for a new drug candidate in its pipeline, and it also provides further evidence for the Company’s belief that the ONCOPREX Delivery System has the ability to be successful using genes other than the TUSC2 gene the Company is already using in clinical trials with REQORSA.
In the third poster, entitled, "Tumor Suppressor Gene TUSC2 suppresses energy metabolism in lung cancer cells with opposite effects in normal bronchial epithelial cells" researchers reported that TUSC2-deficient cancer cells consistently exhibited decreased glycolytic rates and mitochondrial ATP production, leaving these cells without enough energy to support their vital functions. By comparison, when Beas2B, a normal human bronchial epithelial cell line with normal levels of TUSC2, was transfected with a TUSC2 containing plasmid, the glycolytic rate and mitochondrial metabolism was increased. This suggests the mechanism by which REQORSA treatment affects immune and other non-cancerous cells that leads to increased immune response against tumors. The study further suggested that REQORSA may play an important role as a cancer treatment to target and disrupt the metabolism of cancer cells, leading to a decrease in the rate of glycolysis.
These AACR (Free AACR Whitepaper) posters have been made available on Genprex’s website at www.genprex.com.
Quaratusugene ozeplasmid mediated TUSC2 upregulation in EML4-ALK bearing Non-Small Cell Lung Carcinoma can induce cellular apoptosis Mechanism of NPRL2 gene therapy induced anti-tumor immunity in KRAS/STK11mt aPD1 resistant metastatic NSCLC Tumor Suppressor Gene TUSC2 suppresses energy metabolism in lung cancer cells with opposite effects in normal bronchial epithelial cells
About Reqorsa Therapy
REQORSA (quaratusugene ozeplasmid) for NSCLC and small cell lung cancer (SCLC) consists of the TUSC2 gene expressing plasmid encapsulated in non-viral nanoparticles made from lipid molecules (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.
Genprex’s strategy is to develop REQORSA in combination with currently approved therapies and believes 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.
About The Oncoprex Delivery System
Genprex’s ONCOPREX Delivery System is a novel non-viral approach that utilizes lipid-based nanoparticles in a lipoplex form to deliver tumor suppressor genes deleted during the course of cancer development. The platform allows for the intravenous delivery of various tumor suppressor genes, and potentially other genes, to achieve a therapeutic affect without the risk of toxicity often associated with viral delivery systems. Genprex believes this system allows for delivery of a number of cancer-fighting genes, alone or in combination with other cancer therapies, to combat multiple types of cancer.