On March 6, 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 will present at the upcoming 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held April 5-10, 2024 in San Diego, California (Press release, Genprex, MAR 6, 2024, View Source [SID1234640854]). The collaborators will present positive preclinical data from studies of its lead product candidate, Reqorsa Immunogene Therapy (quaratusugene ozeplasmid), as well as NPRL2 gene therapy, which both utilize the Company’s non-viral Oncoprex Delivery System for the treatment of lung cancer.
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"We are delighted to have our academic partners present this compelling body of preclinical evidence that support the therapeutic use of REQORSA to deliver the functioning TUSC2 gene to cancer cells. The data also highlights the potential use of our non-viral ONCOPREX Delivery System to deliver other tumor suppressor genes, such as the NPRL2 gene," said Rodney Varner, Chairman, President and Chief Executive Officer at Genprex. "We are pleased to have favorable results from three preclinical studies presented to an audience of global oncology specialists, providing further validation of the value of REQORSA and ONCOPREX in the fight against cancer."
Featured Genprex-supported posters to be 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 pm – 5:00 p.m. PT
Location: Poster Section 15
Poster Board Number: 7
Abstract Presentation Number: 351
Anaplastic Lymphoma Kinase (ALK) is a strong oncogenic driver in non-small cell lung carcinoma (NSCLC) and contributes to ~5% of NSCLC as a distinct clinicopathological subset.
In this nonclinical study TUSC2 expression in three ALK+ cell lines were evaluated before and after exposure to REQORSA, referred to as TUSC2 gene therapy in the abstract, and to a TUSC2-containing plasmid. Researchers at the University of Michigan Rogel Cancer Center Judith Tam ALK NSCLC research initiative found that overexpressing TUSC2 via REQORSA treatment in ALK+ lung cancer cell lines had the ability to inhibit colony formation by 50%, which indicates that REQORSA inhibits growth of ALK+ lines. Additionally, researchers documented a strong pro-apoptotic response to TUSC2 expression in ALK+ NSCLC. The study found that the use of REQORSA or a TUSC2-containing plasmid to overexpress TUSC2 in ALK+ NSCLC cell lines was effective in decreasing cell growth and proliferation.
Researchers believe the results support further clinical study of REQORSA as an anti-ALK NSCLC treatment strategy.
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
TUSC2 is a tumor suppressor gene often deleted in lung cancers and reduced TUSC2 expression is observed in approximately 80% of lung cancers. TUSC2 is also reduced in mesothelioma, breast, head-and neck, osteosarcoma, glioblastoma, and other cancers, which suggests the important anti-tumor role of TUSC2. Additionally, TUSC2 is known to play a critical role in mitochondrial respiration/energy metabolism as TUSC2 protein localizes to the mitochondria.
Here, researchers investigated how human lung cancer cell lines A549 and H358, with decreased TUSC2 expression, alter their energy metabolism when TUSC2 protein is re-introduced. The study found that the TUSC2-deficient cancer cells consistently exhibited decreased glycolytic rates and mitochondrial ATP production. This is significant as it left 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, which suggests that this may be 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.
Genprex currently has three clinical trials evaluating REQORSA in lung cancer. All three clinical trials have received U.S. Food and Drug Administration (FDA) Fast Track Designation. The Acclaim-1 clinical trial is an open-label, multi-center Phase 1/2 clinical trial evaluating REQORSA in combination with Tagrisso (osimertinib) in patients with late-stage NSCLC with activating epidermal growth factor receptor (EGFR) mutations whose disease progressed after treatment with Tagrisso. Genprex completed the Phase 1 dose escalation portion of the trial and has already dosed the first patient in the Phase 2a expansion portion of the trial. The Acclaim-2 clinical trial is an open-label, multi-center Phase 1/2 clinical trial evaluating REQORSA in combination with Keytruda (pembrolizumab) in patients with late-stage NSCLC whose disease progressed after treatment with Keytruda. The Acclaim-3 clinical trial is an open-label, multi-center Phase 1/2 clinical trial evaluating REQORSA in combination with Tecentriq (atezolizumab) as maintenance therapy in patients with extensive-stage small-cell lung cancer (ES-SCLC) who did not develop tumor progression after receiving Tecentriq and chemotherapy as an initial treatment. The Acclaim-3 clinical trial also has FDA Orphan Drug Designation.
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
Among other cancer types, NSCLC often has reduced NPRL2, a tumor suppressor gene, and the restoration of NPRL2 activates cell cycle arrest and apoptosis.
In this humanized mouse model, researchers investigated the anti-tumor immune responses to NPRL2 gene therapy in pembrolizumab resistant KRAS/STK11mt NSCLC. In the study, induced 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 decreased 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.
Genprex Commentary:
"Today’s bolus of compelling data validates the potential of REQORSA and the ONCOPREX Delivery System as innovative cancer treatments. We were very encouraged to see the data document REQORSA’s anti-tumor properties and demonstrate its ability to suppress cell growth and trigger cancer cell death," said Mark Berger, MD, Chief Medical Officer at Genprex. "These data are particularly significant as decreased TUSC2 expression is seen in approximately 80% of lung cancers, and REQORSA has the potential to address a large patient population. Additionally, data showing NPRL2 gene therapy induced anti-tumor activity further positions Genprex to expand its clinical pipeline with another drug candidate, and it reinforces the value of ONCOPREX’s ability to deliver genes beyond TUSC2. We look forward to continuing to evaluate the ONCOPREX Delivery System using both REQORSA and NPRL2 as potential treatments for lung cancer."