Reqorsa^® Immunogene Therapy May be a Potential Therapy for ALK-Positive Lung Cancer

REQORSA has Anti-Tumor Mechanisms that Target and Disrupt the Metabolism of Cancer Cells

NPRL2 Gene Therapy Induces Effective Anti-Tumor Immunity in Non-Small Cell Lung Cancer Humanized Mouse Model

AUSTIN, Texas, March 6, 2024 /PRNewswire/ -- 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, today announced that its research collaborators will present at the upcoming 2024 American Association for Cancer Research (AACR) Annual Meeting being held April 5-10, 2024 in San Diego, California. 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.

"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 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/STK11^mt 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/STK11^mt 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/STK11^mt 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."

About Genprex, Inc.
Genprex, Inc. is a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes. Genprex's technologies are designed to administer disease-fighting genes to provide new therapies for large patient populations with cancer and diabetes who currently have limited treatment options. Genprex works with world-class institutions and collaborators to develop drug candidates to further its pipeline of gene therapies in order to provide novel treatment approaches. Genprex's oncology program utilizes its systemic, non-viral Oncoprex® Delivery System which encapsulates the gene-expressing plasmids using lipid nanoparticles. The resultant product is administered intravenously, where it is taken up by tumor cells that then express tumor suppressor proteins that were deficient in the tumor. The Company's lead product candidate, Reqorsa® Immunogene Therapy (quaratusugene ozeplasmid), is being evaluated in three clinical trials as a treatment for NSCLC and SCLC. Each of Genprex's three lung cancer clinical programs has received a Fast Track Designation from the FDA for the treatment of that patient population, and Genprex's SCLC program has received an FDA Orphan Drug Designation. Genprex's diabetes gene therapy approach is comprised of a novel infusion process that uses an AAV vector to deliver Pdx1 and MafA genes directly to the pancreas. In models of Type 1 diabetes, GPX-002 transforms alpha cells in the pancreas into functional beta-like cells, which can produce insulin but may be distinct enough from beta cells to evade the body's immune system. In a similar approach, GPX-003 for Type 2 diabetes, where autoimmunity is not at play, is believed to rejuvenate and replenish exhausted beta cells.

For more information, please visit the Company's web site at www.genprex.com or follow Genprex on Twitter, Facebook and LinkedIn.

Cautionary Language Concerning Forward-Looking Statements
Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are made on the basis of the current beliefs, expectations and assumptions of management, are not guarantees of performance and are subject to significant risks and uncertainty. These forward-looking statements should, therefore, be considered in light of various important factors, including those set forth in Genprex's reports that it files from time to time with the Securities and Exchange Commission and which you should review, including those statements under "Item 1A - Risk Factors" in Genprex's Annual Report on Form 10-K for the year ended December 31, 2022.

Because forward-looking statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding: Genprex's ability to advance the clinical development, manufacturing and commercialization of its product candidates in accordance with projected timelines and specifications; the timing and success of Genprex's clinical trials and regulatory approvals; the effect of Genprex's product candidates, alone and in combination with other therapies, on cancer and diabetes; Genprex's future growth and financial status, including Genprex's ability to maintain compliance with the continued listing requirements of The Nasdaq Capital Market and to continue as a going concern and to obtain capital to meet its long-term liquidity needs on acceptable terms, or at all; Genprex's commercial and strategic partnerships, including those with its third party vendors, suppliers and manufacturers and their ability to successfully perform and scale up the manufacture of its product candidates; and Genprex's intellectual property and licenses.

These forward-looking statements should not be relied upon as predictions of future events and Genprex cannot assure you that the events or circumstances discussed or reflected in these statements will be achieved or will occur. If such forward-looking statements prove to be inaccurate, the inaccuracy may be material. You should not regard these statements as a representation or warranty by Genprex or any other person that Genprex will achieve its objectives and plans in any specified timeframe, or at all. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. Genprex disclaims any obligation to publicly update or release any revisions to these forward-looking statements, whether as a result of new information, future events or otherwise, after the date of this press release or to reflect the occurrence of unanticipated events, except as required by law.

Genprex, Inc.
(877) 774-GNPX (4679)

GNPX Investor Relations
investors@genprex.com

GNPX Media Contact
Kalyn Dabbs
media@genprex.com

View original content to download multimedia:https://www.prnewswire.com/news-releases/genprex-collaborators-to-present-positive-preclinical-data-on-the-use-of-reqorsa-and-on-nprl2-gene-therapy-utilizing-non-viral-oncoprex-delivery-system-for-the-treatment-of-lung-cancers-at-the-2024-aacr-annual-meeting-302081087.html

SOURCE Genprex, Inc.