Reqorsa® Gene Therapy Overcomes Acquired Resistance to Lumakras® in Lung Cancer
REQORSA Demonstrated Potent Tumor Suppressive Activity in Mesothelioma
REQORSA Induces Apoptosis in Glioblastoma
AUSTIN, Texas, Oct. 10, 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 EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics being held October 23-25, 2024 in Barcelona, Spain. The collaborators will present posters on positive preclinical data from studies of its lead drug candidate, Reqorsa® Gene Therapy (quaratusugene ozeplasmid), for the treatment of Ras inhibitor resistant lung cancer, mesothelioma and glioblastoma.
"The compelling data made available today validates the potential of REQORSA as a therapeutic treatment for some of the most difficult to treat cancers and diseases, including Ras inhibitor resistant lung cancer, mesothelioma and glioblastoma," said Ryan Confer, President and Chief Executive Officer at Genprex. "We are very encouraged to see the data support potential new indications for REQORSA, which could address unmet medical need for many patient populations. We look forward to continuing our preclinical programs studying REQORSA to explore how we could expand our clinical development pipeline with future clinical studies."
Genprex has filed two provisional patent applications based on data from two of the presentations. One application involves using REQORSA to treat mesothelioma and the other uses REQORSA to treat glioblastoma. Genprex is a co-owner of the applications along with the respective institutions. TUSC2 is the tumor suppressor gene used in REQORSA.
Featured Genprex-supported posters to be presented at the 2024 EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics include:
Title: "TUSC2 Gene Therapy in KRASG12C Mutant NSCLC Overcomes Acquired Resistance to Sotorasib"
Collaborator: The University of Texas MD Anderson Cancer Center
Catalog Number: 384
Presentation Number: PB372
Acquired resistance (AR) to Lumakras® (sotorasib), the first FDA-approved KRASi, poses a significant challenge in the treatment of KRASG12C mutant non-small cell lung cancer (NSCLC). Despite an initial response rate of up to 40%, patients invariably develop resistance, necessitating alternative therapeutic strategies. The mechanisms of AR include the emergence of additional mutations in the KRAS gene, reactivation of KRAS pathway, or activation of alternative signaling pathways. TUSC2, a potent tumor suppressor gene, exhibits multifunctional activities including multikinase inhibition, inhibition of growth & proliferation, induction of cell death and activation of both innate and adaptive immune responses. In this study, researchers demonstrated that TUSC2 gene therapy (REQORSA) effectively overcomes sotorasib AR in KRASG12Cmutant NSCLC mouse xenografts.
The data indicates that TUSC2 transfection significantly reduced colony formation in two AR cell lines. Transfection of TUSC2 also markedly increased apoptosis in AR cells. H23AR xenograft tumors exhibited significantly lower sensitivity to sotorasib than their parental counterparts. However, treatment with REQORSA alone or in combination with sotorasib was highly effective in controlling H23AR tumor growth in mouse xenografts. REQORSA alone also exhibited significantly strong antitumor effect on TC314AR patient-derived xenografts (PDXs) where sotorasib alone showed no significant antitumor activity. However, a synergistic antitumor effect was observed when TC314AR PDX tumors were treated with the combination of REQORSA and sotorasib.
In conclusion, researchers demonstrated that TUSC2 therapy, alone or in combination with sotorasib inhibited colony formation, induced apoptosis, and showed significant antitumor efficacy in KRASG12C mutant acquired resistant xenografts and in PDX tumor xenografts.
Title: "TUSC2 Suppresses Tumorigenic Properties in Malignant Pleural Mesothelioma Cells"
Collaborator: New York University Langone Health
Catalog Number: 364
Presentation Number: PB352
Malignant Pleural Mesothelioma (MPM) is a rare, highly aggressive, asbestos-associated neoplasm with a median survival of 10-12 months. TUSC2 is frequently deleted in multiple cancers and at least one allele is absent in 36% of MPM. Researchers investigated whether TUSC2 transfection could modulate MPM aggressive properties.
In this study, four MPM cell lines and tert-transformed mesothelial LP9 cells were treated with REQORSA and control liposomes for 48h. Treated cells were then evaluated for TUSC2 expression by semi quantitative RT-PCR, Western blot analysis, and functional assays including cell proliferation, invasion, and apoptosis.
The researchers demonstrated that REQORSA treatment resulted in a significant decrease in cell proliferation, cell invasion, and a significant increase in cell apoptosis in all four MPM cell lines. Data also demonstrated potent tumor suppressive activity of the TUSC2 gene delivered by REQORSA, and thus, its re-expression could serve as a potential therapeutic strategy for the treatment of MPM.
Title: "Efficacy of Quaratusugene Ozeplasmid (REQORSA) TUSC2 Gene Therapy in Glioblastoma"
Collaborator: The University of Texas Health Science Center at Houston
Catalog Number: 130
Presentation Number: PB118
Research collaborators previously reported TUSC2 as a novel tumor suppressor for glioblastoma, the most common and deadliest primary brain tumor in adults which is associated with a poor prognosis. In their latest study, patient-derived glioblastoma (GBM) cell lines and patient-derived glioma stem cell (PD-GSC) lines were used. REQORSA was used to restore TUSC2 expression.
Researchers observed that REQORSA significantly reduced GBM cell viability, and the results of a migration assay demonstrated that REQORSA suppressed GBM cell migration independent of its ability to suppress cell viability. In conclusion, REQORSA demonstrates promising in vitro efficacy in GBM and PD-GSCs, and these results support further evaluation of its in vivo anti-tumor efficacy in malignant gliomas using mouse models.
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.
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-based nanoparticles in a lipoplex form. 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® Gene Therapy (quaratusugene ozeplasmid), is being evaluated in two clinical trials as a treatment for NSCLC and SCLC. Each of Genprex's 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-002 for Type 2 diabetes, where autoimmunity is not at play, is believed to rejuvenate and replenish exhausted beta cells.
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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, 2023.
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: REQORSA's potential as a therapeutic treatment in inhibitor resistant lung cancer, mesothelioma and glioblastoma; 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; the effects of any strategic research and development prioritization initiatives, and any other strategic alternatives or other efforts that Genprex takes or may take in the future that are aimed at optimizing and re-focusing Genprex's diabetes, oncology and/or other clinical development programs including prioritization of resources, and the extent to which Genprex is able to implement such efforts and initiatives successfully to achieve the desired and intended results thereof; 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
[email protected]
GNPX Media Contact
Kalyn Dabbs
[email protected]
SOURCE Genprex, Inc.
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