On October 10, 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 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics being held October 23-25, 2024 in Barcelona, Spain (Press release, Genprex, OCT 10, 2024, View Source [SID1234647147]). 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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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 (Free EORTC-NCI-AACR Whitepaper) 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.