Reqorsa (quaratusugene ozeplasmid) / Genprex - LARVOL DELTA

A phase 1/2 clinical trial of quaratusugene ozeplasmid gene therapy and atezolizumab maintenance therapy in patients with extensive stage small cell lung cancer (ES-SCLC). (ASCO 2025) - P1/2 | " Eligible patients have ES-SCLC and have completed 3-4 cycles of induction therapy with etoposide, a platinum agent, and atezo without disease progression, and are thus eligible for maintenance therapy...Dexamethasone, acetaminophen, and diphenhydramine are given prior to each treatment to prevent delayed infusion-related reactions...The Phase 2 portion of the trial opened for enrollment in December, 2024. (NCT05703971)."

Clinical • Gene therapy • P1/2 data • Gene Therapies • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • TUSC2

Genprex to Present Trial Design of Acclaim-3 Clinical Trial Evaluating Reqorsa Gene Therapy in Small Cell Lung Cancer at 2025 ASCO Annual Meeting (PRNewswire) - "The Company will present the trial design of the Acclaim-3 Phase 1/2 clinical trial evaluating Genprex's lead drug candidate, Reqorsa Gene Therapy (quaratusugene ozeplasmid), in combination with Tecentriq as maintenance therapy for the treatment of extensive stage small cell lung cancer (ES-SCLC)....Eligible patients have ES-SCLC and have completed 3-4 cycles of induction therapy with etoposide, a platinum agent, and Tecentriq without disease progression, and are thus eligible for maintenance therapy. REQORSA is administered via IV every 21 days in escalating dose cohorts in Phase 1 and Tecentriq 1200 mg is also administered via IV every 21 days....The Phase 2 portion of the trial will enroll 50 patients which provides 80% power at a one-sided alpha level of 0.05 to detect an 18-week PFS rate of 52% compared to a historical 18-week PFS rate of 34% with Tecentriq alone."

Clinical protocol • Small Cell Lung Cancer

Genprex Signs Exclusive License to Additional Gene Therapy Technology with UTHealth Houston for the Treatment of Glioblastoma (PRNewswire) - "Genprex, Inc...announced it has entered into an exclusive patent license agreement with UTHealth Houston granting Genprex exclusivity and commercial rights relating to its lead drug candidate, Reqorsa Gene Therapy (quaratusugene ozeplasmid) for the potential treatment of glioblastoma. The subject patent is co-owned by Genprex and UTHealth Houston, and the license provides Genprex with patent exclusivity."

Licensing / partnership • Glioblastoma

Genprex Collaborators Report Positive Preclinical Data on the Use of Reqorsa Gene Therapy for the Treatment of Ras Inhibitor Resistant Lung Cancer at the 2025 AACR Annual Meeting (PRNewswire) - "Genprex, Inc...announced that its research collaborators presented positive preclinical data for Reqorsa Gene Therapy (quaratusugene ozeplasmid), for the treatment of KRASG12C mutant non-small cell lung cancer (NSCLC)....The data indicate that TUSC2 transfection significantly reduced colony formation and markedly increased apoptosis in two AR cell lines. Re-expression of TUSC2 in AR PDXOs significantly decreased the viability of organoids compared with the empty vector. The H23AR tumors exhibited significantly lower sensitivity to sotorasib than their parental counterparts. However, treatment with REQORSA was highly effective in controlling tumor growth compared to treatment with sotorasib alone or the control groups. REQORSA alone also exhibited a strong antitumor effect on TC314AR PDXs. Sotorasib alone showed no significant antitumor activity in these models."

Preclinical • Non Small Cell Lung Cancer

Genprex Signs Exclusive Technology License Agreement with New York University Langone Health for the Treatment of Mesothelioma (PRNewswire) - "Genprex, Inc...announced it has signed an exclusive patent license agreement with NYU Langone Health related to the drug candidate, Reqorsa Gene Therapy (quaratusugene ozeplasmid). The therapy is under investigation as a potential treatment for mesothelioma. The subject patent is co-owned by Genprex and NYU Langone Health, and the license provides Genprex with patent exclusivity."

Patent • Mesothelioma

Overcoming sotorasib acquired resistance in KRASG12C mutant NSCLC by TUSC2 gene therapy (AACR 2025) - "The resistant cell lines also showed resistance to adagrasib, another KRASG12C inhibitor...The H23AR tumors, which exhibited no significant sensitivity to sotorasib, showed robust antitumor effects of quaratusugene ozeplasmid, a lipoplex gene therapy containing the TUSC2 gene in both H23AR and TC314AR PDXs...This antitumor effect was correlated with significant infiltration of human CD8 T, NK, DC, and M1 MQ, and downregulation of MDSCs and exhausted T cells. TUSC2 therapy, alone or in combination with sotorasib, induced apoptosis, inhibited colony formation, and showed significant antitumor efficacy in KRASG12C AR tumors"

Gene therapy • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ANXA5 • CD34 • CD8 • KRAS • TUSC2

Genprex Selected to Present Trial Design of Acclaim-3 Clinical Trial Evaluating Reqorsa Gene Therapy in Small Cell Lung Cancer at 2025 ASCO Annual Meeting (PRNewswire) - "Genprex, Inc...today announced that it has been selected to present at the upcoming 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 30 – June 3 in Chicago, Illinois and online. Genprex's abstract was selected for a poster presentation for the Trials in Progress portion of the conference. The Company will present the trial design of the Acclaim-3 Phase 1/2 clinical trial evaluating Genprex's lead drug candidate, Reqorsa Gene Therapy (quaratusugene ozeplasmid), in combination with Tecentriq as maintenance therapy for the treatment of extensive stage small cell lung cancer (ES-SCLC)."

Clinical protocol • Small Cell Lung Cancer

Genprex Announces Research Collaborators' Abstract Published in Cancer Research Supplement Proceedings (GlobeNewswire) - "Genprex collaborators will present the published abstract in a poster presentation at the 2025 AACR Annual Meeting being held April 25-30, 2025 in Chicago, Illinois. The collaborators will present positive preclinical data from a study of Genprex's lead drug candidate, Reqorsa Gene Therapy (quaratusugene ozeplasmid), for the treatment of KRASG12C mutant non-small cell lung cancer (NSCLC)."

Preclinical • Non Small Cell Lung Cancer

Genprex Collaborators to Present Positive Preclinical Data on the Use of Reqorsa Gene Therapy for the Treatment of Lung Cancer at the 2025 AACR Annual Meeting (PRNewswire) - "Genprex, Inc...today announced that its research collaborators will present at the upcoming 2025 American Association for Cancer Research (AACR) Annual Meeting being held April 25-30, 2025 in Chicago, Illinois. The collaborators will present positive preclinical data from a study of its lead drug candidate, Reqorsa Gene Therapy (quaratusugene ozeplasmid), for the treatment of KRASG12C mutant non-small cell lung cancer (NSCLC)."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer

Acclaim-2: Quaratusugene Ozeplasmid (Reqorsa) in Combination With Pembrolizumab in Previously Treated Non-Small Lung Cancer (clinicaltrials.gov) - P1/2 | N=5 | Terminated | Sponsor: Genprex, Inc. | N=180 ➔ 5 | Trial completion date: Dec 2025 ➔ Feb 2025 | Active, not recruiting ➔ Terminated; Enrollment was slow, due to competition with the many other clinical trials for the same patient population, which led to the decision to end enrollment in the trial.

Enrollment change • Trial completion date • Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • PD-L1

Genprex Announces First Patient Dosed in Phase 2 Expansion Portion of Acclaim-3 Clinical Study of Reqorsa Gene Therapy in Combination with Tecentriq to Treat Small Cell Lung Cancer (PRNewswire) - "Genprex...announced that the first patient has been enrolled and dosed in the Phase 2 expansion portion of the Company's Acclaim-3 clinical study of Reqorsa Gene Therapy (quaratusugene ozeplasmid) in combination with Tecentriq (atezolizumab) as maintenance therapy for patients with extensive stage small cell lung cancer (ES-SCLC)....The Phase 2 expansion portion will enroll 50 patients at approximately 10 to 15 U.S. sites. Patients will be treated with REQORSA and Tecentriq until disease progression or unacceptable toxicity is experienced....A Phase 2 interim analysis will be performed after the 25th patient enrolled and treated reaches 18 weeks of follow up. The Company expects to complete enrollment of the first 25 patients in the second half of 2025 for interim analysis."

Trial status • Small Cell Lung Cancer

Genprex Receives Safety Review Committee Approval to Advance to Phase 2 Portion of Acclaim-3 Clinical Trial of Reqorsa Gene Therapy in Combination with Tecentriq in Extensive Stage Small Cell Lung Cancer (PRNewswire) - "Genprex, Inc...today announced that it has completed the Phase 1 dose escalation portion of the Acclaim-3 clinical trial of Reqorsa Gene Therapy (quaratusugene ozeplasmid) in combination with Tecentriq (atezolizumab) as maintenance therapy to treat patients with extensive stage small cell lung cancer (ES-SCLC)....Based on full safety data, which showed no dose limiting toxicities (DLTs), the SRC determined that the Recommended Phase 2 Dose (RP2D) of REQORSA will be 0.12 mg/kg. This was the highest dose level delivered in the Phase 1 portion of the trial. The SRC also recommended the trial advance to the Phase 2 expansion portion of the study, which the Company has now opened for enrollment....Additionally, we will be submitting the results of the Phase 1 portion of the study to a clinical meeting and anticipate data presentation in 2025, and we remain encouraged by the early efficacy demonstrated in ES-SCLC patients."

DSMB • P1 data • Trial status • Lung Cancer • Small Cell Lung Cancer

TUSC2 gene therapy in KRASG12C mutant NSCLC overcomes acquired resistance to sotorasib (EORTC-NCI-AACR 2024) - "These resistant cells also showed resistance to adagrasib, 2nd KRASi. The antitumor immune responses of quaratusugene ozeplasmid on TC314AR PDX tumors are currently being evaluated in the humanized mouse model. In Conclusion, TUSC2 therapy, alone or in combination with sotorasib induced apoptosis, inhibited colony formation, and showed significant antitumor efficacy in KRASG12C mutant acquired resistant xenograft and PDX tumors."

Gene therapy • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD34 • KRAS • PTPRC • TUSC2

Efficacy of Quaratusugene Ozeplasmid TUSC2 Gene Therapy in Glioblastoma (EORTC-NCI-AACR 2024) - "Quaratusugene ozeplasmid (Quar Oze), TUSC2 plasmid DNA complexed with DOTAP-Cl: Cholesterol liposome solution, has been tested in lung cancer clinical trials including ONC-001, ONC-002, and active Acclaim-1 Phase II trial with osimertinib, Acclaim-2 Phase 1/2 trial with pembrolizumab, and Acclaim-3 Phase 1/2 study with atezolizumab. We report, for the first time, that Quar Oze demonstrates promising in vitro efficacy in GBM and PD-GSCs. These results serve as supporting evidence for further evaluation of its in vivo anti-tumor efficacy in malignant gliomas using mouse models.Table 1: Quar Oze Effects on GBM Cells Quar Oze Effects Over Controls P-Values Proliferation Decreased 45% <0.0001 Glioma Stem Cells Decreased 63% 0.017 Apoptosis Increased 32% 0.0029 Cell Migration Decreased 70% <0.0001"

Clinical • Gene therapy • Brain Cancer • CNS Tumor • Glioblastoma • Lung Cancer • Oncology • Solid Tumor • ANXA5 • NEDD4 • TUSC2

Genprex Signs Exclusive License to Additional Gene Therapy Technologies with the University of Michigan for the Treatment of Lung Cancer (PRNewswire) - "Genprex, Inc...announced it has entered into an exclusive license agreement with the University of Michigan, granting Genprex a worldwide, exclusive license to the University's patent rights relating toits lead drug candidate, Reqorsa Gene Therapy (quaratusugene ozeplasmid), in combination with ALK-inhibitors for the potential treatment of ALK-EML4 positive translocated lung cancer."

Licensing / partnership • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Tusc2 modulates cancer immune responses (SITC 2024) - "Experimental group was iv injected with Tusc2-expressing lipoparticles (quaratusugene ozeplasmid, provided by Geneprex, Inc); control group of Tusc2 KO mice was i.v. injected with saline solution...Conclusions This research demonstrated the capacity of quar oze supplementation to Tusc2-deficient mice to modulate immune cells within the TME. Tusc2-dependent changes in immune composition correlated with the reduction in tumor size in quar oze treated group, indicating that Tusc2 lipoparticles may carry anti-tumor potential even in individuals with low Tusc2 expression due to aging, chronic inflammation, metabolic diseases, etc."

IO biomarker • Lung Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • GZMB • TUSC2

Genprex Collaborators Present Positive Preclinical Data on Reqorsa Gene Therapy at the Society for Immunotherapy of Cancer 2024 Annual Meeting (PRNewswire) - "Genprex...announced that its research collaborators at Meharry Medical College will present a poster detailing positive preclinical data from a study of the Company's lead drug candidate, Reqorsa Gene Therapy (quaratusugene ozeplasmid) evaluating TUSC2's role in modulating immune responses in cancer....In the REQORSA supplemented group, the tumor growth was diminished. A significant reduction in T reg and significant increase in Cytotoxic T cells and NK cells were observed within TILs. A significant increase in Granzyme B expression within Cytotoxic T cells and NK cells was shown in REQORSA supplemented mice compared to the control group....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."

Preclinical • Oncology

Genprex Announces Sponsored Research Agreement with The University of Michigan Rogel Cancer Center and Lung Cancer Study Collaboration with ALK Positive (PRNewswire) - "Genprex, Inc...announced the Company has entered into a Sponsored Research Agreement (SRA) with the University of Michigan Rogel Cancer Center to study TUSC2, the tumor suppressor gene used in Genprex's lead drug candidate, Reqorsa Gene Therapy (quaratusugene ozeplasmid), in combination with ALK-inhibitors in ALK-EML4 positive translocated lung cancer....The Company also announced its collaboration with ALK Positive, a non-profit patient-driven research organization dedicated to improving the life expectancy and quality of life for ALK-positive (ALK+) lung cancer patients. As a part of this collaboration, both Genprex and ALK Positive will share the cost of the SRA with the University of Michigan Rogel Cancer Center."

Commercial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Genprex Collaborators Present Positive Preclinical Data on the Use of Reqorsa Gene Therapy for the Treatment of Lung Cancer, Mesothelioma and Glioblastoma (PRNewswire) - "Genprex, Inc...announced that research collaborators delivered poster presentations at the 2024 EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics held October 23-25, 2024 in Barcelona, Spain. The collaborators presented posters on positive preclinical data from studies of Genprex's lead drug candidate, Reqorsa Gene Therapy (quaratusugene ozeplasmid), for the treatment of Ras inhibitor resistant lung cancer, mesothelioma and glioblastoma."

Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Lung Cancer • Mesothelioma • Oncology • Skin Cancer • Solid Tumor

TUSC2 Suppresses Tumorigenic Properties in Malignant Pleural Mesothelioma Cells (EORTC-NCI-AACR 2024) - "Pre-clinical studies demonstrate that systemic delivery of TUSC2 plasmid DNA complexed with DOTAP-Cl:-Cholesterol liposome solution (quaratusugene ozeplasmid; Quar Oze) suppresses tumor growth, inhibits experimental lung metastasis and prolongs animal survival... Our data demonstrate potent tumor suppressive activity of the TUSC2 gene delivered by Quar Oze, and its re-expression could serve as a potential therapeutic strategy for the treatment of MPM. Cell Lines Δ Proliferation % P value Δ Invasion % P value Δ Apoptosis % P value H2595 -62 2.57E-08 -78 1.65E-06 +47 8.31E-07 HP1 -63 1.08E-06 -75 5.43E-06 +43 1.26E-06 H2373 -57 2.40E-05 -71 1.77E-06 +42 8.27E-05 H2591 -59 1.23E-06 -78 2.16E-05 +45 1.99E-05"

Angiosarcoma • Lung Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Sarcoma • Solid Tumor • TUSC2

Acclaim-1: Quaratusugene Ozeplasmid (Reqorsa) and Osimertinib in Patients With Advanced Lung Cancer Who Progressed on Osimertinib (clinicaltrials.gov) - P1/2 | N=158 | Recruiting | Sponsor: Genprex, Inc. | Trial completion date: Dec 2027 ➔ Mar 2029 | Trial primary completion date: Dec 2026 ➔ Mar 2028

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Genprex Receives Safety Review Committee Approval to Advance to Highest Dose Group in Phase 1 Portion of Acclaim-3 Clinical Trial of Reqorsa Gene Therapy in Combination with Tecentriq in Extensive Stage Small Cell Lung Cancer (PRNewswire) - "Genprex, Inc...announced that it has completed the 0.09 mg/kg dose group of the Phase 1 dose escalation portion of the Acclaim-3 clinical trial of Reqorsa Gene Therapy (quaratusugene ozeplasmid) in combination with Tecentriq (atezolizumab) as maintenance therapy for patients with extensive stage small cell lung cancer (ES-SCLC). In addition, the Safety Review Committee (SRC) has approved escalation to the highest dose group of 0.12 mg/kg...There were no dose limiting toxicities (DLTs) in this dose group and the SRC recommended moving up to the highest dose group planned in the trial....The Company continues to anticipate completion of enrollment in the Phase 1 dose escalation portion of the trial and to start the Phase 2 expansion portion in the second half of 2024, dependent on the number of patients needed to be enrolled in the 0.12 mg/kg dose group."

DSMB • Trial status • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Title: "TUSC2 Gene Therapy in KRASG12C Mutant NSCLC Overcomes Acquired Resistance to Sotorasib" (PRNewswire) - "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....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."

Preclinical • Non Small Cell Lung Cancer

Title: "TUSC2 Suppresses Tumorigenic Properties in Malignant Pleural Mesothelioma Cells" (PRNewswire) - "In this study, four MPM cell lines and tert-transformed mesothelial LP9 cells were treated with REQORSA and control liposomes for 48h....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."

Preclinical • Malignant Pleural Mesothelioma

Title: "Efficacy of Quaratusugene Ozeplasmid (REQORSA) TUSC2 Gene Therapy in Glioblastoma" (PRNewswire) - "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."

Preclinical • Glioblastoma