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
Genprex announced that its research collaborators will present positive preclinical data for Reqorsa® Gene Therapy at the 2025 AACR Annual Meeting in Chicago. The study focuses on treating KRASG12C mutant non-small cell lung cancer (NSCLC), particularly addressing resistance to Lumakras® (sotorasib).
The preclinical data demonstrated that TUSC2 gene therapy (REQORSA) effectively overcomes sotorasib acquired resistance in KRASG12C mutant NSCLC mouse xenografts. Key findings show that TUSC2 transfection reduced colony formation in resistant cell lines, increased apoptosis, and decreased organoid viability. The treatment showed significant antitumor efficacy both as a standalone therapy and in combination with sotorasib in resistant tumors.
Genprex ha annunciato che i suoi collaboratori di ricerca presenteranno dati preclinici positivi per Reqorsa® Gene Therapy durante il Meeting Annuale AACR 2025 a Chicago. Lo studio si concentra sul trattamento del cancro polmonare non a piccole cellule (NSCLC) con mutazione KRASG12C, affrontando in particolare la resistenza a Lumakras® (sotorasib).
I dati preclinici hanno dimostrato che la terapia genica TUSC2 (REQORSA) supera efficacemente la resistenza acquisita a sotorasib nei xenotrapianti murini di NSCLC con mutazione KRASG12C. I risultati chiave mostrano che la trasfezione di TUSC2 ha ridotto la formazione di colonie in linee cellulari resistenti, aumentato l'apoptosi e diminuito la vitalità degli organoidi. Il trattamento ha mostrato un'efficacia antitumorale significativa sia come terapia singola che in combinazione con sotorasib nei tumori resistenti.
Genprex anunció que sus colaboradores de investigación presentarán datos preclínicos positivos para Reqorsa® Gene Therapy en la Reunión Anual AACR 2025 en Chicago. El estudio se centra en el tratamiento del cáncer de pulmón no microcítico (NSCLC) con mutación KRASG12C, abordando particularmente la resistencia a Lumakras® (sotorasib).
Los datos preclínicos demostraron que la terapia génica TUSC2 (REQORSA) supera eficazmente la resistencia adquirida a sotorasib en xenoinjertos de ratón con NSCLC mutante KRASG12C. Los hallazgos clave muestran que la transfección de TUSC2 redujo la formación de colonias en líneas celulares resistentes, aumentó la apoptosis y disminuyó la viabilidad de los organoides. El tratamiento mostró una eficacia antitumoral significativa tanto como terapia independiente como en combinación con sotorasib en tumores resistentes.
Genprex는 연구 협력자들이 시카고에서 열리는 2025 AACR 연례 회의에서 Reqorsa® 유전자 치료에 대한 긍정적인 전임상 데이터를 발표할 것이라고 발표했습니다. 이 연구는 KRASG12C 변이 비소세포 폐암 (NSCLC) 치료에 중점을 두며, 특히 Lumakras® (sotorasib)에 대한 저항성을 다룹니다.
전임상 데이터는 TUSC2 유전자 치료 (REQORSA)가 KRASG12C 변이 NSCLC 마우스 제노그래프트에서 sotorasib에 대한 획득 저항성을 효과적으로 극복함을 보여주었습니다. 주요 발견은 TUSC2 전이감이 저항성 세포주에서 집락 형성을 감소시키고, 세포자멸사를 증가시키며, 오르가노이드 생존력을 감소시켰음을 보여줍니다. 치료는 저항성 종양에서 sotorasib과 병용했을 때와 단독 요법으로 모두 상당한 항종양 효능을 보였습니다.
Genprex a annoncé que ses collaborateurs de recherche présenteront des données précliniques positives pour Reqorsa® Thérapie Génique lors de la Réunion Annuelle AACR 2025 à Chicago. L'étude se concentre sur le traitement du cancer du poumon non à petites cellules (NSCLC) avec mutation KRASG12C, en s'attaquant particulièrement à la résistance à Lumakras® (sotorasib).
Les données précliniques ont démontré que la thérapie génique TUSC2 (REQORSA) surmonte efficacement la résistance acquise à sotorasib dans des xénogreffes murines de NSCLC muté KRASG12C. Les résultats clés montrent que la transfection de TUSC2 a réduit la formation de colonies dans des lignées cellulaires résistantes, augmenté l'apoptose et diminué la viabilité des organoïdes. Le traitement a montré une efficacité antitumorale significative tant comme thérapie autonome que combinée avec sotorasib dans des tumeurs résistantes.
Genprex gab bekannt, dass seine Forschungspartner positive präklinische Daten für Reqorsa® Gentherapie auf dem 2025 AACR-Jahrestreffen in Chicago präsentieren werden. Die Studie konzentriert sich auf die Behandlung von KRASG12C-mutiertem nicht-kleinzelligem Lungenkrebs (NSCLC) und befasst sich insbesondere mit der Resistenz gegen Lumakras® (sotorasib).
Die präklinischen Daten zeigten, dass die TUSC2-Gentherapie (REQORSA) die erworbene Resistenz gegen sotorasib in KRASG12C-mutierten NSCLC-Maus-Xenografts effektiv überwindet. Wichtige Ergebnisse zeigen, dass die Transfektion von TUSC2 die Kolonienbildung in resistenten Zelllinien reduzierte, die Apoptose erhöhte und die Lebensfähigkeit der Organoide verringerte. Die Behandlung zeigte sowohl als Einzeltherapie als auch in Kombination mit sotorasib bei resistenten Tumoren eine signifikante antitumorale Wirksamkeit.
- Preclinical data shows effective treatment of drug-resistant lung cancer
- Demonstrated significant antitumor efficacy in resistant tumors
- Successful results both as standalone therapy and in combination with existing treatment
- Potential expansion into multiple cancer types treatment
- Still in preclinical stage, requiring further clinical trials
- Results to laboratory and animal studies, not yet proven in humans
Insights
Genprex's announcement represents positive early-stage validation for its lead candidate Reqorsa in a tough-to-treat subset of non-small cell lung cancer. The preclinical data specifically addresses KRASG12C mutant NSCLC with acquired resistance to sotorasib (Lumakras), highlighting a significant unmet need in lung cancer treatment.
The data demonstrates Reqorsa's multifaceted mechanism as a TUSC2 gene therapy - inhibiting critical signaling pathways (MAPK and mTOR), inducing cancer cell death, and activating immune responses. Most compelling is the efficacy shown in multiple resistant models:
- Reduced colony formation in acquired-resistant cell lines
- Increased apoptosis in resistant cells
- Decreased viability in patient-derived xenograft organoids
- Controlled tumor growth in H23AR xenografts where sotorasib failed
- Demonstrated synergistic effects when combined with sotorasib in resistant models
This represents a strategic opportunity for Genprex, potentially positioning Reqorsa as a solution for the inevitable resistance that develops to KRAS inhibitors. The sotorasib resistance market is particularly relevant as it was the first FDA-approved KRAS inhibitor, but faces limitations due to resistance mechanisms.
However, investors should recognize these are preclinical results being presented at a scientific conference - several steps removed from clinical validation or commercialization. The
Reqorsa® Immunogene Therapy is a Potential Therapy for Ras Inhibitor Resistant Non-Small Cell Lung Cancer
"We are delighted to have our academic partners present positive preclinical data on our lead drug candidate, REQORSA, as a potential therapeutic treatment for Ras inhibitor resistant lung cancer," said Ryan Confer, President and Chief Executive Officer at Genprex. "These preclinical data further validate REQORSA as a potential treatment for many types of cancer, including another subset of lung cancer. We remain highly encouraged by the role that TUSC2 plays in the treatment of lung cancer and by our preclinical programs expanding on the potential use of REQORSA to treat many types of cancer where patient populations continue to have unmet medical needs."
The featured Genprex-supported poster to be presented at AACR 2025:
Title: Overcoming sotorasib acquired resistance in KRASG12C mutant NSCLC by TUSC2 gene therapy
Session Category: Experimental and Molecular Therapeutics
Session Title: Drug Resistance in Molecular Targeted Therapies 3
Session Date and Time: Tuesday, April 29 from 2-5 p.m. CT
Location: Poster Section 17
Poster Board Number: 12
Abstract Presentation Number: 5517
The featured Genprex-supported abstract to be presented at AACR 2025:
Acquired resistance (AR) to Lumakras® (sotorasib), the first FDA-approved KRASi, poses a significant challenge in the treatment of KRASG12C mutant NSCLC. Despite initial responses, patients invariably develop resistance, necessitating alternative therapeutic strategies. The mechanisms underlying AR include the emergence of additional mutations in the KRAS gene, reactivation of the KRAS pathway, or activation of alternative signaling pathways. TUSC2, a potent tumor suppressor gene with immunogenic properties, exhibits multifunctional activity by inhibiting downstream signaling pathways, including MAPK and mTOR; arresting the growth and proliferation of cancer cells; inducing tumor cell death; and activating innate and adaptive immune responses. In this study, researchers demonstrated that TUSC2 gene therapy (REQORSA) effectively overcomes sotorasib AR in KRASG12C mutant NSCLC mouse xenografts.
The data indicate that TUSC2 transfection significantly reduced colony formation in two AR cell lines. Transfection of TUSC2 also markedly increased apoptosis in AR cells. Re-expression of TUSC2 into 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. 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 REQORSA, alone or in combination with sotorasib, induced apoptosis, inhibited colony formation, and showed significant antitumor efficacy in KRASG12C mutant sotorasib-acquired resistant xenograft and PDX tumors.
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 for Type 2 diabetes, where autoimmunity is not at play, GPX-002 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 for Ras inhibitor resistant lung cancer; 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.
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