Genprex Collaborators Find NPRL2 Gene Therapy Using Oncoprex® Delivery System is a Potential Treatment for Anti-PD1 Resistant Non-Small Cell Lung Cancer
Genprex (NASDAQ: GNPX) announced new research findings showing that NPRL2 gene therapy, using their Oncoprex® Delivery System, demonstrates significant potential in treating anti-PD1 resistant non-small cell lung cancer (NSCLC). The study, published in eLife, revealed that NPRL2 treatment alone showed dramatic antitumor effects in KRAS/STK11 double mutant NSCLC xenografts, while pembrolizumab (Keytruda®) alone was ineffective.
The research utilized Genprex's non-viral ONCOPREX Delivery System, which uses lipid nanoparticles to deliver tumor suppressor genes intravenously. The study demonstrated stronger antitumor effects in humanized mice compared to non-humanized NSG mice, indicating that NPRL2's effectiveness works through immune system activation. This breakthrough could potentially target approximately 30% of NSCLCs with KRAS mutations.
Genprex (NASDAQ: GNPX) ha annunciato nuovi risultati di ricerca che mostrano come la terapia genica NPRL2, utilizzando il loro sistema di somministrazione Oncoprex®, dimostri un potenziale significativo nel trattamento del cancro polmonare non a piccole cellule (NSCLC) resistente a anti-PD1. Lo studio, pubblicato su eLife, ha rivelato che il trattamento con NPRL2 da solo ha mostrato effetti antitumorali drammatici in xenotrapianti di NSCLC con mutazione doppia KRAS/STK11, mentre il pembrolizumab (Keytruda®) da solo si è rivelato inefficace.
La ricerca ha utilizzato il sistema di somministrazione ONCOPREX non virale di Genprex, che impiega nanoparticelle lipidiche per somministrare geni soppressori tumorali per via endovenosa. Lo studio ha dimostrato effetti antitumorali più forti in topi umanizzati rispetto ai topi NSG non umanizzati, indicando che l'efficacia di NPRL2 funziona attraverso l'attivazione del sistema immunitario. Questa scoperta potrebbe potenzialmente colpire circa il 30% dei NSCLC con mutazioni KRAS.
Genprex (NASDAQ: GNPX) anunció nuevos hallazgos de investigación que muestran que la terapia génica NPRL2, utilizando su sistema de entrega Oncoprex®, demuestra un potencial significativo en el tratamiento del cáncer de pulmón no microcítico (NSCLC) resistente a anti-PD1. El estudio, publicado en eLife, reveló que el tratamiento con NPRL2 por sí solo mostró efectos antitumorales dramáticos en xenoinjertos de NSCLC con mutación doble KRAS/STK11, mientras que el pembrolizumab (Keytruda®) por sí solo fue ineficaz.
La investigación utilizó el sistema de entrega ONCOPREX no viral de Genprex, que utiliza nanopartículas lipídicas para administrar genes supresores de tumores por vía intravenosa. El estudio demostró efectos antitumorales más fuertes en ratones humanizados en comparación con los ratones NSG no humanizados, lo que indica que la efectividad de NPRL2 funciona a través de la activación del sistema inmunológico. Este avance podría potencialmente dirigirse a aproximadamente el 30% de los NSCLC con mutaciones KRAS.
Genprex (NASDAQ: GNPX)는 NPRL2 유전자 치료가 그들의 Oncoprex® 전달 시스템을 사용하여 항-PD1 저항성 비소세포 폐암(NSCLC) 치료에 상당한 잠재력을 보여주는 새로운 연구 결과를 발표했습니다. eLife에 발표된 이 연구는 NPRL2 치료 단독으로 KRAS/STK11 이중 돌연변이 NSCLC 이식에서 극적인 항종양 효과를 나타냈으며, pembrolizumab(Keytruda®) 단독으로는 효과가 없음을 밝혔습니다.
이 연구는 Genprex의 비바이러스 ONCOPREX 전달 시스템을 활용했으며, 이 시스템은 지질 나노입자를 사용하여 종양 억제 유전자를 정맥 주사로 전달합니다. 이 연구는 비인간화된 NSG 생쥐에 비해 인간화된 생쥐에서 더 강한 항종양 효과를 나타내어 NPRL2의 효과가 면역 체계 활성화를 통해 작용함을 나타냈습니다. 이 혁신은 KRAS 돌연변이가 있는 약 30%의 NSCLC를 표적으로 삼을 수 있습니다.
Genprex (NASDAQ: GNPX) a annoncé de nouvelles découvertes de recherche montrant que la thérapie génique NPRL2, utilisant leur système de livraison Oncoprex®, démontre un potentiel significatif dans le traitement du cancer du poumon non à petites cellules (NSCLC) résistant à l'anti-PD1. L'étude, publiée dans eLife, a révélé que le traitement par NPRL2 seul montrait des effets antitumoraux spectaculaires dans des xénogreffes de NSCLC à double mutation KRAS/STK11, tandis que le pembrolizumab (Keytruda®) seul était inefficace.
La recherche a utilisé le système de livraison ONCOPREX non viral de Genprex, qui utilise des nanoparticules lipidiques pour administrer des gènes suppresseurs de tumeurs par voie intraveineuse. L'étude a démontré des effets antitumoraux plus forts chez des souris humanisées par rapport aux souris NSG non humanisées, ce qui indique que l'efficacité de NPRL2 fonctionne par l'activation du système immunitaire. Cette avancée pourrait potentiellement cibler environ 30 % des NSCLC avec des mutations KRAS.
Genprex (NASDAQ: GNPX) hat neue Forschungsergebnisse angekündigt, die zeigen, dass die NPRL2-Gentherapie mit ihrem Oncoprex®-Lieferungssystem erhebliches Potenzial bei der Behandlung von anti-PD1-resistentem nicht-kleinzelligem Lungenkrebs (NSCLC) zeigt. Die in eLife veröffentlichte Studie ergab, dass die NPRL2-Behandlung allein dramatische antitumorale Effekte in KRAS/STK11-doppelmutierten NSCLC-Xenotransplantaten zeigte, während Pembrolizumab (Keytruda®) allein unwirksam war.
Die Forschung nutzte Genprex' nicht-virales ONCOPREX-Lieferungssystem, das Lipidnanopartikel verwendet, um Tumorsuppressorgene intravenös zu liefern. Die Studie zeigte stärkere antitumorale Effekte bei humanisierten Mäusen im Vergleich zu nicht-humanisierten NSG-Mäusen, was darauf hinweist, dass die Wirksamkeit von NPRL2 durch die Aktivierung des Immunsystems funktioniert. Dieser Durchbruch könnte potenziell etwa 30% der NSCLCs mit KRAS-Mutationen anvisieren.
- NPRL2 gene therapy showed dramatic antitumor effects as a single agent in resistant NSCLC
- Study validates Oncoprex Delivery System's potential for multiple tumor suppressor genes
- Research demonstrates effectiveness in particularly resistant KRAS/STK11 mutant tumors
- Potential market includes 30% of NSCLCs with KRAS mutations
- Combination therapy with pembrolizumab showed minimal additional benefits over NPRL2 alone
Insights
This groundbreaking research represents a significant advancement in addressing one of oncology's most challenging problems: resistance to immunotherapy in non-small cell lung cancer. The study's findings are particularly compelling for several reasons:
The demonstrated efficacy of NPRL2 gene therapy in anti-PD1 resistant cases is remarkable, especially considering that pembrolizumab (Keytruda®), a leading immunotherapy generating over
The Oncoprex® Delivery System's ability to effectively deliver NPRL2 validates its platform potential beyond its current TUSC2 application in Reqorsa®. This versatility significantly enhances Genprex's technological value proposition, as it suggests the platform could be used to deliver multiple tumor suppressor genes, essentially creating a pipeline of targeted therapies.
The mechanism of action, working through dendritic cell mediated antigen presentation and immune cell activation, is particularly noteworthy. This dual approach - combining direct tumor suppression with immune system activation - represents a sophisticated strategy that could potentially overcome multiple resistance mechanisms.
The market implications are substantial, considering that approximately
New publication indicates that NPRL2 gene therapy has marked single-agent activity in anti-PD1 resistant non-small cell lung cancer xenografts
"We are thrilled by the continued advancements of our academic partners on the NPRL2 gene therapy, which supports the therapeutic potential of our non-viral Oncoprex® Delivery System to deliver the NPRL2 tumor suppressor gene therapy," said Ryan Confer, President and Chief Executive Officer at Genprex. "These data indicate the single agent potential of NPRL2 in lung cancer. They also demonstrate that the Oncoprex Delivery System used in Reqorsa® Gene Therapy with the TUSC2 tumor suppressor gene is a platform and can be used with other tumor suppressor genes, such as NPRL2. We are pleased that these positive data also support the therapeutic potential of NPRL2 gene therapy in NSCLC and positions Genprex for the expansion of our clinical development pipeline."
The studies used the Company's non-viral ONCOPREX Delivery System in KRAS/STK11 double mutant anti-PD1 resistant metastatic NSCLC xenografts in humanized mouse models. The ONCOPREX Delivery System is a novel non-viral approach utilizing lipid nanoparticles to deliver tumor suppressor genes that have been deleted during the course of cancer development. The platform allows for the intravenous delivery of various tumor suppressor genes to achieve a therapeutic effect without the risk of toxicity often associated with viral delivery systems.
In the published study, humanized mice were treated with NPRL2 gene therapy, immunotherapy pembrolizumab (Keytruda®), or the combination. A dramatic antitumor effect was mediated by NPRL2 treatment alone, whereas pembrolizumab alone was ineffective, and the combination added little to NPRL2 treatment alone.
A significant antitumor effect was also found in non-humanized NSG mice, although the antitumor effect was greater in humanized mice, suggesting that the effects of NPRL2 gene therapy are achieved through the immune system. This is consistent with a more detailed analysis showing that NPRL2 gene therapy induces antitumor activity against KRAS/STK11 mutant anti-PD1 resistant tumors through dendritic cell mediated antigen presentation and cytotoxic immune cell activation. KRAS/STK11 mutant tumors are particularly resistant to treatment, and demonstrating efficacy in this setting suggests that a wide variety of lung cancers could potentially be targeted. This potentially would include the approximately
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: 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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FAQ
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