STK11

NPRL2 Gene Therapy Induces Anti-Tumor Activity in Anti-PD1 Resistant KRAS/STK11 Mutant Non-Small Cell Lung Cancer in a Humanized Mouse Model Provides Additional Preclinical Validation of Oncoprex® Delivery System With Another Tumor Suppressor Gene AUSTIN, Texas, April 2, 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 have published positive preclinical data for the NPRL2 tumor suppressor gene, utilizing the Company's non-viral Oncoprex® Delivery System, in KRAS/STK11 mutant anti-PD1 resistant non-small cell lung cancer (NSCLC) in a humanized mouse model. NPRL2 is a tumor suppressor gene whose expression is reduced in many cancers including lung, renal, colorectal, glioma, gastric, and hepatocellular carcinoma, and it has been closely correlated with poor clinical outcomes. Genprex's Oncoprex® Delivery System is a novel non-viral approach that utilizes lipid-based nanoparticles in a lipoplex form to deliver tumor suppressor genes deleted during the course of cancer development. The platform allows for the intravenous delivery of various tumor suppressor genes, and potentially other genes, to achieve a therapeutic affect without the risk of toxicity often associated with viral delivery systems. Genprex believes this system allows for delivery of a number of cancer-fighting genes, alone or in combination with other cancer therapies, to combat multiple types of cancer. The manuscript, titled, "NPRL2 gene therapy induces effective anti-tumor immunity in KRAS/STK11 mutant anti-PD1 resistant metastatic non-small cell lung cancer (NSCLC) in a humanized mouse model," was published on the bioRxiv biology preprint server. "These positive preclinical data are very encouraging and support NPRL2 gene therapy as a potential treatment for a sub-group of NSCLC in which patients traditionally are resistant to existing therapies," said Rodney Varner, President, Chairman and Chief Executive Officer at Genprex. "We believe this data could support the potential for a new drug candidate in our pipeline, and it also provides further evidence that the Oncoprex® Delivery System has the ability to be successful using genes other than the TUSC2 gene we are already using in clinical trials with Reqorsa®." The studies evaluated the intravenous injection of NPRL2 gene-loaded cationic lipoplexes (DOTAP-NPRL2) with or without anti-PD1 drugs (pembrolizumab). The studies used a KRAS/STK11 mutant anti-PD1 insensitive cell line, as well as syngeneic mouse LLC2 tumors, which are also anti-PD1 resistant. In both of these mouse models, NPRL2 showed a significantly strong anti-tumor effect whereas anti-PD1 (pembrolizumab) was not effective. The anti-tumor effect was greater in humanized mice than non-humanized mice, suggesting that an immune response contributed to anti-tumor activity. Additionally, a dramatic anti-tumor effect was mediated by NPRL2 treatment with or without a pembrolizumab combination. Bioluminescence imaging on mice showed that 7 out of 10 mice contained an extremely low amount of tumor burden in the NPRL2 treatment group, which was significantly different than in the control or pembrolizumab group. Unlike previous experiments with Reqorsa® Immunogene Therapy (quartusugene ozeplasmid), the Company's lead drug candidate using the TUSC2 tumor suppressor gene, the anti-tumor efficacy of DOTAP-NPRL2 did not involve Natural Killer (NK) cells. The studies also found that tumors with stable NPRL2 expression exhibited significantly slower growth compared to controls. In conclusion, researchers reported that NPRL2 gene therapy induces anti-tumor activity through dendritic cell-mediated antigen presentation and cytotoxic immune cell activation. 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® Immunogene Therapy (quaratusugene ozeplasmid), is being evaluated in three clinical trials as a treatment for NSCLC and SCLC. Each of Genprex's three 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. Interested investors and shareholders are encouraged to sign up for press releases and industry updates by visiting the Company Website, registering for Email Alerts and by following Genprex on Twitter, Facebook and LinkedIn. 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; 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 investors@genprex.com GNPX Media Contact Kalyn Dabbs media@genprex.com Company Codes: NASDAQ-NMS:GNPX

该研究发现，瘤内注射CXCL9/10工程化树突状细胞（CXCL9/10-DC），增强了肿瘤微环境（TME）中的T细胞浸润和活化，在多个同源小鼠非小细胞肺癌模型中产生了有效的肿瘤抑制作用。 加州大学洛杉矶发现 Bin Liu、Steven Dubinett 等人在 Cell 子刊 Cell Reports Medicine 上发表了题为：CXCL9/10-engineered dendritic cells promote T cell activation and enhance immune checkpoint blockade for lung cancer 的研究论文。 该研究使用慢病毒载体构建了表达CXCL9和CXCL10的工程化树突状细胞（CXCL9/10-DC），瘤内注射CXCL9/10-DC能够增强肿瘤微环境中的T细胞浸润和激活，有效抑制小鼠非小细胞肺癌模型的肿瘤发展，瘤内注射CXCL9/10-DC与免疫检查点阻断（ICB）疗法结合，克服了治疗耐药性并建立了全身肿瘤特异性免疫。 这项研究提供了对CXCL9/10-DC介导的宿主免疫激活的机制理解，并支持瘤内注射CXCL9/10-DC的临床转化，以增强ICB疗法在非小细胞肺癌中的疗效。 趋化因子是招募T细胞进入肿瘤微环境的必不可少的可溶性介质。CXCL9和CXCL10（CXCL9/10）是干扰素γ（IFN-γ）诱导的趋化因子，主要由肿瘤内CD103+树突状细胞和肿瘤相关巨噬细胞分泌。 CXCL9/10通过CXCR3信号促进CXCR3+效应T细胞的肿瘤浸润，包括1型T细胞辅助细胞和CD8+细胞毒性T淋巴细胞。除了促进效应T细胞浸润到肿瘤中外，CXCL9/CXCL10/CXCR3信号级联是最佳T细胞激活所必需的。CXCL9表达是癌症患者对ICB反应的最强预测因子之一，此外，肿瘤活检中CXCL9、CXCL10和/或CXCR3的高表达与接受ICB治疗的患者总体生存率的改善相关。这些发现强调了CXCL9/10在肿瘤微环境中作为ICB诱导的抗肿瘤免疫介质的重要作用。 树突状细胞（DC）原位疫苗已成为克服ICB耐药的有前途的方法。瘤内疫苗接种为树突状细胞提供了获得所有可用肿瘤抗原的能力，以促进广泛的抗肿瘤T细胞反应。在临床前研究中，基因修饰的树突状细胞疫苗可以分泌趋化因子，调节肿瘤微环境中的可溶性介质和细胞介质，以促进良好的抗肿瘤反应。 值得注意的是，细胞因子基因工程化树突状细胞作为表达载体的表现优于成纤维细胞，强调了树突状细胞的抗原呈递功能对于最佳疗效的重要性。鉴于CXCL9/10在促进T细胞介导的抗肿瘤免疫反应中的关键作用，研究团队评估了CXCL9/10工程化树突状细胞（CXCL9/10-DC）原位疫苗在小鼠非小细胞肺癌（NSCLC）模型中增强免疫检查点阻断（ICB）疗法的效果。 该研究发现，瘤内注射CXCL9/10工程化树突状细胞（CXCL9/10-DC），增强了肿瘤微环境（TME）中的T细胞浸润和活化，在多个同源小鼠非小细胞肺癌模型中产生了有效的肿瘤抑制作用。瘤内注射CXCL9/10-DC的抗肿瘤效果依赖于CD4+T细胞和CD8+T细胞以及CXCR3介导的T细胞转运和淋巴结中的T细胞输出。 瘤内注射CXCL9/10-DC克服了低肿瘤突变负荷的Lkb1缺陷Kras突变小鼠非小细胞肺癌模型对PD-1/PD-L1阻断的耐药性。此外，瘤内注射CXCL9/10-DC增强了高肿瘤突变负荷的Lkb1缺陷，Kras突变小鼠NSCLC模型对PD-1/PD-L1阻断的相对中等疗效，导致部分肿瘤完全消灭并建立了肿瘤特异性免疫记忆。 这些发现为瘤内注射CXCL9/10-DC作为克服耐药性和增强非小细胞肺癌ICB免疫治疗临床疗效的潜在临床转化提供了证据。

BerGenBio receives positive recommendation from independent Data and Safety Monitoring Board to proceed without study modification BERGEN, Norway, March 20, 2024 /PRNewswire/ -- BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical needs, announced today it has initiated the Phase 2a portion of the BGBC016 clinical study of its selective AXL inhibitor bemcentinib in combination with standard of care therapy in first-line Non Small Cell Lung Cancer (NSCLC) patients harboring a STK11 mutation (STK11m). The initiation of Phase 2a follows a positive recommendation by the independent Drug Safety Monitoring Board (DSMB) which evaluated the safety of the combination of bemcentinib with pembrolizumab (Keytruda®) and doublet chemotherapy in first-line (1L) NSCLC patients enrolled in the Phase 1b portion of the study. Patients with STK11m NSCLC have a significantly poorer response to current therapies, including immune checkpoint inhibitors, when compared with patients with wild-type (non-mutated) STK11. AXL plays a significant role in the survival and spread of cancer and STK11m NSCLC patients have a high expression of AXL suggesting that AXL is an important target to prevent disease progression and resistance to existing therapies. Bemcentinib's selective inhibition of AXL has been shown to improve the response to immune checkpoint inhibition in STK11m patient-derived preclinical models and in early clinical studies. There are currently no targeted therapies available for the STK11m NSCLC patient population, which represents up to 20% of 1L NSCLC patients. Cristina Oliva, Chief Medical Officer of BerGenBio commented, "We are very pleased that no new safety signals have been identified and are encouraged by the recommendation of the DSMB to continue the study as planned. We have therefore, opened the Ph2a portion of the study with the goal of reporting initial efficacy data as the next step in validating the benefit of bemcentinib in combination with standard therapies in 1L NSCLC." Martin Olin, Chief Executive Officer of BerGenBio added, "The high unmet medical need in 1L STK11m NSCLC patients is widely recognized. Bemcentinib represents a novel treatment modality which may significantly improve the outcome for patients, and we are pleased to have achieved this important milestone." Contacts Martin Olin CEO, BerGenBio ASA [email protected] Rune Skeie, CFO, BerGenBio ASA [email protected] Investor Relations / Media Relations Jan Lilleby [email protected] About BerGenBio ASA BerGenBio is a clinical-stage biopharmaceutical company focused on developing transformative drugs targeting AXL as a potential cornerstone of therapy for aggressive diseases, including cancer and severe respiratory infections. The Company is focused on its proprietary lead candidate, bemcentinib, a potentially first-in-class selective AXL inhibitor in development for STK11 mutated NSCLC and severe respiratory infections. BerGenBio is based in Bergen, Norway with a subsidiary in Oxford, UK. The company is listed on the Oslo Stock Exchange (ticker: BGBIO). For more information, visit Forward looking statements This announcement may contain forward-looking statements, which as such are not historical facts, but are based upon various assumptions, many of which are based, in turn, upon further assumptions. These assumptions are inherently subject to significant known and unknown risks, uncertainties, and other important factors. Such risks, uncertainties, contingencies and other important factors could cause actual events to differ materially from the expectations expressed or implied in this announcement by such forward-looking statements. This information is considered to be inside information pursuant to the EU Market Abuse Regulation and subject to the disclosure requirements pursuant to section 5-12 of the Norwegian Securities Trading Act. This information was brought to you by Cision