Rogel Cancer Center: University of Michigan

Research to Study TUSC2 Combined with ALK-Inhibitors Collaboration with Non-Profit Patient-Focused Research Group Expands Potential Lung Cancer Patient Population for Reqorsa® Gene Therapy AUSTIN, Texas , Oct. 24, 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 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. "We are excited to collaborate with the University of Michigan Rogel Cancer Center and ALK Positive, a group that is dedicated to helping patients with this specific subset of lung cancer, to further study how REQORSA in combination with ALK-inhibitors may be a potential therapeutic treatment for ALK+ lung cancer," said Ryan Confer, President and Chief Executive Officer at Genprex. "TUSC2 is often deleted or inactivated in certain types of cancer. Our preclinical data in cell lines with ALK translocations indicate that REQORSA may be effective in combination with ALK inhibitors, and the work in this SRA will build on our earlier studies." As the Company further expands its research program to new tumor targets, REQORSA in combination with ALK-inhibitors could be a potential therapeutic treatment for ALK+ lung cancer. TUSC2 is a tumor suppressor gene that is frequently deleted in lung cancer. In fact, approximately 82% of all non-small cell lung cancers (NSCLCs) have decreased amounts of the TUSC2 tumor suppressor protein. ALK translocations are found in approximately 5% of NSCLCs. Research collaborators at the Rogel Cancer Center's Judith Tam ALK Lung Cancer Research Initiative presented positive preclinical data at the April 2024 American Association for Cancer Research (AACR) Annual Meeting, reporting that REQORSA induced apoptosis in alectinib resistant EML4-ALK positive NSCLC cell lines. Alectinib is an ALK-inhibitor commonly used to treat patients with ALK rearrangements such as EML4-ALK positive NSCLCs. Researchers found that overexpressing TUSC2 using REQORSA treatment in ALK+ lung cancer cell lines inhibited the ability of the cells to form colonies. Ultimately, the study found that the use of REQORSA or a TUSC2-containing plasmid to overexpress TUSC2 in ALK+ NSCLC cell lines was effective in decreasing cell growth and proliferation through the activation of apoptotic pathways. Researchers believe the results of this preclinical work support further clinical study of REQORSA as an anti-ALK NSCLC treatment strategy. Genprex believes this research suggests that REQORSA may be an effective treatment in patients progressing on alectinib. To review the poster presented at the April 2024 AACR Annual meeting, visit Genprex's website. ALK+ lung cancer is a subset of NSCLC that impacts young and relatively healthy individuals. Since the discovery of the ALK-EML4 translocation, there has been research into targeting and treating this malignancy, which has led to approval by the U.S. Food and Drug Administration (FDA) of various ALK-targeted therapies including crizotinib, alectinib and lorlatinib. Although these compounds provide significant benefit in treating ALK-EML4-driven malignancies initially, resistance ultimately develops. The 5-year survival rate of ALK-EML4 translocated lung cancers is 40.9%, which is higher than other types of lung cancer, but the Company believes this percentage leaves substantial room for improvement. About Reqorsa® Gene Therapy REQORSA (quaratusugene ozeplasmid) for NSCLC and small-cell lung cancer (SCLC) consists of the TUSC2 gene expressing plasmid encapsulated in non-viral nanoparticles made from lipid molecules (Genprex's ONCOPREX® Delivery System) with a positive electrical charge. REQORSA is injected intravenously and specifically targets cancer cells, which generally have a negative electrical charge. REQORSA is designed to deliver the functioning TUSC2 gene to cancer cells while minimizing their uptake by normal tissue. REQORSA has a multimodal mechanism of action whereby it interrupts cell signaling pathways that cause replication and proliferation of cancer cells, such as the ALK pathway, re-establishes pathways for programmed cell death, or apoptosis, in cancer cells, decreases cancer cell energy production by decreasing glycolysis, and modulates the immune response against cancer cells. Genprex's strategy is to develop REQORSA in combination with currently approved therapies and believes that REQORSA's unique attributes position it to provide treatments that improve on these current therapies for patients with NSCLC, SCLC, and possibly other cancers. 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, 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: REQORSA's potential as a therapeutic treatment in combination with ALK-inhibitors for ALK-positive 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. (877) 774-GNPX (4679) GNPX Investor Relations [email protected] GNPX Media Contact Kalyn Dabbs [email protected] SOURCE Genprex, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Researchers are one step closer to understanding how pediatric DIPG tumors work. Researchers at the University of Michigan Health Rogel Cancer Center are one step closer to understanding how pediatric DIPG tumors work. Diffuse intrinsic pontine glioma, or DIPG, is the most aggressive pediatric brain tumor and incredibly difficult to treat since surgery isn't feasible and recurrence is likely after radiation. These tumors are often defined by the H3K27M driver histone mutation. Rogel researchers, led by Daniel Wahl, M.D., Ph.D., wanted to understand how this mutation affects DIPG tumor metabolism and influences radiation resistance. "These questions pointed us straight to purine metabolism," said Wahl, associate professor of radiation oncology and neurosurgery. The findings were published in Cancer & Metabolism. Wahl's team has previously explored how purines are metabolized in adult glioblastoma, including a clinical trial to see how blocking purine metabolism improves treatment success. Here, the team tried a similar method of inhibiting purine synthesis. While it worked well in DIPG cells, it was less impressive in animal models. Wahl explains that, unlike many adult glioblastomas, DIPG tumors seem to rely on two different routes to make purines. He likens it to a road with two on-ramps. "In adult GBMs, one of these on-ramps seems to be blocked, almost like it's under construction. If you block the second on-ramp with a drug, it's a real problem for the tumor. But in these pediatric brain tumors, both on-ramps appear to be wide open. So a drug that just blocks one of them doesn't really slow down the DIPGs." Although there isn't a drug available to block this "second" on-ramp, Wahl was able, through genetic silencing, to stop purines from being made inside the cell. "When we did that, radiation worked great," Wahl said. Erik Peterson, lead author and cancer biology graduate student agrees: "A better understanding of how these tumors evade treatment means that we're better equipped to develop new strategies to beat them at their own game and improve the outlook for kids with this disease." Next, the researchers want to build on these findings to better understand why pediatric DIPG tumors rely on a different route from adult tumors, and how they can develop therapies to block it. With this additional work, the research team is hopeful that they could make a dent in this disease for patients in the future. Additional authors: Peter Sajjakulnukit, PhD, Andrew J. Scott, PhD, Caleb Heaslip, Anthony Andren, Kari Wilder-Romans, Weihua Zhou, PhD, Sravya Palavalasa, MBBS, PhD, Navyateja Korimerla, PhD, Angelica Lin, Alexandra O'Brien, Ayesha Kothari, Zitong Zhao, Li Zhang, PhD, Meredith A. Morgan, PhD, Sriram Venneti, MD, PhD, Carl Koschmann, MD, Nada Jabado, MD, PhD, Costas A. Lyssiotis, PhD, Maria G. Castro, PhD Funding: ChadTough Defeat DIPG Foundation, Alex's Lemonade Stand, Rogel Cancer Center,

When white blood cells, meant to protect the body from infection, are overly activated, they eject their DNA into nets, further disrupting the immune system and making patients more likely to develop a potentially severe reaction to immunotherapy. A new study from the University of Michigan Health Rogel Cancer Center reveals a connection between the most common type of white blood cells, which act as a first defense in the body's immune system, and a severe complication of CAR T-Cell immunotherapy. The findings, out now in Blood Advances, show that a process called NETosis, in which neutrophils eject their DNA to create webs, may contribute to the development of cytokine release syndrome (CRS), a potentially life-threatening hyper-activation of the immune system. Further, the team, led by Muneesh Tewari, M.D., Ph.D., Ray and Ruth Anderson-Laurence Sprague Memorial Research Professor in the Department of Internal Medicine, and Sung Won Choi, M.D., M.S., Edith S. Briskin and Shirley K. Schlafer Foundation Research Professor of Pediatrics, identified certain proteins that are biomarkers of NETosis and could predict which patients are likely to develop CRS before they develop symptoms. Tewari explains that there are FDA-approved drugs that can be used to affect neutrophils, like disulfiram used to treat alcohol abuse. Though typically prescribed for other conditions, these drugs could be leveraged to inhibit NETosis and prevent CRS. "We identified biomarkers that are part of the 'nets' the neutrophils cast, and an indication that CRS is likely to occur," Tewari said. "In addition to this strong correlation, we hypothesize that NETosis is also contributing to the development of CRS. We want to test this idea in preclinical models, and eventually in clinical trials, to see if we can inhibit the net formation and reduce the risk of CRS in patients." Over 70% of patients develop cytokine release syndrome; about 15%-20% of those cases are severe and could require admission to an intensive care unit because of low blood pressure, increased heart rate, shortness of breath, or major organs shutting down. Patients can develop cytokine release syndrome within a week after receiving CAR T-cell infusions. Tewari explains that little is known about the mechanisms happening during that first week, before CRS symptoms are present. Given this lack of knowledge, the research team used proteomics analysis to measure hundreds of proteins in blood samples from patients who underwent CAR T-cell therapy, both those who went on to develop CRS and those who didn't. "We found dozens of proteins that seem to be different in patients who go on to develop CRS versus those who don't. We also found less than 10 proteins that seemed to be different before patients developed CRS, even before they got the treatment," Tewari explained. The team also analyzed what proteins in the blood plasma change over time as CRS developed. "We noticed that neutrophil-related proteins were coming up. That tipped us off to think more about neutrophils specifically, which let us to NETosis," Tewari said. The process of NETosis is like its name suggests. When neutrophils are triggered, which normally might happen at the onset of a bacterial infection, for example, they eject their DNA, which is packed tightly inside the nucleus, into structures resembling "nets" that can capture and contain the bacteria. In patients that go on to develop CRS, Tewari explains that while there is "no bacteria, per se," the neutrophils are confused and act as though there's an invader. "We don't yet know why, but in some patients, their neutrophils are already triggered and on high alert. They're already forming these nets, which activates the entire immune system and makes their bodies more prone to over-react by making a flood of cytokines, producing CRS." In addition to pursuing clinical trials to see if certain FDA-approved drugs can help suppress NETosis, Tewari says this study could help reveal how stress affects the body on a cellular level. "We're seeing more and more how a triggered immune system makes a difference in terms of outcomes, especially with cytokine release syndrome," Tewari said. "There's early data to suggest that psychological stress can affect neutrophil function. This study is another piece of the puzzle that could lead to more insights into how stress can negatively impact the body and contribute to illness."