ALK positive Non-Small Cell Lung Cancer

MIAMI--( BUSINESS WIRE )-- Xcovery Holdings, Inc. , an oncology focused pharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for ensartinib, an Anaplastic Lymphoma Kinase (ALK) inhibitor for the treatment of adult patients with metastatic ALK-positive non-small cell lung cancer (NSCLC). The filing is based on the results of the eXalt3, a randomized global phase III study designed to evaluate the efficacy and safety of ensartinib vs crizotinib in the first-line treatment of ALK-positive NSCLC. The FDA granted the application Standard Review and assigned a Prescription Drug User Fee Act (PDUFA) goal date of December 28, 2024. “The FDA’s acceptance of this NDA represents a key milestone for Xcovery in its mission to bring ensartinib as a novel and distinct first-line therapeutic option to ALK-positive NSCLC patients,” said Giovanni Selvaggi, M.D., Chief Medical Officer of Xcovery. “We will continue to work closely with the agency during the review period. This achievement is a testament to our patient-centric vision and has been made possible by the dedication and skills of the entire Xcovery team and stakeholders, with the constant support of the patients, their families and investigators in our clinical trials globally.” Ensartinib is a next generation ALK inhibitor jointly developed by Xcovery and Betta Pharmaceuticals. In the clinical trials, the drug has demonstrated robust and durable responses in ALK-positive NSCLC patients (both systemically and in the brain), with an extensively studied and well manageable safety profile. The results of the eXalt3 were originally published in JAMA Oncology in September 2021. About Xcovery Xcovery is a pharmaceutical company working to improve the lives of patients with cancer by discovering and developing small molecules that precisely target cancer growth mechanisms. Xcovery is developing a pipeline of drugs targeting a wide range of advanced solid tumors with a focus on lung cancer. For more information, visit www.xcovery.com. Forward‐Looking Statements This press release contains forward‐looking statements that are based on company management’s current beliefs and expectations and are subject to currently unknown information, risks and circumstances and actual results may vary from what is being currently projected.

PLYMOUTH, Mass.--( BUSINESS WIRE )--IDRx, Inc., a clinical-stage biopharmaceutical company dedicated to transforming cancer treatment with purpose-built precision therapies, today announced that it has strengthened its leadership team with the appointments of Tim Clackson, Ph.D. as Chief Executive Officer, and Brad Dahms as Chief Financial Officer and Chief Business Officer. Ben Auspitz, IDRx’s co-founder and founding CEO, and also co-founder of Forge Life Science Partners, will become Chairman of the IDRx Board of Directors. “I am thrilled to join the Company at this important stage of our development. At CTOS in November 2023, IDRx announced preliminary clinical data supporting the best-in-class potential of IDRX-42 in patients with GIST, for which a new therapy in the second line or front line has not been approved in nearly two decades,” said Dr. Clackson. “We are well-positioned to address the significant unmet need for patients with GIST, and I am humbled to be a part of such a talented team to further advance IDRX-42.” Dr. Clackson brings three decades of experience building oncology companies, including three oncology drug approvals. Dr. Clackson was most recently Chief Executive Officer of Theseus Pharmaceuticals, a clinical stage biotechnology company focused on development of precision oncology therapies, where he led the Company through its initial public offering and early clinical development for its lead product candidate for the treatment of GIST. Prior to Theseus, Dr. Clackson served as President at Xilio Therapeutics, a privately held oncology company developing tumor-selective immunotherapies, where he led the development of the Company's technology and product strategy. From 1994 to 2018, Dr. Clackson was with ARIAD Pharmaceuticals, where he held several leadership positions including President of Research & Development and Chief Scientific Officer. He played a key role in the company's evolution from early research to a global commercial oncology company, and its subsequent acquisition by Takeda. He led the multi-disciplinary R&D team that internally discovered and developed five clinical-stage product candidates, including ICLUSIG® (ponatinib), approved for patients with treatment-resistant Ph+ leukemias; ALUNBRIG® (brigatinib), approved for ALK+ non-small cell lung cancer (NSCLC); and EXKIVITY™, approved for Exon20 insertion+ NSCLC. Prior to ARIAD, Dr. Clackson was a postdoctoral research fellow at Genentech. He received his Ph.D. in Biology from the University of Cambridge, and his B.A. in Biochemistry from the University of Oxford. Dr. Clackson serves as a Director on the Board of Elevation Oncology and previously served as a. Director on the Boards of Forma Therapeutics (acquired by Novo Nordisk) and the Massachusetts Biotechnology Council (MassBio). “Tim brings an impressive track record of clinical execution with multiple drug approvals and Brad brings a wealth of experience strategically growing and financing companies,” said Mr. Auspitz. “We welcome their leadership as we continue to build the company and advance IDRX-42 with the goal of bringing a new therapy to GIST patients for whom current therapies continue to be limited by drug resistance and toxic side effects from available treatments.” Mr. Dahms was most recently Chief Financial Officer of Theseus Pharmaceuticals, where he led capital raises totaling approximately $230 million, including Theseus’ $180 million initial public offering. Mr. Dahms oversaw financial operations, information technology, business development, and investor/public relations. He led the sale of the Company to Concentra Biosciences. Prior to Theseus, Mr. Dahms served as Chief Financial Officer of Selecta Biosciences, Inc., where he oversaw financial operations, information technology, investor relations, and business development activities. He led Selecta through several significant financing and strategic transactions, including a $730 million licensing agreement for its lead program. Previously, Mr. Dahms was a Senior Vice President in the Healthcare Group at Cantor Fitzgerald & Co., focused on providing strategic and financial advice to life sciences companies. Prior to Cantor, Mr. Dahms held several other investment banking roles, including at RBC Capital Markets in the Healthcare Group, and at J.P. Morgan. Mr. Dahms earned a B.S. in Economics, with honors, from The Ohio State University. “I look forward to working with Tim, Ben, and the team at IDRx to grow the Company with the backbone of IDRX-42,” said Mr. Dahms. “The opportunity in GIST is large and unmet, and we have multiple paths to evaluate as we scale the Company for the benefit of patients and our investors.” About GIST Gastrointestinal stromal tumors (GIST) are the most common subtype of soft tissue sarcoma. Approximately 80% of cases arise from gain of function mutations in the KIT receptor tyrosine kinase, driving the malignancy through constitutive activation of aberrant signaling. Resistance mutations in KIT emerge in ~90% of patients treated with imatinib, the current standard of care for GIST. In unresectable or metastatic GIST, clinical benefits from existing treatments can vary by mutation type. About the IDRx Pipeline IDRX-42 is a potent, oral, highly selective KIT inhibitor targeting all major categories of activating and resistance mutations in patients with KIT-mutant GIST (including variants in exons 9, 11, 13 and 17). IDRX-42 is currently being evaluated in a first-in-human Phase 1/1b study, and clinical data to date suggest this therapy may represent a best-in-class therapy for GIST. IDRx is also developing IDRX-73, a highly selective inhibitor of exon-13-mutant KIT, which could provide future optionality in clinical development. An investigational new drug (IND) application for IDRX-73 was recently cleared by the FDA. About IDRx IDRx is a clinical-stage biopharmaceutical company dedicated to transforming cancer care with intelligently designed precision therapies. IDRx aims to address the limitations of today’s precision cancer medicines with highly potent and selective targeted therapies to stop key tumor escape mechanisms and prolong response to therapy. IDRx’s lead program is IDRX-42, designed to inhibit key genetic drivers and drug-resistant mutations of KIT in gastrointestinal stromal tumor (GIST). IDRx's pipeline also includes a second KIT inhibitor, IDRX-73. Founded in 2021, IDRx’s leadership team has extensive experience in drug development and collectively has been involved in the discovery, development, and commercialization of more than 10 approved drugs. To learn more, please visit www.idrx.com and follow us on LinkedIn .

Reqorsa® Immunogene Therapy May be a Potential Therapy for ALK-Positive Lung Cancer REQORSA has Anti-Tumor Mechanisms that Target and Disrupt the Metabolism of Cancer Cells NPRL2 Gene Therapy Induces Effective Anti-Tumor Immunity in Non-Small Cell Lung Cancer Humanized Mouse Model AUSTIN, Texas, March 6, 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 will present at the upcoming 2024 American Association for Cancer Research (AACR) Annual Meeting being held April 5-10, 2024 in San Diego, California. The collaborators will present positive preclinical data from studies of its lead product candidate, Reqorsa® Immunogene Therapy (quaratusugene ozeplasmid), as well as NPRL2 gene therapy, which both utilize the Company's non-viral Oncoprex® Delivery System for the treatment of lung cancer. "We are delighted to have our academic partners present this compelling body of preclinical evidence that support the therapeutic use of REQORSA to deliver the functioning TUSC2 gene to cancer cells. The data also highlights the potential use of our non-viral ONCOPREX Delivery System to deliver other tumor suppressor genes, such as the NPRL2 gene," said Rodney Varner, Chairman, President and Chief Executive Officer at Genprex. "We are pleased to have favorable results from three preclinical studies presented to an audience of global oncology specialists, providing further validation of the value of REQORSA and ONCOPREX in the fight against cancer." Featured Genprex-supported posters to be presented at AACR 2024 include: Title: "Quaratusugene ozeplasmid mediated TUSC2 upregulation in EML4-ALK bearing Non-Small Cell Lung Carcinoma can induce cellular apoptosis" Session Category: Molecular/Cellular Biology and Genetics Session Title: Apoptosis and Ferroptosis Session Date and Time: Sunday, April 7 from 1:30 pm – 5:00 p.m. PT Location: Poster Section 15 Poster Board Number: 7 Abstract Presentation Number: 351 Anaplastic Lymphoma Kinase (ALK) is a strong oncogenic driver in non-small cell lung carcinoma (NSCLC) and contributes to ~5% of NSCLC as a distinct clinicopathological subset. In this nonclinical study TUSC2 expression in three ALK+ cell lines were evaluated before and after exposure to REQORSA, referred to as TUSC2 gene therapy in the abstract, and to a TUSC2-containing plasmid. Researchers at the University of Michigan Rogel Cancer Center Judith Tam ALK NSCLC research initiative found that overexpressing TUSC2 via REQORSA treatment in ALK+ lung cancer cell lines had the ability to inhibit colony formation by 50%, which indicates that REQORSA inhibits growth of ALK+ lines. Additionally, researchers documented a strong pro-apoptotic response to TUSC2 expression in ALK+ NSCLC. 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. Researchers believe the results support further clinical study of REQORSA as an anti-ALK NSCLC treatment strategy. Title: "Tumor Suppressor Gene TUSC2 suppresses energy metabolism in lung cancer cells with opposite effects in normal bronchial epithelial cells" Session Category: Experimental and Molecular Therapeutics Session Title: Cancer Biology and Metastasis Session Date and Time: Monday, April 8 from 1:30 p.m. – 5:00 p.m. PT Location: Poster Section 22 Poster Board Number: 6 Abstract Presentation Number: 3158 TUSC2 is a tumor suppressor gene often deleted in lung cancers and reduced TUSC2 expression is observed in approximately 80% of lung cancers. TUSC2 is also reduced in mesothelioma, breast, head-and neck, osteosarcoma, glioblastoma, and other cancers, which suggests the important anti-tumor role of TUSC2. Additionally, TUSC2 is known to play a critical role in mitochondrial respiration/energy metabolism as TUSC2 protein localizes to the mitochondria. Here, researchers investigated how human lung cancer cell lines A549 and H358, with decreased TUSC2 expression, alter their energy metabolism when TUSC2 protein is re-introduced. The study found that the TUSC2-deficient cancer cells consistently exhibited decreased glycolytic rates and mitochondrial ATP production. This is significant as it left these cells without enough energy to support their vital functions. By comparison, when Beas2B, a normal human bronchial epithelial cell line with normal levels of TUSC2, was transfected with a TUSC2 containing plasmid, the glycolytic rate and mitochondrial metabolism was increased, which suggests that this may be the mechanism by which REQORSA treatment affects immune and other non-cancerous cells that leads to increased immune response against tumors. The study further suggested that REQORSA may play an important role as a cancer treatment to target and disrupt the metabolism of cancer cells, leading to a decrease in the rate of glycolysis. Genprex currently has three clinical trials evaluating REQORSA in lung cancer. All three clinical trials have received U.S. Food and Drug Administration (FDA) Fast Track Designation. The Acclaim-1 clinical trial is an open-label, multi-center Phase 1/2 clinical trial evaluating REQORSA in combination with Tagrisso® (osimertinib) in patients with late-stage NSCLC with activating epidermal growth factor receptor (EGFR) mutations whose disease progressed after treatment with Tagrisso. Genprex completed the Phase 1 dose escalation portion of the trial and has already dosed the first patient in the Phase 2a expansion portion of the trial. The Acclaim-2 clinical trial is an open-label, multi-center Phase 1/2 clinical trial evaluating REQORSA in combination with Keytruda® (pembrolizumab) in patients with late-stage NSCLC whose disease progressed after treatment with Keytruda. The Acclaim-3 clinical trial is an open-label, multi-center Phase 1/2 clinical trial evaluating REQORSA in combination with Tecentriq® (atezolizumab) as maintenance therapy in patients with extensive-stage small-cell lung cancer (ES-SCLC) who did not develop tumor progression after receiving Tecentriq and chemotherapy as an initial treatment. The Acclaim-3 clinical trial also has FDA Orphan Drug Designation. Title: "Mechanism of NPRL2 gene therapy induced anti-tumor immunity in KRAS/STK11mt aPD1 resistant metastatic NSCLC" Session Category: Immunology Session Title: Inflammation, Host Factors, and Epigenetic Influences on Cancer Development and Treatment Session Date and Time: Monday, April 8 from 9:00 a.m.– 12:30 p.m. PT Location: Poster Section 5 Poster Board Number: 18 Abstract Presentation Number: 1420 Among other cancer types, NSCLC often has reduced NPRL2, a tumor suppressor gene, and the restoration of NPRL2 activates cell cycle arrest and apoptosis. In this humanized mouse model, researchers investigated the anti-tumor immune responses to NPRL2 gene therapy in pembrolizumab resistant KRAS/STK11mt NSCLC. In the study, induced lung metastases in humanized mice were treated through I.V. injection of NPRL2 nanoparticles, made with the ONCOPREX Delivery System, with or without pembrolizumab. The study found that the NPRL2 treatment decreased lung metastases but pembrolizumab had no effect. Additionally, a greater anti-tumor effect was seen in humanized compared to non-humanized mice, demonstrating that immune cells play a role in the effects of the NPRL2 nanoparticle therapy. Study findings suggest that NPRL2 gene therapy induces anti-tumor activity against KRAS/STK11mt tumors through dendritic cell-mediated antigen presentation and cytotoxic immune cell activation. Genprex Commentary: "Today's bolus of compelling data validates the potential of REQORSA and the ONCOPREX Delivery System as innovative cancer treatments. We were very encouraged to see the data document REQORSA's anti-tumor properties and demonstrate its ability to suppress cell growth and trigger cancer cell death," said Mark Berger, MD, Chief Medical Officer at Genprex. "These data are particularly significant as decreased TUSC2 expression is seen in approximately 80% of lung cancers, and REQORSA has the potential to address a large patient population. Additionally, data showing NPRL2 gene therapy induced anti-tumor activity further positions Genprex to expand its clinical pipeline with another drug candidate, and it reinforces the value of ONCOPREX's ability to deliver genes beyond TUSC2. We look forward to continuing to evaluate the ONCOPREX Delivery System using both REQORSA and NPRL2 as potential treatments for lung cancer." 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 nanoparticles. 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-003 for Type 2 diabetes, where autoimmunity is not at play, is believed to rejuvenate and replenish exhausted beta cells. For more information, please visit the Company's web site at or follow 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, 2022. 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