REQORSA Enhances Efficacy of Chemo-Immune Combination Therapy in KRAS-LKB1 Mutant NSCLC in Humanized Mice

REQORSA Overcomes Resistance to Targeted Therapy Osimertinib

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 collaborators presented positive preclinical data for the combination of TUSC2 immunogene therapy (REQORSA™) in combination with chemotherapy and immunotherapies for the treatment of non-small cell lung cancer (NSCLC). Collaborators also presented positive preclinical data for the use of REQORSA in combination with targeted therapies for the treatment of NSCLC. These data were presented in two presentations at the 2021 American Association of Cancer Research (AACR) annual meeting. The TUSC2 gene is a tumor suppressor gene and is the active agent in REQORSA.

“We are pleased to have these positive data that provide further support for the therapeutic potential of REQORSA in combination with immunotherapies and targeted therapies in NSCLC presented before an audience of the world’s leading cancer researchers. These data are particularly encouraging as we look to initiate our upcoming combination Acclaim-1 and Acclaim-2 clinical trials of REQORSA in NSCLC,” said Rodney Varner, President and Chief Executive Officer of Genprex. “We know that many patients inevitably develop resistance to immune checkpoint blockade therapy or EGFR-TKI therapy. These data show that REQORSA in combination with immunotherapies and targeted therapies may provide enhanced efficacy in NSCLC that has become resistant to these regimens, offering hope to a large patient population who currently has limited treatment options.”

Featured Genprex-supported posters presented at AACR 21 include:

The first presentation, entitled “TUSC2 immunogene therapy enhances efficacy of chemo-immune combination therapy and induces robust antitumor immunity in KRAS-LKB1 mutant NSCLC in humanized mice,” showed that the triple combination of chemotherapy, immunotherapy (immune checkpoint blockade) and REQORSA demonstrated strong antitumor efficacy and induced robust antitumor immunity in KRAS-LKB1 (KL)-mutant NSCLC in clinically relevant humanized mice models.

In this study, researchers evaluated the antitumor immune response of a chemo-immunotherapy combination with REQORSA on highly metastatic KL-mutant human lung cancer in humanized mice. Humanized mice were first treated with REQORSA, immunotherapy nivolumab (Opdivo®), or the combination. The results showed synergistic antitumor activity with the combination. Next, humanized mice were treated with REQORSA, immunotherapy pembrolizumab (Keytruda®), or the combination. When REQORSA was added to the chemotherapy and immune checkpoint blockade combination, metastases regression was significantly greater than either REQORSA, REQORSA and pembrolizumab, or chemotherapy and pembrolizumab treatments.

“KRAS is a frequent genomic driver in lung adenocarcinoma,” said Michael Redman, Executive Vice President and Chief Operating Officer of Genprex. “LKB1 (also known as STK11) is a distinct subgroup of KRAS-mutants and is the most prevalent genomic driver of resistance to PD-1 blockade in KRAS-mutant lung cancer.”

The second poster, entitled “Overcoming resistance to osimertinib by TUSC2 gene therapy in EGFR-mutant NSCLC,” showed that REQORSA in combination with targeted therapy osimertinib (Tagrisso®) demonstrated synergistic antitumor efficacy in EGFR mutant osimertinib resistant NSCLC tumors in H1975-OsiR isogenic tumors. Researchers also found that the upregulation of PDK1 was associated with osimertinib resistance.

In this study, researchers developed an osimertinib resistant H1975-OsiR isogenic cell line through continuous exposure to osimertinib. Xenograft tumors from both H1975-parental and H1975-OsiR cells were developed in NSG mice and were treated with osimertinib. Synergistic antitumor activity of REQORSA and osimertinib was found in H1975-OsiR tumors. The combinations showed a robust antitumor effect compared with single agent treatment groups. Reverse phase protein array (RPPA) data showed that PDK1 was significantly upregulated in the REQORSA and osimertinib group when compared with either control, osimertinib alone or REQORSA alone treated H1975-OsiR tumors, indicating that PDK1 may be associated with osimertinib resistance. No PDK1 inhibitor effect was found in the REQORSA treated group, implicating the specific role of PDK1 in osimertinib resistance.

These AACR presentations and posters have been made available on Genprex’s website at www.genprex.com.

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. The Company’s lead product candidate, REQORSA™ (quaratusugene ozeplasmid), is being evaluated as a treatment for non-small cell lung cancer (NSCLC). REQORSA has a multimodal mechanism of action that has been shown to interrupt cell signaling pathways that cause replication and proliferation of cancer cells; re-establish pathways for apoptosis, or programmed cell death, in cancer cells; and modulate the immune response against cancer cells. REQORSA has also been shown to block mechanisms that create drug resistance. In January 2020, the U.S. Food and Drug Administration granted Fast Track Designation for REQORSA for NSCLC in combination therapy with osimertinib (AstraZeneca’s Tagrisso®) for patients with EGFR mutations whose tumors progressed after treatment with osimertinib alone.

The Company is preparing to initiate its Acclaim-1 and Acclaim-2 clinical trials for the treatment of NSCLC. Acclaim-1 is an open-label, multi-center Phase 1/2 clinical trial that combines REQORSA with AstraZeneca’s Tagrisso in patients with late-stage NSCLC with mutated epidermal growth factor receptors (EGFRs), whose disease progressed after treatment with Tagrisso. The Acclaim-2 clinical trial will combine REQORSA with Merck & Co’s Keytruda for NSCLC patients who are low expressors (1% to 49%) of the protein programmed death-ligand 1 (PD-L1).

For more information, please visit the Company’s web site at www.genprex.com 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.

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: 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; Genprex’s commercial and strategic partnerships including the scale up of 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.

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