On February 7, 2024 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, reported the expansion of its nonclinical programs into new indications through Sponsored Research Agreements and Material Transfer Agreements with multiple academic research collaborators to study TUSC2, the tumor suppressor gene used in Genprex’s lead drug candidate, REQORSA (quaratusugene ozeplasmid), and NPRL2, another tumor suppressor gene (Press release, Genprex, FEB 7, 2024, View Source [SID1234639909]). The new indications being evaluated include ALK-positive lung cancer and other additional programs that are not disclosed at this time.

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"We are developing a robust research program to expand the potential tumor targets, and even non-tumor targets, that we may include in future clinical trials for REQORSA," said Rodney Varner, Chairman, President and Chief Executive Officer at Genprex. "Research indicates that the TUSC2 gene used in REQORSA may benefit many types of cancers and potentially the treatment of other diseases. We are exploring opportunities to treat other cancers in which TUSC2 is often deleted or inactivated, and we are evaluating TUSC2 basic biology to better understand how to use our REQORSA treatment. Finally, we are also exploring the use of another tumor suppressor gene, NPRL2, in cancer treatment using our Oncoprex Nanoparticle Delivery System."

Genprex’s expanded nonclinical programs include these additional studies with TUSC2 and NPRL2:

TUSC2 in ALK-EML4 positive translocated lung cancer at the University of Michigan Rogel Cancer Center
TUSC2 in metabolism at Meharry Medical College in Nashville, Tennessee
NPRL2 in lung cancers with a major cancer research center in Houston, Texas
TUSC2 in ALK-EML4 positive translocated lung cancer at the University of Michigan Rogel Cancer Center’s Judith Tam ALK Lung Cancer Research Initiative:

ALK-EML4 positive translocated lung cancer is a subset of non-small cell lung cancer (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 we believe leaves substantial room for improvement.

TUSC2 is a tumor suppressor gene that is frequently deleted in lung cancer. In fact, approximately 82% of all NSCLCs lack or express decreased amounts of 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 are studying the combination of Genprex’s REQORSA, which uses the TUSC2 tumor suppressor gene, with various ALK inhibitors. An abstract submitted by these researchers was accepted for presentation at the 2024 AACR (Free AACR Whitepaper) Annual Meeting.

TUSC2 Control of Mitochondrial Metabolism at Meharry Medical College:

The TUSC2 gene is encoded in the cell’s DNA in the nucleus, but the TUSC2 protein resides in the inner membrane of the mitochondria. This suggests that TUSC2 protein may be one way in which the cell controls energy production, which largely occurs in the inner membrane of the mitochondria. In addition, mice lacking the TUSC2 gene in all cells, or TUSC2 knock-out mice, can exhibit a number of characteristics consistent with underlying metabolic abnormalities, including premature aging, aging-associated pathologies, and decreased survival. Thus, researchers at Meharry Medical College have been exploring TUSC2 effects on mitochondrial metabolism and have had their work accepted for presentation at the 2024 AACR (Free AACR Whitepaper) Annual Meeting.

NPRL2 in Lung Cancers

Following a presentation on NPRL2 at AACR (Free AACR Whitepaper) 2023, additional research has been performed to evaluate the use of lipid nanoparticles containing the tumor suppressor gene, NPRL2, in mouse xenografts with resistant cancers. This work, which validates Genprex’s ONCOPREX Nanoparticle Delivery System technology as a platform, has been selected for a presentation at the 2024 AACR (Free AACR Whitepaper) Annual Meeting.

Genprex’s ONCOPREX Nanoparticle Delivery System, is a novel non-viral approach that utilizes lipid nanoparticles 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.

About Reqorsa Therapy

REQORSA (quaratusugene ozeplasmid) for NSCLC and SCLC consists of the TUSC2 gene expressing plasmid encapsulated in non-viral nanoparticles made from lipid molecules (Genprex’s ONCOPREX Nanoparticle 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, re-establishes pathways for programmed cell death, or apoptosis, in cancer cells, 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.