Genprex Announces Research Agreement with University of Michigan Rogel Cancer Center and ALK Positive Lung Cancer Study Collaboration

Genprex, Inc., a clinical-stage gene therapy company, revealed a new research initiative aimed at studying the tumor suppressor gene TUSC2, employed in their flagship drug candidate Reqorsa® Gene Therapy (quaratusugene ozeplasmid). The collaboration is part of a Sponsored Research Agreement (SRA) with the University of Michigan Rogel Cancer Center and is focused on TUSC2 in combination with ALK-inhibitors to treat ALK-EML4 positive translocated lung cancer. Additionally, Genprex has entered into a collaboration with ALK Positive, a non-profit research group dedicated to enhancing the life expectancy and quality of life for patients with ALK-positive lung cancer. Both Genprex and ALK Positive will share the costs of the SRA with the Rogel Cancer Center.

Ryan Confer, President and CEO of Genprex, expressed enthusiasm about the collaboration, highlighting the potential of REQORSA in combination with ALK inhibitors as a therapeutic treatment for ALK-positive lung cancer. He noted that TUSC2 is often deleted or inactivated in various cancers, and preliminary data indicate that REQORSA may be effective when combined with ALK inhibitors. This new study aims to build on previous research findings.

The expansion of Genprex's research program to target new tumors may reveal that REQORSA combined with ALK-inhibitors could be an effective treatment for ALK-positive lung cancer. TUSC2, a tumor suppressor gene, is frequently found to be deleted in lung cancer cases. Approximately 82% of non-small cell lung cancers (NSCLCs) show reduced levels of the TUSC2 protein, while ALK translocations are detected in about 5% of NSCLCs.

Researchers from the Rogel Cancer Center's Judith Tam ALK Lung Cancer Research Initiative presented promising preclinical data at the April 2024 American Association for Cancer Research (AACR) Annual Meeting. They reported that REQORSA induced apoptosis in alectinib-resistant EML4-ALK positive NSCLC cell lines. Alectinib, an ALK-inhibitor, is commonly used to treat patients with ALK rearrangements like EML4-ALK positive NSCLCs. The study showed that overexpressing TUSC2 using REQORSA in ALK-positive lung cancer cell lines inhibited their ability to form colonies. The researchers concluded that the use of REQORSA or a TUSC2-containing plasmid to overexpress TUSC2 was effective in reducing cell growth and proliferation through apoptosis pathways. These findings support further clinical investigations of REQORSA as a potential treatment for ALK-positive NSCLC.

ALK-positive lung cancer is a subset of NSCLC affecting younger and relatively healthy individuals. Since the discovery of the ALK-EML4 translocation, targeted therapies have been developed, leading to FDA approvals of drugs like crizotinib, alectinib, and lorlatinib. While these therapies offer significant initial benefits, resistance often develops. The five-year survival rate for ALK-EML4 translocated lung cancers stands at 40.9%, suggesting room for improvement.

REQORSA Gene Therapy, designed for NSCLC and small-cell lung cancer (SCLC), consists of the TUSC2 gene encapsulated in non-viral nanoparticles made from lipid molecules, known as Genprex's ONCOPREX® Delivery System. Injected intravenously, REQORSA targets cancer cells, delivering the functional TUSC2 gene while minimizing uptake by normal tissue. REQORSA disrupts cancer cell signaling pathways that lead to replication and proliferation, reinstates apoptosis pathways, decreases cancer cell energy production, and modulates the immune response against cancer cells.

Genprex aims to develop REQORSA in combination with approved therapies, leveraging its unique attributes to enhance current treatments for patients with NSCLC, SCLC, and potentially other cancers. Their oncology program uses the systemic, non-viral Oncoprex® Delivery System, which encapsulates gene-expressing plasmids in lipid-based nanoparticles. The product is administered intravenously and taken up by tumor cells, which then express deficient tumor suppressor proteins. REQORSA is being evaluated in clinical trials for NSCLC and SCLC, both of which have received FDA Fast Track Designations. Additionally, the SCLC program has an FDA Orphan Drug Designation.

Genprex's approach to diabetes gene therapy involves an innovative infusion process using an AAV vector to deliver Pdx1 and MafA genes directly to the pancreas. In Type 1 diabetes models, this transforms alpha cells into insulin-producing beta-like cells. For Type 2 diabetes, the approach rejuvenates and replenishes exhausted beta cells.

Genprex collaborates with renowned institutions to develop drug candidates and advance their gene therapy pipeline, aiming to provide novel treatment approaches for cancer and diabetes patients.