Genprex, Inc. is a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes.The Company’s technologies are designed to administer disease-fighting genes to provide new treatments for large patient populations with limited options. Genprex is working with world-class institutions and collaborators to develop drug candidates to advance its pipeline of gene therapies using novel treatment approaches.
The Company’s oncology program employs its proprietary, non-viral ONCOPREX® Nanoparticle Delivery System, which the Company believes is the first systemic gene therapy delivery platform used to treat cancer in human clinical trials. ONCOPREX encapsulates the gene-expressing plasmids using lipid nanoparticles, with the resulting product dispensed intravenously, where it is then taken up by tumor cells that express deficient proteins. This avoids intertumoral administration and allows the drug to circulate throughout the body, entering cancer cells in the main tumor and distant sites.
Genprex’s lead product candidate, REQORSA™ Immunogene Therapy, 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 (1) interrupt cell signaling pathways that cause replication and proliferation of cancer cells; (2) re-establish pathways for apoptosis, or programmed cell death, in cancer cells; and (3) modulate the immune response against cancer cells. REQORSA has also been shown to block mechanisms that create drug resistance.
In 2020, the U.S. Food and Drug Administration (FDA) granted Fast Track Designation (FTD) to REQORSA for NSCLC in combination therapy with AstraZeneca’s Tagrisso® (osimertinib) for patients whose tumors progressed after treatment with Tagrisso.
In June 2021, Genprex initiated the Phase 1/2 Acclaim-1 study testing REQORSA in combination with Tagrisso. This strategy combines an EGFR drug that stops signals for tumor growth with the gene that signals tumor suppression and cell death. The study has a planned enrollment of about 92 patients at 15 clinical sites.
In 2021, the U.S. FDA granted FTD for REQORSA for NSCLC in combination therapy with Merck & Co’s Keytruda® (pembrolizumab) for patients whose disease progressed after treatment with Keytruda. The designation permits the Company to increase its engagement with the FDA concerning the drug data and requirements for development, as well as provides for the potential of an accelerated or rolling review, with a 6-month timeframe (versus the standard 10-month review).
In March 2022, the Company opened patient enrollment of its Acclaim-2 clinical trial, its open-label, multi-center Phase 1/2 clinical trial evaluating REQORSA in combination with Keytruda® in patients with late-stage NSCLC whose disease progressed after treatment with Keytruda. The first patient was dosed in April 2022. This trial could determine safety, tolerability, and improvement over checkpoint inhibitor immunotherapy alone. The Company expects to begin screening patients in the very near term for their eligibility to participate in the trial.
According to the World Health Organization (WHO), in 2020 lung cancer was the leading cause of cancer deaths worldwide, causing more deaths than colorectal, breast, liver or stomach cancers, with 2.2 million new lung cancer cases and 1.8 million deaths worldwide.In 2022, roughly 236,740 new cases of lung cancer are expected to be diagnosed in the U.S. and 130,180 people will die from the disease, with NSCLC representing 84% of all lung cancers and the five-year survival rate for patients with NSCLC with distant spread being 7%.
Despite advances in surgical techniques, radiation therapy, and systemic therapy, the outlook for patients with lung cancer has improved more slowly than many other cancers over the last 50 years, indicating a significant unmet medical need. Lung cancer mortality rate remains high, with localized stage patients displaying a 57% 5‐year survival prognosis and those patients diagnosed in the distant stage showing a 5‐year survival rate of only 5%.
REQORSA delivers TUSC2, a gene with suppressive actions on pathways for cancer growth and tumor survival, as well as increases in the immune response against cancer. TUSC2 has actions that restore regulatory controls lost in cancer mutations, block certain pathways of cancer growth signaling, and promote pathways of cell death. The behaviors as a suppressor gene and an immune stimulator have given it the name “immunogene therapy.”
Preclinical studies that led to the FTD demonstrated that REQORSA has effects on the immune system that stimulate populations of T-cells and decrease expression of a surface receptor that help cancer cells avoid the immune system (PD-L1), demonstrating possible synergies with Keytruda.
Genprex’s diabetes program (GPX-002) holds promise as a way to replace the beta cells with insulin-producing cells that will evade that immunologic attack. The candidate works well in mice, which have the same mechanisms to control insulin as humans. A Phase 1 clinical trial could be the first gene therapy tested in humans for diabetes.
The Company recently announced that it is expanding its research to include small cell lung cancer (SCLC) as well as NSCLC.Out of the estimated 235,000 patients that are diagnosed each year in the U.S., an estimated 10% to 15% have SCLC and greater than 85% have NSCLC.
Genprex currently holds a worldwide, exclusive license to 18 issued patents and 18 pending patent applications for technologies developed in-house, at the NCI, at MD Anderson, The University of Texas Southwestern Medical Center and the University of Pittsburgh.These patents comprise various therapeutic, diagnostic, technical, and processing claims relating to REQORSA, the ONCOPREX Nanoparticle Delivery System and diabetes technologies.
With a strong balance sheet of $34.6 million in cash as of March 31, 2022 and expert clinical trial management led by Chief Medical Officer and industry veteran Mark Berger, MD who joined Genprex in September 2021 (biography on page 7), Genprex believes that the Company is well positioned to advance its Acclaim-1 and Acclaim-2 clinical trials.