Drug Candidate for Lung Cancer Receives FDA Fast Track Designation

Recently, gene therapy company Genprex announced that it had received US Food and Drug Administration (FDA) Fast Track Designation for Oncoprex, a lead drug candidate that treats non-small cell lung cancer (NSCLC) patients in combination with the EGFR inhibitor omistertin.

Oncoprex specifically targets cancer cells and re-establishes pathways for cancer cell death. In clinical trials the drug has been well tolerated in a cohort of 50 cancer patients. Technology Networks spoke with Rodney Varner, CEO of Genprex, to learn more about the next steps for Oncoprex and how the FDA Fast Track Designation will facilitate the delivery of this drug to cancer patients.

Laura Elizabeth Lansdowne (LL): How is Genprex “reprogramming the course of cancer”?

Rodney Varner (RV): Genprex is reprogramming the course of cancer by developing potentially life-changing gene therapies for cancer patients through unique, innovative science. Genes provide the messaging to our bodies’ cells which control the natural course of the cells’ lives. When defective or missing genes interrupt or interfere with this messaging, cells can prolifertate uncontrollably, leading to cancer. Our novel platform enables us to replace or supplement missing or deficient tumor suppressor genes. In doing so, we can reestablish proper cell signaling and causing cells to replicate and die appropriately, thus inhibiting tumor growth. It is analogous to replacing defective software code.

LL: What are some of the key benefits for using targeted molecular therapies and immunotherapies to treat cancer?

RV: Targeted molecular therapies and immunotherapies target cancer at its core, by focusing on the specific genetic and cellular defects and deficiencies that cause cancer. The therapies are targeted toward cells that have these defects, as opposed to the body in general. Preclinical and clinical data indicate that Genprex’s lead drug candidate Oncoprex is synergistic with a number of these targeted therapies and immunotherapies, meaning that the combination is more effective than either drug alone.

Genprex is bridging a critical gap in cancer treatment by combining its immunogene therapies with approved targeted and immunotherapies to provide treatments to large patient populations who would otherwise not be candidates for those drugs or who cannot currently benefit from the available approved drugs alone.

LL: Can you tell us more about the development of your lead candidate Oncoprex?

RV: Oncoprex consists of a tumor suppressor gene, the TUSC2 gene, which is typically missing or deficient in lung cancer patients. Generally, the missing or malfunctioning gene is what caused the patient’s cancer to spread. By restoring the healthy TUSC2 gene, Oncoprex works to help the cancer cells begin producing the subsequently encoded protein that causes the cancer cells to die.

Oncoprex 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. Oncoprex has also been shown to block mechanisms that create drug resistance.

Molly Campbell (MC): Can you tell us more about the clinical trials in which Oncoprex was tested and the results of the trials?

RV: Currently, a Phase I/II clinical trial is underway evaluating Oncoprex in combination with erlotinib in stage IIIB/IV lung cancer patients without an activating EGFR mutation and in patients with an activating EGFR mutation whose cancer has progressed on erlotinib therapy.So far, the findings show that Oncoprex works synergistically with erlotinib to help destroy the cancer cells and may help patients who have become resistant to erlotinib alone.

• A Phase I clinical trial showed that Oncoprex selectively and preferentially targets primary and metastatic tumor cells, and it established a maximum tolerated dose
  
  
• Interim data from a Phase I/II trial using Oncoprex in combination with erlotinib for NSCLC  showed a 78% disease control rate
  
  
• One patient in the Phase II combination trial had a complete response

We are also conducting preclinical studies to evaluate Oncoprex in combination with checkpoint inhibitors.

• Preclinical data has found Oncoprex to increase effectiveness of anti-PD1 immunotherapy and anti-PD1 immunotherapy combined with platinum chemotherapy in a humanized mouse model
  
  
• Preclinical data has shown that Oncoprex combinated with checkpoint blockade was more effective than checkpoint blockade alone in increasing the survival of mice with human immune cells (humanized mice) that had metastatic lung cancer

MC: Gene therapies currently available on the market are considerably more expensive than alternative therapeutics such as chemically synthesized drugs. How are Genprex working to ensure that Oncoprex is affordable?

RV: Some gene therapies require custom formulation of the drug for each patient. Others require use of viruses for delivery which are difficult to manufacture and for which there is limited manufacturing capacity available. Oncoprex is non-viral, and is not specifically manufactured for each patient. It can be manufactured at larger scale, stored for extended periods, and shipped where it is needed. We believe that for these reasons it will ultimately be priced more in-line with small molecule lung cancer drugs than with currently high priced gene therapies.   

MC: How will FDA Fast Designation help to bring Oncoprex closer to treating cancer patients? What are your next steps?

RV: The FDA Fast Track Designation provides us with a few advantages as we work toward bringing Oncoprex to market. The designation will allow us to potentially expedite our pathway to approval through more frequent conversations, meetings and communication with the FDA, as well as eligibility for accelerated approval and priority review.

Our next step is to initiate a clinical trial evaluating Oncoprex in combination with osimertinib. We believe we will be in a position to begin enrolling patients for that trial by mid-year 2020.

Rodney Varner, CEO of Genprex, was speaking to Laura Elizabeth Lansdowne and Molly Campbell, Science Writers, Technology Networks.