Bringing Gene Therapies To The Masses How one company seeks to provide hope to cancer patients through more effective treatments. Q4 2021 hedge fund letters, conferences and more Cancer is one of the most complex and...

How one company seeks to provide hope to cancer patients through more effective treatments.

Q4 2021 hedge fund letters, conferences and more

Cancer is one of the most complex and difficult to treat diseases, and in 2020, it was estimated that more than 1.8 million new cases of cancer would be diagnosed in the U.S. alone and more than 600,000 patients would die from the disease. As a result, the search for effective cancer treatments remains one of the top priorities in the scientific and medical communities.

Although gene therapy has been enjoying multiple successes in rare diseases, to date success of gene therapy in large patient populations, such as cancer, has been elusive. Some of these successful gene therapies for rare diseases target one specific defective gene that causes the disease. When it comes to cancer, there may be multiple factors that contribute to disease occurrence.

One promising gene therapy treatment approach under development for cancer introduces to a patient so-called "tumor suppressor genes" that are either missing or found in low quantities in the patient. The goal is to improve the effectiveness of medications, enhance the patient's quality of life, and give the patient a better chance at winning the battle against cancer.

Rodney Varner, Chairman, President, and CEO of Genprex, a clinical-stage gene therapy company focused on developing novel gene therapies for very large patient populations, including cancer, discusses how gene therapy could revolutionize cancer treatment and what the company is doing to make that a reality.

Q: What is gene therapy and how does it work?

A: Gene therapy is, in general, the use of therapeutic genes to treat disease. It's useful in diseases where there is a particular gene that causes a disease, or where the gene that is supposed to suppress a disease is absent or not functioning properly.

In gene therapy, a delivery mechanism is used to deliver the missing or defective gene into the cells so that the function of that gene is restored. At Genprex, the active agent in our gene therapy under development to treat non-small cell lung cancer is a tumor suppressor gene called TUSC2, which is found missing or deficient in about 84% of non-small cell lung cancers, which make up the overwhelming majority of all lung cancers.

Q: What have the historical limitations of gene therapy been?

A: Scientists have been attempting to successfully develop a gene-based therapy for more than 30 years. Nearly all have used a virus to deliver the gene to the target. What's done is that a natural virus, like a cold virus, is hollowed out and neutralized so it won't replicate, and DNA is encapsulated in this hollowed-out virus. It's injected into or nearby the patient's cancer tumor, where it carries genetic material into the cell so the therapeutic DNA replaces or supplements the missing DNA in the tumor.

There have been serious limitations, though, to delivering the genes in question to the tumor. Being a virus, the body generally has an immune reaction to it. Historically, many of these immune reactions have been serious. In many cases, viral gene therapy can only be given once because the patient generates an immune defense that could be dangerous after multiple administrations.

Also, viral gene therapies in cancer are given by injection directly into the tumor, or nearby, so the virus is taken up by cancer cells in the tumor. To avoid side effects, gene therapy isn't circulated throughout the body, but that means only the directly targeted tumor is treated. Using this method of gene therapy, metastatic tumors are not able to be treated and any unidentified tumors are not treated. Further, some types of tumors can't be treated with a needle, such as those in the spinal cord or the brain. Genprex has developed a gene therapy using a delivery system that we believe will overcome these limitations.

Q: How is Genprex's approach different from other gene therapies?

A: We've developed a gene therapy that uses a novel non-viral lipid nanoparticle delivery system, instead of a virus. We use the lipid nanoparticle to encapsulate the DNA of the TUSC2 tumor suppressor gene and then inject it into the patient intravenously, instead of a needle injection into the tumor, so the gene therapy circulates throughout the patient's system and attaches to tumors wherever they're found. Our gene therapy restores cells' ability to fight tumors, it doesn't generate an immune response against a virus, and it has shown a favorable safety profile in more than 50 patients treated in our prior clinical trials.

Lipid nanoparticles have been used in drugs for other diseases, but we're the first to use them in gene therapy for cancer in humans. Basically, the lipid nanoparticles are fatty molecules engineered to a certain size. There's a plasmid containing therapeutic DNA encapsulated in the lipid nanoparticles, which are mixed into a liquid solution and injected by IV. They also have an electronic charge, the opposite charge as the cancer cells so they are attracted to them. The lipid nanoparticles carry the DNA through the body, protecting the DNA along the way, and the electrical charge attracts the nanoparticles to the tumors where they're taken up by the tumors at a rate of up to 33 times what they are in normal cells.

Q: What data have you obtained from prior clinical trials?

A: We've done two prior clinical trials. The first one using our lead gene therapy, which we call REQORSATM, alone as a monotherapy against late-stage lung cancer. In that trial, there were 23 patients evaluated, and five of those patients showed a response, either stable disease or better. Also important, the trial showed a very favorable safety profile for REQORSA, as the side effects were minimal compared to other lung cancer drugs.

Then we did a second clinical trial with REQORSA in combination with the cancer drug Tarceva®, which is an EGFR inhibitor, against late-stage lung cancer. Nine patients were evaluated for efficacy in the Phase 2 portion of the trial. Seven of these achieved stable disease or better, and one patient had a complete response, which was the complete elimination of tumors. And again, we saw a very favorable safety profile for REQORSA, similar to what we saw in the first trial.

We treated more than 50 patients in these two clinical trials.

Q: What are the next steps for Genprex?

A: We've received two FDA Fast Track Designations. In order to receive a Fast Track Designation, a company must present all its data related to its drug to the FDA, identify a target patient population where the drug has the potential to be an improvement over existing therapies, and it must be a population that suffers from a serious or life-threatening disease. We are initially targeting lung cancer, which is the leading cause of cancer deaths worldwide.

We've made the Fast Track Designation application twice: one to use REQORSA in combination with TAGRISSO® which is AstraZeneca's largest selling cancer drug. The other application was to use REQORSA with KEYTRUDA®, which is Merck's largest selling drug. And we got both of those Fast Track Designations. Each of our combination therapies targets patients that already take one of these drugs, either TAGRISSO or KEYTRUDA, and become resistant to them. Once patients become resistant to these drugs, their tumors begin to progress again, which happens to the vast majority of these patients.

Our belief is we can extend the time patients can benefit from these drugs and, later, we believe we'll show we can benefit some patients that cannot currently benefit from these existing drugs. Importantly, we're in a position to participate in these large markets. KEYTRUDA has sales of more than $17 billion per year and TAGRISSO has sales of more than $5 billion each year. And we're in a position to participate in those markets without fighting anyone for market share.

We believe our gene therapy drug candidate, REQORSA, will increase the sales of these other existing cancer drugs, not take away from them, all while extending benefits to cancer patients who are in desperate need of new therapies.