“Tragedy should be utilized as a source of strength.” –Old Tibetan saying
When Rodney Varner made the jump from corporate lawyer to chairman and CEO of biotech startup Genprex Inc (NASDAQ:GNPX) and its promising treatment for non-small cell lung cancer, it wasn’t just because he believed in the science. For him, it was also personal.
A cancer survivor, Varner had long been a believer in the science behind Genprex’s lead drug candidate, Oncoprex, having previously served as legal counsel for several biotech startups, including one called Introgen Therapeutics.
So, when Introgen couldn’t raise enough money to develop its lead drug candidate at the height of the financial crisis in 2008 and subsequently went bankrupt, Varner formed a group that included leading scientists and former Introgen CEO David Nance to rescue what they believed was the most promising undeveloped science in Introgen’s pipeline: a gene called TUSC2 (“Tumor Suppressor Gene 2” also known as “FUS1”) delivered to tumor cells by means of a leading edge nanoparticle delivery system, which together became the basis for Oncoprex, a potential treatment for non-small cell lung cancer.
That investment group became the nucleus of Genprex.
The team now includes Dr Julien Pham as president and chief operating officer, and Ryan Confer as chief financial officer. Dr. Jack Roth continues as chairman of the company’s Scientific Advisory Board, and Nobel laureate Dr. James Rothman continues as a strategic advisor to the board of directors. Nance, who also fought a personal battle with cancer, left the company in 2012 and later passed away.
“We already had the knowledge,” Varner told Proactive Investors, “and we were able to move quickly to acquire the technology because bankruptcy is not a favorable environment to develop or market biotechnologies.”
How Oncoprex works
Oncoprex was a technology that Roth, a pioneer in gene therapy, wanted to pursue for several reasons: one, research demonstrated that TUSC2 is a powerful tumor suppressor gene and, two, Oncoprex has fewer side effects with less toxicity than other lung cancer drugs and can be administered systemically to cancer patients.
Oncoprex is basically the TUSC2 gene wrapped in a cholesterol nanoparticle that is engineered to target cancer cells.
“It’s a systemic targeted approach,” Varner explains. “The reason we say ‘targeted’ is because the lipid nanoparticles are designed to be attracted like a magnet to the cancer cells and have an opposite charge.”
The nanoparticles are attracted by the opposite electrical charge of tumors, and they pass more easily through immature blood vessels that grow quickly around tumors.
That’s a big advantage because the nanotechnology can be injected intravenously, so it goes through the whole body, as opposed to many traditional gene therapies using viral delivery systems that have been injected directly into tumors. Thus, Oncoprex can attack metastatic tumors in hard to reach places or are too small to detect. The Nanoparticles are absorbed by tumor cells at rate 10 times to 25 times higher than normal cells, but have little or no effect on normal cells, so toxicity to patients is low relative to other lung cancer drugs.
Genprex has an innovative gene-therapy platform that explores the therapeutic benefit of multiple tumor suppressor genes, multiple potentially synergistic combinations with other cancer drugs, and potential application to multiple types of cancer.
So, a natural question is what is so special about the TUSC2 gene in treating non-small cell lung cancer?
Varner says it’s because it expresses proteins that suppress cancer. Eighty percent of lung cancer patients show a deficiency in the TUSC2 tumor-suppressor gene, so lung cancer is an obvious target for those patients who don’t respond to traditional treatments.
After an early trial showed that Oncoprex alone benefitted some patients with non-small-cell lung cancer, researchers at MD Anderson Cancer Center in Houston, a longtime research partner of Genprex, found “strong synergy” in preclinical research showing that Oncoprex combined with an epidermal growth factor receptor (EGFR) inhibitor such as erlotinib, also known as Tarceva, is more effective than either drug used alone.
Of 23 patients evaluated in the initial Phase 1 clinical trial, Oncoprex on its own showed a benefit in five of the 23 patients with Stage IV metastatic lung cancer that received two or more trial doses; three saw tumor reductions and one patient had a complete response by PET scan, with lung cancer in full remission.
That patient, Varner says, used the additional years of life to see a grandchild born and she earned an additional college degree. “That’s really unusual in the drug-development process, to be able to have an experience like that in late-stage lung cancer.”
The success of that trial led to the current Phase 1/2 trial of Oncoprex combined with Tarceva, a best-selling EGFR inhibitor.
Though EGFR inhibitors are widely used to fight lung cancer as targeted therapies, they only benefit patients with the EGFR mutation (EGFR positive), and that’s only about 10% to 15% of Caucasians and about 30% to 50% of Asians. (Varner has no data for any other groups currently.)
“Our research indicates that we can sensitize patients who don’t have the mutation so that they can benefit from EGFR inhibitors such as Tarceva,” Varner says.
Expanding the business proposition
But that, Varner says, is just one leg of the company’s business proposition.
“By adding our drug to an EGFR inhibitor like Tarceva, we believe that we will be able to expand the patient populations that receive those drugs and benefit from them,” he says.
Another leg addresses patients receiving targeted therapies who almost inevitably become resistant to the popular EGFR inhibitors over time. Research indicates that Oncoprex can “re-sensitize” patients who become resistant to Tarceva, which may expand the number of people who can benefit from the drug and prolong the benefit for those who already receive it.
Preclinical data indicates Oncoprex is also synergistic when combined with immunotherapies such as PD-1 (programmed death-1) and CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), a protein receptor that downregulates immune responses. A Genprex study of lung cancer in mice shows that combining Oncoprex with these immunotherapies is more effective than when they are administered individually.
As a result, Varner says clinical trials are being planned to combine Oncoprex with a popular immunotherapy such as Bristol-Myers Squibb’s (NYSE:BMY) Opdivo or Yervoy.
Insert Oncoprex into a combined worldwide market for targeted therapies and immunotherapies predicted to reach about US$26bn by 2025, and Oncoprex has the makings of a global blockbuster.
In the pipeline
The company is well-prepared for current and upcoming clinical trials as Oncoprex continues its Phase 2 trial and potentially adds an additional clinical trial of Oncoprex combined with one or more immunotherapies.
Genprex went public in April of this year, listing on the Nasdaq under the ticker “GNPX” and raising US$6.4mn. A private investment in public equity, or PIPE, in May raised an additional US$10mln. With a burn rate of US$400,000 per month, the company has about two years of dry powder to conduct its next round of trials.
But Varner and his team are not sitting back and waiting. They are executing an ambitious plan to add an additional clinical trial combining Oncoprex with an immunotherapy while exploring expanding the current Phase 2 trial into an approval trial and applying for Fast Track, Breakthrough, or RMAT designation from the US Food and Drug Administration.
Varner says he expects feedback from the FDA in the next three to six months, but if the regulator rejects the accelerated approval route, then Varner says Genprex will face a longer and more expensive path via a randomized Phase 3 trial. And that would require additional capital.
But one obstacle made be tougher to overcome is that of perception. The company has been criticized openly on a popular investor website for its connection to Introgen, which Varner is quick to dispute.
Only one member of Genprex’s original management team was employed by Introgen, he points out, and that was one of the people who believed in the science the most: David Nance, who has since passed away. None of Genprex’s current executives was employed by Introgen.
Of the four or five drugs in Introgen’s pipeline, Genprex only obtained the rights to Oncoprex, which was in a much earlier stage and is based on totally different science than Introgen’s lead drug candidate at the time, which was in multiple Phase 3 clinical trials.
“When we acquired TUSC2, it was early in Phase 1 – it’s a totally different technology than Introgen’s lead technology, a P53 gene therapy,” Varner explains. “And our technology uses a different delivery system. Introgen’s lead drug candidate was delivered by a modified virus that was injected directly into tumors; whereas Genprex uses a non-viral delivery system that is delivered systemically and thus can reach metastatic tumors and those too small to be recognized, or too difficult to reach for injection. So, we took a different, early Phase 1 gene with a different delivery system and got it on favorable terms from the bankruptcy estate.“
As for Varner, it’s clear he is a true believer in Oncoprex and the science behind it. He took over as CEO in 2012 when Nance stepped down and only started drawing a salary in 2016.
“I was successful and made a good living as a lawyer for 30 years,” says Varner. “But after having cancer myself, it became even more important to me to see Genprex succeed.”
Contact Paul Curcio at [email protected]
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