Nearly two decades ago, University of Arizona radiologist Dr. Evan Unger recognized that an ultrasound imaging contrast agent he pioneered held promise as a way to deliver drugs or therapies to specific areas.
Unger's latest effort: a treatment to make cancer tumors more susceptible to radiation therapy.
His four-year-old Tucson company, NuvOx Pharma, is planning clinical trials of an injectable drug that can infuse tumors with oxygen to make them more susceptible to radiation treatment.
So-called hypoxic, or low-oxygen, tumors are resistant to radiation and in some cases, chemotherapy, said Unger, who in addition to faculty positions at the UA Departments of Medical Imaging and Biomedical Engineering is co-director of the Arizona Cancer Center's Cancer Imaging Program.
NuvOx's technology uses a compound known as dodecafluoropentane, originally developed as an imaging contrast agent, to carry oxygen to tumor cells.
While other so called "oxygen therapeutics" agents have been tested as therapies for stroke, they have required high doses that increase toxicity, Unger said.
The injectable dodecafluoropentane compound NuvOx has developed, known as NVX-108, has a lower boiling point and expands in the bloodstream, allowing a much smaller, safer dose, he said.
"Over a billion dollars was spent studying the other materials, and they all failed because they had high doses and eventually caused side effects in patients," Unger said. "Ours is less than one two-hundredths of the dose (of the others), and we completely reverse radiation resistance in hypoxic tumors."
Though NuvOx's technology is focused on radiation resistance of hypoxic tumors, it also could reverse their resistance to chemotherapy and help prevent DNA instability that can boost unbridled tumor growth, said Dr. Diego Martin, head of the UA Department of Medical Imaging.
"What happens with low oxygen is the tissue becomes more acidic, and the DNA becomes less stable - and that's the most dangerous part of the tumor and also the hardest part to treat," said Martin, whose research work has included tumor monitoring.
Because it was previously tested as an imaging contrast agent on more than 2,000 patients, NuvOx can move quickly into advanced clinical trials, Unger said, adding that the dodecafluoropentane was approved for use in Europe.
In November, the U.S. Food and Drug Administration agreed to allow NuvOx to use the prior clinical data and move ahead to Phase II trials after completing some "bridging" studies, Unger said.
The Phase II trial could start within nine months to a year and last about a year, Unger said.
The company has worked with the Arizona Cancer Center to study the drug's effect on hypoxic tumors, and the UA could be involved in clinical trials as well, he said.
All this research takes a lot of money.
The company has raised about $5 million, including more than $1 million in federal research grants, about $1 million invested by Unger and other founders and family members, and more than $2 million from a group of individual investors.
NuvOx is looking to raise $3.5 million more to complete the Phase II clinical trial in cancer patients and get started on clinical trials for stroke therapy.
NuvOx's technology could tap into drug markets for stroke, heart attack, cancer and bleeding-induced shock, which together represent a total annual market of $8.5 billion in the U.S. alone, Unger noted.
But at least one other company is testing new drugs to overcome hypoxia in tumors, including San Francisco-based Threshold Pharmaceuticals, which is backed by Merck.
And nothing's a sure thing when it comes to drug development.
Unger's first attempt to use contrast agents therapeutically involved an injectable suspension of perfluorocarbon "microbubbles," used with targeted ultrasound to break up blood clots.
The technology showed promise, and his follow-up company, ImaRx Therapeutics, raised about $15 million in an initial public stock offering in 2007.
ImaRx conducted clinical trials for stroke with its SonoLysis microbubble technology with an existing anti-clotting drug. But the company suspended the project in January 2009 after three patients developed serious bleeding.
The company's stock value evaporated, and its assets were sold to investors including ImaRx's former CEO. A successor company, Seattle-based Cerevast Therapeutics, is using ImaRx's original technology to develop an ultrasound device to target clots, though without the microbubbles.
Unger, who along with other investors lost most of his investment in ImaRx, is still dismayed over the failed trial of SonoLysis, which was paired with a drug known to be a bleeding risk.
"I'm glad someone's working on it, but I'm not happy about what happened," Unger said. "It's unfortunate, because the technology works. But I'm more interested in what I'm doing now."
Did you know?
UA radiologist Dr. Evan Unger has a track record of success in imaging technology. He sold one of his first companies, ImaRx Pharmaceuticals, to chemicals giant DuPont for about $40 million in 1999.
Its main product, a contrast agent for sonograms called Definity, was launched in 2001 and has been used to treat more than 3 million patients, according to Massachusetts-based Lantheus Medical Imaging, which now markets the product.
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