By sublicensing Sonus Pharmaceuticals Inc.'s oxygen delivery patents, ImaRx Therapeutics Inc. has positioned itself to begin clinical trials within the next year of its Nan02 Nanobubble therapeutics program.
The Tucson, Ariz.-based company is working to develop portable oxygen delivery treatments to be used in emergency situations, such as on the battlefield. The product is designed to save lives in trauma situations for patients who need quick oxygenation and cannot wait for blood supply.
"The thing that's intriguing to us is we have both orphan drug, unmet need applications," said Evan Unger, president and CEO of ImaRx, "as well as blockbuster potential."
Unger said the company plans to initially target smaller indications, such as carbon monoxide poisoning or hemorrhagic shock. That could lead to much bigger indications in cancer, or in the cardiovascular arena, such as heart attack or critical ischemia. The strategy is to work with the military and concentrate on the smaller indications initially, then to partner for clinical work in a large cardiovascular indication. The first clinical study is expected to begin within a year.
While ImaRx had its own suite of oxygen delivery patents and advanced nanobubble emulsion technologies, it still needed exclusive access to the four U.S. patents from Bothell, Wash.-based Sonus. Those patents cover compositions of matter and methods of using oxygen delivery for treatment of disease. If ImaRx commercializes any products based on the patents, Sonus will receive an undisclosed royalty.
Unger said the nanobubble technology could replace the bulky oxygen tanks brought by military physicians onto the battlefield, and it could treat patients with massive blood loss who are not getting enough oxygen throughout their body.
"It's truly a remarkable technology because it delivers about 400 times more oxygen per unit volume vs. red blood cells," Unger said.
ImaRx scientists noticed that they could make the bubbles with a certain amount of oxygen and that they would "shrink down like raisins" when placed in an oxygen-poor environment and then "poof back up," Unger said.
Preclinical studies supported their early research.
"We gave the bubbles to the rats and were able to keep them alive," Unger said.
Claes Lundgren, the inventor of two of the Sonus patents sublicensed to ImaRx, presented preclinical results at a scientific meeting last November showing that severe shock resulting from as much as 50 percent blood loss was effectively treated using very small doses of nanobubbles.
Patients are treated through the injection of a nanobubble emulsion into the bloodstream where it expands into nanobubbles that circulate through the lungs. Unlike other oxygen delivery therapeutics that leave chemical components in the body for months or years, remaining gas from the nanobubbles is exhaled by the lungs.
"It clears from the body in five or six hours," Unger said.
Unger founded ImaRx Pharmaceutical Corp. in 1990 to develop in vivo diagnostic agents. That company, which was eventually sold to Wilmington, Del.-based DuPont Pharmaceuticals, developed the first injectable microbubble, which resulted in a diagnostic tool, the imaging agent Definity. The product received FDA approval in 2001 and is marketed by New York-based Bristol-Myers Squibb Co. Definity led to the idea of using bubbles to deliver oxygen, said Unger, who founded ImaRx in 2000.
At the same time ImaRx was doing its research, scientists at the State University of New York were conducting similar work. That work moved from the university to Sonus, which then developed its own technology that consisted of stabilized fluorocarbon gas microbubbles for transporting oxygen.
The Sonus agent "failed with the FDA," Unger said, "because of chemistry and manufacturing control concerns, although it was tested in more than 2,000 patients."
Sonus decided to shift its focus to the development of cancer drug therapies based on its Tocosol vitamin E-based technology platform.
Other companies have worked on oxygen therapeutics to bridge the time from trauma sites to hospitals. Evanston, Ill.-based Northfield Laboratories Inc., for instance, is in a Phase III trial with PolyHeme, a hemoglobin-based oxygen therapeutic. (See BioWorld Today, April 12, 2005.)
But Unger said the hemoglobin molecule is a protein that has problems. He believes the ImaRx bubble technology's "rapid clearance and the very large oxygen carrying capacity, and then the absence of any kinds of foreign immunogenic proteins" offers an advantage over products like PolyHeme.
Since its inception in 2000, ImaRx has raised $23.5 million in private capital, and it has received $2.4 million in National Institutes of Health funding.