Written by Whitney L.J. Howell

It’s a familiar emotion – the regret felt over and intense wish to retract an email. Surgeons and interventional cardiologists frequently experience the same thing, only with patients and their blood.

Every day, surgeons operate, knowing a patient could respond poorly to the anti-thrombotic agents that thin their blood to avoid a potential stroke. If their blood thins too much, the situation could be life-threatening. However, Duke University researchers have developed a way to turn off the drug – in effect, reclaiming that email before any permanent damage occurs.

For Bruce Sullenger, Ph.D., Duke Translational Research Institute director, finding a way to inactivate a drug already inside the human body was critical to addressing a pervasive patient-care issue.

“I started talking with a number of surgeons, as well as interventional cardiologists, about the unmet medical needs in this space to improve anti-thrombotics in acute-care settings,” Sullenger said. “They told us that safety is a major issue and concern for both surgeon and cardiologist because when you start to deliver the anti-thrombotic to thin the blood or blood platelets, there’s an increased risk of major bleeding that can be life-threatening in the worst cases.”

Basically, surgeons wanted and needed more control over the drug, including the ability to rein it in. Through his work with RNA aptamers – molecules that bind to and alter specific targets – Sullenger developed a compound that does just that. In effect, it’s an antidote to anti-thrombotics.

This discovery led to the launch of Regado Biosciences Inc., Sullenger’s biopharmaceutical company devoted to producing this anti-thrombotic and antidote pairing. The product, called REG1, is designed for use in patients with acute coronary syndromes, those undergoing coronary interventions, or in those who must have obstructed coronary arteries mechanically opened or widened. It brings together pegnivacogin, the blood-thinning aptamer that targets the coagulant Factor IXa, and its antidote anivamersen.

According to Sullenger, anti-thrombotics are small molecules, but they’re difficult to turn off. So, instead of attacking it with an antibody or other small molecule, his team uses a process called SELEX (Systematic Evolution of Ligands by Exponential Enrichment) to create single strands of RNA, such as anivamersen, called oligonucleotides, that can bind to target ligands or molecules.

Through nucleotide base pairing, these RNA strands bind to the aptamer, turning it off by forcing it to let go of its target protein. Depending upon the dose levels, the antidote can either completely neutralize the aptamer or scale it back by various degrees.

“This strategy gives us an off switch. It’s kind of cute, actually,” he said. “You can make these new drugs to target any protein, and this one encodes information on how to make the antidote to an anti-thrombotic.”

Currently, REG1 is involved in the Phase 3 REGULATE-PCI trial that is set to include 13,200 patients at more than 500 sites worldwide. This trial, which began in September 2013, is comparing REG1 to the current thrombotic inhibitor, bivalirudin, used in patients undergoing percutaneous coronary interventions. The Food & Drug Administration also announced in March that it has placed REG1 on its Fast Track process to expedite its review, getting it to patients faster.

Getting the REG1 therapy to market has been much easier, Sullenger said, because the drug has been under review at the Duke Clinical Research Institute (DCRI).

“It’s been very gratifying to me personally to see this going through Duke,” he said. “Duke has the leading academic research organization in the DCRI, but very few Duke innovations have been developed and gone through its clinical trial program.”

There’s significant opportunity, he said, for other entrepreneurs and innovators on campus to work with the DCRI, taking advantage of its resources and expertise.