Working as a physician assistant (PA) in vascular surgery at Duke University Medical Center for over 13 years, Shawn Gage has treated thousands of patients with a variety of vascular diseases and complications.

About half of them had kidney disease or complete kidney failure and required frequent hemodialysis to filter and cleanse their blood.

Many such patients have synthetic tubes called arteriovenous grafts surgically implanted in their arms, connecting a vein to an artery for better access to their blood.

At each dialysis session, a nurse or technician inserts two large needles into the graft, one to draw blood into a dialysis machine and one to return cleansed blood from the machine to the body.

“It’s a pretty large needle that they have to stick into a very small space,” Gage explains. “Imagine doing that every other day for years. Unlike your own vessel, it doesn’t heal. That graft turns into Swiss cheese.”

Those repeated needle sticks – known as cannulation in medical parlance – can cause grafts to leak, constrict or collapse, leading to serious complications.

“The more a graft is cannulated, scar tissue and blood byproducts build up within the graft, and the smaller the space becomes, the harder it gets to hit the target,” Gage says. “Frequently the technicians miss or completely pass through the space, causing injuries. That simple interface causes the majority of vascular access problems for dialysis patients.”

It was up to Gage and his clinical partner, mentor, and friend, former Duke vascular surgeon Jeffrey Lawson, M.D., Ph.D., to deal with degraded grafts and their complications.

“Jeff and I would fix these problems on a weekly basis in the operating room,” Gage recalls. “Folks with kidney failure and hemodialysis-access problems are an extremely sick and complicated patient population to care for. We made it our mission to do a better job for these patients.”

A “bullet-proof graft”

The duo knew there had to be a way to prevent these types of graft complications, and in February 2010 they hit on one.

“After a case one day, over lunch in the cafeteria, we literally drew it on a napkin,” Gage recalls.

They sketched a design for a new kind of graft, one with two multi-layered chambers that would self-seal after cannulation while resisting accidental needle punctures through the bottom and sides.

“To date there are no other grafts out there that mitigate these needle-access problems,” says Gage, who refers to the device as “the bullet-proof dialysis graft,” despite its simplicity.

“There are no moving parts or pieces, there are no electronics,” he says. “It’s a very simple idea.”

A simple idea perhaps, but a life-changing one for a then-30-year-old PA who had never planned to do anything but practice medicine. Suddenly Gage was not only an inventor but an entrepreneur too.

The InnAVasc AV graft.

“From that point on, really I acquired a second job, a non-paying job, that consumed my nights and weekends to the present day,” he says.

“Tenacious digging”

Although Gage and Lawson had no business, regulatory or engineering background, they knew they had to pursue their product idea to its completion.

Shawn Gage. nnAVasc photo.

“We had to figure out how to march this idea forward so that one day we could potentially help hundreds of thousands of patients as opposed to the 50 to 100 patients that we physically laid hands on and fixed on a weekly basis,” Gage says. “From that point on it was tenacious digging to try to figure out which direction to go next.”

They began by presenting their invention to Duke’s Office of Licensing and Ventures,  which provides initial funding and support for promising technologies and products invented by professors and other employees of the university.

Gage and Lawson needed to win Duke’s support by demonstrating a clinical need and commercial market potential for the graft. To help explain their product idea, they presented a crude product prototype Gage had made.

“I did that with scrap graft pieces and materials that I bought and fashioned from a hardware store,” Gage says. “And I did it in my garage, literally.”

Lawson and Gage believed the potential payoff justified the extra effort.

“If Duke’s tech transfer department decides this is a worthy idea that truly meets an unmet need, there is support available,” Gage explains. “And fortunately, that’s what happened.”

A company is born

Convinced of the graft’s merit, Duke helped the duo draft and file a patent application to protect the product idea. A European patent was granted in May 2015, and a U.S. patent followed in March 2017.

Meanwhile, a litany of other company-startup demands became apparent for advancing the product: incorporating a company, building a better prototype, preparing for manufacturing, determining regulatory pathways, designing pre-clinical and clinical trials, and raising money to pay for all of this expensive work.

“There are several things that have to happen simultaneously, and they’re all coming from different directions,” Gage says. “It’s not really a linear process.”

He and Lawson made incremental progress with InnAVasc Medical, initially backed by their own funds and small innovation grants from the Duke Translational Medicine Institute and the federal Small Business Technology Transfer program. They finally hit a wall and realized they’d need more outside funding.

They hired a president and CEO – the first full-time employee – to run the company and raise money for its operations. He is Joseph Knight, who has a Ph.D. in biomedical engineering, an MBA from Duke and experience at four biomedical device companies.

“That was a huge critical milestone for us because that was a make-or-break point,” Gage says. “If that failed, it may have all been for naught. Our technology may have died on the spot.”

Knight quickly helped InnAVasc raise research funding with a $250,000 loan from the North Carolina Biotechnology Center, a $150,000 Phase I Small Business Technology Transfer grant from the National Institutes of Health, $30,000 from the One North Carolina Small Business Program and $2.9 million in a successful seed round of equity investment from angel investors. More recently, the team secured about $2 million in additional funding from a Phase II Small Business Innovation Research grant to finalize the graft and fund a first-in-human pivotal clinical trial.

InnAVasc expects to begin human trials in Q4 2018 and has hired a second employee, Craig Nichols as a senior development engineer out of the Standford Biodesign Fellowship to help navigate the regulatory processes to come.

Untapped PA power

When Gage was growing up in Indiana and attending Butler University’s PA program, he was focused entirely on becoming a PA to practice medicine, not to be an inventor or entrepreneur.

“I never thought of this as being a career,” he recalls. “It never crossed my mind. I didn’t know it was possible. I had the impression that it was not for people like me.”

Today, with nearly two decades of experience in medicine to his credit, his career evolution makes more sense to him.

“Innovation is really becoming a greater focus in medicine these days,” he says. “And there are lots of innovations to be made by PAs.”

Because PAs are on the front lines of clinical medicine, caring for patients every day, they are perfectly positioned to see problems and possible solutions, he explains.

Despite that connection, most medical inventions to date have come from physicians and engineers, not PAs.

“It’s a pretty rare thing” for a PA to be an inventor, Gage says, even though “PAs bring the same understanding of medicine, patient care, and clinical needs that physicians do.”

Encouraging PAs to think entrepreneurially would “open the door for tens of thousands of new minds to innovate in the medical space,” he says.

“There’s absolutely no reason why PAs can’t be enlightened to this concept and look at their world of medicine through a new lens of innovation to ultimately help hundreds of thousands more patients than they can physically take care of in their own day-to day-practice. We have all the faculties, all the tools and all the intimate understanding of medicine to identify unmet clinical needs.”

Greta Brunet, an NCBiotech senior director of investments who is also an experienced PA, agrees. “The PA profession is one of the fastest-growing in the United States,” she says. “These are individuals who are exposed daily to clinical problems in need of creative solutions. They see what works and what doesn’t when managing the care of their patients. They are well-positioned to develop innovative solutions that could really make a difference.”

More than 115,500 certified PAs work across the country, and about 6,000 of them practice in North Carolina, according to the American Academy of PAs.

The PA profession was established in 1967 when the nation’s first PA program at Duke produced its first three graduates. It has doubled in size every decade since 1980 and grew by 44 percent in the last six years, according to the National Commission on the Certification of Physician Assistants.

The profession is projected to grow an additional 30 percent by 2024.

“Imagine the possibilities,” Brunet says, “if those growing ranks adopted a mindset of innovation and entrepreneurship.”

“If Shawn Gage can do something like this, why can’t other PAs?” she says. “Given the right tools and resources, we can all think outside the box and come up with innovative solutions that could potentially make a real difference.”

Brunet is one of the many specialized NCBiotech experts propelling a 30-year creative transformation for North Carolina life science opportunities. Finding partnerships. Helping to clear the way for great ideas from people throughout the state’s leading academic institutions to beat the odds and find the marketplace. Support from NCBiotech and partners for people like Shawn Gage and Jeffrey Lawson and Joseph Knight and Craig Nichols is why North Carolina remains a global life science leader.

Now that your curiosity is piqued, check this YouTube video for a more comprehensive view of the InnAVasc Medical AV graft.

Copyright, NC Biotech Center 2018