Rakesh Suri and Jordan Miller are the kind of entrepreneurs who are easy to cheer for.
Suri is a heart surgeon at the Mayo Clinic, and Miller is a scientist who arrived in Rochester 5 ½ years ago to help with a research program into cardiac valve disease.
Admittedly they are not typical business underdogs, not as top-of-the-profession staff at the renowned Mayo Clinic. What's to like is how they want to take something out of the lab to help people live longer. And starting a company seems to be the only practical way to get that done.
Neither wants to run the pharmaceutical company they intend to start. They can't even be sure they would want to work for it if gets up and running. Suri described himself as a busy surgeon, and Miller said he now finds himself in a role he once never could have imagined.
Their entrepreneurial dream had a little bit of an unusual spark, too. It started with a request for grant applications from the National Institutes of Health, a regular funder of Mayo's research.
The NIH has noted that it takes more than 13 years on average from discovery to an approved drug, and less than 5 percent of the once promising drugs ever make it that far. The NIH suspected that a lot of known drug compounds that had originally flopped could be retargeted at a disease that is a better fit, inexpensively creating effective new medications.
Miller saw that one of the drugs, put into the NIH program by the French pharmaceutical giant Sanofi, was right in the middle of the work he and his colleagues had been doing. It had been abandoned after Sanofi found in trials that it wasn't all that effective in treating chest pain and peripheral artery disease.
As Miller and Suri explained, Sanofi may not have fully realized what it had in the drug, called Ataciguat. Even a company as large as Sanofi can't have deep expertise in every possible application for a drug.
The Mayo team believes the drug can be effective treating aortic stenosis, the calcification of the aortic heart valve that Suri likened to rust on a car. Too much rust and the valve doesn't let enough blood flow through.
The only real option now for patients with advanced disease is to have the valve replaced. There are two ways to do that, one that's expensive and the other that's enormously expensive. And that's if the patient lives long enough to reach the surgical suite.
The problem typically shows up in people into their retirement years, Suri said, but it could affect perhaps 200 million people globally by 2020.
The drug activates an enzyme called sGC that in turn helps the body prevent further build up of calcium in the valve. The patient maybe can't get back to having the heart valve of a 30-year-old, but the Mayo team has early data suggesting that the drug stops the progression of valve calcification.
Mayo had hoped for the cardiac valve research program to one day come up with new treatments. But no one expected that it would happen this soon.
By starting with a known drug, "we were hooked on this idea that we could go to clinical treatments much more quickly than we ever anticipated," Miller said. They also envisioned more applications beyond aortic valves.
The NIH grant now in place carries the Mayo team through a trial of 100 patients. But that's the end of the NIH money. If the data looks promising but another year of tracking would be helpful, Miller said the NIH won't fund that.
And the 100-patient trial wouldn't be nearly enough to get the drug approved for sale. There would then need to be a much larger, and more expensive, trial.
That's why these business novices right away started planning to get into business.
Fully aware of their own inexperience, they signed up to participate this year in Lean LaunchPad, how-to training for entrepreneurs developed at Stanford University. They were part of the first Mayo group to go through it.
One of the key principles taught there is "getting out of the building," and that's why they found themselves on the street looking to talk to people about aortic stenosis.
Here's their key insight: Physicians like Suri and patients with the disease aren't their customers. These people are in no position to help them get that drug into the market.
Their real customers are big drug companies. And to reach the right drug company executives with the right pitch, they first want to find a financial partner with capital and expertise to get their company off the ground.
From their first discussions with venture capitalists they know one key remaining challenge is to design a trial that gets to "endpoints" that will indicate the drug's effectiveness, endpoints that will make sense to both the FDA and the entrepreneurs.
If the FDA would require them to track patients in the trial for 20 years to conclusively prove that fewer people actually died when they got the medication, it would be such an expensive project that no one would fund it.
Miller and Suri are optimistic this challenge can be met and that they can go on to create an attractive business venture —– with the right talent and some capital.
"Just because you are a gem of the field doesn't mean you'll get found and picked up," Suri said. "We understand that now, that you have to market yourself appropriately, and have the appropriate partners to get there. It's not a marathon. It's a team race."