Entrepreneurial Endeavors

Entrepreneurial Endeavors

These APS members know what it takes to launch a business of your own in physiology.

by Poornima Apte

For 25 years, Sylvie Breton, PhD, has been researching the intercalated cells of the kidney, studying how they regulate the acidity of the blood, at Massachusetts General Hospital (MGH) in Boston. But in 2013, she made a monumental discovery that galvanized her move toward entrepreneurship.

She discovered that intercalated cells could also initiate local inflammation in the kidney. Equally important, the cells triggered this inflammation when the kidney or any secondary organ, such as the heart, was injured. (A kidney might be injured when it is starved of oxygen, a condition known as ischemia). Such an event has a cascading effect: It triggers production of a dangerous molecule, UDP-glucose (UDP-G), which activates a receptor in intercalated cells that causes inflammation. And much like a canary in a coal mine signals danger, UDP-G signals inflammation of the kidney, which can lead to acute kidney injury (AKI) or acute renal failure.

Breton immediately recognized the significance of this discovery. AKI is one of the most common and severe medical complications in hospitalized patients. It increases the chance of death seven-fold, Breton says. “The problem right now is there is no specific therapy for AKI. Also, patients are often diagnosed too late in the process,” she says. But Breton had found a way to signal the onset of trouble. What if, Breton wondered, she could bring this diagnostic marker to the market and develop a related receptor inhibitor as a therapeutic? She could help save millions of lives. That possibility gave her the courage to take a leap of faith and launch a startup.

Across the U.S., in all industries, professionals are jumping into entrepreneurship, but physiologists’ ultimate goal is often to develop therapies to help patients. Along the way, they face challenges, such as protecting their intellectual property, avoiding potential conflicts of interests between lab and company, and navigating legal and logistical hurdles. But developing and following a careful blueprint can lead to successful entrepreneurial endeavors. 

FROM LAB TO STARTUP

In Breton’s case, avoiding intellectual pollution was the first challenge. Before she presented her discovery at a meeting of the American Society of Nephrology, she filed a provisional patent application through MGH, where she is a professor of medicine and the Richard Moerschner Endowed MGH Research Institute Chair in Men’s Health.

Money was the next hurdle to clear. Breton needed to divorce funding for the AKI project from the rest of the work supported by the National Institutes of Health (NIH). Her NIH-funded work was aimed at supporting research on the pH regulatory role of intercalated cells, not the pro-inflammatory role she had discovered. Breton received a couple of internal grants from Partners Healthcare (the parent group of MGH) and pilot grants from the Boston Biomedical Innovation Center. The grants—$200,000 in total—were enough to develop preclinical models to study ischemia of the kidney and show that the receptor inhibitor was effective at protecting the kidney from ischemia.

Realizing that proof-of-concept alone was not enough to have companies test-drive her work, Breton formally launched what started out as Kantum Diagnostics in 2016. Her entrepreneur husband, Jean-François Carbonneau, helped her build the company and create a business plan and venture capital pitch. They raised $3 million in seed funding for the project, which they used to assemble a team of experts. The company now employs four experts and six advisers in drug development and hires occasional consultants.

“You have to protect your discovery and know that what you have is marketable,” Breton advises. “It’s not only about science; it’s also about business. Be ready to listen.” Kantum is now ready to solicit venture capital firms for the next round of capital investment, called series A funding, which is usually designed for early-stage companies.

Although Breton initially went to market with the name Kantum Diagnostics, she quickly realized funding for diagnostic tools was limited. The market needed therapeutics. The new name, Kantum Pharma, captures both. “Above all, you have to know when to pivot,” Breton says.

FROM LAB TO PHARMA

Moving from the study of neurobiology to pharmaceutical marketing, Eric Floyd, PhD, certainly knows how to pivot.

While pursuing a master’s degree in neurobiology at Tennessee State University, Floyd received an APS Porter Physiology Development Fellowship in 1989. It helped him attend the annual meeting of the Society for Neuroscience, where he met one of his many mentors, James Townsel, PhD, then chair of the Department of Physiology at Meharry Medical College in Nashville, Tenn. The Porter Fellowship then funded two years of Floyd’s doctoral research. He earned a PhD in neurophysiology in 1995.

Since then, Floyd has had an illustrious career in pharma, starting at Merck as associate director of regulatory affairs in 1998. He has worked for Aventis, Novartis, Cephalon and others, expanding his knowledge of global pharma regulatory affairs from the U.S. to Europe and beyond.

Early on in his studies, Floyd realized he wanted to do translational research. “I wanted to move from a rat and a primate model into work that could have the greatest impact on patients’ lives,” he says. He found that path in regulatory affairs.

The neuroscience and physiology degrees help him understand the mechanics of the human body under discussion. It was at Merck that another mentor, Larry Bell, MD, gave Floyd more valuable advice: build business acumen. “The pharmaceutical industry is a business. It’s not enough to have the science; you need to be able to translate the science into a product that you can market,” Floyd says. The next step: an MBA in pharmaceutical marketing from Saint Joseph’s University in Philadelphia.

After 18 years of working under the regulatory affairs umbrella, Floyd decided to launch his own regulatory consulting firm, Floyd Regulatory Strategic Consulting. He serves as the principal and has a suite of 15 associates he refers work to through the consultancy. The business consults with companies on all regulatory and clinical development interactions with government agencies such as the U.S. Food and Drug Administration and the European Medicines Agency.

Floyd is also the chief regulatory officer at Neurogene, a startup that focuses on developing life-changing genetic medicines for patients and their families affected by rare, devastating neurological diseases such as Batten disease and Charcot-Marie-Tooth disease. To avoid any potential conflict of interest, any client with a therapeutic area focus on the central nervous system—which overlaps with Neurogene’s work—is supported and managed by other consultants within the group.

If you have a spark of entrepre-neurship, it’s important to “know yourself and know your subject matter,” Floyd says. “Look at the landscape and see where you can create a value proposition.”

Floyd believes in asking for help and in mentorship. “Dr. Robert Silverman and Dr. Larry Bell taught me to understand the data and to effectively communicate that to government agencies,” he says.

Since his Porter Fellowship days, Floyd has come full circle, donating to the program and speaking to Porter Fellows about career opportunities. “I try to serve as a mentor to others that are coming up. We are all trained as scientists, but those skill sets are transferable. They can be applied in many different venues outside the bench. People need to know that.”

FROM INDUSTRY TO BUSINESS OWNER

Craig Plato, PhD, also understands what it takes to strike out on your own. Toward the end of the Great Recession, Plato noticed a trend toward outsourcing in pharma. “There was a perspective that in-house discovery physiology capabilities were no longer ‘critical path’ and those efforts could be done extramurally,” says Plato, the CEO and founder of Plato Biopharma Inc. (PBI) in Westminster, Colo.

The industry shift came at an opportune time for Plato. Having worked for Abbott Labs, Myogen and then Gilead Sciences (which acquired Myogen), he already had years of experience in the in vivo component of pharma and biotechnology. He understood the underpinnings of compound evaluation and drug discovery. In 2009, Gilead consolidated the Colorado operation and moved it to California, offering Plato a move to the Golden State. After a discussion at a conference with friend and industry veteran David Pollock, PhD, past president of APS, Plato instead decided to strike out on his own.

PBI is a research organization that focuses on performing preclinical discovery, physiology and pharmacology studies for large multinationals, biotechs and startups. Since its founding in 2010, PBI has grown from a staff of two to 28.

Just a year before, Plato had set up a new lab for Gilead complete with laboratory equipment. When he launched PBI, he was able to buy those lab assets at a low market price. With a very modest round of funding from local angel investors, and Plato’s own money, PBI was off and running.

Technology transfer was more complicated. Any data that had been generated when Plato was part of Myogen/Gilead had to be redone. “We regenerated all the model systems, all the assays,” he says. The rigors of earning a PhD—he received his doctoral degree in physiology from the Medical College of Wisconsin—set him up for developing procedures from scratch. Such a disciplined and rigorous approach, Plato says, has been instrumental in winning business as companies use PBI to move down the decision tree of a drug discovery project. The methods and data have to be squeaky clean. “I am part of the whole-animal, old-school blood-and-guts physiology cadre—valuable training in industry,” Plato says.

Entrepreneurship in physiology is particularly challenging because of associated complexities, he says. “We’re using animals to model human diseases, but those diseases are multifactorial and often accompanied by medical comorbidities,” he points out. Heart failure, for example, is not just a cardiac problem; it’s a renal and vascular problem, too.

The good news: These complexities also present an opportunity for physiologists, Plato says. “Physiologists are uniquely positioned to understand the multi-organ system interaction. There is so much opportunity for us to add value, perspective and context.”

Plato advises budding entrepreneurs: “Be passionate about your idea. It’s necessary to engage investors, obtain business and attract talent to grow your business. If the founder’s not passionate, no one else will be.”

This article was originally published in the November 2019 issue of The Physiologist Magazine.