Michael Weiss was a 23-year-old medical student when a one-year clinical fellowship landed him in Oxford, England. It was 1980 and the same department where the late, Nobel Prize-winning chemist Dorothy Hodgkin had spent 40 years studying the structure of the diabetic hormone insulin.
Weiss became intrigued by Hodgkin’s research on the 3-D structure of the protein and the complexities of insulin. But there was much still to be revealed about the protein’s inner workings: What caused the protein to bind to some receptors, for instance, and to reject others?
For the first few months in England, his work with insulin and insulin therapy was mostly conceptual. Then during a break, Weiss traveled to Kenya and Egypt, where he witnessed diabetics injecting insulin to stabilize their blood sugar levels.
But the patients did not have access to electricity, and insulin required refrigeration. So the African villagers buried the insulin in the ground in an attempt to keep it from degrading in the sun.
Weiss swore that he would find a way to fix this insulin problem.
“In my enthusiasm of youth, I thought it was something that could be fixed readily,” he says.
Instead, Weiss would spend the next 26 years trying to unlock the mysteries of insulin and its receptors.
In the process, he took a clinical fellowship at Brigham Women’s Hospital in Massachusetts, where he worked one-on-one with diabetes patients, and spent half a decade at the University of Chicago, working on the deconstruction of insulin receptors.
Finally, after decades of research, Weiss, now the chairman of Case Western Reserve University’s Biochemistry Department, has figured out many of insulin’s biochemical secrets. And the results may change the dialogue on current diabetes care.
The first true global pandemic of the 21st century belongs to a disease with a household name: diabetes. The World Health Organization estimates there will be more than 366 million diabetics worldwide by 2030.
Diabetes comes as a result of having too much blood sugar in your body. Insulin is the hormone that regulates blood sugar. People develop diabetes when they don’t have enough insulin in their systems or they’ve become resistant to insulin’s action. The only way to counteract the effect of diabetes is to inject oneself with insulin hormones.
As a result of this huge spike in diabetes, insulin treatments have become one of the largest-selling pharmaceuticals in the world.
The insulin market is currently a $14 billion industry, and drug companies are salivating for faster-acting, more efficient insulin drugs — especially since many of their patents are set to expire in the next three or four years, says Rick Berenson, CEO and executive chairman of
Thermalin Diabetes.
That’s where Weiss’ lab at the Cleveland Clinic’s Global Cardiovascular Innovation Center comes in. Weiss and his collaborators at Case have produced several dozen new types of insulin analogs, or molecules engineered to act like insulin in the blood. But Weiss’ analogs differ drastically from other insulin drugs currently on the market.
Unlike natural insulin, some of Weiss’ molecules don’t have to be refrigerated. They also have longer staying power, lasting up to 500 days without losing potency while most natural insulin has a shelf life of around 30 days once opened.
“In the Western world, this is important for mail-order shipping, which often requires special expensive packaging [for insulin],” Berenson says. “And in the developing world, where 12 Indian villages might share one refrigerator, the [new analog] drastically increases their survival and treatment possibilities.”
In addition, Weiss’ analogs work faster than any other insulin treatment currently on the market, which means they do a better job regulating the peaks and valleys of blood sugar levels because they are absorbed more quickly into the body, Berenson says. They also have fewer side effects than other long-acting insulin treatments, which have been shown to lead to increased cancer risks in some studies.
That’s why Weiss called his former Harvard roommate Rick Berenson in 2007 to tell him about his discoveries and ask for advice in developing his analog patents. Berenson, a serial entrepreneur, had spent 25 years as either CEO or COO of 11 companies.
“I’d been involved in a wood-products company that supplied 10 percent of the world’s drumsticks,” he explains. “I’d been part of an artificial intelligence software startup, Internet startups, and spent the past seven or eight years in the life sciences.”
During the conversation, Weiss asked Berenson if he knew anyone who was interested in the business aspect of insulin. To which Berenson promptly replied: “How about me?”
Weiss formed Thermalin Diabetes Inc. in 2007, and it was reincorporated as a limited liability corporation last year.
Their friendship, which began in a Harvard dorm room over a shared love of Star Trek, slowly developed into a multimillion dollar partnership. Today, the men have raised $2.5 million in private capital to advance the company’s research, including a $250,000 investment from JumpStart, the Cleveland-based nonprofit that invests in early-stage startup companies with potential for growth.
“Thermalin really excited us for a number of reasons,” explains Ted Frank, a venture partner at JumpStart. “For starters, it has a really great market opportunity with the worldwide increase in diabetes. Secondly, Dr. Weiss and Rick Berenson are a great team. Dr. Weiss has been described numerous times to me as one of the top five insulin researchers in the world, and Rick is a wonderful, experienced CEO. And lastly, they have a rich portfolio of possible drug candidates.”
The promise of a new type of insulin analog excites many in the medical community.
“I think Dr. Weiss is a brilliant scientist,” says David Harlan, co-director of the Diabetes Center of Excellence at University of Massachusetts. “He’s thoughtful, insightful and honest, and he’s devoted his career to developing better insulin. ... Dr. Weiss has taken very rational, scientific approaches to meet critical needs in the insulin market. I’m very excited about Thermalin.”
The insulin company has completed its first round of studies on animals and hopes to begin phase two testing this year. That phase will include the crucial step of testing on humans.
“If the analogs work the way we believe they will, they can completely transform people’s lives, taking away the drudgery and corresponding inaccuracies that result when people are not given the right amount of insulin,” Berenson says.
The clinical results of the testing, they believe, will lead to a partnership with a large pharmaceutical company in the next few years, with the drug companies licensing Thermalin’s products.
“Insulin is the largest volume drug in the world,” Berenson says. “Merck and Pfizer are both interested in getting in the game, and Eli Lilly has stopped doing much of their own in-house insulin research.”
New insulin analogs typically capture at least 20 percent of the market share. Final FDA approval of the drug could result in a big payout and a whole new round of innovation in insulin studies which Weiss is already beginning to work on.
“We’re only just getting started,” he says.