CLEVELAND, Ohio — Dr. Michael Weiss started studying insulin in 1985 when he was a clinical fellow in medicine atÂ Brigham & Womenâ€™s Hospital in Boston.
More than two decades later,Â the chairman ofÂ the Biochemistry Department at Case Western Reserve University School of Medicine is helpingÂ to found a business that could earn hisÂ latest discovery — a shelf-stable,Â super fast-acting insulin — the status of “blockbuster drug” some day.
“It’s a great, exciting project,” said Richard Berenson, executive chairman of Thermalin Diabetes Inc., the Cleveland company the former college roommates are starting to commercialize Weiss’Â third-generation insulins.
“Mike has done some amazing work. His lab has been phenomenal,” Berenson said. “In the past year, papers that he’s written about these [insulins] have won Paper of the Week three times from the Journal of Biological Chemistry. Winning that once is a big deal. This is absolutely world-class work. And I’mÂ really happy to help him put the whole thing together.”
The two hope toÂ get Thermalin — the product — and some other next-generation insulins through research, development, clinical testing andÂ ready for the market.
In the early 1980s, Berenson andÂ Weiss were undergraduate roommates at Harvard University. “Mike Weiss went on to get his MD/PhD at Harvard, and then pursued an academic career in science. And I went on to get my JD/MBA at Harvard, and pursued a career in business,” Berenson said.
When Weiss started studying insulin in the mid-1980s, the hormone that enables people’s bodies to convert fuels like sugar to energy already was “considered well-characterized,” Weiss wroteÂ at his faculty Web page.Â Yet “the ensuing decades have uncovered one surprise after another,” Weiss said.
But insulin as a therapy to treat diabetic patients whose bodiesÂ don’t make the hormoneÂ still has its problems. For one, insulin must beÂ refrigerated to remain viable. It also takes some time to work, requiring diabetics to successfully juggle insulin injections with eating and testing for blood sugar levels.
“The problem with insulin as a drug, is that it didn’t evolve to be a drug,” Weiss said in a 2008 video promotion made by Case MBA students. “Insulin is part of a complex physiological network of regulatory molecules that maintains our health. It has not been optimized in evolution to be a drug used to treat patients. And this raises the question, ‘Can we improve it? Can we make a better insulin to enhance the therapy of diabetes and help our patients live longer, healthier lives?’ ”
In recent years, the rise of insulin pumps — devicesÂ worn outside or inside the body that automatically or manually pump insulin into the blood — has presented another problem for insulin. Heat from the body raises the temperature of insulin in the pumps, eventually destroying its effectiveness.
“A major improvement would be to use an implantable pump,” Jonathan Whittaker, assistant professor of nutrition at Case Medical School and a colleague of Weiss, said in the promotional video. “But unfortunately, while we have the technology to produceÂ an implantable pump, the biological problem of maintaining insulin in an active form inside the body over prolonged periods of time provides an insurmountable obstacle.”
Weiss solved the problem by stretchingÂ the double-chained insulin molecule to a single chain, Berenson said.
“Thermalin is a new kind of insulin,” Weiss said. “Like insulin, it’s injected or used in a pump. And like insulin, it causes the blood sugar to go down, and so it can be used to treat diabetes. But it’s improved from insulin, in that, at high temperatures, it lasts for weeks and even months. It’s almost indestructible at high temperatures, and so it affords enormous … lifestyle convenience to patients.”
That means diabetic patients wouldn’t have to carry their Thermalin supplies in coolers. Patients in developing countries or disaster areas who have no access to refrigeration would be able to use Thermalin. So would patients who use insulin pumps.Â ‘The bioetechnology industry has facilitated the development of super-stable insulins like Thermalin, which could be used in an implantable pump,” Whittaker said.
Because its a single-chained molecule, Thermalin also is super fast.Â “You’d be better off if you had a superÂ fast-acting one that you could take with a meal, and it went right to work,” Berenson said. Preliminary evidence also suggests that Thermalin would pose less risk of a cancerÂ or weight-gain than first- or second-generation insulins, he said. Weiss also has developed long-acting insulins, which Thermalin could commercialize in the future.
BerensonÂ isn’t sure yet whether Thermalin will take its insulinsÂ to the market, or whether it will partner withÂ large pharmaceutical companies to do that. He’s done both whileÂ taking severalÂ medical product companiesÂ – InCytu, HeartlanderÂ Surgical, PersonaDX — from research discovery to product with his firm Venzyme, which he calls a venture catalyst. Venzyme isÂ not a venture capital firm but one that connectsÂ promising technologies withÂ sources of money and expertise thatÂ help commercialize them.
It took several years for Case to figure out what to do with the Thermalin technology, Berenson said. Initially positioned as a solution for the insulin pump market –Â tinyÂ – and the developing world market –Â smallÂ – it was thought that bigÂ drug companies wouldn’t be interested in it,Â soÂ “it kind of didn’t go anywhere,” BerensonÂ said. “And then the thinking began to come around,Â beginning of this year.
“So I met with a donor who had been supporting the work at Case by the name ofÂ Dick Dietrich,” he said.Â Dietrich quietly runs theÂ Dietrich Diabetes Research Institute and Diabetes Association of Greater Cleveland.
“IÂ talked to him about the need to do more than justÂ develop the intellectual property, that you had to develop the drug up through proof-of-concept in humansÂ before you were going to get interest from a big pharmaceutical partner,” he said. “And that turned into a plan for doing that and for Dick’s support of our setting upÂ the company.”
Thermalin Diabetes Inc. was created withÂ an option to license Weiss’Â technology,Â spinning the technology out ofÂ Case,Â said Joseph Jankowski,Â associate vice president for technology management in the university’s technology transfer office. “This is one of the coolestÂ technologies that we’ve seen because of the potential to serve mankind,” Jankowski said.
Berenson has raised $150,000 from “family and friends,” including himself, to help Thermalin hire aÂ protein scientist — for which it is now advertising — and protect its intellectual property.Â He’s aiming at closing a round of convertible debt in the next few weeks, andÂ a round of up toÂ $2 million in angel investmentsÂ by the end of the year or early next year.
A $250,000 grantÂ from the federal Small Business Technology Transfer program could help get ThermalinÂ through animal testing next year,Â BerensonÂ said. HeÂ hopes toÂ startÂ clinical trialsÂ “with the goal of getting into humans some time in 2011,” he said. Because Thermalin is a modified insulin, which already is well-understood by the U.S. Food and Drug Administration, Berenson sees a relatively short regulatory and approval pathway for the drug.
Meanwhile, Berenson isÂ presenting his business case toÂ angel investors. “Now, this is a $12 billion a year market that is growing incredibly quickly,” he said, quoting market growth estimates for fast-acting insulins by the World Health Organization.Â “So if you come in with a third-generation insulin analog — by the way, the patents on the current generation run out in a few years — and could capture 15 percent of the market … it’s worth a couple billion dollars to a drug company.”
ThermalinÂ has competitors. Novo Nordisk “has three long-acting insulins in development that they claim you can take once-a-week,” Berenson said. Meanwhile, Eli Lilly has second-generation insulins on the market but has stopped doing mostÂ of itsÂ own insulin research. And Sanofi-Aventis and Merck are shopping for newÂ insulins, he said.
“So we have a lot of big pharmaceutical companies look at this huge market and say, ‘We’d like to play,’ ” Berenson said. “And we know, based on history, that when a new analog comes in, it shakes up the market shares.Â So even if Novo Nordisk has a great product in its pipeline, there are going to be otherÂ companies that want another great product.”
Berenson said he has no fantasies about making a couple billion dollars from Thermalin.Â “But an exit in the regular drug-acquisition range of a couple hundred-million [dollars] is not crazy,” he said. “And this is with a capital efficiency of investment of less than $10 million. So that’s why I think there’s interest in the angel community.”