Interesting. The Glycominds' "Glycochip" should be right up your street, Tuck.
Jerusalem Report (August 27, 2001)
August 27, 2001
How Sweet It Is
By Hanan Sher
Sugar molecules called glycans may cut millions of dollars off drug development costs, and pave the way for tailor-made pharmaceuticals.
A SHOPPING CENTER IN a leafy, detached-home community in central Israel is not where you'd expect to find the cutting edge of the biotech revolution. But next to a computer-games shop, not far from a hairdresser and a non-kosher deli on the second floor of the unpretentious mall in Maccabim, just outside the new city of Modi'in, a two-year-old company is developing biotechnology that could radically cut drug-development costs - and perhaps, even drug prices.
The company is called Glycominds and works with glycans, particles that appear on the surface of living cells and enable the communication between them. "You could also call them sugars or carbohydrates," says Asaf Halevi, the firm's 29-year-old director of business development. "The terms are interchangeable, though there are subtle differences between them."
Whatever you call them, glycans could represent a sweet business opportunity. The main potential clients are major drug companies anxious, for obvious reasons, to cut several hundred million dollars and a big chunk of time out of the $1 billion and 10 years it usually takes to guide a drug from lab experiment to the market.
Glycans have been known for years, but have come into prominence in the post-genome era. To explain, Glycominds co-founder Avinoam Dukler, 35, points to two charts on the wall. "The smaller one maps the 500 known 'targets' for genetics-based drugs," he says. "And the larger is a map of the 30,000 genes analyzed by the Human Genome Project last year." Two new disciplines have developed from the genome project, which classified and catalogued the genetic structure of humans. First came proteomics, the study of proteins, which maintain all cellular functions and, when they mutate, can trigger disease. Beyond proteins, Dukler says, are the sugars, "which direct the proteins to where they are going, and determine how they act." The study of these sugars is called glycomics.
In layman's terms, then, glycans might be equated to the transmitters and receivers of the cellular world. "They are crucial in the function of proteins," Dukler says. "We have seen experiments where scientists knock out the sugar and watch how the protein behaves without it. More than half the time, proteins don't function as expected."
Halevi produces a vastly enlarged image of a protein molecule, surrounded by the glycans, which look like little bubbles and wavy fibers. "Glycans are anchored to the cell, and if something tries to get in - be it a virus, say, or a growth hormone - it does so via the glycans," he explains.
It's also possible to determine what is going on in the cell by its glycans, which Halevi says "vary by the disease state of the cell. If there is a malfunction on a kidney cell and it has to absorb a certain metabolite to make it operate, the sugars that recognize that metabolite are very likely to be found on the surface of that cell."
And, it turns out, glycans are also what differentiate between human blood types - "the glycan present in blood type A is different from the one in B, and it's the glycans that are the cause of the difference in the type," Dukler says - and make the difference between humans and apes.
"The genetics of a human and an ape - or for that matter a fruit fly or a zebra fish - are 98 percent the same," Halevi elaborates. "But on a glycomic level, we are very different." As a result, different glycans are one of the reasons that, say, a protein-based drug may cure cancer in mice, but may not function, or may even be toxic, when administered to humans.
Dukler, a tall, earnest man, cracks a smile. "We like to say it would be better to eat mice and study cows," he intones, "because the glycans in cows and humans are similar, and those in mice and some other mammals don't exist in humans, and some of them cause adverse immune reactions."
CEO DUKLER AND PRESIDENT Nir Dotan, 37, didn't found Glycominds just to develop an academic research tool. In the three years since they hatched the idea over cafeteria coffee at Tel Aviv University, where both were in the last year of their PhD studies, they began looking for ways to turn their knowledge - Dukler's in biotech processing, Dotan's in miniaturized nanotechnology - into a business. They realized that there were tools that streamlined the laborious process of anal-yzing DNA and the complex proteins that make up cells, but none for glycans. And they set out to develop a patented technology that could replicate an individual glycan on a "chip." The result is their Glycochip, which looks more like a slide, and can be inserted into a standard lab device called a reader to scan large numbers of proteins. When protein and glycase match, it's possible to predict how they interact.
Knowing what sugars are attracted to what proteins is vital to the function of any drug, because sometimes sugars are attracted to other blocking agents, which could mean that a drug that otherwise seems perfectly reasonable won't work. And matching is essential because the shape of the molecule often dictates its function.
In addition to the Glycochip, on which they have 11 patents, Glycominds says it has the world's largest database of glycans - about 5,000, almost half of the total number discovered so far.
These sophisticated resources can be marketed to manufacturers of protein-based drugs. There are many such drugs already on the market, including Amgen's Avonex, which uses the beta interferon protein to treat multiple sclerosis. And though protein-based remedies only represent about 10 percent of currently available drugs (the rest are synthetic chemical compounds), the industry sees protein antibodies as its major growth area. Halevi says synthetic drugs are mostly blockers that stop cellular response, while protein-based drugs enhance existing cell reactions. "They're natural and less prone to create other problems in the body," he adds.
Beyond that, natural molecules avoid some of the patent problems inherent in the development of synthetic drugs. "A synthetic molecule can be varied ever so slightly, and the discovery may not be protected," Halevi says. "But there's only one erythropoietin," a blood protein molecule that is the basis of Epogen and Procrit, anti-anemia drugs that together are responsible for $2 billion in sales.
The number of new drugs introduced onto the market each year is falling, mainly due to the astronomical sums spent on development. As glycan tests can spot unanticipated reactions long before the drug goes into expensive clinical trials, hundreds of millions of dollars may be saved. Dukler anticipates that early glycan analysis can increase the success rate on drug development from the current 10 percent to almost 20 percent. He estimates that the total market for this kind of "prioritization" technology could amount to $1 billion a year, and his company hopes to tap in by offering its proprietary analytic services to pharmaceutical firms in exchange for fixed fees, or possibly royalties on the sale of the developed drug.
"The value of such collaboration depends on how much you bring to the table," says Dukler, who's obviously picked up some of the jargon of high-tech financiers. "And value obviously depends on the amount of exclusivity you can offer."
Right now, Glycominds contends that it's sitting in the catbird seat, with the only proven diagnostic tool and the largest glycan database. There are other firms in the field as well, including Neose of the United States, which is working on a way to alter glycan action, and a British firm working on glycan analysis. "The number of companies has doubled in the past year, but our ability to assess hundreds of proteins against glycans at the same time, rather than a laborious one-by-one comparison, makes us the leader," claims Halevi.
THOUGH IT HAS EXPLODED Into prominence over the past couple of years, glycomics isn't a brand new discipline. Indeed, the first instance of protein-carbohydrate binding was discovered in 1897. But it only had a great growth spurt at about the time the Human Genome Project was winding down, when masses of information about the protein content of genes became available.
"Two years ago, when we were putting Glycominds together, I searched the Internet for 'glycomics'," Dukler says. "And I hardly found any entries at all. Today there are hundreds, showing companies and academic papers at conferences. And a university consortium on glycomics is just now in the process of getting a grant from the U.S. National Institutes of Health."
Glycominds started in 1999, after both principals had completed their studies. "Our financing was typical of start-ups, involving the 3-F's - father, friend and fool," shrugs Dukler. "During that first year, our lab was in back of Nir Dotan's home, and the computer center was in mine."
Two rounds of financing followed - $1.3 million from angel investors Dukler won't name and $4 million this summer, when there was already a company with 20 employees, from computer scientists to genetics experts. The latest investors were led by the Tel Aviv Millennium venture capital fund, at a company valuation Dukler won't disclose. "All I can tell you is that the seed-round investors were pleased," he says.
The new money gives Glycominds the ability to move forward slowly in refining its technology and its marketing and expanding its glycan database. They don't expect their first sale until late next year, and are loath to talk about when they'll reach profitability on their balance sheet. It's also a little too early for Dukler and his colleagues to foresee exactly how the business will develop, but he sees reason to believe that, in the beginning, they'll be glad to settle for service agreements with drug companies where they will test specific products. Joint development projects with big concerns on the order of Eli Lilly or Pfizer may come much later.
Even farther in the future, perhaps, glyconomics might branch out into tailor-making drugs for population groups with similar genetics. "Just as today we know sickle-cell anemia is prevalent among blacks and Tay-Sachs appears in Ashkenazi Jews, we may be able to segment the population by glycans," says Halevi. "And if one group's glycans recognize some substance as a foreign object, it may eventually be possible to alter a substance according to their glycan profile." ... |
