Sweet approach to drug development

Promoters say drugs based on glycans, or sugars, can increase the success rate of pharmaceutical development.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. …

Promoters say drugs based on glycans, or sugars, can increase the success rate of pharmaceutical development.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 make possible the communication between them. “You could also call them sugars or carbohydrates,” said 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 said. “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 said, 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 said. “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 produced 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 said.

It’s also possible to determine what is going on in the cell by its glycans, which Halevi said “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.”

Chief Executive Officer 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 Ph.D. 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 analyzing 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 said 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.

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 said. “But there’s only one erythropoietin,” a natural protein molecule from blood 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.