TORONTO - GlycoDesign Inc., focused on enzyme inhibitors involved in synthesizing carbohydrates, raised C$13.65 million (US$9.5 million) from nine venture capital organizations.

The investor confidence shown in Toronto-based GlycoDesign, which has raised a total of C$35 million in venture financing since its inception in 1994, revolves around the fact that its founding scientists were among the first in the world to identify the cell-surface carbohydrate structures that make possible the invasion and spread of cancer.

Carbohydrate biotechnology R&D has grown tremendously in the last few years. The knowledge that carbohydrates on the surface of cells act as recognition signals that regulate the mobility and growth of cells, immune responses, binding of hormones and growth factors - as well as the susceptibility to infection by viruses and bacteria - has given rise to a new wave of glycobiology start-ups.

Mostly, the research approach has concentrated on the development of molecules designed to block cell signaling by preventing the appropriate cell-surface carbohydrates from binding.

In contrast, fast-growing GlycoDesign believes it has found, in its inhibitors of enzymes involved in constructing carbohydrates, a newer and more viable approach to drug development.

This belief has attracted the attention of major Canadian institutional investors, allowing GlycoDesign to complete one of the larger private rounds of financing ever in the Canadian biopharmaceutical industry.

Jeremy Carver, president and CEO of GlycoDesign, and one of the company's founding scientists, told BioWorld International half of the funding came from new investors.

They include: Bank of Montreal Capital Corporation and BioCapital Investments Limited Partnership, both of Montreal; Ventures West VI Limited Partnership, of Vancouver; and Triax Growth Fund, of Toronto. Increasing their stakes in the company were the Toronto-based groups MDS Health Ventures Inc., Working Ventures Canadian Fund, Royal Bank Capital Corporation and Business Development Bank of Canada. Another existing investor taking part was Canadian Medical Discovery Fund of London, in Ontario.

Carver is a former professor in the departments of molecular and medical genetics, biochemistry and medical biophysics at the University of Toronto. He is recognized internationally as a leader in the determination of carbohydrate three-dimensional structures and in the identification of factors that determine the strength with which these molecules bind to proteins.

GlycoDesign has established itself as a world leader in glycobiology and has a unique proprietary technology platform to discover and develop inhibitors of key carbohydrate processing enzymes, referred to as carbohydrate processing inhibitors (CPIs). These CPIs are small molecules which are orally active and rapidly taken up into tissues.

The company's first CPI product and lead compound, GD0039, is an inhibitor of the Golgi apparatus enzyme alpha-mannosidase II (a-MII). This enzyme is involved in the processing of carbohydrates on newly synthesized glycoproteins as they make their way through the Golgi apparatus to the cell surface.

Tumor Growth Slowed In Animals

Blocking the synthesis pathway at a-MII inhibits the formation of highly branched, cancer-associated carbohydrate structures. Inhibition of a-MII has been shown to reduce the rate of tumor growth and metastasis in animal models. In addition, the free base form of GD0039 has been investigated in two Phase I trials involving patients with late-stage metastatic cancer. One patient with head and neck cancer showed an objective 75 percent reduction in tumor size, while two other patients experienced relief from symptoms while on therapy.

Carver said proceeds from the financing will be used to advance the company's discovery and clinical research programs. A Phase II Canadian investigational new drug application in cancer (solid tumors) has recently been approved. Clinical trials will be initiated targeting melanoma and renal cell, lung, breast, head and neck, and colorectal cancers.

Using its integrated technology platform, GlycoDesign is developing other glycosidase and glycosyl transferase inhibitors with potential applications in cancer, inflammation and infection.

GlycoDesign scientists have identified carbohydrate processing enzymes important in inflammation and in certain bacterial and fungal infections. For example, CPI has been shown to enhance the antiproliferative and antiviral effects of interferon in animal models. The company, which is looking for a pharmaceutical collaborator, plans to file two U.S. Phase II investigational new drug applications for GD0039 in hepatitis C and chemo/meloprotection next year. *

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