By Mary Welch

BioStratum Inc. will start Phase I trials of Pyridorin (pyridoxamine) and conduct a diabetes research project in Scandinavia, thanks to a $6 million equity financing deal and a $16 million unrestricted research grant.

The equity funding came from two Scandinavian venture capital firms: HealthCap, managed by Odlander and Fredrikson & Co., in Stockholm, Sweden; and BankInvest, of Copenhagen, Denmark.

¿We didn¿t look too hard for institutional investors in the U.S.,¿ said Wesley Fox, executive vice president of the Research Triangle Park, N.C.-based company. ¿We didn¿t wait until any of the [venture capitalists] came on board. This group stepped up and had a vision of us as a big company, which matched our vision. They really embraced us.¿

The $16 million research grant came from the Novo Nordisk Foundation, of Copenhagen, and was presented by the Queen of Denmark to Karl Tryggvason, BioStratum¿s vice president of research and development and one of the co-founders of the company.

Tryggvason heads a team of researchers from four Scandinavian universities, including the Karolinska Institute, in Stockholm, where he is a professor and a Nobel Prize committee member. He also oversees a staff of about 30 persons at BioStratum AB, a fully owned subsidiary in Stockholm.

The research team will study diabetes patients and people without the disease, in order to determine the role of small blood vessels in causing damage to the kidneys and eyes. Specifically, the project¿s goal is to identify how small blood vessels are affected by diabetes and how these changes lead to kidney disease and blindness.

Tryggvason¿s research has primarily concentrated on the basal lamina, a thin membrane present in nearly all tissues that plays a critical role in cell function, cell growth and tissue development. The basal lamina is also a principal element of the glomerulus, the blood filtration unit of the kidney, and a major site of damage in diabetes.

BioStratum will use the equity financing to take Pyridorin and Angiocol through clinical trials, as well as help commercialize its glomerular gene transfer technology for treating kidney diseases

A Phase I trial for Pyridorin will start this summer, following a planned June filing of the company¿s investigational new drug application for diabetes-related complications. The drug inhibits the formation of advanced glycation end products, molecules that are one of the causes of diabetes complications such as kidney deterioration. Pyridorin is highly specific and constitutes a non-cytoxic approach to treating cancer.

The six-month trial will consist of 20 patients receiving one daily dose of Pyridorin, and 20 patients receiving multiple doses.

BioStratum also is conducting preclinical trials for the indications of uremia and end-stage kidney disease, as well as other undisclosed indications.

Angiocol, a human recombinant protein derived from the non-collagenous domain of type IV collagen, is slated for Phase I trials next year as an adjunctive therapy for the treatment of malignant melanoma. Angiocol starves tumors by restricting blood supply, which in turn disrupts interactions between basal lamina components and specific cell integrin receptors that are needed to support new blood-vessel growth. In preclinical trials, the protein has been tested against three different tumor types.

Formed in 1994, BioStratum has about 20 employees in the U.S. Its Swedish subsidiary serves largely as its research arm.

¿The amount of work [Tryggvason] and his group has done, especially in the last two years, is amazing,¿ Fox said. ¿Papers on all of these subjects will be coming out in the next six to nine months.¿ Advances include new therapeutic approaches for kidney disease based on the effective transfer of genes to the glomerulus; the discovery of nephrin, a key protein of the glomerular ultrafiltration barrier; the identification of second generation small molecule inhibitors of MMP-2 using rational drug design; and the use of anti-laminin technology to detect and image metastatic tumors.

¿This would be the envy of any pharmaceutical company,¿ Fox said.