As BioStratum scientists unravel the molecular mechanisms by which the basal lamina participates in disease processes, novel therapeutic targets and drug candidates have emerged.

In diabetes, the basal lamina is affected by an increase in the level of advance glycation end-products, referred to as A.G.Es., which in turn contribute to the vascular-related complications that develop in diabetes. BioStratum scientists isolated an important precursor to A.G.E. formation, which provided for the development of a unique screening assay that has identified improved inhibitors of A.G.E. formation. One of these, Pyridorin™, has shown superior performance in animal studies of diabetic kidney disease, and is currently in Phase II clinical trials.

The important role of the basal lamina in the growth of new blood vessels has been an active area of investigation for BioStratum scientists. This work has led to the identification of a novel anti-angiogenesis drug candidate, Angiocol™, that inhibits new blood vessel growth by disrupting the assembly of new basal lamina and its interactions with cell receptors. This drug candidate has shown potent anti-angiogenesis and anti-tumor activity in
a number of animal models, and is progressing toward clinical trials.

The basal lamina plays a key role in directing the growth and development of cells and tissues. BioStratum scientists have developed recombinant methods to produce basal lamina molecules. We believe that these proprietary protein molecules are the largest and most complex molecules ever produced using recombinant technology. They represent what we think is a promising new class of regenerative medicines. We are currently evaluating them
in a number of preclinical models of periodontal, vascular and skin diseases.

The basal lamina located in the kidneys is the target of
the rare autoimmune disease Goodpasture syndrome. BioStratum scientists have determined the structure and location of the autoantigenic site in this disease. Analysis of this structure has led to an understanding of what causes a protein to become autoantigenic. This research indicates that an impairment in the way certain proteins
fold and organize in the body is a fundamental cause of many autoimmune diseases. We have identified enzymes that are the probable causes of this impairment, and we have begun preclinical studies targeting these enzymes. Unlike other approaches that target the autoimmune response, this therapeutic approach targets the source
of auto-antigenicity, and therefore the cause of autoimmune disease, opening the door to the possibility of being able to prevent a variety of autoimmune diseases.

The Company operates a wholly-owned subsidiary in Sweden, BioStratum AB. This subsidiary works in collaboration with the Division of Matrix Biology at the Karolinska Institute, Stockholm, Sweden, the laboratory
of Dr. Karl Tryggvason, a cofounder of BioStratum. BioStratum AB functions primarily as a European development unit for BioStratum Incorporated, and has an extensive portfolio of projects, including proprietary genes and novel therapeutic targets for cancer and kidney disease.