BioStratum Reports Drug Candidate Pyridorin™ Demonstrates Improved Performance in Preventing Kidney Disease in Animal Models of Diabetes
- - Results suggest unique post-Amadori inhibition key
to improved efficacy - -

Research Triangle Park, N.C. -- October 29, 1998 -- BioStratum Incorporated today announced the presentation of preclinical results demonstrating the effectiveness of its drug candidate Pyridorin™ in preventing the development
of diabetes induced kidney disease. Presentations on the performance of Pyridorin™ were given at both the Diabetic Complications Conference held at the Joslin Diabetes Center's 100th Anniversary Conference, Boston, MA, and
at the 31st annual meeting of the American Society of Nephrology being held in Philadelphia, PA.

Collaborating scientists from the University of South Carolina led by Dr. John Baynes presented promising preclinical results from Pyridorin™ experiments which employed the streptozotocin (STZ) diabetic animal model. In addition, collaborating scientists from the University
of Kansas Medical Center presented their results from Pyridorin™ experiments based on an AGE-albumin animal model of diabetic nephropathy. Both studies compared
the performance of Pyridorin™ with aminoguanidine at equivalent dosages.

In diabetes, elevated levels of glucose are known to promote the non-enzymatic glycation of proteins, which
are subsequently oxidized into a group of toxic products collectively referred to as advanced glycation end products or AGEs. AGEs induce changes in protein structure and function, particularly in vascular and renal basement membranes, and can cause inflammation and changes
in cell metabolism. AGEs are believed to be a principal causative factor in the development of diabetic nephropathy.

The formation of AGEs can proceed through a number
of non-enzymatic glycoxidative mechanisms. One such pathway is through the oxidation of Amadori intermediates that form on the surface of proteins following non-enzymatic protein glycation. Previous studies at the University of Kansas Medical Center, under a group headed by
Dr. Billy G. Hudson, led to a specific method of isolating protein Amadori intermediates and following their conversion to AGEs.

This advancement provided for a novel in vitro screening method to search for novel post-Amadori inhibitors of AGE formation. Initial screening studies on known inhibitors of AGE formation, including aminoguanidine, showed little post-Amadori inhibitory activity. Subsequent screening studies led to the identification of Pyridorin as a unique and potent inhibitor of the conversion of post-Amadori protein intermediates to AGEs. These advances led BioStratum
to initiate several animal studies to examine the in vivo efficacy of Pyridorin in preventing the development of diabetic nephropathy. As reported at the above mentioned scientific meetings, Pyridorin has been shown to inhibit
the development of diabetic kidney pathologies in the STZ animal model of diabetes. While albuminuria and plasma creatinine levels increased progressively in untreated diabetic animals, both were significantly reduced by Pyridorin treatment. Also, Pyridorin exhibited a significant improvement over aminoguanidine in preventing these pathologies.

These studies also monitored changes in plasma levels
of tryglycerides and cholesterol. It was discovered that Pyridorin reduced the levels of triglyerides and cholesterol in the STZ diabetic animals. As in the case of diabetic kidney disease parameters, Pyridorin showed improved performance over aminoguanidine in reducing triglycerides and cholesterol.

BioStratum collaborators from the University of Kansas reported Pyridorin to be highly effective at preventing
certain nephropathy changes characteristic of early diabetes. These changes were induced by injecting glycated albumin into an animal model. It is believed
that circulating glycated plasma proteins may contribute
to kidney damage through glycoxidative processes that lead to AGE formation. As in the case of the STZ study, treatment with Pyridorin was significantly more effective than aminoguanidine at inhibiting induced kidney pathology.

These results suggest that the specific inhibition of the conversion of protein Amadori intermediates to AGEs is a therapeutically relevant in vivo target, and that drugs which target this conversion may be more effective at inhibiting the development of diabetic kidney disease than drugs that target other mechanisms of AGE formation.

Dr. Archie Prestayko, BioStratum's President and CEO commented, "We believe Pyridorin's unique mechanism of action could be an important advancement to the current management of patients with diabetic nephropathy. We are now conducting IND enabling toxicity studies, and look forward to our Phase I clinical trails that are expected to begin during the second quarter of 1999."

In the U.S. approximately 30 to 40 percent of insulin dependent Type I diabetics and 10-15% of non-insulin dependent Type II diabetics (a total of 1.5 million patients) develop nephropathy, which is the leading cause of end-stage renal failure.

BioStratum is a privately held company developing proprietary therapeutics based on recent scientific advances in basal lamina and related technologies. The company's drug candidates are directed against novel basal lamina extracellular targets involved in degenerative and invasive disease processes fundamental to kidney disease, diabetes and cancer. The company has also developed methods for the production of recombinant basal lamina proteins for use in wound repair and advanced tissue regeneration protocols.