CollaGenex Pharmaceuticals Technology Highlighted at Dental Research Meeting; New Data in Diabetic Patients Suggests Novel Treatment Strategy for Diabetic Complications.

Business Editors/Health/Medical Writers

NEWTOWN, Pa.--(BUSINESS WIRE)--March 13, 2003

CollaGenex Pharmaceuticals, Inc. (Nasdaq: CGPI) today announced that encouraging data from four studies evaluating the use of Periostat(R) to treat patients with dental and medical disorders will be presented at the American Association for Dental Research (AADR) annual meeting in San Antonio, Texas, March 12 - 15, 2003.

Two independent studies provide new insights into the adjunctive use of Periostat in the treatment of periodontitis patients with diabetes. These data demonstrate that the addition of Periostat to a conventional treatment regimen of scaling and root planing (SRP), not only significantly improves clinical periodontal parameters, but also significantly improves markers of diabetic control. Of particular note, both studies reported that patients administered Periostat exhibited a significant reduction in their glycated hemoglobin (HbA1c) levels, a well-established measure of diabetic control that correlates closely with the risk of complications such as kidney, nerve and eye disease. Patients administered placebo did not receive this benefit.

A third abstract describes the impact of Periostat on biomarkers of systemic inflammation in patients with acute coronary syndromes. These data, which expand on preliminary data presented at the November 2002 meeting of the American Heart Association, indicate that Periostat can reduce systemic inflammation and has the potential to reduce the risk for acute myocardial infarction in patients with elevated levels of high sensitivity C-Reactive Protein (hsCRP).

A fourth paper describes the use of Periostat to modulate wound healing in patients undergoing a form of periodontal surgery called Access Flap Surgery. The authors conclude that, compared to placebo, the drug significantly improves both periodontal clinical outcomes and biochemical markers associated with the breakdown of bone and connective tissue, without causing any alterations in the periodontal microflora.

"The findings of these studies suggest a role for Periostat far beyond its use as an adjunct in the treatment of adult periodontitis," noted Brian M. Gallagher, PhD, chairman, chief executive officer and president of CollaGenex Pharmaceuticals. "It is encouraging that the extensive pre-clinical data, which suggest a role for Periostat in the management of the complications of diabetes, have been reinforced by the findings in these clinical studies. The management of periodontitis in diabetic patients is a significant clinical challenge, and the incremental improvements in clinical parameters afforded by Periostat in these studies is highly significant."

Dr. Gallagher continued, "However, perhaps even more important is the suggestion that the administration of Periostat may have a significant effect on levels of glycated hemoglobin, a powerful surrogate for the risk of diabetic complications, as well as hsCRP, a marker for cardiovascular risk. While much work must be done before these preliminary findings can be translated into a recommendation for use, the initial data are sufficiently encouraging to merit further study of the use of Periostat or other IMPACS compounds for the management of these chronic and debilitating diseases."

Dr. Steven P. Engerbretson and colleagues from the Columbia University School of Dental and Oral Surgery will report data from a randomized, controlled study of 45 patients with long-standing type II diabetes and untreated periodontitis. Patients were randomized to receive Periostat (doxycycline 20mg BID for three months), antimicrobial-dose doxycycline (ADD, 100mg BID day one then 100mg QD for 3 weeks), or placebo in addition to SRP. All were taking oral medications or insulin.

At three months, mean levels of glycated hemoglobin (%HbA1c) in the Periostat group were reduced from 7.9+/-1.9%(+/-SD), to 6.3+/-1.1%, whereas there were no changes in either the placebo (p=0.004 vs. Periostat) or ADD (p=0.03 vs. Periostat) groups. Mean serum glucose levels were not significantly reduced during the study in any of the treatment groups. The authors concluded that Periostat decreases HbA1c in patients who are taking normally prescribed hypoglycemic agents.

In a second abstract, Dr. M.N. Al-Ghazi and colleagues, now of King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia but previously at the State University of New York at Buffalo, will report data from a study that evaluated the efficacy of Periostat, in conjunction with SRP, in the treatment of 20 patients with controlled diabetes and generalized adult periodontitis. This study randomized patients with either type I or type II diabetes to receive either Periostat or a matching placebo BID for 12 weeks.

After 12 weeks of therapy, the Periostat group had a statistically significant reduction in clinical periodontal parameters (p Less than 0.05) and a significant reduction in a marker of diabetic inflammation, Reactive Oxygen Species (ROS) generation (p Less than 0.015), compared to controls. Pocket depth (PD) reduction and Clinical Attachment Level (CAL) gain in the test group exceeded that of control sites by 1.7mm and 1.6mm respectively (p Less than 0.001). Additionally, a statistically significant (p Less than 0.03) reduction from baseline in HbA1c was observed in the Periostat group at 12 weeks, whereas there was no change in the control group. The authors concluded that the study suggests that the adjunctive use of Periostat provides effective periodontal treatment in diabetic patients and that the impact of this therapy on reducing Hb1Ac may be of further benefit.

The impact of Periostat on systemic inflammatory disease unrelated to periodontitis will also be reported in an abstract to be presented by Lorne Golub, D.M.D., Professor of Oral Biology at the State University of New York at Stony Brook. Dr. Golub will present positive data from a placebo-controlled study evaluating the impact of Periostat in treating 50 patients with acute coronary syndromes (ACS).

Blood samples taken before and after the 6-month regimen of either Periostat or placebo revealed significant (p Less than 0.05) reductions in three important factors. Investigators noted a 34% reduction in levels of IL-6, a cytokine released from blood cells in response to inflammatory stimuli that is believed to be responsible for the induction of CRP production by the liver, and a 50% reduction in levels of MMP-9, an enzyme thought to cause destabilization of atheromatous plaque, leading to clot formation.

Additionally, levels of high sensitivity C-Reactive Protein (hsCRP), a marker of systemic inflammation associated with risk of acute myocardial events, were reduced 46%. Furthermore, when the ACS patients were stratified into "higher" (Greater than 5 ug/ml) and "lower" (Less than 5ug/ml) baseline hsCRP levels, Periostat therapy produced a 58% (p Less than 0.001) and 23% (p Greater than 0.05) reduction of this biomarker, respectively. Placebo treatment had no significant effect on any parameters. The authors conclude that these data suggest Periostat can reduce both systemic inflammation, including mediators of connective tissue destruction, and potentially the risk for acute myocardial infarction in patients not referred for periodontal therapy. Based on these encouraging data, a longer-term study addressing clinical end-points, both coronary and periodontal, is being planned.

In an abstract entitled "Modulation of Periodontal Wound Healing by Subantimicrobial Doxycycline Hyclate in Patients with Advanced Periodontitis", Dr. R. Gapski and colleagues from the University of Michigan, Ann Arbor, followed 24 patients randomly assigned to Periostat or placebo following periodontal access flap surgery (AFS). Results demonstrated that patients treated with Periostat showed improvements in PD reduction (3.3mm vs 2.1mm; p Less than 0.05) and CAL gains (1.8mm vs 1.1mm; NS) compared to placebo at 6 months. There was no statistical difference between the Periostat and placebo groups in mean counts for any bacterial species analyzed during this trial, and there was a greater reduction in a specific marker of bone loss, C-telopeptide levels, with Periostat therapy compared to placebo. Finally, levels of collagenase type IV were reduced in the Periostat group (by 7.2%) while in the placebo group a 5% increase in collagenase expression was observed. The authors concluded that the use of Periostat following periodontal surgery appeared to enhance efficacy compared to placebo, whether evaluating clinical or biochemical outcomes, and that the drug had no effect on the periodontal microflora for any pathogen analyzed.

Additionally, a special research symposium on the novel uses for tetracyclines, mechanisms of action and clinical findings, will be held on Saturday, March 15 at the AADR meeting. This symposium, entitled "Non-antimicrobial Properties of Tetracyclines: New Therapeutic Uses," is being organized by Dr. Richard Crout, Professor of Periodontics and Director of Research at the West Virginia University School of Dentistry, and sponsored by the Microbiology/ Immunology, Oral Medicine & Pathology, and Pharmacology, Therapeutics, & Toxicology Groups of the AADR.

CollaGenex Pharmaceuticals, Inc. is a specialty pharmaceutical company currently focused on providing innovative medical therapies to the dental and dermatology markets. Currently, the Company's 120-person professional dental pharmaceutical sales force markets Periostat(R), which is indicated as an adjunct to scaling and root planing for the treatment of adult periodontitis and is the first and only pharmaceutical to treat periodontal disease by inhibiting the enzymes that destroy periodontal support tissues and by enhancing bone protein synthesis. The sales force also promotes Vioxx(R), a Merck & Co. drug that CollaGenex co-promotes for the treatment of acute dental pain, Denavir(R), a Novartis Group prescription anti-viral medication for the treatment of cold sores, and Atridox(R), Atrisorb(R) and Atrisorb-D(R), Atrix Laboratories Inc.'s products for the treatment of adult periodontitis.

Research has shown that certain unique properties of the tetracyclines discovered during the development of Periostat may be applicable to other diseases involving inflammation and/or destruction of the body's connective tissues, including acne, rosacea, meibomianitis and cancer metastasis, among others. CollaGenex is further evaluating Periostat, as well as a series of novel, proprietary compounds known as IMPACS(R) (Inhibitors of Multiple Proteases and Cytokines), to assess whether they are safe and effective in these applications. In addition, CollaGenex has licensed the Restoraderm(TM) technology, a unique, proprietary dermal drug delivery system, in order to develop a range of topical dermatological products with enhanced pharmacologic and cosmetic properties.

To receive additional information on the Company, please visit our website at www.collagenex.com which does not form part of this press release.

This press release contains forward-looking statements within the meaning of Section 21E of the Securities and Exchange Act of 1934, as amended. Investors are cautioned that forward-looking statements involve risks and uncertainties, which may affect the Company's business and prospects. The Company's business of selling, marketing and developing pharmaceutical products is subject to a number of significant risks, including risks relating to the implementation of the Company's sales and marketing plans for Periostat, the outcome and consequences of the patent litigation against West-ward, other products that the Company markets, risks inherent in research and development activities, risks associated with conducting business in a highly regulated environment and uncertainty relating to clinical trials of products under development, all as discussed in the Company's periodic filings with the U.S. Securities and Exchange Commission.

Periostat(R), Metastat(R), Dermostat(R), Nephrostat(R), Osteostat(R), Arthrostat(R), Rheumastat(R), Corneostat(R), Gingistat(R), IMPACS(R), PS20(TM), The Whole Mouth Treatment(R), Restoraderm(TM) and Dentaplex(R) are United States trademarks of CollaGenex Pharmaceuticals, Inc.

Periostat(R), Nephrostat(R), Optistat(R), Xerostat(R) and IMPACS(TM) are European Community trademarks of CollaGenex Pharmaceuticals, Inc. Periostat(R), Nephrostat(R), Optistat(R), Xerostat(R), IMPACS(R), Dentaplex(R), Restoraderm(R), Dermastat(R), Periocycline(R), Periostatus(R) and Periostan(R) are United Kingdom trademarks of our wholly owned subsidiary, CollaGenex International Limited. CollaGenex(R), PS20(R), "C" Logo(R) and The Whole Mouth Treatment(R) are European Community and United Kingdom trademarks of CollaGenex International Limited. Periocycline(TM) and Periostan(TM) are European Community Trademarks of CollaGenex International Limited. All other trade names, trademarks or service marks are the property of their respective owners and are not the property of CollaGenex Pharmaceuticals, Inc. or any of our subsidiaries.