CollaGenex Research Highlighted at International Dental Research Meeting.

Business Editors/Health & Medical Writers

NEWTOWN, Pa.--(BUSINESS WIRE)--April 5, 2000

CollaGenex Pharmaceuticals, Inc. (Nasdaq:CGPI), today announced that nine scientific papers highlighting research sponsored by the Company will be presented at the upcoming International Association for Dental Research Meeting in Washington DC, April 5-8.

These papers include new data on the safety and efficacy of Periostat(R), the company's flagship product for the adjunctive treatment of adult periodontitis, as well as exciting pre-clinical data on the properties of the Company's novel IMPACS(TM) (Inhibitors of Multiple Proteases And CytokineS) technology.

Among the papers discussing clinical studies with Periostat is a key safety study, which will be presented by Dr. C. Walker (University of Florida, Gainesville), directly addressing the impact of the drug on the colonic and vaginal microflora. The abstract concludes that "there is no evidence that Periostat exerted an effect on the composition or resistance level of either the fecal or the vaginal microflora," supporting the findings from previous studies reporting no direct effects of the drug on the composition or microbial resistance of the oral microflora.

These data are important because they provide further support to the concept that the clinical benefits of Periostat result from the unique ability of the drug to inhibit the proteolytic enzymes involved in connective tissue destruction, without inducing bacterial resistance to commonly used antimicrobial agents.

In a second presentation, Dr. M. Ryan (SUNY at Stony Brook) will provide further evidence for the unique properties of Periostat in a preliminary study of a group of patients testing positive for a gene thought to be prognostic for the development of severe periodontitis. Genotype positive patients were monitored for expression of proteolytic enzymes and other substances known to cause tissue breakdown in gingival crevicular fluid, the fluid which bathes the tooth surface.

Patients taking Periostat exhibited significantly lower amounts of these substances, whereas traditional periodontal therapy (scaling and root planning) was ineffective in reducing these markers of connective tissue destruction. She concludes that Periostat "may provide genotype positive patients with a therapeutic strategy which specifically addresses their exaggerated host response."

Other papers with potential clinical significance include a study by Dr. Y. Liu et al (SUNY at Stony Brook) which shows that doxycycline, the active ingredient in Periostat(R) can directly affect the reaction of glucose with biological membranes. This is important because this process, known as "glycation", is thought to be responsible for many of the side effects encountered by diabetic patients if their blood glucose levels are poorly controlled.

A second paper from Dr. L. Xu (SUNY at Stony Brook) characterized the enzymes responsible for the breakdown of connective tissue around failing dental implants, a condition known as peri-implantitis. The authors conclude that "these enzymes are even more elevated in peri-implantitis than in adult periodontitis", suggesting a potential role for Periostat in the adjunctive treatment of peri-implantitis.

A third paper from Dr. D.M. Cohen (U. Nebraska) reports a preliminary clinical study using a combination of Periostat and a non-steroidal anti-inflammatory drug in the treatment of a serious blistering disease of the mouth called Cicatrical Pemphigold. The authors report total remission or significant improvement in disease symptoms within two weeks in 9/9 patients treated with this novel combination therapy, suggesting a potential role for Periostat in the treatment of this severely debilitating disorder.

The same combination therapy also significantly reduced the excess enzyme activity in gingival biopsies from a group of patients with adult periodontitis.

Other papers presented at the meeting describe the unique properties of the novel, proprietary CollaGenex core technology, known as "IMPACS(TM)"(Inhibitors of Multiple Proteases And CytokineS). A paper from Dr. J. Thomas (West Virginia U.) confirms that the IMPACS compounds are not antimicrobial agents, despite structural similarities to known antimicrobials. This is important as it supports the application of a wide range of doses of these compounds in clinical trials without concern about development of microbial resistance.

A second paper from Dr. K. Kirkwood (SUNY at Buffalo) describes the ability of the IMPACS technology to down-regulate production by bone forming cells (osteoblasts) of a specific substance responsible for the up-regulation of bone resorption (IL-6).

This finding is encouraging as it helps explain the previously reported data suggesting that IMPACS could be useful in the treatment of bone-destruction disorders, such as osteoporosis and periodontitis. A third paper, from Dr. N. Ramamurthy (SUNY at Stony Brook) describes results from a well-characterized rat model of periodontitis in which the IMPACS were able to prevent the progression of the disease.

Finally, a paper from Dr. H.M. Lee (SUNY at Stony Brook) suggests that the IMPACS have effects not only on host derived protease activity but also on proteases derived from certain bacteria thought to be involved in periodontal breakdown.

"It is encouraging that our ongoing research collaborations conducted under CollaGenex sponsorship continues to contribute to our knowledge about the mechanism of action of Periostat and the IMPACS technology," noted Brian M. Gallagher, PhD, president and CEO of CollaGenex. "These studies will help direct our clinical research effort focused on the expanding potential for Periostat(R) and the IMPACS as unique therapeutics for the treatment of diseases of acute and chronic inflammation and connective tissue destruction."

CollaGenex Pharmaceuticals, Inc. is a specialty pharmaceutical company focused on providing innovative medical therapies to the dental market. The company's lead product, Periostat, was approved by the FDA in September 1998 and is the first and only pharmaceutical to treat periodontal disease by inhibiting the enzymes that destroy periodontal support tissues.

Periostat is marketed to the dental community in the United States by CollaGenex through a professional pharmaceutical sales force composed of approximately 135 sales representatives and managers. Currently, the company's dental sales force is also marketing Vioxx(R), a Merck & Co. drug that the Company promotes for the treatment of acute dental pain, and Denavir(R), a SmithKline Beecham Consumer Healthcare prescription drug for the treatment of cold sores.

Research has shown that the enzyme-suppression technology underlying Periostat may also be applicable to other diseases involving destruction of the body's connective tissues including cancer metastasis and a broad range of inflammatory diseases. CollaGenex is developing a series of novel, proprietary compounds known as IMPACS(TM) (Inhibitors of Multiple Proteases And CytokineS) to address these applications. The Company intends to pursue further research and development of this technology primarily through partnerships with third parties.

For additional information on CollaGenex, please visit the Company's web site at www.collagenex.com, which is not a part of this press release.

This news 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, 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) and IMPACS(TM) are trademarks of CollaGenex Pharmaceuticals, Inc.