Angiogenesis Inhibitor Shows Early Promise in Treatment of Kaposi's Sarcoma.

Business Editors/Hi-Tech Writers

BETHESDA, Md.--(BUSINESS WIRE)--May 18, 2000

Data Presented at International AIDS Malignancy Conference

Demonstrate General Tolerability, Anti-Tumor Effect with Col-3

Researchers today presented positive findings from an 18-patient, NCI-sponsored Phase I dose-escalating study of the angiogenesis inhibitor Col-3 (Metastat(R), CollaGenex Pharmaceuticals, Inc. / Nasdaq: CGPI), administered once daily to patients with Kaposi's sarcoma, a disfiguring and potentially deadly malignancy frequently associated with human immunodeficiency virus (HIV). The data were presented during the 4th International AIDS Malignancy Conference, sponsored by the National Cancer Institute of the National Institutes of Health.

The trial, conducted by the AIDS Malignancy Consortium and sponsored under a Cooperative Research and Development Agreement between the NCI and CollaGenex, demonstrated an overall tumor response rate of 33 percent, with four of nine patients responding at the two highest doses administered and two of nine responding at the lowest dose. The agent was generally well tolerated, particularly at the lowest dose levels. Three patients have continued to receive treatment for more than six months, including one patient who has been on the drug for more than one year.

"One-third of all patients in this study had a positive clinical response, which appears to indicate the inhibition of angiogenesis, a major factor in the pathogenesis of Kaposi's sarcoma. In addition, Col-3 did not cause any serious hematologic toxicities," said lead investigator Bruce J. Dezube, MD, associate in medicine, Beth Israel Deaconess Medical Center, Boston, and assistant professor, Harvard Medical School. "These are promising findings for the AIDS and cancer communities, as Kaposi's sarcoma continues to be the most common malignancy occurring in the setting of HIV, with potentially serious consequences."

The NCI anticipates beginning additional clinical studies to learn more about Col-3's activity in patients with Kaposi's sarcoma.

According to study investigators, Col-3 was well tolerated, with an infrequent incidence of serious adverse events reported, particularly at the lowest doses. The most common drug-related side effects reported were rash and photosensitivity.

Col-3, or Metastat(R), has been developed based on CollaGenex's proprietary IMPACS(TM) (Inhibition of Multiple Proteases and CytokineS) technology. The compound appears to have a dual mechanism of action, with anti-tumor activity conferred by its combined broad inhibition of several tissue destructive enzymes and the down-regulation of various inflammatory cytokines that are implicated in metastasis.

Kaposi's sarcoma (KS) currently is estimated to develop in 20 - 30 percent of HIV-infected people; it most commonly involves the skin, with the hallmark, elliptical lesions appearing on the face, the lower extremities and the oral mucosa. In more severe cases, the disease spreads to the gastrointestinal tract, the lungs and to other organs. Moreover, the negative psychosocial aspects of KS can be significant, with many patients experiencing severe emotional distress, guilt, ostracism and loss of employment.

"Col-3 is an easily administered oral agent that the patient could potentially take over a long period of time," said Dr. Dezube. "This approach to management of KS may be well-suited for this often non-life-threatening condition, which frequently occurs in an otherwise relatively healthy individual who may be averse to a cytotoxic chemotherapy, the most common, current treatment."

Of the 18 patients in the study, more than half had at least 50 KS lesions at baseline, and nearly one-third had tumor-associated edema (excess fluid in tissues). Nearly 90 percent of patients had undergone previous treatment for KS, and most had been treated with antiretroviral therapies.

"It is encouraging to observe the clinical benefit of using the multi-target approach represented by the IMPACS technology, exemplified by Metastat," said Brian Gallagher, PhD, CollaGenex president and chief executive officer. "This potential ability to restore the body's normal balance of biological mediators, which are elevated in cancer and other tissue destructive diseases, may one day offer new hope to patients suffering from Kaposi's sarcoma, as well as other forms of cancer."

CollaGenex Pharmaceuticals, Inc., is a specialty pharmaceutical company focused on providing innovative medical therapies. The company's lead product, Periostat(R) (doxycycline hyclate), was approved by the Food and Drug Administration in September 1998 and is the first and only pharmaceutical to treat periodontal disease by inhibiting the enzymes that destroy periodontal support tissues.

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 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.