CollaGenex Pharmaceuticals Announces Initiation of Phase II Clinical Trial in Kaposi's Sarcoma With Proprietary Angiogenesis Inhibitor.

Business Editors/Health & Medical Writers

NEWTOWN, Pa.--(BW HealthWire)--Aug. 2, 2001

AIDS Malignancy Consortium Sponsored by the National Cancer Institute

Opens a Multi-Center Study to Determine the Response Rate of COL-3

(Metastat(R)) in Patients with HIV-Related Kaposi's Sarcoma

CollaGenex Pharmaceuticals (NASDAQ: CGPI) today announced that the AIDS Malignancy Consortium (AMC), sponsored by the National Cancer Institute (NCI), has opened enrollment for a multi-center study to determine the efficacy of COL-3 (Metastat), an orally active angiogenesis inhibitor developed by CollaGenex Pharmaceuticals, in HIV-related Kaposi's sarcoma (KS).

The AMC previously reported results from an 18-patient, NCI-sponsored Phase I dose-escalating study of Metastat administered orally once-daily to patients with KS. The agent was generally well tolerated, particularly at the lowest dose levels, and exhibited an overall clinical response rate of 44 percent. 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 failed previous treatment for KS, and most had been treated with antiretroviral therapies.

"There is no FDA-approved, orally-administered drug for the treatment of HIV-related Kaposi's sarcoma," said lead investigator Bruce J. Dezube, MD, associate professor of medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA. "The initiation of the Phase II clinical trial with Metastat represents a major step toward developing a new class of agents 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 phase II trial is expected to enroll 70 patients with HIV-related KS at two dose levels of Metastat. The primary objectives of the study are to evaluate the tumor response rate and response duration as well as to evaluate the biologic activity of Metastat by measuring serum levels of pro-angiogenic mediators. Several of these mediators were observed to be down-regulated in subjects enrolled in the phase I trial who responded to Metastat.

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, as well as the down-regulation of various inflammatory cytokines that are implicated in metastasis.

"We are encouraged that the National Cancer Institute and AIDS Malignancy Consortium are proceeding without delay in the clinical development of Metastat following the success of the phase I trial," said Brian M. Gallagher, PhD, chairman, president and chief executive officer of CollaGenex. "This trial will not only further the development of Metastat for Kaposi's sarcoma, but will also be an important proof-of-principle study to establish the clinical benefit of the IMPACS technology, in which multiple biological processes involved in tumor growth and metastasis, including angiogenesis, are targeted with a single drug. If successful, this novel approach to cancer therapy may offer a more effective alternative 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 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. In February 2001, the FDA granted marketing approval for a new tablet formulation for Periostat. Periostat is marketed to the dental community by CollaGenex through a professional pharmaceutical sales force composed of approximately 120 sales representatives and managers. Currently, the Company's dental sales force is also marketing Vioxx(R), a Merck & Co. drug that CollaGenex co-promotes for the treatment of acute dental pain, and Dentaplex(TM), a unique formulation of vitamins and mineral supplements developed by CollaGenex and MediNiche, Inc. to promote oral health.

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 metastases (Metastat) and a broad range of inflammatory diseases. CollaGenex is developing a series of novel, proprietary compounds known as IMPACS (Inhibitors of Multiple Proteases And CytokineS) to address these applications. The Company intends to pursue further research and development of these technologies primarily through partnerships with third parties.

To receive additional information on the Company, please visit our Web site at www.collagenex.com, which is not a part of this press release.

Periostat(R), Metastat(R), IMPACS(R)and Dentaplex(TM)are trademarks of CollaGenex Pharmaceuticals, Inc. CollaGenex(R)and Periostat(R)are trademarks of CollaGenex International Limited VIOXX(R)is a trademark of Merck & Co., Inc.