New Cavity Fighting Agent Significantly More Effective Than Fluoride in Two-Year 726 Patient Toothpaste Study; Children Brushing with Cavistat Paste Had 96% Fewer Cavities.

Business Editors/Health/Medical Writers

ROSLYN HEIGHTS, N.Y.--(BUSINESS WIRE)--June 24, 2003

Study Results to Be Presented June, 28, 2003 at the 81St General

Session of the International Association of Dental Research

Goteborg, Sweden

Ortek Therapeutics Inc. announced today that CaviStat(TM), a new cavity fighting agent, was significantly more effective than fluoride in reducing cavities in a two-year 726 patient toothpaste study. The findings of this clinical trial will be presented at the 81st General Session of the International Association of Dental Research, Goteborg, Sweden on June 28, 2003. According to the study, children who brushed with a CaviStat toothpaste had 96% fewer cavities than children who brushed with fluoride toothpastes. This study, which was sponsored by Ortek, was conducted by researchers at the State University of New York at Stony Brook and the University of Central Venezuela in Caracas.

CaviStat is the first in a new class of cavity fighting compounds that can counter the production of harmful plaque acids while simultaneously promoting remineralization of the teeth. CaviStat contains the amino acid, arginine, in conjunction with bicarbonate and calcium carbonate. These components are food grade, and unlike fluoride, are safe for young children to swallow in a toothpaste and can be added to candies and gum. This is a very important additional benefit of CaviStat since excessive ingestion of fluoride during early childhood can cause dental fluorosis, a discoloring of the permanent teeth. In fact, to reduce the risk of fluorosis for children aged 6 or under, the Center for Disease Control, in an August 2001 report on fluoride use, recommended that toothpaste manufacturers develop a "child-strength" toothpaste with lower concentrations of fluoride.

Cavities are still one of the most prevalent diseases worldwide. It affects people of all age groups. This infectious disease occurs when bacteria on tooth surfaces convert sugars to harmful acids that dissolve the teeth over time. CaviStat(TM) is designed to interrupt this process. Alongside the acid-producing bacteria are other bacteria that metabolize arginine and produce base, which neutralizes the cavity forming acids. This elevated pH environment also promotes absorption of calcium back into the teeth, a process called remineralization.

CaviStat, which is based on over 30 years of research on saliva's substantial role in preventing tooth decay, was developed by Dr Israel Kleinberg, Distinguished Professor and Chairman of the Department of Oral Biology and Pathology at Stony Brook University. Dr Israel Kleinberg said, "CaviStat represents a new direction in the battle against tooth decay. This unique compound can be very beneficial for children and for the millions of adults who are prone to root cavities due to poor saliva production. Reduced saliva flow, which often results in a rapid rise in the development of cavities, is caused by hundreds of prescription and non prescription drugs, cancer therapies and Sjogren's syndrome, an autoimmune disease."

Ortek Therapeutics, Inc. was granted exclusive worldwide licensing rights to CaviStat by the Research Foundation of the State University of New York. Ortek's President, Mitchell Goldberg said, "There has been little innovation in the fight against tooth decay since the introduction of fluoride more than five decades ago. Based on the findings of this study and the large amount of laboratory data, we expect that CaviStat will eventually replace fluoride in the $5 billion worldwide toothpaste market. We are currently evaluating regulatory strategies to commercialize CaviStat as quickly as possible."

STUDY RESULTS EXPLAINED

Objective: Effect of an arginine bicarbonate/calcium carbonate (CaviStat) dentifrice on caries development in 11-12 year olds was assessed over two years.

Methods: 726 Venezuelan children (DMFT between 3 and 6) were examined by one calibrated examiner at baseline, 6 months, and 1 and 2 years using probing and DMFS scoring. The children were divided into two groups and 321 test and 331 control subjects completed the study. The test group received the CaviStat(TM) dentifrice and the controls used a commercially available fluoride paste. All subjects were instructed to brush three times a day for 1 minute followed by swishing for 30 seconds.

Results: After 6 months, the DMFS rose only slightly in both groups being 6.93+/-3.70 in the controls and 6.59+/-3.77 in the test subjects (p is less than 0.05). But at one year, the control DMFS rose to 8.00+/-4.18 whereas the test group DMFS decreased to 5.50+/-4.15 (p is less than 0.000) suggesting remineralization. At two years, the control DMFS leveled off (7.29+/-5.17) whereas test subject scores rose (6.59+/-4.93). DMFS difference was still significant (p is less than 0.05). Lesion size, not accounted for in DMFS scores, evidently increased much more in the controls during this time. DMFS rise from baseline after two years was only +0.03 in the experimental subjects but +0.87 in the controls. The test dentifrice was 96.6% better than the fluoride paste. DMFS scores for the anteriors, premolars and molars identified the contributions of each and the significance of eruption times in their DMFS patterns. DMFS reductions seen in the experimental subjects occurred mostly in the first molars. Later erupting premolars and second molars showed a progressive DMFS rise in controls and a delay and lesser rise in the experimentals.

Conclusion: A CaviStat containing toothpaste was much more effective at reducing the rate of dental caries development than a fluoride toothpaste control. Supported by Ortek Therapeutics, Inc.

About Ortek: Ortek Therapeutics, Inc., a private company, headquartered in Roslyn Heights, New York, is a fully integrated specialty pharmaceutical company primarily engaged in developing and commercializing proprietary products for the treatment of dental disorders. Ortek currently sells ProClude(R), a desensitizing prophylaxis paste, which is only available and applied by dental professionals (visit www.Proclude.com.).