Probuphine GLYPH<H23008> , a long-term treatment for opiate addiction, combines Titan’s propr ietary ProNeura drug delivery technology with buprenorphine, a drug with established efficacy in the treatment of opiate addiction. Probuphine is a small rod composed of ethylene vinyl acetate (EVA) and buprenorphine. The EVA copolymer technology forms a matrix in combination with buprenorphine tha t provides sustained drug release. Preclinical studies by Titan of Probuphine demonstrated targeted concentrations of buprenorphine were achieved and sustained for eight months, with no local toxicity or safety issues. This novel product provides a potential solution to tr eatment challenges associated with oral or injectable drug delivery, including variable drug levels and poor compliance. Titan is planning to begin clinical testing of Probuphine in 2002. Ten Magnified cross-section of EVA copolymer/buprenorphine matrix Probuphine rods Probuphine GLYPH<H23008> Long-Term Delivery of Therapeutics for Drug Addiction Indication(s) Preclinical Phase 1 Phase 2 Phase 3 Opiate Addiction Pr obuphine ™ Long-Term Delivery in Animal Study Est. Minimum 20 Therapeutic Level (Buprenorphine Levels, ng/ml) (Time, Months)