Alternative of Chronic Pain Management proposed by ELAN Pharmaceuticals, Inc. Presented T. Chachibaia Nov.19 Pipeline and Products Elan Corporation, plc is a neuroscience based biotechnology company that is focused on discovering, developing, manufacturing and marketing advanced therapies in neurodegeneration, autoimmune diseases and severe pain. TYSABRI (Crohn's Disease, Rheumatoid Arthritis) and PRIALT (non-opioid analgesic) are registered trademarks of Elan Pharmaceuticals, Inc. AZACTAM and MAXIPIME (Infectious Diseases )are registered trademarks of Bristol-Myers Squibb Company and licensed exclusively in the U.S. to Elan Pharmaceuticals, Inc. An effective non-opioid treatment option for severe chronic pain The PRIALT difference PRIALT is the first intrathecal analgesic approved in February 2005 by EC along with the US approval in December PRIALT is indicated for the management of severe chronic pain in patients for whom intrathecal (IT) therapy is warranted, and who are intolerant of or refractory to other treatment, such as systemic analgesics, adjunctive therapies or IT morphine. PRIALT is for use only in the Medtronic SynchroMed EL, SynchroMed II Infusion System and the CADD-Micro ambulatory infusion pump. PRIALT is a registered trademark of Elan Pharmaceuticals, Inc. SynchroMed is a registered trademark of Medtronic, Inc. CADD-Micro is a registered trademark of the Smiths Medical family of companies. An effective non-opioid treatment option for severe chronic pain The PRIALT difference PRIALT is the first intrathecal analgesic approved in the United States in more than two decades. PRIALT is indicated for the management of severe chronic pain in patients for whom intrathecal (IT) therapy is warranted, and who are intolerant of or refractory to other treatment, such as systemic analgesics, adjunctive therapies or IT morphine. PRIALT is for use only in the Medtronic SynchroMed EL, SynchroMed II Infusion System and the CADD-Micro ambulatory infusion pump. PRIALT is a registered trademark of Elan Pharmaceuticals, Inc. SynchroMed is a registered trademark of Medtronic, Inc. CADD-Micro is a registered trademark of the Smiths Medical family of companies. Pipeline and Products Elan Corporation, plc is a neuroscience based biotechnology company that is focused on discovering, developing, manufacturing and marketing advanced therapies in neurodegeneration, autoimmune diseases and severe pain. TYSABRI (Crohn's Disease, Rheumatoid Arthritis) and PRIALT (non-opioid analgesic) are registered trademarks of Elan Pharmaceuticals, Inc. AZACTAM and MAXIPIME (Infectious Diseases )are registered trademarks of Bristol-Myers Squibb Company and licensed exclusively in the U.S.to Elan Pharmaceuticals, Inc. 2003 Elan Pharmaceuticals, Inc. ELN Last Updated February 22, 2005 Commercial Approvals for NanoCrystal Technology The first United States approval of a product produced incorporating the NanoCrystal technology occurred in August 2000: Wyeths first solid-dose formulation of the immunosuppressant Rapamune (sirolimus) received marketing approval from the U.S. Food & Drug Administration (FDA). Emend (aprepitant, MK 869) was approved by the FDA in March 2003 and launched in the United States by Merck in April NanoCrystal Technology For poorly water soluble compounds, Elan's proprietary NanoCrystal technology can enable formulation and improve compound activity and final product characteristics. The NanoCrystal technology can be incorporated into all dosage forms both parenteral and oral, including solid, liquid, fast-melt, pulsed release and controlled release dosage forms. 2004 Elan NanoSystems licenses NanoCrystal technology to Roche 2003 Elan's NanoSystems licenses NanoCrystal to Janssen 2003 Elan's NanoSystems and Bristol-Myers Squibb sign license a license agreement for NanoCrystal technology Japanese Patent Office Issues Patent Certificate to Elan for Its NanoCrystal-TM- Technology 2005 Elan's Proprietary NanoCrystal Technology is Used by Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&J PRD) in Phase III Clinical Trial of Paliperidone Palmitate Elan NanoSystems licenses NanoCrystal technology to Aventis Commercial Approvals for NanoCrystal Technology The first United States approval of a product produced incorporating the NanoCrystal technology occurred in August 2000: Wyeths first solid-dose formulation of the immunosuppressant Rapamune (sirolimus) received marketing approval from the U.S. Food & Drug Administration (FDA). Rapamune was previously available only as an oral solution in bottles or sachets. The oral solution requires refrigeration storage, and must be mixed with water or orange juice prior to administration. The new tablet developed with NanoCrystal technology provides patients with more convenient administration and storage than Rapamune oral solution. The development of a NanoCrystal dispersion of sirolimus enabled the preparation of a solid dose formulation. Emend (aprepitant, MK 869) was approved by the FDA in March 2003 and launched in the United States by Merck in April Emend is a capsule containing 80 or 125 mg of aprepitant formulated as NanoCrystal drug particles. Whereas the first commercial product that utilized NanoCrystal technology (Rapamune) was a reformulation of an already marketed drug, Emend was developed as an NCE in a NanoCrystal formulation. In 2004 Elan Licenses Its NanoCrystal Technology to Roche. NanoCrystal Technology For poorly water soluble compounds, Elan's proprietary NanoCrystal technology can enable formulation and improve compound activity and final product characteristics. The NanoCrystal technology can be incorporated into all dosage forms both parenteral and oral, including solid, liquid, fast-melt, pulsed release and controlled release dosage forms. QLT USA, Inc. Octreotide Octreotide is being developed by QLT's wholly owned subsidiary, QLT USA, Inc. and makes use of QLT's Atrigel extended-release technology to gradually deliver the drug therapy over a specified period of time. Octreotide and Atrigel's advantages may include high bioavailability and the requirement for small volume injections that are less painful than the current practice of intramuscular injection and leave no muscle damage or scarring. We plan on conducting clinical trials to evaluate both one- month and three-month formulations of octreotide in Atrigel to treat carcinoid tumors syndrome and acromegaly. We are also exploring the drug's potential in treating the diabetic eye disease known as diabetic retinopathy. Patent protection for Atrigel/octreotide is expected up to 2020 and beyond. Neurotech S.A. France Novel Therapies for the eye - ECT Technology Neurotech's core technology platform is Encapsulated Cell Technology (ECT). ECT implants consist of cells that have been genetically modified to produce a desired therapeutic factor (CNTF-ciliary neurotrophic factor) that are encapsulated in a section of semi- permeable hollow fiber membrane. ECT therefore enables the controlled, continuous long-term protein delivery (18 months) in the vitreous cavity of the eye of therapeutic factors directly to the retina, bypassing the blood-retina barrier: neurotrophic factors for the treatment of retinal degeneration in Retinitis Pigmentosa (RP), Geographic Atrophy (serious condition associated with the Dry form of Age-related Macular Degeneration), Glaucoma, Retinal Vein Occlusion and others. anti-angiogenic factors for the treatment of vascular proliferation in Diabetic Retinopathy and the Wet form of AMD, and for the treatment of abnormal vascular permeability for various forms of Macular Edema. ECT based products can be tailored to address the three main clinical manifestations of retinal diseases: degeneration of photoreceptors and/or ganglion cells in the neural retina, vascular proliferation and inflammation.