August 2007 Elan Drug Technologies Creating ValueGeneral present _Aug07_Elan CONFIDENTIAL©2007 – 2 – EDT Pipeline growth EDT Pipeline growth -Patient Focus Patient Focus ELAN DRUG TECHNOLOGIES -OVERVIEW Number of patients Number of Patients Treated Daily with Products using EDT’s Technologies Number of Patients Treated Daily with Products using EDT’s Technologies 1.015M 2.54M 3.36M 7.69M 0 1,000,000 2,000,000 3,000,000 4,000,000 5,000,000 6,000,000 7,000,000 8,000,000 2002 2005 2006 2011General present _Aug07_Elan CONFIDENTIAL©2007 – 3 – Contents • General Overview and Introduction • Technology Overview – NanoCrystal® Technology – Oral Controlled Release Technologies • Facilities Overview – Athlone -solid oral dosage and Sterile Vial filling capabilities • Summary – benefit to you General Overview and IntroductionGeneral present _Aug07_Elan CONFIDENTIAL©2007 – 5 – Elan Drug Technologies – Helping You Bring Products to the Market We Have • Unrivalled expertise in drug formulation, development, scale-up and manufacture • Suite of commercially launched, proprietary, technology-driven solutions • NanoCrystal® Technology for poorly water soluble compounds -four products commercially launched with US$1.5B+ annual sales • Customised oral drug technologies – delayed release, extended release, pulsatile release, chrono-timed delivery – all commercially launched • More than 70 products in various stages of development from feasibility through to Phase 3. • A proud track record of innovation and expertise in drug optimization – in excess of thirty products launched in 39 year history. • Successful collaborations with more than 30 of the world’s leading pharmaceutical companies GENERAL OVERVIEW & INTRODUCTION Helping Bring Products to Market Helping Bring Products to Market General present _Aug07_Elan CONFIDENTIAL©2007 – 6 – Elan Drug Technologies – The Benefits to you Strong Patent Estate • 1,400 + patent estate • Key NanoCrystal® Technology patents • NanoCrystal® Technology plays in the critical <400nm crystalline particle size space NanoCrystal® Technology 490 Issued 587 Applications 1,077 Patents and Patent Applications Oral Controlled Release Technologies 272 Issued 79 Applications 351 Patents and Patent Applications Total 762 Issued 666 Applications 1,428 Patents and Patent Applications 39 years dedicated to Life Cycle Management and Drug Optimization 39 years dedicated to Life Cycle Management and Drug Optimization GENERAL OVERVIEW & INTRODUCTIONGeneral present _Aug07_Elan CONFIDENTIAL©2007 – 7 – Marketed Acorda (Zanaflex Capsules™) Marketed Novartis (Ritalin® LA) Marketed Novartis (Focalin® XR) Marketed King Pharmaceuticals (Avinza®) Marketed Par Pharma (Megace®ES) Marketed Abbott/Fournier (TriCor®) Marketed Wyeth (Rapamune®) Marketed Merck (Emend®) I II III Filed Elan’s Drug Technologies Business Has Solved the Delivery Challenges of More Than 30 Marketed Products. Since 2001 we have launched 8 products in the US, making us one of the most productive drug technology companies during the period Products filed and marketed since 2001 GENERAL OVERVIEW & INTRODUCTIONGeneral present _Aug07_Elan CONFIDENTIAL©2007 – 8 – EDT Pipeline 18 Clinical Stage Development Projects Underway NCE** 3rd party not disclosed Marketed* Internal Project Marketed* Internal Project Marketed* 3rd party not disclosed Marketed* Acorda (Fampridine) NCE** 3rd party not disclosed (Emend® Japan) Marketed* Jazz (Fluvoxamine) Marketed* J&J (Resp. Pal. Depot) NCE** 3rd party not disclosed NCE** Internal Project Marketed* Internal Project NCE** Entremed (Panzem®) Marketed* MAP (Budesonide) NCE** 3rd party not disclosed Marketed* 3rd party not disclosed NCE** 3rd party not disclosed NCE** 3rd party not disclosed NCE** Aventis (not disclosed) I II III Filed Stage of Development * Reformulation or optimization of currently marketed product ** NCE – new chemical entity, not yet on market in any form GENERAL OVERVIEW & INTRODUCTIONGeneral present _Aug07_Elan CONFIDENTIAL©2007 – 9 – Pharma Industry is coming under increasing pressure -Reformulations and Combination Products Will Account for an Increasingly Large Portion of the Industry’s Sales Products currently accounting for US$83Bn in sales will come off patent between 2007-20111. US Drug Approvals (2002-2006)3. 92 77 151 285 2003 2008 Reformulations New Chemical Entities US Rx Drug Sales ($B)2. 243 362 Sources: 1. FDA Orange Book, SEC Filings, USPTO, Merrill Lynch 2. US Ethical Drug Market -Strategies for Sustained Growth -BCC Res GENERAL OVERVIEW & INTRODUCTION Over two-thirds of FDA product approvals are for reformulations (note: generics not included in count) 3. FDA Website 4. http://www.kellogg.northwestern.edu/academic/biotech/articles/strategic_alternatives.pdf “Big Pharma’s crisis in R&D productivity is not going to be solved soon. From declining rates of innovation to increased costs of development, the industry is getting hit from every side” . Strategic Alternatives in the Pharmaceutical Industry, Kellogg School of Management, 20044. “Big Pharma’s crisis in R&D productivity is not going to be solved soon. From declining rates of innovation to increased costs of development, the industry is getting hit from every side” . Strategic Alternatives in the Pharmaceutical Industry, Kellogg School of Management, 20044. Year Reformulations NCE’s 2002 55 17 2003 49 21 2004 69 31 2005 65 20 2006 77 22 Total 315 111 General present _Aug07_Elan CONFIDENTIAL©2007 – 10 – The Opportunity Sources: 1. Merrill Lynch Industry Report, Jan 06. 2. Datamonitor Report, 2007. $96.2B worth of pharmaceutical products will go off patent from 2007-2012 and by 2016 it will be $140B in sales.2 $96.2B worth of pharmaceutical products will go off patent from 2007-2012 and by 2016 it will be $140B in sales.2 Estimated Annual Sales of Major Brands Losing Patent Protection 1 05 10 15 20 25 2007 2008 2009 2010 2011 2012 US$ in billions GENERAL OVERVIEW & INTRODUCTIONGeneral present _Aug07_Elan CONFIDENTIAL©2007 – 11 – 0 50 100 150 200 250 300 350 Strategic pricing Repositioning Customer programs Patent litigation New dosing Individualised therapy Paediatric indications new formulations Branded generics OTC New combos New indications Next generation US$M Reformulations Deliver Excellent Return in Terms of Investment and Perceived Effectiveness 0 1 2 3 4 5 New indications Patent litigation Next generation products New formulations Paediatric indications New dosing Branded generics New Combinations OTC switch Individualised therapy Effectiveness level Clients are increasingly asking us to reformulate their existing products improve the products performance and expand its commercial potential. Clients are increasingly asking us to reformulate their existing products improve the products performance and expand its commercial potential. Perceived effectiveness of LCM strategy (5=“highly effective”) Typical cost of life-cycle management strategy Source: Cutting Edge Information "Defending brand revenue -Pharmaceutical life cycle management planning June 2005.“ The companies surveyed were Abbott, GSK, Alza, Amgen, King, AZ, KOS, Merck, Novartis, Bayer, Pfizer, Biogen Idec, Roche, BMS, Sanofi, Eli Lilly, Schering Plough, Endo, Genentech and Wyeth. ~3.5 GENERAL OVERVIEW & INTRODUCTIONGeneral present _Aug07_Elan CONFIDENTIAL©2007 – 12 – …Reformulations Are Cost Effective 100-200 40 4-5 Optimization/Reformulation 300-500 900 9-12 NCE /Discovery compound Average Peak sales (US$MM) Cost of development (US$MM) Years to develop Sources: 1. TUFTS Centre for Study of Drug Development website 2. Defending brand revenue -Pharmaceutical Lifecycle management planning, June 2005 -Cutting Edge Information Report NCE success rate currently > 1% = Of 5,000 screened, 250 enter pre-clinicals, 1 compound approved NCE success rate currently > 1% = Of 5,000 screened, 250 enter pre-clinicals, 1 compound approved GENERAL OVERVIEW & INTRODUCTIONGeneral present _Aug07_Elan CONFIDENTIAL©2007 – 13 – Elan Drug Technologies GENERAL OVERVIEW & INTRODUCTION Drug Technologies (~850 staff) NanoCrystal® Technology Commercial Scale Manufacturing Oral Controlled Release • NanoCrystal® Technology products, Athlone Ireland • Solid oral dosage products, USA and Ireland • Sterile Fill Finish, Athlone, Ireland • Athlone, Ireland • Gainesville, GA, USA • King of Prussia, PA, USA • Athlone, Ireland General present _Aug07_Elan CONFIDENTIAL©2007 – 14 – Efficacy Studies in Murine Tumor Models Following Paclitaxel IV Injection (MTD)3 x MV 522 (percentage showing tumor reduction) 0% 0% 30% 15%25% 100% 0% 50% 100% ScA 2780 (percentage cured) Mam 16C (percentage cured) NanoCrystal®-Paclitaxel BMS Paclitaxel Mam 16C (percentage in remission) 32% 15% Source:Elan Studies. Note: Sample size for Mam 16C equals 20 for BMS product, 73 for Nano; Sample size for ScA 2780 and MV522 equaled 9 for NanoCrystal® formulations and 9 for BMS formulations. In the study, side effects were reduced and efficacy compared to Taxol were improved. Using NanoCrystal® Technology, we have demonstrated significant tumor reduction in animals GENERAL OVERVIEW & INTRODUCTIONTechnology Overview • NanoCrystal® Technology • Oral Controlled Release TechnologiesGeneral present _Aug07_Elan CONFIDENTIAL©2007 – 16 – Naked Eye Light microscopy Electron microscopy 1 meter 10-5 10-1 10-10 Human Hair Nucleus of Animal Cell Human Virus DNA Atom Scope of Nanotechnology Estimated Value $57bn+ (pharmaceutical market)* What is Nanotechnology ? Nanotechnology Involves Really Small Stuff GENERAL OVERVIEW & INTRODUCTION Rabbit 10-7 10-9 Ribosome 10-8 10-6 10-2 10-3 10-4 * Source Technology Catalysts -Delivery of Poorly Water Soluble Drugs 3rd editionGeneral present _Aug07_Elan CONFIDENTIAL©2007 – 17 – Since dissolution rate is a function of surface area, a nano-formulation will have better bioavailability than a micronized formulation of the same drug where bioavailability is dissolution rate limited. Our Patent position offers scope to manipulate surface area and thus optimize oral pharmacokinetics. Since dissolution rate is a function of surface area, a nano-formulation will have better bioavailability than a micronized formulation of the same drug where bioavailability is dissolution rate limited. Our Patent position offers scope to manipulate surface area and thus optimize oral pharmacokinetics. Relationship between Particle Size and Surface Area 05 10 15 20 25 30 35 40 45 50 10 100 1000 10000 100000 Particle Size (nm) Surface Area (m 2/gram) Range available to competitors Nano Micronized GENERAL OVERVIEW & INTRODUCTION Our Key patents around formulations less than 400nm When it Comes to Improving Dissolution We Can Out-Perform AnyoneGeneral present _Aug07_Elan CONFIDENTIAL©2007 – 18 – NanoCrystal® Technology – key features NanoCrystal® Technology – Proven Innovation for poorly water-soluble compounds • Applicable to any dosage form 1. • Improvement in bioavailability of up to 600%2. • 4 time reduction in dosage volume 3. • 10 fold maximum tolerated dose achieved in cancer drug 4. • Eliminates fed-fasting effect 5. • Fast, Elegant, Simple solution for poorly water soluble compounds 6. Sources: 1. Parenteral, inhaleable, solid oral, liquid dosage forms 2. Emend® bioavailability was improved by 600% 3. Megace® ES dose reduced from 20ml to 5ml 4. Animal studies conducted by Elan in-house on leading anti-cancer product 5. Eliminated/reduced fed/fasted effect in TriCor® and Emend 6. TriCor and Megace reformulated and approved within 36 months TECHNOLOGY OVERVIEW General present _Aug07_Elan CONFIDENTIAL©2007 – 19 – There Are Four Nanocrystal® Technology Based Drugs Now Approved and Marketed in the US Basis for filing 􀂾 Rapamune® (LCM~) Launched by Wyeth in 2001 – Provides a stable tablet formulation (replaced a liquid dosage form) with 23% improvement in bioavailability – Easier storage—no refrigeration required – More precise dosage/dosage linearity 􀂾 Emend® (NCE*) Launched by Merck in 2003 – Elimination of food requirement for drug (drug would otherwise have been abandoned) with 600% improvement in bioavailability 􀂾 TriCor® 145 (LCM~) Launched by Fournier and Abbott in 2004 – Could market lower dosage strength with 9% improvement in bioavailability – Minimized food effect – Patented formulation 􀂾 Megace® ES (LCM~) Filed by Par in June 2004 and approved in July 2005 – Equivalent efficacy achieved with dramatically lower absolute dosage with 28% improvement in bioavailability • Easier administration • Lower API cost • Patented formulation Efficacy/Safety PK 􀀹 􀀹􀀹 Note: *New Chemical Entity (NCE) ~Life Cycle Management (LCM). 􀀹 TECHNOLOGY OVERVIEW General present _Aug07_Elan CONFIDENTIAL©2007 – 20 – NanoCrystal® Technology -Key Attributes Key Attributes • A formulation and manufacturing approach for the delivery of poorly water-soluble drugs • All dosage forms possible • Increases oral bioavailability • Minimizes fed/fasted variability • Decreases time to onset of action • Parenteral formulations at high concentration with minimum excipients • High drug loading possible (up to 30-40% active) • Combine with other drug technologies • Robust -4 products approved by the FDA TECHNOLOGY OVERVIEW NanoCrystal® Technology involves reducing crystalline drug to particles under 400nm. By reducing particle size, we increase the drug’s exposed surface area. We then stabilize the particles to maintain the formulation’s particle size. NanoCrystal® Technology involves reducing crystalline drug to particles under 400nm. By reducing particle size, we increase the drug’s exposed surface area. We then stabilize the particles to maintain the formulation’s particle size.General present _Aug07_Elan CONFIDENTIAL©2007 – 21 – Our Formulation of Megace® ES Is an Example of How Our Technology Enhanced Patient Acceptability, Creating a Branded Opportunity By applying our NanoCrystal® solubility enhancing technology, we ….. • Formulated a superior, more palatable product with a significantly lower dose than the original product – Improved the rate of dissolution and bioavailability – Reduced the total volume per dose by 75% – Created a lower viscosity solution than the original formulation – Improved bioavailability in unfed condition – important given drug indication (for the treatment of anorexia, cachexia, or unexplained significant weight loss in patients with AIDS) After Before GENERAL OVERVIEW & INTRODUCTIONGeneral present _Aug07_Elan CONFIDENTIAL©2007 – 22 – Our Reformulation of Wyeth’s Rapamune® Shows How Our Technology Improved Patient Compliance And Convenience Wyeth’s Rapamune® sirolimus WAS • Novel immunosuppressant • Available as a solution • The formulation required a complicated reconstitution procedure • Reconstituted in orange juice or water only By applying our NanoCrystal® solubility enhancing technology, we ….. • Improved dissolution and oral bioavailability • Enabled preparation of tablet • Enhanced patient convenience and acceptability • Improved patient choice • Provided patent protection Oral tablet form of Rapamune® was launched July 2001 using NanoCrystal® Technology. Our reformulation of Rapamune dominates product sales (over 96%) and continues to be fastest growing product in class. 2006 Rapamune® sales were US$337MM (IMS ex-factory in-market sales). GENERAL OVERVIEW & INTRODUCTIONGeneral present _Aug07_Elan CONFIDENTIAL©2007 – 23 – Reducing Particle Size Improves the Bioavailability of Orally Delivered Water-Insoluble Drugs Improved bioavailability in turn brings one or more practical benefits • Increased rate of absorption • Reduction in required dose • Reduction in fed/fasted variability • Improved dose proportionality • Smaller dosage forms • More convenient dosage forms • Rapid Formulation Development TECHNOLOGY OVERVIEW General present _Aug07_Elan CONFIDENTIAL©2007 – 24 – Nano-Meloxicam Offers an Excellent Example of How Nanotechnology Increases the Rate of Absorption In this instance the practical result is a faster acting pain drug. In this instance the practical result is a faster acting pain drug. 0.000 0.500 1.000 1.500 2.000 2.500 3.000 3.5000 1 2 3 4 5 Time (hrs) ug/ml NCD Lyophilized Wafer Commercial Tablet Blood Levels over time for alternative formulations of meloxicam (n= 5 dogs) Source: Elan study 2002 TECHNOLOGY OVERVIEW General present _Aug07_Elan CONFIDENTIAL©2007 – 25 – Nano-Megestrol Acetate Has Been Proven to Have Improved Pharmacokinetics Relative to Micronized Megestrol Acetate 0 100 200 300 400 500 600 700 800 900 1000 1100 1200 1300 0 4 8 12 16 20 24 Time (hr) Plasma Concentration (ng/mL) Micronized 800 mg fasted Micronized 800 mg fed NanoCrystal® 450 mg fasted NanoCrystal® 450 mg fed Blood Plasma Levels: Megestrol Acetate (Clinical Data) TECHNOLOGY OVERVIEW Source: Elan studyGeneral present _Aug07_Elan CONFIDENTIAL©2007 – 26 – NanoCrystal® Technology Permits Creation of Insoluble Parenteral Products Devoid of Undesirable Co-solvents We have developed our IM depot technology to the point where we have one product in phase I, and another—J&J’s Paliperidone Palmitate—in Phase III. • High drug loading – Can achieve drug loads of up to 45% • Avoidance of harsh vehicles such as organic solvents • Highly developed ability to modulate absorption rate from the injection site – Manipulated through drug crystal size • Readily syringable fluids – Can be syringed through small bore syringes eliminating the need for power syringe drivers • Safety of IV, IM and Sub-Q delivery of NanoCrystal® Technology established clinicallya a. See for example: J.P. Donnelly, J.W. Mouton, N.M.A. Blijlevens, A. Smiets, P.E. Verweij, B.E. DePauw, Dept of Hematology, Dept of Med Microbiology, Univ. Med. Ctr Nijmegen, Canisius Wilhelmina Ziekenhuis, Nijmegen, The Netherlands, “Pharmacokinetics of a 14 day course of itraconzaole NanoCrystal® given intravenously to allogeneic haematopoietic stem cell transplant recipients” Paper presented at the Interscience Conference on Anti-microbials and Chemotherapy, 2001 TECHNOLOGY OVERVIEW General present _Aug07_Elan CONFIDENTIAL©2007 – 27 – In This Example, We Successfully Developed a Long-Acting Depot of an Otherwise Insoluble Compound 05 10 15 20 25 0 10 20 30 40 50 60 70 80 90 100 Time (days) Plasma Concentration (ng/ml) Rabbit 1 Rabbit 2 Rabbit 3 Mean Efficacious level Source: Elan study Blood plasma levels NanoCrystal® formulation of currently marketed compound TECHNOLOGY OVERVIEW General present _Aug07_Elan CONFIDENTIAL©2007 – 28 – NanoCrystal® Technology Brings Several Delivery Benefits Unique to Inhaled and Nasally Delivered Products • More precise delivery to target site (upper versus lower lung): – Site of delivery driven by particle size (smaller particles get deposited lower in the bronchial tree, medium higher up, larger particles get swallowed) – NanoCrystal® Colloidal Dispersion (NCD) formulation allows particle size to be driven by droplet size—easy to manipulate— and not drug crystal size which tends to be hard to manipulate – NanoCrystal® delivery allows efficiency double that of regular formulation • Increased coverage of receptors at site: – NanoCrystal® particles cover a large surface area with drug in contrast to conventional suspension that have islands of concentrated drug • Faster aerosolize time and suitability for use with ultrasonic nebulizers: – Time to aerosolize a therapeutic dose reduced from 10 -15 minutes to 2 seconds – NanoCrystal® dispersions can take advantage of delivery via an ultrasonic nebulizer, whereas conventional suspension would take too long to nebulize • NanoCrystal® dispersion formulations of Budesonide and Fluticasone do not require preservatives: – Particles are less than 100nm and therefore can be filtered through a .22um filter • Lower emitted dose – Reduction in systematic absorption TECHNOLOGY OVERVIEW General present _Aug07_Elan CONFIDENTIAL©2007 – 29 – …And NanoCrystal® Formulations of Pulmonary Corticosteroids Can Be Delivered More Efficiently and Precisely 27% 60% Spray Dried NanoCrystal®s Micronized Drug Substance Percentage of Emitted Dose 0.0 20.0 40.0 60.0 80.0 100.0 120.0 140.0 160.0 180.0 9.0-10.0 5.8-9.0 4.7-5.8 3.3-4.7 2.1-3.3 1.1-2.1 0.7-1.1 0.4-0.7 <0.4 Droplet Aerodynamic Diameter, µm µg of Drug Substance 0 20 40 60 80 100 120 9.0 -10.0 5.8 -9.0 4.7 -5.8 3.3 -4.7 2.1 -3.3 1.1 -2.1 0.7 -1.1 0.4 -0.7 < 0.4 Droplet Size (aerodynamic diameter, µm) µg of Beclomethasone Dipropionate 4.35 54.9 261.3 0.5 5.0 50 Formulation Concentration, mg/mL Micrograms of Drug Delivered per 2 Second Actuation …Further droplet sizes can be manipulated for effective can be delivery of drug into the deep lung …resulting in much higher portion of the emitted dose being deposited in the lung Therapeutic quantities of drug can be quickly administered by ultrasonic nebulizers… …More of the dose is within the target droplet size range… Source: Elan study TECHNOLOGY OVERVIEW General present _Aug07_Elan CONFIDENTIAL©2007 – 30 – Elan has A Range of Manufacturing Scales In Place in Athlone, Ireland; and King of Prussia, Pennsylvania, USA. TECHNOLOGY OVERVIEW Process Batch Scale Process NanoMill®-01 25mg -10g API • 60 units at clients, KOP* and Athlone** NanoMill®-1 10g -100g API • Multiple R&D and cGMP systems at KOP • Formulation development and small scale GLP/cGMP KOP and Athlone NanoMill®-2 1-10kg API • Multiple R&D & cGMP systems at KOP /Athlone • cGMP systems at client sites NanoMill®-10 10-100kg API • 1 R&D and 1 cGMP system at KOP • cGMP systems at client site • Phase III batch campaigns at 25kg scale at KOP • Pivotal batch capability in Athlone up to 100kg NanoMill®-60 100-1000kg API • R&D Pilot Plant at KoP Site (ca. 100kg scale) • cGMP systems at client sites *KOP site – King of Prussia, PA, USA development facility **Athlone – main manufacturing facility in Ireland General present _Aug07_Elan CONFIDENTIAL©2007 – 31 – Our Controlled Release Technology Platform Allows a Range of Release Profiles and Dosage Forms to Be Engineered TECHNOLOGY OVERVIEW Technology Dosage form Release Mechanism Application SODAS® (Spheroidal Oral Drug Absorption System) Beads in a capsule Diffusion Combination of immediate release, controlled release and delayed release profiles, reduction in peakttotrough ratios PRODAS® (Programmable Oral Drug Absorption System) Mini-tablets in a capsule Diffusion Controlled absorption over a period, targeted delivery to absorption sites CODAS™ (Chronotherapeutic Oral Drug Absorption System) Beads in a capsule Diffusion Delivery profile designed to complement the circadian pattern of blood pressure IPDAS® (Intestinal Protective Drug Absorption System) Multi-particulate beads in a tablet Diffusion and erosion Intestinal protectiveGeneral present _Aug07_Elan CONFIDENTIAL©2007 – 32 – Avinza®, Ritalin®LA and Verelan®PM Demonstrate Oral Controlled Release Technologies Applicability in Life Cycle Management Basis for filing 􀂾 Avinza® (LCM~) Launched by Ligand in 2002 – Matches pain coverage of existing BID forms – Minimizes fluctuation in blood levels – Fast onset – Sprinkle dosing – Patent protection 􀂾 Ritalin® LA(LCM~) Launched by Novartis in 2002 – Once-a-day, oral dosage form – Eliminate need for mid-day dosing during school -mimic twice daily dosing regime, with unique bi-modal release profile – Onset consistent with need at start of school day – Patent protection 􀂾 Verelan® PM (LCM~) Launched by Schwarz in 1999 – Reduced dosage form dependence on gastric motility, posture and food – 4.5hr lag in onset of plasma concentrations while patient asleep – Therapeutic concentrations achieved in the high-risk wakening period – cMax occurs approximately 11 hrs after dosing – Therapeutic effect maintained during wakening hours – Sprinkle indication – Patent protection Efficacy/Safety PK Note: ~Life Cycle Management (LCM). 􀀹􀀹 􀀹 Every day 3.3 million patients take products enabled by Elan Drug Technologies Every day 3.3 million patients take products enabled by Elan Drug Technologies TECHNOLOGY OVERVIEW General present _Aug07_Elan CONFIDENTIAL©2007 – 33 – Mean Steady State Plasma Morphine Concentrations 02468 10 12 14 16 180 2 4 6 8 10 12 14 16 18 20 22 24 Hours Duration AVINZA Once Daily ® Morphine solution 6 times daily Plasma concentration ng/ml AVINZA®, a Recently Approved Once-per-day Morphine Product, Demonstrates SODAS® Technology at Work Source: Elan study TECHNOLOGY OVERVIEW Morphine, while a well-known and trusted analgesic…. • has a short half-life • break-though pain a significant problem • no product offered true once-daily dosing Elan’s Criteria For Superior Product (Compared to existing oral products) • Fast onset • Match pain coverage of existing BID forms • Minimize fluctuation in blood levels • Ability to titrate with other strengths (30mg, 60mg, 90mg 120mg) • Sprinkle indication • Patent protection Launched in 2002 under Avinza® trade name, 2006 sales were US$175M Launched in 2002 under Avinza® trade name, 2006 sales were US$175MFacilities Overview • Athlone, Ireland -solid oral dosage and NCD capabilities • Gainesville, GA, USA -solid oral dosage capabilities • Athlone, Ireland -sterile fill finish capabilitiesGeneral present _Aug07_Elan CONFIDENTIAL©2007 – 35 – Elan Drug Technologies -Facilities ELAN DRUG TECHNOLOGIES -FACILITIES Site Athlone, Ireland 􀂄 Dedicated cGMP facility 􀂄 FDA and EMEA approved 􀂄 420,000 sq ft, 2.5BN oral dose capacity 􀂄 Recent (2003/4) $178MM expansion 􀂄 Solid oral dosage forms (including NanoCrystal® and OCR formulations) 􀂄 Sterile fill finish capability 􀂄 Formulation through scaleuu and full scale manufacturing Gainesville, USA 􀂄 Dedicated cGMP facility 􀂄 FDA and DEA approved 􀂄 84,000 sq ft, 500M capacity, recent US$20M expansion 􀂄 Schedule II narcotics 􀂄 Formulation through scaleuu and full scale manufacturing King of Prussia, USA 􀂄 Dedicated cGCP facility 􀂄 FDA approved 􀂄 50,000 sq ft 􀂄 NanoCrystal® Technology, oral, parental and pulmonary delivery modes 􀂄 Formulation through 1/10th scalemanufaacturin and clinical supplies General present _Aug07_Elan CONFIDENTIAL©2007 – 36 – Athlone Gainesville King of Prussia Elan Drug Technologies -Locations ELAN DRUG TECHNOLOGIES -FACILITIES General present _Aug07_Elan CONFIDENTIAL©2007 – 37 – Quality Operations Feasibility and Prototype Development Project Preparation Dossier Support and Process Transfer Formulation and Process Organization Process Scale-up Product Launch and Commercial Supply We perform commercial-scale manufacturing in Athlone, Ireland, and Gainesville, GA, and development work at both those sites and at our dedicated R&D facility in King of Prussia, PA. Research and Development Manufacturing Using These Technologies, We Offer Initial Formulation Development Through to Commercial Manufacturing ELAN DRUG TECHNOLOGIES -FACILITIES General present _Aug07_Elan CONFIDENTIAL©2007 – 38 – Demonstrated by Successful inspections in 2002-2007 • Food & Drug Administration -7 Audits • Irish Medicines Board – 6 Audits • Environmental Protection Agency -13 Audits • Health & Safety Authority -20 Audits • US Drug Enforcement Agency -4 Audits • Client and Consultant -75 Audits • Consent Decree Lifted from Gainesville site in 2006 Inspection Ready status and Continuous Quality Improvement reinforced by • Extensive Self-Inspection program • Corrective And Preventative Action Database Fully Compliant ELAN DRUG TECHNOLOGIES -FACILITIES General present _Aug07_Elan CONFIDENTIAL©2007 – 39 – Athlone Facility Facility Area Approx Sq Feet Laboratories 41,510 GMP area 137,953 Warehouse 44,266 Office/Other 197,624 Total 421,353 • Located on a 40 acre campus, Elan’s Athlone facility has a total area under roof of over 420,000sq ft. with a capacity to manufacture up to 2.5bn solid dosage units a year • In 2003 Elan completed a US$178MM investment in its Athlone site facilities • New facilities make use of best practice technologies. • The new facilities include: • ‘Lights out’ Warehouse and dispensary • NanoCrystal® Dispersion manufacture • In 2005 a further US$ 41MM was invested for sterile bio-manufacturing site (adding further 42,000 sq ft to site) Site Profile # employees Manufacturing 177 Main., Engin., Safety & Envirorn 49 QA /QC/Regulatory/analytical dev 152 Technical Services 32 IT/SAP 27 Global Supply chain 7 Other 96 Total 540 ELAN DRUG TECHNOLOGIES -FACILITIES General present _Aug07_Elan CONFIDENTIAL©2007 – 40 – Solid Dosage Building Solid Dosage Building Fill Finish Building Fill Finish Building Elan Drug Technologies Campus, Athlone, Ireland ELAN DRUG TECHNOLOGIES -FACILITIES General present _Aug07_Elan CONFIDENTIAL©2007 – 41 – Sterile Fill and Finish Facility ELAN DRUG TECHNOLOGIES -FACILITIES General present _Aug07_Elan CONFIDENTIAL©2007 – 42 – Site Capabilities • New biopharmaceutical sterile fill-finish facility • Designed to fill liquid products • Meets FDA/EMEA/JMHLW GMP Guidelines • 42,000 sq ft of cGMP manufacturing capacity • Clinical and commercial scale • 20M unit annual capacity for biologics and small molecules • Multi-product facility, capable of filling a range of vials in liquid form. • Batch sizes from 2L-1,000L • Full service provided ELAN DRUG TECHNOLOGIES -FACILITIES General present _Aug07_Elan CONFIDENTIAL©2007 – 43 – Key Features • Dispensary -Grade C dispensary area with glovebox isolator available for potent or hazardous materials • Compounding -Grade C area, accommodates up to 1,000L • Stopper Unloading -Closed system, unloaded under Grade A conditions • Vial Washing -integrated U shape filling line, with Grade D viewing corridor • Vial Filling -Grade A area, filling 2ml-100ml vials at 120vials per minute, 100% check • Capping/Labelling -adjacent to filling room, Grade A conditions for capping, labelling adjacent in Grade D room. ELAN DRUG TECHNOLOGIES -FACILITIES General present _Aug07_Elan CONFIDENTIAL©2007 – 44 – Our Development Partnerships Gives You Access to… • Highly skilled work-force seasoned in product development -from feasibility through regulatory approval and product launch • Strong IP portfolio including extensive NanoCrystal® Technology patent estate • Broad range of technology solutions from solubility enhancement to controlled release • 39 years experience in pharmaceutical product development • Pioneers and leaders of controlled release and solubility enhancement technologies • 60,500 sq. ft. dedicated fully-equipped R&D facilities between US and Ireland • On-site tech transfer to commercial manufacturing Capabilities Pre-formulation /Characterization • Active, Excipient, In-Process and Finished Product Characterization Formulation • Feasibility Laboratory • cGMP Area -Pilot Scale Formulation Prototype Manufacture • Experimental Design -Formulation /Process Optimization Process Development • Engineering /Process Optimization • Impact Upon Scale-Up Feasibility Studies Product Development Regulatory Strategy and execution Pilot Production Full Scale Production and Packaging SUMMARY General present _Aug07_Elan CONFIDENTIAL©2007 – 45 – Manufacturing Partnerships Leverage… • Experience, proven track record, infrastructure and capacity in solid oral dosage form manufacture -3 billion units annually • 270,000 sq ft of cGMP facility between US and Ireland • Excellent compliance record • Packaging facilities US and Ireland • DEA approved Controlled Substance manufacturing plant in US • Mature infrastructure • Development & tech transfer capabilities • A focus on partnering with customers SUMMARY General present _Aug07_Elan CONFIDENTIAL©2007 – 46 – Elan Drug Technologies – Benefit to You • Unrivalled expertise in drug formulation, development, scale-up and manufacture • Suite of commercially launched, proprietary, technology-driven solutions • More than 70 products in development from feasibility through to Phase 3. • A proud track record of innovation and expertise in drug optimization in 39 year history. • Successful collaborations with majority of world’s leading pharmaceutical companies SUMMARY Helping Bring Products to Market Helping Bring Products to Market