UCB R&D Days September 26th, 2006 – London September 28th, 2006 – New York UCB R&D Day Agenda z Introduction z Discovery Research – Research overview and differentiating technologies – Sclerostin antibody – CDP323 z Oncology – CDP791 – CMC544 z Inflammation – Epratuzumab – Cimzia™ z CNS – UCB 106607 – Brivaracetam / Seletracetam – Epilepsy commercial strategy z Conclusions 1 Introduction Roch Doliveux CEO UCB, Next Generation Biopharma z Unique technologies z Unique platforms z Unique products z Unique team of experts 2 UCB Vision To build a global biopharmaceutical leader, based on unique blending of innovation, entrepreneurship and proven experience, bringing to specialists first, new medicines to treat patients suffering from severe diseases Biopharma - Key Success Factors z Differentiated new medicine z Resources z Flexible and opportunistic z Core processes – Quality, compliance, development, supply chain, finance z People with passion and performance 3 Transformational Merger of UCB with Celltech Quantum Strategic Leap Creating a Global Leader able to Compete in the Biopharmaceutical World UCB, Pharma or Biotech? ... Is a mid-size Pharma company z Partnering with other mid-sized Pharma company z Dependent on licensing for its long term growth ... Is a Biotech company z Willing to make bold moves z Partner with the Best z Unique research capabilities z Productive portfolio of new targets, compounds, new medicines z Big Pharmas and Biotechs looking to partner with us 4 UCB, Next Generation Biopharma z Science-led research – Unique combination of biology with chemistry z Innovative clinical development z Partners and networks z Focused global business units z Unique diverse people base z Patient centric UCB Strategy z Innovation-driven • Science, Patient & People z Specialist Marketing • USA, Europe, Asia z Focus to reach leadership • Neurology, Inflammation, Oncology z Partnering up- and downstream • Access technology and maximise assets z Broadening base • Invest more in R&D • Enhance long term growth 5 UCB, Next Generation Biopharma UCB is shaping a Next Generation Biopharma One With a Clear Strategy One With Passionate Networked Individuals Who focus Who aim high Who perform Discovery Research 6 Research Overview and Differentiating Technologies Neil Weir Senior Vice President Discovery Research UCB has a Rich Research Pipeline tion al a inic d d l se 1 a a a Therapeutic Le Le Indication Prec Ph Area Discovery Optimiz Inflammation TNF Mediated Disease (RA, IBD, Psoriasis) MS Allergy/Asthma SLE Bone Loss Immunomodulators Epilepsy CNS Cognition, dementia Neuropathic pain Oncology Solid Tumours Biological Project Small Molecule Project 7 UCB has a Rich Research Pipeline ion Therapeutic Lead Lead Indication Optimizat Preclinical Phase 1 Area Discovery Inflammation TNF Mediated Disease CDP 146 (RA, IBD, Psoriasis) Anti IL6 MS p38 Kinase Allergy/Asthma inhibitor SLE Alpha 4 Integrin Bone Loss Antagonist Immunomodulators Sclerostin Antibody CNS Epilepsy Cognition, dementia Neuropathic pain Histamine Oncology Solid Tumours Receptor target Biological Project Small Molecule Project UCB has a Rich Research Pipeline ion Lead Lead Therapeutic Indication Phase 1 Discovery Optimizat Preclinical Area Protein Kinase Inflammation TNF Mediated Disease inhibitor (RA, IBD, Psoriasis) MS Allergy/Asthma Anti Il17 SLE Bone Loss Anti Immunomodulators CD40L Anti CNS Epilepsy OX40 Cognition, dementia Neuropathic pain Oncology Solid Tumours GPCR target Protein Kinase Biological Project Protein Kinase target target Small Molecule Project 8 Innovation Novel Drug Design and Novel Target Biology ion Lead Lead Therapeutic Phase 1 Indication Optimizat Preclinical Area Discovery Inflammation TNF Mediated Disease (RA, IBD, Psoriasis) MS Allergy/Asthma SLE Bone Loss Immunomodulators CNS Epilepsy Cognition, dementia Neuropathic pain Oncology Solid Tumours Innovative drug design Innovative disease target biology UCB Target Innovation Linkage of IL17 to CNS Inflammatory Processes Anti-IL17 treatment 3 Treatment control Effects on murine CR-EAE (MS) 2 1 Disease Severity score (+/- Severity Disease sem) 0 0 10 20 30 40 50 PSD Start of Antibody Dosing 9 UCB Addressing Innovative Drug Targets and Discovering Disease Biology Links Increased Bone Formation in ion KO mice Lead Lead Phase 1 Wild type Knockout mice Discovery Optimizat Preclinical Denser Bones Courtesy of Amgen Sclerostin Target and biology discovery, novel approach to bone disease Extensive patenting Innovative drug design Innovative disease target biology NCE Target Innovation Building on Strengths in SV2 Biology and Histamine Receptors 10 Innovation Novel Drug Design Based upon Competitive Technological Strengths z Small Molecules – Protein kinases as targets for drug discovery – Histamine receptor biology and chemistry z Biologicals – Optimal antibody selection – Structure aligned to preferred drug function Antibody Target Epitope Optimisation z Functional mechanism complexity exemplified by Cimzia™ z UCB approach to proactively map underlying functional complexity z UCB very well equipped to address this opportunity 11 Selection of Optimal Therapeutic Epitope Exemplified by Antagonists of IL-6 Signaling Recruitment Receptor of signaling binding IL-6 Hexamer formation Selection of Optimal Therapeutic Epitope Exemplified by Antagonists of IL-6 Signaling 550 Recruitment Receptor of signaling binding 500 Antibody A IL-6 450 Hexamer 400 formation 350 300 Antibody C 250 Cell Proliferation (OD units x1000) 200 0.01 0.1 1 10 100 1000 10000 100000 1000000 pM binding sites 12 Selection of Optimal Therapeutic Epitope Exemplified by Antagonists of IL-6 Signaling similar in vitro potency can result in very different in vivo activity Recruitment Receptor of signaling binding IL-6 550 500 450 Antibody A Hexamer 400 formation 350 300 Antibody C 250 MTT values (OD units x1000)MTT values (OD 200 0.01 0.1 1 10 100 1000 10000 100000 1000000 pM binding sites Selection of Optimal Therapeutic Epitope Exemplified by Antagonists of IL-6 Signaling similar in vitro potency can result in very different in vivo activity Antibody A 2 1 Acute phase protein phase Acute 0 +ve 3 1 0.3 0.1 0.03 0.01 0.003 PBS A (mg/kg) 13 Selection of Optimal Therapeutic Epitope Exemplified by Antagonists of IL-6 Signaling similar in vitro potency can result in very different in vivo activity Antibody A Antibody C 2 2 1 1 Acute phase protein phase Acute Acute phase protein phase Acute 0 0 +ve 3 1 0.3 0.1 0.03 0.01 0.003 PBS +ve 0.30.10.03 0.01 0.003 PBS A (mg/kg) C (mg/kg) Applying Knowledge from Antibody Function to Inform Small Molecule Discovery and how about where antibodies bind to design new small molecule drugs Differentiating UCB 14 UCB Research Pipeline Summary An extensive and innovative Research pipeline Novel target biology and drug design Focussed Research groups working in areas of competitive strength Synergistic Combination of Biological and Small Molecule Medicines Discovery Differentiating Technologies: Selected Lymphocyte Antibody Method Alistair Lawson Director, Antibody Biology 15 Patient-Driven Research Patient Product Technology Innovative Products From Leading Edge Technology Seeing The Potential In-house e.g. Antibody Fragment Technology Platform In-licensed e.g. SLAM (Selected Lymphocyte Antibody Method) UCB Patent Applications UCB SLAM WO2004/051268 WO2004/106377 WO2005/019823 WO2005/019824 16 UCB SLAM Applying High Throughput Screening Technology to Antibody Discovery Immune B Cells Variable Region Sequences ATGCCTAGATAGCTGCTCAAGCT BIAcore FMAT Secondary Assays Primary Screening Masterplates Hit Picking One Thousand Million B Cells → One Antibody UCB SLAM Delivering High Quality Therapeutics Antibody variable regions for therapeutics 17 UCB SLAM Delivering High Quality Research Reagents Antibody variable regions for research reagents Mechanism 1 Blocking Receptor Binding Mechanism 2 Blocking Signaling Determining The Preferred Therapeutic Axis In Vivo Arthritis Model 8 Disease Progression 7 Blocking Signaling 6 5 4 Blocking 3 Clinical Score Clinical Receptor Binding 2 1 0 5 10 15 20 25 30 35 40 45 Days 18 Building on Strengths Exploring New Opportunities Antibody Structural Technology Biology SYNERGY HTS Medicinal Chemistry Pharmacology Differentiating UCB Differentiating Technologies: Antibody to hit Technology Graham Warrellow Vice President - Chemistry UK 19 Pharma’s Basic Research Toolkit 25,000 genes 30,000 proteins Targets Less than 10% amenable to targeting with traditional small molecule drugs “Traditional” Small Molecules p38 pockets, grooves and clefts 20 90% of the Proteins are Currently “Undruggable” with Small Molecules TNFα TNF Receptor large, flat, apparently featureless surfaces The Chemical Universe From Pagliaro et al., 2004 Reproduced with permission of Elsevier Ltd 21 The Chemical Universe From Pagliaro et al., 2004 Reproduced with permission of Elsevier Ltd The few small molecules which do inhibit protein-protein interactions push the boundaries of conventional chemical space 22 23 24 Antibodies inhibit protein-protein interactions and can guide us in exploring uncharted chemical space for a new generation of small molecule drugs 25 Applying Knowledge about where and how antibodies bind Unique information to help us design novel small molecule drugs Making the Dream a Reality Output from SLAM High affinity, function-modifying antibodies Contact information to design pharmacophores Virtual and directed screening Unique hits for small molecule drug design 1 Playing to Our Core Strengths Antibody