David Loew, LCL MabThera



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MabThera The star continues to rise David Loew, LCL MabThera MabThera the star continues to raise Group sales (CHF bn) 4,5 4,0 3,5 3,0 2,5 2,0 1,5 1,0 0,5 0,0 2001 2002 2003 2004 2005 Outstanding clinical data and extensive development program Over 10,000 patients randomized Overall survival benefit combined with excellent tolerability More registrations to come Significant sales growth ahead US/EU: indolent NHL maintenance launch and CLL RoW: indolent & aggressive NHL (all settings) and CLL Long patent protection Limited/no competition 2

Development: from a niche product to a blockbuster 95-97 98/99 00/01 02/03 04/05 06/07 08/09 Indolent NHL Relapsed Aggressive NHL 1 st line Indolent NHL 1 st line Indolent NHL Maintenance NHL CLL 1 st line and relapsed 3 Major opportunities in maintenance and CLL Patient pools & indications EU Filing planned: 2009 CLL relapsed 6% CLL 1st 8% Indolent 1st 19% Approved: 2004 Approved: 2002 Aggressive relapsed 8% Aggressive 1st 28% Indolent relapse 12% Approved: 1998 Indolent maintenance 19% CHMP positive opinion: June 2006 4

MabThera standard of care Aggressive lymphoma B Coiffier et al. Trneny M et al. LH Sehn et al. M Pfreundschuh et al. GELA OS and FFP Czech Registry PFS March 2001 OS and FFP MInT OS and FFP 1.0 0.8 R-CHOP R-Chemo Post-Rituximab 1.0 0.9 0.8 R-Chemo 0.6 0.4 0.2 3.3 y CHOP P = 0.007 0.0 0 1 2 3 4 5 6 Chemo Pre-Rituximab 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 Chemo 20 40 5 10 15 25 30 35 45 50 5 year follow-up 60 years < 60 years <& 60 years < 60 years 5 MabThera standard of care Indolent lymphoma Study M39021; Marcus et al. CVP +/- R Overall survival (%) Control Rituximab 85 89 p (lymphoma related deaths) GLSG; Hiddemann et al. CHOP +/- R Median not reached Median not reached M39023; Herold et al. MCP +/- R 75 89 FL2000; Salles et al.* CHVP= Inf +/- R 86 91 *submitted for publication 6

Indolent maintenance ASH 2005: Two pivotal studies with overall survival benefit! ECOG: 1 st line CVP followed by +/- MabThera 100 90 80 70 60 50 40 30 20 10 0 p = 0.03 HR = 0.5 Observation 75% 42 months Maintenance 91% EORTC: relapse R-CHOP followed by +/- MabThera 100 90 80 70 60 50 40 30 20 10 Overall Logrank test: p=0.011 36 months Maintenance 85.1% Observation 77% 0 (years) 0 1 2 3 4 5 6 0 1 2 3 4 5 6 Years Reduction of risk of death by 50 %! Delay of relapse by more than 3 years! 7 MabThera in CLL Promising phase II data Rx CR (%) Line Study Chlorambucil 3 1 st Intergroup Fludarabine 27 Fludarabine 9 1 st GCLLSG F-C 21 Fludarabine 28 1 st CALGB F + rituximab 47 FC + rituximab 70 1 st MDACC F = Fludarabine C = Cyclophosphamide 8

Potential to further accelerate sales Geographical breakdown Penetration rates Q3-Q4 2005 Key 5 EU US Roche 37% 1 st line indolent Relapsed indolent 62 % 64 % 85 % 77 % US 58% 1 st line aggressive Relapsed aggressive 82 % 68 % 83 % 56 % Japan 5% 1 st line CLL 19 % 57 % Relapsed CLL 30 % 55 % 2005 CHF 4.12 bn Maintenance ind NHL 8 % 19 % Source: Roche market research Q4 2005, Genentech Q3 2005 results Note: CLL and maintenance therapy in indolent NHL are non-approved indications in EU/ROW 9 MabThera Four approaches to drive sales 1. Increase penetration 2. Prolong treatment (maintenance) 3. Launch new indications 4. Accelerate sales in high growth markets 10

Appendix Product profile MabThera Indication Exclusions Dosing Adverse reactions Incidence anhl Incidence inhl Current sales (2005) Further development Non-Hodgkin's Lymphoma: 1 st line and relapse follicular lymphoma Aggressive lymphoma None 375mg/m 2 Very well tolerated, some infusion related reactions at first dose and hematological side effects 170,000/ year 125,000/ year CHF 4,154m Maintenance follicular lymphoma (July 06) Chronic lymphocytic leukemia 1st line: 2009 CLL relapsed: 2010 12

Approval status MabThera in NHL EU MabThera is indicated for treatment of patients with stage III-IV follicular lymphoma who are chemoresistant or are in their second or subsequent relapse after chemotherapy MabThera is indicated for the treatment of previously untreated patients with stage III-IV follicular lymphoma in combination with CVP chemotherapy MabThera is indicated for the treatment of patients with CD20 positive diffuse large B cell non-hodgkin s Lymphoma in combination with CHOP chemotherapy US RITUXAN (Rituximab) is indicated for the treatment of patients with relapsed or refractory, low-grade or follicular, CD20- positive, B-cell, non-hodgkin's lymphoma. RITUXAN (Rituximab) is indicated for the first-line treatment of diffuse large B-cell, CD20-positive, non-hodgkin's lymphoma in combination with CHOP or other anthracycline-based chemotherapy regimens Positive opinion from CHMP received on 1st June 2006 for MabThera maintenance therapy for patients with relapsed/refractory follicular lymphoma responding to induction therapy with chemotherapy with or without MabThera 13 Approval status MabThera in Rheumatoid Arthritis EU MabThera in combination with methotrexate is indicated for the treatment of adult patients with severe active rheumatoid arthritis who have had an inadequate response or intolerance to other diseasemodifying anti-rheumatic drugs including one or more tumor necrosis factor (TNF) inhibitor therapies US RITUXAN (Rituximab) in combination with methotrexate is indicated to reduce signs and symptoms in adult patients with moderately- to severely active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies Positive opinion from CHMP received on 1st June 2006 for MabThera in combination with methotrexate for the treatment of adult patients with severe active rheumatoid arthritis who have had an inadequate response or intolerance to other disease-modifying anti-rheumatic drugs including one or more tumour necrosis factor (TNF) inhibitor therapies 14

Intergroup phase III trial (EORTC 20981) MabThera maintenance in relapsed inhl Overall survival from 2 nd randomization 100 90 80 R-maintenance 3 yrs 85.1 % 70 60 50 40 30 observation 3 yrs 77.1 % 20 10 Overall Logrank test: p=0.011 0 Hazard ratio: 0.52 (years) 0 1 2 3 4 5 6 O N Number of patients at risk : Treatment 39 167 148 99 50 14 2 Observation 23 167 155 112 69 19 4 Mabthera Presented at ASH `05 15