Roche Phamaceuticals Focusing on diffeentiated medicines D. Guido Magni Head of Global Medical Science Lehman Bothes Global Healthcae Confeence, Miami, 26 1 This pesentation contains cetain fowad-looking statements. These fowad-looking statements may be identified by wods such as believes, expects, anticipates, pojects, intends, should, seeks, estimates, futue o simila expessions o by discussion of stategy, goals, plans o intentions. Vaious factos may cause actual esults to diffe mateially in the futue fom those eflected in fowad-looking statements contained in this pesentation among othes: 1. Picing and poduct initiatives of competitos; 2. Legislative and egulatoy developments and economic conditions; 3. Delay o inability in obtaining egulatoy appovals o binging poducts to maket; 4. Fluctuations in cuency exchange ates and geneal financial maket conditions; 5. Uncetainties in the discovey, development o maketing of new poducts o new uses of existing poducts; 6. Inceased govenment picing pessues; 7. Inteuptions in poduction; 8. Loss of o inability to obtain adequate potection fo intellectual popety ights; 9. Litigation; 1. Loss of key executives o othe employees; and... 11. Advese publicity o news coveage Fo maketed poducts discussed in this pesentation, please see full pescibing infomation on ou website www.oche.com 2
R&D pefomance in 25 Stategy and outlook 3 25: An outstanding yea Phama oganic gowth fou times faste than wold maket top ten poducts +32 %, top twenty poducts +31 % Successful launch of seven new poducts/indications Outstanding clinical data in oncology Fou phase tials fo CERA in enal anemia successfully completed Built the base fo enty into a new theapeutic fanchise of Autoimmune diseases 4
Ou objectives in R&D Deliveing clinically diffeentiated medicines Ceate the best medicine by Pioneeing 1 st -in-class theapy Ceating best-in-class in aeas of established mechanisms Maximizing poduct lifecycles though innovative development 5 25: Successful appovals and stong clinical news-flow Building the base fo futue gowth Majo ganted appovals -mcrceu Pegasys - HBV EU and US Pegasys - HCV/HIV coinfection EU and US Xenical - adolescent obesity EU Xenical - pevention of T2D EU and US Boniva - osteopoosis (oal monthly) EU and US Boniva - osteopoosis (iv) US* - adj CC EU and US Taceva - NSCLC EU Taceva - panceatic Ca US Actema - Castleman s disease Jp * Jan. 6, CHMP positive opinion EU Completed phase tials - NSCLC (E4599) - mbc (E21) Heceptin adj. BC (NSABP / NCCTG) Heceptin adj. BC (HERA) Heceptin adj. BC (BCIRG 6) panceatic Ca maintenance inhl (EORTC2891) RA (REFLEX) Actema RA (Japanese tial) Pegasys/Copegus HCV (Japanese tial) CERA enal anemia (BA16739, BA1674, BA17283, BA17284) Lucentis AMD (MARINA) All appovals obtained as planned (16) All phase tials met pimay end-points (15) 6
Making a diffeence fo patients - and boding well fo futue gowth Poduct Heceptin Taceva Actema Indication (clinical tial) NSCLC 1st line (E4599) mbc 1st line (E21) mcrc 2nd-line (E32) BC adjuvant (NSABP B-31/N9831) BC adjuvant (HERA) BC adjuvant (BCIRG 6) inhl elapsed maintenance (GSLG) inhl elapsed maintenance (EORTC 2891) Panceatic cance 1st line (PA3) Panceatic cance 1st line (CR UK) Rheumatoid athitis (Japan) Rheumatoid athitis TNF nonesp. (REFLEX) Benefit 23% eduction in isk of death 5% eduction in isk of cance pogession 24% eduction in isk of death 52% eduction in isk of disease ecuence 46% eduction in isk of disease ecuence 51% eduction in isk of disease ecuence >17 months polongation of PFS 5% eduction in isk of death 19% eduction in isk of death 2% eduction in isk of death ACR2, 5 and 7 of 89%, 7% and 47% ACR2, 5 and 7 of 51%, 27% and 12% 7 An industy leading late stage pipeline Again stengthened Phase / filed pojects 31 7 17* 41 New Initiatives in Autoimmune Diseases CellCept in LN, MG in RA DMARD nonesp. New Initiatives in Cance Taceva in NSCLC in postate, ovaian, CRC, BC Heceptin in gastic Ca Epogin in cance anemia end '4 appoved discontinued new enties end '5 * Including thee pojects peviously combined and now listed as seven single indications 8
An outstanding success ate in R&D Measues taken to impove chances fo success Roche Rx Phase success ate in % 1 8 Additional Indications New M olecula Entities 71 95 1 83 6 4 44 38 45 6 2 '96-' '97-'1 '98-'2 '99-'3 '-'4 '1-'5 1 Data fo Additional Indications only available fo cohot 1-5 Success ate = 1- teminations / (teminations + appovals) 9 R&D pefomance in 25 Stategy and outlook 1
Emeging potfolios in vaious theapeutic aeas Oncology Heceptin Taceva CERA Bondonat Omnitag R1492 epothilone D CAL Chugai DMXAA Antisoma 1 phase I compounds FY 25 - Autoimmune Mabthea Actema CellCept R153 p38 kinase inh. R1594 hum anti CD-2 4 phase I compounds On hand Metabolic R144 GK act. R1438 DPP IV inh. R483 Insulin Sensit. R1658 CETP inh. GLP-1 Ipsen 3 phase I compounds Pomising late stage Neuology 3 phase I compounds 4 phase compounds Emeging mid-tem Ealy stage 11 : A unique development appoach All main cance types, including ealy intevention, in paallel Phase indication mcrc 1st line mcrc 1st line ext. CC adjuvant NSCLC 1st line non-squamous NSCLC 1st line maint. combo Taceva NSCLC 2nd line combo Taceva NSCLC adjuvant mbc 1st line mbc 1st line combo extension BC adjuvant RCC 1st line Panceatic Ca 1st line Ovaian Ca Postate Ca Status Launched US/EU Recuitment completed, EU filing '6 Recuitment ongoing, EU filing post '9 Data pesented, filing '6 Stated Q4 5, EU filing post '9 Recuitment ongoing, EU filing '8 To stat soon Data pesented, filing '6 Stated Q4 5, EU filing '8 Pilot ongoing Recuitment completed, EU filing '7 Recuitment ongoing, EU filing '8 Recuitment ongoing, EU filing post '9 Recuitment ongoing, EU filing post '9 3 d line 2 nd line 1 st line Adjuvant NSCLC CRC Establish as a backbone theapy fo all majo tumos BC 12
25: Roche in Rheumatoid Athitis The fist poducts in the autoimmune fanchise AI diseases RA CHF bn 14 12 1 8 6 4 2 3.9 Sales to teat RA 1 Biologic agents Conventional DMARDs Phase I R1541 (IBD) R1295 (RA) R3421 (AI) BR3-FC (RA) GNE 8.5 11.6 23 28 213 Phase II R153 (RA) R1594 (RA) (RRMS) GNE (LN) GNE Anti-TNF inadequate espondes (REFLEX) - filed in US and EU DMARD inadequate espondes - phase initiated (3 tials), filing in 27 Actema Phase completed in Japan, on tack (5 tials) in RoW Japanese filing in 26, filing in US and EU in 27 (RA DMARD) Actema (RA) Actema (sjia) CellCept (LN) CellCept (MG) Phase (PPMS) GNE (ANCA av) GNE (SLE) GNE Filed (RA TNF) 1 Souce : Decision Resouces Mach 25, US/Top 5 EU/Japan 13 efficacy in RA (REFLEX) ACR esponses at 6 months 1 Mean change in Shap-Genant eosion scoe % p atients 6 5 4 3 2 1 18 5 1 Placebo + MTX (n=21) ACR2 ACR5 ACR7 P <.1 51 P <.1 27 Rituximab 2x1mg + MTX (n=298) P <.1 12 Mean Change in Shap-Genant (Eosion Scoe).8.6.4.2 4 8 12 16 2 24 Weeks Placebo (n=21) Rituximab 2x1mg (n=298) Robustness Analysis : All 24 week data included, missing values imputed with LOCF (no change) significantly impoves ACR esponses 14
in RA Conclusions of 6-month pimay analyses in combination was associated with a highly significant incease in ACR2 esponse ate ove placebo + MTX All seconday and exploatoy endpoints (DAS, EULAR, ACR coe set, FACIT-F) wee highly significantly impoved ove placebo Efficacy demonstated in RF-negative patients Suggestion of effects on joint damage at 24 weeks Well toleated Data filed in US and EU 15 Actema monotheapy in RA (Japanese p) Efficacy ACR esponses at 52 weeks Radiogaphic data (mean scoes) % of patients 1 8 6 4 2 89.2 p <.1 7.1 Actema 8 mg/kg Contol 47.1 35.2 13.8 5.5 145 157 145 157 145 157 Change fom baseline 7 6 5 4 3 2 1 p <.1 6.12 2.91 2.3 1.45 Actema 8 mg/kg Contol 3.21.85 145 157 145 157 145 157 ACR 2 ACR 5 ACR 7 TSS JSN ES TSS: Total Shap Scoe; JSN: Joint Space Naowing; ES: Eosion Scoe Significantly impoved ACR esponses and significantly less adiogaphic pogession with Actema 16
Actema monotheapy in RA Peliminay esults Fist tial showing supeioity of blocking IL-6 with Actema to conventional DMARDs Blocking the IL-6 ecepto with Actema leads to significant impovement in signs and symptoms and educe the pogession of joint damage Advese events ae within expectations 1 - AEs: 96% vs. 87% in Actema vs. DMARDs goup - SAEs: 19% vs. 13% in Actema vs. DMARDs goup Five phase tials in Roche teitoies ongoing 1 most fequently epoted infectious event: nasophayngitis; mild, tansient inceases in LFTs wee obseved in both goups lipid inceases wee mainly epoted in the Actema goup: mean total cholesteol levels became stable (217 + 39.3 mg/dl) at aound the nomal uppe limit 17 Conclusions 18
A ich and low isk Phase pipeline Keeping the high level of commitment Filed o to file soon maintenance inhl RA TNF nonesp. Heceptin adjuvant BC Taceva panceatic Ca Femaa Beast Ca (Japan) Antevas subaach. haemo. Lucentis AMD Sigmat acute heat failue NSCLC mbc CERA enal anemia 1st line CLL adjuvant CC combo Postate Ca Taceva & NSCLC 2nd line RA DMARD failues ANCA ass. vasculitis elapsed CLL mcrc 1st line ext. ovaian Ca Heceptin gastic Ca CellCept lupus nephitis SLE Ongoing adjuvant BC mcrc 1st line combo adjuvant CC RCC mbc 1st line ext. Taceva NSCLC 1st line Heceptin mbc combo homonal Actema RA CellCept myasthenia gavis Bondonat MBP Epogin chemotheapy-induced anemia ED-71 osteopoosis mcrc 2nd line combo panceatic Ca Taceva & NSCLC maintenance Actema sjia PPMS Xolai pediatic asthma To stat soon Taceva adjuvant NSCLC adjuvant NSCLC adjuvant BC Status as of Decembe 31, 25 19 Ou objectives fo 26 Anothe busy yea Filings Majo clinical data Compound R744 (CERA) CellCept Heceptin / R1658 R873 / Taceva R1594 Compound R744 (CERA) Heceptin Heceptin Phase II IIa II II Indication Renal anemia NSCLC 1st line mbc 1st line Indication Renal anemia (coection) Lupus nephitis (Induction phase) mbc combo homonal (TAnDEM) mcrc 2nd line NSCLC 1st line (AVAIL) mcrc 1st line combo extension Dyslipidemia MED NSCLC 2nd line RA mcrc 1st line combo extension Adjuvant BC mbc combo homonal mcrc 1st line combo Data Inteim baing unfoeseen events 2
Majo Roche managed pojected submissions ove the next yeas Phase II Phase R1558 bacteial infections R153 RA R144 type II diabetes R873 male eectile dysfunction R1594 RA (EU) R667 emphysema R744 (CERA) enal anaemia R1492 solid tumos R1273 (Omnitag) solid tumos (EU) NSCLC 1st line (EU) Actema RA / sjia adj. CC combo R1658 dyslipidemia Heceptin adj. BC (EU) Bondonat metastatic bone pain panceatic Ca (EU) NSCLC squamous (EU) mbc 1st line (EU) mcrc 2nd line combo Heceptin gastic Ca (EU) R1438 type II diabetes adj. CC (EU) Heceptin mbc homonal (EU) CellCept lupus nephitis Taceva NSCLC 1st line chemo (EU) R744 (CERA) cance anaemia postate Ca (EU) mcrc 1st line combo extension (EU) mcrc 1st line combo RA DMARD inadeq. esp. (EU) RCC (EU) Taceva+ NSCLC 2nd line (EU) mbc 1st line extension (EU) adj. BC CLL (EU) ovaian Ca (EU) Taceva+ NSCLC 1st line maint (EU) 26 27 28 29 post 29 Status as of Decembe 31, 25 Unless stated othewise, submissions will occu in US and EU 21 The bottom-line Stong pipeline and pefomance ove long tem Rich late-stage pipeline with low isk Emeging ealy potfolio in vaious theapeutic aeas Oncology-fosteing maket leadeship with 5 NME with suvival benefit and additional indications Continuing deliveing fist-in-class medicines ( in cance theapy, and Actema in RA) Vaious best-in-class molecules in development (CERA in anemia, Taceva in cance theapy) Continuing maximizing the value of appoved poducts by effective life cycle management (,,, Pegasys, CellCept) Well-pepaed fo futue gowth 22