Roche Group development pipeline Marketed products development programmes Roche Pharma global development programmes Roche Pharma research and early development Genentech research and early development Roche Group YTD Sept 2012 results Diagnostics Foreign exchange rate information 1 Roche development pipeline Projects in phase 1 Phase I (36 NMEs+2 AIs) Oncology RG7112 RG7116 RG7155 RG7167 RG7204 RG7212 RG7304 RG7356 RG7420 RG7421 RG7388 RG7440 RG7446 RG7450 RG7458 RG7598 RG7599 RG7600 RG7601 RG7602 RG7604 RG7636 RG7666 RG7741 CHU CHU CHU MDM2 ant solid & hem tumors HER3 MAb solid tumors CSF-1R MAb solid tumors CIF/MEK inh solid tumors Zelboraf + ipilimumab met. melanoma Tweak MAb oncology Raf & MEK dual inh solid tumors CD44 MAb solid tumors MEK inh solid tumors MEK inh solid tumors MDM2 ant solid & hem tumors AKT inhibitor solid tumors PD-L1 MAb solid tumors Steap 1 ADC prostate ca. ADC ovarian ca. ADC multiple myeloma ADC oncology ADC oncology Bcl-2 inh CLL and NHL ChK1 inh solid tum & lymphoma PI3K inh solid tumors ADC metastatic melanoma PI3k inh glioblastoma 2L ChK1 inh(2) solid tumors ALK inhibitor NSCLC PI3K inh solid tumors WT-1 peptide cancer vaccine Other disease areas RG7624 CHU CHU RG7795 RG7667 RG7697 RG1662 RG7314 RG7129 RG3645 CHU IL-17 MAb autoimmune diseases IL-6R MAb RA CIM331 atopic dermatitis TLR7 agonist HBV infectious diseases GIP/GLP-1 dual ago type 2 diabetes GABRA5 NAM cogn. disorders V1 receptor antag autism BACE1 inh Alzheimer’s Lucentis sust. deliv. AMD/RVO/DME ACE910 hemophilia A New Molecular Entity (NME) Additional Indication (AI) Oncology Immunology Virology CardioMetabolism Neuroscience Ophthalmology Others RG-No Roche Genentech managed CHU Chugai managed Status as of September 30, 2012 2 Roche development pipeline Projects in phase 2, 3 and registration Phase II (24 NMEs + 14 Als) RG1273 RG1273 RG3502 RG3502 RG3616 RG3638 RG3638 RG3638 RG3638 RG3638 RG3638 RG7160 RG7204 RG7321 RG7422 RG7414 RG7593 RG7596 RG7597 RG7686 RG1569 RG7413 RG7415 RG7416 RG7449 RG7128 RG7227 RG7790 RG1512 RG7652 RG7418 RG1450 RG1577 RG1578 RG7090 RG7412 SST RG7417 Perjeta HER2+ mBC 2nd line Perjeta HER2+ gastric cancer T-DM1 HER2+ EBC T-DM1 gastric cancer Erivedge operable BCC onartuzumab triple-neg mBC, 1st/2nd line1L/2L onartuzumab mCRC 1st line 1L onartuzumab NSCLC non squamous 1st l onartuzumab NSCLC squamous 1st line onartuzumab glioblastoma 1st/2nd line onartuzumab gastric cancer EGFR MAb solid tumors Zelboraf papillary thyroid cancer PI3K inh solid tumors PI3K/mTOR inh solid & hem tumors EGFL7 MAb solid tumors CD22 ADC heme tumors CD79b ADC heme tumors HER3/EGFR m. epithelial tumors glypican-3 MAb liver cancer Actemra systemic sclerosis etrolizumab ulcerative colitis rontalizumab systemic lupus erythem pateclizumab (LT alpha MAb ) RA quilizumab (M1 prime MAb) asthma mericitabine HCV danoprevir HCV setrobuvir HCV inclacumab (P selectin MAb) ACS/CVD PCSK9 MAb metabolic diseases oxLDL MAb sec prev CV events gantenerumab Alzheimer’s MAO-B inh Alzheimer’s mGluR2 antag depression mGluR5 antag tx resistant depression crenezumab Alzheimer‘s arbaclofen autism (ASD) anti-factor D Fab geographic atrophy Phase III (8 NMEs + 23 Als) RG105 RG435 RG435 RG435 RG435 RG435 RG435* RG435 RG1273 RG1415* RG1415 RG3502 RG3502 RG3638 RG7159 RG7159 RG7159 RG7159 RG7204 RG1569 RG1569 RG3637 RG3648 CHU RG1439 CHU RG1594 RG1594 RG1678 RG1678 SST MabThera NHL sc formulation Avastin HER2+ BC adj Avastin HER2-neg. BC adj Avastin NSCLC adj Avastin high risk carcinoid Avastin glioblastoma 1st line Avastin ovarian cancer 1st line Avastin ovarian cancer platinum resist. Perjeta HER2+ EBC Tarceva NSCLC EGFR mut 1st line Tarceva NSCLC adj T-DM1 HER2+ mBC 3rd line T-DM1 HER2+ mBC 1st line onartuzumab NSCLC 2nd/3rd line obinutuzumab CLL obinutuzumab iNHL relapsed obinutuzumab DLBCL obinutuzumab iNHL front-line Zelboraf m. melanoma adj Actemra RA sc formulation Actemra early RA lebrikizumab severe asthma Xolair chronic idiopathic urticaria Suvenyl enthesopathy aleglitazar CV risk reduction in T2D tofogliflozin (SGLT2) type 2 diabetes ocrelizumab RMS ocrelizumab PPMS bitopertin schiz neg symptoms bitopertin schiz subopt control arbaclofen fragile X syndrome Registration (3 NMEs + 8 Als) RG105 Rituxan RG4351 Avastin RG435 Avastin RG5971 Herceptin RG12732 Perjeta RG3502 T-DM1 RG36162 Erivedge RG1052 MabThera RG1569 Actemra RG15691 Actemra RG36453 Lucentis 1 2 3 NHL fast infusion relapsed ovarian cancer mCRC TML HER2+ BC sc form HER2+ mBC 1st line HER2+ pretreated mBC advanced BCC ANCA assoc vascul polyarticular JIA RA DMARD IR H2H AMD 0.5 mg PRN submitted in EU approved in US, submitted in EU submitted in US New Molecular Entity (NME) Additional Indication (AI) Oncology Immunology Virology CardioMetabolism Neuroscience Ophthalmology RG-No CHU SST RG105 Roche Genentech managed Chugai managed Seaside Therapeutics MabThera is branded as Rituxan in US and Japan RG1569 Actemra is branded as RoActemra in EU * approved in the EU Status as of September 30, 2012 3 Changes to the development pipeline Since HY 2012 update on July 26, 2012 New to Phase I 1 NME transitioned from Ph0 RG7697 GIP/GLP-1 dual agonist type 2 diabetes 2 NMEs added by Chugai CHU CIM331 atopic dermatitis CHU ACE910 hemophilia A Removed from Phase I 1 NME reverted to partner RG7256 BRAF inh (2) BRAF mut melanoma 2 NMEs discontinued RG7594 anti-angiogenic solid tumors RG7685 GIP/GLP-1 dual agonist type 2 diabetes New to Phase II 2 NMEs transitioned from Ph1 RG7593 CD22 ADC hem. tumors RG7596 CD79b ADC hem. tumors 2 AIs following FPI RG3638 onartuzumab gastric cancer RG3502 T-DM1 gastric cancer HER2-positive Removed from Phase II 1 NME discontinued RG4929 11 beta HSD inh metabolic diseases New to Phase III 1 AI following FPI RG7204 Zelboraf metastatic melanoma adj. Removed from Phase III 1 AI removed following outcome of HERA 2years RG597 Herceptin Her2-positive adj. BC (2years) New to Registration 1 NME and 1 AI following US and EU submissions RG3502 T-DM1 HER2-positive pretreated mBC (NME) RG435 Avastin mCRC TML 1 AI following EU submission RG1569 Actemra RA DMARD IR H2H Removed from Registration 1 AI following FDA approval RG3645 Lucentis diabetic macular edema 4 NME submissions and their additional indications Projects currently in phase 2 and 3 onartuzumab (MetMAb) gastric cancer obinutuzumab (GA101) DLBCL PI3 kin inh (RG7321) solid tumors EGFR MAb (RG7160,GA201) solid tumors T-DM1 (RG3502) HER2-pos. mBC 1st line T-DM1 (RG3502) HER2-pos. gastric cancer mericitabine HCV obinutuzumab (GA101) iNHL relapsed danoprevir HCV onartuzumab (MetMAb) mNSCLC, 2nd/3rd line aleglitazar CV risk reduction in T2D setrobuvir HCV bitopertin schizophrenia# ocrelizumab PPMS and RMS mGluR5 (RG7090) depression MEK inhibitor ( RG7421) combo Zelboraf met melanoma ü T-DM1 (RG3502) HER2-pos. pretreated mBC 2012 obinutuzumab (GA101) CLL 2013 Unless stated otherwise, submissions are planned to occur in US and EU. ü indicates a submission which has occurred with regulatory action pending # negative symptoms and sub-optimal control Status as of September 30, 2012 2014 2015 Oncology Immunology Virology CardioMetabolism 2016 Neuroscience Ophthalmology NME 5 Submissions of additional indications for existing products Projects currently in phase 2 and 3 Avastin mCRC TML Herceptin sc formulation (EU) ü ü Avastin ovarian cancer platin. resist. Zelboraf met melanoma adj. MabThera sc formulation (EU) Avastin relapsed ovarian cancer (US) papillary thyroid cancer Tarceva (US) NSCLC EGFR mut. 1st line Avastin ovarian cancer 1st line (US) Zelboraf Perjeta HER2-pos. EBC Perjeta ü Avastin HER2-pos. BC adj HER2-pos. mBC 2ndline Actemra RA DMARD IR H2H (EU) ü Avastin glioblastoma 1st line HER2-pos. gastric cancer Actemra sc formulation Tarceva NSCLC adj (EU) Avastin HER2-neg BC adj ü Xolair (US) chronic idiopathic urticaria Avastin NSCLC adj ü Actemra early RA Actemra polyarticular JIA MabThera ANCA assoc vasculitis (EU) Lucentis AMD 0.5 mg PRN (US) 2012 2013 ü indicates submission to Health Authorities has occurred. Unless stated otherwise, submissions are planned to occur in US and EU. Status as of September 30, 2012 Perjeta Tarceva NSCLC adj (US) 2014 Actemra systemic sclerosis Post 2014 Oncology Immunology Virology CardioMetabolism Neuroscience Ophthalmology 6 Major granted and pending approvals 2012 Approved Pending approvals Actemra DMARD IR US EU Erivedge adv. basal cell ca T-DM1 (RG3502) HER2-pos pretreated mBC Filed Aug 2012 Perjeta HER2-pos. mBC 1st line Avastin mCRC TML Filed Aug 2012 Actemra polyarticular JIA Filed June 2012 Lucentis diabetic macular edema Rituxan NHL faster infusion Filed Dec 2011 Lucentis AMD 0.5 mg PRN Filed Apr 2012 Zelboraf met. melanoma Erivedge adv. basal cell ca Filed Nov 2011 Actemra RA DMARD IR H2H Filed Aug 2012 Perjeta (RG1273) HER2-pos. mBC 1st line Filed Dec 2011 Actemra polyarticularJIA Filed June 2012 T-DM1 (RG3502) HER2+ advanced mBC Filed Aug 2012 MabThera ANCA associated vasculitis Filed Apr 2012 Avastin relapsed ovarian cancer Filed Aug 2011 Oncology Immunology Virology CardioMetabolism Status as of September 30, 2012 Neuroscience Ophthalmology NME Avastin mCRC TML Filed Aug 2012 Herceptin sc formulation Filed Mar 2012 7 Major Chugai granted and pending approvals 2012 Approved Pending approvals Pulmozyme Improvement pulmonary function in cystic fibrosis Actemra sc formulation Filed March 2012 Avastin glioblastoma Filed September 2012 Avastin ovarian cancer Filed October 2012 Perjeta HER2-pos. mBC 1st line Filed May 2012 Tarceva NSCLC EGFR mut 1st line Filed June 2012 Boniva/Bonviva osteoporosis Filed July 2012 Oncology Immunology Virology CardioMetabolism Status as of September 30, 2012 Neuroscience Ophthalmology NME 8 We Innovate Healthcare 9 Roche Group development pipeline Marketed products development programmes Roche Pharma global development programmes Roche Pharma research and early development Genentech research and early development Roche Group YTD Sept 2012 sales Diagnostics Foreign exchange rate information 10 MabThera/Rituxan Development programmes Oncology Patient population Front-line follicular non-Hodgkin’s lymphoma Previously untreated chronic lymphocytic leukemia Phase/study Phase III SABRINA Subcutaneous study Study being conducted ex-US Phase Ib SAWYER Subcutaneous study Study being conducted ex-US # of patients N=405 N=225 Design • ARM A: MabThera IV plus chemotherapy (CHOP or CVP) • ARM B: MabThera 1400mg sc plus chemotherapy (CHOP or CVP) Two-stage design: o Stage 1 (dose confirmation, N=127): PK primary endpoint o Stage 2 (N=280): Efficacy primary endpoint (ORR) Responders will continue on maintenance every 8 weeks over 24 months • Two-stage design: - Stage 1 (dose-finding, N=55) Primary endpoint • Pharmacokinetics, safety and efficacy • Part 1: PK (dose selection) • Part 2: PK of MabThera IV vs. MabThera SC (Arm A vs Arm B) Status • Stage 1 primary endpoint (PK noninferiority) met • Expect full stage 1 data presentation Q4 2012 • FPI (stage 2) Q3 2012 - Stage 2 (N=170): CLL dose confirmation: • ARM A: MabThera IV plus chemotherapy (Fludarabine and Cyclophosphamide) • ARM B: MabThera 1600mg sc plus chemotherapy (Fludarabine and Cyclophosphamide) Subcutaneous MabThera : applies Enhanze technology, partnered with Halozyme CHOP = Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone; CVP = Cyclophosphamide, Vincristine and Prednisolone. 11 MabThera/Rituxan Development programmes Oncology Immunology Front-line diffuse large B-cell or follicular non-Hodgkin’s lymphoma ANCA-associated vasculitis Phase/study Phase IIIb RATE* Faster infusion study Phase II/III RAVE* # of patients N=450 N=197 Patient population Design • Prospective, open-label, single arm study • Non-inferiority efficacy and safety study of MabThera/Rituxan and glucocorticoids versus conventional therapy (cyclophosphamide) Primary endpoint • To determine the incidence of Grade 3 or 4 infusion-related toxicities resulting from faster infusion of MabThera/Rituxan • Induction of complete remission at 6 months, defined as a BVAS/WG of 0 and off glucocorticoid therapy Status • Enrolment completed Q4 2010 • Data presented at ASH 2011 • Filed with the FDA in Q4 2011 • Data presented at ACR 2009 • FDA approved use of Rituxan in WG and MPA in Q2 2011 • Submitted to EMA Q2 2012 *In collaboration with Biogen Idec; WG - Wegener's Granulomatosis, MPA - Microscopic Polyangiitis 12 Avastin Ovarian cancer clinical development programme Patient population Front-line metastatic ovarian cancer Phase/stud y # of patients Phase III GOG-0218 Phase III ICON7 N=1,873 N=1,528 Design • ARM A: Paclitaxel and carboplatin for 6 cycles plus 5 cycles of concurrent placebo followed by placebo alone for up to 22 cycles (15 months) • ARM B: Paclitaxel and carboplatin for 6 cycles plus 5 cycles of concurrent Avastin followed by placebo alone for up to 22 cycles (15 months) • ARM C: Paclitaxel and carboplatin for 6 cycles plus 5 cycles of concurrent Avastin followed by Avastin alone for up to 22 cycles (15 months) • ARM A: Paclitaxel and carboplatin for 6 cycles • ARM B: Paclitaxel and carboplatin plus concurrent Avastin for 6 cycles followed by Avastin alone for up to 18 cycles (12 months) Avastin dose • 15 mg/kg q3 weeks • 7.5 mg/kg q3 weeks Primary endpoint • Progression-free survival • Progression-free survival Status • Study met its primary endpoint in Q1 2010 • Data presented at ASCO 2010 and 2011 • Results published in NEJM December 2011 • Study met its primary endpoint Q3 2010 • Data presented at ESMO 2010 and ASCO 2011 • Results published in NEJM December 2011 • EMA approval Q4 2011 • Re-evaluate FDA submission when final overall survival results from all phase III trials are available (expected 2013) ASCO = American Society of Clinical Oncology; ESMO = European Society for Medical Oncology. 13 Avastin Ovarian cancer clinical development programme Patient population Relapsed platinum-sensitive ovarian cancer Relapsed platinum-resistant ovarian cancer Phase/study Phase III OCEANS Phase III AURELIA # of patients N=484 N=361 Design • ARM A: Carboplatin, gemcitabine, and concurrent placebo for 6 cycles, followed by placebo alone until disease progression • ARM B: Carboplatin, gemcitabine, and concurrent Avastin for 6 cycles, followed by Avastin alone until disease progression. • ARM A: Paclitaxel, topotecan or liposomal doxorubicin • ARM B: Paclitaxel, topotecan or liposomal doxorubicin plus Avastin Avastin dose • 15 mg/kg q3 weeks • 10 mg/kg q2 weeks or 15 mg/kg q3 weeks Primary endpoint • Progression-free survival • Progression-free survival Status • • • • • • Study met its primary endpoint Q2 2012 • Data presented at ASCO 2012 • EMA submission expected Q1 2013 Study met its primary endpoint Q1 2011 Data presented at ASCO 2011 EMA submission Q3 2011 Positive CHMP opinion received Q3 2012 Re-evaluate FDA submission when final overall survival results from all phase III trials are available (expected 2013) ASCO = American Society of Clinical Oncology; ESMO = European Society for Medical Oncology. 14 Avastin High risk carcinoid and brain cancer development programmes Patient population High risk carcinoid Newly diagnosed glioblastoma Phase/study Phase III SWOG SO518 Phase III AVAglio # of patients N=424 N=920 Design • ARM A: Depot octreotide plus interferon alpha • ARM B: Depot octreotide plus Avastin • ARM A: Concurrent radiation and temozolomide plus placebo; followed by maintenance TMZ plus placebo for 6 cycles; then placebo until disease progression • ARM B: Concurrent radiation and TMZ plus Avastin; followed by maintenance TMZ plus Avastin for 6 cycles; then Avastin (15mg/kg q3 weeks) monotherapy until disease progression Avastin dose • 15 mg/kg q3 weeks • 10 mg/kg q2 weeks or 15 mg/kg q3 weeks Primary endpoint • Progression-free survival • Progression-free survival • Overall survival • Recruitment completed • Expect data 2013 • Enrolment completed Q1 2011 • Co-primary endpoint of PFS met Q3 2012 Status 15 Avastin Colorectal and breast cancer development programmes Patient population Metastatic colorectal cancer First-line HER2-negative metastatic breast cancer Phase/study Phase III ML18147 TML Phase III MERiDiAN # of patients N=810 N=480 Design • 1st-line treatment with chemotherapy* plus Avastin • Once patients progress, they are randomised to: • ARM A: Chemotherapy* alone • ARM B: Chemotherapy* + Avastin • ARM A: Paclitaxel + Avastin • ARM B: Paclitaxel + Placebo * Physician’s choice Avastin dose • 5 mg/kg q2 weeks or 7.5 mg/kg q3 weeks • 10 mg/kg q2 weeks Primary endpoint • Overall survival • PFS in ITT • PFS in patients with high plasma VEGF-A Status • • • • Primary end point met Q1 2012 Data presented at ASCO 2012 Filed globally Q3 2012 Priority review granted by the FDA October 2012 • FPI Q3 2012 16 Avastin Adjuvant clinical development programme Patient population Adjuvant lung cancer Phase/stud y Phase III ECOG 1505 Phase III ECOG 5103 HER2-negative Phase III BETH HER2-positive N=1,500 N=4,950 N=3,600 • ARM A: Cisplatin plus vinorelbine, docetaxel, gemcitabine or pemetrexed • ARM B: Cisplatin plus vinorelbine, docetaxel, gemcitabine or pemetrexed plus Avastin up to 12 months • ARM A: Anthracycline plus cyclophosphamide (AC) followed by paclitaxel • ARM B: AC plus Avastin followed by paclitaxel plus Avastin • ARM C: AC plus Avastin followed by paclitaxel plus Avastin, followed by Avastin up to 12 months • COHORT 1: Docetaxel/ carboplatin plus Herceptin ± Avastin • COHORT 2: Docetaxel plus Herceptin ± Avastin, followed by 5Fluorouracil, Epirubicin, Cyclophosphamide • 15 mg/kg q3 weeks • 15 mg/kg q3 weeks • 15 mg/kg q3 weeks • Overall survival • Disease-free survival • Disease-free survival • FPI Q3 2007 • Recruitment ongoing • Expect data 2016 • FPI Q4 2007 • Enrolment completed Q2’11 • Expect data 2014 • FPI Q2 2008 • Enrolment completed Q4 2010 • Expect data 2013 # of patients Design Avastin dose Primary endpoint Status Adjuvant breast cancer For both cohorts, patients receive Herceptin ± Avastin to complete one year of targeted therapy 17 Herceptin Standard of care for HER2-positive early breast cancer Patient population Adjuvant HER2-positive breast cancer Early-stage HER2-positive breast cancer Phase/study Phase III HERA Phase III HANNAH Subcutaneous study # of patients N=5,102 N=595 Design • ARM A: Herceptin for 12 months • ARM B: Herceptin for 24 months • ARM C: Observation • ARM A: Chemotherapy* concurrent with Herceptin 600mg sc q3w for the first 8 cycles • ARM B: Chemotherapy* concurrent with Herceptin IV for the first 8 cycles *Chemotherapy = docetaxel then 5-FU, epirubicin, and cyclophosphamide Primary endpoint • Disease-free survival • Serum concentration • Pathologic complete response Status • Final analysis presented at ESMO 2012 • No additional benefit seen in 2 year arm vs. 1 year • 1 year treatment duration confirmed as standard of care • Positive top-line data reported in October 2011 • Data presented at EBCC 2012 • Filed in EU Q1 2012 Subcutaneous Herceptin : applies Enhanze technology, partnered with Halozyme 18 Perjeta First in a new class of HER dimerization inhibitors Patient population Phase/ study # of patients Adjuvant HER2-positive breast cancer First-line HER2-positive metastatic breast cancer Second-line HER2-positive metastatic breast cancer Advanced HER2-positive gastric cancer Phase III APHINITY Phase III CLEOPATRA Phase II PHEREXA Phase IIa JOSHUA N=3,806 N=808 N=450 N=30 Design • ARM A: Pertuzumab (840mg loading, 420 q3w) plus Herceptin for 52 weeks plus chemotherapy (6-8 cycles) • ARM B: Placebo plus Herceptin (52 weeks) plus chemotherapy (6-8 cycles) • ARM A: Pertuzumab (840mg loading, 420mg q3w) plus Herceptin and docetaxel • ARM B: Placebo plus Herceptin and docetaxel • ARM A: Herceptin plus Xeloda • ARM B: Pertuzumab plus Herceptin and Xeloda • ARM A: Pertuzumab (840mg loading, 420mg q3w) plus Herceptin and chemotherapy • ARM B: Placebo plus Herceptin and chemotherapy Primary endpoint • 3-year disease-free survival • Progression-free survival • Progression-free survival • Safety, efficacy Status • FPI Q4 2011 • Met primary endpoint July 2011 • Data presented at SABCS 2011 • Submitted for FDA and EMA approval Q4 2011 • FDA granted approval Q2 2012 • FPI Q1 2010 • FPI Q4 2011 SABCS = San Antonio Breast Cancer Symposium. 19 Tarceva New approaches to treating lung cancer Adjuvant non-small cell lung cancer First-line metastatic non-small cell lung cancer EGFR mutation-positive Phase/study Phase III RADIANT Phase III EURTAC # of patients N=974 (2:1 randomisation) N=174 Patient population Design • Following surgical resection ± adjuvant chemotherapy: • ARM A: Tarceva up to 2 years • ARM B: Placebo up to 2 years • ARM A: Tarceva • ARM B: Chemotherapy (platinum-based doublet) Primary endpoint • Disease-free survival • EGFR IHC and/or FISH-positive • Progression-free survival Status • Enrolment completed Q3 2010 • Expect final results H1 2013 • • • • Study met its primary endpoint Q1 2011 Data presented at ASCO 2011 EU granted approval in Q3 2011 Expect FDA sNDA submission in 2012 Tarceva is a registered trademark of OSI Pharmaceuticals, LLC, an affiliate of Astellas Pharma US, Inc. 20 Zelboraf A selective novel small molecule that inhibits mutant BRAF Adjuvant therapy in patients with resected cutaneous BRAF mutation positive melanoma Previously treated papillary thyroid cancer BRAF mutation positive Metastatic melanoma BRAF mutation positive Phase/study Phase III BRIM8 Phase II Phase Ib # of patients N=725 N=50 N=20 Patient population Design • 52-week treatment • ARM A:Zelboraf 960mg bid • ARM B: placebo • Single ARM: Zelboraf • Single ARM: Zelboraf plus ipilimumab• Primary endpoint • Disease-free survival • Best overall response rate • Safety Status • FPI Q3 2012 • FPI Q2 2011 • FPI Q4 2011 In collaboration with Plexxikon, a member of Daiichi Sankyo Group •Combination study with ipilimumab is in collaboration with Bristol-Myers Squibb. See also combinations with: MEK inhibitor (RG7421) and anti-PD-L1 (RG7446) 21 Zelboraf A selective novel small molecule that inhibits mutant BRAF Patient population Melanoma patients with brain metastases BRAF mutation positive Phase/study Phase II Phase I # of patients N=132 N=20 Design • Single ARM: Zelboraf • Single ARM: Zelboraf Primary endpoint • Overall Response Rate in the brain • Safety Status • FPI Q3 2011 • FPI Q4 2010 • Recruitment completed • Data presented at ESMO 2012 In collaboration with Plexxikon, a member of Daiichi Sankyo Group 22 Erivedge (Vismodegib) A novel small molecule inhibitor of the hedgehog signaling pathway Patient population Advanced basal cell carcinoma Operable basal cell carcinoma Phase/study Pivotal Phase II ERIVANCE Phase II # of patients N=104 N=74 Design • Single ARM: 150 mg GDC-0449 orally once daily until disease progression • Single ARM: 150 mg GDC-0449 orally once daily Primary endpoint • Overall response rate • COHORT 1: Complete clearance (12 weeks Erivedge) • COHORT 2: Durable complete clearance (12 weeks Erivedge) • COHORT 3: Complete clearance (16 weeks Erivedge) Status • Positive results announced Q1 2011 • Data presented at EADO June 2011, ECCO/ESMO Sep 2011, EADV Oct 2011 • EMA submission accepted Q4 2011 • FDA granted approval Q1 2012 • Data published NEJM June 2012 • FPI Q4 2010 • Cohort 1 data presented at Society for Investigative Dermatology (May 2012) In collaboration with Curis 23 Actemra/RoActemra Interleukin 6 receptor inhibitor Early moderate-to-severe rheumatoid arthritis Rheumatoid arthritis DMARD inadequate responders Moderate-to-severe rheumatoid arthritis Moderate-to-severe rheumatoid arthritis Phase/study Phase III FUNCTION Phase III ADACTA Head-to-head study Phase III SUMMACTA Subcutaneous study Phase III BREVACTA Subcutaneous study # of patients N=1,162 N=326 N=1,200 N=600 Patient population Design 104 week treatment 24 week treatment • ARM A: Actemra IV 8 mg/kg • ARM A: Actemra IV 8mg/kg q4w plus pbo MTX q4w plus pbo Adalimumab • ARM B: Actemra IV 8 mg/kg • ARM B: Adalimumab 40mg q4w plus MTX sc q2w plus pbo Actemra • ARM C: Actemra IV 4 mg/kg q4w plus MTX • ARM D: MTX alone • Add-on to DMARD therapy • Weekly dosing for 104 weeks • ARM A: Actemra sc 162mg weekly plus placebo IV q4w • ARM B: Actemra IV 8mg/kg q4w plus placebo sc weekly • Add-on to DMARD therapy • Dosing every two weeks for 104 weeks • ARM A: Actemra sc 162mg q2w • ARM B: Placebo sc q2w Primary endpoint • DAS28 remission at 24 weeks, 1 year and 2 years • DAS28 at 24 weeks • ACR 20 at week 24 • ACR 20 at week 24 Status • FPI Q4 2009 • Primary endpoint met Q3 2012 • Filing expected 2013 • Trial met primary endpoint • Q1 2012 • Data presented at EULAR 2012 • Submitted for EMA approval Q3 2012 • Primary endpoint met Q3 • Trial met primary endpoint 2012 Q2 2012 • Filing expected in 2012 • Filing expected in 2012 • Data to be presented at ACR • Data to be presented at ACR 2012 2012 In collaboration with Chugai MTX = Methotrexate; DMARD = Disease-Modifying Anti-Rheumatic Drugs. 24 Actemra/RoActemra Interleukin 6 receptor inhibitor Patient population Systemic sclerosis Polyarticular-course juvenile idiopathic arthritis Phase/study Phase II faSScinate Proof-of-concept study Phase III CHERISH # of patients N=86 N=188 Design Blinded 48-week treatment with weekly dosing: •ARM A: Actemra sc 162mg •ARM B: Placebo sc Open-label weekly dosing at weeks 49 to 96: •Actemra sc 162mg • Part I: All patients receive Actemra 8mg/kg or 10mg/kg (IV) q4w for 16 weeks • Part II: Patients with adequate response from Part I will be randomized to receive: ŸARM A: Actemra 8mg/kg or 10mg/kg (IV) q4w for up to 24 weeks + SOC* ŸARM B: Placebo + SOC* • Part III: All patients receive Actemra 8mg/kg or 10mg/kg (IV) q4w for up to another 64 weeks Primary endpoint • Change in modified Rodnan skin score (mRSS) at week 24 • Safety • Proportion of patients with a JIA ACR30 flare by week 40 relative to week 16 Status • FPI Q1 2012 • Expect data 2013 • Study met primary endpoint in Q1 2012 • Submitted to FDA and EMA Q2 2012 In collaboration with Chugai *Standard of care: non-steroidal anti-inflammatory drugs, corticosteroids, MTX 25 Xolair Evaluating potential in Chronic Idiopathic Urticaria, an IgE related disease Patient population Phase/study # of patients Chronic Idiopathic Urticaria Patients who remain symptomatic despite treatment* Phase III ASTERIA I Phase III ASTERIA II Phase III GLACIAL N=300 N=300 N=320 Design Add-on therapy to H1 antihistamines 24 week treatment period (q4week) • ARM A: Xolair 300 mg • ARM B: Xolair 150 mg • ARM C: Xolair 75 mg • ARM D: Placebo Add-on therapy to H1 antihistamines 12 week treatment period (q4week) •ARM A: Xolair 300 mg •ARM B: Xolair 150 mg •ARM C: Xolair 75 mg •ARM D: Placebo Add-on therapy to H1 antihistamines, H2 blockers, and/or LTRA 24 week treatment period (q4week) •ARM A: Xolair 300 mg •ARM B: Placebo Primary endpoint • Change from baseline in UAS7 weekly itch score at Week 12 • Change from baseline in UAS7 weekly itch score at Week 12 • Safety Status • Enrollment completed Q1 2012 • Data expected Q4 2012 • Enrollment completed Q4 2011 • Data in-house, under review • Expect data presentation H1 2013 • Enrollment completed Q1 2012 • Data expected Q1 2013 In collaboration with Novartis *Refractory to H1 anti-histamines, H2 blockers, and/or leukotriene receptor antagonists (LTRAs) at the time of randomisation. 26 Lucentis Development programme for wAMD Patient population Neovascular (wet) age-related macular degeneration Phase/study Phase III HARBOR High dose study # of patients N=1,110 Design • Randomised double-masked study comparing efficacy and safety of intravitreal injections of 0.5 mg and 2.0 mg Lucentis administered monthly or PRN in patients with wet AMD Primary endpoint • Mean change in best corrected visual acuity (BCVA) compared to baseline at 12 months Status • 12 month data was presented at AAO meeting October 2011 • 0.5mg PRN sBLA filed with FDA in April 2012 • 24 months data will be presented at AAO meeting Nov. 2012 Genentech retains commercial rights in the United States and Novartis has exclusive commercial rights for the rest of the world. ADA – American Diabetes Association, AAO = American Academy of Opthalmology 27 Roche Group development pipeline Marketed products development programmes Roche Pharma global development programmes Roche Pharma research and early development Genentech research and early development Roche Group YTD Sept 2012 sales Diagnostics Foreign exchange rate information 28 Trastuzumab emtansine (T-DM1, RG3502) Evaluating new treatment options in HER2-positive breast cancer Patients who have progressed on HER2 targeted treatment Pretreated HER2 pos. metastatic breast cancer1 Previously untreated HER2 pos. metastatic breast cancer Phase/ study Phase III TH3RESA Phase III EMILIA Phase III MARIANNE # of patients N=795 N=991 N=1,092 Patient population Design • ARM A: T-DM1 3.6mg/kg q3w • ARM B: physician’s choice • ARM A: T-DM1 3.6mg/kg • ARM A: Herceptin plus q3w taxane • ARM B: Xeloda plus lapatinib • ARM B: T-DM1 3.6mg/kg q3w plus pertuzumab • ARM C: T-DM1 3.6 mg/kg q3w plus placebo Primary endpoint • ORR and Overall survival Co-primary endpoints: • Progression-free survival (PFS) • Overall survival Status • FPI Q3 2011 • PFS data presented at ASCO • FPI Q3 2010 2012 • Recruitment completed Q2 • OS endpoint met Q3 2012 2012 • Data presented at ESMO 2012 • Submitted for FDA and EMA approval Q3 2012 • Progression-free survival assessed by IRF In collaboration with ImmunoGen, Inc. ASCO = American Society of Clinical Oncology 1 Patients must have received prior treatment which included both: a taxane, alone or in combination with another agent, and trastuzumab in the adjuvant, locally advanced, or metastatic setting. 29 Trastuzumab emtansine (T-DM1, RG3502) Evaluating new treatment options in HER2+ breast and gastric cancers Patient population Neoadjuvant/ Adjuvant breast cancer HER2-positive advanced gastric cancer Phase/ study Phase II Cardiac safety study Phase II/III # of patients N=135 N=412 Design • Single ARM: T-DM1 3.6mg/kg q3w administered immediately following completion of anthracycline chemotherapy • ARM A: T-DM1 3.6mg/kg q3w • ARM B: T-DM1 2.4mg/kg q3w • ARM C: docetaxel or paclitaxel Primary endpoint • Cardiac event rate • Safety • Phase II: Dose-finding • Phase III: Overall survival Status • Completed enrollment Q2 2011 • Interim data presented at ASCO 2012 • FPI Q3 2012 In collaboration with ImmunoGen, Inc. ASCO = American Society of Clinical Oncology 30 Onartuzumab (MetMAb, RG3638) Anti-Met monovalent antibody that inhibits HGF-mediated activation Patient population 2nd- and 3rd-line Met-positive metastatic NSCLC 1st line non-squamous NSCLC 1st line squamous NSCLC Phase III MetLung Phase II Phase II N=480 N=260 N=110 Cohort 1 •Arm A: Onartuzumab + Avastin + paclitaxel + platinum-based chemo (cisplatin or carboplatin) •Arm B: Placebo + Avastin + paclitaxel + platinum-based chemo (cisplatin or carboplatin) Cohort 2 •Arm A: Onartuzumab + pemetrexed + platinum-based chemo (cisplatin or carboplatin) Arm B: Placebo + pemetrexed + platinum-based chemo (cisplatin or carboplatin) • Arm A: Onartuzumab + paclitaxel + platinum-based chemo (cisplatin or carboplatin) Phase # of patients Design • ARM A: Tarceva plus onartuzumab • ARM B: Tarceva plus placebo • Arm B: Placebo + paclitaxel + platinum-based chemo (cisplatin or carboplatin) Primary endpoint • Overall survival • Progression-Free Survival in the ITT population • Progression-Free Survival in Metpositive population • Progression-Free Survival in the ITT population • Progression-Free Survival in Metpositive population Status • FPI Q1 2012 • FPI Q2 2012 • FPI Q2 2012 31 Onartuzumab (MetMAb, RG3638) Anti-Met monovalent antibody that inhibits HGF-mediated activation Patient population Phase # of patients Metastatic HER2-negative Gastro esophageal Cancer 1st and 2nd-line triple negative metastatic breast cancer 1st-line metastatic colorectal cancer Avastin-naïve recurrent glioblastoma Phase II Phase II Phase II Phase II N=120 N=180 N=188 N=120 Design • ARM A: Onartuzumab plus • ARM A: Avastin and mFOLFOX paclitaxel plus • ARM B: Placebo plus onartuzumab mFOLFOX • ARM B: Avastin and paclitaxel plus placebo • ARM C: Paclitaxel plus onartuzumab • ARM A: FOLFOX plus Avastin plus onartuzumab • ARM B: FOLFOX plus Avastin plus placebo Primary endpoint • Progression–free survival in • Progression–free survival ITT • Progression-free survival in pre-specified Met-positive patients • Progression–free survival in • Progression-Free Survival ITT in the ITT population • Progression-free survival in • Progression-Free Survival pre-specified Met-positive in Met-positive population patients Status • FPI Q3 2012 • FPI Q3 2011 • FPI Q1 2011 • Enrollment completed July 2012 • Expect data H2 2013 • Arm A: Onartuzumab + Avastin • Arm B: Placebo + Avastin • Arm C: Onartuzumab +Placebo • FPI Q3 2012 32 MEK inhibitor (RG7421, GDC-0973) Selective small molecule inhibitor of mitogenactivated protein kinase Patient population Phase # of patients Previously untreated metastatic melanoma BRAF mutation positive Metastatic melanoma BRAF mutation positive Solid tumors Solid tumors Solid tumors Phase III Phase Ib BRIM7 Phase I Phase Ib Phase Ib N=500 N=~50 N=90 N=212 N=108 Design • ARME A: Zelboraf* plus RG7421 • ARM B: Zelboraf* plus placebo • Dose escalation study evaluating Zelboraf* plus RG7421 • Dose escalation study • Dose escalation • Dose escalation study evaluating study of GDC-0973 in GDC-0973 plus GDCcombination with 0941 (PI3 Kinase GDC-0068 Inhibitor) Primary endpoint • Progression-free survival • Safety/PK • Safety/PK • Safety/PK • Safety/PK Status • Expect FPI Q4 2012 • FPI Q1 2011 • Data presented at ESMO 2012 • FPI Q2 2007 • Data presented at AACR 2011 • Recruitment completed Q3 2011 • FPI Q4 2009 • Updated data presented at AACR and ASCO 2012 • FPI Q2 2012 In collaboration with Exelixis *Zelboraf In collaboration with Plexxikon, a member of Daiichi Sankyo Group 33 Obinutuzumab (GA101, RG7159) Type II, glycoengineered anti-CD20 monoclonal antibody • Phase III clinical trials Front-line chronic lymphocytic leukaemia Patients with comorbidities Indolent non-Hodgkin’s lymphoma MabThera/Rituxan refractory Front-line indolent non-Hodgkin’s lymphoma Diffuse large B-cell lymphoma (DLBCL) Phase/study Phase III CLL11 Phase III GADOLIN Phase III GALLIUM Phase III GOYA # of patients N=780 N=360 N=1,400 N=1,400 Design • ARM A: GA101 1000mg IV plus chlorambucil • ARM B: MabThera/Rituxan plus chlorambucil • ARM C: Chlorambucil alone • ARM A: GA101 1000mg IV plus Bendamustine • ARM B: Bendamustine • ARM A: GA101 1000mg • ARM A: GA101 1000mg IV plus chemotherapy IV plus CHOP followed by GA101 • ARM B: maintenance MabThera/Rituxan plus • ARM B: CHOP MabThera/Rituxan plus chemotherpy followed by MabThera/Rituxan maintenance Primary endpoint • Progression-free survival • Progression-free survival • Progression-free survival • Progression-free survival Status • FPI Q4 2009 • Recruitment completed Q2 2012 • Expect data 2013 • FPI Q2 2010 • Expect data 2015 • FPI Q3 2011 • Expect data 2017 • FPI Q3 2011 • Expect data 2015 Patient population In collaboration with Biogen Idec CHOP = Cyclophosphamide, Doxorubicin, Vincristine and Prednisone 34 Obinutuzumab (GA101, RG7159) Type II, glycoengineered anti-CD20 monoclonal antibody • Phase I/II clinical trials Front-line or relapsed indolent non-Hodgkin’s lymphoma (NHL) Relapsed indolent non-Hodgkin’s lymphoma Relapsed or refractory non-Hodgkin’s lymphoma or chronic lymphocytic leukaemia (CLL) Phase/study Phase Ib GAUDI Phase I/II GAUSS Phase I/II GAUGUIN # of patients N=136 N=202 N=133 Patient population Design • Cohort A: GA101 plus fludarabine + cyclophosphamide • Cohort B: GA101 plus CHOP • Cohort C: GA101 plus bendamustine Phase I portion (extended treatment for 2 years): • Single agent: GA101 Primary endpoint • Safety • Overall response rate • Phase I: Incidence of dose-limiting toxicity • Phase II: Overall best response rate Status • FPI Q1 2009 • Data presented at ASH 2011 Phase I portion: • Initiated Q1 2008 • Data presented at ASH 2009 Phase II portion: • FPI Q3 2009 • Enrolment completed Q3 2010 • Data presented at ASH 2011 Phase I portion: • Initiated Q3 2007 • Updated Phase I NHL and CLL data presented at ASH 2009 Phase II portion: • All cohorts completed enrolment by Q4 2009 • Data presented at ICML/EHA 2011 Phase II portion (extended treatment for 2 years): • ARM A: MabThera/Rituxan • ARM B: GA101 In collaboration with Biogen Idec CHOP = Cyclophosphamide, Doxorubicin, Vincristine and Prednisone; ASH = American Society of Hematology; EHA = European Hematology Association. Phase I portion: • Single agent: GA101 Phase II portion: • Single agent: GA101 35 Lebrikizumab (RG3637) A humanized monoclonal antibody designed to bind specifically to IL-13 • Phase III clinical trials Severe uncontrolled adult asthma Patient population Adult patients whose asthma is uncontrolled with inhaled corticosteroids and a second controller medication Adult patients whose asthma is uncontrolled with inhaled corticosteroids and a second controller medication Phase/stud y Phase III LUTE * Phase III VERSE* # of patients N=1,400 N=1,400 Design Subcutaneous lebrikizumab q4w on top of SOC for 52 weeks followed by 52 week extension on lebrikizumab for a total of 104 weeks, with a 24 week safety followup •ARM A: Lebrikizumab highest dose •ARM B: Lebrikizumab middle dose •ARM C: Lebrikizumab lowest dose •ARM D: Placebo Patients will be tested for periostin level Subcutaneous lebrikizumab q4w on top of SOC for 52 weeks followed by 52 week extension on lebrikizumab for a total of 104 weeks, with a 24 week safety followup •ARM A: Lebrikizumab highest dose •ARM B: Lebrikizumab middle dose •ARM C: Lebrikizumab lowest dose •ARM D: Placebo Patients will be tested for periostin level Primary endpoint • Rate of asthma exacerbations during the 52-week placebo-controlled period • Rate of asthma exacerbations during the 52-week placebo-controlled period Status • FPI Q1 2012 • FPI Q1 2012 *Programs currently under internal review - modifications pending 36 Rontalizumab (RG7415) A humanized monoclonal antibody to interferon alpha Patient population Systemic lupus erythematosus Phase/study Phase II ROSE # of patients N=238 Design • ARM A: Placebo • Part 1 – IV • Part 2 - Subcutaneous • ARM B: Rontalizumab • Part 1 – IV • Part 2 – Subcutaneous Primary endpoint • Proportion of responders at Week 24 Status • Enrolment completed Q3 2010 • Data to be presented at ACR 2012 37 Aleglitazar (RG1439) A balanced PPAR co-agonist - potential to reduce cardiovascular events in type 2 diabetes patients Type 2 diabetes Patients with moderate and mild renal impairment ACS patients with Type 2 diabetes Phase/study Phase II AleNEPHRO Renal function study Phase III AleCARDIO Cardiovascular outcomes study # of patients N=300 N=7,229 Patient population Design • 52 week treatment duration: • ARM A: Aleglitazar (150 µg) • ARM B: Pioglitazone (45 mg) • At least 2.5 years treatment period and until 950 events have occurred • ARM A: Aleglitazar (150 µg) on top of SOC • ARM B: Placebo on top of SOC Primary endpoint • Relative change from baseline in glomerular filtration rate at 60 weeks • Reduction in cardiovascular mortality, nonfatal myocardial infarction and stroke (MACE) Status • Enrollment completed Q2 2011 • Primary endpoint met Q3 2012 • Data to be presented at ASN 2012 • FPI Q1 2010 • Enrollment completed Q2 2012 ACS = Acute Coronary Syndrome; SOC = standard of care. ASN = American Society of Nephrology 38 Aleglitazar (RG1439) A balanced PPAR co-agonist - potential to reduce cardiovascular events in type 2 diabetes patients Patient population Type 2 diabetes (US,China) Stable CVD and type 2 diabetes or prediabetes Phase/study Phase III AleGlucose Glycemic control study Phase III AlePrevent Cardiovascular outcomes study # of patients N=1,400 N=19,000 Design 26 weeks treatment duration •ARM A: Aleglitazar (150 µg) monotherapy, add on to Metformin and Add on to Sulfonylurea with or without Metformin •ARM B: Placebo At least 3 year treatment period and until 1260 events have occurred •ARM A: Aleglitazar 150 µg daily on top of SOC •ARM B: Placebo daily on top of SOC Primary endpoint • Reduction from baseline in HbA1c • Reduction in cardiovascular mortality, nonfatal myocardial infarction and stroke (MACE) Status • Expect FPI Q4 2012 • Expect FPI Q4 2012 ACS = Acute Coronary Syndrome; SOC = standard of care. 39 Bitopertin (GlyT-1, RG1678) A small molecule first-in-class glycin reuptake inhibitor (GRI) Patient population Acute exacerbation of schizophrenia Phase/stud y Phase II CandleLyte Phase III NIGHTLYTE Phase III MOONLYTE Phase III TWILYTE N=300 N=600 N=600 N=600 Design • 4-week treatment period •ARM A: RG1678 daily (10 mg) •ARM B: RG1678 daily (30 mg) •ARM C: Olanzapine •ARM D: Placebo • Add-on therapy to antipsychotics • 52-week treatment period •ARM A: RG1678 daily (10 mg) •ARM B: RG1678 daily (20 mg) •ARM C: Placebo • Add-on therapy to antipsychotics • 52-week treatment period •ARM A: RG1678 daily (10 mg) •ARM B: RG1678 daily (20 mg) •ARM C: Placebo • Add-on therapy to antipsychotics • 52-week treatment period •ARM A: RG1678 daily (5 mg) •ARM B: RG1678 daily (10 mg) •ARM C: Placebo Primary endpoint • PANSS total symptom factor at week 4 • PANSS positive symptom factor at week 12 • PANSS positive symptom factor at week 12 • PANSS positive symptom factor at week 12 Status • FPI Q1 2011 • FPI Q4 2010 • FPI Q4 2010 • FPI Q4 2010 # of patients PANSS = Positive and Negative Syndrome Scale Sub-optimally controlled symptoms of schizophrenia 40 Bitopertin (GlyT-1, RG1678) A small molecule first-in-class glycin reuptake inhibitor (GRI) Patient population Persistent, predominant negative symptoms of schizophrenia Phase/study Phase III SUNLYTE Phase III DAYLYTE Phase III FLASHLYTE # of patients N=630 N=630 N=630 Design • Add-on therapy to antipsychotics • 52-week treatment period •ARM A: RG1678 (10 mg) •ARM B: RG1678 (20 mg) •ARM C: Placebo • Add-on therapy to antipsychotics • 52-week treatment period •ARM A: RG1678 (5 mg) •ARM B: RG1678 (10 mg) •ARM C: Placebo • Add-on therapy to antipsychotics • 52-week treatment period •ARM A: RG1678 (10 mg) •ARM B: RG1678 (20 mg) •ARM C: Placebo Primary endpoint • PANSS negative symptom factor at week 24 • PANSS negative symptom factor at week 24 • PANSS negative symptom factor at week 24 Status • FPI Q4 2010 • FPI Q4 2010 • FPI Q4 2010 PANSS = Positive and Negative Syndrome Scale 41 Ocrelizumab (RG1594) 2nd generation anti-CD20 monoclonal antibody Patient population Relapsing multiple sclerosis (RMS) Primary progressive multiple sclerosis (PPMS) Phase/study Phase III OPERA I Phase III OPERA II Phase III ORATORIO # of patients N=800 N=800 N=630 Design • 96-week treatment period: • ARM A: Ocrelizumab 2x 300 mg IV followed by 600 mg IV every 24 weeks • ARM B: Interferon b-1a • 96-week treatment period: • ARM A: Ocrelizumab 2x 300 mg IV followed by 600 mg IV every 24 weeks • ARM B: Interferon b-1a • 120-week treatment period: • ARM A: Ocrelizumab 2x 300 mg IV every 24 weeks • ARM B: Placebo Primary endpoint • Annualized relapse rate at 96 weeks versus Rebif • Annualized relapse rate at 96 weeks versus Rebif • Sustained disability progression versus placebo by Expanded Disability Status Scale (EDSS) Status • FPI Q3 2011 • FPI Q3 2011 • FPI Q1 2011 42 Mericitabine (RG7128) Nucleoside NS5B polymerase inhibitor Patient population Phase/study Treatment-naive and failure chronic hepatitis C Genotype 1 and 4 Phase IIb DYNAMO 1* Phase IIb DYNAMO 2 Longer duration study N=100 # of patients Design Treatment-naive and failure chronic hepatitis C Genotype 1 and 4 • • • ARM A: Boceprevir + mericitabine (1000 mg BID) + Pegasys and Copegus for 24 weeks ARM B: Boceprevir + mericitabine (1000 mg BID) + Pegasys and Copegus for 24 weeks followed by boceprevir+Pegasys and Copegus for 24 weeks ARM C : Boceprevir+Pegasys and Copegus for 48 weeks N= 168 • • • • Primary endpoint Status ARM A: Telaprevir + mericitabine (1000 mg BID) + Pegasys and Copegus for 12 weeks, followed by + mericitabine (1000 mg BID) + Pegasys and Copegus for 12 weeks ARM B: Telaprevir + mericitabine (1000 mg BID) + Pegasys and Copegus for 12 weeks, followed by + mericitabine (1000 mg BID) + Pegasys and Copegus for 12 weeks, followed by Pegasys and Copegus for 24 weeks ARM C : Telaprevir + mericitabine (1000 mg BID) + Pegasys and Copegus for 12 weeks, followed by Pegasys and Copegus for 36 weeks ARM D: Telaprevir + Pegasys and Copegus for 12 weeks, followed by Pegasys and Copegus for 36 weeks • Sustained virological response (SVR) • Sustained virological response (SVR) • FPI Q4 2011 • Recruitment completed Q3 2012 • FPI Q4 2011 • Recruitment completed Q3 2012 RG7128 licensed from Pharmasset, now part of Gilead * In collaboration with Merck 43 Mericitabine (RG7128) Nucleoside NS5B polymerase inhibitor Hepatitis C patients Treatment-naïve or null-responders to interferon-based treatment Patient population Phase/study Phase II ANNAPURNA # of patients N=180 Design • • • • • ARM A: GT1a including setrobuvir, danoprevir, ritonavir, ribavirin and mericitabine ARM B: GT1a including setrobuvir, danoprevir, ritonavir, ribavirin and mericitabine ARM C: GT1a including setrobuvir, danoprevir, ritonavir and ribavirin ARM D: GT1b including setrobuvir, danoprevir, ritonavir, ribavirin and mericitabine ARM E: GT1b including setrobuvir, danoprevir, ritonavir and ribavirin Primary endpoint • Sustained virological response at week 12 after the end of the study treatment Status • FPI Q2 2012 Recruitment expected to complete in Q4 2012 RG7128 licensed from Pharmasset, now part of Gilead, Setrobuvir – Anadys Pharmaceuticals Inc. acquisiton 44 Danoprevir (RG7227) HCV protease inhibitor Patient population Phase Treatment-experienced chronic hepatitis C patients* Phase IIb Matterhorn Boosted Danoprevir in Triple, Quad and Interferon-free combinations # of patients N=381 Design Danoprevir boosted by low dose ritonavir in IFN-free, triple and QUAD Cohort A: partial responders: •ARM A1: Danoprevir 100 mg bid+ Ritonavir 100mg bid+ mericitabine 1000 mg bid + Copegus for 24 weeks •ARM A2: Danoprevir 100 mg bid + Ritonavir 100mg bid+ Pegasys + Copegus for 24 weeks •ARM A3: Danoprevir 100 mg bid + Ritonavir 100mg bid + mericitabine 1000 mg bid + Pegasys + Copegus for 24 weeks Cohort B: null responders: •ARM B1: Danoprevir 100 mg bid + Ritonavir 100mg bid + mericitabine 1000 mg bid + Copegus for 24 weeks •ARM B2: Danoprevir 100 mg bid + Ritonavir 100mg bid+ mericitabine 1000 mg bid + Pegasys + Copegus for 24 weeks •ARM B3: Danoprevir 100 mg bid+ Ritonavir 100mg bid + mericitabine 1000 mg bid + Pegasys + Copegus for 24 weeks, followed by 24 weeks Pegasys + Copegus Primary endpoint • Sustained virological response 24 weeks after the end of study treatment Status • Recruitment completed Q3 2011 • Preliminary data submitted to AASLD 2012 RG7128 licensed from Pharmasset, now part of Gilead 45 Roche Group development pipeline Marketed products development programmes Roche Pharma global development programmes Roche Pharma research and early development Genentech research and early development Roche Group YTD Sept 2012 sales Diagnostics Foreign exchange rate information 46 Oncology development programmes Small molecules Apoptosis MAPK signaling MDM2 antagonist (RG7112) Molecule MDM2 (4) antagonist (RG7388) MEK inhibitor (CIF, RG7167) Raf/MEK inhibitor (CKI27, RG7304) Advanced solid tumors Hematologic neoplasms (Leukaemia) Solid and hematological tumors Solid tumors Solid tumors Phase Phase I Phase I Phase I Phase I Phase I # of patients N=105 N=90 N=100 N=144 N=52 Patient population Design • Status • Study completed Q2 2011 • Phase Ib initiated Q2 2012 Collaborator Multiple ascending doseescalation study • Multiple ascending doseescalation study • Study completed Q3 2012 • Phase Ib initiated Q3 2012 • Multiple ascending doseescalation study • FPI Q4 2011 • Dose-escalation, followed by expansion into 4 cohorts in specific indications • Initiated Q2 2008 • Phase I study completed recruitment into expansion cohorts end of 2011 • Dose-escalation to MTD • Initiated October Q4 2008 • Phase I study Stopped enrolment in Q4 2010 Chugai 47 Oncology development programmes Monoclonal antibodies Anti-glypican-3 MAb (GC33, RG7686) Molecule Patient population Anti-CD44 MAb (RG7356) Metastatic liver cancer (hepatocellular carcinoma) 2L metastatic liver cancer (hepatocellular carcinoma) Solid tumors Acute myelogenous leukemia Phase Phase Ib Phase II Phase I Phase I # of patients N= 40-50 N=171 N=50-70 N=86 Design • Study US Monotherapy • Study Japan Monotherapy • Combo with SOC dose escalation study Adaptive design study Double blind randomized 2:1 RG7686:placebo Primary endpoint • Safety and tolerability Status • FPI Q4 2008 • Dose Escalation completed for US and Japan monotherapy studies. CSRs drafting is ongoing Collaborator SOC – standard of care • Multiple ascending dose study with extension and imaging arm • Multiple ascending dose study +/- cytarabine • Progression-free survival • Safety (MTD), PK, PD, preliminary clinical activity • Safety (MTD), PK, PD, preliminary clinical activity • FPI Q1 2012 • FPI Q2 2011 • FPI Q3 2012 Patients are stratified according to the level of GPC3 expression in tumor Chugai 48 Oncology development programmes Monoclonal antibodies (continued) Anti-TWEAK MAb (RG7212) GE-huMAb HER3 (RG7116) CSF-1R huMAb (RG7155) Solid tumors Solid tumors Solid tumors Phase I Phase I Phase I N=50 N=105 N-95 Design • Multiple ascending dose study • Multiple ascending dose study with extension cohorts and imaging sub-study • Combination arms with HER1targeted therapies (erlotinib, cetuximab) • •Multiple ascending dose study +/- paclitaxel with extension cohorts Primary endpoint • Safety, PK, PD • Safety, PK • Safety, PK, PD & preliminary clinical activity Status • FPI Q3 2011 • FPI Q4 2011 • FPI Q4 2011 Molecule Patient population Phase # of patients 49 GA201 (RG7160) Glycoengineered enhanced ADCC/anti-EGFR monoclonal antibody Patient population Phase # of patients Design Head and neck squamous cell carcinoma 1st-line metastatic non-small cell lung cancer 2nd-line metastatic colorectal cancer Phase I Mechanism of action study Phase Ib/II Phase II N=45 N=160 N=160 • ARM A: GA201 • ARM B: Cetuximab Treated until disease progression: Squamous §ARM A: GA201 plus cisplatin and gemcitabine §ARM B: Cisplatin and gemcitabine Non-Squamous §ARM A: GA201 plus cisplatin and pemetrexed §ARM B: Cisplatin and pemetrexed Treated until disease progression: KRAS Wild Type §ARM A: GA201 plus FOLFIRI §ARM B: Cetuximab plus FOLFIRI KRAS Mutant §ARM A: GA201 plus FOLFIRI §ARM B: FOLFIRI alone Primary endpoint • Pharmacodynamics • Part 1 – Safety • Part 2 – PFS • PFS Status • Recruitment completed Q1 2012 • Data presented at ASCO 2012 • Non-Squamous Part 2 accrual • complete 1Q 2012. • • Data from Part 1 Non-Sq. presented at • ASCO 2012 • • Squamous Part 1 halted and to be investigated with new study FPI Q2 2011 Recruitment completed Q3 2012 Design presented at ASCO 2012 Expect data in 2013 50 Metabolic development programmes Inclacumab (P-selectin huMAb, RG1512) Molecule GLP-1/GIP dual agonist (MAR709, RG7697) Prevention of saphenous vein graft disease Patients undergoing coronary artery bypass graft (CABG) surgery Acute Coronary Syndrome (ACS) Patients undergoing Percutaneous Coronary Intervention (PCI) Type 2 diabetes Phase/study Phase II Phase II Phase I # of patients N=384 N=516 N=48 Patient population Design 32-week treatment period •ARM A: RG1512 (20 mg/kg) •ARM B: Placebo Single infusion •ARM A: RG1512 (5 mg/kg) •ARM B: RG1512 (20 mg/kg) •ARM C: Placebo • single ascending dose (SAD) study • ARM A: RG7697 sc • AMR B: placebo Primary Endpoint •Sapheneous vein graft reocclusion •Procedural damage (troponin) • Safety, PK Status • FPI Q4 2010 • FPI Q2 2011 • FPI Q3 2012 Collaborator Genmab Marcadia Biotech, Inc. acquisition 51 Neuroscience development programmes Gantenerumab (Anti-Αβ, RG1450) BACE1 inhibitor (RG7129) Prodromal Alzheimer’s Disease Alzheimer’s Disease Phase/study Phase II/III SCarlet RoAD Phase I # of patients N=770 N=175 Molecule Patient population Design 104-week subcutaneous treatment period •ARM A: RG1450 (225 mg) •ARM B: RG1450 (105 mg) •ARM C: Placebo • Single ascending dose-escalation study • Multiple ascending dose-escalation study • CSF biomarker study Primary endpoint • Change in CDR-SOB at 2 years • Substudy: change in brain amyloid by PET at 2 years • Safety • Pharmacokinetics • Pharmacodynamics Status • FPI Q4 2010 • Ph I PET data published in Arch. Neur. Q4 2011 • SAD: completed • MAD: FPI Q3 2012 • CSF: FPI Q3 2012 Collaborator Morphosys CDR-SOB = Clinical Dementia Rating scale Sum of Boxes Siena Biotech 52 Neuroscience development programmes Monoamine oxidase type B (MAO-B) inhibitor (RG1577, EVT-302) Molecule Patient population Alzheimer’s Disease Phase # of patients Phase IIb MAyflOwer RoAD Phase I/II Phase I N=450 N=24 N=6 Design • • • • Primary endpoint • Changes in ADAS-Cog at 52 weeks • Brain enzyme occupancy • Metabolic profile • Route of elimination Status • Expect FPI Q4 2012 • FSI Q3 2012 • Clinical phase completed In collaboration with Evotec 52-week oral treatment ARM A: RG1577 (dose 1) ARM B: RG1577 (dose 2) ARM C: placebo • PET study in AD patients and • healthy volunteers Mass balance study 53 Neuroscience development programmes Metabotropic glutamate receptor pathway mGluR2 antagonist (RG1578) Molecule Patient population mGluR5 antagonist (RG7090) Adjunctive Treatment of Major Depressive Disorder Adjunctive Treatment of Major Depressive Disorder Fragile X Syndrome Phase/study Phase II Phase II Phase II # of patients N=480 N=300 N=180 Design • • • • Primary endpoint Status ARM A: RG1578 5 mg ARM B: RG1578 15 mg ARM C: RG1578 30 mg ARM D: Matching Placebo § ARM A: RG7090 0.5 mg § ARM B: RG7090 1.5 mg § ARM C: Matching Placebo § ARM A: RG7090 0.5 mg § ARM B: RG7090 1.5 mg § ARM C : Matching Placebo • Efficacy - Montgomery Asberg Depression Rating Scale • Efficacy - Montgomery Asberg Depression Rating Scale • Efficacy, Safety and Tolerability • Recruitment ongoing • Expect data H2 2013 • Recruitment ongoing • Expect data H2 2013 • Recruitment ongoing • Expect data H2 2013 54 Neuroscience development programmes GABRA5 negative allosteric modulator (NAM) (RG1662) Molecule Patient population Phase # of patients Down Syndrome Phase I Phase I Phase Ib N=6 N=17 N=33 Design • 28 day multiple dose study in healthy volunteers • Molecular and functional imaging study in individuals with DS and HV • Multi-center, Randomized, Double-blind, Placebocontrolled, Multiple Dose Study in Individuals With Down Syndrome Primary endpoint • PK over 28 days, excretion and metabolism • GABAAalpha5 receptor expression, occupancy and functional connectivity • Safety, tolerability Status • FPI Q3 2012 • FPI Q3 2012 • FPI Q4 2011 55 Neuroscience development programmes V1 receptor antagonist (RG7314) Molecule Patient population Autism Phase # of patients Phase I Phase I N=45 N=up to 24 Design • SAD/MAD umbrella protocol including food effect Primary endpoint • Safety, Tolerability • Safety, tolerability, PK and PD effects of multiple doses of RG7314 with a single dose of risperidone in healthy subjects Status • FPI Q3 2011 • Enrollment completed Q2 2012 • Expect FPI Q4 2012 • DDI study 56 Virology development programme Setrobuvir (RG7790) Molecule Patient population Chronic Hepatitis C Phase Phase II # of patients N= 283 Design • ARM A: Setrobuvir/placebo (200 mg bid) + Pegasys + Copegus for 28-48 weeks* in naïve patients • ARM B: Setrobuvir/placebo (200 mg bid) + Pegasys + Copegus for 48 weeks in treatment experienced patients (paritial responders & relapsers) • ARM C: Setrobuvir (200 mg bid) + Pegasys + Copegus for 48 weeks in treatment experienced patients (null responders) * Response guided treatment Primary endpoint • Sustained virological response 24 weeks after the end of study treatment Status • FPI Q1 2011 • Recruitment completed Q3 2011 Collaborator Anadys Pharmaceuticals Inc. acquisition Being investigated in Phase II in combination with Danoprevir and Mericitabine (see Mericitabine). 57 Roche Group development pipeline Marketed products development programmes Roche Pharma global development programmes Roche Pharma research and early development Genentech research and early development Roche Group YTD Sept 2012 sales Diagnostics Foreign exchange rate information 58 Oncology development programmes Angiogenic signaling Anti-EGFL7 MAb (RG7414) Molecule Patient population Advanced solid tumors First-line metastatic non-small cell lung cancer First-line metastatic colorectal cancer Phase Ib Phase II NILE Phase II CONGO N=~64 N=104 N=128 Phase # of patients Design • ARM A: Anti-EGFL7 plus • Anti-EGFL7 plus Avastin plus Avastin carbo/tax vs Avastin plus • ARM B: Anti-EGFL7 plus carbo/tax Avastin and paclitaxel • RCC expansion/Biopsy Cohort: Anti-EGFL7 plus Avastin • Flat dose Cohort: Anti-EGFL7 plus Avastin • ARM A: Anti-EGFL7 plus Avastin plus FOLFOX • ARM B: Avastin plus FOLFOX Primary endpoint • Safety/PK • PFS • PFS Status • FPI Q1 2010 • Data presented at ASCO 2011 • FPI Q2 2011 • Enrollment completed Q3 2012 • FPI Q4 2011 • Enrollment completed Q3 2012 59 Oncology development programmes Growth factor signaling Anti-HER3 EGFR DAF MAb (RG7597) Molecule Patient population Phase Metastatic epithelial tumors Metastatic/recurrent SCCHN KRAS wild-type metastatic colorectal cancer Phase I Phase II MEHGAN Phase II DARECK N=66 N=110 N=120 # of patients Design • Dose escalation study • ARM A: RG7597 • ARM B: Cetuximab • ARM A: RG7597+FOLFIRI • ARM B: Cetuximab+FOLFIRI Primary endpoint • Safety/PK • Progression-free survival • Progression-free survival Status • FPI Q4 2010 • FPI Q3 2012 • Expect FPI Q4 2012 SCCHN=Squamous Cell Carcinoma of the Head and Neck 60 Oncology development programmes Tumor Immunotherapy Anti-PD-L1 MAb (RG7446) Molecule Patient population Solid tumors Solid tumors Previously untreated metastatic melanoma BRAF mutation positive Phase I Phase I Phase I N=91 N=68 N=44 Phase # of patients Design • Dose escalation study • ARM A: RG7446+Avastin • ARM B: RG7446+Avastin+ chemotherapy • Dose escalation of RG7446Zelboraf* combination Primary endpoint • Safety/PK • Safety/PK • Safety Status • FPI Q2 2011 • FPI Q2 2012 • Expect FPI Q4 2012 *Zelboraf In collaboration with Plexxikon, a member of Daiichi Sankyo Group 61 Oncology development programmes Antibody drug conjugates (ADCs) Molecule Patient population Phase Anti-STEAP1 ADC (RG7450) NME ADC (RG7458 ) Anti-CD22 ADC (RG7593) Anti-CD22 ADC (RG7593) vs. AntiCD79b ADC (RG7596) Anti-CD79b (RG7596) Prostate cancer Ovarian cancer Hematologic malignancies Non-Hodgkin's Lymphoma Hematologic malignancies Phase I Phase I Phase I Phase II Phase I N=49 N=57 N=76 N=120 N=99 # of patients Design • Dose escalation study • Dose escalation study • Dose escalation study • RG7593 plus rituximab • RG7596 plus rituximab • Dose escalation study Primary endpoint • Safety • Safety/PK • Safety • Safety and antitumor activity • Safety Status • FPI Q1 2011 • FPI Q2 2011 • FPI Q4 2010 • FPI Q3 2012 • FPI Q1 2011 Collaborator Seattle Genetics and Agensys Seattle Genetics 62 Oncology development programmes Antibody drug conjugates (ADCs) NME ADC (RG7598) NME ADC (RG7599) NME ADC (RG7600) NME ADC (RG7636) Multiple myeloma NSCLC and ovarian cancer Pancreatic and ovarian cancer Metastatic or unresectable melanoma Phase Phase I Phase I Phase I Phase I # of patients N=30-45 N=70 N=66-96 N=44-64 Molecule Patient population Design • Dose escalation study • Dose escalation study • Dose escalation study • Dose escalation study Primary endpoint • Safety • Safety • Safety • Safety Status • FPI Q3 2011 • FPI Q2 2011 • FPI Q4 2011 • FPI Q1 2012 Collaborator Seattle Genetics 63 Oncology development programmes Small molecules • Phase II studies PI3K signaling PI3 Kinase inhibitor (GDC-0941, RG7321) Molecule Patient population 2L ER+ metastatic breast cancer Previously untreated advanced or recurrent NSCLC Phase II FERGI Phase II FIGARO N=340 N=302 Phase # of patients Design • ARM A: GDC-0941 plus hormonal therapy • ARM B: GDC-0980 plus hormonal therapy • ARM C: Hormonal therapy + placebo • ARM A: GDC-0941 + carboplatin + paclitaxel • ARM B: Placebo + carboplatin + paclitaxel • ARM C: GDC-0941 + carboplatin + paclitaxel + bevacizumab • ARM D: GDC-0941 + carboplatin + paclitaxel + bevacizumab Primary endpoint • PFS • PFS Status • FPI Q3 2011 • FPI Q1 2012 64 Oncology development programmes Small molecules (continued) • Phase I studies PI3K signaling PI3 Kinase inhibitor (GDC-0941, RG7321) Molecule Patient population 2L HER2-positive metastatic breast cancer 1L and 2L advanced non-small cell lung cancer 2L metastatic non-small cell lung cancer Phase Ib Phase Ib Phase Ib N=70 N=30 N=30 Phase # of patients Design • Patients who have progressed • ARM A: GDC-0941 plus on Herceptin-based treatment carboplatin/ paclitaxel (Avastin• ARM A: GDC-0941 plus T-DM1 ineligible patients) • ARM B: GDC-0941 plus • ARM B: GDC-0941 plus Herceptin carboplatin/ paclitaxel plus Avastin (Avastin-eligible patients) • Single ARM: Evaluating GDC0941 plus Tarceva Primary endpoint • Safety • Safety • Safety Status • FPI Q3 2009 • Data presented at SABCS 2010 • FPI Q4 2009 • Data presented at ASCO 2011 • FPI Q3 2009 65 Oncology development programmes Small molecules (continued) • Phase I studies PI3K signaling PI3 Kinase inhibitor (GDC-0941, RG7321) Molecule Patient population Advanced solid tumors Advanced solid tumors or NonHodgkin’s Lymphoma 1L HER2-negative metastatic breast cancer Phase Ia Being conducted in the US Phase Ia Being conducted in the UK Phase Ib N=100 N=55 N=45 Phase # of patients Design • Dose-escalating study • Dose-escalating study • Study includes multiple myeloma extension cohort • Single ARM: Evaluating GDC0941 plus paclitaxel and Avastin Primary endpoint • Safety • Safety • Safety Status • FPI Q4 2007 • Additional data presented at ASCO 2010 and ESMO 2010 • FPI Q1 2008 • Additional data presented at ASCO 2010, ESMO 2010, and ASCO 2011 • FPI Q3 2009 • Data presented at SABCS 2011 66 Oncology development programmes Small molecules (continued) • Phase II studies PI3K signaling PI3 Kinase/mTOR dual inhibitor (GDC-0980, RG7422) Molecule Patient population Renal cell carcinoma 2L ER+ metastatic breast cancer Persistent or recurrent endometrial carcinoma 2L Castration-resistant prostate cancer Phase II ROVER Phase II FERGI Phase II Phase Ib/II N=80 N=340 N=50 N=262 Phase # of patients Design • ARM A: GDC-0980 • ARM B: Everolimus • ARM A: GDC-0941 plus hormonal therapy • ARM B: GDC-0980 plus hormonal therapy • ARM C: Hormonal therapy + placebo • Single-arm GDC-0980 • ARM A: GDC-0068 + abiraterone • ARM B: GDC-0980 + abiraterone • ARM C: Placebo + abiraterone Primary endpoint • PFS • PFS • PFS • Safety (Ph IB) • PFS (Ph II) Status • FPI Q4 2011 • Enrollment completed Q3 2012 • FPI Q3 2011 • FPI Q4 2011 • FPI Q1 2012 67 Oncology development programmes Small molecules (continued) • Phase I studies PI3K signaling PI3 Kinase/mTOR dual inhibitor (GDC-0980, RG7422) Molecule Patient population Metastatic breast cancer Solid tumors Solid tumors Phase Ib Phase Ib Phase Ib N=65 N=80 N=95 Phase # of patients Design Dose escalation study • ARM A: GDC-0980 plus paclitaxel • ARM B: GDC-0980 plus Avastin and paclitaxel • ARM C: GDC-0980 plus Herceptin and paclitaxel Dose escalation study • ARM A: GDC-0980 plus carboplatin and paclitaxel • ARM B: GDC-0980 plus Avastin, carboplatin and paclitaxel • ARM A: GDC-0980 + Xeloda • ARM B: GDC-0980 plus FOLFOX and Avastin Primary endpoint • Safety • Safety • Safety Status • FPI Q4 2010 • FPI Q2 2011 • FPI Q3 2011 68 Oncology development programmes Small molecules (continued) • Phase I studies PI3K signaling PI3 Kinase/mTOR dual inhibitor (GDC-0980, RG7422) Molecule Patient population Refractory solid tumors or NHL Refractory solid tumors or NHL Phase Ia Phase Ia N=75 N=65 Design • Dose escalation study • Dose escalation study Primary endpoint • Safety • Safety Status • FPI Q2 2009 • Data presented at ASCO 2010, ESMO 2010, and ASCO 2011 • FPI Q2 2009 • Data presented at ASCO 2010 and ESMO 2010 Phase # of patients ASCO = American Society of Clinical Oncology; ESMO = European Society for Medical Oncology. 69 Oncology development programmes Small molecules (continued) AKT inhibitor (GDC-0068, RG7440) Molecule Patient population Phase # of patients Solid tumors Solid tumors 2L Castration-resistant prostate cancer Solid tumors Phase Ia Phase Ib Phase Ib/II Phase I N=57 N=90 N=262 N=62 Design • Dose escalation study Dose escalation with: •ARM A: docetaxel or •ARM B: fluoropyrimidine plus oxaliplatin or •ARM C: paclitaxel • ARM A: GDC-0068 + abiraterone • ARM B: GDC-0980 + abiraterone • ARM C: Placebo + abiraterone • Dose escalations study of GDC-0973* in combination with GDC0068 Primary endpoint • Safety/PK • Safety • Safety (Ph IB) • PFS (Ph II) • Safety/PK Status • FPI Q1 2010 • Data presented at ASCO 2011 • Recruitment completed Q2 2012 • FPI Q3 2011 • Data presented at ASCO and ESMO 2012 • FPI Q1 2012 • FPI Q2 2012 Collaborator *GDC-0973 in collaboration with Exelixis Array BioPharma 70 Oncology development programmes Small molecules (continued) Molecule Patient population PI3 Kinase inhibitor (GDC-0032, RG7604) PI3 Kinase inhibitor (GDC-0084, RG7666) MEK inhibitor (GDC-0623, RG7420) Solid tumors Progressive or recurrent high-grade glioma Solid tumors Phase I Phase I Phase I N=45 N=68 N=62 Phase # of patients Design • Dose escalation study • Dose escalation study • Dose escalation study Primary endpoint • Safety/PK • Safety/PK • Safety/PK Status • FPI Q1 2011 • FPI Q2 2012 • FPI Q2 2010 WEHI = The Walter and Eliza Hall Institute 71 Oncology development programmes Small molecules (continued) ChK1 inhibitor (GDC-0425, RG7602) ChK1 inhibitor (GDC-0575, RG7741) Bcl-2 selective inhibitor (GDC-0199, RG7601) Solid tumors or lymphoma Solid tumors or lymphoma Relapsed or refractory CLL and NHL Phase I Phase I Phase I N=75 N=45 N=52 Molecule Patient population Phase # of patients Design • Dose escalation study • Dose escalation study • Dose-escalation study Primary endpoint • Safety/PK • Safety/PK • Safety/PK/Response rate Status • FPI Q3 2011 • FPI Q2 2012 • FPI Q2 2011 • Data submitted for presentation at ASH 2012 Collaborator WEHI = The Walter and Eliza Hall Institute Array BioPharma Abbott and WEHI 72 Immunology development programmes Molecule Patient population Pateclizumab (Anti-LT α, RG7416) Quilizumab (Anti-M1 prime, RG7449) Rheumatoid arthritis Asthma Allergic asthma patientsinadequately controlled Phase/study Phase IIa ALTARA Phase IIa SOLARIO Phase IIb COSTA # of patients N=210 N=28 N=560 Design Primary endpoint Status • ARM A: Anti-LT alpha plus DMARD (leflunomide or methotrexate) • ARM B: Adalimumab plus DMARD (leflunomide or methotrexate) • ARM C: Placebo plus DMARD (leflunomide or methotrexate) • ARM A: Anti-M1 prime • ARM B: Placebo SC administration on top of SoC •ARM A: RG7449 300mg •ARM B: RG7449 150mg •ARM C: RG7449 450mg •ARM D: Placebo • Disease Activity Score (DAS28) at Day 85 • Late airway response (LAR) at Day 86 • Rate of protocol-defined exacerbations from baseline to week 36 • FPI Q4 2010 • Recruitment completed Q2 2012 • FPI Q4 2010 • Enrollment completed Q2 2011 • Data presented at ATS 2012 and ERS 2012 • FPI Q2 2012 DMARD = Disease-Modifying Anti-Rheumatic Drugs 73 Immunology development programmes Molecule Patient population Etrolizumab (rhuMAb-β7, (RG7413) anti-IL17 (RG7624) Ulcerative colitis Autoimmune diseases Phase/study Phase I Phase II EUCALYPTUS Phase Ib # of patients N=48 N=120 N=21 Design • Dose escalation study • ARM A: RhuMAb-β7 (100 mg) plus immunosuppressant • ARM B: RhuMAb-β7 (300 mg) plus immunosuppressant • ARM C: Placebo plus immunosuppressant Primary endpoint • Safety and tolerability • Clinical Remission (Mayo Clinic Score) at Week 10 • Safety and tolerability Status • Enrolment completed Q3 2010 • FPI Q3 2011 • Enrollment completed Q3 2012 • FPI Q1 2012 • Enrollment completed Q2 2012 Collaborator • Randomized, double-blind, placebo-controlled, multiple ascending dose escalation study NovImmune 74 Neuroscience and ophthalmology development programmes Molecule Crenezumab (Anti-Αβ, RG7412) Anti-Factor D (RG7417) Alzheimer’s Disease Geographic atrophy (GA) secondary to age-related macular degeneration Patient population Phase/study Phase II ABBY Cognition study Phase II BLAZE Biomarker study Phase Ib/II MAHALO # of patients N=360 N=72 N=143 Design • ARM A: Anti-Abeta subcutaneous • ARM B: Anti-Abeta IV • ARM C: Placebo • ARM A: Anti-Abeta subcutaneous • ARM B: Anti-Abeta IV • ARM C: Placebo • Part 1: Open-label • Multiple dosing • Part 2: Randomised • ARM A: Anti-Factor D injection • ARM B: Sham Injection Primary endpoint • Change in cognition (ADAS-cog) and Clinical Dementia Rating, Sum of Boxes (CDR-SOB) score from baseline to week 73 • Change in brain amyloid load from baseline to week 69 • Part 1: Safety • Part 2: Growth rate of GA lesions at months 12 Status • FPI Q2 2011 • Enrollment completed Q3 2012 • FPI Q3 2011 • Enrollment completed Q3 2012 • Part 1 FPI Q4 2012 • Part 2 FPI Q2 2011 • Enrollment completed Q4 2011 Collaborator AC Immune 75 Metabolism and virology development programmes Anti-oxLDL (RG7418, BI-204) Anti-PCSK9 (RG7652) NME (RG7667) Secondary prevention of cardiovascular events in patients with ACS Metabolic diseases Infectious diseases Phase/study Phase II Proof of activity study Phase II EQUATOR Phase I # of patients N=144 N=224 N=181 Molecule Patient population Design • ARM A: Anti-oxLDL (single dose) and statin • ARM B: Anti-oxLDL (repeating dose) and statin • ARM C: Placebo and statin SC dosing every 4 weeks • Experimental: five different doses of RG7652 • Placebo • RG7667 • Placebo Primary endpoint • Change in TBR as measured by FDG-PET/CT at week 12 • Absolute change from baseline in LDL-c concentration • Safety, PK Status • Study did not meet primary endpoint • Project will not proceed into phase IIb development • FPI Q2 2012 • FPI Q1 2012 • Recruitment completed Q3 2012 BioInvent 76 We Innovate Healthcare 77