Pipeline summary Marketed products additional indications Global Development late-stage trials pred (Roche Pharma Research & Early Development) gred (Genentech Research & Early Development) Roche Group HY 2015 results Diagnostics Foreign exchange rate information 1
Changes to the development pipeline HY 2015 update New to Phase I New to Phase II New to New to Registration 2 NMEs transitioned from Ph0 RG7944 Therapeutic vaccine - HBV RG6069 NME - fibrosis 3 AIs RG7888 OX40 MAb + atezolizumab solid tumors atezolizumab + lenalidomide - multiple myeloma RG6078 IDO inh + atezolizumab solid tumors 1 NME added by Chugai CHU PTH1 receptor agonist - hypoparathyroidism 1NME transitioned from Ph1 RG7795 TLR7 ago - HBV 1 AI RG3637 lebrikizumab - atopic dermatitis 1 AI transitioned from Ph2 atezolizumab + Avastin - RCC 4 AIs RG105 MabThera - pemphigus vulgaris atezolizumab Dx+ NSCLC adj atezolizumab + abraxane TNBC atezolizumab - muscle invasive bladder cancer (MIBC) adj 1 AI transitioned from Ph2 following EU submission RG435 Avastin + Tarceva EGFR mut+ NSCLC Removed from Phase I Removed from Phase II Removed from Removed from Registration 3 NMEs RG7203 PDE10 inh schizophrenia RG7641 aldosterone synthase inh - met. diseases RG7787 MSLN PE cfp - solid tumors Status as of July 23, 2015 2 NMEs RG7697 GIP/GLP-1 dual agonist - type 2 diabetes RG7929 LptD antibiotic-antibacterial 1 AI RG6062 Esbriet - SSc interstitial lung disease 1 AI (filing no go decision) RG3502 Kadcyla +/- Perjeta HER2+ mbc 1L 2
Roche Group development pipeline RG6016 RG6047 RG6061 RG6078 RG6078 RG7116 RG7155 RG7304 RG7388 RG7450 RG7597 RG7601 RG7601 RG7741 RG7775 RG7802 RG7813 RG7841 RG7842 RG7876 RG7882 RG7888 RG7888 LSD1 inh SERD (2) HIF1 alpha LNA IDO inh IDO inh + atezolizumab lumretuzumab Raf & MEK dual inh idasanutlin atezolizumab atezo+zelboraf+/-cobi atezo+avastin+chemo anti-steap 1 ADC ChK1 inh Phase I (30 NMEs + 14 AIs) mbc solid tumors solid & hem tumors solid tumors m. melanoma solid tumors atezolizumab+cobimetinib solid tumors atezolizumab+ipi/ifn atezolizumab+tarceva NSCLC EGFR+ atezolizumab+gazyva prostate ca. venetoclax+gazyva CLL CLL MDM2 (4) IV prodrug CEA CD3 TCB anti-ly6e ADC ERK inh + cobimetinib AML ER+(HER2-neg) mbc solid tumors solid tumors emactuzumab + atezolizumab s. tumors solid tumors lymphoma atezo+lenalidomide multiple myeloma duligotuzumab + cobi venetoclax CEA IL2v + atezolizumab solid tum & lymphoma AML solid tumors solid tumors solid tumors CD40 imab+atezolizumab solid tumors ADC ovarian ca OX40 MAb solid tumors OX40 MAb + atezolizumab solid tumors Status as of July 23, 2015 solid tumors solid tumors heme indications solid tumors RG6069 RG7625 RG7880 RG6080 RG7689 RG7944 RG7345 RG7893 RG7800 RG7935 RG3645 RG7716 CHU - autoimmune diseases - inflammatory diseases DBO β-lactamase inh - infectious diseases Therapeutic vaccine TAU MAb Nav1.7 inh Lucentis sust. deliv. VEGF-ANG2 MAb New Molecular Entity (NME) Additional (AI) Oncology Immunology Infectious Diseases CardioMetabolism Neuroscience Ophthalmology Other bact. infections AMD/RVO/DME RG-No Roche Genentech managed CHU Chugai managed CLL - fibrosis HBV Alzheimer s pain SMN2 splicer spinal muscular atrophy a-synuclein MAb Parkinson's Disease wamd PTH1 recep. ago hypoparathyroidism RG3502 RG6013 RG6046 RG7155 RG7221 RG7421 RG7440 RG7596 RG7601 RG1569 CHU RG7227 RG7745 RG1577 RG1678 FIXa/FX bispecific MAb ipatasertib polatuzumab vedotin venetoclax Actemra IL-31R MAb danoprevir Flu A MAb sembragiline bitopertin hemophilia A solid tumors atezolizumab NSCLC 2/3L hem tumors ADC RG7599 lifastuzumab vedotin Pt-resist. OC RG7601 RG7601 RG7604 RG7604 RG7686 RG7853 RG3637 RG3637 RG7795 CHU RG1662 Phase II (22 NMEs + 11 Als) Kadcyla SERD emactuzumab vanucizumab cobimetinib+paclitaxel atezolizumab bladder cancer 1/2L RCC venetoclax venetoclax+rituxan taselisib taselisib glypican-3 MAb alectinib lebrikizumab +/- Esbriet lebrikizumab TLR7 agonist URAT1 inh GABRA5 NAM HER2+ NSCLC ER+(HER2-neg) mbc PVNS/solid tumors mcrc TNBC 17p del CLL rel/ref DLBCL FL rel/ref NSCLC sq 2L ER+(HER2-neg) BC neoadj liver cancer ALK+ NSCLC 2L systemic sclerosis IPF atopic dermatitis atopic dermatitis HCV influenza HBV gout Alzheimer s Down Syndrome obsessive compulsive dis. RG7929 RG6083 olesoxime spinal muscular atrophy RG7090 basimglurant TRD RG7314 Status as V1 of receptor July 23, antag 2015 autism RG7412 crenezumab Alzheimer s 3
Roche Group development pipeline RG435 RG7159 RG7159 Avastin Gazyva Gazyva (8 NMEs + 32 Als) glioblastoma 1L RG435 1 Avastin ovarian cancer 1L RG435 1 Avastin rel. ovarian ca. Pt-sensitive RG1273 RG1273 RG1273 RG3502 RG3502 RG3502 RG3502 RG7159 RG7204 NSC RG7601 RG7601 RG7604 RG7853 Perjeta+Herceptin Perjeta+Herceptin Perjeta+Herceptin HER2+gastric ca 1L Kadcyla Kadcyla Kadcyla + Perjeta Kadcyla + Perjeta Gazyva Zelboraf atezolizumab (PD-L1) atezolizumab+chemo atezolizumab+avastin atezolizumab venetoclax+rituxan venetoclax+gazyva alectinib HER2+ mbc 2L HER2+ BC adj HER2+ gastric cancer 2L HER2+ BC adj HER2+ BC adj HER2+ BC neoadj DLBCL1L inhl rituximab-ref follicular lymphoma 1L melanoma adj NSCLC 2L NSCLC non-sq. 1L atezo+chemo+avastin NSCLC non-sq. 1L atezolizumab+chemo atezolizumab Dx+ atezolizumab Dx+ atezolizumab Dx+ atezolizumab+abraxane taselisib NSCLC sq. 1L NSCLC sq. 1L NSCLC non-sq. 1L NSCLC adj TNBC RCC bladder cancer 2L atezolizumab muscle inv. bladder ca adj CLL rel/ref CLL 1L ER+(HER2-neg) mbc ALK+ NSCLC 1L RG105 RG1569 RG3637 RG7413 RG7413 CHU CHU RG1450 RG1594 RG1594 RG7417 MabThera Actemra lebrikizumab etrolizumab etrolizumab Actemra IL-6R MAb gantenerumab ocrelizumab ocrelizumab lampalizumab pemphigus vulgaris giant cell arteritis severe asthma ulcerative colitis Crohn s disease large-vessel vasculitis neuromyelitis optica Alzheimer s RMS PPMS geographic atrophy RG105 RG435 3 Registration (1 NME + 3 Als) MabThera SC Avastin+Tarceva CLL EGFR mut+ NSCLC RG1273 2 Perjeta HER2+ BC neoadj RG7421 cobimetinib +Zelboraf m. melanoma 1 US only : FDA submission decision pending 2 Approved in US, submitted in EU 3 EU only New Molecular Entity (NME) Additional (AI) Oncology Immunology Infectious Diseases CardioMetabolism Neuroscience Ophthalmology Other RG-No Roche Genentech managed CHU Chugai managed RG105 MabThera is branded as Rituxan in US and Japan RG1569 Actemra is branded as RoActemra in EU RG7159 Gazyva is branded as Gazyvaro in EU Status as of July 23, 2015 4
NME submissions and their additional indications Projects currently in phase 2 and 3 taselisib ( RG7604) ER+(HER2-neg) BC neoadj taselisib ( RG7604) NSCLC sq 2L atezolizumab () + abraxane TNBC atezolizumab () Dx NSCLC adj GABRA5 NAM (RG1662) Down syndrome bitopertin (RG1678) obsessive compulsive dis. basimglurant (RG7090) depression V1 receptor antag (RG7314) autism New Molecular Entity Oncology Immunology Infectious Diseases CardioMetabolism Neuroscience Ophthalmology Other SERD (RG6046) ER+(HER2-neg) mbc emactuzumab (RG7155) PVNS and solid tumors vanucizumab (RG7221) colorectal cancer atezolizumab () MIBC adj atezolizumab() NSCLC sq 1L (Dx+) atezolizumab() NSCLC non sq 1L (Dx+) atezolizumab()+ chemo NSCLC sq 1L crenezumab (RG7412) Alzheimer s sembragiline (RG1577) Alzheimer s gantenerumab (RG1450) Alzheimer s lebrikizumab (RG3637) atopic dermatitis ocrelizumab (RG1594) PPMS ipatasertib (RG7440) solid tumors atezolizumab()+ chemo NSCLC non-sq 1L lebrikizumab+/-esbriet (RG3637) IPF ocrelizumab (RG1594) RMS polatuzumab vedotin (RG7596) heme tumors atezolizumab()+chemo + Avastin NSCLC non-sq 1L etrolizumab (RG7413) Crohn s disease lebrikizumab (RG3637) severe asthma olesoxime (RG6083) SMA lifastuzumab (RG7599) Pt resistant OC cobimetinib+paclitaxel TNBC etrolizumab (RG7413) ulcerative colitis venetoclax (RG7601) CLL rel/refractory FIXa /FX bispecific MAb (RG6013) hemophilia A taselisib (RG7604) HER2 neg ER+ mbc venetoclax (RG7601) + Rituxan FL rel/ref TLR7 ago (RG7795) HBV venetoclax (RG7601) 17p del CLL rel/ref atezolizumab () bladder cancer atezolizumab() combo Avastin RCC glypican-3 MAb (RG7686) liver cancer venetoclax (RG7601) + Gazyva CLL 1L danoprevir* (RG7227) HCV alectinib (RG7853 ) Alk+ NSCLC 2L atezolizumab() NSCLC 2/3L alectinib (RG7853) Alk+ NSCLC 1L lampalizumab (RG7417) geographic atrophy 2015 2016 2017 2018 and beyond Unless stated otherwise, submissions are planned to occur in US and EU; * lead market China Status as of July 23, 2015 venetoclax (RG7601) DLBCL Flu A MAb (RG7745) influenza 5
Submissions of additional indications for existing products Projects currently in phase 2 and 3 Gazyva inhl rituximab refractory *Avastin (US) ovarian cancer 1 st L *Avastin (US) rel. ovarian ca. Pt-sens Kadcyla HER2-pos gastric cancer 2L Zelboraf melanoma adj. Gazyva DLBCL 1L Perjeta + Herceptin HER2-pos. mbc 2L Kadcyla HER2-pos. NSCLC Kadcyla+Perjeta HER2-pos. BC neoadj Kadcyla+Perjeta HER2-pos. BC adj Kadcyla HER2-pos. BC adj Avastin +Tarceva (EU) EGFR mut+ NSCLC Avastin (US) GBM Perjeta + Heceptin HER2-pos. BC adj Actemra giant cell arteritis Gazyva follicular lymphoma 1L Perjeta+Herceptin HER2-pos. gastric cancer 1L MabThera pemphigus vulgaris Actemra systemic sclerosis 2015 2016 2017 2018 and beyond *approved in EU Unless stated otherwise, submissions are planned to occur in US and EU. Status as of July 23, 2015 Oncology Immunology Infectious Diseases CardioMetabolism Neuroscience Ophthalmology Other NME 6
Major granted and pending approvals 2015 Approved Pending approvals US Lucentis diabetic retinopathy February 2015 cobimetinib + Zelboraf m. melanoma Filed December 2014 EU Avastin cervical cancer April 2015 Perjeta* HER2+ BC neoadj Filed September 2014 Avastin + Tarceva (RG435) EGFR mut+ NSCLC Filed July 2015 cobimetinib + Zelboraf m. melanoma Filed September 2014 MabThera SC CLL Filed November 2014 Japan-Chugai Xeloda gastric cancer adj Filed December 2014 Bonviva osteoporosis (oral) Filed February 2015 * positive CHMP opinion in Q2 15 Status as of July 23, 2015 Oncology Immunology Infectious Diseases CardioMetabolism Neuroscience Ophthalmology Other NME 7
Cancer immunotherapy pipeline overview Phase I (5 NMEs + 13 AIs) Phase II (1 NME + 2 Als) (1 NME + 10 AIs) RG6078 RG6078 RG7155 RG7802 RG7813 RG7876 RG7888 RG7888 *INCB *CDX IDO inh solid tumors IDO inh + atezolizumab solid tumors emactuzumab + atezolizumab s.tumors atezolizumab atezo+zelboraf+/-cobimetinib atezo+avastin+chemo solid tumors m. melanoma solid tumors atezolizumab +cobimetinib solid tum atezolizumab +ipi/ifn solid tumors atezo+tarceva NSCLC EGFR+ atezolizumab+gazyva lymphoma atezo+lenalidomide multiple myeloma CEA CD3 TCB solid tumors CEA IL2v + atezolizumab solid tumors CD40 imab+atezolizumab solid tumors OX40 MAb solid tumors OX40 MAb + atezolizumab solid tumors atezolizumab + IDO inh solid tumors atezolizumab +varlilumab solid tumors RG7155 emactuzumab PVNS/solid tumors atezolizumab NSCLC 2L atezolizumab NSCLC 2/3L atezolizumab bladder cancer 1/2L RCC NSC atezo+chemo atezolizumab atezolizumab+avastin NSCLC non-sq. 1L atezo+chemo+avastin NSCLC non-sq. 1L atezolizumab+chemo atezolizumab Dx+ NSCLC sq. 1L NSCLC sq. 1L atezolizumab Dx+ NSCLC non-sq. 1L atezolizumab Dx+ atezolizumab+abraxane bladder cancer 2L New Molecular Entity (NME) Additional (AI) NSCLC adj TNBC RCC atezolizumab muscle inv. bladder ca adj *external collaborations: INCB- Incyte INCB024360, CDX-1127- Celldex CD27 MAb Oncology RG-No Roche Genentech managed CHU Chugai managed Status as of July 23, 2015 8
Roche Group development pipeline Combinations Phase I (4 NMEs + 11 AIs) Phase II (1 NME + 2 Als) Registration (1 NME + 1 AI) RG6078 IDO inh + atezolizumab solid tumors RG7421 cobimetinib+paclitaxel TNBC RG435 3 Avastin+Tarceva EGFR mut+ NSCLC RG7155 emactuzumab + atezolizumab s.tum atezo+zelboraf+/-cobimetinib m. melanoma RG7601 RG3637 venetoclax+rituxan lebrikizumab +/- Esbriet FL rel/ref IPF RG7421 cobimetinib +Zelboraf m. melanoma atezo+avastin+chemo solid tumors atezolizumab +cobimetinib solid tum atezolizumab +ipi/ifn solid tumors atezo+tarceva NSCLC EGFR+ atezolizumab+gazyva lymphoma atezo+lenalidomide multiple myeloma (12 AIs) RG7597 duligotuzumab + cobi solid tumors RG7601 RG7813 RG7842 RG7876 RG7888 venetoclax+gazyva CLL CLL CEA IL2v + atezolizumab solid tum ERK inh + cobimetinib solid tumors CD40 imab+atezolizumab solid tum Anti-OX40 + atezolizumab solid tum RG1273 RG1273 RG1273 RG3502 RG3502 NSC Perjeta+Herceptin Perjeta+Herceptin Perjeta+Herceptin HER2+gastric ca 1L Kadcyla + Perjeta Kadcyla + Perjeta atezo+chemo NSCLC non-sq. 1L atezo+chemo+avastin NSCLC non-sq. 1L atezolizumab+chemo HER2+ mbc 2L HER2+ BC adj HER2+ BC adj HER2+ BC neoadj NSCLC sq. 1L New Molecular Entity (NME) Additional (AI) Oncology Immunology RG-No Roche Genentech managed CHU Chugai managed atezolizumab+abraxane TNBC atezolizumab+avastin RCC RG7601 venetoclax+rituxan CLL rel/ref RG7601 venetoclax+gazyva CLL 1L Status as of July 23, 2015 9
Pipeline summary Marketed products additional indications Global Development late-stage trials pred (Roche Pharma Research & Early Development) gred (Genentech Research & Early Development) Roche Group HY 2015 results Diagnostics Foreign exchange rate information 10
Avastin Ovarian cancer clinical development programme Phase/study GOG-0218 Front-line metastatic ovarian cancer ICON7 # of patients N=1,873 N=1,528 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 Progression-free survival Progression-free survival Status Study met its primary in Q1 2010 Data presented at ASCO 2010 and 2011 Results: NEJM 2011 Dec 29;365(26):2484-96 Study met its primary Q3 2010 Data presented at ESMO 2010 and ASCO 2011 Results: NEJM 2011 Dec 29;365(26):2473-83 OS data presented at ECC 2013 EMA approval granted Q4 2011 Re-evaluate FDA submission in 2015 ASCO=American Society of Clinical Oncology; ESMO=European Society for Medical Oncology NEJM=New England Journal of Medicine 11
Avastin Ovarian cancer clinical development programme (continued) Phase/study Relapsed platinum-sensitive ovarian cancer OCEANS # of patients N=484 ARM A: Carboplatin, gemcitabine, and concurrent placebo for 6-10 cycles, followed by placebo alone until disease progression ARM B: Carboplatin, gemcitabine, and concurrent Avastin for 6-10 cycles, followed by Avastin alone until disease progression. Avastin dose 15 mg/kg q3 weeks Progression-free survival Status met Q1 2011 EMA approval received Q4 2012 Final data presented at SGO 2014 Re-evaluate FDA submission in 2015 SGO=Society of Gynecologic Oncology 12
Avastin Brain and breast cancer clinical development programmes Phase/study Newly diagnosed glioblastoma AVAglio First-line HER2-negative metastatic breast cancer MERiDiAN # of patients N=920 N=480 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 ARM A: Paclitaxel + Avastin ARM B: Paclitaxel + Placebo Avastin dose 10 mg/kg q2 weeks or 15 mg/kg q3 weeks 10 mg/kg q2 weeks Progression-free survival Overall survival PFS in ITT PFS in patients with high plasma VEGF-A Status Co-primary of PFS met Q3 2012 Overall survival data presented at ASCO 2013 Filed in EU Q1 2013 Negative CHMP opinion Q3 2014 US filing pending Co-primary s met Q1 2015 Data to be presented at ECC 2015 TMZ=temozolomide ASCO=American Society of Clinical Oncology; ECC=European Cancer Congress 13
Erivedge A novel small molecule inhibitor of the hedgehog signaling pathway Locally advanced or metastatic basal cell carcinoma Idiopathic pulmonary fibrosis Phase/study Phase II STEVIE Phase II # of patients N=1,200 N=129 Single ARM: 150 mg Erivedge orally once daily ARM A: Erivedge 150mg daily ARM B: placebo Safety: Incidence of adverse events Change in forced vital capacity (FVC) Status FPI Q2 2011 Recruitment completed Q3 2014 FPI pending in anticipation of trial design amendment to incorporate new standard of care Esbriet In collaboration with Curis 14
Gazyva/Gazyvaro Type II, glycoengineered CD20 monoclonal antibody Previously untreated or relapsed/refractory chronic lymphocytic leukemia Diffuse large B-cell lymphoma (DLBCL) Phase/study GREEN GOYA # of patients N=800 N=1,418 Single-arm cohort study: Gazyva alone or in combination with different chemotherapy regimens (FC, Bendamustin or Clb), investigation of different strategies to reduce IRRs Safety in combination with different chemotherapy regimens ARM A: Gazyva 1000mg IV plus CHOP ARM B: MabThera/Rituxan plus CHOP Progression-free survival Status FPI Q4 2013 Initial safety data presented at ASH 2014 Recruitment completed Q2 2014 Trial continues after interim analysis in 2015 Final data expected in 2016 In collaboration with Biogen Idec CHOP=Cyclophosphamide, Doxorubicin, Vincristine and Prednisone; ASH=American Society of Hematology 15
Gazyva/Gazyvaro Type II, glycoengineered CD20 monoclonal antibody (continued) Phase/stud y Indolent non-hodgkin s lymphoma MabThera/Rituxan refractory GADOLIN Induction and maintenance study Front-line indolent non-hodgkin s lymphoma GALLIUM Induction and maintenance study # of patients N=411 N=1,401 ARM A: Gazyva 1000mg IV plus bendamustine followed by Gazyva mainteinance ARM B: bendamustine ARM A: Gazyva 1000mg IV plus chemotherapy followed by Gazyva maintenance ARM B: MabThera/Rituxan plus chemotherapy followed by MabThera/Rituxan maintenance Chemotherapy: For follicular lymphoma: CHOP, CVP or bendamustine For non-follicular lymphoma: physician s choice Progression-free survival Progression-free survival Status Trial stopped at interim for efficacy Q1 2015 Data to be presented at ASCO 2015 Expect global filing in 2015 Recruitment completed Expect data in 2017 In collaboration with Biogen Idec CHOP=Cyclophosphamide, Doxorubicin, Vincristine and Prednisone; CVP=Cyclophosphamide, Vincristine and Prednisolone 16
Kadcyla Evaluating new treatment options in HER2-positive early breast cancer HER2-positive neoadjuvant breast cancer HER2-positive early breast cancer high-risk patients Operable HER2-positive early breast cancer Phase/study KRISTINE KATHERINE KAITLIN # of patients N=444 N=1,484 N=1,850 Before surgery patients will receive 6 cycles of: ARM A: Herceptin plus Perjeta plus docetaxel plus carboplatin ARM B: Kadcyla plus Perjeta After surgery patients will receive: ARM A: Herceptin plus Perjeta ARM B: Kadcyla plus Perjeta ARM A: Kadcyla 3.6mg/kg q3w ARM B: Herceptin Following surgery and antracycline-based therapy: ARM A: Herceptin 6mg/kg q3w plus Perjeta 420 mg/kg q3w plus chemo ARM B: Kadcyla 3.6mg/kg q3w plus Perjeta 420mg/kg q3w plus chemo Pathologic Complete Response (pcr) Invasive disease-free survival (IDFS) Invasive disease-free survival (IDFS) Status Enrollment completed Q2 2015 Data expected in 2016 FPI Q1 2013 Enrollment completed Q2 2015 In collaboration with ImmunoGen, Inc. 17
Kadcyla Evaluating new treatment options in HER2-positive breast, gastric and lung cancer Previously untreated HER2 pos. metastatic breast cancer Previously treated locally advanced or metastatic HER2- positive gastric cancer HER2-positive advanced (2L+) NSCLC Phase/stud y MARIANNE Phase II/III GATSBY Phase II # of patients N=1,092 N=412 N=40 ARM A: Herceptin plus taxane ARM B: Kadcyla 3.6mg/kg q3w plus Perjeta ARM C: Kadcyla 3.6 mg/kg q3w plus placebo ARM A: Kadcyla 3.6mg/kg q3w ARM B: Kadcyla 2.4mg/kg weekly ARM C: docetaxel or paclitaxel Single-agent Kadcyla 3.6 mg/kg Progression-free survival assessed by IRF Phase II: Dose-finding : Overall survival Overall response rate and safety Status Study met non-inferiority, showing similar progression-free survival (PFS) among the three arms Q4 2014 Study did not meet PFS superiority for Kadcyla-containing regimens Q4 2014 Data presented at ASCO 2015 Recruitment completed Q1 2015 Data expected in 2015 FPI Q4 2014 In collaboration with ImmunoGen, Inc. ASCO=American Society of Clinical Oncology 18
MabThera/Rituxan Oncology and immunology development programmes Previously untreated chronic lymphocytic leukemia Moderate to severely active pemphigus vulgaris Phase/study Phase Ib SAWYER Subcutaneous study Study being conducted ex-us PEMPHIX # of patients N=225 N=124 Two-stage design: - Stage 1 (dose-finding, N=55) - 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) ARM A: Rituxan ARM B: mycophenolate mofetil Part 1: PK (dose selection) Part 2: PK of MabThera IV versus MabThera SC (arm A vs. arm B) Proportion of patients who achieve a sustained complete remission Status Stage 2 data confirmed non-inferior PK and comparable safety/efficacy of MabThera 1600mg SC vs. MabThera IV Presented at ASH 2014 Filed in EU Q4 2014 FPI Q2 2015 Subcutaneous MabThera : applies Enhanze technology, partnered with Halozyme ASH=American Society of Hematology 19
Perjeta First in a new class of HER dimerization inhibitors Neoadjuvant HER2-positive breast cancer Adjuvant HER2-positive breast cancer Phase/ study Phase II NEOSPHERE Phase II TRYPHAENA APHINITY # of patients N=417 N=225 N=4,803 ARM A: Herceptin plus docetaxel ARM B: Perjeta (840mg loading, 420mg q3w) plus Herceptin and docetaxel ARM C: Perjeta plus Herceptin ARM D: Perjeta plus docetaxel ARM A: FEC followed by Taxane with Herceptin and pertuzumab (H+P given concurrently) ARM B: FEC followed by Taxane with Herceptin + pertuzumab (H+P given sequentially) ARM C: TCH + pertuzumab (H+P given concurrently) ARM A: Perjeta (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) Pathologic complete response (pcr) Safety Invasive disease-free survival (IDFS) Status Positive data presented at SABCS 2010 Biomarker data presented SABCS 2011 Survival data presented at ASCO 2015 Positive safety and efficacy data presented at SABCS 2011 Recruitment completed Q3 2013 Expect data in 2016 FDA approval granted Q3 2013 Filed in EU Q3 2014 Positive CHMP opinion Q2 2015 FEC = Fluorouracil, Epirubicin, and Cyclophosphamide; TCH = Docetaxel, Carboplatin, Herceptin; SABCS=San Antonio Breast Cancer Symposium; ASCO=American Society of Clinical Oncology 20
Perjeta First in a new class of HER dimerization inhibitors (continued) Second-line HER2-positive metastatic breast cancer Advanced HER2-positive gastric cancer Neoadjuvant/adjuvant HER2- positive breast cancer Phase/ study PHEREXA JACOB Phase II BERENICE # of patients N=450 N=780 N=400 ARM A: Herceptin plus Xeloda ARM B: Perjeta plus Herceptin and Xeloda ARM A: Perjeta (840mg loading, 420mg q3w) plus Herceptin and chemotherapy ARM B: placebo plus Herceptin and chemotherapy Neoadjuvant treatment: ARM A: ddac q2w x4 cycles followed by weekly paclitaxel for 12 weeks, with P+H x4 cycles ARM B: FEC+P+H x4 cycles followed by docetaxel+p+h x4 cycles Adjuvant treatment: P+H q3w to complete 1 year of HER2 therapy Hormonal and radiation therapy as indicated Progression-free survival Overall survival Safety Status Recruitment completed Q3 2013 Expect data in 2015 FPI Q2 2013 FPI Q3 2014 ddac=dose-dense doxorubicin plus cyclophosphamide; FEC = fluorouracil, epirubicin, and cyclophosphamide 21
Zelboraf A selective novel small molecule that inhibits mutant BRAF Adjuvant therapy in patients with resected cutaneous BRAF mutation positive melanoma Phase/study BRIM8 # of patients N=475 52-week treatment ARM A: Zelboraf 960mg bid ARM B: Placebo Disease-free survival Status Enrollment completed Q2 2015 Expect data in 2016 In collaboration with Plexxikon, a member of Daiichi Sankyo Group See also combinations with: cobimetinib (MEK inhibitor) and atezolizumab (PD-L1 MAb) 22
Actemra/RoActemra Interleukin 6 receptor inhibitor Systemic sclerosis Giant Cell Arteritis Phase/study Phase II fasscinate Proof-of-concept study focussced GiACTA # of patients N=86 N=210 N=250 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 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 1: 52-week blinded period ARM A: Actemra SC 162mg qw + 26 weeks prednisone taper ARM B: Actemra SC 162mg q2w + 26 weeks prednisone taper ARM C: Placebo+ 26 weeks prednisone taper ARM D: Placebo+ 52 weeks prednisone taper Part II: 104-week open label extension patients in remission followed off of the study drug; Patients with active disease receive open label Actemra SC 162mg qw Change in modified Rodnan skin score (mrss) at week 24 Safety Change in modified Rodnan skin score (mrss) at week 48 Proportion of patients in sustained remission at week 52 Status 48 week data presented at ACR 2014 and all key secondary s showed trend for improved efficacy Breakthrough designation granted Q1 2015 In collaboration with Chugai; ACR=American College of Rheumatology Expect FPI Q3 2015 LPI Q2 2015 Data expected in 2016 23
Esbriet Small molecule with activity in fibrotic diseases Systemic sclerosis-related interstitial lung disease (SSc-ILD) Phase/stu dy # of patients Phase II LOTUSS N=63 Open-label, randomized, parallel-group, safety and tolerability study 2 week vs. 4 week dose titration regimens Safety Status LPI Q3 2014 Data presented at ATS Q2 2015 No further development in SSc-ILD is planned ATS=Annual Meeting of American Thoracic Society 24
Pipeline summary Marketed products additional indications Global Development late-stage trials pred (Roche Pharma Research & Early Development) gred (Genentech Research & Early Development) Roche Group HY 2015 results Diagnostics Foreign exchange rate information 25
Alectinib (ALK inhibitor, RG7853, AF802) New CNS-active inhibitor of anaplastic lymphoma kinase Phase/study Treatment naïve ALK-positive advanced NSCLC ALEX ALK-positive crizotinib-naïve advanced NSCLC Phase I/II AF-001JP Japanese study # of patients N=286 N=70 ARM A: alectinib 600mg BID ARM A: crizotinib 250mg BID Part 1: Dose escalation monotherapy Part 2: Monotherapy, dose selected based on the results of Part 1 Progression-free survival Phase I: Determination of recommended dose Phase II: Safety and efficacy Status FPI Q3 2014 Results published in Lancet Oncology 2013 Jun;14(7):590-8 Approved in Japan with brand name ALECENSA July 2014 In collaboration with Chugai 26
Alectinib (ALK inhibitor, RG7853, AF802) New CNS-active inhibitor of anaplastic lymphoma kinase (continued) Phase/study # of patients ALK-positive advanced NSCLC after progression on crizotinib treatment Phase I/II AF-002JG/NP28761 US study Phase I: N=36 Phase II: N=85 Part 1: Dose escalation monotherapy Part 2: Monotherapy, dose selected based on the results of Part 1 ALK-positive advanced NSCLC after progression on crizotinib treatment Phase I/II ACCALIA/NP28673 Global study N=130 Part 1: Dose escalation monotherapy Part 2: Monotherapy, dose selected based on the results of Part 1 Phase I: Determination of recommended dose Phase II: Safety and efficacy Phase I: Determination of recommended dose Phase II: Safety and efficacy Status Phase I data presented at ECC 2013 Phase I full cohort including CNS data published in Lancet Oncology 2014, Sept.15(10):1119-28 Phase II FPI Q3 2013 analysis positive Q1 2015 Data presented at ASCO 2015 Updated data to be presented at ECC 2015 Phase II FPI Q3 2013 analysis positive Q4 2014 Updated analysis in Q1 2015 Data presented at ASCO 2015 Updated data to be presented at ECC 2015 Expect global filing in 2015 Breakthrough therapy designation granted by the FDA June 2013 In collaboration with Chugai ECC=European Cancer Congress; ASCO=American Society of Clinical Oncology 27
Atezolizumab (PD-L1 MAb, MPDL3280A, ) Novel approach in cancer immunotherapy 1L non-squamous NSCLC PD-L1-selected patients 1L non-squamous NSCLC 1L non-squamous NSCLC Phase/study IMpower 110 IMpower 150 IMpower 130 # of patients N=400 N=1200 N=550 ARM A: atezolizumab monotherapy ARM B: carboplatin or cisplatin + pemetrexed ARM A: atezolizumab + Avastin + paclitaxel + carboplatin ARM B: atezolizumab + paclitaxel + carboplatin ARM C: Avastin + paclitaxel + carboplatin ARM A: atezolizumab + nabpaclitaxel + carboplatin ARM B: nab-paclitaxel + carboplatin Progression-free survival Progression-free survival Progression-free survival Status Expect FPI Q3 2015 FPI Q2 2015 FPI Q1 2015 28
Atezolizumab (PD-L1 MAb, MPDL3280A, ) Novel approach in cancer immunotherapy Adjuvant NSCLC PD-L1-selected patients 1L squamous NSCLC PD-L1-selected patients 1L squamous NSCLC Phase/study IMpower 010 IMpower 111 IMpower 131 # of patients 845 N=400 N=1200 Following adjuvant cisplatinbased chemotherapy ARM A: atezolizumab ARM B: best supportive care ARM A: atezolizumab monotherapy ARM B: gemcitabine + cisplatin or carboplatin ARM A: atezolizumab + nabpaclitaxel + carboplatin ARM B: atezolizumab + paclitaxel + carboplatin ARM C: nab-paclitaxel + carboplatin Disease-free survival Progression-free survival Progression-free survival Status FPI Q2 2015 FPI Q2 2015 FPI Q2 2015 29
Atezolizumab (PD-L1 MAb, MPDL3280A, ) Novel approach in cancer immunotherapy Metastatic NSCLC 2 nd line Locally advanced or metastatic NSCLC PD-L1 positive Locally advanced or metastatic NSCLC PD-L1 positive Locally advanced or metastatic NSCLC (2 nd /3 rd line) Non-small cell lung cancer Phase/study OAK Phase II FIR Phase II BIRCH Phase II POPLAR Phase I # of patients N=1,225 N=130 N=635 N=287 N=32 ARM A: atezolizumab 1200mg q3w ARM B: docetaxel Single arm study: atezolizumab 1200mg q3w Single arm study: atezolizumab 1200mg q3w ARM A: atezolizumab 1200mg q3w ARM B: docetaxel atezolizumab plus Tarceva 1 Overall survival Overall response rate Objective response rate Overall survival Safety Status Recruitment completed Q2 2015 Readout in 2016 Recruitment completed Q2 2014 Data presented at ASCO 2015 Recruitment completed Q4 2014 Readout in 2015 Recruitment completed Q2 2014 Interim data presented at ASCO 2015 FPI Q1 2014 1 Tarceva is a registered trademark of OSI Pharmaceuticals, LLC, a subsidiary of Astellas US, LLC ASCO=American Society of Clinical Oncology 30
Atezolizumab (PD-L1 MAb, MPDL3280A, ) Novel approach in cancer immunotherapy Adjuvant high risk muscle invasive bladder cancer PD-L1- positive patients Locally advanced or metastatic urothelial bladder cancer Phase/study IMvigor 010 IMvigor 211 Phase II IMvigor 210 # of patients N=440 N=767 N=439 After cystectomy: ARM A: atezolizumab monotherapy ARM B: observation Patients who progressed on at least one platinum-containing regimen will receive: ARM A: atezolizumab 1200mg q3w ARM B: chemotherapy (vinflunine, paclitaxel or docetaxel) Cohort 1: Treatment-naive and cisplatin-ineligible patients Cohort 2: Patients with disease progression following or during platinum-containing treatment Progression-free survival Overall survival Objective response rate Status FPI Q3 2015 FPI Q1 2015 Recruitment completed Q1 2015 Readout in 2015 31
Atezolizumab (PD-L1 MAb, MPDL3280A, ) Novel approach in cancer immunotherapy Previously untreated metastatic triple negative breast cancer Untreated advanced renal cell carcinoma Phase/study IMpassion 130 IMmotion 151 Phase II # of patients N=350 N=550 N=305 ARM A: atezolizumab plus nab-paclitaxel ARM B: placebo plus nabpaclitaxel ARM A: atezolizumab plus Avastin ARM B: sunitinib ARM A: atezolizumab plus Avastin ARM B: atezolizumab; following PD: atezolizumab plus Avastin ARM C: sunitinib; following PD: atezolizumab plus Avastin Progression free survival Progression free survival Progression free survival Status FPI Q2 2015 FPI Q2 2015 Recruitment completed Q1 2015 Final readout in 2016 32
Atezolizumab (PD-L1 MAb, MPDL3280A, ) Novel approach in cancer immunotherapy Relapsed/Refractory follicular lymphoma and DLBCL Multiple Myeloma Phase/study Phase I Phase I # of patients N=46 N=46 Stage 1: Safety evaluation atezolizumab plus Gazyva Stage 2: expansion atezolizumab plus Gazyva atezolizumab monotherapy and lenalidomide combination cohorts Safety Safety Status FPI Q4 2014 FPI Q3 2015 33
Atezolizumab (PD-L1 MAb, MPDL3280A, ) Novel approach in cancer immunotherapy Solid tumors Solid tumors Solid tumors Phase/study Phase I Phase I Phase I # of patients N=225 N=160 N=110 ARM A: atezolizumab + Avastin ARM B: atezolizumab + Avastin + FOLFOX ARM C: atezolizumab + carboplatin + paclitaxel ARM D: atezolizumab + carboplatin+ pemetrexed ARM E: atezolizumab + carboplatin+ nab-paclitaxel ARM F: atezolizumab + nabpaclitaxel Part 1: sequential administration of atezolizumab and RG7876 (CD40 MAb) Part 2: concomitant administration of atezolizumab and RG7876 (CD40 MAb) Part 3: study drugs schedule in specific indication per Part 2 Safety/PK Safety Safety Status FPI Q2 2012 Chemo combination data in NSCLC presented at ASCO 2015 FPI Q4 2014 FPI Q1 2015 atezolizumab in combination with emactuzumab (CSF-1R MAb) Part 1: dose escalation Part 2: expansion 34
Atezolizumab (PD-L1 MAb, MPDL3280A, ) Novel approach in cancer immunotherapy Solid tumors Solid tumors Locally advanced or metastatic solid tumors Phase/study Phase I Phase I Phase I # of patients N=224 N=360 N=200 atezolizumab in combination with RG6078 (IDO inhibitor), dose escalation and expansion cohorts Stage 1: Dose escalation of atezolizumab plus RG7888 (OX40 MAb) Stage 2: Expansion atezolizumab plus RG7888 (OX40 MAb) ARM A: atezolizumab plus ipilimumab ARM B: atezolizumab plus interferon alpha-2b Safety Safety Safety Status FPI Q2 2015 FPI Q2 2015 FPI Q3 2014 35
Atezolizumab (PD-L1 MAb, MPDL3280A, ) Novel approach in cancer immunotherapy Previously untreated metastatic melanoma BRAF mutation positive Locally advanced or metastatic solid tumors Phase/study Phase I Phase I # of patients N=44 N=689 Dose-finding study of atezolizumab + Zelboraf 1 and atezolizumab + Zelboraf 1 + cobimetinib (MEK inhibitor) 2 combinations Dose escalation study Safety/PK Safety/PK Status FPI Q4 2012 FPI Q2 2011 Initial efficacy data presented at ASCO 2013 Updated data presented at ECC 2013 Data from bladder cohort presented at ASCO and ESMO 2014 Data from TNBC cohort presented at AACR 2015 Updated lung and bladder data presented at ASCO 2015 1 Zelboraf in collaboration with Plexxikon, a member of Daiichi Sankyo Group; 2 Cobimetinib in collaboration with Exelixis ASCO=American Society of Clinical Oncology; ECC=European Cancer Congress; AACR=American Association for Cancer Research; ESMO=European Society for Medical Oncology 36
Cobimetinib (RG7421, GDC-0973) Selective small molecule inhibitor of mitogenactivated protein kinase kinase Phase/study Previously untreated metastatic melanoma BRAF mutation positive cobrim First-line metastatic triple negative breast cancer Phase II # of patients N=495 N=112 ARM A: Zelboraf 1 plus cobimetinib ARM B: Zelboraf 1 plus placebo ARM A: cobimetinib plus paclitaxel ARM B: placebo plus paclitaxel Progression-free survival Progression-free survival, safety Status met Q3 2014 Data presented at ESMO and SMR 2014 Results published NEJM 2014 Nov 13;371(20):1867-76 Filed in EU Q3 2014 Filed in US Q4 2014 Priority review granted Q1 2015 Updated data presented at ASCO 2015 FPI Q1 2015 In collaboration with Exelixis 1 Zelboraf In collaboration with Plexxikon, a member of Daiichi Sankyo Group; ESMO=European Society for Medical Oncology; SMR=Society for Melanoma Research; NEJM=New England Journal of Medicine; ASCO=American Society of Clinical Oncology 37
Cobimetinib (RG7421, GDC-0973) Selective small molecule inhibitor of mitogenactivated protein kinase kinase (continued) Locally advanced or metastatic tumors Previously untreated metastatic melanoma BRAF mutation positive Locally advanced or metastatic tumors with mutant KRAS Solid tumors Phase/study Phase I Phase I Phase I Phase I # of patients N=90 N=44 N=50 N=142 ARM A: Dose-finding - cobimetinib plus atezolizumab (PD-L1 MAb) ARM B: Doseexpansion - cobimetinib plus atezolizumab (PD- L1 MAb) Dose-finding study of cobimetinib + atezolizumab (PD-L1 MAb) + Zelboraf 1 and atezolizumab (PD-L1 MAb) +Zelboraf 1 combinations Dose finding of cobimetinib plus duligotuzumab (HER3 MAb/EGFR DAF) Dose-finding study of cobimetinib plus RG7842 2 (ERK inhibitor) Safety Safety/PK Safety Safety and tolerability Status FPI Q4 2013 FPI Q4 2012 FPI Q4 2013 FPI Q2 2015 In collaboration with Exelixis 1 Zelboraf In collaboration with Plexxikon, a member of Daiichi Sankyo Group; 2 RG7842 in collaboration with Array BioPharma 38
Polatuzumab vedotin (RG7596) Antibody drug conjugate targeting CD79b for the treatment of B-cell malignancies Non-Hodgkin's lymphoma Non-Hodgkin s lymphoma Relapsed or Refractory follicular lymphoma and DLBCL Phase Phase II ROMULUS Phase Ib/II Phase Ib/II # of patients N=228 N=104 N=224 ARM A: pinatuzumab vedotin plus Rituxan ARM B: polatuzumab vedotin plus Rituxan ARM C: polatuzumab vedotin plus Gazyva PhIb: dose escalation PhII: polatuzumab vedotin in combination with Rituxan or Gazyva and CHP non-randomized PIb: dose escalation PhII: polatuzumab vedotin + BR vs. BR PhII expansion: polatuzumab vedotin +Gazyva non-randomized Safety and anti-tumor activity Safety Safety and response by PET/CT Status Recruitment in arms A&B completed Q1 2014 FPI in Gazyva arm C Q1 2015 Updated data presented at ASCO, ICML and EHA 2015 FPI Q4 2013 FPI Q4 2014 In collaboration with Seattle Genetics ASCO=American Society of Clinical Oncology; ICML=international conference on malignant lymphoma; EHA=European Hematology Association BR=bendamustine and Rituxan; CHP=Cyclophosphamide, Hydroxydoxorubicin, Prednisone 39
Taselisib (RG7604, GDC-0032) Mutant-selective PI3 kinase inhibitor HER2-negative ER-positive metastatic breast caner patients who progressed after aromatase inhibitor therapy Neoadjuvant HER2-negative ERpositive breast cancer Phase SANDPIPER Phase II LORELEI # of patients N=600 N=330 ARM A: taselisib plus Fulvestrant ARM B: placebo plus Fulvestrant ARM A: taselisib plus letrozole ARM B: placebo plus letozole Progression-free survival Response rate and pcr Status FPI Q2 2015 FPI Q4 2014 40
Taselisib (RG7604, GDC-0032) Mutant-selective PI3 kinase inhibitor x Solid tumors and HER2-negative HR-positive breast cancer HER2-negative HR-positive locally recurrent or metastatic breast cancer PI3KCAmut-pos. 2L squamous NSCLC Lung Master Protocol Phase Phase I/II Phase I Phase II Lung-MAP # of patients N=320 N=65 N=120 Phase I taselisib taselisib plus letrozole or fulvestrant taselisib plus docetaxel taselisib plus paclitaxel taselisib vs. chemo Phase II taselisib (multiple doses) plus letrozole or fulvestrant Safety/PK/efficacy Safety Progression-free survival Status Recruitment completed Q2 2014 Updated data presented at SABCS 2014 FPI Q2 2013 FPI Q2 2014 SABCS=San Antonio Breast Cancer Symposium 41
Venetoclax (RG7601, ABT-199/GDC-0199) Novel small molecule Bcl-2 selective inhibitor Untreated CLL patients with coexisting medical conditions Relapsed or Refractory CLL Relapsed or Refractory CLL with 17p deletion Phase/study CLL14 MURANO Phase II # of patients N=432 N=370 N=100 ARM A: venetoclax plus Gazyva ARM B: chlorambucil plus Gazyva ARM A: venetoclax plus Rituxan ARM B: Rituxan plus bendamustine Single-agent venetoclax Progression-free survival Progression-free survival Safety/MTD Status FPI Q4 2014 FPI Q1 2014 Recruitment completed Q2 2014 Data expected in 2015 Breakthrough designation granted in Q2 2015 Joint project with AbbVie in collaboration with WEHI (The Walter and Eliza Hall Institute) CLL=Chronic Lymphocytic Leukemia; ASCO=American Society of Clinical Oncology 42
Venetoclax (RG7601, ABT-199/GDC-0199) Novel small molecule Bcl-2 selective inhibitor (continued) Relapsed or Refractory CLL Relapsed CLL and SLL Relapsed or Refractory or previously untreated CLL Relapsed or Refractory or previously untreated CLL Phase/stud y # of patients Phase II Phase Ib Phase Ib Phase Ib N=40 N=50 N=70 N=74 venetoclax after ibrutinib therapy venetoclax after idelalisib therapy Dose-escalation study in combination with MabThera/Rituxan venetoclax in combination with MabThera/Rituxan and bendamustine venetoclax in combination with Gazyva Overall response rate Safety/MTD Safety/MTD Safety/MTD Status FPI Q3 2014 Recruitment completed Q1 2015 Data presented at ASCO 2014 and EHA 2015 FPI Q2 2013 FPI Q1 2014 Joint project with AbbVie in collaboration with WEHI (The Walter and Eliza Hall Institute) CLL=Chronic Lymphocytic Leukemia; SLL=Small Lymphocytic Lymphoma ASCO=American Society of Clinical Oncology; EHA=European hematology association 43
Venetoclax (RG7601, ABT-199/GDC-0199) Novel small molecule Bcl-2 selective inhibitor (continued) Relapsed or Refractory follicular NHL Front-line DLBCL Relapsed or Refractory NHL Relapsed or Refractory CLL and NHL Phase/study Phase II CONTRALTO Phase I/II CAVALLI Phase I Phase I # of patients N=156 N=230 N=40 N=211 ARM A: venetoclax plus Rituxan ARM B: venetoclax plus Rituxan plus bendamustine ARM C: Rituxan plus bendamustine Dose finding: ARM A: venetoclax+r- CHOP ARM B: venetoclax+g- CHOP Expansion: venetoclax+r/g-chop Dose escalation of venetoclax in combination with Rituxan and bendamustine Dose-escalation study Overall response rate Safety and efficacy Overall response rate Safety/PK/Response rate Status FPI Q4 2014 FPI Q2 2014 FPI Q2 2012 Study resumed Q3 2013 Data presented at ASCO 2015 FPI Q2 2011 Updated CLL, SLL and NHL (DLBCL and FL) data presented at ASCO 2014 Joint project with AbbVie in collaboration with WEHI (The Walter and Eliza Hall Institute) NHL=Non-Hodgkin's Lymphoma; SLL=Small Lymphocytic Lymphoma; CLL=Chronic Lymphocytic Leukemia ASCO=American Society of Clinical Oncology 44
Venetoclax (RG7601, ABT-199/GDC-0199) Novel small molecule Bcl-2 selective inhibitor (continued) Relapsed or refractory multiple myeloma Acute myelogenous leukemia (AML) Phase/study Phase I Phase I Phase II Phase Ib # of patients N=30 N=30 N=54 N=89 Patients receiving Bortezomib and Dexamethasone as standard therapy: Dose escalation cohort: venetoclax+bortezomib+de xamethasone Safety expansion cohort: venetoclax+bortezomib+de xamethasone Dose escalation cohort Safety expansion cohort Dose escalation of venetoclax venetoclax (dose escalation) +decitabine venetoclax (dose escalation) +azacitidine Safety/MTD Safety/MTD Overall response rate Safety Status FPI Q4 2012 Data presented at ASCO 2015 FPI Q4 2012 Data presented at ASCO 2015 FPI Q4 2013 Data presented at ASH 2014 FPI Q4 2014 Joint project with AbbVie in collaboration with WEHI (The Walter and Eliza Hall Institute) ASH=American Society of Hematology 45
Factor IXa/X bispecific (RG6013, ACE910) Factor VIII mimetic for treatment of hemophilia A Hemophilia A inhibitors to Factor VIII Hemophilia A patients with Phase/study Phase I Study in Japan Phase I/II Study in Japan Non-Interventional study # of patients N=82 N=16 N=70 Enrolled 64 HVs and 18 patients Extension study in patients from phase 1 A single arm, multicenter, noninterventional study evaluating bleeding incidence, healthrelated quality of life and safety in patients with Hemophilia A and inhibitors against Factor VIII under standard-of-care treatment Exploratory efficacy and safety Exploratory efficacy and safety Number of bleeds over time, sites of bleed, type of bleed Status Recruitment completed Q2 2014 Data presented at ASH 2014 Recruitment completed Q4 2014 Data presented at ISTH 2015 FPI Q2 2015 In collaboration with Chugai ASH=American Society of Hematology, ISTH=International Society on Thrombosis and Haemostasis 46
Bitopertin (GlyT-1, RG1678) A small molecule first-in-class glycine reuptake inhibitor (GRI) Obsessive-compulsive disorder Phase/study Phase II SKYLYTE # of patients N=99 16-week treatment period Background therapy of selective serotonin reuptake inhibitors (SSRI) ARM A: bitopertin daily (30 mg) ARM B: bitopertin daily (10 mg) ARM C: placebo Change in total score on Yale-Brown Obsessive Compulsive Scale Status Enrollment completed Q4 2014 Data expected in 2015 47
Crenezumab (RG7412) A humanized monoclonal antibody designed to target all forms of amyloid-beta Alzheimer s Disease Phase/study Phase II ABBY Cognition study Phase II BLAZE Biomarker study # of patients N=446 N=91 ARM A: crenezumab SC ARM B: crenezumab IV ARM C: placebo Change in cognition (ADAS-cog) and Clinical Dementia Rating, Sum of Boxes (CDR-SOB) score from baseline to week 73 ARM A: crenezumab SC ARM B: crenezumab IV ARM C: placebo Change in brain amyloid load from baseline to week 69 Status Enrollment completed Q3 2012 Positive trend in cognition was observed in ARM B for people with milder disease Data presented at AAIC 2014 Enrollment completed Q3 2012 Cognition data presented at AAIC 2014 Exploratory amyloid PET analysis suggests reduced amyloid accumulation in ARM B Biomarker data presented at CTAD 2014 In collaboration with AC Immune AAIC=Alzheimer s Association International Conference; CTAD=Clinical Trials on Alzheimer s Disease 48
Crenezumab (RG7412) A humanized monoclonal antibody designed to target all forms of amyloid-beta Phase/study Mild to Moderate Alzheimer's disease Phase I Alzheimer s Prevention Initiative (API) Colombia Phase II Cognition study # of patients N=72 N=300 ARM A: crenezumab dose level 1 ARM B: placebo dose level 1 ARM C: crenezumab dose level 2 ARM D: placebo dose level 2 ARM A: 100 carriers receive crenezumab SC ARM B: 100 carriers receive placebo ARM C: 100 non-carriers receive placebo Safety (incidence and nature of MRI safety findings) Change on Alzheimer's Prevention Initiative (API) Composite Cognitive Test total score Status FPI Q1 2015 FPI Q4 2013 In collaboration with AC Immune 49
Gantenerumab (RG1450) Fully human monoclonal antibody designed to bind to aggregated forms of amyloid-beta Prodromal Alzheimer s Disease Mild Alzheimer s Disease Phase/study Phase II/III SCarlet RoAD Marguerite RoAD # of patients N=799 N=1,000 Status 104-week subcutaneous treatment period ARM A: gantenerumab (225 mg) ARM B: gantenerumab (105 mg) ARM C: placebo Change in CDR-SOB at 2 years Sub-study: change in brain amyloid by PET at 2 years Phase I PET data: Archives of Neurology 2012 Feb;69(2):198-207 Enrollment completed Q4 2013 Dosing stopped due to futility Q4 2014 Data presented at AAIC 2015 104-week subcutaneous treatment period ARM A: gantenerumab ARM B: placebo Change in ADAS-Cog and CDR-SB at 2 years (co-primary) FPI Q1 2014 In collaboration with Morphosys CDR-SOB=Clinical Dementia Rating scale Sum of Boxes 50
Etrolizumab (RG7413) A humanized monoclonal antibody against beta 7 integrin Ulcerative colitis patients who are TNF naïve Phase/study HIBISCUS I Induction study HIBISCUS II Induction study GARDENIA Sustained remission study # of patients N=350 N=350 N=720 ARM A: etrolizumab 105mg SC q4w + adalimumab placebo ARM B: etrolizumab placebo + adalimumab ARM C: etrolizumab placebo + adalimumab placebo ARM A: etrolizumab 105mg SC q4w + adalimumab placebo ARM B: etrolizumab placebo + adalimumab ARM C: etrolizumab placebo + adalimumab placebo Time on treatment 54 weeks ARM A: etrolizumab 105mg SC q4w + placebo IV ARM B: placebo SC q4w + adalimumab SC Induction of remission compared with placebo as determined by the Mayo Clinic Score (MCS) at week 10 Induction of remission compared with placebo as determined by the Mayo Clinic Score (MCS) at week 10 Proportion of patients in sustained clinical remission as determined by Mayo Clinic Score (MCS) at weeks 10, 30 and 54 Status FPI Q4 2014 FPI Q4 2014 FPI Q4 2014 51
Etrolizumab (RG7413) A humanized monoclonal antibody against beta 7 integrin (continued) Phase/study UC patient who are TNF naïve and refractory or intolerant to immunosuppressant and/or corticosteroid treatment LAUREL Maintenance study UC patient who are refractory or intolerant of TNF inhibitors HICKORY Induction and maintenance study # of patients N=350 N=800 Induction phase: ARM A: open label etrolizumab 105mg SC q4w Maintenance study: ARM B: etrolizumab 105mg SC q4w ARM C: placebo Maintenance of remission (at week 62) among randomized patients in remission at Week 10 as determined by the Mayo Clinic Score (MCS) Cohort 1 (open-label): ARM A: etrolizumab induction + placebo maintenance ARM B: etrolizumab induction + maintenance Cohort 2 (blinded): ARM A: etrolizumab induction + maintenance ARM B: placebo induction + maintenance Clinical Remission (Mayo Clinic Score, MCS) at Week 14 Remission maintenance (by MCS, at Week 66) among patients with remission at Week 14 Status FPI Q3 2014 FPI Q2 2014 UC=ulcerative colitis 52
Etrolizumab (RG7413) A humanized monoclonal antibody against beta 7 integrin (continued) Moderate to severe ulcerative colitis Moderate to severe ulcerative colitis Phase/study Phase II SPRUCE Open label extension study COTTONWOOD Open label extension study # of patients N=116 N=2,600 Patients who were enrolled in EUCALYPTUS study and meet enrollment criteria will receive etrolizumab 105 sc q4w Patients who were previously enrolled in etrolizumab phase III studies and meet enrollment criteria will receive etrolizumab 105 sc q4w Safety Long-term efficacy as determined by partial Mayo Clinic Score (pmcs) Incidence of adverse events Status Recruitment completed FPI Q3 2014 53
Etrolizumab (RG7413) A humanized monoclonal antibody against beta 7 integrin (continued) Moderately to severely active Crohn's disease Moderately to severely active Crohn's disease Phase/study BERGAMOT JUNIPER # of patients N=1,250 N=1,250 ARM A: etrolizumab SC 210 mg (induction only) ARM B: etrolizumab SC 105 mg and maintainance ARM C: placebo Etrolizumab SC 105mg q4w Induction and maintenance of clinical remission Safety Status FPI Q1 2015 FPI Q2 2015 54
HCV: Danoprevir (RG7227) IFN-based triple regimen for treatment-naïve patients of Asian origin conducted in China Phase/study Treatment-naïve patients of Asian origin with chronic hepatitis C genotype 1 with or without cirrhosis Phase II DAPSANG # of patients N=61 Without cirrhosis: ARM A: Danoprevir 125 mg bid + Ritonavir 100mg bid+ Pegasys + Copegus for 12 weeks With compensated cirrhosis: ARM B: Danoprevir 125 mg bid + Ritonavir 100mg bid+ Pegasys + Copegus for 24 weeks Safety Status Recruitment completed Q4 2013 Results presented at APASL 2015 In collaboration with Ascletis APASL=Asian Pacific Association for the Study of the Liver 55
Lampalizumab (RG7417) Antibody fragment to selectively block activation of alternative complement pathway Geographic atrophy (GA) secondary to age-related macular degeneration Phase/study CHROMA SPECTRI Phase II # of patients N=936 N=936 N=100 ARM A: lampalizumab 10mg q4w ARM B: lampalizumab 10mg q6w ARM C: placebo ARM A: lampalizumab 10mg q4w ARM B: lampalizumab 10mg q6w ARM C: placebo ARM A: lampalizumab 10mg q2w ARM B: lampalizumab 10mg q4w ARM C: placebo : change in GA area Secondary: change in BCVA and in additional measures of visual function : change in GA area Secondary: change in BCVA and in additional measures of visual function Change in GA area Status FPI Q3 2014 presented at EURETINA 2014 Fast track designation received Q4 2014 FPI Q3 2014 presented at EURETINA 2014 Fast track designation received Q4 2014 FPI Q4 2014 EURETINA=European Society of Retina Specialists 56
Lebrikizumab (RG3637) A humanized monoclonal antibody designed to bind specifically to IL-13 Severe uncontrolled adult asthma Adult patients whose asthma is uncontrolled with inhaled corticosteroids and a second controller medication Phase/study # of patients LAVOLTA I N=1,050 Subcutaneous lebrikizumab q4w on top of SOC for 52 weeks safety follow-up ARM A: lebrikizumab high dose ARM B: lebrikizumab low dose ARM C: placebo Patients will be tested for periostin level LAVOLTA II N=1,050 Subcutaneous lebrikizumab q4w on top of SOC for 52 weeks safety follow-up ARM A: lebrikizumab high dose ARM B: lebrikizumab low dose ARM C: placebo Patients will be tested for periostin level Rate of asthma exacerbations during the 52-week placebo-controlled period Rate of asthma exacerbations during the 52-week placebo-controlled period Status Enrollment completed Q4 2014 Expect data in 2016 Enrollment completed Q4 2014 Expect data in 2016 57
Lebrikizumab (RG3637) A humanized monoclonal antibody designed to bind specifically to IL-13 (continued) Phase/study Adolescent patients whose asthma is uncontrolled with inhaled corticosteroids and a second controller medication ACOUSTICS Idiopathic pulmonary fibrosis Phase II RIFF # of patients N=375 N=300 Subcutaneous lebrikizumab q4w on top of SOC for 52 weeks with 52 week double-blind active treatment extension ARM A: lebrikizumab high dose, week 1-104 or week 52-104 ARM B: lebrikizumab low dose, week 1-104 or week 52-104 ARM C: placebo, week 1-52 Rate of asthma exacerbations during the 52- week placebo-controlled period ARM A: lebrikizumab SC q4w ARM B: placebo ARM C: lebrikizumab SC q4w + Esbriet ARM D: Esbriet Change in FVC at week 52 Status FPI Q3 2013 FPI Q4 2013 (arms A&B) FPI July 2015 (Esbriet arms C&D) SOC=Standard of Care; OCS=Oral Corticosteroids 58
Lebrikizumab (RG3637) A humanized monoclonal antibody designed to bind specifically to IL-13 (continued) Adult asthma Adult asthma mild-to-moderate patients Adult asthma Phase/study Phase II VOCALS STRETTO Phase II CLAVIER Mechanistic biomarker study # of patients N=225 N=300 N=120 ARM A: lebrikizumab high dose SC q4w ARM B: lebrikizumab low dose SC q4w ARM C: placebo ARM A: lebrikizumab SC q4w ARM B: placebo ARM C: Montelukast ARM A: lebrikizumab SC q4w ARM B: placebo Relative change in OCS dose at week 44 Absolute change in FEV1 at week 12 Status FPI Q1 2014 FPI Q2 2014 FPI Q4 2014 Relative change in airway inflammation (eosinophils/mm2) at week 12 59
Lebrikizumab (RG3637) A humanized monoclonal antibody designed to bind specifically to IL-13 (continued) Moderate-to-severe atopic dermatitis Phase/study Phase II TREBLE Phase II ARBAN Safety Study # of patients N=200 N=50 Patients on topical corticosteroids ARM A: lebrikizumab dose 1 ARM B: lebrikizumab dose 2 ARM C: lebrikizumab dose 3 ARM D: placebo ARM A: lebrikizumab ARM B: topical corticosteroids Percentage of patients achieving a 50% reduction in Eczema Area and Severity Index (EASI) score (EASI-50) from baseline to week 12 Safety comparison of lebrikizumab vs. TCS Status FPI Q2 2015 Expect FPI Q3 2015 TCS=topical corticosteroids 60
Ocrelizumab (RG1594) 2nd generation CD20 monoclonal antibody Relapsing multiple sclerosis (RMS) progressive multiple sclerosis (PPMS) Phase/study OPERA I OPERA II ORATORIO # of patients N=800 N=800 N=630 96-week treatment period: ARM A: Ocrelizumab 2x 300 mg iv followed by 600 mg iv every 24 weeks ARM B: Interferon -1a 96-week treatment period: ARM A: Ocrelizumab 2x 300 mg iv followed by 600 mg iv every 24 weeks ARM B: Interferon -1a 120-week treatment period: ARM A: Ocrelizumab 2x 300 mg iv every 24 weeks ARM B: Placebo 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 met Q2 2015 Expect global filing in 2016 met Q2 2015 Expect global filing in 2016 Enrollment completed Q1 2013 Expect data in H2 2015 61
Olesoxime (RG6083) Novel small molecule neuroprotectant that preserves mitochondrial function Spinal muscular atrophy Phase/study Phase II Registrational study # of patients N=165 ARM A: olesoxime ARM B: placebo Motor function measure Status Study completed Q4 2013 Presented at AAN 2014 Collaborator Trophos acquisition 62
Pipeline summary Marketed products additional indications Global Development late-stage trials pred (Roche Pharma Research & Early Development) gred (Genentech Research & Early Development) Roche Group HY 2015 results Diagnostics Foreign exchange rate information 63
Oncology development programmes Small molecules Molecule Idasanutlin (MDM2 antagonist, RG7388) MDM2 antagonist IV prodrug (RG7775) LSD1 inhibitor (RG6016) Raf/MEK inhibitor (RG7304, CKI27) Acute myeloid leukemia Advanced cancers including AML Acute Leukemia Solid tumors Phase Phase I Phase I Phase I Phase I # of patients N=100 N=90 N=30 N=52 Multiple ascending doseescalation study Dose-escalation study ARM A: patients with advanced solid tumors ARM B: patients with r/r AML Multiple ascending dose-escalation study Dose-escalation to MTD MTD MTD MTD MTD and tumor assessment Status FPI Q1 2013 Data presented at ASH 2014 FPI Q2 2014 FPI Q1 2014 Initiated Q4 2008 Enrollment stopped in Q4 2010 Collaborator Oryzon Genomics, S.A. Chugai ASH=American Society of Hematology 64
Oncology development programmes Monoclonal antibodies Molecule Metastatic liver cancer (hepatocellular carcinoma) Glypican-3 MAb (GC33, RG7686) 2L metastatic liver cancer (hepatocellular carcinoma) Phase Phase Ib Phase II # of patients N= 40-50 N=185 Study US monotherapy Study Japan monotherapy Dose escalation study in combo with SOC Safety and tolerability Adaptive design study Double blind randomized 2:1 RG7686: placebo Patients are stratified according to the level of GPC-3 expression in tumor Progression-free survival Status Recruitment completed Q4 2013 Data presented at ASCO 2014 Further steps under evaluation Recruitment completed Q1 2013 Data presented at ASCO 2014 Further steps under evaluation Collaborator Chugai SOC=standard of care; ASCO=American Society of Clinical Oncology 65
Oncology development programmes Monoclonal antibodies (continued) Molecule Lumretuzumab (GE-huMAb HER3 MAb, RG7116) Vanucizumab (Ang2-VEGF MAb, RG7221) Solid tumors HER2-low and HER3- positive metastatic breast cancer Solid tumors Metastatic colorectal cancer Phase Phase I Phase I Phase I Phase II McCAVE # of patients N=105 N=40 N 80 N=140 Multiple ascending dose study with extension cohorts and imaging sub-study Combination arms with HER1- targeted therapies (erlotinib, cetuximab) Multiple ascending dose of RG7116 in combination with Perjeta and paclitaxel Multiple ascending dose study with extension cohorts in solid tumors to assess the PD effects and platinum-resistant ovarian cancer ARM A: Induction: Avastin+mFOLFOX-6; followed by maintenance: Avastin+5-FU/LV ARM B: Induction: RG7221+mFOLFOX-6; followed by maintenance: RG7221+5-FU/LV Safety, PK Safety, PK Safety, PK Progression-free survival Status FPI Q4 2011 Initial data presented at ASCO 2013 FPI Q3 2013 FPI Q4 2012 Dose escalation data presented at ASCO 2014 Ovarian cancer cohort data presented at ASCO 2015 Recruitment completed Q1 2015 Data expected in 2016 ASCO=American Society of Clinical Oncology 66
Oncology development programmes Monoclonal antibodies (continued) Molecule Emactuzumab (CSF-1R humab, RG7155) CEA-IL2v (RG7813) Solid tumors and PVNS Solid tumors Solid tumors Solid tumors Phase Phase I/II Phase I Phase I Phase Ib # of patients N 140 N=110 N~110 N=75 Multiple ascending dose study +/- paclitaxel with extension cohorts RG7155 in combination with atezolizumab (PD-L1 MAb) Part 1: dose escalation Part 2: expansion Single and multiple dose escalation study with extension cohorts Part 1: dose escalation of RG7813 in combination with atezolizumab (PD-L1 Mab) Part 2: dose expansion RG7813 in combination with atezolizumab (PD-L1 MAb) Safety, PK, PD & preliminary clinical activity Status FPI Q4 2011 Biomarker data presented at AACR 2013 and AACR 2014 Data presented at ASCO 2014 Updated data presented at ASCO 2015 Safety Safety, PK, PD Safety, Efficacy, PK, PD FPI Q1 2015 FPI Q4 2013 Imaging data presented at ASCO 2015 FPI in Q2 2015 AACR=American Association for Cancer Research; ASCO=American Society of Clinical Oncology 67
Oncology development programmes Monoclonal antibodies (continued) Molecule CEA CD3 T-cell bispecific (TCB) (RG7802) CD40 imab (RG7876) in combination with atezolizumab (PD-L1 MAb) CEA-positive solid tumors Solid tumors Phase Phase Ia Phase I # of patients N=90 N=160 Multiple ascending dose study with extension cohorts and imaging sub-study Safety, PK, PD, imaging, BM Part 1A: sequential administration of RG7876 and atezolizumab (PD-L1 MAb) Part 1B: concomitant administration of RG7876 and atezolizumab (PD-L1 MAb) Part 2: multiple doses of concomitant RG7876 and atezolizumab (PD-L1 MAb) Part 3: study drugs schedule in specific indications per Part 2 Safety Status FPI Q4 2014 FPI Q4 2014 68
Neuroscience development programmes Molecule Phase Down Syndrome Phase IIB CLEMATIS GABRA5 NAM (RG1662) Down Syndrome Children 6 to 11 Years of Age Phase II # of patients N=180 N=36 For 26 weeks patients will receive: ARM A: RG1662 120mg twice daily ARM B: RG1662 120mg twice daily ARM C: Placebo For 26 weeks patients will receive 1 of 3 dosages of RG1662 PO BID, Including 40 mg, 60 mg, or 120 mg Cognition and adaptive behavior PK, PD, efficacy, safety, and tolerability Status FPI Q2 2014 Expect FPI Q3 2015 NAM=Negative allosteric modulator 69
Neuroscience development programmes (continued) Molecule V1 receptor antagonist (RG7314) SMN2 splicing modifier (RG7800) Basimglurant (mglu5 NAM, RG7090) Autism Spinal muscular atrophy Adjunctive Treatment of Major Depressive Disorder Phase Phase II VANILLA Phase Ib MOONFISH Phase II Marigold # of patients N=225 N=48 N=300 Multi-center, randomized, doubleblind, placebo-controlled proof-ofconcept study in individuals with Autism Spectrum Disorder (ASD) Randomized, double-blind, 12-week, placebo-controlled multiple dose study in adult and pediatric patients ARM A: basimglurant 0.5 mg ARM B: basimglurant 1.5 mg ARM C: matching placebo Safety and efficacy Safety and tolerability Efficacy - Montgomery Asberg Depression Rating Scale Status FPI Q3 2013 Study on hold First cohort closed Study completed Data in-house under review Data presented at ECNP and ACNP 2014 & ASCP 2015 Collaborator PTC Therapeutics/ SMA Foundation ECNP=European College of Neuropsychopharmacology; ACNP=American College of Neuropsychopharmacology ASCP=American Society of Clinical Phsycopharmacology 70
Neuroscience development programmes (continued) Molecule Anti-aSynuclein (RG7935, PRX002) Sembragiline (MAO-B inhibitor, RG1577, EVT-302) MAb Tau (RG7345) Parkinson s disease Alzheimer s Disease Alzheimer s disease Phase Phase I Phase I Phase IIb MAyflOwer RoAD Phase I # of patients N=40 N=up to 60 N=495 N=48 Double-blind, placebocontrolled, single ascending dose study of RG7935 in healthy subjects Double-blind, placebocontrolled, multiple ascending dose study of RG7935 in patients with Parkinson s disease 52-week oral treatment ARM A: RG1577 (dose 1) ARM B: RG1577 (dose 2) ARM C: placebo Randomized, double-blind, placebo-controlled, single ascending dose study of RG7345 in healthy volunteers Safety, tolerability and PK Safety and tolerability Changes in ADAS-Cog at 52 weeks Safety Status Study completed Q1 2015 Data presented at MDS 2015 FPI Q3 2014 Recruitment completed Q2 2014 not met Q2 2015 Results under internal review FPI Q1 2015 Collaborator Prothena Evotec MDS=Movement Disorder Society 71
Infectious diseases development programmes Molecule NME (RG7689) DBO Beta lactamase inhibitor (RG6080) TLR7 agonist (RG7795) HBV therapeutic vaccine (RG7944, INO-1800 and INO- 9112)) Infectious diseases Infectious diseases Chronic hepatitis B Chronic hepatitis B Phase Phase I Phase I Phase II Phase I # of patients N=77 N=40 N=40 N=126 Double-blind, randomized, placebo-controlled, singleascending dose (SAD) and multiple-ascending dose (MAD) study in healthy volunteers Randomized, double-blind, placebo-controlled, singleascending dose study in healthy volunteers Various doses of RG7795 vs. placebo INO-1800, alone or in combination with INO- 9112 Safety, PK/PD Safety, PK Safety, efficacy Safety, tolerability and immunogenicity Status FPI Q4 2014 Study completed FPI Q2 2015 FPI Q2 2015 Collaborator Meiji and Fedora Inovio 72
Ophthalmology and immunology development programmes Molecule VEGF/Ang2 MAb (RG7716) Wet age-related macular degeneration NME (RG7625) Autoimmune diseases Phase/study Phase II Phase I # of patients N=271 N=16 Arm A: SoC (Lucentis, q4w Arm B: 1.5 mg VA2, q4w Arm C: 6mg VA2, q4w / q8w Arm E: Soc q4w x 3 doses, switch group to 6 mg VA2 q4w Single ascending dose (SAD) of RG7625 in healthy volunteers Endpoint Visual acuity (change in BCVA) Safety, PK, PD Status Expect FPI Q3 2015 SAD completed Q2 2015 73
Pipeline summary Marketed products additional indications Global Development late-stage trials pred (Roche Pharma Research & Early Development) gred (Genentech Research & Early Development) Roche Group HY 2015 results Diagnostics Foreign exchange rate information 74
Oncology development programmes Monoclonal antibodies Molecule Duligotuzumab (HER3/EGFR DAF MAb, RG7597) OX40 MAb (RG7888, MOXR0916) Locally advanced or metastatic tumors with mutant KRAS Solid tumors Solid tumors Phase/study Phase I Phase I Phase I # of patients N=50 N=400 N=360 Dose finding of duligotuzumab plus cobimetinib* (MEK inhibitor) RG7888 dose escalation and expansion study RG7888 plus atezolizumab (PD- L1 MAb) dose escalation and expansion Safety Safety Safety Status FPI Q4 2013 FPI Q3 2014 FPI Q2 2015 * Cobimetinib in collaboration with Exelixis 75
Oncology development programmes Antibody-drug conjugates Molecule STEAP1 ADC (RG7450) NME ADC (RG7882) Ly6E ADC (RG7841) Prostate cancer Pt-resistant ovarian cancer or unresectable pancreatic cancer HER2-neg. breast cancer and NSCLC Phase Phase I Phase I Phase I # of patients N=90 N=95 N=115 Dose escalation and expansion study Dose escalation and expansion study Dose escalation study Safety Safety/PK Safety Status Collaborator Dose escalation study: enrollment completed Q1 2014 Expansion study: enrollment completed Q2 2015 Data presented at ASCO 2013-2015 & AACR 2014-2015 Seattle Genetics and Agensys FPI Q2 2014 FPI Q2 2014 Expansion study: FPI Q2 2015 Seattle Genetics ASCO=American Society of Clinical Oncology; AACR=American Association for Cancer Research 76
Oncology development programmes Antibody-drug conjugates (continued) Molecule Lifastuzumab vedotin (NaPi2b ADC, RG7599) NSCLC and ovarian cancer Platinum-sensitive ovarian cancer and NSCLC Platinum-resistant ovarian cancer Phase Phase I Phase Ib Phase II HERAEA # of patients N=96 N=54 N=92 Dose escalation study Dose escalation of RG7599 in combination with carboplatin, with or without Avastin ARM A: RG7599 ARM B: Pegylated liposomal doxorubicin Safety Safety, PK Progression-free survival Status FPI Q2 2011 Data presented at ASCO 2014 FPI Q4 2013 Recruitment completed Q1 2015 Data expected in 2016 Collaborator Seattle Genetics ASCO=American Society of Clinical Oncology 77
Oncology development programmes Small molecules Molecule Indoleamine 2, 3-dioxygenase (IDO) Inhibitor (RG6078, GDC-0919, NLG919) Solid tumors Solid tumors Phase Phase I Phase I # of patients N=36 N=224 Dose escalation study Dose escalation and expansion study of IDO and atezolizumab (PD-L1 MAb) combination Safety Safety, tolerability, and PK Status FPI Q1 2014 Expect FPI Q3 2015 Collaborator NewLink Genetics 78
Oncology development programmes Small molecules (continued) Molecule ChK1 inhibitor (RG7741,GDC-0575) ERK inhibitor (RG7842, GDC-0994) Solid tumors or lymphoma Solid tumors Solid tumors Phase Phase I Phase I Phase I # of patients N=90 N=78 N=142 Stage 1: Dose escalation Stage 2: Cohort expansion Stage 1: Dose escalation Stage 2: Cohort expansion Dose escalation study of RG7842 and cobimetinib (MEK inhibitor)* combination Safety/PK Safety, MTD, PK Safety and tolerability Status FPI Q2 2012 FPI Q2 2013 FPI Q2 2015 Collaborator Array BioPharma *Cobimetinib in collaboration with Exelixis 79
Oncology development programmes Small molecules (continued) Molecule Selective estrogen receptor degrader (SERD) (RG6046, GDC-0810/ARN-810) Metastatic ER+ HER2-neg. breast cancer Selective estrogen receptor degrader (SERD(2)) (RG6047, GDC-0927/SRN-927) Metastatic ER+ HER2-neg. breast cancer Phase Phase I/IIa Phase I # of patients N=141 N=90 Phase I: dose escalation Phase IIa: dose expansion Dose escalation study Safety, PK, MTD Safety Status FPI Q4 2014 Initial data presented at SABCS 2014 and AACR 2015 FPI Q1 2015 Collaborator Seragon acquisition SABCS=San Antonio Breast Cancer Symposium; AACR=American Association for Cancer Research 80
Oncology development programmes Small molecules (continued) Molecule Phase 2L castration-resistant prostate cancer Phase II A.MARTIN Ipatasertib (AKT inhibitor, RG7440, GDC-0068) 1L metastatic gastric or gastroesophageal junction adenocarcinoma Phase II JAGUAR 1L triple-negative breast cancer Phase II LOTUS # of patients N=262 N=153 N=120 ARM A: ipatasertib (400mg) + abiraterone ARM B: ipatasertib (200mg) + abiraterone ARM C: placebo + abiraterone ARM A: ipatasertib + mfolfox6 ARM B: placebo + mfolfox6 ARM A: ipatasertib + paclitaxel ARM B: placebo + paclitaxel Progression-free survival Progression-free survival Progression-free survival Status Enrollment completed Q4 2014 Data expected in 2015 Collaborator Enrollment completed Q4 2014 Data expected in 2015 Array BioPharma FPI Q3 2014 mfolfox6=modified FOLFOX (Folinic acid, Fluorouracil, Oxaliplatin) 81
Oncology development programmes Small molecules (continued) Molecule Ipatasertib (AKT inhibitor, RG7440, GDC-0068) Solid tumors Neoadjuvant TNBC Phase Phase Ib Phase II FAIRLANE # of patients N=120 N=150 Dose escalation with: ARM A: docetaxel ARM B: fuoropyrimidine plus oxaliplatin ARM C: paclitaxel ARM D: enzalutamide Safety ARM A: ipatasertib + paclitaxel ARM B: placebo + paclitaxel Pathologic complete response (pcr) Status FPI Q3 2011 Data presented at ESMO and SABCS 2014 FPI Q1 2015 Collaborator Array BioPharma ESMO=European Society for Medical Oncology; SABCS=San Antonio Breast Cancer Symposium 82
Immunology, infectious disease and neuroscience development programmes Molecule NME (RG7880) Inflammatory diseases NME (RG6069, GDC-3280) Anti-Flu A (RG7745) Nav1.7 (RG7893, GDC-0276) Fibrosis Influenza Pain Phase/study Phase I Phase I Phase IIb Phase I # of patients N=74 N=88 N~300 N~200 Healthy volunteer study Randomized, doubleblind, placebo-controlled, ascending, single- and multiple-oral dose study Hospitalized patients requiring oxygen with severe influenza A ARM A: RG7745 + Tamiflu ARM B: placebo + Tamiflu Phase 1, randomized, placebo-controlled, double blinded study in healthy volunteers Safety and tolerability Safety, tolerability, and PK Safety and efficacy (time to normalization of respiratory function) Safety, tolerability, and pharmacokinetics of single and multiple doses Status FPI Q4 2014 FPI Q2 2015 FPI Q1 2015 FPI Q3 2014 Collaborator Xenon Pharmaceuticals Inc. 83
Pipeline summary Marketed products additional indications Global Development late-stage trials pred (Roche Pharma Research & Early Development) gred (Genentech Research & Early Development) Roche Group HY 2015 results Diagnostics Foreign exchange rate information 84
Diagnostics Division CER growth By Region and Business Area (vs. 2014) Global North America EMEA¹ RoW % CER % CER % CER % CER CHFm growth CHFm growth CHFm growth CHFm growth Professional Diagnostics 2,972 7 648 2 1,203 3 1,121 14 Diabetes Care 1,057 1 193-12 634 1 230 13 Molecular Diagnostics 832 12 331 17 324 17 177-4 Tissue Diagnostics 374 12 222 8 99 17 53 23 Diagnostics Division 5,235 7 1,394 4 2,260 5 1,581 12 CER=Constant Exchange Rates ¹ Europe, Middle East and Africa 85
Diagnostics Division quarterly sales and CER growth 1 Q1 14 Q2 14 Q3 14 CHFm % CER CHFm % CER CHFm % CER Q4 14 Q1 15 Q2 15 CHFm % CER CHFm % CER CHFm % CER Professional 1,521 10 1,512 8 1,493 8 1,648 8 1,425 6 1,547 8 Diagnostics Diabetes 678-4 602-4 581 4 671 1 507 1 550 0 Care Molecular 416 3 392 3 403 8 448 7 401 10 431 14 Diagnostics Tissue 184 10 178 14 175 13 207 10 178 14 196 11 Diagnostics Dia Division 2,799 5 2,684 5 2,652 7 2,974 7 2,511 6 2,724 7 CER=Constant Exchange Rates ¹ versus same period of prior year 86
HY 2015: Diagnostics Division sales Growth driven by Asia Pacific and EMEA 1 CHF 5,235 m CER sales growth 1,394 North America 27% Diagnostics Division 7% Asia Pacific 19% EMEA¹ 5% 1,037 North America 4% Asia Pacific 15% 2,260 189 355 Latin America Japan EMEA 1 7% 4% 43% Latin America Japan -6% 14% CER=Constant Exchange Rates ¹ Europe, Middle East and Africa 87
HY 2015: Diagnostics Division sales Growth driven by Professional Diagnostics CHF 5,235 m CER sales growth 1,057 Diabetes Care 20% Dia Division 7% Molecular Diagnostics 16% Professional Diagnostics 7% 832 Diabetes Care 1% 2,972 374 Tissue Diagnostics 7% Molecular Diagnostics 12% Professional Diagnostics 57% Tissue Diagnostics 12% CER=Constant Exchange Rates 88
Professional Diagnostics CHFbn 3.5 2015 vs. 2014 CER growth +7% 3.0 2.5 2.0 1.5 1.0 0.5 +2% +4% +3% +12% 0.0 HY 13 HY 14 HY 15 Immunodiagnostics Clinical Chemistry POC products Other CER=Constant Exchange Rates 89
Diabetes Care CHFbn 1.4 2015 vs. 2014 CER growth +1% 1.2 1.0 +13% 0.8 0.6-1% 0.4 0.2 0.0 HY 13 HY 14 HY 15 Blood Glucose Monitoring Other CER=Constant Exchange Rates 90
Molecular Diagnostics CHFbn 1.0 2015 vs. 2014 CER growth +12% 0.8 0.6 0.4 0.2 +39% +14% -6% +10% +13% 0.0 HY 13 HY 14 HY 15 Other HPV & Microbiology Blood Screening Biochem Reag & qpcr & NAP Systems Virology CER=Constant Exchange Rates 91
Tissue Diagnostics CHFbn 0.4 0.3 2015 vs. 2014 CER growth +12% -6% -1% +40% 0.2 0.1 +12% 0.0 HY 13 HY 14 HY 15 Advanced Staining Companion Dia Staining Digit Path&Workflow CER=Constant Exchange Rates 92
2015: Key planned product launches Professional Diagnostics Product Description Region cobas c 513 dedicated HbA1C analyzer EU cobas t 411 core lab coagulation analyzer EU Cobas 8100 V2 integrated pre- and post-analytical solution WW CoaguChek Pro II professional system for PT and aptt testing EU HTLV human T-lymphotropic virus diagnostics test EU Cobas h 232 Troponin T Point of Care test version of Elecsys ctnt-hs EU Planned launches may be delayed or not occur as a result of adverse regulatory decisions or other factors 93
2015: Key planned product launches Molecular Diagnostics Product Description Region cobas 6800/8800 medium to high volume automated real-time PCR US cobas 6800/8800 MPX cobas 6800/8800 HBV cobas 4800 HIV-1 cobas 4800 HCV cobas 4800 HBV multiplex bloodscreening test quantitative HBV viral load test quantitative HIV viral load test quantitative HCV viral load test quantitative HBV viral load test US EU EU cobas EGFR Test v2 detection of EGFR in plasma EU cobas Liat Influenza A/B + RSV POC detection US Planned launches may be delayed or not occur as a result of adverse regulatory decisions or other factors 94
2015: Key planned product launches Tissue Diagnostics Product Description Region VENTANA HE 600 automated H&E staining platform WW Planned launches may be delayed or not occur as a result of adverse regulatory decisions or other factors 95
2015: Key planned product launches Diabetes Care Product Description Region Accu-Chek Active no-code Accu-Chek Connect next-gen. bg meter, no coding of test strips bg meter with connectivity to smartphones, mobile applications and cloud WW US Planned launches may be delayed or not occur as a result of adverse regulatory decisions or other factors 96
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