UBS European Conference 2013 Tuesday, 12 November 2013 Karl Mahler, Head of Investor Relations Stefan Frings, Oncology/Immunology Therapeutic Area Head,Roche Partnering
Group: Continued strong sales growth 10% 8% 6% 4% 2% 0% -2% 0% 0% 1% 4% 2% 6% 4% 6% 6% 4% 8% 6% Excluding 340B sales reserves release -4% -6% -3% Q3 10 Q4 10-5% Q1 11 Q2 11 Q3 11 Q4 11 Q1 12 Q2 12 Q3 12 Q4 12 Q1 13 Q2 13 Q3 13 All values at constant exchange rates 2
Roche: Increase in operating profit & margin Group core operating profit (CHF bn) and margin 40.7% 35.0% 37.2% 38.1% 38.5% +10% at CER 9.49 8.40 9.16 8.25 8.64 CER=Constant Exchange Rates HY 2009 HY 2010 HY 2011 HY 2012 HY 2013 3
Pharma market drivers and constraints Balance of these factors will determine future growth Major advances in science and medicine Growth and aging of world population Increasing wealth and access in Emerging Markets Patent expirations Global economic slowdown - Slower expansion of budgets in emerging markets - Increased pricing hurdles in developed world 4
Access and pricing: Challenges and opportunities Behavior stratified into 3 geographic clusters Developed world ex-us (37% of world market, 10% of population) Payers determine price Emerging Markets (28% of world market, 85% of population) Spend limited by GDP per capita United States (35% of world market, 5% of pop) Free, stable pricing 5
low Medical differentiation high Segregation will continue as only true innovation will be rewarded High differentiation True innovators Me-too players?? Generics No / limited differentiation low Willingness to pay for added value high 6
Roche: R&D well balanced from a risk & disease point of view Roche budget trends Oncology Metabolism CNS Inflammation Virology 0% 5% 10% 15% 20% 25% 30% Industry average probability of success Phase I to Registration Source: Bernstein Equity Research, Tufts University and Roche analysis 7
Where science takes us Oncology 9 drugs launched Immunology/ Inflammation 4 drugs launched Neuroscience 3 Phase III Launched Phase III 5 Phase III Avastin MabThera Herceptin Xeloda Tarceva Zelboraf Erivedge Perjeta Kadcyla MetMab anti-pdl1 BCL2i GA101 cobimetinib (MEKi) 1 Phase III etrolizumab Mabthera RA Actemra Lucentis Xolair lebrikizumab 2 lampalizumab 2 bitopertin ocrelizumab gantenerumab Phase II 10 phase II 2 phase II 4 phase II Strong and growing Strongly emerging Earlier stage 1 FPI expected 1H 2014; 2 Phase III decision pending 8
Roche Oncology Stefan Frings Oncology/Immunology Therapeutic Area Head Roche Partnering London, November 2013
Oncology: Hematology franchises Never Settle For Great
MabThera/Rituxan Standard of care in multiple indications Oncology sales split by indications Over 15 years of clinical practice 1997: Relapsed FL Aggressive NHL ~30% Indolent NHL ~50% CLL ~20% 2001: DLBCL (EU) 2004: 1 st line FL (EU) 2006: DLBCL (US) 2007: 1 st line FL (US) 2010: CLL 2011: 1 st line FL maintenance Follicular Lymphoma (FL)=~70% of all indolent NHL; Difuse large B-cell lymphoma (DLBCL) = ~90% of aggressive NHL 11
Never Settle for Great Hematology franchise development overview Exploring combinations with complementary MoA Improving the backbone (anti-cd20) ADC + anti-cd20 MabThera Rituxan Oncology indications: CLL inhl anhl/dlbcl Obinutuzumab (GA101) CLL filed US/EU Phase III rituximab ref. NHL, 1L DLBCL and 1L inhl+maintenance Bcl-2 inh +/- anti-cd20 Phase III R/R CLL, Bcl-2 +rituximab FPI Q1 2014 Phase II CLL (17p del) FPI Q3 2013 Phase I GA101+Bcl-2 Phase II NHL (FL+DLBCL) CD22+rituximab vs. CD79b+rituximab CD79b CD20 CD20 Bcl-2 CD22 12
GA101 in CLL CLL11: Study design CD20 Stage I, n = 590 Additional 190 patients to complete stage II Previously untreated CLL with comorbidities Total CIRS* score > 6 and/or creatinine clearance < 70 ml/min Age 18 years N = 780 (planned) *Cumulative Illness Rating Scale R A N D O M I Z E 1 : 2 : 2 Chlorambucil x 6 cycles GA101 + chlorambucil x 6 cycles Rituximab + chlorambucil x 6 cycles Stage Ia G-Clb vs Clb Stage Ib R-Clb vs Clb Stage II G-Clb vs R-Clb GA101: 1,000 mg days 1, 8, and 15 cycle 1; day 1 cycles 2 6, every 28 days Rituximab: 375 mg/m 2 day 1 cycle 1, 500 mg/m 2 day 1 cycles 2 6, every 28 days Clb: 0.5 mg/kg day 1 and day 15 cycle 1 6, every 28 days 13 Patients with progressive disease in the Clb arm were allowed to cross over to G-Clb 13
Never Settle for Great! Stage two results for GA101 in CLL11 Stage 2 results Total N = 663 Overall response rate (ORR), %* Complete response (CR), %* Gazyva plus chlorambucil N=333 78 21 MabThera/Rituxan plus chlorambucil N=330 65 7 Median PFS, months HR, Cl, p Median OS, months HR, Cl, p Grade 3-5 adverse events, %** Infusion-related reactions*** Neutropenia*** Infections * ** *** 26.7 # 15.2 0.39. 0.31-0.49, p<0.0001 NR NR 0.66, 0.41-1.06, p=0.09 66 47 20 4 33 27 7 7 At end-of-treatment During treatment No deaths (grade 5 AE) in these categories # NR Still immature Not reached 14 14
GA101 in Non Hodgkin s Lymphoma Multiple Head-to-head phase III trials vs MabThera GADOLIN study MabThera-refractory inhl (n=360) Induction GA101 + bendamustine x 6 cycles Bendamustine x 6 cycles CR, PR, SD Maintenance GA101 q2mo x 2 years Primary end-point: PFS Expect data: 2015 GOYA study Previously untreated DLBCL (n=1,400) GA101 x 8 cycles + CHOP x 6 or 8 MabThera x 8 cycles + CHOP x 6 or 8 Primary end-point: PFS Expect data: 2015 GALLIUM study Induction Maintenance First-line inhl (n=1,400) GA101 x 8 cycles + CHOP x 6 or GA101 x 8 cycles + CVP x 8 or GA101 x 6 cycles + benda. x 6 MabThera x 8 cycles + CHOP x 6 or MabThera x 8 cycles + CVP x 8 or MabThera x 6 cycles + benda. x 6 CR, PR GA101 q2mo x 2 years MabThera q2mo x 2 years Primary end-point: PFS Expect data: 2017 15 15
Bcl-2 in R/R CLL: Dose escalation phase I study Phase I in CLL (n=55) Blood May-2012 Jan-2013 Lymph nodes Partial response ongoing >1 year Bone marrow Bcl-2 inhibitor in collaboration with AbbVie 16 Presented at ASCO 2013
Bcl-2 development program in CLL Phase I study Relapsed/Refractory CLL Relapsed/Refractory CLL Bcl-2 dose-escalation 4 cohorts (100-400 mg) Combination GA101+Bcl-2 6 cycles Single agent Bcl-2 to progression Establish the dose of Bcl-2 and safety of the combination (Q4 2013) Activity in expansion cohorts (2H 2014) Adjunct Phase II study Relapsed/Refractory CLL with 17 p deletion Relapsed/Refractory CLL with 17 p deletion GDC-0199 400 mg Treatment to progression Primary end-point: Overall Response Rate FPI: Q2 2013 Expect data: end 2014 Phase III Relapsed/Refractory CLL Relapsed/Refractory CLL Rituximab + GDC-0199 X 6 cycles Rituximab + Bendamustine X 6 cycles GDC-199 2 years Observation Primary end-point: PFS FPI: Q1 2014 Expect data: 2016 17
Anti-PDL1 Immunotherapy 18
Tumor PD-L1 enables cancer immune evasion Anti-PDL1 inhibits binding of PD-L1 to PD-1 and B7.1 Targeting PDL1 Targeting PD-1
MPDL3280A Phase Ia in NSCLC: Best response by PD-L1 IHC Status Diagnostic Population a (n = 53) ORR b % (n/n) PD Rate % (n/n) IHC 3 83% (5/6) 17% (1/6) IHC 2 and 3 46% (6/13) 23% (3/13) IHC 1/2/3 31% (8/26) 38% (10/26) All Patients c 23% (12/53) 40% (21/53) a IHC 3: 10% tumor immune cells positive for PD-L1 (IC+); IHC 2 and 3: 5% tumor immune cells positive for PD-L1 (IC+); IHC 1/2/3: 1% tumor immune cells positive for PD-L1 (IC+); IHC 0/1/2/3: all patients with evaluable PD-L1 tumor IC status. b ORR includes investigator-assessed unconfirmed and confirmed PR. c All patients includes patients with IHC 0/1/2/3 and 7 patients have an unknown diagnostic status. Patients first dosed at 1-20 mg/kg by Oct 1, 2012; data cutoff Apr 30, 2013. Soria et al, ECCO 2013 20
Duration of treatment in responders Sustained response in majority of responders Histology IHC Nonsquamous IHC 0 1 mg/kg IV q3wk Squamous IHC 3 20 mg/kg IV q3wk Nonsquamous IHC 0 10 mg/kg IV q3wk Nonsquamous IHC 1 15 mg/kg IV q3wk Nonsquamous IHC 0 15 mg/kg IV q3wk Squamous IHC 2 15 mg/kg IV q3wk Nonsquamous IHC 3 20 mg/kg IV q3wk Squamous IHC 3 20 mg/kg IV q3wk Figure 1. Duration of treatment and response for NSCLC patients with response dosed by 1 October 2012 in Study PCD4989g Duration of Treatment and Response Nonsquamous IHC 3 20 mg/kg IV q3wk Nonsquamous IHC 0 20 mg/kg IV q3wk Nonsquamous IHC 3 20 mg/kg IV q3wk Nonsquamous IHC 1 15 mg/kg IV q3wk a On study, on treatment On study, post treatment Treatment discontinued Ongoing response First response First PD 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84 NSCLC = Non-small cell lung cancer Time in Study (Weeks) a Patient experiencing On treatment ongoing = Last benefit Dose per + 3 investigator. weeks Time (Weeks) Patients first dosed at 1-20 mg/kg by Oct 1, 2012; data cutoff Apr 30, 2013. Soria et al, ECCO 2013 21
Anti-PDL1 Development: NSCLC FIR Study: Phase II Dx-positive advanced mnsclc PDL1 positive NSCLC Anti-PDL1 1200 mg IV Q3 weeks Ongoing Primary end-point: Overall Response Rate POPLAR Study: Phase II 2/3L mnsclc Metastatic NSCLC (2/3L) Docetaxel 75 mg/m2 IV Q3 wk Anti-PDL1 1200 mg IV Q3 wk Ongoing Primary end-point: Overall Survival OAK Study: Phase III 2/3L mnsclc Metastatic NSCLC (2/3L) Docetaxel 75 mg/m2 IV Q3 wk Anti-PDL1 1200 mg IV Q3 wk Expect FPI: Q1 2014 Primary end-point: Overall Survival 22
Anti-PDL1 in combination with Avastin Tumor Volume, mm 3 Dose expansion Dose escalation Anti-VEGF combination: preclinical data Combination of anti-pdl1 and Avastin (Study GP28328, solid tumors) 2000 1500 Cloudman melanoma a-pd-l1 Control a-vegf Arm A (n=6) Anti-PDL1 q3w Bevacizumab 15mg/kg q3w Arm B (n=6) Anti-PDL1 q2w Bevacizumab 10mg/kg q2w + chemo 1000 500 a-pd-l1 + a-vegf Anti-PDL1 q3w @selected dose Bevacizumab 15mg/kg q3w Anti-PDL1 q2w @selected dose Bevacizumab 10mg/kg q2w + chemo 0 0 10 20 30 40 50 Day 23
Novel molecules in cancer immunotherapy: Preliminary pre-clinical molecules Preliminary pre-clinical data: NME1 + anti-pd-l1 Median tumor volume (mm 3 ) Co-blockade induces tumor rejection and creates resistant to tumor re-challenge Preliminary pre-clinical data: NME2 Tumor volume reduction seen in pre-clinical models with NME2 Internal data 24
Doing now what patients need next 25