Roche Holding Ltd · SIX:RO
Roche — Investor Day (September 2022)
127 slides from Roche's investor day presentation, Sep 12, 2022
Slide 1: Slide 1
Slide 2: Roche Pharma Day 2022
Roche Pharma Day 2022 London, 12 September 2022
Slide 3: Forward-looking statements
This presentation contains certain forward-looking statements. These forward-looking statements may be identified by words such as ‘believes’, ‘expects’, ‘anticipates’, ‘projects’, ‘intends’, ‘should’, ‘seeks’, ‘estimates’, ‘future’ or similar expressions or by discussion of, among other things, str
Slide 4: Welcome
Welcome Bruno Eschli | Head of Investor Relations
Slide 5: Agenda
Agenda Welcome 10:30 – 10:35 BST Bruno Eschli, Head of Investor Relations Pharma Strategy 10:35 – 11:05 BST Bill Anderson, CEO Roche Pharmaceuticals Growth drivers & Commercial Opportunities 11:05 – 11:35 BST Teresa Graham, Head Pharma Global Product Strategy (GPS) 11:35 – 12:00 BST Q&A 12:00 – 12:5
Slide 6: Pharma Strategy
Roche Pharma Day 2022 Pharma Strategy Bill Anderson | CEO Roche Pharmaceuticals
Slide 7: Pharma overview
Pharma overview
Slide 8: Roche delivering consistent high growth
Roche delivering consistent high growth HY 2012 HY 2017 HY 2022 Group CHF 22.4bn CHF 26.3bn (+3.9bn / + 17%) CHF 32.3bn (+6.0bn / +23%) Pharma CHF 17.4bn CHF 20.5bn (+3.1bn / + 18%) CHF 22.3bn (+1.8bn / +9%) AHR Oncology Infectious diseases Ophthalmology AHR Neuroscience Diagnostics Immunology Hemop
Slide 9: Continuous increase in pipeline breadth and depth
Continuous increase in pipeline breadth and depth All-time high for Ph III AIs and industry-leading number of NMEs in the clinic Projects in Ph III & registration Record number of NMEs and AIs (HY 2022) 18 Phase I Phase II 2 NMEs 2% 3% 8% 12% 14 3 14 12% 13 2 2 3% 42% 11 2 60 33 3 10% 24% 1 4 65% 9
Slide 10: Consensus outlook 2021-25
Consensus outlook 2021-25 Continued growth driven by already established medicines Biosimilar gap (21-25)* Consensus sales growth (21-25)* Post-HY 2022 consensus survey Ronapreve 1.6 bn Tecentriq 2.7 bn Ocrevus 2.4 bn Lucentis 1.4 bn Gap Hemlibra 2.4 bn Additional up-side by NMEs not Xolair 1.9 bn 7
Slide 11: Pharma Vision: Addressing changing healthcare needs
Pharma Vision: Addressing changing healthcare needs
Slide 12: Trends shaping healthcare systems and access to healthcare
Trends shaping healthcare systems and access to healthcare The needs from healthcare systems, patients and for access are changing Macro trends Patient trends Access trends Increasing healthcare needs from Patients are empowered, taking Role of public-private partnerships aging populations action al
Slide 13: Our Pharma Vision tackles needs of all health system stakeholders
Our Pharma Vision tackles needs of all health system stakeholders Pharma Vision 2030 Pharma Transformation Providing more patient benefit at less cost to society Decentralised execution across the entire Pharma organisation 1 2 3 (product development, pharma technical, commercial) that follows commo
Slide 14: Transformation improving productivity
Transformation improving productivity HY 2022 vs HY 2016 trends Pharma Technical (PT) Pharma US Pharma International Pharma China Pharma Development (PD) Sales volume growth Sales growth Sales growth Sales growth Number of projects1 +76% +25% +16% +105% +24% Direct spend +6% and OPEX -4% and OPEX +2
Slide 15: Financial impact: Rejuvenating the portfolio and securing the future
Financial impact: Rejuvenating the portfolio and securing the future FY 2021 vs. FY 2017: Pharma Division operational performance FY 2021 FY CHF2021 growth CER growth CHFm abs. CHF CHFmvs abs. FY 2017 CHF vs FY 2017 Sales 45.041 Sales +3.821 -12.8bn 45.045 +5.174 9% -10.9bn 19% thereof AHR 8.315 the
Slide 16: Digital strategy as a key enabler of our Pharma Vision
Digital strategy as a key enabler of our Pharma Vision Clinical Production & Pre-clinic Registration Access Diagnosis Treatment development Supply Research & development Production & supply chain Medicine augmentation Accelerate and de-risk early-stage Today Blockbuster drugs assets in research via
Slide 17: Customer engagement transformation facilitating future growth
Customer engagement transformation facilitating future growth WHY we changed* HOW we are changing* IMPACT we see today* Genentech and Pharma International Successful uptake of new products Roche’s changing portfolio • Empowered teams organised around local 1 launched during the CE transformation hea
Slide 18: Investing into our global manufacturing network
Investing into our global manufacturing network Increasing productivity, guaranting supply security and investing in new technologies Manufacturing sites / networks Biologics Gene therapy Cell therapy Philadelphia* Basel Penzberg Hillsboro Vacaville Singapore SSF Oceanside *Additional investment of
Slide 19: Continued commitment to R&D as driver of future growth
Continued commitment to R&D as driver of future growth
Slide 20: Roche's innovation engines enable high R&D depth and breadth
Roche’s innovation engines enable high R&D depth and breadth Preserving diverse research cultures pRed: Early stage Pharma R&D business unit, Pharma Product Development: Business translating science into medicines pRed unit for late stage Pharma development Product gRed: Early stage Pharma R&D busin
Slide 21: New platform technologies with cyclic peptides and CAR-Ts added
New platform technologies with cyclic peptides and CAR-Ts added *List of pipeline molecules where targets and MOA have been disclosed = Oncology pipeline = Neuroscience and I2O pipeline 21
Slide 22: Partnering and M&A to accelerate pipeline and drive PHC
Partnering and M&A to accelerate pipeline and drive PHC Development stage at time of deal/partnership start Early stage assets Late stage assets Digital & PHC (HBV) (molecular information) (T-cell therapies) (NLRP3 inhibitors) (SRP-9001) (electronic health (SLC (SHP2 inhibitor) (Evrysdi) records) tr
Slide 23: Focus on early stage partnerships enables efficient M&A spend
Focus on early stage partnerships enables efficient M&A spend Recent Biotech market environment may create new partnering opportunities Roche Pharma technology / NME deals 5-year investment by company1 (2017-2021) 27 150 16 16 100 14 12 9 10 8 8 50 5 4 2 0 2017 2018 2019 2020 2021 2022 YTD† AbbVie N
Slide 24: R&D profitability ahead of peers
R&D profitability ahead of peers with increasing share of OPEX allocated to R&D Roche Pharma R&D investment allocation R&D investment and profitability1 (2017-2021, % of OPEX, CHF Bn) Recently approved NME share of NPV (2020, $ Bn) NMEs R&D as % of 20.0 bn ’16-’202 revenue3 Roche 100 217 8 27%* 17.2
Slide 25: Building new R&D focus areas
Building new R&D focus areas
Slide 26: R&D focus area malignant hematology
R&D focus area malignant hematology Pursuing innovative technologies in-house and via partnerships Industry-leading portfolio Roche-Poseida development and commercialization partnership: CAR-T Tools Small molecules Booster Molecule Fully Allogeneic CAR-T Technology that results in ability to produce
Slide 27: R&D focus area ophthalmology
R&D focus area ophthalmology Developing PHC solutions supported by new partnerships Drug pipeline Biomarkers enabling PHC Future technologies diversification Biomarker identification On market Gene therapy • Integration of omics, clinical and imaging • Lucentis, Vabysmo, Susvimo, Luxturna • AAV engi
Slide 28: R&D focus area ophthalmology
R&D focus area ophthalmology Better visual outcomes in the future via diagnostics and combination therapies Current SOC Future SOC Biomarker analyses Personalized treatment options (PHC) Clinical diagnosis support • Imaging Anti-VEGF • Aqueous humor sample • Clinical data Prognosis • Aqueous humor p
Slide 29: R&D focus area Alzheimer's disease
R&D focus area Alzheimer’s disease One Roche commitment to addressing AD unmet needs Pharmaceuticals Gantenerumab • Nearly two decades of scientific investigation with >2,600 patient years on treatment • GRADUATE I/II: Patients with early AD Diagnostics • SKYLINE: Patients at risk of, or at the earl
Slide 30: Making a sustainable impact
Making a sustainable impact
Slide 31: Our pricing approach reflects WHO's fair pricing dimensions
Our pricing approach reflects WHO’s fair pricing dimensions Make innovation available for patients today and tomorrow Patient benefit Benefit and impact a medicine brings to patients, healthcare systems & society System affordability Future innovation Our pricing strategy allows us to Differentiated
Slide 32: Responsible pricing of medicines which change the standard of care
Responsible pricing of medicines which change the standard of care Recent examples of responsible pricing Net price increases in line with medical inflation in the US discount3 ~25% to Rebif in the US US net price increase1 below inflation US net price increase1 above inflation for all medical care
Slide 33: Outlook for 2022 and beyond
Outlook for 2022 and beyond
Slide 34: Key late-stage pipeline readouts
Key late-stage pipeline readouts* TA Compound Indication Data readout Tecentriq Neoadjuvant NSCLC Ph III IMpower030 Tecentriq Adjuvant HCC Ph III Imbrave050 Tecentriq Neoadjuvant / adjuvant TNBC Ph III GeparDouze/NSABP B-59 Venclexta + dexamethasone t(11;14) R/R MM Ph III CANOVA 2022 Gantenerumab Al
Slide 35: Pharma: A solid base to deliver future growth
Pharma: A solid base to deliver future growth Late-stage pipeline to impact future growth momentum: glofitamab, gantenerumab, tiragolumab, crovalimab, SRP-9001, giredestrant, fenebrutinib, inavolisib, zinpentraxin alfa etc. cobas 6800/8800, cobas 5800, cobas Liat, cobas pure, cobas pro (high through
Slide 36: Growth drivers & Commercial Opportunities
Growth drivers & Commercial Opportunities Teresa Graham | Head of Global Product Strategy
Slide 37: NMEs launched in 2022: Vabysmo and Lunsumio
2 NMEs launched in 2022: Vabysmo and Lunsumio First-in-class bispecifics launched in ophthalmology and malignant hematology Roche: Leading in bispecific antibodies • First bispecific mAb that bridges activated factor IX (FIXa) and FX to restore function of missing FVIII 2017 • Approved for severe, m
Slide 38: Pharma portfolio diversification progressing
Pharma portfolio diversification progressing HY 2022 absolute growth of products at CER HY 2022 sales split 3% Hemlibra 30% 4% Ocrevus 17% 6% Evrysdi 106% 15% Phesgo 241% Tecentriq 11% 8% Kadcyla 14% Alecensa 19% CHF 32.3bn Vabysmo n/a 17% 31% Perjeta 5% Xolair 11% Polivy 91% Ronapreve 11% 16% Enspr
Slide 39: Growth drivers & commercial opportunities
Growth drivers & commercial opportunities Oncology • Tecentriq • Targeted therapies • Tiragolumab • HER2+ Franchise • HR+ BC Hematology • Polivy • Lunsumio / glofitamab • Venclexta • Hemlibra Ophthalmology • Vabysmo • Susvimo Neuroscience • Ocrevus • Evrysdi • Gantenerumab Outlook 39
Slide 40: Tecentriq overview
Tecentriq overview Sales development 2019-2022 Sales breakdown by indication 6% 3% 5% SCLC CHFm YoY CER growth NSCLC 1,000 +13% 35% HCC 900 +31% 22% TNBC 800 +54% Bladder 700 28% Others 600 500 +146% Continued uptake of key launches 400 • Near term growth driven by adjuvant NSCLC launch in the 300 U
Slide 41: Tecentriq: First-in-class CIT in adjuvant NSCLC
Tecentriq: First-in-class CIT in adjuvant NSCLC Strong launch ongoing with potential to be first CIT for periadjuvant treatment Further growth potential in Early NSCLC Evolving eNSCLC treatment framework Incidence US/EU5 Surgery 350 300 250 Neoadjuvant only treatment: 75% of patients don’t achieve P
Slide 42: Targeted therapies
Targeted therapies Building a leading portfolio across multiple oncogenic drivers NSCLC Moving into early disease KRAS G12C 12% GDC-6036 • Alecensa ALINA trial in adjuvant ALK+ NSCLC interim data expected in 2023 KRAS Other 16% EGFR 10% Expanding potential with pan-tumor opportunities EGFR ex20 1-2%
Slide 43: Tiragolumab (aTIGIT mAb)
Tiragolumab (aTIGIT mAb) Comprehensive development program ongoing Indication Ph 1 Ph 2 Ph 3 1L NSCLC: PD-L1 high SKYSCRAPER-01 Results 2023 1L ES-SCLC SKYSCRAPER-02 Lung cancer Stage III unres. NSCLC SKYSCRAPER-03 Neoadj / Adj NSCLC SKYSCRAPER-05 1L NSq NSCLC SKYSCRAPER-06 Locally advanced ESCC SKY
Slide 44: High efficacy and safety bar established in HER2+ eBC
High efficacy and safety bar established in HER2+ eBC Continued growth for HER2+ franchise despite new competition Phesgo with strong global launch Kadcyla growth in adjuvant setting Global Phesgo conversion rate* Neoadjuvant Adjuvant cont. PCR (55%) 50% Surgery Residual Disease (45%) HER2+ Adjuvant
Slide 45: Developing a next generation SERDi and PI3Ki
Developing a next generation SERDi and PI3Ki Large addressable population for SERD and PI3K programs Targeting both early and metastatic disease eBC mBC Endocrine Therapy Given until resistance or ET +/- CDK4/6i ET +/- CDK4/6i visceral disease present Giredestrant: Potential for best-in-class SERD S
Slide 46: Growth drivers & commercial opportunities
Growth drivers & commercial opportunities Oncology • Tecentriq • Targeted therapies • Tiragolumab • HER2+ Franchise • HR+ BC Hematology • Polivy • Lunsumio / glofitamab • Venclexta • Hemlibra Ophthalmology • Vabysmo • Susvimo Neuroscience • Ocrevus • Evrysdi • Gantenerumab Outlook 46
Slide 47: Polivy is the first new treatment in >20 years in 1L DLBCL
Polivy is the first new treatment in >20 years in 1L DLBCL 1L DLBCL presents the opportunity for cure Approved in EU, UK, Japan; filed in US, China Clinically meaningful improvement in PFS POLARIX • Strong uptake in early launched countries: recommended by German guidelines1, subsequent doubling of
Slide 48: Lunsumio/glofitamab
Lunsumio/glofitamab Fixed duration, off the shelf, high CR rates with durable responses & manageable safety 3L+ FL pivotal cohort (PFS) • No required hospitalization (low grade, infrequent CRS) Tailored to address diverse patient • High CR rates & attractive profile for and healthcare system needs t
Slide 49: Lunsumio/glofitamab
Lunsumio/glofitamab Potential to be first in-class and best-in-class in FL and DLBCL Filing 2022 Approved (EU) • Lunsumio approved in EU in 3L+ FL; filed with FDA with 3L+ approval expected this year1 glofitamab Lunsumio Monotherapy • Glofitamab positive pivotal data in 3L+ DLBCL; submitted to 3L+ D
Slide 50: Venclexta
Venclexta Ph III studies in MM and MDS reading out in 2022/23 Developing in indications with >$40B market size by 2025 1L CLL $12b $3b Ph III CRISTALLO study in 1L Fit CLL ongoing MDS CLL 13% 7% $22b 1L AML MM First new medicine in AML in 20 years; >40% US market share in 1L unfit patients 17% AML R
Slide 51: Hemlibra continuing to grow across all geographies
Hemlibra continuing to grow across all geographies Hemlibra is the #1 prophylaxis treatment for Hemophilia A in the US/EU Continued market share gains in the US/EU CHFm YoY CER growth • ~35% patient share in US/EU; >65% of patients are on ≥2 weeks dosing • Further penetration expected among severe p
Slide 52: Hemlibra has set a high bar in Hemophilia A
Hemlibra has set a high bar in Hemophilia A Hemlibra is a transformational advance for patients Future development in HA will be more incremental as the unmet need has changed Factor VIII • Up to 90% of patients on Hemlibra experience zero treated bleeds per year1, with convenient dosing (low incent
Slide 53: Growth drivers & commercial opportunities
Growth drivers & commercial opportunities Oncology • Tecentriq • Targeted therapies • Tiragolumab • HER2+ Franchise • HR+ BC Hematology • Polivy • Lunsumio / glofitamab • Venclexta • Hemlibra Ophthalmology • Vabysmo • Susvimo Neuroscience • Ocrevus • Evrysdi • Gantenerumab Outlook 53
Slide 54: Vabysmo data continue to support excellent launch
Vabysmo data continue to support excellent launch At 112 weeks Q16W dosing increases to ≥ 60% in nAMD and DME Dual inhibition of Ang-2 and VEGF-A Durability cited as key priority for retinal diseases (ASRS)1 • First IVT therapy inhibiting two distinct disease pathways by simultaneously binding to An
Slide 55: Vabysmo global growth drivers
Vabysmo global growth drivers Healthcare systems recognize importance of durability to overall outcomes and costs Initial uptake in high unmet need patients Global retina market growing to USD 15 bn1 • Strong customer uptake with switching coming primarily from aflibercept • Uptake across both nAMD
Slide 56: Susvimo, first and only eye implant with Q6M drug delivery
Susvimo, first and only eye implant with Q6M drug delivery > 350 surgeons trained in the US Purposeful launch ongoing in the US Susvimo is the best option for patients who wish to • Focused on ensuring surgical excellence and optimal customer & achieve optimal vision with the fewest treatments patie
Slide 57: Growth drivers & commercial opportunities
Growth drivers & commercial opportunities Oncology • Tecentriq • Targeted therapies • Tiragolumab • HER2+ Franchise • HR+ BC Hematology • Polivy • Lunsumio / glofitamab • Venclexta • Hemlibra Ophthalmology • Vabysmo • Susvimo Neuroscience • Ocrevus • Evrysdi • Gantenerumab Outlook 57
Slide 58: Ocrevus remains #1 treatment in the US and EU-5
Ocrevus remains #1 treatment in the US and EU-5 Global market share reaches 22% with >250K patients treated globally YoY CER growth Best in disease efficacy, safety, and convenience CHFm • Robust, consistent, and sustained delay in disability progression +17% 1,500 • Ocrevus is the first and only th
Slide 59: Evrysdi: On track to becoming the global SMA market leader
Evrysdi: On track to becoming the global SMA market leader Rapid geographic expansion with >85 countries approved; moving into earlier treatment settings FDA approval in patients <2m old achieved in Q2 >7,000 patients treated worldwide • Market share: US >20%, market leader in Germany (>30%) and Jap
Slide 60: Gantenerumab in Alzheimer's disease
Gantenerumab in Alzheimer’s disease Pivotal data expected in Q4; to be presented at CTAD Large patient population and high unmet need Confidence in GRADUATE I/II to deliver clear & robust dataset AD Continuum Distribution 2 • Well powered: two parallel studies with ~1,000 participants each Severe Mo
Slide 61: Growth drivers & commercial opportunities
Growth drivers & commercial opportunities Oncology • Tecentriq • Targeted therapies • Tiragolumab • HER2+ Franchise • HR+ BC Hematology • Polivy • Lunsumio / glofitamab • Venclexta • Hemlibra Ophthalmology • Vabysmo • Susvimo Neuroscience • Ocrevus • Evrysdi • Gantenerumab Outlook 61
Slide 62: Major data readouts in 2022-24 drive growth in mid-term
Major data readouts in 2022-24 drive growth in mid-term tiragolumab + Tecentriq inavolisib RG6058 RG6114 1L PD-L1+ NSCLC 1L HR+ PiK3CAm BC crovalimab giredestrant IA RG6107 RG6171 PNH 1L ER+ mBC gantenerumab SRP-9001 zinpentraxin-alpha New Molecular Entities RG1450 Alzheimer’s RG6356 DMD RG6354 IPF
Slide 63: Late Stage Pipeline Oncology & Hematology
Late Stage Pipeline Oncology & Hematology Levi Garraway | EVP, Head of Global Product Development and Chief Medical Officer
Slide 64: Oncology strategy
Oncology strategy There continues to be a high unmet need across oncology Precision Medicine Novel immunotherapy Rational combinations Early Disease New modalities Right medicines for the Need more options for pts Leverage breadth of Early diagnosis and Bispecifics, right patient who have progressed
Slide 65: Breadth of modalities across oncology development
Breadth of modalities across oncology development Targeted Therapy Cancer Immunotherapy Small molecules ADC mAb Fusion protein Bispecifics Vaccines T Cell therapies Oncogenic driver inh. Antibody drug Checkpoint inhibition Costimulation T-cell redirection / Neoantigen vaccines Allogeneic CAR-T conju
Slide 66: Hematologic malignancies
Hematologic malignancies
Slide 67: Lunsumio (CD20 x CD3 bispecific)
Lunsumio (CD20 x CD3 bispecific) No hospitalization required, fixed duration treatment with high CR rate and durable responses Ph I/II results in 3L+ FL Clinical development program Indication Combination Ph I Ph II Ph III Best percentage change from baseline in tumor SPD CLL R/R CLL Lunsumio 1b/2 2
Slide 68: Glofitamab (CD20 x CD3 bispecific)
Glofitamab (CD20 x CD3 bispecific) Fixed duration treatment with high CR rates and durable responses Ph II results in 3L+ DLBCL Clinical development program 3L+ DLBCL pivotal cohort (DoCR) Indication Combination Ph1 Ph2 Ph3 FL R/R FL glofit + Gazyva 1 2L+ DLBCL glofit + gemox 3STARGLO DLBCL 1L DLBCL
Slide 69: Building a leading portfolio in Multiple Myeloma
Building a leading portfolio in Multiple Myeloma (MM) 4 NMEs with different modalities in clinical development High unmet need remains in Multiple Myeloma Exploring new modalities, targets, and combinations Bispecifics Small molecules Allogeneic CAR-T Cevostamab RG6234 P-BCMA-ALLO1 (FcRH5xCD3) (GPRC
Slide 70: Cevostamab (FcRH5 x CD3) in R/R multiple myeloma
Cevostamab (FcRH5 x CD3) in R/R multiple myeloma Promising activity in heavily pretreated patients FcRH5 x CD3 bispecific antibody Ph I monotherapy results in heavily pretreated R/R MM patients PR VGPR CR sCR 100 T cell Activation 80 Baseline characteristics: Patients (%) ORR: 56.7% CD3 Apoptosis
Slide 71: GPRC5D x CD3 TCB (RG6234) in R/R multiple myeloma
GPRC5D x CD3 TCB (RG6234) in R/R multiple myeloma Novel 2:1 format T cell bispecific with best-in-class potential GPRC5D x CD3 bispecific antibody Ph I monotherapy results in heavily pretreated R/R MM patients Target CD3 Head-to-tail Baseline characteristics: geometry Triple-class refractory: 62.5
Slide 72: Venclexta development program update
Venclexta development program update Upcoming Ph III readouts in R/R MM t(11;14) and 1L HR-MDS Ph III (BELLINI) results (subgroup analysis) Ph Ib results in high risk MDS (HR-MDS) • Up to 20% of MM patients harbor t(11;14) • 84% of patients who received RP2D Ven+Aza (N=51) responded to • Favorable b
Slide 73: Allogeneic CAR-Ts for hematologic malignancies
Allogeneic CAR-Ts for hematologic malignancies Partnership with Poseida Therapeutics Allogenic CAR-Ts have the potential to address Poseida has differentiated technology, clinical limitations of first generation cell therapies experience, and complementary programs • Better scaling, off-the-shelf ad
Slide 74: Solid tumors: Targeted agents
Solid tumors: Targeted agents
Slide 75: Giredestrant in HR+ breast cancer
Giredestrant in HR+ breast cancer Highly differentiated from other next generation SERDs Selective ER degrader (SERD) Well differentiated Ph III development program • Highly potent with improved efficacy versus • 7-15x more potent than other SERDs in development previous SERDs • No DDI observed in c
Slide 76: Early giredestrant data support continued development in ER+ BC
Early giredestrant data support continued development in ER+ BC Efficacy signals obtained in neoadjuvant and in 2/3L setting Ph II (coopERA) results in neoadjuvant ER+/HER- BC Ph II (acelERA) results in locally advanced/metastatic ER+/HER- BC PFS-INV: ESR1m subgroup • First randomized study to show
Slide 77: Inavolisib in PIK3CA-mutant tumors
Inavolisib in PIK3CA-mutant tumors Potential best-in-class PI3Kα inhibitor; Ph III head-to-head trial vs. alpelisib initiated Highly selective PI3Kα inhibitor Ph I (dose escalation and expansion cohort) Inavolisib + palbociclib + letrozole Fold change (inavolisib vs. alpelisib)1 Pi3Kα potency 58x 1
Slide 78: KRAS G12C inhibitor (GDC-6036)
KRAS G12C inhibitor (GDC-6036) Potential best-in-class molecule entered Ph III development KRAS G12C inhibitor Preclinical results Clinical development program • KRAS is the most frequently mutated • Best-in-class potential: more potent and selective in vitro than sotorasib and adagrasib oncogene, o
Slide 79: KRAS G12C inhibitor (GDC-6036)
KRAS G12C inhibitor (GDC-6036) Encouraging anti-tumor activity across NSCLC, CRC, and other solid tumors 2L+ NSCLC monotherapy 2L+ CRC monotherapy Ph Ia Dose escalation / expansion Ph Ia Dose escalation / expansion (19/55 pts) (30/57 pts) • Early clinical data shows encouraging response rates in pre
Slide 80: Camonsertib (RP-3500; RG6526)
Camonsertib (RP-3500; RG6526) Entering the field of DNA damage repair with potential best-in-class ATR inhibitor ATR inhibitor Demonstrated responses in ongoing PhI/II TRESR study • ATR is a key mediator of DNA damage repair (DDR) and is activated in • Ongoing PhI/II (TRESR) demonstrated monotherapy
Slide 81: Solid tumors: Immunotherapy
Solid tumors: Immunotherapy
Slide 82: Tecentriq in adjuvant NSCLC
Tecentriq in adjuvant NSCLC OS trend continues to be supportive of benefit in PD-L1+ patients IMpower010 (OS IA) OS in the PD-L1 TC ≥1%a (stage II-IIIA) OS in the PD-L1 TC ≥50% (stage II-IIIA) excluding EGFR/ALK+ • Improvement in DFS for PD-L1+ Stage II-IIIA (HR=0.66) • OS trend at interim analysis
Slide 83: Tiragolumab development program on-going
Tiragolumab development program on-going Early data (SKYSCRAPER-01) show encouraging efficiency in 1L PDL1+ NSCLC Anti-TIGIT mAb Tiragolumab development program • Fully human IgG1/kappa Ab with intact Fc • SKYSCRAPER-01 did not meet its co-primary PFS endpoint. The co-primary OS endpoint was immatur
Slide 84: PD1 x LAG3 in melanoma
PD1 x LAG3 in melanoma Encouraging early efficacy data in solid tumors PD1 x LAG3 bispecific Ab Phase I dose escalation Improved tumor growth inhibition in preclinical models1 • Bispecific antibody binding to PD-1 (high affinity) and LAG3 (low affinity) • Responses have been observed in both CPI naï
Slide 85: Neoantigen specific therapies
Neoantigen specific therapies Exploring multiple approaches in vaccines and cell based therapies Blood and Mutation Neoantigen Vaccine tumor biopsy identification prediction manufacturing • Autogene cevumeran: Individualized mRNA vaccine directed against patients’ unique tumor neoantigens • VB10.NEO
Slide 86: Moving into early disease in oncology
Moving into early disease in oncology Early diagnosis and treatment increases the chance for cure Phase III adjuvant trial program 1 National Cancer Institute, SEER database, literature review; TNBC=triple negative breast cancer; HR=hormone receptor; BC=breast cancer; NSCLC=non small cell lung cance
Slide 87: Non-malignant hematology
Non-malignant hematology
Slide 88: Non-malignant hematology: Crovalimab
Non-malignant hematology: Crovalimab Exploring across complement-mediated diseases in hematology and beyond Recycling anti-C5 mAb for rapid and Indication Ph I Ph II Ph III sustained complement inhibition 3 COMPOSER 1. High affinity binding Paroxysmal Nocturnal COMMODORE 1 (switch) 2023 2. Preferent
Slide 89: SPK-8011 in hemophilia A
Non-malignant hematology: SPK-8011 in hemophilia A Efficacy and safety data up to 4 years Hemophilia A gene therapy Ph I/II results (SPK-8011-101) ABR post vector administration of participants Durable and Predictable Factor VIII activity up to 4 years with sustained expression (n=16)* AAV-Spark200
Slide 90: Oncology & hematology pipeline with 34 NMEs
Oncology & hematology pipeline with 34 NMEs Industry leading portfolio differentiated on targets and modalities Ph I (23 NMEs) Ph II (4 NMEs) Ph III (5 NMEs) Registration (2 NMEs) RG6007 HLA-A2-WT1 x CD3 PD1 x LAG3 tiragolumab glofitamab RG6076 CD19-4-1BBL RG6139 RG6058 RG6026 Solid tumors Multiple
Slide 91: Late Stage Pipeline Neuroscience, Immunology, Infectious and Rare Diseases
Late Stage Pipeline Neuroscience, Immunology, Infectious and Rare Diseases Paulo Fontoura M.D. Ph. D. | Global Head Neuroscience, Immunology, Ophthalmology, Infectious and Rare Diseases, Clinical Development
Slide 92: Neuroscience and Rare disease
Neuroscience and Rare disease Industry leading portfolio differentiated on targets and technologies Ph I (6 NMEs) Ph II (10 NMEs) Ph III (4 NMEs, 6AI) Launched (3) UBE3A LNA prasinezumab gantenerumab RG6091 RG7935 RG1450 Ocrevus Angelman syndrome RD Parkinson’s prodromal / mild Alzheimer’s RG1594 Mu
Slide 93: Multiple sclerosis: Higher dose Ocrevus and subcutaneous dosing
Multiple sclerosis: Higher dose Ocrevus and subcutaneous dosing Continuing to invest with broad development program Q6M SC Ocrevus Ocrevus higher dose vs 600 mg in RMS and PPMS Brain shuttle CD20 Study design Double-blind treatment (min. of ≥120 weeks) Ocrevuzmab higher dose 1,200/1,800 mg Non-infer
Slide 94: Multiple sclerosis: Fenebrutinib
Multiple sclerosis: Fenebrutinib Only H2H Ph III in PPMS vs Ocrevus BTK inhibitor Ph III program overview Ph III RMS (FENhance) Ph III PPMS (FENtrepid)* *First PPMS study against an active comparator (Ocrevus) • Oral, highly selective and only reversible noncovalent BTK inhibitor in Ph III developme
Slide 95: Spinal muscular atrophy: Evrysdi in type 2/3 SMA (SUNFISH)
Spinal muscular atrophy: Evrysdi in type 2/3 SMA (SUNFISH) Long term data shows sustained increase in motor function Sunfish: A randomized, placebo-controlled, double-blind study with broad inclusion criteria and a large dataset • Long-term efficacy data from the SUNFISH study confirm increases in m
Slide 96: Spinal muscular atrophy: Evrysdi in type 1 SMA (RAINBOWFISH)
Spinal muscular atrophy: Evrysdi in type 1 SMA (RAINBOWFISH) Excellent preliminary efficacy in pre-symptomatic infants CHOP intend and WHO milestone data1 Key conclusions 4 infants have 2 SMN2 copies • Most of the infants treated with Evrysdi for ≥12 months reached near-maximum CHOP-INTEND scores by
Slide 97: Spinal muscular atrophy: Anti-latent myostatin sweeping antibody
Spinal muscular atrophy: Anti-latent myostatin sweeping antibody Ph II/III combination with Evrysdi initiated Anti-latent myostatin sweeping1 Preclinical RG6237 data in mouse models of Combination rationale antibody muscle disease • Risdiplam treats the underlying SMA disease by increasing SMN prote
Slide 98: Enspryng in myasthenia gravis and other Neurology indications
Enspryng in myasthenia gravis (MG) and other Neurology indications Recycling Ab for maximal inhibition of IL-6 signalling Anti-IL-6 receptor mAb Ph III (LUMINESCE) trial design in MG Ph III program expanding Submission FPI (estimate) MG (LUMINESCE) ✔ 2024 FDA Orphan Designation MOG-AD (METEOROID) ✔
Slide 99: DMD: Delandistrogene moxeparvovec (SRP-9001)
DMD: Delandistrogene moxeparvovec (SRP-9001) Encouraging data from ongoing Ph I studies Delandistrogene moxeparvovec Ph Ib ENDEAVOR (Study 103) Ph I (Study 101) Functional LSM change NSAA total score over 4 years in results: NSAA from baseline treated patients vs. EC (unadjusted) mean) • Targeted de
Slide 100: DMD: Delandistrogene moxeparvovec
DMD: Delandistrogene moxeparvovec Ph III (EMBARK) in ambulatory boys (≥4 to <8 yrs) to readout in 2023 Ph III EMBARK study design1 Additional Ph II/III studies • Ph III (EMBARK) fully enrolled, data expected 2023 • Ph III (ENVOL; study 302) in 0-3 year olds to be initiated in Q4 2022 • Ph III (ENVIS
Slide 101: Alzheimer's disease: Gantenerumab SC in prodromal/mild patients
Alzheimer’s disease: Gantenerumab SC in prodromal/mild patients Ph III (GRADUATE 1/2) data to be presented at CTAD on Nov 30th 2022 Anti-Aβ mAb GRADUATE 1/2 trial design Baseline characteristics Graduate 1 Graduate 2 Prodromal AD 54% 55% Mild AD 46% 45% CDR-GS - 0.5 72% 72% CDR-GS - 1.0 28% 28% APOE
Slide 102: Alzheimer's disease: Ph III (SKYLINE) in early patients
Alzheimer’s disease: Ph III (SKYLINE) in early patients Testing gantenerumab in participants at risk for or at the earliest stages of AD Blood based biomarker screening Ph III (SKYLINE) trial design • In an analysis of blood based biomarkers pTau181+Apo ε4 was the best performing combined blood base
Slide 103: Alzheimer's disease: Early clinical development program
Alzheimer’s disease: Early clinical development program Continuing to invest in an area of high unmet need Brain shuttle gantenerumab Anti-Tau mAbs CSF plasma ratio1 semorinemab bepranemab • Brain shuttle gantenerumab is an antibody format composed of gantenerumab and a linked transferrin • Semorine
Slide 104: Parkinson's disease: Prasinezumab with signals of efficacy
Parkinson’s disease: Prasinezumab with signals of efficacy Ph IIb started to further define patient population and endpoints Prasinezumab Ph II (PASADENA) results at 104 weeks • Humanized mAb designed to target aggregated • Ph II (PASADENA) study did not meet its primary endpoint (MDS UPDRS total sc
Slide 105: Angelman's Syndrome: Rugonersen, a selective and potent ASO
Angelman´s Syndrome: Rugonersen, a selective and potent ASO Enabling expression of neuronal E3 ligase (UBE3A ) in neurons Rugonersen (UBE3A-LNA) Ph II (TANGELO) trial design2 TANGELO Today completed started Different dose levels with long intervals between doses Tangelo Part 1 (MAD) Bridging dose Ta
Slide 106: Stroke: Tenecteplase in acute ischemic stroke
Stroke: Tenecteplase in acute ischemic stroke Ph III data (TIMELESS) expected in 2023 Tenecteplase TIMELESS study Advanced Imaging - Enables patient Trial design selection Tenecteplase Stroke core (damaged tissue) Tissue at risk CT perfusion images show salvageable brain tissue exists for some patie
Slide 107: Immunology and Infectious Disease clinical pipeline
Immunology and Infectious Disease clinical pipeline Strong pipeline across multiple disease, Gazyva Ph III data in LN expected 2024 Ph I (8 NMEs) Ph II (7 NMEs) Ph III (1 NMEs, 6AI) undisclosed astegolimab (Anti-ST2) Xolair RG6287 RG6149 RG3648 IBD COPD food allergy undisclosed ASO factor B zinpentr
Slide 108: Immunology: Gazyva in LN, MN and SLE
Immunology: Gazyva in LN, MN and SLE Potential benefit in autoimmune diseases through sustained B cell depletion Glycoengineered anti-CD20 mAb Ph III trial program SLE Ph III trial design to increases B-cell depletion Key screening criteria is ≥1 standard SLE therapy at stable dose: ● Prednisone ≤30
Slide 109: Immunology: Zinpentraxin alfa in fibrotic diseases
Immunology: Zinpentraxin alfa in fibrotic diseases Ph III in IPF started in 2021 Zinpentraxin alfa Ph II results Ph III (STARSCAPE) trial design in IPF Mean change in FVC (%) DOUBLE-BLIND TREATMENT PERIOD 52 WEEKS from baseline to week 28 Randomization Zinpentraxin Key Eligibility Criteria Strata al
Slide 110: Immunology: Antisense oligonucleotide Factor B in IgAN
Immunology: Antisense oligonucleotide Factor B in IgAN Ph II ongoing with promising early results and Ph III start planned for Q1 2023 Antisense oligonucleotide Factor B (ASO FB) The glomerulus in IgA nephropathy Ph II trial design Alternative complement pathway ASO factor B Start of treatemnt Scree
Slide 111: Emerging Ophthalmology Pipeline
Emerging Ophthalmology Pipeline Nilesh Mehta | Global Franchise Head, Ophthalmology
Slide 112: Real-world treatment patterns for DME and AMD
Real-world treatment patterns for DME and AMD Discontinuation, undertreatment and suboptimal vision with aVEGF monotherapy DME treatment discontinuation/switch: nAMD RWD: Infrequent dosing in 1st year correlating with 6yr follow-up data from the IRIS ophthalmology registry1 poor vision gains 40% 8,0
Slide 113: Vabysmo in DME: Personalized treatment intervals
Vabysmo in DME: Personalized treatment intervals aligned with treat and extend pricipals Ph III (YOSEMITE & RHINE) trial design BCVA and CST results • First time treat & extend principals consistently applied in a randomized Ph III • Visual function (BCVA) and anatomy (CST) consistently setting alig
Slide 114: Vabysmo in nAMD: Disease activity determines dosing interval
Vabysmo in nAMD: Disease activity at weeks 20 and 24 determine dosing interval in 1st year Ph III (TENAYA & LUCERNE) trial design Pooled BCVA and CST results • Disease activity criteria utilized at week 20 and 24 to define treatment • Strong visual function (BCVA) and anatomic results (CST) sustaine
Slide 115: Vabysmo in DME and AMD: 2-year follow up data
Vabysmo in DME and AMD: 2-year follow up data Q16W dosing increases to ≥ 60% of patients Treatment intervals up to Q16W with potential to improve outcomes Clinical development program DME DME disease control Comparable BCVA gains and improved anatomic Indication Data Ph1 Ph2 Ph3 outcomes with Vabysm
Slide 116: Vabysmo in DME and AMD: Truckee RWD study
Vabysmo in DME and AMD: Truckee RWD study Emerging real world efficacy and safety for Vabysmo consistent with Ph III Patient characteristics Case example: SRF response to Vabysmo Study Population Population with FU 512 eyes, N=465* 298 eyes, N=270** Variable: Groups: N (%) N (%) Last anti-VEGF Aflib
Slide 117: Susvimo in nAMD: 2-year follow-up data
Susvimo in nAMD: 2-year follow-up data First & only eye implant with continuous drug delivery over 6 months Maintained vision Clinical development program Indication Ph1 Ph2 Ph3 Data DME fixed Q6M PAGODA 2022 DR fixed Q9M PAVILION 2022 nAMD fixed Q9M VELODROME 2025 nAMD (LTE) PORTAL 2025+ PDS Q24W w
Slide 118: Ophthalmology pipeline gaining momentum
Ophthalmology pipeline gaining momentum Further improving the SOC and expanding in new indications Ph I (5 NMEs, 1AI) Ph II (4 NMEs) Ph III (4 AIs) Launched (2NMEs, 1AI) NME Anti-IL-6 Vabysmo Vabysmo RG6351 RG6179 RG7716 RG7716 Retinal disease DME BRVO nAMD NME NME Vabysmo Vabysmo RG7921 RG7774 RG77
Slide 119: Ophthalmology pipeline: aiming to alter trajectory of vision loss
Ophthalmology pipeline Aiming to alter the trajectory of vision loss as experienced today Vision preservation and restoration – technologies Earlier stage disease Later stage disease and approaches for all disease stages iAMD, early nAMD, GA, Retinitis glaucoma glaucoma pigmentosa Prevention Earlier
Slide 120: Novel anti-IL-6 mAb: Addressing the inflammation cascade
Novel anti-IL-6 mAb: Addressing the inflammation cascade in retinal diseases IL-6: Involved in many pathways, including IL-6: Upregulated in retinal diseases inflammation Concentration of IL-6 in the vitreous cavity of patients; mean (range) in pg/ml 1 IL-6 concentration pg/ml Control 12.1 (<30-206.
Slide 121: Novel anti-IL-6 mAb in DME and UME
Novel anti-IL-6 mAb in DME and UME Ph III study in UME to be initiated Anti IL-6 mAb Macular edema is a common end stage complication inPreclinical retinal diseases results3 High unmet need in patients with DME and UME IL-6 Diabetic retinopathy (DME) Uveitis (UME) IL-6 Fc region Caused by long-term
Slide 122: DutaFabs have the potential for long duration of action
DutaFabs have the potential for long duration of action and enhanced efficacy DutaFabs: next generation Designed for increased durability bispecifics Future development opportunities with the port delivery system Target 1 Monospecific Higher dose: Better affinity: Sustained IVT drug concentration (l
Slide 123: Geographic atrophy (GA): A multifactorial and irreversible disease
Geographic atrophy (GA): A multifactorial and irreversible disease Extensive development program covering different MoAs and platform technologies Pathogenesis of GA remains unclear, key risk factors identified >5 mn people globally affected by GA Environmental risks (e.g. smoking, diet) Genetic ris
Slide 124: ASO factor B in GA: Targeting hyperactive complement pathway
ASO factor B in GA: Targeting hyperactive alternative complement pathway via SC delivery ASO factor B Preclinical and Ph1 results Preclinical results in monkeys1 Ph1: Significant dose-dependent reductions in plasma FB levels2 A IONIS-FB-LRx 10 mg IONIS-FB-LRx 20 mg CV B Systemic (A) and ocular (B) A
Slide 125: OpRegen in GA: Replenishing the retinal pigment epithelium
OpRegen in GA: Replenishing the retinal pigment epithelium Encouraging early clinical data presented at ARVO 2022 Potential to counteract RPE Ph1/2a data: Outer retinal structure and visual function improvements in cell loss in GA patients with impaired vision1 Before OpRegen After single Cohort 4 (
Slide 126: PHC solutions support the Roche ophthalmology vision
PHC solutions support the Roche ophthalmology vision while delivering patient benefits and value for Roche Remote Vision Monitoring Apps AI-powered Retinal Imaging Algorithms Accessible, effective and low cost tracking Segmentation and disease or treatment prediction of disease activity to provide c
Slide 127: Doing now what patients need next
Doing now what patients need next