#1Roche#2Roche Roche Pharma Day 2023 London, 11 September 2023#3Roche 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, strategy, goals, plans or intentions. Various factors may cause actual results to differ materially in the future from those reflected in forward-looking statements contained in this presentation, among others: 1 pricing and product initiatives of competitors; 2 legislative and regulatory developments and economic conditions; 3 delay or inability in obtaining regulatory approvals or bringing products to market; 4 fluctuations in currency exchange rates and general financial market conditions; 5 uncertainties in the discovery, development or marketing of new products or new uses of existing products, including without limitation negative results of clinical trials or research projects, unexpected side-effects of pipeline or marketed products; 6 increased government pricing pressures; 7 interruptions in production; 8 9 loss of or inability to obtain adequate protection for intellectual property rights; litigation; 10 loss of key executives or other employees; and 11 adverse publicity and news coverage. Any statements regarding earnings per share growth is not a profit forecast and should not be interpreted to mean that Roche's earnings or earnings per share for this year or any subsequent period will necessarily match or exceed the historical published earnings or earnings per share of Roche. For marketed products discussed in this presentation, please see full prescribing information on our website www.roche.com All mentioned trademarks are legally protected.#4Welcome Bruno Eschli Head of Investor Relations Roche#5Agenda Welcome 10:30-10:35 BST Bruno Eschli, Head of Investor Relations Group Update - 10:35 11:05 BST Thomas Schinecker, CEO Roche Group Pharma Update and On-Market Portfolio 11:05 - 11:40 BST Teresa Graham, CEO Roche Pharmaceuticals Late Stage Pipeline Oncology (Solid Tumors) 11:40-12:00 BST Levi Garraway, CMO and Head Global of Product Development 12:00 12:50 BST Lunch Break - Late Stage Pipeline Hematology 12:50-13:05 BST Charles Fuchs, SVP Global Head of Oncology and Hematology Product Development Late Stage Pipeline Neuroscience, Immunology and Cardiovascular-Metabolism 13:05 13:30 BST Paulo Fontoura, SVP and Global Head of Neuroscience and Immunology Late Stage Pipeline Ophthalmology 13:30-13:45 BST Christopher Brittain, VP and Global Head of Ophthalmology Product Development 13:45-14:30 BST Q&A 14:30-15:00 BST Buffet reception Roche#6Roche Pharma Day 2023 Group Update Thomas Schinecker | CEO Roche Group Roche#7New Leadership Team Performance and Outlook Pharma R&D Excellence Upcoming IR Events Roche#8Corporate Executive Committee since April 2023 Pharma R&D functions from early to late stage and partnering represented Roche K Dr. Thomas Schinecker Chief Executive Officer Roche Group Teresa Graham CEO Roche Matt Sause CEO Roche Diagnostics Pharmaceuticals Dr. Alan Hippe Chief Financial and Information Officer Cristina A. Wilbur Chief People Officer Claudia Böckstiegel General Counsel Prof. Dr. Hans Clevers Head of Pharma Research and Early Development (PRED) Dr. Aviv Regev Head of Genentech Research and Early Development (gRED) Dr. James H. Sabry Global Head of Pharma Partnering Dr. Levi Garraway Head of Global Product Development and Chief Medical Officer Silke Hörnstein Head of Corporate Strategy and Sustainability Barbara Schädler Head of Group Communications 8#9Corporate Executive Committee: New members Experienced leaders with breadth of scientific, commercial and strategic experience Roche Dr. Thomas Schinecker Chief Executive Officer Roche Group Teresa Graham CEO Roche Pharmaceuticals Prof. Dr. Hans Clevers Head of Pharma Research and Early Development (PRED) ☐ Excellent track record in multiple Pharma functions and across the portfolio Accomplished leader with strength in commercial operations combined with scientific depth Matt Sause CEO Roche Diagnostics 20 years at Roche, experience in Diagnostics and Pharma ■ Numerous country general management and global product leadership roles ■ Successful leadership of Diagnostics' North America region Dr. Levi Garraway Head of Global Product Development and Chief Medical Officer Outstanding career at Dana-Farber, Harvard Medical School, and the Broad Institute Award-winning cancer researcher with multiple breakthrough discoveries in cancer genomics and precision medicine Silke Hörnstein Head of Corporate Strategy and Sustainability ■ 20 years at Roche, experience across general management, global product and strategy leadership roles Successfully led Roche Diagnostics' transformation efforts including new strategy and implementation Claudia Böckstiegel General Counsel Barbara Schädler Head of Group Communications a#10Sustainability now represented on CEC level ESG is part of everything we do Develop new medicines, diagnostics and integrated health solutions that address the needs of diverse patient communities • Increase access to our innovations globally with local communities in mind . Care for our employees by prioritizing safety and health, promoting diversity, inclusion and equal opportunities • Halve the environmental impact of our operations and products from 2019-2029 Reduce greenhouse gas emissions to net zero no later than 2050 Society A sustainable future • Partner with suppliers to reduce Environment their greenhouse gas emissions Economy Roche • Invest in innovation and medical advances Contribute to economic growth in over 100 local economies Provide jobs and ensure livelihoods 100#11New Leadership Team Performance and Outlook Pharma R&D Excellence Upcoming IR Events Roche#12Global Roche network delivering patient benefits worldwide Roche Pharmaceuticals + Diagnostics Switzerland (Basel, Kaiseraugst, Rotkreuz) Penzberg, Mannheim Roche Hillsboro Genentech Pharmaceuticals + Diagnostics South San Francisco Oceanside, Pleasanton, Santa Clara Barcelona Indianapolis Philadelphia Johannesburg Pune 14mn Patients treated with Roche medicines in 2022 29bn Test conducted with Roche systems in 2022 1Dow Jones Sustainability Indices Singapore CHUGAI Pharmaceuticals Tokyo Shanghai/Suzhou D in a row ranked as one of the 14 yrs yrs top 3 most sustainable healthcare companies1 12#13Roche Our achievements Roche is continuously shifting the standard of care A legacy of patient and business impact... Blockbuster drugs in 2022, up from 7 in 2012 in neurology and hemophilia A¹ 16 #1 #3 in oncology1 #1 in in vitro diagnostics1 #1 top pharma as ranked by rare. #1 disease patient groups² Pharma in Al readiness³ ...with a track record of establishing standard of care across new therapeutic areas OCREVUS ocrelizumab FOR N 300MG/10ML First and only therapy approved for RMS/PPMS HEMLIBRA emicizumab-kxwh injection for subcutaneous use 150 mg/mL First and only prophylactic treatment for hemophilia A with/without inhibitors VABYSMO First bispecific antibody in AMD and DME 60 mg powder for solution Evrysdi risdiplam First-in-class splicing modifier for the treatment of SMA 1 based on FY 2022 sales (Evaluate/Bloomberg); 2Patient View, 2023; 3CBInsight, 2023; Al-artificial intelligence; RMS=relapsing; PPMS-primary progressive multiple sclerosis; AMD-age-related macular degeneration; DME=diabetic macular edema; SMA-spinal muscular atrophy 13#14Roche delivered consistent growth through biosimilar erosion Successful diversification of our portfolio Roche From three oncology assets driving ~50% of sales in 2012... ... to a diversified portfolio with assets that span multiple therapeutic areas today Diagnostics CHF 10.2bn 21%2 9% 9% Pharmaceuticals 9% CHF 35.2bn AHR1 52% Diagnostics CHF 17.7bn 15%3 8% 16% Pharmaceuticals 17% CHF 45.2bn 30% 14%4 AHR1 2022 2012 AHR1 Oncology Infectious diseases Neuroscience Immunology Hemophilia A Other Diagnostics 1 AHR: Avastin, Herceptin, Rituxan; 2 Includes Metabolism (5%), Ophthalmology (4%), Respiratory (3%), Cardiovascular (3%) and others (6%); 3 Includes Infectious Diseases (5%), Ophthalmology (4%) and others (7%); 4 Reduction in AHR sales due to Loss of Exclusivity and biosimilar competition. Source: Roche Annual Report 2012, Roche Annual Report 2022, Roche Finance Report 2022 14 14#15Young portfolio: 20 NMEs launched since 2015 driving growth Keeping launch momentum with two NMEs approved in 2023 Roche TECENTRIQ atezolizumab VENCLEXTA LUXTURNA voretigene reparvoveczy HEMLIBRA emicizumab-kawh ALECENSA alectinib OCREVUS ocrelinumab COTELLIC xofluza POLIVY ENSPRYNG PHESGO ROZLYTREK Evrysdi. VABYSMO GAVRETO SUSVIMO Lunsumio RONAPREVE mosunetuzumab CHFM 12,000 10,000 8,000 6,000 22% Elevidys* 4,000 COLUMVI 2,000 33% 41% % of Pharma Sales** 50% 2015 | 2016 | 2017 | 2018 | 2019 | 2020 2021 2022 2023 0 HY 2020 Cotellic Luxturna HY 2021 Alecensa Xofluza HY 2022 HY 2023 Phesgo Vabysmo | Evrysdi Lunsumio Tecentriq Polivy Gavreto Ocrevus Rozlytrek Hemlibra Enspryng Ronapreve Susvimo Columvi Young portfolio defined as all launches since end of 2015; * Elevidys: Accelerated US approval by partner company Sarepta; ** Venclexta sales booked by AbbVie and therefore not included 15#16Consensus outlook 2022-26* Growth driven by our young on-market portfolio; potential pipeline up-side Biosimilar gap (22-26) Potential up-side³ Consensus sales growth (22-26) Post-HY 2023 consensus survey Lucentis 1.0 bn Xolair 2.2 bn Ronapreve 1.7 bn Gap 7.7bn Vabysmo 4.3 bn Tecentriq 1.7 bn Hemlibra 1.6 bn Ocrevus 1.5 bn Polivy 1.4 bn Actemra 2.7 bn Evrysdi 1.2 bn Lunsumio 0.7 bn Avastin 2.1 bn Ronapreve 0.2 bn Lucentis 0.3 bn Columvi 0.5 bn Xolair 1.4 bn MabThera 2.1 bn Herceptin 2.1 bn Actemra 1.3 bn Avastin 1.0 bn MabThera 1.1 bn Herceptin 1.1 bn Gazyva Alecensa Enspryng Susvimo Other in-market¹ 0.4 bn 0.3 bn 0.3 bn 0.2 bn (0.5) bn Pipeline Ph III² 2.4 bn Perjeta 4.1 bn Perjeta 3.5 bn thereof Elevidys 0.8 bn Kadcyla 2.1 bn Kadcyla 1.6 bn thereof tiragolumab 0.7 bn Phesgo 0.7 bn Phesgo 1.7 bn thereof giredestrant 0.3 bn thereof crovalimab 0.3 bn 2022 Sales 2026 Sales thereof fenebrutinib Total 0.2 bn 16.1 bn Roche Additional up-side by late-stage NMES / LEs poorly or not yet covered: Oncology (inavolisib, divarasib, tobemstomig, autogene cevumeran), Hematology (SPK- 8011), Ophthalmology (ASO factor B in GA, anti-IL-6 mAb, Enspryng in TED), Neuroscience (Enspryng in gMG, anti-latent myostatin mAb, trontinemab, prasinezumab), Immunology (Gazyva in LN, astegolimab, ASO Factor B in IgAN), Cardiovascular & Metabolism (zilebesiran) *All estimates are based on Post HY 2023 consensus collected by FTI Consulting on behalf of Roche (n=18); 1 Activase/TnKase, Esbriet, Pulmozyme, CellCept, Erivedge, Cotellic, Gavreto, Xofluza, Rozlytrek; Luxturna 2 included in >50% of the sell-side models; ³Assets covered on average by only 17% of the sell side models; NME=new molecular entity; LE=line extensions 16#17Important launches ahead in Diagnostics Diagnostics to deliver mid to high single digit growth in coming years Core & Molecular Lab Mass spectrometry Continuous glucose monitoring (CGM) Next generation sequencing (NGS) Clinical Chemistry Immuno Chemistry Mass Spectrometry 102 >50X Expansion Roche . • Menu expansion driving growth, averaging >25 assay launches/approvals per year¹ • >240 assays running on >100k installed cobasⓇ serum work area instruments >2.5k installed cobas® 6800/8800/ 5800 instruments • ⚫ First fully integrated and automated mass spectrometry • Launch menu complimentary to immunoassay offering, including >40 key parameters at launch • CE launch planned for end of 2024 (FDA approval expected in 2025) • . Subcutaneously inserted sensor to measure glucose values in interstitial fluid Personalized management of diabetes Digital tools to support disease management for users and healthcare professionals • • Unique sequencing by expansion technology, significantly improving nanopore performance Nanopore system delivers flexible run size at competitive cost 1. average 2018-2022; excludes claim extensions for new instruments, excludes Biotin updated assays, COVID-19, Custom Biotech, TiB Molbiol & Genmark, RUOS, IVDR transitions; CGM-continuous glucose monitoring; NGS=next generation sequencing 17#18FY guidance confirmed - strong half year performance Base business with continued strong momentum; COVID sales washed-out by Q1 24 Roche Guidance¹ HY Results Pharma: Key products with strong growth and momentum from ongoing launches Diagnostics: Base business with solid growth Pharma: +8% in CER; +32% from products launched since 2015 Diagnostics: +6% in CER COVID-19 sales for Diagnostics and Pharma expected to decline by roughly CHF 5bn AHR² sales expected to erode by roughly CHF 1.6bn COVID-19 sales: CHF -2.7bn AHR² sales: CHF -0.6bn 1 At Constant Exchange Rates (CER); 2 AHR: Avastin, Herceptin, Rituxan/MabThera 18#19New Leadership Team Performance and Outlook Pharma R&D Excellence Upcoming IR Events Roche#20Roche R&D has multiple proven strengths Strategy and portfolio • Operating . model and structure • Commitment to scientific excellence and discovery of novel modalities (e.g. ADCs, bispecifics) Ability to expand successfully into new therapeutic areas Roche Autonomous early stage R&D units gRED, PRED and Chugai, specialized in their respective domains Successfully launched 20 NMEs in the last 8 years. • Talent, culture Breadth and depth of expertise across a range of disease areas 50 and mindset • Leaders in emerging areas such as computational biology, new disease models, and protein engineering 0101 00101 0101 Capabilities, tech, and Al • Strong organizational loyalty, external reputation and ability to attract top scientific talent • Leveraging thought leadership in generative Al and deep learning approaches NME=new molecular entity; Al-artifical intelligence; ADC=antibody drug conjugate 20 20#21Roche Commitment to innovation After reallocating resources to R&D, focus is now on 'R&D Excellence' HY Roche Pharma R&D investment allocation (2018-2023, % of OPEX, CHF bn) R&D investment and profitability1 Recently approved NME share of NPV (2022, USD bn) NMEs Average R&D as '17-'221 % of revenue 2 margin '223 EBITDA 8.7 8.3 Peer 1 77 156 233 13% 55% 7.7 Peer 2 75 62 138 8 27% 34% 33% 36% 2.9bn Roche 74 141 215 10 24%* 38% 3.0bn 43% Others Peer 3 55 53 166 219 7 13% 33% 3.3bn Peer 4 52 128 180 14 18% 38% Peer 5 47 245 292 5 22% 33% Peer 6 44 120 165 18% 33% 57% 64% 5.4bn 67% 5.8bn Peer 7 34 126 161 9 17% 36% R&D 4.4bn Peer 8 26 133 159 5 23% 45% Peer 9 14 229 243 8 17% 44% Peer 10 11 235 245 11 23% 41% 2018 2022 2023 NMES '17-22 All other drugs 1 Evaluate Pharma, 2017-H1 2022 data; 2 Company financial reports 2018-2022; 3 Bloomberg; *Roche Pharma only 21#22Holistic, end-to-end analysis of our R&D productivity Commitment to delivering the worlds most impactful medicines • Success rate ✓ Volume ✓ Value Effectiveness R&D productivity = Costs Cycle time } Efficiency Holistic and end-to-end Teams from early to late stage development, and commercial involved 'Leave no stone unturned' analysis RWD-real-world data; AI/ML-artificial intelligence/machine learning ☐ Strong base Ability to capitalize on significant past investments, for example: . Breadth of disease area talent . Computational biology expertise Platform technologies ☑» New opportunities RWD and Al/ML, computational biology and advanced analytics . Application of new technologies in R&D Institute of Human Biology (IHB) Roche 22#23Success rate Roche with leading success rate by molecule... ...but higher Phase III failure rate recently Molecule success (PoL Preclinical - Approval) 2018-22 Industry Distribution Peer 13.8% 10.1% 9.9% Peer Roche Peer 8.7% Peer 8.7% Peer 8.0% Peer 6.2% Peer 6.0% Peer 5.4% Peer 4.7% Peer Peer 3.9% 2.9% Median Top quartile 11 Bottom quartile PTS Molecule Success Rate in Phase III* 2009-13 to 2018-22 100% 75% 50% 25% 0% 2009-13 76% 58% 2018-22 Time period 5-year rolling average (Roche) N=12 5-year rolling average (peers) N=106 *Values on the Molecule Success Rate trend in phase III graph represent outcomes in the 2018-22 horizon. Graphs start with 2009-13 data and then show 5-year average trend through 2018-22 horizon; PTS-probability of technical success; Source: KMR Benchmarking analysis 23 Roche#24Volume Number of pipeline assets in Phase I to III Roche ranks #2 in total pipeline volume Total number of pipeline assets by phase*, # Peer 1 12 39 Roche 11 36 Peer 2 11 56 Peer 3 15 29 36 Peer 4 11 30 36 Peer 5 19 25 27 Peer 6 9 29 25 63 63 Peer 7 5 26 30 61 Peer 8 10 28 18 56 Peer 9 st 4 22 29 55 Peer 10 3 19 33 55 Peer 11 12 23 14 49 49 Peer 12 LO 25 12 42 *Excludes pipeline products in pre-registration, registration and filed; Peer 1-12 are other large-cap Pharma Source: Pharmaprojects (February 2023), McKinsey attrition analytics Phase III Phase II Phase I 50 101 51 98 29 96 80 77 71 Roche 24#25Value Pipeline assets segmented by innovation potential Roche ranks #2 in number of NMEs with first-in-class potential Fast-follower Others* Total number of pipeline assets by innovation potential*, # First-in-class Peer 1 45 Roche 36 Peer 2 34 7 17 20 11 15 45 20 Peer 3 33 23 21 Peer 4 29 60 Peer 5 25 10 14 Peer 6 21 8 51 Peer 7 20 10 71 Peer 8 18 Peer 9 17 Peer 10 15 a Peer 11 15 1 LO Peer 12 12 28 19 32 35 43 *NMEs that are neither first-in-class or best-in-disease, or without disclosed MoA, are grouped as 'Others'; Peer 1-12 are other large-cap Pharma Source: Pharmaprojects (March 2023) Roche 25#26Costs R&D spend per NME launch Roche spend is above industry average R&D spend per NME launch², bn USD, 2018-20221 6.2 6.1 5.8 5.7 5.1 5.1 4.4 4.3 4.2 3.9 3.3 2.8 Peer 1 Peer 2 Peer 3 Roche Peer 4 Peer 5 Peer 6 Peer 7 Peer 8 Peer 9 Peer 10 Peer 11 1. Average annual pharmaceutical R&D Spend from 2018-2022 (device and generics R&D spend excluded whenever reported separately). Pre-acquisition R&D spend for mega-merged entities (M&A >$10Bn) is included to account for NME pipeline continuity; Only asset products sales included; 2. Restricted to NMEs launched 2018-23 with visible revenues for that company (any year in visible forecast data). NME = New Molecular Entity (including novel biologics). Partnered launches can be assigned to multiple companies if there are revenues associated with several players; Source: Evaluate Pharma March 2023 04.7 Roche 26#27Cycle time Development timelines compared to industry Roche with faster than average Phase III cycle time, but lagging in Phase II Composite cycle time at a project level, years Preclinical Phl Ph II* Ph III Registration Roche Industry 2013-17 1.0 1.8 2.5 2017-21 1.1 1.9 N=48 N=45 Roche rank: 7/13 8/14 2013-17 1.0 1.9 2.3 2017-21 1.0 2.0 2.4 3.1 N=27 12/14 2.7 3.5 3.3 0.6 9.4 2.6 0.5 9.2 N=39 N=52 3/14 2/14 0.8 8.7 0.7 9.4 N=339 N=178 N=120 N=237 N=316 * Phase II cycle time encompasses Phase Ib expansions (in Oncology), single arm Phase Ils and randomized Phase Ils. A great portion of projects in Phase II are Oncology Phase Ib expansions, where a higher SoC bar in most indications (requiring assessment of time-to-event endpoints in order to ungate a larger Phase III study) might be one of the factors contributing to longer duration over time Composite cycle time only includes projects which successfully completed a certain phase in the time window of interest and is calculated by the sum of each phase cycle time (sum of median CT for all projects which completed Preclinical, Ph1, Ph2, Ph3, Registration in the time window of interest, e.g., 2017-21). This method allows for a more current view of phase completion, as each phase is calculated using the most current CT window. Projects originated externally are included in the calculation (if in-licensed and/or acquired mid-stream, CT calculated from the start of the following phase); Source: KMR Roche 27 27#28Levers to drive R&D excellence were identified E.g., go/no go decisions based on critical review of scientific and commercial risk E.g., leverage RWD and Al to increase research output and focus on clinical stage external innovation E.g., focus on assets with best-in- disease and first-in-class potential, manage portfolio value mix Success rate ✓ Volume R&D productivity Costs ✓ Cycle time E.g., simplify processes, deploy industry-leading. data systems and operational excellence RWD-real-world data; Al-artificial intelligence Value Effectiveness Efficiency E.g., reduce white space between clinical phases, increase speed in development, leverage technology & culture change Roche 28#29Additional dimensions Prioritization of our R&D investments Pharma portfolio management with an end-to-end perspective 100% Go Low risk Low Risk Cost focus Low reward High reward POL 50% 90 0% Low Disease area strategy High Risk Low reward 1 ΠΠ POL-probability of launch; rNPV-risk-adjusted net present value; uNPV=unadjusted net present value High Risk High reward rNPV Bubble size = uNPV High First-in-class/ best-in-disease Move fast and make broad investments Mitigate Risk Gate larger investments on further data readouts Platform technologies 29 Roche#30Portfolio committee established Taking a holistic view and managing R&D productivity end-to-end Roche Head of PRED Hans Clevers Head of Global Product Strategy Cristin Hubbard CEO Group Thomas Schinecker CMO-chief medical officer; POL-probability of launch; rNPV-risk-adjusted net present value POL rNPV Head of Partnering James Sabry Pharma CEO Teresa Graham Head of gRED Aviv Regev Head Product Development/CMO Levi Garraway 80 30#31Pipeline acceleration via partnering Deals of the past two years increasingly focused on clinical stage NMEs* TA NME Indication Partner Development stage P-CD19CD20-ALL01 B-cell malignancies Pre-clin. Phl POSEIDA THERAPEUTICS P-BCMA-ALLO1 Multiple myeloma Phl AR degrader mCRPC Jemincare Phl camonsertib Solid tumors REPARE Phl THERAPEUTICS KSQ-4279 Solid tumors OpRegen Geographic atrophy KSQ -==LINEAGE CELL THERAPEUTICS Phl Ph II ASO factor B IgAN IONIS Ph Il Ph III vixarelimab IPF & SSC-ILD KINIKSA Ph ll zilebesiran Oncology/Hematology Hypertension Ophthalmology 0 Alnylam PHARMACEUTICALS Ph ll Development stage at time of deal Positive proof of concept data Current development stage Immunology Cardiovascular & Metabolism *Table shows clinical stage NME deals completed 2021-2023 YTD; TA-therapeutic area; mCRPC=metastatic castrations-resistant prostate cancer; AR-androgen receptor; IgAN-immunuglobululin A nephropathy; ASO-antisense oligonucleotide; IPF-idiopathic pulmonary fibrosis; SSC-ILD-systemic sclerosis-interstitial lung disease Roche 31#32Evolution of our R&D engines, with impact on the full value chain Leveraging the newest technologies to bring unprecedented changes • Computational Biology, AI/ML and advanced computation Acceleration of biological insights Systematic discovery of targets and biomarkers More efficient target prioritization and development (efficacy, safety, tractability) Digital endpoints delivering new patient insights and building holistic solutions for patients • • • • Organoids: Creating reliable predictive models emulating the human body Roche launched the Institute of Human Biology (IHB) Engineering the most advanced organoids to explore physiology, understand diseases and develop new therapies Accelerate discovery and development of new medicines Core areas: exploratory research, bioengineering, translation & technologies Roche Leader Head of gRED Head of gRED Computation Aviv Regev John Marioni Head of PRED Hans Clevers Head of IHB Matthias Lütolf Roche New technologies enabling unprecedented changes along the full value chains of Pharma and Diagnostics 32 52#33Our Operating Principles: How we shape our culture Putting patients first is at our core; additional key areas to focus on going forward Put patients first I always act as if patients I know are in the room and do what's best for them. Follow the science I seek answers through experiments, data and debate, and act on facts. Act as one team Embrace differences I care, collaborate and commit without boundaries, and trust others to do their part. I seek diverse perspectives, invite opposing views, and challenge myself and others. I push to learn new things even if difficult, and openly share my successes and failures. Accelerate learning Simplify radically I eliminate complexity, reuse with pride, and accomplish more with less. Make impact now Think long term I take accountability to do what's right, deliver value fast, and don't wait for certainty. I choose actions today that benefit future generations. Roche 33#34R&D focus areas to speed up delivery of our medicines 1 Х ✓ 2 4 Set ambitious R&D objectives 5 Strengthen portfolio framework 3 Transform portfolio management & governance 6 Qe + Access the best external innovation Optimize R&D engines and invest in emerging technologies Evolve talent, culture and mindset to achieve objectives Roche 54 34#35New Leadership Team Performance and Outlook Pharma R&D Excellence Upcoming IR Events Roche#36Upcoming IR events on Neuroscience, Digitalization and Diagnostics Roche Neuroscience Update on Oct 30 Virtual event Neuroscience pipeline and strategy • Latest data on: • Ocrevus Ph III (OCARINA II) in MS • fenebrutinib Ph II (FENopta) in MS trontinemab Ph I dose escalation in AD GSM (Gamma secretase modulator) Ph I in AD Roche Digitalization Day on Nov 29 Virtual event Roche experts to present how digitalization (incl. RWD and Al/ML) transforms our Pharmaceuticals and Diagnostics businesses in an unprecedented way Use cases covering early R&D, clinical development, regulatory, manufacturing, supply chain and commercialization to be presented Discussion of novel product opportunities at the interface between Diagnostics and Pharmaceuticals • 999 Roche Diagnostics Day in H1 2024 Hybrid event (virtual/on-site) Management to update on Diagnostics mid- term outlook Deep-dives into the current product portfolio Updates on key development projects, including mass spectrometry (launch scheduled for 2024), continuous glucose monitoring (CGM) and next-generation sequencing (NGS) Angiogenesis 2023 Virtual Monday, 13 February 16:30 to 18:00 CET Roche ESG Day Virtual Tuesday, 23 May 15:30 to 17:00 CEST EHA 2023 Virtual Monday, 12 June 16:30 to 17:30 CEST Roche Pharma Day London Monday, 11 September 10:30 to 14:30 BST MS-multiple sclerosis; AD-Alzheimer's disease; RWD-real-world data; AI/ML-artificial intelligence and machine learning Neuroscience Update Virtual Roche Digitalization Day Virtual Monday, 30 October TBA Wednesday, 29 November TBA ASH 2023 Virtual December TBA Roche Diagnostics Day Virtual/hybrid H1 2024 TBA 36#37Pharma Update & On-Market Portfolio Teresa Graham | CEO Roche Pharmaceuticals Roche#38Pharma Update On-Market Portfolio With Further Growth Potential Significant Growth Opportunities Ahead Roche#39HY 2023: Pharmaceuticals Division sales All regions delivering strong growth, intensifying currency headwinds in Q2 CER=Constant Exchange Rates 2023 2022 Change in % CHFM CHFM CHF CER Pharmaceuticals Division 22,681 22,347 1 8 United States 11,743 11,363 3 7 Europe 4,105 4,104 0 5 Japan 2,210 2,202 0 14 International 4,623 4,678 -1 9 50 39 Roche#40Why we changed our customer engagement model Why we changed Roche's changing portfolio Shifting customer expectations for industry engagement Data and technology as disrupters Price pressures Roche In-person, product-specific field approach not meeting customer needs Industry representative's access to physicians (US) 100% 80% 77% 60% 65% 40% 44% 20% 15-30% 0% 2008 2012 2016 2020 (COVID) Patient influence in healthcare decision making • Providers increasingly refused to meet industry; customers confused by multiple touchpoints • Desire for more scientific exchange and patient/ account support 40 40#41New customer engagement model driving future growth Integrated customer experience and greater agility How we are changing Impact we see today Roche experts Roche Primary Point of Contact 오 2000 CO Empowered teams organized around local healthcare markets, with accountability for the whole portfolio 1 Successful uptake of new products (e.g. Vabysmo) 2 Increased P&L flexibility 3 Flexibility in resource deployment to higher impact channels (e.g. digital patient support) • Improved customer experiences and partnerships with a reduced number of broader and more impactful roles 4 Positive customer feedback • Delivering coordinated, personalized experiences through all channels P&L=Profit and loss Roche 41#42Pharma Corporate Access Goal Opportunities to remove barriers and substantially increase access Roche Inclusive clinical trials Access levers Regulatory filing & reimbursement Affordability Capacity enablement Partnerships Support health equity Mid-term outcomes and diversity in our clinical research and trials EV Substantial acceleration of regulatory filling & reimbursement approval Support development of new, integrated and tailored affordability solutions for different population health/group needs Our mission Accelerate & adapt internal processes Expand local capabilities Support infrastructure development through external partnerships Mobilize partnerships with global/regional organizations to solve a gap in local care Design & deploy fit-for-purpose integrated solutions 42#43Responsible pricing as we advance the standard of care Savings for healthcare systems and lower out-of-pocket costs for patients Key products priced below competitors in the US COLUMVI ~12% glofitamab lower price¹ vs. Epkinly Historical net price increases below CPI in the US US net price increase below inflation? US net price increase above inflation? Roche 2018 -20% lower price² 2019 vs. Eylea High Dose VABYSMO 2020 Evrysdi ~22% lower price³ risdiplam vs. Spinraza 2021 2022 ~36% HEMLIBRA emicizumab-kxwh injection for subcutaneous use lower price4 vs. Altuviiio 2023E* mg/mL -8% -4% 0% 4% 8% US Net WAPPI vs. CPI-U OCREVUSⓇ ocrelizumab FOR N ~25% lower price5 vs. Rebif No impact expected from IRA inflationary penalties 1 Annual cost of Epkinly; 2 discount based on WAC per vial; 3³ discount over 5-yrs (at max Evrysdi price); 4 discount at launch based on WAC, annualized average for prophylaxis in a patient weighing 63.4kg. Based on US label dosing, including 50 IU/kg for Altuviiio. Cost of drug can be highly variable depending on several factors including dosing schedule and disease severity.; 5 discount at launch, based on list price; 6 Genentech's annual average net price increase in the U.S., weighted by sales; 7 source: U.S. Bureau of Labor Statistics; *2023 Net WAPPI of 1.28%; CPI-U forecast of 4.36% (S&P Global Market Intelligence); WAPPI = weighted average portfolio price increase; CPI-Consumer Price Index 43#44Pharma Update On-Market Portfolio With Further Growth Potential Significant Growth Opportunities Ahead Roche#45Building blocks for future growth through 2030 Currently 16 blockbusters on the market Oncology/Hematology Neuroscience Ophthalmology Immunology CVM Emerging assets from early pipeline and BD anti-IL6 mAb ASO Factor B zilebesiran SPK-8011 tobemstomig Roche trontinemab anti-latent myostatin mAb Susvimo Gazyva astegolimab Susvimo Gazyva astegolimab divarasib Elevidys Enspryng fenebrutinib divarisib Elevidys Enspryng fenebrutinib crovalimab tiragolumab inavolisib giredestrant crovalimab tiragolumab inavolisib giredestrant Vabysmo Ocrevus Evrysdi Vabysmo Ocrevus Evrysdi Vabysmo Ocrevus Evrysdi Hemlibra Tecentriq Venclexta Alecensa Hemlibra Tecentriq Venclexta Alecensa Hemlibra Tecentriq Venclexta Alecensa Phesgo Columvi Lunsumio Polivy Phesgo Columvi Lunsumio Polivy Phesgo Columvi Lunsumio Polivy Launched portfolio Mid-term opportunities* CVM = cardiovascular / metabolism; *mid-term defined as filing 2024-2026, **long-term defined as filing after 2026, BD-business development Long-term opportunities** 45#46Building blocks for future growth through 2030 Young on-market portfolio with strong momentum and potential for line extensions Roche Oncology/Hematology Neuroscience Ophthalmology Immunology CVM Emerging assets from early pipeline and BD anti-IL6 mAb ASO Factor B zilebesiran SPK-8011 tobemstomig trontinemab anti-latent myostatin mAb Susvimo Gazyva astegolimab Susvimo Gazyva astegolimab divarasib Elevidys Enspryng fenebrutinib divarisib Elevidys Enspryng fenebrutinib crovalimab tiragolumab inavolisib giredestrant crovalimab tiragolumab inavolisib giredestrant Vabysmo Ocrevus Evrysdi Vabysmo Ocrevus Evrysdi Vabysmo Ocrevus Evrysdi Hemlibra Tecentriq Venclexta Alecensa Hemlibra Tecentriq Venclexta Alecensa Hemlibra Tecentriq Venclexta Alecensa Phesgo Columvi Lunsumio Polivy Phesgo Columvi Lunsumio Polivy Phesgo Columvi Lunsumio Polivy Launched portfolio Mid-term opportunities* Long-term opportunities** CVM = cardiovascular / metabolism; *mid-term defined as filing 2024-2026, **long-term defined as filing after 2026, BD-business development 46 46#47HY 2023: Strong momentum for key growth drivers Vabysmo Ocrevus Hemlibra Evrysdi Phesgo Tecentriq Polivy Perjeta Tamiflu TNKase/Activase Gazyva Alecensa Enspryng Xolair Lunsumio Xofluza Ronapreve Actemra/RoActemra MabThera Herceptin 15% 20% 48% 69% 12% 114% 9% 298% 15% 22% 10% 56% 4% n/a >500% 2% -6% -17% -19% -21% -46% US ■Europe >500% Roche ■Japan Avastin Lucentis International Esbriet -73% -400-300-200 -100 0 100 200 300 400 500 600 700 800 900 1,000 47 Absolute values and growth rates at Constant Exchange Rates (CER)#48Vabysmo: Expecting more than CHF 2bn sales in 2023 Highly successful first launch under new commercial model US patient share since launch* Vabysmo performance update Roche VABYSMO • US market share reaches 18% in nAMD, and 11% in DME in Q2; 1/3 naive patients and 2/3 switches (mostly from aflibercept) • >20% market-share in UK, Switzerland within 1 year of launch; Double-digit market shares achieved in Japan, Australia • Anatomic benefits observed in switch patients in the real world drive confidence for earlier line usage (TRUCKEE)1 nAMD DME 60% 60% 50% 50% 40% 40% 30% 30% 20% 20% 10% 10% 0% 0% Q1 Q2 Q3 Q4 Q1 22 22 22 22 23 Q2 Q1 Q2 Q3 Q4 Q1 Q2 23 22 22 22 22 23 23 • Expect public reimbursement for all EU-5 by end 2023 -Vabysmo Eylea Anti-VEGF mAb** Outlook • Filed for 3rd indication RVO in US/EU (FDA PDUFA date set for 22 December) Further potential to grow our Ophthalmology franchise: Relaunch of Susvimo, satralizumab in TED and anti-IL-6 mAb in UME and DME *Claims data based on Verana shares through July 2023; **Avastin, Lucentis and biosimilars; 1 Khanani et al., Eye 2023; nAMD-neovascular age-related macular degeneration; DME-diabetic macular edema; RVO-retinal vein occlusion; TED-thyroid eye disease; UME=uveitic macular edema; PDUFA=prescription drug user fee act; Eylea (aflibercept) is a registered trademark/product of Regeneron/Bayer 48#49Roche Vabysmo: Disease activity criteria chosen affect durability outcomes Vabysmo nAMD trials use vision or anatomical disease activity criteria, reflecting clinical practice¹ Different ≥Q12W disease criteria as applied to Vabysmo or aflibercept 8 mg patients* aflibercept 8mg ASRS SEATTLE Vabysmo Share of patients assigned to ≥Q12W dosing Assessment done at week 20 Share of patients assigned to ≥Q12W dosing Stringent criteria (as actually applied in our clinical trials) Treatment change if ANY criteria are met (based on criteria used in pivotal trials) 22% "OR" criteria 53% 47% Ph II CANDELA (wk 44) A OR B OR C OR D OR E 78% Less stringent criteria (post hoc analysis**) Treatment change if ALL criteria are met F AND G 4% >Q12W Q8W 96% "AND" criteria 83% >Q12W Q8W 17% Ph III PULSAR (wk 48) Ph III TENAYA/LUCERNE trial with stringent patient-centric criteria resulted in 22% of patients being allocated to Q8W dosing Using less stringent criteria, only 4% of patients would have been assigned to Q8W dosing (post hoc analysis) 1. Zarbin et al. ASRS, 2023; *Criteria: A=> 5 letters BCVA loss vs avg. BCVA over previous 2 scheduled visits, due to nAMD, B=> 10 letters BCVA loss vs highest BCVA recorded over previous 2 scheduled visits, due to nAMD; C=> 50 μm CST increase vs avg. CST over previous 2 scheduled visits; D=≥ 75 μm CST increase vs lowest CST recorded at either of previous 2 scheduled visits; E-Presence of new macular hemorrhage*, due to nAMD activity; F->5 letters BCVA loss vs week 16 BCVA; G=> 25 μm CST increase vs week 16 CST or new macular hemorrhage; **Post-hoc analysis of patients dosing eligibility at week 20, patients not actually assigned based on 'and' criteria in TENAYA/LUCERNE; This analysis is not intended as a cross-trial comparison; This analysis cannot predict whether faricimab-treated patients in TENAYA & LUCERNE would have achieved non-inferiority vs aflibercept 2mg/8mg if the treatment regimen had been modified; additional patients with a missing Week 20 assessment were considered to have met disease activity criteria and were treated Q8W; Q8W=every 8 weeks 49 49#50Susvimo: Continuous 6m delivery preferred by 93% patients vs IVT Commercial US relaunch expected in 2024 and ex-US 2025+ Stronger vision outcomes with potential for extended ≥Q6M dosing Continuous delivery of aVEGF via PD implant 1-2 refill exchanges per year • 93% of patients prefer Susvimo to IVT injections¹ Prefer IVT No Preference Prefer PDS Roche SuSvim o™ ranibizumab injection F 180mg/ml. Ongoing development for the Port Delivery Platform October 2022: SUSVIMO voluntarily recalled due to manufacturing variability; root cause identified and progress made to implement technical solution February 2023: Positive data from pivotal Ph III studies in DME (PAGODA) and DR (PAVILLION) presented at Angiogenesis: • DME: Improved vision (Q6M dosing)² DR: Superior improvement in ≥ 2-Step ETDRS-DRSS (Q9M dosing)³ Trend toward improved safety profile with evolved surgical implantation training and technique²,3 • Q4 2023: Clinical trials expected to restart • Ph lllb (VELODROME) assessing Q9M dosing in nAMD First trials of next generation bispecifics (DutaFabs) 1. Holekamp N et al. ARCHWAY Ph III Trial of the PDS for nAMD, American Academy of Ophthalmology, 129(3), 2022; 2. Campochiaro P et al. Port Delivery System With Ranibizumab in Diabetic Macular Edema: Primary Analysis Results of the Ph III PAGODA Trial, Presented at the Macula Society 46th Annual Meeting, Miami, FL, February 15-18, 2023. 3. Holekamp N et al. Port Delivery System With Ranibizumab in the Treatment of Diabetic Retinopathy Without Center-Involved Diabetic Macular Edema: Primary Analysis Results of the Ph III PAVILION Trial, Presented at the Macula Society 46th Annual Meeting, Miami, FL, February 15-18, 2023. VEGF = Vascular Endothelial Growth Factor; Q6M-every 6 months; PD = Port Delivery; IVT-intravitreal injection; DME-diabetic macular edema; DR-diabetic retinopathy; EDTRDS-DRSS-early treatment diabetic retinopathy study-diabetic retinopathy severity scale; Q9M-every 9 months; nAMD = neovascular age related macular degeneration; 50 50#51Ocrevus: Continued growth in all markets around the world Opportunity to expand overall CD20 class and gain class share 50% 40% MS total patient share (global)* 30% 20% 10% 0% Q1 Q3 Q1 18 18 19 Q3 Q1 Q3 ⚫Ocrevus Other CD20 Q1 Q3 Q1 Q3 Q1 19 20 20 21 21 22 22 23 ABCREPS mAbs Ocrevus performance update • · · • Roche OCREVUS ocrelizumab IR call on October 30 Ocrevus with 22% patient share globally (>300k pts treated) High proportion of patients free of disease progression after 10 years of treatment highlighting importance of early treatment Higher retention rate than other MS medicines Only drug in RMS and PPMS Outlook • · • Orals • Positive Ph III (OCARINA II) results to be presented at ECTRIMS 10 year safety/efficacy data to be presented at ECTRIMS Treatment of choice for family planning: Pregnancy/lactation data to be submitted to health authorities in 2024 Ph III (GAVOTTE/MUSETTE) Ocrevus high dose: Trials fully recruited; potential to further improve control of disability progression Further potential to grow our MS franchise: fenebrutinib has opportunity to disrupt oral class, currently comprising >40% of the global market *Global patient share includes US, 18, JP; ABCREPS includes interferons and Copaxone, Other mAbs includes Tysabri, Lemtrada, and Zinbryta; Other CD20 includes Kesimpta, Briumvi; MS-multiple sclerosis; SC=subcutaneous 51#52Empty#53Evrysdi: Becoming a global SMA market leader >11,000 patients treated worldwide USDm 600 500 400 300 200 100 0 Worldwide SMA sales* Q1 Q3 Q1 Q3 Q1 Q3 Q1 Q3 Q1 Q3 Q1 Q3 Q1 Q3 Q1 16 16 17 17 18 18 19 19 20 20 21 21 22 22 23 -Evrysdi Spinraza Zolgensma Roche Evrysdi •risdiplam 60mg Evrysdi performance update • Significant population of untreated adults remain in key markets • >40% of patients in the US are not on any DMT • Nearly half of Evrysdi new patients starts are treatment naïve • Patients continue to switch to Evrysdi for the following reasons: • tolerability concerns and lack/loss of efficacy (Spinraza) and hope of additional benefit (Zolgensma)1 ⚫ EU label expansion for infants under 2 months achieved in August Outlook • Continued global market share gains driven by switch and naïve • Access driving growth; Evrysdi approved in >100 countries globally Further potential to grow our SMA franchise: Ph II/III combination trial with anti-latent myostatin mAb (GYM329) ongoing *Evaluate pharma; 1. Chiriboga et al, CureSMA 2023; SMA-spinal muscular atrophy; DMT-disease modifying therapy; Evrysdi in collaboration with PTC Therapeutics and SMA Foundation 53 55#54Tecentriq: First PD-1/L1 with subcutaneous formulation Improving convenience for patients, saving resources for healthcare systems SC administration time (in minutes) Tecentriq performance update • Reaching peak share in first-in-class indications (SCLC, HCC) US/EU launch in adjuvant NSCLC ongoing Roche TECENTRIQ atezolizumab A HT SC 7 -77% • Tecentriq SC: Great Britain approval in August Ot 即 IV 30 News August 30, 2023 Roche wins first approval for subcutaneous Tecentriq The subcutaneous formulation of Tecentriq has been approved in the UK for all indications that its intravenous counterpart has received approval. By Phalguni Deswal Outlook • • Tecentriq SC: CHMP opinion expected in Q4; US approval delayed to 2024 ⚫ Ph III (IMvoke010) Tecentriq in adj SCCHN results expected in Q4 • . Ph III (SKYSCRAPER-01) Tecentriq + tiragolumab final OS results in 1L PD-L1+ NSCLC expected in Q4/Q1 ⚫ Ph III (SKYSCRAPER-14) Tecentriq + tiragolumab in 1L HCC initiated Ph III (IMbrave050) in adj. HCC met primary endpoint RFS, OS immature Potential for LES: Ph III in adjuvant SCCHN and pivotal tiragolumab combination program ongoing CER-Constant Exchange Rates; SC-subcutaneous; NSCLC=non-small cell lung cancer; HCC-hepatocellular cancer; SCLC-small cell lung cancer; SCCHN-squamous cell carcinoma of head and neck; OS-overall survival; LE=line extensions; SC with Halozyme's rHuPH20/ Halozyme's human hyaluronidase 4 54#55Growing portfolio in breast cancer: Expanding beyond HER2+ BC Breast cancer cases by subtype¹ Ph III clinical development overview On-market portfolio Pipeline molecules Phl | Ph II | Ph III Herceptin giredestrant (SERD) 69% PERJETA pertuzumab PHESGO® PERTUZUMAB-TRASTUZUMAB >Kadcyla ado-trastuzumab emtansine for injection 10% "TECENTRIQ 10% atezolizumab 4% 7% inavolisib (PI3Ka inhibitor) runimotamab (HER2xCD3) ZN-1041 (HER2 TKI) Giredestrant + palbociclib (perservERA) in 1L ER+/HER2- MBC Giredestrant + CDK4/6 (pionERA) in 1L ER+/HER2- MBC Giredestrant (lidERA) in adjuvant ER+ BC Giredestrant + Phesgo (heredERA) in 1L maint ER+/HER2+ Inavolisib + palbo + fulv (INAVO120) in 1L HR+/HER2-/PI3Km MBC Inavolisib + fulv (INAVO121) post CDK4/6i HR+/HER2-/PI3Km BC Inavolisib + Phesgo (INAVO122) in 1L HER2+/PI3Km BC Unknown TNBC HR-/HER2+ HR+/HER2- HR+/HER2+ Further potential to grow our breast cancer franchise: Expanding into HR+ with two NMEs in Ph III, including in combination with Phesgo 1 Cancer Stats Facts: Female Breast Cancer Subtypes. National Cancer institute. Available at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html (Access date: May 24, 2022; HER2-Human Epidermal growth factor Receptor 2; HR=Hormone receptor; TNBC-Triple negative breast cancer; SERD=Selective estrogen receptor degrader; ER-Estrogen receptor; PI3K-Phosphoinositide 3-Kinase; TKI-Tyrosine kinase inhibitor Roche 55#56Roche PHESGO® Phesgo: Rapid conversion in early launch countries Significantly reducing healthcare costs and resource use Treatment option Phesgo reduces administration time & costs Administration and observation schedule* Strong global launch Global Phesgo conversion rate at 35%* Π 0.5 1.5 hours HIV PIV 5 - 8 min 15-30 min Phesgo • · . 2-6h 1h <-1h- Administration time Ranges driven by differences in loading and maintenance dose Total time 40% ~2.5-7.5 hours 30% 20% 10% ~20-38 min 0% Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 20 21 21 21 21 22 22 22 22 23 23 85% of patients preferred Phesgo for subcutaneous administration over the intravenous formulation of Perjeta and Herceptin Phesgo conversion rate at 35% in early launch countries; conversion in key markets: UK 92%, France, 59%, US: 19%, Germany 16% Phesgo expanding eBC market share • Pivotal Phesgo on-body-injector (OBI) development ongoing Source: O'Shaughnessy J, et al. ESMO 2020 (Abstract 165MO); H-Herceptin; P=Perjeta; IV-Intravenous; *Ranges driven by differences in loading and maintenance dose; *Perjeta/Phesgo conversion rate is based on volumes (vials) and includes all launch countries after the 2nd quarter after the launch (38 countries); Phesgo in collaboration with Halozyme 56 56#57Growing portfolio in malignant hematology Hematologic tumor cases by subtype1 Ph III clinical development overview On-market portfolio 3% 12% Pipeline molecules Lunsumic 9% cevostamab 7% COLUMVI glofitamab forimtamig 14% Rituxan Rituximab GAZYVA obinutuzumab injection VENCLEXTA™ venetoclax tablets 50 100 POLIVY polatuzumab vedotin P-BCMA-ALLO1** IL15/IL15Ra-Fc Phl Ph II Columvi + chemo (STARGLO) in 2L+ DLBCL Lunsumio + Polivy (SUNMO) in 2L+ DLBCL Lunsumio + lenalidomide (CELESTIMO) in 2L+ FL Ph Ill 37% CD19 x CD28 Venclexta + azacitidine (VERONA) in 1L MDS Englumafusp alfa 17% Venclexta + dexamethasone (CANOVA) in t(11;14) R/R MM MM iNHL* DLBCL MDS AML CLL ALL Further potential to grow our hematology franchise: Taking Columvi and Lunsumio into earlier lines, as well as 6 NMEs into new indications 1 Datamonitor: incidence rates includes the 7 major markets (US, Japan, France, Germany, Italy, Spain, UK); *including FL; **In collaboration with Poseida Therapeutics; MM-Multiple myeloma; iNHL-indolent non-hodgkin's lymphoma; DLBCL=Diffuse large B-cell lymphoma; MDS-Myelodysplastic syndromes; AML=Acute myeloid leukemia; CLL=Chronic lymphocytic leukemia; NHL=Non-hodgkin's lymphoma; FL=Follicular Lymphoma Roche 57#58Polivy: Accelerated growth following 1L DLBCL approval Transforming the standard of care in 1L DLBCL again after 20 years Global Polivy sales Polivy performance update CHFM 400 300 200 >500% +17% 100 +91% YoY CER growth • +114% • Currently approved in >80 countries in 1L DLBCL Roche POLIVY polatuzumab vedotin • . Strong 1L DLBCL uptake especially in US, EU and JP Growing patient shares in 1L DLBCL (IPI 0-5), US 13%, Germany 21%, UK 26% and Japan 32% Updated treatment guidelines established Polivy as standard of care in 1L DLBCL in key markets such as US (NCCN category 1), Germany and Japan Outlook • Further growth expected driven by additional approvals and positive reimbursement decisions in EU and international markets Comprehensive development program, including Polivy combinations in 1L/2L+ DLBCL with first-in-class bispecifics Lunsumio and Columvi 0 . HY 20 HY 21 HY 22 HY 23 US Europe International Japan CER=constant exchange rates; DLBCL-diffuse large B-cell lymphoma; IPI=International prognostic index; NCCN=National Comprehensive Cancer Network; Polivy in collaboration with Seagen 58#59Hematology: Shifting the standard of care in CLL, DLBCL, and FL chemotherapy Chronic Lymphocytic Leukemia (CLL) Diffuse Large B cell Lymphoma (DLBCL) Follicular Lymphoma (FL) Roche 1997 Evolution MabThera of SoC: 1L R/R 1L R/R 3L+ 1L 2L+ 3L+ Rituximab chemo clb benda CHOP benda chemo benda Rituxan Rituximab 2013 R+chemo R+clb R+benda R-CHOP R+benda GAZYVA obinutuzumab injection G+chemo G+clb 2019 POLIVY polatuzumab vedotin + New G+Venclexta R+Venclexta MOAS Polivy+ R-CHP Polivy+ R+benda VENCLEXTA venetoclax tablets ng mg Lunsumio Columvi 2022/23 Lunsumi COLUMVI glofitamab = approved R+chemo R+benda G+chemo G+benda Lunsumio Polivy + R-CHP (Ph lb/ll) + Columvi Polivy+ Lunsumio Lunsumio Columvi Lunsumio +lenalidomide Columvi+ GemOx Building on the standard of care with new best-in-class and/or first-in-class combinations CLL-chronic lymphocytic leukemia; DLBCL-diffuse large B-cell lymphoma; FL-follicular lymphoma; R=Rituxan; CHP-cyclophosphamide, doxorubicin, prednisone; R/R=relapsed/refractory; Gem Ox-gemcitabine, oxaliplatin; G-Gazyva; benda-bendamustine; SoC-standard of care; MOA-mechanism of action; Venclexta in collaboration with AbbVie 59#60Hemlibra: Expecting continued market share gains globally The global standard of care with ~40% patient share reached in US/EU5* Steady patient share gains in US and globally 50% 40% 30% 20% 10% 0% US/EU5 total Hemophilia A patient share Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 20 20 20 20 21 21 21 21 22 22 22 22 23 23 -Hemlibra Hemlibra performance update • · ~21,000 patients treated globally Roche HEMLIBRA. emicizumab-kxwh Outstanding profile with >2/3 of patients on monthly or Q2W SC dosing and zero risk of developing inhibitors over time. • Non-inhibitor approved in >100 countries and reimbursed in 58 • Further penetration among moderate/severe patients who remain uncontrolled on FVIII ongoing; high satisfaction amongst switchers Outlook • Focus on access opportunities in non-inhibitors (severe and moderate); some countries already with ~70% non-inhibitor patient share (CA, UK, FR) • Driving growth in key accounts which are below peak share potential • Increasing international access Further growth potential in our Hemophilia A franchise: SPK-8011 gene therapy program and NXT-007 bispecific development ongoing US/EU5 Patient Share within Hemlibra labelled population, source: affiliate data (UK NHS Providers, US sales volume triangulated with IQVIA claims data, DE, ES, IT field force, France volumes); Q2W= every two weeks dosing * 60 60#61Alecensa: Unprecedented Ph III results in adjuvant ALK+ NSCLC Continued >70 market share with further growth potential Roche Global Alecensa sales Alecensa performance update Market leadership in 1L ALK+ NSCLC globally established Growth driven by International markets Outlook . Continued leadership and growth in 1L ALK+ NSCLC globally • CHFM 800 YoY CER growth • +19% +10% +20% 600 +34% 400 200 0 HY 20 US HY 21 HY 22 Europe International Japan HY 23 • Expanding into early disease with ~45% of all ALK+ eNSCLC patients being tested at this stage* • Positive Ph III (ALINA) results of Alecensa in adjuvant ALK+ NSCLC results to be presented at upcoming conference; first-in-class filing ongoing • Ph III (TAPISTRY) tumor-agnostic multi-cohort study including Alecensa ongoing * US data; ZS Primary Market Research, August 1st Release; CER-constant exchange rates; ALK-anaplastic lymphoma kinase; NSCLC-non-small cell lung cancer ALECENSA alectinib 150mp capsules 61#62Roche 2023: Key late-stage newsflow* Regulatory Compound Hemlibra Polivy + R-CHP Vabysmo Tecentriq Columvi (glofitamab) Xofluza Tecentriq + Avastin Tecentriq + chemo Tecentriq Tecentriq + chemo Tiragolumab + Tecentriq Tiragolumab + Tecentriq + chemo Venclexta + dexamethasone Venclexta + azacitidine Alecensa Indication Moderate hemophilia A 1L DLBCL RVO Subcutaneous administration 3L+ DLBCL Influenza (paediatric 1+ yrs.) Adjuvant HCC Neoadjuvant/adjuvant TNBC Adjuvant SCCHN Adjuvant TNBC 1L PDL 1+ NSCLC 1L esophageal cancer t(11;14) R/R MM 1L high risk MDS Milestone EU approval US approval US approval/EU filing US approval/EU filing US/EU approval EU approval Ph III IMbrave050 Ph III IMvoke010 Ph III IMpassion030 EU filing US 2024/ EU filing Ph III GeparDouze/NSABP B-59 2024 Х Q4 2023/Q1 2024 Ph III SKYSCRAPER-08 (China only) Ph III CANOVA Ph III SKYSCRAPER-01 2024 Phase III/ pivotal readouts Phesgo OBI (on body injector) Crovalimab Columvi + GemOx Lunsumio + Polivy Elevidys (Delandistrogene moxeparvovec) Ocrevus 6m SC TNKase Susvimo Susvimo Xolair Adjuvant ALK+ NSCLC HER2+ BC PNH 2L+ DLBCL 2L+ DLBCL DMD RMS/PPMS Stroke patients 4.5-24h DME DR Food allergy Ph III VERONA Ph III ALINA Ph I (pivotal) Ph III COMMODORE 1/2 Ph III STARGLO Ph III SUNMO Ph III EMBARK Ph III OCARINA II Ph III TIMELESS Ph III PAGODA Ph III PAVILION Ph III OUTMATCH ༨.༨༥༨ སྤ་ཚོད་ ༨ Additional 2023 newsflow: * Outcome studies are event-driven: timelines may change Fenebrutinib: Positive Ph II (FENopta) results in RMS • Elevidys US approval in DMD for 4 and 5 years old (Sarepta) • Tiragolumab + Tecentriq + Avastin: Positive Ph I/II (MORPHEUS) results in 1L HCC • Inavolisib + palbociclib + fulvestrant Ph III (INAVO120) data expected Q4 2023 62#63Pharma Update On-Market Portfolio With Further Growth Potential Significant Growth Opportunities Ahead Roche#64Building blocks for future growth through 2030 Several mid-term in-house late-stage projects that can deliver upside Oncology/Hematology Neuroscience Ophthalmology Immunology CVM Emerging assets from early pipeline and BD anti-IL6 mAb ASO Factor B zilebesiran SPK-8011 tobemstomig Roche trontinemab anti-latent myostatin mAb Susvimo Gazyva astegolimab Susvimo Gazyva astegolimab divarasib Elevidys Enspryng fenebrutinib divarisib Elevidys Enspryng fenebrutinib crovalimab tiragolumab inavolisib giredestrant crovalimab tiragolumab inavolisib giredestrant Vabysmo Ocrevus Evrysdi Vabysmo Ocrevus Evrysdi Vabysmo Ocrevus Evrysdi Hemlibra Tecentriq Venclexta Alecensa Hemlibra Tecentriq Venclexta Alecensa Hemlibra Tecentriq Venclexta Alecensa Phesgo Columvi Lunsumio Polivy Phesgo Columvi Lunsumio Polivy Phesgo Columvi Lunsumio Polivy Launched portfolio Mid-term opportunities* CVM = cardiovascular / metabolism; *mid-term defined as filing 2024-2026, **long-term defined as filing after 2026, BD-business development Long-term opportunities** 64#65Adding to in-house opportunities through BD Successful track record of disrupting the SoC and building new franchises Zilebesiran (siRNA targeting AGT) Our proven strengths Roche No AGT synthesis 3 AGT Zilebesiran Renin Angl ACE Angli Aldosteron Strong track record of entering new therapeutic areas and disrupting *** established markets Expertise in advancing inclusive research to address health equity in CVM ABPM ABPM ⚫ siRNA targeting AGT, the precursor protein of all angiotensin peptides . Consistent + durable BP control with potential for improved adherence ⚫ Ph II (KARDIA-1/2) development program ongoing; positive KARDIA-1 results to be presented at upcoming scientific conference; KARDIA-2 data expected in early 2024 Strong Pharma & Diagnostics partnerships with health systems allow for integrated disease management solutions Integrated commercialization expertise utilizing an innovative customer engagement model Prowess in access and policy shaping differentiates Roche in the industry In collaboration with Alnylam Pharmaceuticals siRNAi-small interfering RNA; AGT-angiotensinogen; SoC-standard of care; CVM-cardiovascular & metabolism; BP=blood pressure 65#66Key late-stage pipeline assets with 1bn+ sales potential* Roche Oncology, Hematology tiragolumab NSCLC, HCC, ESCC, SCCHN giredestrant HR+ BC divarasib KRAS+ NSCLC, CRC inavolisib Pi3Km BC crovalimab PNH, aHUS, SCD, LN Tecentriq Adj. SCCHN/HCC, tira combo Columvi 2L DLBCL, 1L DLBCL Lunsumio 2L DLBCL, R/R FL, 1LFL 1bn+ sales potential 2bn+ sales potential Neuroscience, Cardiometabolic Elevidys DMD fenebrutinib RMS, PPMS anti-latent myostatin mAb SMA, FSHD zilebesiran hypertension Ocrevus SC, high dose Enspryng gMG, MOGAD, AIE, TED Immunology, Ophthalmology astegolimab COPD ASO Factor B IgAN, GA anti-IL-6 UME, DME Gazyva LN, SLE, MN Oncology/Hematology Neuroscience Ophthalmology Immunology CVM Trial populations listed in appendix table 8 late-stage NMEs with CHF>2 bn each in peak sales potential 4 late-stage NMEs with CHF >1bn each in peak sales potential 2 marketed products with LEs that could add CHF>2 bn each in peak sales potential 4 marketed products with LEs that could add CHF>1 bn each in peak sales potential *8 with 2bn+ opportunities; LE=line extensions 66 66#67Late Stage Pipeline Oncology (Solid Tumors) Levi Garraway | EVP, Head of Global Product Development and Chief Medical Officer Roche#68Product Development Continued commitment to delivering the worlds most impactful medicines Selected Product Development Leaders R&D Excellence Clinical Science Oncology & Hematology Charlie Fuchs Head of PD/CMO Levi Garraway Medical Affairs Stefan Frings Clinical Science Neuroscience & Rare Diseases, Immunology, Infectious Disease & Ophthalmology Paulo Fontoura 1 2 × Set ambitious R&D objectives 4 5 Access the best external innovation R&D productivity Success rate ✓ Value R&D productivity R&D Research and development Costs ✓ Cycle time Strengthen portfolio framework 3 6 Transform portfolio management & governance Optimize R&D engines and invest in emerging technologies Evolve talent, culture and mindset to achieve objectives Volume Effectiveness Roche Efficiency 68#69Strategic pillars of oncology Precision medicine Right medicines at the right patient inavolisib INAVO 120 (1L HR+ Pi3Km BC) data expected 2023 divarasib Recently published data in NEJM Early disease Novel immunotherapy Early diagnosis and treatment increases the chance for cure Alecensa ALINA (adj ALK+ NSCLC) positive data giredestrant Potential to replace ET in eBC (and mBC) Need more options for patients who have progressed on prior treatment Recent/emerging examples tiragolumab + Tecentriq Ph Ill in 1L HCC initiated Tombestomig (PD1 x LAG3) 00 Rational combinations Leverage breadth of oncology portfolio to explore new combinations Polivy + Columvi +R-CHP Ph Ill trial in 1L DLBCL to be initiated Multiple Ph II trials initiated (e.g. mUC, NSCLC, RCC) giredestrant + Phesgo HeredERA (1L HER2+/HR+ BC) () New modalities Invest in potentially transformative science AR Degrader Ph I trial in mCRPC with FPI in Q2 PROTAB Recent paper published in Nature HCC-Hepatocellular carcinoma; NSCLC-Non-Small Cell Lung Cancer; R-CHP-Rituxan + cyclophosphamide + hydroxydaunorubicin + prednisone; DLBCL-Diffuse large B-cell lymphoma; Pi3K-Phosphoinositide 3-Kinase; NEJM-New England Journal of Medicine; ET-Endocrine therapy; eBC-Early breast cancer; mBC=Metastatic breast cancer; HR=Hormone receptor;adj-adjuvant; mUC=Metastatic urothelial carcinoma; RCC=Renal cell carcinoma; HER2-Human epidermal growth factor receptor 2; mCRPC-Metastatic castration-resistant prostate cancer 69 69 Roche#70Oncology - solid tumor pipeline A leading portfolio differentiated on targets and modalities Ph I (26 NMEs) Ph II Ph III Launched RG6156 EGFRvIII x CD3 RG6185 RG6189 RG6194 belvarafenib (pan-RAF inh) FAP-CD40 RG6058 tiragolumab Multiple indications RG6058 tiragolumab Multiple indications Alecensa RG6058 1L ALK+ NSCLC runimotamab (HER2 x CD3) RG6279 eciskafusp alfa (PD1-IL2v) RG6139 tobemstomig Solid tumors RG6114 inavolisib HR+MBC RG3502 Kadcyla HER2+ BC RG6286 undislcosed RG6292 CD25 MAb RG6323 IL15/IL15Ra-Fc RG6180 autogene cevumeran 1L melanoma RG6171 giredestrant HR+ BC RG1273 Perjeta HER2+ BC mRNA RG6344 BRAF inhibitor (3) RG6353 HLA-G x CD3 RG6411 undisclosed divarasib RG7440 2L NSCLC RG6264 Phesgo HER2+ BC RG6433 SHP2i RG6440 TGFB (SOF10) RG6524 DLL3 trispecific RG65261 camonsertib RG6537 AR Degrader RG65962 ZN-1041 (HER2 TKI) RG66143 KSQ-4279 (USP1 inh) RG7802 cibisatamab mRNA RG7827 FAP-4-1BBL CHU glypican-3 x CD3 CHU codrituzumab CHU CD137 switch antibody CHU RAS inhibitor Small molecule Kadcyla RG3502 RG7446 HER2+ eBC high risk Antibody RG7446 Bispecifics/Trispecifics Tecentriq Multiple indications Neoantigen vaccines Alecensa RG6058 ALK+ NSCLC adj Fusion protein Antibody drug conjugate Cyclic peptides RG6268 Tecentriq Multiple indications Rozyltrek ROS1+ & NTRK+ NSCLC CHU SPYK04 CHU SAIL66 NME=new molecular entities; 'managed by Repare Therapeutics; 2managed by Zion Pharma; ³managed by KSQ Therapeutics Roche 70#71Building blocks for future growth through 2030 4 NMEs in oncology with FIC/BIC potential in late stage development Oncology/Hematology Neuroscience Ophthalmology Immunology CVM Emerging assets from early pipeline and BD anti-IL6 mAb ASO Factor B zilebesiran SPK-8011 tobemstomig Roche trontinemab anti-latent myostatin mAb Susvimo Gazyva astegolimab Susvimo Gazyva astegolimab divarasib Elevidys Enspryng fenebrutinib divarisib Elevidys Enspryng fenebrutinib crovalimab tiragolumab inavolisib giredestrant crovalimab tiragolumab inavolisib giredestrant Vabysmo Ocrevus Evrysdi Vabysmo Ocrevus Evrysdi Vabysmo Ocrevus Evrysdi Hemlibra Tecentriq Venclexta Alecensa Hemlibra Tecentriq Venclexta Alecensa Hemlibra Tecentriq Venclexta Alecensa Phesgo Columvi Lunsumio Polivy Phesgo Columvi Lunsumio Polivy Phesgo Columvi Lunsumio Polivy Launched portfolio Mid-term opportunities* Long-term opportunities** CVM = cardiovascular / metabolism; *mid-term defined as filing 2024-2026, **long-term defined as filing after 2026, BD-business development 71#72Tiragolumab development program continues to expand Continued confidence in anti-TIGIT biological activity based on numerous evidence to date First-in-class anti-TIGIT mAb Clinical development program Roche Myeloid cells Antigen Presentation PD-L1 † MHCI MHC II FOXP3 TIGIT FcR FcR C PVR CD226 Treg TIGIT Suppression Tiragolumab Atezolizumab TCF7 TOX CD8+ T cell ↑ Effector function Tumor Indication Phl Ph II Ph III Lung cancer 1L NSCLC: PD-L1 high Stage III unres. NSCLC Neoadj/Adj NSCLC 1L NSq NSCLC 1L uHCC SKYSCRAPER-01 Results in Q4/Q1 SKYSCRAPER-03 SKYSCRAPER-05 SKYSCRAPER-06 SKYSCRAPER-14/IMbrave 152 Locally advanced ESCC SKYSCRAPER-07 LPI in Q3 GI/GU cancer 1L ESCC SKYSCRAPER-08 Other solid tumors 2L+ PD-L1+ Cervical Ca 1L SCCHN SKYSCRAPER-04 Results in H1 2024 Results in H2 2023 SKYSCRAPER-09 Fixed Dose Combination SKYSCRAPER-11 Subcutaneous . Tiragolumab blocks the binding of TIGIT to its ligand PVR Tiragolumab activates T-cells and also modifies the tumor microenvironment by decreasing suppressive T-regs and activating myeloid cells via its intact Fc region Formulations Comprehensive development program ongoing Ph III SKYSCRAPER-14/IMbrave 152 in 1L unresectable HCC initiated • This could lead to an enhanced anti-tumor immune response when combined with PD-L1 blockade • Ph III SKYSCRAPER-01 continues to the final OS analysis expected in Q4/Q1 (event-driven) 72 mAb= monoclonal antibody; NSCLC-Non-Small Cell Lung Cancer; ESCC-esophageal squamous cell carcinoma; NSq=non-squamous; HCC-hepatocellular carcinoma; uHCC-unresectable hepatocellular carcinoma; SCCHN-squamous cell carcinoma of head and neck; OS-Overall survival; LPI=last patient in; PVR=Poliovirus receptor#73Tiragolumab in 1L NSCLC and 1L HCC SKYSCRAPER-01 continues to final OS analysis; Ph III in HCC initiated Ph III (SKY-01) trial design in 1L PDL1+ NSCLC Ph I/II (MORPHEUS) results in 1L HCC • • Roche 2023 ASCO ANNUAL MEETING Tiragolumab 1200mg IV Q3W Atezolizumab 600mg IV Q3W PD or ORR PFS* 43% 100 HR 0.42 Screening (n=660) R loss of (95% CI: 27.0, 59.1) 95% CI: 0.22, 0.82 1:1 clinical Placebo IV Q3W Atezolizumab 600mg IV Q3W benefit 11% (95% CI: 1.4, 34.7) Probability of PFS (%) 75 50 At the 1st interim primary PFS endpoint not met; however, a numeric improvement was observed in both PFS and OS and curves were separating Inadvertent disclosure of 2nd interim analysis of SKYSCRAPER-01: study is ongoing and remains blinded to patients and investigators We are continuing the study as planned until the final analysis for overall survival . At the 2nd interim OS was immature with a mOS of 22.9m for tiragolumab - Tecentriq vs 16.7m for Tecentriq (HR=0.81); no new safety signals + • 25 +IMbrave 150: atezo+bev (n-336) + MORPHEUS: atezo + bev (n=18) 0 atezo + bev tira + atezo + MORPHEUS: tira + atezo+ bev (n=40) 0 2 4 6 8 + bev 10 12 14 Time (months) 16 18 20 22 24 26 Tiragolumab + Tecentriq + Avastin with an ORR of 43% and a PFS benefit of 58% (HR=0.42) . . Treatment benefit supported by benchmarking vs Ph III IMbrave 150 data No new safety signals Finn R, et al. ASCO 2023; NSCLC=non-small cell lung cancer; HCC-hepatocellular carcinoma; PFS-Progression-free survival; OS-Overall survival; mOS-median overall survival; m=month; Cl=confidence interval; ORR=overall response rate; HR-hazard ratio; PD=progressive disease; IV-intravenous; Q3W-every 3 weeks 73#74Giredestrant in HR+ breast cancer Potential new endocrine backbone potential across eBC and mBC Selective ER degrader (SERD) ER XXIX ER is immobililized, preventing activation of ER target genes ER ER is ubiquitinated & turned over, as a consequence of ER immobilization Broad development program in eBC and mBC Ph III (lidERA) trial design in adjuvant ER+/HER2-BC Clinical development program Giredestrant 30mg QD Screening (n=4,100) R 1:1 Physician's choice of adjuvant endocrine monotherapy Long-term follow-up (5 years) Indication regimen 1L ER+/HER2-mBC giredestrant + palbociclib 1L ER+/HER2- MBC giredestrant + CDK4/6 of choice Phl Ph ll Ph III persevERA pionERA Adjuvant ER+/HER2- BC giredestrant lidERA 1L maintenance ER+/HER2+ mBC giredestrant + Phesgo heredERA • Highest preclinical potency vs. other oral SERDS in development Combinable with all CDKis including: palbociclib, abemaciclib, ribociclib • Well tolerated at all doses, with no dose-limiting toxicity • Girdestrant has the potential to be best-in-class backbone endocrine agent in HR+ BC, either used alone or in combination, replacing standard of care (aromatase inhibitor, fulvestrant or tamoxifen) • A single-arm lidERA substudy will investigate giredestrant + abemaciclib in high risk eBC patients; lidERA is -1 yr ahead of other oral SERD competition in eBC • Initiated additional Ph III (pionERA) trial in 1L mBC (girdestrant + CDK4/6 of choice vs. fulvestrant + CDK4/6 of choice) • First results from Ph III persevERA (1L mBC) expected in 2025 SERD=Selective estrogen receptor degrader; HR-Hormone receptor; ER-Estrogen receptor; HER2-Human epidermal growth factor receptor 2; BC=Breast cancer; mBC=metastatic breast cancer; eBC-early breast cancer; CDKi-Cyclin-dependent Kinase Inhibitor; CDK4/6-CDKI-Cyclin-dependent Kinase 4/6 74 Roche#75Giredestrant data support potential in 1L and adj HR+ BC Tumor response is correlated with higher tumor ER activity sample collection *** ** In eBC, 1L, and ESR1m patients, the tumor is ER pathway dependent 2023 ASCO ANNUAL MEETING 2022 ASCO ANNUAL MEETING Tumor ER pathway activity by time of Ph II (coopERA) results in neoadj setting ო Ki67 response at wk 2 and at surgery Relative reduction in Ki67% from baseline Baseline to week 2 Giredestrant (n = 107). -75% Anastrazole (n=94) -67% Baseline to surgery G+P (n = 93) -81% A+ P (n=91) -74% ER activity Z-score Т C N ୯ eBC pre-1L post-1L post-1L ESR1wt ESR1m 0.00 -0.25- -0.50- -0.75- -1.00- o G+P, Giredestrant + Palbociclib; A+P, Anastrozole + Palbociclib PFS-INV, % Ph II acelERA results in 2/3L setting PFS-INV: ESR1m subgroup giredestrant (n=51) Roche PARIS ESMO Congress 2022 100 PCET (n = 39) 90- HR (95% CI) 80- p-value (log-rank) mPFS, months 0.60 (0.35, 1.03) 0.0610 5.3 3.5 70- 60- 50- 40- 30- 20- 10- 0 0 6 8 10 12 14 Months Exploratory biomarker analysis of acelERA: Post 1L treatment, ER activity was maintained in patients with ESR1m tumors at levels similar to early BC and pre- 1L, while activity was significantly lower in late-line patients with no ESR1 mutation • • Ph II (coopERA) in neoadjuvant setting: Final analysis confirmed greater suppression of Ki67 and rates of complete cycle arrest with giredestrant vs. anastrazole at time of surgery; Ki67 is a biomarker of proliferation associated with improved long-term efficacy outcomes in early stage disease ⚫ Ph II (acelERA) in 2/3L setting: PFS benefit more pronounced in patients with baseline ESR1 mutations (HR 0.61 in ESR1m patients vs. HR 0.81 in all-comers) • Majority of 2L/3L patients appear to be no longer sensitive to endocrine inhibition but ESR1m patients' tumors are still dependent on ER signaling Collier A. et al., ASCO 2023; Fasching P. et al., ASCO 2022; Martin M. et al., ESMO 2022; adj-adjuvant; ORR=objective response rate; PFS=progression-free survival; HR-hazard ratio; HR+=Hprmone receptor positive; ER=estrogen receptor; eBC-early breast cancer; m=months; Cl=confidence interval; ESR1-estrogen receptor 1 75#76Inavolisib in PI3K-mutant breast cancer H2H trial vs alpelisib initiated; Ph III (INAVO120) results in 1L expected Q4 2023 Potential best-in-class PI3Ka inh Potency/selectivity (inavolisib vs. alpelisib) Potential for differentiated safety, efficacy, and combinability Ph I dose escalation and expansion cohort: Clinical development program 58x Inavolisib + palbociclib + letrozole Pi3Ka potency 6x PI3Ka selectivity vs. ẞ 1 26x PI3Ka selectivity vs. 8 Best % change in SLD -20- -40- -60- 1 -80 32x -100 PI3Ka selectivity vs. V GDC-0077 dose (mg) 996 93 99699699 9939 1 5L 0 10 20 30 40 50 Fold change (inavolisib vs. alpelisib)1 Inavolisib ■Alpelisib 60 70 Time Best response PD PD PD SD SD SD SD SD SD SD PR CPR CPR CPR CPR CPR CPR CPR CPR CPR CPR CPR CPR PR CPR Line of therapy (metastatic) 1L 2L 3L 4L 4L 3L 3L 4L 2L 5L 3L 2L 2L 4L 3L 3L 3L 4L 3L 2L 2L 1L 3L treatment (days) 44 58 55 119 84 196 323 168 278 183 347 677 528 353 586 155 712 359 280 508 436 317 380 351 452 31 20% -30% Indication regimen 1L HR+/HER2-PI3Km mBC inavolisib + palbociclib + fulvestrant Phl Ph II Ph III INAVO120 Post CDK4/6i HR+/HER2-PI3Km MBC inavolisib + fulvestrant INAVO121 1L PI3Km and HER+ mBC inavolisib + Phesgo INAVO122 Roche Differentiated from existing PI3K inhibitors: • More potent and selective for PI3Ka subunit • Better in vivo efficacy • Greater safety margins allow for combination Strong efficacy and favorable safety as single agent or in combination with ET +/- CDK4/6i in patients with PI3K-mutant HR+ breast cancer • Ph III INAVO120 in 1L HR+/PI3Km mBC data expected in Q4 2023 • Ph III INAVO121 post-CDKi (head-to-head vs. alpelisib) achieved FPI in Q2 with ET and palbociclib at standard doses . Ph III INAVO122 in 1L HER2+/PI3Km BC (combination with Phesgo) achieved FPI in Q3 ● 40% of HR+/HER2- patients with PI3K mutations Kalinsky K. et al., AACR 2017; Jhaveri, K., et al, SABCS 2019; H2H-head-to-head; inh-inhibitor; ET-endocrine therapy; HR-hormone receptor; mBC=metastatic breast cancer; FPI-first patient in; PI3K-Phosphoinositide 3- Kinase; ET-Endocrine therapy; HR-Hormone receptor; HER2-Human Epidermal growth factor Receptor 2; CDK4/6i-Cyclin-dependent kinase 4 and 6 inhibitors; BC-Breast cancer 76#77赞茶医药 Roche ZN-1041 in HER2+ BC with brain metastases Building on HER2+ breast cancer franchise, exploring novel combinations Potential best-in-class HER2 TKI Encouraging preliminary activity and safety Zion Pharma Ph Ic combination results with trastuzumab and capecitabine results¹ Overall tumor size changed from baseline CNS tumor size changed from baseline TKI AUC br.u/AUC plu Efflux transporter (P-gp/BCRP) substrate? Tucatinib 0.004 Yes Lapatinib 0.010 Yes Neratinib 0.013 Yes Pyrotinib 0.024 Yes Epertinib 0.080 Yes ZN-1041 0.470-0.770 No • Differentiated by high blood-brain-barrier permeability and CNS retention • ZN-1041 is not effluxed by P-gp and BCRP transporters, resulting in better CNS retention (>100-fold vs. tucatinib)1 • Best change (%) 0 -10- -20- -30- -40- -50- -60- -70- -80- -90- -100- Patients Best change (%) 0 -10 -20 -30 -40 -50 -60 -70- -80- -90 -100 Patients Well tolerated and promising Gl safety profile observed compared to other HER2 TKIS • • May be combined with other established anti-HER2 backbones (e.g., Phesgo, Kadcyla, Enhertu) to improve efficacy outcomes, for both prevention and treatment of brain metastases Ph I trial in patients with HER2+ breast cancer ongoing 1 Ma F, et al., ASCO 2023; BC=breast cancer; TKI-tyrosine kinase inhibitor; CNS-central nervous system; AUC-area under the curve; BCRP-breast cancer resistance protein; P-gp-P-glycoprotein; Gl=gastrointestinal; HER2-Human Epidermal growth factor Receptor 2 2023 ASCO ANNUAL MEETING 77#78Divarasib in KRAS G12C-mutant tumors Potential best-in-class molecule; Ph II/III in 2L NSCLC ongoing KRAS G12C inhibitor Best-in-class potential supported by early clinical data Proliferation potency/selectivity GDC-6036 10 101 0.11 Sotorasib 0.11 0.01 Adagrasib NONENE 0.1 0.01 0.0011 0.00011 0.00001- G12C non-G12C 0.011 0.001 0.0001 0.00001- G12C ztg-use 0.001 0.00011 0.00001 G12C non-G12C Overall response rates Roche FDA BTD The NEW ENGLAND JOURNAL of MEDICINE PFS (all doses) in 2L+ NSCLC monotherapy Indication Regimen 2L+ NSCLC Monotherapy 2L+ CRC Monotherapy 2L+ CRC Confirmed ORR 53% (all doses) 56% (400mg dose) 29% (all doses) 36% (400mg dose) 62% Divarasib + cetuximab Percentage of Patients 100 75- 50- 25- mPFS=13.1 months HHH 0- 0 3 6 9 12 15 18 21 24 Months No. at Risk 60 48 37 23 14 17 4 1 0 • • Divarasib is an irreversible covalent inhibitor of mutant KRAS G12C protein resulting in a locked inactive conformation Best-in-class potential being more potent and selective in vitro than sotorasib and adagrasib • Robust clinical benefit in patients with KRAS G12Cm NSCLC and CRC as monotherapy and in combination Manageable safety with reversible adverse events across tumor types Pivotal Ph II/III trial in 2L NSCLC (BFAST) with divarasib cohort ongoing Ph lb trials in 1L NSCLC (KRASCENDO) in combination with pembrolizumab and in 1L, 2L CRC (INSTRINSIC) in combination with cetuximab +/- FOLFOX/FOLFIRI) initiated Purkey H. et al., AACR 2022; Sacher A. et al., NEJM Aug 2023; Desai J, et al., AACR 2023; NSCLC= non-small cell lung cancer; CRC=colorectal cancer; PFS=progression free survival; mPFS=median progression free survival; FOLFOX=folinic acid, fluorouracil and oxaliplatin; FOLFIRI=folinic acid, fluorouracil and irinotecan; ORR-Overall Response Rate 78#79DNA Damage Response (DDR) Building a diversified and differentiated portfolio in DDR Camonsertib (ATR inhibitor) REPARE KSQ THERAPEUTICS KSQ-4279 (first-in-class USP1 inhibitor) . ATRi Stalled DNA replication fork ATR DNA double- strand breaks ATR is a key mediator of cellular DDR and is activated in response to DNA replication stress • Preclinical studies suggest camonsertib to be more selective and potent vs. other ATRi in development with best-in-class potential . • • Ongoing Phl/II (TRESR) demonstrated monotherapy responses in multiple tumors (ovarian, breast, prostate) including patients who received prior PARPI and prior platinum chemotherapy . • Currently investigated as monotherapy and in combo with various agents Ub RAD18 PCNA PCNA FANCD2 FANCI Fanconi Anemia (FA) complex detects and recruits ICL repair proteins FA Complex Ub FANCD2 (Ub FANCI XXXXX XXXXX USP1 USP1 Translesion synthesis Intra-strand Crosslink Repair USP1 is involved in DNA damage repair processes through mechanisms distinct from both PARPI and other targeted therapies KSQ-4279 is a first-in-class small molecule inhibitor of USP1 Combination with PARPi demonstrated strong activity in PARP naïve and PARP resistant mouse models Ph I trial in patients with advanced solid tumors ongoing Camonsertib in partnership with Repare Therapeutics; KSQ-4279 in partnership with KSQ Therapeutics; DDR-DNA Damage Response Roche 79#80Neoantigen vaccine: Autogene cevumeran <+ Cancer Center Memorial Sloan Kettering BIONTECH Roche 1884 Substantially and durably expanded T-cells, correlating with delayed recurrence Phase I results in surgically resectable PDAC (target n=20) ASCO® 2022 Vaccine induced T-cell response associated with longer RFS Tumor and normal DNA N Resection Tumor RNA Neoantigen prediction mRNA manufacture Custom manufacture neoantigen mRNA vaccine Week: 0 6 9 I Dose/cycle: 1 Screen for eligibility Surgery Atezolizumab 1 dose Administer vaccine 17 21 1 2 3 4 5 6 8 Individualized neoantigen vaccine Doses 1-8 mFOLFIRINOX 12 cycles RFS (%) 100 Median RFS: Not reached T 50 50 46 Follow-up Median RFS: 13.7 months 10 11 12 9 0 Individualized neoantigen vaccine Dose 9 06 12 18 T 24 1 30 Months Median follow-up: 18 months Responder (n=8) Non-responder (n=8) P = 0.003 HR: 0.08 (95% CI 0.01-0.40) Autogene cevumeran expanded polyclonal IFNy-producing neoantigen-specific CD8 + T-cells in 50% (n = 8/16) of patients from undetectable levels to large fractions (median 2.9%) of all blood T-cells Randomized trial in PDAC initiated, FPI expected Q3 2023 Planning to initiate additional studies in other tumors Autogene cevumeran in partnership with BioNtech; Balachandran V et al., ASCO 2022; PDAC-pancreatic ductal adenocarcinoma; RFS-relapse free survival 80#81Advancing new modalities across key oncology pathways Bispecifics / trispecifics Neoantigen vaccines Degraders Cyclic peptides Cell Therapies PROTABS (Proteolysis-targeting antibody) TCR T cell Tumor Target Oncogenic pathways/drivers Synthetic lethality/DNA damage response T-cell redirection Synthetic immunity Tumor microenvironment Immunomodulation Adaptive immunity T-cell generation Lineage dependencies Explore biology of early disease and transform treatment of cancer Roche 81#82Late Stage Pipeline Hematology Charles Fuchs | SVP - Global Head of Hematology and Oncology Product Development Roche#83Roche Roche: A leader in malignant and non-malignant hematology Launching new standards of care • Hemlibra in hemophilia A Polivy + R-CHP in 1L DLBCL • Lunsumio in 3L+ FL • Columvi in 3L+ DLBCL Investing in growing & new indications • Established leader in DLBCL, FL, CLL and hemophilia A Expansion potential in malignant (AML, MM, MDS, MCL) and in non- malignant hematology (PNH, aHUS, SCD) 00 Broad portfolio enables novel combinations • • 7 medicines on the market and 10 NMEs in clinical development Novel combinations in NHL (e.g. Polivy + CD20xCD3 bispecifics; Columvi + costimulatory molecules) • Exploring different modalities Bispecific antibodies Antibody drug conjugates Improving patient/ provider experience Fixed duration Simple dosing schedule • Recycling antibody technology . Off-the-shelf availability • Gene therapy • Allogeneic CAR-T Outpatient administration DLBCL-diffuse large B-cell lymphoma; FL-follicular lymphoma; CLL=chronic lymphocytic leukemia; MM-multiple myeloma; AML-acute myeloid leukemia; MDS=myelodysplastic syndromes; MCL-mantle cell lymphoma; CAR- T=chimeric antigen receptor T-cell; R-CHP-rituxan + cyclophosphamide + doxorubicin + prednisone; PNH-Paroxysmal Nocturnal Hemoglobinuria; aHUS-atypical Hemolytic Uremic Syndrome; SCD-Sickle Cell Disease; NHL-Non- Hodgkins lymphoma; NME-New Molecular Entity 83 83#84Broad hematology pipeline enabling novel combinations A pioneer in bispecific antibodies and antibody drug conjugates Phl RG6076 englumafusp alfa Heme tumors RG6026 cevostamab RG6160 r/r MM RG6107 Ph II Columvi 1L ctDNA high risk DLBCL crovalimab SCD go go RG7828 Ph III RG6234 forimtamig MM RG6357 dirloctogene samoparvovec Hemophilia A IL 15/IL 15Ra-Fc RG6323 Heme tumors CD19 x CD28 RG6333 r/r NHL Small molecule ཏྠི ནྟི ཐཱཏི 2བ 1:|:ཀྱི གླེང 1:|:ཀྱི ཀྱང 1 11:|:|:ཀྱི སློང RG6512 FIXax FX Hemophilia P-BCMA-ALLO1 RG6538* MM RG6026 Columvi Heme tumors Lunsumio RG7828 Heme tumors Antibody Bispecifics Gene therapy Fusion protein Antibody drug conjugate Allogeneic CAR-T cells RG6026 Columvi 2L+ DLBCL RG6107 Registration crovalimab PNH Lunsumio 2L+FL & 2L+ DLBCL Launched RG6107 crovalimab aHUS RG6026 Columvi 3L+ DLBCL Venclexta RG7601 RG7828 r/r MM & 1L MDS Lunsumio 3L+ FL RG7596 Polivy 1L & r/r DLBCL RG7601 Venclexta CLL & AML RG6013 Hemlibra Hemophilia A Roche RG7159 Gazyva CLL & FL MabThera RG105 DLBCL, FL & CLL *managed by Poseida Therapeutics; DLBCL-diffuse large B-cell lymphoma; FL-follicular lymphoma; CLL=chronic lymphocytic leukemia; MM-multiple myeloma; AML-acute myeloid leukemia; MDS=myelodysplastic syndromes; PNH=Paroxysmal Nocturnal Hemoglobinuria; aHUS-atypical Hemolytic Uremic Syndrome; SCD=Sickle Cell Disease; NHL=Non-Hodgkins lymphoma; CAR-T-chimeric antigen receptor T-cell 84 ==#85Update late-stage hematology pipeline Malignant hematology: B-cell malignancies Non-malignant hematology: PNH, Hemophilia A Roche#86Building blocks for future growth through 2030 Oncology/Hematology Neuroscience Ophthalmology Immunology CVM Emerging assets from early pipeline and BD anti-IL6 mAb ASO Factor B zilebesiran SPK-8011 tobemstomig Roche trontinemab anti-latent myostatin mAb Susvimo Gazyva astegolimab Susvimo Gazyva astegolimab divarasib Elevidys Enspryng fenebrutinib divarisib Elevidys Enspryng fenebrutinib crovalimab tiragolumab inavolisib giredestrant crovalimab tiragolumab inavolisib giredestrant Vabysmo Ocrevus Evrysdi Vabysmo Ocrevus Evrysdi Vabysmo Ocrevus Evrysdi Hemlibra Tecentriq Venclexta Alecensa Hemlibra Tecentriq Venclexta Alecensa Hemlibra Tecentriq Venclexta Alecensa Phesgo Columvi Lunsumio Polivy Phesgo Columvi Lunsumio Polivy Phesgo Columvi Lunsumio Polivy Launched portfolio Mid-term opportunities* CVM = cardiovascular / metabolism; *mid-term defined as filing 2024-2026, **long-term defined as filing after 2026, BD-business development Long-term opportunities** 98 86#87Update late-stage hematology pipeline Malignant hematology: B-cell malignancies Non-malignant hematology: PNH, Hemophilia A Roche#88• Roche POLIVY polatuzumab vedotin Polivy + R-CHP to become a new SOC in 1L DLBCL POLARIX subgroup data confirm benefit in elderly patients Polivy + R-CHP first new treatment in >20 years in 1L DLBCL Ph III (POLARIX) trial design Ph III (POLARIX) subgroup of ~280 patients (median age 74 yrs), similar baseline characteristics compared to ITT Patients Pola-R-CHP Polatuzumab vedotin (1.8mg/kg)* R-CHP + vincristine placebo • Previously untreated DLBCL R Cycles 1-6 ⚫ Aged 18-80 years 1:1 (1 cycle 21 days) Rituximab 375mg/m² • IPI 2-5 Cycles 7 & 8 • ECOG PS 0-2 R-CHOP R-CHOP++ polatuzumab vedotin placebo Sustained PFS benefit for Polivy+R-CHP (HR 0.76) vs. R-CHOP (mFU 39.7 mo) PFS (probability) 0.8 0.6 1 0.4- PFS UHR: 0.64 p=0.042 OS (probability) 0.8 0.6 0.4 1 OS uHR: 0.74 p=0.296 0.2 -Pola-R-CHP (n=141) -R-CHOP (n=143) 0.2 -Pola-R-CHP (n=141) -R-CHOP (n=143) Unstratified HR: 0.64 (95% CI: 0.41-0.99); p=0.0424 Unstratified HR: 0.74 (95% CI: 0.41-1.31); p=0.2962 0 0 0 6 12 18 24 30 36 0 6 12 18 24 30 36 42 Time (months) Time (months) . Safety comparable with that of R-CHOP Off-the-shelf and fixed duration treatment For all treatment settings, including community Approved in >80 countries Ph III Columvi+Polivy+R-CHP to initiate in 2023 • Clinically meaningful improvement in PFS with a uHR of 0.64 for Polivy+R-CHP vs R-CHOP • OS data immature with a trend for reduction in the risk of death with a uHR of 0.74 • Similarly high treatment exposure across both treatment arms, highlights the tolerability of the Polivy+R-CHP regimen in elderly patients • The safety profile of Polivy+R-CHP in patients aged ≥70 years with 1L DLBCL was generally similar to that of R-CHOP and consistent with that reported for the overall population aged 18-80 years Hu B et al., ASCO 2023; Herrera et al. ASH 2022; DLBCL-diffuse large B-cell lymphoma; PFS=progression free survival; OS= overall survival; mFU=median follow-up; ITT-intent-to-treat; R-CHOP=Rituxan + cyclophosphamide + doxorubicin + vincristine + prednisone; R-CHP-Rituxan + cyclophosphamide + hydroxydaunorubicin + prednisone; HR-hazard ratio; uHR=unstratified hazard ratio; Cl=confidence interval; SOC-Standard of care 88#89Lunsumio and Columvi: Tailored to address diverse patient and healthcare system needs in off-the-shelf approach Lunsumio • Approved in 3L+ follicular lymphoma High CR rate and durable responses Favorable tolerability with low grade CRS • No required hospitalization For outpatient setting, indolent disease (FL) and elderly/unfit patients Roche COLUMVI glofitamab Lunsumi CD20 x CD3 development program moving into earlier lines Lunsumio+lenalidomide Lunsumio Indication 3L+ FL Phi Phil Ph III US/EU approved Readout 2024 Regimen Lunsumio Lunsumio +Polivy 2L+ DLBCL (SCT-ineligible) SUNMO 2L+ FL CELESTIMO r/r CLL 1L DLBCL (elderly/unfit) Lunsumio + Polivy 1L DLBCL (elderly/unfit) Indication Phl Ph II Ph III 3L+ DLBCL US/EU approved Readout 2024 Lunsumio Columvi Approved in 3L+ diffuse large B cell lymphoma • Best in class efficacy potential, high CR rates and durable responses comparable to CAR-Ts • Well tolerated with low grade, predictable CRS; low rate of ICANS and discontinuations Regimen Columvi Columvi GemOx Columvi +CD19x4-1BBL Columvi +CD19xCD28 Columvi + Polivy + R-CHP • Minimal CRS in 1L DLBCL combined with R + chemo For aggressive disease (1L DLBCL, R/R DLBCL, MCL) . 2L+ DLBCL (SCT-ineligible) STARGLO r/r NHL r/r NHL 1L DLBCL Ph III to initiate in 2023 Ph III readouts for Columvi + GemOx in 2L+ DLBCL (STARGLO) and Lunsumio + Polivy in 2L + DLBCL (SUNMO) expected 2024 CR=complete response; CRS-Cytokine Release Syndrome; r/r-relapsed refractory; FL-follicular lymphoma; DLBCL-diffuse large B-cell lymphoma; CLL=chronic lymphocytic leukemia; SCT=stem cell transplantation; NHL-non-Hodgkin's lymphoma; GemOx-gemcitabine oxaliplatin; R-CHP-rituxan + cyclophosphamide + hydroxydaunorubicin + prednisone; ICANS=Immune Effector Cell-associated Neurotoxicity Syndrome; R=Rituximab; MCL Mantle Cell Lymphoma 89#90Lunsumio: Durable efficacy with a manageable safety profile in patients with 3L+ FL after > 2 years of follow-up Efficacy summary CR rate, n (%) ORR, n (%) Pivotal Ph II (GO29781) in 3L+ FL 06- Exploratory analysis of pivotal Ph II: Lunsumio versus last prior therapy1 IRC N=90 OS in patients with a CR at EOT from time of 1st treatment 54 (60) 104 1.01 72 (80) 0.8- mPFS, mo (95% CI) NE (26.3-NE) 0.6 Median follow-up, months 0.4 28.3 (2-38) (range) 24-mo DoCR rate, % (95% CI) 65 (39-90.5) 00 Median DoCR, months (95% CI) 44 NE (23.2-NE) Probability 04- 02- Probability mPFS (95% CI) 0.2 mPFS 12 mo (10-16 mo) NECI: NE-NE) 0.0 112 14 16 18 20 22 24 25 214 Time from first treatment (months) Roche Lunsumic - Mosunetuzumab (N=90) -Prior therapy (N=90) mPFS 24 mo (12 mo-NR) 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 Time (months) • Clinically meaningful outcomes in heavily pretreated r/r FL patients with a CR rate of 60% and median DoCR not reached; 24-month DoCR rate at 65% • 24-month OS rate was 100% in patients with CR at EOT with mOS not reached • No mandatory hospitalization; manageable safety and CRS (mostly low grade and during C1) Fixed-duration treatment: 8 cycles if CR after C8; 17 cycles if PR/SD after C8 • Exploratory analysis demonstrated a 12-month improvement in mPFS with Lunsumio vs last prior therapy in the same patients despite being treated in later lines¹ • Similarly, DoCR was extended with mDoCR not reached with Lunsumio vs 15 months with last prior therapy 1Bartlett et al. ASH 2022; Sehn et al, ICML 2023; FL-follicular lymphoma; PR-partial response; SD-stable disease; DoCR-duration of complete response; ORR-overall response rate; CR=complete response; CRS-cytokine release syndrome; AE-adverse event; EOT-end of treatment; mPFS=median progression-free survival; OS-overall survival; mOS=median overall survival; C=Cycle; mDoCR=median duration of complete response; NE=not estimable 90 00#91Columvi: Durable remissions achieved in 3L+ DLBCL with fixed- duration therapy Efficacy summary CR rate, n (%) [95% CI] ORR, n (%) [95% CI] Pivotal Ph II (NP30179) in 3L+ DLBCL IRC N=155* 62 (40) [32.2-48.2] 80 (52) [43.5-59.7] Median follow-up, months 18.2 (0-33) (range) Ongoing CRs, n/N (%) 42/62 (68) Median DoCR, months 26.9 (18.4-NE) (95% CI) *Intent-to-treat population; CI, confidence interval; NE, not estimable. OS Probability (%) 100 80 60 OS landmark analyses by response at EOT 1 40 CR (N=45) SD/PD (N=57) 20 PR (N=8) + Censored 0 T T 0 3 6 9 12 15 18 21 Time (months) Roche COLUMVI glofitamab Columvi: Fixed duration and simple dosing schedule Glofitamab C1 C2 C3 C4 C5 C6 C7 C8 C9 C10 C 11 C12 Treatment stop Epcoritamab C1 C2 C3 C4 C5 C6 C7 C8 C9 Q4W until PD T 24 27 30 Gazyva pretreatment QW Q2W Q3W Q4W dosing • • Clinically meaningful outcomes in highly refractory r/r DLBCL patients with a CR rate of 40% and a median DoCR of 26.9 months following a fixed treatment Highly durable responses with 70% of patients with a CR at any time remaining in remission at 18 months post-EOT © Majority of patients (92%, 30/45) with a CR at EOT are alive at 12 months after EOT • Following step up dosing in C1, glofitamab is administered in a simple Q3W schedule, with fixed treatment duration of 12 cycles (= 8.5 months) • Fixed-duration treatments help to avoid long term side effects, are convenient, and generate savings for the healthcare system Dickinson M, et al. Hematol. Oncol. 2023;41 (S2):144-6; CR=complete response; ORR=overall response rate; DoCR=duration of complete response; Cl=confidence interval; R/R=relapsed refractory; DLBCL-diffuse large B- cell lymphoma; EOT-end of treatment; CR=Complete response; SD/PD-Stable disease/ Progressive disease; PR=Partial response; C=Cycle 91#92Columvi + Polivy + R-CHP in 1L DLBCL early data encouraging Building upon POLARIX to address remaining unmet need Ph I study design Roche COLUMVI glofitamab POLIVYⓇ polatuzumab vedotin Cycle 1 Cycle 2 Cycle 3-6 Glofit* Glofit+ Glofit+ Pola* Pola* Pola* R R R D8 D15 D8 CHP CHP CHP 21-day DLT window *Pola-R-CHP administered on D1 of each 21-day cycle (maximum 6 cycles); *Glofitamab IV administered in C2-C6, C2 SUD (2.5mg C2D8, 10mg C2D15); target dose (30mg) C3D8 onwards Patient characteristics • 24 patients enrolled, received study treatment** Median age 65.0 years Majority of patients had a high tumor burden Endpoint assessment criteria Response rate assessed by PET-CT 1 Key inclusion criteria Aged ≥18 years, ECOG PS 0-3, IPI score 2-5 • Encouraging Ph I data with Columvi + Polivy + R-CHP demonstrating high CMR rates, irrespective of baseline IPI score, no patients had progressive disease Initiating treatment with Polivy + R-CHP (debulking) was associated with a low rate and mild severity of CRS (3 patients with G1 CRS only) • More mature data to be presented at upcoming conference . Ph III Columvi + Polivy+ R-CHP in 1L DLBCL to be initiated 2023 Dickinson M. et al., ASCO 2023; **as of November 14, 2022; 1. Cheson BD, et al. J Clin Oncol 2014;32:3059-68; R=Rituximab; CHP-Cyclophosphamid, doxorubicin and prednison; DLBCL-Diffuse large B-cell lymphoma; PET-CT-Positron emission tomography-computerized tomography; CRS-Cytokine release syndrome; ECOG Eastern Cooperative Oncology Group performance status; IPI=International Prognostic Index; DLT-Dose-limiting toxicity; IV=Intravenous; CMR=Complete metabolic response; G1-Grade 1; D=Day 92#93Englumafusp alfa (CD19-4-1BBL) in r/r NHL First-in-class B cell-targeted costimulatory T cell agonist Englumafusp alfa + Columvi Pharmacodynamic biomarker data support novel MoA Signal 2 (costimulation) CD19-4-1BBL T cell Tumor cell lysis CD3- CD20 Signal 1 (T cell activation) Glofitamab CD19 CD20 Effector function ↑ Tumor cell killingt Duration of responset Tumor cell (malignant B cell) Modified from Johannes Sam, Roche PRED CD8 T-cell Expansion Change from baseline (C2D8 pre-dose) 8.000- 2.000 0.500 0.125 Pre-dose C2D8 post-dose C2D9 C3D1 pre-dose C3D1 post-dose C3D2 C3D8* C4D1 pre-dose C5D1 pre-dose* RG6076 dose group • Low • Medium • High Glofitamab RG6076 • • Signal 1: NK or T cell activation delivered by Columvi Signal 2: CD19-4-1BBL leads to enhanced NK and T cell activation and promotes a durable immune response First-in-class 4-1BB agonist with B cell targeted co- stimulation of T cells • A dose relationship with reversal of PD1+ terminally differentiated CD8 T-cell expansion in blood is emerging at the C3D8, C4D1, and C5D1 timepoints • Data indicate that CD19-4-1BBL costimulation may lead to a more durable response to Columvi and potentially prevent disease escape Ph I studies for Columvi + CD19-4-1BBL or costimulatory bispecific CD19 x CD28 in r/r NHL ongoing Hutchings et al. ASH 2022; TCB-T cell bispecific; NK-natural killer; R/R=relapsed refractory; NHL-non-Hodgkin's lymphoma; MoA-Mode of action 93 Roche#94Off-the-shelf CAR-Ts for hematologic malignancies Highly differentiated new generation of fully allogeneic CAR-Ts Long-lived self-renewing stem cell memory T cells TSCM Cell Stem cell memory High-fidelity, proprietary gene editing technology POSEIDA THERAPEUTICS Cost, scale and reach Self-renewing • Long-lived • Multipotent • Healthy donor derived MHC I knock-out TCR knock-out Roche • T SCM - ideal cell type for CAR-T due to greater safety and durability • piggy BacⓇ - superior non-viral gene insertion technology Addressing both Graft v Host and Host v Graft alloreactivity with Cas-CLOVER™ Gene Editing • Proprietary booster molecule enables potential to deliver 100's of doses translating into lower cost, lower wait time and broader patient reach Ph I open-label dose-escalation study of P-BCMA-ALLO1 in MM ongoing: Early signs of efficacy and favorable tolerability profile P-CD19CD20-ALLO1 IND approved Q2 2023, Ph I in B-cell malignancies expected to start early 2024 Additional allogeneic CAR-Ts in development for MM and AML • Program in partnership with Poseida; Kocoglu M et al., ESMO I-O 2022; IND=investigational new drug application; CAR-T-chimeric antigen receptor T-cell; MM-multiple myeloma; AML-Acute myeloid leukemia 24 94#95Update late-stage hematology pipeline Malignant hematology: B-cell malignancies Non-malignant hematology: PNH, Hemophilia A Roche#96Crovalimab: Expanding program in complement-mediated diseases Positive Ph III data in PNH filed globally; US filing accepted on 1 Sep Crovalimab (anti-C5 recycling Ab) Broad development program in complement mediated diseases C5 SNP Indication Phl Ph II Ph III COMPOSER Paroxysmal COMMODORE 1 (switch) PNH nocturnal hemoglobinuria COMMODORE 2 (naïve) 5 aHUS Atypical hemolytic uremic syndrome SCD Sickle cell disease COMMODORE 3 (China) COMMUTE-a (adults) COMMUTE-p (pediatric) CROSSWALK-c (chronic) CROSSWALK-a (acute) LN Lupus nephritis Endosome Recycling 4 Receptor, FcRn Lysosome Roche Filed • Uses Chugai's recycling antibody technology (SMART-Ig)1-6 • • Rapid, long-lasting neutralization of C5 in complement mediated diseases Low volume administration supports convenient SC Q4W dosing at home Ph III (COMMODORE 2/1) results in PNH show successful disease control in naïve patients and a favorable benefit-risk profile for patients switching from other C5 inhibitors Clear dosing advantage over current C5 inhibitors with the majority of COMMODORE 2/1 patients preferring crovalimab over previous therapy Filed globally in PNH; first approvals expected in 2024 1 Röth A et al. Blood 2020;135:912-20; 2 Fukuzawa T et al. Sci Rep 2017;7:1080; 3 Sampei Z et al. PLoS One 2018; 13:e0209509; 4 Röth A, Nishimura J. Centro Congressi Federico II 2019; 5 Röth A et al. ASH 2018; 6 Sostelly A et al. ASH 2019; PNH-paroxysmal nocturnal hemoglobinuria; Ab-antibody; SC=subcutaneous; Q4W-every 4 weeks; aHUS-atypical hemolytic uremic syndrome; SCD-Sickle cell disease; LN-lupus nephritis 96 96#97SPK-8011 in hem A: Durable FVIII activity observed up to 5 years FVIII activity accompanied by durable clinical benefit in ABR, joint health and quality of life Study design 5 1011 vg/kg (n=2) 1 1012 vg/kg (n=3) 2 1012 vg/kg (n=9) 1.5 1012 vg/kg (n=10) 1-hour outpatient IV infusion* 52 (+2) weeks 4-year long-term follow-up period (n=24) follow up study: visits every 3-6 months (n=18) Mean FVIII activity OSA (%) Roche FDA BTD Stable FVIII activity levels and improved QoL over long-term follow-up Mean FVIII activity OSA 50 1.5x1012 vg/kg 5x1011 vg/kg 1x1012 vg/kg 2x1012 vg/kg 35 30 15 10 4422250 5 0 >52-104 >104-156 >156-208 >208 Time after vector administration (weeks) Mean (SD) change in Haem-A-QoL TS Change in Haem-A-QoL total score from baseline Year 1 Year 2 Year 3 5050522 -30 -12.3 (16.3) -11.3 -13.4 (15.8) (13.0) n=16 n=15 n=13 Efficacy and safety of single SPK-8011* infusion: • 16 participants with ≥1 year follow-up showed no apparent decrease in FVIII activity over time, with a majority expressing in the mild HA range • 82-99% reductions in ABR and substantial reductions in FVIII consumption, no major safety signals • • Clinically meaningful improvements in joint health by total HJHS score at Year 2 and 3 and in total Haem-A-QoL at Years 1, 2, and 3 Ph III study to open enrolment in 2H 2023 © dirloctocogene samoparvovec; Croteau et al ASH 2022; Data cut-off: Oct 4 2022; analysis includes participants with >52 weeks of follow up (n=16). Grey shaded area indicates the mild range of hemophilia A; FVIII assessments obtained within 5 days of administration of a FVIII infusion were excluded; OSA-one-stage assay; FVIII:C=FVIII coagulant activity; HA=hemophilia A; QoL-Quality of life; ABR=Annualized bleeding rate; M.V. Ragni et al., ISTH 2023, B. Samelson-Jones et al., ISTH 2023 97 97#98Late Stage Pipeline Neuroscience, Immunology and Cardiovascular-Metabolism Paulo Fontoura M.D. Ph. D. | SVP and Global Head of Neuroscience and Immunology Roche#99Building blocks for future growth through 2030 Roche 9 NMEs in Neuroscience, Immunology and CVM with FIC/BIC potential in late stage development Oncology/Hematology Neuroscience Ophthalmology Immunology CVM Emerging assets from early pipeline and BD anti-IL6 mAb ASO Factor B zilebesiran SPK-8011 tobemstomig trontinemab anti-latent myostatin mAb Susvimo Gazyva astegolimab Susvimo Gazyva astegolimab divarasib Elevidys Enspryng fenebrutinib divarisib Elevidys Enspryng fenebrutinib crovalimab tiragolumab inavolisib giredestrant crovalimab tiragolumab inavolisib giredestrant Vabysmo Ocrevus Evrysdi Vabysmo Ocrevus Evrysdi Vabysmo Ocrevus Evrysdi Hemlibra Tecentriq Venclexta Alecensa Hemlibra Tecentriq Venclexta Alecensa Hemlibra Tecentriq Venclexta Alecensa Phesgo Columvi Lunsumio Polivy Phesgo Columvi Lunsumio Polivy Phesgo Columvi Lunsumio Polivy Launched portfolio Mid-term opportunities* CVM = cardiovascular / metabolism; *mid-term defined as filing 2024-2026, **long-term defined as filing after 2026, BD-business development Long-term opportunities** 99 99#100Neuroscience pipeline Industry leading portfolio differentiated on targets and platform technologies M Ph I (5 NMEs) Ph II (10 NMEs) prasinezumab Parkinson's Ph III (1 NME, 5AI) Launched (4) RG7935 rugonersen RG6168 RG6091 Angelman syndrome Enspryng gMG RG1594 RD RD Ocrevus Multiple Sclerosis semorinemab RG6100 Alzheimer's RG6168 Enspryng RG6035 brain shuttle CD20 Multiple Sclerosis MOG-AD RD RG6168 bepranemab* Enspryng NMOSD RG6100 RD Alzheimer's RG6168 Enspryng AIE RD RG6182 MAGLI Multiple Sclerosis trontinemab RG6102 Alzheimer's RG7916 fenebrutinib Evrysdi SMA type 1/2/3 RG7845 RD undisclosed RG6289 Alzheimer's MA Multiple Sclerosis tominersen RG6042 Huntington's RG1594 RG6237 + GYM329+ Evrysdi Ocrevus high dose Multiple Sclerosis RG6356 Elevidys DMD RD RG7916 SMA RD RG6163 undisclosed psychiatric disorders RG1594 GYM329 Ocrevus SC Multiple Sclerosis RG6237 FSHD RD Neuro-immunologic disorders ralmitaront RG7906 Small molecule Antibody Gene therapy Brain shuttle Schizophrenia مه RG7816 alogabat RG7314 Autism spectrum disorder balovaptan PTSD Neuro-degenerative disorders Neuro-developmental disorders Neuro-muscular disorders Psychiatric disorders Locked nucleic acid / antisense RG1662 basmisanil Dup 15q syndrome RD Upcoming readouts Ph III (EMBARK) Elevidys (delandistrogene moxeparvovec) in DMD data expected in Q4 2023 Ph III (LUMINESCE) Enspryng in gMG data expected in H1 2024 FDA approval RD RD Rare disease NME=new molecular entity; Al-additional indication; NMOSD=neuromyelitis optica spectrum disorders; DMD=Duchenne muscular dystrophy; gMG=generalised myasthenia gravis; SMA=spinal muscular atrophy; FSHD=facioscapulohumeral muscular dystrophy; PTSD-post-traumatic stress disorder; MOG-AD=myelin oligodendrocyte glycoprotein antibody-associated disease; AIE-autoimmune encephalitis; MAGL-monoacylglycerol lipase; *Bepranemab partnered with UCB, studies are currently run by UCB Roche 100#101Elevidys, first FDA approved DMD gene therapy by partner Sarepta Ph III (EMBARK) results expected in Q4 Pooled analysis of studies 101/102/103* MDA 2023 Change from baseline in NSAA total score over 1 year** Development program Roche SAREPTA THERAPEUTICS LSM change in NSAA total score from baseline to Year 1 (±SE) 3.0 2.5 2.3 2.0 1.5 1.0 0.5 LSM A=2.4; P<0.0001 0.0 -0.1 -0.5 -1.0 Delandistrogene moxeparvovec (N=52) EC (n=105") Study DMD subgroup PhI Ph II Ph III Comment 101 Ambulatory, 4-7 yrs. 102 103 (ENDEAVOR) 301 (EMBARK) 302 (ENVOL) 303 (ENVISION) Ambulatory, 4-7 yrs. Ambulatory, 3-18 yrs Non-ambulatory, all ages Ambulatory, 4-7 yrs. Ambulatory, 0-3 yrs. Ambulatory, 8-18 yrs Non-ambulatory, all ages US approval (Sarepta) US approval (Sarepta) US approval (Sarepta)* EU filing and US label extension Expansion to younger DMD pts Expansion to older ambulatory and non-ambulatory DMD pts • Positive functional and clinically meaningful results up to 4 years after treatment with consistent safety US accelerated approval achieved by Sarepta in Q2 · First patient treated in the US in August · First ex-US approval in the UAE achieved • Ph III (ENVISION) in older ambulatory and all ages non-ambulatory patients started in Q2 2023 . Ph II (ENVOL) in 0-3 year old ambulatory patients to initiate in H2 2023 • Ph III (EMBARK) results in Q4 2023; data to be filed in the EU / International and to facilitate non-age-restricted expansion of the US label Elevidys (delandistrogene moxeparvovec) accelerated US approval by partner Sarepta Therapeutics; Zaidman, et al. MDA 2023; *For study 103 (ENDEAVOR) only cohort 1 was used; **Functional data from patients who received the 1.33x1014 vg/kg dose of delandistrogene moxeparvovec and the propensity-score-weighted EC cohort were compared; DMD-Duchenne muscular dystrophy; NSAA=North Star Ambulatory Assessment; LSM-least-squares mean; EC-external control; SE-standard error; UAE-United Arab Emirates 101#102Elevidys development program Largest development plans in the broadest patient population Ph III EMBARK study design1 Additional Ph II/III studies Randomisation (N=120) Definitive diagnosis of DMD Confirmed DMD mutation within 1:1 exons 18-44 or 46-79 Roche Elevidys Part 1:52 weeks* Week 129 Week 52 Part 2:52 weeks' Up to 5 years ENVOL Week 645 Week 104 delandistrogene moxeparvovec Muscle Muscle NSAA placebo NSAA biopsy biopsy OLE Study Muscle placebo NSAA biopsy delandistrogene moxeparvovec Muscle NSAA biopsy Part 1 patients will be randomized to treated or placebo (1:1) and stratified according to age and NSAA Primary endpoint Change in NSAA total score from baseline to Week 52 in Part 1 Study 302 21 patients Ages 0-3 Open label •Safety (primary) and Expression (secondary) Excludes mutations 1-17 EU study population ENVISION Study 303 Older ambulatory (n=28) / non-ambulatory patients (n=120) Total 148 patients Double-blind, placebo-controlled No upper age restrictions for non-ambulatory patients • Ambulatory: 8-18 ●Primary endpoint: PUL Excludes mutations 1-17 • Pivotal Ph III (EMBARK) trail: Two part design with an OLE study of up to 5 years; primary endpoint of change in NSAA total score from baseline to Week 52 in Part 1 ⚫ Ph III (ENVOL; Study 302): Open label trial in 0-3 year olds with safety as primary endpoint and expression as secondary ⚫ Ph III (ENVISION; Study 303): Randomized trial in older ambulatory/non-ambulatory patients without an upper age restriction • SV95C-SYDE, first ever digital endpoint approved as primary endpoint by EMA 1.Muntoni et al MDA 2022; *Double-blind, placebo-controlled. *Patients, caregivers, Investigators, and site staff remain blinded. Only a subset of patients will receive a muscle biopsy for expression assessments; DMD=Duchenne muscular dystrophy; NSAA=North Star Ambulatory Assessment; PUL-performance of upper limb; OLE=Open label extension; Delandistrogene moxeparvovec in collaboration with Sarepta Therapeutics; SV95C-Stride Velocity 95th Centile; SV95C-SYDE in collaboration with Sysnav 102#103Fenebrutinib, potential for a best-in-class BTKi in MS Additional Ph II (FENopta) data to be presented at ECTRIMS Fenebrutinib (BTK inhibitor) Macrophage Periphery B cell Ph II (FENopta) results in RMS Total new T1 Gd+ lesions by week and combined* Week 8 Week 12 BTKi dual MOA: inhibits B-cell and myeloid cell B cells/plasmablast Activation via B-cell receptor CNS activation B cell Microglia Myeloid cell Activation via Fc receptor Adjusted mean number of new T1 Gd+ lesions Week 4 0.4 92% (65% to 98%) 22% 0.3 33 (-92% to 68%) 0.2 0.1 0 90% (52% to 98%) Adjusted rate of new T1 Gd+ lesions 0.4 0.3 0.2 0.1 Roche @ean european academy of neurology IR call on October 30 Combined (Weeks 4, 8 and 12) P=0.0022 0 No. of patients 36 70 • Dual MoA targeting both B cells and myeloid cells • Oral, highly selective and only reversible non- covalent BTK inhibitor in Ph III in MS Excellent selectivity limits off-target effects, potential for better safety outcomes . FENopta biomarker study evaluated early impact of fenebrutinib on MRI outcomes and showed significant reductions in brain lesions in RMS patients, meeting primary and secondary endpoints Patients on fenebrutinib 4x likelier to have no new T1 Gd+ & N/E T2 lesions at weeks 4, 8 and 12 vs placebo Safety profile consistent with previous and ongoing trials CSF concentration data from Ph II (FENopta) trial to be presented at ECTRIMS on Oct 10-13th Hua LH et al., EAN 2023; *Results were estimated from a negative binomial model controlling for baseline T1 Gd+ lesion status (presence or absence) and included log number of scans as an offset. Arrows indicate relative reduction (95% CI) of lesions; MS=multiple sclerosis; BTKi-Bruton's tyrosine kinase inhibitor; MoA-mechanism of action; CSF-cerebrospinal fluid; RMS=relapsing multiple sclerosis; Gd+=gadolinium-enhancing; MRI-Magnetic Resonance Imaging; RMS-Relapsing multiple sclerosis; CNS-Central nervous system 103#104Fenebrutinib, pivotal trials in RMS and PPMS ongoing The only BTKi in H2H Ph III trial in PPMS vs Ocrevus Fenebrutinib BTKi competitive landscape¹ Tolebrutinib Evobrutinib Remibrutinib Ph III program overview Non-covalent Reversible WB B cell IC 50° 8nM WB Myeloid cell IC 50° 31nM Ph III H₂N H₂N N Covalent Irreversible Covalent Irreversible Indication Trial design Phl Ph II Ph III RMS vs placebo FENopta Jaye NH₂ RMS vs teriflunomide FENhance 1/2 PPMS vs Ocrevus FENtrepid Covalent Irreversible 10 nM 84 nM 18 nM 166 nM 1660 nM 67 nM Positive data readout, primary and secondary endpoints achieved • Potential to be best-in-class given high potency, high selectivity, reversibility, and only H2H study vs Ocrevus Large safety database of >2,500 pts who have been dosed with fenebrutinib* • Ph III Ph III Ph III FDA partial clinical hold FDA partial clinical hold RMS, RMS, SPMS, RMS PPMS (vs Ocrevus) PPMS (vs Placebo) RMS ● Further solidifying commitment to MS franchise Roche 1. Kramer, et al (2023) nature reviews neurology 289-304; Crawford, et al. (2018) J Med Chem 61, 2227-2245; Francesco, et al., ACTRIMS-ECTRIMS (2017) 200644. Haselmayer, et al. (2019) J Immunol 202, 2888-2906; Angst D, et al. (2020) J Med Chem 63, 5102-5118. MS-multiple sclerosis; H2H-head-to-head; RMS-relapsing multiple sclerosis; PPMS-primary progressive MS; BTK-Bruton's tyrosine kinase; nM=nanomolar; WD=whole blood; *As of Sept 2023: including non-MS Ph I/II studies 104#105Enspryng in neurological disorders gMG, AIE, and MOG-AD First-in-class anti-IL-6R mAb with best-in-disease potential in AcHR+ gMG Enspryng (Anti-IL-6 receptor mAb) gMG: Autoantibodies at the NMJ1 Ph III (LUMINESCE) trial design Neutral pH (7.4) FcRn Anti-AChR Anti-MuSK Nerve terminal Anti-LRP4 MG patients (N=186) MGFA class II-IV, ≥12 yrs • MG-ADL ≥5 Enspryng + SOC 24 weeks Mechanism of anti-MuSKs AChR+, MUSK+, LRP4+ R Mechanism autoantibody positive 1:1 Agrin of anti-AChRs LRP4 ACh Blocked ACh-AChR binding Patients on stable baseline therapy Reduced density Complement of AChR No requirement on previous Acidic pH (6.0) AChE and/or ColQ Cell treatment failure/s AChR- MuSKO Rapsyn. MAC MAC formation and damage of the postsynaptic membrane Placebo + SOC Increased AChR internalization Primary endpoint: and degradation IL-6 receptor gets internalized and degraded Roche • . Recycling mAb with high-affinity to soluble and membrane-bound IL-6R Engineered to enable maximal inhibition of IL-6 signaling • Convenient SC Q4W home administration Mean change from baseline MG-ADL score at week 24 in the AChR+ population • IL-6 blockade has the potential to reduce autoantibody-mediated NMJ damage in gMG . High unmet need: ~10-30% of patients fail SOC therapies with only up to 40% of patients on approved biologics achieve minimal symptom expression² ⚫ Ph III (LUMINESCE) results in gMg expected in 2024 Additional Ph III studies in 2 other autoantibody mediated rare neurological diseases ongoing with first-in- disease potential: Ph III (CIELO) in AIE and Ph III (METEOROID) in MOG-AD 1.Gilhus N.E. et al., Nat Rev Dis Primers. 2019; 2. Howard JF Jr, et al. Lancet Neurol. 2021 IL-6R-interleukin 6 receptor; MG=myasthenia gravis; gMG= generalized myasthenia gravis; AcHR-acetylcholine receptor; NMJ-neuromuscular junction; SC=subcutaneous; Q4W=every 4 weeks; MOG-AD=myelin oligodendrocyte glycoprotein antibody-associated disease; LPI=last patient in; AIE-autoimmune encephalitis; SOC=Standard of care; MGFA-Myasthenia Gravis Foundation of America; MG-ADL-Myasthenia Gravis Activities of Daily Living 105#106Anti-latent myostatin mAb to promote muscle growth in SMA Ph II/III combination trial with Evrysdi ongoing GYM329 (Anti-latent myostatin mAb) Circulating Myostatin Propeptide Complex Latent Myostatin Dimer/Propeptide Complex 100 -1000-13* GYM329 Pre-clinical data in a mouse models of muscle disease Efficent inhibition of latent myostatin, but not GDF11 Latent myostatin Increase in muscle mass and strength in mouse models 250 Combination rationale Roche • Evrysdi treats the underlying SMA disease by increasing SMN M M Muscle Cell Membrane ActRIIB Alk4/Alk5 Muscle Fiber Smad 3 Smad 2 ℗ Smad 4 Smad Complex Gene activation leading to skeletal muscle growth and strength • GYM329 binds latent myostatin, a key negative regulator of skeletal muscle growth and strength Unique sweeping and recycling technology allows less frequent SC dosing and highly specific myostatin inhibition % Inhibition 120 Latent GDF11 100 Mature myostatin Mature GDF11 282842089 0 0.01 0.1 110 Antibody concentration (pg/ml.) 100 Change in muscle mass (g) 8 7 200 Change in grip strength (g) الله الله B10 Vehicle 3 10 GYM-mFc B10 Vehicle GYM-mFe protein throughout the CNS and in peripheral tissues GYM329 targets skeletal muscles to increase their size and strength • GYM329 efficiently inhibits myostatin, but not the related muscle hormone GDF11, making it highly specific compared to other anti-myostatin Abs tested² • GDF11 and myostatin act in opposite directions in muscle strength enhancement • The combination of GYM329 + Evrysdi improved muscle size and strength in an animal model of SMA Ph II/III (MANATEE) of GYM329 and Evrysdi in SMA ongoing 1. A sweeping antibody is a recycling antibody that has been further engineered to bind to FcRn at neutral pH; 2.Muramatsu H. et al., Nature Scientific Reports. 2021; SC=subcutaneous; CNS-central nervous system; mAb-antibody; SMA-spinal muscular atrophy; SMN=survival motor neuron; GDF11-growth differentiation factor 11; GYM329 in collaboration with Chugai 106#107Anti-latent myostatin mAb in the neuromuscular disorder FSHD Ph II (MANOEUVRE) in FSHD, a disorder with high unmet need, ongoing FSHD: Rare genetic disease with high unmet need Ph II (MANOEUVRE) trial design in FSHD Progressive asymmetric skeletal muscle weakness and wasting predominantly in the face, shoulder and upper arm muscles The lower limb and abdominal muscles are also involved Enrollment N=48 GYM329 Pre- ய E R Treatment Placebo (1:1) 4 weeks GYM329 52-week double-blind treatment 52-week active treatment extension Other symptoms can include retinal vascular pathology, hearing loss and respiratory impairment • Genetic muscle disorder driven by ectopic • • expression of the DUX4 transcription factor Estimated global prevalence of 3.2-4.6 per 100,000, affecting adults and children¹ Currently no DMTs against muscle wasting and weakness in FSHD Primary endpoints: Percent change in contractile muscle volume (CMV) of quadriceps femoris as assessed by MRI bilaterally Percentage of participants with adverse events (AEs) • Preclinical studies showed that GYM329 has superior muscle strength-improvement effects in mice compared with other anti-myostatin therapies² • Best-in-Disease potential: Ph II (MANOEUVRE) of GYM329 in FSHD ongoing • GYM329 is further explored in additional diseases and combinations 1. Faux-Nightingale A, et al. Arch Rehabil Res Clin Transl. 2021; 2. Igawa T, et al. Immunol Rev. 2016; DMT-disease modifying therapy; E-enrollment; R=randomization; FSHD-facioscapulohumeral muscular dystrophy; MRI-magnetic resonance imaging; DUX4-double homeobox 4; DMT-Disease modifying therapy; GYM329 in collaboration with Chugai Roche 107#108Alzheimer's disease: Continuing to invest in high unmet need area Leveraging key learnings to develop next generation therapies Clinical development program in Alzheimer's disease Roche Neurology Update Roche IR Event Oct 2023 AD program strategy NME MOA Phl Ph II Ph III Selecting the right population 888 Having the right endpoints Bepranemab Anti-tau mAb Trontinemab Anti-Aẞ mAb Semorinemab Anti-tau mAb Ph Il completed Biomarker Ability to cross the enabled diagnosis blood brain barrier 0 GSM Small molecule Ph I completed • Using prior experience and key learnings to develop effective clinical trials Leading diagnostic solutions, including screening and confirmatory tests, developing novel blood- based and digital biomarker options • Innovative Brain Shuttle technology to enable superior penetration of BBB, leading to deeper and faster Aẞ reduction - potential for better efficacy Investigating MoAs to target various stages of the anti-amyloid cascade with GSM acting early in the pathological process and anti-tau mAbs acting at the end of the cascade . Ph I dose escalation for trontinemab and FIH data for GSM to be presented at CTAD 2023 on Oct 24-27th AD=Alzheimer's disease; BBB-blood brain barrier; mAb-monoclonal antibody; Aẞ-Amyloid ẞ; GSM-gamma secretase modulator; FIH=first in human; MoA-Mode of action 108#109Trontinemab: First Aß-targeting Ab brain shuttle technology Best-in-disease potential: Fast and highly efficient plaque removal after 3-6 months Trontinemab (Brain Shuttle TfR1-binding IgG) Ongoing Ph I/II dose finding study in AD Staggered, parallel-group design, with 4 initial sequential cohorts Blood BBB Brain tissue Transferrin receptor 1 Gantenerumab binder Brain shuttle module Aggregated Aẞ طع Screening up to 12 weeks Cohort 4 Cohort 3 Cohort 2 Cohort 1 Parallel-group, double-blind treatment period D1 Start of treatment 28 weeks W28 primary endpoint Follow-up 28 weeks • • Trontinemab, brain shuttle, is an antibody format composed of gantenerumab and a linked transferrin receptor (TfR1) binding moiety The construct can achieve efficient transport over the blood brain barrier and target Aẞ plaque in the brain¹ • Ongoing Ph I/II study investigating four patient cohors (10-15 patients per cohort) with prodromal or mild-to-moderate AD for 7 months and with an option to expand most promising cohorts • Faster and more efficient plaque removal, could result in a more pronounced delay in disease progression compared to first generation anti-amyloid therapies • Updated data from the ongoing Ph I/II study to be presented at CTAD 2023 on Oct 24-27th 1 Gantenerumab brain shuttle results were compared with historical data obtained from a previous gantenerumab SAD trial (BN18726; 2.Kulic L. et al., ADPD 2021); AD=Alzheimer's disease; TfR1-Transferrin receptor protein 1; IgG-Immuno-globulin G; BBB-blood brain barrier; mAb-monoclonal antibody; Aẞ-Amyloid ẞ; Ab=Antibody Roche 109#110Immunology, Infectious Disease and CVM pipeline Gazyva Ph III data in lupus nephritis expected in 2024; zilebesiran in hypertension added Ph I (8 NMEs) Ph II (8 NMEs) Ph III (1 NMEs, 7 AI) Roche RG6107 crovalimab LN will RG6299 ASO factor B IgA nephropathy RG3648 Xolair Food allergy RG6287 undisclosed aGVHD undisclosed RG6341 RG6149 Chronic cough astegolimab (Anti-ST2) COPD RG6315 undisclosed Immunological disorders Vixarelimab RG6536 RG7159 Gazyva IPF/SSC-ILD Lupus nephritis RG6421 TMEM16A potentiator cystic fibrosis RG7854/RG63 ruzotolimod/xalnesiran/PDL1LNA 46/RG6084 HBV Gazyva RG7159 Membranous nephropathy Lunsumio (mosunetuzumab) RG7828 RG7159 SLE SPK-3006 Gazyva SLE RG6359 Pompe disease CHU anti-HLA-DQ2.5x gluten peptides Celiac disease RG7159 RG6615 zilebesiran Hypertension Gazyva Childhood onset INS CHU RAY121 Immunology RG7159 Xofluza Influenza, pediatric RG6006 ABX MCP bacterial infections RG7845 Xofluza Influenza direct transmission RG6319 LepB inhibitor complicated urinary tract infection RG6449 HBsAg MAb Chronic hepatitis B Immunology Small molecule Infectious diseases Antibody Cardiovascular & metabolism Locked nucleic acid / antisense Gene therapy Upcoming readouts Ph III (REGENCY) Gazyva in LN data expected in 2024 Ph II (KARDIA-2) zilebesiran as add-on to one SoC in uncontrolled hypertension data expected early 2024 NME=new molecular entity; Al-additional indication; LN-lupus nephritis; SLE-Systemic lupus erythematosus; aGVHD=Acute graft-versus-host disease; COPD-Chronic obstructive pulmonary disease; HBV= Hepatitis B virus; INS-idiopathic nephrotic syndrome; IPF-idiopathic pulmonary fibrosis; SSC-ILD=systemic sclerosis-interstitial lung disease 110#111Astegolimab: First-in-class anti-ST2 mAb in COPD Early results show benefit in key endpoints throughout broad patient population Astegolimab (anti-ST2 mAb) astegolimab (anti-ST2) IL-33 macrophage neutrophil anti IL-33 mast cell ST2* cells endothelium eosinophil progenitor eosinophil 48-week exacerbation rate 4 Ph lla (COPD-ST2OP) results¹ Exacerbation rate at 48 weeks RR 0.78 (95% CI 0-53-1-14) p=0.195 AERR=22% Adjusted mean change from baseline in SGRQ-C total score (95% CI) ANWAN SGRQ mean change from baseline Placebo group Astegolimab group Roche • • Astegolimab binds both soluble ST2 and • membrane bound ST2 (IL-33) receptor ⚫ IL-33/ST2 blockade may impact airway remodeling in COPD patients • #3 cause of global deaths; no biologics currently approved in COPD 24 0- Placebo group Astegolimab group Weeks Ph lla (COPD-ST20P): AER reduction of -22% (-37% in EOS low), reduction in SGRQ of -3.3 and increased FEV₁ by +40 ml . Safe and well tolerated • Earlier Ph Il results in asthma with AER reduction of -43% (-54% in EOS low) support efficacy and safety profile in broad population, including EOS low² 1 Yousuf et al. Lancet Respir. Med. 2022;10 (5):469-77; 2Kelsen et al. J Allergy Clin Immunol 2021;148(3)790-8; mAb-monoclonal antibody; ST2=suppression of tumorigenicity 2; IL-33-interleukin-33; COPD-chronic obstructive pulmonary disease; EOS-eosinophils; RR-rate reduction; AER(R)-annualized exacerbation rate (reduction); SGRQ-St. George's respiratory questionnaire; FEV₁-forced expiratory value 111#112Astegolimab: Pivotal program results expected in 2025 Two pivotal trials ARNASA and ALIENTO with similar design currently ongoing Pllb (ALIENTO) / Ph III (ARNASA) trial design Roche Population Astegolimab SC Q2W Former & current smokers, EOS low to high Screening (n=1290) R Astegolimab SC Q4W 1:1:1 Endpoints Primary: AERR at 52 weeks Secondary: SGRQ, FEV₁, E-RS, annualized rate of severe COPD exacerbation Weeks 0 Placebo + 52 • Pivotal program includes up-scaled Ph llb (ALIENTO) and Ph III (ARNASA); results expected in 2025 Primary endpoint of change in AER at 52 weeks, with secondary endpoints focused on disease/ health status (e.g. change in FEV₁/SGRQ) • Broad patient population including former and current smokers, and EOS low to high • Filing expected to be based on combined ARNASA and ALIENTO results • OLE for ALIENTO and ARNASA was initiated in H1 2023 Follow-up COPD-chronic obstructive pulmonary disease; R=randomization; SC=subcutaneous; Q2W/Q4W-every 2/4 weeks; EOS-eosinophils; AER(R)-annualized exacerbation rate (reduction); SGRQ-St. George's respiratory questionnaire; FEV₁-forced expiratory value; E-RS-evaluating respiratory systems; OLE=open label extension 62 62 112#113Astegolimab: Potential for biologic addressing broadest population Aiming to address all COPD patients COPD patient population overview¹ Roche Low 80% High 20% EOS* مر | Smoking Astegolimab target patient population: Low EOS High Former Current Former 70% Current 30% Smoking • Near-term biologics in COPD are focused on EOS high or former smokers only · Astegolimab with a unique potential to cover EOS low to high, as well as former and current smokers 1 Global strategy for prevention, diagnosis and management of COPD: 2023 report; *EOS high defined as ≥300 eosinophil cells per microliter of blood and EOS low defined as <300 eosinophil cells per microliter of blood; COPD-chronic obstructive pulmonary disease; SoC-standard of care; SC=subcutaneous; Q4W-every 4 weeks; EOS-eosinophils 113#114Gazyva with best-in-disease potential in lupus nephritis Potential benefit in autoimmune diseases through sustained B cell depletion Gazyva (glycoengineered anti-CD20 mAb) Ph II (NOBILITY) results in LN1 Complete renal response Clinical trial program Type II anti-CD20 region 50% • Increased direct cell death Decreased CDC . Reduced internalization Indication Phl Ph II Ph III p<0.05 p<0.05 40% p<0.2 LN REGENCY 40% 41% 30% 35% MN MAJESTY 20% 23% 23% 18% Glycoengineered Fc region 10% SLE ALLEGORY • Higher FCYR affinity 0% Increased ADCC/ADCP Week 52 Week 76 Week 104 INS INShore Gazyva + MMF Placebo + MMF Roche · Greater potency than Rituxan in depleting • peripheral and tissue B-cells Ph II (NOBILITY) in LN met both primary and key secondary endpoints with no new safety signals; Placebo-corrected CRR of 22% at week 762,3 • Studies suggest that tissue based B-cells play a ⚫ Ph III (REGENCY) in LN fully recruited with results expected in 2024 major role in lupus nephritis • MN, SLE and INS: Complementary indications of the Gazyva program, with best-in-disease potential in MN, SLE and childhood onset INS 1. Furie R, et al. Ann Rheum Dis 2022; 81:100-107; 2.Furie R et al. Lupus Science & Medicine 2020;7 (Suppl 1):A27; 3.Furie R. et al; ACR 2019; mAb-monoclonal antibody; LN-lupus nephritis; MMF=mycophenolate mofetil; MN=membranous nephropathy; SLE-systemic lupus erythematosus; INS-Idiopathic nephrotic syndrome (Childhood onset INS also known as PNS-Pediatric nephrotic syndrome); CDC=complement-dependent cytotoxicity; ADCC-antibody-dependent cell-mediated cytotoxicity; ADCP-antibody-dependent cellular phagocytosis; CRR=complete renal response; IV-intravenous 114#115Antisense oligonucleotide Factor B in IgAN IONIS Roche Positive Ph II UPCR results at 6 months; Ph III (IMAGINATION) initiated in Q2 2023 Antisense oligonucleotide Factor B (ASO FB) Alternative complement pathway ASO FB C34,0 C3 Clinical development program in IgA nephropathy Early Ph II results³ Ph III (IMAGINATION) trial design Experimental Primary endpoint: Change in UPCR arm C5a C5 AP C5 Convertase Factor D Factor AP C3 Convertase cau Bb Amplification Loop Factor D CBb Bb C36 C3b Factor Factor H C5b C6-C9 C3 iC3b CR1 Factor MAC C3dg Opsonization Inflammation Cell Lysis C3a Inflammation Change from baseline (%) -100 09- -20 0 20 40 Change in UPCR at week 29 (n=10) Estimated Enrollment R N=428 OLE Q4W dosing until week 105 I Placebo arm D D D 1 15 29 W Wk 37 105 ➡ASO FB subcutaneous ➡Placebo subcutaneous • · Globally, IgAN is the most common primary GN that can progress to renal failure High levels of CFB are associated with IgAN 1,2 • ASO FB downregulates CFB production by inhibiting mRNA translation ⚫ Ph II study met its primary endpoint of change in 24-hour urinary protein, with 44% mean reduction in proteinuria from baseline to week 293,4 • Achieved secondary endpoint of change in UPCR from baseline to week 29; kidney function stable during the study³; updated Ph II data to be shared at medical conference in Q4 2023 . Ph III (IMAGINATION) of ASO FB in IgAN initiated in Q2 2023 Figure adapted from: Barbour et al. ASN Annual Meeting 2022; 1. Chiu et al. Front Immunol. 2021; 12: 638309; 2. Yeo et al. Pediatr Nephrol 2018: 33:763-777; 3. Barbour et al. An Exploratory Trial of an Investigational RNA Therapeutic, IONIS-FB-LRx, for Treatment of IgA Nephropathy. ASN 2022 Abstract SA-PO714; 4. IONIS press release 2022: https://ir.ionispharma.com/news-releases/news-release-details/ionis-presents-positive-phase-2-data-patients-iga-nephropathy; ASO-Antisense oligonucleotide; FB-Factor B; IgAN=IgA Nephropathy; CFB-Complement factor B; mRNA-messenger RNA; MoA-Mode of action; UPCR=Urine protein/creatinine ratio; SC-Subcutaneous; Q4W-every 4 weeks; GN=Glomerulonephritis; Ph II trial: NCT04014335; Ph III (IMAGINATION): NCT05797610; ASO Factor B in partnership with IONIS Pharmaceuticals 115#116Zilebesiran with best-in-disease potential in hypertension New MoA with tight upstream blockade of AGT pathway and strong early results Zilebesiran (siRNA targeting AGT) Alnylam Roche PHARMACEUTICALS AGT Zilebesiran No AGT synthesis 0 Renin Angl Angli 나이 ABPM ACE GO ABPM Aldosterone 09 ०० Serum AGT change from baseline % -40- -60- -80- -100- 0 Ph I results in hypertension¹ Change in serum angiotensinogen Mean change in 24-h ambulatory diastolic and systolic blood pressure Placebo 10 mg A25 mg 450 mg +100 mg *200 mg 400 mg ▶800 mg Week 8 Week 24 + Change from Baseline (mm Hg) 30- 30- 25- 15- 15- 10- 10- 5- 0.5 1.1 5- 0- 0- -5- -5- -10- -10- -5.6 -15- -7.9 -15- -5.4 -20- -10.9 -10.4 -9.0 -20- -5.7 -25- -25- -12.5 -9.3 -10.8 -30- -30- -35- -40- -16.8 -35- -22.5 -40 Placebo (N=27) Zilebesiran, 200 mg (N=7) Zilebesiran, 400 mg. (N=8) Zilebesiran, 800 mg (N=8) Zilebesiran, 200 mg (N=6) Zilebesiran, 400 mg (N=8) Zilebesiran, 800 mg (N=8) 12 24 Study week Diastolic blood pressure Systolic blood pressure • siRNA targeting angiotensinogen, the precursor of all angiotensin peptides may avoid RAAS escape • Consistent + durable blood pressure control with potential for improved adherence • Positive Ph I results: >90% reduction of serum AGT for up to 6 months at single SC dose of zilebesiran ≥100mg Decreases in systolic blood pressure (>10 mm Hg) and diastolic blood pressure (>5 mm Hg) by week 8 and sustained at 24 weeks at single SC dose of zilebesian ≥200mg • Well tolerated, only mild-to-moderate injection site reactions and no TRAES, hypotension or significant alterations of renal/liver function 1 Desai et al. N Engl J Med 2023;389:228-38; MoA-mode of action; siRNA-small interfering RNA; SC=subcutaneous; RAAS-renin angiotensin aldosterone system; AGT-angiotensinogen; Angl/II-angiotensin I/II; ACE-angiotensin-converting enzyme; ABPM-ambulatory blood pressure monitoring; SoC-standard of care; TRAES-treatment related serious adverse events; zilebesiran in partnership with Alnylam Pharmaceuticals 116#117Zilebesiran: Comprehensive development program ongoing Positive Ph II (KARDIA-1) results to be presented at upcoming conference Ph II (KARDIA-2) trial design¹ Alnylam Roche PHARMACEUTICALS Clinical development program Ph II (KARDIA-1) topline results Olmesartan Oral QD R 1:1 Primary endpoint Phl Ph II Ph III 24h mean SBP change at month 3 R Amlodipine Oral QD R 12 M OLE* Secondary endpoints KARDIA-1 1:1 N=800 1:1:1 KARDIA-2 Data early 2024 24h mean SBP change at month 6 Indapamide Oral QD R 4 week run- in M M M 1:1 0 3 6 KARDIA-3 To initiate in 2024 Primary endpoint: Office SBP change at month 3 & 6 24h mean SBP change at M3 CVOT based on KARDIA-3 0/A/I QD + Zilebesiran 600 mg SC Q6M 0/A/I QD + Placebo SC Q6M • Ph II (KARDIA-1): Monotherapy in mild/moderate hypertension; met all primary and key secondary endpoints; data to be presented at upcoming scientific conference • Ph II (KARDIA-2): Add-on to one SoC in uncontrolled hypertension; data expected early 2024 ⚫ Ph II (KARDIA-3): Add-on to SoC (2+ treatments) in uncontrolled hypertension with high CV risk; to be initiated in 2024 ⚫ Ph III: CV outcomes (MACE-type endpoint) in uncontrolled hypertension with high CV risk • Ph II (KARDIA-2) fully enrolled and ongoing Ph II (KARDIA-3) results will inform pivotal Ph III trial design • Ph Ill to deliver robust label with CV outcomes benefits at launch • Potential for expansion to other CV indications (e.g. heart failure) *Patients in the OLE phase receive zilebesiran 600 mg SC Q6M; ¹NCT05103332; SBP-systolic blood pressure; SoC-standard of care; CV-cardiovascular; CVOT-CV outcomes trial; MACE=major adverse cardiovascular events; R=randomization; M=month; SC=subcutaneous; Q6M-every 6 months; QD=daily; OLE=open label extension; O=olmesartan; A=amlodipine; l=indapamide; zilebesiran in partnership with Alnylam Pharmaceuticals 117#118Late Stage Pipeline Ophthalmology Christopher Brittain | Vice President and Global Head of Ophthalmology Product Development Roche#119Building blocks for future growth through 2030 5 novel targets in Ophthalmology with differentiated potential in late stage development Roche Oncology/Hematology Neuroscience Ophthalmology Immunology CVM Emerging assets from early pipeline and BD anti-IL6 mAb ASO Factor B zilebesiran SPK-8011 tobemstomig trontinemab anti-latent myostatin mAb Susvimo Gazyva astegolimab Susvimo Gazyva astegolimab divarasib Elevidys Enspryng fenebrutinib divarisib Elevidys Enspryng fenebrutinib crovalimab tiragolumab inavolisib giredestrant crovalimab tiragolumab inavolisib giredestrant Vabysmo Ocrevus Evrysdi Vabysmo Ocrevus Evrysdi Vabysmo Ocrevus Evrysdi Hemlibra Tecentriq Venclexta Alecensa Hemlibra Tecentriq Venclexta Alecensa Hemlibra Tecentriq Venclexta Alecensa Phesgo Columvi Lunsumio Polivy Phesgo Columvi Lunsumio Polivy Phesgo Columvi Lunsumio Polivy Launched portfolio Mid-term opportunities* CVM = cardiovascular / metabolism; *mid-term defined as filing 2024-2026, **long-term defined as filing after 2026, BD-business development Long-term opportunities** 119#120Roche poised for a leading role in Ophthalmology 990 980 댐 OL Roche Opportunities ⚫ aVEGF therapies: transformed patient outcomes over 15-years • Unmet need: superior efficacy and durability Changing landscape: aging population, diabetic epidemic, fast progressing science • • • Products and data Vabysmo: nAMD, DME approved RVO filing completed Susvimo: nAMD approval paused DME, DR filing planned Investment in RWE and VOYAGER study ⚫ Phil data expected '24: ASO fB GA, anti-IL-6 DME • Capabilities Leading in-house imaging data mastery: Al applications, fluid & genetic biomarkers Cell based and optogenetic gene therapy • Leadership ambition Near-term: Vabysmo as IVT SOC relaunch of Susvimo • Accelerate pipeline internally & externally: lead RWE supporting value of innovation Leverage partnering • Expand into adjacent ophthalmology areas expanding with satralizumab into TED • Ph III anti-IL-6 in UME aVEGF-anti-vascular endothelial growth factor A; nAMD-neovascular age-related macular degeneration; DME=Diabetic macular edema; UME-Uveitic macular edema; DR-diabetic retinopathy; RVO-Retinal vein occlusion; GA=geographic atrophy; IL-6-inter-leukin-6; ASO=Antisense oligonucleotide; fB-Factor B; Al-Artificial Intelligence; IVT-Intravitreal; SoC-Standard of care; RWE-Real World Evidence; TED-Thyroid eye disease 120#121Ophthalmology strategy Further improving the standard of care and expanding in new indications Update on key clinical data & outlook Improve outcome across all stages of ocular Vabysmo • New data presented at ASRS 2023: • • ASRS 202. SEATTLE demonstrating reduced risk of epiretinal membrane (ERM) formation vs. aflibercept in patients with DME¹ real-world data reinforcing 1L benefits in DME² and nAMD³ positive anatomical outcomes demonstrated in DME4 and nAMD5 Filed in US and EU Q2/3 2023 in RVO Susvimo (port delivery system) • Return to study enrollment Q4 2023 and US commercialization 2024 • Zifibancimig (VEGF-Ang2 DutaFab) with Ph1b FPI expected Q4 2023 (administration via port delivery system) Ocular Function and Structure Status diseases Earlier stage disease Prevention Anatomic damage Satralizumab Later stage disease ASO factor B BCVA loss Vabysmo Susvimo Today's therapies Blindness Launched Phase II/III OpRegen Restoration Time 1. Glenn et al. ASRS 2023; 2. Gale et al. ASRS 2023, Poster #213; 3. Leng et al. ASRS 2023; 4. Nudleman et al. ASRS 2023; 5. London et al. ASRS 2023; BCVA-Best-corrected visual acuity; DME=Diabetic macular edema; nAMD=Neovascular age-related macular degeneration; RVO=Retinal vein occlusion; FPI-First patient in; ASO=Antisense oligonucleotide 121 Roche#122R&D focus area ophthalmology Better visual outcomes in the future via diagnostics and combination therapies Roche 5 Current SoC Anti-VEGF Anti-VEGF Anti-VEGF Personalized treatment options (PHC) Future SoC Biomarker analyses • Aqueous humor sample • Imaging . Aqueous humor • profiling . Clinical data Genotyping Up ि ه Machine learning algorithm " Clinical diagnosis support Atrophy • Prognosis Early diagnosis Drug choice Dosing regimen New combination therapies Inflammation Fibrosis Angiogenesis Ischemia Increased value for Healthcare ecosystems by delivering better care, improving efficiencies and optimizing resource utilization SoC-standard of care; VGEF-vascular endothelial growth factor; PHC-personalized healthcare 122#123Ophthalmology pipeline gaining momentum Expanding into new disease areas with satralizumab initiating Ph III in TED Roche Phasel Phase II Phase III Launched RG6351 NME Retinal disease RG6179 anti-IL-6 DME RG7716 Vabysmo⭑ BRVO RG7716 Vabysmo nAMD RG6209 NME Retinal disease RG6501 OpRegen¹ GA RG7716 Vabysmo⭑ RG7716 CRVO Vabysmo DME NME RG7921 RVO WWW.000. M ASO factor B² Susvimo Susvimo RG6299 RG6321 RG6321 > > > GA DME nAMD RG6120 Zifibancimig (VEGF-Ang2 DutaFab) nAMD Susvimo RG6321 DR nAMD RVO anti-IL-6 DME/UME RG6179 UME GA Retinal disease FDA approval RG6168 satralizumab TED DR TED Filed in US & EU Upcoming readouts: Data expected for ASO factor B in GA in 2024 Data expected for anti-IL-6 in DME in 2024 and UME in 2025 Antibody DutaFab PDS Wi Antisense oligonucleotide Stem cell therapy 1 In collaboration with Lineage Cell Therapeutics (LCTX); 2 In collaboration with lonis; nAMD-neovascular age-related macular degeneration; DME-diabetic macular edema; UME-Uveitic macular edema; DR-diabetic retinopathy; BRVO-branch retinal vein occlusion; CRVO-central retinal vein occlusion; GA-geographic atrophy; DutaFabs-dual targeting fragment antigen-binding; VEGF-vascular endothelial growth factor; Ang- 2-angiopoietin-2; IL-6=inter-leukin-6; TED-Thyroid eye disease; PDS-Port delivery system; ASO=Antisense oligonucleotide 123#124Susvimo: Adding new indications Positive Ph III results in DME and DR with filing in 2024 Ph III in DME (PAGODA)1 Angiogenesis Feb 10-11 MIAMI Ph III in DR (PAVILION)² Adj. mean change from baseline in BCVA score, (95% CI) PDS 100 mg/mL Q24W IVT ranibizumab Averaged over weeks Difference in adjusted means for BCVA change averaged over weeks 60 and 64, 95% CI 60 and 64 9.6 (8.7, 10.5) NI margin, -4.5 L 0.5 mg Q4W Difference in adj. means 9.4 (8.3, 10.5) Primary endpoint 0.2 (-1.2, 1.6) -10 -8 -6 -4 -2 0 2 4 6 8 10 ETDRS letters Intravitreal ranibizumab PDS 100 mg/mL 0.5 mg Q4W better Q24W better BCVA score change from baseline averaged over weeks 60 and 64 as measured via ETDRS chart Proportion of Patients (CMH Weighted Estimate at Week 52,a) % 100 75 Patients with ≥ 2-step improvement from baseline on ETDRS-DRSS, ITT population 50 80.1% 25 PDS 100 mg/mL Q36W (n = 106) Primary endpoint Difference: 71.1% (95% CI, 61.0%-81.2%; P = < 0.0001b) 9.0% Control (n = 68) Percentage of patients with a >2- step improvement from baseline on the ETDRS-DRSS at week 52 Roche sus vimo ranibizumab injection Forcular implant 100mg/ml. 1. Khanani et al. Angiogenesis 2023; 2. Pieramici et al. Angiogenesis 2023; aThe weighted estimate based on CMH method was stratified by baseline ETDRS-DRSS level (47 vs 53) and baseline intraretinal or subretinal fluid status (present vs absent).Missing ETDRS-DRSS is imputed using the last observed outcome prior to week 52. Patients with missing baseline outcomes are excluded. bCMH test; DME=Diabetic macular edema; DR=Diabetic retinopathy; BCVA-Best corrected visual acuity; ETDRS-Early treatment of diabetic retinopathy study; DRSS-Diabetic retinopathy severity scale; PDS-Port delivery system with ranibizumab; Cl=Confidence interval; IVT=Intravitreal; ITT=Intention to treat; Q24W-Every 24 weeks; Q4W-Every 4 weeks; Q36W-Every 36 weeks 124#125RG6179: Novel anti-IL-6 mAb for intraocular use New data investigating anti-IL-6 in uveitic macular edema shared at ARVO 2023 Anti-IL-6 mAb Uveitic macular edema IL-6 OCT scan: healthy macular IL-6 Roche OARVO. Ph I data (DOVETAIL) presented at ARVO 20231 Change from baseline in BCVA Fc region OCT scan: macular edema Mean (SE) change from baseline in BCVA (letters) 15- Treatment phase 10- 2 8 Weeks Off-treatment phase 0.25 mg 1mg 12 2.5mg 16 20 • Anti-IL-6 mAb binds IL-6 and inhibits all known forms of IL-6 signaling • Specifically designed for intraocular use and optimized for a rapid systemic clearance UME is a common result of intraocular inflammation, with only limited treatment options Inflammation causes vascular leakage & fluid accumulation within the retina² Preliminary clinical data in UME indicating: • . • Improved vision and absence of retinal fluid in all dosing cohorts 25-36% of patients gained 15 letters or more at week 12 All doses of anti-IL-6 were well tolerated across all patients, with no treatment-related serious AEs, sustained IOP increase, or new cataracts Based on these Ph I findings, a Ph III clinical trial program is ongoing 1. Sharma et al. ARVO 2023; 2. Koronis et al. Drug Des Devel Ther. 2019 Feb 19;13:667-680. doi: 10.2147/DDDT.S166092; UME=uveitic macular edema; IOP=intraocular pressure; IL-6=interleukin-6; AE=Adverse event; BCVA-Best-corrected visual acuity; SE-Standard error; OCT-Optical coherence tomography; mAb=Monoclonal antibody 125#126RG6179: Novel anti-IL-6 mAb in UME and DME Two identical Ph III studies in UME initiated Q1 2023 Ph III (Sandcat/Meerkat) trials in UME Roche D1 W4 W8 W12 W16 W20 W48 MEERKAT SANDCAT Adult patients with Anti-IL6 0.25mg Q4W for Anti-IL6 0.25mg PRN 4 weeks UME n=225 per study n=450 total R 1:1:1 Anti-IL6 1.0mg Q4W for 4 weeks Off-treatment Anti-IL6 1.0mg PRN Sham Q4W for 4 weeks Sham Primary endpoint Durability endpoints Study completion Based on the Ph I (DOVETAIL) findings, and supported by PK/PD results, a Ph III study program investigating anti-IL-6 in UME (SANDCAT, MEERKAT) was initiated with FPI in Q1 2023 and data expected 2025 Primary endpoint: Proportion of patients with ≥15 letters BCVA gain from baseline at week 16 . Ph II studies in DME (BARDENAS, ALLUVIUM) also ongoing PK/PD-Pharmacokinetics/Pharmacodynamics; UME-Uveitic macular edema; DME=Diabetic macular edema; PRN=Pro re nata; BCVA-Best-corrected visual acuity; Q4W-Every 4 weeks; IL-6-Interleukin-6; W=Week 126#127Satralizumab in thyroid eye disease Potential disease-modifying treatment option with a well-established safety profile Thyroid eye disease Disease process of TED usually follows the trajectory of Rundle's curve* IL-6 as a potential target for treating TED Roche IL-6 in TED² Ph III (SatraGo-1/SatraGo-2) trial design Orbital volume (CT) in TED patients with or without detectable IL-6 mRNA expression in OF (RT-PCR) W24 W48 W72 D1 W2 W4-Q4W until W20 W24 W26 W28-Q4W until W44 Clinical Manifestations Inflammation Fibrosis Active Phase 1-3 Years Inactive Phase 3+ Years Complex orbital inflammatory autoimmune disease¹ Retroorbital volume (mm²) 2500 P<0.05 P<0.05 P<0.05 2000 1500 1000 500 TU 0 IL-4 + IL-6 + IL-10 Cytokine gene expression in orbital fat tissue R satralizumab n=60 1:1 placebo n=60 Primary endpoint Final in Final person phone visit call satralizumab placebo satralizumab / placebo phone call follow-up • • Most common orbital disease in adults, with symptoms such as redness, dry eye, double vision, protrusion of the eye with periorbital swelling and vision loss¹ Treatment options limited; faster and durable disease modification needed to prevent downstream fibrosis • . IL-6 is a pleiotropic cytokine produced by orbital fibroblasts, macrophages and adipocytes of TED patients, mediating inflammation and fibrosis Satra binds to the IL-6R, preventing IL-6 from binding, inhibiting inflammatory signalling pathways3,4 Two identical Ph III studies investigating Satra in TED (SatraGo-1/SatraGo-2) initiated Q3 2023 * Rundle's curve depicts schematically the typical course of thyroid eye disease severity with time; 1. https://eandv.biomedcentral.com/counter/pdf/10.1186/s40662-014-0009-8.pdf; 2. Hiromatsu et al. J Clin Endocrinol Metab. 2000 Mar;85(3):1194-9; 3. Traboulsee A, et al. Lancet Neurol 2020;19:402–412; 4. Yamamura T, et al. N Engl J Med 2019;381:2114-2124; TED-Thyroid eye disease; CT-Computed tomography; OF-Orbital fat; IL-6=interleukin-6; IL-6R-Interleukin-6 receptor; RT-PCR-Reverse transcriptase polymerase chain reaction; Satra-Satralizumab; W=week; IL-4(10)=Interleukin 4(10) 127#128ASO factor B in GA: Targeting hyperactive alternative complement pathway via SC delivery ASO factor B Gene mRNA Transcription Small molecule drugs Inhibitors or agonists of proteins Disease-causing protein Translation Disease-causing Translation protein Antisense oligonucleotide (ASO) Preclinical and Ph I data Preclinical results in monkeys¹ Roche Systemic (A) and ocular (B) ASO FB protein knockdown achieved with RG6299 SC 1501 Ph I: Significant dose-dependent reductions in plasma FB levels² 20 Placebo 696844 10 mg 696844 20 mg A Biologics Plasma FB Protein (% of BL) 93kD 100- 50- Saline ION-588548 20 40 60 Study Day 80 100 Saline FB ION-588548 FB Mean (+/- SEM) %Change from Baseline FBL (mcg/mL) -20 -40 -60 I -80 BL 8 15 22 29 36 43 -5 57 14 71 个个个个 ↑ ↑ ↑ IONIS-FB-LRX Injection Number of Subjects Visit (day) - 59 85 H T 106 127 • Complement Factor B (CFB): key component of alternative complement pathway; associated with complement hyperactivity seen in GA • Inhibits CFB gene expression & reduces the production of factor B protein B 50kD Advantages of ASO factor B: Placebo: 6 a Tubulin 696844 10 mg 696844 20 mg 12 12 2622 12 12 1622 129 622 622 622 12 12 12 622 122 622 622 Potential for systemic Q4W SC administration, simultaneous treatment of bilateral GA and self-administration at home More suitable option for treatment of early stage disease (e.g. ¡AMD) Ph II GOLDEN ongoing* with data expected 2024; pivotal study in planning stage *Managed by IONIS; 1. Grossman et al., Mol Vis 2017; 2. Guymer RG, et al. Presented at EURETINA 2020; ASO=antisense oligonucleotide; FB-Factor B; GA=geographic atrophy; CFB-Complement factor B; ¡AMD-intermediate age related macular degeneration; SC=Subcutaneous; Q4W-Every 4 weeks; SEM-Standard error of the mean; ASO factor B in-licenced from IONIS pharmaceuticals 128#129OpRegen in GA: Replenishing the retinal pigment epithelium Encouraging early clinical data presented at ARVO 2022 and 2023 Potential to counteract RPE cell loss in Before OpRegen subretinal delivery Photoreceptor degradation GA Roche OARVO. Ph I/lla data: Outer retinal structure and visual function improvements in patients with impaired vision 1,2 Before OpRegen After OpRegen After single OpRegen subretinal Cohort 4 (n=12): Patients with bilateral GA secondary to AMD with BCVA 220/250 and ≤20/64 and GA area ≥4 and ≤11mm2 delivery RPE degeneration and loss OpRegen RPE Cells OpRegen has the potential to counteract RPE cell loss in areas of GA by supporting retinal structure and function . BCVA, ETDRS letters, mean (±SE) SD- 60- > +1.3 letters OCT n= n 12 n12 n 12 n 12 n 11 n 12 50- n=12 n=12 n=11 n 12 n12n=120 12 } +7.6 letters n=12 40- CFP 30- ≥15 Letter Gain at Month 12, n/N (%) 20- Fellow Eye Study Eye 0/12 (0%) 3/12 (25%) 0.0 1.0 2.0 3.0 4.5 6.0 9.0 12.0 Time, months FAF Preliminary evidence of outer retinal structure and visual function improvements with OpRegen was observed in patients with GA and impaired vision (Cohort 4 [n=12]) • Average 7.6 letter gain and 25% of patients with ≥15 Letter gain in Cohort 4 Ph lla trial initiated Q1 2023, continuing to optimize subretinal surgical delivery . OpRegen well tolerated in Ph I/lla GA study with an acceptable safety profile and mostly mild AEs In collaboration with Lineage Cell Therapeutics, Inc. (LCTX); 1. Ho et al. ARVO 2022; 2. Banin et al. ARVO 2023; RPE=Retinal pigment epithelium; GA-Geographic atrophy; AMD-Age-related macular degeneration; BCVA-Best- corrected visual acuity; ETDRS=Early treatment of diabetic retinopathy study; SD-OCT-Spectral-domain optical coherence tomography; CFP-Color fundus photography; FAF=Fundus autofluorescence; AEs=Adverse events; SE=Standard error 129#130Roche Roche application of deep learning in ophthalmology Vabysmo reduces HRF volumes more vs. aflibercept, indicating better disease control ARVO. The application of deep learning to segment hyperreflective foci Representative predictions on YOSEMITE and RHINE (3 separate study eyes, all baseline) Vabysmo shown to reduced HRF volumes significantly more 300- compared to aflibercept Aflibercept 2.0 mg Q8W Faricimab 6.0 mg Q8W Faricimab 6.0 mg T&E Original B-scan B-scan with predictions En face view Adjusted Mean (95% CI) HRF Volume 250- 200 150 100- P value for comparison vs Aflibercept Q8W averaged across all visits: Faricimab Q8W: P = 0.0006 Faricimab T&E: P < 0.0001 Week 1 Week 4 Week 8 Week 12 Week 16 Week 20 Week 24 Week 28 Week 32 Week 36 Week 40 Week 44 Week 48 Visit HRF are small bright objects in the retina in patients with DME and may be imaging biomarkers for inflammation and disease progression DL was used to segment HRF, which were compared with HRF drawn by expert graders ⚫ HRF model predictions were consistent with expert assessments • • A post hoc analysis of YOSEMITE and RHINE demonstrated greater retinal HRF volume reductions in Vabysmo- vs. aflibercept-treated eyes at week 48 Volume reductions indicate suppression of pathways that mediate inflammation • Better resolution of the pathological manifestations of DME with Vabysmo support the therapeutic potential of dual Ang-2/VEGF-A inhibition in retinal diseases Maunz et al. ARVO 2023, Poster # 2697 -B0519; HRF-Hyperreflective foci; DME=Diabetic macular edema; nAMD=Neovascular age-related macular degeneration; DL-Deep learning; Ang-2-Angiopoietin-2; VEGF-A-Vascular endothelial growth factor A; Q8W-Every 8 weeks; T&E-Treat and Extend; CI=Confidence interval 130#131Closing remarks Thomas Schinecker | CEO Roche Group Roche#132Consensus outlook 2022-26* Growth driven by our young on-market portfolio; potential pipeline up-side Biosimilar gap (22-26) Potential up-side³ Consensus sales growth (22-26) Post-HY 2023 consensus survey Lucentis 1.0 bn Xolair 2.2 bn Ronapreve 1.7 bn Gap 7.7bn Vabysmo 4.3 bn Tecentriq 1.7 bn Hemlibra 1.6 bn Ocrevus 1.5 bn Polivy 1.4 bn Actemra 2.7 bn Evrysdi 1.2 bn Lunsumio 0.7 bn Avastin 2.1 bn Ronapreve 0.2 bn Lucentis 0.3 bn Columvi 0.5 bn Xolair 1.4 bn MabThera 2.1 bn Herceptin 2.1 bn Actemra 1.3 bn Avastin 1.0 bn MabThera 1.1 bn Herceptin 1.1 bn Gazyva Alecensa Enspryng Susvimo Other in-market¹ 0.4 bn 0.3 bn 0.3 bn 0.2 bn (0.5) bn Pipeline Ph III² 2.4 bn Perjeta 4.1 bn Perjeta 3.5 bn thereof Elevidys 0.8 bn Kadcyla 2.1 bn Kadcyla 1.6 bn thereof tiragolumab 0.7 bn Phesgo 0.7 bn Phesgo 1.7 bn thereof giredestrant 0.3 bn thereof crovalimab 0.3 bn 2022 Sales 2026 Sales thereof fenebrutinib Total 0.2 bn 16.1 bn Roche Additional up-side by late-stage NMES / LEs poorly or not yet covered: Oncology (inavolisib, divarasib, tobemstomig, autogene cevumeran), Hematology (SPK- 8011), Ophthalmology (ASO factor B in GA, anti-IL-6 mAb, Enspryng in TED), Neuroscience (Enspryng in gMG, anti-latent myostatin mAb, trontinemab, prasinezumab), Immunology (Gazyva in LN, astegolimab, ASO Factor B in IgAN), Cardiovascular & Metabolism (zilebesiran) *All estimates are based on Post HY 2023 consensus collected by FTI Consulting on behalf of Roche (n=18); 1 Activase/TnKase, Esbriet, Pulmozyme, CellCept, Erivedge, Cotellic, Gavreto, Xofluza, Rozlytrek; Luxturna 2 included in >50% of the sell-side models; ³Assets covered on average by only 17% of the sell side models; NME=new molecular entity; LE=line extensions 132#133Doing now what patients need next