#1Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Q4 2021 Results Investor presentation 1 Investor Relations | Q4 2021 Results U NOVARTIS | Reimagining Medicine#2Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Disclaimer This presentation contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995, that can generally be identified by words such as "potential," "expected," "will," "planned," "pipeline," "outlook," or similar expressions, or by express or implied discussions regarding potential new products, potential new indications for existing products, potential product launches, or regarding potential future revenues from any such products; or regarding potential future, pending or announced transactions, including the acquisition of Gyroscope Therapeutics; regarding potential future sales or earnings of the Group or any of its divisions or products; or by discussions of strategy, plans, expectations or intentions; or regarding the Group's liquidity or cash flow positions and its ability to meet its ongoing financial obligations and operational needs; or regarding the strategic review of Sandoz; or regarding our commitment to carbon neutral emissions by 2030 and net zero emissions by 2040. Such forward-looking statements are based on the current beliefs and expectations of management regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. You should not place undue reliance on these statements. In particular, our expectations could be affected by, among other things: liquidity or cash flow disruptions affecting our ability to meet our ongoing financial obligations and to support our ongoing business activities; the impact of the COVID-19 pandemic on enrollment in, initiation and completion of our clinical trials in the future, and research and development timelines; the impact of a partial or complete failure of the return to normal global healthcare systems including prescription dynamics, particularly in oncology and generics; global trends toward healthcare cost containment, including ongoing government, payer and general public pricing and reimbursement pressures and requirements for increased pricing transparency; uncertainties regarding potential significant breaches of data security or data privacy, or disruptions of our information technology systems; regulatory actions or delays or government regulation generally, including potential regulatory actions or delays with respect to the development of the products described in this presentation; the potential that the strategic benefits, synergies or opportunities expected from the transactions described, including Gyroscope Therapeutics, may not be realized or may be more difficult or take longer to realize than expected; the uncertainties in the research and development of new healthcare products, including clinical trial results and additional analysis of existing clinical data; our ability to obtain or maintain proprietary intellectual property protection, including the ultimate extent of the impact on Novartis of the loss of patent protection and exclusivity on key products; safety, quality, data integrity, or manufacturing issues; uncertainties involved in the development or adoption of potentially transformational technologies and business models; uncertainties regarding actual or potential legal proceedings, investigations or disputes; our performance on environmental, social and governance measures; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases such as COVID-19; uncertainties regarding future global exchange rates; uncertainties regarding future demand for our products; and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this presentation as of this date and does not undertake any obligation to update any forward-looking statements as a result of new information, future events or otherwise. DARPin® is a registered trademark of Molecular Partners AG. 2 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#3Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Participants Vas Narasimhan Chief Executive Officer Harry Kirsch Chief Financial Officer John Tsai Head of Global Drug Development and CMO Richard Saynor CEO, Sandoz Marie-France Tschudin President, Novartis Pharmaceuticals Karen Hale Chief Legal Officer Susanne Schaffert President, Novartis Oncology Samir Shah Global Head Investor Relations 3 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#4Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Vas Narasimhan Chief Executive Officer Company overview 4 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#5Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Novartis presents an attractive profile for investors 1 Clear strategy Delivering on strategy as a focused medicines company, powered by technology platforms. 2 Attractive growth profile Confident in 4%+ sales CAGR (2020 to 2026), above peer median growth beyond 2026 High 30s IM margin 3 Strong mid/late- stage portfolio Breadth and depth, 20+ assets with USD ≥1bn potential, fuel further growth to 2030 and beyond 4 Platform leadership Continue to develop leadership across TPD, Cell, Gene, RLT, XRNA platforms 5 Balanced capital allocation Aims to combine investing in core business and returning excess capital to shareholders TPD Targeted Protein Degradation RLT Radioligand Therapy 5 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#6Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Our strategy Focused medicines company powered by technology leadership in R&D, world-class commercialization, global access and data science Where to play | our focus How to win | our five priorities Our aspiration Strengthen our core therapeutic areas Advance our leading technology platforms Embrace operational excellence every day Unleash the power of our people Innovation power Top 3 innovator Returns High 30s IM margin, attractive ROIC1 Accelerate our 4 priority geographies Transform Sandoz Deliver transformative innovation Go big on data and digital 1. Return on invested capital 6 Investor Relations | Q4 2021 Results Build trust with society Growth Consistent above peer median average growth ESG Global leader in material ESG factors NOVARTIS | Reimagining Medicine#7Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Continuing our track record of consistent top-line growth, margin expansion, strong FCF Consistent strong operating performance driven by IM IM Sales USD bn, % CAGR CC +7% 42.0 39.0 37.7 34.9 IM Core Oplnc USD bn, % CAGR CC +13% 15.2 13.6 12.7 11.2 IM Core Margin (%), growth bps cc Group FCF Cont. Ops, USD bn, % CAGR USD +130bps 36.2 +220bps 35.0 +6% 13.3 11.3 +180bps 33.5 32.0 FY 2018 FY 2019 FY 2020 FY 2021 FY 2018 FY 2019 FY 2020 FY 2021 FY 2018 FY 2019 FY 2020 FY 2021 FY 2018 FY 2021 IM Innovative Medicines 7 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#8Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Expect to grow sales 4%+ CAGR 2020-2026 Illustrative Group sales USD billion, cc -9 TasignaⓇ LucentisⓇ XolairⓇ Without any pipeline contribution ~+1.5% CAGR CC LeqvioⓇ3 Lu-PSMA-617 ScemblixⓇ3 Other pipeline CosentyxⓇ KesimptaⓇ KisqaliⓇ ZolgensmaⓇ SandostatinⓇ GilenyaⓇ AfinitorⓇ PiqrayⓇ Sandoz EntrestoⓇ ~+5% CAGR CC if Entresto LoE beyond 20262 +4% CAGR CC 2020 IM Core Margin 35% Future Gx impact up to 20261 In-market growth drivers / Base business IM Division pipeline probabilized Excludes potential impact from US healthcare reform. Compared to R&D Day 2021, removed Ligelizumab in CSU. Votrient. 2. For internal forecasting purposes we do not expect Gx in US at least until 2025. 3. Approved in US. 2026 IM Core Margin High 30s 1. Estimated based on relevant patents; further extensions possible. Additional products include Promacta, Q-Family and 8 Investor Relations | Q4 2021 Results ✓ NOVARTIS | Reimagining Medicine#9Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Delivered strong Q4 performance across our value drivers Growth1 Q4 Group sales +6%; FY +4% Q4 IM sales +7%; FY +6% Q4 Sandoz sales +2%; FY -2% 1 Innovation LeqvioⓇ approved in US CosentyxⓇ Ph3 studies met primary endpoint in HS lanalumab positive Ph2 in Sjögren's T-Charge TM platform positive data in DLBCL and MM 3 Business development (ociperlimab, Gyroscope, ensovibep, UCB0599) Productivity1 Q4 Group core operating income +12%; FY +6% Q4 IM core operating income +15%; FY +10% Q4 IM core margin 33.6% (+2.4%pts cc); FY 36.2% 2 ESG 4 Improved scores for MSCI, ATMI AMR Benchmark, S&P Global Environmental targets on track (-34% Scope 1,2 GHG, -56% waste) Refreshed commitment statement on human rights IM Innovative Medicines division HS-Hidradenitis suppurativa DLBCL - Diffuse large B cell lymphoma MM Multiple myeloma 1. Q4 sales growth for Group, IM and Sandoz includes +1% point impact from a reclassification of contract manufacturing from other revenue to sales. Sandoz FY sales growth also benefited +1% point from this reclassification. Constant currencies (cc), core results are non-IFRS measures; explanation can be found on page 49 of Condensed Financial Report. Unless otherwise noted, all growth rates refer to same period in PY. 9 Investor Relations | Q4 2021 Results ✓ NOVARTIS | Reimagining Medicine#10Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix 1 GROWTH Key growth drivers grew +24% in Q4, representing 54% of IM sales Q4 sales1 Entresto sacubitri/valsartan Sales USD Million 949 Growth vs. PY USD Million Growth vs. PY CC 233 34% Cosentyx 1,243 134 13% (secukinumab) Kesimpta 147 (ofatumumab) 133 KISQALI 285 101 ribociclib zolgensma 342 88 458 Tafinlar. + Mekinist. 50 bal PROMACTA 518 47 (eltrombopag) ILARIS 284 44 (canakinumab) Xolair 373 38 Omalizumab ⒸJAKAVI 408 32 ruxolitinib Xiidra 134 26 MAYZENT. (siponimod) tablets 81 24 Key growth drivers 54% of IM sales, growing 24% in Q4 AimovigⓇ MayzentⓇ 54% PiqrayⓇ nm +24% vs. PY LutatheraⓇ 58% XiidraⓇ 36% 47% KymriahⓇ Kesimpta පු® 14% 38% IlarisⓇ 12% 29% 23% 15% Kisqali® ZolgensmaⓇ JakaviⓇ Tafinlar+MekinistⓇ PromactaⓇ 12% EntrestoⓇ 24% CosentyxⓇ Other² 46% Q4 2018 Q4 2019 Q4 2020 Q4 2021 nm not meaningful 1. Innovative Medicines division. 2. Includes Xolair®, Beovu®, Adakveo®, TabrectaⓇ, LuxturnaⓇ, Enerzair®, Atectura®, ScemblixⓇ and Leqvio®. Constant currencies (cc) is a non-IFRS measure; explanation of non- IFRS measures can be found on page 49 of Condensed Financial Report. Unless otherwise noted, all growth rates refer to same period in PY. 10 Investor Relations | Q4 2021 Results ✓ NOVARTIS | Reimagining Medicine#11Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Double digit FY growth for key brands Cosentyx USD 4.7 bn +17% Entresto zolgensma® KISQALIⓇ 1 GROWTH YCE AZ K KL Kesimpta LEQVIO® USD 3.5 bn USD 1.4 bn USD 0.9 bn USD 0.4 bn nm +40% +46% +36% nm nm Est. CAGR (2020-26) Low double digit Peak sales USD >7bn US LOE 2029+ Est. CAGR (2020-26) Double digit until LoE Peak sales USD >5bn US LOE 2025-2036 Est. CAGR (2020-26) Low to mid teens Peak sales multi-bn¹ US LOE 2031+ Est. CAGR (2020-26) Low 30s² Peak sales multi-bn US LOE 2031+ Est. CAGR (2020-26) nm Peak sales multi-bn US LOE 2031+ Est. CAGR (2020-26) nm Peak sales multi-bn US LOE 2036+ nm - Not meaningful. All growth rates in constant currencies (cc). US LoEs are estimated based on relevant patents; further extensions possible. 1. Including Zolgensma IT. 2. Including Kisqali adjuvant. 11 Investor Relations | Q4 2021 Results ✓ NOVARTIS | Reimagining Medicine#12Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix IM performing well across geographies in 2021 US USD bn, % CC +5% 15.0 14.3 FY 2020 FY 2021 Key growth drivers Cosentyx®, EntrestoⓇ, KesimptaⓇ YCE AZ KKL 12 Investor Relations | Q4 2021 Results Europe USD bn, % cc 13.5 +8% 14.9 FY 2020 FY 2021 China USD bn, % cc +10% 2.8 2.4 FY 2020 FY 2021 1 GROWTH Key growth drivers EntrestoⓇ, ZolgensmaⓇ, KisqaliⓇ, JakaviⓇ CE ZK K L Key growth drivers Cosentyx, EntrestoⓇ, LucentisⓇ YCE AZ K KL NOVARTIS | Reimagining Medicine#13Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Broad pipeline of novel medicines continued to progress in Q4 Approvals Readouts and publications 3 INNOVATION • Negative • Positive ⚫ Mixed results SCEMBLIX® US: CML 3L Cosentyx US: JPSA & ERA LEQVIO US: Hyperlipidemia Kesimpta CN: rMS Submissions Alpelisib US: PROS 177Lu-PSMA-617 EU: mCRPC, post-taxane KYMRIAH (tisagenlecleucel) JP: r/r Follicular lymphoma for IV infusion Suspension Designations Branaplam Alpelisib FDA Fast Track designation in Huntington's disease FDA Priority Review in PROS - Ph3 HS (SUNSHINE and SUNRISE) Ph3 CSU (PEARL 1 and 2)² Prevalence Lp(a) (HERITAGE) Cosentyx® Ligelizumab Pelacarsen lanalumab Ph2b CosentyxⓇ Ensovibep YTB323 PHE885 - Sjögren's Ph2 PSA IV (INVIGORATE-2) Ph2-COVID-19 (EMPATHY) Ph1 - DLBCL Ph1 - Multiple myeloma Major Phase 3 study starts Remibrutinib Ligelizumab MS (REMODEL-1/-2); CSU (REMIX-1/-2) Food allergy (peanut¹); CINDU (PEARL-PROVOKE) Selected milestones 1. NCT04984876. 2. Superiority demonstrated vs. placebo but not vs. omalizumab. See last slide for all abbreviations. 13 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#14Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Important readouts for ianalumab, Cosentyx® and ligelizumab Selected data readouts 3 INNOVATION lanalumab Ph2b Sjögren's Syndrome ■ High unmet need, 400k patients¹, no DMT Primary efficacy endpoint met; dose response defined as change in ESSDAI from baseline at 24 weeks² ESSDAI score change over time Least-squares mean change in ESSDAI score from baseline -6- -8 -10 0 ■ Good tolerability Placebo lanalumab 5 mg lanalumab 50 mg lanalumab 300 mg 8 16 20 24 Time from baseline (weeks) CosentyxⓇ Ph3 HS (SUNRISE/SUNSHINE) ◉ High unmet need in HS3 Primary efficacy endpoint of HiSCR at week 16 met in both studies ■ HiSCR response: ≥50% decrease4 ■ Favorable safety profile confirmed Next steps ■ Studies remain blinded, data will be presented after week 52 Proceeding to 1st submission Q2 ☐ Ligelizumab Ph3 CSU (PEARL1&2) ◉ Superiority demonstrated vs. placebo but not vs. omalizumab Next steps ■ Ph3 start H2 2022 Other indications: Lupus Nephritis (Ph3 to be initiated 2022), SLE and AIH (Ph2), B-cell malignancies (Ph1/2) Next steps ■ Evaluation of Ph3 data continuing ■ Data release on completion H2 2022 ☐ CINDU, food allergy studies continue HiSCR: Hidradenitis Suppurativa Clinical response 1. with moderate to severe SjS disease in G7. 2. Bowman et al, The Lancet 2021, in press. 3. Available treatments do not adequately reduce disease activity or prevent disease progression; -400k patients with moderate to severe HS: 200k patients US, 200k patients EU5; source: British Journal of Derm. 4. in Abscess and Inflammatory Nodule count with no increase in the no. of draining fistulae. 14 Investor Relations | Q4 2021 Results ✓ NOVARTIS | Reimagining Medicine#15Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix First data presented for two lead constructs on T-Charge™ Designed to provide fast access to therapy, increased rates of response and longer durability 3 INNOVATION YTB323 is an autologous CD19-directed CAR-T cell therapy in Ph1 for DLBCL and ALL FMC63 podobo CD8 4-1BB CD3-3 YTB323 ■ DLBCL is the most common type of NHL, ~31% of NHL in Western countries ■ Promising initial efficacy results: 73% CR rate at month three in patients with DLBCL (n=16) Preliminary safety profile similar to Kymriah in JULIET study Next steps ■ Ph3 trial in DLBCL to start in 2022 PHE885 is an autologous BCMA-directed CAR-T cell therapy in Ph1 for MM Cancer cell Fully human antiBCMA scFv CD8 BCMA T-cell 4-1BB- CD3 zeta- PHE885 ■ Multiple Myeloma (MM) comprises ~10% of hematologic malignancies ■ Encouraging preliminary data: 100% ORR in r/r MM patients (n=6) Next steps Dose-finding Ph1 study is ongoing ■ Ph2 initiation in 2022 T-Charge TM platform preserves T-cell stemness: May lead to deep and durable responses, improved long-term outcomes, better safety Rapid manufacturing, lower cost of goods and increased scale DLBCL - Diffuse large B cell lymphoma NHL Non-Hodgkin Lymphoma 15 Investor Relations | Q4 2021 Results 1 NOVARTIS | Reimagining Medicine#16Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix 3 INNOVATION Business development activities adding 4 new mid/late stage high potential medicines GYROSCOPE Acquisition VISION FOR LIFE GT005: One-time subretinal Ph2 gene therapy that could transform care for geographic atrophy, a leading cause of blindness¹ BeiGene Option Ociperlimab: Ph3 TIGIT inhibitor with the potential to treat a wide range of solid tumors; development program includes 6 global trials in lung cancer, ESCC, cervical cancer W Opt-in² MOLECULAR partners Ensovibep: Multi-specific Ph2 DARPinⓇ, specifically designed to block the receptor binding domains of SARS-CoV-2 spike protein ucb Co-development / co-commercialization DLX313 (UCB0599): Potential first-in-class, small molecule, alpha-synuclein misfolding inhibitor in Ph2 Parkinson's Disease DARPin - Designed Ankyrin Repeat Protein. 1. Completion of the transaction is subject to customary closing conditions. Novartis and Gyroscope will continue to operate as separate and independent companies until closing. 2. License Agreement with Molecular Partners signed. 16 Investor Relations | Q4 2021 Results 1 NOVARTIS | Reimagining Medicine#17Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Confident in future growth driven by our strength and depth in cardio-renal, immunology, neuroscience... Selected assets, nearly all with exclusivity into 2030+ Cardio-Renal 3 INNOVATION New for Q4 Immunology Asset LeqvioⓇ Indication Peak Sales Next Milestone/ Status Hyperlipidemia Approved CVRR-LDLC Ph3 ORION-4 and VICTORION-2- PREVENT ongoing 2026+ Iptacopan1 IgAN Ph3 APPLAUSE-IgAN ongoing 20232 C3G Ph3 APPEAR-C3G ongoing 2023 iMN Ph2b ongoing Pelacarsen CVRR-Lp(a) Ph3 Lp(a)HORIZON ongoing 2026+ 2025 Ligelizumab CSU Submission Asset Indication Peak Sales Next Milestone/ Status Submission CosentyxⓇ HS Ph3 SUNRISE, SUNSHINE positive readout 2022 GCA jPsA/ERA Lupus Nephritis Lichen Planus Ph3 ongoing 2024 Aproved (US) in Q4 Ph3 SELUNE ongoing 2026+ Ph2b PRELUDE readout in 2022 2025 Ph3 PEARL 1, 2 readout TBC Food allergy3 CINDU Ph3 ongoing 2025 Ph3 PEARL-PROVOKE ongoing 2025 Neuroscience Remibrutinib¹ CSU Ph3 REMIX-1 and -2 ongoing 2024 Asset Indication Peak Sales Next Milestone/ Status Submission ZolgensmaⓇ SMA IT Ph3 STEER initiating 2025 lanalumab Other indications being explored Sjögren's SLE Ph3 start in 2022 2026+ Ph2a ongoing 2026+ Branaplam Huntington's disease Remibrutinib¹ Multiple sclerosis Ph2b VIBRANT-HD ongoing Ph3 REMODEL-1 and -2 ongoing 2025 2026+ Autoimmune hepatitis Ph2b ongoing 2026+ Lupus Nephritis Ph3 start in 2022 2026+ Iscalimab DLX3134 Parkinson's disease Ph2 ongoing 2026+ Unprobabilized peak sales (USD): <1bn .. 1-2bn ... >2bn Liver Tx Sjögren's HS Ph2b ongoing 2026+ Ph2b ongoing 2026+ Ph2a ongoing 2026+ 'Wild Cards' LNA043 (osteoarthritis: Ph2 ongoing), CSJ117 (asthma: Ph2b ongoing, COPD: Ph2 ongoing), QBW251 (COPD: Ph2b readout H1 2022), SAF312 (COSP: Ph2b ongoing), UNR844 (presbyopia: Ph2b readout H2 2022) 1. Peak sales potential based on all studied indications. 2. Based on 9 months UPCR readout (US accelerated approval). 3. Food Allergy indication falls within the Respiratory & Allergy therapeutic area 4. =UCB0599 17 Investor Relations | Q4 2021 Results ✓ NOVARTIS | Reimagining Medicine#18Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix and strength and depth in oncology 3 INNOVATION Selected assets, nearly all with exclusivity into 2030+ Solid Tumors New for Q4 Hematology Asset KisqaliⓇ Indication Peak Sales Next Milestone/ Status Submission Asset Indication Peak Sales Next Milestone/ Status Submission HR+/HER2- BC (adj) Ph3 NATALEE readout event- 2023 driven, expected end 20221 Canakinumab NSCLC adjuvant Lu-PSMA-617 mCRPC post-taxane mCRPC pre-taxane in 2022 Ph3 CANOPY-A readout 2023 ScemblixⓇ (asciminib) Iptacopan² CML 3L CML 1L PNH aHUS US approved Ph3 ongoing 2025 Readout in 2022 (APPLY-PNH) 2023 Ph3 ongoing 2025 In registration Sabatolimab HR-MDS Ph3 PSMAfore readout 2023 Ph2 STIMULUS-MDS-1 continues to PFS readout³ 2022/2023 event-driven, end 20221 JDQ443 KRAS inhibitor mHSPC 2/3L NSCLC (mono) NSCLC (combo) Ph3 PSMAddition ongoing 2024 AML Ph3 STIMULUS-MDS-2 ongoing Ph2 STIMULUS-AML-1 ongoing 2024 Ph3 start in H2 2022 Ph2 ongoing 2024 YTB323 2026+ CD19 CAR-T Non-Hodgkin's Lymphoma Ph3 start 2022 2024 TNO155 SHP2 inhibitor Solid tumors: multiple combinations being explored in ongoing trials PHE885 Tislelizumab² 2L esophageal cancer NSCLC Other indications Ociperlimab² NSCLC TIGIT mab Other indications In registration H1 2022 EU submission, 2022 H2 2022 2L US submission Ongoing trials Ph3 ongoing4 BCMA CART-T Multiple myeloma Ph2 start 2022 2024 Unprobabilized peak sales (USD): <1bn •• 1-2bn ... >2bn 'Wild Cards' Ongoing trials4; additional Ph3 study initiation H2 2022 NIS793 (mPDAC: Ph3 ongoing, colorectal cancer: Ph2 ongoing) 1. Could move to early 2023. 2. Peak sales potential based on all studied indications; Novartis territories. 3. Planned DMC readout for CR completed, study continues blinded to PFS readout, with submission in 2022/2023 using PFS and/or OS outcomes of Ph2 and/or Ph3 trial. 4. Active trials are being conducted by BeiGene, option deal. 18 Investor Relations | Q4 2021 Results ✓ NOVARTIS | Reimagining Medicine#19Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix 2022 events¹ (expected) NME Lead Regulatory H1 177 Lu-PSMA-617 mCRPC (US/EU) Other readouts H1 sabatolimab HR-MDS Ph2 decisions H1 alpelisib PROS (US) H1 CosentyxⓇ Lichen planus Ph2 PRELUDE H2 ScemblixⓇ 3L CML (JP/EU) H1 Cosentyx® AS IV Ph3 INVIGORATE-1 H2 tislelizumab ESCC 2L (US) H1 icenticaftor COPD Ph2b Submissions H1 H1/H2 H2 H2 H1/H2 JakaviⓇ acute & chronic GVHD (EU/JP) H1/H2 KymriahⓇ r/r follicular lymphoma (US/EU/JP) H1/H2 BeovuⓇ DME (US/EU/JP) ensovibep COVID-19 (US) H1/H2 Cosentyx® HS (EU/US) tislelizumab NSCLC (EU/US) tislelizumab 1L Nasopharyngeal cancer (US) Cosentyx® Psoriatic Arthritis IV (US) H2 UNR844 presbyopia Ph2 READER Ph3/pivotal study H1 CosentyxⓇ peripheral SpA starts H1 OAV101 SMA IT STEER H1 ensovibep COVID-19 (EMPATHY Part B) H2 JDQ443 NSCLC mono H2 ianalumab Sjögren's Syndrome H2 ianalumab Lupus Nephritis H2 ociperlimab solid tumors Submissions- H2 canakinumab NSCLC Ph3 Canopy A H2 177 Lu-PSMA-617 nmCRPC enabling H2 iptacopan PNH Ph3 APPLY-PNH H2 YTB323 2L DLBCL readouts H2 KisqaliⓇ HR+/HER2- BC (adj)2 Ph3 NATALEE H2 OAV101 SMA IT Ph3b STRENGTH H2 177 Lu-PSMA-617 MCRPC1, pre-taxane Ph3 PSMAfore 1. Selected. 2. Event driven, could move to early 2023. 19 Investor Relations | Q4 2021 Results 3 INNOVATION 1 NOVARTIS | Reimagining Medicine#20Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Sandoz stabilizing in Q4; Biosimilars expected to drive future growth Sandoz stabilizing Q4 sales USD 2.5bn (+2% cc)1 FY sales USD 9.6bn (-2% cc)1 FY Biopharma sales USD 2.1bn (+7% cc) Outlook 2022: Sales broadly in line with PY Assumptions Cough & Cold revert to pre-COVID levels ■ Bio continues to outperform where we compete ■ Continued gross margin headwinds due to price erosion and unfavorable mix Biosimilar launches expected to drive material growth from 2024 Significant LOE opportunity Targeting USD 80bn originator sales (2030) Critical success factors Leading pipeline: 15+ assets Manufacturing scale and expertise ✓ Development and regulatory experience Global footprint Experience in commercialization Leading in Europe; expanding US, ROW Strategic review of Sandoz is progressing, expected to provide an update, at latest, by the end of 2022 1. Q4 and FY sales growth for Sandoz includes +1% point impact from a reclassification of contract manufacturing from other revenue to sales. 20 Investor Relations | Q4 2021 Results ✓ NOVARTIS | Reimagining Medicine#21Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix We remain disciplined and shareholder-focused in our capital allocation Investing in the business Investments in organic business USD 9bn R&D¹ USD 1.4bn capital investments Value-creating bolt-ons USD 30bn (approx.) since 2018² 1. Core R&D actuals 2021. 2. Until Q4 2021. 3. Announced on December 16, 2021. 21 Investor Relations | Q4 2021 Results Returning to shareholders Capital allocation priorities Growing annual dividend in CHF USD 7.4bn paid out in 2021; proposed DPS increase +3% CHF; +6% USD Share buybacks USD 2.8bn executed in 2021 USD 15bn (up to; by end 2023)³ NOVARTIS | Reimagining Medicine#22Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Selected ESG highlights from Q4 4 ESG Novartis Biome Sub-Saharan Africa (SSA): Developing innovative / technology-driven solutions in SSA Refreshed human rights commitment statement: Focusing on 12 human rights areas¹ Disability inclusion: Joined The Valuable 500, supporting a global movement to drive systemic change Environmental targets on track: -34% Scope 1,2 GHG emissions excluding offsets²; -56% waste disposal (2025 target: reduce waste disposal by half); engaging top suppliers on 'Green Expectations' Improved scores for MSCI Controversy, ATMI AMR Benchmark, S&P Global ESG rating³ for 2021 1. In line with United Nations Guiding Principles for Human Rights. 2.2021 GHG Scope 3 will be published in H1 2022. 3. Included in the DJSI World, DJSI Europe 22 Investor Relations | Q4 2021 Results ✓ NOVARTIS | Reimagining Medicine#23Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Top 2022 priorities for Novartis 1 Successful launches: Leqvio®, KesimptaⓇ, 177 Lu-PSMA-617, ScemblixⓇ 2 Maintain growth momentum: YCE AZ K KL 3 Progress pipeline: 20+ assets with significant sales potential, approval by 2026, on track 4 Optimize portfolio: Sandoz review, update end 2022; disciplined BD 50 Deliver returns: Continue productivity initiatives, especially manufacturing, business services 6 Reinforce foundations: Culture to drive performance, data science to drive value, ESG leadership 23 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#24Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Marie-France Tschudin President, Novartis Pharmaceuticals 24 Investor Relations | Q4 2021 Results 1 NOVARTIS | Reimagining Medicine#25Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix FY Pharmaceuticals sales grew +7%, growth drivers represent 52% Pharmaceuticals net sales USD bn, % cc Q4 +9%1 FY +7% 26.5 6.8 6.4 24.3 +28% +30% 2.9 3.7 13.7 Representing 10.5 Representing 54% of sales 52% of sales 3.5 3.1 -7% Q4 2020 Q4 2021 13.8 - -9% 12.8 FY 2020 FY 2021 Growth drivers² Mature products³ All % growth relate to cc unless otherwise stated. 1. Q4 sales growth for Pharmaceuticals includes +2% points impact from a reclassification of contract manufacturing from other revenue to sales. 2. ZolgensmaⓇ, KesimptaⓇ, MayzentⓇ, BeovuⓇ, Luxturna®, Leqvio®, Enerzair® and Atectura®, Cosentyx®, Entresto®, Xolair®, Ilaris®, XiidraⓇ and AimovigⓇ. 3. All other brands. 25 Investor Relations | Q4 2021 Results ✓ NOVARTIS | Reimagining Medicine#26Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix CosentyxⓇ maintains strong market position; progressing LCM Sales evolution USD m, % cc Ex-US Cosentyx E AZ K K L US FY 4.0bn +13% FY 4.7bn +17% 1,247 1,243 ■ Maintaining strong growth and market position ■ Demand driven across indications in US, Europe, China Expanding clinical differentiation Hidradenitis suppurativa Ph3 positive 1,175 1,109 1,012 1,053 ◉ Approved for JPSA and ERA in the US 930 944 494 473 460 ■ 423 372 408 354 330 576 614 640 686 715 753 770 645 Approval for PSO flexible dosing in EU ■ GCA Ph2b positive; Ph3 ongoing ☐ Anticipate 10+ indications overall Expect double-digit growth in 2022 Expect historical Q1 sales pattern Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 2020 2021 SpA Spondyloarthritis JPSA - Juvenile psoriatic arthritis ERA - Enthesitis related arthritis PSO-Psoriasis GCA Giant cell arteritis LN- Lupus nephritis LP-Lichen planus 26 Investor Relations | Q4 2021 Results ✓ NOVARTIS | Reimagining Medicine#27Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix EntrestoⓇ grows +40% in 2021 An essential first-choice treatment in chronic heart failure1 Sales evolution USD m, % cc Ex-US US FY 2.5bn +44% FY 3.5bn +40% 949 924 886 789 716 429 632 569 580 481 519 407 354 318 276 272 520 293 308 314 362 382 405 405 Q1 Q2 Q3 2020 ठ Q4 Q1 Q2 Q3 Q4 2021 C Entresto® AZ K &K L Strong momentum across geographies during 2021 ■ US: Growth across cardiology, primary care Europe: Continued strong growth ■ China: FY strong growth, Q4 impacted by stock compensation in anticipation of NRDL price reductions for HTN listing Confidence in future growth across geographies ■ Further patient uptake in EU and US in heart failure¹ ▪ Launch momentum in HTN¹ in Japan and China HTN Hypertension. NRDL National Reimbursement Drug Listing. 1. Approved indications differ by geography. Examples include "indicated to reduce the risk of cardiovascular death and hospitalization for HF in adult patients with CHF. Benefits are most clearly evident in patients with LVEF below normal." (US) HFrEF (EU) HFrEF and HTN (China and JP). 27 Investor Relations | Q4 2021 Results ✓ NOVARTIS | Reimagining Medicine#28Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix ZolgensmaⓇ grows +46% in 2021 to USD 1.4bn Due to geographic expansion as the foundational therapy for SMA Sales evolution USD m, % cc Ex-US US FY 920m FY 1.4bn +46% 375 342 319 315 291 254 249 205 224 200 169 209 170 148 44 100 126 122 105 106 119 126 106 118 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 2020 2021 Q4 highlights CE zolgensma K &K L ■ Driven by expanding access ex-US, +58% sales ■ Over 1800 patients treated worldwide¹ Approval now in 42 countries; access pathways in 26 countries Newborn screening reached ~85% in US, 20% in EU Future outlook Continued growth ex-US ■ Newborn screening: Goal of 38% in EU by YE22 ■ US: Steady US sales driven by incident patients Advancing robust data in SMA with IT² ▪ STEER: Ph3 currently initiating treatment-naive Type 2 patients ■ STRENGTH: Start H2 2022 in patients who have discontinued treatment with nusinersen and/or risdiplam 1. Commercially, via managed access programs and in clinical trials 2. With investigational OAV101 intrathecal administration 28 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#29Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix KesimptaⓇ launch accelerating Clinical differentiation further enhanced by favorable vaccination data Sales evolution USD m, % cc 66 99 50 50 FY: 372m 147 109 Launch progress 14 Q4 2020 Q1 Q2 Q3 Q4 Clinical progress 2021 CEZ K Kesimpta L Strong US sales despite COVID impacting the dynamic segment (market NBRx -12% QoQ) Strong access, increased demand based on compelling benefit-risk NBRx share 13.7%1, prescriber base +11% >8,000 people living with MS treated in US, majority naive or first switch Ex-US: 63 global approvals incl. China, Japan Reassuring data in COVID vaccinated patients (ALITHIOS)² 1. Unadjusted share Q4. Data on file. 2. Cross AH, Delgado S, Habek M, et al. Outcomes of COVID-19 in Patients With Relapsing Multiple Sclerosis Receiving Ofatumumab: Data From the ALITHIOS Study and Post Marketing Surveillance: 37th Congress of ECTRIMS, October 13-15, 2021. Data on file from ALITHIOS, data cut off Sept 25th, 2021. 29 Investor Relations | Q4 2021 Results 1 NOVARTIS | Reimagining Medicine#30Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Leqvio®: US launch underway FDA approved C E AZ K&K LEQVIO® Effective and sustained LDL-C reduction¹ with twice a year maintenance dose administered by HCP Broad label covering 16m US ASCVD patients not at LDL-C goal Go-to-market model designed to overcome clinical barriers and address access, adherence and affordability Sales, reimbursement and medical field teams trained and deployed Robust network of AICs to provide acquisition and administration flexibility Value-based price per dose of USD 3,250 Comprehensive patient and HCP support programs available to ensure timely access Product available from specialty distributors since early January Filed for permanent J-Code, miscellaneous J-Code for temporary use available Expect modest initial ramp as we lay the foundation for multi-blockbuster potential LDL-C - Low Density Lipoprotein Cholesterol ASCVD Atherosclerotic Cardiovascular Disease AIC - Alternative Injection Center HCP Healthcare Professional 1. Across the 6-month dosing interval. 30 Investor Relations | Q4 2021 Results ✓ NOVARTIS | Reimagining Medicine#31Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Summary for Pharmaceuticals Strong performance of growth drivers (+30% FY growth), continuing portfolio rejuvenation ✓ KesimptaⓇ accelerating; LeqvioⓇ launch underway In 2022, expect continued strong momentum from key growth drivers C E AZ KL 31 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#32Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Susanne Schaffert President, Novartis Oncology 32 Investor Relations | Q4 2021 Results 1 NOVARTIS | Reimagining Medicine#33Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix FY Oncology sales grew +4%, overcoming Gx headwinds; portfolio rejuvenation with growth drivers representing 51% of sales Oncology net sales USD bn, % cc Q4 +3% FY +4% 15.5 3.8 3.9 14.7 +17% +17% 1.8 2.1 Representing 6.7 7.9 54% of sales Representing 51% of sales 2.0 1.8 --9% Q4 2020 Q4 2021 8.0 7.6 -7% FY 2020 FY 2021 Growth drivers¹ Mature products, Gx² 1. Include Piqray®, Adakveo®, TabrectaⓇ and Scemblix®, PromactaⓇ/Revolade®, TafinlarⓇ+ MekinistⓇ, KisqaliⓇ, LutatheraⓇ, KymriahⓇ and JakaviⓇ (marketed by Novartis ex-US). 2. Base business - other brands. Gx include Afinitor®, Exjade®/ JadenuⓇ, Glivec® and SandostatinⓇ. All % growth refers relate to cc unless otherwise stated. 33 Investor Relations | Q4 2021 Results ✓ NOVARTIS | Reimagining Medicine#34Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix KisqaliⓇ accelerated growth in Q4 (+58%) behind MONALEESA-2 OS Sales evolution USD bn, % cc Ex-US US CEZ KISQALI K L Robust body of evidence supports positioning Kisqali as standard of care (SOC) in 1L postmenopausal BC +58% ■ Positive OS results in 3 Ph3 trials, including ML-2 285 184 187 102 82 98 Q4 2020 Q4 2021 ■ The only CDK 4/6 inhibitor to demonstrate OS benefit in 1L according to NCCN guidelines Continued growth acceleration and geographic expansion US share gains driven by positive impact of ML-2 OS data ■ 88% YoY growth ex-US reflecting strong market share gains and impact of new data Geographic expansion with public reimbursement recommendation in Brazil and regulatory submission in China aBC advanced breast cancer/eBC - early breast cancer ML-MONALEESA. In phase 3 randomized controlled trials, ribociclib + endocrine therapy has shown overall survival benefit in the first-line setting. 34 Investor Relations | Q4 2021 Results ✓ NOVARTIS | Reimagining Medicine#35Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix TafinlarⓇ+MekinistⓇ, PromactaⓇ/Revolade® and JakaviⓇ with continued double-digit growth Tafinlar®+MekinistⓇ USD m, % cc Ex-US US PromactaⓇ/Revolade® USD m, % cc Ex-US US JakaviⓇ USD m, % cc +12% +14% +12% 518 471 458 408 376 408 272 248 297 259 223 149 161 Q4 2021 246 Q4 2021 Q4 2021 Q4 2020 Continued growth and leadership in both adjuvant and metastatic BRAF+ melanoma and lung Q4 2020 Double-digit growth in all regions driven by sustained efficacy, oral convenience and non-immunosuppressive profile Q4 2020 Strong growth driven by earlier usage in myelofibrosis and polycythemia vera; further uptake expected from GVHD launches GVHD Graft-versus-host disease 35 Investor Relations | Q4 2021 Results 1 NOVARTIS | Reimagining Medicine#36Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Launching SCEMBLIX®, a novel STAMP inhibitor with potential to transform the standard of care in CML • SCEMBLIX® (asciminib) 20 mg. 40 mg tablets Strong clinical profile addressing sizable medical need Superior clinical profile to bosutinib in late line CML1 with early 2x improvement in MMR and >3x fewer discontinuations due to AEs Clinically meaningful efficacy in patients with T3151 CML-CP ~25% of all CML patients addressable with current label Potential to provide another treatment option in 1L CML; Ph3 pivotal trial ongoing (filing in 2025) US launch excellence building on CML experience Executing with excellence, leveraging decades of CML experience Patient assistance program in place with more than 50 patients registered; over 150 enrollments in managed access program Already included in NCCN guidelines; strong medical engagement with >50 US centers in clinical trials HCPs able to secure access for patients, while formulary listings are ongoing STAMP - Specifically Targeting the ABL Myristoyl Pocket. 1. Rea D et al, Blood 2021 Nov 25;138(21). 36 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#37Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Preparing for 177 Lu-PSMA-617 launch in the US, expected H1 2022 Potential new treatment paradigm in mCRPC, based on strong Ph3 VISION data ☐ ☐ ■ ◉ Significant unmet need in mCRPC1 177Lu-PSMA-617 + SOC reduced risk of death by 38%, rPFS or death by 60%, compared to SOC alone² Median OS 15.3 months (rPFS 8.7 months), vs. 11.3 months (rPFS 3.4 months) for SOC alone² 29.8% overall response compared to 1.7% with SOC alone² Safety profile in line with prior experience² Administration advantages (6 one-time infusions) over chronic therapies² Laying the foundation for a steady launch, FDA action expected H1 2022, EMA H2 2022 ✓ Hospital capacity sufficient for launch in VISION population Targeting >225 treatment sites in US, ~200 sites in EU (all LutatheraⓇ treatment sites) PET imaging available; 68Ga-PSMA-11 imaging agent included in NCCN guidelines Leveraging LutatheraⓇ team and experience; incremental FF fully recruited in US, on track in EU Extensive disease state education underway Two ongoing Ph3 studies in mCRPC pre-taxane (PSMAfore) & MHSPC (PSMAddition), potential to expand eligible patient population for 177 Lu-PSMA-617 by 3-4x 1. VISION population: PSMA+ post ARPI and Taxane; approx. 10 months median OS on available treatments in late line mCRPC; 30% five-year survival prognosis; 80%+ of patients PSMA positive. 10.1056/NEJMoa2107322. 2. Sartor, et al. NEJM 2021; doi: 37 Investor Relations | Q4 2021 Results ✓ NOVARTIS | Reimagining Medicine#38Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Summary for Oncology Continued strong execution and portfolio rejuvenation in 2021, with growth drivers up 17% Driving share gains with KisqaliⓇ in CDK4/6 class, ahead of NATALEE adjuvant readout Focusing on launch execution for ScemblixⓇ and 177Lu-PSMA-617; preparing for next wave of launches 38 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#39Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Harry Kirsch Chief Financial Officer Financial review and 2022 guidance 39 Investor Relations | Q4 2021 Results U NOVARTIS | Reimagining Medicine#40Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix 2021 financial results in line with guidance Group full year guidance (Q3 earnings October 2021) In cc Innovative Medicines Sandoz¹ Sales expected to grow mid single digit Core Oplnc expected to grow high single digit Sales expected to decline low to mid single digit Core Oplnc expected to decline mid to high teens Sales expected to grow low to mid single digit Group Core Oplnc expected to grow mid single digit, ahead of sales 1. FY sales growth for Sandoz includes +1% point impact from a reclassification of contract manufacturing from other revenue to sales. 40 Investor Relations | Q4 2021 Results FY 2021 vs. PY +6% +10% + -2% -14% +4% +6% ✓ NOVARTIS | Reimagining Medicine#41Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Strong Q4 with mid single digit sales and double digit core Oplnc growth Group 1 Q4 Change vs. PY2 FY Change vs. PY USD million 2021 2021 % USD % cc % USD % cc Net sales 13,229 4 6 51,626 6 4 Core operating income 3,819 9 12 16,588 8 10 6 Operating income 2,562 -3 -1 11,689 15 13 Net income 16,306 nm nm 24,018 198 195 Ex. Roche divestment gain³ 1,734 -17 -14 9,446 17 15 Core EPS (USD) 1.40 4 7 6.29 9 7 EPS (USD) 7.29 nm nm 10.71 202 200 Ex. Roche divestment gain³ 0.78 -15 -13 4.21 19 17 Free cash flow 3,027 -9 13,282 14 nm - Not meaningful 1. Constant currencies (cc), core results and free cash flow are non-IFRS measures. An explanation of non-IFRS measures can be found on page 49 of the Condensed Financial Report. All % growth relate to cc unless otherwise stated. 2. Q4 sales growth for Group includes +1% point impact from a reclassification of contract manufacturing from other revenue to sales. 3. See slide 54 for the reconciliation of IFRS results vs. results ex. Roche divestment gain 41 Investor Relations | Q4 2021 Results ✓ NOVARTIS | Reimagining Medicine#42Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix 2021 IM core margin increased to 36.2% (+130bps) Innovative Medicines Sandoz Group Q4 2021 FY 2021 Core operating Net sales 1 change vs. PY income2 change vs. PY Core margin 2 Core margin² change vs. PY Net sales 1 change vs. PY Core operating income2 change vs. PY Core margin² Core margin² change vs. PY (in % cc) (in % cc) (%) (%pts cc) (in % cc) (in % cc) (%) (%pts cc) 7 15 33.6 2.4 6 10 36.2 1.3 2 0 20.9 -0.4 -2 -14 21.4 -2.9 6 12 28.9 1.6 4 6 32.1 0.5 1. Q4 sales growth for Group, IM and Sandoz includes +1% point impact from a reclassification of contract manufacturing from other revenue to sales. Sandoz FY sales growth also benefited +1% point from this reclassification. 2. Constant currencies (cc), core results and free cash flow are non-IFRS measures. An explanation of non-IFRS measures can be found on page 49 of the Condensed Financial Report. 42 Investor Relations | Q4 2021 Results ✓ NOVARTIS | Reimagining Medicine#43Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix FY 2021 free cash flow grew to USD 13.3bn mainly driven by higher operating income Group free cash flow¹ USD bn, % USD 11.7 +14% Key drivers vs. PY + 13.3 FY 2020 FY 2021 + - Higher operating income (adjusted for non-cash items) Lower payments related to legal matters Tislelizumab in-licensing (upfront payment USD 650m) 1. Constant currencies (cc), core results and free cash flow are non-IFRS measures. An explanation of non-IFRS measures can be found on page 49 of the Condensed Financial Report. 43 Investor Relations | Q4 2021 Results ✓ NOVARTIS | Reimagining Medicine#443.5 Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Novartis proposes 25th consecutive dividend increase to the AGM: 3.10 CHF / share¹ 3.0 CHF dividend USD dividend 2.5 2.0 1.5 1.0 0.5 CAGR 7.6% in CHF and 9.6%4 in USD 2021 dividend yield 3.9%² 2021 dividend growth 3.3%³ CHF 3.00 USD 3.20 CHF 3.10 USD 3.39 0.0 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 1. Proposal to shareholders at the 2022 Annual General Meeting, taking place on March 4, 2022. 2. Based on closing share price of CHF 80.28 at end of business year 2021 (December 30, 2021). 3. In CHF. 4. Converted at historic exchange rates at the dividend payment dates as per Bloomberg; for 2021, dividend per share translated into US dollars at the December 31, 2021, rate of USD 1.093 to the Swiss franc. 44 Investor Relations | Q4 2021 Results ✓ NOVARTIS | Reimagining Medicine#45Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix 2022 Novartis full year guidance Barring unforeseen events; growth vs. PY in cc Innovative Medicines Sales expected to grow mid single digit Core Oplnc expected to grow mid to high single digit, ahead of sales Sandoz Sales expected to be broadly in line with prior year Core Oplnc expected to decline low to mid single digit Sales expected to grow mid single digit Group Core Oplnc expected to grow mid single digit Key assumptions Our guidance assumes that we see a continuing return to normal global healthcare systems, including prescription dynamics, and that no SandostatinⓇ LAR generics enter in the US 45 Investor Relations | Q4 2021 Results 1 NOVARTIS | Reimagining Medicine#46Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix FY 2022 guidance on other financial KPIs Barring unforeseen events; growth vs. PY in cc Group | full year guidance vs. PY (cc) Core Net Financial Result Core Tax Rate Expenses expected to be broadly in line vs. 2021 Core tax rate expected to be in the 17-17.5% range: ■ +1% vs. PY mathematical impact of Roche divestment¹ ■ +0-0.5% due to profit mix 1. Roche net income from associated companies was recorded after tax thus lowering the average core tax rate in 2021 and prior years. 46 Investor Relations | Q4 2021 Results 1 NOVARTIS | Reimagining Medicine#47Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Expected currency impact for full year 2022 Currency impact vs. PY %pts, assuming late-January exchange rates prevail in 2022 FX impact on Net sales 2 | FX impact on Core operating income 2 I -2 Q4 2021 FY Actual Simulation 47 Investor Relations | Q4 2021 Results I I -3 -3 -4 -4 -5 | Q1 2022 FY Q4 FY Q1 FY I 2021 2022 NOVARTIS | Reimagining Medicine#48Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Vas Narasimhan Chief Executive Officer 48 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#49Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Conclusions In 2021, Novartis delivered mid single digit top-line growth, margin expansion, strong FCF In-market growth drivers continue to perform well across geographies, supporting our confidence in our outlook of 4%+ sales CAGR to 2026 Delivered important innovation milestones, e.g. EntrestoⓇ, 177 Lu-PSMA-617, iptacopan, Kisqali®, Leqvio® Focused on delivering on our pipeline: 20+ potential assets with significant sales for approval by 2026 Balanced capital allocation, continuing to invest in innovation alongside returning capital to our shareholder 49 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#50Participants Company overview Pharmaceuticals Financial performance Appendix Oncology Financial review Conclusion Innovation: Pipeline overview Appendix Innovation: Clinical trials 50 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#51Participants Company overview Pharmaceuticals Financial performance Oncology Financial review Conclusion Innovation: Pipeline overview Appendix Innovation: Clinical trials Novartis is committed to driving consistent growth through 2030 and beyond IM sales evolution Illustrative, USD billion, % CAGR CC +8%¹ 38 39 35 99 >Median (aspiration) ≥4% 42 2 3 2026 2030 >2030 1 2020-2026 |≥4% Focused resources on key growth brands and launches, upscaling next generation engagement models 2 2026-2030 | >peer median Double-down on internal pipeline assets to unlock their full potential and add complementary BD&L 3 >2030 |>peer median Focused investments in technology platforms while staying at the forefront of innovation in small and large molecules нн 2018 2019 2020 2021 1.6% in USD. 51 Investor Relations | Q4 2021 Results U NOVARTIS | Reimagining Medicine#52Participants Company overview Pharmaceuticals Financial performance Oncology Innovation: Pipeline overview Financial review Conclusion Strong FY operational performance from growth drivers Key growth driver sales FY 20211 Driving portfolio rejuvenation Appendix Innovation: Clinical trials Sales USD Million Growth vs. PY Growth vs. PY USD Million CC Key growth drivers 52% of IM sales, growing 25% vs. PY Entresto sacubitrill/valsartan 3,548 1,051 40% AimovigⓇ 52% Cosentyx 4,718 723 17% MayzentⓇ (secukinumab) Piqray® zolgensma 1,351 431 46% 44% Kesimpta 372 357 nm (ofatumumab) 35% PROMACTA (eltrombopag) 2,016 278 15% JAKAVI® 1,595 256 16% 27% KesimptaⓇ XiidraⓇ LutatheraⓇ KymriahⓇ KisqaliⓇ ruxolitinib KISQALI 937 250 36% ribociclib ILARIS 1,059 186 22% (canakinumab) Xolair 1,428 177 12% Omalizumab SUBGYGARDOS OS llarisⓇ ZolgensmaⓇ JakaviⓇ Tafinlar+Mekinist® Promacta® EntrestoⓇ Tafinlar +Mekinist 1,693 151 8% beb KYMRIAH 587 113 22% (tisagenlecleucel) fin MAYZENT. 281 111 CosentyxⓇ Other² FY 2018 FY 2019 FY 2020 FY 2021 65% (siponimod) tablets nm - not meaningful 1. Innovative Medicines division. 2. Includes Xolair®, Beovu ®, Adakveo®, Tabrecta Ⓡ, Luxturna®, Enerzair ®, Atectura ®, LeqvioⓇ and ScemblixⓇ. Constant currencies (cc), core results and free cash flow are non-IFRS measures. An explanation of non-IFRS measures can be found on page 49 of the Condensed Financial Report. 52 Investor Relations | Q4 2021 Results U NOVARTIS | Reimagining Medicine#53Participants Company overview Pharmaceuticals Financial performance Oncology Financial review Conclusion Innovation: Pipeline overview Appendix Innovation: Clinical trials Net debt significantly decreased by USD 23.6bn driven by proceeds from Roche divestment and strong FCF (USD bn) +23.6 20.7 0.6 -0.9 -24.5 -7.4 -0.6 -3.0 Dec 31, 2020 Dividends M&A transactions Treasury share transactions, 13.3 Free Cash Flow net Proceeds from Roche divestment Others Dec 31, 2021 53 Investor Relations | Q4 2021 Results U NOVARTIS | Reimagining Medicine#54Participants Company overview Pharmaceuticals Financial performance Oncology Innovation: Pipeline overview Financial review Conclusion Appendix Innovation: Clinical trials Reconciliation of IFRS results vs. results excluding gain recognized on divestment of Roche investment IFRS USD million unless indicated otherwise results Gain on divestment of our investment in Roche Results excl. gain on divestment of our investment in Roche Operating income from continuing operations 11,689 Net income 24,018 Total basic earnings per share (USD) 10.71 -14,572 -6.50 11,689 9,446 4.21 Reconciliation from IFRS reported net income and basic earnings per share, to net income and basic earnings per share excluding the gain recognized on the divestment of our investment in Roche 2021 Summary of impact of the gain recognized on the divestment of our investment in Roche in USD and constant currencies on net income and basic earnings per share 54 Investor Relations | Q4 2021 Results In USD % Excluding the gain on divestment of our investment In constant currencies % Excluding the gain on divestment of our investment in Roche Percentage in Roche 2021 % % point impact % % Percentage point impact Net income 198 17 181 195 15 180 Total basic earnings per share (USD) 202 19 183 200 17 183 1 NOVARTIS | Reimagining Medicine#55Participants Company overview Pharmaceuticals Financial performance Oncology Innovation: Pipeline overview Financial review Conclusion Appendix Innovation: Clinical trials 20+ potential billion USD+ pipeline assets with approval by 2026 Most are supported by high strength of evidence Selected assets Unprobabilized peak sales USD bn / multi-bn Strength of evidence Moderate Sabatolimab MDS; AML NIS793 PDAC; Colorectal Cancer Pelacarsen CVRR Canakinumab Adj. NSCLC Ociperlimab¹ NSCLC UNR844 Presbyopia Libvatrep (SAF312) Chronic Ocular Surface Pain TNO155, JDQ443² NSCLC; Colorectal Cancer; Combos Iptacopan PNH; C3G; IgAN; aHUS Remibrutinib CSU; MS Zolgensma SMA IT Ligelizumab FA; CINDU Strength of evidence High Kisqali Adj. BC (+endocrine th.) YTB3231 2L DLBCL lanalumab Sjogren's; SLE; AIH; Lupus Nephritis Ensovibep Coronavirus infection Leqvio Hypercholesterolemia Cosentyx Multiple indications 177 Lu-PSMA-617 mCRPC post & pre-taxane; MHSPC Scemblix 3L+ CML; 1L CML Tislelizumab Multiple indications Piqray (alpelisib) PROS; HER2+ adv BC; TNBC; ovarian cancer Most advanced and key indication(s) approved by 2026 Submission Phase III Phase II LCM ✓ Approved Unprobabilized peak sales up to USD 1bn 1. BeiGene option deal. Lutathera 1L G2/G3 NET Kymriah r/r Follicular Lymphoma Tafinlar/Mekinist Solid Tumor Agnostic Beovu DME Jakavi SR GvHD 2. Ph3 to start in 2022. Assets are shown in the phase of the most advanced indication (listed first). Value based on the total of the listed indication(s). indication: High if in Ph3 or when Ph2 results available for the same MoA in the lead indication. Strength of evidence based on the most advanced 55 Investor Relations | Q4 2021 Results U NOVARTIS | Reimagining Medicine#56Participants Company overview Pharmaceuticals Financial performance Oncology Innovation: Pipeline overview Financial review Conclusion Appendix Innovation: Clinical trials Key milestones of pipeline assets with significant sales potential with approval by 2026 Selected assets, most advanced and key indication(s) approved by 2026 High strength of evidence Iptacopan PNH 2024 2025 2026 High strength of evidence Iptacopan C3G Iptacopan aHUS Iptacopan IgAn Remibrutinib CSU Remibrutinib MS Zolgensma SMA IT Ligelizumab CSU Ligelizumab CINDU Ligelizumab Food Allergy Kisqali YTB323 2L DLBCL lanalumab Sjögren's 2022 Ph3 readout 2023 Submission Ensovibep COVID 2022 Submission 2023 2024 2025 2026 Ph3 read/sub Scemblix Approval Ph3 readout Submission Scemblix CML 1L Ph3 readout Submission Ph3 read/sub Alpelisib PROS Approval Ph3 read/sub Piqray Ovarian Cancer Ph3 read/sub Piqray TNBC Ph3 read/sub Ph3 read/sub Ph3 readout Submission Piqray HER2+ adv BC Ph3 read/sub Ph3 data in evaluation Tislelizumab Submissions and approvals of several indications Ph3 readout Submission Ph3 read/sub Ph3 readout¹ Submission Ph3 start Ph3 read/sub Ph3 start lanalumab LN Ph3 start Cosentyx HS Submission Cosentyx Lichen Planus Ph2 readout Cosentyx AS H2H Ph3 readout Submission Cosentyx GCA Ph3 read/sub 177 Lu-PSMA-617 mCRPCR post tax Approval 177 Lu-PSMA-617 mCRPCR pre tax 177 Lu-PSMA-617 mHSPC Ph3 readout¹ Submission Ph3 read/sub NME Lead 1. Event driven, could move to early 2023. 56 Investor Relations | Q4 2021 Results Submission Moderate strength of evidence Sabatolimab MDS 2022 Ph2 readout 2023 2024 2025 2026 Sabatolimab AML Ph3 readout Ph3 readout Submission in 2022/23 Submission Ph3 read/sub NIS793 PDAC Ph3 read/sub Ph3 read/sub Pelacarsen CVRR Ph3 read/sub Canakinumab Adj. NSCLC Ph3 readout Submission Ociperlimab UNR844 Presbyopia Ph3 start Ph2 readout BeiGene option deal Submission Libvatrep COSP Ph2 readout Submission JDQ443 NSCLC JDQ443+TNO155 NSCLC Ph3 start Submission Ph3 start Submission ✓ NOVARTIS | Reimagining Medicine#57Participants Company overview Pharmaceuticals Financial performance Oncology Innovation: Pipeline overview Financial review Conclusion Appendix Innovation: Clinical trials 2021 key pipeline milestones¹ H1 2021 EntrestoⓇ Regulatory HFPEF (US) decisions and opinions KesimptaⓇ Relapsing MS (EU/JP) Major Leqvio® Hyperlipidemia (US)² expected JakaviⓇ submissions TabrectaⓇ BeovuⓇ Asciminib (ABL001) Acute and chronic GVHD (EU/JP) NSCLC (EU) DME (US/EU) H2 2021 CosentyxⓇ Pediatric psoriasis (US/CN/JP) Achieved Mixed results Readout not supportive ✓ H2 CML 3L (US/EU) CosentyxⓇ JIA (US/EU) Asciminib (ABL001) BeovuⓇ CML 3L (JP) Alpelisib (BYL719) KymriahⓇ 177Lu-PSMA-617 Tislelizumab (VDT482) Tislelizumab (VDT482) DME (JP) PROS (US) r/r Follicular lymphoma (US/EU/JP) ✓ mCRPC (US/EU) 2L esophageal cancer (US) NSCLC (EU/US) Major Iptacopan (LNP023) Ph2 - IgAN expected trial readouts* Iptacopan (LNP023) Ph2 - C3G H2 EntrestoⓇ Ph3 - Post-AMI 5 Canakinumab (ACZ885) ECF843 Ligelizumab (QGE031) Ph3 - NSCLC 1L H1 20223 9 Canakinumab (ACZ885) -> Ph3 NSCLC 2L 7 KisqaliⓇ - Ph2 - Dry eye Ph3 - CSU Ph3 aBC (MONALEESA-2 OS) 4 6 177 Lu-PSMA-617 Ph3-mCRPC CosentyxⓇ Ph3 - JIA Remibrutinib (LOU064) CosentyxⓇ Ph2 - CSU Ph3 - HS ✓ ✓ Sabatolimab (MBG453) Ph2 - MDS8 KymriahⓇ Ph3 aNHL 2L 2. Resubmitted to FDA. 3. H1 2022 EU submission, H2 2022 2L US *Achieved = on-time readout of data, irrespective of trial outcome. 1. 2021 Key milestone table may evolve based on read-out outcomes as well as BD&L activities. submission. 4. Program discontinued in broad population of moderate to severe DED. 5. Numerical trends consistently favored EntrestoⓇ vs. active comparator but did not meet primary composite endpoint. The safety profile of EntrestoⓇ was confirmed. No submission planned. 6. Ligelizumab demonstrated superiority compared with placebo PEARL 1 and PEARL 2 trials, but not versus omalizumab, further evaluating PEARL data. 7. Negative readout. 8. Planned DMC readout for CR completed, study continues blinded to PFS readout, with submission in 2022/2023 using PFS and/or OS outcomes of Ph2 and/or Ph3 trial. 9. Ph3 study did not meet primary endpoints. PFS and OS trends support further evaluation with additional analyses ongoing. 57 Investor Relations | Q4 2021 Results U NOVARTIS | Reimagining Medicine#58Participants Company overview Pharmaceuticals Financial performance Oncology Innovation: Pipeline overview Our pipeline projects at a glance Financial review Conclusion Appendix Innovation: Clinical trials Phase 1/2 Phase 3 Registration Total Oncology Pharmaceuticals Cardiovascular, Renal, Metabolism 49 27 6 82 Immunology, Hepatology, Dermatology 26 CO 858 25 2 85 6 0 11 Neuroscience Ophthalmology Respiratory & Allergy Global Health 658 ∞ 8 Biosimilars 0 Total 107 95 13 121 9 1 36 0 11 1 0 7 11 0 9 0 2 54 8 169 58 Investor Relations | Q4 2021 Results 1 NOVARTIS | Reimagining Medicine#59Company overview Pharmaceuticals Participants Financial performance Oncology Innovation: Pipeline overview Novartis pipeline in Phase 1 (1 of 2) Financial review Conclusion Oncology Code AAA603 AAA817 ADPT01 ADPT03 DFF332 DKY709 HDM201 IAG933 Name 177Lu-NeoB Ac-PSMA-617 ADPT01 ADPT03 DFF332 DKY709 + spartalizumab HDM201 + MBG453, venetoclax IAG933 JBH492 JDQ443 JEZ567 LXF821 JBH492 JDQ443 JEZ567 KAZ954 KAZ954 LXF821 LXH254 LXH254 MAK683 MBG453 MCM998 MIK665 NIS793 MAK683 sabatolimab MCM998, LXG250 MIK665 NIS793, spartalizumab NIZ985, spartalizumab NZV930, spartalizumab, NIR178 NIZ985 NZV930 PDR001 PHE885 PHE885 TNO155 TNO155 VAY736 VOB560 VPM087 WNT974 WVT078 YTB323 spartalizumab ianalumab + ibrutinib VOB560 gevokizumab WNT974+ spartalizumab WVT078 YTB323 Mechanism Radioligand therapy target GRPR Radioligand therapy target PSMA BCL11A HIF2A inhibitor Novel immunomodulatory agent MDM2 inhibitor KRAS Inhibitor CD123 CAR-T EGFR CAR-T CRAF inhibitor EED inhibitor TIM3 antagonist BCMA CAR-T, CD19 CAR-T MCL1 inhibitor TGFB1 inhibitor IL-15 agonist CD73 antagonist PD1 inhibitor BCMA cell therapy SHP2 inhibitor BAFF-R inhibitor IL-1 beta antagonist Porcupine inhibitor CD19 CAR-T Indication(s) Multiple solid tumors. Metastatic castration-resistant prostate cancer Colorectal cancer (combos) Sickle cell anemia Renal cell carcinoma Cancers Haematological malignancy. Mesothelioma Haematological malignancy KRAS G12C mutated solid tumors Acute myeloid leukaemia Solid tumors Glioblastoma multiforme NSCLC (combos) Cancers Low risk myelodysplastic syndrome Multiple myeloma Acute myeloid leukaemia (combo) Solid tumors Solid tumors Solid tumors Solid tumors (combo) Multiple Myeloma Solid tumors (combo) Solid tumors (combo) Haematological malignancy Cancers Colorectal cancer, 1st line Solid tumors Multiple myeloma DLBCL and adult ALL 59 Investor Relations | Q4 2021 Results Appendix Innovation: Clinical trials 32 lead indications Lead indication NOVARTIS | Reimagining Medicine#60Company overview Pharmaceuticals Participants Financial performance Oncology Financial review Conclusion Innovation: Pipeline overview Novartis pipeline in Phase 1 (2 of 2) Immunology Code Respiratory & Allergy Name Mechanism Indication(s) Code Name Mechanism FIA586 FIA586 MHS552 MHS552 MHV370 MHV370 Non-alcoholic steatohepatitis (NASH) Autoimmune indications LTP001 LTP001 NCJ424 NCJ424 NG1226 NG1226 Systemic lupus erythematosus Tendinopathy Neuroscience Appendix Innovation: Clinical trials 32 lead indications Lead indication Indication(s) Respiratory diseases Respiratory diseases Cardiovascular, Renal, Metabolism Mechanism Indication(s) Obesity related diseases Code Name Mechanism Indication(s) Code Name MBL949 MBL949 NIO752 NIO752 Tau antagonist Progressive supranuclear palsy Global Health Ophthalmology Code Name Mechanism Indication(s) Code EYU688 KAF156 MHU650 MHU650 Diabetic eye diseases INE963 Name EYU688 ganaplacide INE963 Mechanism NS4B inhibitor 60 Investor Relations | Q4 2021 Results Indication(s) Dengue Malaria prophylaxis Malaria, uncomplicated NOVARTIS | Reimagining Medicine#61Company overview Pharmaceuticals Participants Financial performance Novartis pipeline in Phase 2 Oncology Code AAA601 Name LutatheraⓇ ABL001 ScemblixⓇ BLZ945 BLZ945 Mechanism Indication(s) Radioligand therapy target SSTR GEPNET, pediatrics BCR-ABL inhibitor CSF-1R inhibitor Chronic myeloid leukemia, 2L, pediatrics Solid tumors HGG/LGG, pediatrics Non-small cell lung cancer (Combo) DRB436 Tafinlar® + Mekinist® INC280 TabrectaⓇ INC424 JakaviⓇ JDQ443 JDQ443 BRAF inhibitor + MEK inhibitor Met inhibitor JAK1/2 inhibitor KRAS inhibitor LNP023 iptacopan LXH254 LXH254 CFB inhibitor CRAF inhibitor MBG453 sabatolimab NIR178 NIR178, spartalizumab NIS793 NIS793 PKC412 Rydapt SEG101 Adakveo® TNO155 TNO155 Immunology Myelofibrosis (combo) NSCLC (combo) Oncology Innovation: Pipeline overview Financial review Conclusion Appendix Innovation: Clinical trials 29 lead indications Ophthalmology Name Code CPK850 CPK850 LKA651 LKA651 SAF312 libvatrep UNR844 UNR844 Respiratory & Allergy Mechanism RLBP1 AAV EPO inhibitor TRPV1 antagonist Reduction of disulfide bonds Indication(s) Retinitis pigmentosa Diabetic retinopathy Chronic ocular surface pain Presbyopia Acute GVHD, pediatrics Chronic GVHD, pediatrics Code CMK389 CSJ117 Name CMK389 Mechanism IL-18 inhibitor CSJ117 QBW251 icenticaftor QMF149 Atectura® TSLP inhibitor CFTR potentiator Combo TIM3 antagonist Ad2AR inhibitor, PD1 inhibitor TGFB1 inhibitor Multi-targeted kinase inhibitor P-selectin inhibitor SHP2 inhibitor Autoimmune cytopenias Melanoma (combo) Unfit acute myeloid leukaemia Acute myeloid leukaemia, maintenance Cancers Colorectal cancer (Combos) Acute myeloid leukemia, pediatrics Sickle cell anaemia with crisis, pediatrics Solid tumors (single agent) Lead indication Indication(s) Pulmonary sarcoidosis Asthma Bronchiectasis Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease Asthma, pediatrics Cardiovascular, Renal, Metabolism Code Name CFZ533 iscalimab HSY244 HSY244 Mechanism CD40 inhibitor CFB inhibitor Indication(s) Lupus nephritis Type 1 diabetes mellitus Atrial fibrillation Membranous nephropathy Code Hidradenitis suppurativa Code Name ADPT02 ADPT02 AIN457 Cosentyx® CFZ533 iscalimab CMK389 CMK389 Mechanism Indication(s) Non-alcoholic steatohepatitis (Combos) IL17A inhibitor Lichen planus CD40 inhibitor Sjögren's Liver Tx IL-18 inhibitor Atopic dermatitis DFV890 DFV890 NLRP3 inhibitor Osteoarthritis LNP023 iptacopan Neuroscience Name ADPT06 ADPT06 BLZ945 BLZ945 DLX3132 DLX313 LMI070 branaplam MIJ821 MIJ821 Mechanism CSF-1R inhibitor Alpha-synuclein Inhibitor mRNA splicing modulator NR2B negative allosteric modulator Indication(s) Cognitive impairment Amyotrophic lateral sclerosis Parkinson's disease Huntington's disease Acute depression LJN452 LNA043 LNA043 LOU064 remibrutinib LRX712 LRX712 tropifexor +licogliflozin FXR agonist Familial cold auto-inflammatory syndrome Non-alcoholic steatohepatitis (Combos) ANGPTL3 agonist BTK inhibitor Knee osteoarthritis Sjögren's Osteoarthritis (combos) Global Health Osteoarthritis LYS006 LYS006 Anti-inflammatory Acne MAS825 MAS825 NLRC4-GOF indications Colitis ulcerative Hidradenitis suppurativa Hidradenitis suppurativa MHV370 MHV370 VAY736 ianalumab Sjögren's BAFF-R inhibitor Sjögren's Autoimmune hepatitis LXE408 Systemic lupus erythematosus SKO136 Code Name KAE609 cipargamin KAF156 ganaplacide LXE408 ensovibep Mechanism PfATP4 inhibitor Indication(s) Malaria, severe Malaria, uncomplicated Malaria, uncomplicated Proteasome inhibitor Visceral leishmaniasis Multi-specific DARPin Corona virus infection 1. Clinical hold lifted. 2. UCB0599. 61 Investor Relations | Q4 2021 Results U NOVARTIS | Reimagining Medicine#62Company overview Pharmaceuticals Participants Financial performance Novartis pipeline in Phase 3 Oncology Oncology Innovation: Pipeline overview Financial review Conclusion Appendix Innovation: Clinical trials 8 lead indications Lead indication Code Name AAA617 177Lu-PSMA-617 AAA6011) Lutathera® Mechanism Indication(s) Radioligand therapy target PSMA mCRPC, pre-taxane Metastatic hormone sensitive prostate cancer (mHSPC) Radioligand therapy target SSTR Gastroenteropancreatic neuroendocrine tumors, 1st line in G2/3 BCR-ABL inhibitor BRAF inhibitor + MEK inhibitor Thrombopoietin receptor (TPO-R) agonist Met inhibitor ABL001 ScemblixⓇ ACZ885 canakinumab IL-1b inhibitor BYL719 Piqray® PI3Ka inhibitor CTL019 KymriahⓇ CD19 CAR-T DRB436 Tafinlar® + Mekinist® ETB115 Promacta® INC280 Tabrecta® JDQ443 JDQ443 KRAS inhibitor LEE011 Kisqali® CDK4 Inhibitor LNP023 iptacopan CFB inhibitor MBG453 sabatolimab TIM3 antagonist NIS793 VDT482 NIS793 TGFB1 inhibitor tislelizumab PD1 inhibitor YTB323 YTB323 CD19 CAR-T tumors (GEP-NET 1L G3) Chronic myeloid leukemia, 1st line NSCLC, adjuvant HER2+ adv BC Triple negative breast cancer Ovarian cancer 1L high risk acute lymphocytic leukaemia, pediatrics & young adults Thyroid cancer r/r Severe aplastic anemia Non-small cell lung cancer 2/3L Non-small cell lung cancer HR+/HER2- BC (adj) Paroxysmal nocturnal haemoglobinuria Atypical haemolytic uraemic syndrome Myelodysplastic syndrome Pancreatic cancer 1L Nasopharyngeal Carcinoma 1L ESCC 1L Hepatocellular Carcinoma 1L Bladder Urothelial Cell Carcinoma 2L Diffuse large B-cell lymphoma³) Neuroscience Name Code AMG334 AimovigⓇ BAF312 MayzentⓇ LOU064 Mechanism CGRPR antagonist S1P1,5 receptor modulator remibrutinib BTK inhibitor OAV101 AVXS-101 OMB157 KesimptaⓇ Respiratory & Allergy Code Name IGE025 XolairⓇ QGE031 ligelizumab Indication(s) Migraine, pediatrics Multiple sclerosis, pediatrics Multiple sclerosis SMN1 gene replacement therapy SMA IT administration CD20 Antagonist Multiple sclerosis, pediatrics Indication(s) Mechanism IgE inhibitor Food allergy Auto-injector IgE inhibitor Food allergy Indication(s) Cardiovascular, Renal, Metabolism Name Mechanism siRNA (regulation of LDL-C) Angiotensin receptor/neprilysin inhibitor Congestive heart failure, pediatrics²) Code KJX839 Leqvio® LCZ696 Entresto® Non-small cell lung cancer LNP023 iptacopan CFB inhibitor TQJ230 Pelacarsen ASO targeting Lp(a) 1L Small Cell Lung Cancer 1L Gastric cancer Localized ESCC Biosimilars CVRR-LDLC IgA nephropathy Hyperlipidemia, pediatrics C3 glomerulopathy Secondary prevention of cardiovascular events in patients with elevated levels of lipoprotein (a) (CVRR-Lp(a)) Code Immunology Code AIN457 Name Cosentyx® Mechanism IL17A inhibitor Indication(s) Lupus Nephritis Name GP2411 denosumab SOK583 aflibercept Mechanism anti RANKL mAb VEGF inhibitor Indication(s) Osteoporosis (same as originator) Ophthalmology indication (as originator) AS H2H Psoriatic arthritis (IV formulation) Axial SpA (IV formulation) Giant cell arteritis Hidradenitis suppurativa Ophthalmology QGE031 Code Name RTH258 BeovuⓇ Mechanism VEGF inhibitor ligelizumab IgE inhibitor Indication(s) Diabetic retinopathy LOU064 remibrutinib BTK inhibitor Chronic spontaneous urticaria Chronic inducible urticarial (CINDU) Chronic spontaneous urticaria Global Health Code COA566 Name Coartem® Mechanism Indication(s) Malaria, uncomplicated (<5kg patients) 1. 177 Lu-dotatate in US. 2. Approved in US. 62 Investor Relations | Q4 2021 Results 3. Ph3 to be initiated in 2022. U NOVARTIS | Reimagining Medicine#63Company overview Pharmaceuticals Participants Financial performance Oncology Financial review Conclusion Innovation: Pipeline overview Novartis pipeline in registration Oncology Code Name AAA617 177Lu-PSMA-617 BYL719 alpelisib CTL019 KymriahⓇ INC424 Jakavi® Mechanism Radioligand therapy target PSMA PI3Ka inhibitor CD19 CAR-T JAK1/2 inhibitor VDT482 tislelizumab PD1 inhibitor Indication(s) Metastatic castration-resistant prostate cancer, post-taxane PIK3CA-related overgrowth spectrum r/r Follicular lymphoma Acute GVHD Chronic GVHD 2L ESCC Immunology Code Name AIN457 CosentyxⓇ Ophthalmology Mechanism IL17A inhibitor Indication(s) Cosentyx 300mg auto-injector and pre-filled syringe Code Name RTH258 BeovuⓇ Mechanism Indication(s) VEGF inhibitor Diabetic macular edema 63 Investor Relations | Q4 2021 Results Appendix Innovation: Clinical trials 2 lead indication Lead indication NOVARTIS | Reimagining Medicine#64NEW INDICATIONS Participants Company overview Pharmaceuticals Financial performance Oncology Innovation: Pipeline overview Novartis submission schedule New Molecular Entities: Lead and supplementary indications LEAD INDICATIONS 2022 2023 ligelizumab¹ Lead iptacopan LNP023 QGE031 CSU PNH sabatolimab² Lead MBG453 HR-MDS ensovibep Lead SKO136 COVID19 tislelizumab VDT482 1L Nasopharyngeal Carcinoma tislelizumab VDT482 NSCLC Financial review Conclusion Appendix Innovation: Clinical trials 2024 2025 ≥2026 Lead JDQ443 JDQ443 Lead icenticaftor Lead 177 Lu-NeoB Lead ganaplacide Lead QBW251 AAA603 KAF156 LXE408 Visceral leishmaniasis Lead 2/3L NSCLC (mono) COPD Multiple Solid Tumors Malaria uncomplicated remibrutinib Lead NIS793 Lead branaplam Lead iscalimab Lead LXH254 Lead LMI070 CFZ533 Solid tumors (combos) LOU064 1L Pancreatic cancer Huntington's disease CSU Sjögren's syndrome UNR844 Presbyopia Lead pelacarsen TQJ230 CVRR-Lp(a) Lead cipargamin Lead ianalumab Lead MIJ821 Lead KAE609 VAY736 Acute depression Malaria severe Sjögren's syndrome YTB323 Lead CPK850 Lead libvatrep Lead TNO155 Lead Solid tumors RP SAF312 2L Diffuse large B-cell lymphoma COSP CSJ117 Lead LNA043 Lead tropifexor&licogliflozi Lead Asthma Knee osteoarthritis LJN452 NASH (combos) gevokizumab Lead VPM087 1st line CRC / 1st line RCC LCM 177Lu-PSMA-617 LCM 177Lu-PSMA-617 LCM asciminib LCM asciminib LCM ianalumab LCM AAA617 ABL001 ABL001 VAY736 AAA617 MHSPC CML 1L CML, 2L, pediatrics AIH Pre-taxane LCM iptacopan LCM sabatolimab LCM iptacopan LCM cipargamin LCM iptacopan LCM LNP023 MBG453 C3G Unfit AML LNP023 aHUS KAE609 Malaria uncomplicated LNP023 iMN iptacopan LCM tislelizumab LCM ligelizumab LCM JDQ443 LCM LNP023 VDT482 QGE031 JDQ443 IgAN 1L Small Cell Lung Cancer Food allergy NSCLC (Combo) tislelizumab LCM tislelizumab LCM VDT482 VDT482 1L Gastric Cancer 1L Bladder Urothelial Cell Carcinoma ligelizumab QGE031 CINDU LCM tislelizumab LCM VDT482 1L ESCC remibrutinib LOU064 Multiple sclerosis LCM tislelizumab LCM VDT482 Localized ESCC tislelizumab VDT482 LCM 1L Hepatocellular Carcinoma 1. Ph3 data in evaluation. 2. Filing opportunity in 2022/2023, based on PFS and/or OS outcomes from a dual approach based on parallel Phase 2 and Phase 3 trials. 64 Investor Relations | Q4 2021 Results iscalimab LCM CFZ533 Liver Tx remibrutinib LOU064 Sjögren's syndrome LCM U NOVARTIS | Reimagining Medicine#65Participants Company overview Pharmaceuticals Financial performance Oncology Innovation: Pipeline overview Novartis submission schedule Supplementary indications for existing brands Financial review Conclusion Appendix Innovation: Clinical trials 2022 2023 2024 2025 ≥2026 Cosentyx LCM canakinumab LCM Adakveo LCM aflibercept BioS Atectura LCM secukinumab, AIN457 ACZ885 SEG101 SOK583 PSA IV Adjuvant NSCLC Sickle cell anaemia with crisis ped Neovascular age-related macular degeneration indacaterol + mometasone, QMF149 Asthma, pediatrics Jakavi ruxolitinib, INC424 Myelofibrosis (combination) LCM Leqvio KJX839 CVRR-LDLC LCM Cosentyx LCM Cosentyx LCM Coartem LCM Beovu LCM Aimovig LCM Kesimpta³ LCM Mayzent4 LCM secukinumab, AIN457 AS H2H secukinumab, AIN457 AS IV artemether + lumefantrine, COA566 Malaria uncompl., formula for <5kg brolucizumab, RTH258 Diabetic retinopathy erenumab, AMG334. ofatumumab siponimod, BAF312 Pediatric Migraine Multiple sclerosis, pediatrics Multiple sclerosis, pediatrics Cosentyx LCM denosumab BioS Cosentyx LCM Cosentyx LCM Cosentyx LCM Kymriah LCM Rydapt LCM secukinumab, AIN457 GP2411 secukinumab, AIN457 secukinumab, AIN457 Hidradenitis suppurativa anti RANKL mAb GCA Lichen Planus secukinumab, AIN457 Lupus Nephritis tisagenlecleucel, CTL019 midostaurin, PKC412 1L high risk ALL, pediatrics & young adults Acute myeloid leukemia, pediatrics Entresto EU1 LCM Kisqali LCM Jakavi LCM Piqray LCM sacubitril/valsartan, LCZ696 ribociclib, LEE011 ruxolitinib, INC424 alpelisib, BYL719 Pediatric CHF HR+/HER2- BC (adj) Pediatrics Acute GVHD HER2+ adv BC Tafinlar + Mekinist LCM Lutathera LCM Jakavi LCM Zolgensma LCM dabrafenib + trametinib, DRB436 177Lu-oxodotreotide² ruxolitinib, INC424 HGG/LGG - Pediatrics GEP-NET 1L G3 Pediatrics Chronic GVHD AVXS-101 OAV101 SMA IT Xolair LCM Piqray LCM Leqvio LCM omalizumab, IGE025 alpelisib, BYL719 KJX839 Auto-injector TNBC Ped Hyperlipidemia Piqray LCM Tafinlar + Mekinist LCM alpelisib, BYL719 Ovarian cancer dabrafenib + trametinib, DRB436 Thyroid cancer Promacta LCM eltrombopag, ETB115 r/r severe aplastic anemia Xolair LCM omalizumab, IGE025 Food allergy 1. Approved in US. 2. 177Lu-dotatate in US. 3. Kesimpta and Mayzent: pediatric study in multiple sclerosis run in conjunction (NEOS). 65 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#66Company overview Pharmaceuticals Participants Financial performance CRM IHD Oncology Financial review Conclusion Appendix Innovation: Pipeline overview Innovation: Clinical trials Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations Neuroscience Ophthalmology Respiratory & Allergy Clinical Trials Update Includes selected ongoing or recently concluded global trials of Novartis development programs/products which are in confirmatory development or marketed (typically Phase 2b or later). For further information on all Novartis clinical trials, please visit: www.novartis.com/clinicaltrials. 66 Investor Relations | Q4 2021 Results 1 NOVARTIS | Reimagining Medicine#67Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations Cardiovascular, Renal and Metabolic 67 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#68Participants Financial performance Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations EntrestoⓇ - Angiotensin receptor/neprilysin inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT02678312 PANORAMA HF (CLCZ696B2319) Heart failure in pediatric patients Phase 3 360 Part 1: Pharmacodynamics and pharmacokinetics of sacubitril/valsartan LCZ696 analytes Part 2: Efficacy and safety compared with enalapril Part 1: Sacubitril/valsartan 0.8 mg/kg or 3.1 mg/kg or both; 0.4 mg/kg or 1.6 mg/kg or both (single doses). Part 2: enalapril/placebo 0.2 mg/kg bid (ped. formulation 1mg/ml) and adult formulation (2.5, 5, 10 mg bid); Sacubitril/valsartan (LCZ696)/placebo: Ped. formulation granules (12.5, 31.25 mg in capsules); liquid formulation (1mg/ml and 4mg/ml concentration) and adult formulation (50, 100, 200 mg bid) Pediatric patients from 1 month to < 18 years of age with heart failure due to systemic left ventricle systolic dysfunction NCT02884206 PERSPECTIVE (CLCZ696B2320) Heart failure Phase 3 592 Change from baseline in the CogState Global Cognitive Composite Score (GCCS) Sacubitril/valsartan 50, 100, and 200 mg bid with placebo of valsartan Valsartan 40, 80, and 160 mg bid tablets with placebo for sacubitril/valsartan Patients with chronic heart failure with preserved ejection fraction Target Patients Read-out Milestone(s) 2022; (Analysis of 110 pts from Part 2 formed the basis for pediatric submission in Apr-2019 and approval by the US FDA in Oct-2019 for the treatment of symptomatic HF with systemic left ventricular systolic dysfunction in children aged 1 year and older) 2023 Publication TBD TBD 68 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#69Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations Entresto® - Angiotensin receptor/neprilysin inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT03785405 (CLCZ696B2319E1 - extension study) Heart failure in pediatric patients Phase 3 240 Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) Single arm, open label sacubitril/valsartan (pediatric formulation granules (12.5, 31.25 mg in capsules); liquid formulation (1mg/ml and 4mg/ml concentration) and adult formulation (50, 100, 200 mg bid)) Pediatric patients with heart failure due to systemic left ventricle systolic dysfunction who have completed study CLCZ696B2319 Target Patients Read-out Milestone(s) 2023 Publication TBD 69 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#70Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations LeqvioⓇ - siRNA (regulation of LDL-C) Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients NCT03705234 ORION-4 (CKJX839B12301) Hypercholesterolemia inc. Heterozygous Familial Hypercholesterolaemia (HeFH) Phase 3 ~15000 A composite of major adverse cardiovascular events, defined as: Coronary heart disease (CHD) death; Myocardial infarction; Fatal or non-fatal ischaemic stroke; or Urgent coronary revascularization procedure Arm 1: every 6 month treatment Inclisiran sodium 300mg (given by subcutaneous injection on the day of randomization, at 3 months and then every 6- months) for a planned median duration of about 5 years Arm 2: matching placebo (given by subcutaneous injection on the day of randomization, at 3 months and then every 6-months) for a planned median duration of about 5 years. Patient population with mean baseline LDL-C >= 100mg/dL Read-out Milestone(s) 2026 Publication TBD 70 Investor Relations | Q4 2021 Results 1 NOVARTIS | Reimagining Medicine#71Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations Leqvio® - siRNA (regulation of LDL-C) Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients NCT03060577 ORION-3 (CKJX839A12201E1) Hypercholesterolemia inc. Atherosclerotic Cardiovascular Disease (ASCVD) and ASCVD risk equivalents Heterozygous Familial Hypercholesterolaemia (HeFH) Phase 2 490 LDL-C reduction at Day 210 for Group 1 subjects Changes in other lipids and lipoproteins and reduction of LDL-C of more than 50% for patients that are above LDL-C goal; longer term exposure and safety. Group 1 - inclisiran sodium 300mg sc on Day 1 and every 180 days thereafter for up to 4 years. Group 2- Evolocumab 140mg s.c. injection on Day 1 and every 2 weeks until Day 336, followed by inclisiran sodium 300mg on Day 360, Day 450 and then every 6 months for a planned duration of 4 years. Patients with HeFH or pre-existing atherosclerotic cardiovascular disease (ASCVD) on background statin +/- ezetimibe therapy Read-out Milestone(s) 2021 (actual) Publication TBD NCT03814187 ORION-8 (CKJX839A12305B) Hypercholesterolemia inc. Heterozygous Familial Hypercholesterolaemia (HeFH) and Homozygous Familial Hypercholesterolemia (HoFH) Phase 3 2991 Proportion of subjects achieving pre specified low density lipoprotein cholesterol (LDL-C) targets at end of study Safety and tolerability profile of long term use of inclisiran Inclisiran sodium 300mg on day 1 (placebo patients entered into study from ORION 9, 10 & 11) or placebo on Day 1 (inclisiran patients entered into study from ORION 9, 10 & 11) then inclisiran sodium 300mg on Day 90 and every 6 months for a planned duration of 3 years Patients with HeFH or pre-existing atherosclerotic cardiovascular disease (ASCVD) on background statin +/- ezetimibe therapy and risk equivalents (patients from ORION 3, 9, 10 & 11 studies) 2023 TBD 71 Investor Relations | Q4 2021 Results 1 NOVARTIS | Reimagining Medicine#72Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations LeqvioⓇ - siRNA (regulation of LDL-C) Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients Read-out Milestone(s) Publication NCT03851705 ORION-5 (CKJX839A12302) Hypercholesterolemia inc. Homozygous Familial Hypercholesterolemia (HoFH) Phase 3 56 LDL-C reduction at Day 150 Changes in PCSK9, other lipids and lipoproteins Part 1: inclisiran sodium 300mg on Day 1 and Day 90 or placebo on Day 1 and Day 90 Part 2: inclisiran sodium 300mg on Day 180 for patients who were randomized to the placebo group only, inclisiran sodium 300mg on Day 270 and then every 6 months for a planned duration of 2 years for all patients Patients with HoFH with background statin +/- ezetimibe therapy Primary: Q3-2020 (actual); Final: H2-2021 TBD NCT04652726 ORION-16 (CKJX839C12301) Hyperlipidemia, pediatrics Phase 3 150 Percentage (%) change in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 330 Group 1: Inclisiran sodium 300mg on Days 1, 90, 270, placebo on Day 360, inclisiran sodium 300mg on Days 450 and 630; Group 2: Placebo on Days 1, 90, 270, inclisiran sodium 300mg on Days 360, 450 and 630. Adolescents (12 to less than 18 years) with heterozygous familial hypercholesterolemia (HeFH) and elevated low density lipoprotein cholesterol (LDL-C) 2024 TBD 72 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#73Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations Leqvio® - siRNA (regulation of LDL-C) Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients NCT04659863 ORION-13 (CKJX839C12302) Hyperlipidemia, pediatrics Phase 3 15 Percentage (%) change in low-density lipoprotein cholesterol (LDL-C) from baseline to day 330 Group 1: Inclisiran sodium 300mg on Days 1, 90, 270, placebo on Day 360, inclisiran sodium 300mg on Days 450 and 630;Group 2: Placebo on Days 1, 90, 270, inclisiran sodium 300mg on Days 360, 450 and 630. Adolescents (12 to less than 18 years) with homozygous familial hypercholesterolemia (HoFH) and elevated low density lipoprotein cholesterol (LDL-C) NCT05030428 VICTORION-2P (CKJX839B12302) CVRR Phase 3 15000 1. Time to First Occurrence of 3P-MACE (3-Point Major Adverse Cardiovascular Events) Arm 1: Experimental Inclisiran sodium, Subcutaneous injection Arm 2: Placebo Comparator, Placebo Subcutaneous injection Participants with established cardiovascular disease (CVD) Read-out Milestone(s) 2024 Publication TBD 73 Investor Relations | Q4 2021 Results 2027 TBD NOVARTIS | Reimagining Medicine#74Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations iptacopan - CFB inhibitor NCT03955445 (CLNP023B12001B) C3 glomerulopathy (C3G) Phase 2 Study Indication Phase Patients Primary Outcome Measures NCT04817618 APPEAR-C3G (CLNP023B12301) C3 glomerulopathy Phase 3 68 27 Log-transformed ratio to baseline in UPCR (sampled from a 24 hour urine collection) Arms Intervention Experimental: iptacopan 200mg b.i.d. Placebo Comparator: Placebo to iptacopan 200mg b.i.d. Patients with native C3G Target Patients Read-out Milestone(s) 2023 Publication TBD 74 Investor Relations | Q4 2021 Results Characterize the effect of LNP023 treatment on a composite renal response endpoint at 9 months (1. a stable or improved eGFR and, 2. a reduction in proteinuria and 3. an increase in C3 compared to the CLNP023X2202 baseline visit) Open-label LNP023 200mg bid Patients with C3 glomerulopathy 2025 Wong et al 2021 Nephrology, Dialysis and Transplantation Vol. 36, Suppl. 1: eGFR trajectory NOVARTIS | Reimagining Medicine#75Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations iptacopan - CFB inhibitor Study Indication Phase NCT04154787 (CLNP023D12201) Idiopathic membranous nephropathy (iMN) Phase 2 NCT04578834 APPLAUSE-IgAN (CLNP023A2301) IgA nephropathy Phase 3 Patients 72 450 Primary Outcome Measures Change from baseline of UPCR derived from 24hr urine collections at Baseline and Week 24 Arms Intervention Target Patients Read-out Milestone(s) 2023 Publication TBD 75 Investor Relations | Q4 2021 Results Ratio to baseline in urine protein to creatinine ratio (sampled from 24h urine collection) at 9 months Annualized total estimated Glomerular Filtration Rate (eGFR) slope estimated over 24 months Arm 1 - LNP023 200mg BID Arm 2 - Placebo BID LNP023 low dose LNP023 high dose Rituximab Patients with biopsy proven iMN who are at high risk of disease progression defined on the basis of antibody anti-PLA2R titre and proteinuria Primary IgA Nephropathy patients 2023 (primary endpoint for US initial submission, 9 months UPCR)2025 (24 months) Perkovic et al. 2021, Nephrology Dialysis Transplantation, Vol. 36, Suppl. 1: Study Design Wong et al. 2021, Nephrology Dialysis Transplantation, Vol. 36, Suppl. 1: IPTACOPAN (LNP023): A NOVEL ORAL COMPLEMENT ALTERNATIVE PATHWAY FACTOR B INHIBITOR SAFELY AND EFFECTIVELY STABILISES EGFR IN C3 GLOMERULOPATHY U NOVARTIS | Reimagining Medicine#76Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations pelacarsen - ASO targeting Lp(a) Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT04023552 Lp(a) HORIZON (CTQJ230A12301) Cardiovascular risk reduction Phase 3 7680 Time to the first occurrence of MACE (cardiovascular death, non-fatal MI, non-fatal stroke and urgent coronary re-vascularization) TQJ230 80 mg injected monthly subcutaneously or matched placebo Patients with a history of Myocardial infarction or Ischemic Stroke, or a clinically significant symptomatic Peripheral Artery Disease, and Lp(a) >= 70 mg/dL Target Patients Read-out Milestone(s) 2025 Publication TBD 76 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#77Participants Company overview Pharmaceuticals Financial performance CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology Financial review Conclusion Appendix Innovation: Pipeline overview Innovation: Clinical trials Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations Immunology, Hepatology & Dermatology 77 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#78Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations LNA043- ANGPTL3 agonist Study Indication Phase Patients Primary Outcome Measures NCT03275064 (CLNA043X2202) Knee osteoarthritis Phase 2 133 Articular cartilage bi-layer collagen organisation evaluated with MRI and measured in milliseconds (ms) (Part A only) Number of patients with any adverse events, serious adverse events and death (Part A and Part B) Change in cartilage volume/thickness in the index region (Part B only) NCT04864392 ONWARDS (CLNA043A12202) Knee osteoarthritis Phase 2 550 Change from baseline in the cartilage thickness of the medial compartment of the knee as assessed by imaging Arms Intervention LNA043 40 mg Part B LNA043 20 mg Part B LNA043 20 mg Part A Placebo Part A Placebo Part B LNA043 injection to the knee with dosing regimen A LNA043 injection to the knee with dosing regimen B LNA043 injection to the knee with dosing regimen C LNA043 injection to the knee with dosing regimen D Placebo injection to the knee Target Patients Patients with cartilage lesions of the knee (Part A) and knee osteoarthritis (Part B) Read-out Milestone(s) 2022 Patients with Symptomatic knee osteoarthritis Primary 2024 Publication TBD TBD 78 Investor Relations | Q4 2021 Results 1 NOVARTIS | Reimagining Medicine#79Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations Cosentyx® - IL-17A inhibitor Study Indication Phase Patients NCT03031782 (CAIN457F2304) JPSA & ERA Phase 3 80 Primary Outcome Measures Time to 33 flares Arms Intervention Secukinumab (pre-filled syringe) 75 mg Placebo Juvenile idiopathic arthritis subtypes of psoriatic and enthesitis-related arthritis Target Patients Read-out Milestone(s) H1-2021 Publication H2-2021 NCT03259074 SURPASS (CAIN457K2340) JPSA & ERA Phase 3 837 No radiographic structural progression as measured by modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) Secukinumab 150/300 mg Adalimumab biosimilar 40 mg Patients with active ankylosing spondylitis 2022 Study design manuscript published. Baraliakos et al. Clinical Drug Investigation (2020) 40:269-278. 79 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#80Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations Cosentyx® - IL-17A inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients Read-out Milestone(s) Publication NCT03713619 SUNSHINE (CAIN457M2301) Hidradenitis Suppurativa (HS) Phase 3 471 Proportion of participants with Hidradenitis Suppurativa clinical response (HiSCR) Secukinumab 300 mg every 2 weeks Secukinumab 300 mg every 4 weeks Placebo (every 2 weeks) Placebo (every 4 weeks) Patients with moderate to severe Hidradenitis Suppurativa Primary (week 16): H2-2021; Final: 2022 Study design SHSA 2020; Primary 2022 NCT03713632 SUNRISE (CAIN457M2302) Hidradenitis Suppurativa (HS) Phase 3 471 Proportion of patients with Hidradenitis Suppurativa Clinical Response (HiSCR) Secukinumab 300 mg every 2 weeks Secukinumab 300 mg every 4 weeks Placebo (every 2 weeks) Placebo (every 4 weeks) Subjects with moderate to severe Hidradenitis Suppurativa Primary (week 16): H2-2021; Final: 2022 Study design SHSA 2020; Primary 2022 80 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#81Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations Cosentyx® - IL-17A inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT03769168 (CAIN457F2304E1 - extension study) Psoriatic arthritis Phase 3 64 Number of participants with JIA ACR30 response Secukinumab 75 mg/0.5 ml Secukinumab 150 mg/1.0 ml Patients with juvenile idiopathic arthritis subtypes of juvenile psoriatic arthritis and enthesitis related arthritis Target Patients Read-out Milestone(s) 2025 Publication TBD NCT04156620 INVIGORATE-1 (CAIN457P12301) Axial spondyloarthritis Phase 3 500 The proportion of subjects achieving an ASAS40 (Assessment of SpondyloArthritis International Society criteria) response Secukinumab intravenous (i.v.) regimen Placebo intravenous (i.v.) regimen Patients with active axial spondyloarthritis Primary (week 16): 2022; Final: 2023 2023 81 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#82Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations Cosentyx® - IL-17A inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT04179175 (CAIN457M2301E1) Hidradenitis Suppurativa (HS) Phase 3 745 Proportion of patients with Hidradenitis Suppurativa Clinical Response (HiSCR) Secukinumab 300 mg every 2 weeks Secukinumab 300 mg every 4 weeks Patients with moderate to severe hidradenitis suppurativa completing either of the core trials AIN457M2301 (NCT 0313632) or AIN567M2302 (NCT03713619) Target Patients Read-out Milestone(s) 2025 Publication Study design SHSA 2020 NCT04181762 SELUNE (CAIN457Q12301) Lupus Nephritis Phase 3 460 Proportion of subjects achieving protocol-defined CRR Secukinumab 300 mg s.c. Placebo s.c. Patients with active lupus nephritis (ISN/RPS Class III or IV, with or without co- existing class V features) 2026 2026 82 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#83Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations Cosentyx® - IL-17A inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT04209205 INVIGORATE-2 (CAIN457P12302) Psoriatic Arthritis (PSA) Phase 3 380 The proportion of subjects achieving American College of Rheumatology 50 (ACR50) response criteria Secukinumab intravenous (i.v.) regimen Placebo intravenous (i.v.) regimen Patients with active psoriatic arthritis (PSA) despite current or previous NSAID, DMARD and/or anti-TNF therapy Target Patients Read-out Milestone(s) H2-2021 (Actual) Publication 2023 NCT04300296 PRELUDE (CAIN457S12201) Lichen Planus Phase 2 108 Proportion of patients achieving Investigator's Global Assessment (IGA 0/1) score at 16 weeks +30% delta vs placebo Secukinumab 300 mg s.c. Placebo s.c. Adult patients with biopsy-proven lichen planus not adequately controlled by topical therapies 2022 TBD 83 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#84Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations Cosentyx® - IL-17A inhibitor Study Indication Phase Patients Primary Outcome Measures NCT04930094 (CAIN457R12301) Giant cell arteritis Phase 3 240 Arms Intervention Target Patients Read-out Milestone(s) Publication Number of participants with sustained remission Experimental: Secukinumab 300 mg Placebo Comparator: Placebo Patients with Giant Cell Arteritis (GCA) Primary 2024 Final 2025 TBD 84 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#85Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations ianalumab - BAFF-R inhibitor Study Indication Phase Patients Primary Outcome Measures NCT03217422 AMBER (CVAY736B2201) Autoimmune hepatitis Phase 2 80 Alanine aminotransferase (ALT) normalization Arms Intervention VAY736 Placebo control with conversion to active VAY736 Autoimmune hepatitis patients with incomplete response or intolerant to standard treatment of care Target Patients Read-out Milestone(s) 2026 Publication TBD 85 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#86Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations iscalimab - CD40 inhibitor Study Indication Phase NCT03781414 CONTRAIL I (CCFZ533A2202) Liver transplantation Phase 2 Patients 128 NCT03905525 TWINSS (CCFZ533B2201) Sjögren's syndrome Phase 2 260 Primary Outcome Measures Arms Intervention Proportion of patients with composite event (BPAR, Graft Loss or Death) over 12 months Control/Standard of Care: TAC + MMF + Corticosteroids CFZ533 dose A+ MMF + Corticosteroids CFZ533 dose B + MMF + Corticosteroids Liver transplant recipients Change in EULAR Sjögren's syndrome Disease Activity Index (ESSDAI) score and EULAR Sjögren's syndrome Patient Reported Index (ESSPRI) score Three dose arms of CFZ533 Placebo Target Patients Read-out Milestone(s) 2023 Publication 2023 86 Investor Relations | Q4 2021 Results Patients with Sjögren's syndrome 2022 2022 NOVARTIS | Reimagining Medicine#87Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations iscalimab - CD40 inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients Read-out Milestone(s) Publication NCT04541589 TWINSS Extn (CFZ533B2201E1) Sjögren's syndrome Phase 2 Incidence of Treatment-emergent AES (TEAEs) Change in laboratory evaluations for hematology from baseline to each study visit Change in laboratory evaluations for serum chemistry from baseline to each study visit Change in vital sign measurements from baseline for each post-baseline visit Arm 1 Iscalimab Dose 1 s.c. Q2W Arm 2 Iscalimab Dose 2 s.c. Q2W and Placebo Patients with Sjögren's Syndrome, who participated in the TWINSS core study, CCFZ533B2201(NCT03905525) Primary completion date: 2024 87 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#88Participants Financial performance Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations ligelizumab - IgE inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients Read-out Milestone(s) Publication NCT03580369 Pearl 1 (CQGE031C2302) Chronic spontaneous urticaria Phase 3 1050 Absolute change from baseline in UAS7 (Urticaria Activity Score) at week 12 Ligelizumab dose A q4w for 52 weeks Ligelizumab dose B q4w for 52 weeks Omalizumab 300 mg q4w for 52 weeks Placebo q4w from randomization to wk20, then ligelizumab dose B from wk24 to wk52 Adolescents and adults with chronic spontaneous urticaria inadequately controlled with H1-antihistamines H2-2021 (actual) Past publications: Study design presented at UCARE 2018 Manuscripts - Primary results. PEARL 1/2 pooled data. NEJM or Lancet. H2-2022 - H1-2023 (Dec 2022 or Jan 2023) Congress publications - EADV 2022: Late breaking abstract on primary results (efficacy, safety). H2-2022 as a first publication in Europe - ACAAI 2022: Primary results (efficacy, safety). H2-2022 as a first publication in the USA - AAAAI 2023: secondary results. H1-2023 - AAD 2023: secondary results. H1-2023 NCT03580356 Pearl 2 (CQGE031C2303) Chronic spontaneous urticarial / Chronic idiopathic urticaria? Phase 3 1079 Absolute change from baseline in UAS7 (Urticaria Activity Score) at week 12 Ligelizumab dose A q4w for 52 weeks Ligelizumab dose B q4w for 52 weeks Omalizumab 300 mg q4w for 52 weeks Placebo q4w from randomization to wk20, then ligelizumab dose B from wk24 to wk52 Adolescents and adults with chronic spontaneous urticaria inadequately controlled with H1-antihistamines H2-2021 (actual) Past publications: Study design presented at UCARE 2018 Manuscripts - Primary results. PEARL 1/2 pooled data. NEJM or Lancet. H2-2022 - H1-2023 (Dec 2022 or Jan 2023) Congress publications - EADV 2022: Late breaking abstract on primary results (efficacy, safety). H2-2022 as a first publication in Europe - ACAAI 2022: Primary results (efficacy, safety). H2-2022 as a first publication in the USA - AAAAI 2023: secondary results. H1-2023 - AAD 2023: secondary results. H1-2023 88 Investor Relations | Q4 2021 Results U NOVARTIS | Reimagining Medicine#89Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations ligelizumab - IgE inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT04210843 (CQGE031C2302E1) Chronic spontaneous urticaria Phase 3 1520 The proportion of subjects with well-controlled disease (UAS7 ? 6) at week 12 Ligelizumab Dose 1 and 3 Ligelizumab Dose 2 and 3 Patients who completed studies CQGE031C2302, CQGE031C2303, CQGE031C2202 or CQGE031C1301 Target Patients Read-out Milestone(s) 2026 Publication Study design presented at 2020 EAACI 89 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#90Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations ligelizumab - IgE inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT05024058 PEARL-PROVOKE (CQGE031E12301) CINDU Phase 3 438 1. Change from baseline in Total Fric Score in participants with symptomatic dermographism Arm 1: Experimental Ligelizumab low dose, symptomatic dermographism group Arm 2: Experimental Ligelizumab high dose, symptomatic dermographism Arm 3: Placebo Comparator. Placebo SC q4W, symptomatic dermographism Arm 4: Experimental Ligelizumab low dose, cold urticaria Arm 5: Experimental Ligelizumab high dose, cold urticaria Arm 6: Placebo Comparator: Placebo SC q4w, cold urticaria Arm 7: Experimental Ligelizumab high dose, cholinergic urticaria Arm 8: Placebo Comparator: Placebo SC q4w, cholinergic urticaria Adolescents and adults with chronic inducible urticaria who remain symptomatic despite treatment with H1- Antihistamines Target Patients Read-out Milestone(s) Publication 2024 TBD NCT04984876 PEANUT (CQGE031G12301) Food allergy Phase 3 486 1. Proportion of participants who can tolerate a single dose of ≥ 600 mg (1044 mg cumulative tolerated dose) of peanut protein without dose-limiting symptoms at Week 12 Arm 1: Experimental igelizumab 240 mg subcutaneous injection for 52 weeks Arm 2: Experimental ligelizumab 120 mg subcutaneous injection for 52 weeks Arm 3: Experimental Placebo 8 weeks and ligelizumab 120 mg Arm 4: Placebo subcutaneous injection for first 8 weeks and ligelizumab 120 mg subcutaneous injection for 44 weeks Arm 5: Experimental Placebo 16 weeks and ligelizumab 120 mg/240 mg subcutaneous injection for 36 weeks Arm 6: Experimental Placebo 8 weeks and ligelizumab 240 mg subcutaneous injection for 44 weeks Participants with a medically confirmed diagnosis of IgE-mediated peanut allergy 2025 90 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#91Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations remibrutinib - BTK inhibitor Study Indication Phase Patients Primary Outcome Measures NCT04109313 (CLOU064A2201E1) Chronic spontaneous urticaria (CSU) Phase 2 250 Arms Intervention Long-term safety and tolerability Selected dose of LOU064 taken orally twice a day (morning and evening) from day 1 to week 52 Patients with CSU who have participated in preceding studies with LOU064 Target Patients Read-out Milestone(s) 2022 Publication TBD 91 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#92Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations remibrutinib - BTK inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT05030311 REMIX-1 (CLOU064A2301) Chronic spontaneous urticaria (CSU) Phase 3 450 1. Change from baseline in UAS7 (Scenario 1 with UAS7 as primary efficacy endpoint) 2. Absolute change in ISS7 and absolute change in HSS7 (Scenario 2 with ISS7 and HSS7 as co-primary efficacy endpoints) Arm 1: LOU064 (blinded) LOU064 (blinded) taken orally for 24 weeks, followed by LOU064 (open-label) taken orally open label for 28 weeks. Randomized in a 2:1 ratio (arm 1:arm 2). Arm 2: LOU064 placebo (blinded) LOU064 placebo (blinded) taken orally for 24 weeks, followed by LOU064 (open- label) taken orally for 28 weeks. Randomized in a 2:1 ratio (arm 1:arm 2) Adult participants suffering from chronic spontaneous urticaria (CSU) inadequately controlled by H1-antihistamines in comparison to placebo Target Patients Read-out Milestone(s) Publication 2024 TBD NCT05032157 REMIX-2 (CLOU064A2302) Chronic spontaneous urticaria (CSU) Phase 3 450 1. Change from baseline in UAS7 (Scenario 1 with UAS7 as primary efficacy endpoint) 2. Absolute change in ISS7 an absolute change in HSS7 (Scenario 2 with ISS7 and HSS7 as co-primary efficacy endpoints) Arm 1: LOU064 (blinded) LOU064A (blinded) taken orally b.i.d. for 24 weeks, followed by LOU064 (open- label) taken orally open label for 28 weeks. Randomised in 2:1 ratio (active vs placebo) Arm 2: LOU064 placebo (blinded) LOU064A placebo (blinded) taken orally for 24 weeks, followed by LOU064 (open- label) taken orally open label for 28 weeks. Randomised in 2:1 ratio (active vs placebo) Adult participants suffering from chronic spontaneous urticaria (CSU) inadequately controlled by H1-antihistamines in comparison to placebo 2024 TBD 92 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#93Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations tropifexor, licogliflozin - FXR agonist and SGLT 1/2 inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT04065841 ELIVATE (CLJN452D12201C) Non-alcoholic steatohepatitis (NASH) Phase 2 380 Proportion of patients with resolution of NASH and no worsening of fibrosis OR improvement in fibrosis by at least one stage without worsening of NASH at Week 48 compared with baseline Arm A: combination therapytropifexor + licogliflozin Arm B: tropifexor monotherapytropifexor + licogliflozin placebo Arm C: licogliflozin monotherapylicogliflozin + tropifexor placebo Arm D: licogliflozin placebo + tropifexor placebo Adult patients with biopsy based non-alcoholic steatohepatitis (NASH) and liver fibrosis Target Patients Read-out Milestone(s) Publication 2023 2023 93 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#94Participants Financial performance Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations Neuroscience 94 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#95Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations MIJ821- NR2B negative allosteric modulator (NAM) Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT04722666 (CMIJ821A12201) Acute depression Phase 2 195 Change from baseline to 24 hours in the total score of the Montgomery Åsberg Depression Rating Scale (MADRS) MIJ821 (mg/kg) very low dose for 40 minutes IV infusion on Day 1, Day 15 and Day 29 MIJ821 (mg/kg) low dose for 40 minutes IV infusion on Day 1, Day 15 and Day 29 MIJ821 (mg/kg) high dose for 40 minutes IV infusion on Day 1, Day 15 and Day 29 MIJ821 (mg/kg) very high dose for 40 minutes IV infusion on Day 1, Day 15 and Day 29 Placebo 40 minutes IV infusion of 0.9% sodium chloride on Day 1, Day 15 and Day 29 MIJ821 (mg/kg) high dose for 40 minutes IV infusion on Day 1 or 0.9% sodium chloride Participants who have suicidal ideation with intent Target Patients Read-out Milestone(s) Publication 2023 TBD 95 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#96Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations AimovigⓇ - CGRP receptor antagonist Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients Read-out Milestone(s) Publication NCT03867201 DRAGON (CAMG334A2304) Migraine Phase 3 550 Change from baseline in monthly migraine days during the last 4 weeks of the 12- week treatment period Subcutaneous injection of AMG334 (erenumab) 70 mg Subcutaneous injection of placebo Adult chronic migraine patients Double-blind FIR for 100% of pts 2021; Q4 2021(actual) Extension (open-label): 2024 Planned in H2-2022 for double-blind phase and H1-2025 for open-label extension phase 96 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#97Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations LMI070 - mRNA splicing modulator Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT05111249 VIBRANT-HD (CLMI070C12203) Huntington's disease Phase 2 75 1. Reduction (%) of mHTT protein in cerebrospinal fluid (CSF) 2. Number of treatment emergent adverse events and serious adverse events Arm 1: Experimental; Branaplam 56 mg oral solution once weekly Arm 2: Experimental; Branaplam 112 mg oral solution once weekly Arm 3: Experimental; (C) Branaplam 154 mg oral solution once weekly, OR (X) Branaplam 84 mg oral solution once weekly OR (Y) Branaplam 28 mg oral solution once weekly Arm 4: Placebo; Matching placebo oral solution once weekly Participants with early manifest Huntington's Disease Target Patients Read-out Milestone(s) Publication 2025 TBD 97 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#98Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations KesimptaⓇ - CD20 antagonist Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT03650114 ALITHIOS (COMB157G2399) Multiple Sclerosis Phase 3 2010 Evaluate the long-term safety and tolerability of ofatumumab 20 mg subcutaneous (sc) once every 4 (94) weeks in subjects with RMS from the first dose of ofatumumab Ofatumumab 20 mg every 4 weeks Patients with relapsing MS Target Patients Read-out Milestone(s) 2028 Publication TBD 98 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#99Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations MayzentⓇ - S1P1,5 receptor modulator Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients NCT04926818 NEOS (CBAF312D2301) Multiple sclerosis, pediatrics Phase 3 180 Annualized relapse rate (ARR) in target pediatric participants Arm 1: Experimental ofatumumab - 20 mg injection/ placebo Arm 2: Experimental siponimod - 0.5 mg, 1 mg or 2 mg/ placebo Arm 3: Active Comparator fingolimod - 0.5 mg or 0.25 mg/ placebo Children/adolescent patients aged 10-17 years old with Multiple Sclerosis (MS). he targeted enrollment is 180 participants with multiple sclerosis which will include at least 5 participants with body weight (BW) ?40 kg and at least 5 participants with age 10 to 12 years in each of the ofatumumab and siponimod arms. There is a minimum 6 month follow up period for all participants (core and extension). Total duration of the study could be up to 7 years. Read-out Milestone(s) Publication 99 Investor Relations | Q4 2021 Results 2026 TBD NOVARTIS | Reimagining Medicine#100Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations remibrutinib - BTK inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients Read-out Milestone(s) NCT05147220 REMODEL-1 (CLOU064C12301) Multiple sclerosis Phase 3 800 Annualized relapse rate (ARR) of confirmed relapses Arm 1: Experimental; Remibrutinib - Core (Remibrutinib tablet and matching placebo of teriflunomide capsule) Arm 2: Active Comparator; Teriflunomide - Core (Teriflunomide capsule and matching placebo remibrutinib tablet) Arm 3: Experimental; Remibrutinib - Extension (Participants on remibrutinib in Core will continue on remibrutinib tablet) Arm 4: Experimental; Remibrutinib - Extension (on teriflunomide in Core) (Participants on teriflunomide in Core will switch to remibrutinib tablet) Patients with relapsing Multiple Sclerosis Estimated primary completion 2025 Estimated study completion 2029 NCT05156281 REMODEL-2 (CLOU064C12302) Multiple sclerosis Phase 3 800 Annualized relapse rate (ARR) of confirmed relapses Arm 1: Experimental; Remibrutinib - Core Remibrutinib tablet and matching placebo of teriflunomide capsule Arm 2: Active Comparator; Teriflunomide - Core Teriflunomide capsule and matching placebo remibrutinib tablet Arm 3: Experimental: Remibrutinib - Extension Participants on remibrutinib in Core will continue on remibrutinib tablet Arm 4: Experimental: Remibrutinib - Extension (on teriflunomide in Core) Participants on teriflunomide in Core will switch to remibrutinib tablet Patients with relapsing Multiple Sclerosis Estimated primary completion 2025 Estimated study completion 2029 Publication TBD 100 Investor Relations | Q4 2021 Results TBD 1 NOVARTIS | Reimagining Medicine#101Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations ZolgensmaⓇ - SMN1 gene replacement therapy Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT05089656 STEER (COAV101B12301) Spinal muscular atrophy (IT administration) Phase 3 125 1. Change from baseline in Hammersmith functional motor scale - Expanded (HFMSE) total score at the end of follow-up period 1 in treated patients compared to Isham controls in the ≥ 2 to < 18 years age group Arm 1: Experimental OAV101. Administered as a single, one-time intrathecal dose Arm 2: Sham Comparator: Sham control. A skin prick in the lumbar region without any medication. Patients Type 2 Spinal Muscular Atrophy (SMA) who are ≥ 2 to < 18 years of age, treatment naive, sitting, and never ambulatory Target Patients Read-out Milestone(s) Publication 2024 TBD 101 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#102Participants Financial performance Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations Ophthalmology 102 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#103Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations UNR844 - Reduction of disulfide bonds Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients Read-out Milestone(s) Publication NCT04806503 READER (CUNR844A2022) Presbyopia Phase 2B 225 Characterize the dose response relationship among UNR844 doses 0 mg/mL, 5 mg/mL, 13.3 mg/mL, 23 mg/mL and 30 mg/mL dosed twice-daily after Month 3 of dosing. Change from baseline in Binocular distance-corrected near visual acuity at 40 cm at Month 3. 1:1 randomization - UNR844 0 mg/mL, 5 mg/mL, 13.3 mg/mL, 23 mg/mL and 30 mg/mL dosed twice-daily for three months Presbyopic participants aged 45 to 55 years 2022: Primary endpoint- when all patients have completed the 3 months treatment period 2023: Final analysis -Study completion (all patients have completed 9 months pots treatment period) H1-2023 103 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#104Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations BeovuⓇ - Anti-VEGF Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT03386474 (CRTH258A2301E1) Neovascular age-related macular degeneration (nAMD) Phase 3 NCT04005352 TALON (CRTH258A2303) Neovascular Age-related Macular Degeneration (nAMD) Phase 3B 150 Number of treatment-emergent adverse events Brolucizumab (RTH258) 6 mg/50 μL Aflibercept 2 mg/50 μL Patients with neovascular age-related macular degeneration who have completed the CRTH258A2301 study Average change in Best-corrected visual acuity Distribution of the last interval with no disease activity (in a Treat-to-Control regimen) Arm 1: Brolucizumab 6 mg intravitreal injection Arm 2: Aflibercept 2 mg intravitreal injection Patients with Neovascular Age-related Macular Degeneration (nAMD) who have not previously received anti-VEGF (vascular endothelial growth factor) treatment Target Patients Read-out Milestone(s) 2018 (actual) Publication Manuscript submitted 104 Investor Relations | Q4 2021 Results 2022 TBD NOVARTIS | Reimagining Medicine#105Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations BeovuⓇ - Anti-VEGF Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT04047472 HOBBY (CRTH258A2307) Macular degeneration Phase 3 494 Change from baseline in best-corrected visual acuity (BCVA) at week 48 Brolucizumab (RTH258) 6 mg/50 μL Aflibercept 2 mg/50 μL Chinese patients with neovascular age-related macular degeneration Target Patients Read-out Milestone(s) 2024 Publication TBD 105 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#106Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations BeovuⓇ - VEGF Inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients Read-out Milestone(s) Publication NCT03481634 KESTREL (CRTH258B2301) Diabetic eye disease Phase 3 534 Change from baseline in best-corrected visual acuity (BCVA) Brolucizumab (RTH258) 3 mg/50 μL Brolucizumab (RTH258) 6 mg/50 μL Aflibercept 2mg/50 uL Patients with visual impairment due to diabetic macular edema (DME) Primary: Q4-2020 (actual); Final: Q4-2021 Brown et al., presented at ARVO May 2021 Manuscript submission H2 2021 (Actual) NCT03481660 KITE (CRTH258B2302) Diabetic eye disease Phase 3 356 Change from baseline in best-corrected visual acuity (BCVA) Brolucizumab (RTH258) 6 mg/50 μL Aflibercept 2 mg/50 μL Patients with visual impairment due to diabetic macular edema (DME) Primary: Q3-2020 (actual); Final: Q3-2021 (actual). Brown et al., presented at ARVO May 2021 Manuscript submission H2 2021 (Actual) 106 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#107Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations BeovuⓇ - VEGF Inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT03917472 KINGFISHER (CRTH258B2305) Diabetic macular edema Phase 3 500 Change in best-corrected visual acuity (BCVA) from baseline up to week 52 Brolucizumab (RTH258) 6 mg/50 μL Aflibercept 2 mg/50 μL Target Patients Patients with visual impairment due to diabetic macular edema Read-out Milestone(s) Q3-2021 (Actual) Publication Publication planned for H1-2022 NCT04058067 KINGLET (CRTH258B2304) Diabetic macular edema Phase 3 268 Change in best-corrected visual acuity (BCVA) Brolucizumab (RTH258) 6 mg/50 μL Aflibercept 2 mg/50 μL Chinese patients with visual impairment due to diabetic macular edema 2023 Publication planned for 2023 107 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#108Participants Financial performance Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations BeovuⓇ - VEGF Inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT04278417 (CRTH258D2301) Diabetic retinopathy Phase 3 706 Change from Baseline in BCVA Arm1: RTH258 (brolucizumab) 6 mg/50uL Arm2: Panretinal photocoagulation laser initial treatment followed with additional PRP treatment as needed Patients with proliferative diabetic retinopathy Target Patients Read-out Milestone(s) 2024 Publication TBD 108 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#109Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations libvatrep - TRPV1 antagonist Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT04630158 SAHARA (CSAF312B12201) Chronic ocular surface pain Phase 2 150 Change in mean pain severity Visual Analog Scale Placebo Comparator: SAF312 Placebo. Randomized to a 1:1:1 topical eye drops, twice daily Experimental: SAF312 dose 1. Randomized to a 1:1:1 topical eye drops, twice daily Experimental: SAF312 dose 2. Randomized to a 1:1:1 topical eye drops, twice daily Subjects with CICP persisting at least for 4 months after refractive surgery and chronicity confirmed during the observational period. Target Patients Read-out Milestone(s) Publication 2023 2023 109 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#110Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations Respiratory & Allergy 110 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#111Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations CSJ117 - Inhaled TSLP inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT04410523 (CCSJ117A12201C) Asthma Phase 2 625 Pre-dose FEV1 (Forced Expiratory Volume in 1 second) change from baseline after 12 weeks of treatment. Average change from baseline in pre-dose FEV1 at week 8 & week 12 CSJ117 0.5mg CSJ117 1mg CSJ117 2 mg CSJ117 4 mg CSJ117 8 mg Placebo Asthma patients on background medium or high ICS plus LABA therapy Target Patients Read-out Milestone(s) Publication 2023 2023 111 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#112Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations icenticaftor - CFTR potentiator Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT04072887 (CQBW251B2201) Chronic obstructive pulmonary disease (COPD) Phase 2 956 Trough FEV1 (Forced Expiratory Volume in 1 second) change from baseline after 12 weeks of treatment QBW251 450 mg QBW251 300 mg QBW251 150 mg QBW251 75 mg QBW251 25 mg Placebo COPD patients on background triple inhaled therapy (LABA / LAMA / ICS) Target Patients Read-out Milestone(s) Publication 2022 Primary publications planned for 2022 112 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#113Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations Oncology: Solid Tumors 113 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#114Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations alpelisib - PI3K-alpha inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients Read-out Milestone(s) Publication NCT04589650 EPIK-P2 (CBYL719F12201) PIK3CA-related overgrowth spectrum Phase 2 150 Proportion of participants with a response at Week 24 Arm 1: alpelisib vs. Arm 2: placebo during the 16 first weeks, for each cohort (adult, pediatric), with placebo patients switching to alpelisib thereafter. Pediatric and adult participants with PIK3CA-related overgrowth spectrum (PROS) Primary Analysis: 2023 NA 114 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#115Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations canakinumab - IL-1 beta inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients Read-out Milestone(s) Publication NCT03631199 CANOPY-1 (CACZ885U2301) 1st Line Non-small cell lung cancer (NSCLC) Phase 3 627 Safety run-in part: Incidence of dose limiting toxicities Double-blind, randomized, placebo-controlled part: Progression free survival (PFS) Overall survival (OS) Canakinumab or matching placebo in combination with pembrolizumab and platinum-based doublet chemotherapy Patients with: Histologically confirmed Stage IIIB, IV NSCLC with no prior systemic anticancer therapy Squamous and non-squamous NSCLC No EGFR mutation and ALK rearrangement H2-2021 Johnson B et al. Presented at AACR-NCI-EORTC 2019 (safety run-in) Planned abstract submission to AACR 2022 115 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#116Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations canakinumab - IL-1 beta inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients NCT03447769 CANOPY-A (CACZ885T2301) Adjuvant NSCLC Phase 3 1500 Disease free survival (primary), overall survival (key secondary) Canakinumab 200mg q3w sc for 18 cycles Placebo q3w sc for 18 cycles Patients with: High-risk NSCLC (AJCC/UICC v.8 stage II-IIIA and IIIB (T>5cm N2)) after complete resection and standard of care adjuvant cisplatin-based chemotherapy All histologies Read-out Milestone(s) 2022 Publication TBD 116 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#117Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations NIS793 - TGFẞ1 inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients Read-out Milestone(s) NCT04935359 (CNIS793B12301) Pancreatic cancer, 1st line Phase 3 490 Safety run-in part: Percentage of participants with dose limiting toxicities (DLTs) during the first cycle (4 weeks) of treatment Randomized part: Overall survival (OS) Arm 1: Experimental: Safety run-in part: NIS793+gemcitabine+nab-paclitaxel In the safety run-in part, participants will receive a combination of NIS793, gemcitabine and nab-paclitaxel Arm 2: Experimental: Randomized part: NIS793+gemcitabine+nab-paclitaxel Participants will receive a combination of NIS793, gemcitabine and nab-paclitaxel Arm 3: Placebo Comparator: Randomized part: placebo+gemcitabine+nab- paclitaxel Participants will receive a combination of placebo, gemcitabine and nab-paclitaxel Patients with Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC), first line treatment Primary 2025 Publication TBD 117 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#118Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations TNO155 - SHP2 inhibitor Study Indication Phase Patients Primary Outcome Measures NCT03114319 (CTNO155X2101) Solid tumors (single agent) Phase 1 255 Number of participants with adverse events Number of participants with dose limiting toxicities Arms Intervention Drug: TNO155 Drug: TNO155 in combination with EGF816 (nazartinib) Adult patients with advanced solid tumors in selected indications Target Patients Read-out Milestone(s) 2023 Publication TBD 118 Investor Relations | Q4 2021 Results NCT04000529 (CTNO155B12101) Solid tumors (combo) Phase 1 126 Incidence of dose limiting toxicities (DLTs) during the first cycle of combination treatment during the dose escalation part Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) as per CTCAE v5.0, by treatment Dose tolerability TNO155 and Spartalizumab (PDR001) TNO155 and Ribociclib (LEE011) Patients with advanced malignancies 2022 TBD NOVARTIS | Reimagining Medicine#119Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations 177Lu-PSMA-617 - Radioligand therapy target PSMA Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients Read-out Milestone(s) NCT04689828 PSMAfore (CAAA617B12302) Metastatic castration-resistant prostate cancer, pre-taxane Phase 3 450 Radiographic Progression Free Survival (rPFS) Arm 1: Participants will receive 7.4 GBq (200 mCi) +/- 10% 177Lu-PSMA-617 once every 6 weeks for 6 cycles. Best supportive care, including ADT may be used Arm 2: For participants randomized to the ARDT arm, the change of ARDT treatment will be administered per the physician's orders. Best supportive care, including ADT may be used mCRPC patients that were previously treated with an alternate ARDT and not exposed to a taxane-containing regimen in the CRPC or MHSPC settings Primary Analysis: 2022 Final Analysis: 2025 NCT04720157 PSMAddition (CAAA617C12301) Metastatic hormone sensitive prostate cancer Phase 3 1126 Radiographic Progression Free Survival (rPFS) Arm 1: 177Lu-PSMA-617 Participant will receive 7.4 GBq (+/- 10%) 177Lu-PSMA- 617, once every 6 weeks (+/- 1 week) for a planned 6 cycles, in addition to the Standard of Care (SOC); ARDT +ADT is considered as SOC and treatment will be administered per the physician's order Arm 2: For participants randomized to Standard of Care arm, ARDT +ADT is considered as SOC and treatment will be administered per the physician's order Patients with metastatic Hormone Sensitive Prostate Cancer (mHSPC) Primary Analysis: 2024 Publication TBD 119 Investor Relations | Q4 2021 Results TBD 1 NOVARTIS | Reimagining Medicine#120Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations KisqaliⓇ - CDK4/6 inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT03701334 NATALEE (CLEE011012301C) Adjuvant treatment of hormone receptor (HR)-positive, HER2-negative, early breast cancer (EBC) Phase 3 5101 Invasive Disease-Free Survival for using STEEP criteria (Standardized Definitions for Efficacy End Points in adjuvant breast cancer trials) Ribociclib endocrine therapy Endocrine therapy Pre and postmenopausal women and men with HR-positive, HER2-negative EBC, after adequate surgical resection, who are eligible for adjuvant endocrine therapy Target Patients Read-out Milestone(s) 2022 Publication TBD 120 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#121Participants Financial performance Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations PiqrayⓇ - PI3K-alpha inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT04208178 EPIK-B2 (CBYL719G12301) HER-2 positive breast cancer Phase 3 548 Progression-free survival (PFS) Alpelisib + trastuzumab + pertuzumab Trastuzumab + pertuzumab Target Patients Patients with HER2-positive advanced breast cancer with a PIK3CA mutation Read-out Milestone(s) 2025 Publication TBD NCT04251533 EPIK-B3 (CBYL719H12301) Triple negative breast cancer Phase 3 566 Progression-free Survival (PFS) for patients with PIK3CA mutant status Alpelisib 300 mg + nab-paclitaxel 100 mg/m² Placebo nab-paclitaxel 100 mg/m² Patients with advanced triple negative breast cancer with either Phosphoinositide-3- kinase Catalytic Subunit Alpha (PIK3CA) mutation or Phosphatase and Tensin Homolog Protein (PTEN) loss without PIK3CA mutation 2023 TBD 121 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#122Participants Financial performance Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations PiqrayⓇ - PI3K-alpha inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients NCT04729387 EPIK-O (CBYL719K12301) Ovarian Cancer Phase 3 358 Progression Free Survival (PFS) based on Blinded Independent Review Committee (BIRC) assessment using RECIST 1.1 criteria Arm 1 Experimental: Alpelisib+olaparib: Alpelisib 200 mg orally once daily and olaparib 200 mg orally twice daily on a continuous dosing schedule Arm 2 Active Comparator: Paclitaxel or PLD. Investigator's choice of one of 2 single agent cytotoxic chemotherapies: Paclitaxel 80 mg/m2 intravenously weekly or Pegylated liposomal Doxorubicin (PLD) 40-50 mg/m2 (physician discretion) intravenously every 28 days. Patients with platinum resistant or refractory high-grade serous ovarian cancer, with no germline BRCA mutation detected Read-out Milestone(s) 2023 Publication TBD 122 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#123Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations TabrectaⓇ - MET inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients Read-out Milestone(s) Publication NCT04427072 (CINC280A2301) Non-small cell lung cancer Phase 3 90 Progression free survival (PFS) per blinded independent review committee (BIRC) using RECIST v1.1 Arm 1: 400mg of capmatinib tablets administered orally twice daily Arm 2: Docetaxel 75 mg/m2 by intravenous infusion every 21 days Previously Treated Patients With EGFR wt, ALK Negative, Locally Advanced or Metastatic (Stage IIIB/IIIC or IV) NSCLC Harboring MET Exon 14 Skipping Mutation (MET?ex14). Primary 2022 Final: 2024 TBD NCT04816214 GEOMETRY-E (CINC280L12301) Non-small cell lung cancer Phase 3 245 Run-in part: Incidence of dose limiting toxicities (DLTs) Randomized part: Progression free survival (PFS) Arm 1: Experimental: Combination of capmatinib + osimertinib (run-in part). Arm 2: Experimental: Combination of capmatinib + osimertinib (randomized part) Arm 3: Active Comparator: platinum + pemetrexed based doublet chemotherapy Adult subjects with Non-small Cell Lung cancers as second line therapy Primary: 2025 Final: 2027 TBD 123 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#124Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations Tafinlar + MekinistⓇ - BRAF inhibitor and MEK inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT04940052 (CDRB436J12301) Thyroid cancer Phase 3 150 Progression Free Survival Arm 1: Experimental: Dabrafenib plus trametinib Participants will be treated with dabrafenib twice daily and trametinib once daily Arm 2: Placebo Comparator: Placebo dabrafenib plus placebo trametinib Participants will receive placebo dabrafenib twice daily and placebo trametinib once daily Previously treated patients with locally advanced or metastatic, radio-active lodine refractory BRAFV600E mutation-positive differentiated thyroid cancer Target Patients Read-out Milestone(s) 2024 Publication TBD 124 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#125Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations Tafinlar + MekinistⓇ - BRAF inhibitor and MEK inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients Read-out Milestone(s) Publication NCT02684058 (CDRB436G2201) BRAFV600 mutant gliomas Phase 2 142 Objective response rate Dabrafenib + trametinib (dose based on age and weight) Children and adolescent patients with BRAF V600 mutation positive relapsed or refractory high grade glioma (HGG) or BRAF V600 mutation positive low grade glioma (LGG) Q4 2021 (actual) TBD 125 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#126Participants Financial performance Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations Hematology 126 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#127Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations CRM IHD AdakveoⓇ - P-selectin inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT03814746 STAND (CSEG101A2301) Prevention of Vaso-Occlusive Crises (VOC) in patients with Sickle Cell Disease (SCD) Phase 3 240 Rate of VOC events leading to healthcare visit Crizanlizumab 5.0 mg/kg Crizanlizumab 7.5 mg/kg Placebo Adolescent and adult SCD patients (12 years and older) Target Patients Read-out Milestone(s) 2022 Publication TBD 127 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#128Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations CRM IHD AdakveoⓇ - P-selectin inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients Read-out Milestone(s) Publication NCT03474965 SOLACE-Kids (CSEG101B2201) Prevention of VOC in pediatric patients with SCD Phase 2 100 PK/PD and safety of SEG101 at 5 mg/kg SEG101 (crizanlizumab) at a dose of 5 mg/kg by IV infusion ± Hydroxyurea/Hydroxycarbamide Pediatric SCD patients with VOC H2-2021 (pediatric patients >=12 year old) 2024 (pediatric patients <12 year old) Abstract submission to ASH 2021 128 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#129Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations JakaviⓇ - JAK 1/2 inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT03491215 REACH4 (CINC424F12201) Acute graft versus host disease Phase 2 45 Measurement of PK parameters Overall Response Rate (ORR) Ruxolitinib NCT03774082 REACH5 (CINC424G12201) Chronic graft versus host disease Phase 2 45 Overall Response Rate (ORR) Ruxolitinib 5mg tablets / pediatric formulation Pediatric patients with grade II-IV acute graft vs. host disease after allogeneic hematopoietic stem cell transplantation Pediatric subjects with moderate and severe chronic Graft vs. Host disease after allogeneic stem cell transplantation Target Patients Read-out Milestone(s) 2023 Publication TBD 129 Investor Relations | Q4 2021 Results 2023 TBD NOVARTIS | Reimagining Medicine#130Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations JakaviⓇ - JAK 1/2 inhibitor Study Indication Phase Patients NCT04097821 ADORE (CINC424H12201) Myelofibrosis Phase 1/2 130 Primary Outcome Measures Arms Intervention Incidence of dose limiting toxicities within the first 2 cycles Response rate at the end of cycle 6 Ruxolitinib Ruxolitinib+Siremadlin Ruxolitinib+Crizanlizumab Ruxolitinib+MBG453 Ruxolitinib+LTT462 Ruxolitinib+NIS793 Patients with Myelofibrosis (MF) Target Patients Read-out Milestone(s) Publication 2024 TBD 130 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#131Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations KymriahⓇ - CD19 CAR-T Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT03570892 BELINDA (CCTL019H2301) 2nd line Diffuse large B-cell lymphoma (DLBCL) Phase 3 318 Event-free Survival (EFS) Tisagenlecleucel versus standard of care Adult patients with aggressive B-cell Non-Hodgkin Lymphoma after failure of rituximab and anthracycline- containing frontline immunochemotherapy Target Patients Read-out Milestone(s) 9 Jul 2021 (actual) Publication Bishop et al at SITC 2019 Abstract submission TBD NCT03876769 CASSIOPEIA (CCTL019G2201J) 1st line high risk acute lymphoblastic leukemia (ALL) Phase 2 160 Disease Free Survival (DFS) Single-arm study of tisagenlecleucel Pediatric and young adult patients with 1st line high risk ALL 2025 TBD 131 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#132Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations PromactaⓇ - Thrombopoetin receptor agonist Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients Read-out Milestone(s) Publication NCT03025698 (CETB115E2201) Refractory or relapsed severe aplastic anemia Phase 2 51 PK of eltrombopag at steady state in pediatric patients with SAA Eltrombopag 12.5, 25, 50, 75 mg FCT & 25 mg pFOS Arm A: relapsed/refractory SAA or recurrent AA following IST for SAA: hATG/cyclosporine + eltrombopag or cyclosporine + eltrombopag Arm B: previously untreated SAA: hATG/cyclosporine + eltrombopag Pediatric patients from age 1 <18 years with relapsed/refractory SAA or recurrent AA after IST or previously untreated SAA Primary CSR: 2022 Final CSR: 2025 TBD NCT03988608 (CETB115E2202) Refractory or relapsed severe aplastic anemia Phase 2 20 Hematologic response rate rate up to 26 weeks of treatment Eltrombopag 25 mg film-coated tablets Chinese patients with refractory or relapsed severe aplastic anemia Primary CSR: 2022 Final CSR: 2025 TBD 132 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#133Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations RydaptⓇ - Multi-targeted kinase inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT03591510 (CPKC412A2218) Acute myeloid leukemia, pediatrics Phase 2 20 Occurrence of dose limiting toxicities Safety and Tolerability Chemotherapy followed by Midostaurin Newly diagnosed pediatric patients with FLT3 mutated acute myeloid leukemia (AML) Target Patients Read-out Milestone(s) 2026 Publication TBD 133 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#134Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations asciminib - BCR-ABL inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT04971226 ASC4FIRST (CABL001J12301) Chronic myeloid leukemia, 1st line Phase 3 402 Major Molecular Response (MMR) at week 48 Arm 1: asciminib 80 mg QD Arm 2: Investigator selected TKI including one of the below treatments: -Imatinib 400 mg QD - Nilotinib 300 mg BID - Dasatinib 100 mg QD - Bosutinib 400 mg QD Patients with newly diagnosed philadelphia chromosome positive chronic myelogenous leukemia in chronic phase Target Patients Read-out Milestone(s) 2024 Publication TBD 134 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#135Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations iptacopan - CFB inhibitor - HEM Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients Read-out Milestone(s) Publication NCT03439839 (CLNP023X2201) Paroxysmal nocturnal hemoglobinuria (PNH) Phase 2 16 Reduction of chronic hemolysis, based on LDH level at Week 13 10 patients receiving LNP023 high dose daily over up to approximately 3 years 5 patients receiving LNP023 low dose daily over up to approximately 3 years Patients with PNH, showing signs of active hemolysis despite treatment with SoC (defined as an antibody with anti C5 activity). Primary: Q2-2020 (actual) Extension: 2023 Antonio M. Risitano, MD, PhD1 et al. Presented at EBMT 2020 congress Jan 2021Pubs: Addition of iptacopan, an oral factor B inhibitor, to eculizumab in patients with paroxysmal nocturnal haemoglobinuria and active haemolysis: an open-label, single-arm, phase 2, proof-of-concept trial, Risitano, Antonio M et al. The Lancet Haematology, Volume 8, Issue 5, e344 - e354 NCT03896152 (CLNP023X2204) Paroxysmal nocturnal hemoglobinuria (PNH) Phase 2 13 Reduction of PNH associated hemolysis, based on percentage of patients with 60% reduction in LDH or LDH below upper limit of normal up to 12 weeks of treatment. approximately 2 year Treatment with low LNP023 dose approximately 2 year Treatment with higher LNP023 dose Patients with PNH, showing signs of active hemolysis, not treated with any other complement inhibitor less than 3 months prior to study start Day 1 Primary: Q2-2020 (actual) Extension: 2022 -Jang JH, et al. Presented at Korean Society of Hematology International Conference and 62nd Annual Meeting (ICKSH 2021) -Presented as an oral presentation (encore) at the European Haematology Association (EHA 2021) congress -Planned manuscript submission in Q3 2021 135 Investor Relations | Q4 2021 Results 1 NOVARTIS | Reimagining Medicine#136Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations iptacopan - CFB inhibitor - HEM Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients Read-out Milestone(s) Publication NCT04558918 APPLY-PNH (CLNP023C12302) Paroxysmal nocturnal haemoglobinuria Phase 3 91 Percentage of participants achieving a sustained increase in hemoglobin levels of >= 2 g/dL in the absence of red blood cell transfusions Percentage of participants achieving sustained hemoglobin levels >= 12 g/dL in the absence of red blood cell transfusions Arm 1: Drug: LNP023, taken orally b.i.d. dosage supplied: 200 mg dosage form: hard gelatin capsule Route of Administration: Oral Arm 2: Drug: Eculizumab, administered as intravenous infusion every 2 weeks as per the stable regimen, the maintenance dose is a fixed dose. Dosage supplied: 300 mg/30mL Dosage form: Concentrate solution for infusion Drug: Ravulizumab, administered as intravenous infusion every 8 weeks, the maintenance dose is based on body weight. Dosage Supplied: 300 mg/30mL Dosage f Adult patients with PNH and residual anemia, despite treatment with an intravenous Anti-C5 antibody Primary 2022 Risitano AM, et al. Abstract accepted at the European Hematology Association (EHA 2021) congress (study design abstract; accepted for publication only) NCT04820530 APPOINT-PNH (CLNP023C12301) Paroxysmal nocturnal haemoglobinuria Phase 3 40 Proportion of participants achieving a sustained increase from baseline in hemoglobin levels of ? 2 g/dL assessed, in the absence of red blood cell transfusions Iptacopan (LNP023), taken orally b.i.d. (dosage supplied: 200mg) PNH patients who are naive to complement inhibitor therapy, including anti-C5 antibody 2023 Peffault de Latour R, et al. Abstract accepted at the European Hematology Association (EHA 2021) congress (study design abstract; accepted for publication only) 136 Investor Relations | Q4 2021 Results U NOVARTIS | Reimagining Medicine#137Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations iptacopan - CFB inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT04889430 APPELHUS (CLNP023F12301) Atypical haemolytic uraemic syndrome Phase 3 50 Percentage of participants with complete TMA response without the use of PE/PI and anti-C5 antibody Single arm open-label with 50 adult patients receiving 200mg oral twice daily doses of iptacopan Adult patients with aHUS who are treatment naive to complement inhibitor therapy (including anti-C5 antibody) Target Patients Read-out Milestone(s) 2024 Publication TBD 137 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#138Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations sabatolimab - TIM3 antagonist Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients Read-out Milestone(s) Publication NCT03946670 STIMULUS MDS-1 (CMBG453B12201) Myelodysplastic syndrome Phase 2 120 Complete Remission (CR) rate and Progression Free Survival (PFS) Experimental: Sabatolimab (MBG453) + hypomethylating agents Placebo comparator: Placebo + hypomethylating agents Adult subjects with intermediate, high or very high risk Myelodysplastic Syndrome (MDS) as per IPSS-R criteria 2022-2023 TBD NCT04150029 STIMULUS-AML1 (CMBG453C12201) Unfit acute myeloid leukaemia Phase 2 86 Incidence of dose limiting toxicities (Safety run-in patients only) Percentage of subjects achieving complete remission (CR) Single arm safety and efficacy study of sabatolimab in combination with azacitidine and venetoclax Newly diagnosed adult AML patients who are not suitable for treatment with intensive chemotherapy 2023 TBD 138 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#139Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations sabatolimab - TIM3 antagonist Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT04266301 STIMULUS-MDS2 (CMBG453B12301) Myelodysplastic syndrome Phase 3 500 Overall survival Sabatolimab 800 mg + azacitidine 75 mg/m2 Sabatolimab 800 mg + azacitidine 75 mg/m2 + placebo Patients with intermediate, high or very high risk Myelodysplastic Syndrome (MDS) as Per IPSS-R, or Chronic Myelomonocytic Leukemia-2 (CMML-2) Target Patients Read-out Milestone(s) 2023 Publication TBD 139 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#140Participants Financial performance Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations Biosimilars 140 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#141Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations aflibercept - VEGF inhibitor Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT04864834 Mylight (CSOK583A12301) Aflibercept BioS Phase 3 460 Best-corrected visual acuity (BCVA) will be assessed using the ETDRS testing charts at an initial distance of 4 meters. The change from baseline in BCVA in letters is defined as difference between BCVA score between week 8 and baseline Arm 1 Biological: SOK583A1 (40 mg/mL) Arm 2 Biological: Eylea EU (40 mg/mL) Patients with neovascular age-related macular degeneration Target Patients Read-out Milestone(s) 2023 Publication tbd 141 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#142Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations denosumab - anti RANKL mAb Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT03974100 (CGP24112301) Denosumab BioS Phase 3 522 Percent change from baseline (%CfB) in lumbar spine Bone Mineral Density GP2411 60 mg/mL subcutaneous injection every 6 months ProliaⓇ 60 mg/mL subcutaneous injection every 6 months Postmenopausal women with osteoporosis Target Patients Read-out Milestone(s) 2022 Publication Study data publications expected for 2024 and beyond. The overall study design will be published at WCO and ECTS congresses 2020. 142 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#143Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations Global Health 143 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#144Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations artemether + lumefantrine Study Indication Phase Patients Primary Outcome Measures Arms Intervention NCT04300309 CALINA (CCOA566B2307) Malaria, uncomplicated (<5kg patients) Phase 3 Artemether Cmax Target Patients Read-out Milestone(s) Publication Experimental: artemether lumefantrine (2.5 mg:30 mg) artemether lumefantrine (2.5 mg:30 mg) bid over 3 days, from 1-4 tablets per dose Infants and Neonates <5 kg body weight with acute uncomplicated plasmodium falciparum malaria Primary outcome measure: 2023 TBD 144 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#145Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations CRM IHD ganaplacide - Imidazolopiperazines derivative Study Indication Phase Patients Primary Outcome Measures Arms Intervention Target Patients NCT03167242 (CKAF156A2202) Malaria Phase 2 PCR-corrected adequate clinical and parasitological response (ACPR) KAF156 and LUM-SDF (different combinations) Coartem NCT04546633 KALUMI (CKAF156A2203) Malaria, uncomplicated Phase 2 PCR-corrected and uncorrected Adequate Clinical and Parasitological Response (ACPR) KAF156 and LUM-SDF QD (once daily) for 2 days in fasted condition KAF156 and LUM-SDF QD (once daily) for 2 days in fed condition Malaria patients 12 to < 18 years old with malaria caused by P. falciparum Read-out Milestone(s) Publication Adults and children with uncomplicated Plasmodium falciparum malaria H2-2021 (actual) 2024 No new publications TBD 145 Investor Relations | Q4 2021 Results NOVARTIS | Reimagining Medicine#146Participants Company overview Pharmaceuticals Oncology Financial review Conclusion Appendix Financial performance Innovation: Pipeline overview Innovation: Clinical trials CRM IHD Neuroscience Ophthalmology Respiratory & Allergy Oncology: Solid Tumors Hematology Biosimilars Global Health Abbreviations Abbreviations aHUS ALL ALS aBC AD Adj. AIH Advanced breast cancer Atopic Dermatitis Adjuvant Autoimmune hepatitis atypical Hemolytic Uremic Syndrome Acute lymphoblastic leukemia Amyotrophic lateral sclerosis HF-REF HNSCC HS ΙΑ IgAN iMN IPF AMI Acute myocardial infarction JIA AML Acute myeloid leukemia jPSA/ERA aNHL Agressive non-Hodgkin's lymphoma AS H2H Ankylosing spondylitis head-to-head study versus adalimumab LVEF mCRPC BC Breast cancer MDR C3G C3 glomerulopathy MDS CCF CINDU Congestive cardiac failure Chronic inducible urticaria MS NASH CLL CML Chronic lymphocytic leukemia Chronic myeloid leukemia nHCM nr-axSpA Chronic heart failure with reduced ejection fraction Head and neck squamous cell carcinoma Hidradenitis suppurativa Interim analysis IgA nephropathy Membranous nephropathy Idiopathic pulmonary fibrosis Juvenile idiopathic arthritis Juvenile psoriatic arthritis / enthesitis-related arthritis Left ventricular ejection fraction Metastatic castration-resistant prostate cancer Multi-drug resistant Myelodysplastic syndrome Multiple sclerosis Non-alcoholic steatohepatitis Non-obstructive hypertrophic cardiomyopathy Non-radiographic axial spondyloarthritis CRC Colorectal cancer COPD Chronic obstructive pulmonary disease NSCLC PEF Non-small cell lung cancer Preserved ejection fraction COSP Chronic ocular surface pain PedPsO Pediatric psoriasis CRSWNP Severe chronic rhinosinusitis with nasal polyps PNH CSU Chronic spontaneous urticaria PsA CVRR-Lp(a) CVRR-LDLC DME Secondary prevention of cardiovascular events in patients with elevated levels of lipoprotein (a) Secondary prevention of cardiovascular events in patients with elevated levels of LDLC Diabetic macular edema PROS RA rMS DLBCL Diffuse large B-cell lymphoma refractory RVO Retinal vein occlusion ESCC FL GCA GVHD HCC HD HFPEF Esophageal squamous-cell carcinoma Follicular lymphoma Giant cell arteritis Graft-versus-host disease Hepatocellular carcinoma Huntington's disease Chronic heart failure with preserved ejection fraction SAA SLE SpA SPMS TNBC T1DM Type 1 Diabetes mellitus SMA Type 1 SMA Type 2/3 Paroxysmal nocturnal haemoglobinuria Psoriatic arthritis PIK3CA related overgrowth spectrum Rheumatoid arthritis Relapsing multiple sclerosis Severe aplastic anemia Systemic lupus erythematosus Spinal muscular atrophy (IV formulation) Spinal muscular atrophy (IT formulation) Spondyloarthritis Secondary progressive multiple sclerosis Triple negative breast cancer 146 Investor Relations | Q4 2021 Results U NOVARTIS | Reimagining Medicine