Novartis R&D

Home , Brolucizumab, Canakinumab, Crizanlizumab, Ianalumab, LAG3, Ligelizumab

Novartis AG Investor Relations

Novartis R&D Day London, UK December 5, 2019 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 the development or adoption of potentially transformational technologies, treatment modalities and business models; or regarding potential future or pending transactions, including the potential outcome, or financial or other impact on Novartis, of the proposed acquisition of The Medicines Company; or regarding potential future sales or earnings of the Group or any of its divisions, or potential shareholder returns; or by discussions of strategy, plans, expectations or intentions. 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: global trends toward healthcare cost containment, including ongoing government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; regulatory actions or delays or government regulation generally, including potential regulatory actions or delays with respect to the proposed acquisition of The Medicines Company or the development of the products described in this presentation as well as potential regulatory actions or delays with respect thereto; the potential that the strategic benefits, synergies or opportunities expected from the proposed acquisition of The Medicines Company may not be realized or may be more difficult or take longer to realize than expected; the successful integration of The Medicines Company into the Novartis Group subsequent to the closing of the transaction and the timing of such integration; potential adverse reactions to the proposed transaction by customers, suppliers or strategic partners; dependence on key personnel of The Medicines Company; dependence on third parties to fulfill manufacturing and supply obligations; the inherent uncertainties involved in predicting shareholder returns; the inherent uncertainties involved 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 that commenced in prior years and will continue this year; safety, quality, data integrity or manufacturing issues; uncertainties regarding actual or potential legal proceedings, including, among others, product liability litigation, disputes and litigation with business partners or business collaborators, government investigations generally, litigation and investigations regarding sales and marketing practices, and intellectual property disputes; uncertainties involved in the development or adoption of potentially transformational technologies, treatment modalities and business models; our performance on environmental, social and governance measures; political, economic and trade conditions, including uncertainties regarding the effects of ongoing instability in various parts of the world; uncertainties regarding future global exchange rates; uncertainties regarding future demand for our products; uncertainties regarding potential significant breaches of data security or data privacy, or disruptions of our information technology systems; and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the United States Securities and Exchange Commission (the “SEC”). 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.

Additional Information This presentation is neither an offer to purchase nor a solicitation of an offer to sell securities. On December 5, 2019, Novartis and its indirect wholly owned subsidiary, Medusa Merger Corporation (“Purchaser”), will file a Tender Offer Statement on Schedule TO with the SEC and The Medicines Company will file a Solicitation/Recommendation Statement on Schedule 14D-9 with the SEC, in each case with respect to the tender offer for the outstanding shares of common stock, par value USD 0.001, of The Medicines Company (the “Offer”). The Tender Offer Statement (including the Offer to Purchase, the related Letter of Transmittal and other offer documents) and the Solicitation/Recommendation Statement contain important information that should be read carefully before any decision is made with respect to the Offer. Those materials and all other documents filed by, or caused to be filed by, Novartis, Purchaser or The Medicines Company with the SEC will be available at no charge on the SEC’s website at www.sec.gov. The Schedule TO Tender Offer Statement and related materials will be available for free under the “Investors – Financial Data – SEC Filings” section of Novartis’ website at https://www.novartis.com/investors/financial-data/sec-filings. The Schedule 14D-9 Solicitation/Recommendation Statement and such other documents will be available for free from The Medicines Company under the “Investors & Media” section of The Medicines Company’s website at https://www.themedicinescompany.com/investor/financial/.

2 Novartis R&D Day | December 5, 2019 Agenda Time includes Q&A

13:00-13:30 Opening Vas Narasimhan Portfolio Overview John Tsai

Research 13:30-14:00 NIBR Jay Bradner Platforms Cell Therapy, Gene Therapy, Molecular Glues

Emerging 14:00-15:15 Pharmaceuticals Dave Soergel Assets TQJ230, LNP023, Iscalimab, Ligelizumab, Adriforant, LNA043, Tropifexor Eric Hughes 15:15-15:45 Oncology Jeff Legos MBG453, Asciminib, Canakinumab

15:45-16:00 Break

Late Stage & 16:00-16:40 Pharmaceuticals John Tsai LCM Update Zolgensma®, Cosentyx®, Beovu®, Fevipiprant, Ofatumumab, Inclisiran, Entresto® 16:40-17:30 Oncology Jeff Legos Adakveo®, RLT platform, Piqray®, Kisqali®, Spartalizumab triplet, Kymriah®

17:30-17:45 Closing Vas Narasimhan

3 Novartis R&D Day | December 5, 2019 Vas Narasimhan MD Chief Executive Officer Our strategy Focus Novartis as a leading medicines company powered by advanced therapy platforms and data science

Where to play | our focus How to win | our five priorities

Focus our company Strengthen our core Unleash the power of Deliver transformative Embrace operational and capital our people innovation excellence every day

Accelerate certain Go big on data and digital Build trust with society geographies

5 Novartis R&D Day | December 5, 2019 We are uniquely positioned with scale and focus …

Rx OTC VC Mtech AH Other ≥ 200 Gx Bubble size = company revenue

Size * Market cap USD bn

< 200

Conglomerate Pure-play < 80% of revenues from Rx % Innovative ≥ 80% of revenues from Rx medicines (Rx) sales

* Novartis 2018 sales excl. Alcon Note: Each bubble represents a pharma company; Companies grouped by strategic archetype, not strictly to scale VC = Vaccines, AH = Animal health, Gx = Generics/Biosimilars, OTC = Consumer Health, Mtech = Medical Devices / Diagnostics, Other = revenues not attributable to a specific TA and other revenues linked to royalties, in-licensing, etc. Source: Evaluate Pharma 2019; Market caps per Bloomberg November 27 2019; Annual reports. 6 Novartis R&D Day | December 5, 2019 ... and diversified across TAs while providing exposure to cutting edge platforms

2 Top-selling drug % Presence in advanced therapy platforms Company # of TAs1 of total sales Blockbusters, # Cell Gene RLT RNA 10 8% 15 X X X X Company 1 10 10% 4 X X Company 2 9 13% 11 X X Company 3 9 19% 5 Company 4 9 12% 8 X Company 5 8 16% 11 X X Company 6 6 62% 3 Company 7 6 22% 7 Company 8 6 12% 8 X Company 9 6 16% 6 Company 10 4 19% 4 X X Company 11 4 31% 6 X Company 12 3 22% 8 Company 13 2 39% 4 X X Company 14 2 21% 8 X

1. Only TAs with annual 3rd party sales > $500mn; TA definition as per Evaluate Pharma. 2. Defined as sales from one of the mentioned therapy platforms by 2024 according to Evaluate Pharma Note: RLT = Radioligand therapy. Source: Evaluate Pharma 2019

7 Novartis R&D Day | December 5, 2019 In-market growth drivers, major launches and a rich pipeline expected to sustain our long-term growth

Lifecycle management (LCM)

Continued focus on LCM activities and indication expansion for in-market assets, new launches, as Novel assets well as novel compounds

Pharmaceuticals Oncology Major launches Inclisiran1 MBG453 TQJ230 Asciminib In-market LNP023 Canakinumab growth drivers Iscalimab Spartalizumab Ligelizumab 177Lu-PSMA-617 AD portfolio LNA043 Tropifexor Ofatumumab Fevipiprant

1. Inclisiran is an investigational product of The Medicines Company. The acquisition of The Medicines Company is subject to satisfaction or waiver of customary closing conditions. Until closing, Novartis and The Medicines Company will continue to operate as separate and independent companies

8 Novartis R&D Day | December 5, 2019 John Tsai MD Global Head Drug Development and Chief Medical Officer Advancing a highly productive and valuable pipeline

Scale Value

Projects in clinical Potential blockbusters1 in 160+ development 25+ development Advanced platform therapies Ongoing clinical trials2 16 500+ in clinical development

Major submissions Most valuable pipeline 80+ 3 #1 planned 2020-2022 according to external ranking4

1. Blockbuster defined as peak sales >USD 1bn for either a new molecular entity across all indications or for a single new indication of a previously launched product 2. Across NIBR and GDD 3. Submissions in US/EU/JP/China 2020-22 4. Source: Evaluate Pharma 2018, outlook to 2024. Ranked #1 in terms of: (1) value creation from advanced therapies, (2) highest pipeline value by sales 2018-24, and (3) value creation 2018-24 from recently launched and pipeline products.

10 Novartis R&D Day | December 5, 2019 Significant progress in 2019 5 NME approvals and 30+ major data readouts YTD

5 NME approvals of potential blockbusters Submissions delivered for Over 30 readouts supporting in five separate therapeutic areas multiple key assets submission or enabling transition to Phase 3

Select Examples Select Examples SPMS . Entresto® (JP) . Zolgensma® . Cosentyx® nr-AxSpA (EU) . Cosentyx® SMA . Ofatumumab (US) . Ofatumumab ® ® Breast cancer . Adakveo (US/EU) . Entresto . Beovu® (JP) . Fevipiprant Wet AMD . INC280 (US) . Kisqali® . QVM149 / QMF149 . INC280 Sickle cell disease (EU/JP)

SMA – Spinal muscular atrophy SPMS – Secondary progressive multiple sclerosis AMD – age-related macular degeneration

11 Novartis R&D Day | December 5, 2019 Continuing momentum into 2020/21 10+ Phase 3 program initiations expected per year

2020 2021 Expected TQJ230 CVRR INC280 NSCLC (+PDR001) Phase 3 / LNP023 PNH PDR001 Metastatic melanoma (combo) pivotal trial ® initiations MBG453 MDS Jakavi Myelofibrosis (combo) Tropifexor mono NASH LNP023 IgAN

Alpelisib HER2+ aBC LNP023 C3G

Alpelisib TNBC LOU064 CSU

Alpelisib Ovarian cancer QBW251 COPD

Alpelisib Head & neck cancer ECF843 Dry eye

Alpelisib PROS VAY736 pSjS

Beovu® PDR VAY736 AIH

Coartem® Pediatric malaria

12 Novartis R&D Day | December 5, 2019 Multiple key NME/LCM submissions1 expected over next 5 years

Asciminib CML 3L

Beovu® DME

Alpelisib Canakinumab AVXS-201 PROS NSCLC 1L/2L Rett Syndrome

AVXS-101 Entresto® Beovu® Adriforant SAF312 SMA Type 2/3 Post-acute MI DR / RVO Atopic Dermatitis COSP

Entresto® Jakavi® Canakinumab Kymriah® Cipargamin Tropifexor HFpEF Acute/Chronic GVHD NSCLC Adj r/r ALL Malaria NASH

Fevipiprant Kymriah® Cosentyx® LNP023 Cosentyx® TQJ230 Asthma r/r Follicular Lymphoma HS C3G / IgAN / PNH GCA CVRR

177Lu-PSMA-617 Ligelizumab ECF843 LOU064 Ianalumab UNR844 mCRPC CIU / CSU Dry Eye CSU AIH Presbyopia

Spartalizumab combo MBG453 Kisqali® Alpelisib VPM087 TNBC / HER2+ adv BC, Alpelisib Metastatic Melanoma MDS HR+/HER-BC Ovarian Cancer HNSCC 2/3L 1st line CRC / 1st line RCC 2020 2021 2022 2023 2024

1. First submission in any market of new molecular entity or new indication

13 Novartis R&D Day | December 5, 2019 Building depth across our core therapeutic areas …

PHARMACEUTICALS ONCOLOGY CRM IHD Neuroscience Ophthalmology Respiratory

1 Select commercial

assets 2

Spartalizumab combo LNP023 LNA043 Ofatumumab (OMB157) UNR844 Fevipiprant (QAW039) Metastatic Melanoma Renal diseases Primary Osteoarthritis MS Presbyopia Asthma

177Lu-PSMA-617 TQJ230 Iscalimab (CFZ533) LMI070 ECF843 QVM149 mCRPC CVRR Transplant / Sjögren's SMA Dry Eye Asthma

Canakinumab (ACZ885) Inclisiran3 Ligelizumab (QGE031) SAF312 CSJ117 Select Lung CVRR CSU / CIU Chronic Ocular Pain Asthma pipeline Asciminib (ABL001) Adriforant (ZPL389) QBW251 assets CML AD COPD

MBG453 Tropifexor (LJN452) MDS, AML NASH Featured during R&D Day LOU064 CSU

CRM – Cardiovascular, Renal and Metabolism IHD – Immunology, Hepatology & Dermatology 1. Aimovig® is developed in collaboration with Amgen 2. Luxturna® marketed ex-US 3. Inclisiran is an investigational product of The Medicines Company. The acquisition of The Medicines Company is subject to satisfaction or waiver of customary closing conditions. Until closing, Novartis and The Medicines Company will continue to operate as separate and independent companies

14 Novartis R&D Day | December 5, 2019 ...while strengthening our innovative platforms

GENE THERAPY CELL THERAPY RADIO-LIGAND THERAPY

Select 1 commercial assets

Zolgensma® CPK850 CD19 CAR-T CD19 CAR-T 177Lu-PSMA-617 177Lu-PSMA-R2 SMA Retinis Pigmentosa DLBCL in 1st relapse r/r Follicular Lymphoma mCRPC Prostate Cancer

AVXS-101 IT CD19 CAR-T CD19 CAR-T 177Lu-NeoB SMA r/r DLBCL in combo with pembro Adult r/r ALL Various cancers

AVXS-201 CD19 CAR-T CD19 CAR-T Rett Syndrome r/r CLL in combo with ibrutinib Pediatric NHL Select CD19 CAR-T AVXS-301 CD19 CAR-T 1st line high risk pediatric and pipeline ALS r/r DLBCL in combo with ibrutinib young adult ALL assets AVXS-401 CD19 CAR-T CD19 CAR-T Friedrieich’s Ataxia BCMA&CD19 CD22&CD19 Featured during R&D Day AVXS-501 CD19 CAR-T CD19 CAR-T Undisclosed CD123 EGFRv3

AVXS-601 Undisclosed

1. Luxturna® marketed ex-US Includes preclinical and launched progams

15 Novartis R&D Day | December 5, 2019 Our pipeline at a glance

Number of Pipeline Programs by Phase Phase 1/2 Phase 3 Registration Total ONCOLOGY 57 20 2 79

PHARMACEUTICALS 59 17 9 85 Cardiovascular, Renal, Metabolism 9 3 1 13 Immunology, Hepatology, Dermatology 21 6 2 29 Neuroscience 8 1 1 10 Ophthalmology 5 3 1 9 Respiratory 11 4 3 18 Global Health 5 0 1 6 Total 116 37 11 164

CRM: Cardio Renal Metabolic. IHD: Immunology, Hepatology & Dermatology. NS: NeuroScience.

16 Novartis R&D Day | December 5, 2019 Phase 2 pipeline comprises over 60 projects Lead Indication

Oncology Neuroscience Code Name Mechanism Indication(s) Code Name Mechanism Indication(s) ABL001 asciminib BCR-ABL Inhibitor CML 1L AFQ056 AFQ056 mGluR5 Antagonist Addiction ACZ885 canakinumab IL-1b Inhibitor Sickle cell anaemia BAF312 Mayzent S1P1 Modulator Ped MS Stroke BYL719 alpelisib PI3Kα inhibitor PROS LMI070 branaplam Survival motor neuron protein SMA CTL019 Kymriah CD19 CART r/r DLBCL (+ pembro) MIJ821 MIJ821 NR2B Inhibitor Depression EGF816 nazartinib+capmatinib Opdivo EGFR Inhibitor NSCLC OMB157 ofatumumab CD20 Antagonist Ped MS INC280 capmatinib c-Met Inhibitor NSCLC c-Met Inhibitor + spartalizumab HCC NSCLC Respiratory Disease INC424 Jakavi JAK1 Inhibitor Myelofibrosis (combination) Code Name Mechanism Indication(s) LAG525 LAG525 LAG3 Inhibitor Solid Tumors ACZ885 canakinumab IL-1b Inhibitor Sarcoidosis MBG453 MBG453 TIM3 Antagonist HR-MDS Unfit AML CJM112 CJM112 IL-17A Inhibitor Asthma NIR178 NIR178, spartalizumab Ad2AR Inhibitor, PD1 Inhibitor Cancers CSJ117 CSJ117 TSLP Inhibitor Severe asthma PDR001 spartalizumab PD1 Inhibitor Nasopharyngeal cancer Metastatic melanoma (combo) LOU064 LOU064 BTK Inhibitor Asthma SEG101 crizanlizumab P-selectin Inhibitor Sickle cell anaemia with crisis QAW039 fevipiprant DP2 (CRTh2) Antagonist Rhinitis allergic Nasal polyps COPD ped Asthma Immunology, Hepatology, Dermatology QBW251 QBW251 CFTR Potentiator COPD VAY736 ianalumab BAFF-R Inhibitor IPF Code Name Mechanism Indication(s) AIN457 Cosentyx IL17A Inhibitor SpA IVIV GCA Lichen Planus Cardiovascular, Renal, Metabolism CFZ533 iscalimab CD40 Inhibitor Renal/Liver Tx SjS HS LJC242 tropifexor&cenicriviroc CCR2 Inhibitor, FXR agonist NASH Code Name Mechanism Indication(s) LJN452 tropifexor FXR agonist NASH Nash (combos) CFZ533 iscalimab CD40 Inhibitor Lupus Nephritis LNA043 LNA043 ANGPTL3 Agonist Osteoarthritis LMB763 nidufexor FXR Agonist Diabetic Nephropathy LOU064 LOU064 BTK Inhibitor Chronic spontaneous urticaria SjS LNP023 LNP023 CFB Inhibitor PNH iMN C3G IgAN LYS006 LYS006 - Acne VAY736 ianalumab BAFF-R Inhibitor pSjS AIH SLE Global Health ZPL389 adriforant HRH4 Antagonist Atopic dermatitis Code Name Mechanism Indication(s) KAE609 cipargamin PfATP4 inhibitor Malaria Malaria severe Ophthalmology KAF156 ganaplacide - Malaria Code Name Mechanism Indication(s) LXE408 LXE408 Protozoan Inhibitor Visceral leishmaniasis CPK850 CPK850 RLBP1 AAV RP ECF843 ECF843 rh-Lubricin Dry eye LKA651 LKA651 EPO Inhibitor Diabetic retinopathy SAF312 SAF312 TRPV1 Antagonist COSP UNR844 UNR844 disulfide bonds Modulator Presbyopia

17 Novartis R&D Day | December 5, 2019 Prioritizing early programs that address significant unmet need

LNP023 - oral complement Factor B inhibitor TQJ230 - antisense oligonucleotide

Potential first disease modifying treatment option for several rare renal diseases Potential first medicine approved to treat high Lp(a) Also in development for 1st line PNH

Iscalimab - fully human IgG1 mAb against CD40 MBG453 - anti-TIM-3 monoclonal antibody

Potential to provide “One Potential first-in-class anti-TIM- Transplant for Life” 3 monoclonal antibody Also in development for Sjögren's In development for MDS and and other indications AML

18 Novartis R&D Day | December 5, 2019 Maximizing pipeline potential through asset selection and early LCM

Innovation in Phase 2 pipeline, 2019 Multiple concurrent programs ongoing for key assets

LNP023 in renal disease and PNH Increasing selectivity and prioritization of incoming assets, with early discontinuation of 92% undifferentiated assets

Internal assessment of Iscalimab in transplant and immunological disorders pipeline classifies ~90% as either first in class or First in class or first in indication indication Follower

19 Novartis R&D Day | December 5, 2019 Deploying data & digital technologies to increase asset value and improve processes

Increasing asset value – iscalimab example Transforming trial operations – SENSE Bridge

. Predicting long-term graft survival to accelerate . Tracks, analyzes and predicts the status of 500+ active development trials in 70+ countries involving 80k+ patients in real time . Leveraging remote trial models to decrease trial drop-outs . Other modules operational, enabling, e.g.: . Using digital endpoints to demonstrate safety and efficacy – Site selection . Optimizing trials through real world datasets – Enrollment planning / tracking – Resource planning . Developing smart delivery devices and companion – Drug supply management solutions to improve pt experience, adherence & outcome

20 Novartis R&D Day | December 5, 2019 Operational focus beginning to show results Improving development timelines, decreasing costs and improving productivity

Time Cost Productivity

2019 vs. 2018 2019 vs. 2018 2019 vs. 2018 Indicator (Sept YTD) Trend Indicator (Sept YTD) Trend Indicator (Sept YTD) Trend

Study Patient -12% recruitment 3% Monitoring start-up1 ⬊ +11% ⬈ cost4 efficiency7

Site visit Enrollment2 -24% -8% Dataset ⬊ 5 ⬊ +6% ⬈ cost production8

Data Database -32% analysis -17% Sites lock3 ⬊ ⬊ +1% cost6 performance9

1. Time from final protocol package to first patient first visit (weeks) 2. Time from first patient first visit to 25% enrollment (weeks) 3. Time from last patients last visit to database lock (weeks) 4. Inv Grant Cost per patient (completed trials) 5. Resources cost per monitoring visit 6. Resources cost per page 7. Monitoring visits per clinical research associate per week 8. Internal # pages processed per FTE per month 9. % sites enrolled ≥1 subjects

21 Novartis R&D Day | December 5, 2019 Expect over 50 NDA filings in China 2019-23

Number of NDA filings1

Average # of NDAs expected to double in the next 5 years 50 . 5 average NDA filings per year 2014-2018 x2 . 10 average NDA filings expected per year 2019-2023

26 Goal to deliver >90% of 2024 China submissions simultaneously with global submission

2014-2018 2019-2023

1. NDA submission of new compound + new indication.

22 Novartis R&D Day | December 5, 2019 Takeaways for today

. Building on history of innovation, including recent approvals

Continuing to build depth in core therapeutic areas while exploring adjacencies to further strengthen pipeline

. Sharing robust clinical pipeline highlighting select high potential assets

. Delivering comprehensive LCM efforts to maximize new and in-line brands

. Establishing leading position in platform technologies that is difficult to replicate

23 Novartis R&D Day | December 5, 2019 Q&A Appendix ONC IHD OPHTHA Expected filing timelines for assets featured NS RESP CRM during R&D Day GH BioS 2019 2020 2021 2022 2023 >2023

spartalizumab NME asciminib NME LNP023 NME 177Lu-NeoB NME tropifexor&cenicrivirocNME NME LMI070 NME PDR001 ABL001 PNH 177Lu-NeoB LJC242 SMA m BRAF V600+ melanoma (+Taf/Mek) CML 3L Multiple Solid Tumors NASH

177Lu-PSMA-617 NME MBG453 NME CEE321 NME tropifexor NME CPK850 NME 177Lu-PSMA-617 HR-MDS Atopic Dermatitis LJN452 RP mCRPC NASH

fevipiprant NME ligelizumab NME iscalimab NME LNA043 NME TQJ230 NME QAW039 QGE031 CFZ533 Osteoarthritis CVRR Asthma Chronic urticaria Renal/Liver Tx

adriforant NME AVXS-201 NME ZPL389 OAV201

Atopic dermatitis Rett syndrome LEAD INDICATIONS

Cosentyx LCM Alpelisib LCM canakinumab LCM canakinumab LCM spartalizumab LCM asciminib LCM tropifexor LCM ofatumumab LCM secukinumab, AIN457 BYL719 ACZ885 ACZ885 PDR001 ABL001 LJN452 OMB157 Ped Psoriasis PROS NSCLC 2L Adjuvant NSCLC Malignant melanoma (combo) CML 1L NASH (combos) Ped MS

Cosentyx LCM Cosentyx LCM canakinumab LCM Kisqali LCM Piqray LCM MBG453 LCM Cosentyx fevipiprant LCM secukinumab, AIN457 secukinumab, AIN457 ACZ885 ribociclib, LEE011 alpelisib, BYL719 Unfit AML secukinumab, AIN457 QAW039 nr-axSpA Psoriasis 300mg AI NSCLC 1L HR+/HER2- BC (adj) TNBC, HER2+ adv BC, ovarian cancer GCA Nasal polyps

ofatumumab LCM Cosentyx LCM crizanlizumab LCM Cosentyx LCM Kymriah LCM crizanlizumab LCM Cosentyx fevipiprant LCM OMB157 secukinumab, AIN457 SEG101 secukinumab, AIN457 tisagenlecleucel-T, CTL019 SEG101 secukinumab, AIN457 QAW039 r MS PsA H2H Sickle cell anaemia new formulations SpA IVIV Adult r/r ALL Sickle cell anaemia with crisis Lupus Nephritis ped Asthma

AVXS-101 LCM Kymriah LCM Cosentyx LCM Beovu 177Lu-PSMA-R2 Cosentyx fevipiprant LCM onasemno-gene abepar-vovec, OAV101 tisagenlecleucel-T, CTL019 secukinumab, AIN457 brolucizumab, RTH258 177Lu-PSMA-R2 secukinumab, AIN457 QAW039 SMA type 2/3 (IT formulation) r/r DLBCL 1st relapse Hidradenitis suppurativa Diabetic retinopathy / RVO Prostate cancer Ankylosing spondylitis COPD

Entresto LCM Kymriah LCM Cosentyx LCM fevipiprant LCM Piqray Cosentyx LNP023 LCM valsartan+sacubitril, LCZ696 tisagenlecleucel-T, CTL019 secukinumab, AIN457 QAW039 alpelisib, BYL719 secukinumab, AIN457 iMN HFpEF r/r Follicular lymphoma AS H2H Rhinitis allergic HNSCC 2/3L Lichen Planus

LCM LCM LCM NEW INDICATIONS Beovu LNP023 Kymriah iscalimab brolucizumab, RTH258 C3G / IgAN tisagenlecleucel-T, CTL019 CFZ533 DME r/r DLBCL (+ pembro) SjS

Entresto LCM Kymriah valsartan+sacubitril, LCZ696 tisagenlecleucel-T, CTL019 Post-AMI 1L high risk ALL, pediatrics & young adults

26 Novartis R&D Day | December 5, 2019 Multiple upcoming milestones expected – emerging assets featured during R&D Day

2020 2021 2022

LNP023 Phase2 LNP023 Phase2 Iscalimab Ph2b C3G MN Sjoegrens

Asciminib Ph3 Iscalimab Ph2b Iscalimab Ph2 Iscalimab Ph2b CML (3rd line) Kidney Tx SLE, LN, HS Liver Tx

Readout Tropifexor Ph2b Ligelizumab Ph3 NASH CSU

TQJ230 Ph3 LNP023 Ph3 Adriforant Ph3 LNP023 Ph3 LNP023 Ph3 CVRR PNH Atopic Dermatitis C3G, IgAN MN

MBG453 Ph2 Tropifexor Ph3 LNA043 Ph2b MBG453 Ph2 Iscalimab Ph3 Unfit AML NASH Osteoarthirtis Higher risk MDS (US) Kidney / Liver Tx

MBG453 Ph3 CEE321 Ph2

MDS (EU) Atopic dermatitis Phase Initiation Phase

Asciminib Ph3 MBG453 Canakinumab CML (3rd line) MDS Adjuvant NSCLC

Canakinumab Ligelizumab Ph3 NSCLC (1st line) CSU

Oncology Ophthamology Respiratory Canakinumab Submission NSCLC (2nd line) IHD Neuroscience CRM

27 Novartis R&D Day | December 5, 2019 Multiple upcoming milestones expected – late stage assets & LCM featured during R&D Day

2020 2021 2022

® Cosentyx Ph3 IA Lu-PSMA-617 Ph3 Cosentyx® Ph2 Cosentyx® Cosentyx® Ph3 Cosentyx® Ph2 JIA (JPSA / ERA) Prostate cancer GCA HS HS LP

Fevipiprant Ph3 Beovu® Ph3 Entresto® Cosentyx® Ph2 Asthma DME PAMI Lichen Planus

Zolgensma® Beovu® TALON Wet AMD

Readout SMA type 2

Cosentyx® Ph2 Alpelisib Ph3 Cosentyx Ph3 LN / LP HER2+BC, TNBC, GCA

Ovarian, H&N, PROS Phase Initiation Phase

Entresto® Spartalizumab Combo Beovu® Ph3 Entresto® Cosentyx® Kisqali® HFpEF MM DME PAMI HS Adjuvant BC

Fevipiprant Ph3 Alpelisib (US) Lu-PSMA-617 Ph3 Asthma PROS Prostate cancer Oncology Ophthamology Respiratory

Submission IHD Neuroscience CRM

28 Novartis R&D Day | December 5, 2019 Agenda Time includes Q&A

13:00-13:30 Opening Vas Narasimhan Portfolio Overview John Tsai

Research 13:30-14:00 NIBR Jay Bradner Platforms Cell Therapy, Gene Therapy, Molecular Glues

Emerging 14:00-15:15 Pharmaceuticals Dave Soergel Assets TQJ230, LNP023, Iscalimab, Ligelizumab, AD portfolio, LNA043, Tropifexor Eric Hughes 15:15-15:45 Oncology Jeff Legos MBG453, Asciminib, Canakinumab

15:45-16:00 Break

17:30-17:45 Closing Vas Narasimhan

29 Novartis R&D Day | December 5, 2019 Jay Bradner MD President, Novartis Institutes for BioMedical Research (NIBR) Leading in the science of therapeutics

Focused and maturing pipeline of ~90 new molecular entities prioritized and competitively 1 positioned to change the practice of medicine

Advanced therapeutic modalities, platforms and technologies, including targeted protein 2 degradation, cell and gene therapy, long-acting delivery, and expansive chemical libraries

Integrated research strategy leveraging internal and external innovation, fueled also 3 by strategic out-licensing to capture ROI and enable patient access

31 Novartis R&D Day | December 5, 2019 ~5,600 340 8 ~90 USD 2.6bn NIBR Scientists Discovery Disease New molecular Research & early programs areas entities development

32 Novartis R&D Day | December 5, 2019 A powerful and productive drug discovery engine

1. Kymriah® and Gilenya® were in-licensed into NIBR pre-PoC

33 Novartis R&D Day | December 5, 2019 A prioritized portfolio of ideas and medicines

Strategic disease area Disciplined project selection Ruthless prioritization Best at first-in-class leadership1 ~460

20% ONC/IO 30% ~230 ~320 41% 44% 20% ~90 5% 10% 5% MSD NITD 12% 11% 6% Other OPH 11% 50% 53% 35% RESP 22%

CVM

Terminations ProjectsNew Oct

Apr 2016 2017 2018 2019 -

NEURO -

2019 2018 ATI FIC Target BIC FIC Modality Strategic FIC Indication

Focused commitment Critically evaluated against And commitment to making decisions With emphasis on pursuing in our disease areas expanded set of parameters that enable focused resourcing transformative innovation

1NMEs by Sponsor, ONC/IO - Oncology/Immuno-Oncology; OPH - Ophthalmology; RESP - Respiratory; NEURO - Neuroscience; ATI - Autoimmunity, Transplantation, and Inflammation; CVM – Cardiovascular, Renal and Metabolism; NITD - Novartis Institutes for Tropical Diseases; MSD - Musculoskeletal Diseases; FIC - First-in-Class; BIC - Best-in-Class

34 Novartis R&D Day | December 5, 2019 Our best at first-in-class aspiration

BYL719 Kymriah® TNO155 (alpelisib) CAR-T for B-cell SHP2 inhibitor PI3K inhibitor acute lymphoblastic for advanced solid for breast cancer leukemia tumors including those that harbor KRASG12C mutations

Inflammasome KAF156 LNP023 NLRP3 inhibitors Anti-malarial LMW complement in multiple compound factor B inhibitor indications with potent for paroxysmal anti-plasmodial nocturnal activity hemoglobinuria (PNH)

Schubart et al. | PNAS | April 16, 2019 | vol. 116 | no. 16

35 Novartis R&D Day | December 5, 2019 The new science of therapeutics

Modality / therapeutic concept Chemical biology Pharmacological control

Cell therapy Gene therapy Chemoproteomics Long acting delivery

Cancer cell

T-cell

Nanoparticles Hydrogels

Glues Radioligand therapy DNA encoded libraries Novel IO Rx Delivery

Target

...... Topics covered in this presentation All trademarks are the property of their respective owners.

36 Novartis R&D Day | December 5, 2019 Novartis cell therapy

Manufacturing network Novartis cell therapy portfolio

Les Ulis Fraunhofer Technology Indication Phase (Own) (CMO) CAR-T (EGFRviii) + Glioblastoma Newly acquired site in France for EU First CMO used for clinical Post-FPFV Site under start-up and expansion programs in EU pembrolizumab Multiforme Clinical manufacturing site Commercial supplies agreed up to 3 years after CAR-T (IL3RA) AML Post-FPFV Commercial readiness in H1 2020 launch per indication East Hanover ALL (pediatric (Own) FBRI CAR-T (CD22+/- CD19) Post-FPFV (CMO) and adult) Primary Support clinical manufacturing supply in Japan from Multiple facility for Phase I CAR-T (BCMA+CD19) Post-FPFV Stein early 2019 onwards myeloma innovation products (Own) Commercial readiness in H2 Diffuse large Focused on commercial CBMG CAR-T (CD19) + ibrutinib Post-FPFV Morris Plains supply to EU (CMO) 2020 B cell (Own) Expansion plans 2 stages of expansion: Strategic licensing and Primary NEXT (pod) and Suite ongoing Diffuse large collaboration agreement to CAR-T (CD19) Post-FPFV manufacturing Clinical manufacturing site manufacture and supply Kymriah® B cell / CLL facility for global Commercial readiness in in China capacity with focus H1 2020 Sickle cell North America CRISPR IND enabling Host tech transfer disease site for commercial programs

FPFV: First Patient, First Visit IND: Investigational New Drug

37 Novartis R&D Day | December 5, 2019 Next-generation CART

CAR-T CD22 CAR-T (JJO686) in Ph1 studies in combination with CD19 CAR-T (LXG250) to prevent resistance CD19-targeting therapies have been approved for relapsed/refractory ALL CD19 CD22 However, CD19-negative acquired resistance is inherent to CD19-targeting therapies and patients suffering from subsequent relapses have dismal prognosis

CD19- relapse patient

Cancer cell

CD19 B-Cell malignancies

T-cell AML

CD-19 CART cell attacking a cancer cell | NIBR Solid tumors

All trademarks are the property of their respective owners. Data is investigational. Efficacy & safety not yet established

38 Novartis R&D Day | December 5, 2019 Genome engineering for sickle cell disease

CRISPR Increase in F-cell number and HbF expression upon editing of SCD patient peripheral blood CD34+ stem cells Novarts has extensive experience in Sickle-cell disease, 1 complex CMC , and cell therapy supply chain HbF+ Cell CRISPR editing is selective without the potential risk of insertional mutagenesis and results in more physiologic control of globin switching to increase HbF together with reduced expression of HbS than other approaches Hematology Potent and selective sgRNA identified, IND enabling CRISPR studies completed Machinery

N=3/experiment, 4 independent Ophthalmology experiments, data show mean+SEM

All trademarks are the property of their respective owners. Data is investigational. Efficacy & safety not yet established 1. CMC - chemistry, manufacturing and control

39 Novartis R&D Day | December 5, 2019 Novartis gene therapy

Manufacturing network Novartis AAV portfolio Libertyville (ALV)

Timing: Licensed Product Indication Phase

Zolgensma SMA (IV) Market

Colorado (ACO) North Carolina (ANC) AVXS-101 SMA (IT)1 Phase 1/2 Timing: Q1 2020 Timing: Q1 2020 CPK850 Retinitis Pigmentosa Post-FPFV

AVXS-201 Rett Syndrome IND enabling

SOD-1 Amyotrophic AVXS-301 IND enabling Lateral Sclerosis (ALS)

San Diego (ASD) AVXS-401 Friedreich’s ataxia IND enabling Timing: Operational AVXS-501 Undisclosed Pre-clinical

CMO AVXS-601 Undisclosed Pre-clinical Timing: Licensed

1. FDA placed a partial hold on AVXS-101 intrathecal clinical trials for SMA patients based on findings in a small pre-clinical animal study

40 Novartis R&D Day | December 5, 2019 AAV therapeutics for neuromuscular diseases

AVXS-2011 AVXS-3012 AVXS-4013 Rett syndrome Treatment of male Rett mice ICV SOD1 ALS Friedreich’s Ataxia with AVXS-201 increases survival AVXS-301 ICV dose response (FA) Rescue of neurological ALS is a deficits neurodegenerative NeNeuurrolloogigcaicl Saclo rSecore Rett syndrome is FA is an autosomal 4 disease characterized 4 Wildtype Control 3 Pvalb-cre FXN cKO e Wildtype Control an X-linked neuro- recessive neuro- r Vehicle

by progressive c 2 3 s 5e9 vg

o Pvalb-cre FXN cKO

u developmental degenerative disease r 1E10 vg e Vehicle o 1 degeneration of multiple N c 2 5E10 vg Autism Spectrum that presents early in s 5e9 vg o 0 1e11 vg cell types within the r u 1E10 vg e 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 Disorder childhood leading to 1 1 1 1 1 1 1 1 1 1 1 2

Percent Percent Survival central nervous system progressive Age (Weeks) 5E10 vg (CNS) that work 0 1e11 vg Incidence of about Age (days) Spinocerebellar 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 together to control 1 1 1 1 1 1 1 1 1 1 2 1:10,000 female neurodegeneration motor function Age (Weeks) births Prevalence of 1 in MeCP2 Immunohistochemistry 90% of ALS cases are AVXS-401 improves survival AAV9-GFP Spinal cord 50,000 with survival 90% of cases AVXS-401 treatment of MCK-cre FXN cKO mice in the Brains of Control and sporadic with no family in FAAV XheartS-401 treatme nmodelt of MCK-cre FXN cKO mice transduction to 30s and 40s SuSruvrivaivl aclu crvuer v(Ael l()All) result from AVXS-201–Treated NHPs history. Of the 10% of 8282 120 mutations in methyl familial cases, 20% are 120 Motor Neurons Astrocytes There is currently no 11000 CpG binding linked to mutations in WT VehWicTle Vehicle effective therapy l 80 l 80 a Mck-cre a Mck-cre

i FXN cKO v FXN cKO

r protein 2 (MeCP2) v 60 Vehicle

r the superoxide u 60 Vehicle

3.3E9 vg

3.3E9 vg % 40 1E10 vg dismutase-1 (SOD1) % 40 1E10 vg 3E10 vg 3E10 vg 20 9E10 vg AVXS-201 gene. 20 9E10 vg 0 designed to restore 0 0 20 40 60 80 100 120 140 160 AVXS-301 designed to 0 20 40 60 Day8s0 100 120 140 160 MeCP2 expression Days downregulate SOD1 1 mouse was sac'd in 3.3e9 group due to paralysis of rear legs 1 mouse was sac'd in 3.3e9 group due to paralysis of rear legs

1. “Efficacy and safety in mice and non-human primates of CSF-delivered AVXS-201 for the treatment of Rett syndrome,” K. Foust, et al. ASGCT, 2019. Data is investigational. Efficacy & safety not yet established. 2. “Intrathecal administration of AVXS-301 for amyotrophic lateral sclerosis: survival extension and SOD1 reduction in mice and nonhuman primates,” G. Thomsen, et al. ASGCT, 2019. 3. Data is investigational. Efficacy & safety not yet established.

41 Novartis R&D Day | December 5, 2019 AAV therapeutics for severe eye disease

CPK850 Gene therapy improved dark adaptation Retinitis pigmentosa (RP) in a mouse model of RP

RP results in night blindness from early childhood, gradual

deterioration of visual fields (to legal blindness) and loss of visual wave

acuity typically leading to complete blindness in 40s - Mutations in the RLBP1 gene (15q26) cause autosomal recessive Retinitis Pigmentosa (RP). Prevalence: ~1:800,000 people

Phase 2b start expected Q1 2021 amplitude % Recovery a Recovery of %

Weeks post-injection1 Toddler 10 y.o. 16 y.o. 50 y.o. Night + Light + Visual + Central 2 3 Blindness Sensitivity Field Loss Vision Loss

1. Choi et al., Mol Ther Methods Clin Dev. 2015 Data is investigational. Efficacy & safety not yet established. 2. He et al., PNAS, 2009. 3. Hamel, Orphanet Journal of Rare Diseases 2006. Data is investigational. Efficacy & safety not yet established

42 Novartis R&D Day | December 5, 2019 Molecular glues

Intramolecular glues Intermolecular glues First inhibitors of the SHP2 Tyrosine Phosphatase A structural basis for protein degradation

DCAF15 DDB1 DDA1 Met560 RBM39 a6 LJI439 Asn260 Val559 RBM39 Central Helix Thr262 Phe235

a4 Ala234 Inactive form stabilized

Bussiere, Solomon, Paulk (NIBR), BioRxiv 2019 PDB, 5EHP Fortin et al., Nature | vol 535 | 7 july 2016

Allosteric mechanism of inhibition Recruitment of RBM39 to DCAF15

43 Novartis R&D Day | December 5, 2019 Molecular glues – SHP2 inhibition as cancer therapy

SHP2 is a protein tyrosine phosphatase that Required for RTK signaling Combination efficacy of drives cancer growth signaling in collaboration KRAS G12C and SHP2 inhibitors with Receptor Tyrosine Kinases (RTKs) and MIA PaCa-2 in vitro colony formation KRAS. G12Ci RTK signaling is a major driver of both solid tumors and blood cancers, often driven by -SHP2i highly prevalent oncogenic mutations. RTK +SHP2i driven tumors are sensitive to SHP2 inhibition.

G12C KRAS mutation is observed in many MIA PaCa-2 in vivo xenografts different tumor types, as well. A KRASG12C and SHP2 inhibitor combination results in DRIVE: SHP2 dependence increased anti-tumor activity (preclinical data). correlates with RTK addiction

G12C Clinical evaluation of KRAS inhibitor, p<0.05 MRTX849 (Mirati) and SHP2 inhibitor, TNO155 (Novartis), in patients with advanced solid tumors that harbor KRASG12C mutations. Internal data Investigational. Safety and efficacy have not been established

44 Novartis R&D Day | December 5, 2019 Targeted protein degradation (TPD)

Innovation of a new type of therapeutic Bifunctionals Molecular glue

Ub Ub Ub Ub Ub Ub Ub Next-generation chemistry Target E2 protein

Ub Ub Target Enabling technologies in TIDVAL, LO, PCS E2 E2 protein Access to undruggable targets

E3 E3 Unprecedented degradation complex complex

Minimally structured but highly organized BTK DCAF15 NIBR-wide coalition of the curious BTKc481S mutant TMD8 model DDA1 stabilizes the DCAF15-DDB1 complex and impacts degradation of RBM39 by Indisulam Nimble, facilitated resourcing

Reversible BTK inhibitor Highly visible, accountable Irreversible BTK inhibitor BTK bifunctional degrader 1

BTK bifunctional degrader 2 Unapologetic translational focus High sense of urgency

45 Novartis R&D Day | December 5, 2019 LMI070 in spinal muscular atrophy

SMN RNA SMA Type 1 patients treated with LMI070 up to the age of  1 year show improvement in muscle Compound U1 RNA strength from baseline, whereas untreated SMA Type 1 infants from a small historical control (NeuroNEXT) show a steady decline over time

SMA Type I treated (n = 13) Includes only subjects with 2 SMN copies

U1 Protein Dose was lowered in all patients following a toxicology finding. This led to a loss of motor skills Predictive model generated in NIBR using crystal in some patients (Gray lines) structure of 5’ splice site recognition (Nagai et al. MRC. UK, 2015) NeuroNEXT - Natural history study in SMA Type 1 infants (n = 7) SMA disease characteristics INTEND CHOP Score Total Subset of patients with 2 SMN . Onset <6 months . Hypotonia and weakness . Bulbar muscle weakness . Difficulty breathing & swallowing Age at evaluation (months)

. Inexorable progression to nutritional and CHOP INTEND measures muscle strength in extremely weak infants with a max. total score of 64 points. | Investigational/safety and efficacy have not respiratory failure been established Source: Kolb et al NeuroNEXT, graciously provided prior to publication

46 Novartis R&D Day | December 5, 2019 Ambitions for Novartis Research @ NIBR

Innovating a new science of therapeutics with a suite of advanced technology platforms and a chemical biology discovery engine to approach “undruggable” targets

Focusing and prioritizing research investments to core strategy, while still nurturing exploration of emerging ”white spaces”

Opening our framework and building businesses with non-strategic assets to become the partner of choice to innovators and entrepreneurs

Inventing and translating definitive medicines for life-threatening diseases

47 Novartis R&D Day | December 5, 2019 Q&A Agenda Time includes Q&A

13:00-13:30 Opening Vas Narasimhan Portfolio Overview John Tsai

Research 13:30-14:00 NIBR Jay Bradner Platforms Cell Therapy, Gene Therapy, Molecular Glues

15:45-16:00 Break

17:30-17:45 Closing Vas Narasimhan

49 Novartis R&D Day | December 5, 2019 David Soergel MD Global Head of Cardiovascular, Renal and Metabolism Development Unit TQJ230 Key highlights

Antisense TQJ230 is an antisense oligonucleotide providing a potent and consistent reduction of Lp(a) oligonucleotide targeting TQJ230 expected to be the first disease modifying treatment for elevated Lp(a), reducing CV risk apolipoprotein(a) Phase 3 outcomes trial to be initiated early 2020 with readout mRNA expected 2024 Lipoprotein(a) is an independent risk factor for CVD and currently not treatable

Lipoprotein(a) Lp(a) is an independent, particle Lp(a) levels are primarily genetic and causal risk genetically determined factor for CVD, with and not influenced by diet elevated Lp(a) mediating or exercise MI, stroke, and PAD

Lp(a) consists of an There are currently no LDL-like particle which is approved therapies to covalently bound to apo(a) treat elevated Lp(a)

Apo(a), apolipoprotein(a); ApoB-100, apolipoprotein B-100; CVD, cardiovascular disease; KIV, kringle IV, MI, myocardial infarction, PAD, peripheral artery disease. Lp(a) figure adapted from Tsimikas S. J Am Coll Cardiol 2017;69:692–711.

52 Novartis R&D Day | December 5, 2019 Around one in five people worldwide are at increased risk of developing CVD due to Lp(a)1

An estimated 1.4 billion people globally have elevated Lp(a) levels >50 mg/dL2

North America Asia 20% | 73m 20% | 148m South Asia 10% | 261m Africa

Latin America 20% | 8.1m 25% | 469m Oceania

15% | 97m 30% | 376m

1. Tsimikas et al. J. Am. Coll. Cardiol. 71 (2018) 177–192. 2. Nordestgaard et al. Eur Heart J. 2010 Dec;31(23):2844-53. Figure taken from Tsimikas et al. J. Am. Coll. Cardiol. 71 (2018) 177–192.

53 Novartis R&D Day | December 5, 2019 TQJ230 demonstrated significant Lp(a) reductions in CVD patients1

Phase 2b results - TQJ230 vs. placebo

0 2 4 6 8 10 12 14 16 18 20 22 24 26 TQJ230 is an antisense oligonucleotide 10 N=239 targeting apolipoprotein(a) mRNA2 Pooled placebo (N=48)

20mg Q4W (N=48) Phase 2b data showed1: -15

SEM) 40mg Q4W (N=48) . Dose-dependent Lp(a) reductions up ± to 80% 20mg Q2W (N=48) -40 . 98% of patients achieved Lp(a) ≤50 60mg Q4W (N=47) mg/dL following treatment with 20mg QW (N=48) TQJ230 20 mg once a week for Lp(a) over time over Lp(a) for -65 Mean % ( % changeMean . Good tolerability and safety profile

Weeks Primary analysis -90 timepoint (Week 25-27)

For references see slides 179-180. QW, once a week; Q2W, every 2 weeks; Q4W, every 4 weeks; SEM, standard error of the mean.

54 Novartis R&D Day | December 5, 2019 TQJ230 expected to provide relevant CV risk reduction through potent Lp(a) lowering

Effect on Large reductions in Lp(a) are Treatment / procedure Lp(a) levels1 anticipated to provide clinically relevant CV benefits2 TQJ230 -70 to -99%

Apheresis -30 to -35%3

Other MoA, including Niacin, CETPi, -20% to -30% Mipomersen

Statins +10 to +20%

For references see slides 179-180. CETPi, cholesterol ester transfer protein inhibitors; PCSK9 mAb, proprotein convertase subtilisin/klexin-type 9 (PCKS9) monoclonal antibodies.

55 Novartis R&D Day | December 5, 2019 Phase 3 outcome study planned to start early 2020; patient identification ongoing

Objective: To evaluate the prevalence of normal Objectives: Demonstrate superiority of TQJ230 and elevated Lp(a) levels in patients with vs. placebo in reducing the risk of MACE1 established CVD N = 7680 N = approx. 45 000 Population: Patients with established CVD and Population: Patients with established CVD Lp(a) ≥70 mg/dL on optimal therapy for other CV risk factors FPFV: Q2 2019 FPFV: January 2020 Status: Ongoing Primary outcomes: 2024

For references see slides 179-180. CV, cardiovascular; MACE, major adverse cardiovascular events; MI, myocardial infarction; PAD, peripheral artery disease; QM, once a month; SC, subcutaneous.

56 Novartis R&D Day | December 5, 2019 LNP023 Key highlights

Low molecular weight Targeting the complement pathway offers potential to impact multiple diseases Factor B inhibitor targeting the LNP023 in parallel development for three rare renal diseases and paroxysmal nocturnal hemoglobinuria (PNH) alternative Early data from ongoing open-label Phase 2 studies suggest a complement pathway promising clinical profile

Single pivotal study approach for PNH supported by health authorities

Full Phase 2a/b readouts in 2020-21, designed to enable direct transition into Phase 3; PNH Phase 3 pivotal to start in 2020 Targeted renal diseases often affect young patients and have limited treatment options

IgA Membranous C3 Nephropathy Nephropathy Glomerulopathy

. ~185k patients in US; higher . ~81k patients in US; commonly . ~10k patients in US; commonly incidence in Asia; commonly diagnosed aged 40-60 diagnosed in adolescents and diagnosed aged 20-40 . Most common cause of nephrotic young adults . Clinical features include syndrome in adults . Clinical features include proteinuria, gross hematuria, . ~30% of patients progress to proteinuria, hematuria, nephrotic fatigue and pain ESRD within 10 years syndrome, fatigue . ~30% of patients with proteinuria . ~50% of patients progress to ≥1g/day progress to ESRD within ESRD in 10 years; high rate of 10 years recurrence post-Tx

Abbreviations: ESRD = end stage renal disease

58 Novartis R&D Day | December 5, 2019 Available evidence supports role of alternative complement pathway in these diseases

IgA nephropathy Membranous nephropathy C3 glomerulopathy

Kitamura M (2019) PLoS ONE 14(2): e0211812. Zhang et al. Diagnostic Pathology 2012, 7:109 Herlitz 2012 J Am Soc Nephrol 23: 1229

. GWAS data: CFHR1/3 gene . Kidney biopsies stain positive for AP . ~25% of patients have loss/gain of deletions are protective and LP (>> CP) function in AP genes (e.g., FH) . Kidney biopsies stain positive for AP . Patients have increased levels of . 50-80% of patients have auto-Abs (less often LP, rarely CP) serum FD leading to AP activation . Correlation of glomerular C3 deposit . Some patients have elevated C5b9 . Kidney biopsies stain positive for AP and worse renal outcomes and C3dg in urine (>> CP, not LP)

Abbreviations: A/C/LP = Alternative/Classical/Lectin (complement) Pathway; FD/H = Factor D/H; GWAS = Genome-Wide Association Study

59 Novartis R&D Day | December 5, 2019 LNP023 has the potential to address unmet need in paroxysmal nocturnal hemoglobinuria (PNH)

Unmet need in PNH Unique aspects of LNP023

Rare, potentially life-threatening condition caused by an LNP023, an oral, selective acquired mutation in hematopoietic stem cells and potent first-in-class factor B inhibitor targeting Presents with hemolytic anemia, thrombosis, the alternative complement hemoglobinuria and other severe symptoms pathway and acting upstream of C5, is expected Eculizumab/ravulizumab (Soliris®/Ultomiris®, anti- to block both intra- and complement factor 5 antibodies) significantly reduce Hemolytic erythrocyte extravascular hemolysis with complement MAC intravascular destruction of red blood cells and are only available effective pharmacotherapies

Due to extravascular hemolysis, 30-50% of patients have residual anemia, remain transfusion dependent, and lactate dehydrogenase (LDH) levels remain elevated

60 Novartis R&D Day | December 5, 2019 Early Phase 2 data support advancing LNP023 as a front-line treatment for PNH

In a Phase 2 PNH trial, LNP023 add-on to LDH over time Hb 횫BL→Wk13 160 eculizumab in patients 150 140 with hemolysis delivered 130 120

consistent LDH 110

HB (g/L) HB LDH (U/L) LDH 100 normalization and 90 transfusion-free 80 70 Female subjects hemoglobin increase in NCT03439839 60 BL Wk 13 Study Day all patients

Overlaying individual time profiles of Lactate Dehydrogenase (U/L) levels Overlaying individual time profiles of Lactate Dehydrogenase (U/L) levels 30003000 30003000 Dose Cohort 1 Dose Cohort 2 The ongoing LNP023 25002500 25002500

20002000 20002000 ) monotherapy trial in ) L L / / U U ( (

1500 1500 H 1500H 1500 D D L

L LDH (U/L) LDH eculizumab-naive PNH (U/L) LDH F 10001000 10001000

patients shows early 500500 F 1.5 X ULN 500500 1.5 X ULN ULN M ULN M M M F F 00 00 efficacy (LDH↓) W1W -1 DDay1AY 1 W2W2 W4W4 W6W6 W8W8 W10W10 W12W12 W1W -1 DDay1AY 1 W2W2 W4W4 W6W6 W8W8 W10W10 W12W12 Study Week Study Week

NCT03896152 Subject 2001001 Study3001 0Week02 3002002 4001001 Subject 1001001 Study2001 0Week02 3001001 3001003

61 Novartis R&D Day | December 5, 2019 LNP023 in parallel development for renal diseases and PNH; full Phase 2a/b readouts in 2020-21

2019 2020 2021 2022 2023 2024

IgAN Phase 2 Phase 3

MN Phase 2 Phase 3

C3G Phase 2 Phase 3

PNH Phase 2 Phase 3

. Interim analyses (IA; ) in each Phase 2 study could enable acceleration of Phase 3 start . IA in IgAN Phase 3 study potentially supports filing for accelerated / conditional approvals based on proteinuria reduction . Single pivotal study approach for PNH supported by Health Authorities . Anticipated worldwide filings ≥2023 with projected blockbuster sales potential . Additional specialty indications under consideration

C3G = C3 Glomerulopathy; IgAN = IgA Nephropathy; MN = Membranous Nephropathy; PNH = Paroxysmal Nocturnal Hemoglobinuria

62 Novartis R&D Day | December 5, 2019 Eric Hughes MD Global Head, Immunology, Hepatology and Dermatology Development Unit Iscalimab (CFZ533) Key highlights

Potential to provide “One Transplant for Life” with improved Fully human patient and graft survival and become the new SoC in transplant monoclonal antibody Kidney transplant grafts showed pristine histology, suggesting blocking the CD154- potential to provide calcineurin-free therapy, prolonged graft CD40 pathway survival and fewer side effects Positive proof-of-concept study in Sjögren's syndrome, the second most common rheumatic autoimmune disease after rheumatoid arthritis

Phase 2b studies in kidney transplant and Sjögren’s on track to read out in 2021; Phase 2a readouts in systemic lupus erythematosus, lupus nephritis and hidradenitis suppurativa expected in 2021 Iscalimab blocks CD154-CD40 pathway with broad potential in multiple diseases

Alloreactivity (cellular and humoral) CD40 (48 kDa membrane bound; ~20 kDa soluble form)2 . Constitutively expressed on B cells and APCs (e.g. monocytes, macrophages, dendritic cells) Humoral immunity . Expressed on platelets, and under certain (de novo DSA, Parenchymal CD40/CD154 autoAbs) conditions on eosinophils and parenchymal cells –leukocyte interactions (cytokines, adhesion CD154 (CD40 ligand) molecules) T cell . Induced on a variety of cell types including activated T cells, platelets, and B cells

3 CD154 CD40-CD154 signaling CD40 . Important for germinal center function, antibody Complex CD40-medicated immunity (cytokines, Mφ function, ectopic production, and humoral memory germinal centers) Macrophage . Regulates macrophage, dendritic cell and parenchymal cell function . Implicated in various autoimmune diseases Figure adapted from Mathur RK et al. 20061

APC, antigen presenting cell; DSA, donor-specific antibodies. 1. Mathur RK, et al. Trends Parasitol. 2006;22(3):117-22. 2. Van Kooten C, Banchereau J. J Leukoc Biol. 2000;67(1):2-17. 3. Kawabe T, et al. Nagoya J. Med. Sci. 2011;73:69-78

65 Novartis R&D Day | December 5, 2019 Significant unmet need in transplantation to prolong graft survival and reduce side effects

40k+ new kidney Graft survival probabilities (%) Challenges with existing Standard of Care, transplant annually such as CNI-based therapies 98.6% 97.5% for an estimated 95.3% 93.1% Renal Chronic toxicity → chronic 85.3% toxicity dysfunction → return to dialysis 500k+ people living 95.7% 92.2% 89.8% 64.8% with a functioning 85.6% Cardio- Frequent new-onset post- 75.4% metabolic transplant diabetes, kidney graft in G7 complications hypertension, increased countries cardio-vascular mortality 47.3% Insufficient From recipient immune graft defense leading to progressive

2018 USRDS Annual Data Report protection graft damage → return to Reference Tables, adjusted for age, sex, dialysis race, ethnicity, and primary cause of ESRD. Graft survival is determined as Cancers and Cancers, bacterial and viral the earliest occurrence of either death with graft function or graft failure infections Infectious complications due to requiring dialysis or retransplant. (over-) immunosuppression Deceased Donors Living Donors

66 Novartis R&D Day | December 5, 2019 Pristine graft histology is indicative of improved outcomes

Superior graft quality with iscalimab Direct correlation with graft survival

. The risk for graft loss increases with the Chronic Allograft Damage Index (CADI)

. After 3 years, the graft loss is: – 0% for CADI 0-1 – 5% for CADI 2-4 – 17% for CADI >4

Yilmaz et al 2003, J Am Soc Nephrol 14: 773-779

Graft biopsies are included in two ongoing Ph2b trials: . CIRRUS I – in kidney transplant patients (recruiting ahead of schedule); results expected H1 2021 . CONTRAIL I – in liver transplant patients (started in October 2019); results expected H2 2022

ClinicalTrials.gov, NCT02217410 (completed). Nashan et al, Am Transplant Congress 2018. Farkash et al, Am Transplant Congress 2019.

67 Novartis R&D Day | December 5, 2019 Potential to reimagine transplantion with better graft protection and less toxicity

Today with Standard of Care

. Hypothetical illustration 10 YEARS with a median graft † † Death survival of 20 years vs current 10-year graft 10y median graft Patients return to dialysis: poor Re-transplant with another kidney, survival rate at 47.3% for survival time QoL and high 5y mortality (53%) depletes pool of donor organs deceased donors in the USA (USRDS report 2018) Tomorrow with iscalimab . Graft survival is determined as the earliest occurrence of either death 20 YEARS with graft function or graft failure requiring dialysis or re-transplant 20y median graft survival time Organ pool used for new patients No patients return to dialysis (no re-transplantation required)

68 Novartis R&D Day | December 5, 2019 Sjögren’s syndrome and rationale for CD40 as a therapeutic target

Prevalence and treatment . 2nd most common autoimmune disease after RA; prevalence in adult population 0.4% . No cure or systemic treatment approved

Rationale for iscalimab . A hallmark diagnostic feature of Sjögren's syndrome is B-cell hyperreactivity . T-cells and B-cells infiltrate patients’ salivary glands and upregulate CD40 and CD154 . Positive proof-of-concept study

Fisher et al. Abstr # 1784, Am College of Rheumatology 2017

69 Novartis R&D Day | December 5, 2019 Phase 2b study in Sjögren's syndrome expected to read out in H2 2021

Positive proof-of-concept trial TWINSS

Week 24 48 60 Cohort 1 (high ESSDAI) Iscalimab n = 40 High Dose f/u N= 160 High Dose

R Iscalimab Medium Dose n = 40 Medium Dose f/u

Iscalimab Low Dose n = 40 Low Dose f/u

High Dose f/u Placebo n = 40 Placebo f/u

Iscalimab High Dose n = 50 High Dose f/u R Medium Dose f/u Placebo n = 50 Cohort 2 Placebo f/u (low ESSDAI / high ESSPRI) n = 100 ACR/EULAR 2017 classification criteria fulfilled criteria classification 2017 ACR/EULAR Estimated primary completion date H2 2021

Clear improvement in CFZ533 vs A 48-week, 6-arm, randomized, double-blind, placebo-controlled multicenter trial to assess the placebo (mean delta = 5.6 by week 12) safety and efficacy of multiple CFZ533 doses administered subcutaneously in two distinct populations of patients with Sjögren’s Syndrome

70 Novartis R&D Day | December 5, 2019 Advancing iscalimab in a range of indications through 2020-26

2019 2020 2021 2022 2023 2024 2025 2026 . Phase 2b study in Kidney Kidney Transplantation to support Transplant early registration and Liver conditional approval Transplant . Anticipated launch in Sjögren’s Syndrome 2023 with projected

Systemic blockbuster sales potential Lupus . Additional indications under Erythematosus consideration Lupus Nephritis Phase 2a Hidradenitis Phase 2b Suppurativa Phase 3

71 Novartis R&D Day | December 5, 2019 Ligelizumab (QGE031) Key highlights

~40% of treated chronic idiopathic urticaria (CIU) / chronic Humanized anti-IgE spontaneous urticarial (CSU) patients in top 11 countries not monoclonal antibody adequately controlled Ligelizumab aiming to become first-choice biologic after anti- histamine therapy ~100 fold improved affinity1 to bind to IgE over Xolair®, Phase 2 data showed clear-dose response relationship2 More patients achieved CSU symptom control with ligelizumab vs. Xolair® as early as week 12; complete clinical responses sustained in over 50% of patients throughout 1 year of treatment Phase 3 superiority studies vs. Xolair® ongoing in CSU; first results and filing expected end-2021

1. Manuscript accepted for publication 2. Maurer M., et al, N Engl J Med. 2019. 381(14): 1321–32 CSU/CIU greatly diminishes QoL with unpredictable onset of itch, hives and angioedema

Urticaria classification Unmet need

Urticaria classification1 1.3m+ CIU/CSU patients are still inadequately controlled

Acute Chronic Symptoms daily/almost 1.3m Treatment gap Symptoms for <6 weeks daily for ≥6 wks 1.3m patients inadequately controlled, not receiving Bx 100k 100k (15%) of eligible patients treated with Bx Inducible Spontaneous/ Idiopathic 2.1m Specific trigger, e.g. temperature, No obvious external 2.1m patients controlled pressure, cholinergic specific trigger with up to 4-fold second generation antihistamines

Known causes Unknown causes 3.4 million treated CIU/CSU patients CSU symptoms: spontaneous (almost) daily itch, hives, and/or angioedema in Top 11 countries in 20192

1. Adapted from: Zuberbier T, et al. Allergy 2014;69:868–87. 2. Novartis data on file.

73 Novartis R&D Day | December 5, 2019 Differences between ligelizumab and omalizumab (Xolair®)

Ligelizumab recognizes a different part (epitope) of the IgE molecule than Xolair®

Higher affinity to IgE is due to more stable IgE-ligelizumab complexes being formed (slower off-rate)

More potently inhibits IgE binding to the high affinity IgE receptor (FcϵRI) on effector cells than to the low affinity receptor FcϵRII (CD23)

More potently inhibits mast cell and basophil activation

More potently inhibits IgE production

Gasser P. et al, EAACI 2019

74 Novartis R&D Day | December 5, 2019 Phase 2b study showed clear dose-response and better symptom control than Xolair®

A. Dose-response curve B. The proportion of patients achieving HSS7=01 at Week 12

600.6 Ligelizumab Omalizumab 300 mg 80

500.5 51.2 60 42.4 ) 0.4 % (

e 30.2 s n o p

s 0.3 25.9 e

r 30 40 Active Comparator 0 = 7 S S H 200.2 20

HSS7 = 0 response, % 0response, HSS7 = 100.1 0 0 0.0 HSS7 with = of 0 patients% Placebo Ligelizumab 0 24 40 72 120 160 200 240 Omalizumab Ligelizumab Ligelizumab 0 2 40 7272 QGE012031 dose (mg) 160 200 240 (n = 43) 300 mg q4w 24 mg q4w 72 mg q4w 240 mg q4w 4 Ligelizumab dose, mg (n = 85) (n = 43) (n = 84) (n = 85)

Primary objective achieved: Dose response relationship with respect to complete weekly hives response rate (HSS7=0) at Week 12

Maurer M., et al, N Engl J Med. 2019. 381(14): 1321–32. 1. HSS7=0, No hives over 7 days.

75 Novartis R&D Day | December 5, 2019 PEARL 1 and 2 studies (Phase 3) aim to demonstrate superiority vs. omalizumab

2 multi-center, randomized, double-blind, active/placebo-controlled studies with 1050 patients each 1° endpoint: absolute change from baseline in UAS71 at week 12 2° endpoints: . Complete absence of hives and itch at week 12, % of subjects with no itch, no hives . Improvement of itch severity score . Impact on subjects quality of life . Cumulative number of weeks with no itch, no hives

PEARL 1 and 2 recruiting strongly to finish enrollment in Q3 2020; first results and filing expected end-2021

1. UAS7 = Urticaria Activity Score over 7 days. NCT03580369. NCT03580356

76 Novartis R&D Day | December 5, 2019 Potential to go beyond CSU in other IgE / FceR1- mediated conditions

Chronic Inducible Urticaria (CINDU) Food Allergy

. Epidemiological estimates suggest a . Globally up to 520m people may suffer from food allergy, prevalence of up to 1/3 of CSU including 4-6% of children . Diagnosis is based on induction of . Huge burden for patients and families due to anxiety, itch/hives for >6 weeks by known triggers, social stigma, fear of death from anaphylaxis e.g. cold temperature, cholinergic, . High unmet need for effective, well-tolerated treatments pressure, heat, contact with water, sun

Auto-injector

. Allows for easy use through self-administration (or care-giver administration) in the home setting

77 Novartis R&D Day | December 5, 2019 Adriforant (ZPL389) Key highlights

Oral H4 receptor Despite recent entrants, significant unmet need remains in atopic dermatitis (AD) antagonist Developing first-in-class assets across the full spectrum of AD severity

Moderate to severe AD: Adriforant has blockbuster potential as a pre-biologics oral with pediatric-suitable safety profile; Phase 3 CEE321 program to start in 2021 Mild to moderate AD: CEE321 has potential to be first-in-class Topical Pan-JAK topical “soft” pan-JAK inhibitor, without safety concerns associated with oral JAKs; IND submission ongoing inhibitor Adriforant reduced atopic dermatitis severity by 50%

. First in class H4 receptor antagonist, distinct from antihistamines . Once-daily oral treatment for adults and children suitable for long-term use . Efficacy at 30mg appears to not have plateaued at week 8 . Ongoing Phase 2b study exploring higher dose and longer treatment duration of 16 weeks . Tested in 137 heatlhy volunteers and 281 patients with AD; favorable safety profile . Phase 3 program to start in 2021

Werfel et al. (2019). Efficacy and safety of the histamine H4 receptor antagonist ZPL-3893787 in patients with atopic dermatitis. J Allergy Clin Immunol p. 1830- 1837. EASI: Eczema Area Severity Index

79 Novartis R&D Day | December 5, 2019 CEE321 has potential to be the first-in-class topical “soft”1 pan-JAK inhibitor

CEE321 in skin AD biomarker inhibition . Designed to achieve strong therapeutic effect in skin and no systemic effects, and therefore Epidermis suitable for children . Good skin penetration in human skin ex-vivo . Strong inhibition of atopic dermatitis Dermis P-STAT biomarkers in stimulated human skin . Soft drug confirmed in minipigs: concentration in skin >25000-fold higher than in blood . IND submission ongoing

1 ‘’soft’’ = clinically irrelevant systemic exposure

80 Novartis R&D Day | December 5, 2019 Opportunity in atopic dermatitis market prior to biologics

Mild Moderate Severe

9.4 million diagnosed atopic dermatitis1 patients in the US

Topical “soft” pan-JAKi CEE321

Oral H4R antagonist Adriforant (ZPL389) Managed by a combination of topical Unresolved symptoms on topical Patients treated with injectable therapies (corticosteroids, topical SoC – managed by injectable biologic (DUPIXENT®). Emerging calcineurin inhibitors & EUCRISA™) biologic DUPIXENT® (direct against oral JAKs may have safety questions – need for safe and effective steroid IL4Rα) – need for oral drug for and monitoring requirements free topical therapy patients with better safety than oral JAKs 40% ~ 3.7m1 36% ~ 3.4m1 24% ~ 2.2m1

Significant unmet need for patients unresolved on existing topical therapies in pre-biologic space

1. Source: DRG Report on Atopic Dermatitis DUPIXENT® is a registered trademark of Sanofi Biotechnology EUCRISA™ is a registered trademark of Pfizer

81 Novartis R&D Day | December 5, 2019 LNA043 Key highlights

Cartilage anabolic Novartis has a pipeline of potential disease-modifying drugs targeting inflammation and regeneration of cartilage – LNA043 a agent frontrunner

>200m people globally suffer from osteoarthritis (OA) in the knee or hip; prevalence is rising with an aging and increasingly obese population

Approved treatments target pain and inflammation only, there are no disease-modifying treatments available

LNA043 targets the damaged cartilage, modulates several pathways involved in cartilage development / regeneration; Phase 2b initiation planned for early 2021 Cartilage repair after intra-articular injection of LNA043

Cartilage defect in the knee .... 4 weeks after single intra-articular Lower part of the femoral trochlea LNA043 injection

Well defined defect Regenerated tissue filled with blood with increase in proteoglycans

Cartilage defect is the donor site for an autologous Sodium MRI chondrocyte implantation after cartilage injury

3D reconstructions from powerful 7 Tesla (7T) Magnetic Resonance Imaging (MRI)

83 Novartis R&D Day | December 5, 2019 Pipeline of potential disease-modifying drugs in osteoarthritis

High unmet need Pipeline targeting cartilage and inflammation

Frontrunner

PhasePhase1 1 Inflammasone inhibitor

Pre-clinical Cartilage LNA043 anabolic High-resolution proton-density MRI of tibia-femoral cartilage obtained at 7 Tesla Cartilage anabolic RHH466

PhasePhase1 1 . OA affects >200m people worldwide and will increase Cartilage anabolic with aging and obese population LRX712 . 3rd most rapidly rising condition associated with disability Starting . No disease modifying treatments available, existing Phase 2 in 2021 treatments only impact signs and symptoms (pain); last resort is joint replacement

84 Novartis R&D Day | December 5, 2019 Tropifexor (LJN452) Key highlights

Highly potent FXR NASH is a complex, progressive disease with no approved therapies; while multiple compounds are in development, only agonist limited efficacy demonstrated to date

Novartis is leading oral combination development with tropifexor as the backbone and has built development collaborations (Allergan, Pfizer, IFM, Pliant) to access further MOAs

FLIGHT-FXR Part C interim data highlight the potential of tropifexor with dose-dependent reductions in hepatic fat, ALT and body weight; full readout May 2020 NASH is a complex, progressive disease caused by fat infiltration into the liver

Disease pathology and unmet need

. 6% of the G7 population has NASH . Complex disease with multiple disease processes (fat insult, inflammation, fibrosis) . Expected to be the leading cause of liver transplant in the US by 2021 . Most rapidly growing cause of hepatocellular carcinoma amongst US patients listed for liver transplantation2 . There are currently no approved treatments

86 Novartis R&D Day | December 5, 2019 November data release showed tropifexor impact on weight loss and liver fat reduction

Rapid and sustained decrease in ALT Dose dependent reduction of liver fat Significant weight loss at week 12

Alanine Aminotransferase (U/L) Serum Hepatic Fat Fraction (%) Weight (kg)

0 0 0

-10 -1

-20 -20 -2

-30

-40 -3 -40

Mean Mean change from baseline (95% CI) -4

0 1 2 4 6 8 12 0 1 2 4 6 8 12 Geometric Geometric mean % change from baseline (95% CI) Geometric Geometric mean % change from baseline (95% CI) -60 Analysis Week Analysis Week

Placebo TXR 140 mcg TXR 200 mcg

. Tropifexor is a highly potent FXR agonist . Produces robust, dose-dependent reductions in hepatic fat, weight and serum alanine aminotransferase in patients with fibrotic NASH after 12 weeks of therapy: FLIGHT-FXR Part C interim results . Dose-proportional exposure with no signal of liver injury

87 Novartis R&D Day | December 5, 2019 Given high NASH complexity, we expect combinations to be the future of treatment

Anti-inflammatory/Anti-fibrotic Novartis is aggressively 1 CVC leading oral combination CCR2/5 development with tropifexor as LYS006 Licogli- the backbone, and has built LTA4 flozin hydrolase inh. SGLT1/2 development collaborations (Allergan, Pfizer, IFM, Pliant) to Anti-inflammatory Tropifexor Anti-metabolic Multimodal access further MOAs KHK2 / NLRP3 2 Inflammasome DGAT2 aVb13 integrin inhibitor Anti-fibrotic

1. External clinical collaboration with Allergan. 2. External clinical collaboration with Pfizer. 3. External collaboration with Pliant.

88 Novartis R&D Day | December 5, 2019 Q&A Jeff Legos PhD Global Head, Oncology Development Unit Deep pipeline across four distinct platforms is expected to continue driving differentiation and growth

Targeted therapies Immunotherapies Radioligand Cell & Gene

Anchor commercial assets

ABL001 in CML (3L & 1L add-on) ACZ885 in 177Lu-PSMA-617 in prostate cancer Kymriah® in Select pipeline adjuvant NSCLC st Adakveo® in sickle cell disease ⎼ 177Lu-PSMA-R2 in prostate cancer – r/r DLBCL after 1 relapse assets1 and ⎼ 1st line NSCLC – r/r follicular lymphoma 177 Alpelisib in ⎼ 2nd line NSCLC Lu-NeoB in multiple solid tumors – combinations (pembro; ibrutinib) opportunities ⎼ HER2+ advanced breast cancer PDR001+Tafinlar®+Mekinist® in 177Lu-FF58 in glioblastoma in r/r DLBCL ⎼ TNBC – 1st line high risk pediatric and ⎼ Head & neck metastatic melanoma young adult ALL ⎼ Ovarian cancer PDR001 combinations (platform) in – r/r Adult ALL ⎼ PROS metastatic melanoma INC280 in NSCLC, single agent PDR001+LAG525+carboplatin in TNBC Other targets: BCMA&CD19, Jakavi® in steroid-refractory acute and PDR001+INC280 in 2L NSCLC CD22&CD19, CD123, EGFRv3 chronic GvHD, and combinations (platform) MBG453 in MDS, AML in myelofibrosis VPM087 in CRC and RCC Kisqali® in adjuvant breast cancer For references see slides 179-180

91 Novartis R&D Day | December 5, 2019 Targeted therapies Immunotherapies Radioligand Cell & Gene MBG453 Key highlights

Anti-TIM-3 Due to its selective expression on leukemic stem cells, TIM-3 presents a unique opportunity in MDS/AML to target both immune monoclonal antibody and myeloid cells, in contrast to in solid tumors where data so far are disappointing

MBG453 is the only TIM-3 mAb currently being investigated in MDS and AML, with the potential to be first-in-class

Encouraging efficacy and favorable safety profile emerging from Phase 1 trial to be presented in ASH Oral Session

Broad ‘STIMULUS’ trial program initiated in myeloid malignancies . Pivotal Phase 2 study in Higher-Risk MDS ongoing, with first susbmission expected 2021 . Phase 2 studies in Unfit AML planned to start in H1 2020 High unmet need in MDS and AML

Overall survival Tolerability Lack of innovation

5-yrs survival is poor1: Significant toxicity impacts the No regulatory approvals benefit of current therapies 2 20% for HR-MDS in over 10 years in HR-MDS (intensive chemotherapy, 28.3% for AML hypomethylating agents, HSCT)

. Higher Risk-MDS (HR-MDS) is a more aggressive type of MDS where patients have a worse prognosis and a higher chance of progressing to AML . Unfit AML patients are often older and have general health status that precludes intensive chemotherapy . Age at diagnosis is ~75 years for MDS and ~68 years for AML . G7 annual incidence is ~15,300/year for HR-MDS and ~13,300/year for unfit AML3

For references see slides 179-180 MDS = Myelodysplastic Syndromes; AML = Acute Myeloid Leukemia IPPS (International Prognostic Scoring System) risk categorization in MDS. “Higher Risk” ~34% (11% High Risk, 23% Intermediate-2 risk).

93 Novartis R&D Day | December 5, 2019 Rationale for targeting TIM-3 in hematology: targeting immune and myeloid cells

MBG453 simultaneously targets immune and myeloid leukemic cells

. TIM-3 is an inhibitory receptor1 expressed on2,3,4: – T cells and innate immune cells (myeloid & dendritic cells) – Leukemic stem cells (LSCs) but not normal hematopoetic stem cells . Expression of TIM-3 correlates with severity and progression in MDS and AML2,5 . Anti-leukemic effect of TIM-3 blockade in MDS/AML models2,3 . In vitro data shows that targeting TIM-3 with inhibitory antibody MBG4533,6,7: – Re-awaken immunity to restore an anti-leukemic immune response

* Or antigen-presenting cell (APC) – Selectively target the LSC and blasts ** Other TIM-3 ligands include: Galectin-9, HMGB1, and CEACAM1

For references see slides 179-180

94 Novartis R&D Day | December 5, 2019 Ongoing Phase 1 trial in HR-MDS and AML shows encouraging safety and preliminary efficacy data

Combination of MBG453 and decitabine . Signal of efficacy in combination with hypomethylating agent (decitabine) n Responders with durable responses HR-MDS 16 8 (50%) CR/mCR – HR-MDS responders duration of exposure 3 to 19 months, with no progressions Relapsed-refractory 17 10 (59%) CRi/BM blast response1 – AML responders duration of exposure 2 to 18 AML months AML first line 14 7 (50%) CR/PR/BM blast response2 . Favorable safety profile

1 Including 5 (29%) with a CRi – Most AE consistent with backbone decitabine 2 Including 4 (29%) with a CR or PR therapy (blood cytopenias, febrile neutropenia) BM response: decrease in BM blasts ≥50% from baseline – Limited immune-related AE (2 transaminitis, 1 Update, including durability of response, will be provided in gGT increase, 1 arthritis) an oral session at ASH on December 9 . Short infusion time (30 mins)

Borate (Abstract # 570, ASH 2019)

95 Novartis R&D Day | December 5, 2019 Phase 2 trial, STIMULUS-MDS-1, in HR-MDS ongoing

MBG453 IV Q2W (400 mg Day 8 and Day 22) + Key Patients aged 1:1 randomization Decitabine IV3 or azacitidine SC or IV4 Primary ≥ 18 years with (stratification by secondary endpoints intermediate & high HMA1 and IPSS-R2) endpoint Placebo IV Q2W CR and PFS risk MDS n = 120 OS (Day 8 and Day 22) + Decitabine IV3 or azacitidine SC or IV4

28-day cycles until disease progression

. First patient enrolled in July 2019; enrollment ongoing as planned . US submission planned for 2021 with Phase 2 study . EU submission planned with Phase 3 study (trial start planned for H1 2020) NCT03946670

1. Hypomethylating agent (decitabine or azacitidine). 2. IPSS-R Revised International Prognostic Scoring System. 3. Decitabine: 20 mg/m2 D1–5. 4. Azacitidine: 75 mg/m2 D1–7 or D1–5 and 8–9. D, day.

96 Novartis R&D Day | December 5, 2019 Building MBG453 backbone across myeloid diseases

STIMULUS program

HR-MDS Unfit AML Novel combinations

STIMULUS-MDS-1 STIMULUS-AML-1 MDS/AML: Phase 2 ongoing, started Phase 2 combo HMA + Phase 1 combo with HDM2011 July 2019 venetoclax, planned ongoing H1 2020 STIMULUS-MDS-2 Myelofibrosis: ® Phase 3, planned H1 2020 STIMULUS-AML-2 Phase 1b/2 Jakavi combo Phase 2 combo with HMA, ongoing planned H1 2020

NCT03946670 NCT04150029 NCT03940352, NCT04097821

1. HDM201: mdm2 inhibitor

97 Novartis R&D Day | December 5, 2019 Targeted therapies Immunotherapies Radioligand Cell & Gene Asciminib (ABL001) Key highlights

Novel, potent, and Unmet need remains high in CML specific allosteric As a more specific allosteric inhibitor, asciminib is being studied inhibitor of BCR-ABL1 to determine if it has an improved safety profile over currently approved TKIs

Enrollment in Phase 3 3rd line CML (ASCEMBL) study completed ahead of plan, with readout expected in H2 2020 Unmet needs remain high in CML

High failure rates TKI intolerance / Deep molecular response in later lines1 TKI cycling1,2,3 (DMR) in 1st line4,5,6

~75% of 3rd line patients With each line of therapy >50% of patients in 1st line progress on available more patients become do not achieve DMR, therapies intolerant to existing TKIs which is associated with improved survival and is entry point for TFR

For references see slides 179-180. CML, Chronic Myeloid Leukemia; DMR = MR ≥ 4.0; TFR, Treatment Free Remission; MR, Molecular Response; TKI, Tyrosine Kinase Inhibitor.

99 Novartis R&D Day | December 5, 2019 Asciminib (ABL001): A novel, potent, and specific allosteric inhibitor of BCR-ABL11-4

BCR-ABL1 Protein . Asciminib is different from other TKIs as it is thought to bind to the myristoyl pocket of BCR-ABL1 ATP-competitive TKIs (ATP site) . Asciminib is being studied to determine if it: – Reduces risk of off-target effects with a potentially better safety profile – Is active against TKI-resistant mutations – Can be combined with TKIs to potentially achieve faster and deeper response rates and impede the emergence of drug resistance Asciminib (myristoyl site)

For references see slides 179-180. ATP = Adenosine Triphosphate; TKI = Tyrosine Kinase Inhibitor.

100 Novartis R&D Day | December 5, 2019 ABL001X2101: Promising early efficacy and safety data for single agent asciminib in CML1

100

80 Molecular response Molecular response within 6 mo2,3 within 12 mo3 60

40 ≥ 1-log ≥ 1-log MMR: 20 reduction: MMR: reduction: 42% (16/38) 20% (10/50) 48% (12/25) Patients with response, % with response, Patients 0 30% (10/33) > 0.1% IS ≤ 10% IS Molecular disease > 0.1% IS ≤ 10% IS Disease status at baseline

. First-in-human study enrolled heavily pre-treated CML patients (≥2 TKIs) . Asciminib showed increased response rates in patients who failed on prior TKIs . Asciminib was well-tolerated across a wide-range of doses (20 mg - 200mg BID) ─ Most common grade 3/4 AEs suspected related to asciminib were lipase increase (8%), thrombocytopenia (7%), anemia (5%), and neutropenia (4%)

For references see slides 179-180

101 Novartis R&D Day | December 5, 2019 ABL001A2301: Enrollment for asciminib 3rd line CML study completed 5 months ahead of plan1

Asciminib . CP-CML with ≥ 2 prior 40 mg BID ATP-competitive TKIs (n = 148) . Failure or intolerance of Primary endpoint Survival the most recent TKI2 n = 222 pts MMR at 24 weeks follow-up . No T315I or V299L bosutinib-resistant Bosutinib mutations 500 mg QD (n = 74)3

. Enrollment in pivotal Phase 3 study completed in October 2019 . Read-out planned in H2 2020, first submission in Q1 2021

For references see slides 179-180. ATP = Adenosine Triphosphate; CML-CP = Chronic Myeloid Leukemia in Chronic Phase; TKI = Tyrosine Kinase Inhibitor; MMR = Major Molecular Response.

102 Novartis R&D Day | December 5, 2019 Targeted therapies Immunotherapies Radioligand Cell & Gene Canakinumab Key highlights (ACZ885)

Monoclonal antibody Canakinumab is a potential therapy to address unmet need across Stage ll – IV NSCLC targeting IL-1β First mover advantage in emerging field of tumor-promoting inflammation

1st and 2nd line studies recruiting ahead of schedule, planned filing in 2021

Licensed in additional agents targeting the inflammasome, taking forward in cancer and other inflammatory diseases Broad Novartis development programs with IL-1β

CANTOS Potential

To transform the To leverage inflammasome Canakinumab Anti-inflammatory SoC across all To transform the SoC across pipeline to transform SoC Thrombosis Outcomes Study stages of NSCLC other tumor types beyond cancer

Reduced diagnosis of overt NSCLC and CANOPY program Pancreatic canakinumab in combination Sarcoidosis with canakinumab cancer: with spartalizumab + SoC fatal lung cancer observed in Sickle cell disease Alzheimer’s disease canakinumab arms: CRC/RCC/ gevokizumab in combination GEC: with SoC . Rate of lung cancer: Dose-dependent effect, 67% relative risk reduction TNBC: canakinumab in combination with spartalizumab & LAG525 . Rate of lung cancer mortality: Dose- dependent effect, 77% relative risk MF: canakinumab in combination with MBG453 + NIS793 or reduction Jakavi® Demonstrated the prognostic role of CRP MDS: canakinumab in combination and IL-6 in lung cancer diagnosis with MBG453

104 Novartis R&D Day | December 5, 2019 Worse outcomes in patients with elevated inflammation, supporting role of tumor-promoting inflammation

ASA404A2301: OS by baseline CRP Kaplan-Meier analysis in NSCLC (N=42)

N = 351

N = 255

Based on internal data Source: livanainen S, et al. ESMO Open 2019; 4

Several studies have identified elevated hs-CRP associated with worse outcomes for cancer patients . Elevated hs-CRP is correlated with shorter survival and OS in NSCLC patients . Poor progression-free and overall survival on cancer patients treated with PD-1 inhibitors

105 Novartis R&D Day | December 5, 2019 IL-1β blockade is thought to reduce tumor-promoting factors and increase tumor-suppressive factors

Monocytes Neutrophils 1500 8000 ** * Isotype 6000 aIL-1b 1000 Docetaxel Tumor-promoting Tumor-suppressive 4000 Docetaxel + aIL-1B

r 500 . Tumor-associated . NK cell o 2000

t 0 0

macrophages (TAM) . CD8+ cytotoxic T cell g m gMDSC TAM2 mMDSC

e 1500 8000 1000

. Myeloid-derived p * 6000 800 1000 suppressor cells (MDSC) 600 4000 400 500 . Regulatory dendritic cells 2000 200 . Regulatory T cells 0 0 0 . Neutrophils Syngeneic breast cancer model shows a decrease in immunosuppressive cells following treatment with anti-IL-1β and docetaxel that has the potential to restore the balance

For references see slides 179-180

106 Novartis R&D Day | December 5, 2019 CANOPY: Three Phase 3 studies actively recruiting

CANakinumab Outcomes in Patients with NSCLC StudY

Indication Patient population Trial design Status as of Dec 2019 Planned filing Adjuvant High-risk Stage II-III Canakinumab vs. placebo (n=1500 ~35% patients enrolled 2022 NSCLC with 1:1 randomization) after post- (CANOPY-A) resection chemotherapy

1st line NSCLC Non-mutated, no prior Platinum doublet chemotherapy and >50% patients enrolled 2021 (CANOPY-1) treatment for metastatic pembrolizumab with or without disease or Stage III canakinumab (n=600 with 1:1 unresectable randomization)

2nd line NSCLC Non-mutated with no more than Docetaxel with or without >50% patients enrolled 2021 (CANOPY-2) 2 prior lines of metastatic canakinumab (n=226 with 1:1 treatment (PD-1 ± Chemo) randomization)

Neoadjuvant NSCLC Stage IB - IIIA Canakinumab, First patient expected to Not registrational (CANOPY-N; canakinumab+pembrolizumab or be enrolled in Q4 2019 study Phase ll) pembrolizumab (n=110 with 2:2:1 randomization)

107 Novartis R&D Day | December 5, 2019 Emerging clinical biomarker data from safety run-in consistent with inhibition of IL-1β pathway

% with CRP reduction % of patients with Study Treatment from baseline >30% reduction in CRP1

1st line NSCLC Pembro + chemo + ACZ885 100% (n=5) 40% (2/5)2 (CANOPY-1)

2nd line NSCLC Chemo + ACZ8852 100% (n=3) 67% (2/3)2 (CANOPY-2)

Biomarker data from safety run-in supported starting randomized parts of both CANOPY-1 and 2 . Data is consistent with inhibition of IL-1β signaling at the doses and regimens used . First prospective evidence that canakinumab inhibits the IL-1β pathway in cancer patients

1. 30% reduction defined in Gevokizumab study as biologically relevant level to determine dose. 2. CANOPY-1 and CANOPY-2 results are based on 1.5 fold reduction in CRP, rather than 30% reduction.

108 Novartis R&D Day | December 5, 2019 Q&A Agenda Time includes Q&A

13:00-13:30 Opening Vas Narasimhan Portfolio Overview John Tsai

Research 13:30-14:00 NIBR Jay Bradner Platforms Cell Therapy, Gene Therapy, Molecular Glues

15:45-16:00 Break

17:30-17:45 Closing Vas Narasimhan

110 Novartis R&D Day | December 5, 2019 John Tsai MD Global Head Drug Development and Chief Medical Officer Zolgensma® Key highlights

One-time gene therapy Positive momentum for Zolgensma® following US approval for SMA Regulatory action anticipated in EU Q1 2020 and Japan H1 2020, with additional global filings and approvals anticipated in 2020

Robust clinical development program with SPR1NT data in pre- symptomatic SMA and new STRONG data in SMA Type 2 anticipated in H1 2020 Zolgensma® IV expanding beyond successful US launch

EU Broad access . ~90% commercial lives and ~30% public lives CHMP opinion covered anticipated in Q1 2020

. >50 treating institutions across US - majority Japan of leading academic centers of excellence Decision anticipated Patient demand having prescribed since launch in H1 2020 and opportunity . 30% of newborns screened, expected to reach 70% end of 2020 Canada Decisions Brazil anticipated in 2020 Argentina Broad patient . Even distribution across age, SMA types and Saudi Arabia profile incident and prevalent populations Australia . >50% switches from nusinersen South Korea Taiwan

113 Novartis R&D Day | December 5, 2019 Broad SMA clinical trial program

SMA Type/SMN2 Delivery copy number 2014-2017 Q1 2018 Q2 2018 Q3 2018 Q4 2018 2019 2020 Completion Intravenous Pre- 2022 (IV) symptomatic, Phase 3 2 or 3 copies of 30 patients, fully enrolled – data anticipated at CureSMA (June) SMN2 Type 1 2033 Long-term follow-up 15 patients 13 patients enrolled – data anticipated at CureSMA (June) completed 2020 Phase 3 22 patients, fully enrolled – data anticipated at MDA (March) 2021 Phase 3 32 patients, fully enrolled – data anticipated at ICNMD (July)

2021 Phase 3 2 patients

Intrathecal 3 SMN2 copies 2021 (IT) Phase 1 32 patients; fully-enrolled in mid-dose cohort – data anticipated at AAN (April)

Type 1, 2, 3 TBC Pending

114 Novartis R&D Day | December 5, 2019 Cosentyx® Key highlights

Anti-IL17A Psoriasis, psoriatic arthritis and ankylosing spondylitis approved as foundation indications, with proven sustainable efficacy and monoclonal antibody safety demonstrated in >250,000 patients over the last 5 years

Potential 4th indication in non-radiographic axial spondyloarthritis adds potential to address the complete axSpA spectrum; submitted in Europe, further submissions pending

Ambitious lifecycle management plan ongoing with potential to deliver over 10 indications • Upcoming readouts: Juvenile idiopathic arthritis (JPsA & ERA) Phase 3 interim analysis Q1 2020; giant cell arteritis Phase 2 Q1 2020 • Upcoming trial initiations: PsA/axial SpA IV regimen Phase 3 Q4 2019, lupus nephritis Phase 2 Q1 2020; lichen planus Phase 2 Q2 2020 • Upcoming submissions: Hidradenitis suppurativa Q2 2022 Expanding Cosentyx® from 3 to 10+ indications

Lich. Plan RA AS nr-axSpA HS Super ped. JPsA IV/IV PSO PsA GCA LN Oral IL17 Psor ERA PsA/AS

2014 2015 2020 2022 2023 2024 2025 2026 ≥2027

PsO: Psoriasis ped PsO: Juvenile psoriasis Lich. Plan: Lichen planus AS: Ankylosing spondylitis JPsA ERA: Juvenile arthritis / enthesitis- RA super: Rheumatoid arthritis PsA: Psoriatic arthritis related arthritis GCA: Giant Cell arteritis NR ax-SpA: Non-radiographic axial SpA HS: Hidradenitis suppurativa LN: Lupus nephritis IV PsA/AS: IV regimen in PsA and AS

First potential approvals

116 Novartis R&D Day | December 5, 2019 PREVENT met primary endpoint, submitted in Europe, US submission imminent

ASAS40 response in TNFi-naïve patients . Secukinumab 150mg met ASAS40 primary endpoint at Week 16 and Week 52, with 60 significant improvements in physical function, quality of life and objective signs of inflammation 50 42.2 * † ‡ † § § ‡ . The safety profile of secukinumab was § † * † * 39.8 40 ‡ § § consistent with previous reports § 41.5 35.4 § † § 30 § ‡ ‡ ‡ † ‡ ‡ . Largest interventional trial to date with a biologic 29.2 % responders % 20 19.9 in nr-axSpA (555 patients)

10 Secukinumab 150 mg s.c. Secukinumab 150 mg s.c. Placebo . nr-axSpA indication enables us to address the with loading (N = 164) without loading (N = 166) (N = 171) 0 full spectrum of axSpA 0 4 8 12 16 20 24 28 32 36 40 44 48 52 – EU: submission achieved in Aug 2019 Weeks – US: submission planned in Dec 2019

*p<0.0001; †p<0.001; §p<0.01 and ‡p<0.05 vs placebo. (p values at Weeks 16 and 52 are adjusted for multiplicity of testing). – JP: submission planned in Dec 2019 Data presented as non-responder imputation though Week 52. – CN: submission plan under discussion

117 Novartis R&D Day | December 5, 2019 SUNRISE & SUNSHINE in hidradenitis suppurativa

Disease overview . Chronic skin condition that causes small, painful lumps to form under the skin . Tends to start after/at puberty; mean age of onset: 3rd decade; interval from onset of symptoms to diagnosis: 7.2 years . F>M (2-5:1) . Risk factors: Obesity and smoking . Significant impact on quality of life due to chronic pain/scarring

Prevalence . Affects ~3 million US/EU5 patients

Current treatment . Adalimumab, 40mg weekly, approved in 2015

Two Phase 3, randomized, double-blind, multicenter studies to evaluate the efficacy and safety of secukinumab vs. placebo in patients with moderate to severe hidradenitis suppurativa

Planned enrollment 2x471 patients Population Moderate to severe Primary efficacy endpoint at Week 16 HiSCR Study start date February 2019 Anticipated completion date May 2022

HiSCR, Hidradenitis Suppurativa Clinical Response (defined as ≥50% decrease in Abscess and Inflammatory Nodule (AN) count with no increase in the number of abscesses or in the number of draining fistulae)

118 Novartis R&D Day | December 5, 2019 TitAIN in giant cell arteritis (GCA)

Disease overview . An inflammatory vascular syndrome with features of cranial and/or large-vessel vasculitis and systemic inflammation . Among the most common inflammatory rheumatic diseases in the elderly . Symptoms: Headache, jaw claudication, fever, polymyalgia . Irreversible vision loss due to ischemic events is common and feared

Prevalence . Between 24 and 278 per 100,000 in the EU and US

Current treatment . Glucocorticoids are the standard treatment even though glucocorticoid-related adverse events occur in up to 85% of treated cases . Actemra (IL-6), the only approved biologic for GCA, has a broad label

Phase 2, randomized, double-blind, multicenter study to evaluate the efficacy and safety of secukinumab vs. placebo in patients with newly diagnosed or relapsing GCA

Planned enrollment 50 patients Population Biologic-naïve, new onset or relapsing Primary efficacy endpoint at Week 28 Sustained remission1 Study start date January 2019 Anticipated completion date May 2021

1. Defined as patients without flare (recurrence of GCA signs or symptoms and/or ESR≥30mm/hr and/or CRP≥10mg/L attributed to GCA).

119 Novartis R&D Day | December 5, 2019 PRELUDE in lichen planus

Disease overview . Disorder of unknown origin characterized by flat-topped bumps that are itchy, rough, scaly, and reddish purple in color . Etiology unclear, autoimmune mechanism involving activation of T cells has been proposed . Can affect the skin, mouth, genitalia, scalp, or nails

Prevalence . Estimated in the range of 0.4% to 1% of the general population

Current treatment . First-line treatment typically a topical corticosteroid, such as betamethasone dipropionate or diflorasone diacetate . Systemic steroids, phototherapy, or oral retinoids are also used in some cases

A proof-of-concept study to evaluate the efficacy, safety and tolerability of secukinumab vs. placebo in adult patients with lichen planus

Planned enrollment 108 patients Primary efficacy endpoint at Week 16 Study start date April 2020 IGA ≤2 Anticipated completion date May 2022

120 Novartis R&D Day | December 5, 2019 Beovu® Key highlights

Humanized single- Ex-US marketing applications in wet AMD under review, key region/country decisions due H1 2020 chain Fv antibody Broad clinical program expanding body of evidence in fragment inhibitor of chorioretinal diseases VEGF TALON study, head-to-head superiority study versus aflibercept for durability in wet AMD, with first readout mid 2021 Phase 3 program in DME due to readout in 2020, first submission in 2021 Beovu® submissions completed in key markets with regulatory action dates throughout 2019 and 2020

Selected submission for Beovu® in wAMD

BLA approval MAA validated “Procedure with Feb 2019 March 2019 April 2019 Oct 7, 2019 prior notification” submission submission submission CHMP opinion granted Permanent J code expected Q4 2019 Decision expected Decision expected Decision expected Jan 1, 2020 Feb 2019 Q1 2020 Q1 2020 Q1/Q2 2020 submission

Decision expected Q1 2020

wAMD = Wet Age-Related Macular Degeneration; BLA = Biologics License Application; CHMP = Committee for Medicinal Products for Human Use

122 Novartis R&D Day | December 5, 2019 Beovu® LCM expanding weight of evidence in AMD and exploring potential new indications

AMD DME RVO PDR 2020-20221 20212 20232 20232 CONDOR3 A head-to-head superiority study Phase 3 non-inferiority vs aflibercept evaluating treatment interval duration study vs. laser to support global registration in an identical Treat-to-Control (TtC) regimen Phase 3 head-to-head Phase 3 non-inferiority studies non-inferiority studies vs. of brolucizumab q12w/ q8w vs. aflibercept to support aflibercept q8w to support global registration A head-to-head non-inferiority study vs. aflibercept global registration evaluating the efficacy and safety of q4w treatment

PCV study Randomized, open-label, multicenter study A head-to-head non-inferiority assessing the safety & efficacy of two different study vs. aflibercept evaluating dosing regimens of brolucizumab 6 mg in patients the efficacy and safety of q4w with symptomatic macular PCV treatment

LCM – Life cycle management AMD = Age-related macular degeneration, DME = Diabetic Macular Edema, RVO = Retinal vein occlusion, PDR = Proliferative diabetic retinopathy; q4w = every 4 weeks 1. Expected read outs. 2. First planned submission. 3. Study name not confirmed.

123 Novartis R&D Day | December 5, 2019 TALON study vs. aflibercept reading out 2022

Talon study (n=692) A superiority study Randomized, double-masked, Phase 3b, multicenter study assessing aiming to demonstrate that the efficacy and safety of brolucizumab 6 mg compared to aflibercept 2 mg in TtC regimen in treatment-naïve patients with nAMD brolucizumab allows longer intervals than aflibercept in an identical 1:1 randomization at baseline 4-week-adjustment TtC regimen in Brolucizumab 6mg (n=346) Aflibercept 2mg (n=346) patients with wet AMD

Week 32: Co-primary endpoints Superiority for interval distribution Non-inferiority for BCVA change from baseline

Week 64: End of Study

Interim read out: Q2 2021 Final read out: Q1 2022

BCVA – Best corrected visual acuity. TtC – Treat to Control. nAMD - neovascular age-related macular degeneration.

124 Novartis R&D Day | December 5, 2019 Ofatumumab (OMB157) Key highlights

Monoclonal antibody Ofatumumab is a fully human antibody and B-cell therapy under development for relapsing multiple sclerosis, with a subcutaneous anti-CD20 targeting dosing regimen tailored for MS patients B cells Phase 3 data in two randomized double blind active controlled studies presented September 2019 (ECTRIMS, Stockholm) Planning to complete regulatory filings in December (US) 2019 and January (EU) 2020 Ofatumumab: high efficacy disease-modifying therapy with the potential to be used early and broadly

Strong efficacy results vs. Planned submissions starting teriflunomide (ASCLEPIOS I&II) December 2019 Planned . Superior efficacy for relapses, MRI activity Country submissions . Substantial reductions in 3- and 6-month disability progression1 USA Dec 2019 . No significant safety signals concerning infections/ malignancies EU Jan 2020 . Bioequivalence established between the pre-filled syringe (used in Ph3 study) and the auto-injector (BE Switzerland H1 2020 Study 2102) . Autoinjector supports patient friendly home Japan H2 2020 administration of ofatumumab

1. CDW, confirmed disability worsening and CDP, confirmed disability progression are interchangeable terms, defined by an increase ≥1.5 EDSS points for patients with baseline EDSS of 0, increase of ≥1.0 EDSS points patients with baseline EDSS of 1.0-5.0 and increase of t ≥0.5 EDSS points for patients with baseline EDSS of 5.5

126 Novartis R&D Day | December 5, 2019 Ofatumumab dosing regimen results in fast and sustained depletion of CD20+ B cells1

Lower Limit of Normal 80 cells/µL

8 cells/µL2

Ofatumumab dosing schedule

1. Modeling results based on Ph2a (OMS115102), Ph2b (MIRROR, OMS115102) and COMB157G2102 (BE Study, preliminary data), NVS data on file 2. Most relevant threshold observed in phase 2 data (MIRROR study conducted by GSK) for reduction of new Gd+ T1 lesions

127 Novartis R&D Day | December 5, 2019 Ofatumumab showed significant reductions in 12- and 24-week CDW Post-hoc analysis with revised definition used in OPERA trials1

12-week CDW 24-week CDW

13.3% 10.5%

9.6% 5.6% Risk reduction Risk reduction 36.6% p=0.002 45.9% p<0.001

Hazard ratio (95% CI): 0.634 (0.472; 0.851) Hazard ratio (95% CI): 0.541 (0.381; 0.768)

CDW = Confirmed Disability Worsening 1. Adapted from the OPERA trials, Hauser et al. 2017. A disability “progression” was defined as an increase from the baseline EDSS score of at least 1.0 point (or 0.5 points if the baseline EDSS score was >5.5) that was sustained for at least 12 (24) weeks.

128 Novartis R&D Day | December 5, 2019 Fevipiprant (QAW039) Key highlights

DP2 receptor Fevipiprant targets simple asthma control for patients in the ‘treatment gap’: ~45% of GINA 4/5 patients not sufficiently antagonist controlled despite availability of inhaled therapies and injectable biologics GINA 4/5 patients – particularly those with high blood eosinophils – are the target population for fevipiprant, based on mechanistic / Phase 2 data LUSTER Phase 3 studies in this target population are on track for readout Q1 2020 Fevipiprant development program is expanding in adult and pediatric asthma, as well as with new ongoing studies in asthmatics with nasal polyps and in COPD patients LUSTER to determine benefit in moderate-severe asthma; results on track for Q1 2020

GINA 4/5 asthma is the target population Comprehensive Phase 3 program to define full potential for fevipiprant

. DP2 / PGD2 pathway upregulated Exacerbation Core Results patients with severe, poorly controlled, 52 weeks registration expected Q1 2020 asthma1 GINA 4/5 . Fevipiprant efficacy increases with asthma severity2,3 Safety Core Interim results Up to 3 years registration expected Q1 2020 . Fevipiprant reduced sputum eosinophils GINA 3/4/5 to biologic levels (-72%) in Ph2 (A2208, mod.-sev. asthma)3 Lung function Supportive No significant improvement . Fevipiprant reduced airway smooth 12 weeks studies of FEV1 on top of ICS ± muscle mass by 16% in Ph2 (A2208), GINA 3/4 LABA5,6 thereby showing disease modifying Clean safety profile 7 potential4 confirmed

For references see slides 179-180.

130 Novartis R&D Day | December 5, 2019 . Novartis announced agreement to acquire The Medicines Company

. The acquisition of The Medicines Company is subject to satisfaction or waiver of customary closing conditions. Until closing, Novartis and The Medicines Company will continue to operate as separate and independent companies

. Inclisiran is an investigational product of The Medicines Company

131 Novartis R&D Day | December 5, 2019 Inclisiran Key highlights

GalNac-modified Phase 3 shows potent, durable, consistent LDL-C reduction >50% siRNA inhibiting Durable efficacy with only 2 subcutaneous injections per year, hepatic production of less patient abandonment PCSK9 ORION-4 outcome study designed to confirm MACE and CV mortality benefit over 5 years The Medicines Company expects submission in Q4 2019 in the US and Q1 2020 in Europe

Inclisiran is an investigational product of The Medicines Company. The acquisition of The Medicines Company is subject to satisfaction or waiver of customary closing conditions. Until closing, Novartis and The Medicines Company will continue to operate as separate and independent companies. Significant unmet needs in ASCVD treatment despite availability of PCSK9 mAbs

Significant unmet needs in ASCVD Shortcomings of current PCSK9 mAbs treatments

Adults WW have high LDL-C; ASCVD leading cause of Expensive Prices at launch above cost-effective benchmarks3 40% death WW Reimbursement Leading to 80% of PCSK9i claims being initially Patients across key markets with ASCVD or FH on hurdles rejected4 50m+ current SOC not at goal Affordability Leading to 50% abandonment rate for PCSK9i 7% Treated patients statin intolerant1 hurdles after 90 days5

Up to 26 injections per year6, and cold chain Patients treated with statins +/- ezetimibe do not meet Inconvenient 60%+ goal2 requirement

Persistent and underserved market in ASCVD Inclisiran could help tackle current issues with existing treatments

For references see slides 179-180 Inclisiran is an investigational product of The Medicines Company. The acquisition of The Medicines Company is subject to satisfaction or waiver of customary closing conditions. Until closing, Novartis and The Medicines Company will continue to operate as separate and independent companies.

133 Novartis R&D Day | December 5, 2019 ORION-4 outcome study designed to confirm MACE and CV mortality benefit over 5 years

Protocol overview CTTC model

Eligibility Age > 55 years, with ASCVD Prior MI, ischemic stroke, or peripheral artery disease High-risk patients with LDL-C values above 100 mg/dL

Sample size 15,000 patients (randomized 1:1 inclisiran: placebo)

Primary Composite MACE: powered for >25% reduction endpoint . CHD death . MI . Fatal or non-fatal ischemic stroke . Urgent coronary revascularization procedure

Secondary . A composite of CHD death or MI endpoint . CV death Source: Cholesterol Treatment Trialists (CTT) Collaboration European Heart Journal (2018) 39, 2540–2545 - doi:10.1093/eurheartj/ehx450

134 Novartis R&D Day | December 5, 2019 Entresto® Key highlights

Angiotensin receptor- HFrEF: continuing to expand program with pediatric approval in US, Japan filing, remodeling data from PROVE-HF and neprilysin inhibitor EVALUATE-HF, and initiation of PARACHUTE-HF in Chagas (ARNI) cardiomyopathy HFpEF: PARALLAX trial (primary endpoints change in NTproBNP and 6-minute walk test) accelerated expected readout Dec 2019; regulatory submissions will be held until we have considered those data Post-acute myocardial infarction: planned interim analysis expected Q1 2020, with full readout and submissions 2021 Totality of evidence from PARAGON-HF1 reinforces overall treatment effect in expanded HF population

CV death and total HF hospitalizations and urgent HF visits . Pre-specified contemporary HF endpoint with addition of adjudicated Urgent Heart Failure visits2: 14% RRR (nominal p = 0.04) . Greater clinical benefit in reducing HF hospitalizations in patients with EF in lower end of range studied (<60%) and in women; clinical benefits in men and higher EF observed on secondary endpoints . US FDA and EU regulatory pre-submission interactions completed – PARALLAX-HF HFpEF trial (n = 2500, LVEF> 40%) readout accelerated from Q1 2020 to Dec. 2019 – Functional capacity, quality of life endpoints

For references see slides 179-180 Study narrowly missed primary endpoint, but showed benefit in pre-specified large subgroups including women and patients with lower ejection fraction

136 Novartis R&D Day | December 5, 2019 Q&A Appendix EDSS cutpoints for disability events1 used for the analysis of highly efficacious2 DMTs in MS

Baseline EDSS Ofatumumab Ocrelizumab Natalizumab Alemtumumab

0 +1.5 +1.0 +1.5 +1.5

1-5 +1.0 +1.0 +1.0 +1.0

5.5 +0.5 +1.0 Excluded Excluded

≥6.0 Excluded Excluded Excluded Excluded

1. The generic word “disability events” is used here for the time-to-disability event analysis in the pivotal trials (depending on the timing of the trial (before or after Lublin 2013 revisons of MS) and exact definition used in these events are labled as confirmed disabilitiy worsening (CDW) or as confirmed disabilitiy progression (CDP) in the trial 2. Highly efficacious DMTs is refering to the listed treatment options. Other DMTs used still other versions of disabiltiy events. Pivotal RMS trials with Natalizumab and Alemtuzumab included patients with screening EDSS 0 – 5.0. Ocrelizumab and Ofatumumab included patients 0 - 5.5 at screening For references see slides 179-180

139 Novartis R&D Day | December 5, 2019 Jeff Legos PhD Global Head, Oncology Development Unit Targeted therapies Immunotherapies Radioligand Cell & Gene Adakveo® Key highlights

® First-in-class targeted US approval for Adakveo (SEG101/crizanlizumab) received on November 15, 2019; Novartis well-positioned for launch monoclonal antibody Approved indication for Adakveo® is to reduce the frequency of that binds to P-selectin vaso-occlusive crises in adults and pediatric patients aged 16 years and older with sickle cell disease

EU review process underway, approval expected 2020

Optimizing use and expanding evidence of benefit of Adakveo® via lifecycle management activities Vaso-occlusive crises (VOCs) are the hallmark of sickle cell disease (SCD)

VASO-occlusive crises (VOCs) can impact survival Every vaso-occlusive crisis matters . Every VOC can increase the risk of death, organ damage, and decreased quality of life . VOCs are the primary reason for emergency department visits and hospital admissions, placing a heavy burden on patients and caregivers’ lives . Vaso-occlusion and VOCs can lead to end-organ damage and multi-organ failure . Large unmet need even with the availability of hydroxyurea: 30% discontinue after 2 prescriptions and many those that are compliant still experience VOCs (median of 2.5 VOCs per year)

This analysis included 264 adult patients with sickle cell anemia (HbSS) followed for a median of ~5 years in the United States (The Bethesda Sickle Cell Cohort Study, 2001-2007).

142 Novartis R&D Day | December 5, 2019 Adakveo®1, which binds to P-selectin, now approved by FDA for the reduction of VOCs in patients with SCD

Approved FDA indication Adakveo® is indicated to reduce the frequency of vaso-occlusive crises in adults and pediatric patients aged 16 years and older with sickle cell disease

6.87 Indication Statement 2.98

® 4.00 Adakveo is a selectin blocker 1.63 indicated to reduce the frequency

of VOCs of VOCs of vasoocclusive crises in adults

and pediatric patients aged 16 years Median annualMedianrate

days days hospitalized and older with sickle cell disease Median annual rate of of annualrateMedian

Adakveo (n=67) Placebo (n=65) Adakveo (n=67) Placebo (n=65) (P=.010; HL=-1.0; 95%CI=-2.00, 0.00) (HL=0.00; 95%CI=-4.36, 0.00)

Significant 45% reduction in the median 42% reduction in the median annual rate of Indication allows patients 16+ to begin treatment annual rate of VOCs vs placebo2 days hospitalized vs placebo2 with Adakveo® before transition into adult care

1. Adakveo® is a first-in-class targeted monoclonal antibody that binds to P-selectin. 2. Crizanlizumab efficacy in SUSTAIN trial.

143 Novartis R&D Day | December 5, 2019 Global commercial opportunity concentrated in few key markets

SCD patients in US, EU5, Brazil and Gulf1

Prevalence 288K 100% USA Healthcare Europe Access 266K 92%

Diagnosis 239K 90% Gulf

1+ VOCs 217K 91% Sub-Saharan Africa2 Brazil

Potential patient population 77K 140K for Adakveo® (including >60K in US per approved label) Pediatric Adult

For references see slides 179-180

144 Novartis R&D Day | December 5, 2019 Adakveo® lifecycle management: optimizing use and expanding evidence of benefit

Focus of Adakveo® LCM Vaso-occlusion can have serious multi-organ consequences, starting early in children

Ongoing development activities We are also evaluating

Pediatric Optimal dose indication1 6y+ (7.5mg/kg)

Subcutaneous Renal function formulation

Other organs Priapism

1. Advanced stage program

145 Novartis R&D Day | December 5, 2019 Targeted therapies Immunotherapies Radioligand Cell & Gene RLT Key highlights

® nd Radioligand therapy Lutathera on track for blockbuster status with 2 line GEP-NET platform NETTER-2 study ongoing for 1st line GEP-NET 177Lu-PSMA-617 Phase 2 trial showed strong clinical data; Phase 3 trial read-out expected in H2 2020

RLT platform is expanding into new targets, vectors, and combinations, leading to even greater potential Our vision is to evolve the RLT platform to maximize opportunity and reach

Today 2020 Beyond 2020

. GEP-NETs . Prostate Cancer . Potential in wide range of . Beta emitters (Lu) . Alpha emitters (Ac) cancers (e.g. stroma targets) . Highly expressed (>80%) . Targets expressed across RLT-druggable target various tumors . New isotopes and isotope sources o GRPR+ cancers (NeoB) . New vector formats o Angiogenesis/metastasis (e.g. small biologics) (Integrin) . Combinations . Earlier lines of therapy (e.g. targeting DDR)

GRPR+ = Gastrin-Releasing-Peptide-Receptor-positive tumors.

147 Novartis R&D Day | December 5, 2019 Lutathera® off to a strong start in 2nd line GEP-NET with development ongoing in 1st line

. Approved in US, EU, Canada, Israel, and Switzerland as 2nd line option after somatostatin analogues; filings underway in N = 229 (ITT) Asia LUTATHERA® arm: 27 Octreotide LAR 60 mg: 78 . Current focus on growing share in 2nd line population . On track for blockbuster status in current indication alone . Ongoing NETTER-2 study for Hazard ratio: 0.21 79% reduction in risk of disease st [0.13 – 0.32] P = <0.0001 progression or death 1 line GEP-NET

148 Novartis R&D Day | December 5, 2019 177Lu-PSMA-617 Phase 2 study demonstrated promising initial clinical data and has a large potential opportunity

Prostate cancer2 (in thousands) Sustained response rates in Phase 2 IIT trial expansion1 Current SOC <30% ≥30% ≥50% Incidence + newly 13/50 (26%) 37/50 (74%) 31/50 (62%) recurrent, stage IV 196 100% metastaticPC 00

Castration-resistant 88 -50 (mCRPC) 45% N=50 -100 PSMA+ 70 80% NAADs Patients Cell therapy Treatment emergent adverse events Phase 2 IIT study1 Grade 1 Grade 2 Grade 3 Grade 4 NAADs 3 Dry mouth 29 (58%) 4 (8%) 0 (0%) 0 (0%) 2nd line 75 107% Taxane-based Lymphocytopenia 7 (14%) 13 (26%) 16 (32%) 0 (0%) Thrombocytopenia 11 (22%) 3 (6%) 4 (8%) 1 (2%) chemotherapy Fatigue 15 (30%) 3 (6%) 1 (2%) 0 (0%) Nausea 20 (40%) 4 (8%) 0 (0%) 0 (0%) rd 49 4 Anaemia 3 (6%) 6 (12%) 5 (10%) 0 (0%) 3 line 65% No SOC Neutropenia 6 (12%) 6 (12%) 3 (6%) 0 (0%) Bone Pain 5 (10%) 4 (8%) 0 (0%) 0 (0%) Vomiting 11 (22%) 2 (4%) 0 (0%) 0 (0%) 4th line 25 4 Anorexia 8 (16%) 0 (0%) 0 (0%) 0 (0%) 51% No SOC Dry eyes 4 (8%) 1 (2%) 0 (0%) 0 (0%) Renal injury 4 (8%) 1 (2%) 0 (0%) 0 (0%) 177 Weight loss 3 (6%) 1 (2%) 0 (0%) 0 (0%) Initial Lu-PSMA-617 target patient pool

1. Hofman, Michael (2018, Jun). Lutetium-177 PSMA617 theranostics in mCRPC: interim results of ph2 trial. ASCO 2018, Genitourinary cancer P5040 2. Kantar Health, 2017 & Novartis estimates 3. Higher % of metastatic patients in later lines 4. % of patients in later lines of therapies calculated based on the treatment rate of previous line. All data for US and EU5 in 2017

149 Novartis R&D Day | December 5, 2019 177Lu-PSMA-617 Phase 3 (VISION) trial expected to read-out in H2 2020

Patient inclusion 177Lu-PSMA-617 . 831 patients enrolled . mCRPC . Primary endpoints: . Bone and/or soft tissue Best supportive rPFS and OS care1 disease . Key secondary 2:1 . PSMA-positive scan endpoints: ORR, time to ≥1 prior taxane symptomatic skeletal events . ≥1 prior NAAD2 Best supportive care1

1. Best supportive care – palliative. 2. NAAD = Novel Androgen Axis Drug (abiraterone or enzalutamide).

150 Novartis R&D Day | December 5, 2019 Moving to alpha emitters and new targets

225-Ac-PSMA-617: Phase 1a to commence with an NeoB, novel antagonist, Phase 1-2 underway for RLT alpha emitter targeting GRPRs in solid tumors

. Gastrin-releasing peptide (GRP) regulates functions of the GI and CNS . Theragnostic pair being developed: 68Ga-NeoB as a diagnostic agent, 177Lu-NeoB as therapeutic agent . Completed study: NeoFind Phase 2 showed GRPR expression

68Ga-PSMA-11 PET/CT scans of patient A. Pretherapeutic tumor spread (A), restaging 2 mo after third in subset of patients with breast cancer, prostate cancer, CRC, cycle of 225Ac-PSMA-617 (B), and restaging 2 mo after one additional consolidation therapy (C). NSCLC & SCLC

. Alpha emitters directly induce DNA damage by causing . Ongoing study: NeoRay Phase 1/2a – first-in-human Phase 1 double strand DNA breaks dose escalation in solid tumors ongoing . New study: AcTION Phase 1a dose escalation; FPFV planned for Q1 2020

Potential new targets emerging from NIBR, Peptidream, academia, alpha emitters = broad range of potential RLTs for solid tumors

*Kratochwil et al; J Nucl Med 2016; 57:1941–1944

151 Novartis R&D Day | December 5, 2019 Targeted therapies Immunotherapies Radioligand Cell & Gene Piqray® Key highlights

PI3Kα inhibitor Approved for post-menopausal women and men with HR+/HER2- PIK3CA-mutated advanced breast cancer (aBC), in combination with fulvestrant, following progression on or after an endocrine- based regimen

US launch for alpelisib off to a strong start

Currently approved in 5 countries; EU decision and potential launch expected H1 2020 Alpelisib Expanding alpelisib development into multiple other tumors types, PI3Kα inhibitor and received FDA Breakthrough Therapy designation for PROS indication Piqray® launch off to a strong start in HR+/HER2- advanced breast cancer with PIK3CA mutation

. ~40% of HR+/HER2- breast cancer patients have a PIK3CA mutation, associated with poor prognosis1,2

. Nearly doubled median PFS in SOLAR-1 study3

. PIK3CA testing is recommended by latest NCCN

. Foundation Medicine PIK3CA CDx tissue approval anticipated Q4 2019 to expand FDA approved CDx in the US

. Blockbuster potential in current indication alone

For references see slides 179-180

153 Novartis R&D Day | December 5, 2019 Expanding alpelisib into multiple other tumors types, which have significant potential

. Current indication of HR+/HER2- advanced breast cancer has potential to achieve blockbuster status alone Additional indications . Expanding alpelisib into multiple other beyond breast cancer tumors types and beyond cancer with Additional 1 PROS (2020 ) the EPIK (Exploring PIK3CA/PI3K) indications in 1 Current indication Ovarian Cancer (2023 ) program; development work for 5 new breast cancer 1 in breast cancer Head & Neck Cancer (2025 ) indications initiated HER2+ aBC (20231) HR+/HER2- aBC TNBC (20231) . With this expansion, potential opportunity to serve an additional BREAST CANCER NON-BREAST CANCER ~100k patients, more than tripling the number of patients in the current indication

1. Refers to first filing year PROS = PI3K Related Overgrowth Syndrome

154 Novartis R&D Day | December 5, 2019 Encouraging efficacy data with alpelisib in HER2+ and triple negative breast cancer indications

HER2+ HER2- (including TNBC) BYL719 + T-DM1 in All No prior TDM-1 Prior TDM-1 trastuzumab- and patients exposure (n=4) exposure taxane- resistant (n=14) (n=10) ORR 43% 75% 30% CBR 71% 100% 60% mPFS (months) 8.1 10.8 6.2 Of the 9 pts with evaluable tissue, 4 PIK3CAm+: 3 SD, 1 PD

Duration of response in pts with evaluable tissue

the longest the longest diametersof targetlesions Best Best % change frombaseline sum inof

SD PD Weeks on therapy Complete response Partial response Stable disease Progressive disease

PIK3CA inhibition targets important resistance pathway to anti-HER2 Encouraging efficacy noted with objective response rate of 59% therapy, providing rationale for further study of alpelisib in this setting and CBR of 79%. Efficacy appears similar in patients with HR+ and TNBC (PIK3CA mutation / PTEN loss)

For references see slides 179-180

155 Novartis R&D Day | December 5, 2019 Potential life-changing transformation in treatment of PIK3CA-related overgrowth syndrome with alpelisib

PROS disorders occur in different tissues types and anatomical areas1 . FDA Breakthrough Therapy and Orphan Drug designations received Nov 2019; plans for initial submission (US) in H2 2020 . PROs is a rare, congenital, primarily pediatric disease characterized by malformations and non-malignant tissue overgrowth due to PIK3CA mutations in affected tissues . No approved medical treatments . Encouraging results of 19 patients successfully treated with alpelisib without significant safety issues2 . Health authority interactions ongoing; development work initiated

1. Keppler-Noreuil, et al. Am J Med Genet Part A. 2015. 2.Venot, Q., et al., (2018). Targeted therapy in patients with PIK3CA-related overgrowth syndrome (PROS). Nature, 558(7711), 540.

156 Novartis R&D Day | December 5, 2019 Strong scientific rationale of alpelisib in ovarian and head and neck cancers

Ovarian Head & Neck

Lancet 2019: ph1 clinical data for Olap+BYL in OvCa Lancet 2017: clinical data of BKM120 in HSNCC

In a Phase 1 study, 33% of BRCA non-carrier, platinum-resistant or HNSCC clinical data with buparlisib (pan PI3K inhibitor) with paclitaxel refractory, advanced ovarian cancer patients achieved an overall response demonstrated that PI3K pathway inhibition improved mOS

1. HNSCC = head and neck squamous cell carcinoma. BRCA non-carrier = the breast cancer gene when it is found in its natural non-mutated form.

157 Novartis R&D Day | December 5, 2019 Targeted therapies Immunotherapies Radioligand Cell & Gene Kisqali® Key highlights

CDK4/6 inhibitor Kisqali® is the only CDK4/6 inhibitor to show positive overall survival benefit in 2 pivotal Phase 3 studies, and is unique in the CDK4/6 class on key pharmacokinetic parameters, including affinity to CDK4

Oncologists have reported that OS is their #1 treatment goal for aBC patients

OS benefit seen in pre-, peri-, and post-menopausal patients, and with multiple ET partners

NATALEE adjuvant trial enrolling quickly; potential for registration as early as 2022 based on positive, pre-planned interim analysis Kisqali®: leveraging unique survival benefit and adjuvant development to maximize potential

Metastatic Breast Cancer Adjuvant Breast Cancer

. In both pivotal Phase 3 trials (MONLAEESA-7 Ribociclib 400 mg/d 3 weeks on/1 week off ® & 3), Kisqali demonstrated approximately 36 months (~39 cycles) 30% reduction in risk of death n = 4000 36 months RIBO+ . Comprehensive OS evidence expected to ET 60 months . HR+/HER2- EBC R ® differentiate Kisqali within CDK4/6 class . Pre- and post- 1:1 ET (NSAI 60 months1 menopausal (+Goserelin in premenopausal women and men) . CDK4 is a critical driver of HR+/HER2- aBC1,2 . Stage lI & lll ® and Kisqali inhibits CDK4 8x more than ET only 60 months CDK63,4 ET (NSAI 60 months1 . CDK4/6 market opportunity anticipated to be (+Goserelin in premenopausal women and men) USD 9bn in metastatic setting by 2027 and . CDK 4/6 market opportunity anticipated to be USD 6bn for adjuvant by 2027 OS benefit is considered the single most important outcome that drives physicians’ . Potential for registration for NATALEE (high and intermediate adjuvant breast treatment decisions cancer) as early as 2022 based on positive, pre-planned interim results

For references see slides 179-180 1. Letrozole or anastrozole; treatment with NSAI may start up to 12 months before study treatment start date

159 Novartis R&D Day | December 5, 2019 Targeted therapies Immunotherapies Radioligand Cell & Gene Sparta–DabTram (PDR001) Key highlights

Spartalizumab Potential to become a new standard of care for treating advanced patients with melanoma (PD-1 antibody) plus ® Combination treatment directly attacks the tumor and Tafinlar (dabrafenib) simultaneously harnesses the immune system and Mekinist® Phase 3 study ongoing with submissions planned for 2020 (trametinib) Building on the strong Novartis legacy as a leader in this disease area with an established commercial infrastructure around the world Sparta–DabTram combination Directly attacks the tumor and simultaneously harnesses the immune system

. Despite recent advances, approximately 1 out of 2 patients with advanced melanoma die within 5 years . Tafinlar® plus Mekinist® is the market leader among targeted therapies, competing with PD-1 checkpoint inhibitors . Spartalizumab is an investigational PD-1 antibody that Novartis is developing in combination with other agents for multiple indications . Sparta-DabTram has the potential to deliver MAPK inhibition may favorably alter the tumor microenvironment for an strong and durable responses enabling augmented and potentially synergistic immune response longer survival McArthur GA & Ribas A, J Clin Oncol 2013;31:499–506

161 Novartis R&D Day | December 5, 2019 Strong Phase 2 clinical data supports anti-PD-1 combination with Tafinlar® and Mekinist®

Duration of responsea Overall survival

For references see slides 179-180

162 Novartis R&D Day | December 5, 2019 Encouraging durable anti-tumor activity With a manageable safety profile from pivotal Phase 3 study (COMBI-i) safety run-in / biomarker cohort Best percentage change from baseline in sum of diameters (n=36) Efficacy . The majority of patients had an objective response (78%); high rates of complete responses (42%) . almost 2 years median progression-free survival Safety . AEs consistent with toxicity profiles of each drug . 17% of patients discontinued all 3 drugs due to AEs Conclusion . Preliminary evidence of strong and durable antitumor activity with a manageable safety profile . Randomized Part 3 of the COMBI-i study is ongoing to confirm the added benefit of sparta-DabTram vs placebo-DabTram Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019) 9531-9531.

163 Novartis R&D Day | December 5, 2019 Design of ongoing COMBI-i study with planned filings in 2020

n = 532 (actual enrolled) R Spartalizumab 400mg Key eligibility criteria A N Q4W . Unresectable or metastatic melanoma D dabrafenib 150 mg BID O (stage IIIC/IV) trametinib 2 mg QD PD or M 1:1 . BRAF V600 mutation I unacceptable Z toxicity . Previously untreated A Placebo . No active brain metastasis T I dabrafenib 150 mg BID . ECOG PS ≤ 2 O trametinib 2 mg QD N

Randomization stratification . ECOG PS (0 vs 1 vs 2) . LDH (< 1 x ULN vs ≥ 1 to < 2 x ULN vs ≥ 2 x ULN) Primary endpoint: PFSRECIST v1.1 Secondary endpoints: OS, ORR, DOR, DCR, Safety, PROs, PK

BID, twice per day; DCR, disease control rate; DOR, duration of response; ECOG, Eastern Cooperative Oncology Group; LDH, lactate dehydrogenase; ORR, overall response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PK, pharmacokinetics; PRO, patient-reported outcome; PS, performance status; QD, daily; Q4W, every 4 weeks; ULN, upper limit of normal.

164 Novartis R&D Day | December 5, 2019 Targeted therapies Immunotherapies Radioligand Cell & Gene Kymriah® Key highlights

Kymriah® is an available treatment for pediatric and young adult Autologous CAR-T r/r ALL, and r/r DLBCL patients. cell therapies Country approvals for both indications received in US, EU, Japan, developed using Canada, Switzerland and Australia to date patient’s own blood Real-world evidence (RWE) data through the CIBMTR Registry showed similar initial efficacy and possibly better safety in pediatric ALL and DLBCL compared with the ELIANA and JULIET trials, respectively

Data to be presented at ASH on December 8-9, 2019

Commitment to continued development of CAR-T portfolio with breadth of indications Kymriah® demonstrates consistent efficacy and improved safety outcomes when used in real-world setting

Real World Evidence (RWE) Pivotal studies . Efficacy of Kymriah® from RWE data in CIBMTR 1 2 3 4 ALL pts DLBCL ELIANA JULIET 3 Outcomes (n=105) (n=47) (n=79) (n=115) registry similar to that in pivotal studies ELIANA and JULIET4 despite treatment of a broader 52% ORR (CR) 88% 60% (38%) 82% patient population, including sicker patients with a (38%) poorer prognosis DOR, 6 mo 77% – 80% - . Safety of Kymriah® from RWE data in CIBMTR EFS, 6 mo 68% – 71% - registry similar to and trending better than in OS, 6 mo 94% – 89% - ELIANA3 and JULIET4 with reduction in known

CRS Gr ≥3 13% 4% 48% 23% CAR-T cell therapy adverse events, specifically rates of high-grade cytokine release syndrome Neurotox Gr ≥3 9% 4% 13% 11% and neurologic events

* RWE data cut-off May 31, 2019

For references see slides 179-180

166 Novartis R&D Day | December 5, 2019 Q&A Novartis pipeline Our pipeline projects at a glance

Phase 1/2 Phase 3 Registration Total ONCOLOGY 57 20 2 79

CRM: Cardiovascular, Renal & Metabolism. IHD: Immunology, Hepatology & Dermatology. NS: NeuroScience.

169 Novartis R&D Day | December 5, 2019 Novartis pipeline in Phase 1 (1 of 2) 34 lead indications Lead indication

Oncology Code Name Mechanism Indication(s) 177Lu-NeoB 177Lu-NeoB Radioligand therapy target GRPR Multiple solid tumors 177Lu-PSMA-R2 177Lu-PSMA-R2 Radioligand therapy target PSMA Prostate cancer ADPT01 NIR178, LAG525, spartalizumab, canakinumab, capmatinib LAG3 Inhibitor,PD1 Inhibitor TNBC BLZ945 BLZ945 + spartalizumab CSF-1 Inhibitor + PD1 Inhibitor Solid tumors CSJ137 CSJ137 Growth Factor Inhibitor Anaemia CTL019 Kymriah® CD19 CART Lymphoma DKY709 DKY709 + spartalizumab - Cancers EGF816 nazartinib + LXH254, ribociclib, capmatinib, Opdivo, Mekinist EGFR Inhibitor NSCLC HDM201 HDM201 + MBG453, venetoclax MDM2 Inhibitor Haematological malignancy JEZ567 JEZ567 CD123 CART AML JJO686 JJO686 CD22 CART ALL LHC165 LHC165 + spartalizumab TLR7 Agonist Solid tumors LSZ102 LSZ102, ribociclib, alpelisib SERD BC LXF821 LXF821 EGFR CART, PD1 Inhibitor Glioblastoma multiforme LXH254 LXH254 (combos) cRAF Inhibitor Solid tumors Solid tumors MAK683 MAK683 EED Inhibitor Cancers MAS825 MAS825 - Inflammatory diseases MBG453 MBG453 (combos) TIM3 Antagonist Cancers MCM998 MCM998, LXG250 BCMA CART, CD19 CART Multiple myeloma MIK665 MIK665 MCL1 Inhibitor AML Haematological malignancy AML (combo) MIW815 MIW815 STING Agonist Solid tumors Solid tumors (combo) NIS793 NIS793, spartalizumab TGFB1 Inhibitor, PD1 Inhibitor Solid tumors NIZ985 NIZ985, spartalizumab IL-15 Agonist Solid tumors NJH395 NJH395 - Solid tumors NZV930 NZV930, spartalizumab, NIR178 CD73 Antagonist Solid tumors PDR001 spartalizumab, CJM112, LCL161 PD1 Inhibitor, TIM3 Antagonist AML Solid tumors (combo) Solid tumors (combo) Solid tumors (combo) SQZ622 SQZ622 CD123xCD3 Modulator AML TNO155 TNO155 SHP2 Inhibitor Solid tumors (combo) Solid tumors (combo) VAY736 ianalumab + ibrutinib BAFF-R Inhibitor,BTK Inhibitor Haematological malignancy VOB560 VOB560 - Cancers VPM087 VPM087 IL1B Antagonist 1st line CRC / 1st line RCC WNT974 WNT974 + spartalizumab Porcupine Inhibitor Solid tumors YTB323 YTB323 + ibrutinib CD19 CART Haematological malignancy

170 Novartis R&D Day | December 5, 2019 Novartis pipeline in Phase 1 (2 of 2) 34 lead indications Lead indication

Immunology, Hepatology, Dermatology Code Name Mechanism Indication(s) DFV890 DFV890 - Multiple Indications LRX712 LRX712 - Osteoarthritis MHS552 MHS552 - Autoimmune Indications MHV370 MHV370 - SLE

Neuroscience Code Name Mechanism Indication(s) OAV101 AVXS-101 Survival motor neuron protein SMA type 2/3 (IT formulation)1 gene therapy OAV201 AVXS-201 MECP2 gene therapy Rett syndrome

Respiratory Disease Code Name Mechanism Indication(s) CMK389 CMK389 IL-18 Inhibitor Sarcoidosis

Cardiovascular, Renal, Metabolism Code Name Mechanism Indication(s) HSY244 HSY244 - Atrial fibrillation LTW980 LTW980 - Hypertriglyceridemia MBL949 MBL949 - Diabetes

Global Health Code Name Mechanism Indication(s) KAF156 ganaplacide - Malaria prophylaxis

1. FDA placed a partial hold on AVXS-101 intrathecal clinical trials for SMA patients based on findings in a small pre-clinical animal study

171 Novartis R&D Day | December 5, 2019 Novartis pipeline in Phase 2 27 lead indications Lead indication

Oncology Neuroscience Code Name Mechanism Indication(s) Code Name Mechanism Indication(s) ABL001 asciminib BCR-ABL Inhibitor CML 1L AFQ056 AFQ056 mGluR5 Antagonist Addiction ACZ885 canakinumab IL-1b Inhibitor Sickle cell anaemia BAF312 Mayzent® S1P1 Modulator Ped MS Stroke BYL719 alpelisib PI3Kα inhibitor PROS LMI070 branaplam Survival motor neuron protein SMA CTL019 Kymriah CD19 CART r/r DLBCL (+ pembro) MIJ821 MIJ821 NR2B Inhibitor Depression EGF816 nazartinib+capmatinib Opdivo EGFR Inhibitor NSCLC OMB157 ofatumumab CD20 Antagonist Ped MS INC280 capmatinib c-Met Inhibitor NSCLC c-Met Inhibitor + spartalizumab HCC NSCLC Respiratory Disease INC424 Jakavi® JAK1 Inhibitor Myelofibrosis (combination) Code Name Mechanism Indication(s) LAG525 LAG525 LAG3 Inhibitor Solid Tumors ACZ885 canakinumab IL-1b Inhibitor Sarcoidosis MBG453 MBG453 TIM3 Antagonist HR-MDS Unfit AML CJM112 CJM112 IL-17A Inhibitor Asthma NIR178 NIR178, spartalizumab Ad2AR Inhibitor, PD1 Inhibitor Cancers CSJ117 CSJ117 TSLP Inhibitor Severe asthma PDR001 spartalizumab PD1 Inhibitor Nasopharyngeal cancer Metastatic melanoma (combo) LOU064 LOU064 BTK Inhibitor Asthma SEG101 crizanlizumab P-selectin Inhibitor Sickle cell anaemia with crisis QAW039 fevipiprant DP2 (CRTh2) Antagonist Rhinitis allergic Nasal polyps COPD ped Asthma Immunology, Hepatology, Dermatology QBW251 QBW251 CFTR Potentiator COPD VAY736 ianalumab BAFF-R Inhibitor IPF Code Name Mechanism Indication(s) AIN457 Cosentyx® IL17A Inhibitor SpA IVIV GCA Lichen Planus Cardiovascular, Renal, Metabolism CFZ533 iscalimab CD40 Inhibitor Renal/Liver Tx SjS HS LJC242 tropifexor&cenicriviroc CCR2 Inhibitor, FXR agonist NASH Code Name Mechanism Indication(s) LJN452 tropifexor FXR agonist NASH Nash (combos) CFZ533 iscalimab CD40 Inhibitor Lupus Nephritis LNA043 LNA043 ANGPTL3 Agonist Osteoarthritis LMB763 nidufexor FXR Agonist Diabetic Nephropathy LOU064 LOU064 BTK Inhibitor Chronic spontaneous urticaria SjS LNP023 LNP023 CFB Inhibitor PNH iMN C3G IgAN LYS006 LYS006 Anti-inflammatory Acne VAY736 ianalumab BAFF-R Inhibitor pSjS AIH SLE Global Health ZPL389 adriforant HRH4 Antagonist Atopic dermatitis Code Name Mechanism Indication(s) KAE609 cipargamin PfATP4 inhibitor Malaria Malaria severe Ophthalmology KAF156 ganaplacide - Malaria Code Name Mechanism Indication(s) LXE408 LXE408 Protozoan Inhibitor Visceral leishmaniasis CPK850 CPK850 RLBP1 AAV RP ECF843 ECF843 rh-Lubricin Dry eye LKA651 LKA651 EPO Inhibitor Diabetic retinopathy SAF312 SAF312 TRPV1 Antagonist COSP UNR844 UNR844 disulfide bonds Modulator Presbyopia

172 Novartis R&D Day | December 5, 2019 Novartis pipeline in Phase 3 6 lead indications Lead indication

Oncology Respiratory Disease Code Name Mechanism Indication(s) Code Name Mechanism Indication(s) 177Lu-PSMA-617 177Lu-PSMA-617 Targeted Radioligand Therapy mCRPC IGE025 Xolair® IgE Inhibitor CSU (for CN) Auto-injector Food allergy ABL001 asciminib BCR-ABL Inhibitor CML 3L QAW039 fevipiprant DP2 (CRTh2) Antagonist Asthma Adjuvant ACZ885 canakinumab IL-1b Inhibitor NSCLC 1L NSCLC 2L NSCLC BYL719 Piqray PI3Kα inhibitor HER2+ adv BC TNBC HNSCC 2/3L Ovarian cancer CTL019 Kymriah CD19 CART r/r Follicular 1L high risk r/r DLBCL 1st Adult r/r ALL Cardiovascular, Renal, Metabolism lymphoma ALL, pediatrics relapse Code Name Mechanism Indication(s) and young adults LCZ696 Entresto® AT-II / NEP,NEP,AGTR1,AGTR2 Inhibitor Post-AMI HFpEF ETB115 Promacta® Thrombopoietin receptor (TPO-R) Radiation sickness syndrome Food effect free formulation TQJ230 TQJ230 Anti-Apo(a) ASO targeting Lp(a) CVRR Agonist INC424 Jakavi JAK1 Inhibitor Acute GVHD Chronic GVHD LEE011 Kisqali® CDK4 Inhibitor HR+/HER2- BC (adj) PDR001 spartalizumab PD1 Inhibitor m BRAF V600+ melanoma (+Taf/Mek) Biosimilars SEG101 crizanlizumab P-selectin Inhibitor Sickle cell anemia new formulations Code Name Mechanism Indication(s) GP2411 denosumab anti RANKL mAb Denosumab BioS

Immunology, Hepatology, Dermatology Code Name Mechanism Indication(s) AIN457 Cosentyx IL17A Inhibitor Lupus Psoriasis Hidradenitis AS H2H PsA H2H Nephritis 300mg AI suppurativa QGE031 ligelizumab IgE Inhibitor Chronic spontaneous urticaria

Ophthalmology Code Name Mechanism Indication(s) RTH258 Beovu® VEGF Inhibitor Diabetic retinopathy RVO DME

Neuroscience Code Name Mechanism Indication(s) OMB157 ofatumumab CD20 Antagonist r MS

173 Novartis R&D Day | December 5, 2019 Novartis pipeline in registration 4 lead indications Lead indication

Oncology Cardiovascular, Renal, Metabolism Code Name Mechanism Indication(s) Code Name Mechanism Indication(s) BYL719 Piqray PI3Kα inhibitor HR+/ HER2-- adv BC (postm) 2L (+ fulv) LCZ696 Entresto AT-II / NEP,NEP,AGTR1,AGTR2 Pediatric CCF SEG101 Adakveo® P-selectin Inhibitor Sickle cell disease Inhibitor

Immunology, Hepatology, Dermatology Global Health Code Name Mechanism Indication(s) Code Name Mechanism Indication(s) AIN457 Cosentyx IL17A Inhibitor Ped Psoriasis nr-axSpA LAM320 Lamprene® SMPD1 Inhibitor Tuberculosis

Ophthalmology Code Name Mechanism Indication(s) RTH258 Beovu VEGF Inhibitor nAMD

Neuroscience Code Name Mechanism Indication(s) OAV101 Zolgensma® Gene therapy SMA type 1 (IV formulation)

Respiratory Disease Code Name Mechanism Indication(s) IGE025 Xolair IgE Inhibitor Nasal polyps QMF149 Indacaterol acetate Long acting b2-adrenergic Asthma +mometasone furoate agonist + inhaled corticosteroid QVM149 Indacaterol acetate Long acting b2-adrenergic Asthma +mometasone fuorate agonist + long-acting muscarinic +glycopyrrnium bromide antagonist + inhaled corticosteroid

174 Novartis R&D Day | December 5, 2019 ONC IHD OPHTHA Novartis submission schedule NS RESP Lead and supplementary indications CRM GH BioS 2019 2020 2021 2022 2023 >2023

capmatinib Lead spartalizumab Lead asciminib Lead ECF843 Lead LOU064 Lead 177Lu-NeoB Lead ianalumab Lead UNR844 Lead INC280 PDR001 ABL001 Dry eye Chronic spontaneous urticaria 177Lu-NeoB VAY736 Presbyopia NSCLC m BRAF V600+ melanoma (+Taf/Mek) CML 3L Multiple Solid Tumors pSjS

177Lu-PSMA-617 Lead MBG453 Lead LNP023 Lead VPM087 Lead adriforant Lead QBW251 Lead 177Lu-PSMA-617 HR-MDS PNH 1st line CRC / 1st line RCC ZPL389 COPD mCRPC Atopic dermatitis

fevipiprant Lead ligelizumab Lead denosumab BioS CEE321 Lead AVXS-201 Lead CSJ117 Lead QAW039 QGE031 GP2411 Atopic Dermatitis OAV201 Severe asthma Asthma Chronic urticaria anti RANKL mAb Rett syndrome

iscalimab Lead LMI070 Lead TQJ230 Lead CFZ533 SMA CVRR Renal/Liver Tx

tropifexor&cenicriviroc Lead MIJ821 Lead cipargamin Lead LJC242 Depression KAE609 NASH Malaria

tropifexor Lead CPK850 Lead ganaplacide Lead

LEAD INDICATIONS LJN452 RP KAF156 NASH Malaria

LNA043 Lead SAF312 Lead LXE408 Lead Osteoarthritis COSP Visceral leishmaniasis

ofatumumab LCM canakinumab LCM canakinumab LCM asciminib LCM LOU064 LCM fevipiprant LCM OMB157 ACZ885 ACZ885 ABL001 SjS QAW039 r MS NSCLC 2L Adjuvant NSCLC CML 1L Nasal polyps

indacaterol+mometasone furoate LCM canakinumab LCM spartalizumab LCM MBG453 LCM ianalumab LCM LNP023 LCM QMF149 ACZ885 PDR001 Unfit AML VAY736 iMN Asthma NSCLC 1L Malignant melanoma (combo) AIH

indacaterol+mometasone LCM crizanlizumab LCM fevipiprant LCM crizanlizumab LCM ofatumumab LCM cipargamin LCM +glycopyrrnium SEG101 QAW039 SEG101 OMB157 KAE609 QVM149 | Asthma Sickle cell anaemia new formulations Rhinitis allergic Sickle cell anaemia with crisis Ped MS Malaria

LNP023 LCM iscalimab LCM fevipiprant LCM C3G CFZ533 QAW039 SjS ped Asthma

LNP023 LCM tropifexor LCM fevipiprant LCM NEW INDICATIONS IgAN LJN452 QAW039 NASH (combos) COPD

175 Novartis R&D Day | December 5, 2019 ONC IHD OPHTHA Novartis submission schedule NS RESP Supplementary indications for existing brands CRM GH BioS 2019 2020 2021 2022 2023 >2023

Cosentyx LCM alpelisib, BYL719 LCM Kymriah LCM Kisqali LCM Piqray LCM 177Lu-PSMA-R2 LCM Jakavi LCM Cosentyx LCM secukinumab, AIN457 PROS tisagenlecleucel-T, CTL019 ribociclib, LEE011 alpelisib, BYL719 177Lu-PSMA-R2 ruxolitinib, INC424 secukinumab, AIN457 Ped Psoriasis r/r DLBCL 1st relapse HR+/HER2- BC (adj) TNBC Prostate cancer Myelofibrosis (combination) Ankylosing spondylitis

Cosentyx LCM Tafinlar LCM Kymriah LCM Piqray LCM Piqray LCM Piqray LCM Jakavi LCM Cosentyx LCM secukinumab, AIN457 dabrafenib, DRB436 tisagenlecleucel-T, CTL019 alpelisib, BYL719 alpelisib, BYL719 alpelisib, BYL719 ruxolitinib, INC424 secukinumab, AIN457 nr-axSpA Anaplastic thyroid cancer r/r Follicular lymphoma Ovarian cancer HER2+ adv BC HNSCC 2/3L Pediatrics Acute GVHD Lichen Planus

Cosentyx LCM Tafinlar LCM Promacta LCM Kymriah LCM Kymriah LCM Cosentyx LCM Mayzent LCM secukinumab, AIN457 dabrafenib, DRB436 eltrombopag, ETB115 tisagenlecleucel-T, CTL019 tisagenlecleucel-T, CTL019 secukinumab, AIN457 siponimod, BAF312 Psoriasis 300mg AI Neoplasm Pedia Radiation sickness syndrome Adult r/r ALL r/r DLBCL (+ pembro) GCA Ped MS

Cosentyx LCM Promacta LCM Rydapt LCM Tafinlar LCM Kymriah LCM Cosentyx LCM secukinumab, AIN457 eltrombopag, ETB115 midostaurin, PKC412 dabrafenib, DRB436 tisagenlecleucel-T, CTL019 secukinumab, AIN457 PsA H2H Food effect free formulation Ped AML Tyroid cancer 1L high risk ALL, pediatrics & young adults Lupus Nephritis

AVXS-101 LCM Jakavi LCM Cosentyx LCM Beovu LCM Jakavi LCM onasemno-gene abepar-vovec, OAV101 ruxolitinib, INC424 secukinumab, AIN457 brolucizumab, RTH258 ruxolitinib, INC424 SMA type 2/3 (IT formulation) Chronic GVHD SpA IVIV Diabetic retinopathy Pediatrics Chronic GVHD

Xolair LCM Jakavi LCM Cosentyx LCM Beovu LCM omalizumab, IGE025 ruxolitinib, INC424 secukinumab, AIN457 brolucizumab, RTH258 CSU (for CN) Acute GVHD Hidradenitis suppurativa RVO

Entresto LCM Beovu LCM Cosentyx LCM valsartan+sacubitril, LCZ696 brolucizumab, RTH258 secukinumab, AIN457 HFpEF DME AS H2H

Xolair LCM omalizumab, IGE025 Auto-injector

Xolair LCM omalizumab, IGE025 Food allergy

Entresto LCM valsartan+sacubitril, LCZ696 Post-AMI

Lamprene LCM clofazimine, LAM320 Tuberculosis

176 Novartis R&D Day | December 5, 2019 Indication abbreviations

AIH Autoimmune hepatitis mCRPC Metastatic castration-resistant prostate cancer ALL Acute lymphoblastic leukemia MDR Multi-drug resistant AMI Acute myocardial infarction MDS Myelodysplastic syndrome AML Acute myeloid leukemia MS Multiple sclerosis AS H2H Ankylosing spondylitis head-to-head study versus adalimumab nAMD Neovascular (wet) age-related macular degeneration BC Breast cancer NASH Non-alcoholic steatohepatitis C3G C3 glomerulopathy nr-axSpA Non-radiographic axial spondyloarthritis CCF Congestive cardiac failure NSCLC Non-small cell lung cancer CLL Chronic lymphocytic leukemia PDR Proliferative diabetic retinopathy CML Chronic myeloid leukemia PEF Preserved ejection fraction CRC Colorectal cancer PNH Paroxysmal nocturnal haemoglobinuria COPD Chronic obstructive pulmonary disease PsA H2H Psoriatic arthritis head-to-head study versus adalimumab COSP Chronic ocular surface pain RCC Renal cell carcinoma CSU Chronic spontaneous urticaria PROS PIK3CA related overgrowth spectrum CVRR Secondary prevention of cardiovascular events in patients with elevated levels of lipoprotein (a) RA Rheumatoid arthritis DME Diabetic macular edema rMS Relapsing multiple sclerosis DLBCL Diffuse large B-cell lymphoma refractory ROP Retinopathy of prematurity GCA Giant cell arteritis RP Retinitis pigmentosa GVHD Graft-versus-host disease RVO Retinal vein occlusion HCC Hepatocellular carcinoma SAA Severe aplastic anemia HFpEF Chronic heart failure with preserved ejection fraction SjS Sjögren’s syndrome HF-rEF Chronic heart failure with reduced ejection fraction SLE Systemic lupus erythematosus HNSCC Head and neck squamous cell carcinoma SMA Type 1 Spinal muscular atrophy type 1 (IV formulation) HS Hidradenitis suppurativa SMA Type 2/3 Spinal muscular atrophy type 2/3 (IT formulation) IgAN IgA nephropathy SpA Spondyloarthritis iMN Membranous nephropathy SPMS Secondary progressive multiple sclerosis IPF Idiopathic pulmonary fibrosis TNBC Triple negative breast cancer

177 Novartis R&D Day | December 5, 2019 References References – Emerging Assets

Slide References 54 TQJ230 demonstrated significant Lp(a) reductions in 1. Tsimikas et al. The American Heart Association Scientific Sessions, 2018. Study conducted by Akcea Therapeutics. 2. Viney NJ et al 2016 Lancet. 2016;388(10057):2239- CVD patients1 2253.

55 TQJ230 expected to provide relevant CV risk 1. Tsimikas, S J Am Coll Cardiol 2017; 69(6):692-711. 2. Burgess S, JAMA Cardiol. 2018;3(7):619-627. 3. Time averaged. reduction through potent Lp(a) lowering

56 Phase 3 outcome study planned to initiate early 1. MI, stroke, CV death or urgent coronary revascularization. https://clinicaltrials.gov/ct2/show/NCT04023552 (accessed 06 August 2019) 2020; patient identification ongoing

91 Deep pipeline Projects included are those with planned filings in US and/or EU. 1. All select pipeline assets are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.

93 High unmet need in MDS & AML 1. AML: SEER data 2009-2015; High-risk MDS: Pfeilstocker et al., 2016. 2. Vidaza EMA approval 2008, FDA 2004. 3. MDS Epidemiology: Greenberg et al, 1997/2012; NCCN Clinical Practice Guidelines in Oncology, Myelodysplastic Syndromes, v2.2019. Kantar Health

94 Rationale for targeting TIM-3 in hematology 1. Wolf Y et al., Nature Immunology, 2019. 2. Asamaya T et al., Oncotarget 2017. 3.Kikushige Y et al., Cell Stem Cells, 2010. 4. Goncalves Silva I et al., EBioMedicine, 2017. 5. Kikushige Y et al., Cell Stem Cells, 2015. 6. Dama P et al., J. Immunotherapy Cancer, 2019. 7. Kong Y et al., Blood Cancer J., 2015.

99 Unmet need remains high in CML 1. Akard LP, et al. Clin Adv Hematol Oncol. 2013;11:421-432. 2. Hochhaus A, et. al. Annals of Oncol. 2017;28; iv41–iv51. 3. Hochhaus A, et al. Leukemia. 2016;30:1044– 1054. 4. Cortes JE. Blood Adv. 2018;2:3653-3655. 5. Cortes JE, et al. J Clin Oncol. 2016;34:2333-2340. 6. Steegmann JL, et al. Leukemia. 2016;30:1648-1671.

100 Asciminib (ABL001) 1. Wylie AA, et al. Nature. 2017;543:733–737. 2. Schoepfer J. J Med Chem. 2018;61:8120–8135. 3. Hughes TP, et al. Blood. 2016;128 [Abstract 625]. 4. Réa D, et al. Blood. 2018;132 [Abstract 792].

101 ABL001X2101 1. Patients had ≥ 6 months of treatment exposure or achieved response within 6 months. 2. BCR-ABL1IS reduction achieved. 3. Patients had ≥ 12 months of treatment exposure or achieved response within 12 mo. Sources: Hughes TP. Blood. 2016;128 [abstract 625]. CABL001X2101 study protocol.

102 ABL001A2301 1.Mauro MJ. J Clin Oncol. 2019;37 [abstract TPS7070]. 2. Baccarani M. Blood. 2013;122:872-884. Must meet the definition of treatment failure per the 2013 European Leukemia Net guidelines.

106 IL-1β blockade LEFT: Grivennikov SI, Karin M. Curr Opin Genet Dev. 2010;20:65-71. Hagerling C, et al. Trends Cell Biol. 2015;25:214-20. Li Y, et al. Oral presentation at AACR 2019. Cancer Res. 2019;79 (13 Suppl):abstract CT001. Shrihari TG. Ecancermedicalscience. 2017;11:721. RIGHT: Jayaraman et al; 2019. Targeting IL-1b pathway for cancer immunotherapy. AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. Poster C103.

179 Novartis R&D Day | December 5, 2019 References – Late Stage & LCM Update

Slide References 130 LUSTER to determine GINA – Global Initiative for Asthma. 1. Fajt et al. J Allergy Clin Immunol 2013; 131:1504-1512 2. a. Erpenbeck et al. Pulm Pharmacol Ther 2016;39:54-63. b. Bateman et al. Eur Respir J 2017; 24:50(2). benefit in moderate- 3. Gonem et al. Lancet Respir Med 2016; 4: 699-707 4. Saunders et al. Sci Trans Med 2019; 11, eaao6451 5. In combination with inhaled standard of care – predominantly low-medium dose severe asthma ICS+LABA 6. Detailed analysis of the ZEAL1 & 2 data is ongoing & results to be communicated in H1 2020 7. Based on ZEAL 1 & 2 and a dedicated thorough QT study which demonstrated absence of a QTcF signal with fevipiprant vs. placebo (Novartis data on file) 133 Significant unmet needs Source: DRG (2019), Novartis Commercial team 1. A Comparison of 2 Claims-Based Algorithms by Bellows et al. JMCP September 2017 Vol. 23, No. 9. 2. Boekholdt et al. Very Low LDL-C levels and in ASCVD treatment CVD Risk JACC VOL 64.No 5 2014:485-94. 3. FonarowGC, KeechAC, Pedersen TR, et al. Cost-effectiveness of Evolocumab Therapy for Reducing Cardiovascular Events in Patients With Atherosclerotic Cardiovascular Disease (2017). 4. NavarAM, Taylor BT, FlevitzE, et al. Early challenges for PCSK9 inhibitor prescriptions and patients: rejections and rates unfilled. Abstract 415-08. 5. Hines DM et al. Poster presented at ACC 2017. 6. PCSK9 prescribing informations 136 Totality of evidence from 1. PARAGON-HF: 13% RRR on composite primary endpoint of CV death and total (first and recurrent) HF hospitalization (p=0.059) 2. Urgent Heart Failure Visit = Received IV decongestive therapy PARAGON-HF1 (diuretics, neseritide or other natriuretic peptide, inotropes, and nitroglycerin), and does not result in inpatient hospital admission, regardless of the setting (i.e. in an ER setting, in the physician’s office, an outpatient treatment facility, etc.). 139 EDSS cutpoints for Sources: Ocrelizumab: Hauser et al.(2017), Ocrelizumab versus Interferon Beta-1a in RMS, NEJM. Natalizumab: Rudick et al. (2006), Natalizumab plus Interferon Beta-1a for RMS, NEJM, Polman et al. disability events (2006), A randomized, placebo-controlled trial of Natalizumab for RMS, NEJM. Alemtuzumab: Cohen et al. (2006), Alemtuzumab versus Interferon beta-1a in RMS, NEJM, Coles et al. (2012), Alemtuzumab vs. Interferon beta-1a in RMS, Lancet 144 Global commercial 1. UK, France, Germany, Italy, Spain. Brazil & Gulf included because of high SCD prevalence 2. As part of our longstanding commitment to improve health in Africa, we have entered into broad public- opportunity private partnership with Ghana government to tackle sickle cell disease, including access to available medicine, clinical research & use of digital technologies to achieve global standards of care. Novartis is evaluating in which countries to roll the initiative out further Source: Epi publications, DRG, Countries Forecast Model and Primary Market Research, Komodo claims data, SWAY survey 153 Piqray® launch 1. Sabine V, Crozier C, Brookes C, et al. Mutational analysis of PI3K/AKT signaling pathway in tamoxifen exemestane adjuvant multinational pathology study. Journal of Clinical Oncology. 2014;32:2951- 2958. 2. Juric D, Ciruelos EM, Rubovszky G et al. Alpelisib (ALP) + fulvestrant (FUL) for advanced breast cancer (ABC): Phase 3 SOLAR-1 trial results. Presented at the San Antonio Breast Cancer Symposium (SABCS) (Abstract #GS3-08) on December 6, 2018. 3. Data on file. Novartis Pharmaceuticals Corp; 2018. 155 Encouraging efficacy LEFT: Source: Jain S et al, Phase I study of alpelisib (BYL719) and trastuzumab emtansine (T-DM1) in HER2-positive metastatic breast cancer (MBC) after trastuzumab and taxane therapy, BCRT Apr data in HER2+ 2018. https://doi.org/10.1007/s10549-018-4792-0. RIGHT: Source: Sharma P et al, Clinical and biomarker results from Phase i/ii Study of PI3K inhibitor, BYL719 (Alpelisib) plus nab-paclitaxel in HER2- metastatic breast cancer. ASCO 2018, Abstract # 108. 159 Kisqali 1. Yu Q, Sicinska E, Geng Y, et al. Requirement for CDK4 kinase function in breast cancer. Cancer Cell. 2006;9(1):23-32 2. An H-X, Beckmann MW, Reifenberger G, Bender HG, Niederacher D. Gene amplification and overexpression of CDK4 in sporadic breast carcinomas is associated with high tumor cell proliferation. Am J Pathol. 1999;154(1):113-118 3. Kim S, Tiedt R, Loo A, et al. The potent and selective cyclin-dependent kinases 4 and 6 inhibitor ribociclib (LEE011) is a versatile combination partner in preclinical cancer models. Oncotarget. 2018;9(81):35226-35240;(suppl) 4. Sammons SL, Topping DL, Blackwell KL. HR+, HER2- advanced breast cancer and CDK4/6 inhibitors: mode of action, clinical activity, and safety profiles. Curr Cancer Drug Targets. 2017;17(7):637-649 162 Strong Phase 2 clinical LEFT: aConfirmed response based on investigator assessment per RECIST v1.1. bFrom Kaplan-Meier method for censored data. CBased on Cox regression model with treatment as a covariate data stratified by ECOG PS (0 vs 1) and LDH (LDH >1.1 × ULN vs =1.1 × ULN); owing to the small number of patients enrolled in the ECOG PS 1 and LDH ≤1.1 × ULN strata, these strata were combined. Data cutoff: Jun 26, 2019. RIGHT: aBased on Kaplan-Meier estimate of overall survival. bBased on Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs 1) and LDH (>1.1 × ULN vs ≤1.1 × ULN; owing to the small number of patients enrolled in the ECOG PS 1 and LDH ≤1.1 × ULN strata, these strata were combined. Data cutoff: Jun 26, 2019. 166 Kymriah® demonstrates 1. ALL- Grupp et al (ASH 2019 Abstract #2619). 2DLBCL- Jaglowski et al (ASH 2019 Abstract #766). 3Grupp SA et. al. Blood 2016; 128 (22): 221. 4. Bachanova V, et. al. Clin consistent efficacy Lymphoma Myeloma Leuk 2019 Sep. Vol 19; (Suppl 1); S251-S252. CIBMTR=Center for International Blood & Marrow Transplant Research; RWE=real world evidence; ALL=acute lymphoblastic leukemia; DLBCL=diffuse large B-cell lymphoma; ORR=overall response rate; CR=Complete response; DOR=duration of response; EFS=event-free survival, OS=overall survival; CRS=cytokine release syndrome, Neurotoxicity graded by ICANS (Immune effector cell-associated neurotoxicity syndrome)

180 Novartis R&D Day | December 5, 2019