Novartis Ag · SIX:NOVN
Novartis — CSFB presentation (November 2004)
57 slides from Novartis's conference presentation, Nov 10, 2004
Slide 1: Development Pipeline: Innovation, Focus, Productivity
Development Pipeline Innovation, Focus, Productivity Joerg Reinhardt Gregory Burke Head of Pharma Development Head of Oncology Development CSFB, 10 November 2004 The following information contains certain "Forward-looking Statements" relating to the Company's business, which can be identified by the
Slide 2: Agenda; Strong Business Performance in 9 Months
Agenda • Performance Update • Development Pipeline Update − Key projects • Oncology Pipeline Update • Outlook 3 J Reinhardt & G Burke / Novartis Development / CSFB 10 November 2004 Strong Business Performance Throughout 9 Months Results in Operating Margin Expansion in USD m 9M 2004 9M 2003 in % USD
Slide 3: Sustained Dynamic Sales Expansion
Sustained Dynamic Sales Expansion 9M 2004 sales: USD 20.67 bn 3Q 2004 sales: USD 7.06 bn 9M % sales growth 3Q % sales growth LC 11 LC 11 Pharmaceuticals USD 16 USD 15 LC 5 LC 7 Consumer Health USD 10 USD 11 LC 9 LC 9 Group USD 14 USD 14 5 J Reinhardt & G Burke / Novartis Development / CSFB 10 Novemb
Slide 4: Novartis Pharmaceuticals Continues to Outgrow the Market
Novartis Pharmaceuticals – Continues to Outgrow the Market Market Global quarterly value growth rates, in % Novartis 18 17 16 16 13 13 12 12 11 11 11 11 10 8 8 8 7 7 7 7 7 6 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q31 2002 2003 2004 1 July and August Source: IMS 16 Countries 7 J Reinhardt & G Burke / Novartis
Slide 5: Pharmaceuticals: All Regions with Dynamic Growth
Pharmaceuticals – All Regions with Dynamic Growth Sales Share YTD Sep 2004 Growth of total (USD m) (% LC) sales (%) North America 5 785 +12 43 Europe 4 663 +9 34 Japan 1 461 +9 11 Latin America 590 +17 4 Rest of world 1 029 +14 8 Total 13 528 +11 100 9 J Reinhardt & G Burke / Novartis Development /
Slide 6: Driven by Dynamic Performance of Key Brands
... Driven by Dynamic Performance of Key Brands Top 10 product sales YTD September 2004 in USD m Change in % (LC) YTD Sep 2004 Diovan 2 277 24 Glivec 1 168 38 Lamisil 861 16 Zometa 788 17 Neoral 742 -6 Lotrel 661 11 Sandostatin 602 13 Lescol 552 0 Voltaren 458 -1 Trileptal 376 31 11 J Reinhardt & G
Slide 7: Chronic Constipation Approval in US
Chronic Constipation Approval in US – New Patient Potential Patients with potential Rx treatment in US/Can2 (Mio.) x2 5.6 • First Rx treatment against chronic idiopathic constipation 2.7 • 50% of patients not satisfied with current treatment • 16% TRx uptake in first 4 weeks since approval IBS-C 1 C
Slide 8: Key Oncology Brands Performing Well
Key Oncology Brands Performing Well • Lancet – Improved progression-free survival in GIST1 with 800 vs 400 mg • Expected to be blockbuster in 2004 • 130% TRx growth post MA17 data • Extended Adjuvant approved in US, UK, CH and Mexico 1 Gastrointestinal Stromal Tumor 15 J Reinhardt & G Burke / Novart
Slide 9: Novartis Well Positioned
Novartis Well Positioned • Continued double digit growth ahead of market • Positive margin development • Highly attractive pipeline 17 J Reinhardt & G Burke / Novartis Development / CSFB 10 November 2004 Agenda • Performance Update • Development Pipeline Update − Key projects • Oncology Pipeline Upd
Slide 10: Key Priorities
Key Priorities • Strengthen our industry leading pipeline • Strategically balance our portfolio − Benefit / risk profile focused on promising markets − Innovative new molecular entities (NMEs) − Comprehensive lifecycle management (LCM) • Sustain our top tier development performance − Top ranked prod
Slide 11: Major Pipeline Projects in Registration
9 Major Pipeline Projects in Registration Diovan® VALIANT Submitted (US) Prexige® OA/Pain/primary Submitted (EU) dysmenorrhea Enablex™ Overactive bladder Approvable (US) Certican® Transplantation Approvable (US) Foradil® MDDPI2 Asthma Approvable (US) (Certihaler) Submitted (EU) Zelnorm® IBS-C Submit
Slide 12: Key Anticipated Pipeline Events 2005
Key Anticipated Pipeline Events 2005 Regulatory Data Submissions Decisions • ICL670 Phase III • ICL670 (chronic iron • Focalin XR (US) • LAF237 Phase III overload) • Aclasta (Paget’s • SPP100 Phase Ilb • PTK787 (colorectal disease) (US & EU) combo, phase III mono cancer, if PFS* • Zelnorm IBS (EU) a
Slide 13: Prexige Regulatory Status
Prexige® – Regulatory Status • Europe − Mutual Recognition Procedure (MRP) began September 2004 − CHMP announced review of Cox-2 class with respect to CV safety on 22 October 2004 − Delay of MRP expected • US − TARGET data submitted and under review − Additional studies underway to support 100mg dos
Slide 14: No Difference in APTC or MI Events in TARGET
No difference in APTC or MI Events in TARGET Patients With a High CV Risk or CCV History1,2 % incidence Prexige® 2.0 NSAIDs HR = 1.01 p=NS 1.6 1.23 1.22 1.2 HR = 1.11 (14) (13) p=NS 0.8 0.61 0.56 (7) (6) 0.4 0 APTC3 Events MI Events (n) represents number of patients with events, HR = Hazard Ratio 1H
Slide 15: No Significant Difference in MIs vs Ibuprofen
There is No Significant Difference in Confirmed or Probable MIs (Clinical and Silent) Between Ibuprofen and Prexige® Prexige® HR = 0.47 Incidence % (n) Ibuprofen p = NS 0.35 HR = 0.66 0.30 0.3 p = NS HR = 0.75 p = NS (2) 0.25 0.23 0.21 0.2 (7) (5) 0.16 0.15 0.15 0.14 (4) (5) (1) 0.1 0.05 0 N 4376 43
Slide 16: Type 2 Diabetes: A Global Epidemic
Agenda • Performance Update • Prexige • Development Pipeline Update • LAF237 − Key projects • SPP100 • Oncology Pipeline Update • Zelnorm • Outlook • Xolair • Aclasta • LDT600 31 J Reinhardt & G Burke / Novartis Development / CSFB 10 November 2004 Type 2 Diabetes Mellitus (T2DM): A Global Epidemic 1
Slide 17: LAF237 First-In-Class Incretin Enhancer
The DPP-4 Inhibitor, LAF237, is the First-In-Class ‘Incretin Enhancer’ for the Treatment of T2DM1 LAF237 • First in the new class Incretin O H N Enhancers, that act by enhancing the incretin hormones GLP-1 and HO N N GIP2 • Mechanisms of action includes effects on insulin and glucagon Mixed meal • P
Slide 18: LAF237 Reduces HbA1c Over 1 Year
Sustained Elevation of GLP-1 and GIP Levels Throughout the Day are Achieved with LAF Treatment Day 28, LAF treated patients Day 1, LAF treated patients GLP-1 levels GIP levels Intact GLP-1 (pmol/L) Intact GIP (pmol/L) 25 200 20 150 15 100 10 50 5 0 0 0 5 10 0 5 10 time (hr) time (hr) Source: Study L
Slide 19: Phase II Data Indicate LAF237 is Well Tolerated
Phase II Data Indicate that LAF237 is Well Tolerated • Incidence of nausea and/or vomiting no different from placebo • Low incidence of symptoms of hypoglycemia • No changes in liver enzymes • No increased creatine phosphokinase • No significant change in body weight Data on file, Novartis. 37 J Rei
Slide 20: Treated Hypertension Patients Expected to Grow
Agenda • Performance Update • Prexige • Development Pipeline Update • LAF237 − Key projects • SPP100 • Oncology Pipeline Update • Zelnorm • Outlook • Xolair • Aclasta • LDT600 39 J Reinhardt & G Burke / Novartis Development / CSFB 10 November 2004 Number of Treated Hypertension Patients Expected to
Slide 21: SPP100 Tolerability and Renin Activity
Unmet Needs Remain in Hypertension: ACEis, ARBs and Diuretics Lead to Increased Renin Activity Angiotensin ogen Diuretic ↑ Renin Volume activity depletion ACE- independent pathways Angiotensin I Compensatory feedback mechanisms ACE ACEI ARB AT1 Harmful effects Receptor Angiotensin II Potential harmf
Slide 22: SPP100 Phase IIb/III On Track
Phase IIb/III for SPP100 monotherapy and SPP100/valsartan combination is on track Design: Randomized, placebo-controlled, multifactorial study Primary objective: BP-lowering efficacy of SPP100 75, 150, and 300 mg Secondary objective: Proof of concept on additivity of SPP100 and valsartan Population:
Slide 23: Patients with IBS Have Altered Serotonin Signalling
Patients with IBS Have Altered Serotonin Signalling in The GI Tract SERT-immunoreactivity in human rectal biopsy samples Green fluorescence indicates presence of serotonin transporter (SERT) Biopsy of healthy colon Biopsy of colon of IBS patient Normal SERT levels in these Low SERT levels in these i
Slide 24: Establishing Leadership in Chronic Constipation
Establishing Leadership in Chronic Constipation Zelnorm/Zelmac 6 mg b.i.d. 60 Placebo * * Responders (incr. 1 50 * * * * * * * CSBM/week; %) * * * 40 30 20 10 0 1 2 3 4 5 6 7 8 9 10 11 12 Week • FDA approved Zelnorm for treatment of chronic idiopathic constipation in August 2004 • Males and females
Slide 25: Zelnorm: Promotility Agent for GI Dysmotility Disorders
Zelnorm: Promotility Agent for the Treatment of GI* Dysmotility Disorders (GIDDs) • GIDDs are chronic disorders characterised by multiple symptoms GERD throughout the GI tract (Proof of Concept) IBS-C • Common symptoms include Dyspepsia Approved (US) constipation, abdominal Submitted (EU) (Phase III
Slide 26: Profound Unmet Need Remains for Asthma
Profound Unmet Need Remains for Asthma Patients 80 Disability-adjusted life • Disability-adjusted life 70 years (DALYs) lost DALYs Lost ('000s) years (DALYs) lost due to 60 Ischemic heart disease asthma comparable to 50 n e er ury diabetes, depression, lung s io 40 rok l PD s nc cta nc e te inj es a
Slide 27: Xolair INNOVATE Study
Xolair - The INNOVATE study • Add on Xolair therapy − reduced clinically significant asthma exacerbations − reduced severe asthma exacerbations − reduced emergency visits − improved asthma-related QoL • Submission filed via centralised procedure to European regulatory authority (EMEA) in June 2004,
Slide 28: Quality of Life Significantly Improved
Quality of Life Significantly Improved Overall and Across All Domains Omalizumab AQLQ score (change from baseline, LSM) Placebo 0.95 0.91 1.0 0.91 0.9 0.89 * ** ** ** ** 0.8 0.57 0.6 0.46 0.44 0.46 0.4 0.4 0.2 0 Activities Emotions Symptoms Environment Overall *p=0.002; **p<0.001 AQLQ = Asthma Quali
Slide 29: Proposed European Label
Proposed European Label • Omalizumab is indicated for the prevention of asthma exacerbations and control of asthma symptoms • Add-on therapy for adult and adolescent patients • Severe persistent allergic asthma who remain inadequately controlled • Despite daily high-dose inhaled corticosteroids (ICS
Slide 30: Aclasta: Once-a-Year Bisphosphonate
Aclasta – Once-a-Year Bisphosphonate • The potential future gold standard in osteoporosis • Superior efficacy in Paget’s disease • Potential in rheumatoid arthritis • Highly convenient, highly efficacious, well tolerated • Single annual infusion providing unsurpassed compliance and excellent bone pr
Slide 31: A Complete Clinical Program Is in Progress
A Complete Clinical Program Is in Progress Recently started phase III Trials • Male osteoporosis Submission • PMO Prevention in PMO • CIO1 treatment 2002 2003 2004 2005 2006 2007 2008 Ongoing Phase III Trials Submission in • Fracture trial in PMO Paget’s disease • Recurrent fracture trial Recruitmen
Slide 32: LDT600 Taking Efficacy to a New Level
LDT600 (Phase III) Taking Efficacy to a New Level • 400 m long-term carriers of HBV1 Infected cell worldwide Transcription of pre- − 250 m in Asia-Pacific, 1.5 m in North genomic RNA America, 17 m in EU − 1 m die each year from HBV infection Encapsulation • Current therapies leave substantial (+) st
Slide 33: LDT600 Clinical Development; 10 Highly Innovative Compounds
LDT600 (Phase III) Clinical Development • Comparisons of efficacy & safety vs lamivudine are key element of the program • Studies in compensated patients completed enrollment ahead of schedule; study in decompensated patients will be ongoing at time of submission • To date over 1727 patients are enr
Slide 34: Novartis Oncology
Agenda • Performance Update • Development Pipeline Update − Key projects • Oncology Pipeline Update • Outlook 67 J Reinhardt & G Burke / Novartis Development / CSFB 10 November 2004 Novartis Oncology Novartis Oncology is well poised to bring innovative therapies to the cancer marketplace both in the
Slide 35: Femara: Best-in-Class Aromatase Inhibitor
Agenda • Performance Update • Femara® • Development Pipeline Update • Glivec® − Key projects • Zometa • Oncology Pipeline Update • ICL670 • Outlook • PTK787 • Early pipeline 69 J Reinhardt & G Burke / Novartis Development / CSFB 10 November 2004 Femara - The Best-in-Class Aromatase Inhibitor Unmatch
Slide 36: Updated Extended Adjuvant Data at ASCO
Updated Extended Adjuvant Data at ASCO – 42% Reduction in Breast Cancer Recurrence Risk Femara Placebo HR (n=2575) (n=2582) (95% Cl) P Value DFS* events 92 155 0.58 0.00004 (0.45-0.76) 4-y DFS rate 94.7% 89.8% *Disease-Free Survival, stratified by nodal, hormone receptor, and prior chemotherapy stat
Slide 37: Extended Adjuvant Approvals; BIG 1-98
Extended Adjuvant Regulatory Approvals in Several Markets • Submission of data to Health Authorities in Q2 04 • Approval granted in Mexico in Q2 04; Switzerland, UK in Q3 04 • US approval on Oct 29, 2004 • Approval in Canada imminent, EU (EMEA) approval expected Q1 05 Approval Timeline: Mexico Switz
Slide 38: Market Potential for Extended and Early Adjuvant
Market Potential for Extended and Early Adjuvant Settings is Large Total Patients, US, 5EU and Japan 000s Extended Adjuvant Early Adjuvant (MA-17 setting) (BIG 1-98 setting) 1 200 > 1000 1 000 800 600 400 200-250 200 0 Coming off of Tamoxifen therapy Currently on Tamoxifen each year Source: Novartis
Slide 39: Glivec Heme-Onc Development Program
Agenda • Performance Update • Femara® • Development Pipeline Update • Glivec® − Key projects • Zometa • Oncology Pipeline Update • ICL670 • Outlook • PTK787 • Early pipeline 77 J Reinhardt & G Burke / Novartis Development / CSFB 10 November 2004 Glivec® / Gleevec® Heme-Onc Development Program Market
Slide 40: Glivec in Ph+ ALL and Prostate Cancer
Preliminary Data for Glivec® / Gleevec® in Ph+ Acute Lymphatic Leukaemia Source: Blood, Jun 2004; 103: 4396 – 4407; Dr. Deborah Thomas, MD Anderson Cancer Center 79 J Reinhardt & G Burke / Novartis Development / CSFB 10 November 2004 Glivec® / Gleevec® Plus Taxotere Phase II in Hormone Refractory Pr
Slide 41: Glivec in Refractory Glioblastoma
Promising Preliminary Data in Combination with Hydroxyurea in Refractory Glioblastoma Multiforme Recurrent GBMs Dresemann et. al. Patients 26 CR 1 PR 4 SD 9 CR+PR+SD1 14 PD 12 Median PFS 6 months Median OS 9 months 1 Based on RECIST criteria Source: Proc Am Soc Clin Oncol 23: pg 119, 2004 (poster 15
Slide 42: Recent Japanese Zometa Data
Agenda • Performance Update • Femara® • Development Pipeline Update • Glivec® − Key projects • Zometa • Oncology Pipeline Update • ICL670 • Outlook • PTK787 • Early pipeline 83 J Reinhardt & G Burke / Novartis Development / CSFB 10 November 2004 Recent Japanese Zometa Data Reinforces Efficacy and Sa
Slide 43: Looking to the Future for Zometa
Looking to the Future for Zometa Prevention of bone metastases: Several large randomized clinical trials ongoing : • Breast cancer - 3 studies across the globe, >10 000 patients • Prostate cancer - 3 studies across the globe, >5 000 patients • Lung cancer - 2 studies US/EU , ~ 1 000 patients Prevent
Slide 44: ICL670 Oral Iron Chelator
ICL670 – Oral Iron Chelator Filing in H1 2005 Tridentate iron chelator • An oral, dispersible tablet • Administered once daily • Highly specific for iron • Phase II trials in patients with secondary iron overload has shown iron clearance comparable to deferoxamine • Multinational phase III trials in
Slide 45: PTK787 First Oral Angiogenesis Inhibitor
Agenda • Performance Update • Femara® • Development Pipeline Update • Glivec® − Key projects • Zometa • Oncology Pipeline Update • ICL670 • Outlook • PTK787 • Early pipeline 89 J Reinhardt & G Burke / Novartis Development / CSFB 10 November 2004 PTK7871 - First Oral Angiogenesis Inhibitor in Colorec
Slide 46: PTK787 Broad Spectrum of VEGF Inhibition
PTK787 Shows Broad Spectrum of VEGF Inhibition VEGF-A VEGF-A VEGF-C VEGF-B VEGF-C VEGF-D VEGF-D VEGF-E PTK/ZK PTK/ZK PTK/ZK P P P P P P P P P P P P VEGFR-1/Flt-1 VEGFR-2/KDR VEGFR-3/Flt-4 Angiogenesis Angiogenesis Lymphangiogenesis Tumor metastasis Dvorak HF. J Clin Oncol. 2002;20:4368-4380. 91 J Re
Slide 47: Promising Earlier Pipeline Oncology Opportunities
Agenda • Performance Update • Femara® • Development Pipeline Update • Glivec® − Key projects • Zometa • Oncology Pipeline Update • ICL670 • Outlook • PTK787 • Early pipeline 93 J Reinhardt & G Burke / Novartis Development / CSFB 10 November 2004 Promising Earlier Pipeline Oncology Opportunities…. LB
Slide 48: Earlier Pipeline; Key Trends in Oncology R&D
….Promising Earlier Pipeline Oncology Opportunities AMN107 • Oral signal transduction inhibitor, currently in phase I • Early preclinical experience has shown − AMN107 targets bcr-abl, c-kit, and PDGF receptor − Activity against some bcr-abl mutations that Glivec does not inhibit − AMN107 is not a s
Slide 49: Well Positioned to Capitalize on Trends
Novartis is Well Positioned to Capitalize on these Trends Ç importance of specific • Pipeline that is broad as well as deep pathways • Several projects targeting pathways known to be important in tumorigenesis • Compounds with broad spectrum of activity (e.g., AEE788, RAD001) Ç emphasis on blocking
Slide 50: Targeting Key Cancer Pathways
… And Targeting Key Cancer Pathways Vascular PTK/ZK endothelial cell PTK/ZK AEE788 PTK/ZK Tumor cell Intracellular c-Kit IGF-1R PDGFR Extracellular EGFR VEGFR-1/FLT1 HER2 VEGFR-2/KDR Extracellular VEGFR-3 FLT3 Intracellular Preclinical AMN107 AMN107 AEE788 AEE788 Bcr-Abl mTor RAF AMN107 RAD001 Precl
Slide 51: Benefits of Translational Medicine Approach
Benefits of Translational Medicine Approach Faster • Patient stratification allows for smaller, more Development focused trials • Ability to more quickly select dose • Possibility for earlier read out in biomarker effects Increased • More informed, data rich early clinical trials Probability of • Be
Slide 52: Summary; Oncology Broad and Deep Pipeline
Summary Novartis Oncology well positioned to bring novel, innovative therapies to the cancer marketplace • Exciting programs in near term − Femara: Extended and Early Adjuvant − ICL670: iron overload − PTK787: oral angiogenesis inhibition • In the longer-term, well positioned to capitalize on the ke
Slide 53: Outlook for 2004
Agenda • Performance Update • Development Pipeline Update − Key projects • Oncology Pipeline Update • Outlook 105 J Reinhardt & G Burke / Novartis Development / CSFB 10 November 2004 Outlook for 2004 • Strong business expansion expected to continue • High single-digit sales growth in constant curren
Slide 54: Increase in Number of Blockbusters; Planned Filings
Significant Increase in Number of Blockbusters % of total pharma sales 50% Diovan® Lotrel® • Effective positioning and messaging Glivec®/Gleevec® • Strong field force Zometa® 20% execution Diovan® • Powerful LCM1 Zelmac®/Zelnorm® • Effective DTC2 Elidel® Glivec®/Gleevec® • M&S “Science” Neoral® Fema
Slide 55: Appendix: Pipeline Review
Appendix: Pipeline Review A Focused Portfolio in Attractive Market Segments Phase Business unit / Business franchise I II III & Reg Total Nervous system 2 5 5 12 Cardiovascular, metabolism 2 1 7 10 Primary Arthritis, bone, GI1, HRT2 4 4 6 14 care Infectious Diseases 1 1 1 3 Respiratory, dermatology
Slide 56: Steady Flow of Compounds in Development
Steady Flow of Compounds in Development Number of projects 90 78 80 74 69 67 70 65 60 53 54 50 40 30 20 10 0 Mar 98 Aug 99 Dec 00 Oct 01 Oct 02 Nov 03 Nov 04 111 J Reinhardt & G Burke / Novartis Development / CSFB 10 November 2004 Pipeline Under Constant Review and Renewal 80 70 13 9 60 50 40 78 74
Slide 57: Over Half of Development Projects are NMEs
Over Half of Development Projects are NMEs November 2004: 74 projects NME1 = 40 projects LCM2 = 34 projects 46% 54% 1 New Molecular Entitiy 2 Life Cycle Management 113 J Reinhardt & G Burke / Novartis Development / CSFB 10 November 2004 57