AstraZeneca PLC · LSE:AZN
AstraZeneca — Investor Presentation (2002)
65 slides from AstraZeneca's investor presentation, 2002
Slide 1: Oncology Review
Oncology Review A Brent Vose Vice President and Head of Oncology Therapy Area, R&D Number of cancer patients rising Patients G7 m 8.0 Drivers 7.0 Prostate Increasing 6.0 Incidence 5.0 Ageing Breast Population 4.0 3.0 Earlier Colorectal Diagnosis 2.0 1.0 Gastric Lung 0 2002 2006 2010 Decision Resourc
Slide 2: Five year survival rates
Five year survival rates Incidence G7 2002 ,000 450 400 350 15% % Surviving 300 2007 62% 250 86% 200 22% 97% 150 100 50 0 Breast Prostate Colorectal Gastric Lung Incidence data from Decision Resources ONKOS series – top 7 markets USA, Japan, France, Germany, Italy, Spain, UK All Survival data from S
Slide 3: Cancer Disease Continuum
Cancer Disease Continuum Basic treatment opportunities Risk Factor Diagnosis/ Assessment Diagnosis Progression “At Risk” Early Disease Advanced Disease Treatment opportunities “Prevention” Neo-adjuvant/Adjuvant 1st line 2nd line 3rd line Nolvadex® 20 years Arimidex® 7 years A Cytotoxic therapy in lu
Slide 4: Biological effect areas in cancer
Biological effect areas in cancer b Hormonal agents are T T chronic, well-tolerated, ERE RNA POLII biologically-targeted Coactivator therapies T: Tamoxifen RNA POLII: RNA Polymerase II ERE: Estrogen Response Element Proliferating tumour cells b Many more biological processes understood at Tumour vas
Slide 5: The current AstraZeneca approaches
The current AstraZeneca approaches Hormones Angiogenesis Invasion Zoladex® AZD6474 AZD0530 Nolvadex® AZD2171 Casodex® Arimidex® Faslodex® Vascular Targeting AZD6126 Anti Proliferatives AZD4440 Iressa® AZD3409 Cell Cycle MEK Aurora ERB2 CDK2 ZD4054 A AstraZeneca Development of novel cancer therapies
Slide 6: Oncology programme
Oncology programme b Hormonal Products George Blackledge b Iressa Linda Summerton b Early Portfolio Alan Barge b Oncology Q&A A Oncology Review: Brent Vose 6
Slide 7: AstraZeneca's Hormone Portfolio
AstraZeneca’s Hormone Portfolio A George Blackledge Vice President of Medical Oncology Hormone therapy for breast and prostate cancer b Two of the most common cancers b Hormone therapy a fundamental component of treatment b AstraZeneca is the leading player in both markets b Thousands of lived saved
Slide 8: Strong base business with new products driving growth
Strong base business with new products driving growth +13% +11% 3% +9% 35% 40% 27% 31% 73% 69% 65% 57% 1999 2000 2001 YTD 2002 Nolvadex®/Zoladex®/Tomudex® Casodex®/Arimidex® Faslodex®/Iressa® A Hormonal therapies in cancer – Mechanisms Testis Testosterone Gonadotrophins Prostate x Casodex ® (FSH + L
Slide 9: Hormones are targeted therapy
Hormones are targeted therapy b Our treatments are highly targeted ✦ bind selectively to the receptors ✦ block specific enzymes b Role models for the new generation of anti- cancer treatments b What we have done and will do with hormones we will do with Iressa® and our new compounds A Incidence of c
Slide 10: Prostate Cancer Continuum / Zoladex
Prostate Cancer Continuum Localized Locally Metastatic Hormone HG PIN prostate cancer advanced disease insensitive TIME (years) Tx N0 M0 T3-4 D1.5 D2 D2.5 D3 Elevated PSA Rising PSA after Rising PSA Negative biopsies local therapy after first line hormonal treatment A Zoladex® b AstraZeneca Oncology
Slide 11: Zoladex gives survival benefit
Zoladex® gives survival benefit at 5 years 100 90 79% (72–86%) 80 % patients surviving 70 60 62% 50 (52–72%) 40 30 20 Radiotherapy + Zoladex® 3.6mg (n=205) 10 Radiotherapy alone (n=198) 0 0 1 2 3 4 5 6 7 8 9 10 Time (years) HR 0.50; 95% CI 0.33, 0.76; p=0.001 Bolla et al. 1997, 1999. A Zoladex® 2002
Slide 12: Zoladex: a proven success
Winning in Japan b Zoladex® 10.8mg launched in Japan in April 2002 b Launch ahead of Leuplin® 3 month depot b Gained further market share within the first 4 weeks of launch b Positive survival data and convenience produce a winning medicine A Zoladex® – A proven success b Strong clinical data provid
Slide 13: Casodex: market leader in early prostate cancer
Casodex® – A market leader, expanding treatment options in Early Prostate Cancer b Casodex® building on market leadership with continuing strong growth (MAT Sales $641m Sept 2002) b Casodex® continues to reinforce its position as number one anti-androgen with 69% global market share b Rapid acceptan
Slide 14: Casodex reduces risk for objective progression by 42%
Casodex® reduces risk for objective progression by 42% Proportion 1.0 Casodex® and not Standard Therapy 0.9 progressing 0.8 0.7 Standard Therapy 0.6 0.5 0.4 0.3 0.2 HR 0.58; 95% CI 0.51, 0.66; p<<0.0001 363 (9.0%) progressed on CASODEX 0.1 559 (13.8%) progressed on Standard Therapy 0.0 0 200 400 600
Slide 15: Casodex reduces risk of PSA progression in all trials
Casodex® reduces risk of PSA progression in all 3 trials % 70 HR=0.24 patients Casodex® p<<0.0001 with an 60 Standard Therapy 54.8 event 50 HR=0.37 p<<0.0001 40 HR=0.62 p<<0.0001 33.2 30 24.0 21.6 20 16.4 15.1 10 0 US Europe Scandinavian Trial Trial Trial (n=3292) (n=3603) (n=1218) A Casodex® reduce
Slide 16: Casodex EPC regulatory approvals
Casodex® prevents bone loss Casodex® 150 mg Mean % 3.0 Zoladex® 10.8 mg change 2.0 from baseline 1.0 0.0 -1.0 -2.0 -3.0 -4.0 -5.0 -6.0 24 48 72 96 Follow-up (weeks) A Casodex® – EPC regulatory approvals b Casodex® is approved for usage in early prostate cancer in 26 markets b Regulatory reviews are
Slide 17: Moving annual totals - Casodex brand
Moving annual totals – Casodex® brand 641 650 599 569 578 550 511 457 433 433 450 409 $m 350 250 150 50 Mar-01 Mar-02 Dec-00 Dec-01 Sep-00 Sep-01 Sep-02 Jun-01 Jun-02 -50 A Incidence of common solid tumours in the US Primary 2000 Estimated Tumour Site US Annual Incidence* Breast 184,200 87,000 death
Slide 18: Four key medicines for breast cancer
Four key medicines for breast cancer b Nolvadex® b Zoladex® b Faslodex® b Arimidex® A Breast Cancer Continuum: Consistency of results on 5 Years of Nolvadex® Prevention Data Contralateral BC 13,388 Women 2,818 Women 40 40 30 30 20 20 10 10 0 0 0 1 2 3 4 5 0 1 2 3 4 5 6 Years on Study DCIS Years on S
Slide 19: Improving adjuvant treatment of pre-menopausal breast cancer
Improving the adjuvant treatment of pre-menopausal breast cancer b Around 60% of pre-menopausal breast cancer patients have ER+ve tumours b Standard treatment = surgery followed by radiotherapy and/or adjuvant chemotherapy b Ovarian ablation is an option as effective treatment in pre-menopausal dise
Slide 20: Zoladex role in early breast cancer
Whatever the treatment decision for a patient with ER+ early breast cancer, Zoladex® has a role to play b When Zoladex® is added to Nolvadex® outcome is improved b When Zoladex® replaces chemotherapy outcome is identical with fewer side effects A Summary of NIH 2000 consensus and St. Gallen 2001 gui
Slide 21: Aims of Faslodex development programme
Aims at outset of Faslodex® development programme b To discover a novel antiestrogen, devoid of the partial agonist, estrogen-like activity of Nolvadex® and other available antiestrogens b Faslodex® is the first and only Selective Estrogen Receptor Downregulator Potential Advantages b Greater effica
Slide 22: Faslodex Trial 0021
Faslodex®: Trial 0021 Clinical benefit rates (%) in second-line advanced disease Arimidex® 18.6% 13.9% 3.6% CR PR SD>24wks Faslodex® 24.8% 12.6% 4.9% 0 10 20 30 40 50 Odds ratio for OR (CR+PR) = 1.01 (95% CL 0.59, 1.73); p=0.96 AstraZeneca data on file A Faslodex® A novel, breakthrough approach in b
Slide 23: Faslodex launched in US
Faslodex® – Launched in US b A valuable additional treatment for metastatic breast cancer in postmenopausal women, given as a monthly injection b Phase 3 data confirms pre-clinical and early clinical data: duration of response greater than that of Arimidex® b Launched in US - May 2002 ✦ 100% awarene
Slide 24: Future directions for Faslodex
Future directions for Faslodex® b First line data against tamoxifen show importance of targeting relevant populations ✦ ER/PR +ve patients do better with Faslodex® ✦ highly selective targeted treatments will show the best results in a selected group b Second line submission will be in 2003 in Europe
Slide 25: ATAC trial design
ATAC Trial design Postmenopausal women with invasive breast cancer Surgery ± radiotherapy ± chemotherapy Randomisation 1:1:1 for 5 years Arimidex® 1mg o.d. Arimidex® placebo Arimidex® 1mg o.d. + + + tamoxifen placebo tamoxifen 20mg o.d. + tamoxifen 20mg o.d. Regular follow-up Primary trial endpoints
Slide 26: Kaplan-Meier curves of disease-free survival
Kaplan–Meier curves of disease-free survival in receptor-positive population HR 95.2% CI p-value AN vs TAM 0.78 0.65–0.93 0.0054 Comb vs TAM 1.02 0.87–1.21 0.7786 100 95 Proportion event free (%) 90 85 80 Arimidex® 75 Tamoxifen Arimidex® + tamoxifen 0 0 12 24 36 48 Time to event (months) A Projected
Slide 27: ATAC data means more lives saved
ATAC data means more lives saved b Tamoxifen prevents the relapse of >22,000 women in the US each year b Arimidex® ALONE will prevent the relapse of >25,000 women in the US each year b Worldwide this translates into>100,000 women each year being less at risk of dying from breast cancer A Significant
Slide 28: Arimidex current performance
Arimidex® current performance Arimidex® Share of the Global Aromatase Inhibitors Market fadrozole formestane 0.4% aminoglutethimide 2.5% 0.3% exemestane 12.7% ® Arimidex 53.3% letrozole 30.8% Source : IMS Health MIDAS MAT Q2 02 A Arimidex® current performance: US market Positive reaction to ATAC dat
Slide 29: Arimidex - The future
Arimidex® – The future b Adjuvant ✦ over 16,085 patients have been involved in the development of Arimidex® in early breast cancer b Prevention ✦ two studies involving >17,000 patients are about to start b Neoadjuvant ✦ three studies with ≥604 patients recruited b 4 year follow up data to be present
Slide 30: Hormone therapy - Summary
Hormone therapy – Summary b Building on success – a unique franchise in breast and prostate cancer b Highly selective targeting to receptors and enzymes b New uses and indications for hormone therapies continue to emerge primarily as monotherapy used sequentially – experience to be used in developin
Slide 31: Hormone therapy - Summary
Hormone therapy – Summary b Building on success – a unique franchise in breast and prostate cancer b Highly selective targeting to receptors and enzymes b New uses and indications for hormone therapies continue to emerge primarily as monotherapy used sequentially – experience to be used in developin
Slide 32: Oncology: Iressa
Oncology: Iressa® A Linda Summerton Global Product Director, Iressa® NSCLC NSCLC – Huge unmet need b Leading cause of cancer death in most developed countries (1.1m in 2000). NSCLC is over 80% of all cases b 60-70% of diagnoses are made late, after spread of disease from lungs to other organs - brai
Slide 33: NSCLC Continuum
NSCLC Continuum Many opportunities for novel therapy Locally or Advanced Advanced Pre- Localised regionally metastatic metastatic malignancy tumours advanced disease disease disease - refractory S(+RT) CT +RT CT Novel targeted therapy S=surgery; RT=radiotherapy; CT=chemotherapy A Turning on the EGFR
Slide 34: Outcomes in NSCLC patients from start of 3rd- and 4th-line therapy
Outcomes in NSCLC patients from start of 3rd- and 4th-line therapy 1.0 Objective response 2.3% 3rd line 0.9 0% 4th line 0.8 Survival probability 0.7 Median survival 4.5 months 0.6 1-year survival 5% 0.5 0.4 0.3 0.2 0.1 0.0 0 6 12 18 24 Months after start of 3rd- or 4th-line therapy Massarelli et al.
Slide 35: Quality of tumour response from IDEAL
Quality of tumour response from IDEAL Frequent 10 – 19%, irrespective of prior treatments and low performance status 64% responses in tumours > 10cm2 Rapid 77% of responses within first 4 weeks Durable IDEAL 1: 11 months (range 2-20+ months) 7 ongoing responses (> 15 months) IDEAL 2: 7 months (range
Slide 36: Disease-related symptoms in NSCLC
Disease-related symptoms in NSCLC b Specific symptoms ✦ shortness of breath ✦ cough ✦ tightness in the chest ✦ difficulty breathing ✦ poor appetite and weight loss ✦ fatigue b Type, severity, frequency depend on tumour location, disease burden, and growth rate A Correlation of symptom improvement wi
Slide 37: Patient 0166, IDEAL
Patient 0166, IDEAL 2 Liver: 6.1 cm2 Nodes, bone, lung: nonmeasurable 28 26 24 PS 1 22 20 Concomitant LCS score 18 Most improved infection 16 Breathing PS 2 14 Cough 12 Appetite 10 8 6.1 2.7 2.0 1.0 6 (0) (–56%) (–67%) (–84%) 4 PR PRNM nodes PR 2 0 –2 0 2 4 6 8 10 12 14 16 18 20 22 24 Weeks from ran
Slide 38: Iressa expanded access programme
Iressa® expanded access programme ≤ 3 months ≥ 12 months 44% 28% 3 - 6 months 6 - 12 months 16% 12% Over 21,000 patients enrolled worldwide A Iressa® is well tolerated Iressa® 250mg in over 42,000 patients shows: b Diarrhoea and skin rash common, but only severe (grade 3-4) in 1% patients b Intersti
Slide 39: Iressa regulatory timetable
Iressa® regulatory timetable b Japan – approved July 2002 b USA – ODAC recommendation for accelerated approval September 2002 b Switzerland, Australia, New Zealand, Canada, Brazil – refractory package under review b MAA submission Q1 2003 A Iressa® in Japan b Best ever launch of an oncology product
Slide 40: Ceiling for cytotoxic chemotherapy in 1st line NSCLC?
Ceiling for cytotoxic chemotherapy in 1st line advanced NSCLC? b All recent randomized studies have similar results b Median survival of about 8 months b Paradigm shift needed b Role for novel targeted therapies? Schiller JH, et. al. NEJM 2002 A 1st Line combination therapy INTACT Trials b Rationale
Slide 41: Survival - INTACT
Survival - INTACT 2 1.0 500 mg: 250 mg: Placebo: 0.9 MS: 8.74 mo 9.82 mo 9.92 mo 0.8 Proportion event free 1-Year: 0.37 0.41 0.42 0.7 Log rank: 0.4641 -0.4254 0.6 (p=0.6425) (p=0.6705) 0.5 0.4 0.3 CT + Group 500 mg/day 0.2 CT + Group 250 mg/day CT + Placebo 0.1 0.0 0 4 8 12 16 20 24 Survival time (m
Slide 42: Key learnings for further development of Iressa in NSCLC
Key learnings for further development of Iressa® in NSCLC b Iressa® is an active drug in refractory NSCLC b Combination chemotherapy occupies a short time in the life of a NSCLC patient - the opportunities for a well-tolerated, oral, chronic therapy are therefore significant b Iressa® may replace ch
Slide 43: Head & neck cancer - Phase II
Head & neck cancer – Phase II Response No. (%)* b 47 evaluable patients b ORR: 11% CR 1 (2) (95% CI: 3.5-23.1) PR 3 (6) b Disease control PR (unconf.) 1 (2) (CR/PR/SD): 53% b 3 patients remain on study, 6-9 months SD 21 (45) b 13% had disease PD 22 (47) control > 6 months *NCI audited data A Iressa®
Slide 44: Future potential due to EGFR expression
Future potential due to EGFR expression Primary 2000 Estimated US % of Tumours Tumour Site Annual Incidence* Expressing EGFR Lung 164,100 40%-80% Colorectal 130,200 25%-77% Breast 184,200 14%-91% Head and Neck 30,200 80%-100% Esophageal 12,300 43%-89% Renal Cell 31,200 50%-90% Prostate 180,400 65% B
Slide 45: Is there a sub-population in whom Iressa works best?
Is there a sub-population of patients in whom Iressa® works best? b Results to date indicate level of EGFR expression alone is not predictive for level of activity b Analysis for EGFR and ongoing from IDEAL and INTACT trials b Pharmaco-genomic and proteonomic analyses underway in ongoing NSCLC and o
Slide 46: Activated EGFR as a predictor of response to Iressa
Activated EGFR as a predictor or response to Iressa®? Tumour markers of EGFR activation before and after treatment % p-EGFR 120 % p-MAPK 100 100 80 80 60 60 40 40 20 20 p=0.001 p=0.073 0 0 -20 -20 % Ki67 100 80 60 Pre-Iressa® 40 Post- Iressa® p=0.037 20 0 Baselga J. Personal communication A Iressa®
Slide 47: Genes up- or down-regulated with Iressa resistance
Genes up-or down-regulated with Iressa® resistance Parental Iressa®-resistant line 2 0 13 25 38 50 63 75 88 0 1 2 3 4 5 0 10 20 30 40 50 Geller JA et al. Proc AACR 2002 A Correlation of efficacy with genetic markers? Profiling of responders/non-responders in NSCLC PK sample Microarray Criteria l NSC
Slide 48: Summary
Summary b Iressa® is the first novel targeted therapy from AstraZeneca to reach the market b Iressa® is the first anti-EGFR therapy to reach the market b IDEAL and INTACT have provided clear insight how anti- EGFR agents should and should not be used to treat NSCLC b AstraZeneca remains committed to
Slide 49: Oncology: Early portfolio
Oncology: Early portfolio A Alan Barge Global Product Director The biology of cancer Malignant cell A Oncology: Early portfolio: Alan Barge 1
Slide 50: The biology of cancer
The biology of cancer Endothelial Maintenance Metastatic Angiogenesis Deposit Invasion Secondary Proliferation Proliferation Secondary Angiogenesis Primary Tumour A Translational Science: Understanding the disease, the target and the drug EGFR P P P A Oncology: Early portfolio: Alan Barge 2
Slide 51: Antiproliferative agents
Antiproliferative agents Malignant cell Proliferation ZD4054 AZD3409 Primary Tumour A Anti-proliferative targets - Tumour cells Growth Factor Receptor Receptor TKIs ras Iressa® FAMILY P P P Endothelin antagonist SOS P ZD4054 P P RAF P MEK Downstream Signal P Inhibitors MAPK ZD3409 Nucleus Cell Cycle
Slide 52: ZD4054: Selective Endothelin A Receptor Antagonist
ZD4054 A Selective Endothelin A Receptor Antagonist Æ Proliferation Æ Proliferation ETA ET1 ETA ETB ETB Osteoblast Pain Autocrine Prostate tumour cell Nerve cell Potential actions of an ETA antagonist: b Inhibition of prostate tumour cell proliferation b Promotion of tumour cell apoptosis b Inhibiti
Slide 53: Angiogenesis inhibitors
Angiogenesis inhibitors ZD6474 AZD2171 Angiogenesis Proliferation ZD4054 AZD3409 Primary Tumour A Angiogenesis The generation of new blood vessels from existing vasculature b Activation of endothelial cells by a signal b Vessel destabilisation b Synthesis/release of degradative enzymes b Endothelial
Slide 54: ZD6474 and AZD2171
ZD6474 and AZD2171 Mechanism of action Endothelial cells VEGF Cell membrane P Adapter P molecules VEGFR (KDR/Flt-1) P P P P RTK inhibitors ZD6474/AZD2171 Downstream signal transduction Endothelial cell proliferation and migration Increased vascular permeability A ZD6474 and AZD2171 Broad-spectrum an
Slide 55: Impact of bevacizumab data on anti-angiogenic agents
Impact of recent bevacizumab (Avastin™) data on overall development of anti-angiogenic agents b Avastin™ (Genentech/Roche) failed to improve TTP and survival in combination with capecitabine in metastatic breast cancer b Phase II studies of Avastin™ show monotherapy activity in breast & kidney cance
Slide 56: AZD2171 - Clinical development
AZD2171 - Clinical development AZD2171 VEGFR2 VEGFR1 (KDR) VEGFR3 (Flt-1) (Flt-4) b AZD2171 has activity against VEGF receptors 1, 2 & 3 b Phase 1 clinical studies in refractory solid tumours have begun b Phase 1 studies in relapsed Acute Myeloid Leukaemia and prostate cancer are planned for 2003 A
Slide 57: Vascular Targeting Agents
Vascular Targeting Agents ZD6126 AZD4440 ZD6474 Endothelial AZD2171 Maintenance Angiogenesis Proliferation ZD4054 AZD3409 Primary Tumour A Targeting tumour vasculature b Rapidly proliferating b Chaotic and leaky b Immature u lack of supporting pericytes u reliance on tubulin cytoskeleton u expressio
Slide 58: Translational research with ZD6126
Translational research with ZD6126 vascular targeting agent Endothelial cells Tumour vessel round up and expose Blood flows freely basement membrane Tubulin Endothelium Baseline membrane Viable tumour cells Necrotic tumour cells Vessel congested, Extensive tumour blood flow stopped cell death A Clin
Slide 59: ZD6126 Clinical development
ZD6126 Clinical development b 80 patients treated in Phase I studies at 3 schedules b Clear evidence of dose-dependent biological effect on tumour blood flow b Tolerability limited by asymptomatic cardiac enzyme changes b Phase II evaluation in colorectal, lung, renal and neuro- endocrine tumours pl
Slide 60: Src-kinase: an anti-invasive target
Src-kinase An anti-invasive target Cell mobility is a key element in the process of tumour invasion Aberrant signalling c-met, AXOR12 Cytoskeletal remodelling SRC Kinase Actin polymerisation Motility ROCK, LIMK Aberrant cell-ECM SRC Kinase communication Matrix remodelling Integrin expression uPA, MM
Slide 61: Multiple targeted approaches
Multiple targeted approaches ZD6126 AZD4440 ZD6474 Endothelial Maintenance AZD2171 Metastatic Angiogenesis Deposit Invasion AZD0530 Secondary Proliferation Proliferation Secondary ZD4054 ZD4054 Angiogenesis AZD3409 AZD3409 Primary ZD6474 AZD2171 Tumour A AZ Discovery Delivering CDs into the clinic C
Slide 62: Pharmacogenomics strategy
Pharmacogenomics strategy b Pharmacogenomics offers great potential for identifying new targets for therapeutic intervention b Genomic profiling of individual diseases will identify many potential targets b Ongoing studies with hormonal drugs, Iressa® and new agents focussed on identifying differenc
Slide 63: Targeted cancer therapeutics
Pharmacogenomics - Breast cancer Hormone resistance changes gene expression Tumors: E R T Genes Tam agonist profile Supervised T-Test Ral agonist profile Tam antagonist profile Tam & Ral Antagonist profile Resistance to SERMs: Hierarchial Clustering of Estrogen, Raloxifen, and Tamoxifen-Treated Brea
Slide 64: Summary and conclusions
Summary and conclusions b Hormonal-heritage strong foundation for developing targeted therapeutics in cancer b Focussed Discovery effort in 5 key biological areas b Significant investment in translational science leading to early, focussed clinic entry (ZD4054, AZD2171) b Multiply-targeted VEGF inhi
Slide 65: Cautionary statement regarding forward-looking statements
Cautionary statement regarding forward-looking statements In order to utilise the “Safe Harbor” provisions of the United States Private Securities Litigation Reform Act of 1995, AstraZeneca is providing the following cautionary statement. This presentation contains forward-looking statements with re