AstraZeneca PLC · LSE:AZN
AstraZeneca — Technical Presentation (2002)
14 slides from AstraZeneca's technical presentation, 2002
Slide 1: AstraZeneca Discovery Review
AstraZeneca Discovery Review A Jan M Lundberg Executive Vice President Head of Global Discovery Research Delivery of CDs - improving productivity b ‘Humanising’ discovery b Front-loading risk More, better, faster b High quality standards b Global working A AstraZeneca Discovery Review: Jan Lundberg
Slide 2: 'Humanising' drug discovery: new target from human tissue
‘Humanising’ drug discovery b Integrating patient and pre-clinical information ✦ new targets from human tissues ✦ translational models ✦ predictive response markers ✦ appropriate patient populations • early data in man • re-rationalise disease definition • clinical benefit > side effects A ‘Humanisi
Slide 3: 'Humanising' drug discovery: translational models in drug testing
‘Humanising’ drug discovery: Translational models in drug testing Human OA Knee joint MRI cartilage Focal loss of articular cartilage is a cardinal feature of OA 12 months Guinea pig OA Knee joint MRI A Metalloprotease inhibitor prevents cartilage loss in Guinea Pig Model OA 0.8 0.6 Change in absolu
Slide 4: 'Humanising' drug discovery: predictive response marker in COPD
‘Humanising’ drug discovery: Predictive response marker in COPD In Vivo Elastin Breakdown Proteinase-specific Peptides COPD In Vitro Differential Comparison Control Fraction 38, Mass 1286 500 400 Lung destruction Peptide Index Intensity 300 Connective tissue 200 degradation 100 products 0 Control CO
Slide 5: Front-loading DMPK and toxicology
Front-loading DMPK and toxicology b Earlier DMPK and toxicity studies b Development of bio-markers b Predictive in silico modelling of DMPK and toxicity 1000 Concentration 100 10 1 0 5 10 15 20 25 Time Post-Dose (Hr) A Reducing risk for cardiac complications R V P T ECG Q S hERG current K+ high thro
Slide 6: Criteria for quality CDs
Delivery of CDs - Improving productivity b ‘Humanising’ discovery b Front- Front-loading risk b High quality standards A Criteria for quality CDs b Potent, selective, specific at validated targets b Efficacy in validated animal models b Bioavailable and predictable kinetics b Extensive Safety packag
Slide 7: Target class initiatives
Delivery of CDs - Improving productivity b ‘Humanising’ discovery b Front- Front-loading risk b High quality standards b Global working A Target class initiatives Others Other enzymes 8% G-protein 3% coupled Proteases receptors 16% 37% Nuclear receptors 5% Molecular pumps Kinases Ion channels 3% 14%
Slide 8: GPCR database: integrating biology and chemistry
GPCR database: Integrating biology and chemistry A Sensory neuron specific GPCRs Dorsal root ganglia (DRG) Trigeminal ganglia Spinal cord mRNA Protein Ligand identified Nature Neuroscience 5, 201-209 (2002) Pain relief without systemic side effects A AstraZeneca Discovery Review: Jan Lundberg 8
Slide 9: Chemokines: a GPCR subfamily
Chemokines: A GPCR subfamily Leukocyte recruitment and Angiogenesis activation Blood vessel endothelial cells pericytes Chemokines neutrophils Chemokines macrophages hypoxic tumour cells Nelson & Krensky Immunity 14, 377-386, 2001 6 CDs since 2000 – more to come A Multiple indications for a chemokin
Slide 10: Inflammation asset exploitation; global working with external input
Inflammation asset exploitation Asthma Cancer Rhinitis COPD Arteriosclerosis Multiple Sclerosis Diabetes Inflammation Alzheimer’s Pain Inflammatory Post- Post-operative Bowel Disease Rheumatoid Musculoskeletal Arthritis A Global working - External input to projects More than 200 new collaborations i
Slide 11: Global, collaborative, learning organisation
Links to internal Discovery Search Global Dbs HTS, e-lab, c-lab Gene Expression Compounds,Targets People Network Links to key external Dbs Medline etc Patents Projects – Portfolio Summary External collaborations Global, collaborative, learning organisation A Delivery of CDs - Improving productivity
Slide 12: CD delivery last 3 years: recent CD progress
CD delivery last 3 years Cardiovascular CNS Thrombosis Dyslipidemia Alzheimer’s Depression Overactive Arrhythmia Diabetes disease bladder Inflammation Pain Rheumatoid Osteoarthritis Multiple Acute Neuropathic Chronic Arthritis Sclerosis Pain Pain Pain Cancer Gastrointestinal Pan-carcinoma Gastroesop
Slide 13: Overall CD delivery and progress last 3 years
Overall CD delivery and progress last 3 years b More ✦ increased CD delivery ✦ increased number of CDs into man b Better ✦ quality CD criteria implemented ✦ biomarkers for most CDs b Faster ✦ shorter lead optimisation ✦ shorter timelines CD nomination to first time into man A AstraZeneca Discovery p
Slide 14: 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