Slide 1: Innovative Medicines & Early Development
Innovative Medicines & Early Development Delivering the next wave of scientific innovation Mene Pangalos, Executive Vice President, Innovative Medicines
Slide 2: AstraZeneca is a place where science thrives
AstraZeneca is a place where science thrives 5Rs Framework enables Right target pushing the boundaries of science Right tissue Right safety Truth- Scientific seeking rigour Right patients behaviours Right commercial potential 2 – Innovative Medicines & Early Development
Slide 3: AstraZeneca continues to attract the best scientists
AstraZeneca continues to attract the best scientists A few examples of recent hires into the IMED Biotech Unit Jérémie Boucher, Donald Stanski Principal Scientist, Diabetes Early Clinical Development Previously Harvard Previously Stanford / Novartis / FDA 38 publications including Cell, Nature and 1
Slide 4: Strengthening scientific reputation through a focus on high quality publications
Strengthening scientific reputation through a focus on high quality publications High impact = >15 600 High quality = 5-15 All other 498 500 5 No. of publications 400 204 327 300 12 247 6 172 200 123 143 1 100 73 0 1Q 2014 2Q 2014 3Q 2014 4Q 2014 Total Feedback suppression of PI3Kα signaling in PTEN
Slide 5: Connecting Cambridge & Gothenburg to create a scientific powerhouse in Europe
Connecting Cambridge & Gothenburg to create a scientific powerhouse in Europe AstraZeneca R&D Centre Examples of scientific collaborations Gothenburg Cambridge 5 – Innovative Medicines & Early Development
Slide 6: Application of inhaled technology in modifying respiratory disease
Application of inhaled technology in modifying respiratory disease
Slide 7: Future therapies for respiratory disease supported by advanced inhaled technology platforms
Future therapies for respiratory disease supported by advanced inhaled technology platforms Broad range of inhalation Improved symptom control technologies Cutting edge science to modify disease Next-generation treatments for asthma and COPD 7 – Innovative Medicines & Early Development
Slide 8: Targeted therapies to drive efficacy in asthma
Targeted therapies to drive efficacy in asthma AZD0449: iJAK AZD1419: iTLR9 agonist for inhibitor for asthma early-onset asthma • Well-validated pathway • Sustained correction of Th2 imbalance • STAT signalling critical player • Phase II H1 2015 • FTIM 2015 • Collaboration with Dynavax • Collaborati
Slide 9: AZD7624: Inhaled P38 inhibitor for patients with COPD
AZD7624: Inhaled P38 inhibitor for patients with COPD • Well-validated pathway • Direct targeting of immune cells in lung • Aimed at steroid insensitive patients • Phase II Q4 2014 Phospho p38+ alveolar Inflammatory cytokines in Significant attenuation of LPS- macrophages in COPD lung human alveolar
Slide 10: Leading in DNA damage response (DDR)
Leading in DNA damage response (DDR)
Slide 11: Leading “first in class” DDR portfolio
Leading “first in class” DDR portfolio 11 – Innovative Medicines & Early Development
Slide 12: AZD6738: First-in-class ATR inhibitor for ATM-low NSCLC
AZD6738: First-in-class ATR inhibitor for ATM-low NSCLC AZD6738 increases 53BP1 replication stress nuclear bodies • Leads to tumour cell death • Potent and selective inhibitor • FTIM Q4 2013 Increased 53BP1 nuclear bodies are a marker of AZD6738 sensitivity • Combination with carboplatin 2015 Fold c
Slide 13: AZD6738: First-in-class ATR inhibitor for ATM-low NSCLC
AZD6738: First-in-class ATR inhibitor for ATM-low NSCLC AZD6738 in ATM-low colorectal model • Leads to tumour cell death Control 1.4 • Potent and selective inhibitor 10 mg/kg Volume (cm3) Geometric 1 Mean 25 mg/kg • FTIM Q4 2013 0.6 50 mg/kg 0.2 • Combination with carboplatin 2015 8 13 18 Days post
Slide 14: Breadth of portfolio allows combinations with strong scientific rationale
Breadth of portfolio allows combinations with strong scientific rationale Breast AZD1775 combination with cancer Lynparza & AZD1775 in TNBC Lynparza in a TNBC PDX model Vehicle control 1500 Olaparib Gastric cancer Lynparza & AZD6738 in AZD1775 Olaparib + AZD1775 ATM-deficient GC Tumour voume (mm) 10
Slide 15: Pioneering research in oligonucleotide therapeutics
Pioneering research in oligonucleotide therapeutics
Slide 16: Collaborating with the best partners to harness cutting-edge science in oligonucleotide platforms
Collaborating with the best partners to harness cutting- edge science in oligonucleotide platforms Antisense Messenger RNA Micro RNA oligonucleotides 16 – Innovative Medicines & Early Development
Slide 17: Exclusive agreement with Moderna to harness pioneering messenger RNA technology
Exclusive agreement with Moderna to harness pioneering messenger RNA technology Regenerating blood vessels and Expresses in a variety Intracellular translation of CV cell types cardiomyocytes* MI + Luc modRNA (100 µg) EPC CF 700 VEGF protein (ng/ml) 600 500 400 300 MI + VEGF-A modRNA (100 µg) 200 Pr
Slide 18: Collaboration with Isis Pharmaceuticals to harness pioneering antisense therapeutics
Collaboration with Isis Pharmaceuticals to harness pioneering antisense therapeutics STAT3: Durable partial responses seen • Antisense approach in 2 DLBCL patients in Phase I • Potential to inhibit validated but ‘undrugable’ targets • Gen 2.5 chemistry shows improved potency • Progress: − STAT3RX (A
Slide 19: Collaboration with Isis Pharmaceuticals to harness pioneering antisense therapeutics
Collaboration with Isis Pharmaceuticals to harness pioneering antisense therapeutics Increased responses for combination • Antisense approach of STAT3 ASO with PD-L1 mAb • Potential to inhibit validated but STAT3 ASO / PD-L1 combination gives increased responses in CT-26 colorectal tumour model ‘und
Slide 20: Building a world-class Personalised Healthcare capability
Building a world-class Personalised Healthcare capability
Slide 21: Establishing a leading position in personalised patient care across all therapy areas
Establishing a leading position in personalised patient care – across all therapy areas 90M 1st >70% Dollars invested in Circulating tumour Percentage of clinical diagnostic partnerships DNA-based diagnostic pipeline with a PHC approved for Iressa approach 50% 2nd ~30 Percentage of launches Rank in
Slide 22: Following the science will ensure maintaining a healthy and sustainable pipeline
Following the science will ensure maintaining a healthy and sustainable pipeline Phase I Phase IIa Phase IIb MEDI8111 AZD6738 AZD4901 AZD5213 AZD1722 AZD1775 rhFII bleeding ATR solid tumours NK3 PCOS H3 Tourette NHE3 ESRD-Pi Wee-1 ovarian AZD1979 AZD9150 AZD2115 AZD5213 RDEA 3170 AZD5363 MCH obesity
Slide 23: IMED approach supports delivery of sustainable pipeline
IMED approach supports delivery of sustainable pipeline Reduced IMED spend by 39% (and headcount by 42%) since 2010 Back-up programmes reduced from 48% to less than 2% since 2010 Cost per candidate drug $50-60m (industry benchmark $80-110m) Probability of success increased from ~6% to ~16% since 201
Slide 24: Being open for collaboration where the best scientists thrive
Being open for collaboration in an environment where the best scientists thrive will deliver a sustainable flow of scientific innovation 24 – Innovative Medicines & Early Development
Slide 25: Innovative Medicines & Early Development
Innovative Medicines & Early Development Delivering the next wave of scientific innovation Mene Pangalos, Executive Vice President, Innovative Medicines