Steve Yang Shanghai Bioforum 2012-05-11


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Steve Yang, May 11, 2012. Shanghai Bioforum Translational Medicine, Session S4, Shanghai, China

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Steve Yang Shanghai Bioforum 2012-05-11

  1. 1. R&D Innovation in China and Asia:From Translational Science to DrugDiscoveryBio-Forum 2012 (14th Shanghai InternationalForum on Biotechnology & PharmaceuticalIndustry)I d )Steve Yang, Vice President gR&D Asia & Emerging Markets11 May 2012
  2. 2. Topics Implement Asia R&D Strategy Deliver Translational Science Build Drug Discovery Drive R&D Innovation in China1
  3. 3. Topics Implement Asia R&D Strategy Deliver Translational Science Build Drug Discovery Drive R&D Innovation in China2
  4. 4. AstraZeneca Global R&D Strategy High quality Strong Asia & Culture, early stage l t biologics Emerging E i Capabilities C biliti Leadership, L d hi pipeline pipeline Markets Engagement • Transform leadership – 60% senior leaders from outside p • Payer evidence, Personalized Healthcare, Predictive sciences, and innovative clinical trial design and interpretation • 40% of clinical pipeline is in-licensed • 8 biologics candidates in phase II development 3
  5. 5. AstraZenecas focus for R&D in Asia Ensure patients in Asia benefit from existing products sooner Deliver innovative new medicines focusing on diseases more prevalent in Asia Access R&D innovation Meet unmet needs of Asian patients and capabilities in Asia4
  6. 6. Designed for successRegional strength and experience• Leading oncology company in Japan and China• $2.2 billion sales in Asia Pacific• Significant regional presence, with expansions planned in 2012 One of the first global pharma companies to establish an innovation innovation- driven research laboratory in China One of the few global pharma companies with substantial internal research operations in both China and India ti i b th Chi d I di5
  7. 7. Designed for successsignificant world class presence in Asia i ifi t ld l i A i …Brings us closer to the patients weShanghai, China serve, serve the scientists and medical professionals we collaborate with and the great local talent we can access. Osaka, Japan • Innovation Center China • Clinical Development Operational Hub • Clinical Development Bangalore, India • Clinical Development p • Infection iMed 6 • Pharmaceutical Development
  8. 8. Innovation Center China: History & Milestones Moved to Oncology global the lab translational facility science center AZ announced First Became Part of AZ $100 M R&D project Asia & Emerging investment in started & Markets R&D with China delivered a New Mission 2006 2007 2008 2009 2010 2011 20127
  9. 9. Innovation Center ChinaSolidS lid progress on capability build-up bili b ild Capabilities In vitro pharmacology In vivo pharmacology PK/PD Target selection 2007 2008 2009 20108
  10. 10. Topics Implement Asia R&D Strategy Deliver Translational Science Build Drug Discovery Drive R&D Innovation in China9
  11. 11. Key translational science questions• What disease(s) and how to select patients?• What dose and schedule?• How to combine with current drugs?• How do we know the drug works – what to measure as biomarkers
  12. 12. Patient Selection for AZD (1) Only FGFR2 amplified gastric cancer cells Sensitivity of Gastric Cancer Cells to AZD4547 in are sensitive to AZD MTS assayy 100.000 10.000 M) GI50 (nM 1.000 0.100 0.010 0.001 GC lines FGFR2 CEP10 DAPI
  13. 13. Patient Selection for AZD (2) FGFR2 shRNA inhibits Snu16 (FGFR2 amp) tumor growth in vivo FGFR2 knockdown in SNU-16 inhibit its tumor growth SNU16 control 800 SNU16 treated with Dox SNU16-ShRNA3C8 control 700 Doxycycline SNU16-ShRNA3C8 treated with Dox treatment SNU16-ShRNA2B control SNU16-ShRNA2B treated with Dox Tum Volume (mm3) 600 SNU16-shEGFP control SNU16-shEGFP treated with Dox 500 400 mor 300 200 100 0 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 Study period (Day)
  14. 14. Patient Selection for AZD (3) Primary gastric cancer explant model (FGFR2 amp: FISH 6) Patient tissue Dosing stopped at Day 20 Tumor cell line
  15. 15. Hepatocellular carcinoma (HCC): disease segments ~30% ~5% ~5-10% ~30-40% ~10%Barcelona Clinic Liver Cancer (BCLC) algorithm
  16. 16. HCC Treatment Through TACE TACE (Transcatheter arterial chemoembolization) in Clinic Hepatic artery Catheter Tumor Femoral artery • Catheter insertion into hepatic artery and Two cycles of TACE treatment angiogram g g • Local delivery of chemotherapeutic agent through the catheter • Hepatic arterial embolization by gelfoam
  17. 17. Build the animal model for TACE (1) (3) (2) necrosis1. Generation of orthotopic HCC model2.2 Injection of chemocytotoxic drug through hepatic artery/portal vein3. Hepatic artery ligation
  18. 18. TACE model: Histological and molecular changes Control 7D Post HAL 90% necrosis H&E SHCC034 primary orthotopic HCC pHH3 model • Over 90% necrosis, 7 days after treatment • pHH3 and Aurora B expression inAurora B the residual tumor cells • Ki67 IHC staining in the residual viable cells i bl ll Ki67 Note: HAL: hepatic artery ligation
  19. 19. Tumor response predicts effect of AZD With response to HAL Without response to HAL 1000 HAL(n=4) 1400 00 HAL+AZD1152 25mg/kg PV,D1(n=9) HAL(n=5) 800 HAL+AZD1152 25mg/kg PV,D8(n=4) 1200 HAL+AZD1152 25mg/kg PV,D1(n=5)Tumor volum (mm3) Tumor volum (mm3) HAL+AZD1152 25mg/kg PV,D8(n=5) 1000 600 me me 800 400 AZD1152 PV 600 AZD1152 PV injection, D1 injection, D1 400 200 200 AZD1152 PV AZD1152 PV 0 injection, D8 0 injection, D8 0 8 15 22 29 36 0 8 15 22 29 36 Time after treatment (days) ( y ) Time after treatment (days) • Tumors without response to HAL did not benefit from AZD • Recommendations to clinical trial design: • Exclude patients with disease progression after TACE at the time of AZD administration
  20. 20. Topics Implement Asia R&D Strategy Deliver Translational Science Build Drug Discovery Drive R&D Innovation in China19
  21. 21. Innovation Center China New vision and mission Mission Deliver candidate drugs and ultimately, clinical proof of Vision concepts and valuable t d l bl Deliver innovative medicines medicines addressing unmet medical needs in Asia Maximize commercial potential of in-line products Provide strong Translational Science support20
  22. 22. Innovation Center ChinaUnique advantages Focusing onDisease diseasesarea focus important to Asia Deep expertise inScientificS i tifi Translational Science toexpertise generate clear target Lean and flexible modelOperating leveraging localmodel p capabilitiesExternal Access to increasinginnovation innovation in China AsiaTalentT l t pool l High caliber of talent with solid experience21
  23. 23. Innovation Center ChinaAspirations for the future 2017 beyond 2014 - 2016 2011 - Deliver Proof of 2013 Concepts with Deliver steady balanced candidate portfolio Build up core drugs capabilities22
  24. 24. Topics Implement Asia R&D Strategy Deliver Translational Science Build Drug Discovery Drive R&D Innovation in China23
  25. 25. Asia Clinical Operational Hub in ShanghaiCelebrates First A iC l b t Fi t Anniversary • Supports global, regional and local studies to deliver the global portfolio • An integral part of the AstraZeneca global clinical operation hub network • Concrete progress in recruiting, capability building, and study delivery • Launched in February 2011, plan for continuous growth in 201224
  26. 26. AstraZeneca and Hutchison Medi PharmaGlobal C ll bGl b l Collaboration on V liti ib ti Volitinib • Global licensing, co-development, and commercialization agreement for Volitinib (novel c-Met inhibitor for cancer treatment, currently in Phase I clinical testing) ) • $20M USD upfront payment plus $120M USD potential milestone payments25
  27. 27. AZ - SIMM Preclinical Safety Alliance ReceivedOECD GLP Certification C tifi ti • AstraZeneca and Shanghai Institute of Materia Medica (SIMM) established the long term strategic alliance in preclinical safety evaluation in 2007 • Receiving OECD GLP certification is a major milestone for the AZ SIMM preclinical safety alliance AZ-SIMM26
  28. 28. Asia R&D Strategy Implementation in China Key Themes Drive 1 business in Asia Asia Clinical Operational Hub Deliver Deli er 2 innovative medicines Innovation Center China Access R&D 3 innovation & capabilities27
  29. 29. Driving R&D Innovation in China • A laboratory to understand the diseases that are highly prevalent in China and Asia dA i • A laboratory to explore novel R&D operating models • A laboratory to expand R&D partnership approaches28
  30. 30. What’s Next for Asia and Emerging Markets R&D? • Deliver candidates at Innovation Center China • Implement Asia R&D strategy • Identify new R&D opportunities in other emerging market countries29
  31. 31. Thank you! y
  32. 32. Confidentiality NoticeThis file is private and may contain confidential and proprietary information. If you have received this file in error, please notify us and remove itfrom your system and note that you must not copy, distribute or take any action in reliance on it. Any unauthorized use or disclosure of thecontents of this file is not permitted and may be unlawful. AstraZeneca PLC, 2 Kingdom Street, London, W2 6BD, UK, T: +44(0)20 7604 8007,F: +44 (0)20 7604 8151, www.astrazeneca.comSteve Yang | May 11. 2012 R&D | Asia and Emerging Markets