What does Big Pharma want?

Transcription

1 Tissue banking in the NHS - the advantages for Pathology Departments What does Big Pharma want? Why do we want it? How do we get it? Chris Womack Principal Clinical Histopathologist Oncology Early Drug Development AstraZeneca Alderley Park Cheshire

2 What is Big Pharma?

3 AstraZeneca: Our Purpose Making the most meaningful difference to patient health through great medicines

4 Some facts Corporate HQ in UK; research HQ in Sweden; strong presence in important US market; increasing strength in key emerging markets. Over 65,000 employees worldwide; 18% in the UK, 21% in Sweden, 21% in the US, 40% in Rest of the World. 11 research centres in 7 countries; 11,900 people dedicated to discovering and developing new medicines. 27 manufacturing sites in 19 countries; 14,000 people focused on providing flexible, reliable product supply. Extensive sales & marketing network committed to meeting our customers needs in over 100 countries. A business priority is expanding our presence in Asia Pacific region. Currently we have over 6,000 people in the region.

5 Some figures Sales $m ,559 8, , ,950 R&D investment $m , , ,

6 AZ Research Areas ( RAs ) Global R&D Research Areas DI and IT Safety Assessment Process R&D Corporate Functions Cancer and Infection Cardivascular/ Gastrointestinal Respiratory/ Inflammation CNS/ Pain Control (tamoxifen) Breast cancer Prostate cancer Cholesterol reduction Asthma Scizophrenia Lung cancer Antibiotic Acid reflux disease

7 Pharmaceutical Industry: Key Facts Research Early Development Late Development Regulatory assessment Commercialisation US$900+ million to bring one drug from concept to market 12 years to develop a new medicine One in 5000 new chemical compounds make it to market

8 Risk example Research Early Development Late Development Regulatory assessment Commercialisation Phase I FTIM EOP1 Schedule 6 choices Phase I Multiple Ascending Dose Patients Dose 3 choices 2,880 opportunities to get it wrong Tumour 160 choices

9 Drug discovery and development at AZ Discovery >5,500 employees Research Discovery medicine / translational science Development >6,000 employees Early & Late Development Identifying drug targets and compounds / antibodies for them Selection of quality novel drug targets; novel ways to inhibit targets; safety and quality testing to reach earlier decisions Develop compounds into marketable drugs, run clinical trials, sell and maintain Taking drugs into man; taking novel approaches to modern day drug development (e.g. theranostics) Upgrade the links between basic science and clinical medicine Better understand human diseases and how drugs work Better use pre-clinical data to predict clinical activity

10 Human tissue in AZ drug development decisions In Discovery Utilising human tumour samples to detect potential therapeutic targets Increasing our confidence in the linkage of the target to particular types of cancer and subsets of patients Greater confidence that potential therapies will work in a subset of patients In Early Clinical Development Methodology transfer Proof of mechanism Proof of principle Proof of concept Confidence that potential therapies will work in a subset of patients In Late Clinical Development Greater clinical confidence that potential therapies will work in a subset of patients

11 Human tissue in AZ drug development decisions In Discovery to establish human target-to-disease linkage In Early Clinical Development to predict winners early In Late Clinical Development to select patients most likely to benefit

12 Comprehensive molecular characterisation Cell Panel mutation Tumour samples mutation Sequencing CGH copy number mrna microrna Proteins (incl. PTMs) copy number mrna microrna Proteins (incl. PTMs) Affymetrix RT-PCR Reverse Phase Arrays In Vitro Pathway Modelling In Vivo/Ex Vivo Pathway Modelling IHC

13 Target Disease Linkage: TMA based Target Expression CSA Disease Area Linkage Lung Breast Urology CRC Haem Others Disease Segments (prioritised)

14 TMA analysis toolkit overview TMA_Map.xls Histopathologist Score Toolkit components: Workflow technology Perl mysql Archive database for results Details on demand Scanned image Spotfire templates to accept processed information, in a digestible format to deliver to customers Tissue sample information eroom Folder structure, to store all documentation

15 TMA results handling Performance of antibody summary TMA view Provides visual image of scoring across nuclear, cytoplasm, membrane, stroma, vessels & inflammatory cells. Enables viewing of images and key fields from clinical metadata Easily embedded into scientist report e.g. Cancer Survey Array Multiple tissue types Membrane Cytoplasm Nuclear Missing Core OR No Tumour EXAMPLE Spotfire DecisionSite (Analysis

16 Human tissue in AZ drug development decisions In Discovery to establish human target-to-disease linkage In Early Clinical Development to predict winners early In Late Clinical Development to select patients most likely to benefit

17 Example: Histopathology picking a winner (AZD6244; 2006) 1 tumour shrinks 17 tumours stay the same 8 tumours grow Pre-dose Post-dose Drug target Tumour growth

18 Paired biopsy studies to help dose selection Drug Year Iressa* 2002 Faslodex* 2003 Arimidex* 2004 AZD5438* 2005 AZD AZD *used pre-operative setting

19 Human tissue in AZ drug development decisions In Discovery to establish human target-to-disease linkage In Early Clinical Development to predict winners early In Late Clinical Development to select patients most likely to benefit

20 Example: personalised medicine In an unselected population, there may be patients who are poor responders or who suffer adverse events Safe Responders Poor Responders Adverse events

21 What is personalised medicine? The concept of Personalised Medicine is that these patients can be screened out prior to treatment leaving only patients with good safety and efficacy Safe Responders Poor Responders Adverse events

22 ISEL FISH data FISH +ve Percent surviving n=114, E=68 Cox HR = 0.61 ( ), p = Gefitinib Placebo A dramatic reduction in the risk of death cf to overall population But Time (months)

23 Archival sample analysis: attrition factors 1692 Patients Available for FISH & IHC No sample Consent 560 samples Pathology Tracking Consent 380 evaluable DNA extraction 215 for DNA anal. DNA depletion Available for EGFR mutations EGFR: 26 K-Ras: 12 B-Raf : 0

24 How do we get it?

25 Access to human samples Hospitals (physicians, surgeons, pathologists) Universities Commercial Public/Charity Funded Tissue Banks National Cancer Banks Clinical Trials Historic collections

26 Collaborative opportunities AZ/MCRC Alliance: Anatomy UHSM CMFT SRFT Pennine Lung Cancer Human Cancer Tissue Blood-borne Biomarkers Imaging Radiationrelated Research Steering Group Phase 0/I Pre Clinical

27 Human tissue quality vs. availability Research Early & Late Development Archive: Plentiful Clinical data Variable quality Clinical trials: Obtaining tissue can be challenging Protocol driven

28 Advantages of Centralised Biobanking Facilitate and deliver governance (including eliminating questionable practices) Facilitate accountability for regulation and research ethics Coordination of sample acquisition, storage, distribution and use Facilitate economies of scale for - acquisition (bigger deals more attractive to hospitals and lead to more meaningful collaborations), - processing (maximising donations) - storage (space and equipment standards), - distribution (science-based, transparent and equitable) - use (statistical power to research projects further work in a larger series is required/being conducted ), - disposal (standardised) Develop expertise Improve quality Facilitate and deliver training Womack C, Gray NM. Cell and Tissue Banking 2009

29 AstraZeneca Global Biobank Organisation Reasons to establish a global biobank organisation Secure ethical & legal compliance Informed consents and ethical approvals Global IS systems for sample tracking e.g. in case of withdrawal of consent Promote awareness in all parts of the company Secure fit-for-purpose infrastructure to support business needs Discovery & Development Maximised use of human samples collected proactive acquisitions for common needs

30 Golden Rules for every Human Biological Sample From approved sources only Have an owner to agree acquisition and allow specific use Be assigned to a biobank Have a custodian Have consent for use Be used only in accordance with the consent Have a chain of custody and be traceable (unless anonymised/anonymous) Be uniquely identified and labelled (coded/deidentified) to protect identity of donor. AZ Bioethics Policy - section on Genetic information and Human Biological Samples AZ R&D Policy on Human Biological Samples

31 AZ consent requirements for HBS We need to be sure that consent from a donor (or donor next of kin, if appropriate): allows commercial use; allows withdrawal of consent; specifies whether genetic use is allowed; includes data privacy wording where donors are living includes no intended right to financial gain to the donor; includes whether the HBS can be retained for a specified or indefinite period

32 Reasons to establish a global biobank organisation Secure ethical & legal compliance Informed consents and ethical approvals Global IS systems for sample tracking e.g. in case of withdrawal of consent Promote awareness in all parts of the company Secure fit-for-purpose infrastructure to support business needs Discovery & Development Maximised use of human sample collection proactive acquisitions for common needs

33 HBS are stored in local biobanks at R&D sites - primarily where they will be used Montreal Boston Alderley Charnwood Mölndal Lund Södertälje Wilmington Shanghai Bangalore

34 AZ Biobank organisation oversees biobanking globally AZ Biobank Core Team Montreal Boston Wilmington Mölndal Alderley Lund Södertälje Charnwood Shanghai Bangalore

35 HBS will be tracked globally through a common biobank system AZ Biobank Core Team Montreal Boston Wilmington Mölndal Alderley Södertälje Charnwood Lund Shanghai Bangalore Biobank System

36 Site Biobank at Alderley Park, Cheshire, UK

37 AstraZeneca Big Pharma wants Access to samples and data Quality samples (and data) All material transfer to be legal, ethical and biosafe Collaborative opportunities to share expertise DELIVERY AstraZeneca survey of key internal and external clinical decision makers identified human target expression and disease linkage as the most important problem to be addressed in early cancer drug discovery