Boosting Drug Development T hrough Public-Private Partnerships – The IMI M odel

1. Boosting Drug Development Through Public-Private Partnerships – The IMI Model Hugh Laverty, Senior Scientific Project Manager WRIC Brussels, 05 June 2013

2. Innovative Medicines Initiative:Joining Forces in the Healthcare Sector 2 Billion € I Billion € I Billion € Public Private Partnership

3. IMI focus - Hurdles to better healthcare • Disease heterogeneity • Lack of predictive biomarkers for drug efficacy and safety • Insufficient pharmacovigilance tools • Outdated clinical designs • Socio-economic approaches not adapted to tailored therapies • Insufficient incentives to develop drugs for rare or complex diseases • Poor EU market conditions to create biotech companies • Lack of training programmes focusing on collaborative approaches

4. Key Concepts “Non-competitive” collaborative research for EFPIA companies Competitive calls to select partners ofEFPIA companies (IMI beneficiaries) Open collaboration in public-private consortia (data sharing, wide dissemination of results)

5. - Optimized timelines How it works SMEs Academic research teams Hospitals Step 2 Step 3 Step 4 Step 5 Step 1 • The • Consortium • Signatures & project kick-off • Call Launch • 1st ranked EoI Selection • GB approval of 1st ranked FPP • negotiations start Regulatory authorities Patients’ organisations 18 weeks 9 weeks 6 weeks

6. How it works – Project Architecture A Typical IMI Consortium EFPIA Private Investment in kind (€ 1 billion) Pharma 4 Pharma 1 Pharma 5 Pharma 2 Pharma 6 Pharma 3 SMALL AND MEDIUM-SIZED ENTERPRISES ACADEMIA EU Public Funding cash (€ 1 billion) PATIENTS’ ORGANISATIONS HOSPITALS REGULATORS

7. One IMI IP policy, multiple interests • Flexible Intellectual Property Rights policy allows to accommodate the interests of all stakeholders • Promotes knowledge creation, exploitation and disclosure → open innovation, open access • Ensures fair allocation of rights • Rewards innovation

8. The Evolution of IMI From bottlenecks in industry to bottlenecks in society • Make Drug R&D processes in Europe more efficient and effective • and enhance Europe’s competitiveness in the Pharma sector Idea generation Basic research and non-clinical testing Human testing Regulatory Approval HTA and Pharmacovigi- lance Primary focus of early IMI calls 2007 SRA Shift to addressing challenges in in society and healthcare 2011 SRA SRA – Strategic Research Agenda

9. Key Figures from 40 on-going Projects €587.5 mln EFPIA ‘n kind contribution € 580.7 mlnIMI JU cash contribution ~ 4500 researchers Improved R&D productivity of pharma industries Innovative approaches for unmet public health needs 9regulators 18 patient org

10. Achievements from IMI Projects

11. IMI projects are delivering: • Robust validated models for drug development • Biomarkers and tools predictive of clinical outcomes - efficacy and safety • Potential new drug targets • Improving the design and process of clinical trials • “Big Data” solutions to leverage knowledge • Education and Training for new generation R&D scientists

12. Advancements in Autism research

13. Autism spectrum disorders (ASD): Current situation Sleep-medication Incidence • 1 in 88 births • Males vs females • 4x frequent in males Strong Genetic link • 10-40% defined genetic alterations, High penetrance Treatment • No treatment for core symptoms • Risperdal and Abilify for irritability Synapse disorder • Various targets Anti-depressants Stimulants Anti-convulsants Courtesy: Autism Speaks – Rob Ring

14. Autism spectrum disorders (ASD): European Situation 2012 • No major strategy defined within Europe • No major or concerted efforts in drug discovery • No pre-clinical network • No clinical trial network • No translational network • No regulatory strategy • Late diagnosis and poor awareness (adults) • Poor knowledge of patients needs across life-course (teens into adulthood) • Wide range in treatment strategy with no evidence of efficacy a concerted effort of key stakeholders is needed Private Public Partnership

15. EU-AIMS Launched April 2012

16. Advancements in Autism research Identified 4933 de novo mutation based on sequencing 78 Icelandic parent–offspring trios (219 distinct individuals). As a man ages, de novo mutations increase in his sperm offspring at increased risk of autism or schizophrenia. Developed a new animal model replicating nonsyndromic autism. Demonstrated a reversal of the condition with specific therapy in mice opportunity clinical development of new treatments for autism. Uncovered a key mechanism for controlling synaptic properties NL1 isoform-specific cis-interactions with ionotropicglutamate. Concept paper on the development of Medicinal products for the treatment of Autism Spectrum Disorder 21 March 2013

17. Clinical Investigator Networks COMBACTE Combatting Bacterial Resistance in Europe Establishment and training of European clinical investigators with the expertise and resources required to participate in global trials

19. Innovative rodent touchscreen technology • The rodent touchscreen technology is applied, validated and extended in NEWMEDS (schizophrenia) and PharmaCOG (Alzheimer’s) • Jointly developed as industry standard by Orion, UCAM, Janssen, Lundbeck, Roche, Abbott, Lilly, Pfizer • Pharmacologically validated for testing of pro-cognitive agents

20. Optimizing schizophrenia trials Proposed ways to reduce required numbers of patients needed for antipsychotic trials while preserving 90% power (p<.05) Based on resampling of data from 34 such trials (n=11,670 patients) data from Astra Zeneca, Janssen, Lilly, Lundbeck, Pfizer Sample sizecan be reduced from 79 to 46 patients per arm by targeting trials In addition the trial duration can be reduced from 6 to 4 weeks Current mix =70% female; 20% early episode; 40% enriched Enriched=prominent positive and negative symptoms Early episode=under 3 with 4 or more years of illness Note: Per patient cost 6wk study $70,000-$100,000

21. Systems Biology Approach in Severe Asthma

22. Systems Biology Approach in Severe Asthma Diagnosis and definition of severe asthma: an international consensus Bel EH et al. 66: 910, 2011 An integrative system biology approach to understanding pulmonary diseases Auffray C. et al. 137: 1410, 2010 Developed various “omics” platforms based on genetic, proteomic, metabolomic, breathomic biomarkers Generated a preliminary phenotype ‘handprint’ by combining molecular, histological, clinical and patient-reported data Cohort clinical trial recruitment target reached 1025 subjects, 726 adults, 299 children - 14 Europeancentres 175 000 samples, 1 500 variables measured, and ~ 3 000 data points

23. http://www.ubiopred.european-lung-foundation.org/

24. Patient Reported Outcometools in COPD • Selected activity monitors for precisely capturing the Physical Activity (PA) • Developed a conceptual framework around PA • Selected the most appropriate parameters based on patient input • Conducted pre –validation study on 230 subjects • Official interactions initiated with EMA for qualification advice

25. European Lead Factory • All partners will have access to unique high-quality Joint European Compound Library • ≥ 300.000 compounds from industry partners – €60m • 200.000 compounds from public partners • Industry-like lead discovery platform available for public projects - focus on • value generation • Addressing ‘intractable targets’ • 48 high throughput screening projects per anno • Sustainable model to establish independent business entity

26. European Lead Factory Coordinated by Bayer, Managing Entity: TI Pharma

27. Exploiting Electronic Health Records Academic perspective • Provide tools and services to better plan and conduct academic trials • Facilitate comparative effectiveness research Pharmaceutical perspective • Improve patient recruitment process and study design • Better understanding of real patient populations • Support observational and outcomes research studies in real-world settings • Enable more cost effective research and clinical trials General Healthcare perspective • Facilitate the re-use of EHR data to more efficiently manage public health issues • Enabling safer and more evidence-based diagnosis and treatment

28. ‘Think Big’ Research on human diseases at an unprecedented scale • Access to information on 40 million patients through EHR • Alzheimer’ disease: research on 10-times more subjects than ADNI(Alzheimer's Disease Neuroimaging Initiative) • Metabolics research on > 20,000 obese & Type 2 diabetes subjects • Linkage of clinical and “omics” data • Development of a secure (privacy, legal) modular platform • Continue to build a network of data sources and relevant research • 58 partners (3 consortia + Efpia) • >200 scientists involved • 14 European countries represented • Total budget €56.4m • “3 projects in one” 28

29. Advancements in benefit-risk assessment methodologies • Case study Natalizumab • Indication - Relapsing remitting • approved 2004 • license withdrawn 2005 • reintroduced due to patient demand 2006 • severe side effects: • Progressive Multifocal Leukoencephalopathy • Data source - EPAR • Comparators: • placebo, Avonex, Copaxone

31. Within the next 5 years, the Patients‘ Academy will… • develop and disseminate accessible, well-structured and user-friendly information and education on medicines R&D • build expert capacity by training patient advocates,and competencies among patients and the public • create the leading public library on medicines R&D: 7 languages, “creative commons” license • facilitate patient involvement in R&D to partner up with academia, authorities, industry, ethics committees

32. Mapping Collaborative Networks – Call 1-3 Collaborative publications among IMI researchers Data & analysis: Thomson Reuters (Custom Analytics & IP Solutions)

33. Collaborative activity fostered by IMI Collaborations between researchers engaged in IMI projects – Call 1-3 (until 08) Data & analysis: Thomson Reuters (Custom Analytics & IP Solutions)

34. How public-private partnerships move personalized medicine forward Addressing key scientific challenges Developing tools to translate scientific advances into regulatory guidelines Considering new pathways to accelerate patient access to innovative therapies Providing a neutral platform that fosters collaboration betweenstakeholders

35. IMI - The Neutral Trusted Party Fosters large scale industry collaboration and engagement with scientific community Promotes active involvement of patients, regulators and payers Enables innovation via join effort where singular approach has failed so far Facilitates Intellectual Property agreements

36. The measures of success New model developed & published In house implementation by industry Setting new standards Impact on regulatory guidelines

37. THANK YOU ! www.imi.europa.eu