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

Innovative Medicines Initiative: Joining Forces in the Healthcare Sector

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Disease heterogeneity Lack of predictive biomarkers for drug efficacy and safety Insufficient pharmacovigilance tools Outdated clinical designs Socio-economic approaches not adapted to tailored therapies Insufficient incentives to develop drugs for rare or complex diseases Poor EU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

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

EFPIA IMI Topic Definition & Launch Applicant Consortia EoI Submission 1 st ranked EoI + EFPA Full Project Proposal Submission IMIIMI Governing Board approval Signatures & project kick-off Academic research teams Hospitals SMEs Patients’ organisations Regulatory authorities Step 1Step 2Step 3Step 4Step 5 How it works The Consortium 18 weeks 9 weeks6 weeks 1 st ranked EoI Selection GB approval of 1 st ranked FPP negotiations start Signatures & project kick-off Call Launch - Optimized timelines

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

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

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

Key Figures from 40 on-going Projects 9 regulators 18 patient org 109 SMEs 594 Academic & research teams 363 EFPIA teams € mln IMI JU cash contribution €587.5 mln EFPIA ‘n kind contribution Improved R&D productivity of pharma industries Innovative approaches for unmet public health needs ~ 4500 researchers

Achievements from IMI Projects

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

Advancements in Autism research

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 Autism spectrum disorders (ASD): Current situation Courtesy: Autism Speaks – Rob Ring Anti-depressants Anti-convulsants Sleep-medication Stimulants

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 Autism spectrum disorders (ASD): European Situation 2012 a concerted effort of key stakeholders is needed Private Public Partnership

EU-AIMS Launched April 2012

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. Advancements in Autism research Uncovered a key mechanism for controlling synaptic properties NL1 isoform- specific cis-interactions with ionotropic glutamate. Concept paper on the development of Medicinal products for the treatment of Autism Spectrum Disorder 21 March 2013

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

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

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 size can 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

Systems Biology Approach in Severe Asthma

Systems Biology Approach in Severe Asthma 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 European centres samples, variables measured, and ~ data points An integrative system biology approach to understanding pulmonary diseases Auffray C. et al. 137: 1410, 2010 Diagnosis and definition of severe asthma: an international consensus Bel EH et al. 66: 910, 2011

Patient Reported Outcome tools 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

European Lead Factory All partners will have access to unique high-quality Joint European Compound Library ≥ compounds from industry partners – €60m 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

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

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 ‘ 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”

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

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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

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

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

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 between stakeholders How public-private partnerships move personalized medicine forward

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

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

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