IMI2 Call 5 topics. Hugh Laverty, IMI Senior Scientific Project Manager Webinar FFG Austria 16 July 2015

Transcription

1 IMI2 Call 5 topics Hugh Laverty, IMI Senior Scientific Project Manager Webinar FFG Austria 16 July 2015

2 IMI 2 Call 5 topics Patient perspective elicitation on benefits and risks of medicinal products from development through the entire life cycle, for integration into benefit risk assessments by regulators and health technology assessment bodies Nathalie.Seigneuret@imi.europa.eu Diabetic kidney disease biomarkers Magda.Gunn@imi.europa.eu Inflammation and Alzheimer s disease (AD): modulating microglia function focussing on TREM2 and CD33 Elisabetta.Vaudano@imi.europa.eu Understanding the role of amyloid biomarkers in the current and future diagnosis and management of patients across the spectrum of cognitive impairment (from predementia to dementia) Elisabetta.Vaudano@imi.europa.eu Evolving models of patient engagement and access for earlier identification of Alzheimer s disease: phased expansion study Fatiha.Sadallah@imi.europa.eu Apolipoprotein E (ApoE) biology to validated Alzheimer s disease targets Elisabetta.Vaudano@imi.europa.eu

3 Patient perspective elicitation on benefits and risks of medicinal products, from development through the entire life cycle, to inform the decision-making process by Regulators and Health Technology Assessment bodies Topic 1

4 Need for public-private collaboration There is growing agreement amongst patient groups, industry and health authorities that the patient perspective needs to be better incorporated into the decision-making process for drug development. However, there is uncertainty about how the patient perspective elicitation on benefits and risks can best be performed and incorporated into the review process. A public-private partnership is required to address this topic because of: The magnitude and complexity of the issue The need for a strong collaborative effort to be successful The resources needed

5 Objectives of the full project Establish recommendations with the view of supporting the development of guidance for industry, regulators and HTA bodies on how and when in the product life-cycle to consider patient perspectives on benefits and risks of medicinal products to inform the decision-making process by regulators and HTA bodies. This would be achieved through a review of existing methodology and selection of methodology to take forward for testing via case studies. Recommendations would be developed based on the experience gained through the case studies.

6 Expected impact on the R&D process Improved understanding of when and under what circumstances patient perspective elicitation on benefits and risks of medicinal products is most valuable. Improved understanding of how patient perspective elicitation on benefits and risks can best be performed. Improved understanding of how patient perspectives on benefits and risks can be used to inform decision-making processes. Improved knowledge based on shared experience with applying methodology to collect patient preferences. Progress towards a consensus on these issues between patients, physicians, regulators, HTA bodies, academia and industry stakeholders.

7 Industry, budget and duration AbbVie, Actelion, Amgen, Astellas, Astra Zeneca, Bayer, CSL Behring GmbH, Eli Lilly, J&J, MSD, Merck Serono, Novartis, Pfizer, Roche, Sanofi and Takeda The indicative contribution from EFPIA companies is EUR The financial contribution from IMI 2 is a maximum of EUR Duration: 60 months

8 Expected contributions of the applicants Expertise in: Patient advocacy Patient preference research Health technology outcome research Pharmaceutical and device development Behavioural research Scientific communication to lay audiences Benefit-risk decision-making by regulators and HTA bodies Project management The Applicant consortium is expected to enable effective collaboration with key stakeholders i.e. health-care professionals, regulators and HTA bodies.

9 What s in it for you? Patients organisations Opportunity to share your expertise; support a stronger role for patients as partners in drug development. Academic researchers Opportunities for collaboration; opportunities for applied research. SMEs (Small and Medium Enterprises) Opportunities for collaboration; chance to increase expertise in an area of interest to regulatory agencies and pharmaceutical companies. Regulatory agencies and HTA bodies Address a growing need and desire for patient engagement.

10 Diabetic Kidney Disease Biomarkers (DKD-BM) Topic 2

11 Need for public-private collaboration Global standard of care for patients with DKD has remained unchanged for over a decade: RAAS (Renin-Angiotensin- Aldosterone System) blockade using either an angiotensin converting enzyme (ACE) inhibitor and/or an angiotensin receptor blocker (ARB). Current progression rate to end-stage renal disease (ESRD) and cardiovascular (CV) and overall mortality rates remain unacceptably high. Lack of highly predictive dynamic biomarkers of efficacy and safety. Proteinuria, especially albuminuria, is used in phase 2 clinical trials but has significant liabilities, e.g. substantial intra-patient variability and lack of predictive value for hard outcomes

12 Need for public-private collaboration Identification and validation of novel biomarkers for renal function, prediction of disease progression or clinical safety is too large an endeavour to be handled by a single company or institution. To make material progress in this field, a collaborative program is required that is based on a network of academic medical institutions, the clinical development expertise of the pharmaceutical industry as well as basic and clinical research experts in the areas of: Biomarkers Bioinformatics Preclinical in-vitro and in-vivo DKD models Biomedical approaches including renal imaging

13 Objectives of the full project (i) Generate candidate biomarkers from existing clinical longitudinal data and samples from both T1D and T2D patients, with the possibility to further expand these longitudinal studies (ii) Replicate these biomarkers findings in other, independent cohorts (iii) Back-translate clinical findings to develop and prioritize improved in vitro and in vivo models of DKD, and (iv) Incorporate these novel biomarkers into clinical trials in order to enhance the precision of application to specific DKD patient populations as well as the chances of future success for novel therapeutics

14 Expected impact on the R&D process Significantly advance the understanding of the pathophysiology, heterogeneity and natural history of DKD in patients. Improve the translatability of preclinical models to human DKD. Facilitate the development of standardized biomarker panels with both prognostic and predictive capacity to serve as entry criteria for future clinical trial protocols: Improved stratification of patients regarding their state of disease, responsiveness to and benefit from novel target approaches Reduced size of confirmatory pivotal trials Higher likelihood of favourable Health Technology Assessments by global payers, based on an enhanced efficacy signal seen in biomarker-selected patients

15 Industry, budget and duration AbbVie (coordinator), Eli Lilly, Novo Nordisk, Bayer, Sanofi, and Merck Sharp & Dohme (MSD). The Associated Partner is the Juvenile Diabetes Research Foundation (JDRF). The indicative contribution from EFPIA companies and associated partners is: EUR The financial contribution from IMI 2 is a maximum of EUR Duration: 60 months

16 Expected contributions of the applicants It is envisioned that a multidisciplinary network will be established in response to this topic and it will include: research physicians (nephrologists, endocrinologists and clinical pharmacologists) basic researchers in the field of in vitro and in vivo modelling of DKD, biomarker/diagnostics specialists (who could be SMEs), investigators with access to bio-specimens from longitudinal cohorts bio-informaticians and big data analysts regulatory health authorities imaging specialists translational medicine experts Cross-fertilisation and demonstrated ability to collaborate well with each other and the pharmaceutical companies also showcased in prior working groups/consortia will be critically important for all participants.

17 What s in it for you? Expected Benefits for Selected Applicants: Academic researchers direct beneficiaries of funding mechanism; collaboration with industry partners adds to work multiplier effect. SMEs - direct beneficiaries of funding mechanism; collaboration with industry partners adds to work multiplier effect; access to global regulators & payors during BM negotiations. Productivity multiplier effect from bringing together diverse stakeholders each with complementary resources and expertise.

18 Inflammation and AD: modulating microglia function focussing on TREM2 and CD33 Topic 3

19 Need for public-private collaboration Alzheimer s Disease (AD) affects the nervous system leading to progressive cognitive, behavioural, and general functional decline. The brain microglial/macrophage system was identified in GWAS studies to play a role in progression of AD with CD33 and TREM2 as key players. However, the ultimate causative link between inflammation / microglia activity and AD is still an under-explored area of research. The complexity of understanding this interplay and finding avenues for modulation requires a focused public-private-partnership effort combining basic research and drug development expertise. A consortium of academia and SMEs with access to innovative tools in combined effort with complementary experience of EFPIA is well positioned to shed light on the role of microglia in AD.

20 Objectives of the full project Identify druggable points of interaction in the TREM2 and CD33- signalling pathways to modulate microglial or macrophage function for the treatment of Alzheimer s disease. Explore whether a decrease or an increase of brain microglia phagocytic activity and/or cytokine release causes or prevents neurodegenerative/ageing phenotypes Explore the roles of CD33 and TREM2 in microglia activity / activation & establish tools not yet available to address questions Conduct limited drug / antibody screening to provide tool compounds to contribute to overall objectives Explore differences between rodent and human immune system, and particularly between mice microglia and their human counterparts

21 Expected impact on the R&D process Accelerate research aimed to help understanding progression and development of AD. Deployment of synergisms across consortium partners Sharing precompetitive tools within consortium partners and scientific community Establishment of a tool box to support and facilitate exploring the role of microglia / innate immune response and its relation to AD pathology. Validation of the functional role of CD33 and TREM2 as targets for therapeutic intervention. Identification of druggable points of interaction to modulate CD33- and TREM2-activity or related pathways to treat AD. Establishment of translational tools to support future clinical studies.

22 Industry, budget and duration Janssen, Abbvie, Eli Lilly, Sanofi, Lundbeck, Roche, Orion and Astra Zeneca/MedImmune The indicative contribution from EFPIA companies is EUR The financial contribution from IMI 2 is a maximum of EUR Duration: 60 months

23 Expected contributions of the applicants Expertise in Alzheimer s disease and in neuro-inflammation linked to AD: Expertise on neuro-inflammation studies using in vivo preclinical models of AD or models where key components of microglia are genetically modified (TREM2 and CD33) Analysis of role of brain innate immunity cells and migrating peripheral macrophages Small animal imaging In vivo and ex vivo pharmacology & translational medicine to bridge findings and results of neuro-inflammatory processes/pathways from preclinical species to humans IT (in particular data communication and data basing). Project management.

24 What s in it for you? Access to tools from diverse sources to progress research and close collaboration with leading EFPIA companies in the field of neuroinflammation / AD. Involvement in international consortium consisting of academia, SMEs, and Pharma for an indicative period of 5 years. Identification and validation of brain innate immunity pathways that play a role in progression of AD. Supporting the development of small or large molecules that will modify microglia function to treat AD. Establishing and sharing precompetitive research and development tools for the scientific community to progress AD research.

25 Understanding the role of amyloid imaging biomarkers in the current and future diagnosis and management of patients across the spectrum of cognitive impairment (from predementia to dementia) Topic 4

26 Problem statement Today diagnosis of suspected Alzheimer s disease is still largely based on clinical symptoms and by exclusion which lead to uncertainty. Uncertain diagnosis may lead to: Poor management Reduced treatment effectiveness Less than optimal outcomes Diagnostic uncertainty has also hampered new treatment development: Inclusion in Tx trials of non-ad pathology Trials in subjects with already clear symptomatology may be too late in disease progress

27 Need for public-private collaboration Establishing how β-amyloid imaging w tracers like eg [ 18 F]flutemetamol and [ 18 F]florbetaben can aid diagnosis, case management and clinical trial success requires the concerted action of several stakeholders: academic researchers and treating clinicians reimbursement/health technology assessment authorities in EU member countries patient/disease associations Industry (pharma, diagnostic & imaging) Regulatory Agencies None of these groups could conduct this piece of research on their own.

28 Objectives of the full project Starting from existing Europe-wide clinical and imaging networks the aim is to effectively and accurately assess amyloid imaging status in a large number of subjects with a view to: Establishing the value of the knowledge of amyloid status by Amyloid imaging in Diagnostic current diagnosis and Patient and patient Management management Study decision trees Understanding the use of amyloid imaging to ultimately improve Amyloid clinical Enrichment outcomes Study in novel therapy trials as a result of studying more homogenous, enriched populations. Both of these aims will lead to enhanced treatment and care pathways and bring significant value to future clinical research in the dementia field. It is anticipated that the amyloid enrichment study would be the larger component of the action.

29 Expected impact on the R&D process The impact of the action will be: An increased understanding of how quantitative and regionspecific image analysis techniques could be used in the future to understand pre and post therapy amyloid levels, which in turn may guide the best time-window for intervention, and to better understand the mechanism of action of therapeutics and how these measures influence treatment regimes.

30 Industry, budget and duration GE Healthcare Life Sciences, Janssen and Piramal Imaging The indicative contribution from EFPIA companies is EUR The financial contribution from IMI 2 is a maximum of EUR Duration: 60 months

31 Expected contributions of the applicants It is expected to be multidisciplinary (e.g. academia, hospitals, SMEs, patients and patient organisations, public health organisations, regulatory agencies, health technology bodies). dementia current diagnostic algorithms and patient management; design and execution of multisite clinical trials in accordance to GCP and real world clinical research capabilities; subject recruitment and diagnostic work-up consistent with protocol requirements; Willingness to follow up patients longitudinally; site and subject monitoring capabilities; PET scanning, image acquisition image read training and analysis (with image transfer to central analysis if required) experience in amyloid imaging specifically biostatistics and data management understanding of Regulatory and HTA requirements in EU large program oversight, governance and project management CRO capabilities/management site set up including camera set up scientific and media communications expertise, ethical expertise and outreach to patients and other key stakeholders It may also require mobilising as appropriate, the following resources: a distribution network for short-lived radioisotopes to be shipped to clinical centres, Imaging software and hardware, access to relevant clinical cohorts and patient groups in the routine clinical setting, Involvement of patient organisations.

32 What s in it for you? Academic Researchers Access to amyloid imaging PET tracers and expertise to deliver large meaningful studies that will: influence how suspected AD patients are managed today Further characterise large cohorts Strengthen European AD research networks Patients organisations: Generate data that should directly effect the management of dementia patients positively Increase the chances of successful therapeutic trials by better subject characterisation on European wide scale Regulatory agencies: Work directly with industry and academia to define the future use of amyloid imaging in the context of therapeutic development and clinical use

33 Evolving models of patient engagement and access for earlier identification of Alzheimer s disease Topic 5

34 Need for public-private collaboration More than 34 million people world wide suffer on Alzheimer Disease (AD) Current clinical paradigm does not support or emphasize the need for early detection, diagnosis and urgency for action, as soon as symptoms of AD first begin: Focus is still on later clinical stages of the disease This creates a barrier to access to available treatments and support services, as well as enrollment in Clinical trials We believe there are resources available TODAY that improve patient health and quality of care if diagnosed and engaged earlier in the disease process

35 Need for public-private collaboration We need to better understand the obstacles to engagement for early diagnosis and treatment, and successful strategies to overcome them This will provide information on how to improve the consistency of diagnosis and communication as soon as symptoms begin: for earlier identification of patients and their progression to earlier care, support resources and referrals to provide opportunities for the patients for offering recruitment and participation in clinical trails to impact patient care once disease modifying agents are available

36 Hypothesis and Pre-competitive nature Conducting multi-site experiments of patient access and engagement models in a variety of communities that are successful in the identification and diagnosis of early stages of symptomatic AD will facilitate: driving efficient and earlier identification of patients for entry in to healthcare systems and clinical trial programs development of enhanced resource access models for driving earlier entrance in to the healthcare system development of educational/awareness programs

37 Objectives and Impact Establish multiple key regional project sites across Europe to identify and test models of efficient earlier identification of mild AD dementia and prodromal AD patients, and awareness of AD risk. Compare and contrast various patient access models and how they contribute to improved detection, diagnosis, and clinical research in these communities

38 Objectives and Impact Assess key tools, mechanisms and processes for community engagement and patient identification and resource utilization in various communities. Based on findings, establish archetypes of patient access models for implementation in similar communities, in synergy and collaboration with existing country specific government and non-government stakeholders. Advocate and distribute access models for broader application and for replication.

39 Project Duration and Architecture Phase1: 30 month project timeline Development and implementation of multiple regional models for patient engagement Multiple projects at multiple sites Synergies with existing consortia and organization

40 Project Duration and Architecture Phase 2: competitive renewal and expansion A duration of up to 5 years will only be initiated after a futility analysis of the progress of Phase 1, and contingent on certain milestones being achieved to justify a Phase 2. This Phase 2 extension would aim to provide opportunity to expand successful Phase 1 programs with additional funding. This phased expansion would allow for timely building on the progress and outcomes of the initial deliverables.

41 Industry, budget and duration Lilly and Astrazeneca The indicative contribution from EFPIA companies is EUR The financial contribution from IMI 2 is a maximum of EUR Duration: 30 months

42 Applicant consortium Participation by institution involved in patient care, education, support, and community outreach, as well as those participating in active clinical research programs and patient organizations that have a focus in the countries of concern. In order to meet the key objectives of the project, an emphasis should be placed on variety of healthcare and patient population environments spread across key European countries. This may require a network of: academic basic, translational, clinical research scientists regulatory expertise economic or public health modelling experts professional Project Management Organisation local advocacy organisations Due to the structure of this phased expansion design, we encourage focused and concrete applications that can clearly correspond to the outlined objectives and that can demonstrate successful inclusion of the expertise outlined above.

43 From ApoE biology to validated Alzheimer s disease targets Topic 6

44 Need for public-private collaboration While ApoE4 has been clearly established as the most prominent Alzheimer s disease (AD) susceptibility gene, there has been comparatively little research into the link with disease pathology. Basic questions remain: ApoE biology and pathophysiology is still limited and has not yet resulted in treatment options for ApoE4 carriers. Aim of the project; to clarify further the nature of the ApoE4-related liability in AD and identify novel methods for targeting this liability to more effectively treat the disease and achieve disease modification in this large patient population. Bringing academic scientists with knowledge on ApoE biology and AD, SME s with innovative technologies and pharmaceutical scientists with drug R&D expertise together with this focus will greatly enhance our probability to validate targets and treatment options.

45 Objectives of the full project Overall aim: to identify critical mechanism(s) by which ApoE4 leads to the development of AD as a basis for new treatment approaches based on these basic research findings, and identify biomarkers in support of treating ApoE4-positive patients. Research will seek to understand how ApoE4 leads to AD and not how ApoE4 might fit into the Aβ hypothesis. We need to focus on delivery of our goals in 3 years. This action is anticipated to be the basis of a follow up action building from the assets and results of this initiative, to be launched as a future call.

46 Expected impact on the R&D process Accelerate research aimed to help understanding the role of ApoE on the progression and development of AD: Deployment of synergisms across consortium partners Sharing precompetitive tools within consortium partners and scientific community Maximize impact by combining multiple approaches Establishment of a characterized and high quality tool box to support and facilitate exploring the role of ApoE in AD pathophysiology. Identification of druggable points of interaction to modulate ApoE activity or related pathways to treat AD. Establishment of translational tools to support future clinical studies.

47 Industry, budget and duration AbbVie, Biogen, Janssen and Roche The indicative contribution from EFPIA companies is EUR The financial contribution from IMI 2 is a maximum of EUR Duration: 36 months

48 Expected contributions of the applicants Expertise in AD pathophysiology and disease progression, ApoE and ApoE protein function and biology and interaction with AD: Pre-clinical ApoE relevant models and technologies, induced pluripotent stem cells (ipscs) and transgenic models translational medicine pre-clinical imaging biomarkers IT (in particular data communication, data basing and bioinformatics). Project management.

49 What s in it for you? Access to tools, technologies and expertise from diverse sources to progress research and close collaboration with leading EFPIA companies in the field of ApoE / AD. Involvement in international consortium consisting of academia, SMEs, and Pharma for an indicative period of 3 years. A future call for proposals is anticipated building from the assets and results of this initiative, in case of successful achievement of the expected deliverables. Identification and validation of ApoE-related pathways that play a role in progression of AD. Establishing and sharing precompetitive research and development tools for the scientific community to progress AD research.

50 Budget and Timelines

51 IMI 2 Call 5 budget IMI IMI IMI The indicative contribution from EFPIA companies is EUR The financial contribution from IMI 2 is a maximum of EUR The indicative contribution from EFPIA companies is EUR The indicative contribution of IMI 2 Associated Partners is EUR The financial contribution from IMI 2 is a maximum of EUR The indicative contribution from EFPIA companies is EUR The financial contribution from IMI 2 is a maximum of EUR Research and Innovation action. Two stage submission and evaluation process. Only the applicant consortium whose proposal is ranked first at the first stage is invited for the second stage. Research and Innovation action. Two stage submission and evaluation process. Only the applicant consortium whose proposal is ranked first at the first stage is invited for the second stage. Research and Innovation action. Two stage submission and evaluation process. Only the applicant consortium whose proposal is ranked first at the first stage is invited for the second stage.

52 IMI 2 Call 5 budget IMI IMI IMI The indicative contribution from EFPIA companies is EUR The financial contribution from IMI 2 is a maximum of EUR The indicative contribution from EFPIA companies is EUR The financial contribution from IMI 2 is a maximum of EUR The indicative contribution from EFPIA companies is EUR The financial contribution from IMI 2 is a maximum of EUR Research and Innovation action. Two stage submission and evaluation process. Only the applicant consortium whose proposal is ranked first at the first stage is invited for the second stage. Research and Innovation action. Two stage submission and evaluation process. Only the applicant consortium whose proposal is ranked first at the first stage is invited for the second stage. Research and Innovation action. Two stage submission and evaluation process. Only the applicant consortium whose proposal is ranked first at the first stage is invited for the second stage.

53 IMI2 Call 5 - Timelines Consultation launch: 17 April 2015 Call launch: 9 July 2015 SP submission deadline: 29 September 2015 SP in-house evaluation: early November 2015 FP submission deadline: End February 2016 Project launch: Summer 2016

54 Thank you!