Grants and Support

The Innovative Medicines Initiative (IMI) is a partnership between the European Union and the European pharmaceutical industry. IMI facilitates open collaboration in research to advance the development of, and accelerate patient access to, personalised medicines for the health and wellbeing of all, especially in areas of unmet medical need.

IMI is the world's biggest public-private partnership (PPP) in the life sciences. It is a partnership between the European Union (represented by the European Commission) and the European pharmaceutical industry (represented by EFPIA, the European Federation of Pharmaceutical Industries and Associations). Through the IMI2 programme, a €3.3 billion budget for the period 2014-2020 is available.

The goal of IMI, particularly in its second phase (IMI2, 2014-2020) is to develop next generation vaccines, medicines and treatments, such as new antibiotics. The projects will provide Europeans, including the increasing numbers of older people, with more efficient and effective medicines and treatments. Greater coordination across industry sectors will result in more reliable and faster clinical trials, and better regulation. Research and innovation efforts will also open new commercial possibilities based on new services and products. The research, industry and societal sectors involved in IMI2 will benefit from the cooperation and knowledge sharing which take place in these projects.

(source: IMI website)

LUMC researchers participate(d) in the following IMI projects:

EU IMI Grant - ABIRISK

Title: Anti-biopharmaceutical immunization: prediction and analysis of clinical relevance to minimize the risk

LUMC PI: Dr. Renee Allaart
Department of Rheumatology (link)

Abstract:
A growing number of medicines are based on biological molecules such as proteins and monoclonal antibodies. These novel drugs have resulted in new, more effective treatments for a number of serious conditions. Yet sometimes these medicines trigger a response from the patient’s immune system, which can decrease the effectiveness of the drug or cause severe side effects. The aim of the IMI-funded ABIRISK project is to shed new light on the factors behind this immune response. The project, which represents the first concerted effort to solve this problem, will aid in the creation of new, safer biopharmaceuticals and also generate tools to determine how individual patients are likely to respond to them both in clinical trials and after release to the market.

IMI project website

EU IMI Grant - APPROACH

Title: Applied public-private research enabling osteoarthritis clinical headway

LUMC PI: Prof. dr. Margreet Kloppenburg
Department of Rheumatology (link)

Abstract:
Some 9.6% of men and 18% of women over 60 suffer from osteoarthritis, and a quarter of those affected struggle to carry out ordinary daily activities. However, developing effective treatments for this debilitating condition is extremely challenging. The APPROACH project is creating a platform comprising data on over 10 000 patients and healthy people. The project team will use this data to identify groups of patients with similar profiles; these groups could respond well to specific treatments. This information will ultimately be used to identify patients who could take part in clinical trials of more personalised treatments for osteoarthritis.

IMI project website

EU IMI Grant - BIOMAP

Title: Biomarkers in Atopic Dermatitis and Psoriasis

LUMC PI: Prof. dr. Frits Koning
Department of Immunohaematology and Blood Transfusion (link)

Abstract:
Not yet available.

IMI project website

EU IMI Grant - BTCURE

Title: Be the cure

LUMC PI: Prof. dr. Tom Huizinga
Department of Rheumatology (link)

Abstract:
New developments in our understanding of the pathology of Rheumatoid Arthritis (RA), a chronic disease affecting many patients, show how disease-inducing immune and inflammatory reactions develop from an asymptomatic phase with autoimmune reactions into a phase of non-specific symptoms and then further into the full-blown disease causing pain, joint destruction and functional deterioration.
The ultimate goal for therapeutic development is to identify the disease-causing molecular events early in the disease and then influence immunity and inflammation so that functional deterioration is halted, immunity is re-regulated and the disease is cured.

IMI project website

EU IMI Grant - CARE

Title: Corona accelerated R&D in Europe (CARE)

LUMC PI: Prof.Dr. Eric Snijder
Department of Medical Microbiology (link)

Abstract:
The goal of the CARE project is to deliver treatments for the current COVID-19 outbreak as well as future coronavirus outbreaks. Part of the project will focus on ‘repurposing’, in which drugs designed for other diseases are ‘repurposed’ for a new disease. Because a lot of work has already been carried out on these compounds, repurposing can deliver relatively rapid results. The project also aims to deliver new drugs designed specifically to treat COVID-19 and other coronaviruses. To identify potential drugs, the project will screen 600 000 compounds across different libraries. They will also investigate antibodies capable of neutralising the virus. Potential drugs identified by the project will undergo a range of laboratory tests to refine their design and evaluate and improve their safety and efficacy. Compounds that make the grade will enter clinical trials, where their safety and efficacy will be tested in humans. The CARE project is committed to the FAIR (findable, accessible, interoperable, reusable) principles of open science and will share its scientific results through open access platforms and peer-reviewed journals, as well as via relevant conferences and other events. The team will also work closely with other, similar projects. Ultimately, CARE should both contribute to the world’s response to the current COVID-19 outbreak, and ensure we are better prepared for further coronavirus outbreaks in the future.

IMI project website

EU IMI Grant - COMBACTE-CDI

Title: Combatting Bacterial Resistance in Europe - Clostridium Difficile Infections (COMBACTE-CDI

LUMC PI: Prof. dr. Ed Kuijper
Department of Medical Microbiology (link) 

Abstract:
Clostridium difficile infection (CDI) is one of the most common healthcare-associated infections, with 172 000 cases annually, many of them in the elderly, in Europe alone. Symptoms include diarrhoea and abdominal pain, and it can prove fatal. Despite its immense impact on patients and healthcare systems, researchers lack a good understanding of the epidemiology and clinical impact of CDI across Europe. The goal of the COMBACTE-CDI project is to change that, by delivering extensive data on the extent and impact of CDI across all healthcare sectors in Europe. This information is essential for the development of better methods to prevent and treat CDI. A large part of the project is devoted to a large epidemiology study which will quantify the burden of CDI (including incidence, distribution, recurrence, mortality, and transmission) across the whole healthcare economy. The project will also assess current practices on the management of CDI in Europe (including guidelines, testing, surveillance, treatment, and costs) and their potential impacts. Finally, the project will create a pan-European research platform capable of supporting future proof-of-concept and clinical studies of new prevention and treatment strategies for CDI. In the long term, the knowledge generated by COMBACTE-CDI will aid the development of better strategies to prevent and treat this deadly infection.

IMI project website

EU IMI Grant - DIRECT

Title: Diabetes research on patient stratification

LUMC PI: Dr. Leen ‘t Hart
Department of Molecular Cell Biology (link)

Abstract:
Type 2 diabetes patients are a diverse group; in some, the disease progresses rapidly, while in others it takes a slower course. Similarly, a treatment that works well in one patient may prove less effective in another. This has led researchers to acknowledge that there are actually a number of different subtypes of type 2 diabetes. The goal of the IMI-funded DIRECT project is to identify these subtypes and determine most appropriate treatments for them. The project brings together Europe’s leading researchers from academia, healthcare, and the pharmaceutical industry.

IMI project website

EU IMI Grant - ELF

Title: European Lead Factory

LUMC PI: Prof. dr. Huib Ovaa
Department of Chemical Immunology (link)

Abstract:
The European Lead Factory is a pan-European platform for drug discovery that is giving a major boost to drug discovery in Europe by connecting innovative drug targets to high-quality compounds. Comprising a collection of up to half a million compounds (derived from new public and existing private company collections) and a screening centre, the European Lead Factory offers researchers in academia, small and medium-sized enterprises (SMEs) and patient organisations an unprecedented opportunity to advance medical research and develop new medicines.

IMI project website

EU IMI Grant - EUbOPEN

Title: Enabling and Unlocking biology in the OPEN (EUbOPEN)

LUMC PI: Prof. dr. Huib Ovaa 
Department of Cell and Chemical Biology (link)

Abstract:
The EUbOPEN partnership of excellence will aim to generate the largest freely available set of high-quality chemical inhibitors for human proteins. These compounds will include chemical probes for solute carriers (SLCs), E3-ubiquitin ligases (E3s) and other proteins, and a chemogenomic library (CGL) of 3000-5000 compounds covering one third of the druggable genome. All compounds in the sets will be comprehensively characterised defining their selectivity, potency and cellular activity. The compounds will be annotated with a series of established and novel biochemical and cell-based assays, including many derived from primary patient cells. Diseases of particular focus will be inflammatory bowel disease, cancer and neurodegeneration.
EUbOPEN partners have proven track records leading large international open science projects, developing unencumbered key reagents, and exploring new target areas. A strong commitment to open data and open science will accelerate the dissemination of knowledge and reagents as well as mitigate ethical issues that might arise by working with patient-derived cells.
EUbOPEN will partner extensively with other large projects (e.g. ReSOLUTE, Illuminating the Druggable Genome) to minimize duplication of effort and to maximize global coordination. EUbOPEN will provide via the EFPIA partners the public access to industry’s deep medicinal chemistry skills.
Sustainability of the project’s resources will be ensured through already established partnerships with chemical vendors and cheminformatics/database providers, which will ensure the long-term availability of the new chemical tool sets, all associated profiling data and established protocols.
The EUbOPEN project will form the foundation for future efforts to generate chemical modulators for the entire druggable genome and will develop new technologies significantly shortening hit and lead identification processes.

IMI project website

EU IMI Grant - IDEA-FAST

Title: Identifying Digital Endpoints to Assess FAtigue, Sleep and acTivities in daily living in Neurodegenerative disorders and Immune-mediated inflammatory diseases (IDEA-FAST)

LUMC PI: Dr. Susanne de Bot
Department of Neurology (link)

Abstract:
Fatigue and sleep disturbances are two common and disabling symptoms that affect patients with neurodegenerative disorders (NDD) and immune-mediated inflammatory diseases (IMID). These symptoms are major predictors of poor quality of life and increased healthcare cost. Current questionnaire-based approaches to measure these symptoms have key limitations preventing them from being used as reliable endpoints in clinical trials to evaluate the effect of therapies.
IDEA-FAST aims to address these issues by identifying novel digital endpoints for fatigue and sleep disturbances that will provide more objective, sensitive and reliable measures of the severity and impact of these symptoms in ecological settings. Such digital endpoints will not only help to gain insight into the underpinning mechanisms of fatigue and sleep disturbances, but will also vastly improve the efficiency of clinical trials, ultimately reducing the time and cost to bring new therapies to patients.
To identify these digital endpoints, we will follow the recommendations of the Clinical Trials Transformation Initiative (CTTI). We will identify the characteristics that fatigue and sleep disturbances will have impact, then select the digital measures (endpoints) to quantify them, followed by choosing the appropriate digital device/technology accordingly. We will then perform a pilot study to prioritise a few of these candidate digital endpoints for validation. We will test the performance of these digital endpoints in two NDD and four IMID in a large longitudinal study during which extensive relevant clinical data will be collected. If these digital endpoints were validated, we will seek support from EMA/FDA for their qualification. Patient users’ perspective, ethical, data privacy, legal and other regulatory issues will be taken into consideration in all aspects of our proposal.
The resultant digital biobank from the longitudinal study will become an invaluable resource for future exploitation.

IMI project website

EU IMI Grant - IM2PACT

Title: Investigating Mechanisms and Models Predictive of Accesibility of Therapeutics (IM2PACT) Into the Brain

LUMC PI: Prof. dr Manfred Wührer 
Center for Proteomics and Metabolomics (link)

Abstract:
The overall aim is to further the understanding of the BBB in health and disease states towards the development of innovative brain delivery systems, especially for biopharmaceuticals (e.g., peptides, antibodies, etc.) and the identification of novel disease drug targets (Alzheimer’s Disease, MS, metabolic disease). The related key deliverables will be as follows:

1. Identification and validation of specific genes and/or mechanisms which are altered in brain endothelial cells in disease.
2. Generation, validation and characterisation of robust and predictive iPSC-derived BBB models: The developed models should be more reflective of the in vivo situation than existing models, in the healthy and disease states.
3. New, efficacious and safe mechanisms and technologies of brain delivery: The output of this topic should also result in an expanded and deepened understanding of the fundamental processes that underpin drug-trafficking across the BBB, which in turn can further support endeavours to elucidate novel and more efficacious brain delivery mechanisms.
4. Characterised new genetic models for the diseases of interest in this topic which are better amenable to evaluate disease-modifying agents.
5. Characterised mechanisms of neurotropic virus-mediated BBB and CNS penetration for development of selective brain delivery systems.
6. Established in silico/mathematical models in predicting BBB penetration of therapeutics (such as receptor-or carrier-mediated transcytosis for delivery across the BBB) and pharmacokinetics of biopharmaceutics in different compartments of CNS.
7. Identification of relevant translational readouts which are better amenable to elucidate the role of the BBB in the pathogenesis of neurodegeneration and could eventually lead to new targets for the treatment of the neurovascular causes of the diseases.

IMI project website

EU IMI Grant - imSAVAR

Title: Immune Safety Avatar: nonclinical mimicking of the immune system effects of immunomodulatory therapies (imSAVAR)

LUMC PI: Dr. Valeria Orlova
Department of Anatomy and Embryology (link)

Abstract:
Certain treatments for cancers and autoimmune diseases work by altering the immune system. However, a major challenge for researchers is identifying potential efficacy and safety issues with these treatments early in drug development, before they are tested in humans. Part of the problem is that the tests used early in drug development do not reflect the full complexity of the human immune system. In addition, these tests tend to be based on a healthy immune system, which is different to the immune system of someone who is ill. The imSAVAR project aims to deliver a range of tools that will enhance our ability to assess the efficacy and safety of these immunomodulatory therapies. They also plan to develop new biological markers for diagnosing and predicting immune-mediated safety issues, and explore ways of mitigating them. In the longer term, the project will help to deliver safer medicines for patients and also contribute to the ‘3Rs’ (i.e. the drive to replace, reduce and refine the use of animals in research).

IMI project website

EU IMI Grant - INNODIA

Title: Translational approaches to disease modifying therapy of type 1 diabetes: an innovative approach towards understanding and arresting type 1 diabetes

LUMC PI: Prof. dr. Bart Roep
Department of Immunoheamatology and Blood transfusion (link)

Abstract:
Type 1 diabetes affects 17 million people globally and there is no cure; instead, patients must inject themselves with insulin daily and continually check their blood sugar levels to control their condition. The goal of the INNODIA project is to advance our understanding of type 1 diabetes and address the lack of tools and technologies that will allow clinicians to predict, evaluate and prevent the onset and progression of type 1 diabetes. For patients, this would mean the ability to predict the rate at which their disease will progress. The knowledge and tools generated by the project will help researchers to optimise the design of clinical trials of treatments for preventing and curing this debilitating disease. The project has set up a patient advisory committee to ensure the work is in line with patients’ needs.

IMI project website

EU IMI Grant - INNODIA HARVEST

Title: Translational approaches to disease modifying therapy of type 1 diabetes - HARVESTing the fruits of INNODIA

LUMC PI: Prof. dr. Bart Roep
Department of Immunoheamatology and Blood transfusion (link)

Abstract:
Building on the strong foundations of INNODIA, with its unique, Europe-wide clinical and basic research network for the study of type 1 diabetes (T1D), we propose in INNODIA HARVEST an ambitious program which aims to prevent and arrest T1D via focused objectives targeting consolidation and innovation. First, we will consolidate the INNODIA clinical network as the reference point for conducting studies to prevent or arrest T1D. We will transform our standardized clinical and bioresource platforms into a high-performance clinical trial network, running academic and industry-driven trials alongside small, mechanism-centric, biomarker-rich intervention trials to examine pathobiological pathways to T1D. INNODIA HARVEST will conduct two large studies to arrest T1D at its onset, one academia-driven, beta-cell focused (VER-A-T1D, verapamil) and one industry-driven, immune-focused (Iscalimab-study). We will exploit our original INNODIA Master Protocol allowing novel adaptive trial design to introduce combination therapies that build on complementary mechanisms. Second, we will extend our study design strategy by introducing novel biomarkers, both clinical (continuous glucose monitoring) and experimental (microbiome analysis) to deconvolute disease heterogeneity and identify new endpoints to accelerate identification of effective therapeutics. Third, we will use ‘disruptors’ in small mechanistic studies to channel innovation from clinic to basic research through a reverse immunology and reverse beta-cell biology approach. Finally, we will implement new discovery pipelines for future therapeutics, exploiting tools such as iPSC-derived islet-like cells to promote next generation target identification and drug development. As in INNODIA, the voice of people living with T1D and their families will hold a central place in INNODIA HARVEST to drive implementation of new, patient-proximal outcomes, shape our clinical trials, and bring about a meaningful change in disease perspective.
A major objective of INNODIA Harvest is the execution of at least two new phase 2 trials (studying Verapamil (VER-A-T1D) or Iscalimab (CCFZ533X2207)). Considering the expected time to first patient-in as preparations for trial start can only be initiated after the start of the Action and possible fluctuating recruiting rates, due to the intercurrent COVID epidemic, there is a risk that INNODIA HARVEST will not be able to completely finalize the clinical trials, fully analyse the biomarkers collected and publish the results in the initially proposed 24 months duration. To ensure the finalization of the clinical trials and corresponding full execution of the given budget including eligibility of EFPIA in-kind contribution we propose to extend the duration of the Action from 24 to 36 months.

IMI project website

EU IMI Grant - Open PHACTS

Title: The open pharmacological concepts triple store

LUMC PI: Prof. dr. Barend Mons
Department of Human Genetics (link)

Abstract:
Drug discovery is data-hungry and all major pharmaceutical companies maintain extensive in-house instances of public data. Analysis and hypothesis generation for drug-discovery projects requires assembly, overlay and comparison of data from many sources as well as development of shared identifiers and common semantics.
Expression profiles need to be overlaid with gene or pathway identifiers and reports on compound pharmacology. Alignment and integration of internal and public data and information sources requires a significant effort and the process is repeated across companies, institutes and academic laboratories. This represents significant waste and increases opportunity cost.

IMI project website

EU IMI Grant - PERISCOPE

Title: Pertussis correlates of protection europe

LUMC PI: Prof. dr. Jacques van Dongen
Department of Immunoheamatology and Blood transfusion (link)

Abstract:
Vaccines have helped to cut cases of pertussis (whooping cough) worldwide. However, recent years have seen a rise in cases and the disease remains a leading cause of infant mortality around the world. The PERISCOPE project is working to better understand how the currently available vaccines work, and to aid the development and licensing of the next generation of improved pertussis vaccines. The multi-disciplinary team will focus on three major areas. Firstly, they will set up a comprehensive clinical research programme to study the immune response of people of all ages to pertussis infection and vaccination. Secondly, they will establish tools (clinical and pre-clinical models) to study pertussis infection. Finally, they will develop a battery of state-of-the-art tests, to help reveal the markers of an effective and long-lasting immune response to pertussis infection. PERISCOPE will also seek to study immunisation in pregnancy to gain a better understanding of the impact of maternal antibodies on the infant’s immune responses to pertussis.

IMI project website

EU IMI Grant - PRISM

Title: Psychiatric ratings using intermediate stratified markers: providing quantitative biological measures to facilitate the discovery and development of new treatments for social and cognitive deficits in AD, SZ, and MD

LUMC PI: Prof. dr. Nic van der Wee
Department of Psychiatry (link)

Abstract:
Social withdrawal is a common early symptom of many neurological disorders, including schizophrenia, Alzheimer’s disease, and major depressive disorder. However, the underlying, biological causes of this symptom are still poorly understood and may differ from one disease to another. The PRISM project will carry out a range of tests, including blood tests, brain scans, and measures of behaviour, on patients with these all too common diseases in a bid to determine which biological parameters correlate with specific clinical symptoms, like social withdrawal. The hope is that the project’s findings will shed new light on the causes of mental illness and their symptoms and facilitate the development of much-needed new treatments.

IMI project website

EU IMI Grant - RespiriNTM

Title: Progress novel assets (one FIH start) for non-tubercular mycobacteria that may act synergistically with bedaquiline and cytochrome bc drugs

LUMC PI: Dr. Meindert Lamers
Department of Cell en Chemical Biology (link)

Abstract:
Non-tuberculous mycobacteria, such as Mycobacterium avium complex (MAC) and Mycobacterium abscessus, cause lung diseases resembling TB, mainly in immune-compromised patients or patients suffering from other lung diseases (e.g. cystic fibrosis). The incidence and prevalence of lung diseases caused by NTM are increasing worldwide. Importantly, in the US and Japan, as well as in other areas of the world where TB has declined, NTM disease is already at least three times more prevalent than TB. Treatment of NTM diseases relies on antibiotic combinations, however the drugs active against NTM are rather few and mainly different than those active against TB. These NTM treatments for the most common species (MAC and M. abscessus) are much less active than the current anti-TB regimen is for TB treatment. It is often necessary to administer antibiotic combinations for at least 12-24 months. The long and complex drug regimen that is currently recommended as a treatment against NTM-caused diseases carries the risk of inducing resistance in NTM. Several studies have already shown the existence and emergence of multidrug resistant NTM. The overall objective of RESPIRI-NTM is to find new drug candidates as potential components of a new, more efficient combination drug regimen against NTM that is less prone to resistance and allows shortening of treatment duration for NTM and multidrug-resistant NTM. Such a drug combination will synergistically target the energy metabolism of NTM or complementary targets. To achieve this, we will advance recently discovered inhibitors of the mycobacterial respiratory pathway. In addition, we will perform a novel, phenotypic screen in order to identify novel targets in NTM. Finally, we will also target host-factors that are essential for the intracellular survival of NTM. Together, we present a comprehensive plan to find novel strategies to combat non-tuberculous mycobacteria, shorten treatment time and reduce chances of drug resistance.

IMI project website

EU IMI Grant - RespiriTB

Title: Progress new assets (one pre-new molecular entity and one first-time-in-human start) for tuberculosis that act synergistically with bedaquiline, cytochrome bc or cytochrome bd inhibitors

LUMC PI: Dr. Meindert Lamers
Department of Cell en Chemical Biology (link)

Abstract:
Despite recent progress in biomedical research, Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is still the world’s leading infectious disease killer worldwide. In addition, multi-drug TB is the largest single contributor to anti-microbial resistance and poses a serious threat to global health. Treatment options are limited, and expensive, recommended medicines are not always available in many countries, and patients experience many adverse effects from the drugs. Moreover, due to the long treatment duration, compliance is low leading to more AMR in TB. Thus, there is an acute need for the development of a novel combination regimen with an indication for effective, shorter, and safer treatment of all forms of TB. The overall objective of RESPIRI-TB is to find new drug candidates as potential components of a new, more efficient combination drug regimen against TB that is less prone to resistance and allows shortening of treatment duration for TB, and multidrug-resistant TB. Such a drug combination will synergistically target the energy metabolism of Mtb or complementary targets. To achieve this, we will advance recently discovered inhibitors of the Mtb respiratory pathway. In addition, we will target the Mtb specific molecular mechanism that reduces reactive oxygen species in the cell. Finally, we will also target host-factors that are essential for the intracellular survival of Mtb. Together, we present a comprehensive plan to find novel strategies to combat TB, shorten treatment time and reduce chances of drug resistance.

IMI project website

EU IMI Grant - RHAPSODY

Title: Assessing risk and progression of prediabetes and type 2 diabetes to enable disease modification

LUMC PI: Dr. Leen ‘t Hart
Department of Molecular Cell Biology (link)

Abstract:
Improving diabetes prevention and treatment is the ultimate goal of the RHAPSODY project. Type 2 diabetes affects 285 million people globally and that number is rising fast. RHAPSODY brings together experts from universities, large pharmaceutical companies and biotechs. Their goal is to add to our understanding of the factors that drive the progression of pre-diabetes to diabetes, and the deterioration of the condition of people with diabetes. RHAPSODY aims to develop novel biological markers that will aid in the diagnosis of type 2 diabetes, and the identification of different sub-groups of patients. This information will also help to inform clinical trial design and the development of new strategies to prevent and treat diabetes.

IMI project website

EU IMI Grant - ROADMAP

Title: Real world outcomes across the AD spectrum for better care: Multimodal Data Access Platform

LUMC PI: Prof. dr. Ewout Steyerberg
Department of Biomedical Data Sciences (link) 

Abstract:
Alzheimer’s disease is on the rise in our ageing population, and new, effective treatments are urgently needed. Currently, the safety and benefits to patients of potential treatments are assessed in strictly-controlled clinical trials. However, clinical trials do not provide information on the health benefits for patients in their daily lives in the ‘real world’. The ROADMAP project aims to deliver a series of methods and tools that will allow the scalable, transferable integration of data on patient outcomes in the real world. The tools will be developed and tested through pilot projects and will lay the foundations for a Europe-wide platform on real world evidence in Alzheimer’s disease. The project will also deliver tools for patient engagement and address the ethical, legal and social implications of adopting a real world evidence approach to Alzheimer’s disease. The project is part of IMI’s Big Data for Better Outcomes programme, which aims to facilitate the use of diverse data sources to deliver results that reflect health outcomes of treatments that are meaningful for patients, clinicians, regulators, researchers, healthcare decision-makers, and others.

IMI project website

EU IMI Grant - RTCure

Title: Rheuma Tolerance for Cure

LUMC PI: Prof. dr. Tom Huizinga & Prof. dr. Rene Toes
Department of Rheumatology (link)

Abstract:
In line with IMI2 goals for improved therapies and precision medicine, the aim of this proposal is to prevent and treat RA or its progression by inhibiting maturation/expansion of pathogenic autoimmune responses through immune tolerising treatments of subjects not only in early
stages of joint inflammation (undifferentiated arthritis and early RA) but also in even earlier defined stages i.e. before onset of joint inflammation, when patients have arthralgia and/or bone loss, or sub-clinical stages of joint inflammation. Today, no drugs are approved for these early phases of RA development, where symptoms such as pain and fatigue cause major loss of life quality and where successful interference would prevent onset of disease. Thus, an important part of our work will be to achieve a better understanding of this as yet unexplored phase of disease. In the proposed project we will develop and validate new methods to identify individuals at high risk for RA, tools to monitor disease progress and expand and further develop cohorts suitable for these purposes. Furthermore we will validate and standardise methods to monitor immune tolerance to be used in clinical trials for tolerising therapies for RA. The aim is thus to interfere with the specific immune reactions that contribute to RA symptoms in such a way that a specific and long-lasting therapeutic effect (ultimately a cure) is accomplished for a major proportion of RA patients and prevention of diseases is accomplished in individuals at high risk for RA. Investigator-initiated as well as company-sponsored clinical trials in well stratified patient groups will be performed in collaboration with SMEs and/or contributing pharma companies and their immune effects studied using the same panel of biomarkers allowing for standardisation across protocols. Our ambition is also to disseminate our experiences from RA to other rheumatic and other immune-mediated diseases.

IMI project website

EU IMI Grant - SISAQOL

Title: Establishing international standards in the analysis of patient reported outcomes and health-related quality of life data in cancer clinical trials (SISAQOL)

LUMC PI: Prof.Dr. Martin Taphoorn
Department of Neurology (link)

Abstract:
Measuring and quantifying how a patient feels or functions during treatment is an important endpoint in cancer clinical trials. It is generally accepted that the collection of PRO data in cancer clinical trials allows the inclusion of the patient’s voice in the risk-benefit assessment of therapies. However, no standards exist on how to analyse, interpret or report health-related quality of life (HRQOL) and other patient-reported outcomes (PROs). This initiative wants to pursue efforts in addressing the urgent need for standardization, by setting clear and validated standards that are tailored to and endorsed by all relevant stakeholders. With a strong international and multi-stakeholder Consortium, the initiative aims at finding consensus on suitable methods to analyse valid PRO objectives in cancer randomized clinical trials (RCTs) and ways to communicate these PRO findings in a standardized way that is understandable to all.
To achieve this aim, SISAQOL-IMI will identify valid PRO research objectives and match these with appropriate statistical methods for PRO analysis in cancer RCTs. Translation to the estimands framework will be provided. Furthermore, the possibility of extending these recommendations to single-arm trial designs will be explored. Recommendations on clinically meaningful change for PRO instruments, as well as design considerations and ways for assessing quality of collected PRO data will be developed, and tools and templates for presentation and visualization of PRO findings freely made available. Strong emphasis is put on continuous collaboration with patient advocacy representatives throughout the project.
Increased interpretability, adoption and full use of PRO outcomes for all stakeholders is expected by providing consensus-based and validated recommendations and communication tools for PRO data, ultimately resulting in better communication and shared decision making, improved outcomes, treatment satisfaction and care.

IMI project website

EU IMI Grant - VSV-EBOPLUS

Title: Systems analysis of adult and pediatric responses to the VSV-Zebov Ebola vaccine

LUMC PI: Prof. dr. Tom Ottenhoff
Department of Infectious Diseases (link)

Abstract:
The vesicular stomatitis virus (VSV)-Zaire Ebola vaccine (VSV-ZEBOV) is a recombinant vector-based vaccine in which the VSV envelope glycoprotein was replaced with the Zaire strain Ebola virus glycoprotein. Within one year of the initiation of its clinical development, the VSV-ZEBOV vaccine has demonstrated safety, immunogenicity and a remarkably high protective efficacy against Ebola Virus Disease, using a high vaccine dose (2x107 pfu) in the WHO-sponsored VSV-ZEBOV ring-vaccination trial in adults in Guinea. However, several key questions remain unanswered, including its mode of action, its correlation with protection and reactogenicity, the expected duration of protective efficacy and determinants of long-term responses, the influence of baseline immunity on vaccine “take”, and the vaccine efficacy in children - a most vulnerable population. Following the interruption of the 2014-2015 Ebola Virus Disease (EVD) outbreak, these questions, being central to the future licensing and use of VSV-ZEBOV, may not be addressed by collecting field data. The VSV-EBOPLUS project therefore proposes to use cutting-edge systems biology approaches to address these key questions, capitalizing on the unique availability of large series of extremely well defined samples from clinical vaccine studies with the VSV-ZEBOV vaccine in three different continents (Europe, Africa, US).

IMI project website

EU IMI Grant - VSV-EBOVAC

Title: Vaccine safety and immunogenicity signatures of human responses to VSV-ZEBOV

LUMC PI: Prof. dr. Tom Ottenhoff
Department of Infectious Diseases (link)

Abstract:
VSV-EBOVAC builds on existing work to advance the development of the Ebola vaccine candidate VSV-ZEBOV (‘vesicular stomatitis virus-vectored Zaire Ebola vaccine’). Clinical trials are underway in Europe and Africa, and the VSV-EBOVAC project is using cutting-edge technologies to carry out in-depth analyses of samples taken from clinical trial participants before and after vaccination. This allows them to gather vital information on both the strength of the immune responses triggered by the vaccine and vaccine safety.

IMI project website

EU IMI Grant - ZAPI

Title: Zoonotic anticipation and preparedness initiative

LUMC PI: Prof. dr. Eric Snijder
Department of Medical Microbiology (link)

Abstract:
Many infectious diseases, including influenza and Ebola, can be transmitted to humans from animals (and vice-versa). Known as zoonoses, these diseases represent a serious threat to both human and animal health. ZAPI brings together experts in human and animal health to create new platforms and technologies that will facilitate a fast, coordinated, and practical response to new infectious diseases as soon as they emerge.

IMI project website