The aim of INTERVENE is to develop and test next generation tools for disease prevention, diagnosis, and personalised treatment utilizing the first US-European pool of genomic and health data and integrating longitudinal and disease-relevant -omics data into genetic risk scores. Resulting in unprecedented potential for prediction, diagnosis, and personalised treatments for complex and rare diseases. Some of the largest biobanks in Europe and one in the USA will be securely linked and harmonized in a GDPR-compliant repository with data from more than 1.7 million genomes. INTERVENE will demonstrate the potential and benefits of powerful AI technologies on the next generation of integrative genetic scores (IGS). The clinical and economic benefits of IGS will be evaluated in key disease areas with major public health burden. Here, the newly developed IGS will be taken into clinical environment and their real-world benefits will be evaluated together with clinical experts, European patients advocate groups and medical societies and considering regulatory and ethical implications. Thus, a framework for legally and ethically responsible translation into wider clinical practice will be developed. Moreover, the partners will develop and test the role of IGS in several rare diseases as well as COVID-19 infection and severity. Importantly, to support the application of IGS via public-private partnerships including clinical practitioners, an AI-enabled federated data analysis platform, the ‘IGS4EU’ platform, will be developed for automated IGS generation and interpretation for end-users. Additionally, the IGS4EU platform will allow access of the INTERVENE data and the methodology know-how to the AI community through a competition-based benchmarking environment. In the long term, the IGS4EU platform aims to grow the disease coverage and enable a wide adoption of IGS as a gold standard in clinical research and practice.

Hearing loss is a chronic non-communicable disease disabling over 328 million adults, and 32 million children worldwide. Sensorineural hearing loss due to loss of auditory hair cells was long thought to be irreversible. However, recent animal studies have demonstrated that pharmacological inhibition of cell signalling via Notch receptors using gamma-secretase inhibitors (GSIs) can regenerate hair cells and partially restore hearing capacity. This novel therapeutic concept provides the first promising lead for actual treatment of hearing loss. Clinical validation of these findings is the next crucial stepping stone in the development of a regenerative therapy for hearing loss. The ambition of REGAIN is to repurpose a GSI molecule for this indication by shifting from systemic to local treatment. The objective of the REGAIN project is to demonstrate and exploit the efficacy of locally administered GSIs to improve hearing through regeneration of inner ear hair cells with a lasting effect. The project will involve 1) the upscaling of GMP production of the clinical GSI candidate, 2) the generation of preclinical data on GSI dosing and local safety, 3) medical ethical clinical trial approval and 4) the demonstration of proof of concept for GSI for treatment of patients with recent onset sensorineural hearing loss. Small molecule drugs targeting the underlying biological causes of hearing loss in a safe way are expected to meet a real medical need for millions of patients, who currently rely on the limited benefits provided by hearing aids or cochlear implants. The partners involved in REGAIN represent the current state of the art in regenerative hearing loss research in the EU. REGAIN will break through that current state of the art, and will advance the first highly promising pharmaceutical treatment of hearing loss through clinical testing.

PRECIOUS aims at scaling-up biodegradable nanomedicines for multimodal precision cancer immunotherapy. With 3.5 million cancer patients in Europe every year, new cancer medicines are eagerly awaited, notably for prostate and ovarian cancer. Systemically applied new immunotherapies are promising, but their toxicity is a hurdle. Vaccination against cancer is safe but rather the efficacy can be disappointing, i.e. the microenvironment shuts down anti-tumour immunity. PRECIOUS will tackle 2 bottlenecks: 1. Production of non toxic multimodal nanomedicines, which induce vigorous immune responses, and at the same time reverse immunosuppression 2. Large scale GMP production of nanomedicines, and initiate a multimodal immunotherapy Phase I trial. We want to solve these bottlenecks by: Objective 1: Two types of GMP biodegradable nanoparticles: 1) a nanovaccine, containing tumour antigens and immune activators, and 2) a nanoparticle composed of compounds, which reverses the suppression and reactivates immunity in the tumour. Objective 2: Clinical Phase I trial to show efficacy. Nanomedicines will be used by 1) injection of vaccines to evoke immune responses and 2) injection of nanoparticles in the tumour microenvironment, which slowly release compounds that reverse suppression. To achieve this, a platform is formed with 6 leading industrial partners to produce large scale GMP nanomedicines and an excellent immunomodulator track record, together with 5 renowned academic partners to perform clinical studies. Relevance to call: Large scale GMP production, industrial leadership, nanotechnology and advanced manufacturing KET technologies, translation to the clinic, marketing development.

canSERVs mission is to make cutting-edge and customised research services available to the cancer research community EU wide, enable innovative R&D projects and foster precision medicine for patients benefit across Europe. By connecting, coordinating, and aligning existing oncology and complimentary research infrastructures (RIs) and providing services in a synergistic way transnationally, canSERV will capitalise on the critical mass of experts and cutting-edge services offered by canSERVs RIs and their extended network. canSERV brings together world-class European life science RIs (BBMRI, EURO-BIOIMAGING, ELIXIR, EU-IBISBA, EuroPDX, EU-OPENSCREEN, INSTRUCT, EATRIS, INFRAFRONTIER, EMBRC, ECRIN, EATRIS, MIRRI, ARIE, CCE, EORTC and IARC) that collectively not only covers all aspects along the development pipeline for oncology, but is also capable of interconnecting these technologies providing users a guidance for navigating them through the entire translational value chain. A patient organisation or resp. governance board members wil bring the patients perspective, while the two SMEs, ARTTIC and ttopstart, will provide valuable input regarding stakeholder engagement, and project management activities. A common access management system (CAMS) will be developed based on mature solutions from INSTRUCT and BBMRI. The CAMS will provide a method for selection of services, construction and submission of research proposals, multi-step review of research proposals, and tracking of the access process from approval through delivery to conclusion. Through a united user-intuitive transnational access where a united catalogue of oncology services will be offered, our users will have access to a comprehensive service portfolio. As our ambition is to scale up canSERV to a pan-European collaboration of RIs for accelerating the development and implementation of solutions for the cancer patient community, the sustainability of this network beyond the end of the project will also be addressed.

Prostate Cancer (PCa) is the second leading cause of cancer, among men in Europe. There are currently major unmet needs in this field, such as insufficient knowledge on risk factors that contribute to PCa and on patient characteristics (including genetic profiles) that could facilitate patient stratification. Finally, there is lack of meaningful engagement of all key stakeholders, while the knowledge currently gained from clinical practice and real life data is not being fed back into PCa patients’ care pathways. There is thus a need for better definition of PCa across all stages, improved patient’s stratification at diagnosis, and standardisation of PCa-related outcomes based on real life data. PIONEER’s unique dual approach is to first identify critical evidence gaps in PCa by respected Key Opinion Leaders, and then embark on a research priority setting exercise that reflects the needs of all key stakeholders in PCa management. To achieve this, PIONEER has brought together comprehensive datasets that consists of the most relevant prostate clinical trials and registries, large epidemiological cohorts, electronic heath records, and real-life data from different European (and non-European) patient populations. These unique data sets will be integrated, standardised, harmonised and analysed using approaches that are built on our experience of similar previous IMI projects i.e EMIF, and eTRIKS, and analysed using a unique set of methodologies and advanced analytics methods (OMOP, eHS). PIONEER has already performed a first PCa research priority setting survey, where major stakeholders were asked to identify the current unmet needs in PCa. The five most important open questions will be used as pilot studies to verify PIONEER’s research framework. As such, PIONEER’s deliverables will be outcome-driven, value-based and patient-centric, and relevant to all key stakeholders, as they would have been meaningfully involved from the inception of the project.