The current global COVID-19 pandemic has caused severe health and socio-economic challenges. Despite significant improvements in the treatment of critical COVID-19 patients and advances in vaccine development, there is still an urgent need for safe and effective early-intervention treatments. To reduce disease burden, hospitalization time, and mortality, it is of critical importance to halt disease progression in early (mild-to-moderate) stages. Our new drug, MP1032, has a dual mode of action, targeting two important mechanisms (immune system overactivation and viral replication) in the early development of COVID-19. Its unique mechanism of self-regulation prevents immune-suppression, which is critical for early intervention. In combination with the oral availability, favourable safety profile, rapid and affordable production scale-up, and potential to work against viral variants, MP1032 is the ideal candidate for early treatment of COVID-19, which can also be used safely in high-risk patients. Therefore, the iMPact project aims to clinically validate MP1032 in a Phase II trial for its ability to stop COVID-19 disease progression. The outcome of the project shall serve as a basis for follow-up rapid Phase IIb/III development and market registration. Four international SME’s will work together in the iMPact project to achieve the objectives: 1) To demonstrate the efficacy of MP-1032 in hospitalized COVID-19 patients, 2) To demonstrate the effect of MP1032 on current SARS-CoV-2 variants, 3) To develop a GMP-compliant production scale-up process for MP1032, 4) To ensure that the clinical development plan is in line with regulatory requirements and 5) To collaborate with existing EU research networks. We have 29 clinical sites on board, and the required expertise for upscaling GMP manufacturing and regulatory preparation is available, ensuring that, by October 2022, MP1032 will be ready to progress to Phase IIb/III trials.

Rare Eye Diseases (REDs) are a major cause of visual impairment and blindness in Europe, affecting patients of all ages. The RESTORE VISION Consortium identified a group of 7 REDs all affecting the cornea and ocular surface that cause severe vision impairment and blindness and have inadequate treatment options today. Onset and progression is characterised by overlapping common pathophysiologic mechanisms: defective corneal wound healing, nerve degeneration, stem-cell dysfunction and aberrant vessel ingrowth. The 7 REDs targeted are Aniridia-Associated Keratopathy, Neurotrophic Keratopathy, Limbal Stem Cell Deficiency, Ocular Cicatricial Pemphigoid, EEC Syndrome, Ocular Graft versus Host Disease and Corneal Neovascularisation, affecting over 500k patients in Europe. Current management is often prohibitively expensive, has low efficacy and leads to debilitating side effects, pointing to a critical medical problem and area of unmet medical need. RESTORE VISION brings together actors from across the full value chain: 6 leading research institutions, 3 SMEs and a European patient organisation. We take a ground-breaking approach to improve eye health by verifying disease pathomechanisms, using cutting-edge models for each rare disease to test novel and repurposed compounds and determine drug mechanisms of action, formulating compounds as safe eye drop suspensions or subconjunctival drugs, and performing several first-in-human trials of novel therapies. New therapeutics with game-changing potential will be evaluated for the first time. Our pioneering ‘streams’ approach is based on the repurposing of 6 existing drugs and the development of 3 new compounds, all with solid preliminary data showing remarkable effects in restoring the cell physiology, immune, avascular, neural and signalling environment in the cornea. This innovative approach shortcircuits lengthy and complex regulatory and drug development processes, ensuring rapid translation into the clinic.

With progress in globalization, expansion of human populations into natural habitats, and aggravation of climate change comes an increased risk of viral outbreaks. As demonstrated by the COVID-19 pandemic, not being prepared for such events has devastating consequences on public health, society and the economy. EvaMobs will improve preparedness of the European Union (EU) for the next viral outbreak(s) of pandemic potential by developing a platform for the discovery, development, production and validation of evolvable and rapidly adaptable antivirals. These innovative medicines will be based on small human-derived proteins called monobodies (Mobs). As Mobs can be engineered to have high binding affinity for virtually any viral protein, this platform can be easily adapted to a broad range of viruses, including newly emerging viruses and viral variants. To demonstrate the capacity of this platform it will first be applied to four pathogenic viruses with epidemic and/or pandemic potential: Influenza A, SARS-CoV-2, respiratory syncytial virus, and Zika virus. Deep-learning and computational design tools will allow generation of tailor-made Mobs with cryo-EM elucidating the molecular details of their binding interaction. Simple bacterial expression of Mobs, the development of a semi-automated high-throughput screening platform for evaluation of the Mobs’ stability and target affinity and streamlined in vitro and in vivo preclinical validation, will allow rapid development and selection of stable and potently neutralizing candidates. The Mob with the best preclinical indicators will then be tested in a phase I clinical trial after implementing a stable formulation and GMP production. The optimized platform can then be adapted to other viruses. Therefore, EvaMobs provides an innovative, robust and flexible platform for antiviral biologics development as well as a diverse portfolio of validated drugs, strengthening the EU’s pandemic preparedness.

Sudden cardiac arrest (SCA) causes ~20% of all deaths in Europe. SCA is lethal within minutes if left untreated and survival rates are presently only 5-20%. Therefore, there is a large medical need to improve SCA prevention and treatment. Designing effective individualized prevention and treatment strategies requires knowledge on genetic and environmental risk factors. So far, these efforts have been hampered by the lack of sufficiently large study cohorts of SCA patients with detailed information. Obtaining SCA patient samples is challenging as the condition happens suddenly and unexpectedly. In this project, leading European scientific teams which have created large relevant population cohorts, mostly dedicated to SCA research, join forces to fully exploit available data towards improving SCA management. This will be done by: - Building an unique and growing database of >100.000 (DNA) samples including >20.000 SCA patient samples, by combining existing European databases and infrastructures. - Identifying risk factors (inherited, acquired, environmental) and first-response treatment strategies that may explain the differences in SCA occurrence and survival between European countries - Collaborating with professional networks, such as the European Heart Rhythm Association, and European Resuscitation Council, to translate the outcomes into changes in clinical practice and influencing European health policies on SCA management.

The ELR SCAR project aims to complete preclinical validation of a novel biomaterial, an elastin-like recombinant (ELR) hydrogel, to prevent scar tissue formation in the heart following myocardial infarction (MI), commonly called a heart attack. MI is the endpoint of ischaemic heart disease (IHD). In Europe, the highest rates of IHD worldwide equal ~26.5 million patients. Standards of care interventions after MI have serious limitations in treatment efficacy (many patients are still at risk of developing heart failure) and patient safety. There is a clear medical need for new treatment solutions that prevent scar tissue formation and irreversible cardiac remodelling. Our robust preclinical dataset so far indicates that the ELR hydrogel has this promising functionality via multiple unique characteristics: it provides selective cell adhesion to the endocardium, providing a barrier to scar tissue formation; it offers high biospecificity to the ischaemic microenvironment, and it has an enhanced biodegradability, allowing for safe disintegration in the body. To facilitate endocardial delivery of the ELR hydrogel, we will develop a minimally invasive endocardial catheter in this project. Both components (hydrogel + catheter) will be advanced to the preparedness level for a first-in-human (FIH) validation study for the application as therapeutic intervention post-MI (to be performed after the project). In addition, we will develop the regulatory and IPR strategies in preparation for this clinical validation step. Considering the high societal impact of ischaemic heart disease (IHD) and MI, we will also develop a solid health economic evaluation of possible savings and patient benefits. ELR-SCAR will transform and fundamentally improve clinical practice, resulting in reducing the enormous burden that MI and its leading cause, IHD, place on society and the individual patient.