TIMNano is focused on Computer-Aided Drug Design (CADD) methods and bioinformatics to identify unique molecular fingerprints associated with gastrointestinal (GI) cancers using 3D-bioprinted patient-derived tumors. The project integrates nanotechnology, bioinformatics, immunology, and cancer biology to develop a novel platform utilizing immune cell-targeted biodegradable polymeric nanoparticles (NPs) aimed at enhancing therapeutic efficacy by inducing tumor destruction following optimal T- and B- cell activation. The Targeted Nano-immune Modulator (TNM) platform specifically targets local dendritic cells (DCs) to boost T cell-DC chemotaxis within lymph nodes, thus initiating a robust systemic anti-tumor immune response. This approach combines two complementary tumor-killing strategies. Unlike conventional cancer immunotherapies, TNM stimulates both cytotoxic T cells and powerful B cells, which differentiate into long-lived memory T and B cells, as well as antibody-secreting plasma cells capable of producing high-affinity antibodies. TIMNano aims to progress through the five stages of product development including Good Manufacturing Practice (GMP) production (with technology transfer and scale-up already accomplished), non-clinical efficacy, safety, and toxicokinetic studies, using industrial-scale products within the first 2 years. This will be followed by the subsequent filing of an Investigational Medicinal Product Dossier (IMPD) with the European Medicines Agency (EMA) and then a Phase 1/2 clinical trial will be initiated in the third year of the project. Funding and support from the European Innovation Council (EIC) will be critical in founding a spin-off company and securing additional investments from private investors, venture capital and investment banks, crucial to further complete the clinical development program by ourselves or upon merger and acquisition deal with a larger Pharma company.

While randomized controlled trials (RCTs) remain the mainstay in drug development, approval, and reimbursement, the potential of real world data (RWD) to contribute to the understanding of drug effects is increasingly realized. Evidence, based on RWD – real world evidence (RWE) - can contribute significantly to the evidence to support decision making throughout all phases of (clinical) drug development, as well as improve efficiency in design and conduct of clinical trial programs. The aim of this project is to develop, implement and establish evidentiary standards and methods to address the data and evidentiary needs of regulatory authorities and HTA bodies towards a more efficient use of RWD for the development, registration and assessment of medicinal products in Europe (More-EUROPA).

Drug repurposing can fill an important gap for rare disease patient groups with large unmet medical needs. In comparison to traditional drug development, drug repurposing reduces the time and costs for drug development, regulatory approval, and market authorization. Yet, we need to increase the efficiency of the drug repurposing pathway to provide broader access to new therapeutic modalities for larger groups of patients. SIMPATHIC’s main objective is to accelerate drug repurposing for rare neurological, neurometabolic and neuromuscular disorders. SIMPATHIC’s main accelerating innovation is the simultaneous drug development for groups of patients with different genetic diagnoses but overlapping neurological symptoms and molecular pathomechanisms. SIMPATHIC’s key outputs accelerating the drug repurposing pathway include: Standard operating procedures for culturing stem cell-derived neuronal cell models with proven relevance for clinical symptoms and amenable to high-throughput drug screens; New drug repurposing candidates with proven efficacy in advanced brain-on-a-chip and 3D brain organoid models, as demonstrated by reversal of molecular biomarker signatures and cellular readouts associated with clinical symptoms; Designs of innovative basket clinical trials to which patients with different disorders are recruited, utilizing and aggregating personalized clinical endpoints; A training module for patients and patient organizations to empower them as drivers of the drug repurposing pathway; Blueprints for intellectual property strategies, business models, regulatory dossiers and patient access strategies, developed in co-creation between all relevant stakeholders. SIMPATHIC’s proof-of-concept for the simultaneous development of repurposed drugs for multiple indications will show the path forward to development of personalized treatment opportunities for groups of rare disease patients in a cost- and time-efficient manner.

EU-OPENSCREEN (EU-OS), the distributed European Research Infrastructure for Chemical Biology and early drug discovery, provides world-class services in high-throughput compound screening and medicinal chemistry to users from academia and industry. As one of the largest open-access initiative globally, EU-OPENSCREEN plays an increasingly important role in facilitating early stage drug discovery in Europe. It recently integrated fragment-based drug discovery and chemoproteomics as two new services, but the increasing complexity of modern drug discovery projects requires an even more comprehensive portfolio and integration of emerging technologies. To ensure that EU-OS continues to offer a comprehensive suite of relevant services and support a growing user community to conduct forefront research, IMPULSE will develop, validate and integrate new services in AI/ML, new chemical modalities, and innovative disease-relevant cell models combined with CRISPR-Cas9/RNAi-based genetic screening. IMPULSE will work towards the implementation of common operational and data standards to increase data reproducibility and FAIRness. Bespoke outreach and training activities will raise awareness among key user groups of its new services and advance operational excellence and reproducibility in pre-clinical drug discovery. New models for pre-competitive drug discovery with industry or charities, and growing ERIC member community will reinforce the sustainability and accessibility of EU-OPENSCREEN.

Recent Nobel Prize-winning discoveries on circadian clock (CC) have laid the foundation for ground-breaking approaches to treat many diseases, including Alzheimer’s disease (AD). AD is a current public health priority. Amplifying the demographic burden of the rising numbers of patients is the low success rate of AD therapies. Given that CC genes regulating memory, sleep, and neurodegeneration have altered expression profiles in AD, CC has recently emerged as a viable therapeutic target for new effective drugs. However, how to develop them remains a fundamental challenge. The “Targeting Circadian Clock Dysfunction in Alzheimer’s Disease” Doctoral Network (TClock4AD) is proposed to create a new generation of researchers able to face such challenge by harnessing neurobiology, medicinal chemistry, pharmaceutical nanotechnology, neuroimmunology, big data, bioinformatics, and entrepreneurship. TClock4AD will exploit unique expertise and advanced technologies at 10 leading universities, 3 research centers, a hospital, 10 non-academic institutions including SMEs, a large pharma company, a Health industry association, and a patient organization across EU, UK, Israel, USA and China. TClock4AD will deliver double degrees to 15 doctoral candidates, with triple-i knowledge/skills, broad vision and a business-oriented mindset. Their research activities will be structured around 5 scientific themes to: (1) develop novel artificial intelligence-, proteolysis targeting chimeras- and multitarget-based strategies for new CC drug candidates (2) develop novel drug delivery nanotechnologies, which take into consideration CC (3) investigate innovative in vitro (stem-cells, 3D cultures) & in vivo (Drosophila), as well as organ-on-chip techniques, for preclinical validation of CC drugs (4) get insight into the molecular mechanisms underlying CC in AD and associated drug response in mice and C. elegans models (5) develop innovative biotech business model and exploitation strategies.