TK-NEO is a DNA-based Neoantigen Cancer Vaccine (NCV), for use as therapeutic vaccination in patients with locally advanced or metastatic solid tumours. NCVs are a new form of precision medicine and are a perfect clinical approach for highly heterogeneous tumors in patients with metastatic disease. Takis has developed and patented a unique method for production of patient-specific NCVs based on a 6-week process, from sequencing the specific tumour DNA, synthesis of the right DNA sequence for the specific tumour, delivery through a specific Electroporation (EP) technology used under exclusive license. The solution was proven at pre-clinical stage to reduce to zero a human lung cancer in humanized mice in 60 days and to increase the efficacy several fold with respect to alternative RNA and DNA based NCVs in protecting relapse and boosting immune responses as required for the maintenance of long-term anti-tumor immunity. The strategy to reach the market for TK-NEO is to license the IP of TK-NEO to a large pharma company, after completion of clinical validation trials to demonstrate the applicability and safety of the approach: phase I clinical trials in melanoma are targeted during SME Instrument project, while implementation of a GMP manufacturing to carry out phase II clinical trials and the implementation of the trials will require additional 5M investment. The Total Available Market is constituted by melanoma patients who underwent surgery and first chemotherapeutic treatment, who are estimated in the order of 30.000 patients per year combining EU and US. The objectives of the feasibility study are: 1) to validate the feasibility and the authorization process for the release tests, 2) to confirm investment, cost and pricing for TK-NEO, 3) to define a MoU with VC or with the final client (pharma) for the co-financing of the clinical development of customized TK-NEO and for future licensing.

Despite the continuing development of new and more efficient treatments, cancer remains the second cause of premature death worldwide. Multi-faceted interdisciplinary research efforts in industry and academia on different aspects of cancer have provided a knowledge basis for the development of novel therapeutic approaches. Paul Ehrlich, Nobel laureate in Physiology of 1908, had the early vision that a compound could be made to selectively target a disease-causing organism or tumor. A toxin for the particular tissue could be delivered by an agent of selectivity. Such an ideal therapeutic agent would be a "magic bullet" that only kills the target cells. This ETN initiative with the title Magicbullet::reloaded refers to Ehrlich’s bold idea and builds on the previous experience of the highly successful ETN MAGICBULLET (2015-2018, grant agreement No. 642004). As a consequence of the outstanding results, the ETN Magicbullet::reloaded will expand the field of investigation from peptide-drug conjugates (PDCs) to small molecule-drug conjugates (SMDCs) with a special focus on drugs capable to stimulate tumor immune responses and overcome resistance to immuno-therapy. The consortium has been substantially expanded to perfectly address the needs of the new research direction. The planned ETN will design and synthesize an array of SMDCs (including PDCs), also targeting less investigated tumor antigens, investigate their pharmacokinetic behaviour, their implication on the immune system, as well as their tumor selectivity and antitumor activity. The consortium brings together interdisciplinary expert knowledge in Organic Chemistry, Peptide Chemistry, Medicinal Chemistry, Drug Discovery, Biochemistry, Pharmacology and Cell Biology. This high complementarity is required for the different scientific tasks in the development pipeline. Vice versa, the recruited ESRs will be exposed to a challenging research environment leading to a broad range of scientific competences to be acquired.

Since the end of 2019, the spread of COVID has deeply changed our lifestyle, resulting in historical events and decisions, such as the EU block of non-essential travel among countries (COMM (2020) 499), affecting the whole EU society economically and psychologically. However, as reported in the HERA target priorities, the persistence of the emergency status requires daily actions that tackle the spread of COVID. In this economical, societal and clinical context, the project MIRIA aims to develop wide-range-antimicrobial nanocoatings to be used in hospitals and other environments where cross-contamination and contagion risk are significant issues. In the wake of the covid outbreak, there has been large concern about infection spread of pathogens (i.e., bacteria, fungi, virus, and specifically SARS-CoV-2) via high traffic surfaces (i.e., medical equipment). State of the art and commercial products coating solutions that both target a range of mixed pathogens and different surfaces (e.g., glass, metal, textile) are unfortunately scant. MIRIA solutions aim to fill this void, impacting on EU health, both directly (by creating public safe environments) and indirectly (by reducing COVID spreading and decreasing ill-related work absences and psychological pathologies). A reduction of the work absence of at least 5% with respect to the 2020 value (15M in EU) is expected. MIRIA main challenging ambition is to develop nanocoatings with a 99.99% effectiveness against a wide range of pathogens, especially SARS-CoV-2. This will be based on a four pieces puzzle: the knowledge in anti-microbial materials, nanopowders, nanocoating and pilot plant conduction. These nanocoatings will be brought to pilot scale (TRL6) and, within 3 years after the end of the project, they are foreseen to enter the market (TRL9). The exploitation of MIRIA outputs deeply involves SMEs and the dissemination plan will follow a spill-over strategy in order to involve public and private stakeholders.

Major current hurdles for wide clinical use of AAV vectors are attributable primarily to: (i) host elimination by both immune and non-immune sequestering mechanisms – such neutralization by host antibody responses critically limits the possibility of repeated AAV delivery; (ii) AAVs are prevalent in the environment and hence a large proportion of the population carry AAV antibodies (up to 80%)– this pre-existing immunity renders AAV unable to infect target cells forcing substantial patient cohorts to be excluded from clinical trials. The current proposal is founded on compelling track record in the field and brings together a ‘best-with-best’ multidisciplinary team of international leading academic and EFPIA partners with complimentary expertise in gene therapy, immunology, chemistry, engineering, biotechnology, drug safety, viral vector production, regulatory and clinical trials. The overall goal is to analyse the currently available clinical data and then design preclinical and clinical studies to fill the knowledge gaps in advanced therapies development. Our main aims are to: 1) Develop improved model systems for predicting product immunogenicity in humans. This will be achieved by generating human and NHP 3D hepatic models; 2) Enhance our understanding of gene/cell therapy drug metabolism inside a host of cell types. The plan is to define metabolism of the therapeutic vector genome in different cell types to understand whether rates of degradation, episomal maintenance, or integration, and metabolic stress induced by AAV vector transgene expression vary from cell to cell. We will then adopt strategies to mitigate the loss of vector genomes and improve persistence; 3) Use diverse clinical expertise to establish the clinical factors around pre-existing immunity limiting patient access to advanced therapies therapy; 4) Engage regulators to ensure that the concepts and the data generated through this IMI programme will fill the gaps and support furture trials.