Lessons learned from, and intervention efforts against SARS coronavirus (CoV), MERS-CoV and other emerging viruses provide invaluable information to accelerate the coordinated response against 2019 novel (2019 -n)CoV and the rapid development and manufacture of new diagnostic, prophylactic and therapeutic intervention strategies. A -promising approach to both patient management of emerging viral infections and to better preparedness and response to emerging epidemics is the use of monoclonal antibodies. MANCO aims at contributing to the rapid international response against 2019-nCoV, through preclinical and clinical evaluation of monoclonal antibodies against 2019-nCoV. MANCO will build on and leverage outstanding results from ongoing IMI-funded project #115760 ZAPI, including recently-discovered broadly cross-reactive H2L2 monoclonal antibodies against betacoronaviruses and an established pipeline for rapid identification of specific H2L2 monoclonal antibodies against 2019-nCoV; antibodies that will be selected to proceed to GMP manufacturing in high-yield CHO cell-lines. This project furthermore builds on ZAPI consortium’s experience and expertise for the development and establishment of relevant animal models, to ensure preclinical efficacy and safety, including absence of antibody-dependent enhancement, an issue seen to occur in some immunization studies against feline and SARS CoVs. Based on the generated preclinical data, MANCO will advance one lead (prophylactic and/or therapeutic) monoclonal antibody into a Phase I clinical trial that can be completed within two years of the start of the project, by leveraging clinical expertise, infrastructure and network currently in place for ongoing CEPI-funded projects on candidate vaccines against MERS-CoV (#INID1801) and Rift Valley Fever virus (#INLA1901), and H2020-funded projects on improved vaccines targeting the elderly (ISOLDA #848166) and on universal influenza vaccines, including in LMICs (ENDFLU #874650).

Several crucial steps in wood industries involve extreme operation conditions (such as high temperature and pH) to remove or modify recalcitrant lignin that protects cellulose in the plant cell wall. Enzymes can substitute harsh and energy-demanding chemical treatments for sustainable production of bio-based building blocks and products in wood biorefinery. However, wild enzymes, evolved to act under natural environmental conditions, cannot be integrated into the current industrial processes. WoodZymes partners already have available extremozymes resisting very high temperature and pH that will be further optimized to be used as biocatalysts in wood industries. Enzyme application will include the recovery of phenolic compounds from enzymatic breakdown of technical lignin, and of lignin and hemicellulose compounds from enzymatic delignification and bleaching of kraft pulp (also resulting in more sustainable final cellulosic pulp). Extremophilic enzymes will also be used to valorize the latter compounds as bio-based precursors for adhesives in the manufacture of medium-density fiberboards, and as components of insulation polyurethane foams (substituting fossil building blocks), as well as for obtaining renewable sugar-based papermaking additives. WoodZymes illustrates the potential of extremozymes in the global bio-based economy, contributing to the sustainability and competitiveness of cellulose and board/polyurethane manufacture (as suggested by techno-economic and environmental analyses), and establishing a direct link between the pulp and wood industrial sectors. The feasibility of these objectives is based on a consortium from four EU countries formed by: i) four world-leading companies of the above industrial sectors; ii) a highly-active biotech SME commercializing extremophilic enzymes; and iii) four reputed research institutes of the wood, cellulose, lignin and enzymes sectors, being able to demonstrate the extremozyme-based technology at the pilot scale.

Genetic skeletal diseases (GSDs) are an extremely diverse and complex group of rare genetic diseases that affect the development the skeleton. There are more than 450 unique and well-characterised phenotypes that range in severity from relatively mild to severe and lethal forms. Although individually rare, as a group of related genetic skeletal diseases, GSDs have an overall prevalence of at least 1 per 4,000 children, which extrapolates to a minimum of 225,000 people in the 27 member states and candidate countries of the EU. This burden in pain and disability leads to poor quality of life and high healthcare costs. Metaphyseal chondrodysplasia, type Schmid (MCDS) results from mutations in collagen X and affects <1/100,000 of the population. Mutant collagen X molecules miss-fold during synthesis and are retained within the endoplasmic reticulum (ER) of hypertrophic chondrocytes, thereby causing ER stress. Our extensive pre-clinical studies have shown that carbamazepine (CBZ) can alleviate ER stress caused by the expression of mutant collagen X and restore bone growth in a validated mouse model of MCDS. CBZ is an FDA approved drug used for the treatment of epilepsy and bipolar disorder and received orphan drug designation by the European Commission for the treatment of MCDS in September 2016. MCDS-Therapy was originally proposed as a 5-year collaborative project comprising world-renown clinical centres and SMEs to advance the repurposing of CBZ for MCDS (up to the Marketing Authorization Application dossier) through a multicentre and multinational (EU & AUS) clinical trial (Phase1, Phase2/3). MCDS-Therapy also encompasses biomarker development and health economics assessment studies to deliver, evidence to inform potential further studies of an innovative and affordable (CBZ already exists in a generic form) repurposed therapy for MCDS along with the diagnosis/prognosis tools to personalise the treatment strategy. The original proposal was for completion of this by 2022 however delays associated with the COVID pandemic have resulted in a need to extend the project with completion now forecast by May 2024.