Periodic Reporting for period 1 - ReSpire (Respirable Advanced Therapeutics for Cystic Fibrosis & other Lung Diseases) Período documentado: 2019-02-01 hasta 2019-07-31 Resumen del contexto y de los objetivos generales del proyecto OmniSpirant is an Irish company with the vision of providing its unique Cystic Fibrosis (CF) inhaled exosome gene therapy solution to the European and global healthcare sector to combat the respiratory dysfunction caused by CF, a genetic disorder (caused by mutations in the CFTR gene) affecting the lungs of about 80,000 people worldwide. Our solution is a platform technology that is also applicable to other serious lung diseases such as lung cancer and COPD. Current CF therapies involve chronic use of suppressive antibiotic therapy allied with use of mucolytics to reduce the viscous secretions and anti-inflammatory agents, bronchodilators and inhaled steroids to ease breathing plus physiotherapy to actively help removal of mucus. Some patients may also benefit by adding in new CFTR modulator drugs. CF gene therapy to replace the mutated CFTR gene with a healthy copy would be an ideal treatment, the concept was proven over 20 years ago in simple cell models but has failed to show clinical study benefits to date. The problem is that the thick mucus in the lungs of CF sufferers is a barrier that traps the carriers used to deliver inhaled CFTR gene therapies such as nanoparticles and viral vectors. These trapped gene therapy carriers are mostly cleared from the mucus layer before they can penetrate to reach the underlying cells and introduce their genetic cargo. Clinical trials testing viral gene vectors (such as adenovirus and adeno-associated viruses) and non-viral vectors (liposomes) for inhaled CF gene therapy have failed to provide clinically significant benefits due to inefficient gene transfer to the target lung cells and generation of therapy-inactivating host immune responses. Furthermore, these gene transfer vectors are immunogenic and elicit undesirable inflammatory responses which can reduce lung function. Our solution uses inhaled stem cell exosomes to deliver a working copy of the defective CFTR gene, which can efficiently penetrate the protective mucus barrier and efficiently enter the underlying target cells of the airways. These nano-sized stem cell exosomes are regenerative and anti-inflammatory with the potential to reverse disease damage in the lung, and can be tailored via genetic modification of the parent stem cells to create ideal inhaled gene therapy vectors with the potential to treat virtually any respiratory disease have shown 100% mucus penetration and target cell uptake of our surface engineered exosomes in the gold standard in vitro model, which is game changing compared to the state of the art viral vectors which can achieve only 30% at best.Conclusion of the action: During this Phase 1 Project, OmniSpirant have developed an in-depth understanding of the global market opportunity and assessed the likely criteria demanded by the market, industry, regulatory and healthcare provision systems. The economic viability of the product has been confirmed and a business plan for exploiting the innovation has been constructed. Important partners from industry, academia and the research community have been engaged and some strategic partnerships have been formed. The requirements of these and potential partners have been defined, providing explicit targets for OmniSpirant to achieve. We have also engaged with many investors and reached the final of the European Health Catapult Competition in the Biotech category (to be held in December). A detailed product development plan has been developed and costed, which will fully prepare the product to enter clinical trials. Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha During this project we have carried out the following tasks, carrying out: market, technical and regulatory feasibility studies; an economic viability study and a business innovation plan. This included a full, costed product development plan leading to complete readiness of OmniSpirant CF product to enter Phase I/II clinical trials. Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha) Our competitive advantage and Unique Selling Points lower current effectiveness barriers and make the OmniSpirant exosome technology the only therapeutic delivery method that could provide a truly effective treatment for CF, thus improving both survival rates the quality of life of CF suffers. Importantly, the quality of life for CF patients will increase to point where they are able to work. The OmniSpirant system will, over time, be regarded as an essential weapon in the armoury of health systems in the battle against other serious respiratory conditions affecting major patient populations such as lung cancer and COPD, globally. In the case of inflammatory lung diseases such as CF and COPD, the lung is extensively damaged in the vast majority of cases (e.g. inflammation, fibrosis, loss of structural integrity of alveolar gas exchange regions and severely impaired lung function are present) the innovative therapeutic approach of OmniSpirant is intended to repair this damage via the regenerative effects of stem cell exosomes combined with gene therapy to modify the underlying causes of the disease. Cross section of normal airway and an airway affected by cystic fibrosis
