Periodic Reporting for period 2 - SOLUPORE (Solupore® - Enabling the Manufacture of Affordable New Treatments to Cure Cancer) Reporting period: 2019-05-01 to 2020-04-30 Summary of the context and overall objectives of the project Cancer is a global challenge but there is positive news for cancer patients, particularly those for whom the current treatments such as chemotherapy are not effective. A new game-changing treatment, cell immunotherapy, has been delivering spectacular results and is an entirely new approach to treating cancer. It arms the body’s defenses into fighting the cancer cells from within. In summary, immune cells are removed from the patient’s blood and “engineered” in such a way that the cells identify and attack the disease when they are re-introduced to the patient. Whilst the performance of these new approaches has been outstanding in treating various types of cancer, the challenge is, they are not cost efficient. Swiss pharma giant, Novartis, made history by being the first company to get FDA approval (August 2017) to market its immunotherapy treatment drug, Kymriah™. However, the price tag for this single dose treatment of $475,000 makes it virtually inaccessible to wider patient communities. The predominant cost critical component lies in the very complex manufacturing process which uses virus based transfection to develop cancer-killing cells. In addition, the inherent complexities of treating sick patients using viruses, pharma companies must queue for as long as multiple years before the virus is available. When the virus becomes available, it can take up to 22 days to complete the cell engineering phase. Every day of the cell engineering process counts as the manufacturing takes place in expensive production facilities (typically costing €1,000 per hour). At Avectas, our highly-trained team of scientists has developed Solupore® an innovative, rapid and gentle cell engineering technology. The unique selling point of Solupore® is that it eliminates the need for viruses in the manufacturing process. This removes the significant bottleneck faced by the pharma companies in getting these transformative therapies to market AND it allows for a much simpler regulatory pathway enabling the availability of these lifesaving treatments for European patients. In addition, Solupore® reduces the manufacturing time from 22 days to 16 days. In comparison with today’s state of the art, Kymriah™, it is estimated (Reuters August 2017) that the current manufacturing costs of Kymriah™ is about €200k. Solupore® reduces these manufacturing costs to €115,000. This >40% reduction in the cost of goods combined with the elimination of the queueing time for virus production and the simpler regulatory pathway renders these life-changing therapies economically viable thus making them available to a wider patient community. Avectas has already commercialised a suite of products in the regenerative medicine field under the brand name Spraybase® and is now focused entirely on solving the manufacturing challenges in the immunotherapy space.The overall objectives for this project are to - To develop a scaled prototype of the Solupore technology. - To carry out a demonstration (pilot) study with a target customer- To sign a commercial partnership agreement with a cell immunotherapy company Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far The work completed to date has been focused on the development of the technology that will enable Solupore to be used in a Clinical setting. The main results of the overall project include:Key results in this reporting period include but are not limited to the following: 1. Closing two rounds of funding during the 2 year project and securing €26 million to support the commercialisation and scale up of our technology2. Signing a development and Licensing agreement with Onk Therapeutics 3. Partnership with CDMO CCRM 4. Collaboration with Vycellix 5. Joining the Karolinska Institute NK center of Excellence6. Recognized as one of the ‘15 Most Promising Start Ups’ of 2019 7. Design and development of the scaled SOLUPORE™ device needed to inform the development of the clinically relevant SOLUPORE™ process.8. Successful technology transfer to our CDMO partner, CCRM9. Validation of our technology through preclinical studies including the successful killing of tumour cells in an in-vivo animal study10. Key hires including Senior Director of Technical Operations, Director of Strategy and Finance, and an additional Project Manager 11. Agreements in place to carry out development studies with leading cell therapy companies using their proprietary cargos.12. Generation of ~60 leads for potential new customers.13. Avectas featured in several media and social media campaigns14. Design and development of the scaled Solupore® device needed to enable the development of the clinically relevant Solupore® process. Validating our design concepts with external expertise. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) On completion of this project, Avectas has demonstrated that its Solupore technology can be scaled up to successfully engineer cells efficiently. Crucially, the engineering step will be substantially simpler and shorter than that required for virus-mediated engineering. This will significantly reduce the cost of cell therapy manufacturing because processes will be shorter and simpler. In addition, the bottleneck currently in place regarding access to stocks of virus will be avoided.To date, we have demonstrated the scaling of our technology and shown that the cells are highly functional post the Solupore cell engineering process. We have completed the design of our scaled technology to align with good manufacturing processes (GMP) and regulatory standards whilst in parallel carrying out further functionality data to confirm the gentleness and effectiveness of our technology in comparison to other cell engineering methods. We also completed a successful animal study demonstrating the superiority of our technology and the cells capability post SOLUPORE to kill tumour cells. The ultimate goal was to tech transfer our Solupore technology to a 3rd party and sign a commercial deal with a customer for the use of the Solupore technology and both of these deliverables were met. It has been well documented that the cost of these life-saving cell therapies is a real challenge. Over the course of this past year, we have gained insight to even more challenges in this field. It has become even more evident how much the need for a non-viral delivery technology in the manufacture of cell therapies is now critical in not only bringing down the cost and time to manufacture these life-saving cell therapies but also to address the real challenge with cancer in treating solid tumours. We have learned in the past 12 months that a real focus of the industry is on addressing solid tumours and engineering cells to recognise and navigate the micro-tumour environment so that the cell therapy can have a therapeutic impact on cancer. We have learned from our potential partners that much more complex engineering will be required and they are looking for a non-viral delivery platform, like SOLUPORE™, to address these needs. In addition, it has come to the forefront of this industry that we need to focus on creating Allogeneic products (products made from healthy donors) rather than autologous therapies as this will have a major impact in the cost of manufacturing these life-saving therapies.