Public Funding for Cobra Biologics Limited

To develop, embed and exploit a robust and scalable manufacturing strategy and process for viral vectors.

The project aims to increase yields of Adeno-Associated Viral (AAV) vectors for human gene therapy studies through the improved purification processes and through the adoption of continuous chromatography approaches. The project aims to develop purification processes with improved yields and robustness that can be readily scaled to those required for in-market requirements at a reduced cost of goods than is currently being achieved for these vectors, addressing the critical needs to increase the supply and costs of these medicines.

Cell and gene therapy products are changing the lives of patients receiving treatment as part of clinical trials. Plasmid DNA represents a critical material required to enable the development and production of viral vectors to support both clinical trials and in-market supply for these innovative Gene Therapy products in order to treat patients. This project, lead by Cobra Biologics, aims to perform small scale feasibility studies utilising state of the art single-use technology and 3D printing to deliver critical process information requried to progress towards large scale plasmid DNA manufacturing in the UK. The project will support a larger investment by Cobra Biologics to enhance production capability, enabling retention of UK buisness and developing opportunities to move into new markets for clinical and commercial manufacture. Delivery of an enhanced manufacturing service offering will support existing and new customers' clinical and commercial ambitions, leading to more innovative Gene Therapy medicines reaching patients.

"Successful clinical trials of gene-therapies for a range of disease-indications have led to recent regulatory approvals for commercial use. Commercial-supply of viral vectors is limited by lack of affordable large-scale downstream manufacturing processes,which have several drawbacks in terms of process-related impurities, sample/potency loss and scalability_**,**_ with processing losses as high as 90%. Hence, improved scalable methods that guarantee viral vector yield and safety without compromising infectivity/functionality are urgently needed for high-efficiency gene-therapy manufacturing. VectorFlow brings innovative chemical-free viral-vector extraction/pre-filtration to gene-therapy production. This will overcome a key downstream bioprocessing bottleneck and play a pivotal role in increasing the yield and quality of viable viral-vectors in a scalable, low-cost manner, helping to increase the UK's commercial capacity to manufacture viral-vectors for the development of gene therapies to treat human disease. As a platform downstream bioprocessing technology, the VectorFlow platform can also be expanded to other advanced therapy and biomanufacturing applications to maximise commercial impact within the health and life sciences sector."

Gene therapy is an exciting new wave of medicine whereby therapeutic DNA is delivered into patients' cells to correct genetic disorders, use the body's own cells to make therapeutic proteins, or empower one's immune system to better fight cancer. Development of these advanced therapies is however still at a relatively early stage and current manufacturing processes remain prohibitively expensive. This expense is due in part to inefficient production and purification of the viral vectors that are primarily used to deliver genetic packages into patients' cells. The transformative promise of these therapies will not be realised if they cannot be mass manufactured to produce a therapy that is affordable to healthcare providers such as the NHS. Puridify has been working with several clinical stage companies over the last 3 years to develop a breakthrough purification technology based on nanofibres. This project will allow Puridify to demonstrate the ability to tailor this purification platform for gene therapy developers; providing the lower cost, more efficient and scalable manufacturing processes required to deliver affordable gene therapies to patients.

Cell and Gene therapy products are changing the lives of patients receiving treatment as part of early stage clinical trials. There is a clear need for Cobra Biologics, and the UK, to increase capacity and capability to provide a rapid approach for the production of viral vector material to support both clinical trials and commercial in-market supply. This project to support expansion at Cobra Biologics (Keele, UK) will give the UK world leading capabilities for clinical and commercial production of gene therapy viral vectors. The project will form part of a larger investment made by Cobra to enhance the development and the manufacturing the viral vector products in the UK. The resulting capacity and capability enhancements will support existing and new customers’ clinical and commercial ambitions, leading to more innovative Gene Therapy medicines reaching patients. Furthermore, it will add to and work with the existing infrastructure in the UK for the translation of these innovative medicines from academic interests to commercial reality. The outcome will be to establish Cobra Biologics, and the UK, as an internationally recognised centre of excellence in the field, and establish commercial viral vector manufacturing capability within the UK.

Cell and gene therapy products are changing the lives of patients receiving treatment as part of early stage clinical trials. There is a clear need for a flexible rapid approach to the production of viral vector material to support both clinical trials and in-market supply for these innovative Gene Therapy products in order to rapidly treat patients. This joint project between Cobra Biologics and Symbiosis Pharmaceutical Services aims give the UK world leading capabilities for clinical and commercial production of gene therapy viral vectors . The project will support a larger investment to enhance in the production capabilities of both companies, streamlining and de-risking the manufacturing the viral vector products through operational and commercial alignment. The resulting simplified and enhanced supply chain offering will support existing and new customers’ clinical and commercial ambitions, leading to more innovative Gene Therapy medicines reaching patients. The outcome will be to establish the partner companies, and the UK, as internationally recognised centres of excellence in the field and establish commercial viral vector manufacturing capabilities within the UK.

Gene therapy is becoming an increasingly important method of treatment for a variety of major unmet medical needs especially in the areas of inherited and rare diseases and diseases of the eye, conditions which are life threatening or significantly diminish quality of life. Adeno-associated virus (AAV) vectors are currently the delivery vehicle of choice for gene therapy treatments but the advancement these treatments into clinical trials is currently hampered by the time and expense required to manufacture these vectors. The proposed collaboration between Cobra and Touchlight will develop a fast and less expensive route to manufacture of AAV vectors, which will enable the acceleration of more potential products into clinical testing. This in turn will increase the chances of treatment being developed for a whole range of these currently intractable diseases.

Gene therapy is becoming an increasingly important method of treatment for a variety of major unmet medical needs especially in the areas of inherited and rare diseases and diseases of the eye, conditions which are life threatening or significantly diminish quality of life. Adeno-associated virus (AAV) vectors are currently the delivery vehicle of choice for gene therapy treatments but the advancement of these treatments into clinical trials is currently hampered by the lack of scalabilty needed to manufacture these vectors. The proposed collaboration between Cobra and CPI will develop the scientific understanding to allow scalable flexibile process to be developed to manufacture AAV vectors. This will enable the acceleration of more potential products into clinical testing and ultimately new medicinces. This in turn will increase the chances of treatment being developed for a whole range of these currently intractable diseases.

The project aims to develop a scalable bio-process for recombinant virus production. Adeno Associated Virus (AAV) is a safe and effective gene therapy vector and growing demand for therapy development cannot be met by current methods. Conventional technologies used for safe AAV production are inefficient and often highly toxic to the process. These problems limit scale-up opportunities. To develop an efficient and scalable bioprocess we will: FIRST, optimise viral production using a novel cell delivery reagent, and SECOND develop a novel method for AAV production using a so call “hollow fibre” bioreactors. The new system aims to achieve bulk GMP production of AAV at low cost.

A variety of micro-organisms including E. coli and S. cerevisiae (baker's yeast), are used in commercial bio-production processes to manufacture a number of products, ranging from high-value low-volume products, such bio-therapeutics (e.g. recombinant insulin), to mid-value products, (e.g. biocatalysts and specialised chemicals), to low-value bulk commodity products (e.g. succinic acid and biofuels). This project will seek to develop a robust clone optimsiation platform for the potential use and application in the above industrial sectors, and so would be of great benefit in a number of applied and fundamental areas of biological and biomedical R&D.

To develop innovative screening procedures and high productivity expression and fermentation processes for the production of novel therapeutics proteins in microbial systems.

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