To introduce advanced computational techniques and develop a new platform to accelerate discovery of novel and effective gene therapies to treat currently incurable diseases. To deliver new treatments faster and in a cost-effective manner.

Freeline is requesting a change of scope to project number 104902 – “Using AAV gene therapy to treat rare kidney disease” that would redistribute funds to enable critical safety risk mitigation experiments to be performed within the timelines of the grant.

"The rapid development of Gene Therapy Medicinal Products (GTMPs) requires new manufacturing processes and facilities. Gyroscope Therapeutics Ltd and Freeline Therapeutics Ltd are UK-based SMEs developing gene therapies for different indications but which are both delivered via adeno-associated viral (AAV) vectors. Gyroscope and Freeline intend to co-develop an innovative, suspension-based viral vector manufacturing process, which will provide a shared platform for the manufacture of each company's GTMP products. The major challenge facing commercialisation of gene therapies is the manufacture and supply of products at a commercial scale. Gyroscope and Freeline will develop a proprietary, serum-free, scalable, suspension based manufacturing platform, which will improve product quality, safety, robustness and reduce the costs of goods at commercial scale. Working together with process development specialists at partner organisations the Centre for Clinical Biotechnology (CBC) and the Centre for Process Innovation (CPI), Gyroscope and Freeline will: 1. Establish ways to reduce risk of genetic instability of plasmid starting materials in an integrated approach; 2. Establish a proprietary animal component free and 'chemically defined' suspension cell culture manufacturing process which is scalable and which minimises product heterogeneity while maximising safety, quality and yield; 3. Supply batches of material to confirm comparability of product made using suspension platform material to that produced by current adherent cell culture platforms and so enable process changes to be implemented 4. Generate data to facilitate technology transfer of the developed process at a representative scale to GMP manufacturing facilities for subsequent qualification as a GMP manufacturing process. Ultimately, a successful outcome will address a significant manufacturing challenge for GTMPs, strengthen the UK position as a leader in scientific innovation, offer scope for investment and employment into UK Pharmaceutical manufacturing and bring healthcare benefits to patients."

"The rapid development of novel treatments called Advanced Therapies, such as cell therapies and gene therapies have required new manufacturing facilities and technologies worldwide. Manufacturing of gene therapy viral vectors for human use requires specialised high-quality manufacturing facilities and there is currently insufficient such capacity in the UK and globally. Reliance on overseas CMOs presents challenges in terms of both capacity and lack of flexibility. The Cell and Gene Therapy Catapult has recently opened its manufacturing centre in Stevenage offering an innovative cost-sharing model for small gene therapy companies, such as Freeline, to establish an internal manufacturing capability for their drug substance. The aim of this project is to further develop the UK based supply chain by establishing an integrated, lean partnership between CGTC-MC and Symbiosis, a UK company that specialises in drug product manufacture (fill finish) for clinical sterile drug products and small volume, niche commercial sterile products. This collaboration, between Freeline, CGTC-MC and Symbiosis aims to establish an efficient, secure supply chain to reliably deliver viral vector gene therapy drug products to clinical trials. This will speed the pace at which new gene therapies can be made available to patients. The clinical supply chain delivered by this project will provide a foundation on which to deliver commercial supplies of gene therapy products in the future, thus establishing a secure UK-embedded commercial supply chain. The three UK collaborators will work together to create the new processes and analytical technologies to achieve rapid and seamless transfer of materials between the partners whilst maintaining quality. The project will include alignment of respective quality systems and processes as well as investment in internalising critical quality control tests and establishing new novel rapid methods. Internalising QC will bring about process efficiencies, adding to the security of the supply chain. The new integrated operating model will be demonstrated with the manufacture and supply of a GMP batch of a Freeline gene therapy drug product to a Phase I/II clinical trial for the treatment of a lysosomal storage disorder. The resulting supply chain and technologies will be translated into standard processes which can be offered by CGT-MC and Symbiosis to other future viral vector customers, thus significantly enhancing the UK viral vector manufacturing capability"

The rapid development of novel treatments called Advanced Therapies, such as gene therapies that provide the correct proteins, have required new, manufacturing facilities worldwide. Freeline Therapeutics Limited (Freeline), a UK company that makes gene therapies to treat bleeding and metabolic disorders, will work with the Cell and Gene Therapy Catapult (CGTC) to set up Freeline's UK manufacturing site at the CGTC, at the same time establishing an operating model for virus processes applicable to other gene therapies companies joining the CGTC. This has many advantages: 1. It will help Freeline to make new treatments more quickly so that patients can be treated sooner, the first of these will be for Fabry disease, a rare disease affecting 2.56 in 10,000 people, with diagnosed prevalent cases expected to double in the 7 major markets (GlobalData epidemiologist). 2. Removing Freeline’s reliance on availability of severely restricted European CMO capacity (few capable of clinical & commercial supply), gaining control of its manufacture to support the full product lifecycle. 3. Freeline will be able to make its own approved new therapies in the UK for delivery to patients worldwide, the first of these is anticipated to be for haemophila B a rare bleeding disorder affecting 1 in 30,000 males worldwide. 4. Establishing CGTC as a centre of excellence for large scale manufacture of viral vectors and cell therapies, for UK & International companies to its quality managed, self-contained units, creating employment opportunities for the skilled UK workforce.