Through the development of the WT1 technology Cell and Gene Therapy Catapult paved the way for the advancement of the industry as well as developing in house capabilities.
On 20 June 2017, we announced the sale of Catapult Therapy TCR Limited to Cell Medica, a cellular immunotherapy company based in the UK. Catapult Therapy TCR was set up to develop the WT1 technology which originated at University College London through the research of Professors Hans Stauss and Emma Morris. Cell Medica will continue the development of the underlying technology at the CGT Catapult manufacturing centre and in collaboration with UCL. This project started in 2014 when CGT Catapult, UCL and Imperial College London began a collaboration to accelerate the development of the novel cell therapy for the treatment of acute myeloid leukaemia.
At the beginning of this project the cell therapy industry was in its infancy and almost unrecognisable to the industry we see today. While the promise of cell therapies had been seen in the lab, very few had been translated from the research phase through the regulatory process and into clinical trials. CGT Catapult saw the promise of this gene-modified T-cell therapy and formed Catapult Therapy TCR Limited to expedite the development of this exciting technology.
Through this venture, CGT Catapult not only progressed this potentially lifesaving therapy, but also achieved other outcomes for the benefit of CGT Catapult and the wider industry.
Process development outcomes
The product in question was a gene-modified T-cell receptor therapy targeting WT1-overexpressing cells. The WT1 antigen is expressed in both blood based and solid tumours, making it a good target for cancer treatment. The therapy involved ex-vivo modification by gene therapy of the patient’s T cells, so that they recognise and kill WT1-expressing malignant cells when infused back into the body.
When CGT Catapult initiated the collaboration with Imperial and UCL, the manufacturing process to generate these cells was extremely labour intensive, including 978 manipulations 72% of which were needle-based. This restricted the rate at which the product could be manufactured and resulted in a high cost of goods, a barrier to the adoption of these novel therapies at the time. During the first stage of development the industrialisation team at CGT Catapult improved the process to reduce the cost of goods by 60% and increase throughput by 39%. Subsequent stages of development are expected to build on these improvements.
|Manipulation type||Manual process||First improvements||Second improvements|
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|Tube weld and seal||64||7||399||75||107||57|
The project also enabled CGT Catapult to develop new process and analytical technologies that can now be utilised by the cell and gene therapy industry.
Regulatory and clinical operations outcomes
This project demonstrated that cell and gene therapy trials can be successfully carried out in the UK and expanded to the rest of Europe. At the beginning of this project, regulatory and marketing authorisation requirements were not broadly understood for cell and gene therapies. The process of delivering these modified cells to patients involved liaising with regulatory authorities on the progression of clinical trials through the approval process for gene modified organisms, as well as multi-country activity in the UK, Germany, Belgium and France. Though this process we actively helped demonstrate the appropriate regulatory pathways with both the European Medicines Agency (EMA) and the UK’s Medicines and Healthcare products Regulatory Agency (MHRA).
The phase I/II trial has been conducted by Catapult Therapy TCR, with Professor Emma Morris as Chief Investigator, using the WT-1 T cell therapy to target acute myeloid leukaemia (AML, The interim review of the clinical data has been positive and the project has shown that existing regulation can be applied successfully to cell and gene therapy products and has paved the way for other clinical trials of cell and gene therapies.
In 2015 the manufacturing contract for the WT1 therapy was awarded to Manchester-based company, Cellular Therapeutics Limited (CTL). Through CTL’s support of the Phase I and II trials, it has been demonstrated that products can be successfully transferred to UK manufacturers as well as the feasibility of UK commercially GMP manufactured products being shipped from and to Europe. The experience gained by CTL puts them in a strong position to win further business in the thriving T-cell therapy sector.
Further, the manufacture of this product has exposed and mitigated challenges in managing an effective supply chain for modified T cells.
Cell Medica are in the ideal position to continue the development and ultimately the commercialisation of the WT1 therapy to ensure it reaches the patients who can benefit from it. CGT Catapult will continue to work with Cell Medica and UCL on clinical and process development in the development of a second-generation product and in developing manufacturing systems at the CGT Catapult manufacturing centre in Stevenage.
We are looking forward to an important collaboration with CGT Catapult to initiate manufacturing at the Stevenage GMP facility where we will work together on scale-up strategies for commercial production.
This project reflects the clear mission of CGT Catapult – translating work from UK academia and advancing novel cell therapies to enable further investment and clinical development. The success of CGT Catapult’s work yields positive returns not only for patients, but also for the companies, investors and researchers who represent the future of the UK cell and gene therapy industry.