The Challenge
Autolus, a CAR-T cell therapy company with a vision to deliver life-changing advanced autologous T cell therapies to cancer patients, had a forward-thinking development strategy and a powerful T cell programming technology platform in 2016, and needed to supply its cutting-edge lead therapeutic candidate to more patients. This required Autolus to transition from an early-stage research company to a robust clinical-stage development company with the capability to manufacture its autologous cell therapy candidates in an environment that meets regulatory Good Manufacturing Practice (GMP) requirements.
Significant barriers must be overcome to successfully achieve this transition, as the requisite facilities and infrastructure are expensive to build, difficult to operationalise and require a highly skilled workforce.
The Collaboration
In 2017, Autolus and CGT Catapult received Innovate UK funding to collaborate on developing a commercially scalable manufacturing process for CAR-T products. Autolus contributed expert knowledge and capability in advanced T-cell bioprocessing, with CGT Catapult providing input on design and optimisation of the analytical platforms needed for process characterisation.
In 2018, CGT Catapult opened the Stevenage Manufacturing Innovation Centre (MIC) to support cell and gene therapy developers in scaling their GMP manufacturing operations. Autolus, as pioneers in cell therapy development, were the first company to collaborate with CGT Catapult at the Stevenage MIC. They helped to shape the model that has been so successful in supporting multiple developers to establish independent high throughput GMP autologous cell therapy manufacturing operations. Under the collaboration they occupied one of the first six manufacturing modules within the MIC and transferred their manufacturing process into their manufacturing module.
Autolus worked closely with CGT Catapult to establish the fundamental GMP processes required to manufacture the autologous CAR-T product for their clinical programmes. As well as providing Autolus with a regulatory-compliant manufacturing facility, GMP warehousing, optimisation of cleanroom layout and qualification, validated digital infrastructure and other essentials, this collaboration also allowed CGT Catapult to prove and evolve the model of the MIC, and facilitated licensure of the centre by the Medicines and Healthcare products Regulatory Agency (MHRA).
The collaboration grew to encompass Autolus occupying three MIC modules, allowing the company to scale their operations to match increasing demand for clinical trial material. Additional technology transfers were also undertaken to manufacture critical viral vector starting material for Autolus’s autologous cell therapy candidates and to expand the scale at which they could manufacture them. Autolus also recruited and trained a highly skilled manufacturing team and collaborated with CGT Catapult on an Innovate UK-funded project to establish highly productive, higher-throughput supply chains, utilising component-kitting systems with a third-party logistics provider, to enable more clinical patients to access these transformative therapies.
Autolus’ journey from an early-stage research company to a robust clinical-stage development company has been a phenomenal success story, and they have now established their own commercial-scale manufacturing operations within the cell and gene therapy cluster centred on Stevenage - recognised as one of the largest clusters in Europe and attracts significant inward investment. The £120m redevelopment in the town centre of Stevenage, built on a 70,000ft2 site, will be the UK’s first purpose-built CAR-T manufacturing facility. It is expected to bring 350 jobs to the area and provide Autolus with the initial capacity to manufacture 2000 batches of CAR-T therapy per year with the flexibility to expand as required.
This journey to becoming a clinical-stage development company was facilitated by the UK’s supportive ecosystem at the appropriate time in the company’s development: Leveraging Innovate UK grant funding to support the advancement of their cell therapy; manufacture was de-risked with early batches of cell therapy from the Royal Free Hospital, London; contract development and manufacturing organisation (CDMO) services were leveraged for viral vector and plasmids as appropriate; while independent manufacture was established in our Stevenage MIC, a facility with a commercial license that offered the clear route to allow growth in line with clinical demand.
Where are they now?
Autolus continues to pioneer the development of autologous T cell therapies. In recognition of the need for suitable commercial scale manufacturing facilities, Autolus worked with Reef Group and Merit Holdings to design and construct the UK’s first purpose-built commercial scale CAR-T manufacturing facility. Learnings from the design and construction of CGT Catapult’s Stevenage MIC, helped Merit to deliver a leading-edge modular facility in record time, based on Autolus’ in-depth knowledge of optimised process flows and facility requirements.
Hertfordshire County Council, the Hertfordshire Local Enterprise Partnership and Stevenage Borough Council have long supported the vision of CGT Catapult and many other collaborative partners of building a world-class cell and gene therapy sector, and have been key collaborative partners in the development of a global centre in Stevenage, including progressing the planning permissions rapidly. The Autolus facility, positioned within a town centre location to facilitate regeneration and in close proximity to their clinical manufacturing operations at the CGT Catapult Stevenage MIC, was constructed in record-breaking time - just 17 months after conception.
Autolus expects to file a Biologics License Application (BLA) for its lead CAR T-cell therapy at the end of 2023.