The Swedish biotech Anocca hosted, and sponsored, a workshop on Cell and Gene Therapy (CGT) at the Nordic Life Sciences Day Conference in Stockholm in September 2024 with panellists from NorthX Biologics, AstraZeneca, and CCRM Nordic. The Nordic ecosystem represents a great opportunity in this high-tech life sciences field, with the workshop looking at what’s being done to drive innovation and increase efficiency in the region.

It is envisaged that the CGT field can deliver great societal benefit and that it may increase the sustainability of healthcare systems, with, for instance, CAR-T approaches predicted to deliver a 15% reduction to overall healthcare costs. However, CGT products are still extremely expensive to produce, due to their complexity. A key area of discussion for the workshop was how to collaborate and reduce cost by increasing productivity.

AstraZeneca’s Elsa Abranches, Head of Cell Therapy Bioprocess Development and Manufacturing, outlined how AstraZeneca leverages its scale to increase productivity. The global pharma company moves from innovation to clinically relevant, and commercially viable, products, in oncology, autoimmune, chronic and rare disease. This creates substantial manufacturing needs, which they have started to build up in-house, with consistent reproducibility of work across sites being essential.

Anocca workshop NLSDays 2024

Building the ecosystem

And the ecosystem itself is essential too, as CCRM Nordic’s CEO Fredrik Wessberg set out. The Nordics have a strong healthcare system, coupled with great basic research, which is something to be proud of. There are a lot of stakeholders involved in developing a CGT product, and whilst the field is progressing and maturing, it is still relatively new. To address this, CCRM Nordic, supported by the Swedish Government, who sees the economic and employment potential, set up an initiative to support work within the ecosystem, connecting early academic groups and developing companies to focus on the commercialisation aspects. The complexity of dosage form makes things tricky for small developers, especially as they look to navigate the ecosystem.

Which is what NorthX Biologics, a biopharmaceutical CDMO that has been at the forefront of biologics manufacturing and process development since 1992, supports too. CEO Janet Hoogstraate explained how the company helps drug developers such as biotech companies reach their patients by supporting the manufacturing of advanced biologics, including CGTs. Collaboration is fundamental, as without that there’s stagnation, and the field does not advance. Progress arises from collaboration between functions within organisations and with external partners bringing the right competencies together to listen to each other across internal and external structures, to make a process amenable to GMP production, and to manufacture for patients in Sweden and beyond.

At AstraZeneca, as Elsa outlined, collaboration is part of the drug development philosophy, as it is simply not possible to do everything around the manufacturing of a complex cell therapy on your own. Creating, through collaboration, the right products with the right type of tech, will ensure there’s enough of the CGT ‘cake’ to go around and lift the value of the field. AstraZeneca has over a thousand collaborations, which are especially valuable in novel fields where there’s a need to go where the know-how is, and a lot of that is right here in the Nordics. There is a balance to be struck between innovation, adding IP, and the speed to take medicines to patients. And the need is to be faster, which collaboration accelerates.

Driving innovation

The ability for Nordic companies to thrive in the CGT space requires great innovation, developing, hiring and retaining great talent. Anocca’s CDO Mark Farmery gave a biotech’s perspective; as the company grew quickly, it moved into areas where it needed highly competent teams to work on extremely complex programs. The benefit of being in the talent magnet of the Nordic ecosystem meant that Anocca was able to build a world-class global team from 36 countries. The opportunity for the company, the country, and the Nordic region, is to continue to attract talent into this emerging field, train it, nurture it, and build the collective competences required to lead in cell therapy.  Almost all the senior scientists at Anocca today joined the company during the start-up phase and were recruited from the world-class Swedish academic ecosystem. They have continued to develop along with the company. Giving back to society is also important: Anocca has a long-running apprentice program (BioStart) that it runs in partnership with the local municipality and gives opportunities to younger people. Five of its technical staff have been hired from BioStart.

As Janet spotlighted, a breadth of specific talents are needed, with skilled hands and brains coming from all directions, including cell culture, quality control, automation, and more. Local educational systems need to adapt, and companies need to provide training positions, working closely together, including to develop course programs. In attracting international talent, higher level support from National Government is needed to make it easier to come to the Nordics and work and live here.

Elsa highlighted that the CGT network is already strong in the Nordics, providing like-minded people with complementary disciplines and skill sets. There are also world-class academic institutions, such as the Karolinska Institute ( Stockholm), Lund University (Lund) and Chalmers and Göteborg Universities (Gothenburg), to work with in developing CGTs. In the Nordics, a lot of work has already been done to set out the path from the beginning of development right through to the end, with common partners at different points on the path, such as the hospital ATMP centres, which can help change the paradigm from treating, to curing, diseases. Fredrik added that Nordic university hospitals are especially innovative, setting up Advanced Therapy Medicinal Products centres, actively wanting to work closely with industry to bridge hospitals and commercial players, to help advance products to patients in their centres. There is a willingness to work together.

Anocca workshop NLSDays 2024

Why standardisation should come as standard

The workshop also discussed the development of the actual products, where standardisation is the key. But that covers a bucket full of different terms, as Elsa explained. It can be overwhelming, as there is wide variety of ‘standards’ depending on the medicine, the production method, and the mechanism of its delivery. The process needs breaking down into smaller puzzle pieces, covering everything from reagents and raw materials, through to production and quality control methods. On the process side, the impact on products characteristics (efficacy and safety) when moving from traditional small scale and open systems (such as T-flasks) to closed scaled up or scaled out systems, needs to be evaluated. These choices will also impact the downstream processing: if you cannot isolate cells and keep them healthy, you’re going to have a real challenge. How do you even know the cells are healthy? What’s your process to qualify the product? Quality assays need designing from the beginning, so that comparability testing can be performed and confidence on delivering a safe and effective product to patients is maintained. Not everyone can, or should, work on all these challenges, so collaboration and interaction, including with regulators, becomes critical, so that all the pieces of the puzzle can be put together in and efficient way.

Janet added that there’s a similarity between biologics and CGT. If you think of the final product, you can think backwards on how to characterise it at various steps, and then build in the process controls to provide data for decision making. This all helps with the standardisation process, and if you can do it in real time, with minimal volumes, so much the better, as yields can be low, and you’ll need as much consistent product at the end as you can manufacture.

Mark commented that for Anocca’s product development, the company uses non-viral gene editing in an ex vivo manufacturing approach to produce product at scale. Across this process pathway Anocca had standardised as much as possible, beginning with the end in mind. Anocca has the largest GMP cell therapy production facility in the Nordics, set up to deliver the company with the materials it needs for clinical trials.

Picking up on the importance of knowing what you have, Fredrik highlighted that analytical systems can lag. But it costs nothing to reach out to organisations and see what tech might be shared to help scale the analytical mountain. Regulatory bodies also are now much more willing to have a discussion, so worth making contact there early too. Janet added that regulators can provide key guidance during defining your process and product. A practical example could be a decision on what sort of plastic coatings to use in cell culture systems, and how to analyse for their absence when looking at purity of the final product. Knowing the right assay to use early on, through discussion in the ecosystem, can ensure you don’t find you have missed something important at the end.

The closing message was the Nordic CGT ecosystem is open and willing to connect and share knowledge as these novel technologies are developed. There’s a huge Nordic network of people going through the same process development challenges, so reach out, share your successes, and your failures too, as that’s the surest way to cross the stepping stones to success with a view to helping patients by curing the hardest to treat diseases.