Where globally is innovation occurring and what factors – industry, regulatory, and academia – are helping developers get their products to market? Here, DDW Editor Reece Armstrong explores the global hubs of innovation for cell and gene therapies.
Since the approval of Kymirah in 2017, the cell and gene therapy sector has emerged as an exciting and innovative market, representing some of the most promising drugs the pharmaceutical industry has ever seen.
Globally, the pipeline for therapies in this sector has continued to grow over the years, and in 2021, there were just under 2,500 cell and gene therapies in some stage of clinical development.
The UK stands as one of the key markets for cell and gene therapies. In 2021, the Cell and Gene Therapy Catapult estimated that there 168 ongoing clinical trials for advanced therapy medicinal products (ATMPs) taking place – representing 9% of all global trials in the space. More so, the UK is now home to 29% of all European ATMP companies, making it a key location for global activity in the space.
There are a number of areas in the UK which are recognised as hubs for developers the sector. One of these is the Stevenage Bioscience Catalyst, which is home to companies and organisations including GSK, LifeArc, Cytiva, the Cell and Gene Therapy Manufacturing Catapult, and a growing number of start-ups.
In 2021, GSK expanded its cell processing capabilities for clinical trials at the CGT Stevenage Facility in a move which enhanced the company’s investment in the UK’s cell and gene manufacturing capabilities for clinical trials.
This is particularly important as a roundtable report1 from 2021 highlighted the challenges the UK’s clinical trial environment faces in relation to ATMPs. The report, which featured the likes of Bristol Myers Squibb, Autolus, NHS England and the University of Birmingham, stated that the “UK’s clinical trial environment risks being eroded due to the large costs involved, delays associated with site selection, contracting and patient enrolment, workforce capacity to support trials, and delays resuming trial activity post-Covid-19.”
The Stevenage Bioscience Catalyst is placed within the golden triangle of London, Oxford and Cambridge, and as such, it’s no surprise that there are over 4,000 employees working within the cluster and that affiliated companies have raised over £2.8 billion in funding.
According to the Cell and Gene Therapy Catapult, the campus acts as a “vital focal point for companies looking to develop and commercialise advanced therapy treatments, as well as attracting significant investment from pharmaceutical companies and venture capitals firms.”
Whilst it’s no surprise that many cell and gene therapy companies are clustered in and around London, developers are “struggling to find the sophisticated facilities needed for their core R&D and R&D-intensive manufacturing,” according to Neelam Patel, CEO of London cluster organisation, MedCity.
“In particular these SMEs wanted affordable workspace; better provision of wet laboratory and clean room space in London, available at higher specification but not necessarily at great scale; universities and hospitals to make their equipment and facilities more usefully available; and more endeavour to grow skills and talent,” Patel said.
One example the Cell and Gene Therapy Catapult regards as a benefit for developers in the UK is the effort the government puts in to support the industry.
“For example, the CGT Catapult receives funding from Innovate UK, the UK Government’s innovation champion, allowing it to collaborate with 25 universities and research institutes and 88 companies over the last year,” the organisation told DDW.
In 2021 a new Manufacturing Innovation Centre was opened in Braintree Essex, supported by funding of £100 million from the Department for Business, Energy and Industrial Strategy (BEIS). The Innovation Centre was funded in response to the Covid-19 outbreak and was an example of the government placing investment into a “a flexible facility to progress manufacturing innovation technologies for advanced therapies and support potential national requirements for manufacturing and preparedness for possible future pandemics,” according to the Cell and Gene Therapy Catapult.
Key advantages of the UK
“The research excellence of the UK’s academic institutions, and the expertise of the Cell and Gene Therapy Catapult enable the UK to compete globally. The UK also benefits from expedited pathways to development and adoption of novel medicines through the Innovative Licensing and Access Pathway, co-developed by the Medicines and Healthcare Products Regulatory Agency (MHRA), NICE and the Scottish Medicines Consortium (SMC). - Neelam Patel, CEO of London cluster organisation, MedCity.
“In the renal gene therapy field the most exciting research is definitely in the UK. The knowledge base and applied science is cutting edge and ahead of the field, although we anticipate there will be additional interest arising particularly in the US, as this is a very active area to watch. The UK and Ireland are seeing huge development in CGT entities and based on current construction projects ongoing, this looks set to continue,” – Richard Francis, CEO of Purespring Therapeutics
Unsurprisingly, the US is currently the biggest market in the world for cell and gene therapies. According to the Alliance for Regenerative Medicine’s (ARM’s) Regenerative Medicine: Disrupting the Status Quo report, the sector raised $17.6 billion in investment last year – a 53% jump in investments compared to the year before.
The sector was helped by a number of FDA approvals for therapies throughout the year, including Bristol Myers Squibb and bluebird bio’s CAR-T cell therapy for multiple myeloma; Enzyvant’s tissue therapy Rethymic for paediatric patients with congenital athymia, and Fosun Kite Biotechnology and Kite Pharma’s CAR-T Therpay Yescarta for follicular lymphoma being among those brought to market.
Unlike the UK, where cell and gene therapies are approved only after a rigorous price vs patient benefit assessment process, the United States’ privatised healthcare system coupled with its insurance market mean developers don’t have to worry as much about high prices.
According to Professor Dr Dolores J. Schendel Chief Executive Officer (CEO) and Chief Scientific Officer (CSO) of Medigene, this has resulted in an “alignment of incentives for the development of cell therapies in cancer”, and in the US, “high-cost, relatively experimental treatments can be funded through a healthcare system that puts innovative treatment at a premium. The clinical development landscape is broader, however, with significant effort in areas such as CAR T cell therapies in China and Europe, as well as in the US,” Professor Schendel said.
North Carolina has steadily emerged as the United States’ prominent location for biotech research. Indeed, the state’s Research Triangle Parks consists of 7,000 acres and houses more than 300 companies, making it America’s largest research park and the fourth largest life science hub in the US. The Research Triangle Park has been active in gene therapy research since 1993, when the University of North Carolina at Chapel Hill (UNC) opened the UNC School of Medicine Gene Therapy Center.
Interest in the park continues to grow. Last year, Pfizer opened a $68.5 million facility in Durham North Carolina to support the company’s gene therapy capabilities. The new facility represents a portion of the pharmaceutical company’s six-year project to build three gene therapy manufacturing facilities, totalling an estimated investment of $800 million.
The US’ strength in cell and gene therapies however lies in its spread of activity all across the country.
For example, contract development and manufacturing organisation (CDMO) Catalent has invested heavily in its cell and gene therapy capabilities in the US. The company’s latest $44.5m purchase of a commercial-scale cell therapy manufacturing facility in Princeton, New Jersey means Catalent now has six facilities in the US. Indeed, the spread of the CDMO’s facilities could be indicative of the company wanting to support a market that has steadily been rising. And with the FD expecting to approve 10-20 cell and gene therapies per year by 2025, the necessity for manufacturing is vital.
Perhaps the most well-established hub of cell and gene therapy activity in the US comes from Massachusetts, in particular the Boston and Cambridge areas. Thanks to a combination of academic institutes, high levels of investment, lab/biomanufacturing facilities, and steady job growth, Massachusetts has long remained the country’s leading hub for cell and gene therapies.
In 2020, biopharma companies based in Massachusetts raised a total of $5.8 billion in venture capital, according to the MassBio 2021 Industry Snapshot report2. This continued into the following year and by the first quarter, companies had already raised $4.3 billion. Indeed, in terms of funding offered by the National Institutes of Health (NIH), Massachusetts is second only to California.
The region is expected to continue growing too. BioMed Realty, a prominent life sciences real estate provider, acquired a 7.5-acre site at Assembly Square in Somerville, Massachusetts last year, which it will to turn into a campus for research, technology, and life science tenants.
Key comment US
“We can’t discount the terrific momentum happening on this front in the US. It is very interesting to see how the government steps in to bridge this funding gap through innovative programs like the Clinical Translational Sciences Awards Program which invests more than $550 M/ year specifically for translational medicine.” – Kristin Thompson, Chief Business Officer, eureKARE
Key areas according to experts
“Galway has a vibrant biomedical scientific community. NUI Galway is the major academic institution and has a strong focus on biomedical engineering and regenerative medicine. Galway is a global hub for medical device manufacturing and there are many spin outs in this space. While there is not yet the same strength and depth in cell & gene therapy (CGT), the University houses the Centre for Cell Manufacturing Ireland (CCMI), a fully licensed GMP facility for cell manufacturing. CCMI is an important local resource and runs a successful MSc in Cell Therapy Manufacturing, providing appropriately trained local talent, with many graduates going on to secure posts in companies engaged in CGT. There are two spin outs in the CGT space, Orbsen Therapeutics and ONK Therapeutics. HiTech Health is also involved in contract research in CGT.” - CEO of ONK Therapeutis Chris Nowers
“The gene therapy field has a strong presence in Finland, including both public and private institutions aimed at the use of different gene therapy approaches. For example, in Helsinki, 290 patients were treated under the Advanced Therapies Regulation (EC/1394/2007) which sought to determine rules for patient-by-patient use of gene therapy and cell products.
In this hospital exemption approach, the patients were receiving different forms of gene therapy (as oncolytic viruses) for advanced solid malignancies. The execution of the program outlined by the World Medical Association Declaration of Helsinki, brought abundant knowledge on the use of the approach and the data generated from the use of that after those 821 single treatments generated the foundation of at least two biotech companies. There is another Cell and Gene Therapy company, FinVector, in the city of Kuopio, home of Seppo Ylä-Herttuala whose work on the field for over 30 years is key to explaining the high amount of public and private activity in the area.” – CBO Aino Kalervo, and VP of Business Development Víctor Cervera-Carrascón of Tilt Bio.
Europe is emerging as one of the places with the most potential for cell and gene therapy research. The continent has 230 developers of ATMPs and last year managed to raise €3.3 billion in funding, according to the Alliance for Regenerative Medicine’s (ARM’s) Regenerative Medicine: Disrupting the Status Quo report.
Unfortunately a lack of funding compared to the US for example, could make it difficult for developers to translate research into market-ready therapies. An industry analysis from McKinsey & Company3 shows that between 2005 – 2018, Europe accounted for just 16% of the overall, global cell and gene therapy patent registrations.
The potential is there though. According to the same report, there is a clear unmet need in Europe for cell and gene therapies, meaning that those who can make it to market, will find a clear cohort of patients requiring their therapies.
For instance, McKinsey and Co estimate that for just four cell and gene therapy indications, the patient population is three times as large as an equivalent US cohort, at 385,000 patients.
As with every market, manufacturing will be key to delivering these therapies in a timely manner to patients. Bottlenecks in the production of Covid-19 vaccines highlighted the necessity for manufacturers to be based in-country, since globalised chains can often lead to lengthy delays and shortages.
Lonza is a good example of a company willing to invest in the technology needed to produce these therapies. The company has invested in a range of technologies to automate and scale-up the production of cell therapies. The company’s Cocoon system for instance automates the manufacture of cell therapies and can be used by hospitals as a way to bring the therapy closer to the patient.
As a whole though, Europe has work to do on this front however. McKinsey & Company states that two or the largest plants in the US will match Europe’s total manufacturing capacity for CGTs. For developers just starting out, this could impact where they choose to operate. Indeed, an example of this comes from bluebird bio, with the biopharma company reducing its EU operations for its beta thalassemia therapy Zynteglo last year.
So, work to do in Europe but there are signs of success. Take Novartis’ spinal muscular atrophy (SMA) gene therapy Zolgensma which managed to bring in $363 million in the first quarter of 2022, its growth being primarily driven by expanding access in Europe, the company states.
This positivity is reflected by Kristin Thompson, Chief Business Officer, eureKARE who says: “There is huge potential for European research when it comes to cell and gene therapy development as well synthetic biology approaches that are poised to boost the ingenuity of the industry. We still need more big players to fund basic research before it reaches the proof-of-concept stage to continue driving development here.”