January 15, 2012 (Vol. 32, No. 2)
Sue Pearson Ph.D. Freelance Writer GEN
2011 was a tough year for the U.K.’s biotech industry, especially with several big pharma closures. The good news is that there is new growth in development and manufacturing of biotherapeutics.
Pfizer and Novartis may have shut down their U.K. sites, but as the saying goes, when one door closes another opens. GlaxoSmithKline is evaluating putting a significant biomanufacturing site in the U.K., and Lonza, Fujifilm Diosynth Biotechnologies, and Eden BioDesign are all increasing their capacity in the U.K.
The recent “bioProcessUK” conference brought a cross section of the U.K.’s biotech industry together to reveal even more hope for the future. “This year we estimate at least 500 new jobs have been created in bioprocessing,” stated Mark Bustard, Ph.D., head of bioProcessUK at the HealthTech and Medicines Knowledge Transfer Network, a U.K. government initiative.
“Our current government is recognizing that we have to encourage new types of industry. So it’s investing in bioprocess manufacturing with Technology Strategy Board funding of £8.5 million to fund regenerative medicine projects alone.”
The U.K. is also showing a strong pipeline for biopharmaceutical development. According to Dr. Bustard, the U.K. has at least 205 innovative medicines in development with companies such as Reneuron making good progress with its cellular therapy to treat stroke patients.
Intent on shepherding more biopharma companies to market and keeping them growing, Prime Minister David Cameron recently unveiled a “Strategy for U.K. Life Sciences”. The strategy calls for the U.K. to:
- Launch a £180 million ($278.6 million) Biomedical Catalyst Fund to be overseen by the Medical Research Council (MRC) and TSB. The fund is designed to help startups navigate the “valley of death” between the development of a new drug in the laboratory and the point when it comes to market.
- Spend £130 million ($201.2 million) toward personalized or “stratified” medicine research.
- Create a £50 million ($77.4 million) cell therapy technology innovation center to exploit the promising technology commercially, by spending £10 million ($15.5 million) a year over each of the next five years.
For a full analysis of this strategy, click here.
Having bioprocessing capacity is vital to being able to keep pace with demand for antibody therapies—and, in the future, cell therapies.
“The total global demand for monoclonal antibody products was approximately 8 metric tons in 2010, which we expect to grow to approximately 13.4 metric tons by 2016,” said Howard L. Levine, Ph.D., president and principal consultant at BioProcess Technology Consultants.
“Demand for the top five selling monoclonal antibody products will range from one to two metric tons each, helping to drive an approximately twofold increase in demand for cell culture capacity between now and 2016.
“Globally, the industry-wide utilization of cell culture manufacturing capacity will increase from around 50 percent to nearly 64 percent. However, with approximately 75 percent of the total global bioprocessing capacity controlled by ten companies, those companies without it may find access to it difficult in the future, resulting in the need for additional manufacturing capacity.”
Dr. Levine believes that the development of newer, more potent product types such as antibody drug conjugates (ADCs), which require less antibody concentration per dose, may lower the demand for mammalian cell culture capacity, as these products will require smaller facilities to produce.
Strength in Antibody Technology
One of the U.K.’s strengths is in delivering technology to improve development and manufacturing of antibody therapeutics. The U.K. has capacity and specialist expertise in ADCs, and it’s where some U.S. pharmas and biotechs, including ADC heavyweight Seattle Genetics, are actively choosing to have their antibody conjugation processes performed.
Two companies that illustrated this technical strength at the conference were Oxford BioTherapeutics and Kymab.
Harry Lamble, Ph.D., director of business development at Oxford BioTherapeutics, presented his company’s use of its Oxford Genome Anatomy Project (OGAP®) database, a discovery platform that integrates proteomic data on three-quarters of the human proteome, with genetic and clinical information across 50 different human tissue types and 60 diseases including 25 forms of cancer.
“Using the information in our OGAP database in collaboration with a number of antibody technology firms including BMS, Amgen, and Alere, we have generated novel antibodies to treat cancer,” said Dr. Lamble.
“A number of our lead programs are currently in preclinical development, including ADCs to treat gastric, lung, and other cancers.” Dr. Lamble showed mouse Xenograft data for two programs, which demonstrated that a single 2 mg/kg dose arrested tumor growth during the period of observation in established disease models.
“We view ADCs as transformational and recently entered a collaboration with Seattle Genetics to develop ADCs. Seattle’s recent successes with its ADC—Adcetris for treating Hodgkin lymphoma—indicates that this class of drug could be highly efficacious for treating cancers,” Dr. Lamble concluded.
Tom Shepherd, Ph.D., chief business officer at Kymab, a spin-out from The Wellcome Trust Sanger Institute in Cambridge, presented interesting information on his firm’s transgenic mouse platform, Kymouse™. According to Dr. Shepherd, of the nine fully humanized monoclonal antibodies marketed as therapies, seven are derived from transgenic mouse platforms.
“The first-generation transgenic mice for antibody production in the 1990s carried human genes coding a proportion of the variable and constant region of antibodies randomly integrated into the genome, and these mice could make human monoclonal antibodies,” Dr. Shepherd commented. “However, they suffered from a suboptimal immune response due to deficient signaling of the human constant region, and only carried a proportion of the human genes.”
Subsequently, Regeneron learned from Abgenix and Medarex and kept the mouse constant region, added more human gene diversity, and ensured the gene integration was in the right place, but the lambda light chain was still missing. Therefore, these earlier mice don’t provide the full spectrum of functional human immunoglobin diversity.
“We developed Kymouse because we felt there was a place for improved transgenic mice. Our mouse will contain over 2.5-megabases of human genes in its genome with the entire functional human immunoglobin V, D, and J gene repertoire, including the human heavy kappa and lambda chain genes, which we believe will result in the production of improved monoclonal antibodies.”
In addition to Kymouse, Kymab is also making a new ES cell bank from Kymouse, which it will use to make knock-out and knock-in mice for specific drug targets.
“It would normally take years to cross a knock-out mouse with a fully human antibody transgenic mouse; we can do this in a fraction of the time in vitro using the new ES bank,” Dr. Shepherd claimed. “The Kymouse KO version will eliminate immune tolerance to highly conserved targets, previously an issue with mouse immunization, and Kymouse KI will allow preclinical in vivo testing of the antibodies produced by Kymouse.”
Stem Cell Therapeutics
Another area where the U.K. is beginning to gain expertise is in the production of stem cells to GMP standards, with facilities being developed at a number of sites. These include the U.K. Stem Cell Bank at the National Institute for Biological Standards and Control (NIBSC), an operating center of the Health Protection Agency, and Roslin Cells.
“We have a newly equipped, state-of-the-art GMP facility, which with the backing and expertise of NIBSC means we can support the development of clinical-grade cells,” said Glyn Stacey, director for the U.K. Stem Cell Bank. “This is no small feat, as many underestimate how much time is required to get a fully qualified facility up and running.”
Aidan Courtney, CEO of Roslin Cells, added, “We were initially set up to provide undifferentiated clinical-grade cell lines, but have since extended our activities to include assisting research groups in translating their protocols to GMP. Having recently moved to our new facility at the Scottish Centre for Regenerative Medicine, we are now looking to manufacture advanced therapy medicinal products cells in 2012.
“When working on the translation of a new cell therapy, it is invariably the case that GMP and scale-up need to go hand in hand. It’s vital to have a clear idea of how the cells will be used from the outset, as the characteristics of the cell therapy—the quantity required and how they will be delivered—will determine the process development,” he continued.
“For example, for ophthalmological therapies you may only need 105 cells, but treatments for ischemia may need 108 cells and an artificial liver may require 1011 cells. For us, asking ‘how many cells does the patient need?’ is always the key question.”
“This is a fantastic time to be involved in regenerative medicine, as what we’re doing now will deliver powerful therapies in the next decade,” Courtney concluded. “Undoubtedly, many of the game-changing developments that will make this happen will occur in the application of bioprocessing techniques for the manufacture of cell therapies.”
Speakers at the conference were upbeat and agreed that the U.K. has a strong SME base for bioprocessing, as well as academic hubs of excellence at Cambridge, Manchester, Loughborough, Nottingham, and Leeds, all establishing knowledge transfer hubs. University College London (UCL), Kent, and Imperial College are also creating technical strategies in key bioprocessing niche areas.
Many stated that this sector needs funding schemes such as BRIC (Bioprocessing Research Industry Club) and an environment for business innovation to ensure that research can be translated from concept to commercialization.
“We need the sustained support of the U.K. government in terms of generating the right fiscal policy. Initiatives such as the ‘patent box’, which intends to introduce a 10 percent tax rate for profits arising from patents, will certainly help,” Bustard stated.
UCL’s Mike Hoare, Ph.D., said, “Academia and industry are really pulling together in the U.K. bioprocessing field, and the introduction of BRIC has been a great success. By working together we have been able to enlighten politicians on some key issues, and it has squashed this idea that industry must necessarily be the sole funder of activities relevant to product manufacture.
“The next generation of biological therapies are going to be more complex, and we must understand the fundamentals of scale-up, so it’s important to grow government funding for this research,” he continued.
“We have wonderful mechanisms, especially through the EPSRC and the Technology Strategy Board, of interfacing academia and industry in the U.K., and we have to keep this going,” Dr. Hoare said. “We need to support U.K. companies involved in bioprocessing and provide a highly skilled workforce, but we still have a lot fewer engineers being trained here than we need for the bioprocessing industries.
“We must start outreaching programs to our high schools to ensure we have the next generation of numerate bioscientists and engineers trained and ready to maintain the edge we have in some of the key technologies, because delivering the next generation of therapies is an area of high-value manufacturing that the U.K. economy really needs.”