In 1953, James Watson and Francis Crick discovered the double helix structure of deoxyribonucleic acid (DNA).¹ Their work marked a milestone in the history of science, giving rise to our modern understanding of genetics. Less than 40 years later, in 1990, a 4-year old girl became the first gene therapy patient at the NIH Clinical Center in Maryland, USA.² She had adenosine deaminase (ADA) deficiency, a genetic disease that left her unable to fight infections. The pioneering researchers at NIH inserted ‘normal’ genes for making ADA into the girl’s white blood cells, and reinjected her with her own amended cells. The results were temporary, but successful.
 

The successful trial launched a whole new area of medical research, which we now commonly refer to as ‘gene therapy’. Gene therapy uses biotechnology to insert a new copy of a gene into an individual’s cells and tissues to potentially cure a disease – including genetic diseases in which a defective allele is replaced with a functional one. A vector – most commonly a genetically-altered virus – is used to deliver the therapeutic gene to the patient’s target cells.
 

In July 2012, the world’s first gene therapy, Glybera, received marketing authorization from the European Medicines Agency (EMA). The treatment was developed and produced by uniQure as a ‘fix’ for Lipoprotein Lipase Deficiency (LPLD), a genetic disorder that renders afflicted individuals unable to breakdown triglycerides. It causes recurrent abdominal pain and can lead to acute pancreatitis, pancreatic insufficiency and diabetes. As Glybera presented the first effective cure for this condition, it was clearly ground-breaking stuff.
 

But a common question that has been asked about this breakthrough is how – and why – uniQure carried the first ever gene therapy across the finish line.³

As highlighted by DCAT’s Patricia van Arnum in January 2017, a key issue for the pharma industry is whether it can rebound from a recent low in its innovative outlook.⁴ Based on annual reports in 2016, the top 10 pharma companies’ R&D budgets totalled around $70.5 billion – that’s 17% of their top line spent on research.⁵ However, while it’s broadly acknowledged that biotech is dwarfed by the giant that is pharma, biotech is still pipping them to the post on innovation.

Large pharma companies with aging pipelines are increasingly aggressive when it comes to finding new potential blockbusters. In an effort to re-energize portfolios, pharma is turning to biotech for creative approaches to new indications. In an apparently symbiotic pyramidal arrangement, small biotechs are taking risks with ground-breaking innovative R&D, but then need the backing and finance of big pharma to fully develop and commercialize their products. Recent examples include a collaboration under which Cadila is – according to a September 2017 press release – investing “a significant part of the projected costs of the clinical studies” to develop and commercialize Aplagon’s heparin proteoglycan memetic, and Molecular Devices’ partnership with Cytena, also announced in September, to launch the latter’s ‘CloneSelect Single-Cell-Printer’ in North America.

However, in a number of cases, this symbiosis is achieved not just through collaborative agreements, but through M&As. This is why it surprised so many people that no-one picked up Glybera before it reached the market.³ Instead, that little biotech company won the gene therapy race. This rarity, which must have slipped through a number of eager fingers, occurred amid a flurry of mergers and acquisitions (M&As) that even led Forbes to ask the question: Are M&A replacing R&D In pharma?⁶
 

In May 2016, Forbes listed the top 10 US biotech companies as (from the top): Amgen, Gilead Sciences, Celgene, Biogen, Regeneron Pharmaceuticals, CSL, Alexion, Baxalta, Illumina and Vertex Pharmaceuticals. Soon after that list was published Shire acquired Baxalta for $32 billion. And Amgen has since been recognised as a good acquisition target for Pfizer,⁷ while Regeneron would apparently be a good fit for Sanofi,⁸ and Biogen is said to have drawn interest from both Merck & Co and Allergan.⁹
 

As biotech and pharma companies work more closely together to survive, and to create value, the distinction between the two sectors is becoming increasingly blurred. The two are effectively becoming one, with the emergence and growth of the ‘biopharmaceutical’ sector. This is already leading to different business models, as pharma can’t copy biotech’s [relatively] high-risk R&D approach, and some flexibility is going to be required.
 

The answer, experts say, lies in collaboration. Future business models will need to include more types of cooperation, with large biopharma companies being responsible for coordinating and funding federations and consortia, and having access to more innovation and greater productivity in return.¹⁰ Smaller companies, research institutes and academic medical centres will be responsible for generating original ideas on a fee-for-service basis; in return, they will have more stable, long-term financing, and access to vital regulatory and marketing skills.

Remember UniQure, those people who took everyone by surprise with Glybera a few paragraphs ago? They seem to be already there, collaborating with – according to their website – international pharmaceutical leaders, innovative early-staged companies, academic institutions and other research organizations to advance the company’s portfolio.
 

Cell and gene therapy is recognised as such big business that the British government recently established an independent centre of excellence, ‘The Cell and Gene Therapy Catapult’, to advance the growth of the cell and gene therapy industry. Aimed at bridging the gap between scientific research and full-scale commercialization, and with more than 120 employees focusing on cell and gene therapy technologies alone, it works with partners in academia and industry from across the globe by offering leading-edge technology and knowledge that enable small discovery companies to take products into clinical trials and provide clinical, process development, manufacturing, regulatory, health economics and market access expertise.
 

“Cell and gene therapies are a core component of a revolution in medicine across a broad array of disease areas and continued Government investment is helping us to rapidly evolve the UK as a global hub,” said Keith Thompson, CEO of The Cell and Gene Therapy Catapult, in a statement to the press.
 

A similar initiative is Park Innovaare, a so-called ‘innovation park’ at the Paul Scherrer Institute in Villigen, Switzerland. A recent announcement in September 2017 indicated that the site is being further developed with an extended campus (an additional 35,000 sqm by 2020), paving the way for more biopharma spin-offs and companies to translate their research into industrial applications and commercial success.
 

Realistic expectations, good data sharing, and a commitment to an ‘innovative culture’ on the part of everyone concerned will be key to achieving future success. Combined with other technological developments like personalized medicine, 3D-printed drugs, automated health sensors, artificial intelligence and digitized supply chains, these changes are shaping the future of pharma…. of biopharma.