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Protein modification represents a highly significant and growing source of new products for the biopharmaceuticals market. This case study outlines the development of PolyTherics, a highly successful spin-out company from the UCL School of Pharmacy, and the impact that their enabling technology has had on the pharmaceutical and biotechnology industries. The company was developed as a direct result of new conjugate technology developed by Professor Steve Brocchini and coworkers at the School. The company moved to independent premises in 2006 and now manages a portfolio of over 100 granted and pending patents. Several licensing agreements are in place, including with Celtic Pharma Holdings for haemophilia treatments and Nuron for a multiple sclerosis treatment based on PEGylation conjugation technology. Revenue is expected to be £8m in 2013. The impact of Polytherics is therefore as a significant and effective technology provider to the pharmaceutical and biotechnology industries.
Combinatorial Domain Hunting (CDH) technology is a technique for producing fragments of proteins that are soluble and tractable for biophysical analysis. It was developed between 1999 and 2008 at Birkbeck College, in the laboratory of Dr Renos Savva. This technology was patented in 2001 and the biotech company Domainex Ltd was then formed to commercialise it. In 2007, Domainex merged with a UCL spinout company, NCE Discovery Ltd. The company has attracted over £3m in investment and employs about 31 people. In addition to its contract research programme, it has developed an in-house drug discovery programme utilising CDH. Early in 2012 a patent was filed on a series of inhibitors of the protein kinases IKK03b5 and TBK1, which are validated drug targets for cancer and inflammation, and the first of these are expected to begin clinical trials in 2014.
Novel rapid methods for predicting protein structure, particularly functional loop structures, have been developed by researchers at the University of Oxford. These have been made accessible to a large audience through a suite of computational tools. The methods have had general impact through download and online access and specific impact through extensive use within UCB Pharma. The tools are much faster than other methods, creating equal or better predictions in approximately a thousandth of the time. Commonly exploited by UCB Pharma in their drug discovery pipeline, they have cut computational cost, but, more importantly, they have greatly reduced the time for process improvements. UCB Pharma estimate that the tool pyFREAD alone saves over £5 million in the discovery costs for a single drug molecule. FREAD (a version of pyFREAD coded in C) is also being used more widely, for example by Crysalin Ltd and InhibOx.
Essex research identified a novel bioprocessing matrix which has since been developed into commercial products and recently launched into external markets by Porvair Filtration Group Ltd. The discovery involved the chemical modification of sintered thermoplastic materials in order to attach biological molecules, so conferring highly specific functionalised properties to an otherwise inert base material. This enabled a new approach for protein immobilisation, having technical and practical advantages over existing processes. As a direct result, Porvair has adopted a new technology and invested £900k in R&D over eight years. Essex research has supported a change in business strategy, enabling entry into new markets, which has in turn both safeguarded and created jobs at Porvair.
Serum amyloid P, or pentraxin-2, is a pentameric calcium-binding protein that binds to amyloid fibrils. It has been implicated in the protection of those fibrils from proteolytic digestion and in the immune response to tissue damage. The structure of pentraxin-2 was first solved by Steve Wood and his co-workers in Tom Blundell's lab at Birkbeck in the 1990s. Wood has continued his work on the pentraxins at UCL, and the company Pentraxin Therapeutics Ltd was spun out of UCL to design and develop pentraxin-binding ligands (based on its structure) as potential treatments for Alzheimer's disease and amyloidosis. Promedior Inc. in the US is developing recombinant forms of pentraxin to control fibrosis. Several of these molecules are now in clinical trials.
A novel conjugation technology has been developed to enable site-specific attachment of polyethylene glycol (PEG) to proteins to extend the in vivo half-life of biopharmaceuticals. The technology has been commercialised by an Imperial College spin-out company, PolyTherics Limited. In 2013, the merger of PolyTherics with Antitope Limited, enhanced the company's biopharmaceutical technology development offering. PolyTherics issued new shares to the value of £13.5 million to investors and Antitope shareholders in connection with the merger.
The company has enabled the development of novel forms of interferon 03b2 (for the treatment of multiple sclerosis) and blood factors VIIA, VIII and IX (for the treatment of haemophilia A and B) utilising original Imperial TheraPEG™ technology. This is achieved through licences granted by PolyTherics to Nuron Biotech and Celtic Pharma Holdings who are in early pre-clinical development. PolyTherics has further developed the conjugation technology (ThioBridge™) for its application in the creation of stable, homogeneous antibody-drug conjugates for the targeted cancer therapy.
Polytherics has impacted the UK economy generating intellectual capital, capital investment, new employment and novel compounds to treat disease.
A novel self-assembly process, developed at WestCHEM was shown to provide a step-change for stabilising proteins as dry powders. The spin-out company, XstalBio, was created in 2004 and licensed the patented technology with the aim of developing it for delivery and formulation of therapeutic biomolecules and vaccines. Over the period 2008-2012, eight leading international pharmaceutical and animal health companies paid XstalBio over £2.2M for access to its IP portfolio and to undertake evaluation studies with candidate biomedicines and vaccines. XstalBio employed 8 highly skilled research scientists over this period and 4 further patent families were generated. Boehringer Ingelheim licensed the technology for application to its therapeutic biomolecules and in collaboration with XstalBio built a dedicated €5M pilot plant for manufacture of inhalable dry powders.
The Institute of Cancer Research (ICR) founded the spin out company Domainex in 2002 in collaboration with UCL and Birkbeck. The company was set up on the basis of novel research into the expression of soluble protein domains to provide services to a range of bioscience-based companies. Within the period 2008-2013, Domainex has established profitability and positioned itself as a successful company employing over 30 scientists at its laboratories in Cambridge. It has established programmes and contracts with over 20 international clients in medicinal chemistry, drug discovery, monoclonal antibody development and agrochemical science, making a major commercial impact in all these fields.
Impact: EaStCHEM spin out Albachem (1994), subsequently incorporated into the Almac group, enabling the latter company to become a world leader in the provision of chemically synthesised proteins.
Significance: Chemical synthesis is competitive with recombinant methods for commercial production of the therapeutic polypeptides that represent ~50% of drugs in big pharma pipelines and have a market value in 2008 of over $13B. The value attributable to Ramage's methods for polypeptide syntheses over the REF period is estimated at approximately £6M.
Beneficiaries: Drug manufacturers, contract research organisations, patients, clinicians.
Research: Studies (1993-6) led by Ramage (at the University of Edinburgh) on new methods for high-yield total syntheses and purification of long polypeptides.
Reach: Almac's protein-manufacturing team remains in the UK with 24 staff members. The Almac Group, headquartered in N. Ireland, has 3300 employees globally (1300 outside UK) and sells to 600 companies worldwide.
The spin-out company Intelligent Fingerprinting Ltd. was founded in 2007, based on Professor David Russell's research. The company develops novel technologies using antibody-nanoparticle reagents to detect drugs and drug metabolites in latent fingerprints whilst simultaneously providing high resolution fingerprint images for identification purposes. Combining these technologies with a fluorescence-based hand-held reader provides a non-invasive diagnostic platform for use in the criminal justice sector, institutional testing and hospital environments.
Total funding to date for the company has been >£3.2M in four investment rounds. The company employs 11 staff, who work in dedicated office and laboratory premises within the Norwich Research Park Innovation Centre.
The company received its first purchase order from the UK Home Office in 2012. A distribution agreement is in place with Dallas-based SmarTox Inc. for North American sales of Intelligent Fingerprinting products for `Drugs of Abuse' testing.