Written by Julie Corfield, Areteva Ltd and Chris Christodoulou, MedImmune Ltd, August 2013.
We need to overcome the challenge of innovation gaps for the translational research pathway, if we are to enable the health and wealth of UK plc. The sharing of knowledge across business and academia, implemented in a way that is sustainable, will help.
On 9 July Harriet Fear the CEO of One Nucleus, brought together 300 delegates, including leading experts representing their experience in the public and private sectors, innovators from emerging companies and SMEs, exhibitors as service providers and innovators; all who are in a position to make a difference in translational research. This event was informative and energising; marked by the openness amongst delegates and a willingness to share knowledge, experiences and ideas, which are all essential if UK plc. is to be successful.
One key theme resonating throughout the day was that UK success depends as much on our behaviour and attitudes, as our technical skills. Andy McMenemy summed this up at the end of the day with ‘The Power of Positivity’ where he described overcoming physical and mental stresses in both the Marathon des Sables and his 66 Marathons in 66 Days, across the UK back in 2011.
The morning session included three high-profile speakers who set the scene: the UK economy; the regulatory environment; putting the patient first, all with an emphasis on partnership. This was followed by some short provocative presentations on ‘Game Changing Technologies’.
Economy: Sir William Castell, Chairman of the Wellcome Trust, (previously in industry) made the point that although the UK academic output is impressive, (7.8% of global publications for 3 % of global research funding) there is the need for a much stronger industrial/academic interface, as evidenced in Boston, USA. This interface will enable the convergence of technologies, which are vitally important for innovation, and will enable much higher economic returns to the UK.
In summary, we need to learn from examples of partnerships and technologies that lead to opportunities and innovation, such as: the current opportunity to eradicate foot and mouth globally through the new technology of making vaccines with just a protein shell; the use of HCRT imaging for diagnosis and the advancement of the technology to ultrasound. Partnership and infrastructure investment are new opportunities: the Francis Crick building; Stevenage Bioscience Catalyst; clusters of excellence; public private partnerships such as those established via the Department of Health/MRC competitions and grants. Taking personal responsibility is also important, ‘mentoring’ is one way of learning. It gave him the confidence to ‘be bold’, and to ask for help from the right people to create the right partnerships.
Regulation: Sir Mike Rawlins, Chair of the Eastern Academic Health Science Network focused on the regulatory environment from: bench to bedside to large cohorts in clinical trials; the real world and routine practice; ethics; NHS governance and payer approval.
In summary, it is no surprise there have been many regulatory bottlenecks, stifling both research and the availability of medicines. These are now being addressed with the intent to have unified approaches and organisational change. The establishment of the Health Research Authority and the Academic Health Science Networks are both examples of organisational change. In 2016 we expect a new clinical trials authorisation process to enable leaner product development; implementation of adaptive licensing is a potential problem solver for payers. Enlightened leaders are key to our success.
Patient first: Susan Galbraith, VP and Head of the Oncology iMed in AstraZeneca, focused on ‘following the science and putting the patient first’. For the UK ‘we can still lead in translational research, but will need to think differently’.
A ‘toolbox’ that can be applied across the R&D life cycle, which was not available to her as a clinician, is now beginning to deliver patient benefit.
In summary, building evidence for safety, treatments ‘personalised’ to patients and commercial viability is paramount. This can be achieved by focusing on the right target and linking that to the disease, but can be challenging due to limited access to high quality human tissues and technologies. The UK can lead in this through partnership, across the NHS, industry and academia, by sharing knowledge and data, to enable insight into the challenges, leading to the generation of ideas and innovations. Informatics platforms and know-how are key to this success.
The EGFR target is one example where clinical trials have shown that the screening of patients for a mutation can determine response to treatment to IRESSA, ensuring the patient comes first, in deciding on the approach to treatment. The emphasis is on being able to do this more effectively. Partnership, such as collaborations with CRUK will enable this, resulting in stratified medicines.
The UK Contribution in Game Changing Technologies
Chaired by Sir William, the panel summary is that: Technologies we have in the UK are making significant contributions to translational research. The challenge is to extract the ‘real value’ of them through exploitation, by applying knowledge accrued from their use. Pre-competitive collaboration between academia and industry is essential to making progress; working together, with a less ‘risk averse’ mind-set.
Overriding to this theme was also the need for ‘big data’ integration; the utilisation of open source data to enable interoperability; new business models for the effective implementation of technologies in the NHS; ensuring the appropriate skills are available eg: project managers, to enable public private partnerships to work, and be more flexible for contracting skilled resources; and obviously investment from funders.
The cost-effective use of Genome Sequencing in public health, to pinpoint MRSA outbreaks in a baby unit and thence enable its management was one example covered by Professor Sir Mike Stratton, of the Sanger Institute. The potential use of genome sequencing to select treatments and design clinical trials was considered, as were the challenges posed by the myriad of mutations and the need to consider sensitivities versus resistance. Structural biology, ‘could drive drug discovery if you let it’ Professor Laurence Pearl, a protagonist of Democritus? Examples included how structural biology tools can drive pharmacology and improve selectivity and potency eg: for anti-tumour agents, and result in improved decision-making for progressing potential drugs. Synthetic Genetic Polymers have a real potential to make a difference for reaching intracellular targets. Philip Holliger from the MRC laboratory for Molecular Biology; showed they can replace antibodies that have underperformed in the clinic, because of rapid degradation by acid; by designing the polymers to be non-degradable in the gut. Finally in this session, the value Stem Cells bring both as research tools and as therapies was covered by Nick Thomas of GE Healthcare. It was refreshing to consider how their use could be better placed and not used in a ‘risk adverse’ way; as suggested can be the case when specific approaches are imposed by regulators, for example for hERG.
The early afternoon session had two parallel sessions of Case Studies, covering ‘Collaborations in Translational Research’ chaired by Scott Kahn of Columbia University and ‘Translational Research Challenges’ chaired by Allan Marchington, of Apposite Capital.
The UK has a window of opportunity to focus on establishing and consolidating partnerships and business models for translational research and drug development. Some examples include: Imanova which provides opportunities for partnership in imaging; Cancer Research Technology can provide full services for drug discovery, development and technology transfer. Biologically-themed strategic alliances eg: AstraZeneca, Astex, NICR cover different aspects. Kymab has a proprietary tool – the Kymouse, which is based on embryonic stem cell and re-combineering technologies. The platform is designed to have a superior repertoire of B-cell mediated immune responses to current in vivo systems. ‘We are using the Kymouse™ platform to discover and develop potent and selective therapies’. Kymab is in partnership with a number of companies using it to develop product portfolios.
F-Star is moving from a company with a bi-specific antibody platform to positioning itself as a company with a focus on biology and getting products to the market. Discuva is set to revolutionise antibiotics discovery. The Discuva approach is to solve the problem of how to get antibiotics into bacteria, by phenotypic screening of huge libraries of mutant bacteria containing only a few base changes per cell with the aim of identifying antibiotics to drug resistant pathogens. Definigen is confident that the technology of producing highly functional human hepatocytes from human induced pluripotent stem cells (iPSC) for use in toxicity studies and screening can catapult the group into a successful business. Translational research by Pfizer and IMI EuroPain Consortium on a UV-B model of inflammatory pain in both rat and human was described. The model can be used for target identification and to provide proof of mechanism.
The main conference finished with a session dedicated to ‘Enabling Translational Research in the UK’, chaired by Mark Treherne, CEO of the UK Life Science Investment Organisation. The session focused on the ambition to use the NHS as a research organisation to stratify patients to the appropriate treatment, under the banner of the ‘patient comes first’. The key message for success is effective ‘networking’ to harness capabilities. There had been many opportunities to do that in the day. Oliver Rausch described the role of the Translational Research Partnerships (for Respiratory Disease and Inflammation), established by NOCRI under Department of Health funding. These are intended to utilise the NHS for academic research in partnership with industry via centres of excellence (Biomedical and Research Centres and Units) for proof of concept studies and translational research programmes. The TRPs have the capability to navigate the governance and administrative requirements of the trusts and have access to the NHS infrastructure. On the same theme, Nick Pope of the East Midland Academic Health Science Network explained how it can enable innovation within the NHS, as a ‘broker’ providing the links with people to establish networks. On the basis that they understand the clinical needs, the network can access the appropriate research expertise, commissioners, budget holders and commercial skills. Opportunities to enable businesses come from the Technology Strategy Board, funding via the Biomedical Catalyst, with the intent to deliver growth to the UK life sciences sector by providing solutions to healthcare challenges. Helen Kuhlman referred to the latest funding, announced on 29th July, with scaled funding depending on the stage of a project. It is intended through positive impact to leverage significant private investment in the UK. Significant investment via the Biomedical Catalyst has already been implemented.
Annabel McCleod of the HMRC, reminded the attendees that there is help to enable our research endeavours via R&D Tax Credits. She advised that companies should take the time at the outset of their foundation to investigate the possibility of securing these, rather than later. Public Health England, (Mike Carroll), formerly the Health Protection Agency was described in scope and by reference to its future intent to establish and develop more partnerships; in particular for emerging infectious diseases.
Written by Julie Corfield, Areteva Ltd and Chris Christodoulou, MedImmune Ltd, August 2013.
The One Nucleus blog is written by individuals and is not necessarily a reflection of the views held by One Nucleus.