Perspective

David Fox
Director, External Chemistry Partnerships and RSC Visiting Senior Industrial Fellow
Pfizer Worldwide Medicinal Chemistry
Sandwich
Kent CT13 9NJ

The model for drug discovery is changing and we, as medicinal chemists, must evolve if we are to continue to be at the forefront of breakthroughs in new medicines. This perspective highlights collaborative research, in its various guises, as the key to continued success, drawing upon recent developments in the area.

The challenges for the pharmaceutical industry have been well-documented in terms of the continued downward pressure on pricing, the ever more exacting regulatory hurdles and the rapidly shifting landscape demanding new, unprecedented scientific approaches.¹ For EU-based researchers, the emergence of Asia as a major player creates a truly global environment where the basis for a competitive edge needs to be revisited. Such challenges create exciting new opportunities for those who embrace the need for change and indeed, one might argue that the future prosperity of EU-based medicines research is reliant on transformation in order to build the case for continued inward investment.

So what is the basis of our future competitive edge? In addressing this question it is worth considering four areas of opportunity.² Firstly, we have access to world class science and world class scientists. The recent International Review of Chemistry confirmed that the UK at least is as strong as ever in terms of scholarship and talent.³ Secondly, we have access to funding to support public-private partnerships that is geared towards developing key areas of science aligned to drug discovery. Thirdly, there is a well-established network across industrial and academic researchers that forms the basis of highly effective scientific exchange. The geographical proximity of centres of scientific excellence to industrial research sites and the high density of talent in the EU are key enablers in this respect. Finally, there is a prevailing mindset amongst EU-based researchers that collaboration is genuinely a virtue rather than a threat to one’s scientific achievement.

This last point is particularly important. Across the board in both academic- and industrial research, there has been a step change in the way collaboration is viewed and embraced. This is in response to the highly complex problems that face researchers and where no single discipline expert can provide the solution. The shift in academia towards research centres is testament to this, where research topics cross discipline boundaries and where discipline experts come together in a truly collaborative sense to work in areas of common interest. An equally significant change has taken place in the industrial setting, for similar reasons. Gone are the days where large pharma would assume that because they have hired the best talent if they can’t find a solution from within then the solution probably doesn’t exist. Instead, there is a growing realisation that the scientists within the organisation are one part of a multi-dimensional research effort where additional external scientific know-how needs to be brought to bear in order to arrive at effective solutions. This is especially important at a time when the science underpinning drug discovery is moving at such a pace that it is unrealistic to expect that all the necessary scientific capability to address future challenges can be housed under a single roof.

If collaborative research is the way forward, the EU through the attributes outlined above, provides a particularly fertile environment for scientific partnership to flourish. It is our responsibility now to drive home our advantage in these areas, working collectively where possible rather than competitively, to deliver solutions of global impact. Through such precompetitive collaboration, the baseline capability within drug research is raised to the benefit of all and to the detriment of none, allowing each us to arrive more rapidly at new, competitive scientific discoveries. Such an approach represents a substantial shift in culture but makes sense scientifically, economically and most importantly from the patient’s perspective.

The remainder of this article will highlight three areas where collaborative research involving pharma-based medicinal chemistry is assuming growing significance.

In October 2009, the EPSRC launched a new 3-year scheme to encourage greater scientific exchange between academia and industry. ⁴The knowledge transfer schemes - Knowledge Transfer Account (KTA) and Knowledge Transfer Secondment (KTS) - would serve as vehicles for bringing the fruits of academic research into the industrial environment. Over twenty universities across the UK have received knowledge transfer grants ranging in value from £450K to £8M. This fund sits with a named university grant holder who invites bids from EPSRC-funded academics across the university to support discrete pieces of work (ranging, in our experience at Pfizer, from a few weeks feasibility study to a 1-year post-doc) that serve to demonstrate the industrial applicability of the research. From the academic’s perspective, this scheme provides an opportunity to expand the scope and utility of the research and to address the ‘impact’ agenda that is becoming increasingly important for academic research funding. For the industrial partner, knowledge transfer schemes such as this enable an expert in an emerging scientific field to apply their know-how to a problem of immediate business relevance. Recent examples of knowledge-transfer schemes at Pfizer include the application of chemical biology methods, use of new C-H activation methodology and the investigation of emerging aryl coupling technology. A number of these schemes involve the engagement of a knowledge transfer fellow who spends a significant proportion of their time with the industrial partner. In such cases, the fellow gains invaluable experience of working in an industrial environment and is able to draw upon state-of-the-art equipment and capability. These schemes are heavily subsidised by the KTA or KTS (more so than traditional TSB-funded Knowledge Transfer Partnerships⁵) and while there may be a need for the industrial partner to provide a small cash contribution, the majority of the industry costs are covered by in-kind contributions.

Despite the clear potential of these schemes to deliver high value industry-academia collaborations, they remain relatively untapped and many chemists working in academia and industry appear to be unaware of their existence, let alone the potential value they can bring to their respective research efforts. Looking forward, it will be increasingly important for the community to engage with knowledge transfer schemes to ensure that we as a sector are able to draw as much business value from academic research discoveries.

The academic and industrial chemistry communities are coming closer together and the clear boundary that existed historically between the two is becoming increasingly blurred. In the main, this should be viewed as a positive development with the emerging partnerships between the two being mutually beneficial. Recent examples of this are the 4-year EPSRC-funded pharma synthesis PhDs⁶ where academics have joined together with a consortium of industrial partners (GSK, AstraZeneca, Pfizer and most recently Novartis) and the EPSRC-funded initiative Dial-a-Molecule⁷. Centres for Doctoral Training, such as the Chemical Synthesis centre at Bristol, cross-disciplinary centres such as the Structural Genomics Consortium and an increasing emphasis on iCASE collaborations (with co-authorship by industry and academia) offer further opportunities for industrial scientists to collaborate on academic research projects. While such endeavours ensure that industrial scientists remain connected to academic research to help shape it and define the opportunity space for future research, it is imperative that industry does not end up defining the direction or scope of academic research. This is a difficult balance to achieve but one that we should continue to work towards if we are to derive as much value as possible from university-based research whilst still ensuring there is plenty of space for the unexpected outcome from fundamental, curiosity-driven research. Much of the time, this will come down to individual relationships and one initiative that could be particularly important in this respect is the ‘embedded academics’ model being championed by Professor Joe Sweeney from Reading University and Royal Society Industrial Fellow at AstraZeneca⁸. As part of this scheme, Sweeney has identified a cohort of around a dozen well-respected UK academic chemists who have committed to spend a portion of their time (ranging from days and weeks to months) embedded within an industrial chemistry department. By immersing themselves in this environment, the academics will see at first-hand the technical challenges facing the industry and will develop an understanding of what is and isn’t desirable/achievable within the industrial setting. This insight will provide an informed backdrop to their research activities and could for example help to shape how they exemplify their discoveries to achieve maximum impact. The potential benefit to industry is also wide-ranging; on one level, having regular access to an experienced academic who has a detailed appreciation of the chemists’ projects creates a collaborative interaction that is in stark contrast to the transactional nature of ad hoc consultancy. Beyond this, the regular presence of an academic researcher could help to evolve the way problems are approached and could present new opportunities for continuing professional development (e.g. research proposal writing, publications).

The relationship between industry and academic researchers will assume ever greater importance in the future⁹ and significant effort is ongoing through consortia such as SE Biopharma Skills Consortium¹⁰ and EMTRAIN¹¹ (part of the Innovative Medicines Initiative) to identify the options for future models of collaborative research, education and training.

This final section deals with what is potentially the most transformational and challenging area of collaborative research – cross-pharma precompetitive collaboration. This is a theme that has gained momentum in recent years with cross-industry consortia beginning to assume greater significance. Examples include ViiV Healthcare¹², (a company established by Pfizer and GSK for the co-development of HIV medicines), eTox¹³ (an Innovative Medicines Initiative collaboration on predictive toxicology involving 11 major organisations) and Pistoia Alliance¹⁴ (a partnership to develop data standardisation, involving up to 40 organisations).

In medicinal chemistry, however, such cross-pharma collaborations are still in their infancy, with the EPSRC-sponsored workshop on Chemical Biology being a notable exception¹⁵. In response, the Royal Society of Chemistry recently hosted the first in a series of precompetitive workshops intended to stimulate new collaborations across the sector¹⁶. The workshop, which attracted 60 participants across industry, academia, professional bodies, funding bodies and Sector Skills Councils, centred on two themes; compound attrition and continuing professional development. Following a series of short introductory presentations, scientists drawn largely from industry were given the opportunity to present posters on areas of their research that would benefit from cross-pharma collaboration (e.g. co-development of platforms or tools, data sharing). In the subsequent discussion, up to ten areas were identified where companies are already working (and potentially duplicating effort) and these will be form the basis of a series of targeted consortia. The themes include: developing a better understanding of genetic toxicology of aromatic amines; designing compounds outside of conventional rule-of-five space; new in silico tools for predicting attrition.

Around two-thirds of the participants completed an event feedback form with 100% of respondents supportive of further precompetitive workshops and over 80% of respondents stating that they were likely to engage in a cross-sector collaboration as a result of the day. Based on the success of this inaugural workshop, the Royal Society of Chemistry plans to host further precompetitive workshops for medicinal chemists through 2011. Potential themes for these workshops include: academic collaborations, knowledge transfer and funding opportunities; chemical biology and target selection; transporters and targeted delivery; hit discovery; data analysis and visualisation.

Whilst the first workshop was well-attended by scientists based in large pharmaceutical organisations (including Pfizer, AstraZeneca, GSK, Novartis, Lilly, Merck, Eisai, Takeda) biotechs, SMEs and universities were less well represented. For precompetitive collaboration of this nature is to realise its full potential impact and deliver maximum value to medicinal chemists, it is vital that future workshops successfully draw-in scientists from all sectors of the medicinal chemistry community.

The discovery of new and effective medicines in the future will demand new models for scientific collaboration to deliver solutions to increasingly complex scientific challenges. If we are to succeed as a sector and maintain a competitive edge, we have no choice but to collaborate in order to maximise the return on investment in research, drive continued future investment and ensure retention of the best talent. This has implications for how we train our scientists, such that they develop alongside their discipline excellence, the skills and behaviours they will need to thrive in the complex world of collaborative research.

As medicinal chemists, we have only scratched the surface in terms of what collaborative research can deliver, be it academia-industry partnership or cross-pharma collaboration. Scientists will need to be more receptive to the opportunities for collaboration and open innovation and more confident about working in pre-competitive space. This is a significant but surmountable challenge for an industry that historically has been, by default, secretive and protective and represents an exciting new frontier for medicinal chemists.

By David Fox

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