Interview: A sense of freedom

John Dixon, Director of JD International Consulting, has worked in the industry all his life and continues to care about the future of British science and the discovery of new medicines. He talks to Jane Ellis about using his experience to help the drug discovery process

John Dixon

John Dixon was at the forefront of drug discovery for more than three decades, including more than 20 years as Head of Medicinal Chemistry at Fisons, four years as VP of Preclinical R&D at Astra Charnwood, and then as VP of Drug Discovery at AstraZeneca Charnwood for a further nine years.

When he retired from AstraZeneca in July 2008 he set up JD International Consulting. He admits that it took ‘courage and initiative’ to set up on his own, but found a new sense of freedom after being in the cocoon of AstraZeneca.

Nowadays the corporate world of Big Pharma seldom encourages entrepreneurship, or individuality, and often values conformity. ‘Conformity does not necessarily lead to high quality, originality and creativity in research,’ he says. In the final years before he set up on his own, Dixon spent a large proportion of his working life dealing with distractions that were not contributing to the main objective of scientific discovery.

I have no distractions to take me away from the real mission, which is to concentrate on interesting science

‘These tended to be worse the larger the company. Now that I’m away from corporate life, not a day passes by without me feeling an overwhelming sense of liberation,’ he says. ‘Although the experience was enormously valuable, I’m relieved to be away from the corporate world. Now I have no distractions to take me away from the real mission, which is to concentrate on interesting science that might lead to the development of new medicines.’

His consultancies have covered most aspects of drug discovery and early development in the majority of therapy areas and in all types of organisations within 11 countries. ‘They are many, varied and constantly evolving,’ he says.

As well as getting involved in discovery and development, Dixon helps his clients with outsourcing/collaborations, patent strategy and litigation, and developing new and innovative routes of drug administration. He works with large, medium and small pharmaceutical companies, charities, virtual organisations, CROs and academia.

He has only a small number of Big Pharma clients – ‘they should already have my expertise in house’ – and is more interested in ‘meeting and influencing those who make the decisions’. If the client is an SME, CRO, or medium-sized company, for example, he will see the entire management team or the owner.

I give opinions that they may not like. I don’t peddle generic solutions, I add value

‘I am interested in helping them to be successful. I give opinions that they may not like. I don’t peddle generic solutions, I add value,’ he says. He suggests that Big Pharma could be less receptive to his opinions because it is difficult for people inside a large organisation to be sufficiently open-minded to listen. Small companies, on the other hand, know that they don’t have all the answers and want his help.

‘But it’s not my job to tell them what their strategy should be; I aim to help them understand the difference between achievability and desirability. I tell them when there won’t be a new drug in the short term. I will always say whether they’ve got a chance and what that chance might be. Not enough people are asking: “What is the success of this likely to be?” – some prefer to believe that everything in science is achievable within predetermined and similar timescales and/or budget.’

Dixon knows what achievement feels like: in his Fisons period, for example, five compounds reached Phase III, two of which were marketed. Dixon invented one of these (Dopacard) and one that reached Phase III (Viozan).

He says all of his roles at the Charnwood site provided great personal opportunity. ‘For instance, Fisons presented me with an unusually interesting and rare opportunity for someone in his early 30s.’ He was allowed to build up the department more or less from scratch and it quickly grew to 200 people. Under Astra and AstraZeneca Charnwood Discovery grew to 400-plus.

‘We built up what we now know to be a modern and successful drug discovery organisation,’ he says. ‘We constructed our own philosophy and standards; we had state-of-the-art laboratories and were modern in our thinking.’

Astra really was a different kind of company where science was truly respected

In the 13 years that he was VP of Drug Discovery at Charnwood, the company delivered many candidate drugs – 35 in AstraZeneca alone, most recently in the respiratory area. Currently, several Charnwood compounds are in Phases II and III in more than one therapeutic area. For instance, Brilinta (ticagrelor), a potential blockbuster for thrombotic disorders was discovered and conceived entirely at Charnwood. The project was started at Fisons and completed at Astra. Despite being novel and unfamiliar this project benefited from strong support of Astra senior management in Sweden.

‘Astra really was a different kind of company where science was truly respected. This project took a long time and others could easily have terminated it. Astra did the opposite,’ says Dixon.

Brilinta was later developed under AstraZeneca and achieved marketing approval in Europe and final FDA approval in July 2011. The current expectation for Brilinta sales are very high and already many lives have been saved by this Loughborough discovery.

In the past six years, Dixon has worked with more than 70 drug discovery companies and has not encountered anything quite like Charnwood, he says. ‘I am independent and travel all over the world and I can compare the scientific standards of companies I encounter in my consultancy business with what we built up at Charnwood, and many companies today are still not where we were in drug discovery 15–20 years ago. I feel validated by that; I’m proud of what we built, as are my colleagues. It was an exceptional place with exceptional people and it gave me the confidence to do my current activities.’

Many companies today are still not where we were in drug discovery 15–20 years ago

Dixon feels further vindicated when he is asked for references for former staff. He says they will nearly always get jobs, even in the current period of consolidation and contraction within drug discovery and development, because they are employable, capable and have a long-term creative outlook. Unfortunately for UK science all too often they find jobs abroad.

‘They have courage, judgement and modern thinking and I’m very proud of them,’ he says. ‘At Charnwood we worked in a tough environment and we were used to pushing quality standards in drug discovery, not in a corporate way, but in the right and modern way. One of many examples was drug metabolism and pharmacokinetics (DMPK). Charnwood’s DMPK on drug design was far more stringent and advanced than in other companies.’

There were many other examples of industry leading practices at Charnwood. The fact that many former colleagues have gone out into the wider world, set up their own companies and are providing a livelihood for other research scientists is another a form of validation of what was achieved there. Dixon thinks Big Pharma is an unsustainable business model in the modern world. While the scientific quality in the research departments of Big Pharma companies in the 1990s was undoubtedly high, he says they saturated the capacity in drug development (from budgets to decisionmaking capabilities), leading to log jams and poor decisions. They had to prioritise what they would develop and he believes their decisions were influenced, not by patient need, but by the imagined sums of money that could be earned from blockbuster drugs. Failure to concentrate on the science often made failure more likely.

Drug research was too productive in the 1990s, led by false expectations of riches

‘Drug research was too productive in the 1990s, led by false expectations of riches,’ he says. ‘There was a higher failure rate (95%) than was acceptable but this failure occurred largely in development. Although the standard of research was better than previously and we learned how to discover things of quality, not all of them were explored successfully.

‘The high quality of research was not paralleled in drug development. Having said that, not all research projects paid attention to medical need and were distracted by attractiveness of good science. Nevertheless, if scientific quality is high and strongly connected to patient need, success is more likely and profits follow as a consequence.’

Dixon believes that investment in drug development should be based on achievability and probability, and motivated by need, not greed. He says today the industry is starting to pay more attention to developing drugs for diseases that were always important and difficult and needed serious attention, such as cystic fibrosis, and many other seemingly smaller opportunities.

Investment in drug development should be based on achievability and probability, and motivated by need, not greed

Over the next 10 years, he thinks there should be fewer ‘me too’ improved versions of a competitor’s drug. They will be less likely to get approval from the regulators and carry more likelihood of patents being overturned due to lack of inventiveness.

‘Products that do not show big differences to patient outcomes are less likely to be successful in the approval process,’ says Dixon. ‘This will mean that we’ll see the development of more worthwhile treatments, that will still be difficult to develop, as well as more original discoveries (like Brilinta) – both of which will bring a need for more invention in research.’

Dixon is clearly passionate about the industry that has provided him with a livelihood for more than 30 years and is continuing to do so. He wants to put back into drug discovery the benefit of his experiences at Charnwood by sharing his knowledge with people who come to him for advice. ‘I've been lucky,’ he says. ‘I don’t think it’s good enough to work all my career in the industry and take the money and run.

‘I care about the future of British science and the discovery of new medicines. We will all be patients at some time in our lives and we expect that medicines will be available to treat us. I want to help find new medicines for sick people, maintain the UK’s science base, and provide employment for people who stay in the industry.’

Curriculum Vitae
2008 to presentDirector JD lnternational Consulting Ltd
1999 to 2008Vice President, Drug Discovery, AstraZeneca Charnwood
1995 to 1999Vice President, Preclinical R&D, Astra Charnwood
1972 to 1995Director of Chemistry Fisons plc, Pharmaceutical Division
Education
1971 to 1972University of Liverpool
Post Doctoral Fellowship, Organic Chemistry
1970 to 1971National Research Council of Canada, Ottawa
Post Doctoral Fellowship, Biochemistry Division
1963 to1970University of Leeds
PhD Organic Chemistry
BSc Organic Chemistry

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