Dr Mene Pangalos joined AstraZeneca in 2010 when the company's pipeline was "virtually empty" - that is how he describes it.
BiotechDispatch interviewed the company's global head of R&D during its recent International Media Day in Cambridge.
"When I was hired there was an understanding our R&D organisation hadn't delivered. They'd been spending three or four billion dollars per year, there were no new drugs, and the pipeline wasn't particularly exciting. There was an understanding we needed to 'reboot' our R&D engine.
"There are values important to me in driving a successful R&D organisation - the first and foremost is actually being science-led in terms of decisions and how you work.
"Having science at the top of the agenda in terms of how you go about recruiting people and motivating them, and how you make decisions about what molecules you take into the clinic,” Dr Pangalos told BiotechDispatch.
"The biggest difference was changing the focus from quantity to quality. Our scientists had been set on a direction of quantity, which wasn't unique to AstraZeneca - but we may have been a little late in coming out of that mindset."
Dr Pangalos essentially describes AstraZeneca's former approach as a 'numbers game', with the company simply wanting to scale-up the traditional benchmark of a 10 per cent success rate once molecules enter human trials.
"We put 100 molecules into development, and get 10 out, so let’s just put more into development. What everyone found out, and AstraZeneca found out particularly hard, is that you put more in and you still only get 10 out. We had tooled up and increased our capacity but it simply hadn't worked.
“As a company, we had to move away from rewarding people for the 'quantity' of what they did, and start rewarding them for quality."
He says one of the first steps was to review every R&D decision the company made between 2005 and 2010, with the goal of identifying the characteristics of successful programs - "...and we didn't have many of those," he says - and the same for unsuccessful programs - "...and we had lots of data on that."
"It produced some interesting things. What was important? The right target, how well did we understand the biology, genetic validation, right patient, right safety, right target engagement."
Dr Pangalos says the review found the company managed safety signals by reducing dosages in trials, normally to the point molecules were no longer efficacious. "That is what happens when scientists are rewarded simply for putting molecules into the clinic."
In terms of what now differentiates AstraZeneca, he says every decision the company makes is science-led, "...and if you're not comfortable with that, go somewhere else. The commercial guys have to be interested in science, so do the finance and comms guys, everyone. That became very clear when Pascal Soriot was appointed CEO in 2012. If people aren't interested in what we're doing, and the focus on science, then go and work somewhere else."
The company's commitment to collaboration has also been a significant change, says Dr Pangalos.
"We were very inwardly-focussed. We were focussed on personal bests but we're now focussed on world records. The best way to achieve world records is to work with the best scientists in the world.
"The way you do that is through good science and by being a good collaborator - sharing data and exchanging ideas."
He highlights the company's new R&D facility in the Cambridge Biomedical Campus that will permanently host researchers from publicly-funded institutes.
"In the end, the most gratifying part of the research is when you have a patient receiving the drug. When you have patients come in to meet our scientists, it's fabulous. Pascal has enabled that, allowing our scientists to focus on what they do best - developing medicines for patients and that is part of the fabric of our company now."
In response to the question of what he wants to achieve between now and 2020, Dr Pangalos delivers a very straightforward answer – “more medicines”.
"Our industry is not quick, but we've launched TAGRISSO, we've launched LYNPARZA, which was written off before Pascal joined the company. We have so many molecules coming out of the pipelines, and so many still in the pipeline, and we just can't wait to get in the new building in 2018.
"I want us to be viewed as the best science-driven organisation in the world - that's the aspiration."
While focussed on the science Dr Pangalos is also commercial. "But when you have the decisions driven by the science - do you believe this will deliver a medicine and understand why anyone would want to pay for it - you have the 'right' commercial. We have to be able to demonstrate why a patient would want to take it, a doctor prescribe it and a payor reimburse it. We think about that upfront. That's not easy because you have to think about the world in ten years time but, if you don't start thinking about that, you're always going to be working on incremental benefit.
"No more decisions about defending the franchise. Now it's about where we want to be. As Pascal says, we're not trying to protect the company, we're trying to grow the company."
BiotechDispatch attended AstraZeneca's International Media Day thanks to the support of the company.