AstraZeneca reinforces pipeline with 'open innovation'

Mene Pangalos is the man tasked with nothing less than firing up the discovery engine of Britain’s second-biggest drug maker after its catastrophic fall off the “patent cliff”.

He joined AstraZeneca as head of innovative medicines in 2010, as the company was bracing for patents to expire on a string of its best-selling drugs.

The Nineties had been productive for Astra, but the pipeline had dried up. Its research teams were still churning out plenty of “candidate” medicines, but most of them were failing when tested in real patients.

The company is still paying the price for taking its eye off the ball in the early part of the decade. Sales fell sharply in 2012 and are predicted to keep declining for a number of years.

“Drug candidates are an easy thing to deliver,” says Pangalos, now Astra’s executive vice-president for innovative medicines and early development.

“If you’d measured AstraZeneca as a candidate [drug] machine, we were one of the best companies in the world. [But] when you measured us for successful launches, we were one of the least productive.”

The problem was simple. Astra’s scientists were being rewarded for delivering as many potential drugs as possible, regardless of their long-term potential.

“Research was misdirected, because you were focusing on volume not quality,” he says.

“Making researchers not just hand over a candidate but have to think about how you get it into late-stage development – suddenly their world got turned upside down, because now they weren’t getting rewarded just for a candidate.

“It drives a very different behaviour in terms of how you think about [a drug] from research into development,” he says.

In a nutshell, Pangalos, a neuroscientist by background, is “truth-seeking”. Lofty it may sound, but it is also startlingly obvious.

His mantra is that the more Astra’s scientists understand the diseases they are trying to treat, and the “target” cause pathway, the better they will be at developing the right medicine.

It is now possible for researchers to pinpoint which part of the DNA has been “broken” in certain diseases and so figure out what kind of molecule could intervene to prevent or lessen the consequences.

They start with a so-called “target” – be it a chemical reaction that happens in a diseased cell or a section of DNA – and design a drug around it.

“You’d be amazed at how many times molecules have gone into man, failed and then someone asks the very simple question, 'did you engage the target?’ and people kind of shrug their shoulders,” he says.

He admits AstraZeneca was late to the game, but the shift is starting to pay off.

The pipeline is filling up again, thanks to a mix of acquisitions and new drugs from the company’s own researchers, and Astra’s chief executive, Pascal Soriot, claimed earlier this year that sales will start rising again in 2017 as new products hit the market.

Pangalos’s work was well under way by the time Soriot took the helm in late 2012, but it has taken centre stage under the new boss. Within months of his arrival, Soriot appointed Pangalos to his inner circle as part of a major management shake-up.

“Pascal has really helped drive and accelerate this focus on science and patients. He’s incredibly passionate about it. That just makes it easier for me to do my job.”

The company Pangalos joined is very different from the one he now helps run. Astra has slimmed down its operations in the past few years, shedding thousands of scientist jobs and shutting seven of its 11 research sites.

The leaner company centres on just a few core areas: cancer, cardiovascular and metabolic, which includes diabetes, and respiratory and inflammation, which covers illnesses such as chronic obstructive pulmonary disease (COPD) and rheumatoid arthritis.

“We’re absolutely focused now on winning in our three core areas. You can go anywhere in our organisation and people understand the priorities,” he says.

Pangalos has both driven and witnessed a lot of change in Astra. But what gets him really excited is the revolution quietly unfolding across the once secretive world of pharmaceutical research.

Astra has spent the past few years forging partnerships with groups spanning health charities, academic researchers and even its industry rivals.

The collaborations work by openly sharing early-stage research, mostly into understanding the fundamental causes of a particular disease, and allowing both parties to use the knowledge.

Often they involve Astra scientists sharing a laboratory with researchers from other organisations. Astra even shares a laboratory with scientists from GlaxoSmith-Kline at a research centre at the University of Manchester.

It is a concept that has been around in the tech world for decades but could not seem more alien to Big Pharma, where jealously guarded intellectual property (IP) has long been seen as the lifeblood of the industry.

“Of course we have to protect our IP, but we have a reasonably good understanding of what IP we need to protect and how to protect it,” says Pangalos.

He explains that while it is important for Astra to guard the IP around its drug design, he is happy to share discoveries on how a disease works.

“It enables us to get more out of our research dollars than by just doing things on our own. You’re creating an ecosystem where you can collaborate and get more out of it than if you were just doing something on your own,” he says.

The rise of so-called “open innovation” came about partly out of economic necessity. Pharma companies, staring down a hollow pipeline, had nowhere else to turn once they had exhausted their acquisitive might on up-and-coming biotech firms.

But more fundamental changes have been at play too.

The old “try it and see” model of drug development is losing ground to more intelligent, targeted discovery. Research scientists, armed with the ability to decode the human genome, have a treasure trove of new information at their fingertips.

The new model lends itself more readily to early-stage collaboration as the volume of data is so vast that an “all hands on deck” approach significantly increases the chances of discovering the cause of the disease. Only then can drug developers get to work designing their product.

Astra’s latest collaboration goes beyond early-stage research. It has teamed up with Cancer Research UK and Pfizer to run the first clinical trial in the UK testing several drugs at once.

Normally, patients must enrol for separate clinical trials to try out different drugs, but under the new “Matrix Trial”, lung cancer patients could be supplied with one of 14 drugs supplied by Astra and Pfizer.

Astra may be leading the way on open innovation, but the idea of collaboration is catching on.

This month Boris Johnson, the Mayor of London, launched MedCity, a government-funded initiative to promote collaboration between Britain’s researchers, entrepreneurs and funders.

He hopes increased unity could help the “golden triangle” of London, Oxford and Cambridge steal Boston’s crown as the life science capital of the world.

The centrepiece of AstraZeneca’s transformation, uprooting its research activities and corporate headquarters around the UK to a single site in Cambridge, is also grounded in the idea that knowledge sharing is key to producing innovation.

Astra has already invited scientists from the Medical Research Council into its labs to share basic research, but Soriot hopes informal interactions with other researchers will be as fruitful.

“The more accessible you make yourself to great science by being porous, by encouraging people to flow through your building and by having people in your building, the easier it is for our scientists to have those informal interactions and therefore start new things,” he says.

“We’re saying, 'you know what? We don’t mind if you’re in our labs. We really want to work together.’ That makes us a much more attractive collaborator and it means we give as much as we take. That’s really important.”

He accepts that the logistics will be challenging. Astra employs thousands of people on its research and development site in Cheshire, and at its corporate headquarters in London.

The company will be relocating staff in waves until late 2016. Pangalos will be one of the first to move from Cheshire to Cambridge this year. After all, he’s got to start building those networks.