IDEA Collider | Mene Pangalos, AstraZeneca

https://www.youtube.com/watch?v=AgUJQtQUrEs

IDEA Pharma: A Conversation with Dr. Menelas Pangalos of AstraZeneca

Mike Rea:                          Just a quick note this is Menelas Pangalos, can I have your official title?

Dr. Menelas Pangalos:       I am EVP of Innovative Medicines and early development. I’m at Biotech Unit and also Global Business Development.

Mike Rea:                          Okay, we’ll get on to innovative medicines. This is obviously one of the series of Idea collider interviews with people with actually very interesting thoughts on innovations.

Dr. Menelas Pangalos:       Hopefully. Hopefully interesting.

Mike Rea:                          Definitely interesting and hopefully very useful for the viewers. So, actually let’s starts with our first question, what does AstraZeneca means by innovative medicine?

Dr. Menelas Pangalos:       Yes that's probably the most difficult question because innovation is different things to many people, & I’m sure - I remember when first joined the company & was walking around the site’s; looking at project’s & people were telling me about their innovative programs & they actually - you know, if you think about this as a competitive sport, I think our view of innovation when I first joined was personal best versus world records, And when I think of innovation, I think of world records. You know, you’re cutting edge, the cold face of innovation in terms of whatever area you’re in, whether it’s a technology or whether it’s a therapy area. Disease understanding is actually - you’re making the discoveries rather than following discoveries.

Mike Rea:                          So, that was an almost an internally referenced versus external referenced.

Dr. Menelas Pangalos:       Yeah, so exactly they were very inwardly as an organization we were incredibly inwardly focused & we were getting better internally but when your benchmark is very low, you’re getting better on a very low benchmark actually it’s isn’t getting you anywhere near where you need to be. So, one of the big shifts in our culture which I think is helpful in our innovation is being much more outwardly focused. Seeing what’s happening as a consequence, understanding where we should be pushing ourselves to be even better & who we should be working with to enable us to build on whatever it is that we choose to do.

Mike Rea:                          That’s interesting & the innovative medicines group is focused on forward looking pipeline -?

Dr. Menelas Pangalos:       Yeah, So I run everything from the first target ideation all the way to proof of concept. So, we have to hand over to our latest [inaudible 02:28] organization programs that are ready for phrase III. So, everything from - you know the basic disease understanding – to therefore give you the new targets so you identify & optimizing those programs to generate molecules that are ultimately suitable for phrase III investment. So, there’s therapy area-based research, then we also have our technology platform group to support the therapy areas 

Mike Rea:                          And you’re essentially then combining ways of doing that with choices that you’ve made along the way of which areas to focus on itself.

Dr. Menelas Pangalos:       Choices all the way & one of the things - the big shifts that we made, which actually we made when Pascal joined the company at the end of 2012 is really focus down on the areas where we thought we could be globally competitive or we could be setting world records not personal bests, & so, we really focused organization down on to sort of oncology, cardiovascular, metabolic & renal disease. Which there’s a lot of overlap & than respiratory disease & there’s couple of areas that we not dabbled in but we have small – relatively small investments, less than 5% of our budget goes on there in neuroscience & infections where we tend to pawn all those program with other companies where that’s their core area of competence & where they want to be leading from an innovation perspective.

Mike Rea:                          ok, that’s interesting. So, it’s more like the British Olympic teams approach the winning gold medals. where we can win gold and… 

Dr. Menelas Pangalos:       Go deep & yes, it’s been very interesting because, as we’ve gone deep and as we’ve got more & more focused in those areas. You see that actually you’re starting to build a depth of knowledge & a depth of pipeline that really does make you quite competitive in that space, & the quality of the partnership – you can create the quality of the people who you recruit – the quality of the decision making it all gets better because the commercial organizations also lined up the same way. For me it was like the organization was never all - but I always thought of us as iron filings all going in different directions. When we focus organization on those three core areas, everyone’s thoughts then point in the same direction & they understood, well good looking [inaudible 04:44] 

Mike Rea:                          Yeah, & it’s been interesting. you mentioned when Pascal took over but it seems to be in a purposeful shift at AstraZeneca, because for a long time it wasn’t my favorite company. But this certainly - your publications & the kind of pursuit of a kind of directed improvement Has been clear from the outside. Do you have the room to do that?

Dr. Menelas Pangalos:       Yeah, look I mean - I was hired by the CEO before Pascal joined, a guy called David Brennan who was a super smart guy, very commercially driven. They’ve built a great company with an amazing brand Seroquel, Nexium, Crestor. And what’s interesting is most of those were me too or me better drugs, but nevertheless, very successful in their time & what David realized when he hired me was that the R&D organization wasn’t where it needed to be & they had to try & re-invent themselves & I was the one of the first recruits to try & help with that reinvention. 

Mike Rea:                          What was the first thing that you had to do under that new regime?

Dr. Menelas Pangalos:       Yeah, it was a challenging [blank] - activity wasn’t particularly high so one of the things that I tried to really get the organization bought into reasons why we need to change, to learn from what we’ve done before. So, we looked at all of the projects that were run from 2005 - 2010. We were spending about 5 million dollars a year on R&D. And really trying to look at what differentiated a successful project from a non-successful project. obviously, we had a lot more unsuccessful projects.

Mike Rea:                          What was your definition of successful?

Dr. Menelas Pangalos:       Launch.   your medicine launching or moving into late stage of development at least. But actually, launching is the most important one & looking at what data – what information we have & how programs actually progressed from candidate nomination all the way through to phase III. And what we saw was – actually when we did the analysis, if you measured us by the number of things that we were doing, the numbers of candidates that we’re putting into the clinic or the number of R&D's that we were filing. We were one of the most productive companies in the industry. Secondly only to Pfizer after it had acquired Wyeth. But if you measured us by the number of launches that we had – we were the second least productive company in industry. So clearly there was a disconnect. Our science was getting rewarded, but there were no medicines coming out at the other end & that’s what we had to fix it. 

                                         The take-way message from all of this work was quality over quantity. It’s the quality of what you work on not the quantity of what you do. And then as we dug further there were five things or we call a five R framework that we thought, based on the data that we analyzed would improve your probability of running a successful program and they’re pretty obvious I have to say, pretty intuitive & yet actually quite difficult I think to execute on consistently. 

                                         So, the first of the five R's is around the right target. How well do you understand the biology of the target that you work on? how well do you understand the disease pathophysiology? How it connects – relates to path whether you’re trying to modulate? What genetic validation do you have either in pre-clinical animal models or in human genetics & how do your scientists consequently try to prove or importantly disapprove Your hypothesis. are they asking those killer questions to try and invalidate, not just validate there’s something for hypothesis?

Mike Rea:                          Yeah. So how important is that almost adversarial nature?

Dr. Menelas Pangalos:       It’s really important actually rewarding your scientists for disapproving things as much as approving things & making good decisions – good kills is actually something that we’re very passionate about and very proud about & we celebrate as well.  As I’ll say in a moment the reason why we’re failing now the most is actually because of lack of efficacy in phase II, which means we still don’t understand the targets and the pathways well enough. But we’re getting better, so that’s perhaps the most important of all of the 5 R's.

Mike Rea:                          Okay. I think we talked about this a little bit before that we’ve reframed this role and we're calling it failure; we call the process of early phase – development asymmetric learning. Can you learn faster & better than the other guys?

Dr. Menelas Pangalos:       Exactly.

Mike Rea:                          And if you call it learning it’s not trying to failing anymore.

Dr. Menelas Pangalos:       It’s exactly right & making sure that you fail, you haven’t spent too much money & you don’t just keep on - cause what we were very good at what we saw as we had – our science was very creative. Finding ways of getting to the next hurdle & just for the sake of getting the next hurdle, cause that’s where we're being measured on. So right target, second one right issue. When you have a molecule whether it’s a monoclonal antibody or small molecule or the drug modality, demonstrate first of all in the preclinical models that you can engage the target & understand what your PK / PD relationships are. So, understand you’ve got to inhibit a kinase in a tumor? Do you have to inhibit that kinase for 24 hours? Do you have to inhibit it at 50%, 80%, 100%? Really understand what the relationship is in order to generate the efficacy you are after & then even more importantly you have to have a way of measuring that in the clinic. If you can’t demonstrate target engagement in a clinic, we have a big problem, because then if you fail you have no idea if it’s your molecule is cramp or lousy - excuse my French - or if your hypothesis is wrong. So, a good failure is for me is ones who I know have demonstrated target engagement but the molecule didn't work so biology is wrong. Right. And we hardly had any ways of demonstrating proof medicines – so a number of phase II that we were running. where the molecules failed and you asked the question – I remember these first six months in project meeting, so it didn't work – did we engage the target? Did the receptor antagonist get into the brain? If it’s a schizophrenia program and quizzical blank stares from everybody saying - we have no idea. 

Mike Rea:                          Oh, so you weren't learning well. 

Dr. Menelas Pangalos:       So, you weren't learning anything, not well, you weren't learning anything actually because you had no idea why you are failing, so that doesn't happen anymore. The third one is right safety, so again because our scientists were being rewarded for number of candidates, they were remarkably good - working how to lower the doses to the minimum amount, where they now – because they're not measuring target engagement, engaging the target but they still get the candidate through. And what we saw was that when you had early safety signals, they invariably came back to bite you somewhere during early development or even worse later stage development. So, waiting out your safety signals early, making sure you are working on the right series, on the right scaffolds, that you understand both your target-based toxicity and your molecule-based toxicity, really, really important. So, we spent a lot of time developing our safety models. Fourth of the five R's right patient. To find the patient population in which your medicine is most likely to work. Because if It doesn't work in that patient population, it's not going to work on a broader patient population, and we were again very good at going into broad patient populations. What we saw actually was that as the programme moved through the clinic, the commercial organization got into full steam ahead and wanted to go into broader bigger. Of course AstraZeneca was very much a primary cadre of an organization and so what we saw actually in the data was that the scientists were becoming less confident about their projects and the commercial folks were becoming more confident because the big yourselves the number is getting bigger, but you know a 100% of nothing is not a very big number. So that was the other pieces - to find the patient population and do that experiment first and develop it there and then other things will happen. This is not different, advanced for example we have been doing for quite some time, and then finally the last of the 5R’s is right commercial. By right commercial, I don’t mean is it going to be a billion dollar pick yourselves - what I mean is why would anyone want to take or prescribe the medicine and why would anyone want to reimburse it. So, understanding what your comparators need to be, understanding what the standard of care will be in the time frame that you are going to be launching. It’s a very difficult thing to do, often 10 - 15 years ahead but really challenging the teams to think about where that puck will be when the programmes moves through the clinic or when it launches to make sure they are being ruthless about the comparisons they do. This now goes back to the conversation around being outward looking versus inward looking. And then it was interesting, when we submitted the paper for review, one of the comments that came back from one of the reviewer's was - well if you do all of this you need to add a 6th R which is the right culture. Because what you are actually doing is changing the culture of the company and so you need to talk about how it back ships and he was actually, he or she was actually right because as we start to implement  the 5 R's to every governance meeting we have, through  every project review that we do, what you start to see is is the culturing shifting from one where science is being rewarded for just numbers of candidates, to they are being rewarded for proof of mechanism, for proof of concept, for launches, for diagnostic strategies and for publishing great research papers and it has shifted the culture from one that's being very inwardly focused, personal best to one that's outwardly focused, more collaborative and hopefully setting a few world records.

Mike Rea:                          Which is interesting. So, we, did you use incentive structure as a lever or was that a kind of after effect of getting people to focus in the right place?

Dr. Menelas Pangalos:       So the incentives changed and our global incentives in the company actually changed when Pascal joined where we didn't just have R&D incentives, we had incentives around R&D - which were phase 3 investment decisions, launches, phase II starts, and there's assessing of commercial goals which are around the growth drivers of the company which you can land everybody up in oncology, cardiovascular, metabolic, respiratory etc. and then  some financial goals and we were thrust to meet our objectives, we have to get all of these things - not just the R and D ones. So, the whole organizations actually got very well lined up. But for us the things that we rewarded scientists on were:- the quality of the work they were doing, so these good kills, or good moving forward in a CD package, coming forward you know a lot less candidates coming forward every year than we ever had, we were no longer the most prolific, but the quality was much higher and the teams had to be able to cover every aspect of the programme including what the developing plan looks like going forward to proof of concept. And then the successes, their rewards came and they demonstrated proof of mechanism, demonstrated proof of concept, when they get the phase III investment decision because I don't get to decide what goes into phase III, someone else has to put that through and so that you can’t game the system in that way.

Mike Rea:                          Yes. Interesting. We have always quoted the Brazil Germany World Cup final, cause as you look at the goals, clearly very big divide, but actually Brazil won the game on all of the surrogate metrics. They shot some goals, shot some targets, possession Brazil won.  

Dr. Menelas Pangalos:       But the goals count. Launching drugs count. So, the launching drugs counts and of course the challenges is, when you are in a research team launching a drug somewhere away. We were lucky that we had a few drugs that moved quite fast through the whole process. So, people got a sense that we could actually do this and then the other piece that was a very important measure actually for us is actually just the quality of the publications coming out of the organization. And if you look at where we were, I had an organization of about 5000 people when I joined and we were publishing about 200 papers and one nature or science paper. Today we are half that size, we are about 2500 people, we are publishing between 40 - 50 nature science sell papers a year. So even those, and of course when I first joined it was impossible, you couldn’t do drug discovery and good science, now it’s part of our DNA.

Mike Rea:                          It’s all the same thing.

Dr. Menelas Pangalos:       Yeah and people don't even question that, and of course what happens as a consequence of doing it is, people want to come and work with you, whether it is an academic collaborator, whether it is Biotech or whether it’s someone who actually wants to be a part of AstraZeneca. 

Mike Rea:                          Of course 

Dr. Menelas Pangalos:       So it’s made a huge shift to us and of course our move down to Cambridge is all part of that shift, it’s part of being close to an academic hotbed where there is amazing science because we have become much more open than we ever were, which for me again it’s part of my DNA in terms of being collaborative. Being collaborative in Cambridge is really, really easy because there is so many people you can collaborate with. And of course we have Oxford, London in our doorstep and the rest of the UK and the rest of the world, we have tried to join UK and Sweden together to try and create a European hub and the partnerships we have now which when we have many and some quite unusual, we actually have AstraZeneca scientists work in the same lab as an academic scientist, shared goals and they are working on basic research as well as drug discovery programs. It’s made us much, much more porous than we have ever been.

Mike Rea:                          The thing I mentioned to you before was, we have been doing the pharmaceutical innovation index for 9 years now. And if you look where AstraZeneca started to where Astra Zeneca came number 1 this year. It’s been a rapid turnaround. I think because all the things that you recognize and our index measures, did you launch and did you launch successfully? Did you get reimbursement?  So clearly you have gone from that period when you were doing a lot of internal R&D anywhere to suddenly getting somewhere.

Dr. Menelas Pangalos:       And it’s been - the wins are important. Celebrating the wins when you get them is actually one of the things that galvanized the organization. But you know, I think that are the three key things, being really focused on high quality science, being really collaborative and open, and then executing flawlessly when it comes to moving through the pipeline and launching.

Mike Rea:                          When you said, you came up with the five R’s. Was that a process to come up with or were those the five things that mattered the most or did you go in with -?

Dr. Menelas Pangalos:       No actually look, you know Pfizer had published their three pillars,  these things are very intuitive and most interesting is people ask me about - because these are you know, they're bleeding obvious, you’d think everybody would do it, people ask me - why do you publish this, because it’s like a trade secret. They're not! Everybody should be doing this and I think many companies do, but Actually many companies don’t and when I ask people that join us from other companies about what's different about the way that we do it versus others, it’s that we really do practice this. I don't let well not I; we don't let programs come forward if the odds don't look good, and if they do come forward with a gap, let’s say we’re not sure about right safety, we have a question mark about whether we’re going to have the right dose versus safety liability. It’s the first question we ask in the clinic. So, do you really understand the proof of mechanism, the PKPD and workout the margins, so it really focuses the attention is you understand where your liabilities are in a program to go there first and workout whether you can flip a red to an amber or green – 

Mike Rea:                          So, it’s okay to go at risk as long as you – 

Dr. Menelas Pangalos:       As long as you know what the risk is and you're very clear about what the killer experiment is.

Mike Rea:                          Hoping it’s not there.

Dr. Menelas Pangalos:       Yeah and then of course the first few years projects will come and you say no once, you say no twice, you take teams through it and teams change their behavior.

Mike Rea:                          Oh, you do mean it?

Dr. Menelas Pangalos:       Yeah, yeah. Doesn’t make a difference. It’s kind of important, right. There's got to be some tease to it.

Mike Rea:                          So, is there a definition of innovation at AstraZeneca? Because one of the things we always find is that everyone has a different approach to what it is and what it means.

Dr. Menelas Pangalos:       As I said earlier, it means so many things to different groups. So, for my precision medicine group, innovation would be developing the first plug-based DNA test for EGFO - it’s very different to my oncology therapy, it should be looking to identify a new target or pathway and get the first molecules or the first crystal structure that target with the molecule. So I think innovation really is different things to different groups, I think as I said earlier the most important thing is that whatever we choose to do and whichever areas we’re focusing, whether its Crispr or whether its Protacs or whether it’s a new – some other drug modanity or something around new safety models that improve our prediction, that we are aware of what's out there, so we’re not re-inventing the wheel. We’re working with the very best people and we’re pushing the boundaries of science so that when hopefully we’ve cracked something, when we publish it, people aren't saying ‘so what’. I’d really like us to be viewed as driving science forwards and not just helping ourselves but actually helping the fields that we work in also get better at what they do, and that culture piece is really important because it’s one of the things that I think can make us a little bit different. When we moved to Cambridge, our new building in Cambridge is right in the Addenbrookes campus, the Addenbrookes hospital, its next to the Papworth hospital and then on the other side we’re opposite the laboratory for microbiology, the MRC microbiology. More Nobel laureates than any other institution in the world and an incredibly, if you want high powered science that's one of the places to go in the world and I was talking to John Savalo at the time, he was the CEO of the MR center, ‘wouldn’t it be great, given that we’re going to be in Cambridge to see if we can start working with the MRC, with the LMB’ and so we put a small pot of money together that we co funded and I went and saw Hugh Pelham who was the director at the time and I said, let’s try and do something and of course his natural first inclination was well you know, we’re all very, very smart and you're from industry and we don't want you to suck our brains dry and us get nothing back. Which I think is – I think pharma has moved on a long way over the past few years but I think still in some circles the [inaudible 23:55] of what we do and how we work – and so we worked really, really hard to build a strong relationship with the LMB and to actually make it a very easy way to get – we created this pot of money that basically PI’s from AZ and the LMB, to come and apply for, and they can get a post doc and it’s a two pager and it would be very, very quick and easy and not bureaucratic and Hugh and myself would review this and we’d say yes or no. Based on the quality of the science.

Mike Rea:                          Together?

Dr. Menelas Pangalos:       Together, we did it together. And it was – of course the first round was not particularly well subscribed but today we work with more than half the PI’s in the LMB, collaboratively, and they get back as much as – because they can see that we can do things, we can create molecules for them, we have certain capabilities and technologies that they don't have access to, but more importantly there's actually a lot of overlap in terms of our common interest. And so, when you put us both together, we actually get more powerful because we’re obviously quite plad in our thinking, they're quite basic in their thinking, we put it together and actually magic happens, and we've got some amazing stuff that's going on working with them. 

Mike Rea:                          Which is an interesting – I think your comfort with ‘open’ is an interesting differentiator for you in that way that you described this long-term approach, proof of concept if you like of going in. Have you found it easy to have your scientists behave the right way in the collaboration?

Dr. Menelas Pangalos:       It’s been an evolution right, because initially we were incredibly closed. We didn't want to share anything. Everything was proprietary and you just do it in baby chunks and you chip away, you chip away and eventually people get comfortable and there's many examples, of course we had to do it – because if you think of where we were and having to try and change the culture quickly, one of the best ways of changing the culture is actually bringing external scientists in that can show you what world records they'd make. 

So for example, we did another collaboration with the MRC, we made lots of our molecules, clinical molecules available to MRC scientists to try and find new indications for which then spurred the - NCATs was happening as well, and we’re one of the companies that has the most molecules, both clinical and preclinical in those types of things, you know when we set up the bio park in [inaudible 26:17], park, we had this huge site that was half empty and I used to wander through the corridors going from one group to the other and there would be those empty laboratories, they used to call it tumbleweed labs where you could hear the winds rushing through and it was a demoralizer and from the era when everyone was investing in bricks and infrastructure, bricks and mortar and infrastructure, because they thought they could just industrialize R&D and find out the very hard way that you couldn't, so then the organization shrank and we had these huge buildings. And so, what we did was we said – lets collapse our footprint on the building and let’s bring biotech’s in. So that was actually our first bio park and in contrast to other bio park cities, let’s not have the biotech’s that come in partitioned and walled off. Let’s have them using our cafeteria, our coffee shops, our shared spaces, let’s have them potentially using our equipment if they want to, so they have to buy capital, and we can really try and share our infrastructure, make ourselves good partners, help give them advice when they need it, if they need some regulatory advice some clinical advice, without asking for anything in return, it does start to encourage biotech’s to come in, it makes us again start to forge relationships with other companies and probably most importantly it starts to fill the space up and make you feel vibrant and energetic and full.

Mike Rea:                          Which is an interestingly human approach – there's this great book called Obliquity which talks about getting what you want but approaching it in an oblique way and you're described a lot of internal and external signals about your readiness to embrace the future instead of the past. How important is that -?

Dr. Menelas Pangalos:       And treat people like grown-ups, the other thing is treating people like grown-ups, because again when we first set this up they were like – what do you mean they're going to be wandering around – everyone signs a CDA, if they don't follow what they should be doing they’ll get kicked off the side, so I think if we go in with the assumption that everybody is going to behave themselves and actually follow the appropriate principles, then actually you're pretty safe. You don’t have to have barriers and passes and everything else, and actually we’ve done it in Boston, in Wharton and actually created – we had a half empty building in Boston which is now packed and actually has a waiting list for biotech’s to come in and in Gothenburg as well. Now in Cambridge it’s a little bit different because we’re already in the middle of the biotech cluster so it’s a little bit less important, but for those sites it’s a little bit more isolated and not right in the midst in Kendall square or not in England for example, in Sweden. It makes quite a big difference having this sort of vibrant environment. 

Mike Rea:                          Kendall Square has almost become a hiring hub rather than an innovation spreading hub, because people aren’t necessarily collaborating there, just hiring the folks from – 

Dr. Menelas Pangalos:       Well the nice thing about this – what I find about us being in Cambridge is you know–  you go to a coffee shop or you drop your kids off into school, and you bump into someone, happens to be a hematologist who has just come over, is working and you can start to talk about things that we couldn’t talk about when we were in Cheshire, because the environment is just different. So, it’s actually amazing, how many collaborations and relationships have been initiated through these informal connections. So one of the things that I've been trying to do over the years is try and generate as many opportunities for our scientists to have informal connections, whether it’s with people in the bio houses where the collaborators were, you're just making it easier for the serendipitous to happen and then again innovation can happen.

Mike Rea:                          Yeah planning for serendipity. Absolutely. So, one of the things that's been apparent from the outside is the way that you've approached innovation as an active process and five hours is a very good illustration of that. Do you measure it year on year?

Dr. Menelas Pangalos:       So, we measure lots of things. I have got a great portfolio management group. I measure it but don’t necessarily incentivize on it. So, I think we measure how many proof of mechanisms we have done, we measure our proof of concepts, so obviously we get rewarded for things like phase III investment decisions and launches. We measure how many publications are coming out, from which groups. But I try not to get to, we tend to do - first full three-year holding averages, so no one is ever pressured into doing something in one year and getting a number. And actually, the focus really is on the quality of what people are doing, and how innovative is it, how inventive is it. Is it going to lead to hopefully to break through in the therapy area in terms of capability?

Mike Rea:                          So, you have got trendlines rather than timelines.

Dr. Menelas Pangalos:       Yeah so, we are quite careful about that because I just think it drives the wrong behavior if you are not careful.

Mike Rea:                          Right, People start gaming whatever they are given as a target.

Dr. Menelas Pangalos:       Sounds so brilliant doing that. You know you give whatever target you give them they are good at hitting them. Again, the CD one, it’s amazing what behave - in 2005 - 2010 period, because there were [inaudible 31:30] the number of backups we had in the pipeline. Backup number 1,2,3,4,5,6,7, then of course all the backups had exactly the same probability as the lead molecule. So, we don’t do backups anymore.

Mike Rea:                          Right, I remember sitting in Sweden once, listening to the team saying that it doesn’t matter if this one doesn’t work because you have got a backup - how does that not matter? Just because you are in a job for another couple of years, but - 

Dr. Menelas Pangalos:       Exactly right. Now unless it’s a really, really important program they know they are going to get one shot so they've got the time, they have got to work out the quality of the molecules versus taking a bit more time to get rid of a few more of the work. So, it’s a real balancing acta and for some plans we will have backups, but they are unusual. Less than 5% of our pipeline now has backups.  

Mike Rea:                          Interesting times, and what’s been the biggest learning for you as a director of all of this activity over the period?

Dr. Menelas Pangalos:       You know I've worked in different companies now, there's not a lot I would have done differently. I have seen Wyeth go through - before it was acquired by Pfizer, go through relatively similar transformations of what [inaudible 32:45] said of R&D, time was much more focused on a number of things. But he had a leadership team that was very passionate about science. And so, we were all very much focused on the quality of the science. I think the biggest piece is celebrating the wins, but also celebrating the good failures and then exemplifying them - constantly exemplifying the individuals, teams, projects. You know we were lucky that we had to grow in [inaudible 33:15] in particular, which came from our teams in Orderly Park actually which went from – you know we put the resources behind it and there was a new generation when I arrived and we moved it in the CD and then it went from CD to launch and in about three years, now that was a brilliant thing to have coming along because it was an example of what you can do.  And of course having a quick win, that also made the organization feel better about itself, Limpasa which was written off, we resurrected and brought back to line, even though we’ve never really stopped working on it and the Imed, when Pascal joined me asking me why is this not in phase III, suddenly pumped everyone's chest up and then everything we’ve been doing at Astra has been about rebuilding and then [inaudible 34:04] really well your artistic molecule. So, there's lot of really cool stuff in every area that we’re working in, of course that makes it easier to walk on and keep going. 

Mike Rea:                          So, with what you described sounds like the early stage of an exponential growth rather than just seeing the results - 

Dr. Menelas Pangalos:       I hope so. So, the other piece I love about our company is I think we are a humble company, starting with Pascal and his leadership team all the way through our leaders and our scientist. You know once we got better, I think - I have said this to you previously, we are still failing 80% of the time. Right so we have got lots of room for improvement and very few companies that have been able to continuously in 5 years cycles continue to be at the top end of the productivity chart. So, we have had a good 5 years. That is one set of 5 years so for me the huge chance is making sure we continue to do this. So, the pipeline continues to fuel new launches and new medicines, that No one in the organization gets complaced in any way- shape or form. They remain humble collaborative, open and porous to ideas whether they are from inside or outside.

Mike Rea:                          Which has been an interesting characterization of the change I think and having that humility seems – adds more to AstraZeneca, in my external perception to where it is today. So, what drives you personally in this space?

Dr. Menelas Pangalos:       I have always been - it’s difficult now not to think of myself as a leader, but I always used to get really upset when people called me a line manager or a leader versus scientist. I'm a scientist first and foremost. I get excited about seeing people’s data. Not the bullet points from the power points, the actual data. The graphs the – 

Mike Rea:                          And a scientist in your approach to the day job as well, I guess.

Dr. Menelas Pangalos:       There's a keenness, so I still have a couple of students and I don't spend anywhere near enough time with them but I’ve tried to keep my academic links, but more importantly it’s just to encouraging science, constantly encouraging science, constantly speaking to our scientists. Going and seeing their projects, seeing them present their posters, seeing and encouraging the next generation of science and scientist just to come through. To me that's the first driver is just the quality of the science and being an organization that you can say and be really proud is doing good science. 

Second one is about being collaborative. I’ve always been quite collaborative by nature and I get irritated actually by people that hoard data or think that they can't share things and so – 

Mike Rea:                          Yeah, I’ve noticed cause you're active on twitter too that that's – how do you feel about that as a collaborative exchange.

Dr. Menelas Pangalos:       It’s good so we’ve got this new thing called Workplace which is a spinoff from Facebook and its actually working really well, where you can start to post – so someone will post a bit of scientific data and then you can ask questions and you can generate – Twitter is a great place for – I see it more for news and getting people’s opinions on things that are coming out., particularly if they're from outside of AZ. But this being open to ideas wherever they come from and being porous and you can talk about being collaborative and then you can be collaborative and I really want it to be collaborative. So, I am probably being too open rather than less open. If I ever have to choose if it works for us, I think the risks are relatively small and the upside is huge. And then – there is two things, and then the other piece that I'm incredibly passionate about which – actually Katherine in the room here, was an example is developing our talent. So really I’ve seen it happen all through my career actually as I’ve grown through the industry, but surrounding yourself with people that are smarter than you are, but also pulling people up more rapidly, and I kind of think about my career journey and I’ve been lucky to have some managers that were quite – leaders that were prepared to take risks on me and sort of propelled me up the line, probably more quickly than I was ever expecting, not probably, a lot more than I was ever expecting, but some people getting there – you're sure about that? And I kind of have this same conversation with my leaders and their leaders about take risks on people. If you haven't got people in places that are a little bit uncomfortable and really pushing themselves and finding out they can really swim versus sign, you'll never accelerate people’s careers. So that's something that we spend quite a little time, with my team and their team. So, I spend a little time doing talent development and really trying to pull out the bright sparks faster than they would otherwise have moved

Mike Rea:                          That's interesting. I’m going to ask Katherine; do we have two more minutes? I'm going do the 2-minute timeline. 

Okay so, within a spurt of a 2-minute rule, so what – you clearly read a lot, what books do you go back to as your core – which books do you recommend?

Dr. Menelas Pangalos:       So, the one that's probably closest to my heart from a heartstring’s perspective is probably Roy Vagelos’s autobiography around Science, Medicine and Merck.

Mike Rea:                          That was a great period.

Dr. Menelas Pangalos:       And for me he was – apart from [inaudible 40:04] obviously a Greek heritage like I am, I’ve never had a scientist in my family, so reading his – I just read his book and it was just amazing what he did and Merck for me, as you know I was doing my PhD, that was the prototypical, what a great R&D organization looks like and I actually did a PhD that was sponsored by them and Roy was like a hero. He was one of the first science led CEO’s and he took a company and really to me he epitomized the science at organizations and so – that's probably one of my favorite discovery books that I read in kind of a – I’ve never actually met him, but I would love to meet him and I just think he did an amazing job and actually it so happened when Merck lost that science focus – they got it back now and I think it made a huge difference, that for me has been one of my guiding lights. All through my career. And then when I was at Wyeth actually I met Bill George for the first time and we’ve met him – I’ve been at AstraZeneca a few times, he’s written a book called Discover your True North and that's about what are your guiding principles, what are your true norths and sticking to them, well actually not sticking to them, knowing what they are so you can stick to them and that has been something that again I have used, when I first joined the company I wrote down my list of four or five things that were the most important things for me, but I never should have talked about over the past few minutes and sticking to those principles and not ever letting them go, because they're what define you, and have been really important.

Mike Rea:                          Fantastic. And what are your ambitions for the next five years?

Dr. Menelas Pangalos:       To do this. I think we have the best jobs in the world honestly. Scientists in the organization, we’re able to turn science into medicine and really see the impact of what we do and for me, I’ve completed part one of my journey at AstraZeneca, we now need to show that we can do it again, and that we can hopefully improve even further. It was something that we can continue through, I want to just keep doing that, I love doing what I'm doing.

Mike Rea:                          Fantastic, and one thing that you wished that I’d ask you that I haven't asked you. That's the last question.

Dr. Menelas Pangalos:       How do you relax? As I'm sure you know, you know from speaking to – these are pretty intense jobs, and so my family probably are the thing that brings me down to earth and you're talking about your kid being a guitarist, my kids they're young, they're nine and ten, my wife’s a scientist but they're all very good at when I come home to making me silly daddy and just bringing me completely down to earth and I find that the most relaxing thing out there, being with my family.

Mike Rea:                          Excellent, well thank you so much and I know there's a thousand questions I could have continued to ask you. Hopefully we’ll get to do it again. Thanks. 

Dr. Menelas Pangalos:       Thank you very much.