AstraZeneca PLC (AZN) Earnings Call Transcript & Summary

Ladies and gentlemen, welcome to the AstraZeneca Annual General Meeting 2022. Before we begin today's meeting, please listen carefully to this health and safety announcement. In the unlikely event it becomes necessary to evacuate the building, you will hear a continuous sounding of a fire alarm, followed by the verbal evacuation announcement. Please then leave this room via the emergency exits that are clearly marked. Take a moment now to locate the nearest exit to you. Once outside the building, please proceed to the assembly point at St James's Church, Sussex Gardens. As a courtesy to others, please now turn off all mobile phones. Thank you.

Good afternoon, ladies and gentlemen, and thank you for joining us at the Annual General Meeting of AstraZeneca. In addition to those of you in the room, we're joined today by those viewing the meeting online as we are once again webcasting the meeting. I'd like to extend a particularly warm welcome to those who are in the room as this is the first meeting we have been able to hold in person since 2019. In responding to the pandemic, we all had to get used to doing many of our day-to-day activities virtually. Indeed, I would like to pay tribute to my fellow Directors and the support that we received from the IT and other teams at AstraZeneca, who ensured that we were able to continue to carry out the Board's business effectively. Nevertheless, I'm sure you would agree that however good the equipment, there really is no substitute for being able to meet and engage with people in person. I would, therefore, like to introduce my colleagues on the Board who are all with us here today and with whom you may have been able to talk earlier. From next to me here on my left, we have Andreas Rummelt; Diana Layfield; Tony Mok; Nazneen Rahman; Michel Demare; and our Company Secretary, Adrian Kemp; then Pascal Soriot; Aradhana Sarin; Philip Broadley; Sheri McCoy; Marcus Wallenberg; Deborah DiSanzo; and Euan Ashley. Of course, there are a number of new faces on the board since we last met. Michel, Euan and Diana all took part in last year's virtual shareholder event. Michel joined the Board in 2019. He has a great deal of industrial, financial and board-level experience across a range of sectors including science and technology. Despite having to operate virtually, we successfully recruited Euan and Diana during 2020. We're delighted to have the benefit of Euan's scientific achievements and interests and his entrepreneurial experience on the U.S. West Coast, as well as Diana's broad international business experience, expertise in delivering innovation at scale and her passion for life sciences. Two Directors who joined us in 2021. Both did so following our acquisition of rare disease company, Alexion Pharmaceuticals. Aradhana, our new Chief Financial Officer, is a talented successor to Marc Dunoyer, who stood down from the Board to become Chief Executive Officer of Alexion and Chief Strategy Officer, AstraZeneca. Aradhana held the role of Chief Financial Officer at Alexion. I'm grateful to Marc for his significant contribution and the whole Board is pleased he remains a member of the senior executive team. Andreas was a former member of the Alexion Board and has deep knowledge of its rare diseases business and extensive experience of the pharmaceutical industry. Of course, much of the last 2 years has been overshadowed by COVID-19 pandemic, which has so far killed more than 6 million people around the world and more than 90,000 in the last month alone. I'm sure you're all aware of the role that AstraZeneca has played in combating the disease. So far, together with our partners, we have released for supply more than 2.9 billion doses of our Vaxzevria vaccine to more than 180 countries across every continent. We're proud that approximately 2/3 of these doses have gone to low- and lower middle-income countries, including more than 430 million doses delivered to 130 countries through the COVAX facility. To date, our vaccine is estimated to have helped prevent 50 million COVID-19 cases, 5 million hospitalizations and helped save more than 1 million lives. Thank you. Producing a vaccine on this scale has been a mammoth undertaking involving many people from AstraZeneca. And on your behalf, I would like to thank them all. I would also like to thank Michel for his work chairing the Ad Hoc Board Committee on Vaxzevria during 2021. He, together with Deborah, Diana and Nazneen, ensured we were at all -- we were all fully exposed, focused and supported on all matters relating to our vaccine, ranging from safety and efficacy through manufacturing and supply and to reputational matters. As Pascal will outline shortly, we continue to push the boundaries of science to play our full part in combating this dreadful disease. Dreadful, too, have been the images and stories we have all seen from Ukraine. AstraZeneca has a long and proud history of saving and improving lives around the world. We remain committed to doing so. We're all shocked by the invasion of Ukraine and condemn the unprovoked attacks. Our prime concern is for our employees, patients, refugees and all those impacted by this tragedy. In line with our purpose as a health care company, we are doing everything possible to ensure patients can continue to access our essential and life-saving medicines. We have 200 people in our Ukraine team and are providing all practical support possible to ensure their well-being, physical and financial security. That includes providing temporary accommodation for our team members and their families who have fled to neighboring countries. Patients rely on our medicines and it is more urgent than ever that medical supply chains continue to operate, enabling health systems and workers to deliver essential care. We're therefore doing everything we can to ensure an uninterrupted supply of our medicines to all patients in need. That includes patients in Russia, where we are working together with the wider health care community to ensure non-intended consequences of sanctions do not impact the supply of medicines to the patients who need them. So far, as our wider business in Russia is concerned, we are not starting any new clinical trials at this time, have paused enrollment of new patients into existing studies nor are we planning any new investments in Russia. We are actively providing humanitarian support in Ukraine and neighboring countries. Today, we have committed more than $7 million to response efforts, including specialist relief agencies who are working directly with the Ukrainian Ministry of Health and in Poland, all with an aim of providing health care and humanitarian assistance. AstraZeneca themselves, employees themselves, have made donations of more than $500,000, which the company is matching. The challenges we face and changes we see around us can ask difficult questions of us all. In this respect, I believe AstraZeneca has shown and continues to demonstrate what it takes to be successful. First is the ability to move at speed. As the development of COVID-19 vaccine has shown, we have the opportunity to work more quickly if we work smartly and take full advantage of what our people and digital technology have to offer. We also know that no single group or single organization has all the answers. If we are to overcome the major global challenges, such as the climate crisis and the provision of sustainable health care, then business, academia and government must work together. Finally, I referred earlier to AstraZeneca's purpose of pushing the boundaries of science to deliver life-changing medicines. I firmly believe that companies succeed best when they are truly part of the society and when they are driven by their purposes. This is at the heart of how AstraZeneca operates and why I'm also so proud of our relentless pursuit of the delivery of life-saving medicines and our wider contribution to society and the planet. This brings me to my own position. I have now served as your Chair for 10 years. Typically, Non-Executive Directors step down after 9 years' tenure in line with U.K. corporate governance best practice. Last year, the Board asked me to seek reelection at the AGM to lead the Board's oversight of completion and -- of the acquisition of Alexion. Again, this year, the Board asked me to serve as Chair for 1 final year to facilitate succession planning and the transition to a new Chair. I was honored and happy to accept the Board's request, always mindful of my intention to retire from the Board at the end of next year's AGM. Succession planning for the role of Chair is progressing well. The process is being led by Philip Broadley, our Senior Independent Non-Executive Director, and the whole Board is engaged in the process. The company will make an announcement as soon as the process has concluded. I'd now like all of us to turn to our CEO, Pascal Soriot, to provide some more detail about why 2021 was another landmark year for AstraZeneca as we continued on our strong growth trajectory and why our increased confidence in future growth and cash generation allowed us to increase the annualized dividend. I hope you enjoyed that. While this success is down to the efforts of the whole team at AstraZeneca, I'd like to highlight the role played by Pascal and his leadership of the company. On your behalf, I'd like to thank him for what he has done, continue to do and I hope will continue to do in years ahead. Ladies and gentlemen, thank you, and welcome.

Thank you, Leif, and I would like to join you in welcoming you all today for this meeting. Thank you so much for taking the time to join us and for your interest in our company and your ongoing support over so many years. 2021 was indeed a remarkable year for patients, for science and for our company. As you can see here, there are many statistics on this slide that reflects our many achievements, both on the commercial front, R&D front, but also our commitment to people and the planet. Let me just pick a few. First of all, we now have 13 blockbuster medicines. A blockbuster in our industry is defined as a product that can achieve -- that is achieving $1 billion of sales a year, and we have 13 of those and more to come. And the key message here is that, number one, we have a lot to drive our growth over the next number of years. But number two, we are not depending on 1 or 2 large products like some companies do. And then of course, when you lose a large product, you suffer a lot. We have a very diversified portfolio that will carry us for many years to come. We've been very busy, many launches, so that's the second point I would like to make. We have been successful in almost every single one of them. As an example, in U.S. Oncology, we launched 16 -- over the last couple of years, 16 new indications and products and we lead -- we have a leading share in 15 of those. And I was with the sales force -- the Oncology U.S. sales force recently in Las Vegas, they promised they would lead in the 16th one. So we've done very well. And as you can see here, also the R&D team has been extremely busy with a lot of pipeline progressions and regulatory activity. Finally, on the people and planet front, we are very committed to helping patients around the world access our medicines. But also importantly, we're committed to carbon reduction. As you probably know, we have committed to be carbon-neutral by 2025 for owned operations, so-called Scope 1 and 2, and will be carbon-negative by 2030 for the totality of our activities, including supply chain and partners, so Scope 1, 2 and 3. And finally, I don't want to cover the vaccine again, achievement, Leif has covered this very well. The last thing that is not on this slide is that we -- in the middle of all of this, we welcomed more than 4,000 Alexion employees and they've done a great job. Everything is going very well. And in particular, I would like to welcome our new CFO, Aradhana Sarin, who's already made a big impact on the company, and I'm sure will continue doing very well and has been really a great partner for me and for the rest of the executive team. A few words on our so-called value proposition or our strategy, who are we as a company. And for those of you who followed us for the last few years, I'm sure you have a good idea of what we're trying to achieve. First of all, we focus on science and innovation and it translates into one of our fundamental values, which is we follow the science. And so we are innovation- and science-led. And in our recent past, we have also started integrating data and digital tools to further increase or leverage the strengths we have in R&D. The second is, even though we have a broad portfolio, we are focused in a smaller number of therapy areas. And that number has increased, of course, as we grow as a company. But fundamentally, we're focused in Oncology, where a few years ago, we didn't have much. And today, I would say we are one of the leaders in oncology globally. The second is Cardiovascular, Renal and Metabolism. The third is Respiratory & Immunology. And finally, the newcomer, Rare Disease, with our Alexion team in the last 12 months. The third important point or pillar of our strategy is we have a diversified portfolio of products going from primary care all the way to specialty care and even what you might call ultra specialty care in rare diseases. And what is important is that it really again shows you the diversification of our portfolio and it's important because we have to make sure that our company is not dependent on a few products or geographies, which brings me to the next pillar of our strategy, which is we have a very broad geographic footprint. So one country can do well and another one, not so well, and they balance each other. China, for instance, has been driving our growth over the last number of years, as the U.S. and Europe, we are going through a patent cliff period. Now it's China that is facing challenges as we face price pressures on older products and transition to our future of new products. In the meantime, the U.S., Europe, Japan are picking up growth and balancing each other. So it's really kind of a team effort on a global basis, each geography helping each other. And finally, an important, again, part of our strategy is our commitment to people and society. A few words on Alexion. It was really a landmark acquisition because it enabled us to launch into a very important field of medicine, rare diseases. There are many, many rare diseases in the world. They are rare individually, but collectively, they are actually relatively common. And there's very few options, very few solutions for many of those diseases and our commitment is actually, of course, to continue developing products that will help people who suffer from rare diseases. And one of the things we've done over the last few months is bring the AstraZeneca R&D team and the Alexion R&D team together to look at scientific synergies. So an example of this is Alexion has a tremendous knowledge in the complement cascade and we're using this to look for products in -- that could help us with kidney disease and our cardiovascular renal team has been looking at this. On the other hand, AstraZeneca over the last few years has built capabilities in gene editing, CRISPR, also oligonucleotides siRNA, mRNA, and we're using this to help our Alexion colleagues find new products for rare diseases. And we have established 5 projects with the 2 teams working together to identify new products. Another collaboration that we have been working on is bringing those Rare Disease products to more countries around the world. Alexion was very focused on developed countries with a smaller presence in the emerging markets and no presence in China. And we have really, over the last few months, started working on introducing our new -- our Rare Disease products to the Chinese market. We've established a business unit there, a medical team and R&D team, and we are working very hard to bring those products to Chinese patients as quickly as possible. Finally, in the context of this acquisition, we decided to establish a new R&D center in the Cambridge -- Boston, Cambridge, Massachusetts in Kendall Square. And for those of you who may know Cambridge, Boston, you will know Kendall Square is minutes' walk away from prestigious organizations, institutions like the MIT, the Broad Institute, Harvard, obviously, and many others and a large number of biotech companies. And we are moving R&D -- AstraZeneca R&D team there, who is located in the suburb of Boston, in Waltham. We're moving them there in the heart of Cambridge in Boston and also moving the Alexion headquarter from some -- the south of Boston to Cambridge. So very important developments over the last few months. Let me say a few words about Oncology. As I said a minute ago, many years ago, we had a very small presence in oncology. And today, we have a very, very large portfolio. Many products are growing rapidly. Our #1 product actually is Tagrisso, which I'm very proud to say was discovered and developed in this country, in the U.K. Another important product for us is Lynparza that helps patients with ovarian cancer, prostate cancer and a few others, which was also discovered and developed here in the U.K., and many other products that we've been launching over the last few years. Just want to say a few words about one very important newcomer to the Oncology portfolio called Enhertu, and this is a so-called antibody-drug conjugate. It's a specific technology where you combine an antibody with a toxin and you link them with a linker. And essentially, the antibody takes the toxin to the cancer cells, release the toxin in the tumor and kills the cancer cells. And this product has really demonstrated amazing activity in breast cancer so far, but we are developing it also in lung cancer, where we have new data, and a range of other cancers. More recently, we have tested it in so-called HER2 low breast cancer. Breast cancer patients are split into mainly 2 groups, those who are HER2 positive and so those who are HER2 negative. HER2 positive is about 15%, 20% of breast cancer patients. And this is where Roche, over the last 20-some years, has been developing products like Herceptin, pertuzumab, Kadcyla, to improve the treatment of breast cancer. In a study called D-B03, we showed that Enhertu is superior to Kadcyla, which really was a breakthrough finding. And now we have demonstrated it's also active in HER2 low, where the Roche products have not been able to demonstrate activity. We're going to present this data at the ASCO. They are absolutely breakthrough data that will transform the care of breast cancer. And the FDA, on the back of this, gave us a Breakthrough Designation and also a priority review. And we also got a priority review for the data for lung cancer, a smaller indication in HER2-positive lung cancer. So a very important product for our company. Just for you to keep in mind, the Roche products -- Roche portfolio of HER2 products sales about $11 billion, $12 billion a year and this only HER2 group of about 15%, 20% of patients. HER2 low is actually 3x bigger. So really, still quite a lot of growth coming out of this product, which launched very recently. In BioPharmaceuticals, we also made tremendous progress. One product that is not listed here on this slide is Farxiga, but I want to say a few words about it because we initially developed it as an antidiabetic drug, but more recently in the last couple of years, we show a great benefit in heart failure. And even more recently, we showed great benefit in kidney disease. You may know 700 million people in the world suffer from kidney disease, which is the result of hypertension or diabetes, and it's an incredibly common condition in people who get older. It's under-diagnosed simply because there hasn't been a treatment until now. So there was no point diagnosing it and creating anxiety with patients if you didn't have any solution to offer. Farxiga has demonstrated great efficacy, slowing down the progression of the kidney disease and reducing hospitalization and death as a result of kidney disease. So great progress with this product, which in the first quarter of this year, achieved $1 billion sales in the quarter alone. We also launched recently in respiratory disease, Tezspire, which is a TSLP agent for the treatment of asthma. And so far, all the biologic agents that are used for severe asthma are typically reserved for patients who have a so-called high eosinophil level, which is a subgroup of asthma patients. Tezspire is the first biologic agent that will treat all patients regardless of their phenotype or their biomarker status. So again, a great advance in the treatment of severe asthma and we've launched in the U.S. a few weeks -- months ago and it's really going very, very well. Beyond this, we also have a product called Saphnelo for lupus, which was launched in the U.S. and approved in Japan and Europe and is in launch phase everywhere. Finally, I would want to say a few words about 2 products that are important to our Vaccines & Immune Therapies group. One is a Evusheld, a very important product that is a combination of antibodies that were modified to last longer in the body. And we have demonstrated that they protect people for 6 months and we hope that it would protect people for up to 12 months. It's demonstrated an 83% reduction of the risk of infection up to 6 months and we are following up people in the trials to demonstrate that it lasts longer. And this product is -- has been developed to help immunocompromised people. If you have blood cancer or even some tumor cancer patients, or if you have an immune disease, your immune system is likely to be either depressed or actually completely unable to respond to vaccines. So some people get 2 doses, 3 doses, 4 doses of vaccines and they get 0 response. And they are, of course, very exposed through their disease and the fact they don't respond to vaccines. So this product that now has been ordered by a whole -- great number of countries around the world and is in launch phase, has been developed to protect this population, which is a smaller population of people but represents up to 40% of hospitalized patients for COVID in many countries. And the other one is nirsevimab, which is another antibody we developed for the treatment -- the prevention, sorry, of another viral infection called RSV, which affects babies, essentially newborn infants, and has shown a 70% efficacy against hospitalization from respiratory infection due to this respiratory syncytial virus. Finally, as I said a minute ago, we continue working on making this company a great place to work. And one of our priority areas in the last couple of years has been to increase inclusion and diversity across the entire company. And I'm proud to say, from a gender diversity viewpoint, which is what we are able to monitor on a global basis, we are very well positioned relative to many other companies with a great diversity in our senior ranks across the company and certainly working now on many dimensions of diversity in the company. We have been granted, on the low carbon front, we've been granted the Terra Carta Seal by His Royal Highness, Prince Charles. As part of the Sustainable Markets Initiative, we've been granted this seal -- this award for our commitment to reducing carbon emissions. And Prince Charles was also very kind to come and unveil our Cambridge new R&D center, which we call The DISC, last year, which was a key event for us. We started Q1 very well. You may have seen our revenue grew by 60% in the first quarter, and our EPS, our earnings per share grew by 20%. And we have reconfirmed our guidance, which is a high teens growth for our revenue for the year and mid-to-high 20s growth for EPS. And as you can see on the right-hand side of this chart, the growth is well distributed across the various therapy areas, but also the various geographies. As you can see here, Oncology is now 32% of our sales. But you really see a very nice distribution of our sales and that reflects what I told you earlier, which is we're not depending on 1, 2 products. This has been reflected in so-called TSR, total shareholder return, which captures the growth of our share price, but also the dividend that are added to the share price growth. As you can see here, we have over the last 10 years, a TSR of a bit more than 400%, which is well ahead of our peers in the industry, but also well ahead of the average in the FTSE 100. Finally, just in closing, a few words about our 2025 and beyond outlook. We have said that we believe we can grow at low double-digit total revenue until 2025 on a compound growth basis and I think we are well on track to achieve this. And a question for us as a company is how do we retain our status as a growth company. We want to deliver industry-leading growth post 2025. And we are confident we can achieve this. When you look at this chart, we have a very robust life cycle management supporting our existing products and that will fuel their growth for many years to come. The second reason to be confident is we have a very rich pipeline, late stage pipeline, with 60 new molecular entities in Phase III and a large number of NMEs and life cycle management projects in Phase II and III. We continue to build this pipeline through strategic business development as we -- as we communicated over the last few months. And finally, but very importantly, relative to other companies in our industry, we have a very attractive loss of exclusivity profile. Our patent estate is very strong and most of our products are patent-protected against -- beyond 2030. As you know, we had our fair share of patent expiries over the last 5 to 10 years and the future looks much better. As you can see here, we have only a few products losing patent protection before 2030. Lynparza, which will be replaced by a PARP1 inhibitor, which our team in Cambridge is developing, Cambridge U.K. that is, and has even more potential than Lynparza, we believe. The second is Soliris, but as you know, we are transitioning Soliris to Ultomiris. So we have a future for Soliris. Farxiga, we are actually working on combinations that will protect, not totally the product, but slow down the decline. And so really, at the end of the day, the only product of substance that is without a strategy to sustain it longer is Brilinta, which is overall a slightly smaller product. So we truly believe that through this, we can deliver a very strong growth post 2025. So with this, I would like to thank very much all our employees around the world for the great work they are doing building this company and building our pipeline. We'd like to thank the Board for their support over the last number of years. We would not have been able to do what we did without the constant support and encouragement we received from the Board. And in particular, I would like to thank Leif, who's been a fantastic Chairman and a fantastic partner for me. And finally, I would like to thank you all, our shareholders, for your continued support and your patience over the last few years, getting us to this point today. So thank you so much.

Thank you, Pascal. Let's begin then the main business of the meeting. You have now all received the notice of this meeting, which was published to shareholders on 23rd of March, 2022, and have all seen the resolutions that are being proposed. Accordingly, the requisite notice of this meeting has been given. I propose, therefore, that with your consent, the notice of this meeting should be taken as read. Is that agreed?

Yes.

Good. If you'd like to ask a question today, please be ready with your question in a minute. We'd like to take all questions on whatever subject at this point in the meeting. A summary of the resolutions is being displayed now by way of a reminder. We shall start by answering questions that shareholders registered through our website in advance of the meeting to be asked on their behalf. The first question relates to share buybacks. We have been asked whether it would be sensible to initiate a share buyback program to counteract dilution, for example, from share plans. Pascal, perhaps you would like to take this one?

Yes. Thank you, Leif. Great question. And despite the dilution that has taken place over the last couple of years, the share price has grown tremendously. And our capital priorities are really to continue investing in this company and our future, to reduce our debt and strengthen our credit rating. And certainly, our priority is not to do share buybacks. So we can't see share buybacks happen at least in the near- to mid-erm. And -- but of course, everything can always change, but that's not our strategy or our intent at this point.

Thank you, Pascal. We have also been asked about the possibility of undertaking a stock split on our shares listed in Sweden. And Pascal, another one for you, I think, and perhaps not only limited to Sweden there.

Yes. I mean this one -- again, this is, like for the previous question, by the way, I should have added, it's a Board decision. So it's something that the Board will consider on a regular basis. It's not on the plan today, but I must say this is certainly something that could be considered at some point. But again, a discussion with the Board we'll have to have at the appropriate time.

Good. Thank you, Pascal. As you are all aware, we have been unable to hold shareholder meetings in person for the last 2 years. We know how important engagement between shareholders and the Board is. So last year, we held a virtual shareholder engagement event. We received a question asking why shareholders who hold their shares through a brokerage or nominee structure were not able to attend the virtual shareholder engagement event. I can confirm that this was actually not the case and that such shareholders were entitled and able to attend and ask questions. Needless to say, we are very pleased to be able to return to an in-person meeting this year and to meet with shareholders face to face. We shall now move on to the questions from shareholders in the room. There is a question point in the middle here. So please go there now if you have a question. Please state your name before asking your question and please keep your questions brief and to the point. Very good. Questions?

My name is Rachel Mathai. I am from the CAP Campaign in Cambridge. I just want to ask you about the species of animals that you use.

Your Chairman is now at such age that I have a little problem with hearing. Could you just speak up a little, yes?

Okay. My name Rachel Mathai, I am from the CAP Campaign in Cambridge. I wanted to ask you about the species of animals that you use. In the past, you've disclosed the species in any given year. Last year, however, this was not done. Could you tell me the species of animals that you used in 2021 and in what proportions, please?

Okay. Thank you for the question. I think I'll turn to Nazneen here, who is the Chair of our Science Committee and Sustainability Committee. Nazneen?

Thank you, Rachel, for your question. Yes, in previous years, we have, as part of our sustainability report, sometimes highlighted those individual numbers. Some of the years, we've highlighted other things, so we didn't happen to do that in the last report. Certainly, those numbers are available to you if you want them. Broadly speaking, about 90%, just over 90% of those will be rodents, primarily mice, over 80%, and some rats. That's the majority of them. We do have a small proportion, less than 3%, of larger animals, where it's strictly necessary, but always with those principles of using animals as little as possible and only using larger animals where those are dictated as to the regulations.

Okay. Could you specify the larger animals, please?

Well, there's a range of them. I'm happy to share them with you or to view them after, but a very small number and less than 3% will be of these large ones.

I understand that, but if you could just specify what they are.

Well, there's -- I would -- in terms of the individual types of animals, I think if we can talk offline about the individual ones, I haven't got the exact animal species here. But there's no -- anybody who wants them can access that information.

Okay. Second question?

My name is Aran Mathai and I'm also from the CAP Campaign. In your annual report, you state that you used animals in experiments more times in 2021 than you did in 2020. I note that you follow the 3 Rs, replacement, reduction and refinement, of animal testing. But when the numbers don't actually reduce, isn't this just simply industry propaganda?

I think we'll take -- that's a further question on animal -- Nazneen?

Yes. Thank you for your question. Like yourselves, we look forward to a time when we would not have to use any animals at all. And as you know, we very dramatically reduced the number of animals we've used over the last years. We are guided by principles. So in line with those 3 Rs, we replace wherever possible, but where it is necessary in order to have a system that allows us to ensure that the medicines that we're making are safe to use in people, then we follow the guidelines there and use the appropriate systems that we have to do. So that means we're guided by principles, not by quotas. So depending on the numbers of medicines and the types of medicines. And as you've heard, we've very much increased the number of medicines that we've been developing. That may mean from year to year, that there will be changes in that number. So it's fully consistent with the principles by which we use animals, but that can mean there will be fluctuations from year to year.

How come when you deal with something like carbon, you have a set date where you're hoping to completely be net neutral in terms of carbon emissions. But whereas with animals, you don't have a date when you're going to end your use of animals or have specific targets for reduction each year when it comes to the use of animals?

Do you want me to take that?

Go ahead.

Yes. So I think the principles are the same in the sense that -- and what we're doing here is those principles, that we're reducing as fast as we can and we have done a lot of reductions. But primarily, our objective here is to ensure that the medicines that we're making are safe to use in people. And we don't actually set those rules. They are, as you would hope and expect, set externally and very carefully regulated. Every animal we use is justified. And there's new technology happening all the time. A lot of the reasons we've been able to make those reductions is we are able to now have systems that do accurately reflect what's happening in humans. But as yet, still, we haven't got the complete technology that allows us to do those completely to replacement. So we have to be guided by what is possible, but our commitment to it is still the same.

Thank you.

Good afternoon. My name is [ Julian Fernandez ]. At the outset of the virus and the -- coronavirus and the offering of a vaccine, for various reasons, I didn't want an mRNA. And as a shareholder of AstraZeneca, I was obviously quite keen for the AstraZeneca vaccine. When it came to the -- there was quite resistant -- it was quite difficult to get that. I turned up numerous times to appointments and was told the AstraZeneca had run out or it was just a Pfizer that was available. When it came to the booster, I have been denied AstraZeneca vaccine. I've asked various NHS staff and they have been unable to tell me why, other than it just hasn't been made available unless you are immunosuppressed in some way. I feel suppressed in that I don't want an mRNA vaccine booster. I want an AstraZeneca. Could you tell me why AstraZeneca wasn't available or isn't available as a booster?

It's the decision by the U.K. NHS, the government, of course. It's not anything that we have made as a decision. But do you want to speak a little, Pascal, too?

Yes. Actually, in initial phase, I mean the vaccine was widely available. But of course, I suspect some parts of the country may have been undersupply for a reason or another, but it was really widely available. As far as the booster campaign, the government decided to go with a simpler approach with 1 single technology, mRNA. But it actually is possible to have access to our vaccine if you are allergic to mRNA vaccines or if you have a good reason. In fact, tens of thousands of people in the U.K. have received our Vaxzevria, our vaccine as a booster. Different countries did different approaches. There are many countries around the world that use this vaccine as a booster, as a booster to the Chinese vaccines, the mRNA vaccines or even as a booster to Vaxzevria itself. In the U.K., they decided to go with a simpler approach. But again, as I said, you can actually access this vaccine as a booster if your physician believes it's the right thing for you.

The difficulty is that I simply don't want an RNA, an mRNA-based vaccine. I'd rather that contrary to previous questions, I'd rather that it was tested and derived from -- excuse me, from primates, so there is some kind of safety, historically, to the procedure of manufacture. You mentioned it was a government-based decision. Was there a science behind that decision?

Yes. I should have been more specific. When I mean the government, it was a broad definition. As our Chairman just said a minute ago, there's a committee of experts who look at this and decide on a strategy and that's what the government endorses and put in place. And it's actually a mixture of science, but also simplicity of administration. As you can imagine, in a booster campaign, the quantity of vaccines administered is lower. The use of vaccination centers is reduced, it's done at the pharmacy level or the physician level. So it's much easier to have only 1 technology one 1 type of vaccine and use it all the time. So all these factors are taken into account, but there is definitely a scientific decision supporting the choice.

So that means I'm not going to get my booster? If I stick to wanting AstraZeneca, then -- because I'm not a special case patient, I'm not going to be able to get it?

You'd have to discuss it with your physician, to be honest. I can't...

He will say I'm not a special case.

Yes. Well, I mean we don't make those decisions. So you'd have to talk to your physician and your local MP and see what is available in your region.

It's a political decision. Okay.

Okay.

Good afternoon, Chairman, members of the Board. My name is [ Ian Brindle ] and I'm a shareholder. My question relates to the remuneration report. According to an analysis which was conducted by the High Pay Centre and looked at all FTSE 350 companies that disclosed pay ratios for the year 2020, AstraZeneca was among the companies with the 10 highest pay ratios between Chief Exec and the median employee, which was 197:1, and among the companies with the 5 highest pay ratios between the Chief Exec and the employee at the lower quartile, which was 284:1. While these ratios have decreased in 2021 to 162:1 and 240:1, these are still very substantial gaps between the pay of the Chief Exec and the workforce. Is it an objective of the Board to reduce the size of this gap?

I think the best thing we can say on comparisons like that, that they turn out very differently in different countries. And we are a global company. But I think I'll get the rest of the reasoning to our Chairman of the Remuneration Committee, to Michel?

Yes. Thank you, Chairman. I would say, indeed, it is something we monitor. Like the Chairman said, it can be extremely different from one country to the other. On the other side, I think also as a shareholder, you want to make sure that your company is managed by the best CEO that we can find. And for that, we need also to make sure that from a market perspective, we give him a compensation that is in line with what he is expected to receive, taking also into account, for instance, that AstraZeneca is today the largest market capitalization in the U.K. and that we are a global company also competing with U.S. firms, for instance, where you see the compensations are quite different. So it is obviously an element that comes into consideration, but we have at the same time to make sure that we retain our CEO and that we remain competitive compared to our competitors.

Good. Further questions there?

Good afternoon, [ Dennis Bavie ], small shareholder. As a private shareholder, I was reassured by Pascal's statement about the share buybacks because I think that is something that private shareholders are not so keen on. And it's good to know that the money is going into further research, as an ex-research worker myself. I was -- also, the words -- when you've absorbed or merged with Alexion, the words dilution was used, but I can -- there appears to have been no real effect, again, for shareholders, which seems to have gone very, very well. I was originally going to ask about the question of the use of the AstraZeneca vaccine in the U.K., which has already been answered by a previous question and also a discussion I had with Philip Broadley before the meeting. Likewise, you've covered the question of products coming out of protection, which was another point I was going to raise. So I'll just ask, is the world of antibiotics something that is not within our remit? It's obviously something of great concern to the world, the pharmaceutical world in general, although probably not a particularly profitable concern. So do we now have expertise within the wider company for this? Or is it something which we would normally leave to our competitors?

Good. Thank you. It's a question we get fairly regularly. Pascal?

Yes. Maybe quickly, since you asked this -- you mentioned the vaccine. Let me add something, is that we delivered 2.9 billion doses of this vaccine around the world that -- to be developed with our colleagues at Oxford University. So we are, we believe, 1 of the 2 top suppliers of vaccines around the world and has had a huge impact in many countries, especially low-, middle-income countries. This is a great vaccine. It's very effective and it's very easy to use. As it relates to antibiotics, it's not -- I mean it's not only a question of returns, it's mostly a question of focusing on what you do best. You know, in life, we can't try to do everything. We have focused ourselves on a few therapy areas where we believe we can build the best teams and build a great portfolio and we've done that in Oncology. We're doing this in BioPharmaceuticals, in Rare Disease now. And we can't be everywhere, so we chose a few years back to not be in the antibiotic field. I agree with you, it's a -- there's a big unmet need. But in health care, there's so many unmet needs everywhere that you have to pick and choose what you're going to focus on and pick on your best strengths. So we are not in antibiotics and do not plan to be in the antibiotic field for a long time to come because we don't really have any expertise.

Okay. Thank you. It looks like we have 2 candidates.

Good afternoon, Mr. Chairman. [ Monica Redmond ], small shareholder. I've actually got 4 questions. I apologize if anybody thinks I'm repeating this. I've only been a shareholder about a year and I only got the first view of the annual report when I arrived this afternoon. On Page 63 of the annual report, you cover net debt. You virtually doubled it because of your purchase, about which I have no objection, and your goodwill's rocketed. Now has the Board got a time frame for reducing these 2 items to previous levels? How quickly do you write off your goodwill if at all? And when is the debt up for renewal and how can you get rid of it? [indiscernible] was so profitable, I hope this is possible. Question #2, the risk of competition from generics. Having grown up in a surgery, I think 2013 is -- 2030, I apologize, is rather close for expiry of patents, considering the time frame for developing new products and the testing thereof. How does the Board have a view on competition of this nature? A general comment, #3, anti-inflammatories. I understand this is part of your area of expertise. I would point out that osteoarthritis is suffered by most of the world, especially in my age group, and we'd love some help. What's the current state of research, if you're doing anything? And the last one, a bit left field. Much work has been done in China on developing of chemicals from what you might call herbal remedies or natural products. But you don't hear too much about anything going on for a new world flora, especially for the Amazon Rainforest or the more exotic parts of North America. I wondered if the company had any interest in any of this. Obviously, I haven't been able to look at the whole annual report in about an hour.

Well, I think you did quite well. Aradhana, do you want to speak to or does Philip, you want to speak to -- Aradhana, you'll speak to the first question?

Yes. Thank you very much for your questions. And yes, you did really well looking through the annual report. So as you noted, we did take on substantial debt as a result of the acquisition of Alexion. We are committed as part of our capital allocation policy to a strong investment-grade rating. We do have a strong investment-grade rating from both S&P and Moody's and it is our plan to reduce debt over time. We do have debt maturities coming in '23 and '24, but our debt maturities are actually quite long over time. So there's some short-term, some medium-term and some long-term maturities and we think we can manage that level of debt and debt maturity and service that debt very well with the cash flows that we have. Your second question was around goodwill. And again, as you know, as part of the accounting arrangements, when we do any transaction, the value of that is allocated to intangibles and goodwill. Every quarter and every year, we do assess the value of that. We do take intangible amortization through our P&L. So that's something that we assess on a regular basis for all the transactions that we've done. So with that, maybe I'll hand back over to Leif on the generics question.

Good. I think the competition in generics there, Pascal?

I can cover the 3, if you want. The generics, it's absolutely critical for us to renew our portfolio of products. The model in our industry is you have to develop new products because if you don't develop new products, as you pointed out, generics arrive, they replace your product and you basically have no future as a company. In a way, it's a good model because essentially, what society has to do is pay a fair price for innovative medicines for a defined period of time, which is 10 to 15 years. And after that, society benefits from those products at pennies and cents, really, for the rest of time. Got many, many, many things that are now treating cholesterol or hypertension. We forget that hypertension and cholesterol was not very well treated 30 years ago and people were dying of heart attack at age 50. Today, those are well treated for $0.10 a day, sometimes even less than that. So that's the model. But as a company, it means if we don't renew ourselves, we sort of disappear. But you saw what I presented to you a few minutes ago. We have 120 projects being new products or new line extensions, new indications, in our Phase II, Phase III programs. So we are working really hard to replace -- replenish our pipeline constantly. And that's also why we need to be in very important, very critical science centers, in Cambridge in the U.K., in Cambridge in Boston. We're building strong teams. And finally, you have to have strong teams, you also have to spend money and give them money to progress their projects. And our investment in R&D has gone from $3.5 billion a year 7, 8 years ago to almost $10 billion now. And as you probably saw from Q1, we increased R&D spend by 36% in the first quarter, which reflects the arrival, of course, of the Alexion portfolio but also a continued investment in our pipeline. So on that front, I think we are well placed. The anti-inflammatory question, we have 1 product in development, an NGF inhibitor. It's a biologic agent for severe -- for chronic pain that is difficult to manage with traditional medicines. We will know whether it works. We don't know, of course. That's why we do the clinical work. If it works, it will be a very big opportunity for the company and of course, a great help to patients who suffer from chronic pain. The last question about herbal remedies. Same answer as before with antibiotics. You can't be everywhere. Certainly, herbal remedies have a place, I think, in the therapeutic armamentarium. In China, those are used a lot. And we've looked at it in the past, but always concluded we need to focus on what we are good at.

Okay. Good, Pascal. Thank you. I think we had another candidate for a question there.

Hello. [ Kim Turnblad ], a shareholder. I wonder with the Russian aggression taking part in Ukraine, have you pulled back any business doings in Russia? I know you had cooperation with the Russian Sputnik V, with the vaccine. Yes, have you started pulling back or...?

Do you want to take that?

Yes, sure.

You heard me say a few words about that in my speech.

I think I missed that. I was a bit late.

Okay. Okay. Good. Pascal will tell you a little more detail.

Yes. I mean we had a collaboration, collaboration is probably a big word. It was a clinical trial looking at combining those vaccines because Sputnik has been used in a number of countries around the world. And those countries wanted to have data to see whether they could use our vaccine as a booster, which we demonstrated successfully. But it was a very limited effort. As it relates to our activity in Russia, we have indeed stopped -- I mean I think Leif said it, in fact, we stopped our clinical activities. We stopped our investment in Russia. And essentially, what we are doing is supplying medicines. We have an ethical duty, as any pharmaceutical company, to supply medicines that help patients -- life-saving medicines. And so we've reduced our activity there to what is needed to continue supplying medicines to patients in Russia. But also, of course, very much in Ukraine, and we have a team in Ukraine that we've been supporting. We've been supporting refugees in Ukraine and outside of Ukraine. In Poland, we have a big presence in Warsaw, with a few thousand people there who have been amazing. They've opened their doors to those refugees. You probably know, there's 3.5 million refugees in Poland. We've been helping them with free medicines and also with cash donations. So that's really what we have been focusing on.

Hello. [ Peter Lim ], private investor. First of all, congratulations to the Board for rejecting the Pfizer bid that many years ago, those who are still on the Board, and particularly Pascal, thank you. My question is when the Board was presented with the acquisition, what -- whatever criteria you're using, what was the return criteria -- return amount in terms of IRR or discounted cash flow that you approved the acquisition on?

You mean when we -- how did we calculate on the Pfizer?

Yes. No, no, no. Forget about Pfizer, it's done. The Alexion acquisition, what was the criteria that was presented to the Board and...

For Alexion?

Yes.

Okay.

So I mean we have -- or actually, Aradhana was not there. So we have very strong financial metrics, demanding financial metrics, when we consider business development opportunities or acquisitions. And essentially, we always want to cover our cost of capital and more, of course. And what actually drove our decision-making here was that we thought that Alexion was as a company underestimated. We thought the market is underestimating the value of this company because it's underestimating the quality of the team and the quality of the products. That was number one. Number 2 is we thought by bringing them, the 2 companies together, we can create more value. Because in the emerging markets, in China in particular, we thought our AZ organization can help the Alexion team expand usage and distribution of those products, which is happening now. And also, we thought we could create additional values for scientific synergies. People always look at cost savings when they talk about synergies in the merger. We looked at that, of course, but we mostly looked at scientific synergies, just by bringing the 2 teams together, we thought we can produce more products, and that's exactly what we are doing today. So we had all these factors in mind and our internal rate of return was targeted at covering our cost of capital and more. And I think time will show that it will be a very value-accretive acquisition.

So it did reach the hurdle and you're saying you will be shareholder value accretion?

Absolutely, yes. And future will tell, but we believe we can create a lot more value.

I think you saw not so bad signs in the first quarter here, actually. Okay. Good. Thank you for well thought-through questions. Thank you. Are there any more questions I should -- my leader here tells me I should be asking that formally. Are there any more questions? Hearing none, let's now then move to the voting. I'm appointing Equiniti, the company's registrars, to act as scrutineers. As usual, we will be holding a poll vote on all of the resolutions. I hope you have all the polling cards and pens that you were given at the registration. If you have already lodged the proxy form appointing the chair of the meeting as your proxy and you do not wish to change any of your votes, there is no need to complete the polling card. However, if you wish to change any of your votes, you must complete the polling card in respect of every resolution. We expect to announce the results of the votes later today. You've all received the notice of this meeting together with my letter and the circular that explain what is being proposed. This year, there are 13 resolutions on the agenda. And I would like now to put those resolutions to the meeting. In the interest of efficiency, I will not read out each individual resolution. But to remind you, they are being displayed on the screen and they are, of course, also on your polling cards. I put Resolutions 1 to 8, inclusive and Resolution 13 to the meeting as ordinary resolutions. I put Resolutions 9 to 12 inclusive to the meeting as special resolutions. As usual, a separate vote is being proposed in respect of the election or re-election of each Director. Let me now ask Philip Broadley, our Senior Independent Non-Executive Director, to propose the resolution for my own re-election.

Thank you, Leif. I'd like to propose Resolution 5A for the re-election of Leif Johansson.

Thank you, Philip. Please now mark your polling cards to cast your votes. May I remind you then please to take your completed polling cards and post them into one of the polling boxes. You will find the polling boxes at the doors as you leave the room. You can deposit your completed polling cards into any box. The polling boxes are easy to spot, but please don't hesitate to ask if -- any one of the ushers can help you find one. The poll will close 10 minutes after the end of the meeting. We expect, as I said, to announce the results of the voting later today through our regulatory information service and on our website. You have also been given a short questionnaire to seek your views on AGM arrangements. We would be grateful if all shareholders, both online and here, could take time to complete these questionnaires and deposit them in the polling boxes along with your polling cards to guide us for future AGMs. That, ladies and gentlemen, concludes today's business. Thank you for attending the meeting. May I wish you a safe journey home and good day to you.