AstraZeneca PLC (LON:AZN)

Earnings Call: Q4 2016

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Feb 2, 2017

Hello, everyone. I'm Pascal Soriot, CEO of AstraZeneca. Welcome to this full year and Q4 2016 results presentation for our investors and analysts. We are here live in London, and we also have a number of people on the phone and following us on the webcast. For those of you who are online, the presentation can be downloaded from our website. We plan to spend about 45 minutes on the presentation and would like to leave plenty of time for question and answers. As I'm sure you have a number of questions, we have about 1.5 hour together. So if you want to ask questions on the phone, you can get in the queue already now by pressing star 1. There's also an option to ask questions online as part of the webcast. So please turn to Slide 6. This is our usual Slide 2, sorry. This is our usual forward looking statement that you have here. So if we move to Slide 3. I'm very pleased today to be joined by Maude Dunoyer, our CFO Mark Mallon, our Executive Vice President of Global Product and Portfolio Strategy and Sean Boyne, our EVP of Global Medicines Development and our Chief Medical Officer. So if we move to Slide 4, this is the agenda. I'll give you an overview. Mark will cover the growth platforms. The other Mark will cover the financials, shown the pipeline and then we'll close and open for Q and A. Moving to Slide 5. So this is the highlights of the year, and the performance in the quarter and the year was in line with our expectations. Total revenue decline in the year reflected, as expected, the loss of exclusivity for Crestor, but also the lack of U. S. Flumice sales this season and finally, the tail end of the Nexium loss of exclusivity in the United States. So what we call the new AstraZeneca, which we define as the 3 main CRP areas, of course, cancer, cardiovascular, diabetes and respiratory disease, together with the emerging markets grew by 6% in the year and by 6% in the quarter. We look at this AstraZeneca because it reflects really our strategy of focusing on those core CRP areas and, of course, the emerging markets. The emerging markets, in particular, performed well overall, and we delivered an improved performance in the last quarter. And China, in particular, continues to do very, very well. Farxiga and Symbicort are global leaders in their markets in volume market share and doing very well. There was a modest sequential improvement in respiratory quarter to quarter, and we're very pleased with the launch of Bevespi in the U. S. Mark will talk a little bit more about it, but so far, it is going very well. Farxiga is now our largest diabetes medicine, and it continued to grow very rapidly. Marc will talk more about it. And it is globally in volume, again, still the number one SGLT2 medicine. And we believe this class has enormous potential as more data become available. And certainly, 2017 should continue supporting the class and the first figure. Our new start, Tagrisso, reached $423,000,000 in its 1st 12 months. It's quite a very quite a successful launch for an oncology drug in a third line setting in lung cancer, EGFR mutated. And we haven't yet launched in China. This product is being fast tracked from a regulatory approval viewpoint in China, and we hope to be able to launch pretty soon. So very pleased with the difference it's actually making with 2 patients who have EGFR mutated lung cancer around the world and very much in particular in Asia. As you know, 40% to 45% in Asia, 40% to 45% of patients with lung cancer have an EGFR mutation. Our earnings per share was supported by our continued effort on managing SG and A cost, and those declined as we had indicated they would. We'll continue to invest in R and D to support the pipeline, of course. So in 2017, essentially, we'll be starting to annualize the loss of Crestor and finally start seeing the end of this patent cliff that has created enormous headwind for us over the last 4 years. Just as a quick reminder, 2011, out of close to $30,000,000,000 in sales, we had $19,000,000,000 in sales coming from products about to lose patent protection. They have indeed lost patent protection, and they have declined rapidly. By 2018, the great majority of those sales will be gone, and that's what we have had to replace and we'll continue to work to replace. So turning to Page 6. We continue making good progress with the pipeline, as you can see here. Firstly and importantly, we received acceptance of our regulatory submission in the U. S. For durvalumab for bladder cancer. This was and we had, of course, the second one with benralizumab. But importantly, the FDA granted priority review designation to diorvelumab in bladder cancer, and we look forward to hearing from the FDA over the next period of time. For Tagrisso, we also got priority review designation for ORA3 when we submitted the data. This was our 1st randomized Phase III trial for Tagrisso against chemotherapy. We also received acceptance in Europe. And finally, in still in oncology, Faslodex, which, as we all know, is not a new product but has received the support of new data. FasoDEX achieved 2 regulatory submissions acceptances for first line use in the U. S. And in the UK. Moving to cardiovascular and metabolic disease. You can see here that the DURATION 7 study combining valuiran and with basal insulin met its primary endpoint. This is good news and it comes in the wake of the duration 8 data, which we believe will give us a chance to relaunch Farxiga in Badureon as we introduce the new pen and should have a substantial impact hopefully in 2018 in particular. In the respiratory franchise, we filed Benralizumab, and the filing was accepted, both by the FDA and the EU. This was our 2nd BLA after DERVA. And we expect Benralizumab to make a big difference to the treatment of asthma, but also over time COPD. And finally, outside our 3 courtiers, together with our partner Lilly, we progressed another shared molecule, MEDI-eighteen fourteen, which is a more selective amyloid beta antibody. Another good example of the way we actually manage our pipeline and the way we create value in out of our pipelines for partnerships in areas that are not core to the company. Moving to Slide 7. You say here that staying on the topic of turning points, you can see that we are approaching the time where the loss of Crestor exclusivity will ease the comparison and that will happen in the second half of 2017. In 2016, we saw a large impact from losing Crestor in the U. S. And we still saw some remanent impact of Nexium, of course, and Seroquel. On top of it, we had the impact of FluMist sales that we didn't achieve in the season because of the CDC recommendation not to use flu mist in the U. S. During the season. So as we annualize the negative impact of some of these patent expiry, the focus really becomes even stronger on our 3 main CRP areas, as you can see here, oncology, cardiovascular diabetes, respiratory disease, and they are growing quite nicely together. Oncology, in particular, are growing rapidly because of the success of Lynparza, but more importantly, the success of Tagrisso. Soon enough, this will be hopefully complemented with the launch of diorvelumab and also the rollout of the new indications for Faslodex. In CVMD, Brilinta continues to grow. And in fact, we believe that it should be a blockbuster $1,000,000,000 plus next year. In the meantime, we have continued to do a fantastic job from a cost of goods viewpoint, and this product for profitability is starting to look pretty good. In 2017, both Brilinta and Farxiga, actually not only Brilinta, but also Farxiga should be more than $1,000,000,000 And Farxiga experienced very strong growth in 2016. The respiratory business in 2016 had to face price pressure in the U. S. In particular, but also a little bit in Europe that affected Symbicort, as you all know. But as we move into 'seventeen, we should see the impact of launch of Bevespi and later in the year, the launch of benralizumab. And when we add this together with the emerging markets, we had a growth of about 6% for the year. So if you turn to Slide 8. So if you look at the opportunities we have and we focus on the future, we have seen a steady increase in the number of launches from our 3 main CRP areas, of course, Farxiga, Tagrisso, Lynparza, DuraClear. For the coming year, we expect to launch, as you can see here, durvalumab, Q turn, Bevespi, which is already launched and benralizumab in the 2nd part of 2017. On top of this exciting launch schedule, we have quite a rich news flow in 2017, as you see on the right hand side of this chart here. And we'll have new clinical data coming out for Lynparza, Tagrisso. We'll, of course, have the much debated MYSTIC study results. But also, we have additional study results beyond MYSTIC. We'll have data supporting Tagrisso. And in lung cancer, we have a really great opportunity to build a leadership position in lung cancer with Tagrisso and with our IO platform. As far as Mystic, Sean will talk more about it, but we do remain confident about the potential of this study. There's nothing new that we've been exposed to that would change our view of the study here and the potential outcomes. So if we move to the next slide, Slide 9, you can see here that this is why we spend what we spend in R and D. You can see here we have a very strong pipeline and a lot of assets, a lot of opportunities to support our growth from 2018 onwards. And the question is not whether we will return to growth in 2018 or not. The question is what is going to be the slope of the curve, how fast we will grow. And of course, the answer to this is how many of those projects make it and how strong the clinical data are on top. Of course, we have to deliver a good commercial success. But very much, we will know over the next 12 to 18 months how many of those projects turn out to be positive and therefore, we'll have a good sense for the slope of the curve as far as the return to growth is concerned. But post 2018, there's clearly no doubt we should be growing. You can see lots of assets, and you can see also a couple of assets outside our core TAs. 1 is partnered, I've talked about it earlier in Alzheimer disease with Lilly and another one in ifolumab, we are developing ourselves for lupus. Before I hand over to Marc Malon for the growth platform, I'd like to spend one moment to thank all my colleagues around the world, and I know many of them are listening to us. So I'd like to thank you all for the great work you've done. The progress we've achieved here would not have been possible without your great effort and your commitment to this pipeline, making a difference to patients. I was last night in Cambridge celebrating some of our best scientists, and I can tell you we have an incredibly talented and motivated group of scientists in Cambridge, but also in other parts of the world. So with this, I'll stop here and hand over to Marc. Thank you. Thanks, Pascal, and good afternoon, all of you. I'm really pleased to have an opportunity to spend a few moments talking to you about our growth platforms. And so if we turn to Slide 11, we can get started. So our growth platforms have really continued to demonstrate overall growth and success in 2017. And that's despite challenges we faced with respiratory and the biannual price cuts in Japan. The combined revenue of our 6 growth platforms represent now 2 thirds of total revenue, which is an important milestone. And you can see that from the chart that we've got great momentum with Berlinta, with emerging markets. And actually in 2016, emerging markets surpassed Europe in sales for the first time. And then of course, with new oncology, very exciting milestone for us as we're now approaching $1,000,000,000 on an annualized basis on sales from our new oncology products. If we move to Slide 12, I'll just start by saying sorry, what I want to say is I will just touch on briefly emerging markets in Brilinta. What I want to do is spend most of the time together focusing on respiratory, diabetes, Japan and new oncology where I think maybe most of the questions would be. Slide 13. So starting first quickly on emerging markets. We the key message here is we remain on track for our long term growth objective of mid- to high single digits. And in fact, you can see from the chart here, we achieved that both in the Q4 and for the year in emerging markets. And this strong performance in the Q4 was driven by our growth platforms, by Brilinta, by Farxiga and by Respiratory. We're also excited as we move into 2017 that in China, we're looking at potential approvals for both Tagrisso and Farxiga. If we can move to Slide 14. So moving from emerging markets to respiratory. As Pascal alluded to, 2016 was a significantly challenging year for respiratory. Respiratory product sales declined 3% with the main driver of this being Symbicort. Now Symbicort, importantly to remember, continued to maintain volume share leadership in the ICS Lava class. However, product sales were down 10%, and this reflected challenges in both the U. S. And Europe, which I'll touch on in a moment. Importantly, outside of the U. S. And Europe, we saw strong growth in emerging markets and the established rest of the world. So let's talk about the U. S. For a minute. So in the U. S, Super Core product sales declined 18%, but we continue to drive volume growth. We saw significant pricing pressure on the ICS laborer class from managed care and there was also competition from outside the class, particularly especially in COPD. In regards to 2017, we expect the competitive pressure to moderate only slightly this year, with pricing pressure being the strongest in the first half of the year. Moving to Europe. Symbicort product sales in Europe were down by 12%, and we saw continued pressure from both analog competitors and branded competitors. However, this our business stabilized in Europe during the course of the year. And actually, if you look at the overall EU respiratory business, in the Q4, we grew that business, which is very encouraging as we head into 2017. Wrapping up on emerging markets, delivered 10% growth in respiratory with China product sales up 32% in China. So in summary, despite the challenges, Symbicort continues to be the leader in the ICSLABA class in terms of volume share. And we believe that this ability to continue to maintain leadership really bodes well for our new products, VIVESP and benralizumab, which will be our 1st biologics launch in respiratory. I'd also like to point out that we're really pleased that palmacort has returned to blockbuster status and achieved $1,000,000,000 in sales for the second time in the life of this product. Obviously, this being driven by sales largely coming from emerging markets and in particular, China. And we also wanted to highlight that actually AstraZeneca is the number one company in respiratory and emerging markets based on our numbers. Slide 15. I just want to introduce to you BIVESPIE AeroSphere. So we're very excited that as of the 1st week in January, we have now launched BIVESPIE AeroSphere in the U. S. And the initial feedback from physicians is really encouraging and happy to discuss that in the Q and A period. And importantly, we have really good market access for a newly launched product. This is the 1st and only LAMALABA in a pressurized metered dose inhaler. And it's the 1st medicine that's been approved with AstraZeneca and Pearl's unique co suspension delivery technology, AeroSphere. There's no question the LAMA class is gaining momentum supported by a growing body of evidence and the evolving guidelines. But Vespi AeroSphere will differentiate on strong lung function improvement data. And we're going to be building familiarity with this device and technology as we prepare for future products and in particular, our triple, the PT-ten, which could be here in 2019. Moving to Slide 16. In the year, diabetes sales grew by 11%, shifting to diabetes, despite the intense competition that I think you're all aware of. And importantly for us is that we've seen positive growth from all of our regions globally. We continue to focus on the fastest growing classes, which is the SGLT2s and GLP1s as I think you all know. And so let me just walk you through some of the key points in our success. Our diabetes product sales in the U. S. Grew by 5% despite the intense competition, and Europe showed strong growth of 15% in the year, driven by Farxiga. And finally, emerging markets really impressed with a 25% growth across the franchise, again driven by Farxiga. Farxiga continued to lead the SGLT2 class with a 42% share globally in volume terms and is now the number one diabetes medicine at AstraZeneca with product sales of $835,000,000 72% growth. And I think the middle chart is an important one to look at where you see the stability of Farxiga's volume share even in the face of growing competition. Certainly having a product, dollars 800,000,000 product growing 70% in a year is very exciting. Importantly, we are starting to see some further strengthening of the SGLT2 class taking share from the DPP-four, which is something we'll be heavily focusing on in 2017. In the U. S, Farxiga outgrew the SGLT2 class. Product sales increased 75% in the year in the U. S, driven by improved market access. And Farxiga also delivered strong growth in Europe and Emerging Markets. So in summary, on Farxiga, we've got a brand that is rapidly moving towards the $1,000,000,000 mark and along with Brilinta, which I'll come to in a moment, will be 2 new blockbuster medicines for us in 2017. A word on Bydureon. Bydureon delivered a stable product sales performance in 2016, where modest volume growth was offset by price headwinds. We're really excited that we're going to be improving our offering for Bydureon with a new device that will be is currently approaching submission to the regulatory authorities. And we look forward to launching Q turn or our Saksadapa combination fixed dose combination product in Europe and the U. S. Actually, it's now available in the U. K. And as soon as we get approval in the rest of Europe and the U. S, we'll be launching that. Slide 17, please. Just a few words on Japan. So Japan product sales declined by 3%, driven by the mandated biannual price cuts, but we had steady volume growth of about 2%. Our 3 biggest medicines Crestor, Nexium and Symbicort continue to perform well. We did have Crestor sales impacted by some inventory reductions at our local marketing partner. But those products continue to lead the way in their drug classes. And the result of this is that AstraZeneca, if you look at the middle panel there, grew faster than the market again in 2016. We moved up to in the rankings in Japan to 6th largest company, up from 8th in 2015 and actually moved up from 12th in 2012. So I think you can see the competitiveness and the capabilities and the impact that our Japan team is having. This reflects the impact of obviously our lead primary care products, but importantly, the very successful launch of Tagrisso in Japan. We launched Tagrisso in May in Japan, and we now have over 3,000 patients in Japan treated with Tagrisso. Product sales are growing rapidly, as you can see on the chart, with totaling $82,000,000 of sales in 2016. Importantly, couple of other developments that really will help us in 2017. The treatment guidelines for non small cell lung cancer in Japan were updated to support Tregretia use. And in December, we had approval for the T790 blood based test, which will help us drive further identification. Now Japan team has already done a fantastic job with the biopsy based testing, as they have a 70% testing rate for patients that should be getting the test. But getting the blood based test will obviously further enhance the success we are having in Japan in getting this medicine important medicine to the right patients. Slide 18, please. Brilinta. Brilinta delivered product sales of 839,000,000 in the year and has also shown really great growth across all three regions as we head into 2017. The driving we had 45% growth in the U. S. And 15% growth in Europe. Driving that success was changes in competitor labeling in the U. S, a significant increase in hospital discharge in Europe and discharge share. And then we have been rolling out and launching the 60 milligram, and that will continue throughout 2017 as we get reimbursed for that new dose reimbursement for the new dose. We are very optimistic about the future for Brilinta for several reasons. So first of all, we do have strong clinical data in coronary artery disease that is getting more and more well appreciated by the cardiovascular community. The clinical guidelines have been changing steadily towards recognizing the value that Brilinta offers CFD patients. And then often now, we've seen that Brilinta is in a preferred position. There is a growing body, and we will be adding to that, a real world evidence that is reinforcing the results that we saw in our pivotal trials and the benefits that the Brilinta offers to patients with coronary artery disease. And reimbursement and access for Brillinta is good and largely available across the world. Moving to Slide 19. And now turning not last, but let's say excited in an excited way to new oncology. 2016 really has been an exciting year for us. We saw that the new oncology global product sales, which are, for us, we're talking about Lynparza and Trogrisa globally and also sales of ARRESSA in the U. S. Because ARRESSA was just recently launched in 2015. Together, they were $664,000,000 in the year. All of these products have are based on companion diagnostic tests. So this means that we're really going to be able to focus on getting the medicine to the right patient that where the most benefit will be gained. And Tagrisso was focusing specifically on Tagrisso really had a strong uptake in the U. S, Europe and Japan that I already referenced. Global product sales for Tagrisso were 423,000,000 dollars and we've got 46 regulatory approvals. So the rollout of this product globally has been very rapid. Now underlying U. S. Growth slowed relative in the 4th quarter, relative to the 1st few quarters in the U. S. For Tagrisso. And this is because the existing pool of there was an existing pool of T790 patients that was waiting for this treatment. And as those we're now 12 months into that, some of those people will unfortunately be progressing. And obviously, we had that built up demand as we launched the product. But testing rates in the U. S. Are going to continue to grow. We're at about the 50% mark, and we're expecting approval. We'll be leveraging the blood based test to drive that further and the same in Europe. Globally, regarding the blood blaze test, we are our partner is rolling this test out across the globe, and so that's going to support the higher testing rates everywhere. And very exciting as last point for Tagrisso, and Sean will cover this in a moment. We're looking forward to the approval in the U. S. In U of the AURORA 3 study, which has some very exciting data further demonstrating and confirming the huge patient benefit that Tagrisso offers people with non small cell lung cancer and have the T790 mutation. A couple of words on Lynparza, which has also had an exciting year. Full product sales were $218,000,000 and again, we saw growth throughout the year driven by higher testing rates and strong market penetration. I would and in fact, in some markets, including the U. S, we're actually now close to or getting closer to really capturing all the patients that are part of the first indication for Lynparza, the later line ovarian cancer. But I think we need to remember that Lynparza is the pioneer in PARP technology, in PARP inhibitors. We are very committed to expanding and continuing to grow Lynparza. First, we've got the strong ovarian SOLO-two trial data that we'll be leveraging going forward. And then we've got further label expansion trials outside of ovarian cancer. So to conclude, overall, we feel we had solid performance across our growth platforms. And achieving the milestone of 63% of our total business coming from the growth platforms is really encouraging as we head forward. And I think it's important to remember is that we're driving this growth and we without we will be driving this growth and then adding on top of that really an exciting pipeline that Pascal referenced and that now Sean will come up and give you a little bit more detail on. So thanks. Sorry, Mark first, then Sean. Thanks, Marc, and hello, everyone. I'm going to spend the next few minutes to review the performance of 2016, and I will then move on to the guidance for 'seventeen. If you want to turn to Slide 21. In this first slide, we have the reported P and L performance for the year end and for the Q4. While core EPS declined in the year, the 9% increase in reported EPS was mainly driven by a credit with respect to the Diabetes Alliance acquisition, reflecting a revaluation of the contingent consideration. Please turn to Slide 22. Before we get to the core P and L, we have 4 core adjustments that I would like to you to consider. About half of our restructuring cost in the year related to the streamlining of operations and reduction in cost announced in April last year. We anticipate a full year annualized net saving from this program of $1,100,000,000 in 2018, mostly within SG and A. The majority of the $1,300,000,000 of intangible assets amortization was related to the acquisition of MedImmune 10 years ago as well as the legacy agreement with Merck regarding part of our U. S. Business. And as I mentioned a moment ago, you see a credit in the year with respect to Diabetes Alliance acquisition, reflecting the revaluation of the contingent consideration. The $0.17 that you can see here is in fact the net amount between the intangible amortization and the adjustment of the contingent consideration. To remind you, the payment stream of royalties to BMS will expire in 2025. Finally, the $350,000,000 of other adjustment is partly reflected partly reflects various legal provision as well as a discount unwind on the Acerta Pharma option liability. We provide this information because we want to be as transparent as we can. And by showing you the detail of this core adjustment, you can see the value in providing the core as well as the reported performance. If you can now turn to Slide 23. If you look now closely at the core P and L, the total revenue decline of 5% in the year reflected an 8% fall in product sales with the effect of losing exclusivity on Crestor in the United States, particularly impacting the performance in the second half of the year. External revenue increased by 59% to $1,700,000,000 in line with the commitment I gave at the start of the year. Core gross profit declined by 6% in the year, excluding the impact of externalization. The core gross profit declined by 110 basis points to 82%. In the Q4, the core gross profit margin declined by 260 basis points to 79% as we felt the full effect of the loss of Crestor. Core R and D cost grew by 5% in the year and was limited to a 2% increase for the 4th quarter. Core SG and A cost fell by 9% in the year and by a full 14% in the quarter. I will take you through the details in a moment. The majority of other operating income came through in the quarter as we continue to sharpen our focus on our key therapy areas. The core EPS performance was flattered by a nonrecurring benefit of $0.36 resulting from agreement on transfer pricing between various tax authorities. And this benefit help us deliver the core tax rate of 11%. For 2017, I expect a return to a tax rate between 16% 20%. Please turn to Slide 24. As I've said many times, cost discipline is a key focus for the business, and we delivered some real achievement in the year. We did what we said we'd do, and we delivered our commitment and produced the results in line with guidance. This chart illustrate the good progress we have made in the R and D cost on the top of the slide with a 5% increase in the year, reflecting the absorption of cost at ZS Pharma as well as Acerta Pharma. This compared to 21% increase in the previous year. Without ZS Pharma and Acerta Pharma, the core R and D cost would have been declining by 1% in the year. If I look now at the core SG and A cost, the 9% decline reflecting the new AstraZeneca and was driven by efficiency savings in sales and marketing operations, but also further reduction in all general administration areas. These actions included a material reduction in the sales and head office structure in the U. S. Marketing business. Core SG and A cost as a percentage of total revenue fell to 35.5%, a decline of 1 percentage point at CER and 2 points at actual rates. If we turn now to Slide 25. This covers the R and D costs, and you can see that our investment is stabilizing. In line with our commitment to sharpen our focus on our main therapy areas and increase our investment in oncology, we continue to fund the great science in our pipeline. In fact, we have doubled our absolute investment in oncology since 2013, reflecting the exciting opportunity that we have. We anticipate maintaining the overall level of R and D investment, which leads us to anticipate a similar level of core R and D spend for 2017. Please turn to Slide 26. To conclude, I want to confirm our guidance for 2017, which is at constant exchange rates. I expect a low to mid single digit percentage decline in total revenue, and core EPS is anticipated to decline by low to mid teens percentage. All of this is subject to our base case assumptions of the progression of the pipeline and the news flow that Sean will take you through in a moment. Variation in performance between quarters can be expected to continue with year on year comparison expected to ease in the second half as we begin to annualize the impact from Cresco. Outside of guidance, the total of external revenue and other operating income is expected to be ahead of that in 2016. Sustainable and ongoing income is expected to increase as a proportion of exchange revenue in 2017 and beyond. As I mentioned a moment ago, we anticipate core R and D costs to be broadly in line with 2016, and we plan to make further reduction in the core SG and A cost. Finally, I want to reconfirm our capital allocation priorities. These are unchanged. We will continue to strike a balance between the interest of business, our financial creditors and our shareholders. After providing for investment in the business, supporting the progressive dividend policy and maintaining our strong investment grade credit ratings, we'll keep under review any potential investment in value enhancing and immediately earning accretive opportunities. Thank you for listening, and I will now hand over to Sean. Thank you, Mark, and thank you all for joining us both here and online. It's a great pleasure to be able to share with you our encouraging progress since our last update. And I would like to emphasize that we're very confident in the molecules and the medicines and the trials underlying our pipeline and very enthusiastic about what this year has to bring as was evidenced by the fact that Mark Mallon wanted to forego Mark Donier's time to do the financial results presentation of the year end results and give that to me. So I appreciate that. If we could go on to Slide 28, please. This slide shows you looking back at Q4 in 2016, our main pipeline highlights from the therapy areas that we focus on. So I'd like to start with oncology. Obviously, we're very proud of the U. S. Regulatory submission acceptance of durvalumab in bladder cancer. This is the first ever BLA application for AstraZeneca. And FDA, as we had announced, did awarded a priority review designation. So we expect a regulatory decision under valumab and bladder cancer in Q2 of this year. As Pascal alluded to, the work that people are doing within the company, this the time from data availability to filing was absolutely heroic in this case. So I too would like to thank all of the people who dedicate themselves to bringing our medicines to patients. We also have U. S. And EU regulatory submission acceptances for Tagrisso on ORA3, I'll spend a moment on ORA3, we shared that data in December, I'll spend a moment on that data coming up. That also received a priority review designation from the US FDA. We had regulatory submission acceptances for Faslodex in the US and EU that in first line breast cancer. In CVMD, we have the duration 7 trial that PASCAL met its primary endpoint showing glucose lowering. In this case, that is by durian plus basal insulin versus basal insulin alone and showing a reduction in hemoglobin A1C. That follows on to the positive duration 8 data that we shared earlier in the year, the publication of that came out in The Lancet in December. And that showed the effects of Bydureon plus Farxiga similarly on hemoglobin A1c lowering and also if you look at that publication, some interesting impact on body weight and decreased body weight. FibroGen initiated the rolling regulatory submission for our anemia medicine roxadustat in China. In the respiratory portfolio, Symbicort was approved in younger patients, those between 12 18 years of age. As has been mentioned, benralizumab, our 2nd BLA, was the submission was accepted in the United States and in the EU for severe uncontrolled asthma. And the alliance with Lilly and Alzheimer's disease was expanded beyond our current Phase 3 collaboration of the base inhibitor to include an amyloid beta monoclonal antibody. Now, if we can go on to Slide 29, please. So we have also in recent times with all of this data, been highly visible at conferences and congresses and we're highlighting some of those here at the American Society of Hematology. Acalabrutinib data was shared from ACERTA in 2 interesting patient populations, patients with CLL who are ibrutinib intolerant and also those who have a Richter's transformation, whose CLL turns into aggressive lymphoma. At the San Antonio Breast Cancer Symposium, we shared the data from the FALCON trial of Faslodex in the first line setting in breast cancer. This is what enabled the filings that I mentioned. And then at the World Conference on Lung Cancer, we shared the durvalumab data from the ATLANTIC trial and then also highlighted Tagrisso's OR3 data in second line EGFR mutated lung cancer with the T790M resistance mutation after having received the 1st generation EGFR inhibitors. So let's go to slide 30, please. So this is that data. And it's, I think, very exciting, quite extraordinary. So what we have here is Kaplan Meier curve, progression free survival, you'll see here that the median progression free survival here was 10.1 months with Tagrisso versus 4.4 months with chemotherapy, which is the current standard of care for EGFR mutated patients who progress after an EGFR inhibitor. The hazard ratio here is quite remarkable at 0 point 3 and obviously statistically significant as well. The other thing I think that's fascinating about Tagrisso and was shared there is, we did not exclude CNS patients from this trial. So mid-30s, about 34% of patients had CNS disease, brain metastases on entry to the trial. Interestingly, their progression that's usually a poor prognostic factor, I should add. Their progression free survival hazard ratio was 0.32, very comparable to the patient population as a whole. And this property of Tagrisso to be able to penetrate the blood brain barrier, which by the way, the 1st generation EGFR inhibitors are not able to do, is continuing to be studied in the ongoing BLOOM trial. Let's go on to Slide 31, please. Moving on to a topic that I think is probably near and dear to all your hearts, which is the immuno oncology portfolio. This is an overview of our lung cancer program, both ongoing program, you will know quite a bit about and some recent changes and additions we've made. Obviously, we have multiple trials in earlier Lyme lung cancer. This remains an unmet need, a terrible disease and a reasonably common cancer. The PACIFIC and the MYSTIC trials are fully recruited. And as we've communicated, we expect top line results for progression free survival this year. We've also communicated that the mystic trial analysis plan was updated. As many of you will know, when initially started, MYSTIC was designed with progression free survival as the only primary endpoint. Last year, around this time, we changed the trial to elevate overall survival to a co primary endpoint and that was done because emerging evidence indicates that overall survival better captures the benefit given patients by immunotherapy for cancer. In order to do that and maintain the power of the trial, we increase the size of the trial from 700 to about 1100 patients and we're able to nonetheless with that increase enroll quite quickly. And that allows us to be confident in the power of the trial to detect clinically meaningful differences in these different endpoints. So MYSTIC will now assess progression free survival and overall survival in patients with PD L1 expressing tumors with the opportunity to then look at both durvalumab monotherapy and durvalumab tremolimumab combination therapy. And then it will also look as well in all comers for the combination of dervo plus tremi, recognizing that in the low expressors of PD L1, the monotherapy has limited activity. And this is of course versus the standard of care chemotherapy, so that this trial can stand on its own as a registrational trial for full approval in the first line. The progression free survival, as many of you will know, will be available in mid-twenty 17 with the final overall survival data coming at the latest next year. We have been asked about interim analysis, we do have interim analysis in the trial. We don't disclose the detail of those, but those are for overall survival. Another change we made was to Neptune. Neptune is dervo plus tremie versus standard of care chemotherapy. We expanded with local patients in China to get more experience with in China with the durvatremine combo, that expansion will not delay the availability of the survival data in 2018 at the latest for the global portion of the trial. And then we started an additional trial in Asia, a Phase III trial called PERL. PERL is a durvalumab monotherapy trial versus again standard of care chemotherapy. And this in PD L1 expressing non small cell lung cancer. So what we've done with this is we've really enhanced our options and followed the scientific data, both for our primary strategy, which was the durvatremie combination and durvatremi combination particularly in lower non expressors of PD L1, but also enhanced options in the more established therapeutic hypothesis, which is durvalumab or PD-onePD L1 monotherapy in PD L1 expressing tumors. Can we then go on to Slide 32? Okay. So this again is the data readout slide for the IO program and not just in lung cancer, lung cancer is at the bottom, but across bladder cancer and head and neck cancer as well. So clearly, we have a busy year, 18 months going on here. We expect Arctic data in the first half of twenty seventeen, Mystic PFS data, as I mentioned, mid year, Pacific in the second half of this year, head and neck results from Kestrel in the second half of the year, Kestrel again is the 1st line head and neck cancer. And then first line bladder cancer, Danube and second line head and neck cancer, EAGLE, to come later in 2018. And then as I mentioned just a moment ago, Neptune in first line lung cancer with the durvatramine combo in 2018. Next slide, please. All right. So this lists across the portfolio, the late stage pipeline news flow we expect this year and going into next year. Obviously, we have quite an abundance of regulatory decisions, regulatory submissions and key data readouts that we are expecting in this time. To highlight some of them, as I said, we expect the regulatory decision under Valumab in bladder cancer by Q end of Q2 this year. For Tagrisso, we expect based on the AURA 3 data I'm sorry, for Tagrisso, we expect data readout based on FLORA in the second half of twenty seventeen. FLORA would move Tagrisso into the first line EGFR mutated population and that's versus IRESSA, the existing standard of care. The number of regulatory submissions here is extraordinary. So there is a lot of excitement around this and a lot of work to be done. In 2017, we anticipate data permitting immuno oncology submissions in lung cancer. And again, as I said, the first line data for Tagrisso based on FLUARA. Submissions for Lynparza in ovarian cancer based on the SOLO-two data and as well depending upon the readout from Olympiad in breast cancer. We have the potential for fast market submission in a blood cancer for acalabrutinib. With regard to Lynparza and that SOLO-two data, we've done a top line announcement that the trial was positive. We are going to present that data for everyone to look at the details at the Society of Gynecologic Oncology, which is the annual meeting on women's cancers and that will be in March of this year. We are really looking forward to being able to share that with you, because I know you have questions about PARP inhibition and about where does Lynparza fit in. And I think that being able to talk about the data in detail is going to help clarify that. And in the other key therapeutic areas in CVMD, we expect the Bydureon auto injector submission in the first half of this year. And with benralizumab, we expect the U. S. Regulatory decision based on the submission that we already talked about in the second half of this year for severe uncontrolled asthma. It's busy and it's an exciting time for us. And we are confident that we have the right trials, right trial designs and excellent drugs to make a difference to patients and to continue to grow the new AstraZeneca. And with that, I will hand back to Pascal for closing remarks. Thank you, Sean. So let me just say a few words of conclusion before we open for Q and A. So if I can have the last slide, please. The messages I want to leave you with today are: number 1, our financials are on track, and we our guidance for the year number 2, we have 12 new potential medicines in Phase III and under registration. So a very, very strong pipeline that is starting to deliver. Importantly, beyond the pipeline, we also have tremendous commercial organization around the world. And in particular, in the emerging markets, we have a business that has been steadily growing. We have delivered consistent mid- to high single digit growth rate, in fact, sometimes double digit growth rate overall. And in China, in particular, we have consistently delivered double digit growth rate and outpaced the market growth rate. We've made faster progress in oncology for obvious reasons. We have, of course, great medicines, but also, as you all know, you can develop products in oncology faster than in some other therapy areas. Tagrisso has been a great launch so far and is continuing to do very well, and we have great data to support further growth this year. The immuno oncology programs, of course, are making progress, and this year is going to be an important year for immuno oncology portfolio. And over the next 12 months, we have a very busy news flow. So at the end of the day, net net is we're really getting to an inflection point here. As we end this parent cliff, which often has been a little bit exhausting for our teams around the world, We're getting to the end of the pellet and cliff, the pipeline is starting to deliver, and we see the new AstraZeneca emerge. So we have another year or 1.5 years of managing the end of this pellet and cliff and launching this new product. And in many ways, the R and D organization, as I said a minute ago, has done a fantastic job. And now they are passing the button to the commercial organization around the world who have been playing defense in many respects over the last few years, defending very successfully our old products, retooling, building capabilities in diabetes, in respiratory disease, we're building that. Importantly, building capabilities in oncology, refocusing ourselves, relaunching Brilinta, trying to grow our diabetes business and doing this in the context of a declining SG and A as we are managing our declining top line. And now they are redeploying themselves to preparing the new launches. And I have no doubt they're going to do a great job. They've started doing a great job already with Tagrisso and other products, and there's a lot more coming for them. So the next 12 to 18 months suddenly are going to become suddenly quite exciting for the commercial organization. As you can imagine, launching new products is suddenly more energizing than playing defense as we have been doing for a period of time. So with this, I'll stop here and open the floor for questions. Sorry, go ahead. Just stay on and Sachin. We're just going order on this call. Is that okay? Thank you. It's Matthew Weston from Credit Suisse. Can I ask 3, please? The first on Dervotremi and Mystic Sean, it's fitting that we start there. There's been a lot of debate since you changed the endpoints as to whether or not the combination arm needs to show superiority to durvamono in order for the trial to be fileable. I think we'd all just love your views on that in terms of how you see the filing strategy and absolutely what's necessary? Secondly, Mark, on the numbers. You gave us a trend for what we should expect for R and D over the course of 2017, but you didn't really give us clarity on SG and A. If you could give us some indication as to where those levels are going to settle down the incremental savings possible in 2017, I think that would be very helpful. And then Pascal, a big picture question. I think you set out the pipeline all the extremely exciting opportunities at the company. But clearly, what we have seen in recent months is that a number of members of the and whether that impacts and whether that impacts your ability to deliver commercially and on the pipeline going into 'seventeen and in the midterm. So should we start with the G plus T question? Sean, go ahead. Sure. Thank you for the question. So the for the trial to be positive, durva mano or dervicetrami combo has to be standard of care chemotherapy, okay? And that will enable filing. The question of Durva Mano versus the combo is a little more nuanced in that it will be a benefit risk assessment. So we are quite confident based on data that there will be more toxicity of the combination, in particular, autoimmune toxicities coming with IO. And so it will have to have a benefit above durva mono in order for the combo to be filable. And that benefit would have to offset in our assessment, the assessment of regulators, any toxicity that's seen. So it will be data dependent in that way. It does not have to beat Dervo Mano for Dervo Mano to be filable. Now, I talked a little bit about it before. Our original hypothesis was that what durvatremi combo would bring us is an opportunity to bring IO therapy to patients who weren't benefiting it, that being PD L1 low non expressors. I think as data has emerged in the field, the question of whether durvatremi combo might also bring benefit to PD L1 high expressors is a question that is out there. And so we've enabled the trial to look at those populations. And we'll have to wait and see what the data says. Does that answer your question? Yes. Just on the question on SG and A for 2017. When we were 1 year ago in 'sixteen early 'sixteen, we indicated a material reduction on the SG and A line, and we, in fact, delivered 9%. So I would say we delivered probably a bit more than what we had expected. We are continuing our efforts on SG and A cost reduction, and you can anticipate another reduction in 2017. I'm not going to quantify the reduction, but it's going to be another reduction for the year. Okay, Matt. Thanks for the last question. Let me just cover this question about Tenet Movement. First of all, I don't know how far you go when you say over the last few months. In the recent few months, I mean, 2 of our senior leaders have moved on. And I have to say, they've moved to fantastic jobs, both of them. And it makes me very proud that actually, they actually could get such a such a great job. And it's a reflection that many ways that we have a very deep talent bench at AstraZeneca, and we have people who are able to take those jobs. I know that some people have said, well, do they know something that we don't know? Does it mean the pipeline is not working out? So I know some of you will be at the breakfast meeting tomorrow that we've organized, and Mondher, in particular, will be there. So you can it's a kind of a farewell party for him. Mondher has been a great friend of mine for the last 15 years. Actually, he's recruited by the person who recommended him to me 15 years ago. So it's kind of almost a family affair. So you can ask him questions about what he believes of the pipeline. But net net is they've really been able to grow. So that's one thing I would say. The second is we have a very deep talent pool at AstraZeneca, and we have other people who will grow and take advantage of these opportunities. Jamie Friedman, who is replacing Mondale, and you will meet him tomorrow, was at Medi for the last 4, 5 years, before that at Merck and GSK. He's incredibly talented oncologist who has already started making a big impact on our oncology business. So this is a good example of someone who emerges out of our organization. And maybe the last point I would make is that you really have to look at the people who live and the people who come. So if you look at the people who've left over the last few months, you also have to look at the people who've joined us over the last few months. The first one is sitting there, our CMO, and he's made a tremendous impact on our oncology business and our pipeline overall. And so it's really been really great to have Sean join us. You've met some of you have met David Berman at MedImmune, fantastic scientist leading our oncology business at MedImmune and many others at MedImmune and AstraZeneca across the board. So for me, it is actually part of the industry. It's part of the business we are in. People come, they grow. Hopefully, you can offer them opportunities within AstraZeneca or within your company. Sometimes someone else comes around and offer them a job that we're not able to offer them because that's structurally an option we don't have. And it's really certainly very pleasing to see some of our peers in the industry feel the need to come and recruit some of our talent for jobs they have to fill. So that's what I would say about this. But ask to ask Mondher tomorrow what he thinks of the pipeline and whether he's lost confidence in it or not. Sachin? Tachin Jain, Bank of America. A few questions, please. So firstly, for Mark. You haven't given product sales guidance, but I guess it's implied lower than consensus given the higher one off expectations versus consensus. Just two related questions. Any color on how you're thinking about product sales growth for 'seventeen? And I guess, more importantly, how much of the delta versus consensus is a weaker base business versus lost sales that you're externalizing? And second question, still on the one offs. You've commented on one offs for this year being in a similar level to 2016, which was GBP 3,500,000,000. GBP 3,500,000,000 GBP 3,500,000,000 GBP 3,500,000,000 GBP 3,500,000,000 GBP 3,500,000,000 GBP 3,500,000,000 GBP getting it to GBP 7,000,000 GBP 7,000,000 GBP 7,000,000 GBP 7,000,000 GBP 7,000,000 GBP So you're obviously substantially higher. Is that front loading of what you'd planned over the midterm? Or do you expect this high level to continue? And then the final question is for Sean on Mystic. And I'm sure you're expecting this. Isu, I think Pascal referenced in his introductory comments, confidence in the combination despite external factors. I wonder if you could address what we've seen from Bristol more directly and your perspectives on the delayed filing and their less than effusive commentary on the combination in first line? And I guess the background to this is you have a lot more data Phase 1 than we've seen from 6. So is there any chance of us seeing prior to Mystic? Thanks, Sachin. Let me before Marc and Sean address your questions, let me just say a bit earlier when I said we are confident. We run the studies because we don't know the answer. Of course, we run Mystic to have the answer to whether a combination works better than monotherapy. So I'm not confident to the extent I know what the results of Mystic will be. What I meant to say is that there's nothing new that we have seen that would change our level of confidence. And in fact, our data are not really changing any of our previous views. And Sean will cover this. But the BMS development is, to a great extent, something we were expecting for reasons Sean will be explaining in a minute. But maybe we should start with the financial questions, Marc. Yes. So first of all, on the guidance for product sales, we do not provide guidance for product sales, but we do provide a guidance on the total revenues and have explained this to you earlier on. Regarding your second question, which is part of the total revenue because it contains externalization revenue, the guidance I gave 1 year ago was that there would be an increase of externalization revenue and other income versus the level of 2015. And the total of this revenue and other income in 2015 was 2.5. So I do not remember giving you a guidance for 2 years in a row at €2,000,000,000 If I did, I will have misspoken, but if you could look at it. So what I can confirm today that we have given you a trend for an increase of external revenue and other income for 2016, and you have now quoted the number 3.4%, 3.5%. We are going to have a greater amount in the year 2017, so greater than 3.4, 3.5. Thanks much. Sean, do you want to cover the other question? Yes. Sachin, thanks for the questions. Let me start with the BMS combo question. And if we see read through to MYSTIC and the Dervitrami combo. So we were asked and I talked to some of you around Q3 about BMS's announcement around this approach. And at that time, prior to hearing anything else, we said we thought it was very low probability of regulatory success. And the reasons that we felt that was when you file on a single arm trial, you have you really have to demonstrate an extraordinary treatment effect over the standard of care. Now, if the standard of care is really ineffective, then not much data can actually indicate you have more activity than it. But when you move into the first line of non small cell lung cancer, the standard of Caris doublet chemotherapy, which has a demonstrated PFS and OS benefit, doesn't cure the disease, it's still an unmet need. But to get single arm data that gives regulators confidence that they should put your medicine out there is a big bar. And so that's why we thought that. The other reason we thought that is we've discussed many, many times is we believe that overall response rate, which is primarily the data you will have, underestimates the treatment benefit of I O therapy and of course I O, I O. And so again, that's primarily what you'd be relying on. So that combination of things made us at that time believe it was unlikely. Now we've heard it's not happening, it doesn't change anything for us in terms of that. Again, the I want to reiterate what Pascal said, if we knew the outcome of Mystic, we wouldn't have to do it. But what we're confident in is the power, the design, the analysis plan and that we as the field has moved, we've incorporated what is known as well as we possibly can into that plan. 6, prior to Mystic, we did expand 6, we expanded 6 with second line patients, we added some first line patients. 6 enrollment of that expansion was completed late last year. So we do what all companies do, which is as a deadline for a submission for an abstract comes up, since a non blinded study, we take a look at it and we ask is it mature enough and to be a meaningful presentation. And our conclusion for ASCO was no, it's not mature enough to be any meaningful presentation. So we will look again and aim for meetings later in the year to see if we're ready to present. Sachin, I'm sure you will remember very well that if you're looking for accelerated approval on the basis of a single arm study, you have to beat the standard of care not only with the median, but also the lower end of your confidence interval has to be higher than the upper bound of the confidence interval of the standard of care. So that brings the bar very, very high. That's why we always doubted that a single arm combination study was would be able to deliver an accelerated approval. It seems to have borne out as we expected, but that's what we can say at this stage. Richard Parkes from Deutsche Bank. I've just got three questions as well. And one just to be more sort of specific on Mystic. I think people's sort of nervousness around BMS's decision is not just on their decision not to file early, but also just their overall confidence in the approach seems to be reduced from where it was a few months ago. So I just wondered if you could reassure investors that the response rate you're seeing from the 6 study coming through is consistent with the 35% response rate you saw from that initial cohort? That's the first question. Then a couple of financial ones. The gross margin, I remember in the Q3, you were highlighting that you had a broadly stable gross margin despite impact from Crestor, and I think you pretty much absorbed the full impact there. And I think the reason given was the shift towards more sort of Specialty Care. But now you in the Q4, you've had a 200 basis point negative impact. So I'm just wondering what changed there. And then the final question, looking out to 2018, given the base in 2017, the sort of externalization of other income is now a pretty big proportion, which I'm assuming won't be sustainable at that level. Should we be thinking about a return to top line growth in 2018, but the earnings growth not materializing until 2019? So should we start with the gross margin France questions, Marc, and then Sean can cover Mystic and overseas? Okay. So I think the impact of Crestor is real. It's going to be over time, it's going to disappear. And the transition to a more specialty catapopof portfolio is going to compensate for it. But on the year I mean, on the last quarter of the year 'sixteen and for the year 'seventeen, the reduction of gross margin will be felt. So the gross margin in 'seventeen will be lower than what we see for the year 2016. That's clear. Maybe in the Q3, the impact of Crestor was not for the if you total the 3 quarters were not that high. But as we see the Q4, there was a difference in the percentage of gross margin. And we have reported on the report, there was, on the Q4, 260 basis points on the Q4 alone at CER and 130 point basis points at actual rates. So we are, a way, helped a little bit by the depreciation of the sterling pound and other similar currencies. 2018, Mark? For 2018? 2018, yes. So I think the gross margin is going to be lower in 'seventeen than in 'sixteen. For 'eighteen, I think we should have a very similar gross margin. The question, sorry to interrupt. The question was external revenue and So we're not going to provide guidance today for 2018. We gave you as much as we could. I mean, a lot of details about 'seventeen different lines of P and L, an indication on the total of exchange revenue and other income. I mean, I think I'm going to stop there. I think I can't provide you any more detail for 'eighteen. But I can certainly say that the return to growth is imminent, and it could happen in the course of at the end of 2017 or early 'eighteen. You would also I mean, Richard, you also I'm sure I appreciate the fact that this will be very much influenced by the mix in the portfolio, right, and as a result, being influenced by the clinical news flow and what comes out. You got so many new clinical data coming out over the next 12 months. That will influence the product mix of 2018 and therefore, the speed at which we grow, but also the gross margin our profitability. So I really think that to be able to be more specific on 2018, we need to have a better understanding of what the portfolio will look like, actually. Or Sean? Yes. So with regard to update on 6 data, it's really the same as the answer to question, which is when the data is at a place where it's a meaningful publication, we will submit it and we'll update, but we don't do it at an analyst meeting. And as I said, our confidence in MYSTIC is unchanged. It's a good point that the Durbitremi therapeutic hypothesis is not yet proven in first line or second line non small cell lung cancer. And so it is an experiment, but we believe we're doing the right experiment and the trial is well designed. You also asked about and I would say, I think Pascal said it, our enthusiasm for the trial has just hasn't really hasn't changed. The BMS announcement, part of what you're asking is what did BMS see. I don't know any more than you do about what BMS saw. So I can't say whether their change in tone is reflecting something in the data that if we knew it would reflect our PTS. I'm sorry, I just can't answer that question. I will say that, as I said, the it was our assumption that that accelerated approval path wouldn't work. So to now have confirmation that it's not working, again, doesn't change our confidence because that's what we thought was going to happen anyway. One of the things that we've also learned, not us as a company, but as an industry, I believe is over the last maybe 12, 18 months is that overall survival is really the end game in immuno oncology. And the other thing that we have and more recently reconfirmed that what happened to BMS is really it's not necessarily the best thing to do to kind of look at your data every week or month or something and then publish things because then you have a lot of variability in what you publish. So our approach is we want to get to a stage where we have a sufficient number of patients, maturity in the data, overall survival data and then publish that. And so that would be probably second half of this year at the Audios Congress, we can actually publish that. But we really want to get a mature data set and then share that at that point as opposed to kind of sharing data and doing that too often. And so the basis of the adjustment of the plans around Mystic was our own internal data, but also the external data. As we always said, we would look at Pembro, Nivo data, Prasad Alias more. We would look at our own data and then based on that, inform the final statistical analysis of Mistake and essentially looking at OS as a critical endpoint but also looking at the cutoff points, and that's basically what we've done. Another question in the room, and maybe we'll go online for 1 or 2 questions. Nicolas Bjorgelon, Morgan Stanley. 3 mystic related questions, I'm afraid, or unfortunate. The first one is around the recent changes. I noted a slight change in the wording of the press release where you now refer to PD L1 expressing tumors rather than positive or high expressions. Does that influence your thinking about PD L1 expression and or your cutoff in any way? 2nd, with regards to the readouts and the timelines. I mean, the first patient dosed in Mystic was in Q3 2015 and the last patient commenced dosing in early Q3 2016, which means that you have a minimum of follow-up of at least 12 months up to 24. So basic average, assuming straight line recruitment, 18 months. This is much more than what Merck had in KEYNOTE-twenty 4 in which they demonstrated overall survival. So are we missing something or but basically, what precludes you from showing OS data as early as mid-twenty 17? And the final one is with regards to the dosing regimen of the CTLA-four. Just conceptually, I would like to hear your thoughts on the 2 different approaches, the one of BMS and your approach. As far as I understand, you will dose TRIMI only for 4 cycles, whereas BMS may dose until progression. I mean, what are the pros and cons? Thank you. Straight question, Sean. Yes, yes, yes. Somebody I'm sure has a non mystic question, but maybe we'll have that. So let me try and take them backwards and then I'll make you remind me of the first one. So the question about the overall survival endpoint and maturity, these are event driven analyses. And what we share with you is when the final analysis will be done, we think, right, because if the event rate is slower or faster than we forecast, then the trial matures at a different rate. And overall survival will be mature in 2018. As we get closer, we'll be able to narrow it down to a quarter. As always with these trials, there are IDMCs, there are interim analyses and we don't we just don't share timing for that. So PFS is mid year. We're getting close enough that we can say that. And for overall survival, we're still giving a big range. Yes. In terms of the level of maturity that you're referring to, just keep in mind that maybe we didn't communicate that clear enough before is that we increased the size of Mystic as Sean explained. And we had a team that did a fantastic job, accelerated the recruitment. But the end result of this was that the recruitment accelerated toward the end of the trial, and a large proportion of the patients were recruited in the last 2, 3 months of the trial. So I can't exactly remember the percentages. You may have them or maybe we don't want to communicate them. I don't know, it's up to you really. But a lot of those patients were recruited in sort of June, July, August. And therefore, we don't have as much follow-up as you may think we have, but suddenly, there will be quite a number of patients who will have a reasonable follow-up by May, June this year for sure. Yes, it's well more than half are in the shorter follow-up period just because of the shape of the recruitment curve. Cutoffs, yes, you definitely caught a change in the wording and it does have to do with how we've informed our definition of PD L1 positive in the trial and enabled the analysis plan to look at that population, again, both for dervo monotherapy and for dervo plus trimming combination. We aren't communicating more details around that, obviously, very competitive landscape. So for us, it's important that we keep some of these things to ourselves until we're ready to share information with you from the trial. What was the first one? Oh, yes. Excellent. Yes. So, if you look at the biology of CTLA 4 versus PD-one, PD L1 as a checkpoint inhibitor, it's a little bit of the PD-one, PD L1 pressing on the gas and CTLA-four being a break. And it is our belief from preclinical data and the mechanism of action of CTLA-four that once you have removed that suppressive signal that you should over the months that you would have CTLA-four inhibition, you should allow the stimulation of the immune system as necessary to fight the cancer, if it's going to be able to. And once they're activated, they aren't subject to CTLA for expression suppression anymore. And so that's the basis for that. It's a small data set, but if you look at what's probably the best pharmacodynamic marker of immunotherapy activity is actually autoimmune toxicity. And if you look at the 2 regimens, they actually look quite similar. The one that BMS finished with, not the one they started with, because they started with a much higher dose of CTLA for with much more toxicity. If you go to the interval and dose they finished with, Good. So maybe we before we come back to the room, we'll take one question online. Simas Fernandez at Leerink. Simas, go ahead. Yes, go ahead. Thanks, Thomas. So the first two questions, Sean, there for you, and I'm sure you'll enjoy the first one because you love Tagrisso. And there's so much focus on Mystic these days that this little child called Tagrisso, which has a very, very promising future tends to be overlooked a little bit. Go ahead. Yes. Well, thank you for the question. I love the introduction to it because I am very enthusiastic about Flora. I'm going to have I'm going to get Mark Mellon's help with this too from because there was a question about what's the threshold with regard to payers and access to the market. First of all, just talk about the trial a little bit. As I mentioned, frontline EGF are mutated, ARRESSA versus Tagrisso. The things I'll mention is there, few things we're going to look at there that can really distinguish. Obviously, progression free survival, we need to show that Tagrisso is better, and that it has greater activity. We have a couple of things that lead us to think that that's a possibility. 1, as I mentioned, is the CNS penetration, the ability to cross the blood brain barrier. We know that in the range of 40% of patients when they progress on a 1st generation TKI for EGFR progress in the central nervous system. And those 1st generation medicines just don't penetrate. So they're not being treated there. So that's one opportunity. Second one is the obvious thing. It was designed to suppress T790M mutation, which is the most common mutation that leads to resistance of the 1st generation EGFR inhibitors. And so this suppresses that. So those are the opportunities. In terms of difference and how it relates to the market and payer. Yes, I would just say a couple of comments. I think, you probably won't be satisfied with this, but it's going to be it's variable, right, because the actual first line treatment of lung cancer is quite variable across the world, right? So you're going to have if you're in a health technology assessment market, there will be high expectations about the progression free survival. They're going to be really challenging in getting out into the details of what the economic implications of that are. And that will be probably a higher bar than, say, something in the U. S, where this they're really primarily focused on that is this really extending progression at reasonable amount for patients. And therefore, that will be a driver. Then, of course, outside of the U. S. And Europe, where you have a lot of this is in out of pocket markets. In some cases, you're talking, it's still largely there are markets where chemo is still the primary first line treatment. It's not even the TKIs. And I wouldn't rule those out as good opportunities for FluorA because people may say, why do we go to this interim step, Let me jump to the better therapy if I'm going to be paying out of pocket. So we're going to have to work on this in a case sort of, let's say, a health care system by health care system model, assuming once we see the data. So that's what I would that's the mindset or the framework we're going to have to think about this. The only thing I would add is that, as Mark said, it will be variable. And as Sean said, it will depend on the strengths of the data. But there's one place, one type of patients who were I really do believe it would be hard to not prescribe Tagrisso in an EGFR mutation situation even without the T790 mutation. That's the patient, first line patient who has brand metastasis. Now think about that patient. You have an EGFR mutated lung cancer and you have brand metastasis. What are you going to do? 1st generation EGFR do not penetrate the blood brain barrier. And I just had recently the example, a friend of my wife had this and then she progressed in the her lung disease was controlled and she progressed in the brain very rapidly. This is a type of patient who actually will need Tagrisso. And then beyond this group of patients, the question is, of course, will be what is the strength of the clinical data coming out of Fluor. Arctic, Sean, do you want to cover that? Sure. So the question was ARCTIC results being material, I believe. So unfortunately, the materiality assessment is made in the context of looking at the result of the trial and what would its implications be for the company and do we think that, that would move the share price a variety of things that we talk about? We can't talk about it except in the context of the data. And so that's a determination, it's a really question I think that we can't answer at this point. And SG and A, Marc, I think in 2016, I gave you the percentage of the SG and A ratio of 35.5 percent and also mentioned that we were going to continue our effort to reduce the S and G and A costs. So I think one can surmise that the ratio will continue to go down, maybe not at the same speed as it has gone down in 2016, where in real term, in actual terms, the percentage decrease was about 2%. So I think there will be a further reduction, but maybe not as fast as what we saw in 2016. But I think on the medium and long term, I think this percentage is going to reduce over time. The only thing I would add to this is that I would not use the industry as a benchmark because in the industry, you have all sorts of companies with different portfolios. So the benchmark we tend to use is made of companies that have a more similar portfolio to ours. And those are companies like Lilly and some others. It still is that we have potential for decrease of our SG and A ratio. There's no question about it. You got to keep in mind that we have a quite a unique position in the emerging markets, and we have been driving this pretty hard in particular in China. And in China, we are now getting to a stage where we have a totally unique position. We have representation across the entire value chain. We are number 2. We have 12,000 people. We had 6,000 people 3, 4 years ago. And we have established ourselves in a place that is quite unique for the future. But of course, it's required investment. And so keep all of these points in mind, and we'll continue reducing SG and A, both in value and as a percentage of revenue. And again, maybe that's not a satisfactory response, but the speed at which we can evolve that will very much depend on the portfolio mix we have in the second by next year essentially. So again, it takes us back to the clinical news flow this year, what are the projects that work. I would love to believe everything is going to work, but some things will work better than others, as always. And depending on what we have in our hands, we'll be able to allocate our resources and shift and move the SG and A ratio at a different speed. Should we go back to the room? There was a question here and then we'll go to KF. Okay. Jack Scannell, UBS. Two questions. One is around the diabetes market in the U. S. So you implied that the GLP-one market is having modest negative pricing. In some ways, it looks like a pretty competitive market, right? There's aggressive contracting already, formulary management, a number of players. But other insulin segments would love to have mildly negative pricing, which implies in some ways the pricing power that you've been able to maintain in GLP-one segment is better than, for example, the insulin players see. Is there something structural about the GLP-one segment that makes it different? And do you expect that to continue? That's the first question. The second question is around Alzheimer's. Our view is that U. S. Payers have got in the last few years very, very good at stamping on drugs with high budget impact even if they might save money in the long run. And that is because in the long run, generally someone else insures the patient, right? So it's hard for them to take a long term view. Do you think that matters for assessing the commercial prospects of Alzheimer's projects? And if so, how do you handicap that in your thinking when you're thinking about whether to engage in Alzheimer's or not? Mark, do you want to cover those two questions starting with diabetes versus GLP-one? Yes. So the in terms of the class, I mean, I think there's a number of differences between the injectable business and GLP-one and oral business, right? You can think about, obviously, the severity of the patients. So as physicians thinking about how readily they are willing to switch to therapies, Certainly, the even just the mix of the business, it can be a bit different between, say, the Medicare Part D versus commercial, and there are different pricing pressures there. And also, really, there's some overlap with the competitors, but there's some different ones and they have different approaches. So I think overall in diabetes, we're going to have to deal with pricing pressure. It's going to continue to increase. Right now, this is part of the reason we're staying interested and focused in both because we want to see how this continues to evolve. Right now, we feel very confident with what we've got with Forxiga, and we're able to drive very significant growth and continue to lead that class. And we're continuing to we've got some exciting things coming for Bydureon, which we think will be a differentiator and allow us to compete in the future in that as well. So I don't have a silver bullet or one particular thing that causes the difference, at least in my view. Keep in mind that the insulin prices have been going up very substantially over the last 10 years, and payers knew that. And there was they were quite high, and then they had a long way potentially to go down. So the potential to go down was larger to start with. And secondly, you have the additional dimension of the introduction of analogs. And Lilly have been aggressive in launching their analog of basal insulin. So the dynamics are a little bit different from what you can see in GLP-one. With your question about Alzheimer, I think you're right that to some extent, not completely right, but to some extent, it is true that sometimes payer worry less about things that will prevent events in the future. In the case of Alzheimer, it's again, it will depend on the strengths of the clinical data. But I think if you can actually influence the course of the disease and keep patients stable and at home as opposed to being hospitalized, then essentially payers will be able to see the savings weekly. And in fact, the payer in that instance is going to be the government because most of those patients are going to be on Medicare Part D. So I suspect if we well, if we as an industry, those companies developing products for Alzheimer, if we get good clinical data, we should be able to gain access for those treatments. Okay. Well, by the way, Thomas proposed that we extend to 2.15, so because we saw there were so many questions. Kia, go ahead. So I've got two questions. I'll ask the first one in 2 parts. One's for you, Sean, one's for you, Pascal. So let's assume we all are cognizant of how confident and comfortable you are in the Durbar Remy hypothesis. But in the unfortunate event that we end up some terminal of this year, you open up the data box. And at least at PFS, neither of the two arms are successful. So on the question for you is, what does that mean in terms of the trial mechanics? What happens the day after to patients on the study? And Pascal, the question for you is assuming that the hypothesis fails at OS, what's plan B for returning Astra to growth? You mean if OS doesn't read out a mistake? Yes, or if Dewott Remy order or mono is not positive at OS as well, then what's plan B for returning Astra to growth? Okay. So first question for sure. Sure. So a couple of things. When we do the PFS analysis, we're doing it when PFS is mature, right? So at that point, there will have been many progressions. That's how the maturity of that occurs. So the patients who have progressed, if they're eligible, will have already gone on to another therapy. So that it will be a relatively, I think, modest problem. What happens to the remainder of the patients, whether now you've set it up as negative scenario, I personally would not very. In the positive scenario, I think it depends upon what you're looking at, but then you may, depending upon how positive end up in the situation of having to cross patients over, right. And give you the chemo patients, the IO in the negative scenario, it will be a physician and patient assessment at that point in time, what they feel that they should do, should patients go to chemotherapy who were randomized to the IO. And I think it really will depend upon the details of the data. But again, it's not a large subset of patients because PFS will already be mature at that point in time. Does that answer your question? Yes. Okay. So the second one is that your question about if OS doesn't read out in Mystic, right? And what you mean by that is the combination of Either one. Yes. I mean, the first point is really, I mean, we believe AstraZeneca will grow and the question is at what speed will we grow, as I said earlier, because we are all, I mean, many people are mesmerized by this MISTIC study and to a great extent, rightly so, of course, but you got to look at everything we have. We have Tagrisso. We have Benalizumab to launch. We are launching many products. But also importantly, the massive drag we've been we've had to deal with, this sort of headwinds called patent expiry is slowly but surely getting behind us. Price pressures on Symbicort, they're stabilizing in Europe. We still have some of that in the U. S. Crestor is gone soon enough. So we're not going to have to deal with that to the same extent, right? So I think we will grow. The question is, again, it depends on how many of those projects read that. I mean, FluorA, we don't talk about FLORA, but FLORA is a really fundamental growth driver for us. The new indications for Lynparza, they are also very important, the launch of Benaresimab, as I said. Now so we will grow. The question is at what speed. If you come to Mystic, my comment here is that, again, we tend to look at Mystic in sort of a binary fashion, but it's not binary, it's not black or white. There's all shades of gray there. The total negative scenario, meaning nothing works, including monotherapy, hopefully you agree with me, it's possible, of course, but it's sort of low probability, right? So if we have a monotherapy indication, what it means is we have dorolumab and it becomes a marketing battle. And of course, as we've known all along the way, we are not leading, we are coming later. But remember, in lung cancer, which is the biggest indication, we have a very strong presence, historic presence with Yarisar more recently with Tagrisso. We know those physicians. And by the way, just a little piece of information, there's 80% overlap between the treatment of bladder cancer and lung cancer. The physicians who treat bladder cancer are more or less the same as those who treat lung cancer. So from a sales force effectiveness viewpoint, there's a very strong synergy. And in lung cancer, we are very well positioned. We know those physicians. So it's a marketing battle, but we are in we have a history there. And then from there, the question is, what do we get out of the combination? Do we get benefit versus monotherapy in one subgroup, positive, negative or do we get a benefit in all commerce, of course? And so but I my answer to you would be, we will grow. The question is at what speed, yes. And then the second question, and Mark, I'm going to try my luck in a slightly different way. Assuming the pipeline pans out the way you expect it to pan out, what contribution do you need from externalization and OI for 2018 EPS to grow? [SPEAKER UNIDENTIFIED COMPANY REPRESENTATIVE:] So I think we I'm not going to spoil it hard enough to answer your questions on externalization in 2017. I'm not going to venture on 2018. I mean, we believe that externalization is part of our business model. So the part of externalization should continue and the recurring part of externalization is going to grow over time. So I don't think externalization is going to go away, but the mistake is positive or negative. Now the part of other income after a while may dwindle a little bit. So this part of product that we divest may be impacted by Mystic and also because we have completely finished the management of our portfolio. But I think the externalization, which attracts more attention, is going to stay. This is part of our business model. We will always have products that we discover that we are not best placed to market or market on our own. So this will continue. Remember, as we have always said, that there will be a recurring dimension to those and then the one offs will over time decline. We've also said there will be a time point when the sum of the one off and the recurring actually reduces a bit before hopefully, starts growing again based on the recurring revenue. Some of this externalization relates to pipeline projects, as you know. Some of it is pure divestments, but it's relatively limited. Those are small products, dollars 40,000,000 $50,000,000 in sales that would be better doing better in the hands of someone else and we divest them and crystallize the value or invest it. But a big chunk is also about commercial partnerships. Plendoll is a good example, the anesthetic still. And here with Plendoll, what we've done, for instance, is we felt this is a product that has potential in China. We can't focus on it, first of all, because we have too many things to do. Secondly, because you have to cover too many physicians. We have 7,000 medical representatives in China. A Chinese company has 25,000 to cover the entire country. So we've partnered this product with a Chinese company. We've given them a margin, and they will cover the whole country. So and we're doing this with a number of products. What that means is we have a one off reset. So we drop, of course, because we give them or not give them, we sell them a share of this margin. But then they promote the products, so over time, it will grow again. That's sort of the model. So and we'll keep doing this. Essentially, what we try to do is find value everywhere we can in the portfolio, focusing our investment in our own R and D and our own pipeline and then unlocking value outside everywhere we can and sort of reinvest it. So we'll continue doing it. Maybe we'll take one question from Luca Icy at Cowen Online. Luca, go ahead. Thank you so much for taking my question. Luca Casey, Cowen and Company on behalf of Steve Scala. Three non mystic questions, I guess. So the first is, I think at ASH, we have seen the first two cases of atrial fibrillation for acalabrutinib in patients that were actually previously on IMBRUVICA. So how confident are you that these cases are driven by prior IMBRUVICA's treatment and not by actually acalibrutinib? And maybe more broadly, how does this impact your ability to differentiate the assets? And then second question is on Farxiga. Can you just provide your high level thoughts on how competitive dynamics will change going forward in the U. S. Given that now Jardiance has a proper CV indication on their label? And then third question is on Bydureon. Can you just remind us if there is any interim look at the cardiovascular outcome study for Bydureon? Thank you. Thanks very much, Luca. Sean, do you want to cover the acalaritinib ASH question atrial fibrillation? And maybe also the Badureon cardiovascular data and Mark, if you could cover the Farxiga potential? Well, I guess, I'll start with the BI DRAM one, I think. The so these large cardiovascular outcomes trials have again independent data monitoring committees and interim analyses and then we don't give detail about those things when they're happening. Obviously, it's hard because they're also event driven and then IBMCs don't communicate anything to us if they don't feel they need to. But it's got all the normal structures that a large CV outcomes trial would have. Yes, with regard to acalabrutinib and it's I would say its tolerability profile in general. We remain committed that acalabrutinib has a superior tolerability profile to ibrutinib, if only because there are patients who are not progressing on ibrutinib who discontinue it because they have toxicity. Some of that is atrial fibrillation. Some of that is a variety of other things. We outlined them in a slide deck, actually when we did the deal. When you go into an older patient population such as those that have CLL, you are going to have some atrial fibrillation occur. And the data set we presented at ASH is very small. And what is really going to be important is the longer term chronic therapy data set that we get and recalling as well that we are doing a head to head trial of ibrutinib versus acalabrutinib, which is really going to be the gold standard for looking at tolerability, also potentially efficacy in that trial. And that's what's going to tell us what happens. But the idea that in CLL patients, you were never going to see an atrial fibrillation is probably not very Mark? Yes. So that's a great question when we've certainly spending a lot of time thinking about. And so the first thing I would say is, as we think about sort of the pay that our competitor has and eventually there could be more data from all of the products in SGL 2 is that it's important data. Obviously, in in the limited patient group that, that was focused on, which was a is a minority of the diabetes patients, it had an important benefit. But I guess the question we've been asking ourselves is why hasn't that had a bigger impact on the overall SGL2 class growth rate? And also, actually, even it's been uneven with the share impact that we've seen on the brain. And I think have to remember that 1st and foremost, we're talking about diabetes patients, right? And so for many of these physicians, their first question is what do I need to do to get the glucose under control? How well tolerated, how safe this is going to be versus the products I've been using, which in this case is the DPP-4s. And the DPP-4s are really good products, right? They physicians have become incredibly comfortable with them because they get good glucose reduction and they're very well tolerated. They don't have to worry about them. And so I think the thing that's, we feel like is going to be the key dynamic that we need to look at and see how that is going to happen is, what is going to get physicians to really understand that actually the SGLD2 is a better choice after metformin because of the really good glucose control, because of the weight loss, and then because of also the potential this class has around cardiovascular benefits. And so I think what we'll see evolving over the next couple of years is we will get more CV data, both in clinical trials, but also importantly in real world evidence. I think we believe that will support the CV benefits of this class. But I think the company or as a group of companies, when we can get that combined with the core benefits that this class offers on diabetes control in a way that physicians can really see that it is worth taking something that's very easy for them to do, which is keep using the DPP-4s and use this new class, that's where we will see a really, I think, a significant change in the SGLT2 class growth. And I think the company that can really position the product as having the full benefits is going to be successful. It's I would ask this. I don't think CD outcomes is a silver bullet. It's an important additional piece of information. And for certainly certain patients, it's going to be important. But ultimately, the company that can win by or the class can win is really helping physicians understand why this is a better choice as use after Metformin. And in that case, and why we're continuing to be the leader and why we feel confident about our successes, we think we've got a great set of messages and story about why Forxiga is a better choice after metformin before DP4. Great glucose control, great blood pressure and weight loss benefits. And the overall safety and tolerability profile of the product and the confidence we have at being the most prescribed is a great starting point to have a discussion with physician. And then we'll see where DECLARE comes in. We also are going to be we've been doing some work and you'll be seeing in course of this year some really important, we think, exciting real world evidence that we'll be we'll do publishing and we'll see going forward. But I think that's the key point is we can't forget that these are diabetes patients and we have to treat the whole diabetes patient. Cardiovascular risk is one part of it. It's an important one and it will grow. But we've got to solve to help physicians understand in the diabetes patients why this is better choice than PPB4s. Thanks, Mark. So should we take one last question? Yes. So Thomas allowed me to take one last question. Sorry, David, I'll have take this one here and then we'll have to close. Marietta, I mean, it's Prime Avenue. Just a few very quick financial questions. On the U. S. Pricing pressure, based on your comments and some of your competitors' comments, is it fair to assume that for Symbicort and maybe some other large drugs Q1 pricing will be materially below Q4 'sixteen? And what gives you confidence that pricing pressure is going to moderate in the second half given that we've always heard that contracts can be reopened at any point in time? Quick question on Pulmicort growth in the emerging markets going forward. If you could just give us sort of a rough steer because I believe that the China growth has very much been driven by the rollout of nebulization centers, and it'd just be good to understand where you're at in terms of that. And my final question is to Pascal on your guidance and your comp. I mean, if you literally deliver on your guidance, you don't over deliver and there's no massive devaluation of the U. S. Dollar, Is it fair to assume that, that would have some negative implications for your deferred comp? If you just could give us a rough feel, that be great. So there was going to be one question, it's 3. Let me deal with the last one quickly so we can move on the more interesting questions. The we've always said we're committed to the dividend. We've always said that if something has to go because of price pressure from currencies, and that's really what we're experiencing. The dollar is gaining strength day after day, and it's putting pressure on our ability to deliver the cover at actual rate. It is clear that our comp will be negatively impacted. It's pretty clear. Beyond that, I cannot comment more. We'll continue doing the right thing by the company, and we'll do what we believe is right to do to make sure we maximize the value of this company because in the long run, we all win. The patience to start with, us management and the shareholders win if we do the right thing. So we'll continue trying to achieve our short term goals. But in the end, if we have to prioritize, we'll prioritize, of course, the dividend and the long term. Pulmicort, Marc, maybe you want to cover this one, and let me just quickly cover the Symbicort. We've said that in 2017, we'll see similar price pressure as we've seen in 2016 in the U. S. With some moderation. And we've said that this will be worse in the first half than the second half, and I guess maybe we will leave it at that for today. And then Pimicorp, Mark, since you are the expert in the emerging particularly the kids with asthma, a nebulized solution. And I'll say 2 points on that. So 3 points. So first of all, in China, I think we actually have some sort of sales on pomeloqued vegetables in over 10,000 health institutions. I'm not sure we're reaching half of them yet, right? So this is it's so massive, the number of hospitals, the number and we haven't even we're just beginning to start to communicate about palmocort residues with community health centers. There are 24,000 community health centers. These are the primary care clinics. They're just starting to actually initiate therapy. So there is still a huge amount of work to do. Many places in China still do not kids do not have access to a good option on asthma treatment. The second thing is, they shouldn't even be going to the hospital for this treatment. The real place they should be doing is at in home nebulization. And we've always started working on that last 2 years. That's going to be a multiyear process to educate on that. And then the last point in terms of the rest of emerging markets, we've been spending the last 2 years basically educating them on what we've done in China. And that sort of uplift is just still ahead of us. And we're now seeing nebulization centers come up in Indonesia, in Russia, and other places in the Middle East and Africa. So asthma is a terrible situation. There's a huge number of kids and people, both asthma and COPD around the world. And this is one solution. I mean, ultimately, we'd like to think the fixed dose combination inhalers is the way to go. But for the emerging markets where acute care is still the standard, this is a great solution. So a lot more work to do. Thanks, Marc. With that, we'll hand it here. And thank you so much for your attention.

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