Good morning to those joining from the U.K. and the U.S. Good afternoon to those in Central Europe. Welcome, ladies and gentlemen, to AstraZeneca’s Full Year 2020 Results Conference Call and Webcast for investors and analysts. Before I hand over to AstraZeneca, I'd like to read the Safe Harbor statement. The company intends to utilize the Safe Harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Participants on this call may make forward-looking statements with respect to the operations and financial performance of AstraZeneca. Although we believe our expectations are based on reasonable assumptions, by their very nature, forward-looking statements involve risks and uncertainties and may be influenced by factors that could cause actual results to differ materially from those expressed or implied by these forward-looking statements. Any forward-looking statements made on this call reflect the knowledge and information available at the time of this call. The company undertakes no obligation to update forward-looking statements. Please also carefully review the forward-looking statements disclaimer in the slide deck that accompanies this presentation and webcast. There will be an opportunity to ask questions after today's presentations. [Operator instructions] And with that, I will now hand you over to the company.

Hello, everyone. It’s Pascal Soriot, CEO of AstraZeneca. Welcome to the full year 2020 conference call and our webcast for investors and analysts. As usual, the presentation was posted to astrazeneca.com and we have also sent it to people on our distribution list. Please turn to Slide 2. These are the usual Safe Harbor statements including Alexion-related balance on Slide 3. We will be making comments on our performance using constant exchange rates, or CER, core financial numbers and non-GAAP measures. A reconciliation between non-GAAP and non-GAAP data is contained in the results announcement. All numbers in million U.S. dollars and refer to full year 2020, unless we state otherwise. And finally, compared to by quarters we need to be a little bit more understanding with financial guidance this time due to the ongoing work with Alexion. Thank you for your understanding here as we are limited in our potential comments in particular 2021. Please turn to Slide 4. We plan to review the presentation first and then do a Q&A until 01:15 UK time. If you keep questions short, we will try to keep answers short too. For those on the phone, please join in the queue for questions by pressing star 1. There is also an option to ask questions as part of the webcast. We ask you to please ask one question only. Thanks for your help on this one. In speaking order, I’m joined by: Dave Fredrickson, who is our EVP of the Oncology Business Unit; Ruud Dobber, EVP of the Biopharmaceuticals Business Unit; Marc Dunoyer, our CFO; Mene Pangalos, our EVP of the Biopharmaceuticals R&D Group; and then again Dave to cover for Jose Baselga today, on Oncology R&D before handing back. For the questions later, we also have Pam Cheng, EVP of Operations and…

Thank you, Pascal. We're pleased to report strong growth in total revenue of 24% for the oncology business to $11.5 billion in the year. COVID did continue to have impact with fewer cancer patients diagnosed and treated, but we saw resilience in our business as sales grew across all of our new oncology medicines from regional expansions and new launches. Please turn to Slide 12. Starting with our lung cancer franchise, we're pleased to report that both Tagrisso and Imfinzi showed strong growth in the year at 36% and 39% respectively, with revenue of $4.3 billion and $2 billion. Tagrisso continues its global rollout and is now approved in 87 countries in the first-line setting and we saw continued expansion in countries with national reimbursement, which now totals 40. U.S. Tagrisso revenue was up 24%, where we saw continued single-digit demand growth and we're now focused on bringing Tagrisso to patients with the earlier Stage I cancer setting in the U.S. following the approval based upon the ADAURA Phase III trial as we await regulatory decisions outside of the U.S. In China, we are pleased to be able to successfully negotiate reimbursement to enable even more patients to access Tagrisso as a first-line treatment in the metastatic setting. The majority of Imfinzi revenue continued to come from the United States as the launch of the CASPIAN indication in extensive stage small cell lung cancer continued to take effect, although we did see impacts here from COVID on patient diagnoses. Outside of the U.S. we continue to see revenue of Imfinzi pick up particularly in Europe and emerging markets as we are now able to provide Imfinzi to more small cell cancer patients globally. The unique ability to combine with both cisplatin and carboplatin chemotherapy will further benefit patients. Please turn…

Many thanks, Dave. Today, I’m pleased to talk to you about the BioPharmaceutical's business. Total revenue of BioPharma, comprising New Cardiovascular, Renal and Metabolism and Respiratory and Immunology, was $10 billion in the year growing at 4% despite the COVID pandemic. Starting with new CVRM, revenue was up by 9% with total revenue at $4.7 billion with very strong growth of Farxiga. Farxiga maintains volume market share globally with high double-digit volume growth across all regions as the fastest growing SGLT2 inhibitor. In the United States, Farxiga grew 6% driven by the additional indication in heart failure. Outside the U.S. which accounted for 71% of revenue, we saw strong performances with volume driven growth increasing and China benefiting from the NRDL listing. Brilinta delivered revenue of $1.6 billion with 2% growth as impact from COVID resulted in fewer hospital patients and China experienced the impact on VBP driven price reductions. Sales in the U.S. were up by 3% as an increase in treatments duration offset the negative COVID-19 impact. The majority of U.S. is still in the acute setting and Brilinta continues to outgrow the market in the majority of regions. Please turn to Slide 16. Turning to Respiratory and Immunology, we reported revenue of $5.4 billion, stable in the year, but excluding Pulmicort, Respiratory and Immunology grew 12%. Symbicort sales were strong at $2.7 billion with a growth of 10% in the year. The U.S. saw particularly strong growth up 23%, to $1 billion due to demand growth, following the launch of the authorized generic and a resilient ICS/LABA market. Globally, Symbicort remained the leader in value and volume market share in the ICS/LABA class. Pulmicort was down 32% in the year, with revenue of $996 million dollars, which continues to be impacted by COVID, particularly in China. However,…

Thank you Ruud, and hello everyone. I want to take you through our financial performance in the year, as well as the guidance for 2021. Please turn to Slide, 20. As always, I will start with the reported P&L before commenting on our core results. As Pascal mentioned earlier, total revenue grew by 10% in the year in line with the guidance I provided 12 months ago. In February last year we did not know how much and how long the adverse net impact of COVID-19 was going to be. Within total revenue product sales were up by 11% driven by the success of the new medicines with the majority of collaboration revenue reflected milestone proceeds in respect of Lynparza. Please turn to Slide 21. Turning now to the core P&L, this slide demonstrates the progression of our operating leverage. Our gross margin ratio was unchanged in the year at 80%, in line with expectation outlined last year. Our mix of sales is continually improving, but this was offset in the year by increasing pricing pressures in China, related to the impact of the NRDL, and the VBP program, to which Ruud alluded earlier. Core R&D expenses increased by 10%, partly a result of more investment in the pipeline, including Phase III trial starts for a number of medicines, including the oral SERD and the advancement of datopotamab deruxtecan also known as 1062. Merck, strong contribution in 2017 for the development of Lynparza recorded at that time on our balance sheet, was gradually released to the P&L until 2019. This impacted the comparative performance in 2020. There was also a material investment in the development of brazikumab, although we are refunded for those costs through other operating income. Core SG&A expenses, increased by 4%, driven by more investment in the…

Thank you Marc and hello everyone. I'll now provide an update on our COVID-19 efforts and our Biopharmaceuticals medicines since the last quarter. I'm also joined by Dave Fredrickson, covering for Jose Baselga, who will discuss oncology movements and upcoming news flow across the company. Please turn to Slide 27. In December of 2020, our vaccine received its first authorization for Emergency Supply from the UK MHRA. With recent conditional marketing authorization from the EMEA, we're now authorized for this vaccine in over 50 countries. Yesterday, we also received a positive recommendation for the vaccine from the WHO's SAGE group. This is a really important milestone ahead of an Emergency Use listing by the WHO, which should it be granted, will provide an accelerated pathway to significantly broaden availability of the vaccine around the world. And I think it's important to not forget that from when the agreement was signed with Oxford University to the first approval, only eight months have elapsed. Now just over nine months away, we have the vaccine approved in more than a quarter of all countries around the world. We've recently also published data on the impact of the emerging UK, Kent and South African variants. The vaccine is effective against the new UK variant as it is against the original strain, despite some low neutralizing activity. The South African strain resulted in a loss of efficacy against mild disease, but may still offer protection against severe disease, which is key to relieving the burden on healthcare resources around the world. We've also begun work on adapting the vaccine for these new variants of concern, leveraging our existing clinical trial data and an established supply chain to potentially reduce the time needed to reach production at scale. Finally we also presented our primary pooled analysis…

Thank you, Mene and hello again. I'm happy to take you through oncology R&D news this quarter and I'll start with Tagrisso to continue on the theme of establishing a new standard of care for patients. The groundbreaking ADAURA Phase III data has further confirmed Tagrisso’s capability to reshape future clinical practice. We recently received regulatory approval in the U.S., as well as approvals in four other countries as a result of project Project Orbis, a new review process by FDA and other agencies, and now have further submissions underway in this potentially curative setting. Starting with its approval in 2015 from the Phase III AURA3 trial in second line T790M, we’ve since brought Tagrisso to first line in a broader setting with the FLAURA trial by demonstrating an overall survival benefit. Now with the ADAURA data exhibiting around an 80% reduction in the risk of disease recurrence or death, Tagrisso is the only medicine to show meaningful benefit an adjuvant eGFR-mutated non-small cell lung cancer. Tagrisso’s trajectory is an excellent example of the efforts we're making across our portfolio in oncology. Our aim is to establish new standards of care for patients with a concerted effort in earlier stages of disease. Please turn to Slide 32. Moving on Calquence, a selective BTKI that has shown impressive effectiveness in chronic lymphocytic leukemia, Calquence has delivered unprecedentedly low hazard ratios in both the relapsed refractory and in the frontline settings, within the latter showing efficacy as both the monotherapy and in combination with immuno chemotherapy. We recently announced high level results from the ELEVATE-RR trial, which showed that Calquence met the primary endpoint of non-inferior progression free survival for adults with previously treated high risk CLL versus ibrutinib. In addition, with over 40 months of follow-up, Calquence demonstrated superior safety in…

Thank you, Dave. Please turn to Slide 36. In 2020, performance was strong and resilient, and we delivered the guidance as promised. The 10% increase in revenue was underpinned by the focused R&D and SG&A investment and despite headwinds from the pandemic in many parts of our global business, new medicines were up by 33% and we saw continued performance from oncology and New CVRM. Respiratory & Immunology was stable, but improved a lot in the quarter and emerging markets were up by 10%, which was impacted by COVID-19 on Pulmicort. I think we told you, but Respiratory & Immunology would have grown by 12% due to neutralized effect on Pulmicort. Core operating profits grew by 17% despite 2% lower operating income with a tax rate of 20% core EPS ended $4.02 up by 18% and more than revenue delivering operating leverage as a result guidance was achieved as we promised. Our cash flow is improving, including net cash inflow from operating activities that are now $4.8 billion and support the progressive dividend policy. We continued to see strong progress in the pipeline, mostly on our boards, supporting sales today, and of course tomorrow. This year we are back with more Phase III trial readouts like Calquence recently. Therefore against the COVID-19 pandemic continued with the first authorization for the vaccine. Let me assure everyone today that we are doing our very best to deliver to government's as promised. During this first half, we anticipate Phase III data. Also for the long-acting antibody combination, the potential new release in AZD7442, which you've heard through this presentation is a very exciting product. In 2021, we anticipate another year of double-digit revenue growth in the low teens, with the revenue growth accompanied by even faster growth in core EPS to between $4.75 and $5, all these at constant exchange rates. So let's now go to the Q&A. For those on the front, please remember to press start 1 if you want to ask a question. We will also take written questions from the webcast. And can I please remind everyone to limit questions to one to be fair to all of our callers. Thank you in advance for this. And perhaps now we can take the first question from the conference call. The first question I believe is from [indiscernible].

Hello, can you hear me Pascal?

Yes, I can hear you. Yes.

Great. Now, thank you so much for taking my question. The subject is investing for growth, Pascal. Could you sort of help us understand and sort of frame the [indiscernible], for example on R&D, how are you going to prioritize the various pipeline assets that you have after Alexion, acquisition closes, and you have a sort of wall of what's next opportunities, but with more financial flexibility. I sort of counted 10 in oncology, 12 in biopharma, and you mentioned 11 in Alexion, as well and how you should, and in terms of investing for growth, also, how we should think about the SG&A component of that? And that leads into specifically on to our flow map, if I may. 250,000 diagnosed lupus patients in the U.S. every year and only 25,000 on Benlysta. So, can you sort of help us understand how physicians will choose to use anifrolumab relative to say immunosuppressants or Benlysta or Rituxan and the progress there with the subcutaneous formulation, which you're also investing in as well? Thank you very much.

Thanks Mark. So on the anifrolumab question, maybe many, a little bit later you can cover the subcu formulation, and all you could cover the positioning and basically the commercial opportunity. So let me first cover the first question Mark is, you've said it, we have a pretty strong pipeline, a large portfolio. And that's why we believe we need to continue investing in R&D in particular, well certainly a little bit in SG&A, but much less, of course, because we have a strong infrastructure globally already, but certainly in R&D we will continue to invest. We want to drive top line. I mean, basically we have two goals. One is to drive the top line as fast as possible and the second is to continue the delivering operating leverage over a period of time. So, we're - in terms of prioritize, essentially we have a regular portfolio meeting that looks at all these projects. We have twice a year we review our overall pipeline. We have a strategy meeting, typically in June, July, where we look at all our projects and we compare them, and we compare products and we try to prioritize and the teams come and then they present their projects and we prioritize what they present to us. I mean, there's nothing really special here. We look at the metrics that any other company would look at. I think what we try to do is have good discussions beyond the metrics and get to the bottom of the data and understand the data and challenge ourselves. And that's how we actually prioritize and then build our plan according to this. Really, there's nothing different we do from other companies, except I think maybe spend a lot of time looking at the data, debating and going beyond the numbers that are presented to us. So with this, maybe Jose do you want to cover the anifrolumab question and hand over to Mene for the subcu?

Of course, Pascal and thanks for the question. So first of all, we truly believe that interferon, the interferon mechanism is central to SLE, and therefore we believe we can help a broad patient population. We have seen in our clinical trials that we clearly have a broad efficacy across multiple organs, and but also multiple patient groups, as well as a very impressive OCS reduction. I think one of the most important parts is that and physicians are giving the back, physicians who have experience with anifrolumab about an early response. The current therapies are lacking in an early response, both for physicians and patients it is very important to see a positive impact. So all in all, of course, we're doing an enormous amount of work as we speak, so that we are ready to launch the product in the United States and in other geographies in the second half of the year, but it is a truly very attractive opportunity. And too many patients are still not getting well served as we speak. Clearly, you are referring to Benlysta, overall the penetration is still relatively limited. So we clearly see a huge opportunity moving forward here. Mene, are you going to cover the subcutaneous formulation?

Yes, understood. So with regards to subcu, we presented some data in 2019 on subcu formulation, which was PK/PD study, which was very consistent with previous studies using our IV formulation. We haven't shared timelines to when we'll be pursuing subcu, but I can say that we are pursuing subcu formulations to anifrolumab and we'll give you more concrete plans in terms of timing of launches, as we have them.

Thank you very much.

Thanks Mene. Richard Parkes Exane BNP. Go ahead Richard.

Hi, hopefully you can hear me okay?

Yep, yes, okay. Go ahead Richard.

So consistent -- sort of broadly sort of financial focused your revenue guidance for the year is a little bit more optimistic than consensus, I wondered if you could give us a stare as to where you think maybe consensus was too conservative in terms of revenues. But on the flip side, it seems like your margin assumption is a little bit lower. I'm assuming that you are simply taking a conscious opportunity to reinvest back in the business. So maybe you could just clarify that and where you expect to invest a little bit more aggressively than consensus is assumed? And if you don't mind me just taking a second one on operating cash flow for 2020, if I exclude the benefit from the COVID vaccine funding, the improvement in operating cash flows relatively modest $800 million, despite a significant improvement in reported operating profit, which is $2 billion plus of incremental. So can you help us clarify some of the moving parts? Let's maybe continue to drag and maybe give us a stare on the magnitude of free cash flow improvement in 2021 pre - to the Daiichi payments? Thank you.

Thank you, Richard. I may be, I'll try to cover the first couple of questions and Mark can then add to this and also cover the cash flow question. So if we look at revenue, as you know, we don't guide or don’t comment on a product-by-product basis, but I think you can see it, we have a very broad portfolio, we have a broad geographical coverage and we've talked about it for a period -- for quite -- for a number of years now, but it's starting to have an impact. And so we have a very, very strong portfolio of products driving our top line. I can't really tell you, comment on one or the other product because we don't guide by product, but actually, as it relates to your second question, we do continue to invest in R&D. We do continue to build a company that it is fast growing in the near term, but also has a long runway. Quite often we're asked questions about the succession as if some of us are getting quite old and ready to go. But I can tell you despite our advanced age, it doesn't stop us from thinking long-term. And so we will continue to invest in R&D that's the core, that's the heart of our company and that will continue driving this company in the future. Marc, do you want to add anything, and for the cash flow question as well?

Thank you, Richard for the question on the cash flow. So, if you look at the, so we can look at the net cash flow at the bottom of the cash flow statement or we can look at other intermediary level, but I would recommend that you look at the cash flow for two things, first of all, the cash flow from operations, which has grown in 2020 by $1.8 billion. You have signal, because we have commented upon it, the part that is linked to the vaccine, COVID vaccine for the growth of the cash flow from operations was 62%, including the vaccine, but it was also 26%, excluding the vaccine. So the underlying business, cash flow is growing, cash flow from operation is growing faster than sales and faster than operating profit. So I think that's a very good sign. I would also recommend that you look at the progression of the EBITDA. We had an EBITDA in 2020 of $8.3 billion versus $6.7 billion in the comparative prior year, so an increase of $1.6 billion. So I think these two in my view point to an improvement of profitability, and an improvement in cash conversion.

Thank you.

Thank you, Marc. [Operator Instructions] Any other questions? We have a question from Michael Leuchten at UBS. Michael, over to you.

Thanks so much. I'm going to stick to one on Tagrisso in the adjuvant setting now that you have the companion [ph] listing and the approval, I was just wondering if Dave could talk to the operational challenges that there may be in this setting, moving patients from surgeons to oncologists, what is he doing to ease that and the timeframe around that? And the reason I'm asking is, obviously the prescription trends haven't seen, haven't shown too much of an inflection yet and I do understand that the approval only came late last year. But it does suggest that off label users may be a little bit restricted, which I'm assuming is related to those practical challenges. So any color on that would be very helpful. Thank you.

Dave, you want to cover this and you have to remember Michael also that the pandemic is clearly limiting our ability to interact with physicians, and this has a bigger impact on launches than existing established products. Dave, over to you.

Thanks, Pascal. I think Michael, maybe I'll start with the second part of your question first, which is about the uptake that we might have seen spontaneously prior to approval. I think it's also important to remember, we had high level results just in May of last year. We got to approval in December in the United States. And within that timeframe, we also had a publication take place, but NCCN guidelines weren't updated to reflect the ADAURA data until late last year. And so I think that that's different than perhaps what you might be expecting to see in other places where we're working on a longer timeline, from high level results in the presentation of those data in between that and approval. So I think that actually, together with the pandemic as Pascal raise was part of the aspect of it. I'm really happy to say that the response from physicians in just the one month that we have been promoting ADAURA has been very positive. We already have nearly two thirds of physicians with unaided awareness of the 80% reduction in the risk of recurrence. We are getting very good traction, both from surgeons, as well as from pathology, as well as from medical oncologists. And I think the experiences that we had with PACIFIC of working with the multidisciplinary team have really served us well here in terms of engaging with all of the different specialties that are involved in treating in the early stage. And I think surgeons are very open and interested to learning more about Tagrisso and ADAURA, because it's obviously coming after surgery and not as a substitute or replacement for it. And we really, also are quite pleased that, while it's qualitative, what we're hearing back from physicians is there an intention to use across stages. And so, whether it's 1B, 2 or 3A, we're hearing an intent to use, it's consistent across, which is what we saw in the data. So we do need to continue working on referrals. We need to continue working on driving testing rates, which are only at about 50% in the adjuvant setting. We need to drive use of adjuvant therapy, which is only about 25% today. So the educational barriers are there, but I'm quite pleased with the first month and look forward to continued progress into the year. So that's kind of my outlook.

Thank you.

Thanks, Dave. Luisa Hector of Berenberg. Go ahead Luisa.

Hello, thank you. And I'd also like to take the opportunity just to extend our thanks to all your employees for the hard work on the COVID vaccine. So my question is on the 2021 guidance and some of the moving parts. I just want to understand a little bit the range and whether you could contribute, sorry, specifically comments on ex-U.S. synergies and how that may impact in the year because I think the rights returned to you partway. And do you expect more disposable gains this year or are you pretty much done, because you have a high number coming in Q1? And Tagrisso China, what proportion of your EM [ph] sales are in China? And can you talk a little bit about the impact of the price cut as we go through the quarters, because I think the price got hit sooner than you see the volume uplift from the expansion? Thank you.

[Indiscernible] Marc do you want to cover the guidance questions and maybe Dave will address the Tagrisso China question. And again, Luisa just to remind you, unfortunately this year we are more limited than usual in terms of how much we can comment for the reasons we described before. Over to you, Marc.

Yes. So I think I will take the question of the gains from disposals and how much for the year. So what I can say that other operating income will continue to be a part of our business, but will play less of a role in the medium term. I can't comment specifically on the year 2021. You are already aware of what we have announced obviously. There will be some more, but I can't comment specifically on it. But over the medium term, the other income will continue, but a lower, lesser level.

And the synergies Marc, or do you want to…?

Synergies I mean, yes we are -- yes synergies is going to be, we're going to recover synergies and we are preparing ourselves to transition from, I believe many countries. It will not have a major impact in terms of profitability in the year 2021, because this will be sort of a, part of the year, but other time, of course it's an important area for us.

Thanks Marc. Dave?

So Luisa on the first question, China represents an important part of emerging market sales. We haven't provided the split between China and the rest of emerging markets. But I will also say that emerging markets without China are also an important part of that number. And we saw within that area, really nice demand growth driven by Taiwan, Hong Kong, Russia, Brazil, Korea. On the specific question about China moving forward, within China we did see in the fourth quarter impact from the NRDL stock compensation that we needed to realize as we accrue for stock compensation that we're going to need to make as a result of the NRDL and the lowering of price that will take effect in March. As we saw with Flora, excuse me, as we saw with the second line as we've also seen in other indications, it does take several quarters, or excuse, me several months and maybe as many as two quarters for the volume uptake to start to compensate for the pricing. And it really is a function of how quickly we can get up the curve in terms of adoption within frontline. I will say that I'm pleased that we have the opportunity to expand access to frontline patients in China. You saw the speed with which we were able to grow the business when we got second line NRDL listing and I have every confidence that the team in China is going to be able to do the same with frontline and that the inclusion in the frontline on the NRDL along with the renewal and second line puts us in a strong spot with Tagrisso where in the frontline and in the second line, there's an opportunity to make sure that if a patient hasn't received Tagrisso, that they will get the opportunity to do so. So I think we're well positioned in a competitive environment there.

Thank you, Dave. Keyur Parekh with Goldman. Keyur over to you.

You guys, can you hear me okay? Two quick questions, please, the first one on Enhertu, Dave from your perspective, as we look at kind of the upcoming data sets in the second line and kind of the low HER2, what is the clinical profile that you would like to go to the market with, especially given how established kind of KADCYLA is in that setting? And then separately on the third kind of quite a competitive space from what we can see. So just wondering kind of the UCB the potential for differentiation on your SERD versus some of the others that are probably slightly ahead of SERD? Thank you.

Thanks, Keyur. So Dave maybe you could cover both questions and Cristian could add anything that he thinks is relevant to add to what you will say. Go ahead, David.

Great, thank you so much. I appreciate that. So I mean, I think in terms of the profile that we're looking for in the head-to-head study, what we know from KADCYLA second line study in the EMILIA study was that they were able to demonstrate a median PFS of 9.6 months overall response rate of 43%. And that was in patients that have median lines of therapy of one. We also know that, that study was run at a time before adjuvant Perjeta was really something that was standard of care and I think that's important to keep in mind that we're running now in a context of all the Enhertu studies are running in a context of patients who've all been previously treated with standard of care, which is now trastuzumab and pertuzumab. So we certainly, think that the control arm, which is KADCYLA, should probably in the real world today be performing at or maybe even a little bit slightly below what you saw in EMILIA. And the results that we saw on third line that what our breakthrough therapy designation and approval were based upon, actually are getting into the, 14 months of PFS range and overall response rate to 60%. And so we have every expectation as we bring that into earlier settings that, that should improve. So that's kind of how we're taking a look at the outlook on in Enhertu and I think that'll be a very compelling profile. Susan, I mean, Cristian in terms of the oral SERD and next generation, do you want to comment on some of the aspects of how we think about differentiation?

Sure, Dave, thank you. And thank you for the question. And we presented the data from SERENA-1, our Phase I trial with camizestrant, our oral SERD. And we believe that this drug has best in class potential in terms of providing superior clinical benefit at [indiscernible] dose. You have seen that the 75 mg q.d. that is the dose that we are moving in registration of trials. The results show that median PFS of more than 11 months and a clinical benefit rate exceeding 50%. We know dose reduction or discontinuation, no GI toxicity. This drug is already in two Phase, II trials, SERENA-2 that is comparing camizestrant versus [indiscernible] in patient with metastatic breast cancer and SERENA-3, that is a window of opportunity trial. There are several exciting combinations that we are entering now in Phase III pivotal trials. We've just started the first line combination trial with carbocycline [ph]. So we are, we have a very strong and robust clinical development plan with this drug.

Thanks Cristian and then maybe we could stay on the Sub. There's a question from Steve Scala, Cowen. And Steve's question is, Sanofi says it has a best in class molecule, what data would you point to that might argue otherwise? So we typically don't comment on competitors products, but maybe you could, again sort of comment on what makes our product so different?

I think that what I just mentioned in terms of level of efficacy, as a monotherapy in a very heavily pretreated patient population, pretreated with CDK4/6 inhibitor proceeded with chemotherapy, showing this level of progression free survival, especially disease control rate is quite compelling with our molecule. In addition, our safety profile, especially at the dose that we selected to move into pivotal trials, show a very benign tolerability. We almost -- we do not have dose reduction. We don't have discontinuations for adverse events on 75 mg and compared to maybe other molecule, the GI toxicities, the odd flashes. So those are adverse events that sometimes represented there some for patients and seems to be quite good. So we have a good molecule, and we are developing it in a very solid way.

Thanks, Cristian. So, still oncology, another question from Steve, about Imfinzi and it is a question for you, Leon, I think and Dave maybe can also comment. But so Leon the question is, are you seeing off label use of competitors in China for the PACIFIC regimen?

Yes, I think we are seeing quite a lot of off label usage of competitors in China using off label. But the PACIFIC regimen, Stage 3 lung cancer in China, the market is at the moment quite underdeveloped. We see some, but they're still, we are able to defend a large share for this PACIFIC regiment within [indiscernible] also have some spontaneous usage of the small cell lung cancer. So I think, ultimately, we intended with the good data, we should be owning the state of the stage three even at the self pay situation.

Thank you, Leon. Next question I think, on the – oops sorry Dave. Go ahead Dave.

No just to add on to what Leon was saying, and I think that, for clarity on this. So the off label use of checkpoint inhibitors is something that, as Leon pointed out, he's seeing we're seeing within China, the reason that the Stage 3 is less well developed, is because obviously that requires chemo radiotherapy, multidisciplinary teams. And I think that the work that Leon and his team are doing to develop that marketplace really is putting us in the right position to be able to defend the on label use for Pacific. And so there's certainly a lot of off label competition throughout checkpoint inhibitors. But I think that Leon is clued in on a key piece, which is that we're playing a role in the development of that way of treating patients which doesn't exist. And that's something that we've really developed a skill set on in China. Thanks.

Thanks. Next question is from Andrew Baum of Citi. Andrew, over to you.

Thank you. Questions for Ruud and then one for Mene. So for Ruud, it appeared to me that the anticipated timing of generic entry into the U.S. since we pushed out into the second half of 2018, I just noted the patent term extension got, I just wanted to confirm that's correct, or whether it's still the 25 that you've previously outlined. And then also any comments on how long COVID may result in or seek a demand due to either increased renal or heart failure. And then for Mene on the subjects, assuming we will require novel vaccines to address these some of these variants or emerging variants. How relaxed should we be about the challenges of developing novel vaccines, be it multivalued or otherwise. I'm thinking both from an efficacy point of view, things like antigenic sin anti [indiscernible] antibodies, as well as from a safety point of view. So many thanks in advance for those two questions.

Would you take the first questions and Mene will cover the vaccines?

Yes, absolutely, Pascal. So on your first question Andrew, based on my latest information is still 2025 the only piece is that we're also going to apply for pediatric extension. So that's all gets potentially a six months extension of our patterns are moving in the United States into 2026. Regarding COVID-19 impact on Farxiga and the outlook on heart failure and kidney disease patients, we are very bullish and yes, there is an issue. Our field forces are doing their best to reach out to nephrologist as well as to cardiologist and it's going well if you see the data, but equally of course, there is COVID-19 impact. I'm not going to play it down. The overall if you look at the performance of Farxiga in the last quarter, across all regions of 40% growth. It clearly shows the enormous potential of this, this product file portfolio. And we're very excited as Pascal already mentioned in his opening statement that we were granted priority review for CKD in the United States, as well as in Japan. So yes, there's a little bit of headwinds regarding COVID. But equally, the teams are doing a phenomenal job in order to drive this, this product where it needs to be. Mene?

Thanks, Rudd. There's a lot of questions there Andrew. So I'm going to try and answer as many as I can. So first of all, your first point is, if we need new vaccines, I think the jury is still out, I think with regard to protecting, even with these new variants against severe disease hospitalizations, it may well be that the current crop of vaccines we have are going to be good enough. But if we do end up needing new variants, and I think we're all going to be able to move reasonably quickly. We've started work on new variant vaccines based on the new sequences some time ago, and we're hoping to be in the clinic in the springtime ready for being able to put it into people's arms in the autumn timeframe, so a few weeks behind the mRNAs, but not that far behind. In terms of antigenic sin, whether you're going to have multivariant vaccines, in a single dose or dose sequentially, those are all questions we don't understand. So I think, right now, people are assuming that if you dose with a next gen variant as a boost, that you will drive the immune response to be able to give you protection against the new variant. That's not necessarily true, because you may have already biased the immune response to the original variants. So we're going to have to do those experiments Andrew and actually work that out using immunogenicity neutralization assays. But I think those are all the things that we will be working out over the coming weeks and months.

Thanks, Mene. Next question is from Sachin of Bank of America. Go ahead Sachin.

Thanks for taking my question. Sachin Jain here, Bank of America. Two topics, if I may. Firstly, on tezepelumab, I wonder if you could just discuss the relevance of the source data which didn't show the benefit on steroid reduction. I'm a bit confused that pairing seems to be cited as a reason given the study size isn't that different to the depiction or presenting in the studies and if you could just touch on commercial relevance of having missed that study? And the second one is just back to cash flow. So Marc, I wonder if you could comment to what sort of free cash flow improvement we should see in '21, relative to consensus at around $6.5 billion to $7 billion in operating cash flow. And then related you've been fairly vocal on dividend increases as part of the Alexion acquisition, when you expect you can get more concrete on that in terms of pair ratios are combined free cash flow, and your intent to specifically target income investors, given the dynamics elsewhere in the sector. Thank you.

Thanks, Sachin. Guys I appreciate that. Mene you cover first the source data and the interpretation, and then Rudd can cover the commercial relevance and Marc the financial questions.

Yes, thanks. Thanks, Sachin. So first of all, it's not a pairing of the study that led to the negative side of things, it is the design of the study, and some of the nuances within that. And I think when we present it, become clearer. I don't think it impacts the filing for teze in any way. And actually, the data were very consistent with what we saw with tezepelumab. It's really the placebo arms in performance. We wished when used the data, we still feel confident in the teze indeed provide steroid sparing or reduction over time, and we'll need to read it in there run another study to prove that, but there's nothing about the powering of the study that's led to this result. Ruud?

Yes, thank you, Mene. From a commercial perspective Sachin, we are, I think together with our colleagues of Amgen, we’re very excited about this product irrespective of the source Data. I think it's the first time that a biologic is clearly showing a very strong effect in low eosinophils, none of the other biologicals have been able to show that. So the potential is very substantial, roughly 60% are in what is called the moderate-to-low eosinophils situation. So in that sense, I think there'll be an extremely good product in order to serve those patients. But equally I agree with Mene, we will do more analysis, and we will look whether it makes sense in order to do another study. But in the short term, I don't expect any major impacts based on the source data.

Marc?

So yes, so on the cash flow, I'm not going to be able to give you guidance on the cash flow for 2021. But I think I would like to explain that the sort of benefits that we got on the cash flow in 2020, due to the vaccine will obviously reverse itself in part in 2021. So, this needs to be considered. If we just look at the sort of underlying cash flow, I think you will have a similar trend as when we saw over 2020 versus ‘19, which is a faster growth of the underlying cash flow if we exclude the vaccine. So I think you need to take these two elements in consideration. If we talk about the dividend, so what we have said is with the Alexion, if we do acquire Alexion, we'd have a stronger capacity for dividend expansion. We haven't provided any specific timing, but we have answered the question in the past of whether this would take place in 2021 and we have answered that 2021 will be a very busy year for us. And therefore, post 2021 seems to be a better time to increase the dividend. But we haven't provided a sort of a fixed payout ratio going forward, but clearly stronger capacity to expand the dividend from 2022.

Thanks, Marc. Tim Anderson, Wolfe Research. Tim, over to you.

Thank you. I have a question on Enhertu and specifically on DESTINY-Breast04 in the HER2-low segment. To me of the various readouts occurring in 2021, that's perhaps the most exciting, It's a large segment of the market. It’s one that's untapped with current HER2 therapies. So, it's quite novel. I'm hoping you can characterize the riskiness of this particular trial, and I'll show the commercial meaningful of that particular trial relative to the other readouts. And then on Farxiga and the DELIVER results in the half path heart failure segment, could be quite meaningful, but it's hard for me to handicap the risk of death. So what's your confidence in a positive readout on that trial later in the year? Thank you.

Thanks, Tim. So, Cristian, can you cover the first one? And Dave could add to this and, Mene, if you could cover the second question, but relatively quickly, because we still have a lot of questions and we would like to give everybody a chance.

Sure, thank you. Thank you for the question. And DB04 trial, I am very much in agreement with you, is a very exciting trial. One of the most importantly doubt that we will have the second half of this year, and is a study that is currently comparing in 540 patients and HER-2 best chemo standard-of-care. Chemo standard-of-care is a choice between different cytotoxic are being Paclitaxel, nab-Paclitaxel in [indiscernible]. This is a trial that we are running in 50 patients. It is a trial that is based on the preliminary data that we have been reported enough to low breast cancer in later line of treatment and probably every procedure lead monitor genius patient population. I think the data that we have presented gives us confidence that HER2 in this segment can be definitely superior to monotherapy, the monotherapy that I just mentioned. So and this is a very important trial because based on the results of this trial, we will decide what’s next in this specific segment as to low. And of course, this can give us an opportunity to expand further this segment with combinations or even going earlier in terms of line of therapy.

And anything you want to say very quickly.

Yes, so very quickly, Tim, what I would say is that commercially, it could be very attractive, it will obviously depend upon the data. HER2 low could be as big as three times the size of HER2 positive. But remember HER2 low is a continuous variable. It's not a binary one and so we'll have to see kind of what the data show, when the data come out. But in terms of opportunity, we're certainly excited about it.

Thanks. Mene talk…

Yes, I'm not going to give appropriate tests, I would say that have passed is definitely more challenging. But I think with what we've seen so far across our studies, we feel confident that we should get a hopefully a positive readout, but ultimately the trial readout and we'll see the results and we get them this year.

Thank you.

Thanks, Mene. Since we are Farxiga, there is a question from some facilities, but first year consensus estimates, do you think they are sufficiently reflecting the potential for the drug? Can you update on the potential for patent protection in the long term?

Yes, Pascal thanks for the question. There's some -- we're not commenting too much about the absolute numbers. The only thing I can say that we are very pleased with the very strong performance across all the geographies, that the potential of course of CKD is very, very substantial. It requires a lot of market development, but we are working hard on that. And equally, of course, in many geographies we have just launched heart failure and the attractiveness of Heart failure is evident and is also now seen by international guidelines and local guidelines. So once again, I'm not going to answer your question, but you can hopefully hear my enthusiasm about the potential of Farxiga in the next six, seven years. The potential for patent protection, I think, once again, I think there's a potential in order to extend our patent based on the pediatric in education, if that will be granted. So we are working hard on that piece. And then on top of that, we are doing and Mene was mentioning that quite extensive combination, combination studies with a couple of other assets, which, we will need to wait and to see the results in the next few years.

Thanks, Ruud. And Sam had a question about the vaccine. At what point would we consider making a profit and we still have to define this. And we can in almost all geographies, or we book the sales and keep the profit to ourselves, alternatively, we share with our partners in the various geographies. The next question is Jo Walton of Credit Suisse. Jo, over to you.

Yes, with respect to the one question rule to allow as many people as possible on the call, if we look at the consensus for 2021, it's just over $5 and that's at the top end of your range. However, there only appears to be about $975 million of other operating income within that. Now you've got some base business of other operating income, you've got the Ad free income, you've announced the crystal deal, and you've got the stake, the [indiscernible] stake. So presumably, as people put all of those numbers in, other operating income comes in, comes up quite significantly, that would normally drive profits. So you would perhaps expect more than $5 of earnings. So I think what people will have to do is increase their level of investment, if they're going to keep their earnings still in that $5 range. So my question is, which is the area where we should consider more investment? Is it all discretionary, fantastic R&D and you can spend more on R&D? Or is some of the incremental investment that collectively we haven't gotten our numbers and SG&A investment, it's actually going to take more boots on the ground in order to sell these products. The reason that I asked is partly because the one area that did increase in expense in 4Q was SG&A, up 6% in constant currency, which is a quarter which presumably had some COVID disruption in it. So I'm really trying to get some idea of how that SG&A is going to move going forward? Thank you.

Thanks Jo. Marc this is for you.

Yes. So thank you, Jo for the question. So you're I think you're basically trying in relation of the other income is looks, plausible and possible to me. As far as the -- you're trying to find one cause of potential differences between us and consensus. I think we are very close to we are very close to consensus, but I think you need to look at probably the integrity of the P&L and starting from gross margin, as well as R&D including SG&A, I think, I don't think it's only on one line, that there's a difference. There's obviously the different that you mentioned, on a possible different that you mentioned on other income, I would look at the totality of the lines. And I do apologize, but I can't give you much more indication on each of these lines today, but I would not think it's on one line, I would think it's may be a composite on many lines.

Thank you.

Sorry, we are speaking, speaking in riddles today Jo, but again, as we said, our ability to comment on 2021 is more limited than usual. James Gordon at JPMorgan. James over to you.

James Gordon at JPMorgan. Thanks for taking the questions. One following up on tezepelumab, so we saw the navigator data at triple AI. And the efficacy looked pretty competitive in the high and the low clinical patients. So is the plan just to go through the lows? That's where you're really differentiated? Are you going to be competing against the center and the highs as well because you assume you get approved in both and is those frequency important in this category? [Indiscernible] we're talking about doing long-acting new color, are you going to look to do long-acting version of either of these products or is that not really something that matters in this space? Secondly, Farxiga, so your comments about the generalization are they're 20. And I can see a few different combo approaches that you're doing for kidney disease, which would be a way of extending the new IP. I can't see anything listed at the moment for the combo approach to heart failure. So is there a plan to do combo approaches for heart failure oris that going to be generalized. And then finally, just a clarification, on the COVID antibody, I think Mene made some comments about efficacy for COVID-19 variants. Was that talking about the UK strain also talking about the being confident in efficacy for the South African strain as well.

So, you're pushing luck, James. Three questions like, three questions in one and maybe the first two Rudd, you could cover and then Mene you could say a couple of work on the long-acting antibody.

Yes, of course, Pascal, and thanks for it, James. Regarding tezepelumab and the positioning, clearly, we see this potentially as a best in class molecule and therefore, we will not make a distinction between the high eosinophils and low eosinophils. We are working here with our partner Amgen so we're not going to niche ourselves we will position the product based on in-depth market research, and if that means that we also are going to penetrate in the high eosinophils, we will certainly do that. Regarding your question about how important is dosing, I think it's important it is the less frequent a patient needs to go through a hospital, or a clinic or ideally can inject themselves is a win. But equally of course, this is a class heavily directed by efficacy. And therefore we have seen multiple times that for the patients, most importantly is a strong efficacy and less dosing, but equally of course, if you have a dosing advantage, you will use it. Farxiga, questions about heart failure and the combination. Yes, there are multiple combinations in kidney disease, but equally, we're also looking at combinations in heart failure. There'll be a bit earlier, but where it is possible we will certainly do that. And when the time is there, we will clearly disclose that. Mene?

And just to add, we already have a dosing advance as the center exists every two months with its I mean, we're looking at to see if there's any additional benefit of increasing the dosing schedule with regards to the antibodies. It's against all variants, actually. And it's two independent approaches now that have shown that our cocktail both antibodies and our cocktail actually are still very potent and neutralizing all of the new variants that we talked about South Africa or Kent, and that's in contrast to many of our competitor antibodies were either one or both of the antibodies right actually quite severely impacted so we've, we're in good shape with our antibody cocktail, both the South Africa and Kent variance.

Thanks, Mene. This is an exciting compound for sure. So we have a question from Simon Baker at Redburn. Simon, over to you.

Thanks very much. And this is just the one question out for Dave on Calquence and elevate our study a couple of years ago, a lot of people thought that the Calquence wouldn't take off without until they elevate our study, and yet the sales trajectory has been very impressive in the U.S. So I wonder if you could give us your updated thoughts on the impact of elevate are both in the U.S. market, and also ex-U.S. where obviously, you would have a have had a much earlier stage. Thanks so much.

Great, thanks, Simon. I think I've pretty consistently been talking about the fact that our mindset in the U.S. and indeed across the globe has been that we need to be successful with Calquence irrespective of the outcome of the head-to-head study. I think the results that we talked through today, and the progress that we've made, certainly shows that we're doing that in the frontline setting. We did though, take I think both a smart and a courageous risk in the head-to-head, I'm looking forward very much to sharing those results. We obviously won't have discussions about those results until they're presented. So we continue focusing in on the data that we've got in front of us. And I think that we have the belief that we've got a best in class agent, and we've achieved parody in the U.S. in terms of new patient share in MCL. And I see no reason why we shouldn't continue to move on that trajectory. And we have launches underway across the globe. And I'm pleased that in Germany and in the UK, we're already starting to see positive movement within Europe and looking forward to more approvals in the frontline.

Okay, thanks so much.

Thanks, Simon. Next question is Peter Welford of Jefferies. Just one question, if you don't mind Peter, are you on mute?

Sorry, can you hear me now?

Maybe we can go to.

Sorry, can you hear me now.

Peter.

Just really a point of clarity please on the cash flow and I don’t know whether Marc can comment on this or not, but just with regards to the payouts that we should potentially be thinking about in 2021. I think you've already made two payments, milestones you disclosed, Daiichi and I wonder if you can give us in broad terms the other collaborations and then potentially sort of amounts we should be thinking about in terms of the potential outflows to partners during the course of 2021. Thank you.

Thanks, Peter. Marc?

We don't provide this sort of a schedule of payments for the year for the coming years. But we have -- when we have concluded the deal, the deals, we have usually indicated the various types of payment we make for each of the project. So the question then comes, when is this triggering point? If we pay for development milestone and approval milestone or something else, the question becomes then when is this triggering bond taking place? So I'm not going to be able to comment in detail about that. Apologies.

Thanks, Marc. Emmanuel Papadakis, Deutsche Bank. Emmanuel go ahead.

Thanks for taking the question. Maybe it's a good one on Imfinzi. I mean, it seems to have flattened pretty hard in the U.S. timelines have slipped and several trials, including adjuvant. You've had some interesting comparison studies started including digit combination. And I don't think we've seen anything equivalent yet, started in terms of physical trials from assets above. So you could comment on the outlook, where and when will any further people becoming from Imfinzi side and your perspective on competitive risks over the next few years? Thank you.

Dave?

Thanks, Emmanuel, for the question. So on in Imfinzi, we have with the Pacific indications, certainly in the major early markets that we've launched, gotten to a place of standard-of-care. And as a result, we've seen, kind of more modest sequential growth, particularly in the latter half. With that said, the CASPIAN study is an area that we are really looking forward to making continued inroads into. We have a very nice profile. It's been well received by physicians and oncologists across the globe. The pandemic has affected probably Imfinzi as an infused therapy, more than it has some of the other products within the portfolio. In terms of the pipeline question that you asked, I think we highlighted some of the studies that I'm looking forward to readouts on later this year PACIFIC 2, to HIMALAYA, both of those are important opportunities to continue growth. We also are doing our own work on teacher combinations, in collaboration with Arcus which is something that we've spoken to in the past, or Arcus has spoken to. And so we look forward to continued news flow out of Imfinzi in the rest of the year

Thank you.

Naresh Chouhan of Intron Health.

Hi, there. Thanks for taking my question. Just one on Symbicort please. In the U.S., we've clearly seen the benefit in 2020 from a higher adherence. Should we expect to be expecting a similar level for this year based on pricing and what you've seen today in volumes, is quite a big number, just trying to get a sense of where that's heading. Thank you.

That’s for you Ruud, I think.

Yes, so it's another good question. Once again, we're not going to comment on individual product forecasts, but Symbicort is well placed. It's the leader in the United States in the ICS/LABA Class. There's a huge heritage. So we're bullish regarding the outer loop. But equally, we also need to mention that we are focusing our efforts more and more in breast03 as well. In the COPD, we really believe if there was a high unmet medical needs, the triple class is growing very, very fast, so a lot of the efforts of our field force marketing and medical teams, more and more on breast03 and less on Symbicort moving forward.

Thanks. Thank you. Christopher, Uhde. Go ahead.

Yes, hi there. So my question is about, so COVID therapies. So the AZD7442, I guess it's the same underlying technology as nirsevimab. But the as I understand it, the cogs on the nirsevimab are prohibitive for use in adult prophylaxis in RSV. So what can you say about this in cogs in with 7442? And why, if any, is there a discrepancy? And then I guess, related to COVID therapies, can you comment on, I guess there was a recent study with Symbicort, can you comment on how you see that opportunity?

Thanks Christopher. Very quickly, the first one cost of goods is some, call it reasonable or we see in relation to the selling price of this cocktail -- of course, it's more expensive, because you have to put two antibodies and [indiscernible] but we don't see this as a limitation in terms of the potential of the product. Symbicort, or do you want recover this, this is Symbicort in the COVID patients and the study, the only study with a small amount of patients, but still quite intriguing showing a 90% reduction of progression of disease. Yes, I have not seen before this chromic. Quarter that is apparently. But that is without any doubt. It's a very interesting finding this study was stopped earlier than expected because of the overwhelming efficacy. And we know of course, that corticosteroids have a very dampening effect on the cytokine storm in COVID-19 patients. 8Now the implications for what it means we're still trying to figure it out. But equally Of course, we have seen that Symbicort adherence has increased quite substantially in asthmatics and are more and more reports, that asthmatics because of the fact that they are using a corticosteroid inhaled corticosteroids are ending up less in hospitals, and are showing less severe disease than other patients. So we're following it. We are looking into it, but I think it's a little too early in order to get overly excited that this will be a massive sales opportunity.

Good. I'll just say one more thing is we do have several studies that are ongoing with [indiscernible] Symbicort that are being run externally, just to continue to follow that efficacy.

Very good. So we'll take the last question, Martin [indiscernible]. Go ahead, Martin.

Thank you, for a number of years, your SG&A has been more than 10 percentage points above the weighted industry average. You've made some good progress in 2020 with the increase in sales being achieved with flat, underlying SG&A, but apart from increasing sales, how do you intend to get your SG&A costs more in line with the industry average or an alternative way of looking at it with your current sales force to bring your SG&A in line with the industry average, you need to have product sales of $39 billion, do you think that's achievable?

Marc, do you want to cover this one.

Yes, I think I can only point you to the years, the three past years 2018, '19 and '20 and see the progress that we have made on the SG&A ratio, we have also said that we will always, you know, put enough resources behind the launching of our new products, and on new indications so that we put them on the right trajectory. So this we will continue to do, but since we are promoting products, within the focus areas where we are present, overtime when the sales grow you have these phenomenon of operating leverage at different levels, but in particular on BH 89 [ph]. So we're going to continue efforts on the operating leverage, and over time the SG&A ratio will decline.

Thanks Marc. Just one, maybe one last question Seamus Fernandez of Guggenheim. Seamus, go ahead.

Oh, great, thanks for the question. So mine was just on Roxadustat. I know we're in kind of the final days of FDA discussions, just wanted to get a sense of your confidence in getting the non-dialysis portion approved. And if really the only source of debate is whether or not you have an ESA like, warning on CV risk. Thanks so much.

Mene the - for you.

Competence is high, I would say.

All right, thank you.

Coming on to the question, the short answer competence is high.

Mene.

Okay.

So thank you so much, everybody. And I know we took you over time, but there were so many questions. So I'd like to thank you very much for your interest. And we look forward to meeting your during the Global Award shows that starts tomorrow. It's really going to be a very exciting year, lots of opportunities for us and I look forward to the discussions. And again, once again, thank you so much for your interest and goodbye.