Good morning and good afternoon, and welcome to the Novartis Q4 and Full Year 2018’s Results Release Conference Call and Live Audio Webcast. Please note that during the presentation, all participants will be in listening mode only and the conference is being recorded. [Operator Instructions]. After the presentation, there will be an opportunity to ask questions. [Operator Instructions] A recording of the conference call, including the Q&A session, will be available on our website shortly after the call ends. [Operator Instructions] With that, I would now like to hand over to Mr. Samir Shah, Global Head of Investor Relations. Please go ahead, sir.

Thank you very much and good afternoon, everybody and welcome to the webcast today. Before we actually start, I'd just want to read the Safe Harbor statement. The information presented today contains forward-looking statements that involve known and unknown risks, uncertainties and other factors. These may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. Please refer to the company’s Form 20-F on file with the U.S. Securities and Exchange Commission for a description of some of these factors. Thank you. And with that, I’ll hand across to Vas Narasimhan.

Thank you, Samir, and thanks, everyone, for joining today’s call. With me today in the room is Harry Kirsch, our CFO; Shannon Klinger, our General Counsel; John Tsai our Chief Medical Officer and Head of Global Drug Development; David Endicott, our CEO of Alcon; Paul Hudson, our CEO of Pharma; Richard Francis, our CEO at Sandoz. And I'm proud to welcome Susanne Schaffert, our new CEO of Novartis Oncology. Susanne brings with her over 20 years of experience within the company deep expertise within oncology. She most recently ran our radioligand therapy business post the transaction with AAA and I have full confidence and really look forward to a great contributions running oncology. So if we move to slide 5 through the pictures, you can see that, we really laid out over the course of the last year a clear aim to be a leading medicines company powered by advanced therapy platforms and data science. There are four pillars to the transformation that we're currently undertaking focusing the company, driving growth through cutting-edge platforms, which include continuing to drive our leading pipeline as well as building advanced therapy platforms. Becoming more consistently passionate about productivity and margins and building a new culture that will have a lasting impact on society. And over the course of today's presentation, I'll walk you through the progress, we're making in every one of these dimensions. But before doing that, I'd like to move to slide 6, where you see our full year at numbers where we delivered strong growth with operating leverage in Q4 and in full year 2018. Harry, will go through these numbers in more detail. But I think most importantly, we've delivered against our guidance. We've delivered strong sales and core operating income growth, and we've delivered the operating leverage which…

Thank you, Vas. Good morning good afternoon everybody. As usual my comments will refer to growth rates in constant currencies unless I say otherwise. So on slide 27, just a quick comparison between the guidance we gave in January last year and the final results. As you can see, we came in exactly on guide and even a bit at the upper end for sales. Slide 28, shows the summary of our quarter four and full year performance. We continue to deliver strong growth in quarter four with sales increasing 6%, driving core operating income up 11%. Full year sales up 5% mainly driven by Cosentyx, AAA and our four new addition blockbusters including Entresto. The sales growth and gross margin expansion drove full year core operating income up 8%. Operating income decline in both quarter four and full year. This was mainly due to M&A transactions, higher restructuring costs for productivity programs, and impairment charges. Full year net income increased 64% to $12.6 billion, driven by the gains from the OTC joint venture stake exit in quarter two of 2018. Free cash flow grew 12% during 2018 to $11.7 billion and I'll come back to free cash flow shortly. One of our key priorities, as you know, is operational excellence. And of course, it includes margin expansion. And we have delivered on that priority in 2018. So on slide 29, you see the quarter four and full year core margins of the group and each division. Strong sales uptake in Innovative Medicines drove margin expansion up 100 basis points for the year to 32% of sales, on its way to the mid-30s margin goal by 2022. Sandoz had margin at 20% level despite U.S. pricing pressures due to gross margin improvements. And Alcon full year margin grew to 18%,…

So, thank you, Harry. Maybe we could start with Cosentyx. It's been a very impressive 2018, strong growth driven by demand, and well-positioned across all indications. The year played out pretty much as we predicted in terms of our performance in market share and our growth across the world. I think we have to shout out for our continued superb growth in the U.S., 29% in TRx in dermatology, close to 50% in rheumatology. So, we're really the market leader in the new entrants defining what will be the future era in immunology and around these diseases. We've gained share and we consolidated our position. We've also finessed our access for 2019. And much like we predicted last year we want to make sure that we're available in the first-line setting. We want to make sure that those who need them as most can get it, but I think it's really worth being clear as we go into Q1 our expectation. Our expectation is growth quarter-on-quarter, year-over-year. Our expectation is strong performance year-over-year 2019 over 2018. Yes, reverification, co-pay resets and other nuances in Q1, but we expect to repeat our successes in terms of increasing demand as we saw in 2018. We didn't stop there of course. We have a lot of work to do and we embarked on the ARROW study, a study designed to advance understanding in dermatology and not just to seek a marketing message. It is a study that is set out to try and help understand the extra manifestations and difficult-to-treat patients are more prevalent than you realize. And we'll probably be one of the largest groups overall in the disease area. As we say, it takes more than clear skin to win in this area. And then finally in terms of news flow,…

Thank you, Paul. So actually on slide 40, you see that oncology had a very good year in 2018. We were growing 9%, driven by very strong performance of our growth drivers. And as Vas already mentioned, both Promacta and Tafinlar+Mekinist were both growing over 30%, both reaching blockbuster status. And we are very confident that these two therapies will continue to be clear market leaders in their classes. We are also excited to see data on the combination of Tafinlar+Mekinist with our PD-1 inhibitor later this year. One maybe to mention also is Jakavi led continued strong double-digit growth and almost made it to blockbuster. So going to the next slide. I think Vas clearly mentioned that our aim is to build leadership in advanced therapy platforms and one is clearly our radioligand therapy platform. We are very excited about the performance. Lutathera continues to exceed our expectations, having reached sales of $160 million in the first year of launch in 2018. We see continued strong launch uptake in the U.S. By now we have over 100 centers actively prescribing and over 80% of lives covered. We also saw good progress in Europe with the reimbursement. In the U.K., we already have 19 prescribing centers. It's important to remember that radioligand platform requires managing a highly complex supply chain from securing a reliable isotope over complex manufacturing steps and shipping with no room for delays, given the very short half-life of the product of only three days. We are very proud in AAA that we have vertical integration and really this resulting in a very high reliability of success enabling us to deliver the product within two weeks from taking the order. We believe this gives us a unique differentiated advantage in a growing transformative space that is difficult…

Thank you, Susanne. So in closing as you can see on slide 46, we'll have a busy year in 2019. I won't go through everything on this slide. But the most important overall message is we're focusing as a leading medicines company, we’re focusing on driving growth through a dynamic and exciting platform as well as building -- a pipeline as well as building new platforms for growth. We’re focused on productivity and margins in a way like we've ever been before. And we believe that combination will enable us to have a stronger growth profile and a more attractive business for years to come. So with that, I'll hand it over to Samir to lead the question-and-answer session.

Okay. Operator, we are ready for the Q&A.

Thank you very much. [Operator Instructions] The first question this afternoon comes from the line of Graham Parry from Bank of America Merrill Lynch. Please go ahead with your question.

Hi, thanks for taking my question. So firstly one to Harry on the guidance on current business structure, the mid-single-digit core operating income that's three points below the consensus was. But when you strip out Alcon U.S. generics it looked a little bit closer. So, do you think essentially the street has been too optimistic on those businesses for this year? Or is there anything else you'd point to, for example, expectations around launches for example? Secondly, on Zolgensma, more discussion on the trade press, and you just referred to yourself about being able to spread payments and innovative payment structure. So could you perhaps dig in a little bit more detail on how far those negotiations have gone? And do you think those sort of payment structures will be in place in time for a midyear launch immediately post approval? Or do you see any reimbursement delay here post launch of the product? Could you also just clarify or comment there about breadth of label? Then thirdly on Gilenya, should we read the fact that you're guiding for no generics and also your base-case scenario doesn't have generic in it this year. And on slide 25, you seem to have pushed it towards 2020, 2021 is implying confidence in lack of generic launch. Could you clarify if any of the generics have stated to the court an intent to launch at risk this year? And so should we expect preliminary injunction proceedings from your sales this year? Thanks.

Thanks, Graham. So first on guidance, Harry?

Yeah. Thank you, Graham. So on the guidance, overall, we see continued SEC for a new medicines company, strong growth profile, mid-single-digit growth. Despite a bit higher expected generic headwind, but driven this mid-single-digit in Innovative Medicines and for new focused company by our strong end-market brands and expected launches, but a bit of a headwind from Exjade and Afintor to expect in generics, but I think a really strong growth here with mid-single digits. And to the bottom line, clearly core operating income growing ahead of sales and driving margin expansion. Now when you go now to the current group structure, a bit at lower level given that, for example, the U.S. solids business [Indiscernible] has a different growth or client profile clearly. But of course this guidance also in a certain range, so I would not see a weakness of Alcon, for example, where I'm sure David Endicott can comment where we continue to expect the growth to low to mid-single digit and also margin expansion. So from that standpoint, we see this as a clear guidance for a strong growth profile of the new focused company. And on the other hand also I think, maybe some of the analysts work has not fully reflected the currency effect, so which are there for 2019 which we are mentioning every month on our website. And this is a minus 3% on the bottom line if currencies stay where they are.

Maybe I would just highlight there, I think strategically for us you can see that the new medicines company has this stronger growth profile. We have a clear ability to grow to mid-single digits, a clear ability to generate margin expansion and grow bottom line faster than top line. So we feel good, we're headed in the right direction and encourage investors to focus on that new company that we're creating. So moving to Zolgensma payment structure, Paul?

Thanks, Vas. So as you'd imagine, we had a lot of detailed conversations with payers on leading reimbursement. We – I can tell you unequivocally, we'll be ready with alternative payment models at launch. The installment approach has been well received in conversation, but it's not essential for everybody. But we will be with what we think is the most flexible way to come to market for the payers. And again, our conversations have been very constructive with payers. Don't see an issue there. As for breadth of label, it's too early to say to be honest. But I would add the word constructive again. I think, you expect the regulators, where they see such an opportunity for a foundational therapy to try and be as constructive as possible. So we are on track with where we'd hope to be.

Great. Thanks, Paul. So on Gilenya I'll have Shannon, our legal counsel will take that.

So, Graham, thanks for the question. As you know the compound patent in Gilenya expires in August 2019, so no generic launch prior to that. In July of last year, the Patent and Trademark Office upheld the delivery of our 2027 dosage regimen patent, which means generics can't launch against that patent unless they do so at risk. In parallel to the patent office decision, we did file a lawsuit against 23 generics companies seeking to enforce that 2027 dosage regimen patent. 11 of those companies have refused to indicate whether they will launch at risk or not so we will engage in preliminary injunction proceeding. Just this week, the Court has scheduled on June 21st hearing on our preliminary injunction motion which we hope will give clarity to the status of that preliminary injunction as to the 2027 patent expire August of 2019. The bottom-line in all of this is that you can only see generic launch at risk either if they win the preliminary injunction hearing in June or if the patent is declared invalid either through the IPR process where we expect the appeal to be decided in Q4 of this year or even the first half of next year or if the patent has been validated by the District Court where the hearing is currently set for March of 2020. And it's three to six months after that for us to see a decision. And then, of course, if the decision doesn't go our way, we will appeal. And so we feel good about the guidance we've given and look forward to the arguments in the Court.

Great. Thank Shannon and thanks Graham. Next question?

Thank you. The next question comes from the line of Andrew Baum from Citi. Please go ahead.

Thank you. Three questions please. Firstly, Vas, you were quoted at Davos as talking about the danger of reforming U.S. reimbursement system, the government plans in an overly hasty -- consequences. Were you thinking of any particular part of the proposed reform in mind? On the same topic, could you comment about how you're thinking about proposed net pricing shift by rules of the Safe Harbor? Second on Sandoz, should we imagine that once you've divested U.S. solid, the residual of the Sandoz business will be pruned and optimized is going to be a long-term part of Novartis' structure? Or is this being improved with a few potential divestment down the track, so its core or non-core? And then finally, could you say something regarding your large but still -- yet undisclosed early-stage immuno-oncology assets. There should be a number of combinations with your internal PD-1 as a promising agent. When do we expect the data? Should we expect to deal sometime at year-end? Thank you.

Thanks Andrew. So, first with respect to U.S. reimbursement, I think my comments were really regarding some of the comment that are being made currently in Washington to take I think what could be I think longer term destructive actions, things like importation, reference pricing, et cetera, none of which I expect to have happened. Nonetheless, I would want to be sure that we don't take an action without thinking -- the government doesn't take an action without considering the consequences for the entire system. We've been proponents for looking on how do we ensure rebates and other payments within the supply chain, enable patients have more affordability at the pharmacy counter, continuing to reform programs that may have distortions in them including Part B, 340B, et cetera, ensuring that we have a playing field that enables competition after appropriate amount of patent protection. And we need strong IP, of course, enabling the base, but then after that to limit gaming or other elements that prevent generic entry and prevent the robust generic environment including biosimilars where I think we continue to see U.S. lag Europe in terms of the overall uptake of biosimilars. So, those are some of the elements. I'm sure there are others. So, I think we need a comprehensive approach. Now, with respect to the discussions on the Safe Harbor and removing the Safe Harbor on -- it's difficult still to judge exactly how that will impact our pricing approach until we see the details of what exactly is being proposed, and then how the system will react to those changes. I think we've seen assessments that indicate a range of potential outcomes depending on how this is done. So I think until we see more details it will be difficult to comment. So we'll just…

Next question.

Thank you. The next question comes from the line of Tim Anderson from Wolfe Research. Please go ahead.

Thank you. A couple of questions. You've done a good and comprehensive job articulating various drivers of revenue growth for Novartis through in-line brands and new pipeline launches. But for the sake of your balance, I'm hoping you can also talk about what the drags on top line growth are, not just in 2019 but maybe in 2020 as well so over a couple year period. I'm not talking about systemic headwinds like U.S. price reform but really company-specific headwinds, whether it's competitive challenges to in-line brands or upcoming generic launches that sort of thing. Second question is on emerging markets. In your performance you have one of the larger global footprints among peer companies. If I look at your performance, it's good, it's not great. I'm wondering what could change this versus just how the chips fall in terms of the portfolio of products you saw there. And can you talk about the prospects in China as well? What you see happening in terms of marker reform and whether there are pressures that could push growth lower in China specifically?

Great. Thanks, Tim. I think on revenue growth, I'll name I think a few key drivers in my mind and I'll look around the room to see if any colleagues who want to pick up anything else. As we said the -- as Harry said the generic entries in Exjade and Afinitor, Afinitor, Exjade later this year and Afinitor in early 2020, I think is something we’ll have to overcome. We feel confident we can overcome those two generic entries. I think those will be two key ones we'll have to stay on top of. In addition, of course, as we've discussed the Gilenya situation, let's say, we feel good now about 2019. And we'll have to see how the events evolve over the coming year to see – year and year-and-a-half to see when Gilenya might have any generic entrants in the future. Votrient where we did take an impairment, is largely related to the slowdown we saw in the back half of 2018, primarily driven by the entrants of PD-1 combinations in renal cell carcinoma. That one where overall our other GSK – assets acquired from GSK outperform like Mekinist and Tafinlar as well as Promacta and Revolade. But with Votrient we do expect there to be more headwinds in the coming periods. And then the other, I think, wildcard out there which has been out there for us for 15 years is Sandostatin LAR and any potential generic entrants for Sandostatin LAR. Those are some of the big top line headwinds we see. And again relative to the strength of our in-line brands and the upcoming launches, we feel confident that we can grow consistently over the coming period. Harry, anything else you would…?

You had the main ones. Thank you.

So then moving to emerging growth markets, maybe Paul you want to say a word about where we are and where we are in China specifically?

So I think I can see where you got that section from. Some it's portfolio driven. But if I look at the last couple of years of our increasing investment in China, the sort of I think industry-leading NRDL listing last year, as we transition our portfolio to some of the older medicines and conclude some divestments. We end up with real growth drivers positioned in China. The investment is deployed. So we look forward to gathering some momentum and revisiting China is a real growth opportunity with what we have in market. So watch this space is probably what I would say about China.

Great. Thank you, Paul. Well, any other comments on the emerging growth markets? In the meantime I'll just make some general comments. We continue to see strong growth in our established medicines portfolio in emerging growth markets. Actually, we do very well with that portfolio. I think one of the things we're aiming to do to emerging growth brands – emerging growth brands as well as other strategies to get access to our more Innovative Medicines more quickly in a broad set of geographies. We don't necessarily see that as a near-term growth driver, but hopefully in a medium term we can start to build the innovation interest in these markets to hopefully drive growth in the future.

Okay. We'll move to the next question.

Thank you. The next question comes from the line of Matthew Weston from Credit Suisse. Please go ahead.

Thank you very much. Two questions, if I can. The first on AVXS-101 and the data in Type 2 SMA. You've highlighted, we'll see the data at AAN in May, but filing not scheduled until 2020. So if you can explain why or what additional we're going to see between AAN and what's required for filing, that would be extremely helpful. And then secondly, just regarding your comments on capital deployment Vas, and particularly the comments around bolt-on M&A. Clearly, the dividend's grown for its 22nd year, but only up 2%, which is meaningfully different from where earnings grew and also the earnings guidance outlook. With your comment that you'd like to see a consistent level of bolt-ons and then you flagged $15 billion, are you suggesting that we should be expecting a relatively meaningful number each year? Or just the bolt-ons remain a key element of the strategy?

Great. First on AAN John you want to take that?

Thanks Matthew. Regarding of AVXS-101, as you know STRONG is our Phase I study using our intrathecal formulations for Type 2 patients. That study is ongoing. We have three different dosages being studied and the mid-dose is fully recruited and that study is advancing well. We also know from history that the Type 1 results are predictive of Type 2 and Type 3 patients, so we're looking forward to sharing that information in May with AAN. And based on the results that we get we will use that information for the filing. So that timeline, I think, will be really dependent on what the data shows us and you'll be seeing more about that in May.

And so Harry -- I think Harry want to take some on the dividend before I take on bolt-on M&A.

Yes just -- Matthew I just want to make one comment on the dividend. First of all -- actually two. First of all, we actually see this over multiple years, so we also increased the dividend in years that we didn't have earnings growth or free cash flow growth with major patent expirations as you know. And the other -- and we are quite well placed, I would say, from a percent payout of free cash flow and the dividend yield and the peer growth. And second of all, wanted to remember assuming the high likelihood that Alcon spin gets approved at the AGM, we will not rebase our dividends. So, the remaining Novartis dividends is expected to grow from the current base of CHF2.85, so that I think is another important aspect of our dividend policy.

Great Harry. And then in terms of -- and bolt-on M&A. The way I think about it, the way we think about it is we want to be consistently trying to do M&A in the range of up to 5% of our market cap which would really be in that up to $10 billion range. But I think what drives us is having good assets and assets where we can generate a strong return for the company and build in our core therapeutic areas and in these new technology areas advanced therapy platforms where we want to lead. So, we want to try to hit a target so to say on M&A, but I think we have our minds open to the fact that in order to build a more and more valuable company over time, bolt-on M&A has to be part of that strategy along with our in-line portfolio and that's the way we are going to approach it. Next question?

Thank you. The next question comes from the line of Richard Vosser from JPMorgan. Please go ahead.

Hi, thanks for taking my questions. First question just on Alcon. The margins were called out a little bit lower than expected due to higher promotional spend. So, could you give us some extra color on where the spend was targeted whether we should extrapolate that going forward or whether there's any element of a pull-through from 2019 into 2018? Second question just on Cosentyx, I think, you've highlighted, but please could you just repeat again the Cosentyx will grow quarter-on-quarter as of the fourth quarter -- in the first quarter 2019. But secondly on Cosentyx, could you give us an idea of how you see future competition coming in. I suppose from AbbVie on 2020 on the Cosentyx product? And also maybe give us an idea of how the growth is looking in psoriatic arthritis and ank spond, just whether you're seeing any impact from the JAK inhibitors there? And then final question I suppose on Sandoz. Clearly I think expectations of biosimilar growth in the market and from you. So when we exclude the oral solids business decline, what are the things that are leading to sales being broadly in line year-on-year? Is there any -- are there any other pressures that we should think about there? Thanks very much.

Thanks, Richard. We’ll start with David on margins.

Thanks, Richard for the question. First of all, we are very pleased with another solid sales growth of 4%. We had a strong turnout in surgical at 6%, continued growth in emerging market. That gives us a really good run from where we started at 5% for the full year. So we're feeling good about the revenue side of it. But on the fourth quarter specifically, we continued our planned investments behind some of our core long-term drivers PanOptix, DT1 Multifocal sustained complete. And we continued spending on operational improvements such as the SAP deployment and some of the proposed spin-off areas. So the fourth quarter margin came in where we had planned it to be. And as Harry indicated we were pleased with the 80 basis point improvement over what was our trough year of 2017. So going forward, we haven't given specific margin guidance for 2019 other than to say we intend for it to be accretive to 2018. And there's really no change to that position. But once we are spun off, we intend to be more granular about the 2019 guidance and so we'll go forward from there.

Thanks David. Moving to Paul.

Thanks, Richard. Important to clarify this, want to be as clear as possible. So, what I said was year-on-year growth we're confident in, I said that Q1 2019 over the Q1 2018, again we should expect significant growth. Now, specifically Q1 2019 of Q4 2018, I think that's what you're asking. We will be broadly in line there are some benefit verification, some co-pay reset, some financing, and all those things. But broadly in line, we expect to grow our volume and be close to if not on what we did in Q4. Is that -- I think that's clear enough. On new entrants, with infliximab it’s probably the last major entrant to the market, and which is why it's so pleasing for us to be at least currently a leader of the new entrants. That sets us up for the long-term. Whilst not particularly concerned about the clinical profile of rituximab, I think another I/O 23 will be another I/O 23. I think, AbbVie must be taken somewhat seriously, because of the heritage and leverage in the market. So we are hyper-vigilant about what that could mean, but I can assure you we’re well prepared. And as for the JAK inhibitors, there's been a little bit of a discussion over the last few days based on our survey, which I think will also contain the disclaimer about what it meant in NWRX. I think the question is PSA and AF. NWRX is not really linked to MBRX. We haven't really seen any connection. So I just want to be really clear again. The JAKs have around the 2% new patient share in the U.S. And that is PSA and AF. The JAK safety profile -- the current JAK has maybe a block box warning is not in the same -- can't be compared with the new classes of monoclonal antibodies. So, we expect, of course, promotion as we enter the market, but we think IL-17 and in particular Cosentyx will be the standard of care in AF and PSA. And we see nothing to make us think differently at this point.

Thank you Paul. And on biosimilar growth dynamics and other growth dynamics in Sandoz, Richard?

Thanks for the question, Richard. So, yes, to answer your question, firstly on the growth dynamics. The aim of the transformation Vas has outlined in his presentation today is aimed at driving growth at the top and the bottom line. Now the growth will be tempered somewhat by the transformation and that we'll be rationalized in our SKUs and stepping out of some geographies which we don't see as long-term growth drivers at the top and bottom line. So you sort of have to manage that, but the underlying growth is there. And that's primarily driven by the biosimilars. As you've highlighted, we finished quarter four with a 29% growth, the full year is 24% growth, we launched adalimumab, pegfilgrastim and infliximab in quarter four. So I think we have really good momentum there and we see that continuing. But as we work through that transformation, we are just going to have to deal with that as they – as those SKUs, those geographical exits start to have impact. But underlying growth, we're confident. And there will be margin expansion as we move forward over the years as we get – exit that transformation.

Great. Thank you, Richard. Next question?

The next question comes from the line of Keyur Parekh from Goldman Sachs. Please go ahead.

Good afternoon. I've got three questions, please. The first one on your comments on Sandoz, Vas. I think on your podcast earlier this year you said about 80% of all medicines that Novartis sell is via Sandoz. As you think about rationalizing or prioritizing certain geographies for Sandoz, can you give us a scope for how much complexity you can take out of the broader Novartis complex over the next 12, 18 months? And what that means relative to your ability to refocus on the innovative core? That's question number one. Question number two is, again, kind of, capital allocation, whether you've got a reasonably large asset sitting in your balance sheet in sense of the Roche stake? Any updates there on your thoughts and especially as you look at financing some of the bolt-on transactions you are talking about? How should we think about your willingness to use that stake? And thirdly, in sense of longer-term margin trajectory. Obviously, we'll see some margin upgrade kind of broader margin uplift next year. But as you move toward the mid-30s guidance that you provided to, should we think of it as being linear? Or should we think of it as taking a rest in 2020 as you face some of the drags and then reenergizing after that? Thank you.

Thanks for the question. Maybe I'll take the manufacturing question in the broader context. We have multiple things going on right now in our manufacturing footprint. We have significant amount of idles overall in the footprint across all of the different business lines. And so that's why we've taken the actions we've taken over the course of 2018 with the 16 actions I mentioned. And we'll have additional actions planned over the course of this year to really get the idles down. Then the second is, with respect to the complexity within our manufacturing footprint. And that's more what Richard was referring to there, we know that because of the scale and scope of Sandoz we have, how many SKUs Richard?

25,000.

So we have 25,000 SKUs. And our goal over the course of this year geographic focusing is to exit some of the a SKUs that we think are not going to be as valuable and hopefully also reduce the complexity of the overall operation. And so combined we think, both the Sandoz sharpening of focus as well us our overall broader effort to rationalize our footprint will get us to a better place in terms of manufacturing costs, gross margin, inventory level, cash conversion cycle, all of the downstream elements were having in a more streamlined operation. Now, with respect to the Roche stake, there's no change on our status on the Roche stake. As soon as there is a change, we'll of course update the market. We have more than adequate free cash flow as well as strength of the balance sheet to fund our bolt-on acquisition levels that we are currently at for the future. And then lastly in terms of the long-term margins, we expect our margin accretion to happen in a consistent way over the coming years. We believe we can do that because it's a combination not only of the topline driving this margin expansion, but also the consistent approach we're taking to taking costs out of the various units. So, our expectation is not precisely linear, we don't give that kind of guidance, but a more linear consistent approach to margin expansion over time. So, we'll move to the next question.

Next question comes from the line of Florent Cespedes from Société Générale. Please go ahead.

Good morning. Thank you very much for taking my questions. I have three product-related questions. First on cancer for Susanne. First on BYL, could you share with us how you will position the product, it's now part of the drugs with a blockbuster potential. Could be position as second-line after CDK before AFINITOR, some color on front would be very helpful. Second question still on cancer drugs on Kisqali, how -- did you believe we should think about Kisqali sales trajectory? What should boost the sales and prescriptions? Is it the geographical expansion market access or any new indications? And last but not the least, quick questions on RTH, the filing is a little bit delayed from end of last year to February this year. Do we have to understand that there is anything beyond that? Is there any requirement for additional data or whatever? And could you clarify on this point? Thank you.

So, first on BYL, Susanne.

Thanks, Florent. Thanks for the questions. So, BYL as we said BYL has a potential to be the front line drug for patients, this PIK3CA mutation patients. I mean it's very hard to speculate about the label -- sorry, did you hear me or should I repeat? So, it's hard to speculate about the label at this point. Obviously, there were data in SOLAR-1 for testing, there is positioning after CDK4. And as you might know we have the believe trial running that should collect additional data in this setting. So, we wait for the label and then we can update you further on that. Maybe also on Kisqali actually we are pleased with the uptake in 2018. Actually Kisqali will remain a growth driver for oncology. And I think you mentioned the safe trajectory will come from and probably all three of that is correct. Actually we saw increased momentum from the expansion of the indications into premenopausal patients but also combinations for this drug. As you know we will be further rolling out in Europe and other markets. We see very strong uptake in emerging markets and we also will see additional reimbursement achievement. So I think you mentioned the right three drivers to see increased trajectory.

And on RTH there is no new data request. We are confident in the clinical package, the manufacturing package. And as we said, we plan to file with -- we expect next week with the priority review voucher and expect to launch in 2019. So, no change or no new additions to our package. So, next question please.

The next question comes from the line of Seamus Fernandez from Guggenheim. Please go ahead.

Thanks very much. Just wanted to get a quick update on some of the events that are coming this year. Wanted to get a little bit of an update on the fevipiprant, the timing of data. And then also just broadly speaking as you guys are tracking the growth in the severe asthma market, particularly the eosinophil severe asthma market, how is that market developing relative to your expectations? And what does that say for the opportunity for an oral drug and your thought process? That's my only question.

Great. Thanks, Seamus. On the timelines, John.

Yeah. As you noted earlier and as you heard through the presentation, we have a number of readouts this year. As you said in fevipiprant, and we had the last patient in terms of our studies Z01 and 2 [ph] that's fully recruited. We expect to read out that result in the second half of the year for fevipiprant, in addition to just fevipiprant we also have Cosentyx for non-radiographic axial spondyloarthritis and a prevent trial as well as Entresto in heart failure with preserved ejection fraction. Not to mention, in addition to that also Zolgensma in the Type 2 SMA patient. So 2019 is a year of data for us as we begin to read out that information throughout the year.

And I think we can provide greater clarity on timeline as we have a better sense of database locks et cetera, so we'll keep the market informed. Now in terms of the market potential, Paul?

So just one quick before fevipiprant, Xolair participates not to be asthma population. It became a blockbuster in our territories. It is important to note the IgE approach is an alternate one to IL-5. And we are very nicely positioned there. Your question is really I think about the biologic space in general and what the market opportunity is for that. I think it’s worth reminding ourselves that a lot depends on the readout and the tolerability and efficacy profile, because if you get the right readout, our efficacy could be close to if not equal to the biologics IL-5 in particular. If our tolerability is good, then we would expect to move to the left in the treatment paradigm and rather than worrying about the size of the severe asthma population with those treated with biologics we will be – we’ll file treatment gap if those are struggling on inhaled high dose-inhaled therapies are not considered ready for biologics. That is about three million people we work out. So there is a very nice position, but it's very much going to depend on the profile of the medicine as it reads out but that will be a good spot for us to be in.

Thanks, Paul. Next question.

The next question comes from the line of Peter Welford from Jefferies. Please go ahead.

Hi, thank you. A couple of questions left please. Firstly on Zolgensma, just with regard to the potential discussions with the regulator there. Appreciate you not being specific. But just to understand more biologically and mechanistically, given the current administration rule that you're following and also manufacturing constraint, are there any caps we should consider in terms of eligible populations that could be viable to get the drug before obviously the intrathecal formulation is available? Secondly, then just on Sandoz, curious in the near term given your talk obviously about reducing SKUs and making it an autonomous unit, should we be thinking about any dis-synergies potentially near term in the cost base of Sandoz, I guess, to make that an autonomous unit before, obviously then we see the benefits through longer term? Or is that not likely to be the trend? And then just finally, just on crizanlizumab just curious about with regards to the filings, have any additional data be obtained in-house prior to the data you present at the R&D day? Or is this very much been the case of just compiling the data in a format that's applicable to the regulators. Thank you.

So why don't we start with Sandoz on any dis-synergies or other implications of us moving to an autonomous approach?

I think – thanks for the question, Peter. I think as Vas you outlined earlier, when we did the integration, we believe there were synergies and there indeed were. And we also found out, as we executed there were things we would call dis-synergies, based on the model that we need to compete in a generics marketplace. I think to directly answer your question, we don't see any significant dis-synergies as we become more autonomous within Novartis. I do think we've got to be thoughtful and execute really well on extracting ourselves from that integration, but we've had some good plans. We see obviously what Alcon have done, so I think we've got a good methodology that we can follow. So we're not planning for that at this moment. We don't believe that's going to impact us and our ability to grow margins.

Great. Thanks Richard. On Zolgensma manufacturing capacity, Paul?

So off course, we've prepared well for IV. In fact, we've started a significant amount of work on our second site in North Carolina, so we're going to be in vary good shape. A little bit depends on the breadth of the label and the readout at AAN, if we can get to IT earlier presents an opportunity for us both in patient population and of course in the amount of the therapy that we need to give. So we work all scenarios as you'd expect. It will be a little bit label-dependent, but we're positive that we can be prepared for whatever the need it that presents itself.

Great. Thanks Paul. And then crizanlizumab.

Lastly on crizanlizumab Peter, as you know, we showed the results of our Phase II SUSTAIN trial that we showed that we had a reduction of 45% in terms of the annual rate of sickle pain crises or vaso-occlusive crises. And we received the breakthrough designation in December with the FDA. And in fact that's moving forward and we intend to file in the first quarter of this year. So that's advancing well.

Okay, great. Thanks, John. So next question.

The next question comes from the line of Steve Scala from Cowen. Please go ahead.

Thank you. I have a few questions. First is generic Advair still expected to be launched by the end of the year? I ask because it wasn't on slide 15. Second, do you know the results of the AVXS-101 STRONG and SPRINT studies now? I'm curious how you know that Type 1 predicts Type 2 and 3. And then lastly, what percent of metastatic breast cancer market in the U.S. do you think has already been penetrated by CDK4/6 inhibitors? I ask because I thought companies had been saying it was 60% 70% or even more, but yesterday Pfizer said 50%. So I'm just curious what you think that percentage is. Thank you.

So, first on generic Advair, Richard?

Yes. Thanks for the question Steve. So, we do aim to file the product this year. We're sort of forecasting that we believe that's going to be early 2020. As you said, it was 2019 and it's still as a possibility based on the timelines of the FDA and the broad window they give. I think what maybe -- we're looking at that a bit more conservatively and is the reason we say 2020 now.

So on -- thank you, Richard. On AVX-101 just briefly we -- the studies are open label-studies. So, there's a group of us that of course -- our understanding how the results are evolving, but really our comments were driven by what the overall expect from a biologics standpoint that a strong performance in SMA Type 1 should enable strong performance in SMA 2, 3 and we look forward to providing the full update at AAN in May. And then Susanne on the metastatic breast cancer penetration?

[Indiscernible]

So, 60% Steve is what we have, but we, of course, defer to our colleagues at Pfizer. They have better figures. So, next question?

The next question comes from the line of David Evans from Kepler Cheuvreux. Please go ahead.

Hi, thanks for taking my question. Just thinking a little longer term. As you've done your R&D budgeting for the year, just amongst your combined new platforms cell, gene therapy, ligands, beyond the first wave of market of near-term opportunities can you give us a sense which other earlier-stage programs you're most optimistic on and perhaps the way you are directing increased funding to progress those quicker? Thanks very much.

Yes, so Jay is not here, but maybe I'll just give a higher level on kind of where we are focused. On gene therapy, we are focused on actually a pretty broad platform of internal programs as well as looking externally. Primarily, in neuroscience, in ophthalmology, and in non-malignant hematology, I think are the big areas of focus. Of course, we're open to other areas. And that's of combination of internal programs in our research unit in NIBR as well as what's happening at AveXis. In cell therapy or in lentiviral based therapies, we have a big focus on the next wave of innovation in cards, so trying to get to more rapid manufacturing, more high-affinity CARTs, by specific CARTs. So the next wave of technology, I'd say I'm most interested to see how our rapid manufacturing evolves, that has I think the potential to truly transform our overall approach in the area. And next on radioligand therapy, Susanne can comment around the unit, but in terms of earlier stage assets, what would you say Susanne?

The three assets that have entered Phase I, but I think what -- the synergy between NIBR and AAA I think would also leave us aspiring that there is new targets that we can define. So, we are working on that and we update you in due course.

I mean the power of the radioligand therapy platform is that if we can find antigen that is taken up by a -- with a high affinity in target tumor types. And then all we need to do -- and if it's got enough specificity, if we can link it, then with the radioactive particle, we have a drug. And so we believe this platform is something we can apply to hopefully multiple assets we have within our portfolio to take on the range of solid tumors. So that gives you a little bit of a high level of where we're at. Next question?

The next question comes from the line of Michael Leuchten from UBS.

Thank you for taking my questions. One for Harry, one for Suzanne, and one for Paul please. Just, Harry, going back to the guidance, I'm trying to square why the guidance both current group structure and under the new structure do include one scenario where there isn't any margin guidance. Just wondering how that's possible given the efficiency programs that you are talking about what's growing, especially under the new structure? Second question for Susanne on SEG101, do you need additional infrastructure to position the product? Or is the indication or potential indication close enough to the existing infrastructure so you can leverage it? And then question for Paul. I think your punch line previously for Cosentyx was clear is clear. I think in your remarks you said something like, it takes more than clear skin to win. So is there a change in positioning of the product on the ground and in the U.S. on the back of the data that we've seen recently? Or is it just a different way to talk about it? Thank you.

Thank you. So, first Harry on the guidance.

Yeah, Michael. We expect to expand core margin in any of the scenarios either current growth structure or new focused company. So that's why I mentioned also my comments, we clearly expect core operating income in constant currency to grow ahead of sales and improve margin. So there's no -- from my standpoint scenario whether it wouldn't happen. So, strong expectation internally and strong will to drive this productivity programs and strong launches to expand the margin.

Thank you, Harry. Susanne on SEG101.

Michael thanks for the question. As you know we have a footprint from Exjade, but that is going off patent. And so, therefore, we know the customer base quite well. I mean, for SEG101 this will be a very targeted launch. And there we need some dedicated resources, but this is based on the current footprint.

Great. Thanks, Susanne. And then lastly on skin to win Paul?

So, I’m guided to people listen so intently to my comments. So let's just remind ourselves. I think we said the efficacy bar in psoriasis has been reached and that we set up standard. And we don't think it needs to go beyond that. It wasn't specific relation to Patsy. We feel really good. My comment on it's more than a skin to win is basically about the extra manifestations. It's about those patients that isn't just skin that have nail join scalp et cetera involvement. And in those patients, we really do need to demonstrate our effectiveness. And we’re out there and doing it with indications of long-term data. We set a high bar there as well, so forgive me for a confusing, but psoriasis we're in a good place. And we think we are perhaps in equally good place in…

Thanks, Paul. Next question.

The next question comes from the line of Ronny Gal from Bernstein. Please go ahead.

Good morning and thank you for taking my question. I have two if you don't mind. First, could you give us a little bit update about your Copaxone generic, glatiramer acetate in terms of capacity manufacturing ability to commercialize the product in the United States? And second, now that you're thinking about the separation of essentially to the generics business unit, how do you think about the operating margin of biosimilar-focused business long term once this unit is stabilized and -- or at least that part of it, which is biosimilars, long-term given the current pricing trend in Europe where should we see the operating margin of our business look like? Thanks.

Thanks, Ronny and nice to hear from you. On Copaxone, Richard, you want to try?

Yeah, thanks. Hi, Ronny. See, on Copaxone, so let me talk about it both on 20 milligrams and 40 milligrams. I think on 20 milligrams, obviously, we saw competition coming last year. I think I've been very pleased about how we actually defended our business there with thoughtful pricing, but we pretty much kept our market share fairly stable, so pleased with the team and how they've done that. On the 40 milligrams, as you know, we have the slower start to that last year, based on production. And now we started to go out and actually win some contracts and some business. So I think you'll see that starting to pick up. And we have the production to meet the business we've won and contracted for. And I think you'll see on NRx that we started to actually grow NRx on the 40 milligrams. I would say on the 40 milligrams, this is an opportunity, but I think it's one that’s going to be similar to 20 when we started out on that journey. It's going to take a bit of time to penetrate, but we still think it's an attractive market. So we are focused on it. With regard to…

Biosimilars margins.

Yeah. Biosimilars margins, we're very pleased with the biosimilar margins our there. Now I think your question was more about how do I think these are going to be going forward with the pricing in the market. I mean it's two things I would say is, if you look at our base business in biosimilars, they are -- particularly in Europe, which – some of those are 10 years old, those are still growing at double-digit on sales. So I think it just shows that if you have the right structure behind them you can make these assets continue to grow over time. That said, we are very focused on cost of goods and making sure we have a lean TSC structure in the anticipation that the pricing will come down. But all of those things together make me believe that the biosimilar margin will and return on sales will continue to grow over the short to mid term. I haven't really looked a lot beyond that. Because I don't think we do need to add into our portfolio. Obviously, the Biocon, our internal development which is for -- as well as [Indiscernible] so we're going to have a very broad portfolio which we're going to lay on top of our existing commercial infrastructure which gives us a nice synergistic play, which makes me believe the margins will stay – stake will be growing and stay high.

Great. Thanks, Richard. Next question.

Next question comes from the line of Mark Purcell from Morgan Stanley. Please go ahead.

Yes. Thanks very much for taking my questions. Firstly, on the manufacturing network and innovation, Innovative Medicines. Please could you discuss where you are in respect to capacity across the different divisions. You've given us some color on cellular therapy, less so in terms of gene and radio therapy, where you are and where you're aiming to be in terms of capacity. And can you get there organically? Or will bolt-on acquisitions be a key component of your aspiration when it comes to scale? And separately on Sandoz, could you help us understand the overlap in manufacturing between IM and Sandoz at the moment? Secondly, just like to understand your expectation currently, and also the range of expectations for Entresto generic launches in the United States from a timing perspective. Number three, on U.S. net pricing, you've given a top line guidance, but could you help us understand which products are the most important in terms of the drags and how that changes moving into 2019 from 2018? And then just lastly, for Paul, could the Type 2 approach in psoriasis be to IL-17 and IL-23, what you hope to have preferring could be to the biologic, inject biosimilar drugs currently on the market? Thanks very much.

All right. So first I'll take the manufacturing questions in the interests of time. And in gene therapy, we have our plant in Chicago which is our launch facility. We've already invested in the plant in North Carolina, where we approved doubling the capacity of that facility and we are currently evaluating building out capacity in Europe. We feel confident that in our AAV platform, AAV9, but also other AAVs, we believe we'll have adequate capacity in the near-term. And then over time, we'll have adequate capacity. Given that these indications are not huge numbers of patients, we think we'll be well played. In cell therapy, you heard from Susanne, we have significant capacity expansion ongoing. And then I think we'll have a substantial global capacity to do cell processing, primarily lentiviral based cell processing, but also in the future there are non-viral base cell processing approaches. We can certainly use those as well. And then in terms of radioligand therapy, AAA has I think a very strong network already in Europe and the U.S., but we are evaluating expanding that network as we prepare for the potential prostate cancer and then if we were to move into another solid tumors -- the solid tumors you saw listed, we would need of course a significant capacity expansion. Some of those might involve partnerships or external moves in the case of radioligand therapy, but we're evaluating those currently. Now, with respect to manufacturing overlap today between Innovative Medicines and Sandoz, there's two principal places of overlap. One is packaging where it's also easy to do disintermediate in the overlap, that's the -- a key area of overlap at the moment. And the other is in Biologics production where the same plants do cover Cosentyx, LRS and other parts of our Innovative Medicines portfolio as it cover our biosimilars. And so -- but we believe we can manage that through supply agreement internally once we move to the separated state. So, in terms of Entresto generic launches, Paul any updates on that front?

So -- and I'm not sure I got the question entirely, but I would just make the point that in all major markets, we feel very good about the IP where we stand. There's always some small bits and pieces around but nothing that has any material impact to our overall guidance for the long-term.

In U.S., no change in our guidance in terms of the patent protection for Entresto or the exclusive -- market exclusivity for Entresto. Now, in terms of net pricing, I think, your question was, are there particular products were we have higher exposure to net pricing dynamics? I think as you've heard from Paul, we have a stabilizing situation in general with Cosentyx and Entresto. For almost every medicine we have in our Innovative Medicines portfolio, has some level of rebating. And overall, we -- as I've said -- and I think on a few occasions, we expect to see net prices decline in the U.S. for us in our Innovative Medicines portfolio in the low single-digit range. We wouldn’t break out individual products per se, but I can say that rebating at this point is broad-based within the pharmaceuticals portfolio and we do see it starting to come into oncology as well in certain therapy line. So, rebate levels are much lower in oncology, but we do see them happening every year more and more. So, that, of course, is also leading dynamic on our overall net pricing. I think the last question was on the TIK 2 approach as an alternative to Cosentyx. So, -- and John you want to take that? Maybe John you have--

Yes. Sure as you know for Cosentyx, we had the indications for psoriasis, psoriatic arthritis, and ankylosing spondylitis. I think TIK 2 is currently is entering into Phase III. They are looking at dermatologic manifestations, so I think it's early -- we try not to speculate on other mechanisms.

Okay, thanks.

And I think Paul also has a--

Yes, just because it was -- the question was also related to the approach of Fevipiprant I think in the original question. We made some very sensible choices around fevi, so and as I alluded to my answer earlier, we're setting a standard of efficacy up with biologics, but we hope to have a tolerability profile that puts us in the silent treatment gap. Be interested to see choices made by those of looking after tick twos, whether they go up after efficacy and run the risk of a compromised safety profile or whether they position themselves less and less. So revision as always, but we do believe in the monoclonal antibodies Cosentyx will come out in the lead.

Great. So, next please.

The next question comes from the line of Kerry Holford from Exane BNP Paribas. Please go ahead.

Thank you. Yes, this is Kerry Holford from Exane. Just one question left for me please on Aimovig. I wonder if you could just give us an update on the ex-U.S. rollout, in which countries have you now launch and secure reimbursement. And in the U. S. it’s, obviously, CVS that you covered, I think in favor of Lily in Teva’s products. So I would just like to know whether you played a role in those for negotiation in the U.S. or is that something being done by your partner? And if you were involved what was the thought processes behind those negotiations? Was it simply a question, the highest rebate wins? Thanks.

Paul two questions on Aimovig, EU rollout, and reimbursement discussions and then our role on formulary discussions in the U.S.

So we're pretty much at the beginning in Europe, approval followed by rolling reimbursement, as you know takes a bit of time to get all of the major European markets where we hope to be in those conversations right now. I can tell you the unprecedented unmet need for those taking the out-of-pocket route, shows the demand that we saw in the U.S. is likely to manifest itself in Europe and the other markets. So we think we'll be equally well-positioned there. Amgen, of course, take the lead on access and pricing in the United States and so that's perhaps a question better left for them. But in the spirit of we work through a lot of things together we have very good access in the U.S. and we -- I'm not sure it's been shared or whatever shared on the Amgen call, but it's worth noting given the amount of free drug and no paperwork being offered by competition, we have a slightly artificial environment at the moment that will settle down in terms of MBRX share in Europe – sorry, in the U.S. But the number of paid subscriptions for Aimovig in the U.S. has climbed in Q3 from 35% to Q4, 50%. So the -- so trying to run a sensible business will win the day and we look forward to things settling down in the U.S.

Very good. Thanks, Paul. Next question.

The next question comes from the line of Naresh Chouhan from Intrinsic Health. Please go ahead.

Hi, there. Thanks for taking my question. Just one on Entresto, the scripts looked like they are accelerating. So some help in trying to understand what's driving that. Is that the PIONEER data? Or has there been some additional rebates and that's driven that volume? And then you've, obviously, laid out the extent of manufacturing capacity that's being added both on cell and gene therapy. So how should we think about CapEx over the next few years? And is that low to increase materially? Or are we expecting similar levels over the next few years? Thanks.

First Entresto, Paul?

So thank you. There has been a modest acceleration. We're not declaring victory, because as I mentioned earlier on some systems in the U.S. and there's one or two major European markets that have decided to go very quickly based on PIONEER data because of what it means for patients and how it reduces the overall readmission costs frankly in health systems. But we have some work to do to industrialize that, the length and breadth of the major markets. So whilst, we're pleased with the effort, we'll continue to climb. That is our expectation through the year and beyond and through PARAGON and beyond.

On CapEx Harry?

So on CapEx, as you know over a few years back we were at 5% plus of sales. We brought that down by our focus and then manufacturing footprint work capacity utilization increases to a range of 3.5%, so last year 3.5% and 2017 3.4% of sales and 2018. And we expect the CapEx to be a bit fluctuating, but in the 3% to 4% range. So nothing material is due to the new platforms.

Thanks Harry. Last question, go ahead please.

Next question comes from the line of Marietta Miemietz from Prime Avenue. Please go ahead.

Yes, thanks for taking my questions. I have a couple please. One is on the midterm margins. How much of the $2 billion in savings targeted by 2020 have been achieved? And how fast do you think you can come up with a new program that will be somewhat similar in scope maybe another $1 billion to $2 billion in savings? And more importantly maybe at the Q2 stage you hinted that you might upgrade your midterm pharma margin target as when you have more visibility on Gilenya LOE. And now you're basically giving short-term guidance, excluding Gilenya generic, but the Pharma margin target has stayed the same. So I'm just wondering, are you basically looking to update the midterm pharma margins target later this year or early next year when some of the things Shannon mentioned have panned out? Or is there something else that's holding you back? And the second question is on Sandoz when you say it's becoming autonomous without any dissynergies is that literally just talking about in indigo carve-out? Or is there actually more to it operationally? And could you elaborate a little bit least on the strategy for the insulin biosimilars and how big that potentially -- could potentially become? And I was just a little bit surprised to see you enter that space because the previous management team basically said a number of years back that they wouldn't touch biosimilars with the barge pole because it was much lower margins than other biosimilars and you needed a massive scale to compete. And I think if anything the space seems to have become a lot more competitive since then. So what has actually changed? Has the access to the very low-cost insulin by Gilenya changed the economics? And can you give us a rough idea of the gross margin? Or is it just that the going in biosimilars and generics is so tough that now insulins are looking better on a relative basis? Or are you simply aiming for -- you actually aiming for a significant market share? Or is that really something that completes your portfolio for affordable medicines as part of the ESG efforts any color there will be helpful? Thank you very much.

Thank you Marietta. Harry on margin dynamics and cost savings.

Yes. I think overall Vas laid out three major elements of our productivity efforts. One, being the network transformation and the other two being business services and procurement. I would say on the business service and procurement we are starting so we have some impact, but the majority is still to come. And on the network transformation, we are already kind of in the middle. So, I would say kind of we have started kind of 25% there and we keep going. All of this is, of course, included in our mid-term -- in our 2019 margin and the mid-term aspiration growth to mid-30s for Innovative Medicines. But we have started but I would say on the specialty business services and procurement, still major impact to come. And in terms of Gilenya and the mid-term aspiration grow by 22 of IM margins. I mean we have several variables which either pushes or pulls that drive headwinds or tailwinds on that. But overall, we clearly see a very strong sales growth, growth momentum. Of course, we have some generics exposure as we discussed earlier. And a single variable would not change for that our aspiration to go to the mid-30s. And then we update as we go this year or in 2018, we did an increase of 100 basis points in Innovative Medicine from 31 to 32. So, I think that's a good starting point from getting to the mid-30s.

Great. Thanks Harry. In terms of the Sandoz carve-out, really where we focus on is on business services and manufacturing, it's very early days. Our focus -- real focus in these areas right now is preparing for the Alcon spin. That's where we're going to spend most of our energy for the first half of this year. And then we'll turn to Sandoz and try to enable Sandoz to be an autonomous unit. There will be stand-up costs, of course, associated with some of these areas within Sandoz. We don't mean to imply otherwise, but we don't expect the stand-up costs to change our expectations of margin improvement from the transformation within Sandoz, really that's what we were trying to communicate. And then lastly on the strategy to enter insulin biosimilars, Richard?

Yes, thanks for the question. So, the way we look at it we think about our portfolio about a couple of things. Firstly, what is the opportunity from a business point of view, what is the access need from our medical point of view, and then how do we leverage our current infrastructure? And I think the exciting thing about the insulin market is; one, this is a huge market, over $10 billion net sales and growing in the U.S. We're also seeing the pricing of that market continue to go up so that market has been growing year-on-year. I think one of the things we thought about in the past is firstly there are going to be disruptive innovation that's going to come along and change the care -- the standard of care that's given to these patients. We don't believe that's the case. One of the things we think about is that manufacturing is one of the barriers -- the volumes required to really enter this market and be successful are huge. And I think that's something that in the past I think we probably looked and it's all passed now where we want to spend our capital. But a great thing is with the partnership that we have with Gilenya is to have a manufacturing capability -- first manufacturing capability they make insulins in China already. And so we have an ability to work -- developing a portfolio with bringing to market cost effectively because we can leverage our commercial infrastructure and we can leverage their manufacturing capacity because there's no innovation coming forward. We actually think this is an attractive market and I think we've seen over the last year or two a number of people actually pull out of this market for whatever strategic reasons they've had. But that even -- makes it even more attractive. So, I think this is more -- we think this is an opportunity, we found a way with a good partnership to maximize it. So, I think this actually is a good growth driver.

Great. Thanks everyone for joining today's call. We went quite a bit over time, but we appreciate everybody's questions. We appreciate our investors' commitment to investing in our company and we look forward to providing you updates in the months to come. Thank you.

Thank you very much for joining today's Novartis's conference call.