Thanks and good morning and good afternoon to everybody and thank you for taking the time to join us on this Q4 and Full Year Results Presentation. 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. And thank you again for joining us and I will hand across to Vas Narasimhan. Vas?

Thank you, Samir. I also wanted to say thank you all for joining today’s conference call. If we move to Slide 3, with me today, I have a number of my ECN colleagues, Harry, Susanne, Marie-France, John Tsai, Richard and Shannon and will be available to take your questions and also will be joining me for parts of the presentation. So if we move to Slide 5. Over the past 3 years, we have been executing on the strategy we set out in 2018 to focus the company, focus on certain geographies to accelerate our growth and to focus on five strategic priorities that we remain committed to and believe in the long run will enable Novartis to sustainably grow and sustainably have impact on healthcare around the world and deliver on our purpose to re-imagine medicine. Now, when you look at some of the proof points, as we have set out on this journey, we believe we are making good progress, always more to do, always things to learn. So, we are making good progress. We are 100% focused now as a medicines company. We have a leading pipeline across 10 therapeutic areas, 4 advanced therapy platforms, unique in that having only 8% of our sales in one product and over 15 blockbusters. We have achieved $2 billion in cost savings over the last 3 years, a leading data science platform that’s enabling us to weather this pandemic and I believe sets us up for the medium and long-term, consistently improving ESG scores now with sector leading performance in four key indices and from a culture standpoint, record high engagement scores across multiple different measures. Now, moving to Slide 6, when you look at how the strategy is translated into operational performance, we see solid operational performance over the…

Thank you, Vas. So going on to Slide 16, good morning, good afternoon and pleased to update you on the 2020 performance for pharma. We grew 5% year-over-year in a challenging environment and our growth drivers Cosentyx and Entresto showed continued momentum and now account for $6.5 billion in revenues. But the story that stands out here is the shift that you see in our portfolio. The contribution from growth drivers and launches went from 33% to 43% and that demonstrates our replacement power in light of several patent expiries expected. We’re delivering strong operational performance in the end market growth drivers. We also made progress in the next wave of potential launches, providing the basis for growth in 2021 and beyond. Slide 17, once again, Cosentyx delivered double-digit growth and reached $4 billion for the full-year. Our focus is on continuing to compete strongly to maintain our position in dermatology and accelerate in rheumatology. We know what we need to do to grow. We need to make sure we maintain broad access and balance that with a long-term value of Cosentyx and you can expect us to continue to do that. We will expand into new geographies. In fact, we are now the only innovative biologic with broad NRDL listing in China and we’ll make sure that we’re competitive in the marketplace with our industry-leading approach to data and presence, as well as a number of new indications as we deliver on our ambitious lifecycle management program. There is still tremendous opportunity in this market and between the data, the access and our outstanding teams, we have what it takes for Cosentyx to continue to grow. On Slide 18, Entresto continues to deliver 44% full-year growth and the momentum continues across all of the geographies. As you know, we’re…

Thank you, Marie-France. So moving to Slide 24, the Oncology business had solid performance despite significant generic erosion and COVID-19 impact, delivering 3% growth and reaching $14.7 billion. In Q4, we have seen very good momentum across our portfolio, mainly driven by the strong uptake of our recent launches and continued strong performance of our growth drivers, and these brands could also more than compensate for the continued generic erosion of Afinitor and Exjade in the U.S. and Sandostatin LAR in the EU. Due to the pandemic, some areas of our business as mentioned by Vas, like the hospital initiated therapies and specifically breast cancer therapies, continued to experience delays in new patient starts as well as concerns about patient management during COVID. And but I have to say, our teams really stepped out and deleveraged our robust digital capabilities and embarked on omni-channel launches for Tabrecta in the U.S. and Piqray and Adakveo in Europe, and are very pleased that this launch has continued gaining momentum despite limited face to face interactions with physicians. Moving to Slide 25, Kisqali. Kisqali delivered a very strong performance in 2020 with full year sales up 45%, reaching $870 million. And this is driven by the unprecedented overall survival benefit from two pivotal Phase 3 clinical trials. We are also very pleased to see Kisqali continue growing and gaining market share despite the overall slowdown of the CDK4/6 market, driven by suppressed patient screening, and overall decrease in new patient starts. At a recent Congress in San Antonio, we were very proud to share that Kisqali demonstrated the longest median overall survival among all Phase 3 trials in advanced breast cancer, reaching nearly 5 years of survival in pre-menopausal patients and additionally, we presented the pooled data from MONALEESA studies that confirmed efficacy…

Thank you, Susanne. Good morning, good afternoon, everyone. Now I’m going to walk you through some of the financials for the fourth quarter and full-year as well as provide you with our ‘21 guidance. As always, my comments refer to results of continuing operations and growth rate in constant currencies unless otherwise noted. So turning to Slide 31, we compare our actual results here with our 2020 latest guidance and as you know, we’ve revised our core operating income guidance upward in October and I’m pleased to say that we met both core operating income and the sales guidance. On sales, given the resurgence of COVID-19 in quarter four, we ended at the low end of the 3% to 4% range as we mentioned during the quarter three investor call. Now Slide 32 shows the summary of the performance for quarter four and full year. I will focus on the full year results on the right hand side. Full year performance was solid, with sales growing 3% at both core operating income and core EPS growing 13%. Sales were of course mainly driven by Entresto, Zolgensma and Cosentyx. Core operating income growth was driven by higher sales, some lower spend and significant productivity programs. Operating income grew 19%, driving net income growth of 20%. We will come back to the free cash flow number, which was $11.7 billion a little later. Overall, clearly a solid yearly performance, especially given the challenging business environment we are all in. Next, let’s focus on the core margins on Slide 33, again showing on the right hand full-year and left hand quarter four. For the full-year, continuing operations’ core margin was 31.7%, growing 280 basis points in constant currencies, with strong improvements in both divisions. Innovative Medicines’ margin reached 35% as outlooked, up 220…

Great. Thank you, Harry. Turning to Slide 42, just a final word on our ESG progress as a company. I think as many of you know, we have placed a high priority in being a leader in our sector on ESG across our four main areas of focus through our materiality assessment. Some of the highlights include the issuance of the first industry sustainability-linked bond for access to medicines, our commitment for full carbon plastic and water neutrality by 2030. We were just ranked today number two in the access to medicines index that was just announced and continue to see strong progress in our D&I and other corporate citizenship efforts. All of this has led to improvements in our ESG rankings and we continue to work to being a leader in the ESG efforts across the sector in the years ahead. So moving to Slide 43, as we noted in our meet the management meeting in November, we’re confident we will grow top and bottom line every year through 2025 and meet external expectations of 4% growth, reaching $60 billion in sales in 2025 and reaching the consensus margin of 37.6% in 2025. And we’ll look forward to continuing to demonstrate our progress on this front as we move through the quarters ahead. So closing on Slide 44, as you see, we delivered on our strategic and operational commitments in advance to our strategic priorities in 2020, despite the challenging business environment, our third year of sales core operating income and margin improvement, I think demonstrating the operational effectiveness of the organization. We are progressing our pipeline deep mid and late-stage pipeline as well as important milestones in 2020 and as I noted, expect top and bottom line growth every year through 2025. So with that, we can open the line for questions. I would ask that if the questioners could limit themselves to two questions. We do have a number of people in the queue already. Thank you. Operator?

Thank you. [Operator Instructions] Your first question today comes from the line of Mark Purcell from Morgan Stanley. Please go ahead. Your line is open.

Yes, thank you very much for taking my questions. It’s Mark Purcell from Morgan Stanley. So, just two. Firstly for Harry, Harry, could you just help us further with the sort of phasing of growth through the course of the year? So as you said, for Q1, underlying growth roughly flat, should we assume a similar thing for Q2, which sort of sets you out for 8% to 9% sales growth in the second half of the year to reach the guidance? And is there anything you see in terms of phasing of Sandoz, which we may not have as much visibility on which is different to that pattern? And then secondly, Vas, maybe one for you, with tislelizumab and the BeiGene deal, obviously this is exporting innovation out of China for one of the first products to do so. So, is there a potential challenger in terms of exporting the product at a lower price point when it comes to negotiating pricing agreements with governments globally or is the lower price points in China potentially something you could use to advantage when it comes to transferring the value into potential combinations of your next generation assets, so, thinking of things such as TIM-3, SHP2, CD73, etcetera. So that will be useful to get some context there?

Terrific. Thanks Mark. Harry, on phasing of growth.

Yes. Thank you, Mark. Yes, the last year was quite interesting with the forward buy, if you will, as healthcare systems strived to get some inventory and also the patient level longer scripts have been given, so we had this $400 million roughly effect of forward buy, or stocking in quarter one and then they de-stocked in quarter two. That’s roughly three points on our quarter. So of course then quarter two would have the reversed positive effect. In other effects we have in quarter two is that, Lucentis, basically many patients skipped or doctors skipped one injection, that’s now fully back. So quarter two, we should see some good growth. And so the first half, I would say, we do expect to be broadly in line with prior year, maybe low single-digit growth as totality, I had first declared in quarter one and then some good quarter in quarter two is the expectation. That - this is broadly in line with prior year, especially what we have seen in the last two quarters. Now, if you think about the second half of 2020, quarter three was zero, quarter four was plus one, and that was the environment that we expect the next couple of quarters to be in. So that’s why we believe that is a reasonable scenario. Of course it is unprecedented volatility and therefore we have to plan in different scenarios. So then, as you say, in the second half, we do expect some very good growth, but again we talk ranges and have to see how quickly then the healthcare systems open up. So I think that phasing of half one, half two, and then if you have to do this quarter one stocking, quarter two de-stocking of last year, should give good feeling for how to model the quarters. I don’t want to get into Innovative Medicines, where the Sandoz I think we get too granular, but you have seen last year the quarter one, quarter two of both divisions and I think that should be helpful.

Thanks, Harry. On tislelizumab, broadly speaking, our goal is to maximize the value of this asset. We have an asset, they can participate in the $50-plus billion PD1 market around the world. We have the full commercial flexibility to maximize the value of the product. And then our goal of course is to leverage the medicine across the full combinations possible across Novartis Oncology portfolio. So we have a number of combination studies already planned and we believe having a hopefully soon approved PD1 in U.S. and then later also in Europe will enable us to accelerate our own combination programs across the full range of our portfolio. I can’t comment and it’s too soon I think and premature to comment on pricing strategies, etcetera, but I think once the deal closes and we are further along, we can of course provide more granularity and Susanne can provide more granularity on our commercial strategies.

Thank you.

Next question, operator?

Thank you. Your next question comes from the line of Laura Sutcliffe from UBS. Please go ahead. Your line is open.

Hello, thank you. Two product specific questions, please. Firstly, for Zolgensma in the U.S., I think you said at your last ratio results you had 74% newborn coverage and your goal now is I think 80% by the end of the year if I heard it right. Does that mean that you think that access is only really going to expand sort of incrementally in the U.S. this year and sort of in practical terms there won’t be very much extra or is there a more optimistic scenario in there? And then secondly, on Kesimpta, do you have a rough idea of when you expect that you will start to see the majority of sales come from paid-for products rather than free products? Thank you.

Yes, thanks, Laura. So on Zolgensma, what we ended up seeing in 2020 was newborn screening coverage in the US in the high-60s and our goal is to get that into the high-80s in over the course of 2021. And in that setting, we would expect again Zolgensma to have a very high market share in states that have newborn screening. Alongside that, we also are working hard to get better – even further Medicaid coverage with hopefully getting a significant number of additional states fully putting in place Medicaid program. So we haven’t seen this as a significant barrier. We do think that will ease the ability to get patients started. I would still say, in general, I mean, the biggest constraint right now in Zolgensma, my growth is more of the pandemic than the underlying demand. We see very good dynamics, very solid AAV testing rates around the world. We see strong interest for governments to put in place reimbursement programs. But it does take more time in the pandemic and we do see physicians delaying starts with Zolgensma simply because of the initiation procedures involved with such a therapy. So, we’re hopeful that as the pandemic recedes or healthcare systems stabilize, we will see an acceleration over the course of the year. Now turning to Kesimpta, Marie-France?

So thank you, Laura. Our bridging program is available for commercial patients for up to 12 months, so we’ve had a generous program, and I can tell you that the majority of Kesimpta patients are currently on this bridging program. We expect the conversion to paid products with a share of free goods to decline from 70% to 30% over the course of the year and that will obviously drive up the sales ramp up. But what’s important here is that we expect three quarters of the ‘21 sales to be realized in the second half of the year. And this of course assumes the pandemic recovery in line with group guidance. What I can say in the meantime is that the team is doing an incredible job with the launch. We’ve seen access and we’ve beat our own internal benchmarks on access. We’re seeing naive patients at 17%. We have leading share of attention. We’ve made sure that we focused on making fast initiations and making it easy. So we’re in good shape; we’re building the foundation; we have a good free goods program and we’re hoping to accelerate the sales in the second half of the year.

Great. Thanks, Marie-France. Thanks, Laura. Next question, operator?

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

Thank you very much. Two questions, please. One, Vas, at the CMD in late November, you expressed confidence in consensus and I think a lot of investors took that to mean each year rather than just 2025. Now the ’21 guide seems to be somewhat below consensus. So you obviously had good visibility on the challenges of COVID in late November. So can you just help people if there is anything that’s fundamentally changed since late November or really it’s just the patented growth out to 2025 that potentially was misinterpreted? And then secondly, on Entresto, in pEF, again just referencing that meet management, you put it in the $500 million to $1 billion peak sales bucket. Now that you’ve heard the AdComm commentary and you’ve obviously had further interaction with FDA. Do you think that peak sales potential is conservative given the number of patients that you’ve just laid out in the presentation today?

Yes, thanks, Matthew. On the first point, our intention in the meet the management was to provide confidence over the five year period and not to provide any, sort of, annual milestones with respect to consensus. So certainly if that was misinterpreted, I apologize that we were not clear enough. I think what we did say is, we plan to consistently grow sales and core operating income. We do that this year, we grow core operating income ahead of sales. We also have tried to be consistent that the margin progression will not be at a steady pace, but we will get to the high-30s as we outlined as well. So I think we’re on track. Nothing fundamentally has changed. And when I - when we look at that 4% growth after 2025 and the margin at around the 38%, we feel very good with our ability to achieve that with the portfolio that we have in hand. Now, with respect to HFpEF, maybe I’ll turn it over to Marie-France to give a little bit of the range of patient numbers and potential.

Thank you, Vas. So the AdComm discussion really reinforced the unmet need for Entresto’s value in the treatment of pEF and we see this is specifically in this group of patients with ejection fraction before normal. But it’s difficult at this point to give you a specific range, because that’s going to depend on the addressable patient pool, which will obviously depend on the label. What I can say is that the total pEF population is about 3 million patients in the US and about 2 million of them have an ejection fraction below normal. We also know in this market and this is critical, I referenced it before, that it’s important to have guidelines. So our uptake is going to be gradual as those guidelines are updated and we’re going to continue to keep our consensus around $4 billion to $5 billion for total Entresto. So we’ve previously guided $3 billion to $4 billion on rEFs and we are guiding for $4 billion to $5 billion on rEFs and pEFs together.

Great. Thanks, Marie-France. Thanks, Matthew. Next question, operator?

Thank you. Your next question comes from the line of Steve Scala from Cowen. Please go ahead. Your line is open.

Thank you. The inclisiran situation in the U.S. is perplexing. 2 months ago, Novartis had been anticipating a year end 2020 approval. Then said the facility review only related to paperwork and might not be needed and now the product appears delayed a year in the U.S. So something seems not right and I’m wondering what perspective you can add? The second question, Vas, you said Zolgensma potential was $2 billion. Is that the first time Novartis has provided that number and what does that include for addressable SMA patient groups as well as other indications? Thank you.

Yes. Thanks, Steve. On the inclisiran topic, it’s been certainly a interesting journey for us as well. I mean, this is a situation where we had a facility, routine inspection would have happened in May. Due to the pandemic, the FDA converted this to a paper-based inspection. The third-party provided a documentation and the entire interaction has been purely based in writing. There have been no verbal conversations and these of course have happened in writing with the third-party facility. Our best estimates over the course of last year were based on our discussions with the review team and our understanding that there were no safety, efficacy, or CMC related concerns that were product specific. We ultimately all learned and we did as well at the CRL that FDA wanted additional documentation and some additional control changes within this facility. It’s notable this facility is approved in our European Medicines file fully approved and is part of the launch network for the launch of Leqvio in Europe. We are working as fast as we can with the third-party. Ultimately it’s the third-party’s responsibility to provide answers to those questions to the FDA. I think we are trying to provide realistic guidance given that we’re in a pandemic of Q2 to Q3 and then it will be up to the FDA ultimately to determine if they still want an in-person inspection, when they want to conduct that inspection and how long they would take to complete that process in the review. I mean, that’s – those are the facts as we know them and we’ll continue to work as fast as we can to get this medicine approved in the U.S. and launch. I think what’s important is what Marie-France and the team mentioned – which she mentioned. If anything, this is an opportunity for us to prepare even better for the launch. We don’t have to launch this medicine in the midst of a pandemic. We have the opportunity now to build an even stronger launch preparedness effort and then hopefully get off to a strong start as soon as the product is approved. With respect to Zolgensma, I think historically we’ve said that we are comfortable with the 2025 consensus, which I believe is in that range of $1.9 billion to $2 billion. And so that’s the basis of this – the comment that I made. It’s based on Zolgensma IV and based on Zolgensma IV in the current indications of under two years old in the U.S. and up to 22 kilograms outside of the U.S. As I mentioned, we continue to work for – to get AVXS-101 IT fully licensed and we’ll keep – give you an update once we clear the preclinical topic and finalize the Phase 3 development program.

Thank you.

Thanks, Steve. Next question, operator?

Thank you. Your next question comes from the line of Graham Parry, Bank of America. Please go ahead.

Thanks for taking my question. So, firstly a question on COVID impacts on your ‘21 guide. So roughly how many percentage points do you think COVID is negatively impacting revenue growth in 2021? And on margins, how much wiggle room are you giving yourself that given the likelihood that you are going to get more COVID savings so as we look into 2022 you are really setting yourselves up here for quite an easy base for ‘22 growth? And then secondly, a question on kind of CANOPY-1, there has been quite a lot of investor discussion around timing of interims. I think some investors interpreted management comments made recently that there’s definitely no interims in first half of ‘21. So can you clarify if that’s correct, or if you are just saying you are just not disclosing timing and just leave us guessing if it could happen at any point between now and the final analysis in Q4? Thank you.

Thanks, Graham. On COVID-19 impact, I’ll give it to Harry. Harry?

Thank you very much, Graham. So very exact numbers are hard to grab, right, of what is purely COVID, but as we compare to all our forecast and of course then analytics around it, which we’re doing constantly, I would say, starting with the impact we experienced in 2020, between 2% and 3% points of sales growth we would attribute as a negative. On the bottom line, given the cost discipline, as well as some of the natural adverse spend as we have - as you have seen, we have made up more than that and could even increase our core operating income guidance. Now for 2021, half year effect, we have some little under 2% on the top line what we expect. So again, it depends very much on quarter two, quarter three goal. We have several scenarios which we try to put here. One, the guidance is never easy, but I think we have to be a bit careful around when our patient visits and initiations is back to a pre-COVID normal which we do expect as of the summer as of Q3. And then on the bottom line, I just want to mention one thing. As you know that we had significant savings and under-spend. Of course, we keep our ways of working, saving on travel, and internal meetings and so on, leveraging digital, but we have basically put that into the base for ’21 on the cost side. And now to assume we can do a significant effort like this again on top of already a quite a lot of savings in 2020. One has to be careful that we would not under-invest into the launches and pre-launches. So we clearly see margin improvement, but after 280 basis points here in constant currencies to - we have to also ensure we have the right level of investments as we expect the markets will open up for more face-to-face promotion also as of the summer.

Thanks, Harry. And then on interim guidance maybe rather than giving specifics on CANOPY-1, in general, we have interim data readouts across our programs. We were no longer disclosing the timing of those interim readouts. We would rather have investors focus on the full data readout full timing of data readouts based on the powering of these studies, or power of course the readout at the close of the study. And so we continue to guide to CANOPY-2 in the first half, CANOPY-1 in the second half, CANOPY-Adjuvant in ’22. Thanks, Graham. Next question, operator?

Thank you. Your next question comes from the line of Emmanuel Papadakis from Deutsche Bank. Please go ahead. Your line is open.

Thank you very much. Emmanuel Papadakis from Deutsche Bank. Couple of questions, please. Perhaps the first one I could take is on the SHP2. Just if you could give us a bit of clarity in terms of timing where we might see that first KRAS combination data, I know you had been in the clinic since Q2 last year with partner in the U.S., Mirati. So just comment on timing and the degree of confidence you have based on the data you’ve presumably seen in-house, if that will have a major role to play in the future targeted lung therapy space? And then perhaps a second on the iptacopan breakthrough designation in PNH and C3G, Alexion has been historically quite clear, they don’t expect the oral complement assets to challenge C5 agents as the mainstay of therapy rather only in refractory patients or those with breakthrough hemolysis. So would you disagree with that view? Was the breakthrough designation also covering naive patients or just the refractory subgroups, for example? And just a bit of thoughts in terms of the mid-term outlook in that space? And then maybe if I could just tack-on, in C3G, we’ve had reasonably promising Phase 2 data from avacopan in the ACCOLADE study in December. Company there is talking about potential for filing. That would put you very significantly behind. So just timings and indeed differentiation on that sort of things as well would be helpful? Thank you.

Thanks, Emmanuel. So, on the SHP2, John?

Yes, sure. Thanks for the question, Emmanuel. On the SHP2 inhibitor, we’ve been working with Mirati and we have a clinical collaboration in terms of moving forward. We’ve had a couple of patients in combination with their KRAS G12C adagrasib. We’re beginning to see the initial results. I think there was one case study that was presented at an oncology conference at the end of the year last year. We hope to reach proof-of-concept later this year and move forward based on those results. So, the exact timing in terms of the Phase 2 and Phase 3s will be forthcoming in probably the mid this time - middle of this year is how we would move forward. So, also I think you had a number of questions regarding iptacpan and I believe specifically you were asking about our approach with iptacpan in PNH and combinations. As you know and just for the folks online here, iptacpan is our first-in-class complement the Factor B inhibitor that acts upstream of C3 and C5. And as Alexion has their anti-C5, what we note is that, we’re targeting both intravascular hemolysis which is the C5 inhibitors, which target the intravascular, but we also target the C3. So, we know that about 70% of the patients currently who have PNH are inadequately controlled with C5 inhibitors. So, we have designed a superiority trial in terms of moving forward in – so we do feel like that would be a superiority trial that would give us the indication to move forward in [indiscernible]

And then John, avacopan in C3G, I think that’s the C5 inhibitor, so I think they are acting downstream, if I’m not mistaken.

Exactly. That is downstream. And, Emmanuel, I think you had a third question on IgA, if you could just ask that question, because I didn’t write down that specific third question.

No, John, that was a question on timing of C3G and when we would plan to get to a filing in C3G for iptacopan.

Yes. So for iptacopan and C3G, what we’ve noted is that we have a Phase 2 data read out in the first half of this year and based on that, we’re looking to move forward in potential Phase 3 program and potential filing next year – or 2023.

And I just want to highlight again for iptacopan. Our goal is a first-line indication. I think Susanne and her team have a strong hematology presence in the U.S. So we believe we can launch this product successfully in first-line with respect to PNH and then of course in the full range of indications in the coming year. Thank you for the question, Emmanuel. Next question, operator?

Thank you. Your next question comes from the line of Richard Parkes from Exane BNP. Please go ahead. Your line is open.

Hi, thanks for taking my questions. Two questions. Firstly on Kesimpta, I just wondered to what degree the launch and the cost overall is being impacted by patients delaying treatment initiation due to worries over immunosuppression or lack of - potential lack of response to COVID vaccination. I’ve noticed a couple of recent publications underlying a 2 times increased risk of severe COVID with B-cell depleted folks. Just wondered if you could comment on that and what degree that impact on the cost might linger longer term as we come out of the pandemic? And then secondly on Entresto, just a clarification, based on the patient populations that you’re pointing to for the preserved ejection fraction indication, it sounds like you think the labeling discussions will be around kind of the ejection fraction cutoffs rather than necessarily restricting by [indiscernible]. So just wondered if you could confirm that? And if you are able to quantify what you think the opportunity for Entresto is in the PARADISE-MI something that would be really helpful? Thank you.

So, Marie-France, both on Kesimpta and Entresto?

Yes. So, on Kesimpta, I think the important thing is that we’re really leaving no stone unturned in this launch. And as I mentioned before, I think we’re in pretty good shape on all our metrics to really bring this product as a first-line DMT to market. We are, however, feeling the effect of the pandemic and you can see that mostly in the overall ability of our teams to perform their patient visits. Now, there is some noise in the market around vaccination or delaying hesitation by HCPs on switching therapies. And that is a reality that we’re seeing right now. However, what I can say is that we are currently running some clinical trials in vaccinations. We also have data in this regard. Looking at other vaccinations in B-cell therapies and in other biologics that give us confidence that we will be able to make sure that patients and physicians feel comfortable with using Kesimpta in regardless of COVID and regardless of vaccination. So there are currently a lot of real world evidence databases that are quite encouraging. We’re looking at this not only for Kesimpta but across the broad range of products, including Cosentyx as well. The important thing is that patients get treated. And despite the fact that our selling cycle is a little longer, we’re not slowing down. We’re continuing to build the foundation for this product. And I do believe that, that you can expect to see the B-cell market grow significantly, not only because of the work that we’re doing, but because this is really bringing a high efficacy therapy to patients upfront and that could radically change the way that physicians think about and treat multiple sclerosis patients. So, we’ve said that we are ready we just need this market to bounce back.

And then Marie-France, on Entresto HFpEF ejection fraction versus male/female and then also what PARADISE-MI potential?

So when we go back to what I said before, it really depends on the addressable pool of patients. We’re very encouraged by the conversations that we’ve heard coming out of the AdComm and now we’re in discussions with FDA around the exact wording of the label. And it will depend on the patient pool. As I said before, this is a significant population, but it’s also an under-diagnosed population. So we’ll have to take things as it comes. It’s very encouraging as we have seen from the PARAGON data that there are groups of patients that do benefit and there is a general consensus with physicians that this is not an exact science. So having an ejection fraction below normal and looking at precise rate is not something that is an exact science. So we’re working to make sure that we can bring this product to the largest population possible and where it makes. And on AMI, so we’ll obviously have to wait for the size - for the results of the trials. But our data tells us there are about 7 million AMI events every year across the globe, and one in four will develop heart failure. So in the US alone, we’re talking about 800,000 patients suffering from AMI every year, and these might benefit from Entresto. So, we’ve got strong access for this product that we’ve built over the years we’ve got a great team. And we hope to bring Entresto to a large incremental population if the results of the trial are positive.

Thank you, Marie-France. Thanks, Richard. Next question, operator.

Thank you. Your next question comes from the line of Simon Baker, Redburn. Please go ahead. Your line is open.

Thanks for taking my questions. Two if I may please. Firstly on the newer modalities, on Zolgensma, as you give us some details at the beginning on the countries, you expect to add to reimbursement, could you tell us the current number of countries, where Zolgensma is reimbursed. And on Kymriah you said particularly good performance in the fourth quarter against expectations. Could you just give us some color on any pandemic disruption you’ve seen there and the extent to which that’s been offset by the expanding footprint for Kymriah that you discussed? And then finally a quick question on Tislelizumab, could you give us the location of the manufacture for the trial and commercial material that you will be using? Thanks so much.

Yes, so on – thanks Simon, on Zolgensma, outside of the U.S., of course, we have access in Germany through the standard access path there. We have reimbursement in Japan. And we are working very – and we have a limited reimbursement program right now in a few other European countries, particularly Italy, notably Italy. Well, we hope to be able to accomplish in the first half of this year is to establish reimbursement pathways in the UK, Italy, Spain, Canada, and a number of other markets. We will see those discussions, as I mentioned, have been a little delayed due to the pandemic. But we are hopeful we can accelerate them. And then on top of that, our key priority for us is to enable access in emerging markets, particularly, Turkey, Brazil but amongst other emerging markets as well where there is significant SMA populations that could – children who could benefit from Zolgensma. So we hope to see a steady pace of getting reimbursement decisions over the coming year. Kymriah, Susanne?

Yes. Thank you, Simon. So we were really pleased with the performance of Kymriah also in Q4, a very strong growth, and this was really driven by double-digit growth across the geographies in the U.S., in Europe and Japan, and this is despite COVID. I would say, the growth is partly driven by the expanding or in new markets as I said, there is now 27 markets that have reimbursement for at least one of the Kymriah indications. We increased manufacturing capacity, which means that we could serve all the demand and I have to say, you were asking if there is impact from COVID and yes, there is because some treatments are delayed. But on the other side, I think risk in the market Kymriah has performed exceptionally well. We have gained market share and I think this is probably driven by the strong data that we – also real world evidence we have evidence could demonstrated efficacy and also safety is even better than in the JULIET trial. So, I think very, very strong, and I think very safe product that would not require ICU space and I think this led probably to the decision by many centers to go for Kymriah.

Yes. Thank you, Susanne. And then on tislelizumab manufacturing, the product is produced by an established third party – European established third-party, I am not sure under our agreements what – and given the ongoing review what I can and can’t disclose. I propose, we, our IR teams simply get back to you once we do the appropriate checks, but very reputable top class third-party manufacturer from based out of Europe. So next question, operator.

Thank you. Your next question comes from the line of Kerry Holford from Berenberg. Please go ahead. Your line is open.

Thank you. It’s Kerry Holford from Berenberg. A couple of questions left for me please. Firstly, on the BeiGene PD-1, I wonder if you could just talk through why you took the decision to bring that on board and given you have Spartalizumab and what data set really offer, that was taken over just timing or is it something announced here that we should be aware of should we see Spartalizumab continue that is ongoing combination studies from that asset as well. And then secondly on branaplam you highlighted in the slide Phase 2b is due to start in Huntington’s in the second half of the year. I wonder why not earlier, is it related to stimulated delays, additional data preparation you need to do in the first half and could that Phase 2b study be seen in the pivotal trial. Thank you.

Yes, thanks, thanks, Kerry. On BeiGene, it does not change the status of our own PD-1, we view them as complementary. Our own PD-1 was primarily focused, Spartalizumab was focused on a few select indications that was the strategy we took that medicine will continue on those indications. BeiGene has taken a very broad development program across the main PD-1 indications without overlap on Spartalizumab and so we’re excited to bring that medicine to market across the full range of indications. Sussane anything you want to add on, on this point?

Yes. I’ve asked to add, I think that really we were impressed by the very broad development program that BeiGene is running in global programs having really 15 potentially registration enabling trials ongoing. And I believe for us also advantage is that BeiGene has tested Tislelizumab in very important indications in monotherapy that’s different from Spartalizumab like non-small cell lung cancer, gastric cancer and so on. And therefore, we are excited to bring this product to market ex-China.

And then John on branaplam timelines for Huntington’s.

Yes branaplam timelines. Maybe Kerry just one last item on the last question there is, we also have a number of targeted therapies that we could use in combination. And if we have an approved PD-1 is actually fits very well in terms of a complementary portfolio. So I think that’s something that we thought about given timelines as you noted in the question. Specifically on branaplam as you highlighted, we will get the Phase 1 results in the first half of this year. With those results, what we intend to do is take it to the health authorities and have discussions and if timelines allow we certainly will move as quickly as possible. If it’s realistic, we will absolutely have Phase 2b in the first half of this year, but it really depends on the feedback from the health authorities, because we will have to have discussions both with the FDA as well as European agencies. So your last question or the last part of that question was, will this allow for a registrational study in Phase 2b that really will also depend on the discussions that we have and as well as the data that we’ll see in the Phase 1 program. So I think we’ll be able to share more with you as we have these discussions and when we see the data.

Thanks, John. Thanks, Kerry. Next question, operator.

Thank you. Your next question comes from the line of Peter Welford from Jefferies. Please go ahead, your line is open.

Hi, yes. Thanks for taking my questions. Firstly, just going to another pipeline asset Iscalimab, and when do you, you just give us a bit of clarity on the path forward for filing at that now, see a commentary that the regulatory suggested you can follow. You don’t think base in kidney transplant, sorry based on the ongoing study. And so, what is the planned timing on that. Can you use liver and kidney together or is another trial started or planning to be started, and how do you think about that and what sort of endpoints that regulators requiring. And then secondly just on the Generics obviously guidance was now understand Gilenya generics during the course of this year from Harry I guess makes sense on Gilenya, I presume. We still got to wait for clarity from the call before you give us timing on that one. Started in the U.S., can you just give us some clarity on, I guess what sort of research or visibility you have on that and sort of your confidence that we won’t see a U.S. Sandostatin generic this year. Thank you.

So, John, on Iscalimab.

Yes, thanks, Peter. On Iscalimab this is our anti-CD40 as you know we had intentions and moving forward. We still have intentions and moving forward with two or three indications renal transplant, liver transplant as well as Sjogren’s. We took an aggressive clinical strategy given that there’s really been no improvement or change of standard of care for renal transplant 35 years of the Calcineurin inhibitors. I think we noted previously and discussions, whether that was meeting with Novartis management or other calls where we were using a digital endpoint and we were having really good discussions with the agency on using this aggressive approach using this digital endpoint. At the end of the year last year, they came back and they noted that they wanted to still use the same endpoint as previously, which is BPAR, Biopsy Proven Acute Rejection. Having that as feedback, we felt like we wanted to ensure that we have a path forward which would be full Phase 3. So, which would be the same timelines as developing your traditional transplant drugs, noting that we do feel like there’s also potentially faster path through Sjogren’s and we’re awaiting the Sjogren’s Phase 2b result and once we have those results we will be able to disclose the overall timelines on the Sjogren’s program which may be faster than transplant program.

Thanks, John. On Sandostatin LAR generics in the U.S., Susanne.

Yes, Peter, I mean, as you know, there is one generic company that has a chief marketing as a recession in Europe and is doing a very targeted commercialization currently being really commercialized only in eight markets including Germany, France and UK. Our guidance for the U.S. is based on the fact that the same company has application running in the U.S. since a while [indiscernible]. We have no update at this point, but given also the situation this COVID we expect that this process could take longer, but there is no concrete update and there is no new information.

Thanks, Susanne. Just a quick note for Simon for we did a quick check and I can confirm that the tislelizumab is produced at the Boehringer Ingelheim production site in Shanghai, so next question, operator.

Thank you. Your next question comes from the line of Keyur Parekh from Goldman Sachs. Please go ahead. Your line is open.

Good afternoon. Thank you. And first of all Vas congratulations on the progress you’ve made on the ESG front, especially with the access to medicine going with number two. And now, kind of two questions from me broad picture, please. First, kind of your slide on the BeiGene collaboration suggest that you’re open to a broader strategy collaboration with BG maybe I’m over interpreting that sentence but would love to hear kind of what you are envisaging there, is this kind of a corporate collaboration, is it a collaboration from an oncology perspective, is this from the what is to still suffering to China wire them for you to import innovation, just anything you can add to that would be great. And then secondly, as you look at kind of the bigger picture growth that you are suggesting you’re comfortable with consensus through 2025 which is a 4% top line growth to my mathematics consensus has a 7%, 8% EPS growth. If you aren’t successful at delivering that that would put you in the middle of or in-line with your peer group, shortly your ambitions are bigger and higher than that. So I was wondering if you might tell us what your kind of ambition are and where you think you might actually get to? Thank you.

Yes, thanks, Keyur. And thanks for the comments as well on ESG. We’re very pleased with the collaboration with BeiGene in China and I think it fits with our broader goal is to double the size of our Chinese business as I noted. We are one of the fastest growing multinationals, I noted all the NR lifting the upcoming approvals. We are, and continue to explore partnership discussions with a number of local Chinese players I think specifically BeiGene, of course, has a broader portfolio has a strong oncology presence in China. Of course, we are looking forward to continuing a strong collaboration with them, but also with other strong local Chinese players as makes sense for our portfolio. So no specific plans or decisions but I think more just to highlight that our ambitions in China are significant and we think we’re on the right track with very strong teams across GDD and John’s organization as well as Mary-France’s and Susanne’s commercial teams. In terms of the mid, mid to long-term ambitions. I think, nothing more to add, of course, as a CEO who once our company to lead and be at the leading medicines company in the industry have very high ambitions. But I think more appropriate me for me to keep those ambitions to myself and continue to simply say we’re comfortable as we stated with our sales and margin outlook for the consensus out to 2025 and we’ll do our best to deliver a world-class pipeline portfolio and execution across all five strategic priorities to get that. And then most important in my mind is to continue a strong growth trajectory beyond 2025 as well, because we of course play this for the very long game. Thanks, Keyur. Next question, operator.

Thank you. Your next question comes from the line of Andrew Baum from Citi. Please go ahead, your line is open.

Hi there. Emily Hutchinson from Citi on behalf of Andrew Baum, and just one question please. On Cosentyx, can you talk, we anticipate performance in the U.S. in 2021 given our net exclusion from a couple of national formularies. Thank you.

Thank you, Emily. And this is the longest I’ve ever gone in an IRR call in this role about a Cosentyx question. So Marie-France on Cosentyx.

Yes, I’m very happy to get at least one question on Cosentyx. So the first thing I’d say is, I think we need to put this in perspective, because our overall access position in the U.S. remains incredibly strong. In fact, you heard me say that before early line access is a key pillar to our strategy. However, we’re always going to balance access with long-term sustainability for Cosentyx and you can expect us to continue to do that. Now specifically on the ESI decision which is what you’re referring to, you can obviously expect to see some impact on volume from this account and that will also be reflected in our NBRx share but know that we’re confident in our ability to grow Cosentyx based on our three strategic pillars. We talked about access we talk about the competitive product profile across four indications and then very importantly our lifecycle management opportunities that could bring up to six indications in the future. So, we’ve consistently delivered double-digit growth despite the competition and despite the fact that there is a lot going on in this market. And you’ll see us do that again in 2021. These access decisions are short-term decisions, it is not going to change the long-term trajectory for Cosentyx or our ability to reach 5 billion and beyond.

Thanks Mary-France. I’d ask the next set of analysts to please limit themselves to one question, just in the interest of time. Next question, operator.

Thank you. Your next question comes from the line of Seamus Fernandez from Guggenheim. Please go ahead. Your line is open.

Thanks very much. So I just wanted to get an update on Iscalimab and Sjogren’s disease. I think previously you had stated that you are planning for even an interim towards the end of this year, perhaps even a final look at those data. So I just wanted to get an update on Iscalimab and Sjogren’s disease and maybe if you could just give us a little color on the ability to recruit patients are continue recruiting patients into that study if recruitment is completed, then obviously that question is irrelevant. Thanks.

John, on Iscalimab?

Yes, Iscalimab, thanks for the question Seamus. As Vas disclosed earlier, we’re really not disclosing the interims moving forward. So as we’re moving forward, the recruitment is, has been a little bit slower than we anticipated. We’re not fully recruited in the Phase 2b for Iscalimab yet. So the recruitment continues and those timelines really will depend on when we finish our recruitment. So we’ll provide further updates in terms of the exact timing of completion of that trial.

Thanks, John. Next question, operator.

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

Hi, thanks for taking my question. Question on Zogenix in the intrathecal form, just could you give us a - some help on the design of the pivotal trial. Would you look to broaden the age range beyond the 2 to 5 years, which was the original by strong trial design, and given your – the thoughts on what’s happened to other gene therapies. What do you think the regulators would need in terms of duration, durability to see particularly in our space Type 2 estimate patients. Thanks so much.

Yes. Thanks, Richard. With the, we’re in discussions now with FDA on finalizing that clinical trial design. I think the discussions are very positive both on dose and duration, but we haven’t finalized the design hopefully by Q1 will be able to give you at least a perspective on what the agreed design of this study is assuming we get off clinical hold later on in the year. So still more to come. And we’ll keep you posted. Next question, operator.

Thank you. Your next question comes from the line of Florent Cespedes from Societe Generale. Please go ahead. Your line is open.

Good afternoon. Thank you very much for taking my question. A quick one for Richard on dose. Could you please share with us how do you see the dynamic of the non-biosimilar business because we understand what is driving this business. But for the rest of the portfolio is a bit more difficult to understand that. Could you maybe elaborate on this mid-term dynamic of the non-biosimilar business. Thank you.

Richard? We still have Richard on the line.

Sorry, sir. Richard line is still connected.

Okay. I’ll just quickly answer the question. I think that the, the dynamics we see right now biosimilar is primarily growth in Europe, in Japan, in the U.S., it continues to be a mixed picture of course hopeful that with our next wave of assets we can get a much broader set of assets launched in the U.S., 15 projects now progressing through our biosimilars portfolio. In terms of small molecules, the softness we saw was primarily an anti-infectives in Europe as well as the legacy or the oral solids business we’ve brought back from Aurobindo what we’re hopeful. Now is that hopefully we see demand starts to pick up again over the course of this year, but much more important is revitalizing our pipeline and revitalizing our first to file engine in the U.S. and being at market formation in Europe. We think the combination of those two pillars the biosimilars pipeline and the first to file pipeline should get us to that mid mid-single-digit growth rate over time. Thank you. Alright. Next question, operator. I think we have just a few more left.

Thank you. Your next question comes from the line of Naresh Chouhan from Intron. Please go ahead, your line is open.

Hi there, thanks for taking my question. And just one on M&A, please. You’ve had a couple of large deals, which have resulted in some issues where it can be argued that those assets were developed internally. The slight year-to-date potent arising would have been probably much less likely to have occurred I think can be AveXis dates in terms of issues, led by a CDMO issues and given that even the most diligent acquirers would have been probably unlikely to have found those issues, does it dim your enthusiasm for future deals of this size given the risks involved. And if I may just sneak that does the $60 billion sales number include M&A or is that just organic growth. Thanks.

Yes, thanks, Naresh. On the second part just organic growth, we’re not including M&A I think less about I mean, look, I think when we got into new technology areas, which we believe we need to do in the long run to be a leader to be competitive to drive growth. We are going to learn new things. I think certainly the fact that we are doing the small interfering RNA and novel gene therapies as part of the reason we have some of the challenges that we do, but I would say it’s less about that and more. We have enough on our plate with a full internal pipeline, we’ve done a number of deals, which we’re currently working on fully scaling. We have 4 platforms. We want to get too global leadership on. So we have plenty, plenty to do. Always opportunistically thinking about M&A, but that’s not an focus at the moment we want to execute on the strategy and plan we have ahead of us and that’s what we’re focused on at the moment. Next question, operator.

Thank you. Your next question comes from the line of Emily Field from Barclays. Please go ahead.

Hi, thanks for taking my question. I just had a quick question on 2021 and the impact of taking on Tislelizumab. I was just wondering if you could give us a sense of the order of magnitude of the incremental development cost that you’ll be taking on with this asset and is that mostly coming from R&D and the initiation of these combination trials. Thank you.

Yes. Harry, you want to provide some color on that or clarity on that.

Yes. Thank you. So it’s a bit complicated, but first of all, we do account for the appropriate, if you will share of development costs of the current registration trials in our core P&L. It’s about one point of core operating income growth, if you will, from a dilution standpoint, but it will not be a cash expense because the current portfolio is being executed by BeiGene and is part of our upfront payments. So it’s not a cash expense was an expense to given the structure of the deal, we always want to ensure that our core results on the core accounting is of the highest quality as well.

Okay, that is very helpful, thanks.

Last question, operator.

Thank you. Your last question today comes from the line of Mark Purcell from Morgan Stanley. Please go ahead.

Hi, well, thank you for taking my follow-up. Vas it’s just another clarification investor question actually on tislelizumab. The question was the 15 registration trials that Susanne mentioned I think I’ll switch if those which regions and in which indications are you going to be able to follow. So I guess the question is really reflecting if you need any additional data in specific countries such as the U.S. or parts of Europe in any specific indications. Thank you for the follow-up.

Yes. Thanks Mark. So I’ll just quickly take it. We have rights in U.S., Europe and a number of other ex-U.S. markets. BeiGene keeps rights in parts of Asia and Latin America, the clinical trial portfolio, clinical trials currently being conducted already conducted with support filings in a full range of indications of the second-line lung which they hope to complete this year first line lung colorectal cancer, head and neck. Susanne, are there others that I’m missing?

No I think gastric is also there. Yes, head and neck you mentioned. And I mean these are global programs. That’s probably worth to mention they enrolling not only Chinese patients, but also from other geographies. And I think what is important in this setting that the comparator is strong. And for example, we are excited about the second-line data in non-small cell – BeiGene reported very strong over survival data versus DOCSIS. So I think that’s how you have to see this that the clinical program we believe is very robust and would allow for filings ex-U.S. sorry, ex-China.

Thank you.

Thanks, Mark and thanks everyone for joining today’s call. We appreciate it. Appreciate your interest in our company as well as all the investors appreciate your support of Novartis and we’ll look forward to keeping you up to speed over the course of this year. Please stay healthy, and thank you again.