Novartis AG

And thank you for taking the time to join us on this Q4 full year. Good morning and good afternoon to everybody. And thank you for taking the time to join us on this Q4 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 20F 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'll hand across to Raz Narasimhan. Thanks.

Thank you, Samira. I also wanted to say thank you all for joining today's conference call. If we move to slide three, with me today, I have a number of my ECN colleagues, Harry, Susanna, Murray Frantz, John Tsai, Richard, and Shannon. And we'll be available to take your questions and also will be joining me for parts of the presentation. So if we move to slide five, Over the past three years, we've been executing on a 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 reimagine medicine. Now, when you look at some of the proof points, As we've set out on this journey, we believe we're making good progress. Always more to do, always things to learn, but we're making good progress. We're 100% focused now as a medicines company. We have a leading pipeline across 10 therapeutic areas, four advanced therapy platforms, unique in that having only 8% of our sales in one product and over 15 blockbusters. We've achieved $2 billion in cost savings over the last three 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 six, when you look at how the strategy is translated into operational performance, We see solid operational performance over the past three years, with sales growing 5% from $42 billion now to approaching $49 billion, core opt-in growing double-digit at 10%, exceeding now $15 billion. And we've reached our initial goal of innovative medicines core margin to 35% on our way to our midterm goal of the high 30s, which we are well on track to achieve. Now, turning to this year's performance, sorry, the 2020 performance and Q4 performance, on slide seven, you can see a breakdown of some of the key drivers. As you saw in our release, net sales for the full year were up 3% and core operating income up 13%. Our overall performance in Q4, as well as the full year, were driven by our key growth drivers, Entresto and Cosentix, continuing to demonstrate double-digit growth. A broad range of oncology medicines also demonstrating double-digit growth. And taken together, we now have over half of our sales coming from our key growth drivers and launches in innovative medicines, positioning us well for the future and positioning us well to overcome challenges the patent expiries we have in this period and continue to drive growth through 2025 and beyond. Now moving to slide eight, I wanted to dive into a few of the products and Sandoz before turning it over to my colleagues. First on Zilgensma, full year sales were 920 million in the first full year since launch. Medicine is now registered in 37 countries. We're making very good progress in the rollout of this medicine around the world. As you saw in Q4, we had sales of $254 million, which were lower than Q3. This was driven primarily by COVID-19-related impacts, delaying new starts as hospitals face disruption, and we saw physicians delaying starts or switches to the product, as well as delays in reimbursement decisions in some of the European and emerging markets we're currently working with. We expect this impact to continue through the first half of 2021. We would expect sales in that Q3, Q4 range before an acceleration in the second half of the year. But we remain confident in the longer-term potential of the medicine in the IV form to reach ultimately $2 billion. It remains the treatment of choice for newly diagnosed patients. We're seeing about 15% of patients in the EU in the older than two-year age range. We're on our way to get access in nine EU countries, which would be about 25% of the population. And we have important formal reimbursement decisions in 15 countries over the coming year to two years. So taken together, we think we're on the right track. When you look at the IT program, we continue to await the animal data, which we expect to have in the middle of this year, to the back half of this year, though. Remove the partial clinical hold if the data confirms the safety profile. We are working with the FDA to finalize the design of a pivotal confirmatory study, which we then rapidly plan on implementing. We continue to progress our 10 early stage programs in gene therapies with two INDs and clinical trial starts planned in 2021. So moving to slide nine, I also wanted to say a word regarding our performance in China. Now, as you saw in our release, we were very pleased with our growth in China with sales growing 16%, second fastest amongst multinationals in China. Our goal is to double our sales in the country by 2024, making China the second largest market for Novartis in the world. Our key growth drivers, similar to what we see in other geographies, are Entresto, Cosentex, as well as our other oncology strategic bands. What's very notable, I think, is the number of NRDL listings we achieved. We believe the highest in the industry in 2020. We also have a rich pipeline with seven approvals expected in 2021. So taken together, we think we're on the right track to reach our goals in China and really continue to drive dynamic growth in this important market. Moving to slide 10. With respect to Sandoz, you saw in the full year Sandoz managed the sales guidance largely in line for the full year and the quarter. Importantly, Sandoz was able to drive 15% core operating income growth, moving its core margin up to 24.2%. Some of the pushes and pulls for Sandoz are continued strong biopharmaceuticals performance with 19% growth, primarily in the European markets. but also held back a bit by our retail declines we saw driven by COVID-19 and the U.S. oil solids business that we now retain. I think taking a longer-term view on Sandoz, we remain determined to build a business that can grow mid-single-digit with margins in the mid-to-high 20s, really competitive with the top end of the peer set. And we expect to be able to do that through a robust biosimilar pipeline, as well as high LOE coverage amongst small molecules through the 2024 period. Now, moving to slide 11. I did want to say a word about the company's efforts to overcome the COVID-19 challenges we see in the marketplace. Harry will talk a little bit more about our guidance. But certainly, when you look at the healthcare system's performance over the back half of last year, we continue to see a situation where healthcare systems didn't return fully to their pre-pandemic status. Here on the left-hand side of the chart, you see two examples in dermatology. We continue to see patient visits and NBRX below the pre-pandemic levels. On the bottom, you can see in the oncology markets, depending on the cancer setting, you have biopsy and surgery rates below pre-pandemic levels, also the CDK4-6 market. So for the first half of 2021, we expect to continue to see challenges for certain therapeutic areas, such as dermatology and ophthalmology, as well as in Sandoz retail. We expect that some of our new launches will be impacted, though we expect to continue to see solid progress, and you'll hear more about that from Mary France, on preparing for these launches to accelerate in the back half of the year, such as Cosimta and Mazin. And we also know products that involve hospital initiation, such as Kimriah, Lutathera, and Vilgensma, will face a tougher situation in the first part of the year. Again, we would plan to overcome that in this period and then hopefully see acceleration in the second half of the year. So moving to slide 12. Returning to our innovation performance and innovation milestones in Q4, we saw the approval of Lectio in the EU six months ahead of schedule. We saw the positive FDA adcom for Entresto and preserved ejection fraction heart failure, as well as a number of other notable achievements, a number of designations achieved for Toclopan and Ligalizumab, I think demonstrating the potential of these medicines as they continue to progress in late-stage development. We also signed an important in-licensing deal on Tisalizumab with Beijing for anti-PD-1, which we hope we'll be able to file later this year in the U.S. and other markets. I also wanted to say a word, as I know there have been a number of questions on Lectio and an update on the CRL. Now, first and foremost, it's important to note that there are no safety, efficacy, or product-related concerns with respect to Lectio in the CRL. As I mentioned, the EU fully approved this product out of the same facilities that we also filed for the US FDA. The CRL was related to facility inspection-related conditions, primarily related to documentation and certain control systems at a third-party manufacturer in Europe. We expect, based on the third party's readiness to complete the request made by FDA, to be able to submit the documentation and other requests of FDA in the Q2, Q3 time period. We still do not know if the FDA will ultimately want to inspect this facility. As noted previously, the FDA had originally planned to inspect this facility in May of 2020. They're currently not conducting overseas inspections in situations like this, so we'll continue to have to work with the FDA to try to expedite that inspection. And we're concurrently working on a tech transfer to add our own Novartis facility in Shaftanau, for the production supply chain of Lyfeio. So we remain confident we will get this product approved as fast as possible and then continue our plans to launch this medicine in a highly effective way, which Marie-France will go through in a bit more detail in a moment. Now moving to slide 13, other innovation milestones that we expect for 2021. Multiple major approvals, Cosimta in the EU, Entresto, a half pass for an expanded indication for Entresto. A number of major submissions you can see listed here, including Asimeneb in CML. We have also a range of major readouts which would enable submissions in 2021, notably canakinumab, sabatolumab, MBG453, and lupusma, amongst others. We also will hope to see the readouts of ligaluzumab and cosentix, which would enable submissions in 2022. And I also wanted to say a word on our next wave of assets, which you can see on slide 14. Here we lay out the five life cycle management programs, five pharmaceutical programs, five oncology programs, and five wildcards we highlighted in our Meet the Management meetings. And in many of these programs, we have milestones expected in 2021. You can also see the milestone chart in the appendix of this document. I'll note a few. We expect the Paradise Post-MI trial to read out in the first half of 2021. I already mentioned Cosentix and Hydradonitis Superativa, the Kiskali Mona Lisa 2 OS in the second half of 21. We'll see important mid-stage readouts for Eptaclopan in IgA nephropathy and C3G. We'll see also an important Phase IIb start for Branoplam in Huntington's disease. And then, of course, the range of oncology milestones as well across the various oncology molecules. Important to note, in all of these projects, we have full teams working to accelerate them and working as fast as possible to maintain their progress through the pandemic and beyond. Particularly, we're looking forward to continuing to advance our SHIP2 inhibitor and our C. raf inhibitor as well in the oncology portfolio. So I hope that gives you an overview of our story, well, mid- and long-term story most importantly, but also our story in Q4 and for 2021. And with that, I'll hand it over to Mary Franz. Mary Franz.

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 percent year-over-year in a challenging environment, and our growth drivers, Cosentix 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 percent, and that demonstrates our replacement power in light of several patent expiries expected. We're delivering strong operational performance in the in-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, Cosentex 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 Cosentix. And you can expect us to continue to do that. We'll expand into new geographies. In fact, we're 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 Cosentix to continue to grow. On slide 18, Entrusto continues to deliver 44% full-year growth, and the momentum continues across all of the geographies. As you know, we're the only single-use medicine proven to be superior to previous standard of care, and thus we're in a strong competitive position. It's also great to see that the American College of Cardiologists expert consensus now recommends that heart failure patients go direct to ARNI, and this puts Entresto in a pole position for the 75% of patients who are still on previous standard of care. We also have exciting opportunities for growth with expansion in China and Japan, as well as our lifecycle management program for PEPs, or preserved ejection fraction, and post-AMI. If we move to the next slide, the ADCOM discussion for PEPs reinforced the unmet need, as well as entrust those value in the treatment of preserved ejection fraction, and specifically in patients with ejection fraction below normal. Ultimately, the addressable patient pool will depend on the label. What I can tell you is that the total population is about 3 million in the U.S., and about 2 million of them have an ejection fraction below normal. We know from our deep experience in RUF that guidelines matter in this market, so our update will be gradual as the guidelines evolve. Overall, we're very comfortable with Entresto's peak consensus, and we're confident that Entresto is going to continue on its impressive growth trajectory. If we move to slide 20 and on to Cosimta, we've said we have high expectations for this product. Our team is executing very effectively on the launch. In fact, we have beat all of our plans on gaining access. We're seeing broad adoption. We have leading share of attention. Onboarding is fast and initiation is simple. But we do feel that it is more challenging to launch during a pandemic. We cannot move as fast as we would like due to the limited face-to-face access to physicians. And what we're also seeing is a hesitancy to switch as physicians and patients prefer to wait. But this does not change our ambition for this product. We think that B-cell therapies have the potential to account to up to 40 percent of market share in MS, and we're positioning Kesimpta as a first-choice DMT as we relentlessly track for the highest customer satisfaction. We have the foundational elements in place. We're focusing on breadth. And with our free drug program, once we're out of this pandemic and we can pull our full promotional power behind Kesimpta, we will really see the potential of this product. If we move on to slide 21, We're also enthusiastically preparing for the launch of Lectio. Lectio received EU approval in December, and we expect a slow and steady start. We also plan to roll out our first population health agreement with the UK NHS in quarter three. In the U.S., as you've heard, we have a manufacturing-related delay, which we're working to resolve. But what is important to remember is that we're thinking about this launch very differently. Our aim is to partner with healthcare systems on ASCVD management to overcome the non-clinical barriers to tackling this disease at scale. We're now using this time to advance our engagement with healthcare systems and to set up the needed infrastructure so that we can be stronger out of the gate once we get the green light from FDA. Slide 22, 2020 was definitely a year like no other. but the external environment did not stop us from doing what we're passionate about, and that is bringing medicines to patients. Our teams have worked hard and demonstrated great agility and resilience, and I am very proud of this team. Our 2021 strategy builds on the good work done. Number one, we want to maintain the momentum on Cosentix and Entresto, penetrating markets further and delivering on our lifecycle management programs. Two, executing our launches. ramping up Casimta, bringing Lectio to market, and restoring confidence in VOV. And three, getting ready for the next wave of launches. Geographically, we have a clear focus on the U.S. and China, and we're putting our customers at the core of our strategy. You will see us working in a much more personalized fashion with physicians, leveraging the investments that we've made in data and digital, and with healthcare systems to deliver access to more patients faster. Over to Suzanne.

Thank you, Marie-France. So moving to slide 24, the oncology business had solid performance despite significant generic erosion and COVID 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 Affinitor and XJJNU in the U.S. and send us that in LAR in the U.S. Due to the pandemic, some areas of our business, as mentioned by Vaas, like the hospital-initiated therapies and specifically breast cancer therapies, continue to experience delays in new patient starts as well as concerns about patient management during COVID. But I have to say our teams really stepped out and we leveraged our robust digital capabilities and embarked on solutions omni-channel launches for Tabrecta in the U.S. and Picre and Adacrio in Europe. We are very pleased that this launch has continued gaining momentum despite limited face-to-face interactions with physicians. Moving to slide 25 and Kiskali. Kiskali delivered a very strong performance in 2020. This full year saves up 45%. reaching $870 million, and this is driven by the unprecedented overall survival benefit from two pivotal Phase III clinical trials. We are also very pleased to see Kiskali 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 Qiskali demonstrated the longest median overall survival among all phase 3 trials in advanced breast cancer, reaching nearly five years of survival in premenopausal patients. And additionally, we presented the pooled data from Mona Lisa studies, that confirmed efficacy across luminal and estrogen therapy-resistant HER2-enriched patient subtypes. And these data confirmed that Kiskali's ability to selectively inhibit CDK4 may store endocrine sensitivity in these very aggressive tumors. On the development side, the Natalie Ativan study in intermediate and high-risk populations is enrolling incredibly well, and we are on track for final readout in 2022. So overall, we are very pleased with the performance of Kiskali and remain very confident in this brand. Moving to slide 26. Also, Kimraya had an excellent year with sales up 68% driven by strong double-digit growth across all geographies despite pandemic conditions. We continue to expand our global presence with now over 290 centers qualified to administer Kimraya across 27 markets. Commercial manufacturing for Kimraya has been expanded with the recent approval of FBRI in Japan. And this is building on previous approvals of Stein and Leslie earlier in the year. In 2020, we made also significant progress in expanding our global manufacturing capacity with a 70% increase compared to previous year. And we also continue to improve the robustness of our process, leading to an increased manufacturing success rate. On the development side, we were pleased to share the new data from the ELARA trial, showing that Chimriah is effective in pre-readed patients with relapsed or refractory follicular lymphoma. Submission for this important indication is expected later this year. And we have also presented the Juliet updated efficacy results, which showed continued durable responses for patients with relapsed or refractory DLPCLs. We also continue to invest in our CAR T therapies with already two new CAR T assets in phase one trials being manufactured on a completely novel CAR T platform. With this technology, we expect to increase manufacturing reliability, shorten the turnaround times, and the preservation of certain T cell subpopulations. Moving to next slide. We'd like to share with you the exciting data we have recently presented at ASH on Asiminib, our first-in-class stamp inhibitor that has the potential to transform CML treatment standards. In the Phase III Assemble trial, Asiminib nearly doubled the major molecular response rate at 24 weeks compared to Bosutinib in patients resistant to or intolerant of at least two prior TKI's. Asiminib also demonstrated favorable safety profile, underscoring that stamp inhibition reduces the off-target adverse events typical for TKI. The U.S. FDA has granted fast-track designation early in December, and we are on track with the U.S. and EU submissions in the first half of 2021. We also continue evaluating multiple development options for Asiminib in early treatment lines in CML and looking forward to update you in the future. Moving to slide 28. I would like to give an outlook also on 2021. We will continue to maximize our growth drivers, and we expect continued growth from Kiskali. We are going to leverage the increased manufacturing capacity to drive further growth in Kimraya, and for Lutathera, we plan to unlock the potential in the community setting in the U.S. and grow use in earlier lines. We expect also continued growth from our growth drivers, Revolet Promacta, Chaka Vee, and Tafila Mechanist. We are also committed to deliver on our launches. We will further expand Picre in the U.S. and gain momentum in Europe. And we hope to continue strong on our Dacrio, expanding to larger accounts in the U.S. and continue global rollout. We will further maximize the first mover advantage with Tabracta in the U.S. and will continue driving awareness of CML and the unmet need and the importance of stamp inhibitors. Last but not least, we will prepare for our next big bets. Lutetium PSMA, by advancing our commercial organization for the readout of vision trials later this year, and also focus the medical education on canakinumab to establish the importance of pro-tumor inflammation. Another important focus for us is the medical education on Sabatolimab to build awareness for the dual mechanism of action of TIM3 in MDS and AML. And as Vaz said, we are advancing our early assets TNO155 and LXH254 in a broad range of combination studies. Moving to slide 29, just to give an update on the recently announced deal to in-license tizolizumab from BiGene. This is a late-stage PD-1 inhibitor specifically engineered to minimize binding to the FC-gamma receptor on macrophages. Tizolizumab has 15 potentially registration-enabling clinical trials currently ongoing, with first ex-China filing expected in 2021. With this deal, Novartis obtains development and commercial rights on key markets ex-China, including U.S., Europe, and Japan. It is a very attractive asset for us as we look to expand our presence in the checkpoint inhibitor space, and it provides us with an opportunity to launch a PV1 sooner in broad and important indications such as lung cancer. We have identified also multiple potential combination opportunities for with the Novartis portfolio across all of our four therapeutic platforms. So we are very excited about collaborating with Biogen to bring tizolizumab to patients around the world, and we are looking forward to Friday with more updates after the transaction is closed later this year. And with that, I hand over to Hari.

Thank you, Susanne. Good morning, good afternoon, everyone. I'm now going to walk you through some of the financials for the fourth quarter and full year, as well as provide you with our 2021 guidance. As always, my comments refer to the results of continuing operations and growth rates 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 a low end of 3% to 4% range, as we mentioned during the quarter three investor call. Now, slide 32 shows you 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% and both co-operating income and core EPS growing 13%. Sales were, of course, mainly driven by Presto, Zolgensma, and Cosantix. 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 the left-hand quarter four. For the full year, continuing operations core margin was 31.7%, growing 280 basis points in constant currencies per with strong improvements in both divisions. Innovative medicine's margin reached 35% as outlooked, up 220 basis points, allowing us to achieve our previously announced mid-30s core margin target a couple of years earlier than planned. And Zender's margin grew by 330 basis points to 24.2%. Clearly, our three-year margins show We are well on track to deliver on our innovative medicines margin targets of the high 30s in the midterm, as well as our Sunday's margin target of mid to high 20s in the midterm. Let's go to the next slide. As mentioned earlier, free cash flow for the full year was $11.7 billion, down 10% per year. Obviously, this was because higher operating income was more than offset by the payments related to legal matters and higher development proceeds in the prior year. Now turning to our full year 2021 guidance on slide 35, we expect sales to grow low to mid single digit and core operating income to grow mid single digit ahead of sales driving core margin increase. Within the divisions, we expect innovative medicine sales to grow mid-single digit and Sandoz top line to be broadly in line with the prior year. The Sandoz guidance is due to the impact of COVID on our retail business and expected decline of U.S. oil solid business. The key assumption for this guidance, importantly, is that we see a return to normal global healthcare systems and prescribing dynamics by the middle of 2021. And in addition, we assume that no Jelenia and no Sambostata NDR generics enter in 2021 in the U.S. Please also note that the overall generic impacts is expected to be in the range of the negative minus 3% of sales, similar to what we saw in 2020. We expect there to be continued generic erosion on brands, including Affinitor, XJ, PMAG, also some mature off-top brands, and Diorvan. On slide 36, I would like to explain the dynamics that we expect to see in quarter one. given that we had quite a significant COVID impact last year, quarter one, which of course would impact the growth rate. So as you recall, there was a significant forward purchasing in quarter one of last year. There were approximately three points of growth that largely reversed in quarter two, with no overall impact on the full year 2020. So as a result, in quarter one, 2021, we anticipate sales to decline low to mid-single digits year on year. The Q1 underlying performance, excluding the stocking effect, is expected to be probably in line with prior year due to the continued COVID-19 impact on healthcare systems and patient visits. Turning to slide 37. In 2021, we do expect further margin expansion, as mentioned earlier, with cooperating income growth. And the magnitude, however, will be lower compared to 2020, where we increased core margins by 280 basis points. Expected positive drivers of future cooperating income growth include the continued performance of our growth drivers, the launch uptake of Cosinta and other launches, as well as productivity programs and continuing adoption of our new ways of working. Growth will be partly offset by increased launch and pre-launch investments, mainly Casimta and Exbio, as well as development costs for Tislolizumab, which we recently unlicensed from Beijing, of course, only after the completion of the transaction. We will also likely see further investments into growth drivers as we expect physician access to normalize from the middle of the year. On slide 38, I would like to add some perspective on other key financial elements of the expected bottom line performance. As you can see, we expect core net financial expenses to be broadly in line with 2020 and also the 2021 core tax rate to be around 16%. Next slide, please. So as you can see here on slide 39, we are pleased to propose our 24th consecutive dividend increase to 3 Swiss francs per share. This is an increase of 2%, with our dividend yields remaining above 3%, and fully in line with our dividend policy of increasing our dividend every year in Swiss francs. And finally, on slide 40, As currencies constantly change, I want to bring to your attention the estimated currency impact on our results using the current exchange rate. So if late January rates prevail for 2021, we would see a full year impact of currencies on sales around 3% to 4% positive and on co-operating income 3% positive. For quarter one, As you can see here, sales would be positive 4%, and I'm cooperating income at positive 2%. And as you know, we update these expected currency impacts every month on our website. With that, I head back to the house.

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've 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 to 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 and advanced 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're 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. Ladies and gentlemen, as a reminder, if you wish to ask a question today, please press star and 1 on your telephone and wait for your name to be announced. If you wish to cancel your request, please press the hash key. Once again, please press star and 1 if you wish to ask a question. Your first question today comes from the line of Mark Purcell from Morgan Stanley. Please go ahead. Your line is open.

Yeah, thank you very much for taking my questions. It's Mark Purcell from Morgan Stanley. So just to firstly for Harry, Harry, could you just help us further with a 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 up 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 the phasing of Sandoz, which we may not have as much visibility on, which is different to that pattern? And then secondly, Vaz, maybe one for you, with Tisolizumab and the BiGene deal, obviously this is exporting innovation out of China for one of the first products to do so. Is there a potential challenge here 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 point in China potentially something you could use to your advantage when it comes to transferring the value into potential combinations of your next generation assets? So thinking of things such as TIM3 shipped to CD73, et cetera. So that would be useful to get some context there. Terrific. Thanks, Mark. Harry, on phasing of growth?

Yeah, thank you, Mark. Last year was quite interesting with the forward buy, if you will, as healthcare systems tried to get some inventory and also the patient level longer scripts have been given. So we have this 400 million roughly effect of forward buy or stocking in quarter one, and then they're destocked in quarter two. That's roughly three points on our quarter. So, of course, then quarter two, you know, would have the reversed positive effect. Another effect we had 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. First decline in quarter one, and then some good growth in quarter two is the expectation. That is broadly in line with prior year. It's basically what we have seen the last two quarters. 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, there's 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 destocking of last year should give a good feeling for how to model the quarters. I don't want to get into innovative medicines versus sundials. 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 Tisalizumab, broadly speaking, our goal is to maximize the value of this asset. We have an asset that can participate in the $50 billion plus PB1 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's market. oncology portfolios. So we have a number of combination studies already planned and we believe having a hopefully soon approved PD-1 in US 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, in premature to comment on pricing strategies, et cetera, but I think once the deal closes and we're further along, we can, of course, provide more granularity, and Susanna can provide more granularity on our commercial strategies. 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 those old gentlemen in the U.S., I think you said at your last set of results that 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 Kiss Sensor, do you have a rough idea of when you expect that you'll start to see the majority of sales come from paid-for products rather than free products? Thank you.

Yeah, thanks, Laura. So on Zulgensma, what we ended up seeing in 2020 was newborn screening coverage in the U.S. in the high 60s, and our goal is to get that into the high 80s over the course of – 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 programs. Though 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 growth is more the pandemic than the underlying demand. We see very good dynamics, very solid AAV testing rates around the world. We see a 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'll see an acceleration over the course of the year. Now turning to Cassandra, Mary France.

So thank you, Lawrence. 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 Kasimta patients are currently on this bridging program. We expect a 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. 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 our 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 focus 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, Mary Font. Thanks a lot. 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, Vass, 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 tell people if there is anything that's fundamentally changed since late November, or really it's just the pattern of growth out to 2025 that potentially was misinterpreted? And then secondly, on Entresto in PEF, Again, just referencing that meat management, you put it in the 500 to a billion peak sales bucket. Now that you've heard the adcom 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?

Yeah, thanks, Matthew. On the first point, you know, our intention to meet the management was to provide confidence over the five-year period and not to provide any sort of annual milestones with respect to content. So certainly if that was misinterpreted, I apologize that we weren't 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 this 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 we look at that 4% growth out to 2025 and the margin out to a rounded 38%, we feel very good with our ability to achieve that with the portfolio that we have in hand. Now, with respect to... Pat, maybe I'll turn it over to Mary France to give a little bit of the range of patient numbers and potential.

Thank you, Beth. So the ICON discussion really reinforced the unmet need for interest of value in the treatment of PEPs, and we see this 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 patient 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 U.S., 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 interest so-so. So, we previously guided $3 billion to $4 billion on REFs, and we are guiding $4 billion to $5 billion on REFs and PEFs together.

Male Speaker 1 Great. Thanks very much. Thanks, Matthew. Next question, operator?

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

Thank you. The Inquisiran situation in the U.S. is perplexing. Two 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.

Yeah, thanks, Steve. On the Inquisren topic, it's been certainly an 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 the 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, we did it as well with 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 LyfeBO in Europe. We're 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're trying to provide realistic guidance given that we're in a pandemic of Q2 to Q3, and then it'll 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 take to complete that process in the review. I mean, 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 launched. I think what's important is what Mary France and the team mentioned, what she mentioned, anything that's 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're comfortable with the 2025 consensus, which I believe is in that range of $1.9 to $2 billion. And so that's the basis of the comment that I made. It's based on Zolgensma IV and based on Zolgensma IV in the current indications of 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 to get AV-Access 101 IT fully licensed, and we'll give you an update once we clear the preclinical topic and finalize the phase three development program.

Thank you.

Thanks, Steve. Next question, operator.

Thank you. Your next question comes from the line of Graham Perry, 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 there, given the likelihood that you are going to get more COVID savings there? an easy base for 22 growth. And then secondly, a question on Canopy 1. There's 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're just saying you're just not disclosing timing and just leave us guessing if it could happen 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, on what is purely COVID. But as we compare to our forecast and, of course, the analytics around it, which we're doing constantly, I would say starting with the impact we expect we experienced in 2020 between two and three percent 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 underspend, as you have seen, we have made up more than that, you know, and could even increase our cooperating income guidance. Now, for 2021, A half-year effect, we have a little under 2% on the top line, what we expect. So, again, it depends very much on quarter two, quarter three go. We have several scenarios which we try to put here in one guidance, and they are easy. But I think we have to be a bit careful around when our patient visits and initiations back to pre-COVID normal, which we do expect as of the summer, as of Q3. And then in the bottom line, I just want to mention one thing. As you know, we have significant savings and underspend. Of course, we keep our ways of working, saving on travel and in-travel meetings, and so on, leveraging digital. But we have basically put that into the base for 2021 on the cost side. And now to assume we can do a significant effort like this again on top of already quite a lot of savings in 2020, one has to be careful that we would not underinvest into the launches and pre-launches. So we clearly see margin improvement, but after 280 basis points a year in constant currencies, 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, Eric. And then on interim guidance, maybe rather than getting specific on CAMPB1, in general, we have interim data readouts across our programs. We're no longer disclosing the timing of those interim readouts. We'd rather have investors focus on the full timing of data readouts based on the powering of these studies. They're powered, of course, to read out. you know, 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, Ryan. 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. Take a couple of questions, please. Perhaps the first one I could take is on the SHIP-2. Just if you could give us a bit of clarity in terms of timing, what we might see that first KRAS combination data. I know you've been in the clinic since Q2 last year with your partner in the U.S. Maritime Team. So just comment on timing and the degree of confidence you have based on the data you've presumably seen in-house that that will have a major role to play in the future targeted lung therapy space. And then perhaps a second on the TACAPAN breakthrough designation and PNH and C3G. Lexin has been historically quite clear they don't expect the oral complement assets to challenge C5 agents as the mainstay in 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 midterm outlook and that space. And then maybe if I could just tack on, in C3G, we've had reasonably promising phase two dates from Avacapan in the Accolade study in December. The company there is talking about potential for filing. That would put you very significantly behind. So just timings and, indeed, differentiation on that side of things as well would be helpful. Thank you. Thanks, Emmanuel. So I'm going to shift to you, John.

Yeah, sure. Thanks for the question, Emanuel. On the SHIP2 inhibitor, you know, we've been working with Varadi, and we have a clinical collaboration in terms of moving forward. We've had a couple of patients in combination with their KRAS G12C adagracid. 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 two and phase threes will be forthcoming in probably the mid-middle of this year is how we would move forward. Also, I think you had a number of questions regarding Iptacopan, and I believe specifically you were asking about our approach with Iptacopan and PNA. As you know, and just for the folks online here, pacopans are first in class complement B, 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. So we do feel like that would be a superiority trial that would give us the indication to move forward in single agent. Okay.

And then, John, Evaclipam and C3G, I think that's a C5 inhibitor. So I think they're acting downstream, if I'm not mistaken.

Exactly. That is downstream. And, Manuel, 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 of C3G for Evaclipam.

Yeah, so for TACOPAN and C3G, what we've noted is that we have a Phase 2 data readout in the first half of this year, and based on that, we're looking to move forward in a potential Phase 3 program and potential filing next year, or 2023.

I just want to highlight again for TACOPEN, our goal is a first-line indication. I think Suzanne 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. Next question operator.

Thank you. Your next question comes from the line of Richard Parks from Exam BMP. Please go ahead. Your line is open.

Hi. Thanks for taking my questions. Two questions. Firstly, on Casemta, I just wondered to what degree the launch and the cost overall is being impacted by patients delaying treatment initiation due to either worries over immunosuppression or potential lack of response to COVID vaccination. I've noticed a couple of recent publications underlying it. two times increased risk of severe COVID with B-cell depleters. So just wondered if you could comment on that, on what degree that impact on the class might linger longer term as we come out of the pandemic. And then secondly, on Entrasto, 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 ejection fraction cutoffs rather than necessarily restricting by sex. 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 setting, that would be really helpful. Thank you.

So Mary France, Birdman, Kisinta and Entresto.

Yeah, so on Casenta, 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 effects 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 hesitations 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 and B-cell therapies and in other biologics. that give us confidence that we'll be able to make sure that patients and physicians feel comfortable with using CoSynta regardless of COVID and regardless of vaccination. So there are currently a lot of real-world evidence databases that are quite encouraging. And we're looking at this not only for CoSynta but across a broad range of products, including CoSyntax 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 this foundation for this product. And I do believe that you can expect to see the BSL 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 up front, 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.

Mary Frantz on the Entrusto half-bath ejection fraction versus male-female and then also 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 adcom, 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 underdiagnosed 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's a general consensus with physicians that this is not an exact science. So having an injection fraction below normal and looking at precise rates 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 sense. And on AMI, so we'll obviously have to wait 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 U.S. 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, Marifa. Thanks, Richard. Next question up, Reader.

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, too, if I may, please. Firstly, on the newer modalities. On Zolgensma, Vaz, you gave 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 Kimraya... It was a particularly good performance in the fourth quarter against expectations. Could you just give us some colour on any pandemic disruption you've seen there and the extent to which that's been offset by the expanding footprint for Kimriah that you discussed? And then finally, a quick question on Tisalizumab. 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 Zulgensma, 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 have a limited reimbursement program right now in a few other European countries, particularly Italy, notably Italy. What we hope to be able to accomplish in the first half of this year is to establish reimbursement pathways in the U.K., Italy, Spain, Canada, and a number of other markets. We'll see those discussions, as I mentioned, have been a little delayed due to the pandemic, but we're hopeful we can accelerate them. And then on top of that, a key priority for us is to enable access in emerging markets particularly Turkey, Brazil, but amongst other emerging markets as well, where there are significant SMA populations of children who could benefit from Zolgensma. So we hope to see a steady pace of getting reimbursement decisions over the coming year. Kimraya, Susanna?

Yeah, thank you, Simon. So we were really pleased with the performance of Kimraya. It is also in Q4, 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 despite COVID. I would say that the growth is partially driven by the expanding in new markets. As I said, there is now 27 markets that have reimbursement for at least one of the Kimraya 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 within the market, Kimuraia has performed exceptionally well. We have gained market share. And I think this is probably driven by the strong data that we also in real-world evidence could demonstrate that efficacy is And also safety is even better than in the Juliet dry. 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.

Yeah, thank you, Susanna. And then on Tiflizumab manufacturing products, The product is produced by an established third party, a European established third party. I'm not sure under our agreements what, and given the ongoing review, what I can and can't disclose. I propose our IR team simply gets back to you once we do the appropriate checks. But a very reputable, you know, top-class third party manufacturer based out of Europe. So next question, Operator?

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

Thank you. Yes, Kerry Holford from Barenburg. A couple of questions left for me, please. Firstly, on the Biogen PD-1, I wonder if you can just talk through why you took the decision to bring that on board, giving you Aspartilizumab, and what did that affect you? really offer that yours did not? Was it just timing? Or, you know, is there something else here in the world to be aware of? Should we assume Spartan Laser Map is now the head, or will you continue those ongoing combinations, that asset as well? And then secondly, on the brand and plan, you highlight in the slides Phase 2B is due to start in Huntington's in the second half of the year. I wonder why not any earlier. Is this With related delays, is there additional data preparation you need to do in the first half? And could that Phase IIb study be seen as a pivotal trial? Thank you.

Yeah, thanks, Carrie. On BiGene, it does not change the status of our own PD-1 Bb2MS complementary trial. Our own PD-1 was primarily focused, spartalizumab was focused on a few select indications. That was a strategy we took with that medicine. We'll continue on those indications. Biogen 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. Susanna, anything you want to add on this point?

Yeah, just to add, I think that really we were impressed by the very broad development program that Bioteam is running in global programs, having really 15 potentially registration-enabling trials ongoing. I believe for us also an advantage is that BiGene has tested Tizolizumab in very important indications in monotherapy that's different from Spiralizumab, like non-small cell lung cancer, gastric cancer, and so on. Therefore, we're excited to bring this product to market at XChina.

And then, John, on Brana plan timelines?

Yeah, Brana plan 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, it 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 Rana Plan, 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 So your last question, or 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, 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. Next, Gary. Next question, operator.

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

All right, yes, thanks for taking my questions. Firstly, just going to another pipe-bound asset, Iscalimab. Wouldn't you just give us a bit of clarity on the path forward for filing of that now? I see a commentary that the regulatory interactions suggest that you can't file, you don't think, based on kidney transplant, sorry, based on the ongoing study. So what is the planned timeline there? Can you use liver and kidney together or is another trial started? or for planning to be started and how do you think about that and what sort of end points and the regulators requiring um and then secondly just on the the generics obviously guiding towards no sanderstat and gillenia generics during the course of this year from harry i guess make sense on gillenia i presume we still got to wait for clarity from the court before you give us timing on that one that's understated 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. understatement LAR generic this year? Thank you.

John on the Scala map.

Yeah, thanks, Peter. On Escalimab, this is our anti-CD40, as you know. We had intentions of moving forward, and we still have intentions of 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 in 35 years other than tests and urine inhibitors. I think we've noted previously in discussions, whether that was Meet 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 DPAR, biopsy-proven acute we wanted to ensure that we have a path forward, which would be full phase three, which would be the same timelines as developing your traditional transplant drugs. Noting that, we do feel like there's also a potentially faster path through Sjogren's, and we're awaiting the Sjogren's phase two B result, and once we have those results, we'll be able to disclose the overall timelines on the Sjogren's program, which may be faster than the transplant program.

Thanks, John. On Sandestat and LAR generics in the U.S., Susanna?

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

Thanks, Susanna. Just a quick note for Simon from Reverend. We did a quick check, and I can confirm that the tisalizumab is produced at the Boehringer Ingelheim production site in Shanghai. So next question, operator.

Thank you. Your next question comes from the line of K.R. 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 up number two. Now, kind of two questions for me, broad picture, please. First, kind of your slide on the BG collaboration suggests that you're open to a broader strategic 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 for Novartis to sell stuff into China via 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 are comfortable with consensus through to 2025, which is a 4% top line growth. To my mathematics consensus has a 7, 8% EPS growth. If you are successful at delivering that, that would put you in the middle of or in line with your peer group. Surely your ambitions are bigger and higher than that. So I was wondering if you might tell us what your kind of ambitions are and where you think you might actually get to.

Thank you. Thanks, K.R., and thanks for the comments as well on ESG. We're very pleased with the collaboration with Beijing and China, and I think it fits with our broader goals to double the size of our Chinese business. As I noted, we are one of the fastest-growing multinationals. I noted all the NRDL listings in the upcoming months. We're continuing to explore partnership discussions with a number of local Chinese players. I think specifically Beijing, of course, has a broader portfolio, has a strong oncology presence in China. And, of course, we're 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 and Susanna's commercial teams. In terms of the mid- to long-term ambitions, I think nothing more to add, of course, as CEO who wants our company to lead and be a leading medicines company in the industry, have very high ambitions, but I think more appropriate for me to keep those ambitions to myself and continue to simply say we're comfortable as we've stated with our sales and margin outlook from the consensus out to 2025, and we'll do our best to deliver a world-class pipeline portfolio and execution across all five of our 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, K.R. Next question, operator.

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

Oh, hi there. Emily Hutchinson from Citi on behalf of Andrew Baum. Just one question, please. On Cosentix, can you talk to the anticipated performance in the U.S. in 2021, given an exclusion from a couple of national formularies? Thank you.

Thank you, Emily. And this is the longest I've ever gone in an IR call in this role about a Cosentix question. So, Mary France on Cosentix.

Yeah, I'm very happy to get at least one question on Cosentix. 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 Cofentix. 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 Cosentix based on our three strategic pillars. We talked about access. We talked 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's not going to change the long-term trajectory for Quotentix. or our ability to reach $5 billion and beyond.

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

John, on Excalibur?

Yeah, on Escalimab, thanks for the question, Samus. As Vas disclosed earlier, we're really not disclosing the interims moving forward. So as we're moving forward, the recruitment has been a little bit slower than we anticipated. We're not fully recruited in the Phase 2B for Escalimab yet. So the recruitment continues, and those timelines really will depend on when we finish recruitment. So we'll provide further updates. of completion of that trial.

Thanks, John. Next question, operator.

Thank you. Your next question comes from the line of Richard Foster from J.P. Morgan. Please go ahead. Your line is open.

Hi. Thanks for taking my question. Question on Zolgensma and the intrathecal form. Could you give us some help on the design of the pivotal trial? Would you look to broaden the age range beyond the two to five years, which was the original, I suppose, strong trial design. And given 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, I suppose, type 2 SMA patients? Thanks very much.

Yeah, thanks, Richard. So 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 we'd be able to give you at least a perspective on what the agreed design of the 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 Florian 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 those. Could you please share with us how do you see the dynamic of the non-biosimilar business? Because we see and understand what is driving this business. But for the rest of the portfolio, it's a bit more difficult to understand. Could you maybe elaborate on this, on the midterm dynamic of the non-biosimilar business? Thank you. Richard?

See if we still have Richard. Richard, are you on the line?

Richard's line is still connected. Sorry, sir. Richard's line is still connected.

Okay. I'll just quickly answer the question. I think the The dynamics we see right now are similar, primarily growth in Europe and Japan. In the U.S., it continues to be a mixed picture. Of course, hopeful that in our next wave of assets, we can get a much broader set of assets launched in the U.S. with 15 projects now. progressing through our biosimilars portfolio. In terms of small molecules, the softness we saw was primarily in anti-infectives in Europe, as well as a legacy of the oil solids business we brought back from Urbinda. What we're hopeful now is that hopefully we see demand start 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 up to that mid-single-digit growth rate over time. Thank you. All right. Next question, operator. I think we have just a few more left.

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

Hi there, thanks for taking my question. Just one on M&A, please. You've had a couple of large deals which have resulted in some issues where we argue that if those assets were developed internally, the likelihood of those problems arising would have been probably much less likely to have occurred. And given that even the most diligent of 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 one in, does the $60 billion sales number include M&A, or is that just organic growth?

Yeah, thanks, Naresh. And the second part, just organic growth, we're not including M&A. I think less about, I mean, look, I think when we go 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 small interfering RNA and novel gene therapies is 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 four platforms we want to get to global leadership on. So we have plenty to do. Always opportunistically thinking about M&A, but that's not in 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 tizolizumab. I was just wondering if you could give us a sense of the order of magnitude of the incremental development costs 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.

Yeah, Harry, you want to provide some color on that or clarity on that?

Yeah, 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 Beijing, and it's part of our upfront payment. So it's not a cash expense, but an expense given the structure of the deal. We always want to ensure that our core results and the core accounting is of the highest quality as well.

Okay, that sounds very helpful. Thanks.

Last question, Operator?

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

Well, thank you for taking my thought. Vaz, it's just another clarification investor question actually on Tesla Lizumab. The question was the 15 registration trials that Susanna mentioned and being asked which regions and which indications are you going to be able to file. So I guess the question is really reflecting if you need any additional data in a specific country such as the U.S. or parts of Europe in any specific indications. Thank you for the follow-up.

Yeah, thanks, Mark. So I'll just quickly take it. You know, we have rights in U.S., Europe, and a number of other ex-U.S. markets. Beijing keeps rights in parts of Asia and Latin America. The clinical trials currently being conducted are already conducted with support filings in a full range of indications. So second-line lung, which they hope to complete this year, first-line lung, colorectal cancer, head and neck. Susanna, are there others that I'm missing?

No, I think gastric is also there. Yeah, I had a neck you mentioned. And I mean, these are global programs. That's probably worth to mention. They're 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 rambler patients. Biogen 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-China.

Thank you. That was kind of great. Thanks, Mark. And thanks, everyone, for joining today's call. We appreciate it, appreciate your interest in our company, as well as to 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.