Good morning and good afternoon and welcome to the Novartis Q4 and Full Year 2020 Results Release Conference Call and Live Audio Webcast. Please note that during the presentation, all participants will be in a listen only mode and the conference is being recorded. After the presentation, there will be an opportunity to ask questions. A recording of the conference call, including the Q and A session, will be available on our website shortly after the call With that, I would like to hand over to Mr. Samir Shah, Global Head of Investor Relations.
Please go ahead, sir.
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 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'll hand across to Ratnar Sinan. Ratnar?
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 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 5, Over the past 3 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 5 strategic priorities that we remain committed to and believe in the long run Will enable Novartis to sustainably grow and sustainably have impact on health care around the world and deliver on our purpose to reimagine medicine. Then 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, We're making good progress.
We're 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 and one product and over 15 blockbusters, we've achieved $2,000,000,000 And 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 4 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 past 3 years with sales growing 5% from $42,000,000,000 now to Approaching $49,000,000,000 core op and growing double digit at 10%, exceeding now $15,000,000,000 And we've reached our goal our initial goal of Innovative 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 7, 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 Tecentriq, 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 The patent expiries we have in this period and continue to drive growth through 2025 beyond. Now moving to Slide 8.
I wanted to dive into a few of the products in Sandoz before turning it over to my colleagues. First on ZOLGENSMA, full year sales were CAD 920,000,000 1st 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 $254,000,000 which were lower than Q3.
This was driven primarily by COVID-nineteen related impact, Delaying new starts as hospitals faced 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 twenty twenty one, where 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 $2,000,000,000 It remains the treatment of choice for newly diagnosed patients. We're seeing about 15% of patients in the EU in the older than 2 year age range. We're on our way to get access in 9 EU countries, which would be about 25% of the population.
And we have important formal decisions in 15 countries over the coming year to 2 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 2 INDs and clinical trial starts planned in 2021.
Now moving to Slide 9. 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%, 2nd fastest amongst multinationals in China. Our goal is to double our sales in the country by 2024, making China the 2nd largest market for Novartis in the world. Our key growth drivers similar to what we see in other geographies are Entresto, Cosentyx as well as our other oncology strategic brands.
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 7 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. So moving to Slide 10. With respect to Sandoz, you saw in the full year Sandoz matters 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, A continued strong biopharmaceuticals performance of 19% growth, primarily in the European market, but also held back a bit by Our retail declines we saw driven by COVID-nineteen and the U. S. Oral 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 2020 is 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-nineteen challenges we see in the marketplace. Harry will talk a little bit more about our guidance. But certainly, when you look at the Healthcare Systems 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 levels.
Here on the left hand side of the chart, you see 2 examples in dermatology. We continue to see patient visits in 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 CDK4six market. So for the first half of the 2021, we expect to continue to see challenges for certain therapeutic areas such as dermatology in 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.
You'll hear more about that from Marie France, on preparing for these launches to accelerate in the back half of the year, such as Cosimta and Mayzent. And we also know products that involve hospital initiation such as Kymriah, Lutathera and ZOLGENSMA will face A tougher situation in the 1st 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. Moving to Slide 12. Returning to our innovation performance and innovation milestones in Q4, we saw the approval of Lekvio in the EU 6 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 atacopan and legalizumab, 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 tislelizumab with BeiGene for anti PD-one, 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, like video and an update on the CRL.
Now, 1st and foremost, It's important to note that there are no safety, efficacy or product related concerns with respect to LifeBio in the CRL. As I mentioned, the EU fully approved this product out of the same facilities that we also filed for the U. S. FDA. The CRL was related to facility inspection related conditions, primarily related to documentation and controls Certain control systems at a 3rd party manufacturer in Europe.
We expect based on the 3rd 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 are 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 Shasta now for the production supply chain of Latvia.
So we remain confident we will get this product approved as fast as possible and then continue our plans to launch this medicine, which 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, Kasympa in the EU, Entresto, a HFpEF for an And an indication for Entresto, a number of major submissions you can see listed here, including asiminib in CML. We have also a range of major readouts that which would enable submissions in 2021, notably canakinumab, sabotelimab, MBG-four fifty three and luPSMA amongst others. We also will hope to see the readouts of ligolizumab and Cosentyx, 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 5 lifecycle management programs, 5 pharmaceutical programs, 5 oncology programs and 5 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 amide trial to read out in the first half of 2021.
I already mentioned Cosentyx and hydroadenitis, Suppurativa, the Kisqali MonaLisa II OS in the second half of twenty twenty one. We'll see important mid stage readouts for ataclopan in IgA nephropathy and C3 gs. We'll see also an important Phase 2b start for branoplim in Huntington's disease. And then, of course, the range of oncology milestones as well across the oncology 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 continue to advance our SHP2 inhibitor and our CRASP as well in the oncology portfolio. So I hope that gives you an overview of our story of well, mid- and long term story most importantly, but also our story in Q4 for 2021. And with that, I'll hand it over to Mary Frans. Mary Frans?
Thank you, Vas. So going on to Slide 16. Good morning, good afternoon. I'm 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 $500,000,000 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 $4,000,000,000 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'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 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 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 consensus now recommends that heart failure patients go direct to Arnie. And this puts Entresto in a pole position for the 75% of patients who are still on standard sorry, 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 PUS or preserved ejection fraction in post AMI. If we move to the next slide, the AdCom discussion for PEPs reinforce the unmet need as well as Entresto's value in the treatment of preserved ejection fraction and specifically in patients with ejection contraction below normal.
Ultimately, the addressable patient pool will depend on the label. What I can tell you is that the total PEP population is about 3,000,000 in the U. S. And about 2,000,000 of them have an ejection fraction below normal. We know from our deep experience in Rush 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 Cosimpta, 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% of market share in MS, and we're positioning Cosinta 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 Kacinta, 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 Lexvio.
Lexvio 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 3. 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 1, we want to maintain the momentum on Cosentyx and Entresto, penetrating markets further and delivering on our lifecycle management programs 2, executing our launches ramping up Kacintha, bringing Lexvio to market and restoring confidence in VeoView and 3, 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 SEK 14,700,000,000. 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 XJade NU 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. But I have to say, our teams really stepped out and we leveraged our robust digital AbiliTees embarked on 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 Kisqali. Kisqali delivered a very strong performance in 2020, with full year sales up 45 and reaching SEK 870,000,000. And this is driven by the unprecedented overall survival benefit from 2 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 CDK for 6 markets, driven by suppressed patient screening and overall decrease in new patient starts.
At a recent Congress Since San Antonio, we were very proud to share that Kisqali demonstrated the longest median overall survival among all Phase III trials in advanced breast cancer, reaching nearly 5 years of survival in premenopausal patients. And additionally, we presented the pooled data from MONALISA studies that confirmed efficacy across luminal and estrogen therapy resistant HER2 enriched patient subtypes. And these data confirm that Kisqali's ability to selectively inhibit CDK4 may store endocrine sensitivity in these very aggressive tumors. On the development side, In NATALI, Ativan study in intermediate and high risk population is enrolling incredibly well and we are on track for final readout in 2022. So overall, we are very pleased with the performance of Kisqali and remain very confident in this brand.
Moving to Slide 26. Also Kymriah had an excellent year with sales up 68% driven by strong double digit growth across all geographies despite pandemic conditions. We continue to and our global presence with now over 290 centers qualified to administer Kymriah across 27 markets. Commercial manufacturing for Kymriah has been expanded with the recent approval of FBRI in Japan. And this is building on previous approvals of Stein and Lesley 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 continued 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 ILLARA trial showing that Kymriah is effective in pre readied patients with relapsed or refractory follicular lymphoma. Submission for this important indication is expected later this year. And we have also presented the truly updated efficacy results, which showed continued durable responses for patients with relapsed or refractory DLBCL.
We also continue to invest in our CAR T therapies with already 2 new CAR T assets in Phase 1 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 subpopulation. Moving to next slide. We'd like to share with you the exciting data we have recently presented at ASH on aciminib, our 1st in class DAMP inhibitor that has the potential to transform CML treatment standards. In the Phase III ASEMBLE trial, acivilinib nearly doubled the major molecular response rate at 24 weeks compared to bosutinib in patients resistant to or intolerant of at least 2 prior TAEIs.
Aciminib also demonstrated favorable safety profile, underscoring that STAMP inhibition reduces the off target adverse events typical for JKIs. 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 twenty twenty one. We also continue evaluating multiple development options for aciminib 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 Kisqali.
We are going to leverage the increased manufacturing capacity to drive further growth in Kymriah. 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 Revolay, Promacta, Chakavy and Tafila Mekinist.
We are also committed to deliver on our launches. We will further expand Pickray in the U. S. And gain momentum in Europe. And we hope to continue strong on our Dacchio expanding to larger accounts in the U.
S. And continue global rollout. We will further maximize the 1st mover advantage with Tabrecta 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 trial later this year and also focused medical education on Canakinomab to establish the importance of protumor inflammation. Another important focus for us is the medical education on sabotelimab to build awareness for the dual mechanism of action of TIM-three in MDS and AML. And as Vas said, we are advancing our early assets TNO-one hundred and fifty five and LXH-two fifty four in a broad range of combination studies. Moving to Slide 29, just to give you an update on the recently announced deal to in license tislelizumab from BiGene.
This is a late stage PD-one inhibitor specifically engineered to minimize binding to the Fc gamma receptor on macrophages. Dislelizumab has 15 potentially registration enabling clinical trials currently ongoing with first ex China filing expected in 2021. With this deal, Novartis obtains development on 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 PD-one sooner in broad and important indications such as lung cancer.
We have identified also multiple potential combination opportunities with the Novartis portfolio across all of our 4 therapeutic platforms. So we are very excited about collaborating with Biogen to bring tislelizumab to patients around the world. And we are looking forward to provide you with more updates after the transaction is closed later this year. And with that, I hand over to Hari.
Thank you, Susanna. Good morning, good afternoon, everyone. And now going to walk you through some of the financials for the Q4 full year as well as provide you with our 2021 guidance. As always, my comments refer to 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-nineteen in quarter 4, We ended at the low end of the 3% to 4% range, as we mentioned during the quarter 3 investor call. Now Slide 32 shows you a summary of the performance for quarter 4 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 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 $11,700,000,000 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 4. For the full year, continuing operations core margin was 31.7%, growing 2 80 basis points in constant currencies with strong improvements in both divisions. Innovative Medicines margin reached 35% as outlooked, up 2 20 basis points, allowing us to achieve our previously announced mid-30s core margin target a couple of years earlier than planned. And Zendesk margin grew by 330 basis points to 24.2%.
Clearly, our full 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 Sandoz 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 EUR 11,700,000,000 down 10% versus prior year. Obviously, this was because higher operating income was more than offset by the payments related to legal matters and higher divestment 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 Gilenya and no Sandostatin LAR generics enter in 2021 in the U. S. Please also note that the overall generic impact 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 Affininto, XJ8, KeyWag, also with some mature Oftar brands and Diovan.
On Slide 36, I would like to explain the dynamics that we expect to see in quarter 1, given that we had quite a significant COVID impact last year quarter 1, which of course would impact the growth rate. So as you recall, there was a significant forward purchasing in quarter 1 of last year. There were approximately 3 points of growth that largely reversed in quarter 2 with no overall impact on the full year 2020. So as a result, in quarter 1, 2021, we anticipate sales to decline low to mid single digits year on year. The quarter one underlying performance excluding the stocking effect is expected to be broadly in line with prior year due to the continued COVID-nineteen impact on healthcare systems and patient visits.
Turning to Slide 37. In 2021, we do expect further margin expansion, as mentioned earlier with core operating income growth. And the magnitude, however, will be lower compared to 2020, where we increased core margins by 2 80 basis points. Expected positive drivers of future core operating income growth include the continued performance of our growth drivers, the launch uptick 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 Kysinta and Lexio as well as development costs for atiselizumab, which we recently unlicensed From Beijing, of course, on the after the completion of the transaction.
We will also likely see further investments into growth drivers as we expect physician access to normalize from 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 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 CHF 3 per share 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 consistently 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 core operating income 3% positive. For quarter 1, as you can see here, sales would be positive 4% and on core operating income of positive 2%. And as you know, we update these expected currency impacts every month on our website. With that, I hand back to Lars.
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 4 main areas of focus through our materiality assessment. Some of the highlights include the issuance of the 1st industry sustainability linked bond for access Our commitment for full carbon, plastic and water neutrality by 2,030.
We were just ranked Today, number 2 in the access to medicines index that was just announced and continue to see strong progress in our DNI 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 $60,000,000,000 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 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 Our strategic priorities in 2020 despite the challenging business environment, our 3rd 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 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 2 questions, we do have a number of people in the queue already.
Thank you. Operator?
Thank 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 Possel from Morgan Stanley. So just to 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 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 phasing of Sandoz, Which we may not have as much visibility on, which is different to that pattern. And then secondly, if I was maybe one for you. With To salutumab 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 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 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 things such as TIM-three, SHIP-two, 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 Last year was quite interesting with the forward buy, if you will, as health care systems try to get some inventory and Also, the patient level longer scripts have been given. So we have this $400,000,000 roughly effect of forward buy or stocking in quarter 1 And then they're destocking in quarter 2. That's roughly 3 points on our quarter.
So, of course, then quarter What have the reverse positive effect, another effect we had in quarter 2 is that Lucentis, Basically, many patients skipped or doctors skipped one injection. That's now fully back. So, quarter 2, 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, right? 1st decline in quarter 1 and then some good growth in quarter 2 was the expectation.
That is broadly in line with prior year, especially what we have seen the last two quarters. Now if you think about the second half of twenty twenty, quarter 3 was 0, quarter 4 was plus 1. 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 health care systems open up. So I think that phasing of half 1, half 2 And then if you have to do this quarter 1 stocking, quarter 2 destocking of last year should give a 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 1, quarter 2 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 that can participate in the $50,000,000,000 plus TB1 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 combination possible across Novartis' Oncology portfolio. So we have a number of combination studies already planned and we believe Having a hopefully soon approved PD-one 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're further along, we can, of course, provide more granularity and Susanna can provide more granularity on our commercial strategies. Next, I'll take a 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. 2 product specific questions, please. Firstly, for Zolgensma 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 Tristempta, 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.
Yes. Thanks, Laura. So on Zolgensma, 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 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 programs. 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 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. We do see physicians delaying starts with Zolgensma simply because And 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 Kysynta, Mary Frances.
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 Kacensa patients are currently on this bridging program. We expect the conversion to paid products with 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 3 quarters of the 2021 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, Marfant. 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 2021 guide seems to be somewhat below consensus.
So you obviously have 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 PES, Again, just referencing that meat management, you put it in the €500,000,000 to €1,000,000,000 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.
Yes. Thanks, Matthew. On the first point, our intention to meet the management was to provide confidence over the 5 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 we look at that 4% Growth after 2025 and the margin at rounded 38%. We feel very good with our ability to achieve that with the Portfolio that we have in hand. Now with respect to half past, maybe I'll turn it over to Mary Frantz to give a little bit of the range of patient numbers and
Thank you, Beth. So the Icon discussion really reinforced the unmet need for Entresto's value in the treatment of 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 addressable patient pool, which will obviously depend on the label. What I can say is that the total pep population is about 3,000,000 patients in the U. S.
And about 2,000,000 of them have fraction be below normal. We also know in this market, and this is critical, I referenced it before that it's is 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 $4,000,000,000 to $5,000,000,000 for total Entresto sales. So we previously guided $3,000,000,000 to $4,000,000 on REF, and we are guiding 4% to 5% on Rev and PEF together.
Great. Thanks, Marifan. 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 $2,000,000,000 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 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 Paper based inspection.
The 3rd 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 3rd party facility. Our best Our 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 Product specific, we ultimately all learned and 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 Latvia in Europe. We're working as fast as we can with the 3rd party.
Ultimately, it's the 3rd 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 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 take to complete that process and 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 Mary France and the team mentioned, what 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're comfortable with the 2025 consensus, which I believe is in that range of 1,900,000,000 to 2,000,000,000 And so that's the basis of this comment that I made. It's based on Zolgensma IV And based on Zolgensma IV in the current indications of under 2 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-one hundred and one IT fully licensed and we'll keep we'll give you an update Once we clear the preclinical topic and finalize the Phase III development program. 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 2021 guide. So roughly, how many percentage points do 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. So as we look into 2022, you're really setting yourselves up here for quite an easy base For 'twenty two 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 twenty twenty one. 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-nineteen impact, I'll give it to Harry. Harry?
Thank you very much, Graeme. 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 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 underspent, as we have as you have seen, We have made up more than that, and it could even increase our core operating income guidance. Now for 2021, half year effect, we have some a little under 2% on the top line, what we expect.
So, again, it depends very much how quarter 2, quarter 3 go. We have several scenarios, which we try to For Tier 1, the guidance never easy, but I think we have to be a bit careful around when our Patient visits and initiations 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, right, we have significant savings and underspend. 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 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 here 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, Terry. And then on interim guidance, maybe rather than getting specific on Canopy 1, 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 Data readouts, full timing of data readouts based on the powering of these studies or powered, of course, to readout At the close of the study. And so we continue to guide to Canopy II in the first half, Canopy I in the second half, Canopy Adjuvant in 'twenty two.
Thanks, Ram. 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. A couple of questions, please. Perhaps the first one I could take is on the SHIP-two. 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. Marathi. 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. 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 midterm outlook in That space. And then maybe if I could just tack on. In C3 gs, we've had reasonably promising Phase 2 days 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 Thank you.
Thanks, Emmanuel. So on the SHIP-two, John?
Yes, sure. Thanks for the question, Emmanuel. On the SHIP-two inhibitor, We've been working with Verati and we have a clinical collaboration in terms of moving forward. We've had a couple of patients In combination with their KRAS G12C adagracin, 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 II and Phase III will be forthcoming and probably This time, middle of this year is how we would move forward. So also I think you had a number of questions Regarding, Ipacopan. And, I believe specifically you were asking about our approach, with itpacopan and PNH And combinations. As you know, and just for the folks online here, pacapan is our 1st in class Compliment 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 single agent.
And then John, avacopan And in C3, 33 gs, I think that's a C5 inhibitor. So I think they're acting downstream, if I'm not mistaken.
Exactly. That is down 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 C3 gs and when we would plan to get to a filing in C3 gs for atacopan? Yes.
So For atacopan and C3 gs, 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 potential Phase 3 program and potential filing next or 2023.
And I just want to highlight again for Atacofan, our goal is a first line 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 Fully 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 Parkes from Exane BNP. Please go ahead. Your line is open.
Hi. Thanks for taking my questions. Two questions. Firstly, on KASEMTA. I just wonder to what degree the launch and the class overall is being impacted by patients delaying treatment initiation due to Either worries over immunosuppression or lack of potential lack of response to COVID vaccination.
I noticed a couple of recent publications underlying a Two times increased risk of severe COVID with B cell depletes. So just wondered if you could comment on that and what degree that impact on the class 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 ejection fraction cutoffs rather than necessarily restricting bisects. 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 semi
So Mary Frantz, both on Kacinta and Entrepta.
Yes. So on Kacinta, I think the important thing is that we're really leaving no 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 HVPs 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'll be able to make sure that patients and physicians feel comfortable with using Kacinta in 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 Cosentyx 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 this foundation for this product. And I do, believe that you can expect to see the So market growth 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, Mary Frunt, on the Entresto HFpEF ejection fraction versus malefemale 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 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's a general consensus with physicians that this is not an exact science.
So having an ejection 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 size for the results of the trials. But our data tells us there are about 7,000,000 AMI events every year across the globe and 1 in 4 We'll 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, Marfa. 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. 2, if I may, please. Firstly, on the newer modalities. On Zolgensma, Vas, 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 Kymriah, It was a particularly good performance in the Q4 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 manufacturer 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 Past there, we have reimbursement in Japan. And we're working very 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 UK, 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 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. It is also in Q4, for 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 Kymriah indication. 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, TIMORAIA 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 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, Sunana. And then on tislelizumab manufacturing, The product is produced by an established third party 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 we our IR team simply gets back to you once we do the Appropriate checks, but a very reputable top class third party manufacturer based out of Europe. So next question, operator?
Thank you. Your next question comes from the line of Keri Holford from Berenberg. Please go ahead. Your line is open.
Thank you. Yes, Keri Holford from Berenberg. A couple of questions left For me, please. Firstly, on the BiGene PD-one, I wonder if you can just talk through why You took the decision to bring that on board. Given you have spartolizumab and what did that asset Where the offer that you all signaled, was it just timing?
Or is there something else here in the world to be aware of? Should we assume spartolizumab is now And will you continue those ongoing combinations that asset as well? And then secondly, on the Branopram, You highlight in the slide Phase 2b is due to start in Huntington's in the second half of the year. I wonder why not any earlier. Is this COVID related delays?
Is there 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, Carrie. On BiGene, it does not Change the status of our own PD-one. We view them as complementary. Our own PD-one was primarily focused, spartolizumab was focused on a Q select indications, that was the strategy we took with that medicine.
We'll continue on those indications. 5gene has taken a very broad development program across the main PD-one indications without overlap on spartolizumab. And so we're excited to bring that medicine to market across the full range of indications. So then anything you want to add on this point?
Yes. Vas, just to add, I think that really we were impressed by the very Broad development program that BiTEEN is running in global programs, having really 15 potentially patient enabling trials ongoing. And I believe for us also advantage is that Biogen has tested Tislelizumab in very important indications in monotherapy that's different from spardalizumab like non small cell lung
cancer, gastric cancer and so on. And therefore, we are excited
to bring this And therefore, we are excited to bring this product to market ex China.
And then John on the BranaPlan timelines for Huntsville.
Yes. BranaPlan 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 haven't approved PD-one, 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 ran a plan, as you highlighted, we We'll 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 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 And 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, 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.
Hi, yes. Thanks for taking my questions. Firstly, just going to another pipeline asset, It's Galimab. Would you just give us a bit of clarity on the path forward for filing of that now? I see a commentary that the regulatory interaction suggests 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 planned to be started and how do you think about that and what sort of endpoints the regulators requiring? And then secondly, just on the generics, Obviously, guiding towards no Sandostatin Gilenya generics during the course of this year from Harry, I guess, makes sense on Gilenya. I presume we're still going to wait The clarity from the call before you give us timing on that one.
The Sandostatin 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. Somnostatin LAR generic this year? Thank you.
So, Greg, John on eskalimab?
Yes. Thanks, Peter. On eskalimab, this is our anti CD40 as you know. We had intentions in moving forward and we still have intentions of moving forward with 2 or 3 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 cast in urine inhibitors.
I think we noted previously in Discussions whether that was 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 a potentially faster path through Sjogren's and we're awaiting the Sjogren's Phase 2b result and once we have those results, we'll be able to disclose the overall time lines on the Sjogren's program, which may be faster than the transplant program.
Thanks, John. On sandostatin LARA generics in the U. S, Suzanna?
Yes, 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 8 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. 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 whoever 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, Vaz, congratulations on the progress you've made on the ESG front, especially with the access to medicine going up number 2. 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 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.
Yes. Thanks, Teodor, and thanks for the comments as well on ESG. We're very pleased with the collaboration with Beijing 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 NRDL listings in the upcoming Approvals.
We're continuing 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. 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 GBV and John's organization as well as Marie France and Susanna's commercial teams. In terms of the mid- to long term ambitions, I think Nothing more to add.
Of course, as a CEO who wants our company to lead and be the leading medicines Company in the industry have very high ambitions, but I think more appropriately 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 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 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. Just one question, please. Oncotonics, can you talk to the anticipated performance in the U. S.
In 2021, given I know 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 without a Cosentyx question. So, Mary Frantz, 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 talked about the competitive product profile across 4 indications. And then very importantly, our lifecycle management opportunities that could bring up to 6 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 Cosentyx or our ability to reach $5,000,000,000 and beyond.
Thanks, Maher Frans. I'd ask the next set of analysts to please limit themselves to one question just in the interest Next question, operator.
Thank you. Your next question comes from the line of Seamus Fernandes from Guggenheim. Please go ahead. Your line is open.
Thanks very much. So really just wanted to get an update on Aeskalumab in Sjogren's disease, I think previously you had stated that you were planning for either an interim towards the end of this year or perhaps even Towards the end of this year, perhaps even a final look at those data. So just wanted to get an update on Astalumab 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 That study if recruitment is completed then obviously that question is irrelevant. Thanks.
John on escalumab?
Yes. It's Galmap. 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 has been a little bit slower than we anticipated.
We're not fully recruited in the Phase To be for epsilonab yet. So the recruitment continues and those timelines really will depend on when we finish 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 Fossa from JPMorgan. Please go ahead. Your
Question on Zolgensma and the intrathecal form. Just Could you give us 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, I suppose, 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, I suppose, type 2 SMA patients?
Thanks very much.
Yes. 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 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 Sandoz. Could you please share with us how do you see the dynamic of the non biosimilar Business because we see 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 sorry, sir. Richard's line is still connected.
Okay. Well, I'll just quickly answer Good question. I think the dynamics we see right now, biosimilar is primarily growth in Europe and Japan. In the U. S, it continues to be A mixed picture, of course.
Hopeful that it was our next wave of assets we can get a much broader set of assets launched in the U. S. With 15 projects now are 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 oral the oral solid business we brought back from Aurobindo. What we're hopeful now is that, hopefully, we see demand start to pick up again over the course 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 single digit growth rates over time. 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 Khohan from Intron. Please go ahead. Your line is open.
Hi there. Thanks for taking my question. And just one on M and A, please. We'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, I'm thinking the AveXis data in terms of issues, the Lakebayo 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? If I may, just Nick, does the €60,000,000,000 sales number include M and A? Or is that just organic growth? Thanks.
Yes. Thanks, Naresh. On the second part, just organic growth, we're not including M and A. I think less about I mean, look, I think when we get 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 4 platforms we want to get to global leadership on. So we have plenty to do, Always opportunistically thinking about M and 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 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 the incremental development costs that you'll be taking on with this asset? And is that mostly coming from R and 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 and 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 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's very helpful. Thanks.
Last question, operator.
Thank you. Your last question today comes from the line of Mark Patell from Morgan Stanley. Please go ahead.
Well, thank you for taking my thought. Vas, it's just another clarification investor question actually on tislelizumab. The question was the 15 registration trials that Susanne mentioned. I'm being asked which of those 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.
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. Beijing keeps rights in parts of Asia and Latin America. The clinical trial portfolio clinical trials currently being conducted are already conducted Would 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. Yes, I had a neck you mentioned. And I mean, these are global programs. That's probably worth to mention. They're rolling 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 2nd line data in non small cell number. Biogen reported very strong over survival data versus Doxa. So I think that's how you have to see this, that the clinical programs we believe is very robust and would allow for filings ex U. S.
Sorry, ex China.
Thank you. That was kind of.
Thanks, 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.
Thank you. That does conclude our conference for today. Thank you for participating. You may all disconnect.