Novartis AG
Q2 2021 Earnings Call Transcript

Published: 21 Jul 2021

[Operator:]

Good morning and good afternoon, and welcome to the Novartis' Q2 2021 Results Release Conference Call and Live Webcast. Please note that during the presentation all participants will be in a listen-only mode, and the conference is being recorded. A recording of the conference call including the Q&A session will be available on our Web site shortly after the call ends.

[Samir Shah:]

Thank you very much, and good morning and good afternoon, everybody; big thank you to all of you again for participating in this call, and spending the time to listen to our quarterly results. The information presented today contains forward-looking statements that involve known and unknown risks, uncertainties and other factors. These may cause the actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. For a description of some of these factors, please refer to the company's Form 20-F and its most recent quarterly results on Form 6-K that respectively were filed with and furnished to the U.S. Securities and Exchange Commission. So, thank you again. And with that, I I'll hand across to Vas Narasimhan.

[Vas Narasimhan:]

Thank you, Samir, and thanks everyone for joining today's conference call. Today with me I have members of our executive team, and also we'd like to introduce Karen Hale, our new Chief Legal Officer. Karen joins us from the biopharmaceutical industry with over 20 years experience in a broad range of medical devices and pharmaceuticals. So, welcome Karen. So, if we can move to slide five, I wanted to start by reflecting on the journey we've been on as a company, as we focus the company, rolled out our strategy, and delivered consistent performance over the recent period. Going back to the first-half of 2018, when you look at our financial performance over the first-halves of the -- for the subsequent four years, our sales have grown at 6% CAGR, our core operating income at a 13% CAGR. And we've grown our Innovative Medicines margin from 31.8% to 36.8% in the first-half of 2021, demonstrating that our operational execution has been strong. Now when you look ahead, we remain confident in our growth outlook, as we outlined in Meet the Management last year, where we highlighted a 4% CAGR off of our 2019 actuals to a 2025 sales goal of $60 billion or more, and a consensus IM margin, that is currently at 37.6%, that we remain confident that we can achieve. So, a strong performance track record, and a strong growth outlook remains the story for Novartis. Now, going to slide six, when you look at our strong performance in Q2, it was strong across all of the key elements that we believe will drive long-term value for our patients as well as for shareholders. Our sales growth was strong, and Harry will go through that in a bit more detail. We had strong productivity, with good core operating income growth and good margin expansion. We continued our innovation agenda, which will be critical to driving the growth to 2025 and, importantly, beyond. And we also continued on our journey to be a leader in ESG, with some important milestones. And I'll talk about each of these areas in turn.

[Marie-France:]

Thank you, Vas. Good morning, good afternoon to all and please to update you on our Q2 pharma performance. If we move to slide 19, we delivered 12% growth versus prior year and an additional billion dollars in revenues. As you can also see, we also continue to make progress in our portfolio shift. Our growth drivers and launches are showing excellent momentum with 35% growth. And these now contribute to more than 50% of our top-line. Thanks to our strong focus on execution. You can expect this shift to continue as we invest behind our growth drivers and launches, and also actively manage the mature portfolio. If we move to slide 20, Cosentyx delivered 21% growth. U.S. volume growth in Q2 is now back in line with the market and sales were up 11% quarter-over-quarter. Our field force activity is above pre-COVID levels. And as we see the market regaining momentum, we also intend to capture more volume. Ex-U.S. we had really strong growth in Europe. And in China, we quadrupled sales versus Q1 following the NRDL listing in March. So full-year we're on track to deliver double-digit growth based on our broad access, our ongoing geographic expansion and the continued investment. We can now proudly say that 500,000 patients have been treated with Cosentyx. And with our ambition to expand to 10 indications we know that many more can benefit, will continue to invest with additional approvals in the short-term and with our Hidradenitis Suppurativa readout towards the end of the year. If we move to the next slide, Entresto saw another very strong quarter with 46% growth. In the U.S. you can see from the NBRx growth that we're really capitalizing on the ACC consensus recommendations, and also on the expanded label. In Europe, the ESC guidelines now recommend and trust was first-line and that is further reinforcing our position as first choice. China we tripled sales compared to previous year on the back of strategic account expansion. In fact, China is now in trust of second biggest market. So this team is strongly focused on execution and educating prescribers on guidelines, activating patients and ensuring the guidelines become protocol at hospital level. You can expect to see the usual summer slowdown, however full-year, we will stay strong as we address the remaining 70% of patients who do not yet benefit from Entresto. If I move to slide 22, the Zolgensma is continuing its growth trajectory as we open up reimbursement in new markets. As you heard Vas say earlier, we've got compelling data and pre-symptomatic patients. And that's really important for us to continue to work to implement newborn screening. As we know the earlier we treat the more transformational the outcomes are for these babies. In the U.S., 80% of newborns are being screened and this is allowing treatment within a few weeks of birth. Ex-U.S. we expect to see Italy and the U.K. and additional reimburse markets to drive the growth in the second-half. And even though you can continue to expect some volatility in the quarterly pattern, we're on track to exceed blockbuster status this year. Our preclinical studies for IT are progressing well. And we're actually ready to start our Phase 3 as soon as the FDA gives us the green light. Over time, the ITU formulation could more than double the number of patients who could benefit from Zolgensma. If we move to the next slide, with Kesimpta our focus is on broad adoption in early lines of therapy. We've added 500 new prescribers and we've doubled the number of patients on Kesimpta versus Q1. We also see that half of the Kesimpta usage is a naive or first switch. And this is exactly where we want to be. The BSO class is currently leading the recovery of the dynamic market and Kesimpta has got the second highest NBRx share in the MS space. So, this positions as well as the market opens up further. As we move to the second-half of the year, we know what we need to do to double demand and we're doing what is needed for a strong Q4. We're maintaining our leading share of voice to really increase the awareness of Kesimpta. We also believe that our PIRA and our IgG data provide important clinical differentiation. So we're fully focused on what we need to do. We're also fully focused on delivering a positive customer experience. In fact, 80% of patients are receiving their first dose within five days. And our patient support services are enabling fast and easy initiation. If I move onto slide 24, and move on to Leqvio. We all know that ASCVD is the leading cause of death and unfortunately mortality is on the rise. There are effective treatments, we know that too, but patients are not at goal due to access, adherence and affordability challenges. And this is why we're taking a different approach on how we bring Leqvio to market. In the U.S., we've got a new action date for January, and we're preparing for launch. Our access strategy could actually enable two thirds of patients at launch to access Leqvio with $0 co-pay. So we're working with healthcare systems on broad adoption. We're using our existing infrastructure to identify patients and also to set up buy-and-bill administration. In the UK, we're partnering with the NHS to bring Leqvio to more than 300,000 patients at risk of a second CV event over the next three years and we're on track for that launch in Q3. We understand this approach will take time and further evidence generation, but this level of ambition is absolutely necessary if we want to drive better outcomes for ASCVD patients. So in summary, an excellent quarter, we're fully focused on our strategy to maximize our growth drivers, deliver our launches, and also prepare for the next wave of innovative medicines. As we further accelerate our portfolio shifts, we're also transforming our business. We want to be much more customer centric and also pursue innovative approaches to launch our products in partnership with healthcare systems around the world. So coming out of Q2, we had good momentum across the globe, which we expect will continue in the second-half. I want to take a moment to recognize the fantastic teams around the work for their hard work and for delivering these results. Over to you, Susanne.

[Susanne Schaffert:]

Thank you, Marie-France. And moving to slide 26, I'm very pleased to give an update on the oncology business. So the oncology business showed very solid performance in the second quarter, delivering 7% of growth with sales reaching $3.9 billion. Our growth drivers and reason launches are showing good momentum with 19% growth versus prior year driven by Kisqali, Jakavi, Promacta/Revolade and Kymriah. And together these products now contribute to half of the overall oncology sales allowing us to more than offset losses from continued generic erosion of Glivec, Afinitor, and Exjade/Jadenu in the U.S. In Q2, the oncology market continued to be affected by COVID-19. Oncologists are reporting that as caseload, depending on geography is still a 25% to 50% below pre-COVID level and most affected areas are our breast cancer portfolio, recent launches and hospital initiated therapies like Kymriah and Lutathera. Looking at Kymriah, this grew globally 19%, and it was driven by strong ex-U.S. growth and geographic expansion. In the U.S., we remain very competitive. However, overall demand in the class has slowed down. Lutathera says we're growing 10% in Q2, the ex-U.S. growth was double-digit, and we also saw positive signals in the U.S. as it is emerging from COVID and referrals started to increase. So, overall, we remain confident that patient visits to hospitals will increase and treatment patterns will further improve in the second-half of the year, leading to acceleration of growth in these segments. Moving to slide 27, I wanted to share a bit on our performance in the U.S. U.S. remains our biggest market globally, and is contributing to over 40% of our overall oncology sales. Our growth brands and launches contribute to 49% of sales. The U.S. market is slowly recovering from the pandemic with oncologist caseload now reaching 75% of pre-COVID level. However, testing rates for the most common tumor types remain suppressed in Q1 delaying diagnosis and new prescriptions. In Q2, we have seen partial recovery of our growth drivers and recent launches together growing 10% versus previous year, and also accelerating whilst previous quarter. So this was mainly driven by Kisqali, Promacta and Taf/Mek. Overall, this continued recovery of the market we expect acceleration of sales in the U.S. in the second-half of the year. Moving to Kisqali on slide 28, Kisqali delivered strong performance in second quarter, growing 36% with sales of $225 million. The uptake was mainly driven by continued momentum and patient share gains ex-U.S. and particularly in Europe. Kisqali is the market leader in premenopausal setting in France, Italy, and Spain. And in the U.S., we have also seen Kisqali sales getting traction, delivering 17% versus previous quarter driven by increased demand in new patients start. We see increased field force reach in those accounts where access restrictions were lifted and we also continue to leverage digital engagement based on dynamic targeting. At ASCO, we presented updated OS data from our MONALEESA-3 trial that showed consistent OS benefit with a median OS of 4.5 years. And with this data, Kisqali demonstrated the longest OS in post-menopausal patients and it's the only CDK 4/6 inhibitor with data in first-line responsive trend. We believe that these excellent results may be attributed to the unique profile of Kisqali versus other CDK 4/6 inhibitors with a preferential inhibition through CDK 4 over CDK 6 and a high concentration to inhibit the target. In addition, we are going into the adjuvant setting with our NATALEE study, exploring Kisqali in both intermediate and high-risk population. And just to remind you that this population represents around 70% of the adjuvant early breast cancer population, and there's a clear unmet medical need. I'm very pleased to report that the enrollment of the NATALEE study is completed, and we are on track for readout in 2022. Moving to slide 29, as you heard from Vas, we are very excited about data from the VISION trial that positions lutetium-PSMA valid to potentially address the unmet needs of more than 80% of men with late-stage advanced prostate cancer, who express PSMA receptors. And just to remind you that prostate cancer is the second most diagnosed cancer globally and in the majority of cases, patients unfortunately develop metastasis by the time of castration-resistant prostate cancer diagnosis. Earlier in June, we got a breakthrough therapy granted by the FDA and filing to FDA is on track for the second-half of 2021. We are fully in launch preparation with focus on the top 200 treatment centers and are also working on raising awareness on a clinical relevance of PSMA. Very pleased to see growth in the PSMA awareness has doubled among the target physicians over the last month. And just to reassure you that we have adequate capacity to meet the demand for the current launch. So our focus will be on driving referrals from community centers where 70% of prostate cancer patients are treated. When you model the lutetium-PSMA launch, keep in mind that hospitals need to set up processes and licenses and patients need to be selected through PSMA PET scannings. And these factors are likely to drive a more gradual uptake at launch versus what you saw with the Ebola's effect on Lutathera. Moving to the next slide, slide 30, I would like to talk about a launch preparation for Asciminib, the first STAMP inhibitor that has the potential to transform CML treatments standards again. In the Phase 3 ASCEMBL study, Asciminib nearly doubled the major molecular response at 24 weeks compared to Bosutinib. We have completed filings for FDA and EMA earlier in June and FDA has granted two breakthrough therapy designations and Fast Track designations for Asciminib and is reviewing the file and the real-time oncology review. As we are preparing for the launch, our focus is on raising awareness on the importance of STAMP inhibition to overcome resistance and minimizing off target events typical for TKIs. Aided awareness has already reached 75% and just to remind you the third-line indication for Asciminib, already blockbuster potential. But we are also very excited by the potential benefit that Asciminib may provide to CML patients in first-line setting. Despite the advancements in treatment of CML over the last 20 years, there are still around 50% of patients who relapse or intolerant to Imatinib in first-line and more than 30% of patients suffer from TKI related non-hematological AEs. We believe that in earlier lines of CML treatment, I'm assuming it may prevent resistance to currently available TKIs and therefore, we are initiating a Phase 3 study of Asciminib versus investigators selected TKIs enrollment plan to start in the second-half of '21. So, moving to slide 31, we have made great progress on our innovation agenda and '21 is a very important year in terms of readouts and submission. In addition to the Vision data, we had multiple readouts, like positive data from Iptacopan in PNH, Alpelisib in PROS, KYMRIAH follicular lymphoma and OS data for Lutathera. Canakinumab readout in second line non-small cell lung cancer did unfortunately not show positive data. But it is very important to mention that we have two more studies ongoing in first line and RD1 non-small cell lung cancer with the first line trial on track to read out in second-half of '21. Later in the year, we're also expecting KYMRIAH to read out in second line non-Hodgkins lymphoma, and Kisqali OS data from MONALEESA-2. In terms of submission, we have completed submissions for GVHD for JAKAVI in Europe and Japan, Tabrecta in Europe and Asciminib in third line U.S. and Europe and for H2, we're on track for filing of Lutetium PSMA, KYMRIAH in follicular lymphoma and second line non-Hodgkin's lymphoma and Tislelizumab in non-small cell lung cancer and second line esophageal cancer; so, exciting times ahead for oncology. Big thank you to all the teams, and with that, I hand over to Harry.

[Harry Kirsch:]

Yes, thank you, Susanne. Good morning, and good afternoon, everybody. So I'm now going to walk you through some of the financials for the second quarter and the first-half of the year. And as always, my comments refer to growth rates in constant currencies unless otherwise noted. So, in Slide 33, you'll see the summary of our operation performance for the second quarter and the first-half. We had a strong quarter two, resulting in a solid first-half performance, despite the impact of COVID during the period. Quarter two net sales grew 9% to $13 billion driven by our key growth drivers, and core operating income grew 13% to $4.3 billion, mainly driven by the highest sales and favorable gross margin, partly offset by higher investments. Core EPS growth was also up 16% to $1.66 and free cash flow grew 17% in U.S. dollars to $4.2 billion. Of course, we appreciate the benefit on comparison from the low base in quarter two, 2020 due to the COVID destocking in the prior year. However, even when excluded, we still return to healthy growth with sales up 5% in core operating income growing 4% quarter two 2021 underlying. Our half one performance was solid, with 3% growth on the top line and 2% on the bottom line. Core EPS grew 5% to $3.17 and free cash flow was $6 billion. Of course for half one, the quarter two, quarter one destocking stocking from the prior-year has washed out, so these values represent underlying growth of half one, 2021. Next slide, please. So, on slide 34, I want to dive into our performance during the quarter by division. Innovative Medicines delivered a strong quarter with plus 10% top line and plus 14% bottom line growth and a margin of 37%. Even if we adjust for last year's lower base, we still saw strong growth with Innovative Medicines sales increasing 7% and core operating income up 6%. The Innovative Medicines performance was driven by continued strong double-digit growth of our key growth drivers including Cosentyx, Entresto, Zolgensma and the oncology launch brands. And as Vas mentioned earlier in the presentation, our growth drivers and launches are thriving portfolio rejuvenation, and now account for over half of our Innovative Medicines sales. Of course the pandemic still impacts our business, particularly Sandoz retail and anti-infective segment, however the Sandoz business is now beginning to stabilize with sales up last 5% in quarter two and bottom line growing 3% although growth did also benefit from prior-year destocking. Now turning to our full-year guidance on slide 35, we confirm full-year guidance for both the group sales and core operating income. For sales, we continue to expect low to mid-single digit growth in 2021 and for the bottom line, we expect mid-single digit growth ahead of sales. For Innovative Medicines and Sandoz, we're also not making any changes. We continue to expect Innovative Medicines division sales to grow mid-single digits, and core operating income to grow mid to high single-digit ahead of sales. And for Sandoz, we continue to expect sales to decline in the low to mid-single digit range, and core operating income to climb low to mid-teens. The key assumption for the guidance is that we see a continuation of the return to normal global healthcare systems and prescribing dynamics in the second-half of this year. And in addition, we continue to assume that no Gilenya, no Sandostatin LAR generics would enter in 2021 in the U.S. On next slide, we provide some detail on our expectations for the second-half of the year, we expect top line growth to accelerate from 3% in half one to mid-single digits, bringing us to the low to mid-single digit range for the full-year. Our assumption is that this will be driven by growth acceleration as we continue to return to normal prescribing behaviors, as well as further Sandoz stabilization. We expect core operating income growth will be high single digit in half two reaching our mid-single digit expectation for the full-year. Core operating income growth will be driven by higher sales and ongoing productivity programs partly offset by increased investments in our growth drivers and pipeline. This possible that we could reach the higher end of the ranges we have provided. But as you know, the COVID situation still remains fluid. Finally, on slide 37, as currencies are constantly changing, I want to bring to your attention the estimated currency impact on our results using the current exchange rates. So if mid-July rates prevail for the remainder of 2021, the full-year impact of currencies on sales would be positive 2% and on core operating income positive 2% to 3% points. For quarter three, it will be positive 1% on sales and positive one to two points on core operating income. And as a reminder, we always update this estimated currency impact on our website on a monthly basis. And with that, I'll hand back to Vas.

[Vas Narasimhan:]

Thank you, Harry. So, moving to the next slide, when you look at 2021, we have a broad range of catalysts still to go, goes like good pipeline delivery over the course of the year. So we look forward to keeping you updated as we continue to advance these assets and programs. I'd also note, our mid-stage pipeline continues to generate, I think exciting new innovations which we hope will emerge and be able to add to our pipeline over the course of the second-half. Now moving to the last slide just to close, as I noted at the beginning, our consistent long-term performance over the recent years is driving our confidence for the future and the continued growth outlook for the company. We've had strong performance in Q2 driven by key growth drivers as you've seen throughout the presentation. And we've also continued to advance our pipeline of novel medicines, you've seen the positive readouts across Iptacopan, Lu-PSMA and others and we're reconfirming our full-year 2021 guidance, our commitment to drive long-term accretive growth and again, thank you for your commitment to the company. And so with that, I'll ask the operator to open the line for questions.

[Operator:]

Thank you.

[Vas Narasimhan:]

Operator, if I could say one thing. If questioners could limit themselves to two questions, we would appreciate it. Thank you.

[Operator:]

Thank you. Your first question today comes from the line of Wimal Kapadia from Bernstein. Please go ahead. Your line is open.

[Wimal Kapadia:]

Oh, great, thanks very much for taking my questions. I'm Wimal Kapadia from Bernstein. I'm just curious how Novartis are thinking about the potential impact of SGLT2 for interest of following the recent positive data and preserved ejection fraction population. drugs have quite a robust profile in heart failure, reasonably well-priced and have demonstrated efficacy on top and an interest in naïve patient, so do you expect to see any impact, I'm just curious in your level of confidence that these drugs will not be used out of interest? My second question is just on Iptacopan, probably lots of interesting data recently for the drug across multiple indications, but I'm just curious how Novartis is thinking about it from a commercial perspective, I appreciate it'll come down to timelines, and which indications demonstrate efficacy in Phase 3. But they're quite a different size of markets and competitive dynamics are quite different. So, ultimately, how Novartis is going to prioritize, should we see success across multiple indications, particularly given the acceptable price points by indications could be quite different and competition from the likes of Alpelisib could limit the potential? Thank you.

[Vas Narasimhan:]

Thanks, Wimal. So, first on SGLT2, Marie-France.

[Marie-France:]

So, thanks for the question. As you rightly said, the SGLT2s are add-ons. And so, we expect them to continue to be used predominantly in diabetes patients even if we think about the new readout of past, we've really only seen the press release, and we'd have to look at the full data because the trials were really quite different. The bottom line is actually Entresto is in a unique position. And it's got a broad label in the U.S. that's covering five out of six patients with chronic heart failure, we're very strong with the cardiologists, and we're going to focus on making sure that 70% of the breast patients who are in previous standard of care switch to Entresto. So, I think between the compelling data, the strong guideline support that we have, the commercial infrastructure, the excellent team that we have in place, we have what it takes to continue the momentum with Entresto. And if patients need an add-on, then SGLT2 is the right thing to do.

[Vas Narasimhan:]

And then, thanks Marie-France, and with respect to Iptacopan, I think our overall strategy, as you can see is to fully leverage the unique mechanism and profile of this medicine across the range of indications we've outlined. Now of course, it will be data-driven, and the sequencing will be determined by size of data, but our goal is, on the one hand, to disrupt existing markets with the fact that we have a safe oral, that can be given broadly to patients who at the moment are taking at least, at the moment taking IVs on an ongoing basis. And so, we think there's a very attractive profile there. And then to enter into completely new market segments in renal disease, haematological illnesses that currently don't have a very strong standard of care. And so, that's how you're going to see us approach to fully maximize the asset across the full range of numerous indications for pursuing. Thanks, Wimal. Next question?

[Wimal Kapadia:]

Thank you.

[Operator:]

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

[Graham Parry:]

Great, thanks for taking my questions. So first one is on Kesimpta. Just wondering what percentage of drug dispenses free drug in first-half and how you expect that to be in second-half because you said you expect demand to double 2H and I think if you take the first-half sales and add-on twice that you get to around consensus of 350. But if you're getting less free drug, could you actually beat the consensus number? And then secondly, on the NATALEE trial, now that recruitment is complete, can you narrow the window down to when in 2022 you might see the data even just as that, do you think it's the first-half or a second-half event? Thank you.

[Vas Narasimhan:]

Thanks, Graham. Okay, Marie-France?

[Marie-France:]

Yes, so our key focus is really on broad adoption in early lines of therapy. And I say that because I think it's really important for our strategy that everyone understand that we want to ensure the value of high efficacy B-cell therapy early. As I said in my opening comments, we have about 500 new prescribers and we've also got about twice as many patients on consensus Q1, all patients are starting on free drugs. And even though our free to paid conversion is happening really quickly, there's always a bit of a lag, so in the second-half of the year, we know what we have the fundamentals in place. We know we still have some scaling to do around familiarity of the brand given that Kesimpta is new in market, and we're going to focus, we're going to continue our focus on leading share of voice on the differentiation and really on consistently enabling fast and easy initiation. So, for the full-year, we're comfortable with external expectations. We know what we need to do to double demand in Q2 and really deliver a strong Q4. Medium term, we expect Kesimpta to be a major growth driver for the company.

[Vas Narasimhan:]

Thanks Marie-France and then on NATALEE timing, John?

[John Tsai:]

Yes, thanks for the question, Graham. On NATALEE, which is our adjuvant study for Kisqali, as we disclosed earlier last year, that we've increased the recruitment from 4,000 to 5,000 patients and this includes both the intermediate and high risk patients who have had advanced breast cancer. Our final result that we expect to read out is going to be at the end of next year and that's how it's currently powered. As we said previously, we're not disclosing interims. So we're currently powered for the end of the year next year for our final readout.

[Vas Narasimhan:]

Thanks, John. So, thanks a lot for the questions, Graham. Next question, Operator?

[Operator:]

Thank you. Your next question comes from Jo Walton from Credit Suisse. Please go ahead. Your line is open.

[Jo Walton:]

Thank you. My first question is about marketing spend. So we saw in the second quarter of last year, clearly, very little on the sales side and a dramatic constriction of everybody's marketing spend, and then can you give some idea of how you've opened that up, what sort of level of your marketing capacity you're at now in the second quarter as you enter the third quarter, and how you think marketing spend might be able to be sustained at perhaps a lower level going forward, I don't know more use of digital or whatever. But if we can get a sense of whether you feel or how confident you're in a reduction in your long-term marketing spend, because of all the things that you've learned with COVID and my second question would be to ask for a bit more detail on China. You've talked about drugs, where you've tripled sales, quadrupled sales; can you just give us a little bit of an idea of your level of investment, and your level of ambition in China, please?

[Vas Narasimhan:]

Yes, thanks, Jo. So first on marketing spend trends, I'll hand it to Harry. Harry?

[Harry Kirsch:]

Yes, hi, Joe. So on the marketing spend, it's actually playing out as we guided to earlier in the year, which is as you pointed out, quarter two spend is quite higher than last year quarter two where basically all major markets were locked down, maybe other than China, but also the U.S. So that's why we guided also that in the first-half, we wouldn't see margin improvement. And I think with the sales of 3% and core operating income of 2%, we saw that also playing out. So I would expect continued especially quarter three where also last year spend levels were low that marketing and sales growth is not at a certain healthy level given the investment needs. But of course, within our guidance, be it on our productivity programs on manufacturing and overall the expected sales growth that then in the second-half also, as we had more normal, I would say spend levels in quarter four last year, that displays out laid out that half two will have some very nice margin improvement that leads to the full-year guidance of margin improvement. Now in the mid-term, I do expect that SG&A will be together with manufacturing, productivity on cost of goods be the major driver of our margin increases, especially Innovative Medicines to the highest 30s, and certainly a change in mix somewhat a bit more to work through digital, but still face to face in most markets being important, especially for launch initiation. But I would expect that SG&A is one of the major drivers to continue to improve in the mid-term our margin.

[Vas Narasimhan:]

Thanks, Harry. And on China, Jo, first to take a step back, a few years ago, we began an investment effort in China, really putting in the necessary infrastructure, both in pharma and oncology building out sales forces to really enable us to drive longer term growth. And then second, we adopted a development strategy to bring our full portfolio of medicines to China as well as including China in our Phase 3 programs at the start, so that given the changes in the regulatory framework there that would enable us . So, fast forward today, we're growing in the high teens percentages in China overall from a business we're on track on our stated goal to double the size of our China business from the 2020 baseline. We expect to be if current trends prevail, one of the top three players amongst multinationals, if not more in China by 2024, 2025 that's driven primarily by new medicines. So, overcoming any of the medicines that ultimately get tendered, our newer portfolio driving the growth, we have 50 potential approvals in that timeframe continued strong success on the NRDL as things that you saw with Cosentyx. So we expect China to become the second largest market for Novartis in the world, and we see profitable accretive growth being driven from there, and we'll continue to look to invest prudently in China over the years to come. So, thanks for the questions. Next question, Operator?

[Operator:]

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

[Andrew Baum:]

Thank you. I have a couple of questions, please. First on Kisqali and the NATALEE trial, given the outcome of the PENELOPE-B trial with Ibrance, how comfortable are you that your disease treats bible data that you'll have at the end of next year. How significant has sufficient duration on it to satisfy the FDA without wanting to see further follow-up? And then second question on business development. We've seen a rash of your competitors doing newer develop neurodegenerative fields, we've obviously had the surprising approval of Aducanumab, how is that influencing your interest in the neurodegenerative space? And then, if you could also comment on your Chairman's recent comments of Novartis his interest in mRNA as a platform? Many thanks.

[Vas Narasimhan:]

Yes, thanks, Andrew. On the Kisqali situation, John, you want to take that?

[John Tsai:]

Sure. Thanks for the question, Andrew. And as we've taken a look, as I said earlier, we've increased the number of patients in our NATALEE trial from 4000, 5000, including both intermediate and high-risk patients. As we look at these -- this patient population, there's a couple of things that we focus on. One is we have a longer treatment duration, looking at a duration of three years for the overall treatment. So that should give us confidence in the approach. We've also looked at the adherence of patients, particularly in the first year. As we look at these patients, as you know, in the early treatment of these patients micrometric metastatic disease is important. And what we've seen, at least across both arms is that the patients are at hearing and staying on drug at the 400 milligram dose. So with those two specific components, we feel comfortable with the readout at the end of next year.

[Vas Narasimhan:]

Thanks John. And so on business development, we of course, are watching the changes in the approach to use of the accelerated approval pathway. As we've already noted, in neurodegenerative disease, as we have the ongoing program in Huntington's disease entering Phase 2B, and we'll certainly consider how best to potentially bring that forward, if there's a way to accelerate regulatory submission assuming positive clinical trials. And then also internally, we've had new neurodegeneration efforts within the country for many decades. As you know, and we continue to have programs targeting Alzheimer's disease, Huntington's as well as other neurodegenerative diseases, both using biologics, RNA interference, siRNAs and ASOs as well as gene therapies. So that will continue. No specific comments on ED&L. In the neurodegenerative space, of course, we're looking as always for attractive assets to bring in given our broad based efforts in neuroscience. On mRNA again, not much more to add, I think we've watched as how mRNA continues to have value in the COVID space and are curious to see could mRNA have applicability more broadly within the vaccine space. We have our own ingoing -- ongoing efforts internally, obviously, within Inclisiran in manufacturing for siRNAs with Pelacarsen, with any sense of nucleotides were a substantial manufacturer of those technologies, and also have internal efforts on RNA interference, so that work will continue. And we'll continue to evaluate if there is any sensible approaches in mRNA, more broadly, but nothing imminent, at the moment. So thanks, Andrew, for the questions. Next question, Operator?

[Operator:]

Thank you. Your next question comes from the line of Mario Purcell from Morgan Stanley. Please go ahead. Your line is open.

[Mario Purcell:]

Yes, thank you very much. First of all, Kesimpta I wondered if you give us the NBRx share in the U.S. currently. And then in terms of thinking about those 13 launches anticipated by the end of 2021, how we should think about the advantages and disadvantages of a sub-cut formulation for a B cell therapy in those launch markets outside the U.S. And then secondly on Inclisiran two parts first part. What are your latest thoughts around FDA site inspection? How should we think about the future supply split between yourself and the third-party? And then you sort of mentioned these new initiatives, the initiating the inception, which are kicking off now ahead of outcomes data in 2026. Could you elaborate a little bit more on those initiatives and others, you're looking to increase new evidence base behind Inclisiran before we wait for those outcomes data? Thank you.

[Vas Narasimhan:]

Thanks, Mark. So, first on Kesimpta, subcutaneous outside the U.S., Marie-France?

[Marie-France:]

Yes, so, Kesimpta is an important launch for us outside of the U.S. And if I just -- if I look at Europe alone, we've got 420,000 patients living with MS. And many of these patients are on low efficacy therapies. Actually, many more patients are on low efficacy therapies versus the U.S. So what we also now you're working -- currently working through reimbursement and to accelerate access. But what we also know is that a lot of these patients don't have access to infusion centers. So our research tells us that physicians and patients will appreciate a self-administered high efficacy therapy that can be used in the comfort of a patient's home. So, right now we're working with each country through their own reimbursement system. And we know what we need to do to bring Kesimpta as quickly as possible to patients around the globe. On your NBRx question, currently, our NBRx share in the U.S. is 11%.

[Vas Narasimhan:]

And I would also note on Kesimpta, if you look at one case study in the U.K., our ability to get rapid access there I think demonstrates the value in ex-U.S. markets of a subcutaneous formulation where the overall cost effectiveness of a therapy is high on the system's mind. On Inclisiran, just on the manufacturing side of things, in the U.S. our attention at the moment is to focus production out of our shaft and our Novartis zone shafts are now a facility, we can't predict on whether or not the FDA will inspect. Its notable that this site is regularly inspected has been recently this very line has been recently inspected by FDA using a remote inspection and approved for use in a given indication. And so, we'll have to see what the FDA ultimately determines. But I think it's notable that this is a line that's regularly used and inspected by the FDA. And then in terms of the data initiatives, maybe Marie-France on the efforts to build out data on Inclisiran.

[Marie-France:]

Yes, so I mean, you saw some of that on the slide. And obviously, learning from Entresto, we know that we need to build evidence generation. You know about our efforts on the outcome data Inclisiran for. We're also looking at primary prevention studies. But we're also looking to complement with the V initiate trial, for example, on the different ways of accessing, enclosed around when it comes to acute coronary syndrome, or use or no use of Ezetimibe. So that's the level of evidence and generation that we want to build around the product so that we can ensure fast tech uptake.

[Mario Purcell:]

Thank you.

[Vas Narasimhan:]

Yes, and I just want to add that that, we continue to work with various important parties. So we hope to have updates over the second-half of the year on our partnership with the MHS on Inclisiran and that's something we've highlighted in the past that will be a very important proof point that Inclisiran can be used at a large scale in healthcare systems. We're also partnering with major organizations in the United States, such as the American Heart Association, and we hope to announce others, which I think will also demonstrate that we can generate evidence, but also generate large scale utilization volume demand for medicine. So we'll keep you updated as this happened. Next question, Operator?

[Operator:]

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

[Emmanuel Papadakis:]

Thanks for taking the question. I'm from Deutsche Bank. Maybe a question on Sabatolimab, the MDS-1 effective deferral for PFS readouts, in the original theory, long-term guidance has been for a filing on the CR readout in the second-half of this year. So what can we interpret on efficacy from that data monitoring decision or recommendation to continue until the PFS readout? Unless I'm mistaken that's a couple of years away. So, does that impact your guidance around that being potential blockbuster billion dollar plus indication?

[,:]

[Vas Narasimhan:]

Yes, thanks, Emmanuel. So, first on the Sabatolimab CR readout, John?

[John Tsai:]

Yes, for the Sabatolimab, as you know, this is our TIM-3 compound, our first-in-class IO therapy for myelodysplastic syndrome and AML. As we designed the study, we always had two primary end points, the first primary end point being complete remission and the second end point being progression-free survival. And as we readout the complete remission, we reached the number of endpoints in the earlier part of this year. At that point, the DMC, Data Monitoring Committee, came back and told us to continue the study as originally planned. So you've seen the slide that was shared earlier by Vas in terms of the number of readouts. As you've seen, we actually look at not only MDS, but also AML. So as we look at this, we do think that this is a differentiated asset for not only for us to think about high risk MDS, but also AML based on the fact that it has a good safety profile and potentially pending results, the efficacy, in terms of durability of response. So we await the results in 2022 and 2023.

[Vas Narasimhan:]

And I think Emmanuel, as we highlighted there's multiple different filing options depending on how the other results play out. It doesn't change our beliefs that the medicine given it's the first-in-class asset that has a different mechanism than any existing therapy or late-stage therapy that can be a significant billion dollar-plus medicine. On Zolgensma, on the incremental NBS and how we're doing with newborn screening, Marie-France, do you want to say a word about that?

[Marie-France:]

Yes, I would just say that, so that in the U.S. the newborn screening is high, outside the U.S., I mean, it really is a market by market, so it's gradual. I mean, I can give you some information. Germany will be implemented by -- from October, we'll see parts of Belgium screening. From the beginning of this year, we know that Poland is implementing gradually. We've got other countries across Europe that are doing this. So, it's a mixed picture. We're very committed to it. We know that it's really important to start Zolgensma early. We saw that from the SPR1NT data and how amazing the results are when babies are treated early. So it is a priority for us. And then, of course, medium-term, our goal is to bring Zolgensma to older children once we get the IT formulation.

[Vas Narasimhan:]

Yes. And just another word on that, thanks Marie-France, on the there is no updates, Emmanuel. We continue to work through resolving the FDA's concerns, but we do have the protocol finalized agreement with the FDA on the Phase 3 design or preparing operationally for the studies execution with a belief that indication can continue to be a multi-billion dollar indication for the company. And as soon as we have any updates on the preclinical topic and resolution with the FDA, we will, of course, provide it. Thank you. Next question, Operator?

[Operator:]

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

[Richard Parkes:]

Hi, thanks very much for taking my questions, just two questions. Firstly, on sales and margins both beat your expectations for 2Q that you set out with the 1Q results. I am just wondered if you could discuss what surprised you positively and confidence that those trends will continue given that you haven't updated guidance. And just wondered if you could add your thoughts on impact of the delta variance and maybe what you've adjusted your planning and solutions for healthcare systems opening up on the basis of that. And then, secondly, just a question on some of your legacy oncology assets in the U.S. specifically Promacta, Zolgensma and Tafinlar, if I look at sales per scrip over the last few quarters, at least in the first-half, it looks like sales per scrip has been growing in double digits, which seems to imply quite significant price increases. I just wondered whether you could discuss that trend and whether there are any other factors such as channel mix that might be impacting that. Thank you.

[Vas Narasimhan:]

Thanks, Richard. First on sales and margins outlook, Harry?

[Harry Kirsch:]

Yes, the line was a bit hard to understand, Richard, could you briefly repeat.

[Vas Narasimhan:]

Yes, Harry, I think the question was, were there any things that surprised us versus the Q2 guidance we gave after Q1, on how Q2 would play out and how do we potentially see if the Delta variant impacting our guidance for the rest of the year?

[Harry Kirsch:]

Yes, okay, thank you. So, Richard, obviously, we delivered a bit more than what we thought, right. So we saw in U.S. a bit faster reopening, I would say, most of our brands. Sandoz is pretty much in line with expectation, but innovative medicines, some better, some better momentum overall. And then also very good work from our manufacturing colleagues on productivity in addition to always perfect supply levels. But overall I would say slightly ahead of our internal expectations in quarter two.

[Vas Narasimhan:]

Yes, thanks. Richard, I think on the delta variant, we continue to monitor the situation. What we are expecting is that given that healthcare systems have seen the impact of when they -- how they shutdown to patients with non-communicable diseases and the substantial impact that has. We remain optimistic that healthcare systems will ensure that patients get the care they need while dealing with any surges that may or may not happen with respect to COVID-19. Now on Promacta, Taf/Mek, U.S. performance, Susanne.

[Susanne Schaffert:]

Yes, thanks a lot. And Richard, on Promacta actually we are very, very pleased with the performance as you rightly note, 18% growth, and it's really across all geographies and it is volume driven. And it's really still our main indications, ITP and SAA. To give you a little bit more granularity on the U.S., we had 11% growth, and maybe just remind you there was a label update earlier this year that makes Promacta even more competitive. We are seeing share gains increasing NBRx. And of course it is the efficacy driving that it's also the oral convenience and it's the non-immunosuppressive benefit over competitors and therefore very strong performance. Ex-U.S., we saw 26% growth rose previous year. It's very strong underlying performance in major markets like the EU. And also just to mention very strong performance in China, where we got NDRL listing end of last, so very pleased with Promacta. Similar on Tabrecta, we could -- sorry on Mekinist + Tafinlar, we could really stabilize market share and are very competitive versus new entries, very pleased with the growth also across geographies. And also to mention for China, we are very pleased. We got a tough Mek included into the NRDL list, so really strong growth on volume base across geographies.

[Vas Narasimhan:]

Thanks. Thanks, Susanne. Thanks, Richard. Next question, Operator?

[Operator:]

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

[Seamus Fernandez:]

Great. Thanks for the question. So just a two quick ones, as we think about the opportunity in MDS and for the TIM-3 assets, I was just hoping you could give us a little bit more color on the evolution. I just wanted to follow up on the previous question. And specifically as it relates to the CR response there is that -- your conclusion there that the proceeding to the PFS benefit is a clear positive moving into the subsequent events or is this just a continuation of the trial, which could be viewed as somewhat disappointing on that side of it for the high risk MDS patient population? The second question obviously you guys are talking quite strongly about the opportunity for Asciminib just in the third-line setting blockbuster potential. Can you just talk about that relative? Is that predominantly relative to Bosutinib as sort of the primary opportunity and kind of replacing that asset, you're replacing that product sales? Or is it really speaking to a broader opportunity in the third line setting because of potential for duration of use expanding upon how that products used so far? Thanks.

[Vas Narasimhan:]

Yes, Seamus. Just in the interest of time on the MDS, I think with the CRV -- I would say, neutrals to positive, I mean, neutral is saying, because we're blinded, so we don't know what the DMC saw, but I think the fact that the study will continue now to the next endpoints and the positive mechanisms that we see in the previous data that we've seen on the product. We remain optimistic that both in MDS and AML we can get some positive results and bring meaningful innovation to patients. As John noted, the studies have a range of different designs including a third study that also takes into account Venetoclax, so a doublet and a triplet design. So I think we have the bases covered, and we look forward to getting the additional readouts over the coming year-and-a-half. On the sale potential of a summative, Susanne, do you want to say a word about this?

[Susanne Schaffert:]

Yes, I'm happy to take that. Vas, and maybe just on the opportunity on Sabatolimab just why we are very excited is, because it's a completely novel mechanism. It's a TIM-3 so. It has the potential to be the first immune-oncology therapy in hematology, in MDS and AML. And why we believe that is important is because obviously, there is now has been made progress on having more efficacious treatments, but what we all know durability and also safety profile is still remaining challenging. And therefore, we are very excited that Sabatolimab would have this attribute to add really huge value to this medical need. And on Asciminib to maybe lead you a little bit through just to remind you a little bit on the dynamics in CML. So there is still 10% to 15% of patients that progress to third line. But what you also have to know there is a significant number of patients that remain in second line, just because of lack of options for these patients.

[,:]

[Vas Narasimhan:]

Great, thanks, Susanne. Thanks. Next question, Operator?

[Operator:]

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

[Kerry Holford:]

Thank you. Yes. Come on for me, please. Just on the second-half outlook, obviously raised pro forma operating profit growth in the slide today, but you're not updated the growth drivers in the root, and although you're not changed the outlook of Sandoz in the second-half. What is it within this division that continued caution? That second-half outlook just by those improvements you've seen in Q2. And then only cleared through around and just I think a question was asked earlier, but just to clarify, what are your plans for the manufacturing of that drug in the future? Can you remind us where the XUS suppliers manufactured? Should we understand that the global manufacturing site is now the Austrian site or should we anticipate further significant investment at some point perhaps in the U.S.? Thank you.

[Vas Narasimhan:]

Yes. Thanks, Kerry. So first on the Sandoz outlook on the second-half, Harry.

[Harry Kirsch:]

Yes, thank you, Kerry. So we have to remember how quarter one and quarter two have developed here. So clearly, you saw a very steep decline of quarter one, and then you saw that 5% growth of Sandoz in the second quarter. But underlying if you take the prior year this talking out minus one, so we saw as expected stabilization, but we have a first-half with a 5% decline. So in order to be at the lower to mid-single digit decline the full-year, we continue to expect stabilization around broadly in line for the second-half for Sandoz and I think that at this moment a very reasonable assumption. Of course, we can all make scenarios around cuff and colds and flu season in quarter four and the market dynamics for that. We have taken the midpoint scenario on this. So overall, I would say of course volatility given the COVID situation and how to cuff and cold season would be. But overall, I would say our guidance is quite starting from the minus 5% decline half one quite reasonable that Sandoz would stabilize; they have a few for us to find launches in the second-half. So that helps the FTC also the pricing and the U.S. continues to develop. So I would say not all overly cautious, but realistic.

[Vas Narasimhan:]

Thanks, Harry. And then Kerry on manufacturing it's important to note when you take a step back, our overall goal is to have Novartis be the primary manufacturing of both the upstream and downstream parts of this siRNA for Inclisiran. And we've made the necessary investments to do that we have substantial manufacturing capacity to synthesize the siRNA. And then as we've noted, in the U.S. will move to using our shaft and our facility. And over time globally, the primary manufacturing will be done out of Novartis facilities being supplemented by CMOS as needed. The primary reason to do this is one we believe that medicine will be as we've noted one of our most significant medicines. And then second, from a cost standpoint, our goal is to drive significantly down the cost of goods to enable large scale use of the medicine in the secondary prevention study, and eventually, perhaps in the primary prevention study. Right now, ex-U.S., we do use third parties for both the primary and the secondary. But again, over time, the evolution will be the Novartis owned facilities, and those investments have already been either started or completed. Thanks, Kerry. Next question, Operator?

[Operator:]

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

[Peter Welford:]

Hi, thanks for taking my questions. Just two please. Firstly, on oncology, just looking at some of the hospital administer drugs in particular, those are some of those that require either biomarker diagnostics companion diagnostics to use that he looks as though the second quarter for some of those drugs was sort of relatively weak compared to the first quarter and certainly wasn't sort of an uptick. I'm thinking the likes of Kymriah and Lutathera, for instance, also as well I think things even to break through other drugs. I wanted you to just comment on what's what you're seeing there with regards to why I guess we're not seeing Q-on-Q improvements in oncology, and how we should think about that perhaps in the second-half of the year in the gating factors. And then, second is wondering about the Harry's comments that we could reach the higher end of the output ranges, that COVID situation remains fluid. Should we take that to mean that if COVID situation pans out, as we currently see the higher end of the ranges is where we should be thinking or should we take that as thinking that you just don't know and you still see your uncertainty? I guess curious is sort of where you're thinking with regards to the current COVID situation, and whether the situation has to deteriorate significantly, so that's been not valid? Thank you.

[Vas Narasimhan:]

Thanks, Peter. So just briefly, Susanne, on the hospital administered oncology?

[Susanne Schaffert:]

Yes. Thank you, Vas, and thank you Peter for the question. So, as I mentioned in my presentation, these areas that you mentioned hospital initiated areas, but also of course, where you have new launches, this is still impacted by COVID, especially when you look at the U.S. that only 75% of patients are back versus pre-COVID levels. So, we still like a force of or a quarter of patient's volume that we usually saw. And that is impacting, for example, diagnostics. It's impacting screening, and that's of course subtractor would be such a brand where you see lower biopsies, you see lower testing with all rates overall, as to say when you look this in the ones that are tested data at ERA-EDTA and testing for CMED is increasing, but it's just suppressed patient volumes and this is same what we see for hospital initiated product. Just to give you some figures on Kymriah, as I said 19% versus previous year. But we saw that especially in the U.S., the whole class saw a reduced demand, and while we stay very competitive as Kymriah, and that is really linked to recent also manufacturing success rate that the customers are very pleased about. It's really the demand that we saw in the whole class going down. And on Lutathera, there is some early positive signs in the U.S. We have seen growth versus previous year, as some now referrals are started, but it's still very, very suppressed. And we remain confident that with now the market opening up centers, taking more patients and this should improve and accelerate.

[Vas Narasimhan:]

Yes, thanks Susanne. And then Peter on the outlook, you know what as Harry noted, its multiple dynamics. Of course, we're monitoring, but if the business dynamics continue, as we currently see them if oncology can continue its recovery. If Sandoz remains in the stable situation, given the strong growth we're seeing in our growth drivers, there's certainly the potential for us to be at the higher end of the guidance and will of course keep you updated in quarter three. Next question, Operator?

[Operator:]

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

[Laura Sutcliffe:]

Hello, thanks. First question is on Leqvio, please. Have you faced any patients in the U.K. under your program there yet? I think you said the program was starting this quarter. And what setting will lose early doses be given in these patients being seen in the hospital? Or have you managed to get it into primary care from the word go? And then second question is just on Entresto. Could you maybe talk a little bit about the uptake in the past population? Thanks.

[Vas Narasimhan:]

Yes, thanks Laura. So first on Leqvio the agreement, we're still working through the final stages with the NHS and we have not hit those patients in the U.K. The agreement, though, has the aspiration that this would be rolled out in primary care from day one at scale, trying to address the ASCVD population and get the U.K. towards its long-term goal in cardiovascular health. So, we hopefully will have updates in the coming months on that pioneering initiative, which we hope will catalyze the U.S. global impact over the coming years. In Entresto HFpEF, and I'll just start taking the questions given the time and Entresto HFpEF. We do see I think the uptake already and you can see that in the NBRx, but it's still early days. And I think as we continue the rollout in the education as well as the awareness on the guidelines, we would expect to see continued growth for in Entresto. We see a strong outlook for the brand. We're confident will be in that 4 billion to 5 billion range. And as we continue to see the trajectory, we'll provide further updates on the long-term outlook for Entresto in the coming months. Thanks, Laura. Next question, Operator?

[Operator:]

Thank you. Your next question comes from Tim Anderson from Wolfe Research. Please go ahead. Your line is open.

[Tim Anderson:]

Thank you. On Cosentyx thinking about Omalizumab, they've got some good exposure recently with publication of their data in the New England Journal beats your product on efficacy has a one side effect of oral candidiasis. How much do you think this product will impact Cosentyx? And do you think that one side effect is a material impairment to their product and your view? And then on Tislelizumab you're partnered PD-1, how realistic we believe compete in a setting like long in western markets. Can you and your partner assure as you won't be disruptive on price. I asked because you ask Merck guys for price erosion over time in the category. I'm wondering who's going to be driving them?

[Vas Narasimhan:]

[,:]

On Tislelizumab, you've seen the esophageal cancer filing, we're moving towards first and second line non-small cell lung cancer, we do believe that the -- we'll be able to market this medicine from a competitive standpoint given our long presence, particularly outside the U.S., but also in the U.S., we'll be prudent in how we think about the pricing. But we do think we can make a compelling value proposition. Longer term, the real opportunity for us is in combination will be taking forward Tislelizumab in combination with our SHP2 inhibitor in combination with some of our RLT agents amongst other opportunities. And so we're going to work to both maximize on the combination side as well as take as much as we can have of a very large PD-1 market given the broad range of indications we expect the agent to have. Thanks. Next question, Operator?

[Operator:]

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

[Simon Baker:]

Thanks for taking my questions. Two please, if I may. Just going back to Leqvio, I wonder if you could give us some idea of the ramp to 300,000 patients given the unusual situation, having not only agreed reimbursement but also utilization. And then secondly, moving on to Sandoz, Harry you gave the principal drivers for expansion of the IM margin over time. I wonder if you could do the same for the Sandoz margin. Thanks so much.

[Harry Kirsch:]

Yes, thanks Simon. So for Leqvio in the U.K. is going to be driven by our ability to work with the U.K. to get primary care physicians to diagnose these patients out of the NHS data systems and then rapidly get them on to Leqvio, I think it'll be a slow initial ramp and then we hope to see a rapid ramp-up. In the U.S., we've done a very good job of targeting the relevant integrated health systems to hopefully be prepared to have a reasonable uptake initially, but again, it will take time to get those centers on board. In parallel, we'll also have a traditional launch with our traditional sales and marketing approach leveraging the interests of field force and reach. So, on approval in the U.S., we'll go very obviously out very strongly. It will take time to get the brand up but then once we think we get momentum, we expect the brand as we've guided to be a very significant multibillion dollar medicine for the company. Mid-term Sandoz margins will be driven by a portfolio shift and with the biosimilar portfolio, a large number of biosimilars in the mid-20s, we expect to get forward, I get into the market and some of them first-in-class first hopefully to market such as Natalizumab amongst others. And then on top of that, the ability to launch additional injectables and oral solids while continuing to drive down cost of goods, so you'll have a mix shift to higher margin products as well as the continued efficiency gains and cost of goods. And then lastly, Richard and team are working hard to optimize the manufacturing and sales set of leveraging digital technologies. And I think that will be the other element that will help us get to those mid to high 20s margins in Sandoz. Thanks, Simon. Next question, Operator?

[Operator:]

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

[Steve Scala:]

Thank you. I have two questions. First on AVXS-101, can any findings from the preclinical intrathecal safety studies be shared with us today, so that's the first question? And then on the second question relates to the Kisqali adjuvant interim look in NATALEE, I'm curious if this look has already occurred if it has, then it would seem to be a material update and you would have announced it. So I assume that it has not yet occurred but please confirm? Thank you.

[Vas Narasimhan:]

Yes, thanks Steve. On AVXS-101, I see the preclinical data we've seen today do not indicate any concerns. However, we need to complete the relevant assessments and of course, ultimately agree with FDA and the listing of clinical hold. And so we'll keep you updated as that progresses and NATALEE interim has not occurred. But as we've guided to we're not no longer guiding to interim analysis timings and focusing on the final outcomes. John, as you mentioned earlier in the call, we expect that to be in the back half of next year. And of course as we learn more in that study we'll keep you updated. Thanks, Steve. Next question, Operator?

[Operator:]

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

[Naresh Chouhan:]

Hi there, thanks for taking my questions. Two please, in the U.K. we recently seen decrease in hospitals, partly due to COVID and partly because obviously, trying to work through. We've seen electives and oncology appointments been delayed as a result. Are you seeing any signs of anything similar in the U.S. as go to a few states where hospitalization are right there pretty quickly, I was wondering whether or not that's early signs of that in the U.S. And secondly on similar, do you expect interactions to be flat on label pivotal in the earlier studies and expect that to impact especially with generic spots of in the market. Thank you.

[Vas Narasimhan:]

Yes, thanks, Naresh. On the U.S., we currently don't see any shifts in utilization better notable, other than what we've already seen in the call oncology is below pre-COVID levels. Cardiovascular is also below pre-COVID levels, so Entresto continuous to have very strong performance and patients with heart failure seem to be getting the medicine as expected. So, nothing that we can flag at this point, and also no clinical trials are enrolling on time. So we have learned a lot about managing, I think the healthcare systems have learned a lot about managing COVID, we've learned a lot about managing our trials and the up tick of our medicines during COVID. So hopefully, we can navigate this next period successfully. But certainly something we're watching very, very closely. I think it's too soon to comment on specifics on Asciminib's label. I would know that the safety profile was remarkably clean when you look at the, it was a head to head study versus Bosutinib across all relevant safety markers. It was a very clean profile patient stayed on drugs. So we're optimistic that overall the Asciminib profile will be attractive, which is a part of the reason as well, as Susanne mentioned, we're quite confident that if it ultimately proves superior can be a very effective first line therapy. Next question, Operator? Thanks, Naresh.

[Operator:]

Thank you. Your next question comes from Marshall . Please go ahead. Your line is open.

[Unidentified Analyst:]

Good afternoon. Thank you for taking my question. I would like to come back on the Sandoz business and thank you for your previous answer on the H2. We understand the next step with the top line improvement driven by the pipeline with biosimilars and the function of decision of generics, but could you share with us your vision on the improvement of the portability mid-term. Do you see any concrete operation or leverage on the cost or due to the improvement of the top line expected and the affiliated cost plus the price erosion, should we consider stabilization of this activity for the next year, if you could give us more color maybe to help us to manage core EBIT margin in the next quarter, and thank you very much.

[Vas Narasimhan:]

Yes, Marshall, I don't think I fully picked up the question but I'll give my best answer. So when you look at Sandoz evolution over time from a margin standpoint, first right now our goal is to invest and create a very strong pipeline performance in this period of time both biosimilars and oral solids. So in the coming years, you're not going to see big shifts in the margin or the operating leverage, but our belief is given, Richard is driving very strong efficiency gains across all the relevant P&L items and we continue to expect important pipeline delivery in biosimilars in respiratory and oral solid. When that pipeline delivery happens, then we expect the margin in the mid-term to be accretive and move up into that mid to high 20s. So the shape is going to be stable for the period next few years and then we expect that acceleration and margin improvement for Sandoz as that portfolio ultimately comes through. So I think that's the best way to think about it. And I think that we have one more question, operator, could we go to the last question. Thank you.

[Operator:]

Thank you. Your last question today comes from Keyur Parekh from Goldman Sachs. Please go ahead. Your line is open.

[Keyur Parekh:]

Thank you. And thank you for taking my questions. Vas, if I may, your introductory comments on Sandoz talking about the strategic vision in the long-term seemed almost like setting the narrative for a 2022 decision on the longer term outlook for Sandoz. Am I over interpreting your comments or is that the timeframe in which we should expect a broad decision on whether Sandoz is a part of Novartis or not longer term? That's question number one. And then question number two, we're getting very close to on an annualized basis kind of the peak sales numbers you provided for Cosentyx and kind of Entresto. So I'm wondering kind of why we haven't seen updated kind of peak sales estimates for those two products. Is that anything from a competitive or a market perspective that worries you or was this just not the right opportunity for you to address the longer-term peak opportunity for those products? Thank you.

[Vas Narasimhan:]

Thanks, Keyur and good to hear from you. On Sandoz, there's no updates or changes and our goal right now is to put Sandoz in a strong position, invest in the business so that it can be on a track to be the leading generics company in the world, which we think it can be from a financial as well as impact standpoint if and when we take any decisions or and start a process will of course, let you know. But right now, our focus is on the operational performance of Sandoz and supporting Richard and his team to driving that mid-single digit growth and margin expansion that that we've outlined. I think on your second question, I think we're very pleased with the trajectory of Entresto and Cosentyx, you're correct if you're approaching the sales outlook of $4 billion to $5 billion, we got into Entresto and $5 billion plus in Cosentyx. Our current plan is that meet the management will provide an updated outlook on both of those brands, especially as we understand better the dynamics but certainly would want to highlight we're confident in both of those brands to be very strong pillars of Novartis in the years to come. So, thanks everyone for joining today's conference call. Apologies, we ran a bit over. We'll keep you updated. Thank you for the interest in the company and please stay safe and healthy and we'll look forward to speaking soon. Thank you.

[Operator:]

Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.