Novartis AG ($NOVN)

Good morning and good afternoon, and welcome to the Novartis Q1 2026 Results Release Conference Call and Live Webcast. [Operator Instructions] The conference is being recorded. [Operator Instructions] A recording of the conference call, including the Q&A session, will be available on our website shortly after the call ends. With that, I would like to hand over to Ms. Sloan Simpson, Head of Investor Relations. Please go ahead, madam.

Thank you, Sharon. Good morning and good afternoon, and welcome to everyone to our Q1 2026 conference call. The information presented today contains forward-looking statements that involve known and unknown risks, uncertainties and other factors. These may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. 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. [Operator Instructions] And with that, I will hand across to Vas.

Thank you, Sloan, and thanks, everyone, for joining today's call. So if we go to Slide 4. As you saw this morning, we delivered a strong start to the year across our priority brands and launches, which is really where our focus is at the moment. These brands and launches are what's going to drive our mid- to long-term growth and where we believe now we have demonstrated that there's strong momentum behind these medicines. sales for the quarter, you saw that those growth drivers were up 34% in constant currency. Our base business was largely stable, but we did see significant GX erosions as we've guided to, and Mukul will go through some of the dynamics for that over the course of the rest of the year. On core op inc, we were down 14%, driven by the sales decline as well as the increased investments in R&D, which we also guided to. When you look at some of the pipeline highlights a number of important highlights, including the continued progress for Rhapsido across a number of indications. Ianalumab received a breakthrough therapy designation and priority review in Sjogren's disease as well as a few other important milestones, which we'll go over the course of the call. Importantly, we're maintaining our full year sales and core operating guidance for the year. Now moving to the next slide. When you look at those growth drivers in a little bit more detail, that 34% was driven, in particular, by very strong performance we saw in Kisqali, Pluvicto, Kesimpta, Leqvio driven by our strong launch overseas, particularly in China and the continued performance of Scemblix. So I'll look forward to going through now some of the dynamics for each of our key brands over the course of the remaining slides. Now moving to Slide 6. In quarter 1, Kisqali grew 55%. And as you know, Kisqali now is -- has a lot of momentum, both in early breast cancer and metastatic breast cancer and given our global launches, we're starting to see a pickup of the ex U.S. markets. So focusing in on the U.S., you can see our NBRx share now in the early breast cancer setting is very strong, 65% plus 2% now versus prior quarter. In addition, in metastatic breast cancer, we have 47% NBRx and 41% TRx. So taken together, we're in a very strong position in metastatic and early breast cancer. And when we look at that data in more detail, we see that Kisqali has a strong position, not only in the overlapping segment with our competitor in early breast cancer, but also in our unique segment, particularly the Node 1 high risk and the Node 0 high-risk patients. And going forward, our focus will be very much continuing to expand Kisqali's utilization in those early breast cancer populations. Now turning to the ex U.S. I think one of the markets that we're keenly focused on is our performance in Germany, where we saw outstanding performance in quarter 1. You can see in early breast cancer, our shares are approaching 80% now in Germany. Overall, we were growing 50% in constant currencies in the first quarter. We have continued metastatic breast cancer leadership across our key markets with 50% NBRx share. And we also see growth accelerating now as we have more EBC launches across a range of markets, 69 countries and we reimbursed now in 40 of those markets. Some of the other markets, we're paying close attention to in the U.K. We have 78% early breast cancer. And we have a strong early start in China where we do have now NRDL listing. So looking ahead, Kisqali is a brand we expect to have continued strong momentum over the course of this year. So turning to Slide 7. Kesimpta had also a solid quarter, 26% growth ahead of both the MS and B-cell markets. In the U.S., we saw a 21% TRx growth versus prior year. That was 2 points ahead of the market and 1.5 points B-cell class share increase versus prior year. Importantly, when we look at our NBRx market share, both in the overall market, we reached 17% and the B-cell class we reached 28%. So we're gaining share [indiscernible] B-cell class competitors as well as the older drugs that still -- nearly the majority of patients are taking in the U.S. Overall, we continue to see a significant runway for Kesimpta. I think a lot of that performance in the U.S. is down to strong operational execution. We've gotten much better, I think, at targeting the right patient groups -- the right physician groups as well as owning our messaging around the unique benefits of Kesimpta as a self-administered monthly therapy. So excited about that. We also continue to progress now or every 2-month dose Kesimpta, which we're looking forward to reading out next year. Now in the ex U.S. setting, 31% constant currency growth, strong growth in Europe. We estimate 1 in 6 MS patients now are in Kesimpta. We see 79% of patients that are coming on to Kesimpta either as naive or first switch in the EU5. We also have continued NBRx leadership at 9 out of 10 major markets. We do find, in general, outside of the U.S., a strong interest in self-administered medicines that can get patients out of the hospital or out of needing ongoing visits for infusion. So very amenable to the Kesimpta's profile. And we see an opportunity for continued expansion with 2/3 of BMT treated patients continuing to not be on a B-cell therapy in our key markets. Now moving to Slide 8. Pluvicto continued its strong rollout, particularly driven by the pretax MCRPC setting. We saw strong demand. And we also saw good progress on our U.S. rollout. Starting with the U.S., we saw the U.S. sales grew 76% in the quarter with 70 -- over 70% of that business now coming from the pre-taxane setting, and that's coming from a mix of urologists and community oncologists. Right now, we estimate about over 60% of our NBRxs are coming from the community. And I think that demonstrates we've not successfully made RLT, a medicine that can be prescribed in the community setting for patients who prefer to access care in the community. Outside of the U.S., we saw 48% growth with NBRx is up 92%. This was driven by strong EU uptake, but also, I think, a notable solid start in Japan where we're seeing very strong interest in Pluvicto, so we're excited about that. And the initial stages of a launch as well in China. As a reminder, we have manufacturing sites that are being build and getting up to speed now in Japan and China, which will allow us to serve the Asian market. So diving a little bit deeper to think about some of those growth drivers. A key element of our story is driving depth in the existing sites and expansion into urology that continues, and I think we're making good progress on that front. And then we also expect the hormone-sensitive approvals in the second half. There, we expect the hormone-sensitive indication to increase the total patient pool available to Pluvicto by 75%, so a substantial expansion and one that I think will enable us to get the next inflection of growth for Pluvicto. You can see here at the bottom of the slide, some of the data on the number of sites, so over 830 sites now prescribing in the U.S., 580 in the ex U.S. I think that all just gives us confidence that we've been able to make RLT standard that's available now broadly in the communities that we serve and also sets us up well for the future radioligand therapy portfolio over the coming years. Now moving to Slide 9. Leqvio had a really strong quarter, and that was driven primarily by our performance outside of the U.S. with strong growth in China as well as in Europe and Japan. Now first, let's start with the U.S., where we saw 31% growth in the quarter. We continue to outpace the advanced lipid-lowering market, but I think in the U.S., the next inflection point we would expect is when we get the outcomes data in the first part of next year with -- in the secondary prevention setting, and that will be an important milestone for us. Now when you think about some of the other data, the highlights we're seeing, we're seeing that we are expanding in the Medicare Part B population, up 11 points versus prior year. That's about 2/3 of our current business. And we also see that our TRxs are consistently up 41% versus prior year. So I think all heading in the right direction, consistent, steady growth across the U.S. in the buy and bill segment. Outside of the U.S., 106% constant currency growth, that was led by China, the NRDL listing unlock significant demand. It is early days. So I think we'll have to see how the coming quarters evolve in China to really understand how much of this was a bolus versus a steady demand. But I think the early benchmarks that we're looking at suggests very strong demand in China and something that we're excited about for our future siRNA portfolio. Now lastly, in terms of evidence base for Leqvio, I mentioned the importance of the outcomes trials. So we also are advancing -- we received an FDA approval for adolescents in 2 specific rare disease indications, and that will be important as well from a long-term pediatric exclusivity standpoint. Leqvio is included in the ACC and AHA guidelines. And I think many of you likely saw that the guidelines highlight aggressive lipid management now even at younger ages for patients. So I think that really points to not just statin use, but adding statin and PCSK9 use wherever possible. So I think that all points to a positive outlook for the medicine. Now moving to the next slide. Scemblix was up 79%, I think, really outstanding performance for this brand, both in the U.S. and ex U.S. We see in the U.S., very strong performance in the frontline setting and outside the U.S., both second, third line and frontline now starting to pick up. Let's take each of those in sequence. So first in the U.S. now we've reached 31% first-line NBRx share. You can see the steady climb upwards in the graph. So very excited about that. And then hopefully, soon, we'll be consistently the leader in NBRx brand scripts in the United States. When you look at the -- we're also a leader across all lines now with 42% share. So I think that also demonstrates the breadth of interest in Scemblix. Outside of the U.S., we grew 68%. That's driven primarily by our third line leadership, 73% share across our key markets. But we are seeing early line indications now starting -- the indications are a new advanced. We're approved in 63 countries. You can see in the chart here that the NBRx share in the first line in Japan, we've already reached 50%. In Germany, we're seeing early traction as well with 11% NBRx in the front line. And of course, for the long-term outlook for the brand, our goal is to make this the standard of care in the frontline setting across all major geographies. And as you can see in the data, we're well on our way to deliver that goal. Now moving to Slide 11. Now Cosentyx had a broadly stable quarter, and we were impacted by some of the onetime effects that we had in the prior quarter in 2025. So when you net out those effects, we would estimate that our global sales growth was about 2%. In the U.S., we were roughly flat to 1% growth. So I think that indicates that we're stable and I think set up well now as a new indication come online for Cosentyx. And that's going to be very, very important to ultimately achieve our peak sales goal. So when you look at some of the data, when you look at the hidradenitis suppurativa/NBRX naive share, you can see here pretty consistently around 50%. We did see a slight dip in January because of the degree verification and the availability of biosimilars, but we see that now climbing back up. So we expect to be stable in that 50% range. Importantly as well, for IV patient share, we see steady growth up to now 14%. And so both of these will continue to be important. We are hoping that the HHS market continues to develop not just for Cosentyx, but as we'll address later remibrutinib now will also have a readout later this year in HS. So we want to see this market expand for the patients who need better therapies are getting them. Outside of the U.S., we were up 3%, that's primarily driven by growth in Europe and emerging markets. We continue to see competitive pressures in China with multiple local NRDL entrants. And so there's a long list of competitors that we have, and we've had very strong share performance in China now over many years, but our goal will be to maintain now share and hopefully can stabilize this well performance in China over the coming quarters. We continue to advance the new indications. Importantly, the PMR submission happened across geographies, and we expect the FDA approval in the second half. And we also received FDA approval for the pediatric HS indication. We completed EMA submission as well. So all on track on that front. Now moving to Slide 12. I wanted to just say a few words on our renal portfolio by talking about each of the key brands. So first, let's talk about Fabhalta. Sales were up 103% in quarter 1 with NBRx leadership now, both in PNH and C3G. In PNH at the moment, we're seeing 50% NBRx share as well as important and significant contributions from some of our key ex U.S. markets. In C3G, 56% NBRx share that were now approved in 46 countries. So both of those indications really having solid and consistent performance. Now importantly, in IgAN, I think we believe our uptake in U.S. patients will continue to build in patients with persistent proteinuria and glomeruli inflammation. So here, we're a later line therapy. But I think very important was the 2-year Phase III APPLAUSE IgAN data, which was published in the New England Journal. It showed an impressive slowing and kidney function decline of 49% versus placebo and a reduction in progression to kidney failure by 43%. The FDA has granted us priority review for the traditional approval. So I think that just indicates the strength of the Fabhalta data in IgAN. For Vanrafia, we see steady U.S. uptake in a very competitive field, I think, as all of you know. That launch is ongoing. We have about 11% NBRx share. We see a significant market expansion opportunity with most patients still on supportive care as that market grows, we hope that Vanrafia will ultimately benefit as a really effective and safe vascular agent endothelin agent. And we do expect traditional FDA approval to drive future growth. You saw in the quarter, we top lined the ALIGN data, and we do expect to submit that data to FDA and EMA in the first half. We will present that data in full and while we didn't reach statistical significance, we feel confident that the data is compelling, will allow that full approval to ultimately happen. Now moving to Slide 13. Now Rhapsido CSU launch off to a strong start in the U.S., and we have the early steps now to begin the rollout as well outside of the U.S. And I think when you look at the profile we're building, pipeline and a bill potential, significant medicine here that could address a range of different dermatology and immunology indications. So starting with the CSU launch, the U.S. uptake, we see 3,000 prescribers to date, across allergists and dermatologists now prescribing the medicine, 6,000 patient starts and we're seeing very positive feedback on the speed of the onset of action. And we estimate an NBRx share now of 24%, which I think is very good in these early phases of launch. We are having early access wins, but I would say that access will build over the course of the year. So it will take us the full year to get to where we want to ultimately get to from an access standpoint. And that will be important as well because that's what allows us to bridge from 3 drugs to ultimately paid scripts. So that will be a steady uptake over the course of year, not a fast inflection. And then outside of the U.S., the China commercial launch and the European EC approval that we've received will enable us to hopefully have a solid launch to Rapid in the second half of the year. We did also have the positive CIndU readout, primary endpoint in chronic-conducible urticaria. We saw significantly higher rates of complete responses versus placebo across all 3 CIndU types. First time a medicine has delivered that. Well tolerated with a favorable safety profile. We're on track now for the FDA approval in the first subtype of CIndU and FDA submission of the other 2 types in the second half. Now building on the overall profile for Rhapsido, when you look at the next slide, Slide 14. We did release as well the Phase II results for remibrutinib in food allergy to support a fast-acting oral option for these patients. We also have -- are on track now to initiate the Phase III study. You can see here on the left the data that we read out. The 100-milligram dose provided 86.7% of responders, which I think a very impressive result. Our modeling indicates that the 75-milligram BID would be the appropriate dose for the patients moving forward. So that's the dose we've taken forward into the Phase III study. Our focus will be a multi-allergen prevention study. So I think that's really exciting across a broad range of age 12 years all the way up to 65 years. And as I mentioned, anticipate initiation in the second half. This has the potential to address a significant unmet need, 3.5 million high-risk eligible patients across major markets. So very excited to add this to the indication less, hopefully, for Rhapsido. Then moving to Slide 15. Also in the quarter, we completed the acquisition of Avidity, adding 3 late-stage medicines for neuromuscular disease. And I just wanted to highlight 2 data points from the quarter. We did release the 1-year results for DMD exon 44 skipping medicine, which was presented at the Muscular Dystrophy Association to a standing ovation, which I think shows the impact that this medicine could have for these patients. You can see here the creatine kinase declines, which are remarkable. And you can, I think, really -- experts have opined that is really a revolution with this medicine. We're excited to also build after this a range of additional exon skipping medicines for DMD. We are expecting the submission now in the first half as we work through some of the additional CMC topics to make sure that the file is fully submission-ready. And then with Del-desiran, we had the final results for the Phase I/II study MARINA trial published in the New England Journal. Those are results you all know well. But I think to highlight the excellent profile that we've seen with this medicine, and we're on track for the Phase III readout for the HARBOR study in the second half. Now moving to Slide 16. I did want to say a word on the pipeline readouts for the rest of the year. We have quite a bit happening and we're excited about that. So in the first half, I already mentioned the Rhapsido CIndU positive readout. We did have ianalumab readout in warm autoimmune hemolytic anemia, which did not meet significance, so we won't be taking that forward. But we don't expect that to be a read-through to ITP, where we already have positive second line data, and we'll look forward to the first-line data in the second half. We also have data in-house now for votoplam, which confirm our approach for the Phase III study based on that data, we feel very comfortable taking the 10-milligram dose now forward into the pivotal Phase III readout. We are, in collaboration with our partner, PTC, now discussing the best next steps for that medicine, including further interactions as well with the FDA, and we'll keep everyone apprised as we continue to progress that medicine forward. We also are on track as well for the FSHD biomarker cohort readout as well. Our plan would be to ultimately disclose that data after we've had any discussions with FDA to understand better if the data meets the standard for an accelerated approval. We do not have that data in-house yet, but we do expect it over the course of the remainder of the first half. Other important readouts include, of course, the pelacarsen readout, which I'm sure we can discuss. The remibrutinib MS readout, which will have 2 replicate studies. The Del-desiran DM1 study, which I also mentioned. And then we've accelerated now the Rhapsido HS program into the second half of this year. That study enrolled extremely quickly. So very excited because that will give us another first oral option for patients with HS. We also have our QCZ4A4 siRNA for hypertension Phase II data reading out. And then lastly, VHB RLS-TRM2 antibody reading out as well in the second half. So with that, I will hand it over to Mukul.

Thank you very much, Vas, and good morning, good afternoon, everyone. I will now take you through our financial results for the first quarter, which, as Vas mentioned, was strong despite significant U.S. generic entries. As always, my comments refer to growth rates in constant currencies, unless otherwise noted. Slide 18, please. Our Q1 results, as expected, were impacted by UX Gx erosion with sales down 5% and core op inc down 14%. And Worth noting is that we did have a positive gross net in our base from Q1 last year that also had a negative impact on the overall quarterly growth rate. Core margin in Q1 declined 4.1%. This was mainly due to higher R&D investments as well as the impact of generics on the gross margin. These results were fully in line with our internal expectations and how we see 2026 P&L phasing through the year panning out. Most importantly, our growth drivers continue to show very positive growth momentum something that Vas has shared earlier on in the presentation, with growing at 34% in Q1. Slide 19, please. What's great to see is that our continued focus on free cash flow generation has paid off in Q1. The lower core open was compensated by favorable working capital movement and this brought back the free cash flow broadly in line with previous year quarter 1. Our strong cash flow continues to support our reinvestment into our business, including bolt-on M&A as well as gives us the opportunity to return capital to our shareholders through dividends and share buybacks. Slide 20, please. We remain committed to our talent shareholder-friendly capital allocation strategy, alongside an increased R&D, in the first quarter, we closed Avidity acquisition, and we also announced 2 early-stage deals to support our oncology and immunology disease franchises. On the other hand, for the return of capital to our shareholders front, we did pay $9.1 billion in dividend in March and April, as previously announced, and in addition, we continue to progress with our up to $10 billion share buyback program. This program still has around $6.1 billion remaining and is targeted to complete end of 2027. Slide 21. With that, I'll move to the guidance piece. So with our Q1 results, we are now reaffirming our full year 2026 guidance. We continue to expect 2026 to have low single-digit sales growth and low single-digit decline in core operating income. Worth noting is that this is the year we are growing the top line of the company through the largest LOE period that the company has seen. Core net financial expense will be around $1.7 billion and core tax rate would be about 16.5%. And these 2 parameters are consistent with our previous estimates. Slide 22, please. We continue to expect 2026 to be a year of 2 halves, H1 growth will be impacted by a tough previous year base following U.S. generic entries for Entresto, Promacta and Tasigna mid-last year. And with that, in the base, we had guided H1 sales to decline low single digit and core opening to decline low double digits. With our Q1 results now in the bank, we are on track to meet that guidance with Q2 sales expected to decline low single digits and core op inc expected to decline high single digit to low double digit. In half 2, the impact of the U.S. generic entries and the base will start to minimize and this will allow strong growth of our priority brands and launches to show through the overall P&L. And hence, we continue to expect H2 sales growth of mid-single digit and core op inc growth of mid- to high single digits. And that brings us to our full year guidance. Next slide, please. If exchange rates remain at late April levels, we expect positive plus 2% impact on full year sales and positive 1% on full year core operating income. As a reminder, updated exchange rate assumptions are published monthly on our website. And that concludes my remarks, and I'll hand it back to Vas.

Great. Thank you, Mukul, and welcome as well, Mukul, his first quarter here as CFO is off to a tremendous start. So overall, we've delivered a strong start in 2026 across our priority brands and launches, and we remain fully confident with our mid- to long-term growth outlook. We continue to advance our pipeline, completed the Ability acquisition and are well set up for multiple readouts in the second half remain on track to deliver our full year guidance. And we'll also look forward to those readouts, which could enable us to raise our mid- to long-term growth outlook. So with that, we can open the line for questions here.

[Operator Instructions] We will now go to our first question, and the first question today comes from the line of Peter Verdult from BNP Paribas.

Pete Verdult, BNP. Just 1 question, just a deep dive, please, Vas, on HS. Could you perhaps talk about NBRx during the presentation, but could you talk about current volume price dynamics for Cosentyx in HS, the target clinical profile for Rhapsido in HS? And how, if the data is positive, you would intend to position both assets in the market?

Yes, Peter. Absolutely. So overall, with Cosentyx, we've had stable, I'd say, gross to net across our indication suite this year. So I think we've been able to manage things pretty well. So overall, with this [indiscernible] we saw very solid volume growth in the quarter with HS. More of the headwinds that we saw with some of the older indications. But nothing notable in terms of increased gross to nets for Cosentyx in the quarter. So when you think about remibrutinib, the Phase II data indicated, I think, impressive -- well, early but impressive results in disease management. I think we'll ultimately have to see how the Phase III results play out. But the ambition would be to play -- as we have with remibrutinib in CSU and plan to do in CIndU, is to hopefully have an oral option that could be placed ahead of biologics. And so clearly, having 2 medicines would be helpful. We would have the oral option and ultimately, the biologic option as well. But I think this is really dependent on the data set. This is a heterogeneous population, and we're going to have to see how the data looks before we can fully define the positioning.

Your next question comes from the line of Sachin Jain from Bank of America.

I actually have a follow-on to the prior question on HS, if I may. So you sort of commented that, but what's your target efficacy profile relative to existing biologics just given the Phase II was hard to interpret with the inverse dose response and very placebo-adjusted rates? And then in your mind, is HS or MS likely a bigger indication?

Yes. I mean I think -- I don't know if I have the details Sachin, and we may have to follow up with you on our expectations on the Phase III study of the design in HS. But I would still say, it's all really going to depend, in terms of your second part of your question, the overall data profile that we see. I think clearly, if remi and MS proves itself both in relapse rate and disability progression to be better than the anti-CD20s, then, of course, the opportunity here is massive. I think if it's in line or ultimately a little bit worse than I think HS could be a similarly sized indication. We know the HS market is growing. We've guided it to be a $5 billion market, growing -- certainly, the potation potential is there to be much larger. And it might be that a safe and effective oral option would be really attractive. So I think it's really going to be dependent on that MS readout to understand the size of the MS opportunity. But I think it's exciting that we have 2 shots on goal with 2 -- with remi to add to what's 2 already very compelling indications that we have going forward. But we'll get back to you on your question on the HS.

Your next question comes from the line of Richard Vosser from JPMorgan.

A question about China. You referenced competition for Cosentyx, but we also saw much lower growth in general in China across Q1 despite the strong start for Leqvio. So should we expect more slower international growth for Entresto, Cosentyx going forward? And slower overall China development? Or can Leqvio continue to post drag China growth to double digits? And I have 1 quick linked question on Leqvio. How much of the peak do you think can come from China given the strong start?

Yes. Thanks, Richard. So overall, the dynamics in China, we've seen a stabilization in the early part of this year. I don't think we're back to the pre 2025 growth levels, but we do see a stabilization overall in the market as well and in our key segments. And so we feel confident that our China business can be in that high single-digit to low double-digit growth range. So that's been positive overall. I think -- but there's no question it won't get back to the really high growth rates we saw a few years ago. . We also see a higher number of competitors entering in, in each segment as well, which is something we have to just be ready for when we do launch in China. Nonetheless, very large market, highly attractive. And I think you've seen the strong performance that we've had. I think for Leqvio, we have guided that Entresto can be $1 billion medicine across its indications. And certainly, we have the aspiration to make Leqvio as big or bigger than Entresto over time. It's early days. I think understanding the trajectory of how we get there. But I would say we see very solid demand for the medicine. And I think if we could make it in the range of Entresto, that would be a success.

Your next question comes from the line of Simon Baker from Rothschild.

I will stick to the one. Taking up on your offer, Vas, could you give us your updated levels of confidence on the timing and outcome of the pelacarsen HORIZON study?

Yes, Simon. So I don't think I have anything new to add unfortunately because we don't have any new information. But I think we, of course, continue to make sure that the study is on track, no change in our expected readout. We do expect a readout in the early part of the second half of the year. So no change with respect to that. I think if we get a positive result overall, that regardless of the relative risk reduction, we'll find a way to ultimately launch the medicine. I think what we'll be really looking for is, are there either the 90-milligram prespecified subgroup or other subgroups where we can really demonstrate a significant benefit for patients that I think will help with the uptake, but we have no insight yet as to what that be. We've modeled it extensively. We continue to believe that we've done the RIGHT study and are fully powered for relative risk reduction in the 70-milligram per DL and higher patient population and relative risk reduction in the 90-milligram per DL patient population. As a reminder, the median level of the study is 108. So we definitely have enrolled the right patient group. And so we'll ultimately have to see. I think some of the other dynamics that will be important is cardiovascular versus stroke and how those different elements contribute to the primary outcome. We do have a MACE 4 endpoint here, so we do include stroke. And I think some of the recent literature would suggest stroke is going to be an important element of the story for Lp(a). So we'll see how that unfolds. So exciting, but we'll also have to see. I do want to highlight as well that as I've articulated in the past, this will be a slow building market simply because we need the testing rates to get much higher, so this will be, assuming it all plays out as we hope, of multiple iterations. But our DII 235 is ready to go into Phase III studies, which could be a once-yearly Lp(a) injection. So we're quite excited about that as well to be ready. Lastly, I would note that ACC and AHA have now added that everybody in the United States should receive an LP(a) test once in their life. And that's an important milestone to hopefully get testing rates up and to start to build the market over time.

Your next question comes from the line of Matthew Weston from UBS.

My question is about Rhapsido. Vas, now that we're heading to EU approval, Rhapsido is going to be one of the first pricing discussions for a multibillion dollar product since MFN. So assuming that you've had some early discussions with European governments, are you seeing countries inclined to pay higher prices for innovation in Europe?

Thanks, Matthew. So first, it's important to note Rhapsido only has an MFN impact for Medicaid because the approval happened before the signing of our MFN agreement. Our first launch that will have, I think, clear MFN-related implications across all segments in the U.S. would be ianalumab. So I think that's just 1 clarification. Nonetheless, I'll still answer the question in terms of the ongoing discussions with government. We are engaging with governments across Europe as well as in Japan to hopefully get to a better place. I think we're not seeing the progress that we had hoped to see at the pace that we had hoped to see. So I think there has to be some urgency here because I do expect across the industry, there will be difficult decisions companies will have to take in terms of how they launch or ultimately progress medicines. We're already in a situation where, depending on how you look 30% to 40% of medicines in Europe -- available in the U.S. don't ultimately come to Europe. You could have that number grow. You have, in general, significant delays for introduction of medicines into the European Union. So there's a lot of work to do. We certainly have, I think, proposals to all the key governments and most important, in my mind, are Japan and Germany, but we haven't seen the progress that we need to see. So this is something we'll have to continue to advocate for over the next year because I think it's really a 2027 story, where you start to see the impact of MFN on launches in Europe.

Your next question comes from the line of James Gordon from Barclays.

James Gordon from Barclays. The question was on hormonal breast cancer. So [indiscernible] in the U.S. approval for adjuvant hormone breast cancer well before the year-end because they've used a and I suggested this could be an $11 billion-plus product across adjuvant second line, but mostly in adjuvant. So -- and that seems to assume a big broad uptake. I think the logic is that, that could be used instead of someone using CDK4 for some of the patients. So based on what you know about hormonal breast cancer, do you think that's plausible, do you think even from the end of this year, you could see some pressure in CDK4 use because people instead would just do a SERD. So any thoughts on that, please.

Yes. We don't see that in the same way. I mean what we expect -- continue to expect is that physicians will want to use something to ultimately impact the hormonal access and then cyclin-dependent kinase access, especially for patients that we're talking about here which are patients that are Node 0, Node 1, Node 2 or more and have other risk factors that indicate they have a higher risk of recurrence of breast cancer. So that's point one. That's all of our market research suggest that. And I think part of the reason the major oral SERD companies are partnering with us to do combination studies as they ultimately see it in a similar way as well. I can't comment on patients who are very early or less high-risk early breast cancer patients, we used to call them kind of Stage 1. I think that would be a separate topic that you can talk to our competitor about, but that's not something that we see. I would also say that it is not a straightforward thing to replace established therapies like aromatase inhibitors that have been used for decades. So I think this is something that will take time. I think when you look at the data in almost any class of drug, when you're trying to replace a very established therapy, it requires a lot of education and a lot of work and that ramp will come up over time. So we don't view this as having an impact on the Kisqali outlook. Particularly now that in the first-line setting, it seems clear that CDK4/6 remain the standard of care for the remainder of Kisqali's life cycle. Our focus very much is on CDK2, CDK2/4, CDK4 to make sure that we can lifecycle Kisqali, you saw us bring in Pikevation, which we think has the opportunity to be a pan-mutant PIK3CA that has the ability to avoid some of the toxicity profiles that we've seen with hyperglycemia and off-target toxicities. So that could be an exciting medicine that hopefully might be able to be used broadly in approximately 50% of patients who have those mutations over time and then developing the combination drug studies, which we continue to do with the oral SERD companies.

Your next question comes from the line of Michael Leuchten from Jefferies.

Vas, question for you on Avidity. So Dine Therapeutics presented the ACHIEVE data recently with a splicing correction at month 3 to 11 at a higher rate than we've seen with Del-desiran. And they also showed positive trends in MDHI, I think we haven't seen any data for Del-desiran. Can you elaborate on how this data fits with your decision to pursue Avidity as opposed to other assets?

Yes, absolutely. No, I think, obviously, the way biomarker data, splicing correction data ultimately correlates with function is to be determined. And I think this is obviously a complex topic given that the target here is in the nucleus. And so it's definitely something where you're going to have different profiles for the different drugs, given that we're comparing here an siRNA versus an ASO versus other technologies that are being deployed. When we look at the data set that ultimately was published in the New England Journal of Medicine, very clear that you saw compelling data with the hand opening time. We saw functional endpoints going in the right direction. And so we saw everything the way we would expect it, and we have the opportunity here with a fully enrolled fully powered Phase III study that's going to read out well ahead of the competition. And I think once that happens, would make it harder for accelerated approval to ultimately happen in the field as historical precedents have shown. So I think being first to market with the key -- first-to-market medicine with a key -- with a compelling profile is going to be very attractive. And then I would also say that with the Avidity acquisition, we have not only DM1, but we also have the opportunity to be the first medicine even if we need to complete the Phase III study in FSHD. So it would be first to market, DM1, first-to-market FSHD. And now we're increasingly excited as well about the opportunity we're seeing in the pipeline to address more forms of DMD as well as apply the technology of anti-antibody whether sRNAs or ASOs to our own internal pipeline. So taken together, we think that was the right decision and everything that we've seen since completing the acquisition continues to confirm that.

Your next question comes from the line of Graham Parry from Citigroup.

So on remibrutinib in MS, you now have 3 trials read out with an Aubagio control arm giving you a pretty good view on the annualized relapse rate in that population. So to what extent can you compare that data to your blinded data in the remibrutinib Phase III relapsing MS trials. And to the extent you can comment, does that give you any increased confidence in the ability to meet the endpoint? And also, could you just reconfirm at this stage, you're not seeing any drug-induced liver injury or high elevations of ALT in the blinded data.

Yes. Thanks, Graham. So I don't have any comment on the ARR data. I'm not up to speed on any blinded views that we have or have not taken on the ARR data. But we do track the blinded safety data quite carefully. And I think all of the data that we've looked at and that I've also seen indicate that we don't see any any contribution if we assume that the historical rates that we've seen with teriflunomide in historical studies for liver -- drug-induced liver injury, enzyme elevations, et cetera, there is no contribution from the remibrutinib arm because all we see in the blinded data would be consistent with what 1 would see from having teriflunomide in the study. So that gives us a high degree of confidence given that all these patients are now are well past 3 months, where normally you would see any liver injury showed up. So it gives us a high degree of confident of the safety profile for remibrutinib is clean and consistent with what we've seen in CSU, in CIndU, in the Phase II HS study in the Phase II food allergy study. So now we have a pretty large portfolio of studies that have indicated the clean profile of remibrutinib with no insights so far on ARR, and I think we'll obviously read out the studies this summer, and we'll see where we are.

Your next question comes from the line of Thibault Boutherin from Morgan Stanley. .

So my question is just on Rhapsido. The previous communication was that you should see limited sales in Q4 last year, Q1 this year because of the free scripts before we see a step-up in Q2. And actually, we saw quite decent sales in the first 2 quarters. So I guess, question is how much stocking have we seen so far? And should we still expect a step up in Q2 as we bridge to paid script? And in general, if you could help us with the dynamic in terms of bridge for the rest of the year.

Yes, absolutely. I would say, first on stocking, we've seen stocking levels that are in line with what we've seen historically for brands. So I don't think there's a significant -- anything that's out of what we would expect from a stocking perspective. I think when you look at the early data, as I mentioned, 6,000 patient starts, 3,000 prescribers, about 1/4 of the top CSU physicians prescribing the medicine. So that's all, I think, in the right direction. We think that the early script data probably has to be interpreted carefully because we are using sampling and bridge programs, and as payer coverage expands, we will start to see the conversion from free to paid, but that's going to be a stepwise process over the course of the year. We have some early access wins ESI, Cigna, Optum, and we have been able to secure first-line post antihistamine coverage across those commercial plans. So I think overall, that gives us confidence. But I would expect it to be a steady increase in these initial months, not a hockey stick, simply because it does take time to get all of that in place and then ultimately start bridging patients. We would expect them to see an acceleration in 2027 as we then have a payer coverage in place and then we're well suited to have a significant launch. It doesn't change our long-term outlook. As we've guided, we think this can be a very large medicine in CSU alone. And then when you add indu on top and then hopefully, MS hopefully HS and then down line additional indications, food allergy, et cetera. We have a really exciting path ahead of us for the medicine.

Your next question comes from the line of James Quigley from Goldman Sachs.

I've got one on Del-desiran in DM1. So as we're heading into the data, what are you thinking would be a clinically meaningful impact on video hand opening time? And to what extent are the secondary endpoints is even more important here in interpreting the data into an overall benefit from a functionality perspective? And then also any comments you have on the recent early data from Sarepta in the same indication. So where do you think Del-desiran will be differentiated relative to the emerging competitors?

Yes. I think we'll be in a position to kind of comment on a specific event video hand opening time, but we do believe it's a well-understood endpoint. And if you reach statistical significance, we think that would be an important milestone. And all of our physician discussions would suggest that would be sufficient to warrant broad use of the medicine. I think importantly as well, we're going to be looking at additional functional outcomes such as the quantitative muscle testing and patient reported ported outcomes as well as a 10-meter walk and run test. I think all of that will help us to further characterize the treatment effect. Now when we look at some of the competitor data, I think it's important to note it's quite early. And as we know in these medicines that ultimately, you need a relatively broad patient group because of the diversity of manifestations of the disease. So I wouldn't want to over interpret what we're seeing. Certainly, it's exciting that there are many medicines coming forward to treat DM1 patients. But we feel like because of the large data set that we have now, over 100 patients treated across multiple disease states, 500 infusions, up to 4 years of multiyear exposure, that gives us a longitudinal data set that can really help us interpret the impact we're seeing. And I think most important for us is the muscle manifestations. I know there's been a lot of discussion as well about CNS. But I think in this particular disease, what really matters is muscle mobility and managing those muscle-related manifestations and that's very much our focus. So having, I think, 54-week follow-up long-term data on a large cohort of patients, gives you a very robust read, and I think we feel confident that based on everything we've seen in the Phase II study that we're set up well as well as we can be towards that Phase III readout.

Your next question comes from the line of [indiscernible] from ODDO BHF.

[indiscernible] from ODDO BHF. A big picture question for Vas. On your last slide, you highlighted that there will be multiple readouts in H2 that can raise your midterm to long-term growth outlook. Maybe, Vas, could you be a little bit more specific and give us a bit more color or from where do you see the potential upside coming from?

Yes. Thanks, [ Floren ]. When you look at what we guided to last fall, I mean our focus was very much on what we had in hand and a probabilized view of our pipeline. And I think when then some of these medicines if they ultimately come forward and we unprobilized that can lead to significant upside versus where we are today. I think, obviously, the big readout is not surprisingly, I think to all of you will certainly be remibrutinib -- for the 5-year term, remibrutinib in MS, remibrutinib in HS, Del-desiran, the DM1. We also believe ianalumab in first-line ITB can be $1 billion-plus indication. I think pelacarsen will be significant. I think it will take longer to build over time. And I think overall, the combination of pelacarsen plus DII 235 will give us a very significant opportunity. But in that kind of 5-year term, I think that medicine will take time to build up. But I think those are the medicines where if we see some wins, it could allow us to once we do the modeling to reevaluate the 5% to 6% growth that 2030 and hopefully drive additional upsides. So I think that's a great story. And I would say also in 2027, we have a number of readouts -- important readouts as well. Avolatimab in stroke prevention. We will have as well the -- we'll have as well the Kesimpta data as well as some other Phase II readouts as well as starting to read out as well our immune reset portfolio. So I think a number of readouts coming that could further bolster the long-term outlook of the company.

Your next question comes from the line of Kerry Holford from Berenberg.

Question from me on Pluvicto, please. So following the recent European filing withdrawal in that pre-taxane setting, just keen to hear whether you plan to run any additional trials to address the EMA requirements. And if not, does the lack of pre-taxane in approval in that region have any impact on your peak sales forecast for that drug?

Yes. Thanks, Kerry. So no impact on the peak sales forecast. We continue to expect $5 billion-plus. We had assumed all along that navigating the European feedback on the comparator arm would be a challenge. We evaluated multiple ways to try to address it, and we try to make the best arguments that we could. But ultimately, we thought it was prudent at that point to withdraw. We do see continued strong uptake in the vision population in Europe. It's important to note as well in Japan and in China, we are able to both have the PSA IV and PSMA vision populations, which are critical long-term markets. And the next step now for Europe will be the hormone-sensitive setting where we -- because Pluvicto is used in combination with an ARPI versus an ARPI, there, the comparator arm is what EMA would want. And I think would allow us then if we're to move forward now, we have the strong -- as you know, our PFS data, we're waiting on the OS data. Once we have that OS data, we should be able to file in Europe and then expand the patient population there. So I think that was the best outcome we decided rather than running additional studies that would take many years to just withdraw the file and wait for the HSBC readout.

Your next question today comes from the line of Steve Scala from TD Securities.

Some of your competitors are becoming increasingly vocal about extending big LOEs at the end of the decade. Novartis is the notable exception. It could be attributed to nothing more than communication practices. But if Novartis feels it has a good shot at delaying Cosentyx LOE then why not note that? And if this is an area of active pursuit, what is it that you're doing, co-formulation extended dosing? And related to all this, if Karen Hale is in the room, can she compare and contrast the store experience at AbbVie?

Yes. Thanks, Steve. So Karen Hale is in the room, but I'll spare her from having to compare her thoughts with AbbVie. I think it would be not the appropriate setting to do that, but we appreciate the question. I mean, of course, we have extensive efforts to defend our IP and then look at other ways to formulate our medicines. I mean a good example is Kesimpta 2 months, which we do have now, planned readout. We have additional efforts as well as the life cycle managed Kesimpta into longer intervals as well, which are still in the early phases of efforts. We'll see how that progresses. All of that would generate new IP, I think -- and so that one is clear. I think with Cosentyx, we have a number of cell line formulation and other patents that we continue to prosecute. We, as a practice, don't add those in as potential scenarios until we've gotten further along and I think in the litigation phase to really understand where those trials ultimately fit. So I think with Cosentyx, with Kesimpta, many efforts. I think we've discussed extensively with Kisqali the efforts around CDK2, CDK2/4, the Picavation efforts as well. Harder with a small molecule, as you know, to come up with significant reformulation efforts, but something that we're certainly looking at. I would point out even for medicines like Semble, we're actively already working on ways to hopefully extend that franchise even further. You know with Leqvio, we moved from 6 months also to 12 months and also to look at combinations of Leqvio to target other siRNA targets within cardiovascular disease things like HMG reductase, amongst others. So I think we have quite a broad effort to always think about this. But we don't want to overpromise at this stage, sitting here in 2026, 1 may or may have not happen 5 years from now. But rest assured, those efforts are ongoing. And as soon as we have something that we think is credible to put forward, we certainly will let the markets know.

Your next question today comes from the line of Naresh Chouhan from Intrinsic Health.

Just one, please, on Cosentyx. As we think about the margin impact of the Cosentyx LOE, is it fair to assume that you've already started optimizing the profitability as would be typical ahead of any other LOE?

Thanks, Naresh. I'll give that Mukul.

Yes. Nares, thanks for the question. Yes, absolutely, I would confirm that. I think as we have previously indicated, I think we are -- we projected an LOE in the U.S. for Cosentyx in 2029. There is also an IRA event in 2028 that we have factored into our numbers. And this is all baked into our back to 40% latest by 2029 guidance on the margin.

Your next question comes from the line of Seamus Fernandez from Guggenheim Securities.

This is [indiscernible] on behalf of Seamus Fernandez. We're encouraged by the advancement of your IL-15, the GIA632 into vitiligo. Can you share your thoughts on how you think about the market size of biologic eligible vitiligo patients? And if you don't mind, tying that into your thoughts on atopic dermatitis and the market opportunity there?

Yes, thanks. I mean the IL-15 is something we did mention at the meet the management, and we are quite excited by the profile of the of this medicine. For those of you who are not aware, this is a medicine that we in-licensed, it's overexpressed in patients with atopic dermatitis, but we also see the opportunity to address a number of other diseases over time, including vitiligo. And so it's early days. I mean, these Phase II studies are ongoing. The Phase IIa study in atopic dermatitis is now recruiting. The vitiligo study is set to begin. Obviously, if we can show meaningful improvements over the standard of care in atopic dermatitis or can obviously become a standard of care in vitiligo. These would be very large indications. I wouldn't be in a position to give you precise numbers, but obviously, very large market opportunities. And we are actively looking at moving that IL-15 across multiple other immunology indications over time. So I think as we progress, we'll of course keep you posted. And may I will also in atopic dermatitis, we also have the GHD program, which also IL-13, IL-18, which we're also on track.

[Operator Instructions] The next question comes from the line of Matthew Weston from UBS.

It's a quick follow-up about my first question about Rhapsido and ex U.S. And I was intrigued by your comment around you coming in for U.S. approval before MFN. Just thinking about the CNS indication, which I think you've said previously is going to have a separate brand name, but obviously the same active ingredient at a different dose. Does that mean it would also be excluded from MFN considerations because of the original approval or is that something that we'd have to think of in MS?

Yes. So our current assumption, Matthew -- it's a very good question. Our current assumption -- working assumption is that this is based on the chemical compound in question. So all -- because remibrutinib has an approval that even with different brand names that all of the subsequent remibrutinib indications would be susceptible to the Medicaid element of the MFN story, but not the overall MFN across all segments of U.S. reimbursement environment. I would say that is our current working assumption. And if that changes, we'll let you know. But our current expectation is that would be how remibrutinib would be treated. As would be the case for other medicines where such as Zolgensma, where we have but while the dose is changing, of course, the underlying gene therapy is the same. So that is our assumption for all of those medicines.

Your next question comes from the line of Michael Leuchten from Jefferies.

Question for Mukul, please. The gross margin is pressured by negative mix effect. Obviously, that is partly driven by the generic erosions and partly by the new products having payaways. Is there a scale factor in here that we should take into consideration as we think about the first half, second half of the year or is the gross margin just plain and simple mix driven?

Yes. So I think there is -- as you rightly said, I think there's 2 things at play here. If you look at Q1, the overall decrease in the margin is 4.1%, 3 percentage points of that comes from R&D spend and 1 percentage point comes from the GX impact on gross margin. Now GX impact on gross margin pretty much. I think if we take 2025 as a base, pretty much H2 base is what we should -- what you guys should model going into this year, and that should be the base. And as far as R&D spend, is concerned, I think we have to take into account not just the Avidity deal that we did, but we also did 3 other pretty significant deals And I think they -- they all came into the P&L from Q2 onwards. So in Q1, all of these 3 deals plus 1 month of Avidity is incremental. And going forward, I think part of it is already in the base. So the incremental R&D spend would start to run on our P&L.

Your next question comes from the line of Thibault Boutherin from Morgan Stanley.

Just a question on your comments on votoplam and the potential discussion with FDA on the Phase II. We had Phase II data some time ago. Have you seen anything new in the full data open-label extension that makes you more confident on the potential for the FDA to accept a fast-track approval?

Yes. I think as I said, we feel like the results that we've seen confirm our plan design in Phase III and also confirmed that the 10-milligram dose is the right dose to take forward. I think at this point, we're still in discussions with our partner company on the right approach with PTC on the right approach with any further engagement with FDA. And I think as soon as we have clarity on that, we'll, of course, and have those discussions with FDA, we can keep the market updated. But I think no further comment until those discussions are complete.

Your next question comes from the line of Graham Parry from Citigroup.

Just on Cosentyx if you could qualify the gross to net adjustments, both in the base year and this year or the quarter. And previously, you talked about U.S. growing mid-single-digit growth over the midterm to an $8 billion peak on that asset. Just that was absent from the release and slide stage, I just wondered if that still sound?

Yes. So on the gross net and adjustments for Cosentyx from quarter 1 last year. .

Yes. So I think if we exclude the gross to net impact on Cosentyx. Cosentyx moves into a positive growth territory for the U.S. I think to be exact, around 1% -- 0% to 1%, closer to 1% for the quarter. We have to think of -- and then I think if you think of an overall basis, we spoke -- we have 2 percentage points in our base for gross net in the U.S. in Q1 2025. And I think we also have a positive impact this year. The net comes to about 1% on an overall P&L.

And I think, Graham, when you look going forward, yes, we continue to expect to be in this mid-single-digit range globally. And I think that will be a mix of U.S. and ex U.S., and we're going to have to think, see how the coming quarters evolve, but that's our current expectation is that we would be in that mid-single-digit range. Clearly, the peak sales for Cosentyx would most likely be in 2027, given the IRA event in 2028 would impact the overall pricing in Medicare, but also into the Medicaid best price in 2028. So all of those dynamics are unfolding alongside the PMR launch and the ongoing launch in IV.

Your next question comes from the line of James Quigley from Goldman Sachs.

My second question. So just following up on the remibrutinib food allergy data from the Phase II that are supporting the Phase III trial. So what is it in the modeling that you saw that makes the 75-milligram the most appropriate dose given the data we've seen for the 100 milligram and the 25 milligram. Is there a a bridge between where the efficacy is between the 2 or would the 75-milligram dose had the same target engagement at 100 milligrams?

That's a great question. So we modeled this really carefully based on the full data set that we have. And we do believe that at 75 milligrams, we do have full target engagement, and we should be able to achieve efficacy that approaches the 100-milligram dose. But and so we felt like this was a reasonable approach to take, particularly given that we want to move into the adolescent population, and FDA would surely asked us to use the minimum required dose to achieve the efficacy required. So based on all our modeling, we believe we can get the necessary target engagement at 75 milligrams and then deliver the efficacy that you saw in the study, which as you could see, was really very compelling.

We will now take our last question for today. And the last question comes from the line of Steve Scala from TD Securities.

Slide 25 no longer mentions MFN, whereas the same slide in the Q4 deck did I'm just curious why. I heard your earlier responses to Matthew's questions, but Slide 25 suggests that Novartis is increasingly confident in its ability to deal with MFN, and I'm just wondering what has changed as we start 2026?

Okay. So I think no change in our perspective on MFN. I mean we don't -- we fully factored in MFN into the guidance that we've given, both for this year and the 5-year period. So that's fully factored. And if anything, I think we've gotten even better now in modeling the MFN impact. So we've made clear assumptions on the impact on the existing portfolio of medicines for the Medicaid effect as well as on future launches, a set of assumptions on launch phasing for drugs that have a full MFN effect, and then we'll ultimately, of course, see how this all unfolds. We also have signed the agreement to allow us to not have an impact from tariffs with the commercial agreement that we signed with the U.S. government as well as scaling up, as you've seen, our manufacturing plants around the United States to allow us to produce fully in the U.S. for the U.S. such that we wouldn't expect any tariff impact. So all that to say, I guess, at this point, we feel confident enough with MFN that we don't need to mention it anymore. Hence, that's why you're not seeing it on the slides. I think that is all the questions. So thank you all very, very much for an engaging discussion. I know we have some follow-ups, so we'll get back to you. We appreciate your time, as always, and we look forward to keeping you up to date in the months ahead. Have a great day.

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