Novartis - Q4 2025

Transcript

Operator (participant)

Good morning and good afternoon, and welcome to the Novartis Q4 full year 2025 Results Release Conference Call and Live Webcast. Please note that during the presentation all participants will be in listen-only mode, and the conference is being recorded. After the presentation there will be an opportunity to ask questions by pressing star 1 and 1 at any time during the conference. Please limit yourself to one question and return to the queue for any follow-ups. 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.

Sloan Simpson (Global Head Investor Relations)

Thank you, Sarah. Good morning and good afternoon, everyone, and welcome to our Q4 2025 earnings 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. Please refer to the company's Form 20-F on file with the U.S. Securities and Exchange Commission for a description of some of these factors. The discussion today is not a solicitation of a proxy nor an offer of any kind with respect to the securities of Avidity Biosciences or SpinCo. The parties have filed relevant documents with the U.S. SEC including a proxy statement for the transactions and a registration statement for the spinoff. We urge you to read these materials that contain important information when they become available.

Before we get started, I also want to remind our analysts to please limit yourselves to one question at a time, and we'll cycle through the queue as needed. With that, I will hand over to Vas.

Vasant Narasimhan (CEO)

Terrific. Thank you, Sloan, and great to be with everyone today. With me in the room are Harry Kirsch, our Chief Financial Officer, and Mukul Mehta, our Chief Financial Officer designate who will be taking over for Harry in mid-March. So let's dive into the results. When we start on slide five, Novartis delivered high single-digit growth as you saw earlier this morning, and importantly we achieved our 40% core margin goal two years ahead of plan. I think that demonstrates the strong operational performance of the company. On the full year our sales were up 8%, core operating income was up 14%, as I mentioned the 40.1% core margin. At CHF 21.9 billion now on core operating income, I think it's significant growth over the years.

In Q4 sales did decline, impacted by both the gross-to-net, which we'll talk about a bit more, as well as the Entresto LOE, and core operating income is up 1%. We did have some important pipeline highlights which we'll cover over the course of the call, but I think a few I wanted to highlight up front. First, remibrutinib. We achieved the submission in the most common type of CIndU that was based on positive phase III results as well as interactions with the FDA. We'll have the remaining readouts for the two other subtypes of chronic inducible urticaria over the first half of this year. With pelabresib we now have a path forward for both the E.U. and the U.S. I'll go through that data and the path forward on a future slide. So overall we met our upgraded full year 2025 guidance.

We expect to grow in 2026 through the largest patent expiry in Novartis history, which I think demonstrates the strong performance we have on our key growth brands as well on our pipeline replacement power. Now moving to slide six. The growth drivers in the quarter continued their strong trajectory as well as on the full year. Here you see the full year numbers. You can see Kisqali was up 57% on the full year, Kesimpta was up 36%, Scemblix up 85%, Pluvicto on the PSMA launch having dynamic growth as well. We'll talk about each of these brands in turn. Overall a 35% growth in this portfolio, and this is the portfolio that will carry us through the end of the decade as well as with many of these brands taking us into the mid-2030s. Now moving to slide seven.

On Kisqali we grew 57% in the quarter to on the year to CHF 4.8 billion, outpacing the market for CDK4/6. Now when you look at the chart on the lower left, our growth was 44% in Q4. When you remove the U.S. RD adjustments, our global sales grew at 54%, and our U.S. sales growth was at 62%. So in our view versus the consensus, the entire miss really came from these RD one-time RD adjustments. We remain fully confident on the $10 billion peak sales outlook for the brand. And what's underpinning that confidence is the very strong volume growth we're seeing across geographies. When you look at the middle panel, U.S. EBC NBRX is now above 60% and holding steady. I think that really demonstrates the strong preference providers have for Kisqali, particularly in settings where we are uniquely positioned.

In Germany we have over 80% NBRX share in the early breast cancer setting, which I think shows again this early strong performance for the launch in Germany, which we hope to carry over now to other ex-U.S. markets. Going to the last panel, yeah, I already went through many of the key, key elements, but I think I wanted to also note that EBC NBRX share is leading in both the overlapping and the exclusive population. Outside of the U.S. we have important launches in Italy and Spain coming up in 2026. Finally we continue to bolster the data profile for Kisqali, both with data that we recently presented at San Antonio and ESMO.

We'll continue to follow up these patients over the long run, and that should allow us to continue to have mature OS data over time, which we think will continue to bolster the portfolio. So very excited. Kisqali continues to have the outlook to be the largest brand in Novartis's history. Now moving to slide eight. Kesimpta grew 36% to $4.4 billion on the year. You can see a continued steady performance of this brand driven by the continued expansion of the B cell class within MS. In the U.S. we had 27% growth in quarter four. Importantly, we see increasing adoption in naive patients, which are now 50% of our NBRXs now in first line. Outside of the U.S. we are leading now in NBRX share on 9 out of 10 of the major markets that we track.

The core opportunity we see ex-U.S. going forward is to continue to expand B cell therapies in the 67% of patients who are not on B cell therapies and receiving disease-modifying therapies in MS. So we continue to generate additional value for Kesimpta. We've continued to progress also our every-two-month formulation for Kesimpta. So I think we're on a solid track with this brand to fully achieve our peak sales guidance of $6 billion+. Now moving to the next slide. Pluvicto now really showing dynamic performance with the PSMA for launch, 42% constant currency growth. We reached $2 billion in sales now overall globally. And that strong performance was driven primarily in the U.S. where we continue to see strong uptake in the pre-taxane setting. Sales grew 75%. We saw a 4x increase in our PSMA share since approval, now reaching 16% in that setting.

We also see continued growth on provider set across provider settings, including the highest growth in community where we now have over 790 treatment sites. Outside of the U.S., importantly, we've secured approvals in Japan and China, which also allowed us to continue to drive that ex-U.S. strong growth. And we expect that growth to accelerate now with the Japan and China launches upcoming. Now the next phase for Pluvicto, as we expect to kind of get to the peak of the PSMAfore population over the course of this year, will be the launch in the hormone-sensitive setting, which adds about 75% additional patients to the patients we already have from the Vision and PSMAfore population. That SNDA has been submitted to the FDA as well as the NMPA in China and PMDA in Japan.

We have the right foundation for that launch to be, we think, a rapid uptake with two-thirds of eligible hormone-sensitive patients already with existing treaters or providers. So the capacity is well established. I did want to flag as well that we have new manufacturing sites that are coming online in California, in Florida, as well as in Japan and China. We have over 440 treatment sites now outside of the U.S. as well. So we've really taken this to scale, which positions us well for the Pluvicto launches, ongoing Lutathera business, as well as our future RLT portfolio. Now moving to slide 10. Leqvio reached blockbuster status in the quarter. An important milestone for this brand as we continue that steady trajectory that we often see for cardiovascular launches. 57% growth on the full year, 46% on the quarter.

In the U.S. we continue to outpace the overall advanced lipid-lowering market. Our real focus is increasing depth in the health systems we've prioritized where there are strong capabilities within the buy-and-bill setting, strong interest in getting patients to goal, also focusing more on specialty areas as we've guided in the past. We saw 33% growth in the setting versus the prior year. Now a key milestone for us outside of the U.S. will be the NRDL listing, which we achieved in China and is already now started in the first part of January. As you have heard on previous calls, we had very strong uptake in China in the private setting, and now with the NRDL listing the early signals are very strong for rapid uptake in the China market for Leqvio. We're quite excited about that, and it's a key focus area for us in 2026.

We continue to build the evidence base for Leqvio, important publications in various journals mostly focused on adherence rates as well as our ability to drive LDL-C down to goal regardless of which background therapy patients are on. Now moving to slide 11. Scemblix had another strong quarter. We've reached again blockbuster status with this brand, and we have NBRX leadership in the U.S. and Japan. 87% growth in Q4. Now if I could focus your attention on the middle panel. In the U.S. we've reached 41% NBRX share now across all lines of therapy, and we plan to continue to grow that. But the most important thing for us now is to drive the growth in the first line setting where we're trending ahead of our plan. We're already now in the mid-20% range in the front line setting. We want to drive that up.

I think as we've now secured broad access, we have the opportunity now to continue to make Scemblix the medicine of choice on the front line for patients with CML. Now outside of the U.S. we also continue to have our leadership in the third line setting with 72% share across the major markets that we track. The early line indication is now approved in 60 countries, and we've already just launched in Germany. We expect to get other E.U. markets online in the front line with launches expected in 2027. I think one ex-U.S. market to note, which I think shows the ability we have to drive Scemblix outside of the U.S., is in Japan where we already have 45% front line market share, NBRX share, and 74% second line NBRX share. So really strong outlook, confident in the $4 billion+ outlook for this medicine.

Now moving to slide 12. Cosentyx grew 8% overall in the year, getting to $6.7 billion on the steady march up to our $8 billion peak sales guidance. You can see the 11% growth on the quarter. In the U.S. we had 9% growth. That was driven by higher demand we saw both in hidradenitis and in IV. Right now we're the number one prescribed IL-17 across indications, and that's really because of the strong access that we have, front line access. In HS now we are the NBRX leader in naive patients with 51% share and 47% overall. And the naive market is two and a half times the switch market. Certainly we've seen our competitor get traction in the switch market, but we're very much focused in that naive market where we have a really strong position. And the IV is also steadily advancing, 8%.

It's a steady growth, 200 new accounts, and we expect that to continue over the coming years. Outside of the U.S., no major changes, continued very strong growth, leading originator biologic in the E.U. and China. And overall we would forecast Cosentyx to have on average mid-single digit growth over the coming years as we get to that $8 billion peak sales potential. I did want to also flag that we have completed the submission with the U.S. FDA for polymyalgia rheumatica, and so we're excited about that as an additional launch now for Cosentyx. And we're also on track to file in the E.U. and Japan in the first half. Now moving to slide 13. Our renal portfolio has continued its rollout, I think, with steady progress.

Separate from that we also have amended our zigakibart phase III protocol, which I wanted to talk about in a bit more detail. Starting with our renal portfolio, our IgAN portfolio contributed 50% of the NBRx market growth versus prior year, driven equally by VANRAFIA and Fabhalta. So I think we see steady uptake across these two brands. Also in C3G Fabhalta continued steady adoption across the top accounts, and we hope to see that accelerate now over the course of 2026. Outside of the U.S. Fabhalta is now approved in C3G in 45 countries. VANRAFIA had its E.U. submission. So I think across these three brands we have the opportunity to continue to build out a strong position.

We do expect to be able to provide the full data set on the Fabhalta eGFR readout in IgAN soon, and also move forward with the filing for a full approval in IgAN for Fabhalta. Now on Zigakibart and we also expect I should also note the VANRAFIA full eGFR data set in the first half. On Zigakibart we have made the decision in order to optimize the overall label positioning and the competitive positioning to align our UPCR readout with the interim eGFR readout, which we expect in the first half of 2027. And we expect that to support our BLA for a full approval. This was a decision based on an analysis of the phase I and II data. We think we have the opportunity to be second to market with both proteinuria and the eGFR benefit.

So that I think is going to hopefully position us well to have a fourth renal agent in our portfolio. We also have combination trials underway because we certainly see the opportunity in having a hemodynamic agent, having a Fabhalta, and having a zigakibart, the opportunity to use combinations to optimize care for these patients. Now moving to slide 14. Rhapsido's U.S. launch, which is obviously something we're very closely tracking, is delivering encouraging results. We are optimistic with already what we're seeing in the early days for this launch. We see strong demand with an encouraging mix of patients, both patients who are post-antihistamines as well as post-biologic failure. We have a strong and positive response from allergists and dermatologists.

The sampling and bridge program has over 2,000 HCP starts, and I think that when we benchmark that versus other highly successful dermatology launches, it's right in line with some of the most successful dermatology launches. We're also seeing early access wins. I think access will be now the gating factor. Every few months we expect to bring on additional access on board. That will allow a steady pickup in sales over the course of the year with more of a steady pickup in the second half of the year. And I think it's really that second half I would encourage everyone to watch as we get that access together. And as a reminder, I think you all know well, clean safety, no box warnings, no contraindication, no required routine lab monitoring, no liver safety issues in the label, fast relief across a broad population as fast as two weeks.

Anecdotally, we hear reports as fast as a day or two days patients are starting to see benefit. And it's the only oral therapy approved by FDA who remains symptomatic despite antihistamine therapy. Now moving to slide 15. Now Rhapsido is one of these brands that we hope over time could become one of the largest brands in Novartis's history. This is an opportunity over multiple indications. I mentioned CSU launch, the CIndU now positive data that we have in hand for one type, two more types coming, an HS readout in 2028. We have positive food allergy data, which we'll be presenting in Q1 of this year. That's leading us to now initiate a broad phase III program in food allergy.

We are on track for the RMS readouts second half of this year, but really mid of this year is the opportunity that we had to readout the two RMS studies, SPMS and Myasthenia Gravis, ongoing. So when you take that together, you really clearly have an opportunity with a medicine with a clean safety profile and strong efficacy as an oral option to have a significant long-term sales potential. Now moving to slide 16. Now ITVISMA, which we haven't had as much attention, but it's something we continue to believe has a significant overall sales potential, total potential for this brand across the IV and IT of $3 billion+. This is a U.S. approval that brings the one-time gene therapy to children's two years and older. It's a broad label across patients who are nonsitters, sitters, and walkers. No AAV9 antibody titer limit for this treatment.

There's a strong value proposition, single administration, durable efficacy, solid safety profile. So we see a multi-blockbuster opportunity for this brand. 7,500 children, teens, and adults have not been treated yet with Zolgensma IV. We also have an extensive experience in the U.S. and ex-U.S. with this medicine. Outside of the U.S., we've already been approved in the UAE one day after the FDA approval, and Europe and Japan submissions are completed. As a reminder for Zolgensma, actually our sales are larger outside of the U.S. than in the U.S. So there's certainly a significant opportunity ex-U.S. for ITVISMA. Now moving to slide 17.

As I mentioned on the first slide, for pelabresib, we read out in quarter four the 96-week data from the phase III manifest program, which both on safety and efficacy has now given us a path forward to, we believe, get this medicine registered, assuming successful regulatory and clinical phase III trials. In that study, we showed deep and durable responses and a comparable safety profile to ruxolitinib and myelofibrosis. You can see the data here on the left in terms of the spleen response. When you look at the data that we presented, we had a deep and durable spleen volume reduction for the spleen volume 35% reduction landmark, 91.5% versus 57.6%. We also saw sustained improvements in symptom scores and anemia. We had two times as many patients reaching goal with the spleen volume reduction and the TSS 50. So we believe this medicine has disease-modifying potential.

We saw improvements in bone marrow pathology on the anemia. There was importantly now from a mortality standpoint fewer deaths and progressions observed with pelabresib and ruxolitinib versus ruxolitinib alone. The overall safety now is proven comparable with ruxolitinib, including comparable leukemic transformation rates, which was one of the topics that was holding this program back. With this data set, we have now an agreement with the E.U. to file in 2026 based on this data. In the U.S., China, and Japan, we'll be starting a new phase III study focused on patients who have high TSS 50 at baseline, where we believe we have the data set now to show we can achieve the regulatory milestone to ultimately get approval. Now moving to slide 18. I did want to also take a moment to mention our impact on global health.

As I think many of you know, Novartis has been in global health for nearly 100 years, working on malaria and other neglected tropical diseases. With our Coartem medicine 25 years ago, we started a real sea change in the treatment of malaria, reaching now well over a billion patients with Coartem. And now with the recent data we presented in November, we have the opportunity to bring the first new malaria medicine, novel medicine, such as Coartem, in 25 years. This is KAF156, ganaplacide plus lumefantrine. It disrupts the parasite's internal protein system. Very positive data here. You see on the adjusted basis, 99.2% cure rate versus 96.4% versus a five-day course, a three-day course, opportunity to block transmission, very solid safety profile. So we're quite excited to bring this forward as part of our mission in global health. Now moving to slide 19.

Now taken together, very good year for us from a pipeline standpoint in 2025. You can see we've met the vast majority of our milestones and trial starts. And I think that really shows the strong execution machinery we have now in R&D at the company, very aligned across research and development and strong execution across our global development organization. And turning to slide 20. For 2026, we're on track for seven pivotal readouts with the potential to strengthen the midterm outlook that we're guiding to, including the mid-single digit sales growth we expect in the 2030s. A few particular readouts which I haven't mentioned, which I'll call out. On the left side, you can see Pelacarsen for CVRR. We do expect a readout middle of this year.

It will be second half, and it will be middle of this year, which if positive, would allow us for a U.S. submission this year. We also are on track for our submissions for ianalumab and Sjögren's disease, and as well as the Delpacibart zotadirsen DMD U.S. submission, which assuming the closure of the Avidity deal would also happen in the first half of this year. Number of pivotal readouts. I mentioned Pelacarsen. There will be the ianalumab readouts in hematology, which could have significant potential to drive that brand to very large long-term potential. Of course, Remibrutinib, as well as the Delpacibart etedesiran DM1 phase III readout, again, assuming the closure of the Avidity. We also have the additional readout of the DUX4 interim data readout as well, which could support an accelerated launch in FSHD. However, that we would characterize as an upside case.

And then a number of key study initiations you can see on the right-hand side of the chart. So another exciting pipeline year to continue to bolster our long-term growth profile. Now moving to slide 21. I will hand it over now to Harry.

Harry Kirsch (CFO)

Yeah, thank you, Vas. Good morning. Good afternoon, everybody. I now walk you through our financial results for the fourth quarter and the full year of 2025, which, as Vas mentioned, was very strong despite midyear significant U.S. generic entries. And as always, my comments refer to growth rates in constant currencies unless otherwise noted. So on slide 22, 2025 marked another year of excellent execution. So over the last five years, as you can see here, we delivered an 8% sales average growth rate and a 15% core operating income average growth rate driven by strong commercial execution, a great late-stage readout, and disciplined productivity programs. This translated on the right side into more than 1,000 basis points of core margin expansion in constant currencies. And as you can see, in reported currencies, allowed us to reach our midterm core margin target of 40% two years earlier than planned.

As you may recall, we initially planned for 2027. Now we have achieved it in 2025. With these results, I hope you agree, but I believe we have really elevated the company to a new level of sales performance, margin profile, and as I'll discuss later, free cash flow generation. On slide 23, just a quick summary. You see that we have delivered our full-year guidance in 2025 after upgrading twice throughout the year. We guided to high single-digit sales growth, and we delivered 8%. For core operating income, we guided to low teens and achieved 14%. This is a strong result in a year, as I mentioned, where U.S. generic entries for Entresto, Promacta, and Tasigna happened. It speaks really for the momentum of our priority brands, as Vas really laid out, as well as disciplined cost management. Turning to slide 24.

So here are a few more details. For the full year, we delivered the described solid top and bottom line growth, record a core margin, and record free cash flow, almost CHF 18 billion. The core margin in the year improved by 210 basis points to 40.1%, and core EPS rose 17% to $8.98. Free cash flow grew 8% to CHF 17.6 billion. Now for the quarter, on the right side here, as expected, the U.S. generics had an impact, which we see in Q4, and then Mukul will lay it out, first half of next year or of 2026, but then again back to growth. Anyway, sales declined 1% while its operating income increased by 1%. And the results were a little bit noisy due to some U.S. R&D adjustments.

A positive impact in quarter four of 2024, so last year financially, and a negative impact this year in quarter four 2025, mostly on generic brands. So excluding these adjustments, underlying quarter four sales growth would have been positive 3%. As said, the vast majority of the growth from net adjustments were Entresto and other generic brands like Promacta in the U.S. Core EPS in the quarter, $2.03, up 2%. Now on slide 25, you can see our continued progress on free cash flow generation, which reached $17.6 billion, all-time high for the company in 2025. I think it shows you also, beside the financial, the power of being a pure-play pharma company. As you know, many years back, with even six businesses or even before the Alcon and Sandoz spin, these numbers were usually the $10-$12 billion range.

Now this is the earnings power of a focused and very successful pharma business. We remain, of course, focused on ensuring that the growth and core operating income translates into high-quality earnings and strong cash flow generation. This robust cash flow allows us to reinvest in the business, pursue bolt-on acquisitions, and continue to return attractive capital to the shareholder through growing dividend and share buybacks. On page 26, a quick reminder on our unchanged capital allocation strategy. As you see, we continue to execute our balanced, shareholder-friendly capital allocation in 2025. We invested more than $10 billion in R&D, an 8% increase versus prior year, announced four acquisitions, 10 licensing deals, strengthening our key platforms and pipeline across all of our four therapeutic areas.

On returning capital to our shareholders, we completed our CHF 15 billion share buyback program in early July, and we launched a new up to CHF 10 billion program targeted to be completed by the end of 2027. Approximately CHF 7.7 billion of that remains to be executed. In addition, we distributed CHF 7.8 billion in dividends during the first half of 2025. Now speaking of dividends, turning to slide 27, we are proposing a dividend of CHF 3.70 per share, a 6% increase in Swiss francs and even double-digit in dollars. And it's our 29th consecutive dividend increase in Swiss francs since company creation 1996, and including years following the Sandoz and Alcon spins when we did not rebase the dividend at all. This reflects our long-term and longstanding commitment to a growing dividend in Swiss francs per share. That concludes my remarks.

Before handing over, I'd like to briefly acknowledge that this will be my final earnings call as CFO of Novartis. It has been a privilege to serve in this role the last 13 years and to work alongside Vas and so many other great colleagues to help guide the company through a period of significant transformation and performance improvement. I'm very pleased to hand over to Mukul, a longtime colleague. In fact, we both started maybe at different stages of our career in 2003 at Novartis and very intensively worked together, especially the last 10 years. So with that, I turn over to Mukul to take you through 2026 guidance.

Mukul Mehta (CFO Designate)

Yeah. A big thank you to you, Harry, for everything. It is an honor to step into the role that you're leaving me with. And I look forward to getting to know everybody on the line in the months to come. So if you can go on slide number 29, please. For 2026, we expect sales to grow low single digit and core operating income to decline low single digit. And this reflects the one-two percentage points of core margin dilution related to the Avidity deal that we had previously indicated. Importantly, in 2026, we will be growing top line through a period of highest GX impact in our company's history. At the same time, we will make sure that we continue to invest in R&D. We fund our launches appropriately while driving forward with the productivity improvement plans that the company has.

As previously noted, we expect to close the Avidity deal in the first half of 2026. Looking ahead, we remain very confident in our 5%-6% sales CAGR in the 2025-2030 period, and we expect to return to 40%+ core margin in 2029, as laid out in our capital markets study. For 2026, we expect core net financial expenses to be around $1.7 billion. This is higher than the 2025 levels, and this is largely due to the anticipated funding cost related to the Avidity deal, which we have previously indicated is primarily going to be debt funded. We also expect the core tax rate to remain around 16.5%. Moving to slide 30, please. As we have previously indicated as well, 2026 is going to be a year of two halves. We continue to expect strong volume growth from our priority brands throughout 2026.

We have to understand that for the first half of the year, we will have a tough prior year base with Entresto, Promacta, and Tasigna generics having entered the U.S. market mid-2025. With that, we expect the first half of the year sales to decline low single-digit and core operating income to decline low double-digit. Additionally, Q1 will be impacted by the 2% positive gross-to-net impact that we had in the base Q1 2025, which will weigh on the quarter-on-quarter growth rate in Q1. That said, in the second half of the year, we expect a clear improvement with sales growing mid-single-digit and core operating income growing mid- to high single-digit. This takes us to our full-year guidance of low single-digit on top line. So moving to slide 31, please.

If exchange rates remain at their late January levels, we expect a positive two-three percentage point impact on our full-year sales and a positive one percentage point impact on core operating income. As a reminder, which Harry conveyed previously, we publish updated FX estimates monthly on our website. That concludes my remarks, and I hand it over back to Vas.

Vasant Narasimhan (CEO)

Yeah, thank you, Mukul. I want to take a moment as well to acknowledge Harry Kirsch's incredible contributions to Novartis over 23 years. Over my tenure as CEO, now entering my ninth year, Harry has been by my side as we've transformed the company into a pure play and, I think, unlocked really outstanding shareholder returns, outstanding financial performance, but probably less visible as the strength of the finance organization Harry's built, as well as the culture he's created in the company around productivity, financial discipline, and operational excellence. He'll sorely be missed, but will continue his legacy in the years to come. And a big welcome to Mukul, who I've known for many, many years. He'll be a great addition to the team and continue the strong track record of Novartis finance in delivering strong operational execution. Now moving to the next slide.

I did want to take a moment to build on Mukul's comments on our confidence in our 5%-6% sales CAGR to 2025-2030. That includes the impact of Entresto in 2026, as well as the U.S. MFN agreement's impact. You can see in the chart, we do expect some generic impacts, though a lot of that is front-loaded in the early part of the 5-year trajectory here. A number of brands where we believe we can drive dynamic growth in the middle column. And then lastly, a strong set of assets that we probabilized in our pipeline.

This ranges from ianalumab, our various Pluvicto, and Actinium PSMA, Pelacarsen, as well as the Avidity assets, among others, that give us the opportunity to not only hopefully deliver the 5%-6%, but if we're successful on those pipeline assets, we could even drive higher growth in the period. So moving to slide 34 and in closing, strong performance in 2025. We delivered the guidance that we outlooked and got to our 40% core margin early. Our priority brands continue to outperform, and that's what's going to drive our growth through the second half of 2026 and then through the five years to come. We're advancing the pipeline meaningfully in 2020. We advanced it meaningfully in 2025, but it's seven pivotal readouts this year. And we're confident in that mid to long-term growth guidance. So with that, we can close this section and move to questions.

Operator, we can open the line. Thank you.

Operator (participant)

Thank you. To ask a question, you will need to press star one and one on your telephone and wait for your name to be announced. And to withdraw your question, please press star one and one again. Please stand by while we compile the Q&A roster. Thank you. We'll start with our first question, and this is from Sachin Jain from Bank of America. Please go ahead.

Sachin Jain (VP)

Hi there. Thanks for taking my questions. Perhaps I just kick off with thanking Harry for his support and insight over the years. The questions, I guess, for Vas on remibrutinib. You've talked about avoiding liver monitoring in MS given no Hy's Law. Competition recently has been vocal avoiding monitoring in the label when monitoring has been involved in the studies could be difficult. So why don't you just give us any color on FDA conversations around this topic and whether monitoring in the studies picked up events that required dose changes. Then a quick follow-on on efficacy, any color on what you're targeting on relapse rate progression given we have no phase II to go off here. Thank you.

Vasant Narasimhan (CEO)

Yeah, thanks, Sachin. So I think first on liver, I think we should first take a step back and note that we already have an approval and an approved label without any liver safety discussion in the label, which just points to the fact that remibrutinib structurally does not have the off-target toxicities we believe that the structures of some of the other molecules do. And so we didn't have any of that in the existing CSU label. I think out of an abundance of caution, given the findings of the other competitors, FDA asked us for limited liver monitoring to our understanding that's more limited than the liver monitoring that our competitors have had to add to their programs. And our full plan is assuming that we and as we've seen today, no liver signals in our study.

We fully plan to advocate to FDA that we should stick to the current label in the absence of any information to really any data to really change the current label with respect to that. I'd also note that in general, for competitors, when there is a Hy's Law case, at least to our understanding, whether it's one, two, three cases, that generally leads to REMS programs, leads to monitoring, does lead to warnings and precautions just given the safety risk that that creates for patients who have alternative therapies. In RRMS, there's numerous alternative therapies, so safety is absolutely paramount. So I think that's our overall perspective on the safety. We're very confident in overall Remy safety and assuming two positive phase III trials this summer, the potential for this to be a very significant medicine.

Now, with respect to efficacy, I think it's very fair to point out we don't have phase II data. We went to phase III based on the findings that we saw from competitors. But I think given that we know that we hit the target very well at 25 milligrams b.i.d. and we move up to 120 milligrams b.i.d. in this study, we think we'll definitely have strong target saturation. We think the molecule is very well designed. We look at the PK and the PD of the molecule. So that gives us confidence that assuming the class is effective against RRMS, we will have a compelling profile from an efficacy standpoint. And with the safety profile and with the fact that we're established now in the market having already launched, should give us a strong value proposition. Thanks, Sachin. Next question.

Sachin Jain (VP)

Thank you.

Operator (participant)

Thank you. We'll take our next question today, and this is from Simon Baker, Rothschild & Co., Redburn. Please go ahead.

Simon Baker (Partner and Head of Global Biopharma Research)

Thank you for taking my questions. Two, if I may, please. Firstly, just continuing on remibrutinib and going off from Sachin's question, I just wonder if you could give us your updated thoughts on the commercial opportunities here in MS because it kind of feels like that your enthusiasm for remibrutinib in MS has increased over time. A couple of years ago, there was talk of almost MS playing second fiddle to CSU. So just updated perspectives on your thoughts on the commercial opportunity. And then moving on to Pelacarsen, you've now guided to a 2H26 readout. Given this is an event-based study, could you just give us any thoughts on potential risks and risk mitigation for this what appears to be significantly lower event rate?

Does this run the risk of creating additional noise in the study, or is that more than offset by the powering assumptions and the design that you've built in there? Any thoughts on that would be very helpful. Thanks so much.

Vasant Narasimhan (CEO)

Yeah, thanks, Simon. So first on the commercial opportunity, I think it's really going to be data-driven. I think our base case assumption is that an oral drug will struggle to have the same level of efficacy as monoclonal antibodies in hitting the B-cell pathways in MS. And because of that, still, B-cell monoclonal antibodies will be the dominant class, but there will be a large number of patients that would want an oral option who don't want to go through injectable therapy. I mean, as I noted in my slide, still 25% of patients in the U.S. and 65% outside of the U.S. are on DMTs and are not on injectable B-cell therapy. So there's a large market there on its own.

And then I think it will depend if the efficacy and safety profile overall, particularly the efficacy profile in the case of Remy in our hands, is compelling enough to have a broader market. So I think we'll certainly see based on the data. But even if we take it as a given that there is a large B-cell monoclonal class out there, there is a large market or opportunity beyond that, which we think is important. And that, of course, the question is, with the brain-penetrant properties of our molecule, does that lead to other opportunities, either in SPMS or in the control of RRMS to provide another dimension? And that will all be data-driven as well. So in this case, I'll exceptionally take the second question, but if everyone could limit themselves to one question. Pelacarsen, so we expect a mid-year readout.

The study is going to completion in terms of the number of events that we had originally outlined. We had powered up the study, you'll recall, during the process of the phase III. So we feel like we're adequately powered to demonstrate both at the 70 mg/dL cutoff and the 90 mg/dL cutoff, the CVRR that we're targeting. And so I don't think there's necessarily any risk associated with going in full. I think what it does indicate is that the event rates are lower than what we had modeled from the published literature. And I think that's just something that is just the reality now that we've found. We suspect it has to do with the fact that we've really optimally managed these patients for all other risk factors, particularly LDL lowering.

And I think that, of course, has an impact on event rates as well. So we'll see. And we're excited to see this data and hopefully creating an entire new class of medicines that can help a whole group of patients that have no other option. And so I think with a positive study, we have the opportunity to give these patients a hopeful solution against sudden cardiac death and some of the other things that can happen for patients with elevated Lp(a).

Simon Baker (Partner and Head of Global Biopharma Research)

Great. Thank you very much.

Vasant Narasimhan (CEO)

Next question, operator.

Operator (participant)

Thank you. The next question today is from Matthew Weston, UBS. Please go ahead.

Matthew Weston (Managing Director of Pharmaceutical Research)

Thank you very much. Can I also add my thanks to Harry for all his support and best of luck for the future, Harry? Vas, Kisqali is building into a fantastic and highly profitable medicine for Novartis. I guess the only challenge is it has an LOE just after your 2030 time window. What are the options in-house to extend the franchise further in breast cancer? Given the SERD data that we've seen from a competitor, what other options are there from BD that could potentially or is oncology, I should say, a category where BD looks like somewhere you should supplement the Novartis pipeline?

Vasant Narasimhan (CEO)

Yeah. So I think there's actually two questions in there, but I'll also take both of these, Matthew, because it's you, Matthew. With respect to Kisqali, I think right now we guide to a mid-2031 with the pediatric exclusivity that we would expect for this brand in the U.S. I think it's longer outside of the U.S. depending on the market. Our core goal at the moment is our CDK2, CDK2/4, and CDK4 programs, all of which now are in the clinic. And we're advancing as fast as we can to see which of these medicines can provide either additional benefit in the post-Kisqali setting or either in combination, and we'll see what we ultimately learn. Of course, we also are advancing our radioligand therapy portfolio. We have two HER2 RLTs now in the clinic.

Those will be important to watch, as well as a neobomasin RLT as well in breast cancer. So number of shots on goal. And I think those will all be very important for us to continue to lifecycle manage Kisqali, as you rightfully point out, beyond the mid-2030s. I always think about it as a full-year 2032 effect for this brand. Now, I think with respect to BD and M&A, I think absolutely. I mean, we see amongst our therapeutic areas that clearly oncology is one we'll have to focus on. So we'll continue to focus there. As we have, I would say we've had just more opportunities and traction in the last years in cardiovascular, immunology, and neuroscience. You've seen us do a large number of deals in those spaces.

But we'll continue to see, and of course, it's a high priority to continue to build oncology now that we have the scale we're building from Scemblix, Pluvicto, Kisqali. And so if we find good opportunities, good assets, we'll certainly go after them. Next question.

Operator (participant)

Thank you. Next question is from Peter Verdult, BNP Paribas. Please go ahead.

Peter Vardult (Managing Director of Pharmaceuticals Equity Research)

Yeah, thanks. I'm Peter Verdult, BNP Paribas. Vas, just on Rhapsido and ianalumab, given we're now in an MFN world, how should we be thinking about ex-U.S. launch plans for what are clearly emotionally significant assets? Basically, just pushing my luck to see how specific you're comfortable being about changing in rest of world launch strategies for important assets like Rhapsido and ianalumab. Thank you.

Vasant Narasimhan (CEO)

Yeah. So I think this is high in our minds. We're working through our strategies here on Rhapsido. Given that it's already launched, of course, we would be exposed on the first pillar of the MFN approach, which is on the Medicaid rebate. It's more limited. And I think there we can manage. We think we have good options to manage the ability to launch Rhapsido globally. Of course, we'll have tighter pricing corridors, but that's something we think we can manage. ianalumab is more complex as we get to launches in 2027 in the G7-plus countries. There, of course, it's on the entire market of U.S. net price, not just Medicaid. And so we're working through strategies. Absolutely, it's our aspiration to get these medicines launched in all of these markets given the patients that need them. But we certainly can't adversely affect the U.S. market.

We're just going to have to be thoughtful about looking at where there are opportunities to price appropriately for the value that ianalumab brings. Given the PPP adjustments and some of the other elements of how pricing is looked at, are there things we can do to manage this? It's all in the works. I think we'll have a better sense over the course of this year on ianalumab. But on Rhapsido, we feel confident we have a way forward to get a global launch moving ahead.

Peter Vardult (Managing Director of Pharmaceuticals Equity Research)

Thank you.

Vasant Narasimhan (CEO)

Next question.

Operator (participant)

Thank you. Next question is from Steve Scala from TD Cowen. Please go ahead.

Steve Scala (Pharmaceutical Analyst)

Well, thank you so much. On Pelacarsen, Novartis has said previously that a delay in the Horizon trial readout would stem either from overestimating the baseline risk or underestimating the treatment effect. Do you have a sense of what is at work here? I would think the baseline risk, if it were overestimated, would question the value of lowering Lp(a) in the first place. And I would think that Novartis should have a better handle on treatment effect based on early studies. So any color of Novartis's view at this point would be helpful. Thank you.

Vasant Narasimhan (CEO)

I wish we knew, Steve. Honestly, obviously, I can only give you an opinion. I can't actually give you facts because we're completely blinded and we have no database insights. We believe that we have appropriately estimated the baseline risk. And that's after many rounds of looking at it. So it might be that that baseline risk is more prominent at higher Lp(a) thresholds. I think in my mind, it really comes down to what Lp(a) threshold are we appropriately thinking about the baseline risk and how at and this is, again, I think no way to know if this is correct. But my assumption is that at lower Lp(a) levels, there could be more interactions with LDL and other risk factors, and that Lp(a) becomes more dominant as you get to higher Lp(a) levels.

Because the risk goes up almost linearly, that a higher Lp(a) level, that becomes the dominant risk factor. So the studies obviously have some portion of patients at the 70-90 to 70-100. We've, I think, announced in our papers that overall our median is 108. So that's kind of our best guess in terms of the risk profile and how we've estimated it. Obviously, we would love for this to be that our treatment effect is larger than we expect. And that would be the reason for this, but there's just no way to know that at this time.

Steve Scala (Pharmaceutical Analyst)

Thank you.

Vasant Narasimhan (CEO)

Next question.

Operator (participant)

Thank you. Next question comes from Richard Vosser, J.P. Morgan. Please go ahead.

Richard Vosser (Managing Director)

Hi. Thanks for taking my question. Just a question on ITVISMA. Just how should we think about the ramp of that product in the U.S. and ex-U.S.? Could imagine that there are some patients that are potentially waiting for the therapy. So have you seen warehoused patients, and how should we think about the launch? Thanks so much.

Vasant Narasimhan (CEO)

Yeah. Thanks, Richard. In general, for gene therapies, we see often a pretty fast ramp as we get through the kind of prevalent pool of patients. And then it kind of comes down to a more steady state. And I think over the next two-three years, we would expect really ITVISMA to penetrate the majority of the kind of relevant patient pool that it has and then come back down, as we saw with Zolgensma, more to a steady state because of the nature of the one-time therapy. So I think relative to other brands, the ramp will be on the faster side. It won't be in six months. But I think over the first few years, we'll get to peak relatively quickly and then come down from there. And we do have, I think, warehoused patients. We do have patients that we really understand.

We also have strong access, we think, in many markets. And as we build that access forward, I think that will really allow us to maximize the medicine. Next question.

Operator (participant)

Thank you. Next question is from Graham Parry from Citi. Please go ahead.

Graham Parry (Managing Director)

Great. Thanks for taking my questions. So reiterate the best wishes for Harry, of course. And then the question on Kisqali and the outlook for the year. So how much of the gross-to-net impact that was impacting fourth quarter carries through into the next year because of a different channel mix versus how much is one-off? And so to what extent does that give you an easy base for comparison in 2025 into 2026? And then any thoughts you have on the risk that oral SERDs might pose to encroaching on CDK4/6 combinations in the adjuvant setting? Thank you.

Vasant Narasimhan (CEO)

Thanks, Graham. Great to have you back. On Kisqali, I think the higher gross-to-net, we believe, is a one-time effect where we saw higher Medicare utilization than we had forecast in 2025. We do expect, as the early breast cancer launch continues to accelerate and our mix shifts to younger and younger patients, that this will net out back towards where we had historically expected. I think we should be fine from that point forward. Harry wants to add something.

Harry Kirsch (CFO)

Yeah. Hi, Graham. Thank you very much. And by the way, everybody, for your nice words. So on Kisqali, I mean, one thing to note is that actually in quarter one of 2025, we had a positive gross-to-net at Mukul, as Mukul pointed out. So in quarter one, that's a higher base due to one-timers. As Vas mentioned, the quarter four, what we have noted here out of period adjustments. So if you take that out, it's really the true quarter four performance. And then in quarter four of 2026, there should be a bit of a lower base because of this negative this year. But overall, basically, these gross-to-net adjustments are all out of period. So one-timers and the underlying is what you see.

Vasant Narasimhan (CEO)

Then with respect to the oral SERDs, we've had a lot of discussion. We feel confident that when we look at the profile of Kisqali and what we hear from physicians, that physicians want a CDK4/6 inhibitor for patients who can benefit. They, of course, need to look for an endocrine therapy option. Certainly, the oral SERDs now have the opportunity over time to become the standard-of-care endocrine therapy option. We already know that roughly half of patients in the early breast cancer setting in the U.S. are already now on a CDK4/6. As we continue to penetrate that base of patients, we think that the opportunity will be CDK4/6 plus the choice of historical endocrine therapy or the oral SERDs. That's how this market will play out.

At the margin, could there be some physicians who choose an older endocrine therapy plus a CDK4/6 or an oral SERD and not a CDK4/6? Certainly, that dynamic will happen. But we don't expect that to be the predominant approach in the U.S. or in any of the other core markets. That's what gives us confidence in the $10 billion-plus guidance that we have and are sticking to. Next question.

Operator (participant)

Thank you. Next question today is from Seamus Fernandez at Guggenheim Securities. Please go ahead.

Seamus Fernandez (Senior Managing Director)

Oh, thanks very much. And just would echo, Harry will miss you for sure. Vas, hoping you could maybe give us your thoughts on the overall food allergy opportunity within your overall portfolio. Obviously, Xolair has done extraordinarily well in this space with excellent growth opportunity. Just hoping to get your perspective on that as well as the opportunity that you see potentially within your broader portfolio, not just for the BTK but beyond. Thanks so much.

Vasant Narasimhan (CEO)

Yeah. Thanks, Seamus. We've had a long history looking at food allergy. It goes back to a medicine some of you will remember called QGE031, which was a high-affinity anti-IgE that was supposed to be a follow-on for Xolair. In the end, we weren't able to show a stronger effect than Xolair has ultimately shown in food allergy. So we know the space well. Once we saw the phase II data for Remibrutinib and food allergy, I think it changed our perspective to really think now, how could we build this out to be a significant market opportunity? So we'll be sharing that data, as I mentioned, in the coming month or two. And with that dataset and now the agreement with FDA on how to advance into phase III studies, we see the option for a safe oral medicine to be able to hopefully be given broadly to patients.

You know that a lot of the patients in food allergy that are most interested or at risk to be treated are children. So versus ongoing injections, having an oral, high-efficacy, safe option, we think would be pretty compelling. So I think overall, we see food allergy as a multi-billion-dollar opportunity. Certainly, with the potential to make something major out of this, we're going to obviously run through the phase III program. We're excited to share the phase II data as well. Then beyond that, now we are evaluating, are there other opportunities within the pipeline earlier at Novartis and, of course, externally, as always, to see, could we further bolster our food allergy portfolio? So I think it's definitely a shift, but something we're getting quite excited about. Next question.

Operator (participant)

Thank you. Next question is from James Gordon at Barclays. Please go ahead.

James Gordon (Director)

Hello. James Gordon from Barclays. Thanks for taking the question. The question was on Pelacarsen and what a win now looks like. So you talked about a potentially lower event rate. But where is the latest magnitude of efficacy bar? Because I think the original design was a 20% benefit in the broader population and a 25% benefit in a narrow population with a longer study and maybe some other tweaks. Is that still the minimum? Is there a possibility that you could actually have a benefit for either of those groups that was statistically significant but didn't quite hit that hurdle? If so, would that still be a product with strong commercial prospects?

Vasant Narasimhan (CEO)

Yeah. Thanks, James. So you are correct. It is powered for 20% in the 70 mg/dL group and 25% for the 90 mg/dL group. We can win on the study with a relative reduction that's lower than that. And so certainly, there is the opportunity to win with CVR in the mid-teens. I think we'd have to evaluate, I think, for patients who have no other option. And if we were to win at that lower level, what would be the right approach to bring it to market? And that's something we'll have to see based on the data. But that's certainly something we'd have to look at. Of course, we hope for, I mean, how much higher CVR impact either at the lower cutoff or the higher cutoff. But we're going to ultimately have this to be data-driven.

There have been no other changes, though, from a protocol standpoint, from a study design standpoint. Everything is as it was when we originally started the study with respect to powering, etc.

James Gordon (Director)

Thank you.

Vasant Narasimhan (CEO)

Next question.

Operator (participant)

Thank you. Next question is from Michael Leuchten from Jefferies. Please go ahead.

Michael Leuchten (Managing Director)

Thank you. Question for Harry, please, given it's your last time with us. And thank you, Harry. The SG&A expenses in the fourth quarter were extremely tight. Very good performance. Dara helped you to gear the margin underlying terms. As I think about the margin for 2026, obviously, you do have the Avidity dilution. But if that SG&A control continues, I struggle to see how you're going to get as much dilution, especially if Avidity doesn't quite close as quickly as maybe it could. So can you just talk about the repeatability of that SG&A performance in the fourth quarter into 2026?

Harry Kirsch (CFO)

Yeah. Thank you, Michael. Actually, any 2026 question is kind of for Mukul. So I will hand over in a second. But historically, we always had quite an increase in quarter four. So we took this year to say, "Look, this is inefficient to have such a peak in a quarter where you have one to two weeks of Christmas and you have also in the U.S. Thanksgiving and so on. It shouldn't be actually a big peak here." So we took that in order to even it out. And overall, we will continue. And Mukul, of course, will drive productivity programs. But Avidity, just one thing.

I mean, a day before quarter three earnings, when we took you all through the Avidity deal, we said it would be a one-two percentage point margin dilution effect given the unusually high development cost burden the next two-three years of a late-stage development product with a very expensive medicine from a CRO, especially when it is under contract manufacturing. So not everybody has figured this into the consensus. It's okay when people don't follow everything we say, but we have mentioned it to you. And one-two points, if you say 1.5, that's pretty much what you get when you have a low single-digit increase on sales and a low single-digit decrease in core operating income. So we feel we have implemented exactly that. Without Avidity, it would have been unchanged margin, basically. But, Mukul, what do you think?

Mukul Mehta (CFO Designate)

Yeah. No, Harry said it all. I think the short answers, the short add-ons to the answer that Harry gave was the SG&A cost control productivity plans within the organization is something that we as a company feel very proud of and what has been achieved in the last four or five years. And as we go into our next five-year journey, this will absolutely continue going forward. There is a certain bit of margin dilution that we had predicted. And that's the reason that we gave clarity on H1, H2. Because if you look at how once the GX for this year are going to come off the base, we actually see core operating income starting to grow. And that kind of sets the base or sets the expectations for what to expect of our P&L in the next four years to come.

Vasant Narasimhan (CEO)

Thank you both. Next question.

Operator (participant)

Thank you. We'll take the next question. This is from Thibault Boutherin from Morgan Stanley. Please go ahead.

Thibault Boutherin (Executive Director of Equity Research)

Yes. Thank you. Just a question on Cosentyx and the dynamic in the HS market. It looks like the shares have been stabilizing for some time between Cosentyx and the main competitor in terms of NBRX and TotalScript. So from here, is it fair to assume that both drugs would grow in line with the market? And I think Novartis used to say the HS market, we should expect a growth around 15%. So I just want to know if it's the type of growth that you're still seeing today.

Vasant Narasimhan (CEO)

Yeah. Thanks for the question, Thibault. So you rightfully point out we've seen stabilization in the overall NBRX share in the market. As I noted, we're kind of in this 48%-50% range. And then we see the two other medicines splitting the remainder. We're doing very well in the naive population. And then in the switched segment, we see our competitor performing very well. So I think that's kind of the dynamic. We've seen that dynamic kind of stabilize now. So we would expect that dynamic to continue going forward. So I think all brands will grow based on the market. Now, clearly, the market potential here is quite large. It's just a matter of how effective we are at getting patients to come in to get treatment. So we continue to see this kind of $3 billion-$5 billion market opportunity.

But could it be larger if we were able to mobilize with two competitors and potentially more future competitors coming in, the market growing faster, certainly? And we'd, of course, want to capitalize on that. And that's part of the reason why we study Rhapsido in HS because we see the opportunity here to build this market, hopefully with a high-efficacy, safe oral to then go make the market even larger. So something we'll continue to work to build and hopefully get more of these patients who are kind of lost to treatment, probably were on a TNF, ultimately not successful, get those patients back into the medical home and back on therapy. Next question.

Operator (participant)

Thank you. Just a reminder, if you would like to ask a question, you will need to press star one and one on your telephone and wait for your name to be announced. We will now take the next question. This is from James Quigley from Goldman Sachs. Please go ahead.

James Quigley (Executive Director)

Great. Thank you for taking my questions. And my thanks and congrats to Harry as well for the next chapters. My question's on the Lp(a) portfolio. So as you showed in the slides, you've started a new phase II trial for DII235. Firstly, what are the dosing intervals they're going to be testing for that drug? And secondly, at the meet-the-management event, Vas, you were saying that if Horizon were positive, that could then lead to a decision to move some of the longer-acting Lp(a) straight into phase III. So are there other assets in the portfolio that you're holding back, waiting for Horizon to move into phase III? Is this phase II a function of a push-out in Horizon, or is it just you want to see more data beforehand before making a final decision here on which assets to take forward? Thank you.

Vasant Narasimhan (CEO)

Yeah. Thanks, James. So for DIA235, our partner, Argo Biosciences, I think publicly released that this has had already strong data in the early phase II study and has a potential for an annual dosing interval. And we are prepared to move that program directly into phase III based on the Horizon dataset. So there's no change in our plan. There might be different things happening between our studies and their studies, etc. But our strategy very much is based on the Horizon readout to then, based on the data we've seen with DIA235 on an annual dosing interval, to move that forward then into late-stage studies. We do have, of course, a range of other programs earlier stage as well on a range of cardiovascular assets.

We've talked about that in the past: HMG-CoA reductase, annual PCSK9, of course, the angiotensin 2 siRNA, and then combination programs as well that we're working on both at the six-month interval and at the one-year interval. And so both because we need to life-cycle-manage Leqvio, but also be prepared that if Pelacarsen's positive, the Horizon's positive, to be ready to come with what we think will be the preferred market option. We want to be ready for all these eventualities.

Great. Thank you.

Operator (participant)

Thank you. The next question is from Peter Verdult, BNP Paribas. Please go ahead.

Peter Vardult (Managing Director of Pharmaceuticals Equity Research)

Thanks, Peter Verdult, BNP. Just a follow-up for you, Vas, on the pipeline. Just on this basket of cell therapy programs in autoimmune, I think some of them do readout next year. Just wonder if you've got it in the top of your head in terms of which ones, which indications, and perhaps a general temperature check on your behalf in terms of your level of enthusiasm for these programs. Thank you.

Vasant Narasimhan (CEO)

Yeah. Thanks, Peter. We remain enthusiastic. We have a huge effort internally on YTB as a first instance, currently in pivotal studies aligned with FDA over 4 indications, and then with follow-on programs that are now in proof-of-concept studies, in 4 additional indications as well, and then additional exploratory work that's ongoing. And then behind that, trispecific and bispecific monoclonals also to explore, can there be alternative options for certain patient groups in the immune reset? I think the first readouts we'll have will be in SLE lupus nephritis. That's building off of the data we presented last year on 23 or 24 patients where we showed, I think, pretty spectacular results for those patients in terms of rewinding the progress of their disease other than the permanent damage that had happened to the kidneys. And so quite exciting data.

That's allowed us, I think, to move forward on that study quite quickly. But we also are advancing all the other programs. And some of them, if we're fortunate, might even be able also to readout next year depending on enrollment patterns and enrollment timelines. So we're advancing these as fast as possible. Depending on the program, many of them have alignment with FDA that we can file off of a single arm and then continue on to provide data on randomized datasets. Others need the randomized upfront. So that all varies based on indication. But I think a lot of the enthusiasm and focus inside the company. Thank you.

Operator (participant)

Thank you. We'll now take the next question. This is from Michael Leuchten from Jefferies. Please go ahead.

Michael Leuchten (Managing Director)

Oh, thank you for the follow-up. Vas, just on Scemblix, you helpfully provide the shared data across lines of therapy for the product. It looks like it's plateauing in first line in the U.S. a little bit over the last few quarters. What's stopping the momentum to continue?

Vasant Narasimhan (CEO)

Yeah. Thanks, Michael. So we have looked into that. One thing to note is the data is very noisy because with CML, it's a rare disease. Most physicians only see one or two patients. And so the data here always is getting restated. Overall, our view based on our internal assessments is we continue to see steady share growth on the frontline setting. Actually, I would say our frontline share growth is ahead of our plan and our original planning assumptions. And so we see the opportunity here to really continue to grow. We have really strong broad access. One of the biggest things we're trying to overcome is the perception that we don't have strong access. So get that access perception to where we want it to be.

And then, of course, as we've outlined in the past, you do have Gleevec loyalists out there who want to stay with a product that they've used for a long period of time. That will be more of a refractory group. But to get from the mid-20s up to the 40%-50% share range is absolutely what our ambition is, and we see a path to get there.

Michael Leuchten (Managing Director)

Thank you.

Vasant Narasimhan (CEO)

Next question. Or I think this might be the last question, operator.

Operator (participant)

Thank you. The last question today is from James Quigley from Goldman Sachs. Please go ahead.

James Quigley (Executive Director)

Hello. Thank you for taking the follow-up. I've got one quick one on Zigakibart. The data's been pushed out a little bit in order to have the eGFR data on the label at launch. But as you think about sort of the strategy here with your other assets, whether you had the UPCR data first and then adding the eGFR data, is this a case that the data were quite close together so it was worth having a delay? Just trying to understand the rationale here versus the other mechanism. Or is there something around the Zigakibart mechanism that could lead to a stronger benefit on eGFR relative to UPCR? Thank you.

Vasant Narasimhan (CEO)

Yeah. It's a great question, James. I think when we looked at the number of competitors entering in the anti-abral space, we asked ourselves, given we already have a strong portfolio in the nephrologist's office, what would give us the most compelling data package to kind of cut through all of the various launches that are ongoing? And we felt coming right away with hopefully the second medicine with a full approval, clear proteinuria reduction and eGFR benefit would give us a very compelling proposition. I mean, theoretically, assuming everything goes as we hope, we would have three medicines in IgAN with eGFR outcomes benefit across Fabhalta, VANRAFIA, and Zigakibart. And that would give us a very compelling proposition. So we thought that was prudent given that the time that passes here is 3 quarters. It's not the end of the world.

And then we would have a much more compelling dataset to provide to FDA.

James Quigley (Executive Director)

Got it. Thank you.

Vasant Narasimhan (CEO)

All right. Well, thank you all very much for joining the conference call. We'll look forward to keeping you up to speed. We wish you all a great 2026. Thank you.

Operator (participant)

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